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Allergic contact dermatitis is a critical issue in the development of new chemicals. Minor impurities with strong skin-sensitizing properties can be generated as byproducts. However, it is very difficult to identify these skin sensitizers in product mixtures. In this study, fluorescent nitrobenzoxadiazole-labeled glutathione (NBD-GSH) was synthesized to identify small amounts of skin sensitizers in reaction mixtures. Twelve known skin sensitizers and three nonsensitizers were reacted with NBD-GSH. Adducts formed only with the skin sensitizers, which allowed for their detection by a fluorescence detector. Liquid chromatography-mass spectrometry (LC-MS) analyses showed that NBD-GSH reacted with the skin sensitizers via its thiol and amino groups. An adduct of NBD-GSH with the strong skin sensitizer 1-chloro-2,4-dinitrobenzene was detected with a limit of detection of 6 × 10-8 mol/L by high-performance liquid chromatography with fluorescence detection. When a reaction mixture from primary alcohol oxidation was incubated with NBD-GSH, a NBD-GSH adduct formed with skin-sensitizing aldehyde impurities and could be specifically detected by LC-MS with fluorescence detection. This method will be useful for detection and identification of small amounts of skin sensitizers in raw materials, intermediates, reaction mixtures, and end products in the chemical industry.

Summary Background Standard treatment for untreated advanced-stage follicular lymphoma is rituximab plus chemotherapy. The incidence of histological transformation of follicular lymphoma has been reported only in heterogeneously treated populations and rarely with long-term follow-up. Additionally, the incidence of secondary malignancies after treatment, without high-dose therapy for follicular lymphoma, is largely unknown. The aim of our study was to assess progression-free survival, overall survival, incidence of secondary malignancies, and incidence of histological transformation in a 10-year follow-up analysis of the JCOG0203 trial. Methods In the phase 2–3 randomised JCOG0203 trial, previously untreated patients with stage III or IV indolent B-cell lymphoma, including grades 1–3 follicular lymphoma, from 44 hospital centres in Japan, were randomly assigned (1:1) by use of a minimisation method to receive six cycles of R-CHOP (rituximab [375 mg/m2], given on day 1, plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2, capped at 2·0 mg] given intravenously on day 3, and oral prednisone [100 mg once daily on days 3–7]) every 3 weeks (R-CHOP-21) or every 2 weeks (enabled by mandatory granulocyte-colony stimulating factor administration once daily for 6 days, starting on day 8; R-CHOP-14) without rituximab maintenance. Age, bulky disease (nodal or extranodal mass ≥10 cm in diameter on CT), and institution were used as adjustment factors. Investigators enrolled participants, and assignment to trial groups was done with a computer-assisted randomisation allocation sequence that took place centrally at the Japan Clinical Oncology Group Data Center, without the intervention of investigators. Interventions were not masked for patients or investigators. Data were collected 10 years after enrolment of the last patient. The primary endpoint of the phase 3 part of the study was progression-free survival, and the primary endpoint of the phase 2 part of the study was the proportion of patients who achieved a complete response. Accrual was 4·5 years, and follow-up was 3 years after registration was closed. Data were updated on the cutoff date of Feb 28, 2017. Intention-to-treat analyses (ie, progression-free survival, overall survival, and incidence of secondary malignancies) were predefined, to be done at 10 years after the last patient was enrolled. An additional analysis of the incidence of histological transformation was defined 15 years after the protocol, on May 8, 2017, in a supplementary analysis plan, and assessed at 10 years after the last patient was enrolled. Follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00147121. Findings Between Sept 1, 2002, and Feb 28, 2007, 300 patients were enrolled, and 149 (50%) were assigned to the R-CHOP-21 group and 151 (50%) were assigned to the R-CHOP-14 group. After eligibility was assessed, one patient was excluded from the R-CHOP-21 group. 10-year progression-free survival was not different between groups (R-CHOP-21 33%, 95% CI 25–41; R-CHOP-14 39%, 31–47; hazard ratio 0·89, 95% CI 0·67–1·17). In 248 patients with grade 1–3a follicular lymphoma, progression-free survival was 39% (33–45) at 8 years and 36% (30–42) at 10 years. The cumulative incidence of histological transformation was 3·2% (95% CI 1·5–6·0) at 5 years, 8·5% (5·4–12·4) at 8 years, and 9·3% (6·1–13·4) at 10 years after enrolment. At 10 years, the cumulative incidence of secondary malignancies was 8·1% (5·1–12·0) and the cumulative incidence of haematological secondary malignancies was 2·9% (1·3–5·5). Interpretation R-CHOP is a viable option for first-line treatment in patients with newly diagnosed advanced follicular lymphoma. Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death. Funding National Cancer Center and Ministry of Health, Labour and Welfare of Japan.

Introduction. The electrodiagnosis of CTS continues to evolve with renewed interest centering on the clinical use of mid-palmar stimulation and inching study. We reanalyzed our data (Neurology 1979;29: 581 [abstract]) on distal conduction abnormalities in DPN and CTS to discuss pros and cons of currently available nerve conduction techniques. Methods. We stimulated the median nerve at the wrist and mid palm to record muscle responses from the abductor pollicis brevis and sensory potentials from the index finger in 40 nerves from 22 DPN patients, 38 nerves from 24 CTS patients and 50 nerves from 25 normal controls (NL). Of these DPN patients, 24 median nerves were examined by a sensory inching study with 1 cm incremental stimulation. Results. The wrist-to-palm segment showed a significant (P Conclusion. Mid-palmar stimulation and inching method can distinguish diffuse slowing in DPN from a localized change in CTS along the distal segment of the median nerve.

Summary Background Intravascular large B-cell lymphoma (IVLBCL) is a rare disease for which there is no available standard treatment. We aimed to ascertain the safety and activity of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) with high-dose methotrexate and intrathecal chemotherapy as CNS-oriented therapy for patients with previously untreated IVLBCL. Methods PRIMEUR-IVL is a multicentre, single-arm, phase 2 trial at 22 hospitals in Japan. Eligible patients had untreated histologically confirmed IVLBCL, were aged 20–79 years, had an Eastern Cooperative Group performance status of 0–3, and had no apparent CNS involvement at diagnosis. Patients received three cycles of R-CHOP (rituximab 375 mg/m2 intravenously on day 1 [except cycle one, which was on day 8]; cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2·0 mg] intravenously on day 1 of cycle one and day 2 of cycles two and three; and prednisolone 100 mg/day orally on days 1–5 of cycle one and days 2–6 of cycles two and three) followed by two cycles of rituximab with high-dose methotrexate (3·5 g/m2 intravenously on day 2 of cycles four and five) every 2 weeks and three additional cycles of R-CHOP. Intrathecal chemotherapy (methotrexate 15 mg, cytarabine 40 mg, and prednisolone 10 mg) was administered four times during the R-CHOP phase. The primary endpoint was 2-year progression-free survival. Efficacy analyses were done in all enrolled patients; safety analyses were done in all enrolled and treated patients. The trial is registered in the UMIN Clinical Trials Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165); the trial is ongoing for long-term follow-up. Findings Between June 16, 2011, and July 21, 2016, 38 patients were enrolled, of whom 37 were eligible; one patient was excluded because of a history of testicular lymphoma. Median follow-up was 3·9 years (IQR 2·5–5·5). 2-year progression-free survival was 76% (95% CI 58–87). The most frequent adverse events of grade 3–4 were neutropenia and leucocytopenia, which were reported in all 38 (100%) patients. Serious adverse events were hypokalaemia, febrile neutropenia with hypotension, hypertension, and intracerebral haemorrhage (reported in one [3%] patient each). No treatment-related deaths occurred during protocol treatment. Interpretation R-CHOP combined with rituximab and high-dose methotrexate plus intrathecal chemotherapy is a safe and active treatment for patients with IVLBCL without apparent CNS involvement at diagnosis, and this regimen warrants future investigation. Funding The Japan Agency for Medical Research and Development, the Center for Supporting Hematology-Oncology Trials, and the National Cancer Center.

Acute promyelocytic leukemia (APL) in human immunodeficiency virus (HIV)-infected individuals is very rare. There is currently no consensus regarding the use of anti-cancer drugs with highly active anti-retroviral therapy (ART) in these patients due to their small number. We herein report two cases of APL with HIV-infected patients. Both cases received all-trans-retinoic acid-containing chemotherapies and achieved complete remission. ART was continued throughout the treatment course. The clinical course of these cases suggests that it is preferable to perform standard chemotherapy for APL with ART if patients have an adequate performance status.

Background/aim Neuroblastoma (NB) is the most common extracranial solid tumor in childhood; treatments with greater effectiveness are required for NB, especially in advanced cases. This study aimed at evaluating the combined effect of anaplastic lymphoma kinase (ALK) inhibitor alectinib and histone deacetylase inhibitor vorinostat on NB cell lines harboring wild-type or mutated ALK. Materials and methods Cytotoxicity was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. Protein expression was analyzed using western blotting. Results Combination treatment with alectinib and vorinostat had a synergistic effect on growth inhibition of the NB cell line with ALK R1275Q mutation. Cleavage of caspase-3 and poly-(ADP-ribose) polymerase increased, indicating enhanced caspase-dependent apoptosis. In addition, this combination reduced the protein levels of MYCN proto-oncogene and nuclear factor kappa B, both of which are important for NB tumorigenesis and progression. Conclusion Combined treatment with alectinib and vorinostat might be a novel therapeutic option for NB harboring the ALK R1275Q mutation.

Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology.

An optical-wireless code-shift-keying (CSK) system utilizing dual modified pseudo orthogonal M-sequence sets (DMPOMs) has been proposed by authors. DMPOM is generated by merging modified pseudo orthogonal M-sequence sets (outer code), bi-orthogonal code and orthogonal M-sequences (inner code). In this paper, bit error rate (BER) of the optical-wireless CSK/asynchronous CDMA is investigated in 2-user communication. Consequently, for the realization of the CSK/CDMA, it is effective to utilize the inner codes generated by different feedback taps.

We report a fabrication of transparent ZnO thick films by a chemical bath deposition using zinc acetate ethanolic–aqueous solutions with cetyltrimethylammonium chloride (CTAC). In this system, CTAC plays a particular role in nucleation and crystal growth of ZnO, and the micrometer-thick ZnO films formed on ZnO-buffered glass substrates. The resultant ZnO thick films show a high transmittance of around 80% in the visible region. An orientation of ZnO nuclei formed on the substrates in the early stage is different from a c-axis orientation of the ZnO-buffer layer, and the resultant ZnO thick films also show the unusual orientation. The detailed information on the orientation of these ZnO films was analyzed based on X-ray diffraction (XRD) 2θ/θ scan measurements at angles between in-plane and out-of-plane geometries. According to the results, the c-axis of ZnO is tilted at around 40–50° with respect to the film normal, and the micrometer-thick ZnO films exhibit the (112)-plane orientation by adjusting the CT...

The high density code-shift-keying (CSK) using Pseudo Noise (PN) codes generated by combining modified pseudo orthogonal M-sequence sets (MPOMs) with biorthogonal code has been proposed. In this paper, synchronous code division multiple access (SCDMA) capability of the proposed system is clarified under the optical-wireless channel. Consequently, simulation results are in good agreement with theoretical calculation results. In the proposed system, it is found that the performance deterioration is considerably small when the number of users ≦ 3. Moreover, the proposed system remarkably outperforms the conventional system when the number of users ≧ 2.

In this paper, a design of two-layered pseudonoise (PN) code for optical-wireless code-shift keying (CSK) is considered. One of the important issues encountered in optical-wireless CSK systems is to design a PN code for enhancing code division multiple access (CDMA) capability and a ratio N/L between the number of codes (N) and the PN code length (L). In this paper, a CSK system using two-layered PN codes which consist of outer-codes with L o chips and inner-codes with L I chips is proposed. Since the receiver of the proposed system can use the two-step demodulation scheme, it is expected that the proposed system suppress the performance degradation caused by co-channel interference. Consequently, N/L of the proposed system achieves more than 1. Moreover, when the length of the inner code is L / and the length of outer code is L O , the proposed system can accommodate N / — 1 users without co-channel interference in synchronous CDMA.

Introduction: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity characterized by selective growth of lymphoma cells in the lumina of small vessels. IVLBCL has been listed in the WHO classification, which improves recognition of the disease. However, no standard therapy has been established based on the results of prospective studies. We previously reported promising efficacy of rituximab (R)-containing chemotherapy for IVLBCL (JCO 2008) and a high incidence of central nervous system (CNS) recurrence (25% at 3 y) after R-chemotherapy (Lancet Oncol 2009, Cancer Sci 2010). To explore a more effective first-line treatment, we conducted a phase 2 trial of R-CHOP combined with CNS prophylaxis including R-high-dose methotrexate (R-HDMTX) and intrathecal chemotherapy with MTX, cytarabine (Ara-C), and prednisolone (PSL) (IT). Methods: Major inclusion criteria were untreated, histologically confirmed IVLBCL, age 20-79 y, ECOG PS 0-3, and no apparent CNS involvement at diagnosis. Patients received 3 cycles of R-CHOP followed by 2 cycles of R-HDMTX (3.5 g/m2; 2 g/m2 for ≥70 y) every 2 weeks, and 3 additional cycles of R-CHOP. IT (MTX 15 mg, Ara-C 40 mg, PSL 10 mg) was performed twice during the first 3 cycles of R-CHOP and twice during the final 3 cycles of R-CHOP (4 times in total). If patients achieved complete response (CR), they were observed without any therapy until relapse or disease progression. The primary endpoint was 2-y progression-free survival (PFS), and secondary endpoints included 2-y overall survival (OS), CR rate, cumulative incidence of CNS recurrence at 2 y, patterns of progression, and adverse events. The threshold 2-y PFS was estimated to be 35%, with expected 2-y PFS estimated to be 60%. With a statistical power of 90% and a one-sided, type I error of 5%, a projected sample size of 37 was calculated in anticipation of 10% ineligible patients. The trial was registered in the UMIN Clinical Trials Registry (UMIN000005707). Results: 38 IVLBCL patients were enrolled between June 2011 and July 2016. One patient was found to be ineligible after completion of the protocol treatment due to a past history of lymphoma. The protocol treatment was completed in 34 (89%) of 38 patients. The diagnosis of IVLBCL was histologically confirmed by central pathological review in all enrolled patients. The baseline characteristics of the 37 eligible patients were: male sex, 16 (43%); median age, 66 (range 38-78) y; ECOG PS >1, 15 (41%); stage IV, 37 (100%); serum LDH >ULN, 36 (97%); WBC Conclusion: This phase 2 trial met its primary endpoint and showed favorable outcomes with a low cumulative incidence of CNS recurrence and acceptable toxicity profiles. These results indicate that R-CHOP combined with CNS prophylaxis including R-HDMTX and IT could be a reasonable treatment option for untreated IVLBCL without apparent CNS involvement at diagnosis. Disclosures Shimada: Takeda Pharmaceutical: Honoraria; MSD: Research Funding; Otsuka Pharmaceutical: Research Funding; Janssen Pharmaceutical: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Eisai: Honoraria, Research Funding; Chugai Pharmaceutical: Consultancy, Honoraria; Kyowa Kirin: Honoraria, Research Funding; AstraZeneca: Honoraria. Yamaguchi:Ono Pharmaceutical: Research Funding; Teijin Pharma: Honoraria; MSD: Honoraria; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Sumitomo Dainippon Pharma: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Astellas Pharma: Research Funding; Sorrento: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Meiji Seika Kaisha: Honoraria; Kyowa Hakko Kirin: Honoraria, Research Funding; Eisai: Honoraria; Chugai: Honoraria, Research Funding. Atsuta:Chugai Pharmaceutical Co., Ltd.: Honoraria; Kyowa Kirin Co., Ltd: Honoraria; Mochida Pharmaceutical Co. Ltd: Honoraria; Janssen Paharmaceutical K.K.: Honoraria. Matsue:Celgene: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Ono Pharmaceutical: Honoraria; Novartis Pharma K.K: Honoraria; Janssen Pharmaceutical K.K.: Honoraria. Kusumoto:Chugai Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Research Funding; Kyowa Kirin Co., Ltd.: Honoraria, Research Funding. Nagai:Eisai: Honoraria, Research Funding; HUYA Bioscience International: Research Funding; AstraZeneca: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen Pharmaceutical: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria, Research Funding; Sanofi: Honoraria; Otsuka Pharmaceutical: Research Funding; SymBio Pharmaceuticals Limited: Honoraria, Research Funding; Solasia Pharma K.K.: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; IQVIA: Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; MSD: Honoraria; Novartis Pharma: Honoraria; Mundi Pharma: Honoraria, Research Funding; Bayer Pharma: Honoraria, Research Funding; AbbVie: Research Funding. Fukuhara:Mundi: Honoraria; Celgene Corporation: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria; Eisai: Honoraria, Research Funding; Janssen Pharma: Honoraria; Kyowa-Hakko Kirin: Honoraria; Mochida: Honoraria; Nippon Shinkyaku: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Zenyaku: Honoraria; AbbVie: Research Funding; Bayer: Research Funding; Gilead: Research Funding; Solasia Pharma: Research Funding. Miyazaki:Eisai: Honoraria; Chugai: Honoraria; Kyowa Hakko Kirin: Honoraria, Research Funding; Celgene: Honoraria; Ono Pharmaceutical: Research Funding; Astellas Pharma: Research Funding; Takeda: Honoraria; SymBio Pharmaceuticals: Honoraria; Nippon Shinyaku: Honoraria; Janssen Pharmaceutical: Honoraria. Okamoto:Kyowa Kirin Co., Ltd.: Other: Scholarship donation; Chugai Pharmaceutical Co., Ltd.: Other: Scholarship donation; Takeda Pharmaceutical Co., Ltd.: Other: Scholarship donation; Taiho Pharmaceutical Co., Ltd.: Other: Scholarship donation. Uchida:Eisai: Honoraria. Tsukasaki:Daiichi Sankyo: Consultancy; Kyowa Kirin: Honoraria; Huya: Consultancy, Honoraria, Research Funding; Byer: Research Funding; Mundi Pharma: Honoraria; Ono Pharmaceutical: Consultancy; Eisai: Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Masaki:Tanabe Mitsubishi: Research Funding; Taiho: Research Funding; Kyowa Kirin: Research Funding; Astellas Pharma: Research Funding; Chugai Pharmaceutical: Research Funding; Ono Pharmaceutical: Research Funding; Pfizer: Research Funding; Eisai: Research Funding; Taisho Toyama: Research Funding; Daiichi Sankyo: Research Funding; Teijin: Research Funding; Takeda Pharmaceutical: Research Funding. Kiyoi:Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Bristol-Myers Squibb: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Astellas Pharma Inc.: Honoraria, Research Funding; Takeda Pharmaceutical Co., Ltd.: Research Funding; Zenyaku Kogyo Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co.,Ltd.: Research Funding; FUJIFILM Corporation: Research Funding; Eisai Co., Ltd.: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Pfizer Japan Inc.: Honoraria; Perseus Proteomics Inc.: Research Funding; Daiichi Sankyo Co., Ltd: Research Funding. Suzuki:Chugai Pharmaceutical Co.,Ltd.: Honoraria; Meiji Seika: Honoraria; Merck Sharp & Dohme: Honoraria; Takeda Pharmaceutical Co., Ltd.: Honoraria; Bristol-Myers Squibb: Honoraria; Kyowa Hakko Kirin: Honoraria; Celgene: Honoraria; Eisai: Honoraria; ONO Pharmaceutical Co., Ltd.: Honoraria; Janssen: Honoraria; AbbVie: Honoraria; Novartis: Honoraria.

This paper reports the doping properties of polycrystalline silicon (poly-Si) deposited by atmospheric pressure plasma enhanced chemical transport and its application to a piezo-resistive pressure sensor. The doping is done by the chemical transport of dopants in Si sources. The structural and electronic properties reveal that most of the dopants are chemically transported at the same rate as the chemical transport of Si and activated as grown. A piezo-resistive pressure sensor is fabricated with the doped poly-Si film. All processes are carried out below 250 °C. The piezo-resistor shows the good linearity of the resistance change rate with the stress. These results indicate that our Si deposition method has adequate potential for nonvacuum and low temperature MEMS processes.

SUMMARY The characteristics of silicon films deposited at 700 Torr by plasma-enhanced chemical transport were investigated. The Si films were polycrystalline and the Hall mobility was 1.9 cm2/Vs. These results indicate that our Si films are comparable with polycrystalline Si deposited by conventional plasma-enhanced CVD. We fabricated a strain gauge sensor using our silicon film. The output voltage showed a good linearity to the pressure. © 2013 Wiley Periodicals, Inc. Electron Comm Jpn, 96(8): 26–31, 2013; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.11467

We report on a local ambient gas control technologies for atmospheric pressure plasma process using our new curtain gas structure. First, local ambient gas control with the curtain gas structure was investigated by computational fluid dynamic code. After confirmation of the feasible cleanness level with this structure, which is comparable to impurity level in semiconductor grade material gas (below 1 ppm), we fabricated a prototype apparatus. Measuring gas distribution by a gas analyzer, local ambient gas control was confirmed experimentally. Next, we attempted H 2 /He plasma generation in open air with H 2 concentration even above explosive limit in air (4.1 %) and achieved stable glow discharge with H 2 concentration of 0–40 %. In addition, reduction of copper oxides was demonstrated by H2 plasma exposure. These results show high potential of our method for atmospheric MEMS processes.

A novel crystal-growth system and morphology control of ZnO are achieved by using cetyltrimethylammonium chloride (CTAC), a general surfactant, in a new role. We synthesize ZnO via the layered hydroxide zinc acetate (LHZA) in ethanolic-aqueous zinc acetate solution. The CTAC surfactant plays three roles in the nucleation and crystal growth. First, it suppresses the formation of a strong concentration gradient in the solution. Second, it reduces the rates of nucleation and crystal growth of LHZA through diffusion-rate control in the solution. Finally, it expedites the formation of ZnO by increasing the solution pH. The competitive reaction, controlled by CTAC, between the nucleation and crystal growth of LHZA and the formation and crystal growth of ZnO results in the formation of a novel ZnO morphology. This morphology is composed of layered, nearly spherical particles, which are formed by the stacking of nanosheets with single-crystal-like, mesoporous structures.

Angioimmunoblastic T-cell lymphoma (AITL) is a major type of peripheral T-cell lymphoma (PTCL). To elucidate the clinicopathologic characteristics and prognosis of AITL in Japan, we retrospectively analyzed 207 patients with AITL. The median patient age was 67 years (range, 34-91 years), with 73% of patients older than 60 years. With a median follow-up of 42 months in surviving patients, 3-year overall survival (OS) was 54% and progression-free survival (PFS) was 38%. The International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) were predictive for OS in this analysis. Multivariate analysis found that age older than 60 years, elevated white blood cell (WBC) and IgA levels, the presence of anemia and thrombocytopenia, and extranodal involvement at > 1 site were significant prognostic factors for OS, and IgA, anemia, and mediastinal lymphadenopathy were significant prognostic factors for PFS. A novel prognostic model consisting of the prognostic factors for OS was successfully constructed. In conclusion, IPI and PIT were still useful for prognostication of AITL, and other factors, including those not used in IPI, such as IgA, anemia, WBC count, thrombocytopenia, and mediastinal lymphadenopathy, also significantly affected prognosis. Future investigations for IgA as a unique prognostic factor are warranted.

The characteristics of silicon films deposited at 700 Torr by plasma enhanced chemical transport were investigated. The Si films were poly-crystalline, and the hall mobility was 1.9 cm2/Vs. These results indicate that our Si films are comparable with poly-crystalline Si deposited by conventional plasma enhanced CVD. We fabricated a strain gauge sensor using our silicon film. The output voltage showed a good linearity to the pressure.

The development of a novel mist-jet technology for ejecting a water mist containing silicon microparticles is described and demonstrated. A desired pattern can be drawn successfully on a large substrate using a silicon head specially designed for highly purified mist. The demonstration was performed using water containing silicon microparticles. The ejected mist droplet diameter was observed to be approximately 2.8 μm stimulated by an ultrasonic driving frequency of 5 MHz. The substrate was mobilized by a motorized stage at an optimum speed of 60 mm/s and a working temperature of 100°C for dehydration. The letters "BEANS" were drawn in silicon on a 200 mm × 200 mm glass substrate without any required surface treatment. A silicon-coated substrate was prepared by mist-jet ejection on a 10 mm × 10 mm area for thickness uniformity measurement using stylus surface profiler. The silicon pattern achieved uniformity to a standard deviation of 20 nm at a thickness of 380 nm.

Background: Mantle cell lymphoma (MCL) is a moderately aggressive lymphoma and its pathogenesis is not fully understood. The genetic hallmark of MCL is the chromosomal translocation t(11;14)(q13;q32), causing upregulation of cyclin D1. However, approximately 10% of MCL does not harbor this typical alteration. Besides, the chromosome 5p15 region is recurrently targeted by chromosomal translocations in B-cell malignancies including MCL. The pathogenesis of the MCL cases as described above were not clear, and next generation sequencing analysis would be some help for understanding them. We experienced a MCL case which lacks t(11;14) and has a translocation involving 5p15 locus, and performed whole genome sequencing (WGS) analysis of this patient to elucidate its pathological mechanisms. Case: A 62 years old woman with long history of MCL. The karyotype of this patient was 47, XX, +5, t(5;18)(p15;q21), and did not have t(11;14). The pathological findings of resected spleen and bone marrow biopsy showed medium size B cell proliferation with overexpressed cyclin D1 and SOX11, and the diagnosis as MCL was re-confirmed. Methods and Results: We confirmed a chromosome translocation t(5;18) by WGS. Its breakpoint was localized in the intergenic region, so this translocation did not create a fusion gene. This region on chromosome 5 contains the telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) genes, and WGS analysis also identified SET-binding protein 1 (SETBP1) as the gene located near the breakpoint on chromosome 18. The expression of TERT and SETBP1 of this case was assessed by RT-PCR, and found that both genes were significantly increased compared to EBV-immortalized human B-lymphocyte cell lines. In addition, WGS analysis found the BRAF V600E mutation, which is quite rare among hematologic malignancies excluding hairy cell leukemias. Next, we investigated the role of these aberrations in the overexpression of cyclin D1. In this study, we used some non-hematologic cancer cell lines for transfection assays. The forced expression of TERT did not show any effect on the cyclin D1 expression in several cancer cell lines that we examined. However, BRAF wild type increased the cyclin D1 level in the breast cancer cell lines, MCF-7 and MDA-MB-231. Moreover, the BRAF V600E transfectant showed more upregulated level of cyclin D1 compared to BRAF wild type. These data suggested the possibility of the association of BRAF in the regulation of cyclin D1 expression. Conclusion: Our data suggested that the genes located around the breakpoint would not be related to the regulation of cyclin D1 expression in the MCL case with t(5;18), and that BRAF might contribute to the upregulation of cyclin D1. Disclosures Iida: Chugai Pharmaceutical Co., Ltd.: Research Funding. Nagai:Janssen Pharmaceutical K.K.: Honoraria, Research Funding; Abbvie G. K.: Research Funding; Bayer Yakuhin Ltd.: Research Funding; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Gilead Sciences Inc.: Honoraria, Research Funding; Zenyaku Kogyo Co., Ltd.: Honoraria, Research Funding; Solasia Pharma K.K.: Research Funding; Esai Co., Ltd.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Mundipharma K.K.: Honoraria, Research Funding; Kyowa Hakko Kirin Co., Ltd.: Honoraria, Research Funding; Ono Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Sanofi K. K.: Honoraria; Roche Ltd.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Research Funding; SymBio Pharmaceuticals Limited: Research Funding; AstraZeneca plc.: Research Funding; HUYA Bioscience International: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding.

Background: CHOP plus rituximab (R-CHOP) is the standard of care for previously untreated DLBCL. R-CHOP comprises CHOP and one-dose rituximab in each 21-day cycle; however, the schedule of rituximab administration has not been fully optimized. Dose-dense rituximab was expected to increase its peak concentration to enhance the synergistic effect with chemotherapy at early phase of treatment. To compare weekly administration of rituximab combined with CHOP (RW-CHOP) with standard R-CHOP in patients with previously untreated DLBCL, we conducted a multicenter, randomized phase II/III study (JCOG0601, UMIN000000929). Methods: Previously untreated patients with CD20+ DLBCL were eligible. Other major inclusion criteria were as follows: aged 20-79 years; ECOG performance status 0-2, at least 1 measurable lesion and preserved organ functions. At the beginning of the study, patients with advanced stage disease and the low or low-intermediate risk group by the International Prognostic Index (IPI) were eligible. These criteria were amended in September 2010 to allow enrollment of the patients with any IPI risk and any clinical stage because of slow accrual. Patients were randomly assigned to standard R-CHOP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 [max 2 mg], all IV on day 1, and prednisone 100 mg/day PO [40mg/m2 for aged >65] on days 1-5, every 3 weeks) or RW-CHOP (standard CHOP with eight doses of weekly rituximab [375mg/m2 IV on days1, 8, 15, 22, 29, 36, 43 and 50]). Six cycles of CHOP were given in stage I non-bulky patients, 8 cycles were given in stage I bulky and II-IV patients, and rituximab was given 8 times regardless of cycles of CHOP. Randomization was stratified by institution, presence or absence of bulky mass and patient age. The primary endpoint of phase III part was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AE). Assuming 3-year PFS in the R-CHOP arm to be 77% and expecting a 7% increase in 3-year PFS of the RW-CHOP arm, required sample size was 211 per arm with a one-sided alpha of 5%, power of 80%, an accrual period of 7 years, and a follow-up period of 3 years. Results: Between December 2007 and December 2014, a total of 422 patients were randomized to study treatments but primary analysis was performed in 421 patients: 213 to the R-CHOP arm and 208 to the RW-CHOP arm, because of one consent withdrawal. Baseline characteristics of 421 eligible patients were as follows (R-CHOP vs. RW-CHOP): median age, 61 vs. 62 years; male sex, 54.5% vs. 55.8%; Ann Arbor stage I/II/III/IV, 14.6/32.9/26.8/25.8% vs. 16.3/42.8/20.2/20.7%; and IPI score ≤2, 77.0% vs. 87.5%. With a median follow-up of 63.4 months (range: 3.2-119.2) among all patients, there was no significant difference in PFS between the arms (hazard ratio [HR], 0.95; 90.6% confidence interval [CI], 0.68 to 1.31; one-sided log-rank P = 0.39). The 3-year PFS and OS were 79.2% and 88.7% with the R-CHOP arm and 80.3% and 90.4% with the RW-CHOP arm, respectively. The complete response rate and overall response rate were 77.0% and 93.0% in the R-CHOP arm and 82.2% and 91.8% in the RW-CHOP arm, respectively. Major AEs were hematological toxicities and infections. Grade (G) 3/4 neutropenia and G 3/4 thrombocytopenia were observed in 97.7% and 8.0% in the R-CHOP arm and 97.1% and 5.3% in the RW-CHOP arm, respectively. G3 febrile neutropenia was occurred in 33.8% in the R-CHOP arm and in 22.1% in the RW-CHOP arm. The frequency of severe AE was 2.3% in the R-CHOP arm and 3.8% in the RW-CHOP arm. Safety profile was comparable. No unexpected AEs were experienced. Conclusion: In combination of standard CHOP and rituximab, dose-dense weekly rituximab at early phase of treatment did not improve the PFS in patients with untreated DLBCL. Figure. Figure. Disclosures Ohmachi: Celgene: Honoraria; Takeda Pharmaceutical Co., Ltd,: Honoraria; Pfizer: Honoraria; Chugai Pharma: Honoraria; Kyowa Hakko Kirin: Honoraria; Eisai: Honoraria; Janssen: Honoraria; Meiji Pharma: Honoraria. Kinoshita:Takeda: Honoraria; Takeda: Research Funding; Ono: Research Funding; MSD: Research Funding; Solasia: Research Funding; Janssen: Honoraria; Ono: Honoraria; Zenyaku: Research Funding; Eisai: Research Funding; Gilead: Research Funding. Tobinai:Kyowa Hakko Kirin: Honoraria, Research Funding; Zenyaku Kogyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; HUYA Bioscience International: Consultancy, Honoraria; SERVIER: Research Funding; Abbvie: Research Funding. Fukuhara:Sumitomo Dainippon: Research Funding; Solasia: Research Funding; Symbio: Research Funding; Sanofi: Research Funding; Pfizer: Research Funding; Otsuka Pharmaceutical: Research Funding; Ono: Honoraria, Research Funding; Novartis pharma: Research Funding; Nippon-shinyaku: Research Funding; MSD: Research Funding; Mundipharma: Honoraria, Research Funding; Mitsubishi Tanabe: Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Japan Blood Products Organization: Research Funding; Janssen: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Eisai: Honoraria, Research Funding; Boehringer Ingelheim: Research Funding; Daiichi-Sankyo: Research Funding; Chugai: Research Funding; Celgene: Research Funding; Baxalta: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Bayer Yakuhin: Research Funding; Alexionpharma: Research Funding; AbbVie: Research Funding; Astellas: Research Funding; Nihon Ultmarc: Research Funding; Taiho: Research Funding; Teijin Pharma: Research Funding; Zenyaku Kogyo: Honoraria, Research Funding; Takeda: Honoraria. Uchida:Takeda Pharmaceutical: Honoraria; Chugai Pharmaceutical: Honoraria; Kyowa Hakko Kirin: Honoraria; Meiji Seika Pharma: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Nippon Shinyaku: Honoraria; Novartis: Honoraria; Teijin: Honoraria; Celgene: Honoraria; Mundipharma: Honoraria; Janssen Pharma: Honoraria; Otsuka Pharmaceutical: Honoraria; Eisai: Honoraria. Yamamoto:Solasia Pharma: Research Funding; Bristol-Myers Squibb: Honoraria; Novartis: Honoraria, Research Funding; ARIAD Pharmaceuticals: Research Funding; Bayer: Research Funding; Celgene: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Ono: Consultancy, Honoraria, Research Funding; AbbVie: Research Funding; Boehringer Ingelheim: Consultancy; Chugai: Consultancy, Honoraria, Research Funding; Meiji Seika Pharma: Consultancy; MSD: Research Funding; Takeda: Honoraria, Research Funding; Zenyaku: Research Funding; Kyowa Hakko Kirin: Honoraria; Otsuka: Honoraria; Pfizer: Honoraria; Sumitomo Dainippon: Honoraria; Mundipharma: Consultancy, Honoraria; HUYA: Honoraria; SymBio: Research Funding; Gilead Sciences: Research Funding. Miyazaki:Kyowa Hakko Kirin,: Honoraria, Research Funding; Celgene: Honoraria; Chugai Pharma,: Honoraria, Research Funding; Sumitomo Group: Research Funding; Nippon Shinyaku: Research Funding; Takeda: Research Funding; Astellas Pharma: Research Funding; Shionogi Pharmaceutical: Research Funding; Daiichi Sankyo: Research Funding; Eisai: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Teijin Pharma: Research Funding; Ono Pharmaceutical: Research Funding; Toyama Chemical Co: Research Funding; Mochida Pharmaceutical Co. Ltd.: Research Funding; Novo Nordisk: Research Funding. Tsukamoto:Kyowa-Kirin: Research Funding; Pfizer: Research Funding; Chugai: Research Funding; Eisai: Research Funding. Iida:Teijin Pharma: Research Funding; Toyama Chemical: Research Funding; Ono: Consultancy, Honoraria, Research Funding; Kyowa-Hakko Kirin: Research Funding; Chugai: Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Astellas: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Gilead: Research Funding; MSD: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Sanofi: Consultancy. Yoshida:Taiho Pharma: Honoraria; Takeda Pharma: Honoraria; Celegene: Honoraria; Chugai Pharma: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding. Masaki:Ono: Research Funding; Kyowa Hakko Kirin: Research Funding; Phizer: Research Funding; Astellas: Research Funding; Eisai: Research Funding. Yakushijin:Mundipharma Co.,: Research Funding; Chugai Co.,: Research Funding; Kyowa-kirin Co.,: Research Funding; Merch Sharp & Dohme Corp.,,: Research Funding; Daiichi-Sankyo Inc.,: Research Funding; Eisai Co.: Research Funding. Suehiro:Kyowa Hakko Kirin: Research Funding; Ono Pharmaceutical: Research Funding; Chugai Pharmaceutical: Research Funding; Takeda Pharmaceutical: Research Funding. Nosaka:Bristol-Myers Squibb: Honoraria; Ono Pharmaceutical Co.LTD.: Honoraria; Eisai Co. Ltd.,: Honoraria; Kyowa Kirin Pharmaceutical Development, Inc.,: Honoraria; Chugai Pharmaceutical Co.LTD.,: Honoraria; Celgene Co. LTD.,: Honoraria. Dobashi:Celgene Co.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Zenyaku Kogyo Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co. Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Pfizer Inc.: Research Funding; Sysmex Co.: Research Funding. Kuroda:Chugai Pharma: Honoraria, Research Funding. Takamatsu:Taisho Toyama Pharmaceutical: Research Funding; TAIHO Pharmaceutical: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding; Ono Pharmaceutical: Research Funding; Astellas Pharma: Research Funding; Kyowa Hakko Kirin: Research Funding; Chugai Pharma: Research Funding; Takeda Pharmaceutical: Research Funding; Celgene: Honoraria. Maruyama:Ono Pharmaceutical: Honoraria, Research Funding; Fujifilm: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Asahi Kasei Pharma: Honoraria; AstraZeneca: Research Funding; Solasia Pharma: Research Funding; Pfizer: Research Funding; Nippon Boehringer Ingelheim: Research Funding; Dai-Nippon-Sumitomo: Honoraria; Dai-ichi-Sankyo: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Biomedis International: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Novartis: Research Funding; Otsuka: Research Funding; Amgen Astellas BioPharma: Research Funding; Zenyaku Kogyo: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Abbvie: Research Funding; Astellas Pharma: Research Funding; Mundipharma International: Honoraria, Research Funding. Ando:Eisai: Research Funding; Meiji Seika Pharma: Research Funding; Takeda Pharmaceutical: Research Funding; Kyowa Hakko Kirin: Research Funding; Japan Blood Products Organization: Research Funding. Ishizawa:Eisai: Honoraria; Janssen: Honoraria; Chugai: Honoraria; Celgene: Honoraria; Otsuka: Research Funding; Sanofi: Research Funding; Phizer: Research Funding. Ogura:Celltrion: Consultancy, Research Funding; Mundi Pharma: Consultancy; SymBio: Research Funding; Takeda: Honoraria; Cellgene: Honoraria; MeijiSeika Pharma: Consultancy. Hotta:SymBio: Consultancy; CellSeed Inc.: Membership on an entity's Board of Directors or advisory committees. Tsukasaki:Celgene: Honoraria; Eisai: Research Funding; Chugai Pharma: Honoraria, Research Funding; HUYA: Consultancy, Research Funding; Ono Pharma: Consultancy; Daiich-Sankyo: Consultancy; Mundy Pharma: Honoraria; Kyowa-hakko/Kirin: Honoraria; Seattle Genetics: Research Funding. Nagai:HUYA Bioscience International: Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Ono Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Gilead Sciences Inc.: Honoraria, Research Funding; Bayer Yakuhin Ltd.: Research Funding; Sanofi K. K.: Honoraria; Zenyaku Kogyo Co., Ltd.: Honoraria, Research Funding; Solasia Pharma K.K.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Roche Ltd.: Honoraria; Esai Co., Ltd.: Honoraria, Research Funding; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; SymBio Pharmaceuticals Limited: Research Funding; Janssen Pharmaceutical K.K.: Honoraria, Research Funding; Kyowa Hakko Kirin Co., Ltd.: Honoraria, Research Funding; Mundipharma K.K.: Honoraria, Research Funding; AstraZeneca plc.: Research Funding; Abbvie G. K.: Research Funding.

Chiral separation by high performance liquid chromatography (Chiral HPLC) is one of the most powerful methods for estimating optical and chemical purity of chiral compounds. However, it has a weakness in that much time and effort are required to prepare authentic samples. A novel chiral liquid chromatography-circular dichroism-NMR (LC-CD-NMR) technique, on the other hand, requires only crude chiral compounds that include enantiomers as minor impurities. In this study, chiral LC-CD-NMR was constructed by connecting a conventional LC-NMR system with a CD detector. A pyridylalanine derivative mixture was prepared to mimic technical grade material in an early phase of development. By chiral LC-CD-NMR, the enantiomer peak is identified by an opposite sign of the CD Cotton effect curve and an identical (1)H NMR spectrum to that of the main component. Using NMR as a detector, this method is superior in ability to discriminate enantiomers from other isomers indistinguishable by MS. Furthermore, this method is also applicable for selecting the best separation conditions of chiral HPLC. The degrees of separation (Rs) between the main component and its enantiomer in several chiral columns were compared. Even with modern chromatographic methods, establishing the best chiral HPLC conditions in an early phase of development is difficult: chiral LC-CD-NMR is a suitable solution.

A study of the effect of a gibberellin A3 + A4 mixture (GAs) on pre-harvest fruit drop of Japanese pear cv. Housui is reported. The GAs was applied alone or in combination with N-(2-Chloro-4-pyridyl)-N′-phenylurea (CPPU) in a lanolin paste to the abscission zone at the spur-end of the pedicel. The results showed that the GAs and CPPU combination treatment increased the pedicel–spur retention force relative to that of the untreated controls. Histological studies showed an accelerated rate of cambium division and the development of secondary xylem in the abscission zone near the spur-end of pedicels treated with the GAs plus CPPU paste, which delayed the formation of the abscission zone. Fruit quality (sugar, acid, firmness, color) was not adversely affected by the application of GAs plus CPPU, although the application of GAs alone promoted ripening. In contrast, the addition of CPPU to the two GAs delayed fruit ripening, which was measured as ethylene efflux. All treatments were without adverse effects on return bloom, measured as bud size. The CPPU plus GAs treatment also suppressed the incidence of water core, whereas the application of the GAs alone accelerated water core in this water core susceptible pear variety.

Starch synthase IIIa (SSIIIa)-deficient rice (Oryza sativa) mutants were generated using retrotransposon insertion and chemical mutagenesis. The lowest migrating SS activity bands on glycogen-containing native polyacrylamide gel, which were identified to be those for SSIIIa, were completely absent in these mutants, indicating that they are SSIIIa null mutants. The amylopectin B2 to B4 chains with degree of polymerization (DP) ≥ 30 and the M r of amylopectin in the mutant were reduced to about 60% and 70% of the wild-type values, respectively, suggesting that SSIIIa plays an important part in the elongation of amylopectin B2 to B4 chains. Chains with DP 6 to 9 and DP 16 to 19 decreased while chains with DP 10 to 15 and DP 20 to 25 increased in the mutants amylopectin. These changes in the SSIIIa mutants are almost opposite images of those of SSI-deficient rice mutant and were caused by 1.3- to 1.7-fold increase of the amount of SSI in the mutants endosperm. Furthermore, the amylose content and the extralong chains (DP ≥ 500) of amylopectin were increased by 1.3- and 12-fold, respectively. These changes in the composition in the mutants starch were caused by 1.4- to 1.7-fold increase in amounts of granules-bound starch synthase (GBSSI). The starch granules of the mutants were smaller with round shape, and were less crystalline. Thus, deficiency in SSIIIa, the second major SS isozyme in developing rice endosperm affected the structure of amylopectin, amylase content, and physicochemical properties of starch granules in two ways: directly by the SSIIIa deficiency itself and indirectly by the enhancement of both SSI and GBSSI gene transcripts.

Dionaea muscipula Ellis accumulates a large amount of plumbagin ( 1 ), which operates as an antifeedant against predators. Content of 1 reached 0.5% weight of the fresh trap lobes. It was found that other carnivorous plants also accumulated similar naphthoquinone-type strong antifeedant. Thus, naphthoquinone analogs are widely used as an antifeedant among the carnivorous plants. By using several analogs of 1 , we clarified that both the high volatility and high redox potential of 1 are important for its strong antifeedant activity. It was known that plumbagin stimulates the mitochondrial electron transport system as a result of intercepting electrons. These results suggested that the Droseraceae family possesses a universal defensive mechanism against predators, that is, accumulation of volatile naphthoquinone with high redox potential as defensive substance. Thus, it is estimated that highly volatile naphthoquinone of moderately high redox potential would be used as an antifeedant of weak toxicity.

Several subtypes of voltage-dependent calcium channels (VDCCs) are present in the presynaptic terminals. In the mammalian hippocampus, P/Q-, N-, and R- but not L-type VDCCs are involved in the fast transmitter release from large mossy fiber (MF) boutons, which are associated with CA3 pyramidal cell dendrites. We investigated whether L-type VDCCs are indeed absent in these large MF boutons. With the use of Sr2+ as the Ca2+ substitute, the stimulus-evoked Sr2+ increment (delta[Sr2+]pre) was evaluated fluorometrically. Delta[Sr2+]pre appeared to be proportional to Sr2+ inflow through VDCCs and was specifically attenuated by conventional VDCC subtype-selective antagonists. The P/Q-type selective omega-agatoxin IVA (AgTx(IVA)) blocked delta[Sr2+]pre with an IC50 of 28 nM and by 30-35% at its maximum effective concentration of 0.5 microM. The N-type selective omega-conotoxin GVIA (CgTx(GVIA)) blocked delta[Sr2+]pre with an IC50 of 15 nM and by 20-25% at its maximum effective concentration of 1 microM. The R-type selective SNX-482 blocked delta[Sr2+]pre with an IC50 of 79 nM and by 20-25% at its maximum effective concentration of 1 microM. The effects of these toxins did not overlap at their maximum effective concentrations and about 70-80% of delta[Sr +]pre was blocked by the simultaneous exposure to these toxins. delta[Sr2+]pre component that is resistant to AgTx(IVA), CgTx(IVA), and SNX-482 was significantly potentiated by an L-type agonist, (S)-(-)-Bay K8644, and attenuated by an L-type antagonist, nimodipine, suggesting that L-type VDCCs are present in large MF terminals. The L-type agonist, (+/-)-Bay K8644, also potentiated Sr2+ inflow into individual boutons identified as large MF boutons under confocal microscopy. Almost similar results were observed for Ca2+ inflow-dependent fluorescence increments. L-type VDCCs appear to be present in large MF boutons and mediate a substantial Ca2+ inflow into presynaptic terminals during action potentials.

Albiziahexoside (1), a new hexaglycosylated saponin, was isolated from leaves of Albizzia lebbeck. Saponin 1, which is an analog of cytotoxic albiziatrioside A (2), did not show cytotoxicity. However, 1 is a potential source of 2 and related bioactive saponins for medicinal use because leaves, which can be regenerated after collection, contain 1 in substantial quantity.

The low process characteristics of light intensity modulation direct overwrite (LIMDOW) magneto-optical disk with magnetically induced super resolution (MSR) function, especially front aperture detection (FAD) type were investigated. To improve low power margin in FAD-LIMDOW disks, exchange coupling between memory and writing layers should be large on copy temperature. It was confirmed that RE (Rare Earth) -rich composition was suitable for FAD readout and memory layer, and that high recording density LIMDOW disk with wide power margin was obtained.

Potassium (2R,3R)-2,3,4-trihydroxy-2-methylbutanoate (1) was identified as a leaf-closing substance in the nyctinastic plant, Leucaena leucocephala. Compound 1 showed strong leaf-closing activity toward L. leucocephala and was not effective against other nyctinastic plants. The potassium ion was indispensable for the bioactivity of 1. Compound 1 gradually lost its bioactivity because of the exchange of the counter cation during isolation. A leaf-opening substance was also observed in the same plant.

Hodgkin lymphoma became to be a curative disease. The standard treatment has been established for Hodgkin lymphoma, but its optimization still is explored. Risk stratification is critical in terms of optimization. The favorable patients would be treated with less toxic regimens. PET results are now used to evaluate the treatment response, and recently interim PET has been shown as a good predictor of prognosis. Interim PET is now incorporated into the treatment strategy of Hodgkin lymphoma in clinical trials. Molecular targeting drugs have been developed. Brentuximab vedotin, a kind of antibody drug conjugate, showed favorable clinical results for relapsed Hodgkin lymphoma.

A strict anaerobic bacterium, strain Y51, was isolated from soil contaminated with tetrachloroethene (PCE). Strain Y51 is capable of very efficiently dehalogenating PCE via trichloroethene (TCE) to cis-1,2-dichloroethene (cis-1,2-DCE) at concentrations as high as 960 microM and as low as 0.6 microM. Strain Y51 was gram-negative, motile with some lateral flagella, and curved rod-shaped. On the basis of the 16S rDNA sequence, the organism was identified to be a species within the genus Desulfitobacterium. Strain Y51 also had dehalogenation activities toward polychloroethanes such as hexa-, penta-, and tetrachloroethanes, from which dichloroethenes were produced as the final products. The cell extracts mediated the dehalogenation of PCE with reduced methyl viologen as an electron carrier at the specific rate of 5.0 nmol min(-1) mg cell protein(-1) (pH 7.2, 37 degrees C). Dehalogenation was highly susceptible to air oxidation, and to potential alternative electron acceptors such as nitrite or sulfite.

Intra–arterial infusion therapy following alteration of pelvic blood flow and concurrent radiation therapy was performed in 13 patients with muscle invading bladder cancer (T2, 2; T3, 6; T4, 5). The internal iliac artery of the opposite side was embolized and the ipsilateral gluteal and obturator arteries were embolized by metallic coils. A catheter was placed in the ipsilateral internal iliac artery. CDDP was administered daily at a dose of 7–9 mg/body over 1 minute. Radiation was done by Microtron using 10 MV x–ray. Total dose was 4500–7060 cGy. Evaluation was done by cystoscopy, radiography and biopsy. Eight patients achieved complete response (CR) histologically. Others had partial response (PR). All CR patients had no recurrence. The observation period was between 3 and 29 months, with a mean of 11 months. This treatment modality is effective for locally advanced bladder cancer.

An angucycline series compound P371 A1 (1) from Streptomyces sp. P371 was established to have a novel structure comprising an ureido group at one of four sugar units on the basis of 2D NMR techniques. 1 exhibited an inhibitory activity against the pentagastrin-stimulated acid secretion as well as protective acitvities against HCl/ethanol- and indomethacin-induced gastric lesions.

土壌中のテトラクロロエチレン (PCE) の嫌気的脱塩素化処理を目的として, 汚染土壌を詰めたカラムを用いて実験した。脱塩素化菌群の集積培養液を植種源として, また豆腐製造廃液を電子供与体として用い, 29ヵ月間, 汚染土壌を浸漬したところ, 土壌中のPCEの約35%および間隙水中の88%以上がジクロロエチレン (DCE) まで脱塩素された。しかし, エチレンまでの完全脱塩素化は進行しなかった。一方, 汚染土壌の上部に電子供与体となるウッドチップを詰めて, 下部から溶出液を採取する半連続カラム実験を行ったところ, 25日後の溶出液中には, DCEだけが検出された。それとともに, DCEの溶出量が増加し, 計算では, 汚染土壌中のPCEの完全溶出年数は11.7年から4.5年に減少した。このカラム実験でも, 完全脱塩素化は困難であったことから, カラム溶出液中のDCEの好気的分解を検討した。その結果, トルエンまたはフェノールを添加した場合にDCEの分解が認められた。また, 遺伝子組換え菌の静止菌体の利用が特に有効であった。

テトラクロロエチレン (PCE) 汚染土壌, 井水について, 嫌気性微生物による脱塩素化物である塩化ビニル (VC) を調査するとともに, その生成要因について検討した。VCは数箇所の井水で検出された。また, 脱塩素化生成物を多く含む井水中にはPCEをジクロロエチレン (DCE) に脱塩素する橙色の色素産生菌が存在していた。PCEのVC化, さらにエチレン (ET) 化には, 汚染井水の貯留槽の沈殿物の添加が不可欠であり, グルコースやシステインの添加がこの反応をさらに促進した。完全分解系 (PCEからET) と不完全分解系 (PCEからDCE) の二種のPCE分解系を井水から構築し, 脱塩素反応の差について検討した。その結果などから, 不完全分解は通性嫌気性菌群で可能であるが, 完全分解には, さらに嫌気性を要求する細菌群が関与する必要があると思われた。完全分解系では, 21mg/lのPCEを25℃, 16日間でETまで完全に脱塩素した。

CD20 is expressed in most B-cell lymphomas and is a critical molecular target of rituximab. Some B-cell lymphomas show aberrant CD20 expression, and rituximab use in these patients is controversial. Here we show both the molecular mechanisms and the clinical significance of de novo diffuse large B-cell lymphomas (DLBCL) that show a CD20 immunohistochemistry (IHC)-positive and flow cytometry (FCM)- negative (IHC[+]/FCM[−]) phenotype. Both IHC and FCM using anti-CD20 antibodies L26 and B1, respectively, were analyzed in 37 of the 106 cases of de novo DLBCL; 8 (22%) of these cases were CD79a(+)/CD20(+) with IHC and CD19(+)/CD20(−) with FCM. CD20 (MS4A1) mRNA expression was significantly lower in IHC(+)/FCM(−) cells than in IHC(+)/FCM(+) cells (P = 0.0005). No genetic mutations were detected in MS4A1 promoter and coding regions. Rituximab-mediated cytotoxicity in the CDC assay using IHC(+)/FCM(−) primary cells was significantly lower than in IHC(+)/FCM(+) cells (P

In Japan, the water quality standards for items requiring surveillance for drinking water in 1992 and environmental water in 1993 stipulate that the concentration of antimony is 2 μg/l or less. Recently cases of water contamination by antimony have been reported throughout Japan. We have measured antimony concentrations in the aquatic environment in north Kyushu district of Japan by atomic absorption spectrometry with hydride generation and found them to be in the range 0.0 to 0.8 μg/l all of which were less than the water quality standards at the present time. However, wastewater containing high concentration of antimony may contaminate aquatic environment in future. Studies have since been carried out to remove antimony from polluted wastewater. We tried to use ferric chloride as coagulant and dechlorination tap water containing approximately 10 μg/l antimony as the sample solution. Of the sample solution, pH of which was 7 - 8 and included the ferric chloride, pH was controlled by adding either hydrochloric acid or sodium hydroxide. The efficiency of removal of antimony reached a maximum at pH 4.0 - 5.5. When ferric chloride concentration was more than 30 mg/l at pH 4.5, 80 - 90% antimony was removed. However, when the original antimony concentration was 250 μg/l, up to 200 mg/l ferric chloride had to be added. Therefore, from water originally polluted by antimony at concentrations of 2 - 250 μg/l, almost complete removal of antimony is expected by adding ferric chloride to become 200 mg/l and adjusting the pH to 4.5.

Anandamide is an endogenous ligand for cannabinoid receptors. We tried to isolate and purify "anandamide amidohydrolase' which hydrolyzes anandamide to arachidonic acid and ethanolamine. The enzyme activity was found in the microsomal fraction of porcine brain homogenate. The enzyme was solubilized in 1% Triton X-100, and partially purified by hydrophobic chromatography to a specific activity of about 0.3 mumol/min per mg protein (37 degrees C). Apparent K(m) for anandamide was about 60 microM. The enzyme reacted also with ethanolamides of linoleic, oleic, and palmitic acids at lower rates. This enzyme preparation also converted arachidonic acid to anandamide in the presence of 250 mM concentration of ethanolamine. Several lines of evidence including experiments using various inhibitors suggested that the anandamide synthase and amidohydrolase activities were derived from a single enzyme protein.

We investigated the doping properties of polycrystalline silicon (poly-Si) deposited by atmospheric pressure plasma enhanced chemical transport and fabricated a strain gauge with the doped poly-Si film. The doping was done by the chemical transport of the dopant in Si sources. The electronic properties reveal that most of the dopants were transported as Si atoms. A strain gauge was fabricated with the doped poly-Si film. All processes were carried out below 350 °C. The strain gauge showed the good linearity of the resistance change rate with the stress. These results indicate that our Si deposition method has adequate potential for low temperature MEMS processes.

Background: Increased phosphatidylinositol-3-kinase delta (PI3Kd) activity drives proliferation and survival of malignant B-cells and mediates trafficking to lymphoid tissues. Idelalisib, a first-in-class, selective, oral inhibitor of PI3Kd, is approved in combination with rituximab for patients with relapsed CLL and as monotherapy in patients with relapsed/refractory (R/R) follicular lymphoma (FL) in North America and the EU. Methods: Six Japanese patients were enrolled between October 2014 and November 2014. This is an open-label 6+6 study design for continuous dosing of idelalisib 150mg BID in patients with R/R CLL and iNHL until PD or intolerable toxicity. The primary objective was to evaluate the 28-day safety, tolerability and pharmacokinetics of idelalisib and its metabolite GS-563117. The primary endpoint was the incidence of dose-limiting toxicity (DLT) defined as grade 4 hematological toxicities persisting for >14 days, grade ≥3 non-hematological toxicities, grade >3 laboratory abnormalities, red cell transfusion, and a therapeutic platelet transfusion. Key inclusion criteria were: age ≥20 yrs, patient of Japanese ancestry. Key exclusion criteria were known histological transformation to an aggressive histology, history of iNHL or CLL with CNS involvement. Response assessments as per modified Hallek 2008 and Cheson criteria 2007 were performed using CT scans at pre-determined time points by investigators. Results: Baseline characteristics included 3 patients each with CLL (2/3 refractory, 1/3 relapsed) or FL (3/3 refractory), and median age was 64 years (range 49-74). Median number of prior Rx regimens was 3.5 (range 1-6). Prior therapies included bendamustine plus rituximab (67%), R-CHOP (67%), and R-CVP (33%). No Japanese patients experienced a DLT within the 28-day window. The PK of idelalisib and GS-563117 were comparable between Japanese and non-Japanese patients; non-Japanese PK data predicted from preceding Phase 2 and Phase 3 studies. The most common treatment-emergent any grade/≥ grade 3 AEs in increasing frequency were gastritis (33%/0%), pyrexia (33%/0%), transaminases increased (33%/33%), chest pain (17%/0%), decreased appetite (17%/17%), diarrhea (17%/17%), neutrophil count decreased (17%/17%) and common laboratory abnormalities were decreased WBC (50%/17%), decreased neutrophil count (50%/17%), increased ALT (33%/17%), and increased AST (17%/17%). At the time of this analysis, a total of 3 patients experienced serious AEs (50%); decreased appetite, diarrhea, and increased transaminases. Investigator response assessments were 5/6 (83%) patients achieving partial response (PR) and 1/6 (17%) stable disease. Conclusions: Continuous dosing of idelalisib demonstrated a manageable safety profile with promising efficacy in Japanese patients with R/R CLL and FL. The PK of idelalisib and GS-563117 were comparable between Japanese and non-Japanese patients. The study was registered at ClincalTrials.gov (NCT02242045). Disclosures Kinoshita: Gilead Sciences: Research Funding. Fukuhara:Gilead Sciences: Research Funding. Nagai:Gilead Sciences: Research Funding. Izutsu:Gilead Sciences: Research Funding. Kobayashi:Gilead Sciences: Research Funding. Higuchi:Gilead Sciences: Research Funding. Harigae:Gilead Sciences: Research Funding. Tokunaga:Gilead Sciences: Research Funding. Adewoye:Gilead Sciences: Employment, Equity Ownership. Robeson:Gilead Sciences: Employment, Equity Ownership. Sharma:Gilead Sciences: Employment, Equity Ownership. Fukui:Gilead Sciences: Research Funding. Gao:Gilead Sciences: Employment, Equity Ownership. Christenson:Gilead Sciences: Employment, Equity Ownership. Tobinai:Gilead Sciences: Research Funding.

✓ The effects of tyrphostin, a selective protein tyrosine kinase inhibitor, on epidermal growth factor (EGF)-stimulated cell growth and EGF-receptor tyrosine kinase activity were studied in four human glioma cell lines. Stimulation by EGF induced variable enhancements of cell growth as well as tyrosine phosphorylation of EGF receptor and intracellular target proteins in all glioma cell lines. The level of immunoreactive EGF receptor detected with antibodies against extra- and intracellular domains was moderate in all four glioma cell lines, but markedly decreased with the latter antibody in two glioma cell lines. This variation was associated with considerable reduction of the EGF-stimulated tyrosine autophosphorylation level. Tyrphostin inhibited dose-dependently the EGF-stimulated cell growth and tyrosine autophosphorylation in all glioma cell lines, and the optimum time for the maximum inhibitory effect on tyrosine autophosphorylation was 12 to 18 hours after treatment with tyrphostin. The antiproliferative activity of tyrphostin nearly correlated quantitatively with its potency as an inhibitor of the EGF-stimulated EGF receptor tyrosine kinase activity. Tyrphostin had no significant effect on the immunoreactive EGF receptor levels, on the affinity constants and numbers of EGF receptor, or on the down-regulation and specific internalization of EGF receptor in any glioma cell line, suggesting that the effects of tyrphostin are not likely to be the results of reduction in EGF receptor and EGF binding capacity. In addition, the serum-stimulated cell growth was also inhibited dose-dependently by higher concentrations of tyrphostin in all glioma cell lines. It might be suggested, therefore, that tyrphostin inhibits EGF-stimulated cell growth by a specific suppression of EGF receptor tyrosine kinase activity, and at higher concentrations there appears to be some degree of either nonspecific inhibition or inhibition of serum-stimulated protein tyrosine kinase activity to induce the cell growth inhibition of gliomas.

Fifteen strains of Tetrachloroethylene (PCE)-degrading bacteria were isolated on agar plates from contaminated soils and a culture fluid which was acclimated to PCE with a subsoil of pond. Two strains of the isolates and others degraded PCE to trichloroethylene (TCE) and to cis-1,2-dichloroethylene (DCE) via TCE, respectively. Most of identified isolates were Bacillus species, which is the most common genus of bacteria found in soils. The acclimation of PCE-degrading bacteria with a subsoil of pond was performed readily. These results suggest that some indigenous PCE-degrading bacteria which are present in a PCE-polluted environment grow rapidly and readily acquire a higher degrading ability in the presence of favorable organic compounds as electron donors. The best PCE-degrading bacterium (Pseudomonas species) of isolates thoroughly degraded 160mg·l-1 of PCE to DCE within 4 days at 30°C.