Novel Tissue Protective Agents for the Treatment of Acute Radiation-induced BMF
2013-03-01
induced apoptosis in the following hematopoietic cell lines: HL-60, NB-4 cells, 32Dc13 and EML cell line. Experimental design and methods: HL-60, a...et al., 1999). EML Cell line (ATCC CRL-11691), a bone marrow cell line obtained by immortalizing bone marrow cells from male BDF1 mice with a...Membrane preparations were made from HL-60, NB-4, 32Dc13 and EML cells attempts were made to co-immunoprecipitate the CD131 molecule with EPOR in
Avci, Cigir Biray; Dodurga, Yavuz; Gundogdu, Gulsah; Caglar, Hasan Onur; Kucukatay, Vural; Gunduz, Cumhur; Satiroglu-Tufan, N Lale
2013-12-01
Neuroblastoma (NB), originating from neural crest cells, is the most common extracranial tumor of childhood. Retinoic acid (RA) which is the biological active form of vitamin A regulates differentiation of NB cells, and RA derivatives have been used for NB treatment. PPARα (peroxisome proliferator-activated receptor) plays an important role in the oxidation of fatty acids, carcinogenesis, and differentiation. URG4/URGCP gene is a proto-oncogene and that overexpression of URG4/URGCP is associated with metastasis and tumor recurrence in osteosarcoma. It has been known that URG4/URGCP gene is an overexpressed gene in hepatocellular carcinoma and gastric cancers. This study aims to detect gene expression patterns of PPARα and URG4/URGCP genes in SH-SY5Y NB cell line after RA treatment. Expressions levels of PPARα and URG4/URGCP genes were analyzed after RA treatment for reducing differentiation in SH-SY5Y NB cell line. To induce differentiation, the cells were treated with 10 μM RA in the dark for 3-10 days. Gene expression of URG4/URGCP and PPARα genes were presented as the yield of polymerase chain reaction (PCR) products from target genes compared with the yield of PCR products from the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. SH-SY5Y cells possess small processes in an undifferentiated state, and after treatment with RA, the cells developed long neurites, resembling a neuronal phenotype. PPARα gene expression increased in RA-treated groups; URG4/URGCP gene expression decreased in SH-SY5Y cells after RA treatment compared with that in the control cells. NB cell differentiation might associate with PPARα and URG4/URGCP gene expression profile after RA treatment.
Carvalho, Fernanda Caroline; Soares, Sandro Gomes; Tamarozzi, Mirela Barros; Rego, Eduardo Magalhães; Roque-Barreira, Maria-Cristina
2011-01-01
ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus (jackfruit), interacts with N-glycosylated receptors on the surface of several cells of hematopoietic origin, triggering cell migration, degranulation, and cytokine release. Because malignant transformation is often associated with altered expression of cell surface glycans, we evaluated the interaction of ArtinM with human myelocytic leukemia cells and investigated cellular responses to lectin binding. The intensity of ArtinM binding varied across 3 leukemia cell lines: NB4>K562>U937. The binding, which was directly related to cell growth suppression, was inhibited in the presence of Manα1-3(Manα1-6)Manβ1, and was reverted in underglycosylated NB4 cells. ArtinM interaction with NB4 cells induced cell death (IC50 = 10 µg/mL), as indicated by cell surface exposure of phosphatidylserine and disruption of mitochondrial membrane potential unassociated with caspase activation or DNA fragmentation. Moreover, ArtinM treatment of NB4 cells strongly induced reactive oxygen species generation and autophagy, as indicated by the detection of acidic vesicular organelles in the treated cells. NB4 cell death was attributed to ArtinM recognition of the trimannosyl core of N-glycans containing a ß1,6-GlcNAc branch linked to α1,6-mannose. This modification correlated with higher levels of N-acetylglucosaminyltransferase V transcripts in NB4 cells than in K562 or U937 cells. Our results provide new insights into the potential of N-glycans containing a β1,6-GlcNAc branch linked to α1,6-mannose as a novel target for anti-leukemia treatment. PMID:22132163
[Studies on red orpiment induction of NB4 and HL-60 cell apoptosis].
Bai, Y; Huang, S
1998-09-01
To study the possible mechanism of red orpiment, which is main component of composite indigo naturalis tablets, in the treatment of acute promyelocytic leukemia(APL). The effect of red orpiment on induction of APL cell line NB4 and HL-60 apoptosis were studied by cell morphology, DNA gel electrophoresis and flow cytometry assay. Red orpiment induced NB4 and HL-60 cell apoptosis. When treated with different concentration of red orpiment(25-200 micrograms/ml) for 16 hours, both NB4 and HL-60 cells showed typical apoptosis features. If decreased the concentration of red orpiment to 12.5 micrograms/ml, the NB4 cell still showed apoptosis features while the HL-60 cell did not when cultured for 72 hours. Arsenic disulfide(As2S2) had the same effect as red orpiment did under the same experiment condition. It is the main component, As2S2 of the red orpiment that can induces NB4 and HL-60 cell apoptosis. and the red orpiment is responsible for the high CR rate of APL induced by the composite indigo naturalis tablets.
Calreticulin Regulates VEGF-A in Neuroblastoma Cells.
Weng, Wen-Chin; Lin, Kuan-Hung; Wu, Pei-Yi; Lu, Yi-Chien; Weng, Yi-Cheng; Wang, Bo-Jeng; Liao, Yung-Feng; Hsu, Wen-Ming; Lee, Wang-Tso; Lee, Hsinyu
2015-08-01
Calreticulin (CRT) has been previously correlated with the differentiation of neuroblastoma (NB), implying a favorable prognostic factor. Vascular endothelial growth factor (VEGF) has been reported to participate in the behavior of NB. This study investigated the association of CRT and VEGF-A in NB cells. The expressions of VEGF-A and HIF-1α, with overexpression or knockdown of CRT, were measured in three NB cells (SH-SY5Y, SK-N-DZ, and stNB-V1). An inducible CRT NB cell line and knockdown CRT stable cell lines were also established. The impacts of CRT overexpression on NB cell apoptosis, proliferation, and differentiation were also evaluated. We further examined the role of VEGF-A in the NB cell differentiation via VEGF receptor blockade. Constitutive overexpression of CRT led to NB cell differentiation without proliferation. Thus, an inducible CRT stNB-V1 cell line was generated by a tetracycline-regulated gene system. CRT overexpression increased VEGF-A and HIF-1α messenger RNA (mRNA) expressions in SH-SY5Y, SK-N-DZ, and stNB-V1 cells. CRT overexpression also enhanced VEGF-A protein expression and secretion level in conditioned media in different NB cell lines. Knockdown of CRT decreased VEGF-A and HIF-1α mRNA expressions and lowered VEGF-A protein expression and secretion level in conditioned media in different NB cell lines. We further demonstrated that NB cell apoptosis was not affected by CRT overexpression in stNB-V1 cells. Nevertheless, overexpression of CRT suppressed cell proliferation and enhanced cell differentiation in stNB-V1 cells, whereas blockage of VEGFR-1 markedly suppressed the expression of neuron-specific markers including GAP43, NSE2, and NFH, as well as TrkA, a molecular marker indicative of NB cell differentiation. Our findings suggest that VEGF-A is involved in CRT-related neuronal differentiation in NB. Our work may provide important information for developing a new therapeutic strategy to improve the outcome of NB patients.
NASA Astrophysics Data System (ADS)
Tormoen, Garth W.; Recht, Olivia; Gruber, András; Levine, Ross L.; McCarty, Owen J. T.
2013-10-01
Patients with acute myelogenous leukemia (AML) are at risk for thrombotic complications. Risk to develop thrombosis is closely tied to leukemia subtype, and studies have shown an association between leukocytosis and thrombosis in AML M3. We evaluated the relative roles of cell count and the surface expression of tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a purified system and promoted experimental thrombus formation. In contrast, the TF-negative AML cell line, HEL, exhibited only prothrombinase activity and did not affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14 shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin increased their extrinsic tenase activity and PS expression. Clot initiation time inversely correlated with logarithm of PS index, defined as the product of multiplying leukocyte count with cell surface PS exposure. We propose that leukemia cell PS index may serve as a biomarker for procoagulant activity.
ASK1 regulates the survival of neuroblastoma cells by interacting with TLX and stabilizing HIF-1α.
Sobhan, Praveen K; Zhai, Qiwei; Green, Lydia C; Hansford, Loen M; Funa, Keiko
2017-01-01
Elevated expression of TLX (also called as NR2E1) in neuroblastoma (NB) correlates with unfavorable prognosis, and TLX is required for self-renewal of NB cells. Knockdown of TLX has been shown to reduce the NB sphere-forming ability. ASK1 (MAP3K5) and TLX expression are both enhanced in SP (side population) NB and patient-derived primary NB sphere cell lines, but the majority of non-SP NB lines express lower ASK1 expression. We found that ASK1 phosphorylated and stabilized TLX, which led induction of HIF-1α, and its downstream VEGF-A in an Akt dependent manner. In depleting ASK1 upon hypoxia, TLX decreased and the apoptosis ratio of NB cells was enhanced, while low-ASK1-expressing NB cell lines were refractory in TUNEL assay by using flow cytometry. Interestingly, primary NB spheres cell lines express only high levels of active pASK1Thr-838 but the established cell lines expressed inhibitory pASK1Ser-966, and both could be targeted by ASK1 depletion. We report a novel pro-survival role of ASK1 in the tumorigenic NB cell populations, which may be applied as a therapeutic target, inducing apoptosis specifically in cancer stem cells. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Sunami, Yoshitaka; Araki, Marito; Hironaka, Yumi; Morishita, Soji; Kobayashi, Masaki; Liew, Ei Leen; Edahiro, Yoko; Tsutsui, Miyuki; Ohsaka, Akimichi; Komatsu, Norio
2013-01-01
Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular differentiation in leukemic cells. The sirtuin inhibitors tenovin-6 and BML-266 induce granulocytic differentiation in the acute promyelocytic leukemia (APL) cell line NB4. This differentiation is likely caused by an inhibition of SIRT2 deacetylase activity, judging from the accumulation of acetylated α-tubulin, a major SIRT2 substrate. Unlike the clinically used differentiation inducer all-trans retinoic acid, tenovin-6 shows limited effects on promyelocytic leukemia–retinoic acid receptor α (PML-RAR-α) stability and promyelocytic leukemia nuclear body formation in NB4 cells, suggesting that tenovin-6 does not directly target PML-RAR-α activity. In agreement with this, tenovin-6 induces cellular differentiation in the non-APL cell line HL-60, where PML-RAR-α does not exist. Knocking down SIRT2 by shRNA induces granulocytic differentiation in NB4 cells, which demonstrates that the inhibition of SIRT2 activity is sufficient to induce cell differentiation in NB4 cells. The overexpression of SIRT2 in NB4 cells decreases the level of granulocytic differentiation induced by tenovin-6, which indicates that tenovin-6 induces granulocytic differentiation by inhibiting SIRT2 activity. Taken together, our data suggest that targeting SIRT2 is a viable strategy to induce leukemic cell differentiation. PMID:23460888
Mestieri, Leticia Boldrin; Gomes-Cornélio, Ana Lívia; Rodrigues, Elisandra Márcia; Faria, Gisele; Guerreiro-Tanomaru, Juliane Maria; Tanomaru-Filho, Mário
2017-01-01
The aim of this study was to evaluate the cytotoxicity and bioactivity of calcium silicate-based cements combined with niobium oxide (Nb2O5) micro and nanoparticles, comparing the response in different cell lines. This evaluation used four cell lines: two primary cultures (human dental pulp cells - hDPCs and human dental follicle cells - hDFCs) and two immortalized cultures (human osteoblast-like cells - Saos-2 and mouse periodontal ligament cells - mPDL). The tested materials were: White Portland Cement (PC), mineral trioxide aggregate (MTA), white Portland cement combined with microparticles (PC/Nb2O5µ) or nanoparticles (PC/Nb2O5n) of niobium oxide (Nb2O5). Cytotoxicity was evaluated by the methylthiazolyldiphenyl-tetrazolium bromide (MTT) and trypan blue exclusion assays and bioactivity by alkaline phosphatase (ALP) enzyme activity. Results were analyzed by ANOVA and Tukey test (a=0.05). PC/Nb2O5n presented similar or higher cell viability than PC/Nb2O5µ in all cell lines. Moreover, the materials presented similar or higher cell viability than MTA. Saos-2 exhibited high ALP activity, highlighting PC/Nb2O5µ material at 7 days of exposure. In conclusion, calcium silicate cements combined with micro and nanoparticles of Nb2O5 presented cytocompatibility and bioactivity, demonstrating the potential of Nb2O5 as an alternative radiopacifier agent for these cements. The different cell lines had similar response to cytotoxicity evaluation of calcium silicate cements. However, bioactivity was more accurately detected in human osteoblast-like cell line, Saos-2.
Yang, Hong Wei; Chen, Ying Zhang; Piao, Hui Ying; Takita, Junko; Soeda, Eiichi; Hayashi, Yasuhide
2001-01-01
Abstract Recently, loss of heterozygosity (LOH) studies suggest that more than two tumor suppressor genes lie on the short arm of chromosome 1 (1p) in neuroblastoma (NB). To identify candidate tumor suppressor genes in NB, we searched for homozygous deletions in 20 NB cell lines using a high-density STS map spanning chromosome 1p36, a common LOH region in NB. We found that the 45-kDa subunit of the DNA fragmentation factor (DFF45) gene was homozygously deleted in an NB cell line, NB-1. DFF45 is the chaperon of DFF40, and both molecules are necessary for caspase 3 to induce apoptosis. DFF35, a splicing variant of DFF45, is an inhibitor of DFF40. We examined 20 NB cell lines for expression and mutation of DFF45 gene by reverse transcription (RT)-polymerase chain reaction (PCR) and RT-PCR-single-strand conformation polymorphism. Some novel variant transcripts of the DFF45 gene were found in NB cell lines, but not in normal adrenal gland and peripheral blood. These variants may not serve as chaperons of DFF40, but as inhibitors like DFF35, thus disrupting the balance between DFF45 and DFF40. No mutations of the DFF45 gene were found in any NB cell line, suggesting that the DFF45 is not a tumor suppressor gene for NB. However, homozygous deletion of the DFF45 gene in the NB-1 cell line may imply the presence of unknown tumor suppressor genes in this region. PMID:11420752
Energy metabolism of leukemia cells: glycolysis versus oxidative phosphorylation.
Suganuma, Kazuto; Miwa, Hiroshi; Imai, Norikazu; Shikami, Masato; Gotou, Mayuko; Goto, Mineaki; Mizuno, Shohei; Takahashi, Miyuki; Yamamoto, Hidesuke; Hiramatsu, Akihito; Wakabayashi, Motohiro; Watarai, Masaya; Hanamura, Ichiro; Imamura, Akira; Mihara, Hidetsugu; Nitta, Masakazu
2010-11-01
For generation of energy, cancer cells utilize glycolysis more vigorously than oxidative phosphorylation in mitochondria (Warburg effect). We examined the energy metabolism of four leukemia cell lines by using glycolysis inhibitor, 2-deoxy-d-glucose (2-DG) and inhibitor of oxidative phosphorylation, oligomycin. NB4 was relatively sensitive to 2-DG (IC(50): 5.75 mM), consumed more glucose and produced more lactate (waste product of glycolysis) than the three other cell lines. Consequently, NB4 was considered as a "glycolytic" leukemia cell line. Dependency on glycolysis in NB4 was confirmed by the fact that glucose (+) FCS (-) medium showed more growth and survival than glucose (-) FCS (+) medium. Alternatively, THP-1, most resistant to 2-DG (IC(50): 16.14 mM), was most sensitive to oligomycin. Thus, THP-1 was recognized to be dependent on oxidative phosphorylation. In THP-1, glucose (-) FCS (+) medium showed more growth and survival than glucose (+) FCS (-) medium. The dependency of THP-1 on FCS was explained, at least partly, by fatty acid oxidation because inhibitor of fatty acid β-oxidation, etomoxir, augmented the growth suppression of THP-1 by 2-DG. We also examined the mechanisms by which THP-1 was resistant to, and NB4 was sensitive to 2-DG treatment. In THP-1, AMP kinase (AMPK), which is activated when ATP becomes limiting, was rapidly phosphorylated by 2-DG, and expression of Bcl-2 was augmented, which might result in resistance to 2-DG. On the other hand, AMPK phosphorylation and augmentation of Bcl-2 expression by 2-DG were not observed in NB4, which is 2-DG sensitive. These results will facilitate the future leukemia therapy targeting metabolic pathways.
Signal Transduction Pathways through TRK‐A and TRK‐B Receptors in Human Neuroblastoma Cells
Kuroda, Hiroshi; Horii, Yoshihiro; Moritake, Hiroshi; Tanaka, Takeo; Hattori, Seisuke
2001-01-01
Little is known about the signal transduction pathways of TRK family receptors in neuroblastoma (NB) cells. In this study, an NB cell line, designated MP‐N‐TS, was established from an adrenal tumor taken from a 2‐year‐old boy. This cell line expressed both TRK‐A and TRK‐B receptors, which is rare in a single NB cell line. Therefore, the MP‐N‐TS cell line was used to determine whether the signal transduction through these constitutive receptors is functional. Three neurotrophins, nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF) and neurotrophin‐4/ 5 (NT‐4/5), induced tyrosine phosphorylation of panTRK, and BDNF and NT‐4/5 induced tyrosine phosphorylation of TRK‐B. Tyrosine phosphorylation of panTRK and/or TRK‐B by the neurotro‐phins was inhibited in the presence of a tyrosine kinase inhibitor K252a. Tyrosine phosphorylation of Src homologous and collagen (She), extracellular signal‐regulated kinase (ERK)‐l and ERK‐2, and phospholipase C‐γl (PLC‐γl) was increased by the three neurotrophins and the increase was inhibited in the presence of K252a. Activation of Ras, detected as the GTP‐bound form of Ras, was induced by the three neurotrophins. The neurotrophins did not modulate the expressions of TRK‐A or TRK‐B mRNA, but they did induce the expression of c‐fos mRNA. Exogenous NGF induced weak neurite outgrowth, whereas exogenous BDNF and NT‐4/5 induced distinct neurite outgrowth. Exogenous BDNF and NT‐4/5 increased the number of viable cells, while NGF did not. Our results demonstrate that the signal transduction pathways through TRK‐A and TRK‐B in MP‐N‐TS cells are functional and similar, and the main downstream signaling pathways from the three neurotrophins are mitogen‐activated protein kinase (MAPK) cascades through She, activated Ras, ERK‐1 and ERK‐2, and the transduction pathway through PLC‐γl. Further, BDNF and NT‐4/5 increased cell viability. The MP‐N‐TS cell line should be useful for clarifying the TRK‐A and TRK‐B signaling pathways responsible for the different prognoses in patients with NB. PMID:11223544
The in vitro study of apoptosis in NB4 cell induced by citral.
Xia, Hailong; Liang, Wei; Song, Qin; Chen, Xiaowen; Chen, Xin; Hong, Jian
2013-01-01
Citral, 3,7-dimethyl-2,6-octadienal, is a key component of the essential oils extracted from several lemon-scented herbal plants. Besides its antifungal activity, the anticancer effect of citral was studied in recent years. In this study, we investigated the effect of citral on the acute promyelocytic leukemia cell line NB4. Citral treatment had an antiproliferative effect in NB4 cells via the induction of apoptosis assessed by morphology, proliferation assay, DNA electrophoresis, Annexin V-FITC/PI staining and caspase-3 activation. And citral induced apoptosis of NB4 cells in a dose- and time-dependent manner. In addition, citral treatment induced decreased mitochondrial membrane potential, indicating that citral induced apoptosis via the mitochondrial pathway. Bax up-regulation and Bcl-2 down-regulation on mRNA level and NF-κB down-regulation on protein level was found in this study, suggesting that Bcl-2, Bax and NF-κB may be involved in the mechanism of the apoptotic effect of citral on NB4 cells. These data suggest that citral has a potential therapeutic effect on leukemia.
Xiong, Xilin; Li, Yang; Liu, Ling; Qi, Kai; Zhang, Chi; Chen, Yueqin; Fang, Jianpei
2018-06-13
Arsenic trioxide (As 2 O 3 ), a drug that has been used in China for approximately two thousand years, induces cell death in a variety of cancer cell types, including neuroblastoma (NB). The tyrosine kinase receptor (Trk) family comprises three members, namely TrkA, TrkB and TrkC. Various studies have confirmed that TrkA and TrkC expression is associated with a good prognosis in NB, while TrkB overexpression can lead to tumor cell growth and invasive metastasis. Previous studies have shown that As 2 O 3 can inhibit the growth and proliferation of a human NB cell line and can also affect the N-Myc mRNA expression. It remains unclear whether As 2 O 3 regulates Trks for the purposes of treating NB. The aim of the present study was to investigate the effect of As 2 O 3 on Trk expression in NB cell lines and its potential therapeutic efficacy. SK-N-SH cells were grown with increasing doses of As 2 O 3 at different time points. We cultured SK-N-SH cells, which were treated with increasing doses of As 2 O 3 at different time points. Trk expression in the NB samples was quantified by immunohistochemistry, and the cell cycle was analyzed by flow cytometry. TrkA, TrkB and TrkC mRNA expression was evaluated by real-time PCR analysis. Immunohistochemical and real-time PCR analyses indicated that TrkA and TrkC were over-expressed in NB, and specifically during stages 1, 2 and 4S of the disease progression. TrkB expression was increased in stage 3 and 4 NB. As 2 O 3 significantly arrested SK-N-SH cells in the G2/M phase. In addition, TrkA, TrkB and TrkC expression levels were significantly upregulated by higher concentrations of As 2 O 3 treatment, notably in the 48-h treatment period. Our findings suggested that to achieve the maximum effect and appropriate regulation of Trk expression in NB stages 1, 2 and 4S, As 2 O 3 treatment should be at relatively higher concentrations for longer delivery times;however, for NB stages 3 and 4, an appropriate concentration and infusion time for As 2 O 3 must be carefully determined. The present findings suggested that As 2 O 3 induced Trk expression in SK-N-SH cells to varying degrees and may be a promising adjuvant to current treatments for NB due to its apoptotic effects.
Mesenchymal change and drug resistance in neuroblastoma.
Naiditch, Jessica A; Jie, Chunfa; Lautz, Timothy B; Yu, Songtao; Clark, Sandra; Voronov, Dimitry; Chu, Fei; Madonna, Mary Beth
2015-01-01
Metastatic initiation has many phenotypic similarities to epithelial-to-mesenchymal transition, including loss of cell-cell adhesion, increased invasiveness, and increased cell mobility. We have previously demonstrated that drug resistance is associated with a metastatic phenotype in neuroblastoma (NB). The purpose of this project was to determine if the development of doxorubicin resistance is associated with characteristics of mesenchymal change in human NB cells. Total RNA was isolated from wild type (WT) and doxorubicin-resistant (DoxR) human NB cell lines (SK-N-SH and SK-N-BE(2)C) and analyzed using the Illumina Human HT-12 version 4 Expression BeadChip. Differentially expressed genes (DEGs) were identified. Volcano plots and heat maps were generated. Genes of interest with a fold change in expression >1.5 and an adjusted P < 0.1 were analyzed. Immunofluorescence (IF) and Western blot analysis confirmed microarray results of interest. Matrigel invasion assay and migration wounding assays were performed. Volcano plots and heat maps visually demonstrated a similar pattern of DEGs in the SK-N-SH and SK-N-BE(2)C DoxR cell lines relative to their parental WT lines. Venn diagramming revealed 1594 DEGs common to both DoxR cell lines relative to their parental cell lines. Network analysis pointed to several significantly upregulated epithelial-to-mesenchymal transition pathways, through TGF-beta pathways via RhoA, PI3K, and ILK and via SMADs, as well as via notch signaling pathways. DoxR cell lines displayed a more invasive phenotype than respective WT cell lines. Human SK-N-SH and SK-N-BE(2)C NB cells display characteristics of mesenchymal change via multiple pathways in the transition to a drug-resistant state. Copyright © 2015 Elsevier Inc. All rights reserved.
Meng, Ran; Zhou, Jin; Sui, Meng; Li, ZhiYong; Feng, GuoSheng; Yang, BaoFeng
2010-01-01
This study aimed to investigate the effects of arsenic trioxide (As(2)O(3)) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 micromol/L As(2)O(3) in vitro, and the primary APL cells were treated with 2.0 micromol/L As(2)O(3) in vitro and 0.16 mg kg(-1) d(-1) As(2)O(3) in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As(2)O(3) use, but the mutation spots were remarkably increased after As(2)O(3) treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: r (NB4-As2O3)=0.973818, and r (APL-As2O3)=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As(2)O(3) aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As(2)O(3) in APL treatment.
Cerna, Tereza; Hrabeta, Jan; Eckschlager, Tomas; Frei, Eva; Schmeiser, Heinz H.
2018-01-01
Neuroblastoma (NBL) originates from undifferentiated cells of the sympathetic nervous system. Chemotherapy is judged to be suitable for successful treatment of this disease. Here, the influence of histone deacetylase (HDAC) inhibitor valproate (VPA) combined with DNA-damaging chemotherapeutic, ellipticine, on UKF-NB-4 and SH-SY5Y neuroblastoma cells was investigated. Treatment of these cells with ellipticine in combination with VPA led to the synergism of their anticancer efficacy. The effect is more pronounced in the UKF-NB-4 cell line, the line with N-myc amplification, than in SH-SY5Y cells. This was associated with caspase-3-dependent induction of apoptosis in UKF-NB-4 cells. The increase in cytotoxicity of ellipticine in UKF-NB-4 by VPA is dictated by the sequence of drug administration; the increased cytotoxicity was seen only after either simultaneous exposure to these drugs or after pretreatment of cells with ellipticine before their treatment with VPA. The synergism of treatment of cells with VPA and ellipticine seems to be connected with increased acetylation of histones H3 and H4. Further, co-treatment of cells with ellipticine and VPA increased the formation of ellipticine-derived DNA adducts, which indicates an easier accessibility of ellipticine to DNA in cells by its co-treatment with VPA and also resulted in higher ellipticine cytotoxicity. The results are promising for in vivo studies and perhaps later for clinical studies of combined treatment of children suffering from high-risk NBL. PMID:29304031
Michaelis, M; Rothweiler, F; Agha, B; Barth, S; Voges, Y; Löschmann, N; von Deimling, A; Breitling, R; Wilhelm Doerr, H; Rödel, F; Speidel, D; Cinatl, J
2012-01-01
Adaptation of wild-type p53 expressing UKF-NB-3 cancer cells to the murine double minute 2 inhibitor nutlin-3 causes de novo p53 mutations at high frequency (13/20) and multi-drug resistance. Here, we show that the same cells respond very differently when adapted to RITA, a drug that, like nutlin-3, also disrupts the p53/Mdm2 interaction. All of the 11 UKF-NB-3 sub-lines adapted to RITA that we established retained functional wild-type p53 although RITA induced a substantial p53 response. Moreover, all RITA-adapted cell lines remained sensitive to nutlin-3, whereas only five out of 10 nutlin-3-adapted cell lines retained their sensitivity to RITA. In addition, repeated adaptation of the RITA-adapted sub-line UKF-NB-3rRITA10 μM to nutlin-3 resulted in p53 mutations. The RITA-adapted UKF-NB-3 sub-lines displayed no or less pronounced resistance to vincristine, cisplatin, and irradiation than nutlin-3-adapted UKF-NB-3 sub-lines. Furthermore, adaptation to RITA was associated with fewer changes at the expression level of antiapoptotic factors than observed with adaptation to nutlin-3. Transcriptomic analyses indicated the RITA-adapted sub-lines to be more similar at the gene expression level to the parental UKF-NB-3 cells than nutlin-3-adapted UKF-NB-3 sub-lines, which correlates with the observed chemotherapy and irradiation sensitivity phenotypes. In conclusion, RITA-adapted cells retain functional p53, remain sensitive to nutlin-3, and display a less pronounced resistance phenotype than nutlin-3-adapted cells. PMID:22476102
Michaelis, M; Rothweiler, F; Agha, B; Barth, S; Voges, Y; Löschmann, N; von Deimling, A; Breitling, R; Doerr, H Wilhelm; Rödel, F; Speidel, D; Cinatl, J
2012-04-05
Adaptation of wild-type p53 expressing UKF-NB-3 cancer cells to the murine double minute 2 inhibitor nutlin-3 causes de novo p53 mutations at high frequency (13/20) and multi-drug resistance. Here, we show that the same cells respond very differently when adapted to RITA, a drug that, like nutlin-3, also disrupts the p53/Mdm2 interaction. All of the 11 UKF-NB-3 sub-lines adapted to RITA that we established retained functional wild-type p53 although RITA induced a substantial p53 response. Moreover, all RITA-adapted cell lines remained sensitive to nutlin-3, whereas only five out of 10 nutlin-3-adapted cell lines retained their sensitivity to RITA. In addition, repeated adaptation of the RITA-adapted sub-line UKF-NB-3(r)RITA(10 μM) to nutlin-3 resulted in p53 mutations. The RITA-adapted UKF-NB-3 sub-lines displayed no or less pronounced resistance to vincristine, cisplatin, and irradiation than nutlin-3-adapted UKF-NB-3 sub-lines. Furthermore, adaptation to RITA was associated with fewer changes at the expression level of antiapoptotic factors than observed with adaptation to nutlin-3. Transcriptomic analyses indicated the RITA-adapted sub-lines to be more similar at the gene expression level to the parental UKF-NB-3 cells than nutlin-3-adapted UKF-NB-3 sub-lines, which correlates with the observed chemotherapy and irradiation sensitivity phenotypes. In conclusion, RITA-adapted cells retain functional p53, remain sensitive to nutlin-3, and display a less pronounced resistance phenotype than nutlin-3-adapted cells.
Veneziani, Irene; Brandetti, Elisa; Ognibene, Marzia; Pezzolo, Annalisa; Pistoia, Vito
2018-01-01
Neuroblastoma (NB), the most common extracranial solid tumor of childhood, causes death in almost 15% of children affected by cancer. Treatment of neuroblastoma is based on the combination of chemotherapy with other therapeutic interventions such as surgery, radiotherapy, use of differentiating agents, and immunotherapy. In particular, adoptive NK cell transfer is a new immune-therapeutic approach whose efficacy may be boosted by several anticancer agents able to induce the expression of ligands for NK cell-activating receptors, thus rendering cancer cells more susceptible to NK cell-mediated lysis. Here, we show that chemotherapeutic drugs commonly used for the treatment of NB such as cisplatin, topotecan, irinotecan, and etoposide are unable to induce the expression of activating ligands in a panel of NB cell lines. Consistently, cisplatin-treated NB cell lines were not more susceptible to NK cells than untreated cells. The refractoriness of NB cell lines to these drugs has been partially associated with the abnormal status of genes for ATM, ATR, Chk1, and Chk2, the major transducers of the DNA damage response (DDR), triggered by several anticancer agents and promoting different antitumor mechanisms including the expression of ligands for NK cell-activating receptors. Moreover, both the impaired production of reactive oxygen species (ROS) in some NB cell lines and the transient p53 stabilization in response to our genotoxic drugs under our experimental conditions could contribute to inefficient induction of activating ligands. These data suggest that further investigations, exploiting molecular strategies aimed to potentiate the NK cell-mediated immunotherapy of NB, are warranted. PMID:29805983
Nakaguro, Masato; Kiyonari, Shinichi; Kishida, Satoshi; Cao, Dongliang; Murakami-Tonami, Yuko; Ichikawa, Hitoshi; Takeuchi, Ichiro; Nakamura, Shigeo; Kadomatsu, Kenji
2015-01-01
Neuroblastoma (NB) is a childhood malignant tumor that arises from precursor cells of the sympathetic nervous system. Spontaneous regression is a phenomenon unique to NBs and is caused by differentiation of tumor cells. PES1 is a multifunctional protein with roles in both neural development and ribosome biogenesis. Various kinds of models have revealed the significance of PES1 in neurodevelopment. However, the roles of PES1 in NB tumorigenesis and differentiation have remained unknown. Here we show that NB cases with MYCN amplification and clinically unfavorable stage (INSS stage 4) express higher levels of PES1. High PES1 expression was associated with worse overall and relapse-free survival. In NB cell lines, PES1 knockdown suppressed tumor cell growth and induced apoptosis. This growth inhibition was associated with the expression of NB differentiation markers. However, when the differentiation of NB cell lines was induced by the use of all-trans retinoic acid, there was a corresponding decrease in PES1 expression. Pes1 expression of tumorspheres originated from MYCN transgenic mice also diminished after the induction of differentiation with growth factors. We also reanalyzed the distribution of PES1 in the nucleolus. PES1 was localized in the dense fibrillar component, but not in the granular component of nucleoli. After treatment with the DNA-damaging agent camptothecin, this distribution was dramatically changed to diffuse nucleoplasmic. These data suggest that PES1 is a marker of NB outcome, that it regulates NB cell proliferation, and is associated with NB differentiation. PMID:25557119
Lau, C B S; Ho, C Y; Kim, C F; Leung, K N; Fung, K P; Tse, T F; Chan, H H L; Chow, M S S
2004-07-02
Coriolus versicolor (CV), also known as Yunzhi, is one of the commonly used Chinese medicinal herbs. Although recent studies have demonstrated its antitumour activities on cancer cells in vitro and in vivo, the exact mechanism is not fully elucidated. Hence, the objective of this study was to examine the in vitro cytotoxic activities of a standardized aqueous ethanol extract prepared from Coriolus versicolor on a B-cell lymphoma (Raji) and two human promyelocytic leukemia (HL-60, NB-4) cell lines using a MTT cytotoxicity assay, and to test whether the mechanism involves induction of apoptosis. Cell death ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis. The present results demonstrated that CV extract at 50 to 800 microg/ml dose-dependently suppressed the proliferation of Raji, NB-4, and HL-60 cells by more than 90% (p < 0.01), with ascending order of IC50 values: HL-60 (147.3 +/- 15.2 microg/ml), Raji (253.8 +/- 60.7 microg/ml) and NB-4 (269.3 +/- 12.4 microg/ml). The extract however did not exert any significant cytotoxic effect on normal liver cell line WRL (IC50 > 800 microg/ml) when compared with a chemotherapeutic anticancer drug, mitomycin C (MMC), confirming the tumour-selective cytotoxicity. Nucleosome productions in HL-60, NB-4 and Raji cells were significantly increased by 3.6-, 3.6- and 5.6-fold respectively upon the treatment of CV extract, while no significant nucleosome production was detected in extract-treated WRL cells. The CV extract was found to selectively and dose-dependently inhibit the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway. Copyright 2004 Elsevier Inc.
Corrias, Maria Valeria; Levreri, Isabella; Scaruffi, Paola; Raffaghello, Lizzia; Carlini, Barbara; Bocca, Paola; Prigione, Ignazia; Stigliani, Sara; Amoroso, Loredana; Ferrone, Soldano; Pistoia, Vito
2012-01-01
The high molecular weight melanoma-associated antigen (HMW-MAA) and the cytoplasmic melanoma-associated antigen (cyt-MAA/LGALS3BP) are expressed in melanoma. Their serum levels are increased in melanoma patients and correlate with clinical outcome. We investigated whether these molecules can serve as prognostic markers for neuroblastoma (NB) patients. Expression of cyt-MAA and HMW-MAA was evaluated by flow cytometry in NB cell lines, patients’ neuroblasts (FI-NB), and short-term cultures of these latter cells (cNB). LGALS3BP gene expression was evaluated by RT–qPCR on FI-NB, cNB, and primary tumor specimens. Soluble HMW-MAA and cyt-MAA were tested by ELISA. Cyt-MAA and HMW-MAA were expressed in NB cell lines, cNB, and FI-NB samples. LGALS3BP gene expression was higher in primary tumors and cNB than in FI-NB samples. Soluble cyt-MAA, but not HMW-MAA, was detected in NB cell lines and cNBs supernatants. NB patients’ serum levels of both antigens were higher than those of the healthy children. High cyt-MAA serum levels at diagnosis associated with higher incidence of relapse, independently from other known risk factors. In conclusion, both HMW-MAA and cyt-MAA antigens, and LGALS3BP gene, were expressed by NB cell lines and patients’ neuroblasts, and both antigens’ serum levels were increased in NB patients. Elevated serum levels of cyt-MAA at diagnosis correlated with relapse, supporting that cyt-MAA may serve as early serological biomarker to individuate patients at higher risk of relapse that may require a more careful follow-up, after being validated in a larger cohort of patients at different time-points during follow-up. Given its immunogenicity, cyt-MAA may also be a potential target for NB immunotherapy. PMID:21660451
Inhibitory effects of Agaricus blazei extracts on human myeloid leukemia cells.
Kim, Chi-Fai; Jiang, Jing-Jing; Leung, Kwok-Nam; Fung, Kwok-Pui; Lau, Clara Bik-San
2009-03-18
Agaricus blazei has been used as an adjuvant in cancer chemotherapy and is found to inhibit the growth of various types of tumor cells. Our study has adopted a systematic and bioassay-guided approach to optimize the extraction of Agaricus blazei for anti-leukemic bioactive components. The tumor-selective growth inhibitory activity of the extracts on leukemic cell lines was evaluated in vitro and in vivo using tumor-bearing nude mice. Agaricus blazei extracts were prepared using different methods. MTT and tritiated thymidine incorporation assays were used to evaluate the in vitro anti-leukemic effects. The most potent extract was further investigated using NB-4 cells-bearing nude mice and mechanistic studies using DNA fragmentation assay and cell death detection ELISA. The JAB80E70 extract showed the most potent tumor-selective growth inhibitory activity against human leukemia NB-4 and K-562 cells. This is the first report of anti-leukemic activity of JAB80E70 in athymic nude mice bearing NB-4 cells. Using DNA fragmentation assays and cell death detection ELISA, JAB80E70 was found to induce apoptosis in NB-4 cells. However, the polysaccharide enriched fractions failed to show significant cytotoxicity on NB-4 cells in vitro. The JAB80E70 extract exhibited potent anti-leukemic effect in vitro and in vivo. The effect can be attributed, at least in part, to the induction of apoptosis. Besides, polysaccharides in Agaricus blazei may not possess direct anti-leukemic activity in vitro.
Antiproliferative and apoptotic effect of LY2090314, a GSK-3 inhibitor, in neuroblastoma in vitro.
Kunnimalaiyaan, Selvi; Schwartz, Victoriana K; Jackson, Iris Alao; Clark Gamblin, T; Kunnimalaiyaan, Muthusamy
2018-05-11
Neuroblastoma (NB) is a devastating disease. Despite recent advances in the treatment of NB, about 60% of high-risk NB will have relapse and therefore long-term event free survival is very minimal. We have reported that targeting glycogen synthase kinase-3 (GSK-3) may be a potential strategy to treat NB. Consequently, investigating LY2090314, a clinically relevant GSK-3 inhibitor, on NB cellular proliferation and may be beneficial for NB treatment. The effect of LY2090314 was compared with a previously studied GSK-3 inhibitor, Tideglusib. Colorimetric, clonogenic, and live-cell image confluency assays were used to study the proliferative effect of LY2090314 on NB cell lines (NGP, SK-N-AS, and SH-SY-5Y). Western blotting and caspase glo assay were performed to determine the mechanistic function of LY2090314 in NB cell lines. LY2090314 treatment exhibited significant growth reduction starting at a 20 nM concentration in NGP, SK-N-AS, and SH-SY-5Y cells. Western blot analysis indicated that growth suppression was due to apoptosis as evidenced by an increase in pro-apoptotic markers cleaved PARP and cleaved caspase-3 and a reduction in the anti-apoptotic protein, survivin. Further, treatment significantly reduced the level of cyclin D1, a key regulatory protein of the cell cycle and apoptosis. Functionally, this was confirmed by an increase in caspase activity. LY2090314 treatment reduced the expression levels of phosphorylated GSK-3 proteins and increased the stability of β-catenin in these cells. LY2090314 effectively reduces growth of both human MYCN amplified and non-amplified NB cell lines in vitro. To our knowledge, this is the first study to look at the effect of LY2090314 in NB cell lines. These results indicate that GSK-3 may be a therapeutic target for NB and provide rationale for further preclinical analysis using LY2090314.
Chavali, P L; Saini, R K R; Zhai, Q; Vizlin-Hodzic, D; Venkatabalasubramanian, S; Hayashi, A; Johansson, E; Zeng, Z-j; Mohlin, S; Påhlman, S; Hansford, L; Kaplan, D R; Funa, K
2014-10-30
Nuclear orphan receptor TLX (Drosophila tailless homolog) is essential for the maintenance of neural stem/progenitor cell self-renewal, but its role in neuroblastoma (NB) is not well understood. Here, we show that TLX is essential for the formation of tumor spheres in three different NB cell lines, when grown in neural stem cell media. We demonstrate that the knock down of TLX in IMR-32 cells diminishes its tumor sphere-forming capacity. In tumor spheres, TLX is coexpressed with the neural progenitor markers Nestin, CD133 and Oct-4. In addition, TLX is coexpressed with the migratory neural progenitor markers CD15 and matrix metalloproteinase-2 (MMP-2) in xenografts of primary NB cells from patients. Subsequently, we show the effect of TLX on the proliferative, invasive and migratory properties of IMR-32 cells. We attribute this to the recruitment of TLX to both MMP-2 and Oct-4 gene promoters, which resulted in the respective gene activation. In support of our findings, we found that TLX expression was high in NB patient tissues when compared with normal peripheral nervous system tissues. Further, the Kaplan-Meier estimator indicated a negative correlation between TLX expression and survival in 88 NB patients. Therefore, our results point at TLX being a crucial player in progression of NB, by promoting self-renewal of NB tumor-initiating cells and altering their migratory and invasive properties.
Chavali, P L; Saini, R K R; Zhai, Q; Vizlin-Hodzic, D; Venkatabalasubramanian, S; Hayashi, A; Johansson, E; Zeng, Z-j; Mohlin, S; Påhlman, S; Hansford, L; Kaplan, D R; Funa, K
2014-01-01
Nuclear orphan receptor TLX (Drosophila tailless homolog) is essential for the maintenance of neural stem/progenitor cell self-renewal, but its role in neuroblastoma (NB) is not well understood. Here, we show that TLX is essential for the formation of tumor spheres in three different NB cell lines, when grown in neural stem cell media. We demonstrate that the knock down of TLX in IMR-32 cells diminishes its tumor sphere-forming capacity. In tumor spheres, TLX is coexpressed with the neural progenitor markers Nestin, CD133 and Oct-4. In addition, TLX is coexpressed with the migratory neural progenitor markers CD15 and matrix metalloproteinase-2 (MMP-2) in xenografts of primary NB cells from patients. Subsequently, we show the effect of TLX on the proliferative, invasive and migratory properties of IMR-32 cells. We attribute this to the recruitment of TLX to both MMP-2 and Oct-4 gene promoters, which resulted in the respective gene activation. In support of our findings, we found that TLX expression was high in NB patient tissues when compared with normal peripheral nervous system tissues. Further, the Kaplan–Meier estimator indicated a negative correlation between TLX expression and survival in 88 NB patients. Therefore, our results point at TLX being a crucial player in progression of NB, by promoting self-renewal of NB tumor-initiating cells and altering their migratory and invasive properties. PMID:25356871
Lawson, N D; Krause, D S; Berliner, N
1998-11-01
The EML and MPRO cell lines express a dominant negative retinoic acid receptor alpha that causes a block at specific stages of myelopoiesis. The EML cell line is multipotent and gives rise to erythroid, lymphoid, and myeloid lineages depending on the presence of appropriate cytokines. The MPRO cell line is promyelocytic and undergoes neutrophilic differentiation when induced with all-trans retinoic acid in the presence of granulocyte/macrophage colony-stimulating factor. Previous studies have shown that both of these cell lines undergo morphological differentiation into neutrophils. In this study, we show that unlike other models of neutrophil differentiation such as NB4 and HL60, both EML and MPRO cell lines undergo complete, normal granulocytic differentiation programs. Similar to HL60, MPRO and EML induce expression of CD11b/CD18 and also exhibit downregulation of CD34 on differentiation. In contrast to HL60 and NB4, EML and MPRO cell lines coordinately upregulate secondary granule transcripts for lactoferrin and neutrophil gelatinase. Furthermore, we have confirmed previous observations that serum can induce a low level of differentiation in MPRO cells and that it is possible to grow these cells in serum-free medium, thereby eliminating this effect. Based on these studies, it appears that these lines can serve as a model for normal retinoic acid-induced neutrophil differentiation and provide insight into the role of the retinoic acid-responsive pathway in normal and leukemic myelopoiesis.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Yue; Li, Ge; Wang, Ke
As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in treatment of acute promyelocytic leukemia (APL). However, clinical application of ATRA has limitations. Our previous studies suggested that 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, could induce differentiation of APL cells in vivo and in vitro. To explore the underlying mechanism of ATPR, the effect of ATPR on autophagy of APL cells was observed in the present study. The results showed that the differentiation effect of ATPR on APL cells was accompanied with autophagy induction and PML-RARαmore » degradation via activating Notch1 signaling pathway. Moreover, inhibition of autophagy using 3-methyladenine (3-MA) or small interfering RNA (siRNA) that targets essential autophagy gene ATG5 abrogated the ATPR-induced cell differentiation. Furthermore, when pretreated with DAPT, a γ-secretase inhibitor, the Notch1 signaling pathway was blocked in APL cells, followed by the reduction of ATPR-induced autophagy and differentiation. Taken together, these results suggested that autophagy play an important role in ATPR-induced cell differentiation, which may provide a novel approach to cure APL patients. - Highlights: • ATPR induces autophagy in APL cell line NB4 cells. • Autophagy induction is essential for cell differentiation in NB4 cells. • Notch1 signaling is involved in ATPR-induced autophagy and differentiation in NB4 cells.« less
Asou, H; Koike, M; Elstner, E; Cambell, M; Le, J; Uskokovic, M R; Kamada, N; Koeffler, H P
1998-10-01
We have studied the in vitro biological activities and mechanisms of action of 1,25-dihydroxyvitamin D3 (1,25D3) and nine potent 1,25D3 analogs on proliferation and differentiation of myeloid leukemia cell lines (HL-60, retinoic acid-resistant HL-60 [RA-res HL-60], NB4 and Kasumi-1). The common novel structural motiff for almost all the analogs included removal of C-19 (19-nor); each also had unsaturation of the side chain. All the compounds were potent; for example, the concentration of analogs producing a 50% clonal inhibition (ED50) ranged between 1 x 10(-9) to 4 x 10(-11) mol/L when using the HL-60 cell line. The most active compound [1, 25(OH)2-16,23E-diene-26-trifluoro-19-nor-cholecalciferol (Ro 25-9716)] had an ED50 of 4 x 10(-11) mol/L; in contrast, the 1,25D3 produced an ED50 of 10(-9) mol/L with the HL-60 target cells. Ro 25-9716 (10(-9) mol/L, 3 days) was a strong inducer of myeloid differentiation because it caused 92% of the HL-60 cells to express CD11b and 75% of these cells to reduce nitroblue tetrazolium (NBT). This compound (10(-8) mol/L, 4 days) also caused HL-60 cells to arrest in the G1 phase of the cell cycle (88% cells in G1 v 48% of the untreated control cells). The p27(kip-1), a cyclin-dependent kinase inhibitor which is important in blocking the cell cycle, was induced more quickly and potently by Ro 25-9716 (10(-7) mol/L, 0 to 5 days) than by 1,25D3, suggesting a possible mechanism by which these analogs inhibit proliferation of leukemic growth. The NB4 promyelocytic leukemia cells cultured with the Ro 25-9716 were also inhibited in their clonal proliferation (ED50, 5 x 10(-11) mol/L) and their expression of CD11b was enhanced (80% positive [10(-9) mol/L, 4 days] v 27% untreated NB4 cells). Moreover, the combination of Ro 25-9716 (10(-9) mol/L) and all-trans retinoic acid (ATRA, 10(-7) mol/L) induced 92% of the NB4 cells to reduce NBT, whereas only 26% of the cells became NBT positive after a similar exposure to the combination of 1,25D3 and ATRA. Surprisingly, Ro 25-9716 also inhibited the clonal growth of poorly differentiated leukemia cell lines (RA-res HL-60 [ED50, 4 x 10(-9) mol/L] and Kasumi-1 [ED50, 5 x 10(-10) mol/L]). For HL-60 cells, Ro 25-9716 markedly decreased the percent of the cells in S phase of the cell cycle and increased the expression of the cyclin-dependent kinase inhibitor, p27(kip-1). In summary, 19-nor vitamin D3 compounds strongly induced differentiation and inhibited clonal proliferation of various myeloid leukemia cell lines, suggesting a therapeutic niche for their use in myeloid leukemia.
The Shc protein RAI promotes an adaptive cell survival program in hypoxic neuroblastoma cells.
Criscuoli, Mattia; Filippi, Irene; Osti, Daniela; Aldinucci, Carlo; Guerrini, Giuditta; Pelicci, Giuliana; Carraro, Fabio; Naldini, Antonella
2018-05-01
Neuroblastoma (NB) is a highly malignant pediatric solid tumor where a hypoxic signature correlates with unfavorable patient outcome. The hypoxia-inducible factor (HIF)-1α plays an important role in NB progression, contributing to cell proliferation and invasiveness. RAI belongs to the Shc family proteins, it is mainly neuron specific and protects against cerebral ischemia. RAI is also expressed in several NB cell lines, where it promotes cell survival. In this work, hypoxia differently affected cell survival and pro-apoptotic program in two NB cell lines, either expressing RAI (SKNBE) or not (SKNMC). RAI expression appeared to promote NB cell survival and to reduce some pro-apoptotic markers under hypoxia. Accordingly, the RAI silencing in SKNBE cells resulted in a reduction of cell survival and HIF-1α expression. Furthermore, using SKNMC cells stably expressing RAI, we defined a role of RAI in NB cell responses to hypoxia. Of interest, in hypoxic SKNMC cells expressing RAI HIF-1α protein levels were higher than in control cells. This was associated with a) an increased cell survival; b) an increased expression of anti-apoptotic markers; c) a pro-autophagic and not pro-apoptotic phenotype; and d) an increased metabolic activity. We may conclude that RAI plays an important role in hypoxic signaling in NB cells and the interplay between RAI and HIF-1α may be relevant in the protection of NB cells against hypoxia. Our results may contribute to a further understanding the physiology of NB cells and the molecular mechanisms involved in their survival, with important implications in NB progression. © 2017 Wiley Periodicals, Inc.
The Netrin-4/ Neogenin-1 axis promotes neuroblastoma cell survival and migration
Villanueva, Andrea A.; Falcón, Paulina; Espinoza, Natalie; Luis, Solano R.; Milla, Luis A.; Hernandez-SanMiguel, Esther; Torres, Vicente A.; Sanchez-Gomez, Pilar; Palma, Verónica
2017-01-01
Neogenin-1 (NEO1) is a transmembrane receptor involved in axonal guidance, angiogenesis, neuronal cell migration and cell death, during both embryonic development and adult homeostasis. It has been described as a dependence receptor, because it promotes cell death in the absence of its ligands (Netrin and Repulsive Guidance Molecule (RGM) families) and cell survival when they are present. Although NEO1 and its ligands are involved in tumor progression, their precise role in tumor cell survival and migration remain unclear. Public databases contain extensive information regarding the expression of NEO1 and its ligands Netrin-1 (NTN1) and Netrin-4 (NTN4) in primary neuroblastoma (NB) tumors. Analysis of this data revealed that patients with high expression levels of both NEO1 and NTN4 have a poor survival rate. Accordingly, our analyses in NB cell lines with different genetic backgrounds revealed that knocking-down NEO1 reduces cell migration, whereas silencing of endogenous NTN4 induced cell death. Conversely, overexpression of NEO1 resulted in higher cell migration in the presence of NTN4, and increased apoptosis in the absence of ligand. Increased apoptosis was prevented when utilizing physiological concentrations of exogenous Netrin-4. Likewise, cell death induced after NTN4 knock-down was rescued when NEO1 was transiently silenced, thus revealing an important role for NEO1 in NB cell survival. In vivo analysis, using the chicken embryo chorioallantoic membrane (CAM) model, showed that NEO1 and endogenous NTN4 are involved in tumor extravasation and metastasis. Our data collectively demonstrate that endogenous NTN4/NEO1 maintain NB growth via both pro-survival and pro-migratory molecular signaling. PMID:28038459
Dorneburg, Carmen; Fischer, Matthias; Barth, Thomas F E; Mueller-Klieser, Wolfgang; Hero, Barbara; Gecht, Judith; Carter, Daniel R; De Preter, Katleen; Mayer, Benjamin; Christner, Lisa; Speleman, Frank; Marshall, Glenn M; Debatin, Klaus-Michael; Beltinger, Christian
2018-06-20
To investigate whether lactate dehydrogenase A (LDHA), an important component of the LDH tetramer crucial for aerobic glycolysis, is associated with patient outcome and constitutes a therapeutic target in neuroblastoma (NB). Expression of LDHA mRNA and protein was determined in 709 and 110 NB patient samples, respectively, and correlated to survival and risk factors. LDHA and LDHB were depleted in human NB cell lines by CRISPR/Cas9 and shRNA, respectively, and aerobic glycolysis, clonogenicity and tumorigenicity were determined. Expression of LDHA in relation to MYCN was measured in NB cell lines and in the TH-MYCN NB mouse model. Expression of LDHA, both on the mRNA and the protein level, was significantly and independently associated with decreased patient survival. Predominant cytoplasmic localization of LDHA protein was associated with poor outcome. Amplification and expression of MYCN did not correlate with expression of LDHA in NB cell lines or TH-MYCN mice, respectively. Knockout of LDHA inhibited clonogenicity, tumorigenicity and tumor growth without abolishing LDH activity or significantly decreasing aerobic glycolysis. Concomitant depletion of LDHA and the isoform LDHB ablated clonogenicity while not abrogating LDH activity or decreasing aerobic glycolysis. The isoform LDHC was not expressed. High expression of LDHA is independently associated with poor outcome of NB and NB cells can be inhibited by depletion of LDHA or LDHB. This inhibition appears to be unrelated to LDH activity and aerobic glycolysis. Thus, investigations of inhibitory mechanisms beyond attenuation of aerobic glycolysis are warranted, both in NB and normal cells. Copyright ©2018, American Association for Cancer Research.
Expression of C-terminal deleted p53 isoforms in neuroblastoma
Goldschneider, David; Horvilleur, Emilie; Plassa, Louis-François; Guillaud-Bataille, Marine; Million, Karine; Wittmer-Dupret, Evelyne; Danglot, Gisèle; de Thé, Hughes; Bénard, Jean; May, Evelyne; Douc-Rasy, Sétha
2006-01-01
The tumor suppressor gene, p53, is rarely mutated in neuroblastomas (NB) at the time of diagnosis, but its dysfunction could result from a nonfunctional conformation or cytoplasmic sequestration of the wild-type p53 protein. However, p53 mutation, when it occurs, is found in NB tumors with drug resistance acquired over the course of chemotherapy. As yet, no study has been devoted to the function of the specific p53 mutants identified in NB cells. This study includes characterization and functional analysis of p53 expressed in eight cell lines: three wild-type cell lines and five cell lines harboring mutations. We identified two transcription-inactive p53 variants truncated in the C-terminus, one of which corresponded to the p53β isoform recently identified in normal tissue by Bourdon et al. [J. C. Bourdon, K. Fernandes, F. Murray-Zmijewski, G. Liu, A. Diot, D. P. Xirodimas, M. K. Saville and D. P. Lane (2005) Genes Dev., 19, 2122–2137]. Our results show, for the first time, that the p53β isoform is the only p53 species to be endogenously expressed in the human NB cell line SK-N-AS, suggesting that the C-terminus truncated p53 isoforms may play an important role in NB tumor development. PMID:17028100
ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance
Rothweiler, Florian; Voges, Yvonne; Balónová, Barbora; Blight, Barry A.; Cinatl, Jindrich
2016-01-01
The CDK inhibitor SNS-032 had previously exerted promising anti-neuroblastoma activity via CDK7 and 9 inhibition. ABCB1 expression was identified as major determinant of SNS-032 resistance. Here, we investigated the role of ABCB1 in acquired SNS-032 resistance. In contrast to ABCB1-expressing UKF-NB-3 sub-lines resistant to other ABCB1 substrates, SNS-032-adapted UKF-NB-3 (UKF-NB-3rSNS- 032300nM) cells remained sensitive to the non-ABCB1 substrate cisplatin and were completely re-sensitized to cytotoxic ABCB1 substrates by ABCB1 inhibition. Moreover, UKF-NB-3rSNS-032300nM cells remained similarly sensitive to CDK7 and 9 inhibition as UKF-NB-3 cells. In contrast, SHEPrSNS-0322000nM, the SNS-032-resistant sub-line of the neuroblastoma cell line SHEP, displayed low level SNS-032 resistance also when ABCB1 was inhibited. This discrepancy may be explained by the higher SNS-032 concentrations that were used to establish SHEPrSNS-0322000nM cells, since SHEP cells intrinsically express ABCB1 and are less sensitive to SNS-032 (IC50 912 nM) than UKF-NB-3 cells (IC50 153 nM). In conclusion, we show that ABCB1 expression represents the primary (sometimes exclusive) resistance mechanism in neuroblastoma cells with acquired resistance to SNS-032. Thus, ABCB1 inhibitors may increase the SNS-032 efficacy in ABCB1-expressing cells and prolong or avoid resistance formation. PMID:27517323
Jo, Sungsin; Lee, Young Lim; Kim, Sojin; Lee, Hongki; Chung, Heekyoung
2016-07-01
Arsenic trioxide (ATO) is a therapeutic agent for acute promyelocytic leukemia (APL) which induces PML-RARA protein degradation via enhanced UBE2I-mediated sumoylation. PCGF2, a Polycomb group protein, has been suggested as an anti-SUMO E3 protein by inhibiting the sumoylation of UBE2I substrates, HSF2 and RANGAP1, via direct interaction. Thus, we hypothesized that PCGF2 might play a role in ATO-induced PML-RARA degradation by interacting with UBE2I. PCGF2 protein was down-regulated upon ATO treatment in human APL cell line, NB4. Knockdown of PCGF2 in NB4 cells, in the absence of ATO treatment, was sufficient to induce sumoylation-, ubiquitylation- and PML nuclear body-mediated degradation of PML-RARA protein. Moreover, overexpression of PCGF2 protected ATO-mediated degradation of ectopic and endogenous PML-RARA in 293T and NB4 cells, respectively. In 293T cells, UBE2I-mediated PML-RARA degradation was reduced upon PCGF2 co-expression. In addition, UBE2I-mediated sumoylation of PML-RARA was reduced upon PCGF2 co-expression and PCGF2-UBE2I interaction was confirmed by co-immunoprecipitation. Likewise, endogenous PCGF2-UBE2I interaction was detected by co-immunoprecipitation and immunofluorescence assays in NB4 cells. Intriguingly, upon ATO-treatment, such interaction was disrupted and UBE2I was co-immunoprecipitated or co-localized with its SUMO substrate, PML-RARA. Taken together, our results suggested a novel role of PCGF2 in ATO-mediated degradation of PML-RARA that PCGF2 might act as a negative regulator of UBE2I via direct interaction. Copyright © 2016 Elsevier B.V. All rights reserved.
Helminth-conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo.
Connor, Lisa M; Tang, Shiau-Choot; Camberis, Mali; Le Gros, Graham; Ronchese, Franca
2014-09-15
Dendritic cells (DC) are critical for the initiation of immune responses; however, their role in priming IL-4-producing Th2 cells in vivo is not fully understood. We used a model of intradermal injection with fluorescent-labeled, nonviable larvae from the helminth parasite nonviable Nippostrongylus brasiliensis L3 larvae (Nb), a strong inducer of Th2 responses, together with IL-4-GFP reporter mice that enable a sensitive detection of IL-4 production to examine the contribution of DC to the priming of IL-4-producing CD4(+) T cells in vivo. We found that parasite material is taken up by two distinct DC populations in draining lymph nodes: a mostly CD11c(int)MHC class II (MHCII)(hi)CD11b(+)Ly6C(-) dermal DC population and a CD11c(hi)MHCII(int)CD11b(+)Ly6C(+) monocyte-derived DC population. After Nb treatment, these two DC populations appeared in the draining lymph nodes in comparable numbers and with similar kinetics; however, treatment with pertussis toxin blocked the migration of dermal DC and the priming of IL-4-producing T cells, but only partially affected monocyte-derived DC numbers. In line with this observation, transfer of OVA-loaded CD11c(int)MHCII(hi) DC from Nb-treated mice into naive hosts could sensitize OVA-specific CD4(+) T cells to IL-4 production, whereas transfer of CD11c(int)MHCII(hi) DC from naive mice, or CD11c(hi)MHCII(int) DC from Nb-treated or naive mice, induced CD4(+) T cell expansion but no IL-4 production. Phenotypic analysis of Nb-loaded CD11c(int)MHCII(hi) DC revealed expression of programmed death ligand 2, CD301b, IFN regulatory factor 4, and moderate upregulation of OX40 ligand. However, thymic stromal lymphopoietin and OX40 ligand were not required for Th2 priming. Thus, our data suggest that appropriate stimuli can induce DC to express the unique signals sufficient to direct CD4(+) T cells to Th2 differentiation. Copyright © 2014 by The American Association of Immunologists, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Huai, Lei; Wang, Cuicui; Zhang, Cuiping
2012-06-08
Highlights: Black-Right-Pointing-Pointer Metformin induces differentiation in NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces activation of the MEK/ERK signaling pathway in APL cells. Black-Right-Pointing-Pointer Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces the relocalization and degradation of the PML-RAR{alpha} fusion protein. Black-Right-Pointing-Pointer The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acutemore » promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RAR{alpha} and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.« less
Anti-tumor effect of AZD8055 against neuroblastoma cells in vitro and in vivo.
Xu, Dong-Qing; Toyoda, Hidemi; Yuan, Xiao-Jun; Qi, Lei; Chelakkot, Vipin Shankar; Morimoto, Mari; Hanaki, Ryo; Kihira, Kentarou; Hori, Hiroki; Komada, Yoshihiro; Hirayama, Masahiro
2018-04-15
Neuroblastoma (NB) is one of the most common solid tumors in children. High-risk NB remains lethal in about 50% of patients despite comprehensive and intensive treatments. Activation of PI3K/Akt/mTOR signaling pathway correlates with oncogenesis, poor prognosis and chemotherapy resistance in NB. Due to its central role in growth and metabolism, mTOR seems to be an important factor in NB, making it a possible target for NB. In this study, we investigated the effect of AZD8055, a potent dual mTORC1-mTORC2 inhibitor, in NB cell lines. Our data showed that mTOR signaling was extensively activated in NB cells. The activity of mTOR and downstream molecules were down-regulated in AZD8055-treated NB cells. Significantly, AZD8055 effectively inhibited cell growth and induced cell cycle arrest, autophagy and apoptosis in NB cells. Moreover, AZD8055 significantly reduced tumor growth in mice xenograft model without apparent toxicity. Taken together, our results highlight the potential of mTOR as a promising target for NB treatment. Therefore, AZD8055 may be further investigated for treatment in clinical trials for high risk NB. Copyright © 2018 Elsevier Inc. All rights reserved.
Hassani, Saeed; Khaleghian, Ali; Ahmadian, Shahin; Alizadeh, Shaban; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H
2018-01-01
PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4. Analysis of promoter methylation status of 22 cell cycle related genes in NB4 revealed that CCND1, CCNE1, CCNF, CDKN1A, GADD45α, and RBL1 genes were methylated 60.7, 84.6, 58.6, 8.7, 33.4, and 73.7%, respectively, that after treatment with 2 μM ATO for 48 h, turn into 0.6, 13.8, 0.1, 6.6, 10.7, and 54.5% methylated. ATO significantly reduced the expression of DNMT1, 3A, and 3B. ATO induced the expression of CCND1, CCNE1, and GADD45α genes, suppressed the expression of CCNF and CDKN1A genes, which were consistent with decreased number of cells in G1 and S phases and increased number of cells in G2/M phase. In conclusion, demethylation and alteration in the expression level of the cell cycle related genes may be possible mechanisms in ATO-induced cell cycle arrest in APL cells. It may suggest that ATO by demethylation of CCND1 and CCNE1 and their transcriptional activation accelerates G1 and S transition into the G2/M cell cycle arrest.
Marrow-Derived Antibody Library for Treatment of Neuroblastoma
2013-09-01
to capture the auto-immune response reaction in neuroblastoma patients using phage display and B cell hybridoma technologies. The scope of this...project is to use NB patient-derived materials to create NB cell lines, xenograft models, NB specific phage display libraries and to identify and...the auto-immune response reaction in neuroblastoma patients using phage display and B cell hybridoma technologies. The scope of this project is to
Ghanizadeh-Vesali, Samad; Zekri, Ali; Zaker, Farhad; Zaghal, Azam; Yousefi, Meysam; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H
2016-06-01
Aurora B kinase as a chromosomal passenger protein plays multiple roles in regulating mitosis and cytokinesis. The function of Aurora B in leukemic cells has made it an important treatment target. In this study, we explored the expressions of Aurora (A, B, and C) kinases in newly diagnosed acute promyelocytic leukemia (APL) patients. In addition, we investigated the effects of AZD1152 as a specific inhibitor of Aurora B on cell survival, DNA synthesis, nuclear morphology, apoptosis induction, cell cycle distribution, and gene expression in an APL-derived NB4 cell line. Our results showed that Aurora B was overexpressed in 88 % of APL patients. AZD1152 treatment of NB4 cells led to viability reduction and G2/M arrest followed by an increase in cell size and polyploidy induction. These giant cells showed morphological evidence of mitotic catastrophe. AZD1152 treatment induced activation of G2/M checkpoint which in turn led to transient G2/M arrest in a p21-independent manner. Lack of functional p53 in NB4 cells might provide an opportunity to escape from G2/M block and to endure repeated rounds of replication and polyploidy. Treated cells were probably eliminated via p73-mediated overexpression of BAX, PUMA, and APAF1 and downregulation of survivin and MCL-1. In summary, AZD1152 treatment led to endomitosis and polyploidy in TP53-mutated NB4 cells. These giant polyploid cells might undergo mitotic catastrophe and p73-mediated apoptosis. It seems that induction of polyploidy via AZD1152 could be a novel form of anti-cancer therapy for APL that may be clinically accessible in the near future.
NASA Astrophysics Data System (ADS)
Magrasó, Anna; Fontaine, Marie-Laure
In the current manufacturing process of novel LaNbO 4-based proton conducting fuel cells a thin layer of the electrolyte is deposited by wet ceramic coating on NiO-LaNbO 4 based anode and co-sintered at 1200-1300 °C. The chemical compatibility of NiO with acceptor doped LaNbO 4 material is crucial to ensure viability of the cell, so potential effects of other phases resulting from off-stoichiometry in acceptor doped LaNbO 4 should also be explored. Compatibility of NiO with Ca-doped LaNbO 4 and its typical off-set compositions (La 3NbO 7 and LaNb 3O 9) are investigated in this work. It is shown that while NiO does not react with Ca-doped LaNbO 4, fast reaction occurs with La 3NbO 7 or LaNb 3O 9. La 3NbO 7 and NiO form a mixed conducting perovskite phase LaNi 2/3Nb 1/3O 3, while LaNb 3O 9 and NiO form either NiNb 2O 6 or Ni 4Nb 2O 9 depending on the annealing temperature. This implies that manufacturing LaNbO 4-based proton conducting fuel cells requires a strict control of the stoichiometry of the electrolyte.
Maser, Tyler; Rich, Maria; Hayes, David; Zhao, Ping; Nagulapally, Abhinav B; Bond, Jeffrey; Saulnier Sholler, Giselle
2017-06-01
Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and other catecholamines by O-methylation. Tolcapone, a drug commonly used in the treatment of Parkinson's disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells. In this study, we demonstrate that Tolcapone kills neuroblastoma (NB) cells in preclinical models by inhibition of COMT. Treating four established NB cells lines (SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90) and two primary NB cell lines with Tolcapone for 48 h decreased cell viability in a dose-dependent manner, with IncuCyte imaging and Western blotting indicating that cell death was due to caspase-3-mediated apoptosis. Tolcapone also increased ROS while simultaneously decreasing ATP-per-cell in NB cells. Additionally, COMT was inhibited by siRNA in NB cells and showed similar increases in apoptotic markers compared to Tolcapone. In vivo xenograft models displayed inhibition of tumor growth and a significant decrease in time-to-event in mice treated with Tolcapone compared to untreated mice. These results indicate that Tolcapone is cytotoxic to neuroblastoma cells and invite further studies into Tolcapone as a promising novel therapy for the treatment of neuroblastoma. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Blaheta, Roman A; Daher, Frederick H; Michaelis, Martin; Hasenberg, Christoph; Weich, Eva M; Jonas, Dietger; Kotchetkov, Rouslan; Doerr, Hans Willhelm; Cinatl, Jindrich
2006-01-01
Background Drug resistance to chemotherapy is often associated with increased malignancy in neuroblastoma (NB). One explanation for the link between resistance and malignancy might be that resistance facilitates cancer progression and invasion. To investigate this hypothesis, adhesion, transendothelial penetration and NCAM (CD56) adhesion receptor expression of drug-resistant versus drug-sensitive NB tumor cells were evaluated. Methods Acquired drug resistance was mimicked by exposing parental UKF-NB-2, UKF-NB-3 or IMR-32 tumor cells to increasing concentrations of vincristine- (VCR) or doxorubicin (DOX) to establish the resistant tumor cell sublines UKF-NB-2VCR, UKF-NB-2DOX, UKF-NB-3VCR, UKF-NB-3DOX, IMR-32VCR and IMR-32DOX. Additionally, the malignant behaviour of UKF-NB-4, which already possessed the intrinsic multidrug resistance (MDR) phenotype, was analyzed. UKF-NB-4 exposed to VCR or DOX were designated UKF-NB-4VCR or UKF-NB-4DOX. Combined phase contrast – reflection interference contrast microscopy was used to separately evaluate NB cell adhesion and penetration. NCAM was analyzed by flow cytometry, western blot and RT-PCR. Results VCR and DOX resistant tumor sublines showed enhanced adhesion and penetration capacity, compared to their drug naïve controls. Strongest effects were seen with UKF-NB-2VCR, UKF-NB-3VCR and IMR-32DOX. DOX or VCR treatment also evoked increased invasive behaviour of UKF-NB-4. The process of accelerated tumor invasion was accompanied by decreased NCAM surface and protein expression, and down-regulation of NCAM coding mRNA. Transfection of UKF-NB-4VCR cells with NCAM cDNA led to a significant receptor up-regulation, paralleled by diminished adhesion to an endothelial cell monolayer. Conclusion It is concluded that NB cells resistant to anticancer drugs acquire increased invasive capacity relative to non-resistant parental cells, and that enhanced invasion is caused by strong down-regulation of NCAM adhesion receptors. PMID:17181871
Luo, Peihua; Lin, Meili; Li, Lin; Yang, Bo; He, Qiaojun
2011-01-01
Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Differentiated human NBs are associated with better outcome and lower stage; induction of differentiation is considered to be therapeutically advantageous. All-trans retinoic acid (ATRA) has been shown to induce the differentiation of neuroblastoma (NB) cell lines. The proteasome inhibitor bortezomib inhibits cell growth and angiogenesis in NBs. Here, we investigated the synergistic effect between bortezomib and ATRA in inducing NB cell differentiation in different NB cell lines. Bortezomib combined with ATRA had a significantly enhanced antiproliferative effect. This inhibition was characterized by a synergistic increase in neuronal differentiation. At the same time, the combination therapy showed little neuronal toxicity which was assessed in primary cultures of rat cerebellar granule cells by the MTT assay, PI staining. The combination of bortezomib and ATRA triggered increased differentiation through the activation of proteins, including RARα, RARβ, RARγ, p-JNK and p21, compared with ATRA treatment alone. Using JNK inhibitor SP600125 to block JNK-dependent activity, the combination therapy-induced neuronal differentiation was partially attenuated. In addition, p21 shRNA had no effect on the combination therapy-induced neuronal differentiation. The in vivo antitumor activities were examined in human NB cell xenografts and GFP-labeled human NB cell xenografts. Treatment of human NB cell CHP126-bearing nude mice with ATRA plus bortezomib resulted in more significant tumor growth inhibition than mice treated with either drug alone. These findings provide the rationale for the development of a new therapeutic strategy for NB based on the pharmacological combination of ATRA and bortezomib. PMID:22087283
EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications.
Li, Zhenghao; Takenobu, Hisanori; Setyawati, Amallia Nuggetsiana; Akita, Nobuhiro; Haruta, Masayuki; Satoh, Shunpei; Shinno, Yoshitaka; Chikaraishi, Koji; Mukae, Kyosuke; Akter, Jesmin; Sugino, Ryuichi P; Nakazawa, Atsuko; Nakagawara, Akira; Aburatani, Hiroyuki; Ohira, Miki; Kamijo, Takehiko
2018-05-01
The polycomb repressor complex 2 molecule EZH2 is now known to play a role in essential cellular processes, namely, cell fate decisions, cell cycle regulation, senescence, cell differentiation, and cancer development/progression. EZH2 inhibitors have recently been developed; however, their effectiveness and underlying molecular mechanisms in many malignancies have not yet been elucidated in detail. Although the functional role of EZH2 in tumorigenesis in neuroblastoma (NB) has been investigated, mutations of EZH2 have not been reported. A Kaplan-Meier analysis on the event free survival and overall survival of NB patients indicated that the high expression of EZH2 correlated with an unfavorable prognosis. In order to elucidate the functional roles of EZH2 in NB tumorigenesis and its aggressiveness, we knocked down EZH2 in NB cell lines using lentivirus systems. The knockdown of EZH2 significantly induced NB cell differentiation, e.g., neurite extension, and the neuronal differentiation markers, NF68 and GAP43. EZH2 inhibitors also induced NB cell differentiation. We performed a comprehensive transcriptome analysis using Human Gene Expression Microarrays and found that NTRK1 (TrkA) is one of the EZH2-related suppression targets. The depletion of NTRK1 canceled EZH2 knockdown-induced NB cell differentiation. Our integrative methylome, transcriptome, and chromatin immunoprecipitation assays using NB cell lines and clinical samples clarified that the NTRK1 P1 and P2 promoter regions were regulated differently by DNA methylation and EZH2-related histone modifications. The NTRK1 transcript variants 1/2, which were regulated by EZH2-related H3K27me3 modifications at the P1 promoter region, were strongly expressed in favorable, but not unfavorable NB. The depletion and inhibition of EZH2 successfully induced NTRK1 transcripts and functional proteins. Collectively, these results indicate that EZH2 plays important roles in preventing the differentiation of NB cells and also that EZH2-related NTRK1 transcriptional regulation may be the key pathway for NB cell differentiation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schlehofer, J.R.; Ehrbar, M.; zur Hausen, H.
1986-07-15
The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. Asmore » reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells.« less
Lu, Jiaxiong; Guan, Shan; Zhao, Yanling; Yu, Yang; Woodfield, Sarah E; Zhang, Huiyuan; Yang, Kristine L; Bieerkehazhi, Shayahati; Qi, Lin; Li, Xiaonan; Gu, Jerry; Xu, Xin; Jin, Jingling; Muscal, Jodi A; Yang, Tianshu; Xu, Guo-Tong; Yang, Jianhua
2017-08-01
Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most cases of hereditary neuroblastoma (NB) and the constitutively active kinase activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK kinase is a potential therapeutic target for NB. In this study, we show that the novel ALK inhibitor alectinib effectively suppressed cell proliferation and induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling. In addition, alectinib enhanced doxorubicin-induced cytotoxicity and apoptosis in NB cells. Furthermore, alectinib induced apoptosis in an orthotopic xenograft NB mouse model. Also, in the TH-MYCN transgenic mouse model, alectinib resulted in decreased tumor growth and prolonged survival time. These results indicate that alectinib may be a promising therapeutic agent for the treatment of NB. Copyright © 2017 Elsevier B.V. All rights reserved.
Mei, Yuzhen; Yang, Xiuling; Huang, Changjun
2018-01-01
The whitefly-transmitted geminiviruses induce severe developmental abnormalities in plants. Geminivirus-encoded C4 protein functions as one of viral symptom determinants that could induce abnormal cell division. However, the molecular mechanism by which C4 contributes to cell division induction remains unclear. Here we report that tomato leaf curl Yunnan virus (TLCYnV) C4 interacts with a glycogen synthase kinase 3 (GSK3)/SHAGGY-like kinase, designed NbSKη, in Nicotiana benthamiana. Pro32, Asn34 and Thr35 of TLCYnV C4 are critical for its interaction with NbSKη and required for C4-induced typical symptoms. Interestingly, TLCYnV C4 directs NbSKη to the membrane and reduces the nuclear-accumulation of NbSKη. The relocalization of NbSKη impairs phosphorylation dependent degradation on its substrate-Cyclin D1.1 (NbCycD1;1), thereby increasing the accumulation level of NbCycD1;1 and inducing the cell division. Moreover, NbSKη-RNAi, 35S::NbCycD1;1 transgenic N. benthamiana plants have the similar phenotype as 35S::C4 transgenic N. benthamiana plants on callus-like tissue formation resulted from abnormal cell division induction. Thus, this study provides new insights into mechanism of how a viral protein hijacks NbSKη to induce abnormal cell division in plants. PMID:29293689
Rybicki, A C; Musto, S; Schwartz, R S
1995-11-01
Homozygous normoblastosis (nb/nb) mice, whose red blood cell (RBC) membranes are nearly completely deficient in full-length 210-kD ankyrin, were used to study interactions between ankyrin and protein 4.2 (P4.2). Although it is unclear whether or not these proteins interact in the membrane, both ankyrin and P4.2 bind to the cytoplasmic domain of band 3 (cdb3). In addition to the complete deficiency of full-length ankyrin, nb/nb RBC membranes are also partially spectrin deficient, resulting in morphologically spherocytic and mechanically fragile cells. A new finding was that nb/nb RBC membranes are severely (approximately 73%) P4.2 deficient compared with wild type (+/+) or high reticulocyte mouse RBC membranes. Metabolic labeling of nb/nb reticulocytes showed active P4.2 synthesis at levels comparable with high reticulocyte controls suggesting that the nb/nb P4.2 deficiency was not the result of defective P4.2 synthesis. Reconstitution of nb/nb inside-out vesicles (IOVs) with human RBC ankyrin restored ankyrin levels to approximately 80% of +/+ IOV levels and increased binding of exogenously added human RBC P4.2 by approximately 60%. These results suggest that ankyrin is required for normal associations of P4.2 with the RBC membrane.
Inhibition of Axl improves the targeted therapy against ALK-mutated neuroblastoma
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Fei; Li, Hongling; Sun, Yong, E-mail: sunfanqi2010@163.com
2014-11-28
Highlights: • First reported Axl is co-expressed with ALK in neuroblastoma tissues and cell lines. • Axl activation promotes cell growth and impairs the efficiency of ALK inhibitor. • Further found silence of Axl leads to increased sensitivity to ALK inhibitors. • Axl inhibitor promotes the efficiency of targeted therapy in vitro and in vivo. • Axl activation should be considered in the clinical application of ALK inhibitors. - Abstract: Neuroblastoma (NB) patients harboring mutated ALK can be expected to potentially benefit from targeted therapy based on ALK tyrosine kinase inhibitor (TKI), such as crizotinib and ceritinib. However, the effectmore » of the treatment varies with different individuals, although with the same genic changes. Axl receptor tyrosine kinase is expressed in a variety of human cancers, but little data are reported in NB, particularly in which carrying mutated ALK. In this study, we focus on the roles of Axl in ALK-mutated NB for investigating rational therapeutic strategy. We found that Axl is expressed in ALK-positive NB tissues and cell lines, and could be effectively activated by its ligand GAS6. Ligand-dependent Axl activation obviously rescued crizotinib-mediated suppression of cell proliferation in ALK-mutated NB cells. Genetic inhibition of Axl with specific small interfering RNA markedly increased the sensitivity of cells to ALK-TKIs. Furthermore, a small-molecule inhibitor of Axl significantly enhanced ALK-targeted therapy, as an increased frequency of apoptosis was observed in NB cells co-expressing ALK and Axl. Taken together, our results demonstrated that activation of Axl could lead to insensitivity to ALK inhibitors, and dual inhibition of ALK and Axl might be a potential therapeutic strategy against ALK-mutated NB.« less
Kai, Hisahiro; Fuse, Takuichi; Kunitake, Hisato; Morishita, Kazuhiro; Matsuno, Koji
2014-06-30
The inhibitory effects of blueberry leaves on the proliferation of adult T-cell leukemia (ATL) cell lines have previously been reported. A comparison of blueberry leaf extracts from different cultivars and seasonal variation were investigated regarding their effects on ATL cell line proliferation. The inhibitory effects of 80% ethanol leaf extracts from different blueberry cultivars collected from April to December in 2006 or 2008 were evaluated using two ATL cell lines. The bioactivities of leaf extracts of rabbit-eye blueberry ( Vaccinium virgatum Aiton; RB species), southern highbush blueberry ( V. spp.; SB species), northern highbush blueberry ( V. corymbosum L.; NB species), and wild blueberry ( V. bracteatum Thunb.; WB species) were compared. Of these, leaves of the RB species collected in December showed a significantly stronger inhibitory effect in both cell lines than the SB, NB, or WB species. These results suggest elevated biosynthesis of ATL-preventative bioactive compounds in the leaves of the RB species before the defoliation season.
Kai, Hisahiro; Fuse, Takuichi; Kunitake, Hisato; Morishita, Kazuhiro; Matsuno, Koji
2014-01-01
The inhibitory effects of blueberry leaves on the proliferation of adult T-cell leukemia (ATL) cell lines have previously been reported. A comparison of blueberry leaf extracts from different cultivars and seasonal variation were investigated regarding their effects on ATL cell line proliferation. The inhibitory effects of 80% ethanol leaf extracts from different blueberry cultivars collected from April to December in 2006 or 2008 were evaluated using two ATL cell lines. The bioactivities of leaf extracts of rabbit-eye blueberry (Vaccinium virgatum Aiton; RB species), southern highbush blueberry (V. spp.; SB species), northern highbush blueberry (V. corymbosum L.; NB species), and wild blueberry (V. bracteatum Thunb.; WB species) were compared. Of these, leaves of the RB species collected in December showed a significantly stronger inhibitory effect in both cell lines than the SB, NB, or WB species. These results suggest elevated biosynthesis of ATL-preventative bioactive compounds in the leaves of the RB species before the defoliation season. PMID:28933373
Effects of Trypanocidal Drugs on the Function of Trypanosomes.
1979-09-01
1.1 x 10 3 3.0 x 106 4 2.5 x 106 5 3.0 x 106 a = One-third of the RPMI medium was changed dail-. ATCC CCL 44 EBTr ( NBL -4) (Embryonic trachea...Bovine, Bos taurus) HISTORY The EBTr ( NBL -4) cell line was initiated by A.J. Kniazeff, W.A. Nelson-Rees and N.B. Darby, Jr., from the minced, whole
Halder, Sujata; Cotmore, Susan; Heimburg-Molinaro, Jamie; Smith, David F.; Cummings, Richard D.; Chen, Xi; Trollope, Alana J.; North, Simon J.; Haslam, Stuart M.; Dell, Anne; Tattersall, Peter; McKenna, Robert; Agbandje-McKenna, Mavis
2014-01-01
The recognition of sialic acids by two strains of minute virus of mice (MVM), MVMp (prototype) and MVMi (immunosuppressive), is an essential requirement for successful infection. To understand the potential for recognition of different modifications of sialic acid by MVM, three types of capsids, virus-like particles, wild type empty (no DNA) capsids, and DNA packaged virions, were screened on a sialylated glycan microarray (SGM). Both viruses demonstrated a preference for binding to 9-O-methylated sialic acid derivatives, while MVMp showed additional binding to 9-O-acetylated and 9-O-lactoylated sialic acid derivatives, indicating recognition differences. The glycans recognized contained a type-2 Galβ1-4GlcNAc motif (Neu5Acα2-3Galβ1-4GlcNAc or 3′SIA-LN) and were biantennary complex-type N-glycans with the exception of one. To correlate the recognition of the 3′SIA-LN glycan motif as well as the biantennary structures to their natural expression in cell lines permissive for MVMp, MVMi, or both strains, the N- and O-glycans, and polar glycolipids present in three cell lines used for in vitro studies, A9 fibroblasts, EL4 T lymphocytes, and the SV40 transformed NB324K cells, were analyzed by MALDI-TOF/TOF mass spectrometry. The cells showed an abundance of the sialylated glycan motifs recognized by the viruses in the SGM and previous glycan microarrays supporting their role in cellular recognition by MVM. Significantly, the NB324K showed fucosylation at the non-reducing end of their biantennary glycans, suggesting that recognition of these cells is possibly mediated by the Lewis X motif as in 3′SIA-LeX identified in a previous glycan microarray screen. PMID:24475195
[Harringtonine induces apoptosis in NB4 cells through down-regulation of Mcl-1].
Wu, Chunxiao; Shen, Hongqiang; Xia, Dajing
2013-07-01
To investigate the growth inhibition effect, cytotoxicity and apoptotic induction of harringtonine (HT) in human acute promyelocytic leukemia (APL) NB4 cells,and the related mechanism. NB4 cells were treated with HT. Total cell numbers were counted by hemocytometer, and cell viabilities were determined by trypan blue exclusion. Apoptotic cells were determined by fluorescence microscopy and FACS after staining with AO and EB or PI, respectively. The cleavage of PARP and the activation of Bax and the expression of anti-apoptotic proteins were determined by Western Blot. siRNA was used to silence the expression of target genes. Primary cells were isolated following Ficoll-Hypaque density gradient centrifugation method. HT inhibited cell growth and induced apoptosis of NB4 cells in a dose- and time-dependent manner. Apoptosis induced by HT was correlated with the down-regulation of Mcl-1 and the cleavage of PARP, while HT did not affect the protein level of Bax and Bak or change the protein level of Bcl-2. The silence of Bcl-XL sensitized HT-induced apoptosis in NB4 cells.Apoptosis induced by HT in primarily cultured APL cells was also correlated with the down-regulation of Mcl-1. HT inhibits cell growth and induces apoptosis in NB4 cells and primarily cultured APL cells, which may be associated with down-regulation of Mcl-1.
Mandili, Giorgia; Marini, Cristina; Carta, Franco; Zanini, Cristina; Prato, Mauro; Khadjavi, Amina
2011-01-01
Background Neuroblastic tumors account for 9–10% of pediatric tumors and neuroblastoma (NB) is the first cause of death in pre-school age children. NB is classified in four stages, depending on the extent of spreading. A fifth type of NB, so-called stage 4S (S for special), includes patients with metastatic tumors but with an overall survival that approximates 75% at five years. In most of these cases, the tumor regresses spontaneously and regression is probably associated with delayed neuroblast cell differentiation. Methodology/Principal Findings In order to identify new early markers to follow and predict this process for diagnostic and therapeutics intents, we mimicked the differentiation process treating NB cell line SJ-NK-P with all-trans-retinoic acid (ATRA) at different times; therefore the cell proteomic pattern by mass spectrometry and the phosphoproteomic pattern by a 2-DE approach coupled with anti-phosphoserine and anti-phosphotyrosine western blotting were studied. Conclusions/Significance Proteomic analysis identified only two proteins whose expression was significantly different in treated cells versus control cells: nucleoside diphosphate kinase A (NDKA) and reticulocalbin-1 (RCN1), which were both downregulated after 9 days of ATRA treatment. However, phosphoproteomic analysis identified 8 proteins that were differentially serine-phosphorylated and 3 that were differentially tyrosine-phosphorylated after ATRA treatment. All proteins were significantly regulated (at least 0.5-fold down-regulated). Our results suggest that differentially phosphorylated proteins could be considered as more promising markers of differentiation for NB than differentially expressed proteins. PMID:21573212
Yu, Man; Tong, Jian-Hua; Mao, Mao; Kan, Li-Xin; Liu, Meng-Min; Sun, Yi-Wu; Fu, Gang; Jing, Yong-Kui; Yu, Long; Lepaslier, Denis; Lanotte, Michel; Wang, Zhen-Yi; Chen, Zhu; Waxman, Samuel; Wang, Ya-Xin; Tan, Jia-Zhen; Chen, Sai-Juan
1997-01-01
In a cell line (NB4) derived from a patient with acute promyelocytic leukemia, all-trans-retinoic acid (ATRA) and interferon (IFN) induce the expression of a novel gene we call RIG-G (for retinoic acid-induced gene G). This gene codes for a 58-kDa protein containing 490 amino acids with several potential sites for post-translational modification. In untreated NB4 cells, the expression of RIG-G is undetectable. ATRA treatment induces the transcriptional expression of RIG-G relatively late (12–24 hr) in a protein synthesis-dependent manner, whereas IFN-α induces its expression early (30 min to 3 hr). Database search has revealed a high-level homology between RIG-G and several IFN-stimulated genes in human (ISG54K, ISG56K, and IFN-inducible and retinoic acid-inducible 58K gene) and some other species, defining a well conserved gene family. The gene is composed of two exons and has been mapped by fluorescence in situ hybridization to chromosome 10q24, where two other human IFN-stimulated gene members are localized. A synergistic induction of RIG-G expression in NB4 cells by combined treatment with ATRA and IFNs suggests that a collaboration exists between their respective signaling pathways. PMID:9207104
Qu, Hongxia; Zheng, Liduan; Jiao, Wanju; Mei, Hong; Li, Dan; Song, Huajie; Fang, Erhu; Wang, Xiaojing; Li, Shiwang; Huang, Kai; Tong, Qiangsong
2016-09-06
Heparanase (HPSE) is the only endo-β-D-glucuronidase that is correlated with the progression of neuroblastoma (NB), the most common extracranial malignancy in childhood. However, the mechanisms underlying HPSE expression in NB still remain largely unknown. Herein, through analyzing cis-regulatory elements and mining public microarray datasets, we identified SMAD family member 4 (Smad4) as a crucial transcription regulator of HPSE in NB. We demonstrated that Smad4 repressed the HPSE expression at the transcriptional levels in NB cells. Mechanistically, Smad4 suppressed the HPSE expression through directly binding to its promoter and repressing the lymphoid enhancer binding factor 1 (LEF1)-facilitated transcription of HPSE via physical interaction. Gain- and loss-of-function studies demonstrated that Smad4 inhibited the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo. Restoration of HPSE expression prevented the NB cells from changes in these biological features induced by Smad4. In clinical NB specimens, Smad4 was under-expressed and inversely correlated with HPSE levels, while LEF1 was highly expressed and positively correlated with HPSE expression. Patients with high Smad4 expression, low LEF1 or HPSE levels had greater survival probability. These results demonstrate that Smad4 suppresses the tumorigenesis and aggressiveness of NB through repressing the HPSE expression.
Fluorescence spectra of Cr3+ dimers in LiNbO3
NASA Astrophysics Data System (ADS)
Jia, Weiyi; Liu, Huimin; Knutson, R.; Yen, W. M.
1990-06-01
Fine spectral structure has been observed in both fluorescence and excitation spectra of Cr3+:LiNbO3 on the high-energy side of the broadband emission from 4T2 at 10 K. The lifetimes of the structures are found to be much longer than the lifetime of the broadband 4T2 fluorescence. These sharp lines are assigned to the 2E-->4A2 emissions (R lines) from two types of Cr3+ sites arising from charge compensation; Cr3+ ions are found to substitute both for Li+ and for Nb5+ sites and to form dimerlike pairs.
Michaelis, M; Rothweiler, F; Barth, S; Cinatl, J; van Rikxoort, M; Löschmann, N; Voges, Y; Breitling, R; von Deimling, A; Rödel, F; Weber, K; Fehse, B; Mack, E; Stiewe, T; Doerr, H W; Speidel, D; Cinatl, J
2011-01-01
Six p53 wild-type cancer cell lines from infrequently p53-mutated entities (neuroblastoma, rhabdomyosarcoma, and melanoma) were continuously exposed to increasing concentrations of the murine double minute 2 inhibitor nutlin-3, resulting in the emergence of nutlin-3-resistant, p53-mutated sublines displaying a multi-drug resistance phenotype. Only 2 out of 28 sublines adapted to various cytotoxic drugs harboured p53 mutations. Nutlin-3-adapted UKF-NB-3 cells (UKF-NB-3rNutlin10 μM, harbouring a G245C mutation) were also radiation resistant. Analysis of UKF-NB-3 and UKF-NB-3rNutlin10 μM cells by RNA interference experiments and lentiviral transduction of wild-type p53 into p53-mutated UKF-NB-3rNutlin10 μM cells revealed that the loss of p53 function contributes to the multi-drug resistance of UKF-NB-3rNutlin10 μM cells. Bioinformatics PANTHER pathway analysis based on microarray measurements of mRNA abundance indicated a substantial overlap in the signalling pathways differentially regulated between UKF-NB-3rNutlin10 μM and UKF-NB-3 and between UKF-NB-3 and its cisplatin-, doxorubicin-, or vincristine-resistant sublines. Repeated nutlin-3 adaptation of neuroblastoma cells resulted in sublines harbouring various p53 mutations with high frequency. A p53 wild-type single cell-derived UKF-NB-3 clone was adapted to nutlin-3 in independent experiments. Eight out of ten resulting sublines were p53-mutated harbouring six different p53 mutations. This indicates that nutlin-3 induces de novo p53 mutations not initially present in the original cell population. Therefore, nutlin-3-treated cancer patients should be carefully monitored for the emergence of p53-mutated, multi-drug-resistant cells. PMID:22170099
Farace, Cristiano; Oliver, Jaime Antonio; Melguizo, Consolacion; Alvarez, Pablo; Bandiera, Pasquale; Rama, Ana Rosa; Malaguarnera, Giulia; Ortiz, Raul; Madeddu, Roberto; Prados, Jose
2015-01-01
The presence of cancer stem cells (CSCs) or tumor-initiating cells can lead to cancer recurrence in a permissive cell-microenvironment interplay, promoting invasion in glioblastoma (GBM) and neuroblastoma (NB). Extracellular matrix (ECM) small leucine-rich proteoglycans (SLRPs) play multiple roles in tissue homeostasis by remodeling the extracellular matrix (ECM) components and modulating intracellular signaling pathways. Due to their pan-inhibitory properties against receptor tyrosine kinases (RTKs), SLRPs are reported to exert anticancer effects in vitro and in vivo. However, their roles seem to be tissue-specific and they are also involved in cancer cell migration and drug resistance, paving the way to complex different scenarios. The aim of this study was to determine whether the SLRPs decorin (DCN) and lumican (LUM) are recruited in cell plasticity and microenvironmental adaptation of differentiated cancer cells induced towards stem-like phenotype. Floating neurospheres were generated by applying CSC enrichment medium (neural stem cell serum-free medium, NSC SFM) to the established SF-268 and SK-N-SH cancer cell lines, cellular models of GBM and NB, respectively. In both models, the time-dependent synergistic activation of DCN and LUM was observed. The highest DCN and LUM mRNA/protein expression was detected after cell exposure to NSC SFM for 8/12 days, considering these cells as SLRP-expressing (SLRP+) CSC-like. Ultrastructural imaging showed the cellular heterogeneity of both the GBM and NB neurospheres and identified the inner living cells. Parental cell lines of both GBM and NB grew only in soft agar + NSC SFM, whereas the secondary neurospheres (originated from SLRP+ t8 CSC-like) showed lower proliferation rates than primary neurospheres. Interestingly, the SLRP+ CSC-like from the GBM and NB neurospheres were resistant to temozolomide (TMZ) at concentrations >750 μM. Our results suggest that GBM and NB CSC-like promote the activation of huge quantities of SLRP in response to CSC enrichment, simultaneously acquiring TMZ resistance, cellular heterogeneity, and a quiescent phenotype, suggesting a novel pivotal role for SLRP in drug resistance and cell plasticity of CSC-like, allowing cell survival and ECM/niche modulation potential.
Wang, Xisi; Wang, Lijun; Su, Yan; Yue, Zhixia; Xing, Tianyu; Zhao, Wen; Zhao, Qian; Duan, Chao; Huang, Cheng; Zhang, Dawei; Jin, Mei; Cheng, Xianfeng; Chen, Shenglan; Liu, Yi; Ma, Xiaoli
2018-06-14
To evaluate plasma cell-free DNA (cfDNA) as a promising biomarker for neuroblastoma (NB) tumor burden. Seventy-nine eligible patients with newly diagnosed NB were recruited from Beijing Children's Hospital between April 2016 and April 2017. Additionally, from September 2011 to June 2017, 79 patients with stable NB were evaluated with a median follow-up time of 21 months. Approximately 2 mL of peripheral blood was drawn upon enrollment, and plasma cfDNA levels were measured via quantitative polymerase chain reaction (qPCR). Total cfDNA analysis was performed using the long interspersed nuclear element 1 (LINE-1) 79 bp fragment, and DNA integrity was calculated by the ratio of the LINE-1 300 bp fragment to the LINE-1 79 bp fragment. A total of 79 NB patients with a median age of 36 months comprised the group of newly diagnosed NB patients. The main primary tumor site was the retroperitoneal and adrenal region (81%). Three or more metastatic sites were found in 17.7% of patients. Stable NB patients older than 18 months comprised 98.7% of the stable NB patients. Neuron-specific enolase (NSE), lactate dehydrogenase (LDH), and cfDNA levels were dramatically increased in the newly diagnosed NB patients and significantly different from those in the stable NB patients. Moreover, the concentration of cfDNA was much higher in patients with larger tumors. By analyzing the area under the receiver operator characteristic (ROC) curve (AUC), the areas of total cfDNA, NSE, and LDH levels were 0.953, 0.929, and 0.906, respectively. The sensitivity and specificity data clarified that the level of circulating cfDNA in plasma can be considered as a reliable biomarker for describing tumor load in NB. The plasma cfDNA concentration was as good as the levels of LDH and NSE to discriminate the tumor burden in children with NB. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Melguizo, Consolacion; Alvarez, Pablo; Bandiera, Pasquale; Rama, Ana Rosa; Malaguarnera, Giulia; Ortiz, Raul; Madeddu, Roberto; Prados, Jose
2015-01-01
The presence of cancer stem cells (CSCs) or tumor-initiating cells can lead to cancer recurrence in a permissive cell–microenvironment interplay, promoting invasion in glioblastoma (GBM) and neuroblastoma (NB). Extracellular matrix (ECM) small leucine-rich proteoglycans (SLRPs) play multiple roles in tissue homeostasis by remodeling the extracellular matrix (ECM) components and modulating intracellular signaling pathways. Due to their pan-inhibitory properties against receptor tyrosine kinases (RTKs), SLRPs are reported to exert anticancer effects in vitro and in vivo. However, their roles seem to be tissue-specific and they are also involved in cancer cell migration and drug resistance, paving the way to complex different scenarios. The aim of this study was to determine whether the SLRPs decorin (DCN) and lumican (LUM) are recruited in cell plasticity and microenvironmental adaptation of differentiated cancer cells induced towards stem-like phenotype. Floating neurospheres were generated by applying CSC enrichment medium (neural stem cell serum-free medium, NSC SFM) to the established SF-268 and SK-N-SH cancer cell lines, cellular models of GBM and NB, respectively. In both models, the time-dependent synergistic activation of DCN and LUM was observed. The highest DCN and LUM mRNA/protein expression was detected after cell exposure to NSC SFM for 8/12 days, considering these cells as SLRP-expressing (SLRP+) CSC-like. Ultrastructural imaging showed the cellular heterogeneity of both the GBM and NB neurospheres and identified the inner living cells. Parental cell lines of both GBM and NB grew only in soft agar + NSC SFM, whereas the secondary neurospheres (originated from SLRP+ t8 CSC-like) showed lower proliferation rates than primary neurospheres. Interestingly, the SLRP+ CSC-like from the GBM and NB neurospheres were resistant to temozolomide (TMZ) at concentrations >750 μM. Our results suggest that GBM and NB CSC-like promote the activation of huge quantities of SLRP in response to CSC enrichment, simultaneously acquiring TMZ resistance, cellular heterogeneity, and a quiescent phenotype, suggesting a novel pivotal role for SLRP in drug resistance and cell plasticity of CSC-like, allowing cell survival and ECM/niche modulation potential. PMID:26230845
Markhoff, Jana; Weinmann, Markus; Schulze, Christian; Bader, Rainer
2017-04-01
Nowadays, biomaterials can be used to maintain or replace several functions of the human body if necessary. Titanium and its alloys, i.e. Ti6Al4V are the most common materials (70 to 80%) used for structural orthopedic implants due to their unique combination of good mechanical properties, corrosion resistance and biocompatibility. Addition of β-stabilizers, e.g. niobium, can improve the mechanical properties of such titanium alloys further, simultaneously offering excellent biocompatibility. In this in vitro study, human osteoblasts and fibroblasts were cultured on different niobium specimens (Nb Amperit, Nb Ampertec), Nb sheets and Ti-42Nb (sintered and 3D-printed by selective laser melting, SLM) and compared with forged Ti6Al4V specimens. Furthermore, human osteoblasts were incubated with particulates of the Nb and Ti-42Nb specimens in three concentrations over four and seven days to imitate influence of wear debris. Thereby, the specimens with the roughest surfaces, i.e. Ti-42Nb and Nb Ampertec, revealed excellent and similar results for both cell types concerning cell viability and collagen synthesis superior to forged Ti6Al4V. Examinations with particulate debris disclosed a dose-dependent influence of all powders with Nb Ampertec showing the highest decrease of cell viability and collagen synthesis. Furthermore, interleukin synthesis was only slightly increased for all powders. In summary, Nb Ampertec (sintered Nb) and Ti-42Nb materials seem to be promising alternatives for medical applications compared to common materials like forged or melted Ti6Al4V. Copyright © 2016 Elsevier B.V. All rights reserved.
Romania, Paolo; Castellano, Aurora; Surace, Cecilia; Citti, Arianna; De Ioris, Maria Antonietta; Sirleto, Pietro; De Mariano, Marilena; Longo, Luca; Boldrini, Renata; Angioni, Adriano; Locatelli, Franco; Fruci, Doriana
2013-01-01
Neuroblastoma (NB), the most common solid cancer in early childhood, usually occurs sporadically but also its familial occurance is known in 1-2% of NB patients. Germline mutations in the ALK and PHOX2B genes have been found in a subset of familial NBs. However, because some individuals harbouring mutations in these genes do not develop this tumor, additional genetic alterations appear to be required for NB pathogenesis. Herein, we studied an Italian family with three NB patients, two siblings and a first cousin, carrying an ALK germline-activating mutation R1192P, that was inherited from their unaffected mothers and with no mutations in the PHOX2B gene. A comparison between somatic and germline DNA copy number changes in the two affected siblings by a high resolution array-based Comparative Genomic Hybridization (CGH) analysis revealed a germline gain at NKAIN2 (Na/K transporting ATPase interacting 2) locus in one of the sibling, that was inherited from the parent who does not carry the ALK mutation. Surprisingly, NKAIN2 was expressed at high levels also in the affected sibling that lacks the genomic gain at this locus, clearly suggesting the existance of other regulatory mechanisms. High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines and in the most aggressive NB lesions as well as in the peripheral blood of a large cohort of NB patients. Consistent with a role of NKAIN2 in NB development, NKAIN2 was down-regulated during all-trans retinoic acid differentiation in two NB cell lines. Taken together, these data indicate a potential role of NKAIN2 gene in NB growth and differentiation. PMID:24205241
Romania, Paolo; Castellano, Aurora; Surace, Cecilia; Citti, Arianna; De Ioris, Maria Antonietta; Sirleto, Pietro; De Mariano, Marilena; Longo, Luca; Boldrini, Renata; Angioni, Adriano; Locatelli, Franco; Fruci, Doriana
2013-01-01
Neuroblastoma (NB), the most common solid cancer in early childhood, usually occurs sporadically but also its familial occurance is known in 1-2% of NB patients. Germline mutations in the ALK and PHOX2B genes have been found in a subset of familial NBs. However, because some individuals harbouring mutations in these genes do not develop this tumor, additional genetic alterations appear to be required for NB pathogenesis. Herein, we studied an Italian family with three NB patients, two siblings and a first cousin, carrying an ALK germline-activating mutation R1192P, that was inherited from their unaffected mothers and with no mutations in the PHOX2B gene. A comparison between somatic and germline DNA copy number changes in the two affected siblings by a high resolution array-based Comparative Genomic Hybridization (CGH) analysis revealed a germline gain at NKAIN2 (Na/K transporting ATPase interacting 2) locus in one of the sibling, that was inherited from the parent who does not carry the ALK mutation. Surprisingly, NKAIN2 was expressed at high levels also in the affected sibling that lacks the genomic gain at this locus, clearly suggesting the existance of other regulatory mechanisms. High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines and in the most aggressive NB lesions as well as in the peripheral blood of a large cohort of NB patients. Consistent with a role of NKAIN2 in NB development, NKAIN2 was down-regulated during all-trans retinoic acid differentiation in two NB cell lines. Taken together, these data indicate a potential role of NKAIN2 gene in NB growth and differentiation.
Qu, Hongxia; Zheng, Liduan; Jiao, Wanju; Mei, Hong; Li, Dan; Song, Huajie; Fang, Erhu; Wang, Xiaojing; Li, Shiwang; Huang, Kai; Tong, Qiangsong
2016-01-01
Heparanase (HPSE) is the only endo-β-D-glucuronidase that is correlated with the progression of neuroblastoma (NB), the most common extracranial malignancy in childhood. However, the mechanisms underlying HPSE expression in NB still remain largely unknown. Herein, through analyzing cis-regulatory elements and mining public microarray datasets, we identified SMAD family member 4 (Smad4) as a crucial transcription regulator of HPSE in NB. We demonstrated that Smad4 repressed the HPSE expression at the transcriptional levels in NB cells. Mechanistically, Smad4 suppressed the HPSE expression through directly binding to its promoter and repressing the lymphoid enhancer binding factor 1 (LEF1)-facilitated transcription of HPSE via physical interaction. Gain- and loss-of-function studies demonstrated that Smad4 inhibited the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo. Restoration of HPSE expression prevented the NB cells from changes in these biological features induced by Smad4. In clinical NB specimens, Smad4 was under-expressed and inversely correlated with HPSE levels, while LEF1 was highly expressed and positively correlated with HPSE expression. Patients with high Smad4 expression, low LEF1 or HPSE levels had greater survival probability. These results demonstrate that Smad4 suppresses the tumorigenesis and aggressiveness of NB through repressing the HPSE expression. PMID:27595937
Sidarovich, Viktoryia; De Mariano, Marilena; Aveic, Sanja; Pancher, Michael; Adami, Valentina; Gatto, Pamela; Pizzini, Silvia; Pasini, Luigi; Croce, Michela; Parodi, Federica; Cimmino, Flora; Avitabile, Marianna; Emionite, Laura; Cilli, Michele; Ferrini, Silvano; Pagano, Aldo; Capasso, Mario; Quattrone, Alessandro; Tonini, Gian Paolo; Longo, Luca
2018-04-25
Novel druggable targets have been discovered in neuroblastoma (NB), paving the way for more effective treatments. However, children with high-risk NB still show high mortality rates prompting for a search of novel therapeutic options. Here, we aimed at repurposing FDA-approved drugs for NB treatment by performing a high-content screening of a 349 anti-cancer compounds library. In the primary screening we employed three NB cell lines, grown as 3D multicellular spheroids, which were treated with 10 μM of the library compounds for 72 hours. The viability of 3D spheroids was evaluated using a high-content imaging approach, resulting in a primary hit list of 193 compounds. We selected 60 FDA-approved molecules and prioritized drugs with multi-target activity, discarding those already in use for NB treatment or enrolled in NB clinical trials. Hence, 20 drugs were further tested for their efficacy in inhibiting NB cell viability, both in 2D and 3D models. Dose-response curves were then supplemented with the data on side-effects, therapeutic index and molecular targets, suggesting two multiple tyrosine kinase inhibitors, ponatinib and axitinib, as promising candidates for repositioning in NB. Indeed, both drugs showed induction of cell cycle block and apoptosis, as well as inhibition of colony formation. However, only ponatinib consistently affected migration and inhibited invasion of NB cells. Finally, ponatinib also proved effective inhibition of tumor growth in orthotopic NB mice, providing the rationale for its repurposing in NB therapy. Copyright ©2018, American Association for Cancer Research.
Palyanova, Natalia V; Pankova, Tatyana M; Starostina, Marina V; Kicha, Alla A; Ivanchina, Natalia V; Stonik, Valentin A
2013-05-03
The neuritogenic and neuroprotective activities of six starfish polar steroids, asterosaponin Р₁, (25S)-5α-cholestane-3β,4β,6α,7α,8,15α,16β,26-octaol, and (25S)-5α-cholestane-3β,6α,7α,8,15α,16β,26-heptaol (1-3) from the starfish Patiria pectinifera and distolasterosides D₁-D₃ (4-6) from the starfish Distolasterias nipon were analyzed using the mouse neuroblastoma (NB) C-1300 cell line and an organotypic rat hippocampal slice culture (OHSC). All of these compounds enhanced neurite outgrowth in NB cells. Dose-dependent responses to compounds 1-3 were observed within the concentration range of 10-100 nM, and dose-dependent responses to glycosides 4-6 were observed at concentrations of 1-50 nM. All the tested substances exhibited notable synergistic effects with trace amounts of nerve growth factor (NGF, 1 ng/mL) or brain-derived neurotrophic factor (BDNF, 0.1 ng/mL). Using NB cells and OHSCs, it was shown for the first time that starfish steroids 1-6 act as neuroprotectors against oxygen-glucose deprivation (OGD) by increasing the number of surviving cells. Altogether, these results suggest that neurotrophin-like neuritogenic and neuroprotective activities are most likely common properties of starfish polyhydroxysteroids and the related glycosides, although the magnitude of the effect depended on the particular compound structure.
Palyanova, Natalia V.; Pankova, Tatyana M.; Starostina, Marina V.; Kicha, Alla A.; Ivanchina, Natalia V.; Stonik, Valentin A.
2013-01-01
The neuritogenic and neuroprotective activities of six starfish polar steroids, asterosaponin Р1, (25S)-5α-cholestane-3β,4β,6α,7α,8,15α,16β,26-octaol, and (25S)-5α-cholestane-3β,6α,7α,8,15α,16β,26-heptaol (1–3) from the starfish Patiria pectinifera and distolasterosides D1–D3 (4–6) from the starfish Distolasterias nipon were analyzed using the mouse neuroblastoma (NB) C-1300 cell line and an organotypic rat hippocampal slice culture (OHSC). All of these compounds enhanced neurite outgrowth in NB cells. Dose-dependent responses to compounds 1–3 were observed within the concentration range of 10–100 nM, and dose-dependent responses to glycosides 4–6 were observed at concentrations of 1–50 nM. All the tested substances exhibited notable synergistic effects with trace amounts of nerve growth factor (NGF, 1 ng/mL) or brain-derived neurotrophic factor (BDNF, 0.1 ng/mL). Using NB cells and OHSCs, it was shown for the first time that starfish steroids 1–6 act as neuroprotectors against oxygen-glucose deprivation (OGD) by increasing the number of surviving cells. Altogether, these results suggest that neurotrophin-like neuritogenic and neuroprotective activities are most likely common properties of starfish polyhydroxysteroids and the related glycosides, although the magnitude of the effect depended on the particular compound structure. PMID:23644925
Csomós, Krisztián; Német, István; Fésüs, László; Balajthy, Zoltán
2010-11-11
Treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA) results in terminal differentiation of leukemic cells toward neutrophil granulocytes. Administration of ATRA leads to massive changes in gene expression, including down-regulation of cell proliferation-related genes and induction of genes involved in immune function. One of the most induced genes in APL NB4 cells is transglutaminase 2 (TG2). RNA interference-mediated stable silencing of TG2 in NB4 cells (TG2-KD NB4) coupled with whole genome microarray analysis revealed that TG2 is involved in the expression of a large number of ATRA-regulated genes. The affected genes participate in granulocyte functions, and their silencing lead to reduced adhesive, migratory, and phagocytic capacity of neutrophils and less superoxide production. The expression of genes related to cell-cycle control also changed, suggesting that TG2 regulates myeloid cell differentiation. CC chemokines CCL2, CCL3, CCL22, CCL24, and cytokines IL1B and IL8 involved in the development of differentiation syndrome are expressed at significantly lower level in TG2-KD NB4 than in wild-type NB4 cells upon ATRA treatment. Based on our results, we propose that reduced expression of TG2 in differentiating APL cells may suppress effector functions of neutrophil granulocytes and attenuate the ATRA-induced inflammatory phenotype of differentiation syndrome.
Wong, Kaitlyn E; Mora, Maria C; Sultana, Nazneen; Moriarty, Kevin P; Arenas, Richard B; Yadava, Nagendra; Schneider, Sallie S; Tirabassi, Michael V
2018-06-01
Outcomes of children with high grade neuroblastoma remain poor despite multi-agent chemotherapy regimens. Rhodiola crenulata extracts display anti-neoplastic properties against several cancers including breast cancer, melanoma, and glioblastoma. In this study, we evaluated the anti-neoplastic potential of Rhodiola crenulata extracts on human neuroblastoma cells. Through this work, cell viability and proliferation were evaluated following treatments with ethanol (vehicle control) or Rhodiola crenulata extract in neuroblastoma, NB-1691 or SK-N-AS cells, in vitro. HIF-1 transcriptional activity was evaluated using a dual luciferase assay. Quantitative real-time polymerase chain reaction was utilized to assess the expression of HIF-1 targets. Selected metabolic intermediates were evaluated for their ability to rescue cells from Rhodiola crenulata extract-induced death. Lactate dehydrogenase, pyruvate kinase, and pyruvate dehydrogenase activities and NAD + /NADH levels were assayed in vehicle and Rhodiola crenulata extract-treated cells. The effects of Rhodiola crenulata extracts on metabolism were assessed by respirometry and metabolic phenotyping/fingerprinting. Our results revealed striking cytotoxic effects upon Rhodiola crenulata extract treatment, especially prominent in NB-1691 cells. As a greater response was observed in NB-1691 cells therefore it was used for remaining experiments. Upon Rhodiola crenulata extract treatment, HIF-1 transcriptional activity was increased. This increase in activity correlated with changes in HIF-1 targets involved in cellular metabolism. Serendipitously, we observed that addition of pyruvate protected against the cytotoxic effects of Rhodiola crenulata extracts. Therefore, we focused on the metabolic effects of Rhodiola crenulata extracts on NB-1691 cells. We observed that while the activities of pyruvate kinase and pyruvate dehydrogenase activities were increased, the activity of lactate dehydrogenase activity was decreased upon Rhodiola crenulata extract treatment. We also noted a decline in the total NAD pool following Rhodiola crenulata extract treatment. This correlated with decreased cellular respiration and suppressed utilization of carbon substrates. Through this work, we observed significant cytotoxic effects of Rhodiola crenulata extract treatment upon treatment on NB-1691 cells, a human neuroblastoma cell line with MYCN amplification. Our studies suggest that these cytotoxic effects could be secondary to metabolic effect induced by treatment with Rhodiola crenulata extract.
Gao, Q; Chen, C F; Dong, Q; Hou, L; Chen, X; Zhi, Y L; Li, X; Lu, H T; Zhang, H Y
2015-12-08
The aim of this study was to establish a metastatic human neuroblastoma (NB) mouse model by xenograft in order to study the metastatic mechanisms of NB. A human NB cell line was obtained from a 5-year-old patient and cultured in vitro. A suspension of these cells was subcutaneously inoculated into nude mice at the right flank next to the forelimb. The biological characteristics of the developed subcutaneous and metastatic tumors were analyzed by hematoxylin and eosin staining. The expression of the tumor marker neuron-specific enolase was determined by immunohistochemistry, and the invasive ability of metastatic tumors was examined by a Matrigel invasion assay. DNA microarray analyses were performed to examine the metastasis-related gene expression. Our results showed that tumors grew in 75% of the mice injected with NB cells and the rate of metastasis was 21%. The xenograft tumors retained the morphological and biological characteristics of the NB specimen from the pediatric patient. Neuron-specific enolase was highly expressed in both subcutaneous and metastatic tumors. The metastatic tumor cells possessed a higher invasive capability than the primary NB cells. The expression of 25 metastasis-related genes was found to be significantly altered in metastatic tumors compared to primary tumors, including RECK, MMP2, VEGF, MMP3, and CXCL12. In conclusion, we successfully established a human NB xenograft model with high tumor-bearing and metastatic rates in nude mice, providing an ideal animal model for the in vivo study of NB.
Loi, Monica; Di Paolo, Daniela; Soster, Marco; Brignole, Chiara; Bartolini, Alice; Emionite, Laura; Sun, Jessica; Becherini, Pamela; Curnis, Flavio; Petretto, Andrea; Sani, Monica; Gori, Alessandro; Milanese, Marco; Gambini, Claudio; Longhi, Renato; Cilli, Michele; Allen, Theresa M; Bussolino, Federico; Arap, Wadih; Pasqualini, Renata; Corti, Angelo; Ponzoni, Mirco; Marchiò, Serena; Pastorino, Fabio
2013-09-10
Molecular targeting of drug delivery nanocarriers is expected to improve their therapeutic index while decreasing their toxicity. Here we report the identification and characterization of novel peptide ligands specific for cells present in high-risk neuroblastoma (NB), a childhood tumor mostly refractory to current therapies. To isolate such targeting moieties, we performed combined in vitro/ex-vivo phage display screenings on NB cell lines and on tumors derived from orthotopic mouse models of human NB. By designing proper subtractive protocols, we identified phage clones specific either for the primary tumor, its metastases, or for their respective stromal components. Globally, we isolated 121 phage-displayed NB-binding peptides: 26 bound the primary tumor, 15 the metastatic mass, 57 and 23 their respective microenvironments. Of these, five phage clones were further validated for their specific binding ex-vivo to biopsies from stage IV NB patients and to NB tumors derived from mice. All five clones also targeted tumor cells and vasculature in vivo when injected into NB-bearing mice. Coupling of the corresponding targeting peptides with doxorubicin-loaded liposomes led to a significant inhibition in tumor volume and enhanced survival in preclinical NB models, thereby paving the way to their clinical development. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
Neutron-induced reaction cross-sections of 93Nb with fast neutron based on 9Be(p,n) reaction
NASA Astrophysics Data System (ADS)
Naik, H.; Kim, G. N.; Kim, K.; Zaman, M.; Nadeem, M.; Sahid, M.
2018-02-01
The cross-sections of the 93Nb (n , 2 n)92mNb, 93Nb (n , 3 n)91mNb and 93Nb (n , 4 n)90Nb reactions with the average neutron energies of 14.4 to 34.0 MeV have been determined by using an activation and off-line γ-ray spectrometric technique. The fast neutrons were produced using the 9Be (p , n) reaction with the proton energies of 25-, 35- and 45-MeV from the MC-50 Cyclotron at the Korea Institute of Radiological and Medical Sciences (KIRAMS). The neutron flux-weighted average cross-sections of the 93Nb(n , xn ; x = 2- 4) reactions were also obtained from the mono-energetic neutron-induced reaction cross-sections of 93Nb calculated using the TALYS 1.8 code, and the neutron flux spectrum based on the MCNPX 2.6.0 code. The present results for the 93Nb(n , xn ; x = 2- 4) reactions are compared with the calculated neutron flux-weighted average values and found to be in good agreement.
Tsutsumimoto, Takahiro; Williams, Paul; Yoneda, Toshiyuki
2014-01-01
Neuroblastoma (NB), which arises from embryonic neural crest cells, is the most common extra-cranial solid tumor of childhood. Approximately half of NB patients manifest bone metastasis accompanied with bone pain, fractures and bone marrow failure, leading to disturbed quality of life and poor survival. To study the mechanism of bone metastasis of NB, we established an animal model in which intracardiac inoculation of the SK-N-AS human NB cells in nude mice developed osteolytic bone metastases with increased osteoclastogenesis. SK-N-AS cells induced the expression of receptor activator of NF-κB ligand and osteoclastogenesis in mouse bone marrow cells in the co-culture. SK-N-AS cells expressed COX-2 mRNA and produced substantial amounts of prostaglandin E2 (PGE2). In contrast, the SK-N-DZ and SK-N-FI human NB cells failed to develop bone metastases, induce osteoclastogenesis, express COX-2 mRNA and produce PGE2. Immunohistochemical examination of SK-N-AS bone metastasis and subcutaneous tumor showed strong expression of COX-2. The selective COX-2 inhibitor NS-398 inhibited PGE2 production and suppressed bone metastases with reduced osteoclastogenesis. NS-398 also inhibited subcutaneous SK-N-AS tumor development with decreased angiogenesis and vascular endothelial growth factor-A expression. Of interest, metastasis to the adrenal gland, a preferential site for NB development, was also diminished by NS-398. Our results suggest that COX2/PGE2 axis plays a critical role in the pathophysiology of osteolytic bone metastases and tumor development of the SK-NS-AS human NB. Inhibition of angiogenesis by suppressing COX-2/PGE2 may be an effective therapeutic approach for children with NB. PMID:26909300
Heidrich, Katharina; Wirthmueller, Lennart; Tasset, Céline; Pouzet, Cécile; Deslandes, Laurent; Parker, Jane E
2011-12-09
Pathogen effectors are intercepted by plant intracellular nucleotide binding-leucine-rich repeat (NB-LRR) receptors. However, processes linking receptor activation to downstream defenses remain obscure. Nucleo-cytoplasmic basal resistance regulator EDS1 (ENHANCED DISEASE SUSCEPTIBILITY1) is indispensible for immunity mediated by TIR (Toll-interleukin-1 receptor)-NB-LRR receptors. We show that Arabidopsis EDS1 molecularly connects TIR-NB-LRR disease resistance protein RPS4 recognition of bacterial effector AvrRps4 to defense pathways. RPS4-EDS1 and AvrRps4-EDS1 complexes are detected inside nuclei of living tobacco cells after transient coexpression and in Arabidopsis soluble leaf extracts after resistance activation. Forced AvrRps4 localization to the host cytoplasm or nucleus reveals cell compartment-specific RPS4-EDS1 defense branches. Although nuclear processes restrict bacterial growth, programmed cell death and transcriptional resistance reinforcement require nucleo-cytoplasmic coordination. Thus, EDS1 behaves as an effector target and activated TIR-NB-LRR signal transducer for defenses across cell compartments.
MESTIERI, Leticia Boldrin; TANOMARU-FILHO, Mário; GOMES-CORNÉLIO, Ana Livia; SALLES, Loise Pedrosa; BERNARDI, Maria Inês Basso; GUERREIRO-TANOMARU, Juliane Maria
2014-01-01
Objective Mineral Trioxide Aggregate (MTA) is composed of Portland Cement (PC) and bismuth oxide (BO). Replacing BO for niobium oxide (NbO) microparticles (Nbµ) or nanoparticles (Nbη) may improve radiopacity and bioactivity. The aim of this study was to evaluate the radiopacity and cytotoxicity of the materials: 1) PC; 2) White MTA; 3) PC+30% Nbµ; 4) PC+30% Nbη. Material and Methods For the radiopacity test, specimens of the different materials were radiographed along an aluminum step-wedge. For cell culture assays, Saos-2 osteoblastic-cells (ATCC HTB-85) were used. Cell viability was evaluated through MTT assay, and bioactivity was assessed by alkaline phosphatase activity assay. Results The results demonstrated higher radiopacity for MTA, followed by Nbµ and Nbη, which had similar values. Cell culture analysis showed that PC and PC+NbO associations promoted greater cell viability than MTA. Conclusions It was concluded that the combination of PC+NbO is a potential alternative for composition of MTA. PMID:25591023
Mestieri, Leticia Boldrin; Tanomaru-Filho, Mário; Gomes-Cornélio, Ana Livia; Salles, Loise Pedrosa; Bernardi, Maria Inês Basso; Guerreiro-Tanomaru, Juliane Maria
2014-01-01
Mineral Trioxide Aggregate (MTA) is composed of Portland Cement (PC) and bismuth oxide (BO). Replacing BO for niobium oxide (NbO) microparticles (Nbµ) or nanoparticles (Nbη) may improve radiopacity and bioactivity. The aim of this study was to evaluate the radiopacity and cytotoxicity of the materials: (1) PC; (2) White MTA; (3) PC+30% Nbµ; (4) PC+30% Nbη. For the radiopacity test, specimens of the different materials were radiographed along an aluminum step-wedge. For cell culture assays, Saos-2 osteoblastic-cells (ATCC HTB-85) were used. Cell viability was evaluated through MTT assay, and bioactivity was assessed by alkaline phosphatase activity assay. The results demonstrated higher radiopacity for MTA, followed by Nbµ and Nbη, which had similar values. Cell culture analysis showed that PC and PC+NbO associations promoted greater cell viability than MTA. It was concluded that the combination of PC+NbO is a potential alternative for composition of MTA.
Conduction below 100 °C in nominal Li 6ZnNb 4O 14
Li, Yunchao; Paranthaman, Mariappan Parans; Gill, Lance W.; ...
2015-09-15
The increasing demand for a safe rechargeable battery with a high energy density per cell is driving a search for a novel solid electrolyte with a high Li + or Na + conductivity that is chemically stable in a working Li-ion or Na-ion battery. Li 6ZnNb 4O 14 has been reported to exhibit a σ Li > 10 -2 S cm -1 at 250 °C, but to disproportionate into multiple phases on cooling from 850 °C to room temperature. An investigation of the room-temperature Li-ion conductivity in a porous pellet of a multiphase product of a nominal Li 6ZnNb 4Omore » 14 composition is shown to have bulk σ Li 3.3 x 10 -5 S cm -1 at room temperature that increases to 1.4 x 10 -4 S cm -1 by 50 °C. 7Li MAS NMR spectra were fitted to two Lorentzian lines, one of which showed a dramatic increase with increasing temperature. As a result, a test for water stability indicates that Li + may move to the particle and grain surfaces to react with adsorbed water as occurs in the garnet Li + conductors.« less
Saeki, Norihisa; Saito, Akira; Sugaya, Yuki; Amemiya, Mitsuhiro; Ono, Hiroe; Komatsuzaki, Rie; Yanagihara, Kazuyoshi; Sasaki, Hiroki
2018-01-01
Overall survival for the high-risk group of neuroblastoma (NB) remains at 40-50%. An integrative genomics study revealed that LIM domain only 1 (LMO1) encoding a transcriptional regulator to be an NB-susceptibility gene with a tumor-promoting activity, that needs to be revealed. We conducted chromatin immunoprecipitation and DNA sequencing analyses and cell proliferation assays on two NB cell lines. We identified three genes regulated by LMO1 in the cells, LIM and senescent cell antigen-like domains 1 (LIMS1), Ras suppressor protein 1 (RSU1) and relaxin 2 (RLN2). LIMS1 and RSU1 encode proteins functioning with integrin-linked kinase (ILK), and inhibition of LIMS1, ILK or RLN2 by shRNA reduced cell proliferation of the NB cells, which was also suppressed with an ILK inhibiting compound Cpd 22. The downstream of LMO1-regulatory cascade includes a tumor-promoting LIMS1/ILK pathway, which has a potential to be a novel therapeutic target. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Liu, Xiaoming; Chen, Chen; Li, Shuailong; Dai, Yuhua; Guo, Huiqin; Tang, Xinghua; Xie, Yu; Yan, Liushui
2016-10-17
Up to now, GdNbO 4 has always been regarded as an essentially inert material in the visible region with excitation of UV light and electron beams. Nevertheless, here we demonstrate a new recreating blue emission of GdNbO 4 nanocrystalline phosphors with a quantum efficiency of 41.6% and host sensitized luminescence in GdNbO 4 :Ln 3+ (Ln 3+ = Eu 3+ /Tb 3+ /Tm 3+ ) nanocrystalline phosphors with abundant color in response to UV light and electron beams. The GdNbO 4 and GdNbO 4 :Ln 3+ (Ln 3+ = Eu 3+ /Tb 3+ /Tm 3+ ) nanocrystalline phosphors were synthesized by a Pechini-type sol-gel process. With excitation of UV light and low-voltage electron beams, the obtained GdNbO 4 nanocrystalline phosphor presents a strong blue luminescence from 280 to 650 nm centered around 440 nm, and the GdNbO 4 :Ln 3+ nanocrystalline phosphors show both host emission and respective emission lines derived from the characterize f-f transitions of the doping Eu 3+ , Tb 3+ , and Tm 3+ ions. The luminescence color of GdNbO 4 :Ln 3+ nanocrystalline phosphors can be tuned from blue to green, red, blue-green, orange, pinkish, white, etc. by varying the doping species, concentration, and relative ratio of the codoping rare earth ions in GdNbO 4 host lattice. A single-phase white-light-emission has been realized in Eu 3+ /Tb 3+ /Tm 3+ triply doped GdNbO 4 nanocrystalline phosphors. The luminescence properties and mechanisms of GdNbO 4 and GdNbO 4 :Ln 3+ (Ln 3+ = Eu 3+ /Tb 3+ /Tm 3+ ) are updated.
Nanobarcoding: detecting nanoparticles in biological samples using in situ polymerase chain reaction
Eustaquio, Trisha; Leary, James F
2012-01-01
Background Determination of the fate of nanoparticles (NPs) in a biological system, or NP biodistribution, is critical in evaluating an NP formulation for nanomedicine. Current methods to determine NP biodistribution are greatly inadequate, due to their limited detection thresholds. Herein, proof of concept of a novel method for improved NP detection based on in situ polymerase chain reaction (ISPCR), coined “nanobarcoding,” is demonstrated. Methods Nanobarcoded superparamagnetic iron oxide nanoparticles (NB-SPIONs) were characterized by dynamic light scattering, zeta potential, and hyperspectral imaging measurements. Cellular uptake of Cy5-labeled NB-SPIONs (Cy5-NB-SPIONs) was imaged by confocal microscopy. The feasibility of the nanobarcoding method was first validated by solution-phase PCR and “pseudo”-ISPCR before implementation in the model in vitro system of HeLa human cervical adenocarcinoma cells, a cell line commonly used for ISPCR-mediated detection of human papilloma virus (HPV). Results Dynamic light-scattering measurements showed that NB conjugation stabilized SPION size in different dispersion media compared to that of its precursor, carboxylated SPIONs (COOH-SPIONs), while the zeta potential became more positive after NB conjugation. Hyperspectral imaging confirmed NB conjugation and showed that the NB completely covered the SPION surface. Solution-phase PCR and pseudo-ISPCR showed that the expected amplicons were exclusively generated from the NB-SPIONs in a dose-dependent manner. Although confocal microscopy revealed minimal cellular uptake of Cy5-NB-SPIONs at 50 nM over 24 hours in individual cells, ISPCR detected definitive NB-SPION signals inside HeLa cells over large sample areas. Conclusion Proof of concept of the nanobarcoding method has been demonstrated in in vitro systems, but the technique needs further development before its widespread use as a standardized assay. PMID:23144562
PML-RARα stabilized by zinc in human acute promyelocytic leukemia NB4 cells.
Zhu, Bo; Wang, Jia-Yu; Zhou, Jun-Jie; Zhou, Feng; Cheng, Wei; Liu, Ying-Ting; Wang, Jie; Chen, Xiao; Chen, Dian-Hua; Luo, Lan; Hua, Zi-Chun
2017-10-01
Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene. Previous studies have highlighted the importance of PML-RARα degradation in the treatment against APL. Considering the presence of two zinc fingers in the PML-RARα fusion protein, we explored the function of zinc homeostasis in maintaining PML-RARα stability. We demonstrated for the first time that zinc depletion by its chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARα degradation in NB4 APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway. In contrast, autophagy protected TPEN-mediated PML-RARα degradation in NB4 APL cells. We further demonstrated that crosstalk between zinc homeostasis and nitric oxide pathway played a key role in maintaining PML-RARα stability in NB4 APL cells. These results demonstrate that zinc homeostasis is vital for maintaining PML-RARα stability, and zinc depletion by TPEN may be useful as a potential strategy to trigger PML-RARα degradation in APL cells. We also found that TPEN triggered apoptosis of NB4 APL cells in a time-dependent manner. The relationship between PML-RARα degradation and apoptosis triggered by TPEN deserves further study. Copyright © 2017 Elsevier Inc. All rights reserved.
Cimmino, Flora; Spano, Daniela; Capasso, Mario; Zambrano, Nicola; Russo, Roberta; Zollo, Massimo; Iolascon, Achille
2007-07-01
Neuroblastoma (NB) is an infant tumor which frequently differentiates into neurons. We used two-dimensional differential in-gel electrophoresis (2D-DIGE) to analyze the cytosolic and nuclear protein expression patterns of LAN-5 cells following neuronal differentiating agent all-trans-retinoic acid treatment. We identified several candidate proteins, from which G beta2 and Prefoldin 3 may have a role on NB development. These results strength the use of proteomics to discover new putative protein targets in cancer.
Extracellular redox state regulates features associated with prostate cancer cell invasion.
Chaiswing, Luksana; Zhong, Weixiong; Cullen, Joseph J; Oberley, Larry W; Oberley, Terry D
2008-07-15
We have examined the possible role of extracellular reduction-oxidation (redox) state in regulation of biological/biochemical features associated with prostate cancer cell invasion. DU145, PC-3, and RWPE1-derived human prostate cancer (WPE1-NB26) cell lines were used for the present in vitro analysis. Increasing levels of nitric oxide using S-nitroso-N-acetylpenicillamine resulted in a decrease in cell invasion ability, whereas increasing levels of extracellular superoxide radical (O(2)(*-)) using xanthine/xanthine oxidase resulted in an increase in cell invasion ability in these three cell lines. WPE1-NB26 cells exhibited an increased glutathione/glutathione disulfide ratio in the medium in comparison with RWPE1 cells (immortalized but nonmalignant prostate epithelial cells), suggesting an alteration of extracellular redox state of WPE1-NB26 cells. We hypothesized that O(2)(*-) production at or near the plasma membrane or in the adjacent extracellular matrix at least partially regulated prostate cancer cell invasion. Using adenovirus-mediated extracellular superoxide dismutase (EC-SOD) gene transduction to enzymatically decrease O(2)(*-) levels, we showed that in the presence of heparin, adenovirus EC-SOD gene transduction resulted in an increase in the expression of EC-SOD outside the cells with resultant inhibition of cell invasion ability. This inhibition correlated with reduced metalloproteinase [matrix metalloproteinase (MMP) 2/membrane type 1-MMP] activities and increased levels of extracellular nitrite. Our results suggest a prominent role of extracellular redox status in regulation of cell invasion, which may provide opportunities for therapeutic interventions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Su, Cunjin; Shi, Aiming; Cao, Guowen
2015-05-15
There are no appropriate drugs for metastatic neuroblastoma (NB), which is the most common extra-cranial solid tumor for childhood. Thioredoxin binding protein (TXNIP), the endogenous inhibitor of ROS elimination, has been identified as a tumor suppressor in various solid tumors. It reported that fenofibrate exerts anti-tumor effects in several human cancer cell lines. However, its detail mechanisms remain unclear. The present study assessed the effects of fenofibrate on NB cells and investigated TXNIP role in its anti-tumor mechanisms. We used MTT assay to detect cells proliferation, starch wound test to investigate cells migration, H{sub 2}DCF-DA to detect intracellular ROS, siRNAmore » to interfere TXNIP and peroxisome proliferator-androgen receptor-alpha (PPAR-α) expression, western blot to determine protein levels, flow cytometry to analyze apoptosis. Fenofibrate suppressed proliferation and migration of NB cells, remarkably increased intracellular ROS, upregulated TXNIP expression, promoted cell apoptosis. Furthermore, inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. Our results indicated the anti-tumor role of fenofibrate on NB cells by exacerbating oxidative stress and inducing apoptosis was dependent on the upregulation of TXNIP. - Highlights: • We found that fenofibrate suppressed proliferation and migration of NB cells. • We found that fenofibrate remarkably increased intracellular ROS, upregulated TXNIP expression, and promoted cell apoptosis. • Inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. • Our results indicated the anti-tumor role of fenofibrate on NB cells was dependent on the upregulation of TXNIP.« less
Pandey, Shashank K; Nookaraju, Akula; Fujino, Takeshi; Pattathil, Sivakumar; Joshi, Chandrashekhar P
2016-11-01
Functional characterization of two tobacco genes, one involved in xylan synthesis and the other, a positive regulator of secondary cell wall formation, is reported. Lignocellulosic secondary cell walls (SCW) provide essential plant materials for the production of second-generation bioethanol. Therefore, thorough understanding of the process of SCW formation in plants is beneficial for efficient bioethanol production. Recently, we provided the first proof-of-concept for using virus-induced gene silencing (VIGS) approach for rapid functional characterization of nine genes involved in cellulose, hemicellulose and lignin synthesis during SCW formation. Here, we report VIGS-mediated functional characterization of two tobacco genes involved in SCW formation. Stems of VIGS plants silenced for both selected genes showed increased amount of xylem formation but thinner cell walls than controls. These results were further confirmed by production of stable transgenic tobacco plants manipulated in expression of these genes. Stems of stable transgenic tobacco plants silenced for these two genes showed increased xylem proliferation with thinner walls, whereas transgenic tobacco plants overexpressing these two genes showed increased fiber cell wall thickness but no change in xylem proliferation. These two selected genes were later identified as possible members of DUF579 family involved in xylan synthesis and KNAT7 transcription factor family involved in positive regulation of SCW formation, respectively. Glycome analyses of cell walls showed increased polysaccharide extractability in 1 M KOH extracts of both VIGS-NbDUF579 and VIGS-NbKNAT7 lines suggestive of cell wall loosening. Also, VIGS-NbDUF579 and VIGS-NbKNAT7 lines showed increased saccharification rates (74.5 and 40 % higher than controls, respectively). All these properties are highly desirable for producing higher quantities of bioethanol from lignocellulosic materials of bioenergy plants.
Recent advances in nanostructured Nb-based oxides for electrochemical energy storage
NASA Astrophysics Data System (ADS)
Yan, Litao; Rui, Xianhong; Chen, Gen; Xu, Weichuan; Zou, Guifu; Luo, Hongmei
2016-04-01
For the past five years, nanostructured niobium-based oxides have emerged as one of the most prominent materials for batteries, supercapacitors, and fuel cell technologies, for instance, TiNb2O7 as an anode for lithium-ion batteries (LIBs), Nb2O5 as an electrode for supercapacitors (SCs), and niobium-based oxides as chemically stable electrochemical supports for fuel cells. Their high potential window can prevent the formation of lithium dendrites, and their rich redox chemistry (Nb5+/Nb4+, Nb4+/Nb3+) makes them very promising electrode materials. Their unique chemical stability under acid conditions is favorable for practical fuel-cell operation. In this review, we summarized recent progress made concerning the use of niobium-based oxides as electrodes for batteries (LIBs, sodium-ion batteries (SIBs), and vanadium redox flow batteries (VRBs)), SCs, and fuel cell applications. Moreover, crystal structures, charge storage mechanisms in different crystal structures, and electrochemical performances in terms of the specific capacitance/capacity, rate capability, and cycling stability of niobium-based oxides are discussed. Insights into the future research and development of niobium-based oxide compounds for next-generation electrochemical devices are also presented. We believe that this review will be beneficial for research scientists and graduate students who are searching for promising electrode materials for batteries, SCs, and fuel cells.
Recent advances in nanostructured Nb-based oxides for electrochemical energy storage.
Yan, Litao; Rui, Xianhong; Chen, Gen; Xu, Weichuan; Zou, Guifu; Luo, Hongmei
2016-04-28
For the past five years, nanostructured niobium-based oxides have emerged as one of the most prominent materials for batteries, supercapacitors, and fuel cell technologies, for instance, TiNb2O7 as an anode for lithium-ion batteries (LIBs), Nb2O5 as an electrode for supercapacitors (SCs), and niobium-based oxides as chemically stable electrochemical supports for fuel cells. Their high potential window can prevent the formation of lithium dendrites, and their rich redox chemistry (Nb(5+)/Nb(4+), Nb(4+)/Nb(3+)) makes them very promising electrode materials. Their unique chemical stability under acid conditions is favorable for practical fuel-cell operation. In this review, we summarized recent progress made concerning the use of niobium-based oxides as electrodes for batteries (LIBs, sodium-ion batteries (SIBs), and vanadium redox flow batteries (VRBs)), SCs, and fuel cell applications. Moreover, crystal structures, charge storage mechanisms in different crystal structures, and electrochemical performances in terms of the specific capacitance/capacity, rate capability, and cycling stability of niobium-based oxides are discussed. Insights into the future research and development of niobium-based oxide compounds for next-generation electrochemical devices are also presented. We believe that this review will be beneficial for research scientists and graduate students who are searching for promising electrode materials for batteries, SCs, and fuel cells.
HIGH-RESOLUTION FOURIER TRANSFORM SPECTROSCOPY OF Nb i IN THE NEAR-INFRARED
DOE Office of Scientific and Technical Information (OSTI.GOV)
Er, A.; Güzelçimen, F.; Başar, Gö.
In this study, a Fourier Transform spectrum of Niobium (Nb) is investigated in the near-infrared spectral range from 6000 to 12,000 cm{sup −1} (830–1660 nm). The Nb spectrum is produced using a hollow cathode discharge lamp in an argon atmosphere. Both Nb and Ar spectral lines are visible in the spectrum. A total of 110 spectral lines are assigned to the element Nb. Of these lines, 90 could be classified as transitions between known levels of atomic Nb. From these classified Nb i transitions, 27 have not been listed in literature previously. Additionally, 8 lines are classified for the firstmore » time.« less
68Ga-DOTATOC and FDG PET Imaging of Preclinical Neuroblastoma Models.
Provost, Claire; Prignon, Aurélie; Cazes, Alex; Combaret, Valérie; Delattre, Olivier; Janoueix-Lerosey, Isabelle; Montravers, Françoise; Talbot, Jean-Noël
2016-09-01
Somatostatine receptors subtype 2 (SSTR2) are regarded as a potential target in neuroblastoma (NB) for imaging and promising therapeutic approaches. The purpose of this study was to evaluate and compare the SSTR2 status by (68)Ga-[tetraxetan-D-Phe1, Tyr3]-octreotide ((68)Ga-DOTATOC) positron-emission tomography (PET) and the tumour metabolic activity by (18)F-fluorodeoxyglucose (FDG) PET in different experimental models of NB. Three cell lines of human NB with different levels of expression of SSTR2 were grafted into nude mice. Animals were imaged with FDG and (68)Ga-DOTATOC and the maximum standardized uptake value (SUVmax) was determined to quantify tracer uptake. Ex vivo biodistribution of (68)Ga-DOTATOC and immunohistochemical analysis of NB xenografts were performed. Compared with FDG, the SUVmax of (68)Ga-DOTATOC uptake by the tumour was lower but the ratio to background was higher; there was a strong positive correlation between SUVmax values observed with the two tracers (r(2)=0.65). Sorting the cell lines according to uptake of FDG or (68)Ga-DOTATOC, injected activity per gram of tissue, Ki67 index or expression of SSTR2 assessed visually led to the same classification. (68)Ga-DOTATOC allows preclinical imaging of NB according to the intensity of the expression of SSTR2. In contrast with what has been reported for neuroendocrine tumours, in this NB model, the (68)Ga-DOTATOC uptake was positively correlated with FDG uptake and with Ki67 index, usual markers of tumour aggressiveness. If confirmed in humans, this result would favour a theranostic application of (68)Ga-DOTATOC in NB, even in advanced stages. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
NASA Astrophysics Data System (ADS)
Miyajima, Shigeyuki; Shishido, Hiroaki; Narukami, Yoshito; Yoshioka, Naohito; Fujimaki, Akira; Hidaka, Mutsuo; Oikawa, Kenichi; Harada, Masahide; Oku, Takayuki; Arai, Masatoshi; Ishida, Takekazu
2017-01-01
We successfully derived the time-dependent flux of pulsed neutrons using a superconducting Nb-based current-biased kinetic inductance detector (CB-KID) with a 10B conversion layer at Japan Proton Accelerator Research Complex. Our CB-KID is a meander line made of a 40-nm-thick Nb thin film with 1 - μm line width, which is covered with a 150-nm-thick 10B conversion layer. The detector works at a temperature below 4 K. The evaluated detection efficiency of the CB-KID in this experiment is 0.23 % at the neutron energy of 25.4 meV. The time-dependent flux spectra of pulsed neutrons thus obtained are in good agreement with the results obtained by the Monte Carlo simulations.
NASA Astrophysics Data System (ADS)
Sidorov, N. V.; Teplyakova, N. A.; Palatnikov, M. N.; Bobreva, L. A.
2017-09-01
Crystals of LiNbO3congr and LiNbO3:Mg (0.19-5.91 mole %) were studied by IR and Raman spectroscopy. It was found that the intensities of the bands corresponding to the stretching vibrations of the OH groups in the IR spectra of LiNbO3:Mg crystals change and components of the bands disappear with increase of the Mg content. This was explained by disappearance of the OH groups close to {Nb}_{Li}^{4+}-{V}_{Li}- defects as a result of displacement of NbLi defects by Mg cations. In the Raman spectra of the LiNbO3:Mg (5.1 mole %) compared with the congruent crystal the lines corresponding to the vibrations of oxygen atoms in the oxygen octahedra and the stretching bridge vibrations of the oxygen atoms along the polar axis become broader, and new low-intensity lines that may correspond to pseudoscalar vibrations of A2-type symmetry also appear. The broadening of the lines is due to deformation of the oxygen octahedra caused both by increase of the Mg content in the crystal structure and by change in the localization of the protons. Suppression of the photorefraction effect in the LiNbO3:Mg crystals with Mg contents above the threshold level can be explained by change in the localization of the protons in the structure and by screening of the space charge field.
Bai, Guohua; Li, Ying; Chu, Henry K; Wang, Kaiqun; Tan, Qiulin; Xiong, Jijun; Sun, Dong
2017-04-04
Cytoskeleton is a highly dynamic network that helps to maintain the rigidity of a cell, and the mechanical properties of a cell are closely related to many cellular functions. This paper presents a new method to probe and characterize cell mechanical properties through dielectrophoresis (DEP)-based cell stretching manipulation and actin cytoskeleton modeling. Leukemia NB4 cells were used as cell line, and changes in their biological properties were examined after chemotherapy treatment with doxorubicin (DOX). DEP-integrated microfluidic chip was utilized as a low-cost and efficient tool to study the deformability of cells. DEP forces used in cell stretching were first evaluated through computer simulation, and the results were compared with modeling equations and with the results of optical stretching (OT) experiments. Structural parameters were then extracted by fitting the experimental data into the actin cytoskeleton model, and the underlying mechanical properties of the cells were subsequently characterized. The DEP forces generated under different voltage inputs were calculated and the results from different approaches demonstrate good approximations to the force estimation. Both DEP and OT stretching experiments confirmed that DOX-treated NB4 cells were stiffer than the untreated cells. The structural parameters extracted from the model and the confocal images indicated significant change in actin network after DOX treatment. The proposed DEP method combined with actin cytoskeleton modeling is a simple engineering tool to characterize the mechanical properties of cells.
NASA Astrophysics Data System (ADS)
Nayfeh, O. M.; Chao, D.; Djapic, N.; Sims, P.; Liu, B.; Sharma, S.; Lerum, L.; Fahem, M.; Dinh, V.; Zlatanovic, S.; Lynn, B.; Torres, C.; Higa, B.; Moore, J.; Upchurch, A.; Cothern, J.; Tukeman, M.; Barua, R.; Davidson, B.; Ramirez, A. D.; Rees, C. D.; Anant, V.; Kanter, G. S.
2017-08-01
Optically active rare-earth Neodymium (Nd) ions are integrated in Niobium (Nb) thin films forming a new quantum memory device (Nd:Nb) targeting long-lived coherence times and multi-functionality enabled by both spin and photon storage properties. Nb is implanted with Nd spanning 10-60 keV energy and 1013-1014 cm-2 dose producing a 1- 3% Nd:Nb concentration as confirmed by energy-dispersive X-ray spectroscopy. Scanning confocal photoluminescence (PL) at 785 nm excitation are made and sharp emission peaks from the 4F3/2 -< 4I11/2 Nd3+ transition at 1064-1070 nm are examined. In contrast, un-implanted Nb is void of any peaks. Line-shapes at room temperature are fit with Lorentzian profiles with line-widths of 4-5 nm and 1.3 THz bandwidth and the impacts of hyperfine splitting via the metallic crystal potential are apparent and the co-contribution of implant induced defects. With increasing Nd from 1% to 3%, there is a 0.3 nm red shift and increased broadening to a 4.8 nm linewidth. Nd:Nb is photoconductive and responds strongly to applied fields. Furthermore, optically detected magnetic resonance (ODMR) measurements are presented spanning near-infrared telecom band. The modulation of the emission intensity with magnetic field and microwave power by integration of these magnetic Kramer type Nd ions is quantified along with spin echoes under pulsed microwave π-π/2 excitation. A hybrid system architecture is proposed using spin and photon quantum information storage with the nuclear and electron states of the Nd3+ and neighboring Nb atoms that can couple qubit states to hyperfine 7/2 spin states of Nd:Nb and onto NIR optical levels excitable with entangled single photons, thus enabling implementation of computing and networking/internet protocols in a single platform.
NASA Astrophysics Data System (ADS)
Grey, I. E.; Vanderah, T. A.; Mumme, W. G.; Roth, R. S.; Guzman, J.; Nino, J. C.; Levin, I.
2008-03-01
The crystal structure of the phase previously reported to occur at 4:9 Bi 2O 3:Nb 2O 5 has been determined using single-crystal X-ray and powder neutron diffraction ( P6 3/ mmc; a=7.4363(1) Å, c=19.7587(5) Å; Z=2). The structural study combined with phase equilibrium analyses indicate that the actual composition is Bi 3.32Nb 7.09O 22.7. This binary compound is the end-member of a family of four phases which form along a line between it and the pyrochlore phase field in the Bi 2O 3:Fe 2O 3:Nb 2O 5 system. The structures are derived from the parent pyrochlore end-member by chemical twinning, and can also be described as unit-cell intergrowths of the pyrochlore and hexagonal tungsten bronze (HTB) structures. The dielectric properties of the three chemically twinned pyrochlore phases, Bi 3.32Nb 7.09O 22.7, Bi 9.3Fe 1.1Nb 16.9O 57.8 and Bi 5.67FeNb 10O 35, were characterized. All exhibit low-temperature, broad dielectric relaxation similar to that of the Bi-Fe-Nb-O pyrochlore. At 1 MHz and ≈175 K the observed relative permittivites were 345, 240, and 205, respectively, compared to 125 for the Bi-Fe-Nb-O pyrochlore. The higher relative permittivities observed for the chemically twinned pyrochlore derivatives are ascribed to the presence of HTB blocks in their structures: The Bi atoms located in the HTB blocks feature highly asymmetric coordination environments compared to pyrochlore, and the magnitude of the relative permittivity increases with the proportion of Bi located within the HTB portions of the structures.
Entezari, Maliheh; Dabaghian, Fataneh Hashem; Hashemi, Mehrdad
2014-01-01
Cancer is one of the main causes of mortality in the world which is created by the effect of enviromental physico-chemical mutagen and carcinogen agents. In the last years, many studies have been performed on the anticancer effects of flavonoids. Echinophora platyloba DC plant (Khousharizeh) is one of the indigenous medicinal plants which is used as a food seasoning and medicine in Iran. The extract was evaluated in terms of antimutagenicity properties by a standard reverse mutation assay (Ames Test). This was performed with histidine auxotroph strain of Salmonella typhimurium (TA100). Thus, it requires histidine from a foreign supply to ensure its growth. The afore mentioned strain gives rise to reverted colonies when expose to carcinogen substance (Sodium Azide). The other objective of this study was to examine the in vitro cytotoxic activity of cell death of crude methanolic extracts prepared from Echinophora platyloba on Acute Promyelocytic Leukemia cell line (NB4). Cytotoxicity and viability of methanolic extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. In Ames test the extract prevented the reverted mutations and the hindrance percent was 93.4% in antimutagenicity test. Data obtained from this assay indicated that the extract significantly reduced the viability of NB4 cells and inhibited cell growth in a dose dependent manner. This study demonstrates the antimutagenicity effect of Echinophora Platyloba and suggests that it has a potential as an anticancer agent.
Tian, Ruicheng; Chen, Jing; Gao, Hongxiang; Xie, Chenjie; Shan, Yuhua; Zhang, Zhen; Gu, Song; Xu, Min
2018-01-01
The proto-oncogene MYC can trigger the unfolded protein response (UPR). The double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK), one of three primary branches of the UPR, is a key regulator of autophagy, promoting tumorigenesis. Upon activation of PERK, there is an increase in phosphorylation of the eukaryotic initiation factor-2 alpha (eIF2α), which in turn, activates the transcription factor-4 (ATF4), responsible for an increased expression of LC3, a common autophagy marker. PERK is repressed upon GLI1 and GLI2 induction. GANT-61 is an inhibitor of GLI1 and GLI2, known to reduce autophagy in MYCN non-amplified, but not in MYCN amplified neuroblastoma (NB) cells. In our study, we tested the effect of the joint administration of a PERK inhibitor (GSK2606414) and the GLI inhibitor GANT-61 to MYCN amplified and MYCN non-amplified NB cells. Our results suggest that inhibition of PERK impairs GANT-61 induced autophagy in NB cells with MYCN amplification, but had no effect on the MYCN non-amplified NB cells. In summary, PERK seems to be a good therapeutic target for NB. Inhibition of PERK reduces autophagy in MYCN amplified NB cells, thus amplifying the efficacy of the GLI inhibitor GANT-61 in reducing proliferation of this type of cancer cells. PMID:29581853
Li, Liu; Song, Hao; Zhong, Liang; Yang, Rong; Yang, Xiao-Qun; Jiang, Kai-Ling; Liu, Bei-Zhong
2015-01-01
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). With the application of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), APL becomes one of best prognosis of leukemia. However, ATRA and ATO are not effective against all APLs. Therefore, a new strategy for APL treatment is necessary. Here, we investigated whether lithium chloride (LiCl), a drug used for the treatment of mental illness, could promote apoptosis in human leukemia NB4 cells. We observed that treatment with LiCl significantly accelerated apoptosis in NB4 cells and led to cell cycle arrest at G2/M phase. Moreover, LiCl significantly increased the level of Ser9-phosphorylated glycogen synthase kinase 3β(p-GSK-3β), and decreased the level of Akt1 protein in a dose-dependent manner. In addition, LiCl inhibition of c-Myc also enhanced cell death with a concomitant increase in β-catnin. Taken together, these findings demonstrated that LiCl promoted apoptosis in NB4 cells through the Akt signaling pathway and that G2/M phase arrest was induced by increase of p-GSK-3β(S9).
Löschmann, Nadine; Michaelis, Martin; Rothweiler, Florian; Zehner, Richard; Cinatl, Jaroslav; Voges, Yvonne; Sharifi, Mohsen; Riecken, Kristoffer; Meyer, Jochen; von Deimling, Andreas; Fichtner, Iduna; Ghafourian, Taravat; Westermann, Frank; Cinatl, Jindrich
2013-12-01
Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclin-dependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3(r)CDDP(1000) in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition-mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases.
Löschmann, Nadine; Michaelis, Martin; Rothweiler, Florian; Zehner, Richard; Cinatl, Jaroslav; Voges, Yvonne; Sharifi, Mohsen; Riecken, Kristoffer; Meyer, Jochen; von Deimling, Andreas; Fichtner, Iduna; Ghafourian, Taravat; Westermann, Frank; Cinatl, Jindrich
2013-01-01
Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclin-dependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3rCDDP1000 in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition-mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases. PMID:24466371
2018-01-01
We report the synthesis and characterization of four neutral organometallic tethered complexes, [Ru(η6-Ph(CH2)3-ethylenediamine-N-R)Cl], where R = methanesulfonyl (Ms, 1), toluenesulfonyl (Ts, 2), 4-trifluoromethylbenzenesulfonyl (Tf, 3), and 4-nitrobenzenesulfonyl (Nb, 4), including their X-ray crystal structures. These complexes exhibit moderate antiproliferative activity toward human ovarian, lung, hepatocellular, and breast cancer cell lines. Complex 2 in particular exhibits a low cross-resistance with cisplatin. The complexes show potent catalytic activity in the transfer hydrogenation of NAD+ to NADH with formate as hydride donor in aqueous solution (310 K, pH 7). Substituents on the chelated ligand decreased the turnover frequency in the order Nb > Tf > Ts > Ms. An enhancement of antiproliferative activity (up to 22%) was observed on coadministration with nontoxic concentrations of sodium formate (0.5–2 mM). Complex 2 binds to nucleobase guanine (9-EtG), but DNA appears not to be the target, as little binding to calf thymus DNA or bacterial plasmid DNA was observed. In addition, complex 2 reacts rapidly with glutathione (GSH), which might hamper transfer hydrogenation reactions in cells. Complex 2 induced a dose-dependent G1 cell cycle arrest after 24 h exposure in A2780 human ovarian cancer cells while promoting an increase in reactive oxygen species (ROS), which is likely to contribute to its antiproliferative activity.
Retinoic acid-induced CHD5 upregulation and neuronal differentiation of neuroblastoma.
Higashi, Mayumi; Kolla, Venkatadri; Iyer, Radhika; Naraparaju, Koumudi; Zhuang, Tiangang; Kolla, Sriharsha; Brodeur, Garrett M
2015-08-07
Chromodomain-helicase DNA binding protein 5 (CHD5) is an important tumor suppressor gene deleted from 1p36.31 in neuroblastomas (NBs). High CHD5 expression is associated with a favorable prognosis, but deletion or low expression is frequent in high-risk tumors. We explored the role of CHD5 expression in the neuronal differentiation of NB cell lines. NB cell lines SH-SY5Y (SY5Y), NGP, SK-N-DZ, IMR5, LAN5, SK-N-FI, NB69 and SH-EP were treated with 1-10 μM 13-cis-retinoic acid (13cRA) for 3-12 days. qRT-PCR and Western blot analyses were performed to measure mRNA and protein expression levels, respectively. Morphological differences were examined by both phase contrast and immunofluorescence studies. Treatment of SY5Y cells with 13cRA caused upregulation of CHD5 expression in a time- and dose-dependent manner (1, 5, or 10 μM for 7 or 12 days) and also induced neuronal differentiation. Furthermore, both NGP and SK-N-DZ cells showed CHD5 upregulation and neuronal differentiation after 13cRA treatment. In contrast, 13cRA treatment of IMR5, LAN5, or SK-N-FI induced neither CHD5 expression nor neuronal differentiation. NB69 cells showed two different morphologies (neuronal and substrate adherent) after 12 days treatment with 10 μM of 13cRA. CHD5 expression was high in the neuronal cells, but low/absent in the flat, substrate adherent cells. Finally, NGF treatment caused upregulation of CHD5 expression and neuronal differentiation in SY5Y cells transfected to express TrkA (SY5Y-TrkA) but not in TrkA-null parental SY5Y cells, and both changes were blocked by a pan-TRK inhibitor. Treatment with 13cRA induces neuronal differentiation only in NB cells that upregulate CHD5. In addition, NGF induced CHD5 upregulation and neuronal differentiation only in TrkA expressing cells. Together, these results suggest that CHD5 is downstream of TrkA, and CHD5 expression may be crucial for neuronal differentiation induced by either 13cRA or TrkA/NGF signaling.
Cytostatic response of NB69 cells to weak pulse-modulated 2.2 GHz radar-like signals.
Trillo, María A; Cid, María Antonia; Martínez, Maria Antonia; Page, Juan E; Esteban, Jaime; Úbeda, Alejandro
2011-07-01
The present study investigates the response of two human cancer cell lines to a 24-h treatment with a 2.2-GHz, pulse-modulated (5 µs pulse duration, 100 Hz repetition rate) radar-like signal at an average SAR = 0.023 W/kg, using a newly designed setup for in vitro exposure to radiofrequency (RF) fields. A complete discretized model of the setup was created for numerical dosimetry using finite-difference time-domain (FDTD) software, SEMCAD X. The average dose of RF radiation absorbed by the cultures was calculated to be subthermal (ΔT < 0.1 °C). The RF exposure induced a consistent, statistically significant reduction in the cell number (13.5% below controls, P < 0.001) in the neuroblastoma NB69 line. This effect was accompanied with slight but statistically significant increases in the proportions of cells in phases G0/G1 and G2/M of the cell cycle (6% and 9%, respectively; P < 0.05 over controls). By contrast, the hepatocarcinoma cell line HepG2 did not respond to the same RF treatment. These results indicate that a pulse-modulated RF radiation with high instantaneous amplitude and low average power can induce cytostatic responses on specific, sensitive cancer cell lines. The effect would be mediated, at least in part, by alterations in the kinetics of the cell cycle. Copyright © 2011 Wiley-Liss, Inc.
NASA Astrophysics Data System (ADS)
Gao, Sen-Pei; Qian, Yan-Nan; Wang, Biao
2015-08-01
Visible converted emissions produced at an excitation of 286 nm in ZnNb2O6 ceramics doped with rare-earth ions (RE = Eu3+, Tm3+, Er3+ or a combination of these ions) were investigated with the aim of increasing the photovoltaic efficiency of solar cells. The structure of RE:ZnNb2O6 ceramics was confirmed by x-ray diffraction patterns. The undoped ZnNb2O6 could emit a blue emission under 286-nm excitation, which is attributed to the self-trapped excitons’ recombination of the efficient luminescence centers of edge-shared NbO6 groups. Upon 286-nm excitation, Eu:ZnNb2O6, Tm:ZnNb2O6, and Er:ZnNb2O6 ceramics showed blue, green, and red emissions, which correspond to the transitions of 5D0 → 7FJ (J = 1-4) (Eu3+), 1G4 → 3H6 (Tm3+), and 2H11/2/4S3/2 → 4I15/2 (Er3+), respectively. The calculated CIE chromaticity coordinates of Eu:ZnNb2O6, Tm:ZnNb2O6, and Er:ZnNb2O6 are (0.50, 0.31), (0.14, 0.19), and (0.29, 0.56), respectively. RE ion-co-doped ZnNb2O6 showed a combination of characteristic emissions. The chromaticity coordinates of Eu/Tm:ZnNb2O6, Eu/Er:ZnNb2O6, and Tm/Er:ZnNb2O6 were calculated to be (0.29, 0.24), (0.45, 0.37), and (0.17, 0.25). Project supported by the National Natural Science Foundation of China (Grant Nos. 10572155 and 10732100) and the Research Fund for the Doctoral Program of Ministry of Education, China (Grant No. 20130171130003).
Ahn, Joon-Woo; Kim, Moonil; Lim, Jeong Hwa; Kim, Gyung-Tae; Pai, Hyun-Sook
2004-06-01
Calpain, a calcium-dependent cysteine protease, plays an essential role in basic cellular processes in animal cells, including cell proliferation, apoptosis, and differentiation. NbDEK encodes the calpain homolog of N. benthamiana. In this study, virus-induced gene silencing (VIGS) of NbDEK resulted in arrested organ development and hyperplasia in all the major plant organs examined. The epidermal layers of the leaves and stems were covered with hyperproliferating cell masses, and stomata and trichome development was severely inhibited. During flower development, a single dome-like structure was grown from the flower meristem to generate a large cylinder-shaped flower lacking any floral organs. At the cellular level, cell division was sustained in tissues that were otherwise already differentiated, and cell differentiation was severely hampered. NbDEK is ubiquitously expressed in all the plant tissues examined. In the abnormal organs of the NbDEK VIGS lines, protein levels of D-type cyclins (CycD)2, CycD3, and proliferating cell nuclear antigen (PCNA) were greatly elevated, and transcription of E2F (E2 promoter binding factor), E2F-regulated genes, retinoblastoma (Rb), and KNOTTED1 (KN1)-type homeobox genes was also stimulated. These results suggest that phytocalpain is a key regulator of cell proliferation and differentiation during plant organogenesis, and that it acts partly by controlling the CycD/Rb pathway.
NASA Astrophysics Data System (ADS)
Chiriac, Horia; Petreus, Tudor; Carasevici, Eugen; Labusca, Luminita; Herea, Dumitru-Daniel; Danceanu, Camelia; Lupu, Nicoleta
2015-04-01
The heating potential, cytotoxicity, and efficiency of Fe68.2Cr11.5Nb0.3B20 magnetic nanoparticles (MNPs), as such or coated with a chitosan layer, to decrease the cell viability in a cancer cell culture model by using high frequency alternating magnetic fields (AMF) have been studied. The specific absorption rate varied from 215 W/g for chitosan-free MNPs to about 190 W/g for chitosan-coated ones, and an equilibrium temperature of 46 °C was reached when chitosan-coated MNPs were subjected to AMF. The chitosan-free Fe68.2Cr11.5Nb0.3B20 MNPs proved a good biocompatibility and low cytotoxicity in all testing conditions, while the chitosan-coated ones induced strong tumoricidal effects when a cell-particle simultaneous co-incubation approach was used. In high frequency AMF, the particle-mediated heat treatment has proved to be a critical cause for decreasing in vitro the viability of a cancer cell line.
Combinatorial growth of oxide nanoscaffolds and its influence in osteoblast cell adhesion
NASA Astrophysics Data System (ADS)
Acevedo-Morantes, Claudia Y.; Irizarry-Ortiz, Roberto A.; Caceres-Valencia, Pablo G.; Singh, Surinder P.; Ramirez-Vick, Jaime E.
2012-05-01
We report a novel method for high-throughput investigations on cell-material interactions based on metal oxide nanoscaffolds. These scaffolds possess a continuous gradient of various titanium alloys allowing the compositional and morphological variation that could substantially improve the formation of an osseointegrative interface with bone. The model nanoscaffold has been fabricated on commercially pure titanium (cp-Ti) substrate with a compositional gradients of tin (Sn), chromium (Cr), and niobium (Nb) deposited using a combinatorial approach followed by annealing to create native oxide surface. As an invitro test system, the human fetal osteoblastic cell line (hFOB 1.19) has been used. Cell-adhesion of hFOB 1.19 cells and the suitability of these alloys have been evaluated for cell-morphology, cell-number, and protein adsorption. Although, cell-morphology was not affected by surface composition, cell-proliferation rates varied significantly with surface metal oxide composition; with the Sn- and Nb-rich regions showing the highest proliferation rate and the Cr-rich regions presenting the lowest. The results suggest that Sn and Nb rich regions on surface seems to promote hFOB 1.19 cell proliferation and may therefore be considered as implant material candidates that deserve further analysis.
De la Calle, J L; Mena, M A; González-Escalada, J R; Paíno, C L
2002-11-30
Intrathecal grafting of cells as biological pumps to deliver monoamines, endorphins, and/or trophic factors, has been shown to be effective in treating chronic pain both in experimental animals and in clinical trials. We have tested whether intrathecal implantation of neuroblastoma cells reduces heat hyperalgesia and cold allodynia in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Behavioral tests and cerebrospinal fluid (CSF) collection were performed before CCI, 1 week later (after which, vehicle or NB69 cells were intrathecally injected) and at 4, 7, and 14 days post-injection. Both CSF sampling and injection of the cells were performed by direct lumbar puncture. Intrathecal grafting of 4 x 10(6) NB69 neuroblastoma cells reduced to basal levels the nociceptive response to heat in nerve-injured hindpaws, while the response of control limbs remained unchanged. Similarly, the allodynic response to cold elicited by acetone evaporation decreased in the animals implanted with NB69 cells. An increase in the concentrations of dopamine and serotonin metabolites of around 150% was observed in the CSF of animals that received grafts of NB69 cells. These data suggest that the monoamines released by NB69 cells in the intrathecal space produce analgesia to neuropathic pain in rats. Copyright 2002 Elsevier Science Inc.
B-site cation order/disorder and their valence states in Ba3MnNb2O9 perovskite oxide
NASA Astrophysics Data System (ADS)
Xin, Yan; Huang, Qing; Shafieizadeh, Zahra; Zhou, Haidong
2018-06-01
Polycrystalline samples Ba3MnNb2O9 synthesized by solid state reaction and single crystal samples grown by optical floating zone have been characterized using scanning transmission electron microscopy and electron energy loss spectroscopy. Three types of B-site Mn and Nb ordering phase are observed: fully ordered 1Mn:2Nb; fully disordered; nano-sized 1Mn:1Nb ordered. No electronic structure change for crystals with different ordering/disordering. The Mn valence is determined to be 2+, and Nb valence is 5+. Oxygen 2p orbitals hybridize with Mn 3d and Nb 4d orbitals. Factors that affect the electron energy loss near edge structures of transition metal white-lines in electron energy loss spectroscopy are explicitly illustrated and discussed.
Growth and photo-response of NbSe2 and NbS2 crystals
NASA Astrophysics Data System (ADS)
Patel, Kunjal; Solanki, G. K.; Pataniya, Pratik; Patel, K. D.
2018-05-01
Transition metal dichalcogenides(TMDCs) have attracted intense research efforts due to their drastic properties change as we move towards ultra-thin crystalline layers from their bulk counterparts. Many well studied members of this family such as MoS2, WS2, WSe2, WS2 etc. have shown potential for flexible electronic devices including photovoltaic applications. The TMDCs like NbSe2 and NbS2 are relatively less studied layered compounds consisting of staked sandwiches of Se-Nb-Se/S-Nb-Se tri-layers with strong covalent/ionic intra layer bonds and weak Van der Waals interlayer interactions. In the present work, author have grown the crystals of NbSe2 and NbS2 by Direct Vapour Transport (DVT) technique and the material composition is confirmed using EDAX data. Photoelectrochemical (PEC) solar cell measurements are performed under monochromatic light illumination at different intensities and various solar cell parameters are calculated. These crystalline semiconductor electrodes were also analysed by photocurrent-voltage characteristics in a PEC solar cell structure (Cu/NbSe2/(0.1M K4Fe(CN)6 + 0.1M K3Fe(CN)6) and Cu/NbS2/(0.1M K4Fe(CN)6 +0.1M K3Fe(CN)6)). Blue coloured light gave the maximum efficiency. For further analysis of photodetection properties of the grown crystals, Ag painted broad low contact resistance electrical contacts were drawn from the crystals and its transient photoresponse was studied to evaluate different detector parameters.
NASA Astrophysics Data System (ADS)
Fontaine, M.-L.; Larring, Y.; Haugsrud, R.; Norby, T.; Wiik, K.; Bredesen, R.
For breakthrough development in solid oxide fuel cells, novel cell architectures integrating better performing materials and cost-effective manufacturing processes with potential for mass production must be realised. The present work addresses this on the basis of the recent discovery of acceptor doped rare-earth ortho-niobate proton conductors and the development of a versatile fabrication process. La 0.995Sr 0.005NbO 4- δ/NiO anodes are produced by tape-casting and co-lamination of green layers. Their porosity is finely tuned by using a pyrolyzable pore former. La 0.995Sr 0.005NbO 4- δ electrolytes are spin-coated using ceramic-based suspensions. Fully dense electrolytes with thickness ranging from 9 μm to 26 μm are obtained after sintering in air at 1350 °C. The cathode layers are then screen-printed. To match thermal expansion and to avoid chemical reaction between the functional layers, special attention is paid to the design of cathode architectures. CaTi 0.9Fe 0.1O 3- δ, La 2NiO 4+ δ and La 4Ni 3O 10 mixed oxygen ion and electron conducting oxides are investigated as either monophase or La 0.995Sr 0.005NbO 4- δ-based composite electrodes. The latter gives the whole cell an innovative "semi-monolithic" concept, which can take advantage of the chemical and mechanical stability of La 0.995Sr 0.005NbO 4- δ, as well as of inherent material integration. Most promising cell architectures are finally selected based on thermo-mechanical and chemical compatibility of all functional layers.
Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma.
Pezzolo, Annalisa; Sementa, Angela Rita; Lerone, Margherita; Morini, Martina; Ognibene, Marzia; Defferrari, Raffaella; Mazzocco, Katia; Conte, Massimo; Gigliotti, Anna Rita; Garaventa, Alberto; Pistoia, Vito; Varesio, Luigi
2017-05-04
Neuroblastoma (NB) is a common and often lethal cancer of early childhood that accounts for 10% of pediatric cancer mortality. Incidence peaks in infancy and then rapidly declines, with less than 5% of cases diagnosed in children and adolescents ≥ 10 y. There is increasing evidence that NB has unique biology and an chronic disease course in older children and adolescents, but ultimately dismal survival. We describe a rare constitutional 3p26.3 terminal microdeletion which occurred in an adolescent with NB, with apparently normal phenotype without neurocognitive defects. We evaluated the association of expression of genes involved in the microdeletion with NB patient outcomes using R2 platform. We screened NB patient's tumor cells for CHL1 protein expression using immunofluorescence. Constitutional and tumor DNA were tested by array-comparative genomic hybridization and single nucleotide-polymorphism-array analyses. Peripheral blood mononuclear cells from the patient showed a 2.54 Mb sub-microscopic constitutional terminal 3p deletion that extended to band p26.3. The microdeletion 3p disrupted the CNTN4 gene and the neighboring CNTN6 and CHL1 genes were hemizygously deleted, each of these genes encode neuronal cell adhesion molecules. Low expression of CNTN6 and CNTN4 genes did not stratify NB patients, whereas low CHL1 expression characterized 417 NB patients having worse overall survival. CHL1 protein expression on tumor cells from the patient was weaker than positive control. This is the first report of a constitutional 3p26.3 deletion in a NB patient. Since larger deletions of 3p, indicative of the presence of one or more tumor suppressor genes in this region, occur frequently in neuroblastoma, our results pave the way to the identification of one putative NB suppressor genes mapping in 3p26.3.
HERNÁNDEZ-BULE, MARÍA LUISA; ROLDÁN, ERNESTO; MATILLA, JOAQUÍN; TRILLO, MARÍA ÁNGELES; ÚBEDA, ALEJANDRO
2012-01-01
Recently, a number of electric and electrothermal therapies have been applied to the treatment of specific cancer types. However, the cellular and molecular mechanisms involved in the response to such therapies have not been well characterized yet. Capacitive-resistive electric transfer (CRET) therapy uses electric currents at frequencies within the 0.45–0.6 MHz range to induce hyperthermia in target tissues. Preliminary trials in cancer patients have shown consistent signs that CRET could slow down growth of tumor tissues in brain gliomas, without inducing detectable damage in the surrounding healthy tissue. Previous studies by our group have shown that subthermal treatment with 0.57-MHz electric currents can induce a cytostatic, not cytotoxic response in HepG2 human hepatocarcinoma cells; such effect being mediated by cell cycle alterations. In contrast, the study of the response of NB69 human neuroblastoma cells to the same electric treatment revealed consistent indications of cytotoxic effects. The present study extends the knowledge on the response of NB69 cells to the subthermal stimulus, comparing it to that of primary cultures of human peripheral blood mononuclear cells (PBMC) exposed to the same treatment. The results showed no sensitivity of PBMC to the 0.57 MHz subthermal currents and confirmed that the treatment exerts a cytotoxic action in NB69 cells. The data also revealed a previously undetected cytostatic response of the neuroblastoma cell line. CRET currents affected NB69 cell proliferation by significantly reducing the fraction of cells in the phase G2/M of the cell cycle at 12 h of exposure. These data provide new information on the mechanisms of response to CRET therapy, and are consistent with a cytotoxic and/or cytostatic action of the electric treatment, which would affect human cells of tumor origin but not normal cells with a low proliferation rate. PMID:22843038
Hernández-Bule, María Luisa; Roldán, Ernesto; Matilla, Joaquín; Trillo, María Angeles; Ubeda, Alejandro
2012-10-01
Recently, a number of electric and electrothermal therapies have been applied to the treatment of specific cancer types. However, the cellular and molecular mechanisms involved in the response to such therapies have not been well characterized yet. Capacitive-resistive electric transfer (CRET) therapy uses electric currents at frequencies within the 0.45-0.6 MHz range to induce hyperthermia in target tissues. Preliminary trials in cancer patients have shown consistent signs that CRET could slow down growth of tumor tissues in brain gliomas, without inducing detectable damage in the surrounding healthy tissue. Previous studies by our group have shown that subthermal treatment with 0.57-MHz electric currents can induce a cytostatic, not cytotoxic response in HepG2 human hepatocarcinoma cells; such effect being mediated by cell cycle alterations. In contrast, the study of the response of NB69 human neuroblastoma cells to the same electric treatment revealed consistent indications of cytotoxic effects. The present study extends the knowledge on the response of NB69 cells to the subthermal stimulus, comparing it to that of primary cultures of human peripheral blood mononuclear cells (PBMC) exposed to the same treatment. The results showed no sensitivity of PBMC to the 0.57 MHz subthermal currents and confirmed that the treatment exerts a cytotoxic action in NB69 cells. The data also revealed a previously undetected cytostatic response of the neuroblastoma cell line. CRET currents affected NB69 cell proliferation by significantly reducing the fraction of cells in the phase G2/M of the cell cycle at 12 h of exposure. These data provide new information on the mechanisms of response to CRET therapy, and are consistent with a cytotoxic and/or cytostatic action of the electric treatment, which would affect human cells of tumor origin but not normal cells with a low proliferation rate.
Shashoua, V E; Nolan, P M; Shea, T B; Milinazzo, B
1992-06-01
Northern blot, immunoprecipitation, and gel electrophoretic data demonstrate that the mouse neuroblastoma NB2a/d1 cells express ependymin mRNA and synthesize and release into the culture medium a protein with immunoreactivity and electrophoretic mobility properties identical to ependymin. This is a brain extracellular glycoprotein that has been implicated in the consolidation process of memory formation and neuronal regeneration. In labeling experiments with 35S-methionine, dibutyrylcyclic3',5'-adenosine-monophosphate (dbcAMP) was found to stimulate the expression of ependymin mRNA and the enhanced synthesis and release of ependymin into the culture medium at the same time that dbcAMP stimulation of neurite outgrowth takes place. These results are consistent with the proposed role of the protein in the mechanism of neuronal regeneration and synaptogenesis. The data indicate that the NB2a/d1 cell line is a good model system for studies of the functional properties of ependymin.
Yao, Chih-Jung; Yang, Chia-Ming; Chuang, Shuang-En; Yan, Jiann-Long; Liu, Chun-Yen; Chen, Suz-Wen; Yan, Kun-Huang; Lai, Tung-Yuan; Lai, Gi-Ming
2011-01-01
Tien-Hsien Liquid (THL) is a Chinese herbal mixture that has been used worldwide as complementary treatment for cancer patients in the past decade. Recently, THL has been shown to induce apoptosis in various types of solid tumor cells in vitro. However, the underlying molecular mechanisms have not yet been well elucidated. In this study, we explored the effects of THL on acute promyelocytic leukemia (APL) NB4 cells, which could be effectively treated by some traditional Chinese remedies containing arsenic trioxide. The results showed THL could induce G2/M arrest and apoptosis in NB4 cells. Accordingly, the decrease of cyclin A and B1 were observed in THL-treated cells. The THL-induced apoptosis was accompanied with caspase-3 activation and decrease of PML-RARα fusion protein. Moreover, DNA methyltransferase 1 and oncogenic signaling pathways such as Akt/mTOR, Stat3 and ERK were also down-regulated by THL. By using ethyl acetate extraction and silica gel chromatography, an active fraction of THL named as EAS5 was isolated. At about 0.5–1% of the dose of THL, EAS5 appeared to have most of THL-induced multiple molecular targeting effects in NB4 cells. Based on the findings of these multi-targeting effects, THL might be regarding as a complementary and alternative therapeutic agent for refractory APL. PMID:19897545
Leukemia cells demonstrate a different metabolic perturbation provoked by 2-deoxyglucose.
Miwa, Hiroshi; Shikami, Masato; Goto, Mineaki; Mizuno, Shohei; Takahashi, Miyuki; Tsunekawa-Imai, Norikazu; Ishikawa, Takamasa; Mizutani, Motonori; Horio, Tomohiro; Gotou, Mayuko; Yamamoto, Hidesuke; Wakabayashi, Motohiro; Watarai, Masaya; Hanamura, Ichiro; Imamura, Akira; Mihara, Hidetsugu; Nitta, Masakazu
2013-05-01
The shift in energy metabolism from oxidative phosphorylation to glycolysis can serve as a target for the inhibition of cancer growth. Here, we examined the metabolic changes induced by 2-deoxyglucose (2-DG), a glycolysis inhibitor, in leukemia cells by metabolome analysis. NB4 cells mainly utilized glucose as an energy source by glycolysis and oxidative phosphorylation in mitochondria, since metabolites in the glycolytic pathway and in the tricarboxylic acid (TCA) cycle were significantly decreased by 2-DG. In THP-1 cells, metabolites in the TCA cycle were not decreased to the same extent by 2-DG as in NB4 cells, which indicates that THP-1 utilizes energy sources other than glucose. TCA cycle metabolites in THP-1 cells may be derived from acetyl-CoA by fatty acid β-oxidation, which was supported by abundant detection of carnitine and acetylcarnitine in THP-1 cells. 2-DG treatment increased the levels of pentose phosphate pathway (PPP) metabolites and augmented the generation of NADPH by glucose-6-phosphate dehydrogenase. An increase in NADPH and upregulation of glutathione synthetase expression resulted in the increase in the reduced form of glutathione by 2-DG in NB4 cells. We demonstrated that a combination of 2-DG and inhibition of PPP by dehydroepiandrosterone (DHEA) effectively suppressed the growth of NB4 cells. The replenishment of the TCA cycle by fatty acid oxidation by carnitine palmitoyltransferase in THP-1 cells, treated by 2-DG, might be regulated by AMPK, as the combination of 2-DG and inhibition of AMPK by compound C potently suppressed the growth of THP-1 cells. Although 2-DG has been effective in preclinical and clinical studies, this treatment has not been fully explored due to concerns related to potential toxicities such as brain toxicity at high doses. We demonstrated that a combination of 2-DG and DHEA or compound C at a relatively low concentration effectively inhibits the growth of NB4 and THP-1 cells, respectively. These observations may aid in the identification of appropriate combinations of metabolic inhibitors at low concentrations which do not cause toxicities.
Vines, Douglass C.; Scollard, Deborah A.; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Besanger, Travis
2017-01-01
Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131I-MIBG therapy, low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177Lu-DOTA-TATE therapy. PMID:29097943
Zhang, Libo; Vines, Douglass C; Scollard, Deborah A; McKee, Trevor; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Vali, Reza; Shammas, Amer; Besanger, Travis; Baruchel, Sylvain
2017-01-01
Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68 Ga-DOTA-TATE uptake and 177 Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68 Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68 Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177 Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro , NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131 I-MIBG therapy, low 123 I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68 Ga-DOTA-TATE uptake and antitumor efficacy of 177 Lu-DOTA-TATE. 68 Ga-DOTA-TATE PET is superior to 123 I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177 Lu-DOTA-TATE therapy.
Differentiation and Characterization of Myeloid Cells
Gupta, Dipti; Shah, Hetavi Parag; Malu, Krishnakumar; Berliner, Nancy; Gaines, Peter
2015-01-01
Recent molecular studies of myeloid differentiation have utilized several in vitro models of myelopoiesis, generated from either ex vivo differentiated bone marrow progenitors or induced immortalized myeloid cell lines. Ex vivo differentiation begins with an enriched population of bone marrow-derived hematopoietic stem cells generated by lineage depletion and/or positive selection for CD34+ antigen (human) or Sca-1+ (mouse) cells, which are then expanded and subsequently induced in vitro in a process that recapitulates normal myeloid development. Myeloid cell lines include two human leukemic cell lines, NB-4 and HL-60, which have been demonstrated to undergo retinoic acid–induced myeloid development, however, both cell lines exhibit defects in the upregulation of late-expressed neutrophil-specific genes. Multiple murine factor–dependent cell models of myelopoiesis are also available that express the full range of neutrophil maturation markers, including: 32Dcl3 cells, which undergo G-CSF-induced myeloid maturation, EML/EPRO cells, which develop into mature neutrophils in response to cytokines and retinoic acid, and ER-Hoxb8 cells, which undergo myeloid maturation upon removal of estradial in the maintenance medium. In this unit, the induction of myeloid maturation in each of these model systems is described, including their differentiation to either neutrophils or macrophages, if applicable. Commonly used techniques to test for myeloid characteristics of developing cells are also described, including flow cytometry and real time RT-PCR. Together, these assays provide a solid foundation for in vitro investigations of myeloid development with either human or mouse models. PMID:24510620
Morphology based scoring of chromosomal instability and its correlation with cell viability.
Yadav, Shubhlata; Bhatia, Alka
2017-09-01
The aim of this study was to devise the quantitative scoring system for Chromosomal instability (CIN) based on morphological indicators like MPM, NB, NPB, CS, La and MN in cancer cell line and to correlate it with cell viability and death. Human hepatocellular carcinoma (HepG2) cells were treated with drugs like Diethylstilbestrol 0-100μM, Griseofulvin 0-40μg/ml, Vincristine sulphate 0-25μg/ml, Mitomycin C 0-600ng/ml, Bleomycin 0-10μg/ml, Doxorubicin 0-30μg/ml for 24h. Following this, the CIN was assessed by counting the morphological indicators like Micronuclei (MN), Nuclear Buds (NB), Nucleoplasmic bridges, Laggards, Multipolar mitosis and chromatin strings/1000 cells in Giemsa stained smears by light microscopy and by determining the percentage of aneuploid cells by flow cytometry. The cell viability was assessed by MTT assay and percentage of apoptotic cells was determined by flow cytometry. The MN and NB were most frequently seen indicators and main determinants of morphological CIN. However, the morphological CIN score did not show any correlation with cell viability and apoptosis. Aneuploidy however was found to correlate positively with cell viability and NB score in our study (P-value <0.05). The study for the 1st time attempted to develop a scoring system for CIN based on morphological parameters. However, a no correlation was observed between the later and cell viability or apoptosis. More robust techniques to quantify CIN may perhaps be more helpful in exploring the true link between CIN and cell viability in future. Copyright © 2017 Elsevier GmbH. All rights reserved.
Acousto-Optic Adaptive Processing (AOAP).
1983-12-01
2.03 mm 136 mm 41.6 mm Dense Flint Glass .58 1.06 48.6 21.7 LiNbO3 .65 2.24 250 46 1011 1 -: PbMoO4 .207 1.25 84.3 25.3 .- Slow Shear TeO2 .0586...mm 41.6 m Dense Flint Glass 5.9 1.06 3.2 21.7 LiNbO3 6.6 2.24 16.3 46 PbMoO4 2.1 1.25 5.5 25.6 TeO2 ’" ’" (slow,•...: Shear) 0.59 0.21 0.15 4.32 It is...was observed. 3.1.3 Delay Line The delay line used for the initial experiment is an Isomet Type 1201 AO modulator. This is a glass unit operat- ing at
Surface Chemistry of La0.99Sr0.01NbO4-d and Its Implication for Proton Conduction.
Li, Cheng; Pramana, Stevin S; Ni, Na; Kilner, John; Skinner, Stephen J
2017-09-06
Acceptor-doped LaNbO 4 is a promising electrolyte material for proton-conducting fuel cell (PCFC) applications. As charge transfer processes govern device performance, the outermost surface of acceptor-doped LaNbO 4 will play an important role in determining the overall cell performance. However, the surface composition is poorly characterized, and the understanding of its impact on the proton exchange process is rudimentary. In this work, the surface chemistry of 1 atom % Sr-doped LaNbO 4 (La 0.99 Sr 0.01 NbO 4-d , denoted as LSNO) proton conductor is characterized using LEIS and SIMS. The implication of a surface layer on proton transport is studied using the isotopic exchange technique. It has shown that a Sr-enriched but La-deficient surface layer of about 6-7 nm thick forms after annealing the sample under static air at 1000 °C for 10 h. The onset of segregation is found to be between 600 and 800 °C, and an equilibrium surface layer forms after 10 h annealing. A phase separation mechanism, due to the low solubility of Sr in LaNbO 4 , has been proposed to explain the observed segregation behavior. The surface layer was concluded to impede the water incorporation process, leading to a reduced isotopic fraction after the D 2 16 O wet exchange process, highlighting the impact of surface chemistry on the proton exchange process.
Matikainen, S; Ronni, T; Lehtonen, A; Sareneva, T; Melén, K; Nordling, S; Levy, D E; Julkunen, I
1997-06-01
IFNs are antiproliferative cytokines that have growth-inhibitory effects on various normal and malignant cells. Therefore, they have been used in the treatment of certain forms of cancer, such as chronic myelogenous leukemia and hairy cell leukemia. However, there is little evidence that IFNs would be effective in the treatment of acute myelogenous leukemia, and molecular mechanisms underlying IFN unresponsiveness have not been clarified. Here we have studied the activation and induction of IFN-specific transcription factors signal transducer and activator of transcription (STAT) 1, STAT2, and p48 in all-trans-retinoic acid (ATRA)-differentiated myeloid leukemia cells using promyelocytic NB4, myeloblastic HL-60, and monoblastic U937 cells as model systems. These cells respond to ATRA by growth inhibition and differentiation. We show that in undifferentiated NB4 cells, 2',5'-oligoadenylate synthetase and MxB gene expression is not activated by IFN-alpha, possibly due to a relative lack of signaling molecules, especially p48 protein. However, during ATRA-induced differentiation, steady-state STAT1, STAT2, and especially p48 mRNA and corresponding protein levels were elevated both in NB4 and U937 cells, apparently correlating to an enhanced responsiveness of these cells to IFNs. ATRA treatment of NB4 cells sensitized them to IFN action as seen by increased IFN-gamma activation site DNA-binding activity or by efficient formation of IFN-alpha-specific ISGF3 complex and subsequent oligoadenylate synthetase and MxB gene expression. Lack of p48 expression could be one of the mechanisms of promyelocytic leukemia cell escape from growth-inhibitory effects of IFN-alpha.
Ba0.06(Na,Bi)0.94Ti1-x(Ni1/3Nb2/3)xO3 ceramics: X-ray diffraction and infrared spectroscopy studies
NASA Astrophysics Data System (ADS)
Mishra, R. K.; Prasad, Ashutosh; Chandra, K. P.; Prasad, K.
2018-05-01
Non-lead ceramic samples of Ba0.06(Na0.5Bi0.5)0.94Ti1-x(Ni1/3Nb2/3)xO3; 0 ≤ x ≤ 1.0 were prepared by standard high temperature ceramic synthesis method. Rietveld refinements of X-ray diffraction data of these ceramics were carried out using FullProf software and determined their crystal symmetry, space group and unit cell dimensions. Rietveld refinement revealed that Ba0.06(Na0.5Bi0.5)0.94TiO3 has a monoclinic structure with space group P4/m while B0.06(Na0.5Bi0.5)0.94(Ni1/3Nb2/3)O3 has tetragonal (pseudo-cubic) structure with space group P4/mmm. Partial replacement of Ti4+ ion by pseudo-cation (Ni1/33 +Nb2/3 5 +) 4 + resulted in the change of unit cell structure from monoclinic to tetragonal. SEM studies were carried out in order to access the quality of the prepared ceramics which showed a change in grain sizes with the increase of (Ni1/33 +Nb2/3 5 +) 4 + content. FTIR spectra confirmed the formation of perovskite type solid solutions.
Selection of a novel CD19 aptamer for targeted delivery of doxorubicin to lymphoma cells.
Hu, Yan; Li, Xiaoou; An, Yacong; Duan, Jinhong; Yang, Xian-Da
2018-06-01
CD19 is overexpressed in most human B cell malignancies and considered an important tumor marker for diagnosis and treatment. Aptamers are oligonucleotides that may potentially serve as tumor-homing ligand for targeted cancer therapy with excellent affinity and specificity. In this study, we selected a novel CD19 aptamer (LC1) that was a 59-nucleotide single strand DNA. The aptamer could bind to recombinant CD19 protein with a K d of 85.4 nM, and had minimal cross reactivity to bovine serum albumin (BSA) or ovalbumin (OVA). Moreover, the aptamer was found capable of binding with the CD19-positive lymphoma cells (Ramos and Raji), but not the CD19-negative cell lines (Jurkat and NB4). An aptamer-doxorubicin complex (Apt-Dox) was also formulated, and selectively delivered doxorubicin to CD19-positive lymphoma cells in vitro . The results indicate that aptamer LC1 can recognize CD19-positive tumor cells and may potentially function as a CD19-targeting ligand.
Xu, Jeff S; Huang, Jiwei; Qin, Ruogu; Hinkle, George H; Povoski, Stephen P; Martin, Edward W; Xu, Ronald X
2010-03-01
Accurate assessment of tumor boundaries and recognition of occult disease are important oncologic principles in cancer surgeries. However, existing imaging modalities are not optimized for intraoperative cancer imaging applications. We developed a nanobubble (NB) contrast agent for cancer targeting and dual-mode imaging using optical and ultrasound (US) modalities. The contrast agent was fabricated by encapsulating the Texas Red dye in poly (lactic-co-glycolic acid) (PLGA) NBs and conjugating NBs with cancer-targeting ligands. Both one-step and three-step cancer-targeting strategies were tested on the LS174T human colon cancer cell line. For the one-step process, NBs were conjugated with the humanized HuCC49 Delta C(H)2 antibody to target the over-expressed TAG-72 antigen. For the three-step process, cancer cells were targeted by successive application of the biotinylated HuCC49 Delta C(H)2 antibody, streptavidin, and the biotinylated NBs. Both one-step and three-step processes successfully targeted the cancer cells with high binding affinity. NB-assisted dual-mode imaging was demonstrated on a gelatin phantom that embedded multiple tumor simulators at different NB concentrations. Simultaneous fluorescence and US images were acquired for these tumor simulators and linear correlations were observed between the fluorescence/US intensities and the NB concentrations. Our research demonstrated the technical feasibility of using the dual-mode NB contrast agent for cancer targeting and simultaneous fluorescence/US imaging. (c) 2009 Elsevier Ltd. All rights reserved.
Peng, Ying; Qi, Yicheng; Huang, Fengjiao; Chen, Xinxin; Zhou, Yulin; Ye, Lei; Wang, Weiqing; Ning, Guang; Wang, Shu
2016-11-29
Resistin, belongs to cysteine-rich secretory protein, is mainly produced by circulating leukocytes, such as neutrophils monocytes and macrophages in humans. To date, few but controversial studies have reported about resistin concentrations in hyperthyroid patients, especially in Graves' disease (GD). We undertaked a controlled, prospective study to explore the serum resistin concentration in GD patients before and after -MMI treatment. In addition, we also investigated the main influencing factor on serum resistin level and discuessed the potential role of serum resistin plays in GD patients. 39 untreated GD (uGD) patients, including 8 males and 31 females, were enrolled in our investigation. All of these patients were prescribed with MMI treatment, in addition to 25 healthy controls. Anthropometric parameters and hormone assessment were measured. Enzyme-linked immunosorbent assay was used to detect serum resistin concentration in different stages of GD patients. Furthermore, neutrophil cell line NB4 with or without T3 treatment to detect the effect of thyroid hormones on resistin expression. The serum resistin level and neutrophil counts in untreated GD patients were significantly declined. And all of these parameters were recovered to normal after MMI treatment in ethyroid GD (eGD) and TRAb-negative conversion (nGD) patients. Resistin concentration exhibited a negative correlation with FT3 and FT4, but a positive correlation with absolute number of neutrophiles in uGD patients, whereas did not correlate with thyroid autoimmune antibodies and BMI. Neutrophile cell line, NB4, produced decreased expression of resistin when stimulated with T3. Our study showed a decrease of serum resistin level in GD patients and we suggested that the serum resistin might primarily secreted from circulating neutrophils and down-regulated by excessive thyroid hormones in GD patients.
Foglietta, Federica; Serpe, Loredana; Canaparo, Roberto; Vivenza, Nicoletta; Riccio, Giovanna; Imbalzano, Erica; Gasco, Paolo; Zara, Gian Paolo
2014-01-01
Histone modification has emerged as a promising approach to cancer therapy. The short-chain fatty acid, butyric acid, a histone deacetylase (HD) inhibitor, has shown anticancer activity. Butyrate transcriptional activation is indeed able to withdraw cancer cells from the cell cycle, leading to programmed cell death. Since butyrate's clinical use is hampered by unfavorable pharmacokinetic and pharmacodynamic properties, delivery systems, such as solid lipid nanoparticles (SLN), have been developed to overcome these constraints. In order to outline the influence of butyrate delivery on its anticancer activity, the effects of butyrate as a free (sodium butyrate, NB) or nanoparticle (cholesteryl butyrate solid lipid nanoparticles, CBSLN) formulation on the growth of different human cancer cell lines, such as the promyelocytic leukemia, HL-60, and the breast cancer, MCF-7 was investigated. A detailed investigation into the mechanism of the induced cytotoxicity was also carried out, with a special focus on the modulation of HD and cyclin-dependent kinase (CDK) mRNA gene expression by real time PCR analysis. In HL-60 cells, CBSLN induced a higher and prolonged expression level of the butyrate target genes at lower concentrations than NB. This led to a significant decrease in cell proliferation, along with considerable apoptosis, cell cycle block in the G0/G1 phase, significant inhibition of total HD activity and overexpression of the p21 protein. Conversely, in MCF-7 cells, CBSLN did not enhance the level of expression of the butyrate target genes, leading to the same anticancer activity as that of NB. Solid lipid nanoparticles were able to improve butyrate anticancer activity in HL-60, but not in MCF-7 cells. This is consistent with difference in properties of the cells under study, such as expression of the TP53 tumor suppressor, or the transporter for short-chain fatty acids, SLC5A8.
Enhanced mutagenesis parallels enhanced reactivation of herpes virus in a human cell line.
Lytle, C D; Knott, D C
1982-01-01
U.v. irradiation of human NB-E cells results in enhanced mutagenesis and enhanced reactivation of u.v.-irradiated H-1 virus grown in those cells ( Cornelis et al., 1982). This paper reports a similar study using herpes simplex virus (HSV) in NB-E cells. The mutation frequency of HSV (resistance of virus plaque formation to 40 micrograms/ml iododeoxycytidine ) increased approximately linearly with exposure of the virus to u.v. radiation. HSV grown in unirradiated cells gave a slope of 1.8 X 10(-5)m2/J, with 3.2 X 10(-5)m2/J for HSV grown in cells irradiated (3 J/m2) 24 h before infection. There was no evidence for mutagenesis of unirradiated virus by irradiated cells, as seen with H-1 virus. Enhanced reactivation of irradiated HSV in parallel cultures increased virus survival, manifested as a change in slope of the final component of the two-component survival curve from a D0 of 27 J/m2 in unirradiated cells to 45 J/m2 in irradiated cells. Thus, enhanced mutagenesis and enhanced reactivation occurred for irradiated HSV in NB-E cells. The difference in the enhanced mutagenesis of HSV (dependent on damaged DNA sites) and of H-1 virus (primarily independent of damaged DNA sites) is discussed in terms of differences in DNA polymerases. PMID:6329698
Cafestol, a diterpene molecule found in coffee, induces leukemia cell death.
Lima, Cauê S; Spindola, Daniel G; Bechara, Alexandre; Garcia, Daniel M; Palmeira-Dos-Santos, Caroline; Peixoto-da-Silva, Janaina; Erustes, Adolfo G; Michelin, Luis F G; Pereira, Gustavo J S; Smaili, Soraya S; Paredes-Gamero, Edgar; Calgarotto, Andrana K; Oliveira, Carlos R; Bincoletto, Claudia
2017-08-01
To evaluate the antitumor properties of Cafestol four leukemia cell lines were used (NB4, K562, HL60 and KG1). Cafestol exhibited the highest cytotoxicity against HL60 and KG1 cells, as evidenced by the accumulation of cells in the sub-G1 fraction, mitochondrial membrane potential reduction, accumulation of cleaved caspase-3 and phosphatidylserine externalization. An increase in CD11b and CD15 differentiation markers with attenuated ROS generation was also observed in Cafestol-treated HL60 cells. These results were similar to those obtained following exposure of the same cell line to cytarabine (Ara-C), an antileukemic drug. Cafestol and Ara-C reduced the clonogenic potential of HL60 cells by 100%, but Cafestol spared murine colony forming unit- granulocyte/macrophage (CFU-GM), which retained their clonogenicity. The co-treatment of Cafestol and Ara-C reduced HL60 cell viability compared with both drugs administered alone. In conclusion, despite the distinct molecular mechanisms involved in the activity of Cafestol and Ara-C, a similar cytotoxicity towards leukemia cells was observed, which suggests a need for prophylactic-therapeutic pre-clinical studies regarding the anticancer properties of Cafestol. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
NASA Astrophysics Data System (ADS)
Zhang, Taihong; Yun, Sining; Li, Xue; Huang, Xinlei; Hou, Yuzhi; Liu, Yanfang; Li, Jing; Zhou, Xiao; Fang, Wen
2017-02-01
Transition metal compounds (TMCs), as a representative family of functional materials, have attracted great attention in the field of renewable energy. Herein, Nb3.49N4.56O0.44 and NbN are prepared from the nitridation of NbO2 in an NH3 atmosphere. These dual-functional Nb-based compounds were applied to dye-sensitized solar cells (DSSCs) and anaerobic digestion (AD), and the efficiency and stability of these DSSCs and AD systems were systematically evaluated. The Nb3.49N4.56O0.44 counter electrode (CE) exhibited considerable electrocatalytic activity and stability in I3- reduction in DSSCs, achieving photovoltaic performance comparable with Pt (6.36% vs. 7.19%). Furthermore, as accelerants, Nb-based compounds can greatly improve the AD environment, increasing substrate utilization and decreasing the hazards in the digestate. Compared with the control sample (409.2 mL/g·VS and 29.55%), substantially higher cumulative biogas production (437.1-522.7 mL/g·VS) and chemical oxygen demand removal rates (56.08%-65.19%) were achieved using Nb-based accelerants in the AD system. The nitridation technique is an effective and general means of converting Nb-based oxides into oxynitrides and nitrides. The Nb-based compounds with high electrocatalytic activities showed promise for DSSCs applications, while greatly enhancing the biodegradability of the AD system as accelerants. These findings could pave the way for multifunctional applications of TMCs in renewable energy fields.
XANES study of hydrogen incorporation in a Pd-capped Nb thin film
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ruckman, M.W.; Reisfeld, G.; Jisrawi, N.M.
X-ray absorption near-edge structure (XANES) measurements were used to probe the H-charging-induced electronic structure changes of a 2400 {Angstrom} Nb film capped with Pd. These results are discussed in terms of {ital ab initio} linear augmented plane-wave (LAPW) band-structure calculations for this material. The Pd-L{sub 3}-edge XANES clearly manifested the spectral (Pd-d state related) changes expected for Pd-hydride formation, a white line feature degradation, and the appearance of a Pd-H antibonding feature at 6 eV above the threshold. The Nb-L{sub 2,3} edge changes with H charging show a distinct enhancement of the white line strength; a feature 6 eV abovemore » the edges, associated with Nb-H antibonding states in analogy with the Pd results; the suppression of a threshold-onset feature of Nb metal; and a shift of the centrum of the white line feature towards the threshold. Comparison of the Nb sphere projection of the d{sub 3/2} component of the LAPW density of states (DOS) to the Nb-L{sub 2}-edge spectra yields good basic agreement with the observed spectral changes. In particular, the substantial theoretical reduction in the DOS at, and just above, the Fermi energy (E{sub f}) is directly related to the near threshold Nb-L{sub 2,3} spectral changes. The more modest white line enhancement in the theoretical DOS is noted and discussed. Nb-K-edge XANES are also discussed in terms of the Nb-site p-state projected LAPW DOS. This last comparison indicates a p-state reduction near E{sub f} upon H charging of the Nb. {copyright} {ital 1998} {ital The American Physical Society}« less
Morgan, Kevin; Stavrou, Emmanouil; Leighton, Samuel P; Miller, Nicola; Sellar, Robin; Millar, Robert P
2011-06-15
Human metastatic prostate cancer cell growth can be inhibited by GnRH analogs but effects on virus-immortalized prostate cells have not been investigated. Virus-immortalized prostate cells were stably transfected with rat GnRH receptor cDNA and levels of GnRH binding were correlated with GnRH effects on signaling, cell cycle, growth, exosome production, and apoptosis. High levels of cell surface GnRH receptor occurred in transfected papillomavirus-immortalized WPE-1-NB26 epithelial cells but not in non-tumourigenic RWPE-1, myoepithelial WPMY-1 cells, or SV40-immortalized PNT1A. Endogenous cell surface GnRH receptor was undetectable in non-transfected cells or cancer cell lines LNCaP, PC3, and DU145. GnRH receptor levels correlated with induction of inositol phosphates, elevation of intracellular Ca(2+) , cytoskeletal actin reorganization, modulation of ERK activation and cell growth-inhibition with GnRH agonists. Hoechst 33342 DNA staining-cell sorting indicated accumulation of cells in G2 following agonist treatment. Release of exosomes from transfected WPE-1-NB26 was unaffected by agonists, unlike induction observed in HEK293([SCL60]) cells. Increased PARP cleavage and apoptotic body production were undetectable during growth-inhibition in WPE-1-NB26 cells, contrasting with HEK293([SCL60]) . EGF receptor activation inhibited GnRH-induced ERK activation in WPE-1-NB26 but growth-inhibition was not rescued by EGF or PKC inhibitor Ro320432. Growth of cells expressing low levels of GnRH receptor was not affected by agonists. Engineered high-level GnRH receptor activation inhibits growth of a subset of papillomavirus-immortalized prostate cells. Elucidating mechanisms leading to clone-specific differences in cell surface GnRH receptor levels is a valuable next step in developing strategies to exploit prostate cell anti-proliferation using GnRH agonists. Copyright © 2010 Wiley-Liss, Inc.
Naaman, Hila; Rall, Glenn; Matullo, Christine; Veksler-Lublinsky, Isana; Shemer-Avni, Yonat; Gopas, Jacob
2017-01-01
Measles virus (MV) infects a variety of lymphoid and non-lymphoid peripheral organs. However, in rare cases, the virus can persistently infect cells within the central nervous system. Although some of the factors that allow MV to persist are known, the contribution of host cell-encoded microRNAs (miRNA) have not been described. MiRNAs are a class of noncoding RNAs transcribed from genomes of all multicellular organisms and some viruses, which regulate gene expression in a sequence-specific manner. We have studied the contribution of host cell-encoded miRNAs to the establishment of MV persistent infection in human neuroblastoma cells. Persistent MV infection was accompanied by differences in the expression profile and levels of several host cell-encoded microRNAs as compared to uninfected cells. MV persistence infection of a human neuroblastoma cell line (UKF-NB-MV), exhibit high miRNA-124 expression, and reduced expression of cyclin dependent kinase 6 (CDK6), a known target of miRNA-124, resulting in slower cell division but not cell death. By contrast, acute MV infection of UKF-NB cells did not result in increased miRNA-124 levels or CDK6 reduction. Ectopic overexpression of miRNA-124 affected cell viability only in UKF-NB-MV cells, causing cell death; implying that miRNA-124 over expression can sensitize cells to death only in the presence of MV persistent infection. To determine if miRNA-124 directly contributes to the establishment of MV persistence, UKF-NB cells overexpressing miRNA-124 were acutely infected, resulting in establishment of persistently infected colonies. We propose that miRNA-124 triggers a CDK6-dependent decrease in cell proliferation, which facilitates the establishment of MV persistence in neuroblastoma cells. To our knowledge, this is the first report to describe the role of a specific miRNA in MV persistence.
Vitamin K3 analogs induce selective tumor cytotoxicity in neuroblastoma.
Kitano, Toru; Yoda, Hiroyuki; Tabata, Keiichi; Miura, Motofumi; Toriyama, Masaharu; Motohashi, Shigeyasu; Suzuki, Takashi
2012-01-01
We investigated the cytotoxicity of eight vitamin K3 (VK3) analogs against neuroblastoma cell lines (IMR-32, LA-N-1, NB-39, and SK-N-SH) and normal cell lines (human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF)) using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. 2-[(2-Methoxy)ethylthio]-3-methyl-1,4-naphthoquinone (VK3-OCH(3)) showed especially potent cytotoxic activities against neuroblastoma cells compared with normal cells. In a Hoechst 33342 staining experiment, apoptotic morphologies characterized by cell shrinkage, nuclear condensation, and nuclear fragmentation were observed in IMR-32 and LA-N-1 cells after 48 h of treatment with 10(-5) M of VK3-OCH(3). To clarify the molecular mechanisms of apoptosis induced by VK3-OCH(3), we examined the expression of apoptosis related proteins using a Proteome Profiler Array and western blotting. Heme oxygenase (HO)-1 was remarkably increased by VK3-OCH(3) compared with the control (173% in IMR-32 and 170% in LA-N-1 at 24 h). Moreover, caveolin-1 was induced by VK3-OCH(3) at 48 h. In addition, VK3-OCH(3) arrested the cell cycle at the G2/M phase in IMR-32 cells. These results suggest that VK3-OCH(3) exhibited a selective antitumor activity via HO-1-related mechanisms.
Liu, Anthony P Y; Lee, Pamela P W; Kwok, Janette S Y; Leung, Rock Y Y; Chiang, Alan K S; Ha, Shau-Yin; Cheuk, Daniel K L; Chan, Godfrey C F
2018-06-19
Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft-versus-NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T-cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median age at haploHSCT=6.45 y, range: 3.49-11.02 y). Indications were relapsed in 7 and refractoriness in 3; disease status at haploHSCT was CR in 2, PR in 6, and PD in 2. All patients received peripheral blood stem cell grafts after ex vivo T-cell depletion (CD3/CD19-depletion=1; TCR-αβ/CD19-depletion=4; CD3/CD45RA-depletion=4; and TCR-αβ/CD45RA-depletion=1). Conditioning regimens were fludarabine-based. Neutrophils engrafted on median D + 10 (range: D + 9 to +13), and platelets engrafted (≥20 × 10 9 /L) on median D + 8 (range: D + 5 to D + 14). Early T- and NK-cell recovery were evident. Of the 10 patients, acute rejection developed in 1 (who died of PD despite rescue HSCT), and 1 died of sepsis before engraftment; 8 experienced full donor-chimerism post-HSCT. Among the 8, 6 experienced CR, 1 died of PD, and 1 died of pulmonary hypertensive crisis before evaluation. At publication, 4 were in remission (2.8, 7.4, 28.5, and 58.9 months). No significant GvHD occurred. HaploHSCT with selective ex vivo T-cell depletion may be a safe and useful salvage strategy for relapsed/refractory NB. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
NASA Astrophysics Data System (ADS)
Ding, Shoujun; Zhang, Haotian; Zhang, Qingli; Chen, Yuanzhi; Dou, Renqin; Peng, Fang; Liu, Wenpeng; Sun, Dunlu
2018-06-01
In this work, GdNbO4 polycrystalline with monoclinic phase was prepared by traditional high-temperature solid-state reaction. Its structure was determined by X-ray diffraction and its unit cell parameters were obtained with Rietveld refinement method. Its luminescence properties (including absorbance, emission and luminescence lifetime) were investigated with experiment method and the CIE chromaticity coordinate was presented. Furthermore, a systematic theoretical calculation (including band gap, density of states and optical properties) based on the density function theory methods was performed on GdNbO4. Lastly, a comparison between experiment and calculated results was conducted. The calculated and experiment results obtained in this work can provide an essential understanding of GdNbO4 material.
Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.
Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André
2015-11-01
Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging. Copyright © 2015 Elsevier Ltd. All rights reserved.
Katsivela, Eleftheria; Wray, Victor; Pieper, Dietmar H.; Wittich, Rolf-Michael
1999-01-01
Bacterial strain LW1, which belongs to the family Comamonadaceae, utilizes 1-chloro-4-nitrobenzene (1C4NB) as a sole source of carbon, nitrogen, and energy. Suspensions of 1C4NB-grown cells removed 1C4NB from culture fluids, and there was a concomitant release of ammonia and chloride. Under anaerobic conditions LW1 transformed 1C4NB into a product which was identified as 2-amino-5-chlorophenol by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. This transformation indicated that there was partial reduction of the nitro group to the hydroxylamino substituent, followed by Bamberger rearrangement. In the presence of oxygen but in the absence of NAD, fast transformation of 2-amino-5-chlorophenol into a transiently stable yellow product was observed with resting cells and cell extracts. This compound exhibited an absorption maximum at 395 nm and was further converted to a dead-end product with maxima at 226 and 272 nm. The compound formed was subsequently identified by 1H and 13C NMR spectroscopy and mass spectrometry as 5-chloropicolinic acid. In contrast, when NAD was added in the presence of oxygen, only minor amounts of 5-chloropicolinic acid were formed, and a new product, which exhibited an absorption maximum at 306 nm, accumulated. PMID:10103229
Computer-aided control of electrolysis of solid Nb2O5 in molten CaCl2.
Wu, Tian; Xiao, Wei; Jin, Xianbo; Liu, Chao; Wang, Dihua; Chen, George Z
2008-04-07
Low energy production of Nb powders via computer-aided control (CAC) of two-electrode electrolysis of porous Nb2O5 pellets (ca. 1.0 g) has been successfully demonstrated in molten CaCl2 at 1123 K. It was observed that potentiostatic electrolysis of the oxide in a three-electrode cell led to a cell voltage, i.e. the potential difference between the working (cathode) and counter (anode) electrodes, that decreased to a low and stable value within 1-2 h of the potential application until the end of the electrolysis (up to 12 h in this work). The cell voltage varied closely according to the current change. The stabilised cell voltage was below 2.5 V when the cathode potential was more positive than that for the reduction of Ca2+, leading to much lower energy consumption than that of constant voltage (>3.0 V) two-electrode electrolysis, as previously reported. Using a computer to program the variation of the cell voltage of two-electrode electrolysis according to that observed in the potentiostatic three-electrode electrolysis (0.05 V vs. Ca/Ca2+), a Nb powder with ca. 3900 ppm oxygen was produced in 12 h, with the energy consumption being 37.4% less than that of constant voltage two-electrode electrolysis at 3.0 V. Transmission electron microscopy revealed thin oxide layers (4-6 nm) on individual nodular particles (1-5 microm) of the obtained Nb powder. The oxide layer was likely formed in post-electrolysis processing operations, including washing in water, and contributed largely to the oxygen content in the obtained Nb powder.
Complex Lyα Profiles in Redshift 6.6 Ultraluminous Lyα Emitters
NASA Astrophysics Data System (ADS)
Songaila, A.; Hu, E. M.; Barger, A. J.; Cowie, L. L.; Hasinger, G.; Rosenwasser, B.; Waters, C.
2018-06-01
We report on a search for ultraluminous Lyα-emitting galaxies (LAEs) at z = 6.6 using the NB921 filter on the Hyper Suprime-Cam on the Subaru telescope. We searched a 30 deg2 area around the north ecliptic pole, which we observed in broadband g‧, r‧, i‧, z‧, and y‧ and narrowband NB816 and NB921, for sources with NB921 < 23.5 and z‧-NB921 > 1.3. This corresponds to a selection of log L(Lyα) > 43.5 erg s‑1. We followed up seven candidate LAEs (out of 13) with the Keck DEIMOS spectrograph and confirmed five z = 6.6 LAEs, one z = 6.6 AGN with a broad Lyα line and a strong red continuum, and one low-redshift ([O III] 5007) galaxy. The five ultraluminous LAEs have wider line profiles than lower-luminosity LAEs, and one source, NEPLA4, has a complex line profile similar to that of COLA1. In combination with previous results, we show that the line profiles of the z = 6.6 ultraluminous LAEs are systematically different from those of lower-luminosity LAEs at this redshift. This result suggests that ultraluminous LAEs generate highly ionized regions of the intergalactic medium in their vicinity that allow the full Lyα profile of the galaxy—including any blue wings—to be visible. If this interpretation is correct, then ultraluminous LAEs offer a unique opportunity to determine the properties of the ionized zones around them, which will help in understanding the ionization of the z ∼ 7 intergalactic medium. A simple calculation gives a very rough estimate of 0.015 for the escape fraction of ionizing photons, but more sophisticated calculations are needed to fully characterize the uncertainties.
Wirthmueller, Lennart; Zhang, Yan; Jones, Jonathan D G; Parker, Jane E
2007-12-04
Recognition of specific pathogen molecules inside the cell by nucleotide-binding domain and leucine-rich repeat (NB-LRR) receptors constitutes an important layer of innate immunity in plants. Receptor activation triggers host cellular reprogramming involving transcriptional potentiation of basal defenses and localized programmed cell death. The sites and modes of action of NB-LRR receptors are, however, poorly understood. Arabidopsis Toll/Interleukin-1 (TIR) type NB-LRR receptor RPS4 recognizes the bacterial type III effector AvrRps4. We show that epitope-tagged RPS4 expressed under its native regulatory sequences distributes between endomembranes and nuclei in healthy and AvrRps4-triggered tissues. RPS4 accumulation in the nucleus, mediated by a bipartite nuclear localization sequence (NLS) at its C terminus, is necessary for triggering immunity through authentic activation by AvrRps4 in Arabidopsis or as an effector-independent "deregulated" receptor in tobacco. A strikingly conserved feature of TIR-NB-LRR receptors is their recruitment of the nucleocytoplasmic basal-defense regulator EDS1 in resistance to diverse pathogens. We find that EDS1 is an indispensable component of RPS4 signaling and that it functions downstream of RPS4 activation but upstream of RPS4-mediated transcriptional reprogramming in the nucleus.
Swiderski, Michal R; Birker, Doris; Jones, Jonathan D G
2009-02-01
In plants, the TIR (toll interleukin 1 receptor) domain is found almost exclusively in nucleotide-binding (NB) leucine-rich repeat resistance proteins and their truncated homologs, and has been proposed to play a signaling role during resistance responses mediated by TIR containing R proteins. Transient expression in Nicotiana benthamiana leaves of "TIR + 80", the RPS4 truncation without the NB-ARC domain, leads to EDS1-, SGT1-, and HSP90-dependent cell death. Transgenic Arabidopsis plants expressing the RPS4 TIR+80 from either dexamethasone or estradiol-inducible promoters display inducer-dependent cell death. Cell death is also elicited by transient expression of similarly truncated constructs from two other R proteins, RPP1A and At4g19530, but is not elicited by similar constructs representing RPP2A and RPP2B proteins. Site-directed mutagenesis of the RPS4 TIR domain identified many loss-of-function mutations but also revealed several gain-of function substitutions. Lack of cell death induction by the E160A substitution suggests that amino acids outside of the TIR domain contribute to cell death signaling in addition to the TIR domain itself. This is consistent with previous observations that the TIR domain itself is insufficient to induce cell death upon transient expression.
Investigating free radical generation in HepG2 cells using immuno-spin trapping.
Horinouchi, Yuya; Summers, Fiona A; Ehrenshaft, Marilyn; Kawazoe, Kazuyoshi; Tsuchiya, Koichiro; Tamaki, Toshiaki; Mason, Ronald P
2014-10-01
Oxidative stress can induce the generation of free radicals, which are believed to play an important role in both physiological and pathological processes and a number of diseases such as cancer. Therefore, it is important to identify chemicals which are capable of inducing oxidative stress. In this study, we evaluated the ability of four environmental chemicals, aniline, nitrosobenzene (NB), N,N-dimethylaniline (DMA) and N,N-dimethyl-4-nitrosoaniline (DMNA), to induce free radicals and cellular damage in the hepatoma cell line HepG2. Cytotoxicity was assessed using lactate dehydrogenase (LDH) assays and morphological changes were observed using phase contrast microscopy. Free radicals were detected by immuno-spin trapping (IST) in in-cell western experiments or in confocal microscopy experiments to determine the subcellular localization of free radical generation. DMNA induced free radical generation, LDH release and morphological changes in HepG2 cells whereas aniline, NB and DMA did not. Confocal microscopy showed that DMNA induced free radical generation mainly in the cytosol. Preincubation of HepG2 cells with N-acetylcysteine and 2,2'-dipyridyl significantly prevented free radical generation upon subsequent incubation with DMNA, whereas preincubation with apocynin and dimethyl sulfoxide did not. These results suggest that DMNA induces oxidative stress and that reactive oxygen species, metals and free radical generation play a critical role in DMNA-induced cytotoxicity. Copyright © 2014. Published by Elsevier Inc.
Wt-p53 action in human leukaemia cell lines corresponding to different stages of differentiation.
Rizzo, M G; Zepparoni, A; Cristofanelli, B; Scardigli, R; Crescenzi, M; Blandino, G; Giuliacci, S; Ferrari, S; Soddu, S; Sacchi, A
1998-05-01
Recent studies support the potential application of the wt-p53 gene in cancer therapy. Expression of exogenous wt-p53 suppresses a variety of leukaemia phenotypes by acting on cell survival, proliferation and/or differentiation. As for tumour gene therapy, the final fate of the neoplastic cells is one of the most relevant points. We examined the effects of exogenous wt-p53 gene expression in several leukaemia cell lines to identify p53-responsive leukaemia. The temperature-sensitive p53Val135 mutant or the human wt-p53 cDNA was transduced in leukaemia cell lines representative of different acute leukaemia FAB subtypes, including M1 (KG1), M2 (HL-60), M3 (NB4), M5 (U937) and M6 (HEL 92.1.7), as well as blast crisis of chronic myelogenous leukaemia (BC-CML: K562, BV173) showing diverse differentiation features. By morphological, molecular and biochemical analyses, we have shown that exogenous wt-p53 gene expression induces apoptosis only in cells corresponding to M1, M2 and M3 of the FAB classification and in BC-CML showing morphological and cytochemical features of undifferentiated blast cells. In contrast, it promotes differentiation in the others. Interestingly, cell responsiveness was independent of the vector used and the status of the endogenous p53 gene.
NASA Astrophysics Data System (ADS)
Mårtensson, Nils; Nyholm, Ralf
1981-12-01
Photoelectron spectroscopy has been used to determine M and N core-level widths for the elements Nb-Te (Z=41-52). The analysis is based on direct comparisons of the lifetime contributions to different core levels. Absolute determinations are made for the narrow 3d levels. In the metals Nb-Rh (Z=41-45) an M4M5N45 Coster-Kronig decay channel is observed through a broadening of the 3d32 core-electron lines. The rate of this Coster-Kronig process is found to have its maximum for Ru and Rh. For Pd a much reduced, but still significant, broadening of the 3d32 level is detected. This observation is discussed in terms of itinerant versus quasiatomic contributions to the Coster-Kronig process. For Z>=47 (Ag) the Coster-Kronig channel is closed. For Nb-Rh the M4M5N45 process can be used for absolute determinations of the 3d linewidths. In this connection also the properties of the M45N45N45 Auger process are discussed. The accuracy of the present method makes it possible to investigate small differences between the 3p12 and 3p32 level widths. For several elements the unusual result is obtained that the 3p32 level is broader than the 3p12 level. This finding is in good agreement with theoretical predictions. The 4s and 4p spectra of the currently investigated elements are strongly influenced by configuration-interaction (CI) effects. However, the 4s line shapes are found to be quite normal for all the 5th-period elements. For Z<=45 (Rh) the 4p12 level is found to be broadened due to N2N3N45 super-Coster-Kronig processes. For Z<=46 (Pd) the shape of the 4p32 core-electron lines can reasonably well be reproduced by broadened 3d52 line profiles. For Z>=47 (Ag) this can, however, not be achieved. This marks a transition into a region of Z values where CI effects become particularly important. The accuracy of the present method for determining core-level widths can be judged from a comparison between our analysis of the 4p levels and x-ray studies of the Mζ transition. The results indicate that core-level widths can be determined with an accuracy of about 0.2 eV even for fairly broad and asymmetric electron lines.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Risskov Sørensen, Daniel; Nielsen, Ulla Gro; Skou, Eivind M., E-mail: ems@kbm.sdu.dk
2014-11-15
A systematic study of composite powders of niobium oxide phosphate (NbOPO{sub 4}) and phosphoric acid (H{sub 3}PO{sub 4}) has been performed in order to characterize the material's ability to perform as an electrolyte material in medium temperature fuel cells and electrolyzers. Powders of H{sub 3}PO{sub 4} contents between 13.1 and 74.2 M% were produced and characterized with powder X-ray diffraction, {sup 31}P MAS NMR and impedance spectroscopy. NMR revealed that a significant degree of dehydration and vaporization of H{sub 3}PO{sub 4} takes place above 200 °C, and increases with temperature. At 500 °C the NbOPO{sub 4} and H{sub 3}PO{sub 4}more » has reacted to form niobium pyrophosphate (Nb{sub 2}P{sub 4}O{sub 15}). Impedance spectroscopy showed an increase in conductivity with increasing acid concentration, whereas the conductivity decreased slightly with increasing temperature. The highest conductivity measured was 2.5·10{sup −3} S/cm for a sample containing 74.2 M% of H{sub 3}PO{sub 4}. Lastly, it was shown that NbOPO{sub 4} has no significant conductivity of its own. - Graphical abstract: Conductivity of NbOPO{sub 4}/H{sub 3}PO{sub 4} composites as a function of equivalent P{sub 2}O{sub 5} content. The conductivity is insignificant for pure NbOPO{sub 4}. - Highlights: • Composites have been made from NbOPO{sub 4} and H{sub 3}PO{sub 4}. • The composites composition has been investigated with solid state NMR. • The composites have shown clear signs of acid dehydration upon heating. • The conductivity of the composites increases for increasing acid content. • NbOPO{sub 4} has no significant conductivity of its own.« less
Martínez, María Antonia; Úbeda, Alejandro; Moreno, Jorge; Trillo, María Ángeles
2016-04-06
The proliferative response of the neuroblastoma line NB69 to a 100 µT, 50 Hz magnetic field (MF) has been shown mediated by activation of the MAPK-ERK1/2 pathway. This work investigates the MF effect on the cell cycle of NB69, the participation of p38 and c-Jun N-terminal (JNK) kinases in the field-induced proliferative response and the potential involvement of reactive oxygen species (ROS) in the activation of the MAPK-ERK1/2 and -p38 signaling pathways. NB69 cultures were exposed to the 100 µT MF, either intermittently for 24, 42 or 63 h, or continuously for periods of 15 to 120 min, in the presence or absence of p38 or JNK inhibitors: SB203580 and SP600125, respectively. Antioxidant N-acetylcysteine (NAC) was used as ROS scavenger. Field exposure induced transient activation of p38, JNK and ERK1/2. The MF proliferative effect, which was mediated by changes in the cell cycle, was blocked by the p38 inhibitor, but not by the JNK inhibitor. NAC blocked the field effects on cell proliferation and p38 activation, but not those on ERK1/2 activation. The MF-induced proliferative effects are exerted through sequential upregulation of MAPK-p38 and -ERK1/2 activation, and they are likely mediated by a ROS-dependent activation of p38.
Martínez, María Antonia; Úbeda, Alejandro; Moreno, Jorge; Trillo, María Ángeles
2016-01-01
The proliferative response of the neuroblastoma line NB69 to a 100 µT, 50 Hz magnetic field (MF) has been shown mediated by activation of the MAPK-ERK1/2 pathway. This work investigates the MF effect on the cell cycle of NB69, the participation of p38 and c-Jun N-terminal (JNK) kinases in the field-induced proliferative response and the potential involvement of reactive oxygen species (ROS) in the activation of the MAPK-ERK1/2 and -p38 signaling pathways. NB69 cultures were exposed to the 100 µT MF, either intermittently for 24, 42 or 63 h, or continuously for periods of 15 to 120 min, in the presence or absence of p38 or JNK inhibitors: SB203580 and SP600125, respectively. Antioxidant N-acetylcysteine (NAC) was used as ROS scavenger. Field exposure induced transient activation of p38, JNK and ERK1/2. The MF proliferative effect, which was mediated by changes in the cell cycle, was blocked by the p38 inhibitor, but not by the JNK inhibitor. NAC blocked the field effects on cell proliferation and p38 activation, but not those on ERK1/2 activation. The MF-induced proliferative effects are exerted through sequential upregulation of MAPK-p38 and -ERK1/2 activation, and they are likely mediated by a ROS-dependent activation of p38. PMID:27058530
A 16 deg2 survey of emission-line galaxies at z < 1.5 in HSC-SSP Public Data Release 1
NASA Astrophysics Data System (ADS)
Hayashi, Masao; Tanaka, Masayuki; Shimakawa, Rhythm; Furusawa, Hisanori; Momose, Rieko; Koyama, Yusei; Silverman, John D.; Kodama, Tadayuki; Komiyama, Yutaka; Leauthaud, Alexie; Lin, Yen-Ting; Miyazaki, Satoshi; Nagao, Tohru; Nishizawa, Atsushi J.; Ouchi, Masami; Shibuya, Takatoshi; Tadaki, Ken-ichi; Yabe, Kiyoto
2018-01-01
We present initial results from the Subaru Strategic Program (SSP) with Hyper Suprime-Cam (HSC) on a comprehensive survey of emission-line galaxies at z < 1.5 based on narrowband imaging. The first Public Data Release provides us with data from two narrowband filters, specifically NB816 and NB921 over 5.7 deg2 and 16.2 deg2 respectively. The 5 σ limiting magnitudes are 25.2 mag (UltraDeep layer, 1.4 deg2) and 24.8 mag (Deep layer, 4.3 deg2) for NB816, and 25.1 mag (UltraDeep, 2.9 deg2) and 24.6-24.8 mag (Deep, 13.3 deg2) for NB921. The wide-field imaging allows us to construct unprecedentedly large samples of 8054 H α emitters at z ≈ 0.25 and 0.40, 8656 [O III] emitters at z ≈ 0.63 and 0.84, and 16877 [O II] emitters at z ≈ 1.19 and 1.47. We map the cosmic web on scales out to about 50 comoving Mpc that includes galaxy clusters, identified by red sequence galaxies, located at the intersection of filamentary structures of star-forming galaxies. The luminosity functions of emission-line galaxies are measured with precision and are consistent with published studies. The wide field coverage of the data enables us to measure the luminosity functions up to brighter luminosities than previous studies. The comparison of the luminosity functions between the different HSC-SSP fields suggests that a survey volume of >5 × 105 Mpc3 is essential to overcome cosmic variance. Since the current data have not reached the full depth expected for the HSC-SSP, the color cut in i - NB816 or z - NB921 induces a bias towards star-forming galaxies with large equivalent widths, primarily seen in the stellar mass functions for the H α emitters at z ≈ 0.25-0.40. Even so, the emission-line galaxies clearly cover a wide range of luminosity, stellar mass, and environment, thus demonstrating the usefulness of the narrowband data from the HSC-SSP for investigating star-forming galaxies at z < 1.5.
ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma.
Pieraccioli, Marco; Nicolai, Sara; Pitolli, Consuelo; Agostini, Massimiliano; Antonov, Alexey; Malewicz, Michal; Knight, Richard A; Raschellà, Giuseppe; Melino, Gerry
2018-06-25
Derangement of cellular differentiation because of mutation or inappropriate expression of specific genes is a common feature in tumors. Here, we show that the expression of ZNF281, a zinc finger factor involved in several cellular processes, decreases during terminal differentiation of murine cortical neurons and in retinoic acid-induced differentiation of neuroblastoma (NB) cells. The ectopic expression of ZNF281 inhibits the neuronal differentiation of murine cortical neurons and NB cells, whereas its silencing causes the opposite effect. Furthermore, TAp73 inhibits the expression of ZNF281 through miR34a. Conversely, MYCN promotes the expression of ZNF281 at least in part by inhibiting miR34a. These findings imply a functional network that includes p73, MYCN, and ZNF281 in NB cells, where ZNF281 acts by negatively affecting neuronal differentiation. Array analysis of NB cells silenced for ZNF281 expression identified GDNF and NRP2 as two transcriptional targets inhibited by ZNF281. Binding of ZNF281 to the promoters of these genes suggests a direct mechanism of repression. Bioinformatic analysis of NB datasets indicates that ZNF281 expression is higher in aggressive, undifferentiated stage 4 than in localized stage 1 tumors supporting a central role of ZNF281 in affecting the differentiation of NB. Furthermore, patients with NB with high expression of ZNF281 have a poor clinical outcome compared with low-expressors. These observations suggest that ZNF281 is a controller of neuronal differentiation that should be evaluated as a prognostic marker in NB. Copyright © 2018 the Author(s). Published by PNAS.
NbF5 and TaF5: Assignment of 19F NMR resonances and chemical bond analysis from GIPAW calculations
NASA Astrophysics Data System (ADS)
Biswal, Mamata; Body, Monique; Legein, Christophe; Sadoc, Aymeric; Boucher, Florent
2013-11-01
The 19F isotropic chemical shifts (δiso) of two isomorphic compounds, NbF5 and TaF5, which involve six nonequivalent fluorine sites, have been experimentally determined from the reconstruction of 1D 19F MAS NMR spectra. In parallel, the corresponding 19F chemical shielding tensors have been calculated using the GIPAW method for both experimental and DFT-optimized structures. Furthermore, the [M4F20] units of NbF5 and TaF5 being held together by van der Waals interactions, the relevance of Grimme corrections to the DFT optimization processes has been evaluated. However, the semi-empirical dispersion correction term introduced by such a method does not show any significant improvement. Nonetheless, a complete and convincing assignment of the 19F NMR lines of NbF5 and TaF5 is obtained, ensured by the linearity between experimental 19F δiso values and calculated 19F isotropic chemical shielding σiso values. The effects of the geometry optimizations have been carefully analyzed, confirming among other matters, the inaccuracy of the experimental structure of NbF5. The relationships between the fluorine chemical shifts, the nature of the fluorine atoms (bridging or terminal), the position of the terminal ones (opposite or perpendicular to the bridging ones), the fluorine charges, the ionicity and the length of the M-F bonds have been established. Additionally, for three of the 19F NMR lines of NbF5, distorted multiplets, arising from 1J-coupling and residual dipolar coupling between the 19F and 93Nb nuclei, were simulated yielding to values of 93Nb-19F 1J-coupling for the corresponding fluorine sites.
The General Isothermal Oxidation Behavior of Cu-8Cr-4Nb
NASA Technical Reports Server (NTRS)
Thomas-Ogbuji, L. U.; Gray, Hugh R. (Technical Monitor)
2002-01-01
Oxidation kinetics of Cu-8Cr-4Nb was investigated by TGA (thermogravimetric) exposures between 500 and 900-C (at 25-50 C intervals) and the oxide scale morphologies examined by microscopy and micro-analysis. Because Cu-8Cr-4Nb is comprised of fine Cr2Nb precipitates in a Cu matrix, the results were interpreted by comparison with the behavior of copper (OFHC) and 'NARloy-Z' (a rival candidate material for thrust cell liner applications in advanced rocket engines) under the same conditions. While NARloy-Z and Cu exhibited identical oxidation behavior, Cu-8Cr-4Nb differed markedly in several respects: below approx. 700 C its oxidation rates were significantly lower than those of Cu; At higher temperatures its oxidation rates fell into two categories: an initial rate exceeding that of Cu, and a terminal rate comparable to that of Cu. Differences in oxide morphologies paralleled the kinetic differences at higher temperature: While NARloy-Z and Cu produced a uniform oxide scale of Cu2O inner layer and CuO outer layer, the inner (Cu2O) layer on Cu-8Cr-4Nb was stratified, with a highly porous/spongy inner stratum (responsible for the fast initial kinetics) and a dense/blocky outer stratum (corresponding to the slow terminal kinetics). Single and spinel oxides of Nb and Cr were found at the interface between the oxide scale and Cu-8Cr-4Nb substrate and it appears that these oxides were responsible for its suppressed oxidation rates at the intermediate temperatures. No difference was found between Cu-8Cr-4Nb oxidation in air and in oxygen at 1.0 atm.
Controlled modification of resonant tunneling in metal-insulator-insulator-metal structures
NASA Astrophysics Data System (ADS)
Mitrovic, I. Z.; Weerakkody, A. D.; Sedghi, N.; Ralph, J. F.; Hall, S.; Dhanak, V. R.; Luo, Z.; Beeby, S.
2018-01-01
We present comprehensive experimental and theoretical work on tunnel-barrier rectifiers comprising bilayer (Nb2O5/Al2O3) insulator configurations with similar (Nb/Nb) and dissimilar (Nb/Ag) metal electrodes. The electron affinity, valence band offset, and metal work function were ascertained by X-ray photoelectron spectroscopy, variable angle spectroscopic ellipsometry, and electrical measurements on fabricated reference structures. The experimental band line-up parameters were fed into a theoretical model to predict available bound states in the Nb2O5/Al2O3 quantum well and generate tunneling probability and transmittance curves under applied bias. The onset of strong resonance in the sub-V regime was found to be controlled by a work function difference of Nb/Ag electrodes in agreement with the experimental band alignment and theoretical model. A superior low-bias asymmetry of 35 at 0.1 V and a responsivity of 5 A/W at 0.25 V were observed for the Nb/4 nm Nb2O5/1 nm Al2O3/Ag structure, sufficient to achieve a rectification of over 90% of the input alternate current terahertz signal in a rectenna device.
Topolska-Woś, Agnieszka M.; Shell, Steven M.; Kilańczyk, Ewa; Szczepanowski, Roman H.; Chazin, Walter J.; Filipek, Anna
2015-01-01
CacyBP/SIP [calcyclin-binding protein/Siah-1 [seven in absentia homolog 1 (Siah E3 ubiquitin protein ligase 1)] interacting protein] is a multifunctional protein whose activity includes acting as an ERK1/2 phosphatase. We analyzed dimerization of mouse CacyBP/SIP in vitro and in mouse neuroblastoma cell line (NB2a) cells, as well as the structure of a full-length protein. Moreover, we searched for the CacyBP/SIP domain important for dimerization and dephosphorylation of ERK2, and we analyzed the role of dimerization in ERK1/2 signaling in NB2a cells. Cell-based assays showed that CacyBP/SIP forms a homodimer in NB2a cell lysate, and biophysical methods demonstrated that CacyBP/SIP forms a stable dimer in vitro. Data obtained using small-angle X-ray scattering supported a model in which CacyBP/SIP occupies an anti-parallel orientation mediated by the N-terminal dimerization domain. Site-directed mutagenesis established that the N-terminal domain is indispensable for full phosphatase activity of CacyBP/SIP. We also demonstrated that the oligomerization state of CacyBP/SIP as well as the level of post-translational modifications and subcellular distribution of CacyBP/SIP change after activation of the ERK1/2 pathway in NB2a cells due to oxidative stress. Together, our results suggest that dimerization is important for controlling phosphatase activity of CacyBP/SIP and for regulating the ERK1/2 signaling pathway.—Topolska-Woś, A. M., Shell, S. M., Kilańczyk, E., Szczepanowski, R. H., Chazin, W. J., Filipek, A. Dimerization and phosphatase activity of calcyclin-binding protein/Siah-1 interacting protein: the influence of oxidative stress. PMID:25609429
Petit, A; Delaune, A; Falluel-Morel, A; Goullé, J-P; Vannier, J-P; Dubus, I; Vasse, M
2013-11-01
Neuroblastoma malignant cell growth is dependent on their undifferentiated status. Arsenic trioxide (As2O3) induces neuroblastoma cell differentiation in vitro, but its mechanisms still remains unknown. We used three human neuroblastoma cell lines (SH-SY5Y, IGR-N-91, LAN-1) that differ from their MYCN and p53 status to explore the intracellular events activated by As2O3 and involved in neurite outgrowth, a morphological marker of differentiation. As2O3 (2μM) induced neurite outgrowth in all cell lines, which was dependent on ERK activation but independent on MYCN status. This process was induced either by a sustained (3 days) or a transient (2h) incubation with As2O3, indicating that very early events trigger the induction of differentiation. In parallel, As2O3 induced a rapid assembly of promyelocytic leukemia nuclear bodies (PML-NB) in an ERK-dependent manner. In conclusion, mechanisms leading to neuroblastoma cell differentiation in response to As2O3 appear to involve the ERK pathway activation and PML-NB formation, which are observed in response to other differentiating molecules such as retinoic acid derivates. This open new perspectives based on the use of treatment combinations to potentiate the differentiating effects of each drug alone and reduce their adverse side effects. Copyright © 2013 Elsevier Ltd. All rights reserved.
He, Kang; Duan, Guoqing; Li, Yanyang
2018-06-15
Neuroblastoma (NB) is the most predominant extracranial solid tumor of infancy in the world. However, current chemotherapy has limited efficacy for more advanced stages of NB due to acquired chemoresistance or acute toxicity in NB patients. Therefore, effective novel anti-NB drugs are desperately needed. The present study aimed to investigate the effects of dehydroeffusol (DHE), a phenanthrene isolated from J. effuses, on NB cells and its underlying mechanism. The results showed that DHE treatment effectively inhibited NB cell viability in a dose-dependent manner. Moreover, DHE treatment suppressed the epithelial-mesenchymal transition (EMT) process in NB cells by promoting the expression of E-cadherin (E-cad) and restraining the expressions of N-cadherin (N-cad) and vimentin. Also, the invasive capacity and expression of MMP-2 and MMP-9 in NB cells were inhibited by DHE. Furthermore, DHE suppressed the hedgehog (Hh) and the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways in NB cells. In conclusion, DHE effectively inhibited the viability and EMT through inactivating the Hh and the Akt/mTOR signaling pathways in NB cells, providing a novel evidence that DHE may be a potential anti-NB drug candidate. Copyright © 2018 Elsevier B.V. All rights reserved.
Nanobarcoding for improved nanoparticle detection in nanomedical biodistribution studies
NASA Astrophysics Data System (ADS)
Eustaquio, Trisha
Determination of the fate of nanoparticles (NPs) in a biological system, or NP biodistribution, is critical in evaluating a NP formulation for nanomedicine. Unlike small-molecule drugs, NPs impose unique challenges in the design of appropriate biodistribution studies due to their small size and subsequent detection signal. Current methods to determine NP biodistribution are greatly inadequate due to their limited detection thresholds. There is an overwhelming need for a sensitive and efficient imaging-based method that can (1) detect and measure small numbers of NPs of various types, ideally single NPs, (2) associate preferential NP uptake with histological cell type by preserving spatial information in samples, and (3) allow for relatively quick and accurate NP detection in in vitro (and possibly ex vivo) samples for comprehensive NP biodistribution studies. Herein, a novel method for improved NP detection is proposed, coined "nanobarcoding." Nanobarcoding utilizes a non-endogenous oligonucleotide, or "nanobarcode" (NB), conjugated to the NP surface to amplify the detection signal from a single NP via in situ polymerase chain reaction (ISPCR), and this signal amplification will facilitate rapid and precise detection of single NPs inside cells over large areas of sample such that more sophisticated studies can be performed on the NP-positive subpopulation. Moreover, nanobarcoding has the potential to be applied to the detection of more than one NP type to study the effects of physicochemical properties, targeting mechanisms, and route of entry on NP biodistribution. The nanobarcoding method was validated in vitro using NB-functionalized superparamagnetic iron oxide NPs (NB-SPIONs) as the model NP type for improved NP detection inside HeLa human cervical cancer cells, a cell line commonly used for ISPCR-mediated detection of human papilloma virus (HPV). Nanotoxicity effects of NB-SPIONs were also evaluated at the single-cell level using LEAP (Laser-Enabled Analysis and Processing, Intrexon, San Diego, CA), and NB-SPIONs were found to be less toxic than its precursor, carboxylated SPIONs (COOH-SPIONs).
An Alu-like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells.
Castelnuovo, Manuele; Massone, Sara; Tasso, Roberta; Fiorino, Gloria; Gatti, Monica; Robello, Mauro; Gatta, Elena; Berger, Audrey; Strub, Katharina; Florio, Tullio; Dieci, Giorgio; Cancedda, Ranieri; Pagano, Aldo
2010-10-01
Neuroblastoma (NB) is a pediatric cancer characterized by remarkable cell heterogeneity within the tumor nodules. Here, we demonstrate that the synthesis of a pol III-transcribed noncoding (nc) RNA (NDM29) strongly restricts NB development by promoting cell differentiation, a drop of malignancy processes, and a dramatic reduction of the tumor initiating cell (TIC) fraction in the NB cell population. Notably, the overexpression of NDM29 also confers to malignant NB cells an unpredicted susceptibility to the effects of antiblastic drugs used in NB therapy. Altogether, these results suggest the induction of NDM29 expression as possible treatment to increase cancer cells vulnerability to therapeutics and the measure of its synthesis in NB explants as prognostic factor of this cancer type.
Lee, Chin-Cheng; Lin, Che-Pin; Lee, Yueh-Lun; Wang, Giueng-Chueng; Cheng, Yuan-Chih; Liu, H Eugene
2010-05-01
Meisoindigo, a derivative of Indigo naturalis, has been used in China for chronic myeloid leukemia. In vitro cell line studies have shown that this agent might induce apoptosis and myeloid differentiation of acute myeloid leukemia (AML). In this study, we explored its mechanisms and potential in AML. NB4, HL-60, and U937 cells and primary AML cells were used to examine its effects and the NOD/SCID animal model was used to evaluate its in vivo activity. Meisoindigo inhibited the growth of leukemic cells by inducing marked apoptosis and moderate cell-cycle arrest at the G(0)/G(1) phase. It down-regulated anti-apoptotic Bcl-2, and up-regulated pro-apoptotic Bak and Bax and cell-cycle related proteins, p21and p27. Furthermore, it induced myeloid differentiation, as demonstrated by morphologic changes, up-regulation of CD11b, and increased nitroblue tetrazolium reduction activity in all cell lines tested. In addition, meisoindigo down-regulated the expression of human telomerase reverse transcriptase and enhanced the cytotoxicity of conventional chemotherapeutic agents, cytarabine and idarubicin. As with the results from cell lines, meisoindigo also induced apoptosis, up-regulated p21 and p27, and down-regulated Bcl-2 in primary AML cells. The in vivo anti-leukemic activity of meisoindigo was also demonstrated by decreased spleen size in a dose-dependent manner. Taking these results together, meisoindigo is a potential agent for AML.
Bousquet, Marina; Quelen, Cathy; Rosati, Roberto; Mansat-De Mas, Véronique; La Starza, Roberta; Bastard, Christian; Lippert, Eric; Talmant, Pascaline; Lafage-Pochitaloff, Marina; Leroux, Dominique; Gervais, Carine; Viguié, Franck; Lai, Jean-Luc; Terre, Christine; Beverlo, Berna; Sambani, Costantina; Hagemeijer, Anne; Marynen, Peter; Delsol, Georges; Dastugue, Nicole; Mecucci, Cristina; Brousset, Pierre
2008-10-27
Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we have shown that this translocation is associated with a strong up-regulation of miR-125b (from 6- to 90-fold). In vitro experiments revealed that miR-125b was able to interfere with primary human CD34(+) cell differentiation, and also inhibited terminal (monocytic and granulocytic) differentiation in HL60 and NB4 leukemic cell lines. Therefore, miR-125b up-regulation may represent a new mechanism of myeloid cell transformation, and myeloid neoplasms carrying the t(2;11) translocation define a new clinicopathological entity.
Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells.
Ly, Tony; Endo, Aki; Lamond, Angus I
2015-01-02
Previously, we analyzed protein abundance changes across a 'minimally perturbed' cell cycle by using centrifugal elutriation to differentially enrich distinct cell cycle phases in human NB4 cells (Ly et al., 2014). In this study, we compare data from elutriated cells with NB4 cells arrested at comparable phases using serum starvation, hydroxyurea, or RO-3306. While elutriated and arrested cells have similar patterns of DNA content and cyclin expression, a large fraction of the proteome changes detected in arrested cells are found to reflect arrest-specific responses (i.e., starvation, DNA damage, CDK1 inhibition), rather than physiological cell cycle regulation. For example, we show most cells arrested in G2 by CDK1 inhibition express abnormally high levels of replication and origin licensing factors and are likely poised for genome re-replication. The protein data are available in the Encyclopedia of Proteome Dynamics (
Shoae-Hassani, Alireza; Hamidieh, Amir Ali; Behfar, Maryam; Mohseni, Rashin; Mortazavi-Tabatabaei, Seyed A; Asgharzadeh, Shahab
2017-09-01
Immune cell-derived exosomes can increase immunity against tumors. In contrast, tumor-derived exosomes can reduce the immunity and can change the tumor microenvironment to further develop and provide metastasis. These effects take place by an alteration in the innate and adaptive immune cell functions. In this experiment, we studied the natural killer (NK) cells' effectiveness on tumor cells after expansion and thereafter incubated it with exosomes. The exosomes were derived from 2 populations of NK cells: (1) naive NK cells and, (2) NK cells previously exposed to neuroblastoma (NB) cells. Moreover, we have studied the NB-derived exosomes on NK cell function. The molecular load of the characterized exosomes (by means of nanoparticle-tracking analysis, flow cytometry, scanning electron microscopy, and western blot) from NK cells exposed to the NB cell revealed their expression of natural killer cell receptors in addition to CD56, NKG2D, and KIR2DL2 receptors. These exosomes were used to treat NK cells and thereafter administered to NB tumor cells both in vitro and in vivo. Our results showed some kind of NK cells' education by the exosomes. This education from NK cells previously exposed to NB cell-derived exosomes caused efficient and greater cytotoxicity against NB tumors, but NB-derived exosomes act as tumor promoters by providing a tumor supporting niche. Hence, this method of preparing the exosomes has a dramatic effect on activation of anti-NK cells against NB cells.
Naora, H; Nishida, T; Shindo, Y; Adachi, M; Naora, H
1998-04-01
Apoptosis is induced by the transcriptional inhibitor actinomycin D (Act D) in various cell types, particularly many leukemic cell lines such as HL-60. A common feature of these cell lines is their high constitutive expression level of the nbl gene, which was originally isolated by virtue of its abundance in a Namalwa Burkitt lymphoma cDNA library. In contrast, cell lines which constitutively express nbl at low levels appear not to undergo typical apoptotic death in response to Act D. Apoptotic induction by Act D in cells which normally express nbl at high levels was found in this study to be closely associated with a decline in nbl mRNA levels, raising the possibility that apoptosis could be induced by lowering nbl expression levels in such cells. Transient expression of nbl antisense sequences in HL-60 cells decreased cell viability, and induced typical apoptotic morphology such as cell shrinkage, chromatin condensation and nuclear fragmentation. Incubation with nbl antisense oligomers also induced similar features in HL-60 cells and in another high nb-expressing cell line, Jurkat, but had little effect in HepG2 cells which constitutively express nbl at low levels. These findings suggest that lowering constitutively high levels of nbl expression can induce apoptosis.
NASA Astrophysics Data System (ADS)
Deng, Shengjue; Luo, Zhibin; Liu, Yating; Lou, Xiaoming; Lin, Chunfu; Yang, Chao; Zhao, Hua; Zheng, Peng; Sun, Zhongliang; Li, Jianbao; Wang, Ning; Wu, Hui
2017-09-01
Ti2Nb10O29 has recently been reported as a promising anode material for lithium-ion batteries. However, its poor electronic conductivity and insufficient Li+-ion diffusion coefficient significantly limit its rate capability. To tackle this issue, a strategy combining nanosizing and crystal-structure modification is employed. Ti2Nb10O29-x mesoporous microspheres with a sphere-size range of 0.5-4 μm are prepared by a one-step solvothermal method followed by thermal treatment in N2. These Ti2Nb10O29-x mesoporous microspheres exhibit primary nanoparticles, a large specific surface area (22.9 m2 g-1) and suitable pore sizes, leading to easy electron/Li+-ion transport and good interfacial reactivity. Ti2Nb10O29-x shows a defective shear ReO3 crystal structure with O2- vacancies and an increased unit cell volume, resulting in its increased Li+-ion diffusion coefficient. Besides Ti4+ and Nb5+ ions, Ti2Nb10O29-x comprises Nb4+ ions with unpaired 4d electrons, which significantly increase its electronic conductivity. As a result of these improvements, the Ti2Nb10O29-x mesoporous microspheres reveal superior electrochemical performances in term of large reversible specific capacity (309 mAh g-1 at 0.1 C), outstanding rate capability (235 mAh g-1 at 40 C) and durable cyclic stability (capacity retention of 92.1% over 100 cycles at 10 C).
Downregulation of bone morphogenetic protein receptor 2 promotes the development of neuroblastoma.
Cui, Ximao; Yang, Yili; Jia, Deshui; Jing, Ying; Zhang, Shouhua; Zheng, Shan; Cui, Long; Dong, Rui; Dong, Kuiran
2017-01-29
Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. In this study, we examined the expression of bone morphogenetic protein receptor 2 (BMPR2) in primary NB and adjacent non-tumor samples (adrenal gland). BMPR2 expression was significantly downregulated in NB tissues, particularly in high-grade NB, and was inversely related to the expression of the NB differentiation markers ferritin and enolase. The significance of the downregulation was further explored in cultured NB cells. While enforced expression of BMPR2 decreased cell proliferation and colony-forming activity, shRNA-mediated knockdown of BMPR2 led to increased cell growth and clonogenicity. In mice, NB cells harboring BMPR2 shRNA showed significantly increased tumorigenicity compared with control cells. We also performed a retrospective analysis of NB patients and identified a significant positive correlation between tumor BMPR2 expression and overall survival. These findings suggest that BMPR2 may play an important role in the development of NB. Copyright © 2016 Elsevier Inc. All rights reserved.
Observations on the long-lived Mossbauer effects of 93mNb
Cheng, Yao; Yang, Shi-Hui; Lan, Michael; Lee, Chih-Hao
2016-01-01
Several observations of the Nb long-lived Mossbauer phenomena are presented, in consequence of an irradiation increased by an order of magnitude compared with previous work. These are 1) two β decays of 182Ta and 92mNb are enhanced, i.e., 182Ta is now 200 times faster than in previous results while 92mNb is twice as fast as normal; 2) γs emitted from two β decays compete to eject electrons in a winner-takes-all rule, rather than by superposition; 3) abrupt spectral changes reveal three decay phases of 182Ta; 4) the biphoton γγ of 93mNb is released from the sample for the first time; 5) the γγ distribution is narrow, in contrast to the broad γγ spectrum obtained from independent nuclei; 6) Nb K-lines super-radiate along the long sample axis; 7) collective scattering of multipolar MeV γs. The manipulation of nuclear decay speeds demonstrated here highlights a potential application of this work in cleaning up the nuclear wastes. PMID:27824073
MicroRNA-1247 inhibits cell proliferation by directly targeting ZNF346 in childhood neuroblastoma.
Wu, Tingting; Lin, Yun; Xie, Zhongguo
2018-05-24
Neuroblastoma (NB) represents the most common extracranial solid tumor in children. Accumulating evidence shows that microRNAs (miRs) play an important role in the carcinogenesis of NB. Here, we investigated the biological function of miR-1247 in NB in vitro. We found miR-1247 was downregulated in NB tissues and cells using quantitative PCR analysis. Gain- and loss-of-function studies demonstrated that miR-1247 significantly suppressed cell proliferation and induced cell cycle G0/G1 phase arrest and cell apoptosis of NB cells in vitro by using MTT, colony formation assay and Flow cytometry analysis. Luciferase assay suggested ZNF346 was the target of miR-1247 and its expression could be downregulated by miR-1247 overexpression using Western blotting. Furthermore, downregulation of ZNF346 by siRNA performed similar effects with overexpression of miR-1247 in NB cells. Our findings suggested miR-1247 directly targeted to repress ZNF346 expression, thus suppressing the progression of NB, which might be a novel therapeutic target against NB.
Ribeiro, Ana Lúcia Roselino; Hammer, Peter; Vaz, Luís Geraldo; Rocha, Luís Augusto
2013-12-01
The main aim of this work was to assess the electrochemical behavior of new Ti35Nb5Zr and Ti35Nb10Zr alloys in artificial saliva at 37 °C to verify if they are indicated to be used as biomaterials in dentistry as alternatives to Ti6Al4V alloys in terms of corrosion protection efficiency of the material. Electrochemical impedance spectroscopy (EIS) experiments were carried out for different periods of time (0.5-216 h) in a three-electrode cell, where the working electrode (Ti alloys) was exposed to artificial saliva at 37 °C. The near-surface region of the alloys was investigated using x-ray photoelectron spectroscopy (XPS). All alloys exhibited an increase in corrosion potential with the immersion time, indicating the growth and stabilization of the passive film. Ti35Nb5Zr and Ti6Al4V alloys had their EIS results interpreted by a double-layer circuit, while the Ti35Nb10Zr alloy was modeled by a one-layer circuit. In general, the new TiNbZr alloys showed similar behavior to that observed for the Ti6Al4V. XPS results suggest, in the case of the TiNbZr alloys, the presence of a thicker passive layer containing a lower fraction of TiO2 phase than that of Ti6Al4V. After long-term immersion, all alloys develop a calcium phosphate phase on the surface. The new TiNbZr alloys appear as potential candidates to be used as a substitute to Ti6Al4V in the manufacturing of dental implant-abutment sets.
Cytotoxicity induced by nanobacteria and nanohydroxyapatites in human choriocarcinoma cells
NASA Astrophysics Data System (ADS)
Zhang, Mingjun; Yang, Jinmei; Shu, Jing; Fu, Changhong; Liu, Shengnan; Xu, Ge; Zhang, Dechun
2014-11-01
We explored the cytotoxic effects of nanobacteria (NB) and nanohydroxyapatites (nHAPs) against human choriocarcinoma cells (JAR) and the mechanisms of action underlying their cytotoxicity. JAR cells were co-cultured with NB and nHAPs for 48 h, and ultrastructural changes were more readily induced by NB than nHAPs. Autophagy in the plasma of JAR cells were observed in the NB group. The rate of apoptosis induced by NB was higher than that for nHAPs. The expression of Bax and FasR proteins in the NB group was stronger than that for the nHAP group. NB probably resulted in autophagic formation. Apoptosis was possibly activated via FasL binding to the FasR signaling pathway.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Biswal, Mamata, E-mail: Mamata.Biswal-Susanta_Kumar_Nayak.Etu@univ-lemans.fr; Body, Monique, E-mail: monique.body@univ-lemans.fr; Legein, Christophe, E-mail: christophe.legein@univ-lemans.fr
2013-11-15
The {sup 19}F isotropic chemical shifts (δ{sub iso}) of two isomorphic compounds, NbF{sub 5} and TaF{sub 5}, which involve six nonequivalent fluorine sites, have been experimentally determined from the reconstruction of 1D {sup 19}F MAS NMR spectra. In parallel, the corresponding {sup 19}F chemical shielding tensors have been calculated using the GIPAW method for both experimental and DFT-optimized structures. Furthermore, the [M{sub 4}F{sub 20}] units of NbF{sub 5} and TaF{sub 5} being held together by van der Waals interactions, the relevance of Grimme corrections to the DFT optimization processes has been evaluated. However, the semi-empirical dispersion correction term introduced bymore » such a method does not show any significant improvement. Nonetheless, a complete and convincing assignment of the {sup 19}F NMR lines of NbF{sub 5} and TaF{sub 5} is obtained, ensured by the linearity between experimental {sup 19}F δ{sub iso} values and calculated {sup 19}F isotropic chemical shielding σ{sub iso} values. The effects of the geometry optimizations have been carefully analyzed, confirming among other matters, the inaccuracy of the experimental structure of NbF{sub 5}. The relationships between the fluorine chemical shifts, the nature of the fluorine atoms (bridging or terminal), the position of the terminal ones (opposite or perpendicular to the bridging ones), the fluorine charges, the ionicity and the length of the M–F bonds have been established. Additionally, for three of the {sup 19}F NMR lines of NbF{sub 5}, distorted multiplets, arising from {sup 1}J-coupling and residual dipolar coupling between the {sup 19}F and {sup 93}Nb nuclei, were simulated yielding to values of {sup 93}Nb–{sup 19}F {sup 1}J-coupling for the corresponding fluorine sites. - Graphical abstract: The complete assignment of the {sup 19}F NMR lines of NbF{sub 5} and TaF{sub 5} allow establishing relationships between the {sup 19}F δ{sub iso} values, the nature of the fluorine atoms (bridging or terminal), the position of the terminal ones (opposite or perpendicular to the bridging ones), the fluorine charges, the ionicity and the length of the M–F bonds. Display Omitted - Highlights: • The {sup 19}F δ{sub iso} values of NbF{sub 5} and TaF{sub 5} have been determined. • The {sup 19}F chemical shielding tensors have been calculated using the GIPAW method. • A confident assignment of the {sup 19}F NMR lines of NbF{sub 5} and TaF{sub 5} is obtained. • The relationships between the {sup 19}Fδ{sub iso} values and the M–F bonds features are established.« less
High rate performance supercapacitor based on Nb2O5 nanoparticles
NASA Astrophysics Data System (ADS)
Ahmed, Sultan; Ahmed, Ahsan; Rafat, M.
2018-05-01
In the present communication, we report the successful preparation of Nb2O5 nanoparticles from precursor NbCl5 using hydrothermal method, followed by thermal annealing. The surface morphology of the as-prepared material was studied using scanning electron microscopy (SEM) while crystal structure and vibrational response was characterized using X-ray diffraction (XRD) and Raman spectroscopy. The observed results indicate the successful synthesis of Nb2O5 nanoparticles. The electrochemical properties of the material was investigated in two-electrode assembly in 1 M LiClO4 solution using the techniques of electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Both EIS and CV studies show high rate performance of the assembled supercapacitor cells. Fabricated cell offers low response time (˜17.1 ms), and the shape of CV pattern remains almost rectangular, even for high scan rates (˜20 V s-1).
Thermal depinning of a single superconducting vortex
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sok, Junghyun
1995-06-19
Thermal depinning has been studied for a single vortex trapped in a superconducting thin film in order to determine the value of the superconducting order parameter and the superfluid density when the vortex depins and starts to move around the film. For the Pb film in Pb/Al/Al 2O 3/PbBi junction having a gold line, the vortex depins from the artificial pinning site (Au line) and reproducibly moves through the same sequence of other pinning sites before it leaves the junction area of the Pb film. Values of the normalized order parameter Δ/Δ ° vary from Δ/Δ °=0.20 at the firstmore » motion of the vortex to Δ/Δ °=0.16 where the vortex finally leaves the junction. Equivalently, the value of the normalized superfluid density changes from 4% to 2.5% for this sample in this same temperature interval. For the Nb film in Nb/Al/Al 2O 3/Nb junction, thermal depinning occurs when the value of Δ/Δ ° is approximately 0.22 and the value of ρ s/ρ so is approximately 5%. These values are about 20% larger than those of a Pb sample having a gold line, but the values are really very close. For the Nb sample, grain boundaries are important pinning sites whereas, for the Pb sample with a gold line, pinning may have been dominated by an array Pb 3AU precipitates. Because roughly the same answer was obtained for these rather different kinds of pinning site, there is a reasonable chance that this is a general value within factors of 2 for a wide range of materials.« less
Ribatti, D; Nico, B; Pezzolo, A; Vacca, A; Meazza, R; Cinti, R; Carlini, B; Parodi, F; Pistoia, V; Corrias, M V
2006-01-01
Tumour progression in neuroblastoma (NB) patients correlates with high vascular index. We have previously shown that the ACN NB cell line is tumorigenic and angiogenic in immunodeficient mice, and that interferon-γ (IFN-γ) gene transfer dampens ACN tumorigenicity. As IFN-γ represses lymphocyte-induced tumour angiogenesis in various murine models and inhibits proliferation and migration of human endothelial cells, we have investigated the antiangiogenic activity of tumour-derived IFN-γ and the underlying mechanism(s). In addition, we characterised the tumour vasculature of the ACN xenografts, using the chick embryo chorioallantoic membrane assay. We show that the ACN/IFN-γ xenografts had a lower microvessel density and less in vivo angiogenic potential than the vector-transfected ACN/neo. The vascular channels of both xenografts were formed by a mixed endothelial cell population of murine and human origin, as assessed by the FICTION (fluorescence immunophenotyping and interphase cytogenetics) technique. With respect to ACN/neo, the ACN/IFN-γ xenografts showed more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive human and murine endothelial cells, suggesting that inhibition of angiogenesis by IFN-γ was dependent on the induction of apoptosis, likely mediated by nitric oxide. Once the dual origin of tumour vasculature is confirmed in NB patients, the xenograft model described here will prove useful in testing the efficacy of different antiangiogenic compounds. PMID:16721359
Yang, Jing; Ikezoe, Takayuki; Nishioka, Chie; Tasaka, Taizo; Taniguchi, Ayuko; Kuwayama, Yoshio; Komatsu, Naoki; Bandobashi, Kentaro; Togitani, Kazuto; Koeffler, H Phillip; Taguchi, Hirokuni; Yokoyama, Akihito
2007-09-15
Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. We have recently shown that hematopoietic malignant cells including those from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) aberrantly expressed Aurora A and B kinases, and ZM447439, a potent inhibitor of Aurora kinases, effectively induced growth arrest and apoptosis of a variety of leukemia cells. The present study explored the effect of AZD1152, a highly selective inhibitor of Aurora B kinase, on various types of human leukemia cells. AZD1152 inhibited the proliferation of AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells with an IC50 ranging from 3 nM to 40 nM, as measured by thymidine uptake on day 2 of culture. These cells had 4N/8N DNA content followed by apoptosis, as measured by cell-cycle analysis and annexin V staining, respectively. Of note, AZD1152 synergistically enhanced the antiproliferative activity of vincristine, a tubulin depolymerizing agent, and daunorubicin, a topoisomerase II inhibitor, against the MOLM13 and PALL-2 cells in vitro. Furthermore, AZD1152 potentiated the action of vincristine and daunorubicin in a MOLM13 murine xenograft model. Taken together, AZD1152 is a promising new agent for treatment of individuals with leukemia. The combined administration of AZD1152 and conventional chemotherapeutic agent to patients with leukemia warrants further investigation.
Calcium-regulatory proteins as modulators of chemotherapy in human neuroblastoma.
Florea, Ana-Maria; Varghese, Elizabeth; McCallum, Jennifer E; Mahgoub, Safa; Helmy, Irfan; Varghese, Sharon; Gopinath, Neha; Sass, Steffen; Theis, Fabian J; Reifenberger, Guido; Büsselberg, Dietrich
2017-04-04
Neuroblastoma (NB) is a pediatric cancer treated with poly-chemotherapy including platinum complexes (e.g. cisplatin (CDDP), carboplatin), DNA alkylating agents, and topoisomerase I inhibitors (e.g. topotecan (TOPO)). Despite aggressive treatment, NB may become resistant to chemotherapy. We investigated whether CDDP and TOPO treatment of NB cells interacts with the expression and function of proteins involved in regulating calcium signaling. Human neuroblastoma cell lines SH-SY5Y, IMR-32 and NLF were used to investigate the effects of CDDP and TOPO on cell viability, apoptosis, calcium homeostasis, and expression of selected proteins regulating intracellular calcium concentration ([Ca2+]i). In addition, the impact of pharmacological inhibition of [Ca2+]i-regulating proteins on neuroblastoma cell survival was studied. Treatment of neuroblastoma cells with increasing concentrations of CDDP (0.1-10 μM) or TOPO (0.1 nM-1 μM) induced cytotoxicity and increased apoptosis in a concentration- and time-dependent manner. Both drugs increased [Ca2+]i over time. Treatment with CDDP or TOPO also modified mRNA expression of selected genes encoding [Ca2+]i-regulating proteins. Differentially regulated genes included S100A6, ITPR1, ITPR3, RYR1 and RYR3. With FACS and confocal laser scanning microscopy experiments we validated their differential expression at the protein level. Importantly, treatment of neuroblastoma cells with pharmacological modulators of [Ca2+]i-regulating proteins in combination with CDDP or TOPO increased cytotoxicity. Thus, our results confirm an important role of calcium signaling in the response of neuroblastoma cells to chemotherapy and suggest [Ca2+]i modulation as a promising strategy for adjunctive treatment.
A Low Noise NbTiN-Based 850 GHz SIS Receiver for the Caltech Submillimeter Observatory
NASA Technical Reports Server (NTRS)
Kooi, J. W.; Kawamura, J.; Chen, J.; Chattopadhyay, G.; Pardo, J. R.; Zmuidzinas, J.; Phillips, T. G.; Bumble, B.; Stern, J.; LeDuc, H. G.
2000-01-01
We have developed a niobium titanium nitride (NbTiN) based superconductor- insulator-superconductor (SIS) receiver to cover the 350 micron atmospheric window. This frequency band lies entirely above the energy gap of niobium (700 GHz), a commonly used SIS superconductor. The instrument uses an open structure twin-slot SIS mixer that consists of two Nb/AlN/NbTiN tunnel junctions, NbTiN thin-film microstrip tuning elements, and a NbTiN ground plane. The optical configuration is very similar to the 850 GHz waveguide receiver that was installed at the Caltech Submillimeter Observatory (CSO) in 1997. To minimize front-end loss, we employed reflecting optics and a cooled beamsplitter at 4 K. The instrument has an uncorrected receiver noise temperature of 205K DSB at 800 GHz and 410K DSB at 900 GHz. The degradation in receiver sensitivity with frequency is primarily due to an increase in the mixer conversion loss, which is attributed to the mismatch between the SIS junction and the twin-slot antenna impedance. The overall system performance has been confirmed through its use at the telescope to detect a wealth of new spectroscopic lines.
Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells
Ly, Tony; Endo, Aki; Lamond, Angus I
2015-01-01
Abstract Previously, we analyzed protein abundance changes across a ‘minimally perturbed’ cell cycle by using centrifugal elutriation to differentially enrich distinct cell cycle phases in human NB4 cells (Ly et al., 2014). In this study, we compare data from elutriated cells with NB4 cells arrested at comparable phases using serum starvation, hydroxyurea, or RO-3306. While elutriated and arrested cells have similar patterns of DNA content and cyclin expression, a large fraction of the proteome changes detected in arrested cells are found to reflect arrest-specific responses (i.e., starvation, DNA damage, CDK1 inhibition), rather than physiological cell cycle regulation. For example, we show most cells arrested in G2 by CDK1 inhibition express abnormally high levels of replication and origin licensing factors and are likely poised for genome re-replication. The protein data are available in the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/), an online, searchable resource. DOI: http://dx.doi.org/10.7554/eLife.04534.001 PMID:25555159
Development of a gas cell-based laser ion source for RIKEN PALIS
NASA Astrophysics Data System (ADS)
Sonoda, T.; Wada, M.; Tomita, H.; Sakamoto, C.; Takatsuka, T.; Noto, T.; Iimura, H.; Matsuo, Y.; Kubo, T.; Shinozuka, T.; Wakui, T.; Mita, H.; Naimi, S.; Furukawa, T.; Itou, Y.; Schury, P.; Miyatake, H.; Jeong, S.; Ishiyama, H.; Watanabe, Y.; Hirayama, Y.
2013-04-01
We developed a prototype laser ionization gas cell with a beam extraction system. This device is for use of PArasitic Laser Ion-Source (PALIS), which will be implemented into RIKEN's fragment separator, BigRIPS as a part of SLOWRI. Off-line resonant laser ionization for stable Co, Cu, Fe, Ni, Ti, Nb, Sn, In and Pd inside the gas cell, ion extraction and transport to the high-vacuum region via SPIG and QMS have been confirmed (Sonoda et al, Nucl Instrum Meth B 295:1, 2013).
Zhao, Xueheng; Brusadelli, Marion G; Sauter, Sharon; Butsch Kovacic, Melinda; Zhang, Wujuan; Romick-Rosendale, Lindsey E; Lambert, Paul F; Setchell, Kenneth D R; Wells, Susanne I
2018-06-01
Purpose: Mutations in Fanconi anemia (FA) genes are common in sporadic squamous cell carcinoma of the head and neck (HNSCC), and we have previously demonstrated that FA pathway depletion in HNSCC cell lines stimulates invasion. The goal of our studies was to use a systems approach in order to define FA pathway-dependent lipid metabolism and to extract lipid-based signatures and effectors of invasion in FA-deficient cells. Experimental Design: We subjected FA-isogenic HNSCC keratinocyte cell lines to untargeted and targeted lipidomics analyses to discover novel biomarkers and candidate therapeutic targets in FA-deficient cells. Cellular invasion assays were carried out in the presence and absence of N-butyldeoxynojirimycin (NB-DNJ), a biosynthetic inhibitor of the newly identified class of gangliosides, to investigate the requirement of ganglioside upregulation in FA-deficient HNSCC cells. Results: The most notable element of the lipid profiling results was a consistent elevation of glycosphingolipids, and particularly the accumulation of gangliosides. Conversely, repression of this same class of lipids was observed upon genetic correction of FA patient-derived HNSCC cells. Functional studies demonstrate that ganglioside upregulation is required for HNSCC cell invasion driven by FA pathway loss. The motility of nontransformed keratinocytes in response to FA loss displayed a similar dependence, thus supporting early and late roles for the FA pathway in controlling keratinocyte invasion through lipid regulation. Conclusions: Elevation of glycosphingolipids including the ganglioside GM3 in response to FA loss stimulates invasive characteristics of immortalized and transformed keratinocytes. An inhibitor of glycosphingolipid biosynthesis NB-DNJ attenuates invasive characteristics of FA-deficient HNSCC cells. Clin Cancer Res; 24(11); 2700-9. ©2018 AACR . ©2018 American Association for Cancer Research.
A 3-Protein Expression Signature of Neuroblastoma for Outcome Prediction.
Xie, Yi; Xu, Hua; Fang, Fang; Li, Zhiheng; Zhou, Huiting; Pan, Jian; Guo, Wanliang; Zhu, Xueming; Wang, Jian; Wu, Yi
2018-05-22
Neuroblastoma (NB) is the most common extracranial solid tumor in children with contrasting outcomes. Precise risk assessment contributes to prognosis prediction, which is critical for treatment strategy decisions. In this study, we developed a 3-protein predictor model, including the neural stem cell marker Msi1, neural differentiation marker ID1, and proliferation marker proliferating cell nuclear antigen (PCNA), to improve clinical risk assessment of patients with NB. Kaplan-Meier analysis in the microarray data (GSE16476) revealed that low expression of ID1 and high expression of Msi1 and PCNA were associated with poor prognosis in NB patients. Combined application of these 3 markers to constitute a signature further stratified NB patients into different risk subgroups can help obtain more accurate prediction performance. Survival prognostic power of age and Msi1_ID1_PCNA signature by receiver operating characteristics analysis showed that this signature predicted more effectively and sensitively compared with classic risk stratification system, compensating for the deficiency of the prediction function of the age. Furthermore, we validated the expressions of these 3 proteins in neuroblastic tumor spectrum tissues by immunohistochemistry revealed that Msi1 and PCNA exhibited increased expression in NB compared with intermedial ganglioneuroblastoma and benign ganglioneuroma, whereas ID1 levels were reduced in NB. In conclusion, we established a robust risk assessment predictor model based on simple immunohistochemistry for therapeutic decisions of NB patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.
NASA Astrophysics Data System (ADS)
Sohn, Kyung-Rak; Song, Jae-Won
2002-03-01
Using a side-polished single-mode fiber covered with a polished LiNbO 3 overlay and an intermediate coupling layer, tunable fiber-optic comb filters are demonstrated. The device behaviors based on the modal properties of the fiber and the planar LiNbO 3 waveguide are analyzed by two dimensional beam propagation methods (2-D BPM) and discussed the role of an intermediate coupling layer in terms of coupling efficiency. We also show that the thermo-optic effects of this layer can be utilized to tune the comb filter. When the polished x-cut LiNbO 3 with 200 μm thickness is used as a multimode overlay waveguide, the comb output spectra with free spectral range of 4 nm are measured in 1550 nm wavelength range. The tuning rate as a function of the refractive index of an intermediate coupling layer, Δλ/ Δnb, is about -0.129 nm/-0.001. The experimental results are in good agreement with the calculated results.
Merhi, Faten; Auger, Jacques; Rendu, Francine; Bauvois, Brigitte
2008-12-01
Epidemiologic studies support the premise that Allium vegetables may lower the risk of cancers. The beneficial effects appear related to the organosulfur products generated upon processing of Allium. Leukemia cells from patients with acute myeloid leukemia (AML) display high proliferative capacity and have a reduced capacity of undergoing apoptosis and maturation. Whether the sulfur-containing molecules thiosulfinates (TS), diallyl TS (All(2)TS), dipropyl TS (Pr(2)TS) and dimethyl TS (Me(2)TS), are able to exert chemopreventative activity against AML is presently unknown. The present study was an evaluation of proliferation, cytotoxicity, differentiation and secretion of AML cell lines (U937, NB4, HL-60, MonoMac-6) in response to treatment with these TS and their related sulfides (diallylsulfide, diallyl disulfide, dipropyl disulfide, dimethyl disulfide). As assessed by flow cytometry, ELISA, gelatin zymogaphy and RT-PCR, we showed that Pr(2)TS and Me(2)TS, but not All(2)TS and sulfides, 1) inhibited cell proliferation in dose- and time-dependent manner and this process was neither due to cytotoxicity nor apoptosis, 2) induced macrophage maturation, and 3) inhibited the levels of secreted MMP-9 (protein and activity) and TNF-alpha protein, without altering mRNA levels. By establishing for the first time that Pr(2)TS and Me(2)TS affect proliferation, differentiation and secretion of leukemic cell lines, this study provides the opportunity to explore the potential efficiency of these molecules in AML.
Nb5+-Doped SrCoO3-δ Perovskites as Potential Cathodes for Solid-Oxide Fuel Cells.
Cascos, Vanessa; Alonso, José Antonio; Fernández-Díaz, María Teresa
2016-07-15
SrCoO 3- δ outperforms as cathode material in solid-oxide fuel cells (SOFC) when the three-dimensional (3C-type) perovskite structure is stabilized by the inclusion of highly-charged transition-metal ions at the octahedral positions. In a previous work we studied the Nb incorporation at the Co positions in the SrCo 1- x Nb x O 3- δ system, in which the stabilization of a tetragonal P4 / mmm perovskite superstructure was described for the x = 0.05 composition. In the present study we extend this investigation to the x = 0.10-0.15 range, also observing the formation of the tetragonal P4 / mmm structure instead of the unwanted hexagonal phase corresponding to the 2H polytype. We also investigated the effect of Nb 5+ doping on the thermal, electrical, and electrochemical properties of SrCo 1- x Nb x O 3- δ ( x = 0.1 and 0.15) perovskite oxides performing as cathodes in SOFC. In comparison with the undoped hexagonal SrCoO 3- δ phase, the resulting compounds present high thermal stability and an increase of the electrical conductivity. The single-cell tests for these compositions ( x = 0.10 and 0.15) with La 0.8 Sr 0.2 Ga 0.83 Mg 0.17 O 3- δ (LSGM) as electrolyte and SrMo 0.8 Fe 0.2 CoO 3- δ as anode gave maximum power densities of 693 and 550 mW∙cm -2 at 850 °C respectively, using pure H₂ as fuel and air as oxidant.
Park, Jung Tae; Chi, Won Seok; Jeon, Harim; Kim, Jong Hak
2014-03-07
TiO2 nanoparticles are surface-modified via atom transfer radical polymerization (ATRP) with a hydrophilic poly(oxyethylene)methacrylate (POEM), which can coordinate to the Ag precursor, i.e. silver trifluoromethanesulfonate (AgCF3SO3). Following the reduction of Ag ions, a Nb2O5 doping process and calcination at 450 °C, bi-functional Nb-doped TiO2/Ag ternary nanostructures are generated. The resulting nanostructures are characterized by energy-filtering transmission electron microscopy (EF-TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and UV-visible spectroscopy. The dye-sensitized solar cell (DSSC) based on the Nb-doped TiO2/Ag nanostructure photoanode with a polymerized ionic liquid (PIL) as the solid polymer electrolyte shows an overall energy conversion efficiency (η) of 6.9%, which is much higher than those of neat TiO2 (4.7%) and Nb-doped TiO2 (5.4%). The enhancement of η is mostly due to the increase of current density, attributed to the improved electron transfer properties including electron injection, collection, and plasmonic effects without the negative effects of charge recombination or problems with corrosion. These properties are supported by intensity modulated photocurrent/voltage spectroscopy (IMPS/IMVS) and incident photon-to-electron conversion efficiency (IPCE) measurements.
Warren, Mikako; Matsuno, Ryosuke; Tran, Henry; Shimada, Hiroyuki
2018-03-01
This study evaluated the utility of Phox2b in paediatric tumours. Previously, tyrosine hydroxylase (TH) was the most widely utilised sympathoadrenal marker specific for neural crest tumours with neuronal/neuroendocrine differentiation. However, its sensitivity is insufficient. Recently Phox2b has emerged as another specific marker for this entity. Phox2b immunohistochemistry (IHC) was performed on 159 paediatric tumours, including (group 1) 65 neural crest tumours with neuronal differentiation [peripheral neuroblastic tumours (pNT)]: 15 neuroblastoma undifferentiated (NB-UD), 10 NB poorly differentiated (NB-PD), 10 NB differentiating (NB-D), 10 ganglioneuroblastoma intermixed (GNBi), 10 GNB nodular (GNBn) and 10 ganglioneuroma (GN); (group 2) 23 neural crest tumours with neuroendocrine differentiation [pheochromocytoma/paraganglioma (PCC/PG)]; (group 3) 27 other neural crest tumours including one composite rhabdomyosarcoma/neuroblastoma; and (group 4) 44 non-neural crest tumours. TH IHC was performed on groups 1, 2 and 3. Phox2b was expressed diffusely in pNT (n = 65 of 65), strongly in NB-UD and NB-PD and with less intensity in NB-D, GNB and GN. Diffuse TH was seen in all NB-PD, NB-D, GNB and GN, but nine of 15 NB-UD and a nodule in GNBn did not express TH (n = 55 of 65). PCC/PG expressed diffuse Phox2b (n = 23 of 23) and diffuse TH, except for one tumour (n = 22 of 23). In composite rhabdomyosarcoma, TH was expressed only in neuroblastic cells and Phox2b was diffusely positive in neuroblastic cells and focally in rhabdomyosarcoma. All other tumours were negative for Phox2b (n = none of 44). Phox2b was a specific and sensitive marker for pNT and PCC/PG, especially useful for identifying NB-UD often lacking TH. Our study also presented a composite rhabdomyosarcoma/neuroblastoma of neural crest origin. © 2017 John Wiley & Sons Ltd.
Bousquet, Marina; Quelen, Cathy; Rosati, Roberto; Mansat-De Mas, Véronique; La Starza, Roberta; Bastard, Christian; Lippert, Eric; Talmant, Pascaline; Lafage-Pochitaloff, Marina; Leroux, Dominique; Gervais, Carine; Viguié, Franck; Lai, Jean-Luc; Terre, Christine; Beverlo, Berna; Sambani, Costantina; Hagemeijer, Anne; Marynen, Peter; Delsol, Georges; Dastugue, Nicole; Mecucci, Cristina; Brousset, Pierre
2008-01-01
Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we have shown that this translocation is associated with a strong up-regulation of miR-125b (from 6- to 90-fold). In vitro experiments revealed that miR-125b was able to interfere with primary human CD34+ cell differentiation, and also inhibited terminal (monocytic and granulocytic) differentiation in HL60 and NB4 leukemic cell lines. Therefore, miR-125b up-regulation may represent a new mechanism of myeloid cell transformation, and myeloid neoplasms carrying the t(2;11) translocation define a new clinicopathological entity. PMID:18936236
Liu, Han; Li, Mingqian; Cai, Shunfeng; He, Xinyi; Shao, Yongqi; Lu, Xingmeng
2016-11-01
Nosema bombycis is an obligate intracellular parasitic fungus that utilizes a distinctive mechanism to infect Bombyx mori Spore germination can be used for host cell invasion; however, the detailed mechanism remains to be elucidated. The ricin-B-lectin (RBL) gene is significantly differentially regulated after N. bombycis spore germination, and NbRBL might play roles in spore germination and infection. In this study, the biological function of NbRBL was examined. Protein sequence analysis showed that NbRBL is a secreted protein that attaches to carbohydrates. The relative expression level of the NbRBL gene was low during the first 30 h post-infection (hpi) in BmN cells, and high expression was detected from 42 hpi. Gene cloning, prokaryotic expression, and antibody preparation for NbRBL were performed. NbRBL was detected in total and secreted proteins using western blot analysis. Subcellular localization analysis showed that NbRBL is an intracellular protein. Spore adherence and infection assays showed that NbRBL could enhance spore adhesion to BmN cells; the proliferative activities of BmN cells incubated with anti-NbRBL were higher than those in negative control groups after N. bombycis infection; and the treatment groups showed less damage from spore invasion. We therefore, propose that NbRBL is released during spore germination, enhances spore adhesion to BmN cells, and contributes to spore invasion. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
ATL response to arsenic/interferon therapy is triggered by SUMO/PML/RNF4-dependent Tax degradation.
Dassouki, Zeina; Sahin, Umut; El Hajj, Hiba; Jollivet, Florence; Kfoury, Youmna; Lallemand-Breitenbach, Valérie; Hermine, Olivier; de Thé, Hugues; Bazarbachi, Ali
2015-01-15
The human T-cell lymphotropic virus type I (HTLV-1) Tax transactivator initiates transformation in adult T-cell leukemia/lymphoma (ATL), a highly aggressive chemotherapy-resistant malignancy. The arsenic/interferon combination, which triggers degradation of the Tax oncoprotein, selectively induces apoptosis of ATL cell lines and has significant clinical activity in Tax-driven murine ATL or human patients. However, the role of Tax loss in ATL response is disputed, and the molecular mechanisms driving degradation remain elusive. Here we demonstrate that ATL-derived or HTLV-1-transformed cells are dependent on continuous Tax expression, suggesting that Tax degradation underlies clinical responses to the arsenic/interferon combination. The latter enforces promyelocytic leukemia protein (PML) nuclear body (NB) formation and partner protein recruitment. In arsenic/interferon-treated HTLV-1 transformed or ATL cells, Tax is recruited onto NBs and undergoes PML-dependent hyper-sumoylation by small ubiquitin-like modifier (SUMO)2/3 but not SUMO1, ubiquitination by RNF4, and proteasome-dependent degradation. Thus, the arsenic/interferon combination clears ATL through degradation of its Tax driver, and this regimen could have broader therapeutic value by promoting degradation of other pathogenic sumoylated proteins. © 2015 by The American Society of Hematology.
Novel MDM2 inhibitor SAR405838 (MI-773) induces p53-mediated apoptosis in neuroblastoma
Lu, Jiaxiong; Guan, Shan; Zhao, Yanling; Yu, Yang; Wang, Yongfeng; Shi, Yonghua; Mao, Xinfang; Yang, Kristine L.; Sun, Wenjing; Xu, Xin; Yi, Joanna S.; Yang, Tianshu; Yang, Jianhua; Nuchtern, Jed G.
2016-01-01
Neuroblastoma (NB), which accounts for about 15% of cancer-related mortality in children, is the most common childhood extracranial malignant tumor. In NB, somatic mutations of the tumor suppressor, p53, are exceedingly rare. Unlike in adult tumors, the majority of p53 downstream functions are still intact in NB cells with wild-type p53. Thus, restoring p53 function by blocking its interaction with p53 suppressors such as MDM2 is a viable therapeutic strategy for NB treatment. Herein, we show that MDM2 inhibitor SAR405838 is a potent therapeutic drug for NB. SAR405838 caused significantly decreased cell viability of p53 wild-type NB cells and induced p53-mediated apoptosis, as well as augmenting the cytotoxic effects of doxorubicin (Dox). In an in vivo orthotopic NB mouse model, SAR405838 induced apoptosis in NB tumor cells. In summary, our data strongly suggest that MDM2-specific inhibitors like SAR405838 may serve not only as a stand-alone therapy, but also as an effective adjunct to current chemotherapeutic regimens for treating NB with an intact MDM2-p53 axis. PMID:27764791
NASA Astrophysics Data System (ADS)
Li, Jianhua; Qiu, Jichuan; Guo, Weibo; Wang, Shu; Ma, Baojin; Mou, Xiaoning; Tanes, Michael; Jiang, Huaidong; Liu, Hong
2016-03-01
Second harmonic generation (SHG) nanocrystals have recently been reported to label cancer cells and other functional cell lines due to their unique double-frequency property. In this paper, we report for the first time the use of lithium niobate (LiNbO3, LN) nanocrystals as SHG labels for imaging stem cells. Rat mesenchymal stem cells (rMSCs) were labeled with LN nanocrystals in order to study the cellular internalization of the nanocrystals and the influence on stem cell differentiation. The results showed that LN nanocrystals were endocytosed by the rMSCs and the distribution of the internalized nanoparticles demonstrated a high consistency with the orientation of the actin filaments. Besides, LN-labeled rMSCs showed a concentration-dependent viability. Most importantly, rMSCs labeled with 50 μg per mL of LN nanocrystals retained their ability to differentiate into both osteogenic and adipogenic lineages. The results prove that LN nanocrystals can be used as a cytocompatible, near-infrared (NIR) light driven cell label for long-term imaging, without hindering stem cell differentiation. This work will promote the use of LN nanocrystals to broader applications like deep-tissue tracking, remote drug delivery and stem cell therapy.Second harmonic generation (SHG) nanocrystals have recently been reported to label cancer cells and other functional cell lines due to their unique double-frequency property. In this paper, we report for the first time the use of lithium niobate (LiNbO3, LN) nanocrystals as SHG labels for imaging stem cells. Rat mesenchymal stem cells (rMSCs) were labeled with LN nanocrystals in order to study the cellular internalization of the nanocrystals and the influence on stem cell differentiation. The results showed that LN nanocrystals were endocytosed by the rMSCs and the distribution of the internalized nanoparticles demonstrated a high consistency with the orientation of the actin filaments. Besides, LN-labeled rMSCs showed a concentration-dependent viability. Most importantly, rMSCs labeled with 50 μg per mL of LN nanocrystals retained their ability to differentiate into both osteogenic and adipogenic lineages. The results prove that LN nanocrystals can be used as a cytocompatible, near-infrared (NIR) light driven cell label for long-term imaging, without hindering stem cell differentiation. This work will promote the use of LN nanocrystals to broader applications like deep-tissue tracking, remote drug delivery and stem cell therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00785f
Kotapalli, Sudha Sravanti; Dasari, Chandrashekhar; Duscharla, Divya; Kami Reddy, Karthik Reddy; Kasula, Manjula; Ummanni, Ramesh
2017-12-01
Tumor protein D52 (TPD52), a proto-oncogene is overexpressed in a variety of epithelial carcinomas and plays an important role in cell proliferation, migration, and cell death. In the present study we found that the treatment of IMR-32 neuroblastoma (NB) cells with retinoic acid (RA) stimulates an increase in expression of TPD52. TPD52 expression is detectable after 72 h, can be maintained till differentiation of NB cells suggesting that TPD52 is involved in differentiation. Here, we demonstrate that TPD52 is essential for RA to promote differentiation of NB cells. Our results show that exogenous expression of EGFP-TPD52 in IMR-32 cells resulted cell differentiation even without RA. RA by itself and with overexpression of TPD52 can increase the ability of NB cells differentiation. Interestingly, transfection of IMR-32 cells with a specific small hairpin RNA for efficient knockdown of TPD52 attenuated RA induced NB cells differentiation. Transcriptional and translational level expression of neurotropic (BDNF, NGF, Nestin) and differentiation (β III tubulin, NSE, TH) factors in NB cells with altered TPD52 expression and/or RA treatment confirmed essential function of TPD52 in cellular differentiation. Furthermore, we show that TPD52 protects cells from apoptosis and arrest cell proliferation by varying expression of p27Kip1, activation of Akt and ERK1/2 thus promoting cell differentiation. Additionally, inhibition of STAT3 activation by its specific inhibitor arrested NB cells differentiation by EGFP-TPD52 overexpression with or without RA. Taken together, our data reveal that TPD52 act through activation of JAK/STAT signaling pathway to undertake NB cells differentiation induced by RA. J. Cell. Biochem. 118: 4358-4369, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Inductance analysis of superconducting quantum interference devices with 3D nano-bridge junctions
NASA Astrophysics Data System (ADS)
Wang, Hao; Yang, Ruoting; Li, Guanqun; Wu, Long; Liu, Xiaoyu; Chen, Lei; Ren, Jie; Wang, Zhen
2018-05-01
Superconducting quantum interference devices (SQUIDs) with 3D nano-bridge junctions can be miniaturized into nano-SQUIDs that are able to sense a few spins in a large magnetic field. Among all device parameters, the inductance is key to the performance of SQUIDs with 3D nano-bridge junctions. Here, we measured the critical-current magnetic flux modulation curves of 12 devices with three design types using a current strip-line directly coupled to the SQUID loop. A best flux modulation depth of 71% was achieved for our 3D Nb SQUID. From the modulation curves, we extracted the inductance values of the current stripe-line in each design and compared them with the corresponding simulation results of InductEX. In this way, London penetration depths of 110 and 420 nm were determined for our Nb (niobium) and NbN (niobium nitride) films, respectively. Furthermore, we showed that inductances of 11 and 119 pH for Nb and NbN 3D nano-bridge junctions, respectively, dominated the total inductance of our SQUID loops which are 23 pH for Nb and 255 pH for NbN. A screening parameter being equal to one suggests optimal critical currents of 89.6 and 8.1 μA for Nb and NbN SQUIDs, respectively. Additionally, intrinsic flux noise of 110 ± 40 nΦ0/(Hz)1/2 is calculated for the Nb SQUIDs with 3D nano-bridge junctions by Langevin simulation.
Xu, Wei; Li, Ming; Wen, Cuie; Lv, Shaomin; Liu, Chengcheng; Lu, Xin; Qu, Xuanhui
2018-03-30
A biocompatible Ti-28Nb-35.4Zr alloy used as bone implant was fabricated through the powder metallurgy process. The effects of mechanical milling and sintering temperatures on the microstructure and mechanical properties were investigated systematically, before in vitro biocompatibility of full dense Ti-28Nb-35.4Zr alloy was evaluated by cytotoxicity tests. The results show that the mechanical milling and sintering temperatures have significantly effects on the density and mechanical properties of the alloys. The relative density of the alloy fabricated by the atomized powders at 1500 °C is only 83 ± 1.8%, while the relative density of the alloy fabricated by the ball-milled powders can rapidly reach at 96.4 ± 1.3% at 1500 °C. When the temperature was increased to 1550 °C, the alloy fabricated by ball-milled powders achieve full density (relative density is 98.1 ± 1.2%). The PM-fabricated Ti-28Nb-35.4Zr alloy by ball-milled powders at 1550 °C can achieve a wide range of mechanical properties, with a compressive yield strength of 1058 ± 35.1 MPa, elastic modulus of 50.8 ± 3.9 GPa, and hardness of 65.8 ± 1.5 HRA. The in vitro cytotoxicity test suggests that the PM-fabricated Ti-28Nb-35.4Zr alloy by ball-milled powders at 1550 °C has no adverse effects on MC3T3-E1 cells with cytotoxicity ranking of 0 grade, which is nearly close to ELI Ti-6Al-4V or CP Ti. These properties and the net-shape manufacturability makes PM-fabricated Ti-28Nb-35.4Zr alloy a low-cost, highly-biocompatible, Ti-based biomedical alloy.
Calcium-regulatory proteins as modulators of chemotherapy in human neuroblastoma
Florea, Ana-Maria; Varghese, Elizabeth; McCallum, Jennifer E.; Mahgoub, Safa; Helmy, Irfan; Varghese, Sharon; Gopinath, Neha; Sass, Steffen; Theis, Fabian J.; Reifenberger, Guido; Büsselberg, Dietrich
2017-01-01
Neuroblastoma (NB) is a pediatric cancer treated with poly-chemotherapy including platinum complexes (e.g. cisplatin (CDDP), carboplatin), DNA alkylating agents, and topoisomerase I inhibitors (e.g. topotecan (TOPO)). Despite aggressive treatment, NB may become resistant to chemotherapy. We investigated whether CDDP and TOPO treatment of NB cells interacts with the expression and function of proteins involved in regulating calcium signaling. Human neuroblastoma cell lines SH-SY5Y, IMR-32 and NLF were used to investigate the effects of CDDP and TOPO on cell viability, apoptosis, calcium homeostasis, and expression of selected proteins regulating intracellular calcium concentration ([Ca2+]i). In addition, the impact of pharmacological inhibition of [Ca2+]i-regulating proteins on neuroblastoma cell survival was studied. Treatment of neuroblastoma cells with increasing concentrations of CDDP (0.1−10 μM) or TOPO (0.1 nM−1 μM) induced cytotoxicity and increased apoptosis in a concentration- and time-dependent manner. Both drugs increased [Ca2+]i over time. Treatment with CDDP or TOPO also modified mRNA expression of selected genes encoding [Ca2+]i-regulating proteins. Differentially regulated genes included S100A6, ITPR1, ITPR3, RYR1 and RYR3. With FACS and confocal laser scanning microscopy experiments we validated their differential expression at the protein level. Importantly, treatment of neuroblastoma cells with pharmacological modulators of [Ca2+]i-regulating proteins in combination with CDDP or TOPO increased cytotoxicity. Thus, our results confirm an important role of calcium signaling in the response of neuroblastoma cells to chemotherapy and suggest [Ca2+]i modulation as a promising strategy for adjunctive treatment. PMID:28206967
Round Robin Test of Residual Resistance Ratio of Nb$$_3$$Sn Composite Superconductors
Matsushita, Teruo; Otabe, Edmund Soji; Kim, Dong Ho; ...
2017-12-07
A round robin test of residual resistance ratio (RRR) was performed for Nb 3Sn composite superconductors prepared by internal tin method by six institutes with the international standard test method described in IEC 61788-4. It was found that uncertainty mainly resulted from determination of the cryogenic resistance from the intersection of two straight lines drawn to fit the voltage vs. temperature curve around the resistive transition. As a result, the measurement clarified that RRR can be measured with expanded uncertainty not larger than 5% with the coverage factor 2 by using this test method.
Round Robin Test of Residual Resistance Ratio of Nb$$_3$$Sn Composite Superconductors
DOE Office of Scientific and Technical Information (OSTI.GOV)
Matsushita, Teruo; Otabe, Edmund Soji; Kim, Dong Ho
A round robin test of residual resistance ratio (RRR) was performed for Nb 3Sn composite superconductors prepared by internal tin method by six institutes with the international standard test method described in IEC 61788-4. It was found that uncertainty mainly resulted from determination of the cryogenic resistance from the intersection of two straight lines drawn to fit the voltage vs. temperature curve around the resistive transition. As a result, the measurement clarified that RRR can be measured with expanded uncertainty not larger than 5% with the coverage factor 2 by using this test method.
Double perovskite Ca2GdNbO6:Mn4+ deep red phosphor: Potential application for warm W-LEDs
NASA Astrophysics Data System (ADS)
Lu, Zuizhi; Huang, Tianjiao; Deng, Ruopeng; Wang, Huan; Wen, Lingling; Huang, Meixin; Zhou, Liya; Yao, Chunying
2018-05-01
A novel Mn4+-doped Ca2GdNbO6 (CGN) phosphor was prepared by high-temperature solid-state reaction. The crystal structure was investigated by X-ray diffraction patterns and unit cell structure. Mn4+ replaced the location of Nb5+ in the CGN lattice, and the value of energy gap (Egap) decreased from 2.16 eV to 1.13 eV, indicating that Mn4+ ions play a great influence on the absorption of CGN hosts. The broad excitation band from 250 nm to 550 nm matches well with commercial near-UV light emitting diodes, and the emission peak centered at 680 nm is due to 2E→4A2g transition in Mn4+ ions. The CIE chromaticity coordinates (0.698, 0.303) of CGN:Mn4+ phosphor was close to standard red color coordinates (0.666, 0.333). These investigations demonstrate CGN:Mn4+ phosphor as an efficient red phosphor for potential applications.
Tumor SHB gene expression affects disease characteristics in human acute myeloid leukemia.
Jamalpour, Maria; Li, Xiujuan; Cavelier, Lucia; Gustafsson, Karin; Mostoslavsky, Gustavo; Höglund, Martin; Welsh, Michael
2017-10-01
The mouse Shb gene coding for the Src Homology 2-domain containing adapter protein B has recently been placed in context of BCRABL1-induced myeloid leukemia in mice and the current study was performed in order to relate SHB to human acute myeloid leukemia (AML). Publicly available AML databases were mined for SHB gene expression and patient survival. SHB gene expression was determined in the Uppsala cohort of AML patients by qPCR. Cell proliferation was determined after SHB gene knockdown in leukemic cell lines. Despite a low frequency of SHB gene mutations, many tumors overexpressed SHB mRNA compared with normal myeloid blood cells. AML patients with tumors expressing low SHB mRNA displayed longer survival times. A subgroup of AML exhibiting a favorable prognosis, acute promyelocytic leukemia (APL) with a PMLRARA translocation, expressed less SHB mRNA than AML tumors in general. When examining genes co-expressed with SHB in AML tumors, four other genes ( PAX5, HDAC7, BCORL1, TET1) related to leukemia were identified. A network consisting of these genes plus SHB was identified that relates to certain phenotypic characteristics, such as immune cell, vascular and apoptotic features. SHB knockdown in the APL PMLRARA cell line NB4 and the monocyte/macrophage cell line MM6 adversely affected proliferation, linking SHB gene expression to tumor cell expansion and consequently to patient survival. It is concluded that tumor SHB gene expression relates to AML survival and its subgroup APL. Moreover, this gene is included in a network of genes that plays a role for an AML phenotype exhibiting certain immune cell, vascular and apoptotic characteristics.
PD and PDT for hepatoblastoma? Preclinical considerations
NASA Astrophysics Data System (ADS)
Stepp, Herbert; Bergmann, Florian; Johansson, Ann; Heide, Michael; Metzger, Roman; Rolle, Udo; Till, Holger
2011-07-01
Objective: Provide preclinical data on the feasibility of 5-aminolevulinic acid (5-ALA) -based photodetection (PD) and Photodynamic Therapy (PDT) of early childhood tumors. Methods: Hepatoblastoma (HuH6), neuroblastoma (MHH-NB11) and N1-fibroblast cell lines were tested for their relative capacities to synthesize Protoporphyrin IX (PpIX) from 5-ALA and for their susceptibility to PDT in vitro. HuH6-cells were also inoculated in the peritoneum of rats. The pharmacokinetics of porphyrin accumulation was measured in 9 rats by laparoscopic spectroscopy. 5-ALA was applied by i.p. injection of 500 mg/kg bw. In another 21 animals, tumors (n=20), liver (n=5) and peritoneum (n=4) were treated by PDT laparoscopically. 48 h after irradiation, animals were again incubated with 5-ALA and then sacrificed and tissues were removed for further investigation. Results: Both tumor cell lines showed higher levels of porphyrin fluorescence than the fibroblasts. Cell viability testing proved the HuH6 cells to be most susceptible to PDT. Pharmacokinetic measurements of PpIX in xenografted tumors showed a peak at 80-200 min after i.p. injection of 5-ALA. Irradiation resulted in pronounced photobleaching at all irradiated sites and necrosis of tumor and liver tissue, whereas peritoneum appeared to remain unaffected. Necrosis induced by PDT could be seen in fluorescence microscopy due to the lack of porphyrin synthesis in necrotic tissue after the re-incubation with 5-ALA.
Results from the first single cell Nb 3Sn cavity coatings at JLab
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eremeev, Grigory
2015-09-01
Nb 3Sn is a promising superconducting material for SRF applications and has the potential to exceed the limitations of niobium. We have used the recently commissioned Nb 3Sn coating system to investigate Nb 3Sn coatings on several single cell cavities by applying the same coating procedure on several different single cells with different history and pre-coating surface preparation. We report on our findings with four 1.5 GHz CEBAF-shape single cell and one 1.3 GHz ILC-shape single cavities that were coated, inspected, and tested.
NASA Astrophysics Data System (ADS)
Sanloup, C.; Cochain, B.; de Grouchy, C.; Glazyrin, K.; Konôpkova, Z.; Liermann, H.-P.; Kantor, I.; Torchio, R.; Mathon, O.; Irifune, T.
2018-02-01
Niobium (Nb) is one of the key trace elements used to understand Earth’s formation and differentiation, and is remarkable for its deficiency relative to tantalum in terrestrial rocks compared to the building chondritic blocks. In this context, the local environment of Nb in silica-rich melts and glasses is studied by in situ x-ray absorption spectroscopy (XAS) at high pressure (P) up to 9.3 GPa and 1350 K using resistive-heating diamond-anvil cells. Nb is slightly less oxidized in the melt (intermediate valence between +4 and +5) than in the glass (+5), an effect evidenced from the shift of the Nb-edge towards lower energies. Changes in the pre-edge features are also observed between melt and glass states, consistently with the observed changes in oxidation state although likely enhanced by temperature (T) effects. The oxidation state of Nb is not affected by pressure neither in the molten nor glassy states, and remains constant in the investigated P-range. The Nb-O coordination number is constant and equal to 6.3+/-0.4 below 5 GPa, and only progressively increases up to 7.1+/-0.4 at 9.3 GPa, the maximum P investigated. If these findings were to similarly apply to basaltic melts, that would rule out the hypothesis of Nb/Ta fractionation during early silicate Earth’s differentiation, thus reinforcing the alternative hypothesis of fractionation during core formation on reduced pre-planetary bodies.
Paria Sena, Robert; Babaryk, Artem A; Khainakov, Sergiy; Garcia-Granda, Santiago; Slobodyanik, Nikolay S; Van Tendeloo, Gustaaf; Abakumov, Artem M; Hadermann, Joke
2016-01-21
The crystal structure of the K6.4Nb28.2Ta8.1O94 pseudo-tetragonal tungsten bronze-type oxide was determined using a combination of X-ray powder diffraction, neutron diffraction and transmission electron microscopy techniques, including electron diffraction, high angle annular dark field scanning transmission electron microscopy (HAADF-STEM), annular bright field STEM (ABF-STEM) and energy-dispersive X-ray compositional mapping (STEM-EDX). The compound crystallizes in the space group Pbam with unit cell parameters a = 37.468(9) Å, b = 12.493(3) Å, c = 3.95333(15) Å. The structure consists of corner sharing (Nb,Ta)O6 octahedra forming trigonal, tetragonal and pentagonal tunnels. All tetragonal tunnels are occupied by K(+) ions, while 1/3 of the pentagonal tunnels are preferentially occupied by Nb(5+)/Ta(5+) and 2/3 are occupied by K(+) in a regular pattern. A fractional substitution of K(+) in the pentagonal tunnels by Nb(5+)/Ta(5+) is suggested by the analysis of the HAADF-STEM images. In contrast to similar structures, such as K2Nb8O21, also parts of the trigonal tunnels are fractionally occupied by K(+) cations.
Alfonso, Pilar; Pampín, Sandra; Estrada, Jorge; Rodríguez-Rey, José Carlos; Giraldo, Pilar; Sancho, Javier; Pocoví, Miguel
2005-01-01
Gaucher disease (GD) is a disorder of glycosphinglipid metabolism caused by deficiency of lysosomal acid beta-glucosidase (GC), resulting in progressive deposition of glucosylceramide in macrophages. The glucose analogue, N-butyl-deoxynojirimycin (NB-DNJ, Miglustat), is an inhibitor of the ceramide-specific glucosyltransferase (CSG) which catalyzes the first step of glycosphingolipids biosynthesis and is currently approved for the oral treatment of type 1 GD. Using site-directed mutagenesis, we constructed plasmids containing wild-type and several mutations in glucocerebrosidase (GBA) gene. The plasmids were transfected into COS-7 cells and stable transfected cell lines were obtained by geneticin (G418) selection. Cells were cultured during 6 days with medium with or without 10 microM NB-DNJ. The addition of NB-DNJ to COS-7 cell medium leads to 1.3-, 2.1-, 2.3-, 3.6-, and 9.9-fold increase in the activity of S364R, wild-type, N370S, V15M, and M123T GC, respectively. However, no significant changes were observed in the activity of the L444P, L336P, and S465del mutated proteins, but a small decrease in the rare P266L variant was observed. These results suggest that NB-DNJ, in addition to the inhibitory effect on CSG, also works as a "chemical chaperone", increasing the activity of acid beta-glucosidase of wild-type and several GC mutated proteins, including the most frequent N370S mutation. The specific location of the Miglustat binding site in GC is unknown. Potential binding sites in the enzyme have been searched for using computational molecular docking. The searching strategy identified three potential GC binding sites for Miglustat, one being the substrate-binding site of the enzyme, which was the best-ranked site by AutoDock program. Therefore, it is possible that Miglustat exerts its chaperoning activity on acid beta-glucosidase by acting as an inhibitor bound at the active site. This increase on the activity of the acid beta-glucosidase would imply that Miglustat is not only a substrate reducer but also an inhibitor of the GC degradation, with very promising clinical implications for the treatment of GD patients.
Degradation of Chloronitrobenzenes by a Coculture of Pseudomonas putida and a Rhodococcus sp.
Park, Hee-Sung; Lim, Sung-Jin; Chang, Young Keun; Livingston, Andrew G.; Kim, Hak-Sung
1999-01-01
A single microorganism able to mineralize chloronitrobenzenes (CNBs) has not been reported, and degradation of CNBs by coculture of two microbial strains was attempted. Pseudomonas putida HS12 was first isolated by analogue enrichment culture using nitrobenzene (NB) as the substrate, and this strain was observed to possess a partial reductive pathway for the degradation of NB. From high-performance liquid chromatography-mass spectrometry and 1H nuclear magnetic resonance analyses, NB-grown cells of P. putida HS12 were found to convert 3- and 4-CNBs to the corresponding 5- and 4-chloro-2-hydroxyacetanilides, respectively, by partial reduction and subsequent acetylation. For the degradation of CNBs, Rhodococcus sp. strain HS51, which degrades 4- and 5-chloro-2-hydroxyacetanilides, was isolated and combined with P. putida HS12 to give a coculture. This coculture was confirmed to mineralize 3- and 4-CNBs in the presence of an additional carbon source. A degradation pathway for 3- and 4-CNBs by the two isolated strains was also proposed. PMID:10049867
Two-Dimensional Nb-Based M 4 C 3 Solid Solutions (MXenes)
Yang, Jian; Naguib, Michael; Ghidiu, Michael; ...
2015-10-15
Two new two-dimensional Nb 4C 3-based solid solutions (MXenes), (Nb 0.8,Ti 0.2) 4C 3T x and (Nb 0.8,Zr 0.2) 4C 3T x (where T is a surface termination) were synthesizedas confirmed by X-ray diffractionfrom their corresponding MAX phase precursors (Nb 0.8,Ti 0.2) 4AlC 3 and (Nb 0.8,Zr 0.2) 4AlC 3. In our report we discuss Zr-containing MXene. We also studied intercalation of Li ions into these two compositions, and Nb 4C 3T x in order to determine the potential of those materials for energy storage applications. Lithiation and delithiation peaks at 2.26 and 2.35 V, respectively, appeared in the casemore » of Nb 4C 3T x, but were not present in Nb 2CT x. After 20 cycles at a rate of C/4, the specific capacities of (Nb 0.8,Ti 0.2) 4C 3T xand (Nb 0.8,Ti 0.2) 4C 3T x were 158 and 132 mAh/g, respectively, both slightly lower than the capacity of Nb 4C 3T x.« less
NASA Astrophysics Data System (ADS)
Tellekamp, M. Brooks; Greenlee, Jordan D.; Shank, Joshua C.; Doolittle, W. Alan
2015-09-01
In order to consistently grow high quality niobium oxides and lithium niobium oxides, a novel solid/liquid state oxygen source, LiClO4, has been implemented in a molecular beam epitaxy (MBE) system. LiClO4 is shown to decompose into both molecular and atomic oxygen upon heating. This allows oxidation rates similar to that of molecular oxygen but at a reduced overall beam flux, quantified by in situ Auger analysis. LiClO4 operation is decomposition limited to less than 400 °C, and other material limitations are identified. The design of a custom near-ambient NbCl5 effusion cell is presented, which improves both short and long term stability. Films of Nb oxidation state +2, +3, and +5 are grown using these new tools, including the multi-functional sub-oxide LiNbO2.
Singh, Alok R.; Joshi, Shweta; Vega, Francisco M.; Guo, Pinzheng; Xu, Jingying; Groshen, Susan; Ye, Wei; Millard, Melissa; Campan, Mihaela; Morales, Guillermo; Garlich, Joseph R.; Laird, Peter W.; Seeger, Robert C.; Shimada, Hiroyuki
2017-01-01
Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies showed that the angiogenic integrin αvβ3 was increased in high-risk metastatic (stage 4) NB compared with localized neuroblastomas. Herein, we show that integrin αvβ3 was expressed on 68% of microvessels in MYCN-amplified stage 3 neuroblastomas, but only on 34% (means) in MYCN-non-amplified tumors (p < 0.001; n = 54). PTEN, a tumor suppressor involved in αvβ3 signaling, was expressed in neuroblastomas either diffusely, focally or not at all (immunohistochemistry). Integrin αvβ3 was expressed on 60% of tumor microvessels when PTEN was negative or focal, as compared to 32% of microvessels in tumors with diffuse PTEN expression (p < 0.001). In a MYCN transgenic mouse model, loss of one allele of PTEN promoted tumor growth, illustrating the potential role of PTEN in neuroblastoma pathogenesis. Interestingly, we report the novel dual PI-3K/BRD4 activity of SF1126 (originally developed as an RGD-conjugated pan PI3K inhibitor). SF1126 inhibits BRD4 bromodomain binding to acetylated lysine residues with histone H3 as well as PI3K activity in the MYCN amplified neuroblastoma cell line IMR-32. Moreover, SF1126 suppressed MYCN expression and MYCN associated transcriptional activity in IMR-32 and CHLA136, resulting in overall decrease in neuroblastoma cell viability. Finally, treatment of neuroblastoma tumors with SF1126 inhibited neuroblastoma growth in vivo. These data suggest integrin αvβ3, MYCN/BRD4 and PTEN/PI3K/AKT signaling as biomarkers and hence therapeutic targets in neuroblastoma and support testing of the RGD integrin αvβ3-targeted PI-3K/BRD4 inhibitor, SF1126 as a therapeutic strategy in this specific subgroup of high risk neuroblastoma. PMID:28881723
Martin, Guenter; Biryukov, Sergey V; Schmidt, Hagen; Steiner, Bernd; Wall, Bert
2011-03-01
SPUDT cells including two fingers are only known thus far for so-called NSPUDT directions. In that case, usual solid-finger cells are used. The purpose of the present paper is to find SPUDT cell types consisting of two fingers only for pure mode directions. Two-finger (TF) cells for pure mode directions on substrates like 128°YX LiNbO(3) and YZ LiNbO(3) were found by means of an optimization procedure. The forward direction of a TF-cell SPUDT on 128°YX LiNbO(3) was determined experimentally. The properties of the new cells are compared with those of conventional SPUDT cells. The reflectivity of TF cells on 128°YX LiNbO(3) turns out to be two to three times larger than that of distributed acoustic reflection transducer (DART) and Hanma-Hunsinger cells at the same metal layer thickness.
Ion, Raluca; Gordin, Doina-Margareta; Mitran, Valentina; Osiceanu, Petre; Dinescu, Sorina; Gloriant, Thierry; Cimpean, Anisoara
2014-02-01
The materials used for internal fracture fixations and joint replacements are mainly made of metals which still face problems ranging from higher rigidity than that of natural bone to leaching cytotoxic metallic ions. Beta (β)-type titanium alloys with low elastic modulus made from non-toxic and non-allergenic elements are desirable to reduce stress shielding effect and enhance bone remodeling. In this work, a new β-type Ti-23Nb-0.7Ta-2Zr-0.5N alloy with a Young's modulus of approximately 50 GPa was designed and characterized. The behavior of MC3T3-E1 pre-osteoblasts on the new alloy, including adhesion, proliferation and differentiation, was evaluated by examining the cytoskeleton, focal adhesion formation, metabolic activity and extracellular matrix mineralization. Results indicated that the pre-osteoblast cells exhibited a similar degree of attachment and growth on Ti-23Nb-0.7Ta-2Zr-0.5N and Ti-6Al-4V. However, the novel alloy proved to be significantly more efficient in sustaining mineralized matrix deposition upon osteogenic induction of the cells than Ti-6Al-4V control. Further, the analysis of RAW 264.7 macrophages cytokine gene and protein expression indicated no significant inflammatory response. Collectively, these findings suggest that the Ti-23Nb-0.7Ta-2Zr-0.5N alloy, which has an increased mechanical biocompatibility with bone, allows a better osteogenic differentiation of osteoblast precursor cells than Ti-6Al-4V and holds great potential for future clinical prosthetic applications. Copyright © 2013 Elsevier B.V. All rights reserved.
Adhesion of Streptococcus sanguis CH3 to polymers with different surface free energies.
van Pelt, A W; Weerkamp, A H; Uyen, M H; Busscher, H J; de Jong, H P; Arends, J
1985-01-01
The adhesion of the oral bacterium Streptococcus sanguis CH3 to various polymeric surfaces with surface free energies (gamma s) ranging from 22 to 141 erg cm-2 was investigated. Suspensions containing nine different bacterial concentrations (2.5 X 10(7) to 2.5 X 10(9) cells per ml) were used. After adhesion for 1 h at 21 degrees C and a standardized rinsing procedure, the number of attached bacteria per square centimeter (nb) was determined by scanning electron microscopy. The highest number of bacteria was consistently found on polytetrafluorethylene (gamma s = 22 erg cm-2), and the lowest number was found on glass (gamma s = 141 erg cm-2) at all bacterial concentrations tested. The overall negative correlation between nb and gamma s was weak. However, the slope of the line showing this decrease, calculated from an assumed linear relationship between nb and gamma s, appeared to depend strongly on the bacterial concentration and increased with increasing numbers of bacteria in the suspension. Analysis of the data for each separate polymer showed that the numbers of attached cells on polyvinyl chloride and polypropylene were higher but that those on polycarbonate were lower than would be expected on basis of a linear relationship between nb and gamma s. Desorption experiments were performed by first allowing the bacteria to attach to substrata for 1 h, after which the substrata and attached bacteria were removed to bacterial suspensions containing 10-fold lower bacterial concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:4004241
Heidelmann, Markus; Barthel, Juri; Cox, Gerhard; Weirich, Thomas E
2014-10-01
The atomic structure of Cs0.44[Nb2.54W2.46O14] closely resembles the structure of the most active catalyst for the synthesis of acrylic acid, the M1 phase of Mo10V2(4+)Nb2TeO42-x. Consistently with observations made for the latter compound, the high-angle electron scattering signal recorded by scanning transmission electron microscopy shows a significant intensity variation, which repeats periodically with the projected crystallographic unit cell. The occupation factors for the individual mixed Nb/W atomic columns are extracted from the observed intensity variations. For this purpose, experimental images and simulated images are compared on an identical intensity scale, which enables a quantification of the cation distribution. According to our analysis specific sites possess low tungsten concentrations of 25%, whereas other sites have tungsten concentrations above 70%. These findings allow us to refine the existing structure model of the target compound, which has until now described a uniform distribution of the niobium and tungsten atoms in the unit cell, showing that the similarity between Cs0.44[Nb2.54W2.46O14] and the related catalytic compounds also extends to the level of the cation segregation.
NASA Astrophysics Data System (ADS)
Popa, Monica; Calderon Moreno, Jose Maria; Vasilescu, Cora; Drob, Silviu Iulian; Neacsu, Elena Ionela; Coer, Andrej; Hmeljak, Julija; Zerjav, Gregor; Milošev, Ingrid
2014-06-01
This article analyses the microstructure, electrochemical behavior, and biocompatibility of a novel Ti-20Nb-10Zr-5Ta alloy with low Young's modulus (59 GPa) much closer to that of bone, between 10 and 30 GPa, than Ti and other Ti alloys used as implant biomaterial. XRD and SEM measurements revealed a near β crystalline microstructure containing β phase matrix and secondary α phase, with a typical grain size of around 200 μm. The corrosion behavior in neutral Ringer solution evidenced: self-passivation behavior characterizing a very resistant passive film; an easy passivation as a result of favorable influence of the alloying elements Nb, Zr, and Ta that participate with their passive oxides to the formation of the alloy passive film; low corrosion and ion release rates corresponding with very low toxicity. In MEM solution, the novel alloy demonstrated very high corrosion resistance and no susceptibility to localized corrosion. Biocompatibility was evaluated on in vitro human osteoblast-like and human immortalized pulmonary fibroblast cell (Wi-38) lines and the new Ti-20Nb-10Zr-5Ta alloy exhibited no cytotoxicity. The new Ti-20Nb-10Zr5Ta alloy is a promising material for implants due to combined properties of low elastic modulus, very low corrosion rate, and good biocompatibility.
Liu, Xiaodan; Liao, Wang; Peng, Hongxia; Luo, Xuequn; Luo, Ziyan; Jiang, Hua; Xu, Ling
2016-01-01
Abnormal expression of miRNAs is intimately related to a variety of human cancers. The purpose of this study is to confirm the expression of miR-181a and elucidate its physiological function and mechanism in pediatric acute myeloid leukemia (AML). Pediatric AML patients and healthy controls were enrolled, and the expression of miR-181a and ataxia telangiectasia mutated (ATM) in tissues were examined using quantitative PCR. Moreover, cell proliferation and cell cycle were evaluated in several cell lines (HL60, NB4 and K562) by using flow cytometry after transfected with miR-181a mimics and inhibitors, or ATM siRNA and control siRNA. Finally, ATM as the potential target protein of miR-181a was examined. We found that miR-181a was significantly increased in pediatric AML, which showed an inverse association with ATM expression. Overexpressed miR-181a in cell lines significantly enhanced cell proliferation, as well as increased the ratio of S-phase cells by miR-181a mimics transfection in vitro. Luciferase activity of the reporter construct identified ATM as the direct molecular target of miR-181a. ATM siRNA transfection significantly enhanced cell proliferation and increased the ratio of S-phase cells in vitro. The results revealed novel mechanism through which miR-181a regulates G1/S transition and cell proliferation in pediatric AML by regulating the tumor suppressor ATM, providing insights into the molecular mechanism in pediatric AML.
Guo, Weiwei; Lv, Hongjin; Sullivan, Kevin P; Gordon, Wesley O; Balboa, Alex; Wagner, George W; Musaev, Djamaladdin G; Bacsa, John; Hill, Craig L
2016-06-20
A wide range of chemical warfare agents and their simulants are catalytically decontaminated by a new one-dimensional polymeric polyniobate (P-PONb), K12 [Ti2 O2 ][GeNb12 O40 ]⋅19 H2 O (KGeNb) under mild conditions and in the dark. Uniquely, KGeNb facilitates hydrolysis of nerve agents Sarin (GB) and Soman (GD) (and their less reactive simulants, dimethyl methylphosphonate (DMMP)) as well as mustard (HD) in both liquid and gas phases at ambient temperature and in the absence of neutralizing bases or illumination. Three lines of evidence establish that KGeNb removes DMMP, and thus likely GB/GD, by general base catalysis: a) the k(H2 O)/k(D2 O) solvent isotope effect is 1.4; b) the rate law (hydrolysis at the same pH depends on the amount of P-PONb present); and c) hydroxide is far less active against the above simulants at the same pH than the P-PONbs themselves, a critical control experiment. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Tailoring Ba3Ca1.18Nb1.82O9-δ with NiO as electrolyte for proton-conducting solid oxide fuel cells
NASA Astrophysics Data System (ADS)
Zhu, Zhiwen; Guo, Enyan; Wei, Zhaoling; Wang, Huiqiang
2018-01-01
A strategy of tailoring Ba3Ca1.18Nb1.82O9-δ (BCN) is proposed, aiming to improve the sinterability and conductivity of BCN material for fuel cell applications. The new Ba3Ca1.18Nb1.77Ni0.05O9-δ (BCNNi) material shows a significant improvement in sinterability compared with BCN, leading to a high densification for BCNNi after sintering at as low as 1400 °C. In addition, the BCNNi exhibits a conductivity of 4.59 × 10-3 S cm-1 at 700 °C that is not only higher than that for BCN which only reaches 3.45 × 10-3 S cm-1 at the same temperature but also shows a significant improvement compared with that for BCN-based materials in literature reports. As a result, the cell with the BCNNi electrolyte shows a peak power density of 84 mW cm-2 at 700 °C which is also one of the largest ever reported for this type of cells. Further electrochemical studies indicate that the high conductivity of BCNNi electrolyte membrane benefits the fuel cell performance.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Titarenko, Yu. E., E-mail: Yury.Titarenko@itep.ru; Batyaev, V. F.; Titarenko, A. Yu.
The cross sections for nuclide production in thin {sup 93}Nb and {sup nat}Ni targets irradiated by 0.04- to 2.6-GeV protons have been measured by direct {gamma} spectrometry using two {gamma} spectrometers with the resolutions of 1.8 and 1.7 keV in the {sup 60}Co 1332-keV {gamma} line. As a result, 1112 yields of radioactive residual nuclei have been obtained. The {sup 27}Al(p, x){sup 22}Na reaction has been used as a monitor reaction. The experimental data have been compared with the MCNPX (BERTINI, ISABEL), CEM03.02, INCL4.2, INCL4.5, PHITS, and CASCADE07 calculations.
Broadly tunable picosecond ir source
Campillo, A.J.; Hyer, R.C.; Shapiro, S.L.
1980-04-23
A picosecond traveling-wave parametric device capable of controlled spectral bandwidth and wavelength in the infrared is reported. Intense 1.064 ..mu..m picosecond pulses (1) pass through a 4.5 cm long LiNbO/sub 3/ optical parametric oscillator crystal (2) set at its degeneracy angle. A broad band emerges, and a simple grating (3) and mirror (4) arrangement is used to inject a selected narrow-band into a 2 cm long LiNbO/sub 3/ optical parametric amplifier crystal (5) along a second pump line. Typical input energies at 1.064 ..mu..m along both pump lines are 6 to 8 mJ for the oscillator and 10 mJ for the amplifier. This yields 1 mJ of tunable output in the range 1.98 to 2.38 ..mu..m which when down-converted in a 1 cm long CdSe crystal mixer (6) gives 2 ..mu..J of tunable radiation over the 14.8 to 18.5 ..mu..m region. The bandwidth and wavelength of both the 2 and 16 ..mu..m radiation output are controlled solely by the diffraction grating.
Broadly tunable picosecond IR source
Campillo, Anthony J.; Hyer, Ronald C.; Shapiro, Stanley J.
1982-01-01
A picosecond traveling-wave parametric device capable of controlled spectral bandwidth and wavelength in the infrared is reported. Intense 1.064 .mu.m picosecond pulses (1) pass through a 4.5 cm long LiNbO.sub.3 optical parametric oscillator crystal (2) set at its degeneracy angle. A broad band emerges, and a simple grating (3) and mirror (4) arrangement is used to inject a selected narrow-band into a 2 cm long LiNbO.sub.3 optical parametric amplifier crystal (5) along a second pump line. Typical input energies at 1.064 .mu.m along both pump lines are 6-8 mJ for the oscillator and 10 mJ for the amplifier. This yields 1 mJ of tunable output in the range 1.98 to 2.38 .mu.m which when down-converted in a 1 cm long CdSe crystal mixer (6) gives 2 .mu.J of tunable radiation over the 14.8 to 18.5 .mu.m region. The bandwidth and wavelength of both the 2 and 16 .mu.m radiation output are controlled solely by the diffraction grating.
Xu, Wei; Li, Ming; Wen, Cuie; Lv, Shaomin; Liu, Chengcheng; Lu, Xin
2018-01-01
A biocompatible Ti-28Nb-35.4Zr alloy used as bone implant was fabricated through the powder metallurgy process. The effects of mechanical milling and sintering temperatures on the microstructure and mechanical properties were investigated systematically, before in vitro biocompatibility of full dense Ti-28Nb-35.4Zr alloy was evaluated by cytotoxicity tests. The results show that the mechanical milling and sintering temperatures have significantly effects on the density and mechanical properties of the alloys. The relative density of the alloy fabricated by the atomized powders at 1500 °C is only 83 ± 1.8%, while the relative density of the alloy fabricated by the ball-milled powders can rapidly reach at 96.4 ± 1.3% at 1500 °C. When the temperature was increased to 1550 °C, the alloy fabricated by ball-milled powders achieve full density (relative density is 98.1 ± 1.2%). The PM-fabricated Ti-28Nb-35.4Zr alloy by ball-milled powders at 1550 °C can achieve a wide range of mechanical properties, with a compressive yield strength of 1058 ± 35.1 MPa, elastic modulus of 50.8 ± 3.9 GPa, and hardness of 65.8 ± 1.5 HRA. The in vitro cytotoxicity test suggests that the PM-fabricated Ti-28Nb-35.4Zr alloy by ball-milled powders at 1550 °C has no adverse effects on MC3T3-E1 cells with cytotoxicity ranking of 0 grade, which is nearly close to ELI Ti-6Al-4V or CP Ti. These properties and the net-shape manufacturability makes PM-fabricated Ti-28Nb-35.4Zr alloy a low-cost, highly-biocompatible, Ti-based biomedical alloy. PMID:29601517
Imatinib and Nilotinib Off-Target Effects on Human NK Cells, Monocytes, and M2 Macrophages.
Bellora, Francesca; Dondero, Alessandra; Corrias, Maria Valeria; Casu, Beatrice; Regis, Stefano; Caliendo, Fabio; Moretta, Alessandro; Cazzola, Mario; Elena, Chiara; Vinti, Luciana; Locatelli, Franco; Bottino, Cristina; Castriconi, Roberta
2017-08-15
Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells. In NB, neither drug reduced the expression of ligands for activating NK receptors or upregulated that of HLA class I, B7-H3, PD-L1, and PD-L2, molecules that might limit NK cell function. Interestingly, TKIs modulated the chemokine receptor repertoire of immune cells. Acting at the transcriptional level, they increased the surface expression of CXCR4, an effect observed also in NK cells and monocytes of patients receiving imatinib for chronic myeloid leukemia. Moreover, TKIs reduced the expression of CXCR3 (in NK cells) and CCR1 (in monocytes). Monocytes also decreased the expression of M-CSFR, and low numbers of cells underwent differentiation toward macrophages. M0 and M2 macrophages were highly resistant to TKIs and maintained their phenotypic and functional characteristics. Importantly, also in the presence of TKIs, the M2 immunosuppressive polarization was reverted by TLR engagement, and M1-oriented macrophages fully activated autologous NK cells. Our results contribute to better interpreting the off-target efficacy of TKIs in tumors and to envisaging strategies aimed at facilitating antitumor immune responses. Copyright © 2017 by The American Association of Immunologists, Inc.
NASA Astrophysics Data System (ADS)
Mayanovic, R. A.; Anderson, A. J.; Bassett, W. A.; Chou, I.
2006-05-01
Understanding the structural properties of trace elements in hydrous silicate melts in contact with a hydrothermal fluid is fundamentally important for a better assessment of the role of such elements in silicate melts being subjected to hydrothermal processes. We describe the use of synchrotron x-ray microprobe techniques and the modified hydrothermal diamond-anvil cell for in-situ spectroscopic analysis of individual phases of a silicate-melt/fluid system. Synchrotron X-ray fluorescence (XRF) and Nb K-edge X-ray absorption fine structure (XAFS) measurements were made on sectors ID20 and ID13 at the Advanced Photon Source, at the Argonne National Laboratory, on a Nb-bearing granitic glass in H2O and separately in a 1 M Na2CO3 aqueous solution at temperatures ranging from 25 to 880 °C and at up to 700 MPa of pressure. Individual phases of the Nb-glass/fluid system (at low temperatures) or the hydrous-silicate-melt/fluid system (at elevated temperatures) were probed using an X-ray beam focused to a diameter of 5 μm at the location of the sample. XRF analysis shows that the Nb partitions selectively from the hydrous silicate melt into the aqueous fluid at high temperatures in the Nb-glass/Na2CO3/H2O system but not so in the Nb-glass/H2O system. Analysis of XAFS spectra measured from the hydrous silicate melt phase of the Nb-glass/H2O sample in the 450 to 700 °C range shows that the first shell contains six oxygen atoms at a distance of ~1.98 Å. Our results suggest that reorganization of the silicate structure surrounding Nb occurs in the melt when compared to that of the starting glass. The X-ray absorption near edge structure (XANES) spectra show a pre-edge peak feature located at ~18995 eV that exhibits sharpening and becomes more intensified in the 450 to 700 °C range. Fitting of the Nb K-edge XANES spectra measured from the melt is accomplished using FEFF8.28 and an atomic model NbSi4O6-4(Na, K). The model is based on the structure of fresnoite (Ba2TiSi2O8), in which an NbO6 octahedron unit is substituted for the TiO5 unit, four Na and four K atoms are placed alternately on nearby Ba atom sites, and four Si atoms are arranged in a single plane intersecting the NbO6 unit. The results from fitting indicate that the local structure of Nb in the silicate melt is altered from its local structure in the quenched glass before heating and in the glass after heating in the diamond anvil cell. The importance of in situ analysis of melts and hydrothermal fluids at various temperatures and pressures is discussed in the context of our study.
Park, Jong Hoon; Noh, Jun Hong; Han, Byung Suh; Shin, Seong Sik; Park, Ik Jae; Kim, Dong Hoe; Hong, Kug Sun
2012-06-01
Niobium doped hierarchically organized TiO2 nanostructures composed of 20 nm size anatase nanocrystals were synthesized using pulsed laser deposition (PLD). The Nb doping concentration could be facilely controlled by adjusting the concentration of Nb in target materials. We could investigate the influence of Nb doping in the TiO2 photoelectrode on the cell performance of dye-sensitized solar cells (DSSCs) by the exclusion of morphological effects using the prepared Nb-doped TiO2 anostructures. We found no significant change in short circuit current density (Jsc) as a function of Nb doping concentration. However, open circuit voltage (Voc) and fill factor (FF) monotonously decrease with increasing Nb concentration. Dark current characteristics of the DSSCs reveal that the decrease in Voc and FF is attributed to the decrease in shunt resistance due to the increase in conductivity TiO2 by Nb doping. However, electrochemical impedance spectra (EIS) analysis at open circuit condition under illumination showed that the resistance at the TiO2/dye/electrolyte interface increases with Nb concentration, revealing that Nb doping suppress the charge recombination at the interface. In addition, electron life time obtained using characteristic frequency in Bode plot increases from 14 msec to 56 msec with increasing Nb concentration from 0 to 1.2 at%. This implies that the improved light harvesting can be achieved by increasing diffusion length through Nb-doping in the conventional TiO2 photoelectrode.
NASA Astrophysics Data System (ADS)
Nakamura, Y.; Manabu, A.; Morimoto, T.; Ushio, T.; Kawasaki, Z.; Miki, M.; Shimizu, M.
2009-12-01
In this paper, we present observations of positive cloud-to-ground (+CG) lightning flashes obtained with the VHF BDITF (VHF Broadband Digital InTerFerometer) and the ALPS (Automatic Lightning Discharge Progressing Feature Observation System). The VHF BDITF observed two- (2D) and three-dimensional (3D) developments of lightning flashes with high time resolution. The ALPS observed the luminous propagation of the local process at low altitudes within its observational range. At 2028:59 JST on 8 August, 2008, we observed the 3D spatiotemporal development channels of +CG lightning flash with the VHF BDITF and the RS with the lightning location and protection (LLP) system. This flash is divided before and after the RS. In the former stage, the in-cloud negative breakdown (NB) progress about 15 km horizontally between 6 and 10 km high. The LLP system detects the RS near the initiation point of that negative breakdown (NB) at the end of the former stage. In the latter stage, the new NB runs through the same path as the first NB before the RS. The luminous intensity of the RS near the ground obtained with the ALPS is synchronized with the development of the new NB. The time variation of luminous intensity by the ALPS has two peaks. The time difference of these peaks is corresponding to the blank of the VHF radiation. Since the new NB following the RS runs through the path of the first NB, the positive breakdown (PB), which is not visualized by the VHF BDITF, could be considered to progress from the starting point of the first NB and touches to the ground. The RS current propagates and penetrates in the opposite direction as visualized subsequent NB. This suggests the first NB and the PB progress together. This +CG lightning flash has the bi-directional leader. To assume the path of the PB is straight line, the velocity of the PB is about 4 × 104 m/s.
Total Synthesis of Gramistilbenoids A, B, and C.
Harmalkar, Dipesh S; Lu, Qili; Lee, Kyeong
2018-04-27
Stilbenes are biologically active metabolites of plants that have the potential to attenuate a broad range of human diseases. Gramistilbenoids are a class of natural products with a stilbene skeleton, isolated from the bamboo orchid ( Arundina graminifolia), and with significant cytotoxicity against cancer cell lines (NB4, A549, SHSY5Y, PC3, and MCF7). These are the first identified naturally occurring diphenylethylenes to possess a hydroxyethyl unit. However, some of these compounds are not abundant in nature, and thus, their synthesis is advantageous. This paper reports the first synthesis of gramistilbenoids A (1), B (2), and C (3), with overall yields of 10, 2, and 8% respectively. These natural products were synthesized using key reactions, such as Horner-Wadsworth-Emmons olefination, Stille coupling, and hydroboration-oxidation.
NASA Astrophysics Data System (ADS)
Rosenthal, A.; Hauri, E. H.; Hirschmann, M. M.; Davis, F. A.; Withers, A. C.; Fogel, M. L.
2012-12-01
Inventories of C in the mantle and magmatic fluxes of C between the mantle and the Earth's outer envelopes are poorly constrained in part owing to challenges in determining undegassed C concentrations of pristine basalts. Saal et al. [1] proposed that the behavior of Nb could be used as a proxy for C, owing to apparently similar behavior of the two elements in Siqueiros Transform MORB, but higher C/Nb ratios in popping rocks [2] call into question the applicability of the C/Nb proxy. Here, we present experimentally determined carbon partition coefficients (D's) between nominally volatile-free mantle minerals (olivine, OL; orthopyroxene, OPX; clinopyroxene, CPX; garnet, GA) and melts at 0.8-3 GPa, and 1250-1500°C. We conducted piston-cylinder experiments using an olivine-tholeiite + 4 wt% CO2, doped with Nb, Rb, U, Th, and 13C to enhance detection limits. To promote growth of crystals big enough for SIMS analyses, experiments were either long (<6 days), or at an initial higher temperature (T) before cooling slowly to a target T. We also produced SIMS calibration glass standards with varying amounts of C, and subject to ongoing analyses. We analyzed carbon (12C, 13C), H, F, and trace elements (Nb, Rb, Ba, U, Th, K) of both mineral phases and quenched liquids in subsets of experimental runs (21 in graphite-lined Pt-capsules, 6 in Fe-doped Pt-lined capsules) using both Cameca IMS 6F and NanoSIMS instruments. D's measured for 12C and 13C are close to 5x10-4, in most cases D13C>D12C, but a few have the opposite. Continuous exchange of the liquid (initially rich in 13C) with the graphite capsules (rich in 12C) may yield D's with 13C>12C. D's with 12C>13C are likely owing to either low count rates or comparatively high analytical contamination. Concentrations in minerals vary from 0.20-3.46 ppm for C, 25-176 ppm for H2O, and 0.05-1.21 ppm for F, whereas liquids tend to much higher values (C≤0.9 wt%; H2O≤1.5 wt%; F≤34 ppm; P≤0.25 wt%; S≤43 ppm; Cl≤77 ppm). Resulting D's indicate that C is highly incompatible in all major mantle mineral phases, with D's for OL, OPX and CPX of close to 5x10-4, and for GA ~2.2x10-4. D's for H2O (2x10-4 to ~3x10-2) and F (~2.3x10-3 to ~5.8x10-2) are comparable to those found in previous studies. Trace element partition determinations are in progress, but comparison to previous studies indicates that carbon is significantly more incompatible during mantle melting than Nb, U, or Th, and has behavior approximately similar to Ba. We therefore suggest that undegassed C/Ba ratios may be useful indicators of C fluxes and concentrations in basalt source regions where very low degrees of melting might fractionate C/Nb ratios. [1] Saal, A, Hauri, EH, Langmuir, CH, Perfit, M (2002) Nature 419, 451-455. [2] Cartigny, P, Pineau, F, Aubaud, C, Javoy, M (2008) Earth Planet Sci Lett 265, 672-685.
Biopsy of embryos produced by in vitro fertilization affects development in C57BL/6 mouse strain
Sugawara, Atsushi; Ward, Monika A.
2012-01-01
Preimplantation genetic diagnosis (PGD) is considered highly successful in respect to its accuracy in detecting genetic anomalies but the effects of embryo biopsy on embryonic/fetal growth and development are less known, particularly in conjunction with in vitro fertilization (IVF). Here, we compared biopsied (B) and non-biopsied (NB) mouse embryos for their developmental competence. Embryos C57BL/6 (B6) and B6D2F2 (F2) generated by IVF were subjected to single blastomere biopsy at the 4-cell stage, and were either cultured for 120 h and subjected to differential inner cell mass (ICM) and trophoblast (T) staining, or were transferred into the uterine tubes of surrogate mothers after 72 h of culture, to examine their pre- and post-implantation development, respectively. Non-biopsied embryos from the same IVF cohorts served as controls. Embryo biopsy negatively affected preimplantation development to blastocyst in C57BL/6 (69 vs 79%, P<0.01) but not in B6D2F1 mice (89 vs 91%, P=NS). Although B6 embryos had lower total cell number than F2 (B6: 47 and 61 vs. F1: 53 and 70; B and NB, respectively, P<0.05) there were no differences between B and NB blastocysts in %ICM (B6: 19.8 vs 19.8; F2: 20.9 vs 20.4, P=NS) and ICM:T ratio (B6: 4.7 vs 4.7; F2: 4.4 vs. 4.7) in both mouse strains. Post-implantation development to live fetuses of B embryos as compared to NB counterparts was impaired in C57BL/6 (6 vs 18%, P<0.001) but not in B6D2F1 mice (26 vs 35%, P=NS). We conclude that blastomere biopsy impairs embryonic/fetal development in mice known to be sensitive to in vitro culture and manipulations. Such mice model infertile couples with poor quality gametes seeking help in assisted reproduction technologies (ART) clinics. PMID:23174776
NASA Technical Reports Server (NTRS)
Anderson, Kenneth Reed
2000-01-01
Ternary Cu-Cr-Nb alloys, particularly Cu-8 Cr-4 Nb (in at.%), have demonstrated good thermal stability as well as high strength and conductivity at elevated temperatures. The initial powder material has a bimodal size distribution of Cr2Nb precipitates. Primary Cr2Nb precipitates are approx. 1 micron, and secondary Cr2Nb particles are 30-200 nm. The particle coarsening was analyzed and found to follow LSW-type behavior, This study provides a detailed examination of the stability and strengthening effects of Cr2Nb particles. This investigation also revealed that the primary particles provide direct grain boundary pinning and indirect grain boundary strengthening but virtually no Orowan strengthening. The secondary particles found within grains do provide Orowan strengthening. For extruded material, grain bound-ary strengthening (Hall-Petch effect) accounts for two-thirds of the strength with Orowan effects contributing the remainder. The proven advantages of Cu-Cr-Nb were the motivation to improve these attributes via microstructural refinement. Mechanical milling (MM) of Cu- 4 Cr-2 Nb and Cu-8 Cr-2 Nb produced an increase in hot pressed Vickers hardness of 122% and 96%, respectively. The increase in hardness was more due to Cu grain-size refinement than to Cr,,Nb refinement. This study also demonstrated enhanced stability of MM Cu-4 Cr-2 Nb. Hot pressed 4 h milled Cu-4 Cr-2 Nb experienced only a 22% drop in hardness when annealed at 1273 K for 50 h versus a 30% drop for extruded Cu-8 Cr-4 Nb. The goal of improving the strength and stability of Cu-4 Cr-2 Nb to better than such properties for as- extruded Cu-8 Cr-4 Nb has been met. In addition, a figure-of-merit (FOM) coupling hardness and thermal conductivity was maximized for the case of 4 h milled Cu-4 Cr-2 Nb material. Overall, Cu-Cr-Nb alloys not only possess high strength, conductivity and thermal stability but also can be further developed to improve strength and stability.
Lin, Wen; Xie, Xiangyang; Deng, Jianping; Liu, Hui; Chen, Ying; Fu, Xudong; Liu, Hong; Yang, Yang
2016-01-01
A new drug-targeting system for CD13(+) tumors has been developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, the CPP-doxorubicin conjugate (CPP-DOX) was entrapped in the asparagine-glycine-arginine (NGR) peptide modified NB (CPP-DOX/NGR-NB) and the penetration of CPP-DOX was temporally masked; local ultrasound stimulation could trigger the CPP-DOX release from NB and activate its penetration. The CPP-DOX/NGR-NBs had particle sizes of about 200 nm and drug entrapment efficiency larger than 90%. In vitro release results showed that over 85% of the encapsulated DOX or CPP-DOX would release from NBs in the presence of ultrasound, while less than 1.5% of that (30 min) without ultrasound. Cell experiments showed the higher cellular CPP-DOX uptake of CPP-DOX/NGR-NB among the various NB formulations in Human fibrosarcoma cells (HT-1080, CD13(+)). The CPP-DOX/NGR-NB with ultrasound treatment exhibited an increased cytotoxic activity than the one without ultrasound. In nude mice xenograft of HT-1080 cells, CPP-DOX/NGR-NB with ultrasound showed a higher tumor inhibition effect (3.1% of T/C%, day 24), longer median survival time (50 days) and excellent body safety compared with the normal DOX injection group. These results indicate that the constructed vesicle would be a promising drug delivery system for specific cancer treatment.
Bao, Fei; Huang, Xiaozhen; Zhu, Chipan; Zhang, Xiaoyan; Li, Xin; Yang, Shuhua
2014-06-01
Plant defense responses are regulated by temperature. In Arabidopsis, the chilling-sensitive mutant chs2-1 (rpp4-1d) contains a gain-of-function mutation in the TIR-NB-LRR (Toll and interleukin 1 receptor-nucleotide binding-leucine-rich repeat) gene, RPP4 (RECOGNITION OF PERONOSPORA PARASITICA 4), which leads to constitutive activation of the defense response at low temperatures. Here, we identified and characterized two suppressors of rpp4-1d from a genetic screen, hsp90.2 and hsp90.3, which carry point mutations in the cytosolic heat shock proteins HSP90.2 and HSP90.3, respectively. The hsp90 mutants suppressed the chilling sensitivity of rpp4-1d, including seedling lethality, activation of the defense responses and cell death under chilling stress. The hsp90 mutants exhibited compromised RPM1 (RESISTANCE TO PSEUDOMONAS MACULICOLA 1)-, RPS4 (RESISTANCE TO P. SYRINGAE 4)- and RPP4-mediated pathogen resistance. The wild-type RPP4 and the mutated form rpp4 could interact with HSP90 to form a protein complex. Furthermore, RPP4 and rpp4 proteins accumulated in the cytoplasm and nucleus at normal temperatures, whereas the nuclear accumulation of the mutated rpp4 was decreased at low temperatures. Genetic analysis of the intragenic suppressors of rpp4-1d revealed the important functions of the NB-ARC and LRR domains of RPP4 in temperature-dependent defense signaling. In addition, the rpp4-1d-induced chilling sensitivity was largely independent of the WRKY70 or MOS (modifier of snc1) genes. [Correction added after online publication 11 March 2013: the expansions of TIR-NB-LRR and RPS4 were amended] This study reveals that Arabidopsis HSP90 regulates RPP4-mediated temperature-dependent cell death and defense responses. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.
Tuning Nb–Pt Interactions To Facilitate Fuel Cell Electrocatalysis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ghoshal, Shraboni; Jia, Qingying; Bates, Michael K.
High stability, availability of multiple oxidation states, and accessibility within a wide electrochemical window are the prime features of Nb that make it a favorable candidate for electrocatalysis, especially when it is combined with Pt. However, Nb has been used as a support in the form of oxides in all previously reported Pt–Nb electrocatalysts, and no Pt–Nb alloying phase has been demonstrated hitherto. Herein, we report a multifunctional Pt–Nb composite (PtNb/NbOx-C) where Nb exists both as an alloying component with Pt and as an oxide support and is synthesized by means of a simple wet chemical method. In this work,more » the Pt–Nb alloy phase has been firmly verified with the help of multiple spectroscopic methods. This allows for the experimental evidence of the theoretical prediction that Pt–Nb alloy interactions improve the oxygen reduction reaction (ORR) activity of Pt. In addition, such a combination of multiphase Nb brings up myriad features encompassing increased ORR durability, immunity to phosphate anion poisoning, enhanced hydrogen oxidation reaction (HOR) activity, and oxidative carbon monoxide (CO) stripping, making this electrocatalyst useful in multiple fuel cell systems.« less
Electrochemical studies on niobium triselenide cathode material for lithium rechargeable cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ratnakumar, B.V.; Ni, C.L.; DiStefano, S.
1989-01-01
Niobium triselenide offers promise as a high energy density cathode material for ambient temperature lithium rechargeable cells. The electrochemical behavior of NbSe/sub 3/ in the battery electrolyte, i.e., 1.5m LiAsF/sub 6//2 Me-THF is reported here. A detailed study has been carried out using various ac and dc electrochemical techniques to establish the mechanism of intercalation of three equivalents of Li with NbSe/sub 3/ as well as the rate governing processes in the reduction of NbSe/sub 3/. Based on the experimental data, an equivalent circuit has been formulated to represent the NbSe/sub 3/-solution interface. The kinetic parameters for the reduction ofmore » NbSe/sub 3/ were evaluated from the ac and dc measurements. Finally, the structural change in NbSe/sub 3/ on lithiation during initial discharge which results in higher cell voltages and different electrochemical response as compared to virgin NbSe/sub 3/ was identified to be a loss of crystallographic order, i.e., amorphous by x-ray diffraction.« less
Liu, Na; Ding, Feng; Wang, Liu; Liu, Peng; Yu, Xiaolong; Ye, Kang
2016-05-01
A laboratory-scale bio-permeable reactive barrier (bio-PRB) was constructed and combined with enclosed in-well aeration system to treat nitrobenzene (NB) and aniline (AN) in groundwater. Batch-style experiments were first conducted to evaluate the effectiveness of NB and AN degradation, using suspension (free cells) of degrading consortium and immobilized consortium by a mixture of perlite and peat. The NB and AN were completely degraded in <3 days using immobilized consortium, while 3-5 days were required using free cells. The O2 supply efficiency of an enclosed in-well aeration system was assessed in a box filled with perlite and peat. Dissolved O2 (DO) concentrations increased to 8-12 mg L(-1) in 12 h for sampling ports within 12 cm of the aeration well. A diffusion coefficient as 33.5 cm(2) s(-1) was obtained. The DO concentration was >4 mg L(-1) when the aeration system was applied into the bio-PRB system. The NB and AN were effectively removed when the aeration system was functional in the bio-PRB. The removal efficiency decreased when the aeration system malfunctioned for 20 days, thus indicating that DO was an important factor for the degradation of NB and AN. The regain of NB and AN removal after the malfunction indicates the robustness of degradation consortium. No original organics and new formed by-products were observed in the effluent. The results indicate that NB and AN in groundwater can be completely mineralized in a bio-PRB equipped with enclosed in-well aeration system and filled with perlite and peat attached with degrading consortium.
Pradhan, D; Wren, A W; Misture, S T; Mellott, N P
2016-01-01
Applying sol gel based coatings to orthopedic metallic implant materials can significantly improve their properties and lifespan in vivo. For this work, niobium (Nb2O5) and titanium (TiO2) oxides were prepared via solution processing in order to determine the effect of atomic arrangement (amorphous/crystalline) on bioactivity. Thermal evaluation on the synthesized materials identified an endotherm for Nb2O5 at 75 °C with 40% weight loss below 400 °C, and minimal weight loss between 400 and 850 °C. Regarding TiO2 an endotherm was present at 92 °C with 25% weight loss below 400 °C, and 4% between 400 and 850 °C. Phase evolution was determined using High Temperature X-ray Diffraction (HT-XRD) where amorphous-Nb2O5 (450 °C), hexagonal-Nb2O5 (525 °C), orthorhombic-Nb2O5 (650 °C), amorphous-TiO2 (275 °C) and tetragonal TiO2 (500 °C) structures were produced. Simulated body fluid (SBF) testing was conducted over 1, 7 and 30 days and resulted in positive chemical and morphological changes for crystalline Nb2O5 (525 °C) and TiO2 (500 °C) after 30 days of incubation. Rod-like CaP deposits were observed on the surfaces using Scanning Electron Microscopy (FE-SEM) and Grazing Incidence-X-ray Diffraction (GI-XRD) shows that the deposits were X-ray amorphous. Cell viability was higher with the TiO2 (122%) samples when compared to the growing cell population while Nb2O5 samples exhibited a range of viability (64-105%), partially dependent on materials atomic structure. Copyright © 2015 Elsevier B.V. All rights reserved.
Spontaneous rat nephroblastoma: ultrastructure of a transplant line.
Hard, G C; Noble, R L
1982-08-01
Tumor tissue derived from a nephroblastoma arising spontaneously in an Nb hooded rat and carried for 56 generations as a subcutaneous syngeneic transplant was examined by electron microscopy. Histologically, the transplant showed the typical pattern of dense clusters or sheets of basophilic epithelioid cells set within ramifying tracts of fibrous mesenchyme. At the ultrastructural level, the tumor cells within dense clusters were arranged in anastomotic cords that circumscribed clear intervening spaces. The tumor cells were a monomorphic population possessing the morphologic characteristics of blast cells, including polyribosomes as the predominant cytoplasmic organelle. Furthermore, the close contiguity of cells within the cords, their polyhedral form, and their connection by intercellular junctions established the tumor cell type as epithelial. Consistent with benign stroma, mesenchymal tracts contained highly differentiated, mature fibroblasts, collagen, phagocytes, cells of the lymphoid series, and normal blood vessels. No transitional forms between epithelium and mesenchyme suggestive of bipotential differentiation were seen. Although the data represent only a single transplantation line, the observations support the contention (based on light microscopic appraisal of a number of primary tumors) that nephroblastoma in te rat can be a purely epithelial neoplasm.
NASA Astrophysics Data System (ADS)
Pradeep PremKumar, K.; Duraipandy, N.; Manikantan Syamala, Kiran; Rajendran, N.
2018-01-01
In the present study, Nb2O5 (NZ0) composite coatings with various concentrations of zinc (NZ2, NZ4 & NZ6) are produced on 316L SS by sol-gel method with the aim of improving its antibacterial activity, bone formability and corrosion resistance properties. This work studied the surface characterization of NZ0, NZ2, NZ4 & NZ6 coated 316L SS by ATR-FTIR, XRD, HR-SEM with EDAX. The synthesized coatings were different in the morphological aspects, NZ0 shows mesoporous morphology whereas irregular cluster like morphology was observed for the zinc incorporated coatings. The chemical composition of the NZ0 and NZ4 composite coatings were studied by XPS and the results revealed that the zinc exist as ZnO and Nb as Nb2O5 in the coatings. The increase in the concentration of zinc in Nb2O5 increases the hydrophilic nature identified by water contact angle studies. The potentiodynamic polarization studies in simulated body fluid reveals the increase in polarization resistance with decrease in current density (icorr) and electrochemical impedance spectroscopic studies with increase in charge transfer resistance (Rct) and double layer capacitance (Qdl) were observed for NZ4 coated 316L SS. The inhibition of Staphylococcus aureus and Escherichia coli bacteria were identified for NZ4 coated 316L SS by bacterial viability studies. The NZ4 coated 316L SS showed better Osseo-integration by spreading the MG 63 osteoblast cells. The study results imply that zinc incorporated Nb2O5 (NZ4) composite coating exhibits antibacterial activity and also enhance the corrosion resistance and biocompatibility of the 316L SS.
Gel shift analysis of the empA promoter region in Vibrio anguillarum.
Denkin, Steven M; Sekaric, Pedja; Nelson, David R
2004-10-29
The induction of metalloprotease encoded by empA in Vibrio anguillarum occurs at high cell density in salmon intestinal mucus. Previously we have shown that there are significant differences in empA expression in two strains of V. anguillarum, M93Sm and NB10. It is hypothesized that differences in empA regulation are due to differences in binding of regulatory elements. Two strains of V. anguillarum, M93Sm and NB10, were examined and compared for the presence of DNA regulatory proteins that bind to and control the empA promoter region. Gel mobility shift assays, using a digoxigenin (DIG)-labeled oligomer containing a lux box-like element and the promoter for empA, were done to demonstrate the presence of a DNA-binding protein. Protein extracts from NB10 cells incubated in Luria Bertani broth + 2% NaCl (LB20), nine salts solution + 200 microg/ml mucus (NSSM), 3M (marine minimal medium), or NSS resulted in a gel mobility shift. No gel mobility shift was seen when protein extracts from either LB20- or NSSM-grown M93Sm cells were mixed with the DIG-labeled empA oligomer. The azocasein assay detected protease activity in all incubation conditions for NB10 culture supernatants. In contrast, protease activity was detected in M93Sm culture supernatants only when incubated in NSSM. Since the luxR homologue in V. anguillarum, vanT, has been cloned, sequenced, and shown to be required for protease activity, we wanted to determine if vanT mutants of NB10 exhibit the same gel shift observed in the wild-type. Site-directed mutagenesis was used to create vanT mutants in V. anguillarum M93Sm and NB10 to test whether VanT is involved with the gel mobility shift. Both vanT mutants, M02 and NB02, did not produce protease activity in any conditions. However, protein extracts from NB02 incubated in each condition still exhibited a gel shift when mixed with the DIG-labeled empA oligomer. The data demonstrate that protein extracts of V. anguillarum NB10 cells contain a protein that binds to a 50 bp oligomer containing the empA promoter-lux box-like region. NB10 cells express empA during stationary phase in all growth conditions. The DNA binding protein is not present in M93Sm extracts. M93Sm cells express protease activity only when incubated at high cell density in fish gastrointestinal mucus. The gel shift observed with NB10 cells is not due to VanT binding. The data also suggest that the DNA binding protein is responsible for the less restrictive expression of empA in NB10 compared to M93Sm.
Whelan, Jarrett T.; Chen, Jianming; Miller, Jabin; Morrow, Rebekah L.; Lingo, Joshuah D.; Merrell, Kaitlin; Shaikh, Saame Raza; Bridges, Lance C.
2012-01-01
Retinoids are essential in the proper establishment and maintenance of immunity. Although retinoids are implicated in immune related processes, their role in immune cell adhesion has not been well established. In this study, the effect of 9-cis-retinoic acid (9-cis-RA) on human hematopoietic cell adhesion was investigated. 9-cis-RA treatment specifically induced cell adhesion of the human immune cell lines HuT-78, NB4, RPMI 8866, and U937. Due to the prominent role of integrin receptors in mediating immune cell adhesion, we sought to evaluate if cell adhesion was integrin-dependent. By employing a variety of integrin antagonist including function-blocking antibodies and EDTA, we establish that 9-cis-RA prompts immune cell adhesion through established integrin receptors in addition to a novel integrin-independent process. The novel integrin-independent adhesion required the presence of retinoid and was attenuated by treatment with synthetic corticosteroids. Finally, we demonstrate that 9-cis-RA treatment of primary murine B-cells induces ex vivo adhesion that persists in the absence of integrin function. Our study is the first to demonstrate that 9-cis-retinoic acid influences immune cell adhesion through at least two functionally distinct mechanisms. PMID:22925918
Abdominal-B and caudal inhibit the formation of specific neuroblasts in the Drosophila tail region
Birkholz, Oliver; Vef, Olaf; Rogulja-Ortmann, Ana; Berger, Christian; Technau, Gerhard M.
2013-01-01
The central nervous system of Drosophila melanogaster consists of fused segmental units (neuromeres), each generated by a characteristic number of neural stem cells (neuroblasts). In the embryo, thoracic and anterior abdominal neuromeres are almost equally sized and formed by repetitive sets of neuroblasts, whereas the terminal abdominal neuromeres are generated by significantly smaller populations of progenitor cells. Here we investigated the role of the Hox gene Abdominal-B in shaping the terminal neuromeres. We show that the regulatory isoform of Abdominal-B (Abd-B.r) not only confers abdominal fate to specific neuroblasts (e.g. NB6-4) and regulates programmed cell death of several progeny cells within certain neuroblast lineages (e.g. NB3-3) in parasegment 14, but also inhibits the formation of a specific set of neuroblasts in parasegment 15 (including NB7-3). We further show that Abd-B.r requires cooperation of the ParaHox gene caudal to unfold its full competence concerning neuroblast inhibition and specification. Thus, our findings demonstrate that combined action of Abdominal-B and caudal contributes to the size and composition of the terminal neuromeres by regulating both the number and lineages of specific neuroblasts. PMID:23903193
Xiaopeng, Wang; Fantao, Kong; Biqing, Han; Yuyong, Chen
2017-11-01
Ti-Nb-Sn-hydroxyapatite (HA) composites were prepared by mechanical alloying for different times (unmilled, 4, 8 and 12h), followed by pulse current activated sintering. The effects of the milling time on the electrochemical corrosion resistance and bioactivity of the sintered Ti-35Nb-2.5Sn-15HA composites were investigated. Potentiodynamic polarization test results indicated that the sintered Ti-35Nb-2.5Sn-15HA composites exhibited higher corrosion resistance with increasing milling time. The corrosion potential and current of the Ti-35Nb-2.5Sn-15HA composite sintered by 12h milled powders were - 0.261V and 0.18μA/cm 2 , respectively, and this sintered composite showed a stable and wide passivation region. The hemolysis rate of the sintered Ti-35Nb-2.5Sn-15HA composites reduced with increasing milling time and the lowest hemolytic rate of the composites was 0.87%. In addition, the in vitro cell culture results indicated that the composite sintered by 12h milled powders had good biocompatibility. These results indicate the significant potential of Ti-35Nb-2.5Sn/xHA composites for biomedical implant applications. Copyright © 2017 Elsevier Ltd. All rights reserved.
Commissioning results of Nb 3Sn cavity vapor diffusion deposition system at JLab
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eremeev, Grigory; Clemens, William A.; Macha, Kurt M.
2015-09-01
Nb 3Sn as a BCS superconductor with a superconducting critical temperature higher than that of niobium offers potential benefit for SRF cavities via a lower-than-niobium surface resistance at the same temperature and frequency. A Nb 3Sn vapor diffusion deposition system designed for coating of 1.5 and 1.3 GHz single-cell cavities was built and commissioned at JLab. As the part of the commissioning, RF performance at 2.0 K of a single-cell 1.5 GHz CEBAF-shaped cavity was measured before and after coating in the system. Before Nb 3Sn coating the cavity had a Q 0 of about 10 10 and was limitedmore » by the high field Q-slope at E acc ≅ 27 MV/m. Coated cavity exhibited the superconducting transition at about 17.9 K. The low-field quality factor was about 5∙10 9 at 4.3 K and 7∙10 9 at 2.0 K decreasing with field to about 1∙10 9 at E acc ≅ 8 MV/m at both temperatures. The highest field was limited by the available RF power.« less
Stonebloom, Solomon; Ebert, Berit; Xiong, Guangyan; ...
2016-04-18
We report pectins are a group of structurally complex plant cell wall polysaccharides whose biosynthesis and function remain poorly understood. The pectic polysaccharide rhamnogalacturonan-I (RG-I) has two types of arabinogalactan side chains, type-I and type-II arabinogalactans. To date few enzymes involved in the biosynthesis of pectin have been described. Here we report the identification of a highly conserved putative glycosyltransferase encoding gene, Pectic ArabinoGalactan synthesis-Related (PAGR), affecting the biosynthesis of RG-I arabinogalactans and critical for pollen tube growth. T-DNA insertions in PAGR were identified in Arabidopsis thaliana and were found to segregate at a 1:1 ratio of heterozygotes to wildmore » type. We were unable to isolate homozygous pagr mutants as pagr mutant alleles were not transmitted via pollen. In vitro pollen germination assays revealed reduced rates of pollen tube formation in pollen from pagr heterozygotes. To characterize a loss-of-function phenotype for PAGR, the Nicotiana benthamiana orthologs, NbPAGR-A and B, were transiently silenced using Virus Induced Gene Silencing. NbPAGR-silenced plants exhibited reduced internode and petiole expansion. Cell wall materials from NbPAGR-silenced plants had reduced galactose content compared to the control. Immunological and linkage analyses support that RG-I has reduced type-I arabinogalactan content and reduced branching of the RG-I backbone in NbPAGR-silenced plants. Arabidopsis lines overexpressing PAGR exhibit pleiotropic developmental phenotypes and the loss of apical dominance as well as an increase in RG-I type-II arabinogalactan content. Together, results support a function for PAGR in the biosynthesis of RG-I arabinogalactans and illustrate the essential roles of these polysaccharides in vegetative and reproductive plant growth.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stonebloom, Solomon; Ebert, Berit; Xiong, Guangyan
We report pectins are a group of structurally complex plant cell wall polysaccharides whose biosynthesis and function remain poorly understood. The pectic polysaccharide rhamnogalacturonan-I (RG-I) has two types of arabinogalactan side chains, type-I and type-II arabinogalactans. To date few enzymes involved in the biosynthesis of pectin have been described. Here we report the identification of a highly conserved putative glycosyltransferase encoding gene, Pectic ArabinoGalactan synthesis-Related (PAGR), affecting the biosynthesis of RG-I arabinogalactans and critical for pollen tube growth. T-DNA insertions in PAGR were identified in Arabidopsis thaliana and were found to segregate at a 1:1 ratio of heterozygotes to wildmore » type. We were unable to isolate homozygous pagr mutants as pagr mutant alleles were not transmitted via pollen. In vitro pollen germination assays revealed reduced rates of pollen tube formation in pollen from pagr heterozygotes. To characterize a loss-of-function phenotype for PAGR, the Nicotiana benthamiana orthologs, NbPAGR-A and B, were transiently silenced using Virus Induced Gene Silencing. NbPAGR-silenced plants exhibited reduced internode and petiole expansion. Cell wall materials from NbPAGR-silenced plants had reduced galactose content compared to the control. Immunological and linkage analyses support that RG-I has reduced type-I arabinogalactan content and reduced branching of the RG-I backbone in NbPAGR-silenced plants. Arabidopsis lines overexpressing PAGR exhibit pleiotropic developmental phenotypes and the loss of apical dominance as well as an increase in RG-I type-II arabinogalactan content. Together, results support a function for PAGR in the biosynthesis of RG-I arabinogalactans and illustrate the essential roles of these polysaccharides in vegetative and reproductive plant growth.« less
Zhang, Enren; Wang, Feng; Zhai, Wenjing; Scott, Keith; Wang, Xu; Diao, Guowang
2017-04-01
Single-chamber microbial fuel cells (S-MFCs) with bio-anodes and activated carbon (AC) air-cathodes showed high nitrobenzene (NB) tolerance and NB removal with concomitant electricity production. The maximum power over 25Wm -3 could be obtained when S-MFCs were operated in the NB loading range of 1.2-6.2molm -3 d -1 , and stable electricity production over 13.7Wm -3 could be produced in a NB loading range of 1.2-14.7molm -3 d -1 . The present S-MFCs exhibited high NB removal performance with NB removal efficiency over 97% even when the NB loading rate was increased to 17.2molm -3 d -1 . The potential NB reduced product (i.e. aniline) could also be effectively removed from influents. The findings in this study means that single-chamber MFCs assembled with pre-enriched bio-anodes and AC air-cathodes could be developed as effective bio-electrochemical systems to remove NB from wastewaters and to harvest energy instead of consuming energy. Copyright © 2017 Elsevier Ltd. All rights reserved.
Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance.
Lifshitz, Veronica; Priceman, Saul J; Li, Wenzhao; Cherryholmes, Gregory; Lee, Heehyoung; Makovski-Silverstein, Adar; Borriello, Lucia; DeClerck, Yves A; Yu, Hua
2017-11-01
Drug resistance is a major barrier for the development of effective and durable cancer therapies. Overcoming this challenge requires further defining the cellular and molecular mechanisms underlying drug resistance, both acquired and environment-mediated drug resistance (EMDR). Here, using neuroblastoma (NB), a childhood cancer with high incidence of recurrence due to resistance to chemotherapy, as a model we show that human bone marrow-mesenchymal stromal cells induce tumor expression of sphingosine-1-phosphate receptor-1 (S1PR1), leading to their resistance to chemotherapy. Targeting S1PR1 by shRNA markedly enhances etoposide-induced apoptosis in NB cells and abrogates EMDR, while overexpression of S1PR1 significantly protects NB cells from multidrug-induced apoptosis via activating JAK-STAT3 signaling. Elevated S1PR1 expression and STAT3 activation are also observed in human NB cells with acquired resistance to etoposide. We show in vitro and in human NB xenograft models that treatment with FTY720, an FDA-approved drug and antagonist of S1PR1, dramatically sensitizes drug-resistant cells to etoposide. In summary, we identify S1PR1 as a critical target for reducing both EMDR and acquired chemoresistance in NB. Mol Cancer Ther; 16(11); 2516-27. ©2017 AACR . ©2017 American Association for Cancer Research.
Ishizuka, Yoshiaki; Koshinaga, Tsugumichi; Hirano, Takayuki; Nagasaki-Maeoka, Eri; Watanabe, Yosuke; Hoshi, Reina; Yoshizawa, Shinsuke; Sugito, Kiminobu; Kawashima, Hiroyuki; Uekusa, Shota; Fukuda, Noboru; Soma, Masayoshi; Fujiwara, Kyoko
2018-07-01
Neuropilin 1 (NRP1) is a transmembrane glycoprotein, which regulates many aspects of cellular function by functioning as co-receptor of various ligands. Recent studies have suggested that NRP1 promotes tumorigenesis, not only by activating the growth of tumor vessels, but also by activating the growth or migration of tumor cells themselves. The present study was performed to elucidate the roles of NRP1 in the development and/or progression of neuroblastoma (NB). In contrast to previous observations in various types of cancer, the analysis of public datasets indicated that lower levels of NRP1 expression were significantly associated with a shorter survival period of patients with NB. Consistent with this finding, wound-healing assay and Matrigel invasion assay revealed that NB cells in which NRP1 was knocked down exhibited increased migratory and invasive abilities. Further analyses indicated that β1 integrin expression was markedly increased in NB cells in which NRP1 was knocked down, and NB cells in which β1 integrin was knocked down exhibited decreased migratory and invasive abilities. The results presented herein indicate that NRP1 exerts tumor suppressive effects in NB, at least in part by regulating the expression of β1 integrin.
X-ray diffraction and infrared spectroscopy studies of Ba(Fe1/2Nb1/2)O3-(Na1/2Bi1/2)TiO3 ceramics
NASA Astrophysics Data System (ADS)
Chandra, K. P.; Yadav, Anjana; Prasad, K.
2018-05-01
Ceramics (1-x)Ba(Fe1/2Nb1/2)O3-x(Na1/2Bi1/2)TiO3; 0≤x≤1.0 were prepared by conventional ceramic synthesis technique. Rietveld refinements of X-ray diffraction data of these ceramics were carried out using FullProf software and determined their crystal symmetry, space group and unit cell dimensions. Rietveld refinement revealed that Ba(Fe1/2Nb1/2)O3 has cubic structure with space group Pm 3 ¯ m and Na1/2Bi1/2)TiO3 has rhombohedral structure with space group R3c. Addition of (Na1/2Bi1/2)TiO3 to Ba(Fe1/2Nb1/2)O3 resulted in the change of unit cell structure from cubic to tetragonal (P4/mmm) for x = 0.75 and the X-Ray diffraction peaks slightly shift towards higher Bragg's angle, suggesting slight decrease in unit cell volume. SEM studies were carried out in order to access the quality of the prepared ceramics which showed a change in grain shapes with the increase of (Na1/2Bi1/2)TiO3 content. FTIR spectra confirmed the formation of perovskite type solid solutions.
3D surface topography study of the biofunctionalized nanocrystalline Ti-6Zr-4Nb/Ca-P
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jakubowicz, J., E-mail: jaroslaw.jakubowicz@put.poznan.pl; Adamek, G.; Jurczyk, M.U.
2012-08-15
In this work surface of the sintered Ti-6Zr-4Nb nanocrystalline alloy was electrochemically biofunctionalized. The porous surface was produced by anodic oxidation in 1 M H{sub 3}PO{sub 4} + 2%HF electrolyte at 10 V for 30 min. Next the calcium-phosphate (Ca-P) layer was deposited, onto the formed porous surface, using cathodic potential - 5 V kept for 60 min in 0.042 M Ca(NO{sub 3}){sub 2} + 0.025 M (NH{sub 4}){sub 2}HPO{sub 4} + 0.1 M HCl electrolyte. The deposited Ca-P layer anchored in the pores. The biofunctionalized surface was studied by XRD, SEM and EDS. In vitro tests culture of normalmore » human osteoblast (NHOst) cells showed very good cells proliferation, colonization and multilayering. Using optical profiler, roughness and hybrid 3D surface topography parameters were estimated. Correlation between surface composition, morphology, roughness and biocompatibility results was done. It has been shown by us that surface with appropriate chemical composition and topography, after combined electrochemical anodic and cathodic surface treatment, supports osteoblast adhesion and proliferation. 3D topography measurements using optical profiler play a key role in the biomaterials surface analysis. - Highlights: Black-Right-Pointing-Pointer Nanocrystalline Ti-6Zr-4Nb/Ca-P material was produced for hard tissue implant applications. Black-Right-Pointing-Pointer Calcium-phosphate results in surface biofunctionalization. Black-Right-Pointing-Pointer The biofunctionalized surface shows good in-vitro behavior.« less
The Impact of Standard Semiconductor Fabrication Processes on Polycrystalline Nb Thin Film Surfaces
NASA Technical Reports Server (NTRS)
Brown, Ari David; Barrentine, Emily M.; Moseley, Samuel H.; Noroozian, Omid; Stevenson, Thomas
2011-01-01
Polycrystalline superconducting Nb thin films are extensively used for submillimeter and millimeter transmission line applications and, less commonly, used in microwave kinetic inductance detector (MKID) applications. The microwave and mm-wave loss in these films is impacted, in part, by the presence of surface nitrides and oxides. In this study, glancing incidence x-ray diffraction was used to identify the presence of niobium nitride and niobium monoxide surface layers on Nb thin films which had been exposed to chemicals used in standard photolithographic processing. A method of mitigating the presence of ordered niobium monoxide surface layers is presented. Furthermore, we discuss the possibility of using glancing incidence x-ray diffraction as a non-destructive diagnostic tool for evaluating the quality of Nb thin films used in MKIDs and transmission lines. For a given fabrication process, we have both the x-ray diffraction data of the surface chemistry and a measure of the mm-wave and microwave loss, the latter being made in superconducting resonators.
The Impact of Standard Semiconductor Fabrication Processes on Polycrystalline Nb Thin Film Surfaces
NASA Technical Reports Server (NTRS)
Brown, Ari David; Barrentine, Emily M.; Moseley, Samuel H.; Noroozian, Omid; Stevenson, Thomas
2016-01-01
Polycrystalline Nb thin films are extensively used for microwave kinetic inductance detectors (MKIDs) and superconducting transmission line applications. The microwave and mm-wave loss in these films is impacted, in part, by the presence of surface nitrides and oxides. In this study, glancing incidence x-ray diffraction was used to identify the presence of niobium nitride and niobium monoxide surface layers on Nb thin films which had been exposed to chemicals used in standard photolithographic processing. A method of mitigating the presence of ordered niobium monoxide surface layers is presented. Furthermore, we discuss the possibility of using glancing incidence x-ray diffraction as a non-destructive diagnostic tool for evaluating the quality of Nb thin films used in MKIDs and transmission lines. For a given fabrication process, we have both the X-ray diffraction data of the surface chemistry and a measure of the mm-wave and microwave loss, the latter being made in superconducting resonators.
Merhi, Faten; Tang, Ruoping; Piedfer, Marion; Mathieu, Julie; Bombarda, Isabelle; Zaher, Murhaf; Kolb, Jean-Pierre; Billard, Christian; Bauvois, Brigitte
2011-01-01
The natural phloroglucinol hyperforin HF displays anti-inflammatory and anti-tumoral properties of potential pharmacological interest. Acute myeloid leukemia (AML) cells abnormally proliferate and escape apoptosis. Herein, the effects and mechanisms of purified HF on AML cell dysfunction were investigated in AML cell lines defining distinct AML subfamilies and primary AML cells cultured ex vivo. HF inhibited in a time- and concentration-dependent manner the growth of AML cell lines (U937, OCI-AML3, NB4, HL-60) by inducing apoptosis as evidenced by accumulation of sub-G1 population, phosphatidylserine externalization and DNA fragmentation. HF also induced apoptosis in primary AML blasts, whereas normal blood cells were not affected. The apoptotic process in U937 cells was accompanied by downregulation of anti-apoptotic Bcl-2, upregulation of pro-apoptotic Noxa, mitochondrial membrane depolarization, activation of procaspases and cleavage of the caspase substrate PARP-1. The general caspase inhibitor Z-VAD-fmk and the caspase-9- and -3-specific inhibitors, but not caspase-8 inhibitor, significantly attenuated apoptosis. HF-mediated apoptosis was associated with dephosphorylation of active Akt1 (at Ser(473)) and Akt1 substrate Bad (at Ser(136)) which activates Bad pro-apoptotic function. HF supppressed the kinase activity of Akt1, and combined treatment with the allosteric Akt1 inhibitor Akt-I-VIII significantly enhanced apoptosis of U937 cells. Our data provide new evidence that HF's pro-apoptotic effect in AML cells involved inhibition of Akt1 signaling, mitochondria and Bcl-2 members dysfunctions, and activation of procaspases -9/-3. Combined interruption of mitochondrial and Akt1 pathways by HF may have implications for AML treatment.
Merhi, Faten; Tang, Ruoping; Piedfer, Marion; Mathieu, Julie; Bombarda, Isabelle; Zaher, Murhaf; Kolb, Jean-Pierre; Billard, Christian; Bauvois, Brigitte
2011-01-01
Background The natural phloroglucinol hyperforin HF displays anti-inflammatory and anti-tumoral properties of potential pharmacological interest. Acute myeloid leukemia (AML) cells abnormally proliferate and escape apoptosis. Herein, the effects and mechanisms of purified HF on AML cell dysfunction were investigated in AML cell lines defining distinct AML subfamilies and primary AML cells cultured ex vivo. Methodology and Results HF inhibited in a time- and concentration-dependent manner the growth of AML cell lines (U937, OCI-AML3, NB4, HL-60) by inducing apoptosis as evidenced by accumulation of sub-G1 population, phosphatidylserine externalization and DNA fragmentation. HF also induced apoptosis in primary AML blasts, whereas normal blood cells were not affected. The apoptotic process in U937 cells was accompanied by downregulation of anti-apoptotic Bcl-2, upregulation of pro-apoptotic Noxa, mitochondrial membrane depolarization, activation of procaspases and cleavage of the caspase substrate PARP-1. The general caspase inhibitor Z-VAD-fmk and the caspase-9- and -3-specific inhibitors, but not caspase-8 inhibitor, significantly attenuated apoptosis. HF-mediated apoptosis was associated with dephosphorylation of active Akt1 (at Ser473) and Akt1 substrate Bad (at Ser136) which activates Bad pro-apoptotic function. HF supppressed the kinase activity of Akt1, and combined treatment with the allosteric Akt1 inhibitor Akt-I-VIII significantly enhanced apoptosis of U937 cells. Significance Our data provide new evidence that HF's pro-apoptotic effect in AML cells involved inhibition of Akt1 signaling, mitochondria and Bcl-2 members dysfunctions, and activation of procaspases -9/-3. Combined interruption of mitochondrial and Akt1 pathways by HF may have implications for AML treatment. PMID:21998731
Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients.
Semeraro, Michaela; Rusakiewicz, Sylvie; Minard-Colin, Véronique; Delahaye, Nicolas F; Enot, David; Vély, Frédéric; Marabelle, Aurélien; Papoular, Benjamin; Piperoglou, Christelle; Ponzoni, Mirco; Perri, Patrizia; Tchirkov, Andrei; Matta, Jessica; Lapierre, Valérie; Shekarian, Tala; Valsesia-Wittmann, Sandrine; Commo, Frédéric; Prada, Nicole; Poirier-Colame, Vichnou; Bressac, Brigitte; Cotteret, Sophie; Brugieres, Laurence; Farace, Françoise; Chaput, Nathalie; Kroemer, Guido; Valteau-Couanet, Dominique; Zitvogel, Laurence
2015-04-15
The immunosurveillance mechanisms governing high-risk neuroblastoma (HR-NB), a major pediatric malignancy, have been elusive. We identify a potential role for natural killer (NK) cells, in particular the interaction between the NK receptor NKp30 and its ligand, B7-H6, in the metastatic progression and survival of HR-NB after myeloablative multimodal chemotherapy and stem cell transplantation. NB cells expressing the NKp30 ligand B7-H6 stimulated NK cells in an NKp30-dependent manner. Serum concentration of soluble B7-H6 correlated with the down-regulation of NKp30, bone marrow metastases, and chemoresistance, and soluble B7-H6 contained in the serum of HR-NB patients inhibited NK cell functions in vitro. The expression of distinct NKp30 isoforms affecting the polarization of NK cell functions correlated with 10-year event-free survival in three independent cohorts of HR-NB in remission from metastases after induction chemotherapy (n = 196, P < 0.001), adding prognostic value to known risk factors such as N-Myc amplification and age >18 months. We conclude that the interaction between NKp30 and B7-H6 may contribute to the fate of NB patients and that both the expression of NKp30 isoforms on circulating NK cells and the concentration of soluble B7-H6 in the serum may be clinically useful as biomarkers for risk stratification. Copyright © 2015, American Association for the Advancement of Science.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kamil, Elynor L.; Morgan, Harry W.T.; Hayward, Michael A., E-mail: michael.hayward@chem.ox.ac.uk
The B-cation deficient perovskite phases Ba{sub 6}Nb{sub 4}RuO{sub 18} and LaBa{sub 4}Nb{sub 3}RuO{sub 15} were prepared by ceramic synthesis. Neutron powder diffraction analysis indicates that rather than the 6-layer and 5-layer cation-deficient perovskite structures expected for these phases (by analogy to the known structures of Ba{sub 6}Nb{sub 4}TiO{sub 18} and LaBa{sub 4}Nb{sub 3}TiO{sub 15}) they adopt 5-layer and 4-layer B-cation deficient perovskite structures respectively, and are better described as Ba{sub 5}Nb{sub 3.33}Ru{sub 0.81}O{sub 15} and Ba{sub 3.16}La{sub 0.84}Nb{sub 2.36}Ru{sub 0.72}O{sub 12}. The factors that lead to the compositionally analogous Nb/Ru and Nb/Ti phases adopting different structures are discussed on themore » basis of the difference between d{sup 0} and non-d{sup 0} transition metal cations. - Graphical abstract: The ruthenium-containing B-cation deficient perovskite phases, Ba{sub 5}Nb{sub 3.33}Ru{sub 0.81}O{sub 15} and Ba{sub 3.16}La{sub 0.84}Nb{sub 2.36}Ru{sub 0.72}O{sub 12}, adopt 5-layer and 4-layer structures respectively, rather than the 6-layer and 5-layer cation-deficient structures adopted by the analogous titanium-containing phases Ba{sub 6}Nb{sub 4}TiO{sub 18} and LaBa{sub 4}Nb{sub 3}TiO{sub 15}. Display Omitted - Highlights: • B-cation deficient perovskite containing paramagnetic cations. • B-cation deficient structure determined by neutron powder diffraction. • Low ‘solubility’ of BaRuO{sub 3} in Ba{sub 5}Nb{sub 4}O{sub 15} leads to novel structure.« less
Superconducting Nb DHEB Mixer Arrays for Far-Infrared Spectroscopy
NASA Technical Reports Server (NTRS)
Gerecht, E.; Reintsema, C. D.; Grossman, E. N.; Betz, A. L.; Boreiko, R. T.
2001-01-01
We are developing a heterodyne focal plane array with up to eight elements to study lines of the interstellar medium and planetary atmospheres with frequencies of 2 THz and above. Our fabrication process utilizes selective ion milling techniques to produce Nb Diffusion-Cooled Hot Electron Bolometric (DHEB) mixers from a bilayer thin film of Au/Nb deposited on a silicon substrate. A micro-bridge of 10 nm thick Nb forms the HEB device. The first generation of devices with lateral dimensions of 100 nm by 80 nm were fabricated at the feed of a broadband spiral antenna with a frequency response designed for up to 16 THz. Harmonic multiplier sources becoming available within the next few years should have sufficient power to provide a local-oscillator source for small-format, quasi-optically coupled arrays of these mixers. First generation devices measured at our laboratory have demonstrated a critical temperature (Tc) of 4.8 K with a 0.5 K transition width. These DHEB mixers are expected to have an optimum operational temperature of 1.8-2.0 K. The current four element array mixer block will ultimately be replaced by a dual polarization slot-ring array configuration with up to eight elements.
Niobium Doping Effects on TiO2 Mesoscopic Electron Transport Layer-Based Perovskite Solar Cells.
Kim, Dong Hoe; Han, Gill Sang; Seong, Won Mo; Lee, Jin-Wook; Kim, Byeong Jo; Park, Nam-Gyu; Hong, Kug Sun; Lee, Sangwook; Jung, Hyun Suk
2015-07-20
Perovskite solar cells (PSCs) are the most promising candidates as next-generation solar energy conversion systems. To design a highly efficient PSC, understanding electronic properties of mesoporous metal oxides is essential. Herein, we explore the effect of Nb doping of TiO2 on electronic structure and photovoltaic properties of PSCs. Light Nb doping (0.5 and 1.0 at %) increased the optical band gap slightly, but heavy doping (5.0 at %) distinctively decreased it. The relative Fermi level position of the conduction band is similar for the lightly Nb-doped TiO2 (NTO) and the undoped TiO2 whereas that of the heavy doped NTO decreased by as much as ∼0.3 eV. The lightly doped NTO-based PSCs exhibit 10 % higher efficiency than PSCs based on undoped TiO2 (from 12.2 % to 13.4 %) and 52 % higher than the PSCs utilizing heavy doped NTO (from 8.8 % to 13.4 %), which is attributed to fast electron injection/transport and preserved electron lifetime, verified by transient photocurrent decay and impedance studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Mechanical and Thermal Properties of Two Cu-Cr-Nb Alloys and NARloy-Z
NASA Technical Reports Server (NTRS)
Ellis, David L.; Michal, Gary M.
1996-01-01
A series of creep tests were conducted on Cu-8 Cr-4 Nb (Cu-8 at.% Cr-4 at.% Nb), Cu-4 Cr-2 Nb (Cu-4 at.% Cr-2 at% Nb), and NARloy-Z (Cu-3 wt.% Ag-0.5 wt.% Zr) samples to determine their creep properties. In addition, a limited number of low cycle fatigue and thermal conductivity tests were conducted. The Cu-Cr-Nb alloys showed a clear advantage in creep life and sustainable load over the currently used NARloy-Z. Increases in life at a given stress were between 100% and 250% greater for the Cu-Cr-Nb alloys depending on the stress and temperature. For a given life, the Cu-Cr-Nb alloys could support a stress between 60% and 160% greater than NARloy-Z. Low cycle fatigue lives of the Cu-8 Cr-4 Nb alloy were equivalent to NARloy-Z at room temperature. At elevated temperatures (538 C and 650 C), the fatigue lives were 50% to 200% longer than NARloy-Z samples tested at 538 C. The thermal conductivities of the Cu-Cr-Nb alloys remained high, but were lower than NARloy-Z and pure Cu. The Cu-Cr-Nb thermal conductivities were between 72% and 96% that of pure Cu with the Cu-4 Cr-2 Nb alloy having a significant advantage in thermal conductivity over Cu-8 Cr4 Nb. In comparison, stainless steels with equivalent strengths would have thermal conductivities less than 25% the thermal conductivity of pure Cu. The combined results indicate that the Cu-Cr-Nb alloys offer an attractive alternative to current high temperature Cu-based alloys such as NARloy-Z.
[Study of oxygen consumption in infants of diabetic mothers].
Courpotin, C; Keenan, W J; Sutherland, J M; Gerbeaux, J
1975-01-01
The energy expenditure (VO2) was measured during the first 36 hours of life in 10 infants of diabetic mothers (IDM) and in 16 normal newborns (NB). The mean VO2 was 5,72 ml/kg/min +/- 0,4 for the NB and 4,94 ml/kg/min. +/- 0,3 for the IDM. The respiratory quotients were similar for both groups. Blood glucose determination from all IDM were greater than 44 mg%. Although the low VO2 for IDM is unexplained, several hypothesis might be anticipated: either lack of utilization of abundant endogenous glycogen stores or increased metabolism of glucose by the cells.
Fan, Xiaozhou; Wang, Luofu; Guo, Yanli; Xiong, Xingyu; Zhu, Lianhua; Fang, Kejing
2016-01-01
Ultrasound (US)-targeted microbubble destruction has been widely used as an effective drug-delivery system. However, nanobubbles (NBs) have better stability and stronger penetration than microbubbles, and drug delivery assisted by US-targeted NB destruction (UTND) still needs to be investigated. Our aim was to investigate the effect of doxorubicin (DOX) on the inhibition of prostate cancer growth under UTND. Contrast-enhanced US imaging of transplanted PC3 prostate cancer in mice showed that under a combination of 1 W/cm2 US power and a 100 Hz intermittent pulse with a “5 seconds on, 5 seconds off” mode, NBs with an average size of (485.7±33) nm were effectively destroyed within 15 minutes in the tumor location. PC3 cells and 20 tumor-bearing mice were divided into four groups: a DOX group, a DOX + NB group, a DOX + US group, and a DOX + NB + US group. The cell growth-inhibition rate and DOX concentration of xenografts in the DOX + NB + US group were highest. Based on another control group and these four groups, another 25 tumor-bearing mice were used to observe the treatment effect of nine DOX injections under UTND. The xenografts in the DOX + NB + US group decreased more obviously and had more cellular apoptosis than other groups. Finally, electron microscopy was used to estimate the cavitation effect of NBs under US irradiation in the control group, NB group, US group, and NB + US group. The results of scanning electron microscopy showed that PC3 cells in the DOX + NB + US group had more holes and significantly increased cell-surface folds. Meanwhile, transmission electric microscopy confirmed that more lanthanum nitrate particles entered the parenchymal cells in xenografts in the NB + US group compared with the other groups. This study suggested that UTND technology could be an effective method to promote drugs to function in US-irradiated sites, and the underlying mechanism may be associated with a cavitation effect. PMID:27536100
Corrosion behavior and oxide properties of Zr 1.1 wt%Nb 0.05 wt%Cu alloy
NASA Astrophysics Data System (ADS)
Park, Jeong-Yong; Choi, Byung-Kwon; Yoo, Seung Jo; Jeong, Yong Hwan
2006-12-01
The corrosion behavior and oxide properties of Zr-1.1 wt%Nb-0.05 wt%Cu (ZrNbCu) and Zircaloy-4 have been investigated. The corrosion rate of the ZrNbCu alloy was much lower than that of the Zirclaoy-4 in the 360 °C water and 360 °C PWR-simulating loop condition without a neutron flux and it was increased with an increase of the final annealing temperature from 470 °C to 570 °C. TEM observations revealed that the precipitates in the ZrNbCu were β-Nb and ZrNbFe-precipitate with β-Nb being more frequently observed and that the precipitates were more finely distributed in the ZrNbCu alloy. It was also observed that the oxides of the ZrNbCu and Zircaloy-4 consisted of two and seven layers, respectively, after 1000 days in the PWR-simulating loop condition and that the thickness of a fully-developed layer was higher in the ZrNbCu than in the Zircaloy-4. It was also found that the β-Nb in ZrNbCu was oxidized more slowly when compared to the Zr(Fe, Cr) 2 in Zirclaoy-4 when the precipitates in the oxide were observed by TEM. Cracks were observed in the vicinity of the oxidized Zr(Fe, Cr) 2, while no cracks were formed near β-Nb which had retained a metallic state. From the results obtained, it is suggested that the oxide formed on the ZrNbCu has a more protective nature against a corrosion when compared to that of the Zircaloy-4.
Zhang, Qi; Du, Xinhang; Tan, Shengwei; Tang, Dian; Chen, Kongfa; Zhang, Teng
2017-07-13
Nb 2 O 5 is added to a borosilicate sealing system to improve the thermo-mechanical stability of the sealing interface between the glass and Fe-Cr metallic interconnect (Crofer 22APU) in solid oxide fuel cells (SOFCs). The thermo-mechanical stability of the glass/metal interface is evaluated experimentally as well as by using a finite element analysis (FEA) method. The sealing glass doped with 4 mol.% Nb 2 O 5 shows the best thermo-mechanical stability, and the sealing couple of Crofer 22APU/glass/GDC (Gd 0.2 Ce 0.8 O 1.9 ) remains intact after 50 thermal cycles. In addition, all sealing couples show good joining after being held at 750 °C for 1000 h. Moreover, the possible mechanism on the thermo-mechanical stability of sealing interface is investigated in terms of stress-based and energy-based perspectives.
Lorenz, Jonas; Kubesch, Alica; Korzinskas, Tadas; Barbeck, Mike; Landes, Constantin; Sader, Robert A; Kirkpatrick, Charles J; Ghanaati, Shahram
2015-12-01
This study compared the material-specific tissue response to the synthetic, hydroxyapatite-based bone substitute material NanoBone (NB) with that of the xenogeneic, bovine-based bone substitute material Bio-Oss (BO). The sinus cavities of 14 human patients were augmented with NB and BO in a split-mouth design. Six months after augmentation, bone biopsies were extracted for histological and histomorphometric investigation prior to dental implant insertion. The following were evaluated: the cellular inflammatory pattern, the induction of multinucleated giant cells, vascularization, the relative amounts of newly formed bone, connective tissue, and the remaining bone substitute material. NB granules were well integrated in the peri-implant tissue and were surrounded by newly formed bone tissue. Multinucleated giant cells were visible on the surfaces of the remaining granules. BO granules were integrated into the newly formed bone tissue, which originated from active osteoblasts on their surface. Histomorphometric analysis showed a significantly higher number of multinucleated giant cells and blood vessels in the NB group compared to the BO group. No statistical differences were observed in regard to connective tissue, remaining bone substitute, and newly formed bone. The results of this study highlight the different cellular reactions to synthetic and xenogeneic bone substitute materials. The significantly higher number of multinucleated giant cells within the NB implantation bed seems to have no effect on its biodegradation. Accordingly, the multinucleated giant cells observed within the NB implantation bed have characteristics more similar to those of foreign body giant cells than to those of osteoclasts.
Gel shift analysis of the empA promoter region in Vibrio anguillarum
Denkin, Steven M; Sekaric, Pedja; Nelson, David R
2004-01-01
Background The induction of metalloprotease encoded by empA in Vibrio anguillarum occurs at high cell density in salmon intestinal mucus. Previously we have shown that there are significant differences in empA expression in two strains of V. anguillarum, M93Sm and NB10. It is hypothesized that differences in empA regulation are due to differences in binding of regulatory elements. Results Two strains of V. anguillarum, M93Sm and NB10, were examined and compared for the presence of DNA regulatory proteins that bind to and control the empA promoter region. Gel mobility shift assays, using a digoxigenin (DIG)-labeled oligomer containing a lux box-like element and the promoter for empA, were done to demonstrate the presence of a DNA-binding protein. Protein extracts from NB10 cells incubated in Luria Bertani broth + 2% NaCl (LB20), nine salts solution + 200 μg/ml mucus (NSSM), 3M (marine minimal medium), or NSS resulted in a gel mobility shift. No gel mobility shift was seen when protein extracts from either LB20- or NSSM-grown M93Sm cells were mixed with the DIG-labeled empA oligomer. The azocasein assay detected protease activity in all incubation conditions for NB10 culture supernatants. In contrast, protease activity was detected in M93Sm culture supernatants only when incubated in NSSM. Since the luxR homologue in V. anguillarum, vanT, has been cloned, sequenced, and shown to be required for protease activity, we wanted to determine if vanT mutants of NB10 exhibit the same gel shift observed in the wild-type. Site-directed mutagenesis was used to create vanT mutants in V. anguillarum M93Sm and NB10 to test whether VanT is involved with the gel mobility shift. Both vanT mutants, M02 and NB02, did not produce protease activity in any conditions. However, protein extracts from NB02 incubated in each condition still exhibited a gel shift when mixed with the DIG-labeled empA oligomer. Conclusions The data demonstrate that protein extracts of V. anguillarum NB10 cells contain a protein that binds to a 50 bp oligomer containing the empA promoter-lux box-like region. NB10 cells express empA during stationary phase in all growth conditions. The DNA binding protein is not present in M93Sm extracts. M93Sm cells express protease activity only when incubated at high cell density in fish gastrointestinal mucus. The gel shift observed with NB10 cells is not due to VanT binding. The data also suggest that the DNA binding protein is responsible for the less restrictive expression of empA in NB10 compared to M93Sm. PMID:15516264
Niobium in R And (S6, 6e) and HR 1105 (S5, 3)
NASA Astrophysics Data System (ADS)
Davis, D. N.
Lines of the first multiplet of niobium are strong in R And and HR 1105. These lines are also present in other S stars: HR 8714, R Cam, V Cnc, R CMi, and T Sgr. They are also visible in the M stars, Beta-Peg and Mu-UMa. An approximation to the abundance ratio, Nb/Fe, has been deduced from pairs of lines having nearly equal intensity. In R And, the ratio is about 200 times the solar value. It is hoped that good plates will soon be obtained for the near infrared region, so that the significant Nb/Rb abundance ratio may be determined.
Zuscik, M J; Piascik, M T; Perez, D M
1999-12-01
The functionality of a 3422-base pair promoter fragment from the mouse alpha(1B)-adrenergic receptor (alpha(1B)AR) gene was examined. This fragment, cloned from a mouse genomic library, was found to have significant sequence homology to the known human and rat alpha(1B)AR promoters. However, the consensus motif of several key cis-acting elements is not conserved among the rat, human, and mouse genes, suggesting species specificity. Confirming fidelity of the murine promoter, robust in vitro expression of a chloramphenicol acetyltransferase (CAT) reporter was detected in known alpha(1B)AR-expressing BC(3)H1, NB41A3, and DDT(1)MF-2 cells transiently transfected with a promoter-CAT construct. Conversely, minimal CAT expression was detected in known alpha(1B)AR-negative RAT-1 and R3T3 cells. These findings were extended by transfecting the same promoter-CAT construct into various primary cell types. In support of the hypothesis that alpha(1)ARs are differentially expressed in the smooth muscle of the vasculature, primary cultures of superior mesenteric and renal artery vascular smooth muscle cells showed significantly stronger CAT expression than did vascular smooth muscle cells derived from pulmonary, femoral, and iliac arteries. Primary osteoblastic bone-forming cells, which are known to be alpha(1B)AR negative, showed minimal CAT expression. Indicating regulatory function through cis-acting elements, RAT-1, R3T3, NB41A3, BC(3)H1, and DDT(1)MF2 cells transfected with the promoter-CAT construct all showed increased CAT production when challenged with forskolin or hypoxic conditions. Additionally, tissue-specific regulation of the promoter was observed when cells were simultaneously challenged with both forskolin and hypoxia. These results collectively demonstrate that a 3.4-kb PvuII fragment of the murine alpha(1B)AR gene promoter can: 1) drive tissue-specific production of a CAT reporter in both clonal and primary cell lines; and 2) confer tissue-specific regulation of that CAT reporter when induced by challenge with forskolin and/or hypoxic conditions.
Improvement of stability of Nb 3 Sn superconductors by introducing high specific heat substances
Xu, X.; Li, P.; Zlobin, A. V.; ...
2018-01-24
High-J c Nb 3Sn conductors have low stability against perturbations, which accounts for the slow training rates of high-field Nb 3Sn magnets. While it is known that adding substances with high specific heat (C) into Nb 3Sn wires can increase their overall specific heat and thus improve their stability, there has not been a practical method that is compatible with the fabrication of long-length conductors. In this work, we put forward a scheme to introduce such substances to distributed-barrier Nb 3Sn wires, which adds minimum difficulty to the wire manufacturing process. Multifilamentary wires using a mixture of Cu and high-Cmore » Gd 2O 3 powders have been successfully fabricated along this line. Measurements showed that addition of Gd 2O 3 had no negative effects on residual resitivity ratio or non-Cu J c, and that flux jumps were remarkably reduced, and minimum quench energy values at 4.2 K, 14 T were increased by a factor of three, indicating that stability was significantly improved. We also discussed the influences of the positioning of high-C substances and their thermal diffusivity on their effectiveness in reducing the superconductor temperature rise against perturbations. Based on these results, we proposed an optimized conductor architecture to maximize the effectiveness of this approach.« less
Improvement of stability of Nb 3 Sn superconductors by introducing high specific heat substances
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, X.; Li, P.; Zlobin, A. V.
High-J c Nb 3Sn conductors have low stability against perturbations, which accounts for the slow training rates of high-field Nb 3Sn magnets. While it is known that adding substances with high specific heat (C) into Nb 3Sn wires can increase their overall specific heat and thus improve their stability, there has not been a practical method that is compatible with the fabrication of long-length conductors. In this work, we put forward a scheme to introduce such substances to distributed-barrier Nb 3Sn wires, which adds minimum difficulty to the wire manufacturing process. Multifilamentary wires using a mixture of Cu and high-Cmore » Gd 2O 3 powders have been successfully fabricated along this line. Measurements showed that addition of Gd 2O 3 had no negative effects on residual resitivity ratio or non-Cu J c, and that flux jumps were remarkably reduced, and minimum quench energy values at 4.2 K, 14 T were increased by a factor of three, indicating that stability was significantly improved. We also discussed the influences of the positioning of high-C substances and their thermal diffusivity on their effectiveness in reducing the superconductor temperature rise against perturbations. Based on these results, we proposed an optimized conductor architecture to maximize the effectiveness of this approach.« less
LARP Long Quadrupole: A "Long" Step Toward an LHC
Giorgio Ambrosio
2017-12-09
The beginning of the development of Nb3Sn magnets for particle accelerators goes back to the 1960âs. But only very recently has this development begun to face the challenges of fabricating Nb3Sn magnets which can meet the requirements of modern particle accelerators. LARP (the LHC Accelerator Research Program) is leading this effort focusing on long models of the Interaction Region quadrupoles for a possible luminosity upgrade of the Large Hadron Collider. A major milestone in this development is to test, by the end of 2009, 4m-long quadrupole models, which will be the first Nb3Sn accelerator-type magnets approaching the length of real accelerator magnets. The Long Quadrupoles (LQ) are âProof-of-Principleâ magnets which are to demonstrate that Nb3Sn technology is sufficiently mature for use in high energy particle accelerators. Their design is based on the LARP Technological Quadrupole (TQ) models, under development at FNAL and LBNL, which have design gradients higher than 200 T/m and an aperture of 90 mm. Several challenges must be addressed for the successful fabrication of long Nb3Sn coils and magnets. These challenges and the solutions adopted will be presented together with the main features of the LQ magnets. Several R&D lines are participating to this effort and their contributions will be also presented.
Effect of [Li]/[Nb] ratio on composition and defect structure of Zr:Yb:Tm:LiNbO3 crystals
NASA Astrophysics Data System (ADS)
Liu, Chunrui; Dai, Li; Wang, Luping; Shao, Yu; Yan, Zhehua; Xu, Yuheng
2018-04-01
Zr:Yb:Tm:LiNbO3 crystals with various [Li]/[Nb] ratios (0.946, 1.05, 1.20 and 1.38) were grown by the Czochralski technique. Distribution coefficients of Zr4+, Yb3+ and Tm3+ ions were analyzed by the inductively coupled plasma-atomic emission spectrometer (ICP-AES). The influence of [Li]/[Nb] ratio on the composition and defect structure of Zr:Yb:Tm:LiNbO3 crystals was investigated by X-ray diffraction and IR transmission spectrum. The results show that as the [Li]/[Nb] ratio increases in the melt, the distribution coefficients of Yb3+ and Tm3+ ions both increase while that of Zr4+ ion deceases. When the [Li]/[Nb] ratio increases to 1.20 in the melt, Zr:Yb:Tm:LiNbO3 crystal is nearly stoichiometric. In addition, when the [Li]/[Nb] ratio reaches up to 1.38, NbLi4+ are completely replaced and Li+ starts to impel the Zr4+, Yb3+ and Tm3+ into the normal Li sites.
Zhang, Changsheng; Cai, Hongmin; Huang, Jingying; Song, Yan
2016-09-17
Variations in DNA copy number have an important contribution to the development of several diseases, including autism, schizophrenia and cancer. Single-cell sequencing technology allows the dissection of genomic heterogeneity at the single-cell level, thereby providing important evolutionary information about cancer cells. In contrast to traditional bulk sequencing, single-cell sequencing requires the amplification of the whole genome of a single cell to accumulate enough samples for sequencing. However, the amplification process inevitably introduces amplification bias, resulting in an over-dispersing portion of the sequencing data. Recent study has manifested that the over-dispersed portion of the single-cell sequencing data could be well modelled by negative binomial distributions. We developed a read-depth based method, nbCNV to detect the copy number variants (CNVs). The nbCNV method uses two constraints-sparsity and smoothness to fit the CNV patterns under the assumption that the read signals are negatively binomially distributed. The problem of CNV detection was formulated as a quadratic optimization problem, and was solved by an efficient numerical solution based on the classical alternating direction minimization method. Extensive experiments to compare nbCNV with existing benchmark models were conducted on both simulated data and empirical single-cell sequencing data. The results of those experiments demonstrate that nbCNV achieves superior performance and high robustness for the detection of CNVs in single-cell sequencing data.
WANG, STEPHANIE S.; HSIAO, RUTH; LIMPAR, MARIKO M.; LOMAHAN, SARAH; TRAN, TUAN-ANH; MALONEY, NOLAN J.; IKEGAKI, NAOHIKO; TANG, XAO X.
2014-01-01
In the present study, we investigated the anticancer effects of the mitochondrial inhibitors, metaiodobenzylguanidine (MIBG), metformin and phenformin. 131I-MIBG has been used for scintigraphic detection and the targeted radiotherapy of neuroblastoma (NB), a pediatric malignancy. Non-radiolabeled MIBG has been reported to be cytotoxic to NB cells in vitro and in vivo. However, the mechanisms behind its growth suppressive effects have not yet been fully elucidated. Metformin and phenformin are diabetes medications that are being considered in anticancer therapeutics. We investigated the anticancer mechanisms of action of MIBG and metformin in NB. Our data revealed that both drugs suppressed NB cell growth and that the combination drug treatment was more potent. MIBG reduced MYCN and MYC expression in MYCN-amplified and non-MYCN-amplified NB cells in a dose- and time-dependent manner. Metformin was less effective than MIBG in destabilizing MYC/MYCN. The treatment of NB cells with metformin or MIBG resulted in an increased expression of genes encoding biomarkers for favorable outcome in NB [(ephrin (EFN)B2, EFNB3, EPH receptor B6 (EPHB6), neurotrophic tyrosine kinase, receptor, type 1 (NTRK1), CD44 and Myc-interacting zinc finger protein (MIZ-1)] and tumor suppressor genes [(early growth response 1 (EGR1), EPH receptor A2 (EPHA2), growth arrest and DNA-damage-inducible, beta (GADD45B), neuregulin 1 (NRG1), TP53 apoptosis effector (PERP) and sel-1 suppressor of lin-12-like (C. elegans) (SEL1L)]. Accordingly, metformin and MIBG augmented histone H3 acetylation in these cells. Phenformin also exhibited histone modification and was more effective than metformin in destabilizing MYC/MYCN in NB cells. Our data suggest that the destabilization of MYC/MYCN by MIBG, metformin and phenformin and their effects on histone modification are important mechanisms underlying their anticancer effects. PMID:24190252
Wang, Stephanie S; Hsiao, Ruth; Limpar, Mariko M; Lomahan, Sarah; Tran, Tuan-Anh; Maloney, Nolan J; Ikegaki, Naohiko; Tang, Xao X
2014-01-01
In the present study, we investigated the anticancer effects of the mitochondrial inhibitors, metaiodobenzylguanidine (MIBG), metformin and phenformin. 131I-MIBG has been used for scintigraphic detection and the targeted radiotherapy of neuroblastoma (NB), a pediatric malignancy. Non-radiolabeled MIBG has been reported to be cytotoxic to NB cells in vitro and in vivo. However, the mechanisms behind its growth suppressive effects have not yet been fully elucidated. Metformin and phenformin are diabetes medications that are being considered in anticancer therapeutics. We investigated the anticancer mechanisms of action of MIBG and metformin in NB. Our data revealed that both drugs suppressed NB cell growth and that the combination drug treatment was more potent. MIBG reduced MYCN and MYC expression in MYCN-amplified and non-MYCN-amplified NB cells in a dose- and time-dependent manner. Metformin was less effective than MIBG in destabilizing MYC/MYCN. The treatment of NB cells with metformin or MIBG resulted in an increased expression of genes encoding biomarkers for favorable outcome in NB [(ephrin (EFN)B2, EFNB3, EPH receptor B6 (EPHB6), neurotrophic tyrosine kinase, receptor, type 1 (NTRK1), CD44 and Myc-interacting zinc finger protein (MIZ-1)] and tumor suppressor genes [(early growth response 1 (EGR1), EPH receptor A2 (EPHA2), growth arrest and DNA-damage-inducible, beta (GADD45B), neuregulin 1 (NRG1), TP53 apoptosis effector (PERP) and sel-1 suppressor of lin-12-like (C. elegans) (SEL1L)]. Accordingly, metformin and MIBG augmented histone H3 acetylation in these cells. Phenformin also exhibited histone modification and was more effective than metformin in destabilizing MYC/MYCN in NB cells. Our data suggest that the destabilization of MYC/MYCN by MIBG, metformin and phenformin and their effects on histone modification are important mechanisms underlying their anticancer effects.
Analyses of Nb-1Zr/C-103, vapor anode, multi-tube AMTEC cells
NASA Astrophysics Data System (ADS)
King, Jeffrey C.; El-Genk, Mohamed S.
2000-01-01
A high performance, Nb-1Zr/C-103, vapor anode, multi-tube AMTEC cell design is presented. The cell measures 41.27 mm in diameter, is 125.3 mm high, and has eight BASE tubes connected electrically in series. The hot structure of the cell (hot plate, BASE tubes support plate, hot plenum wall, evaporator standoff, evaporator wick, and side wall facing the BASE tubes) is made of Nb-1Zr. The cold structure of the cell (condenser, interior cylindrical thermal radiation shield, the casing and the wick of the liquid sodium return artery, and side wall above the BASE tubes) is made of the stronger, lower thermal conductivity niobium alloy C-103. This cell, which weighs 163.4 g, could deliver 7.0 We at 17% efficiency and load voltage of 3.3 V, when using TiN BASE electrodes characterized by B=75 A.K1/2/m2.Pa and G=50 and assuming BASE/electrode contact resistance of 0.06 Ω-cm2 and leakage resistance of the BASE braze structure of 3 Ω. For these performance parameters and when the interior cylindrical C-103 thermal radiation shield is covered with low emissivity rhodium, the projected specific mass of the cell is 23.4 g/We. The BASE brazes and the evaporator temperatures were below the recommended limits of 1123 K and 1023 K, respectively. In addition, the temperature margin in the cell was at least + 20 K. When electrodes characterized by B=120 A.K1/2/m2.Pa and G=10 were used, the cell power increased to 8.38 We at 3.5 V and efficiency of 18.8%, for a cell specific mass of 19.7 g/We. Issues related to structure strength of the cell and the performance degradation of the BASE and electrodes are not addressed in this paper. .
Evolution of magnetic properties of CaMn1-x Nb x O3 with Nb-doping
NASA Astrophysics Data System (ADS)
Markovich, V.; Fita, I.; Wisniewski, A.; Puzniak, R.; Martin, C.; Mogilyansky, D.; Jung, G.; Gorodetsky, G.
2015-08-01
Magnetic and structural properties of Nb-doped CaMnO3 have been studied and the effect of doping with 0.02 ⩽ x ⩽ 0.1 has been investigated. Substitution of Nb5+ ion for the Mn4+ site of the parent matrix causes one-electron doping with the chemical formula \\text{CaMn}1-2x4+\\text{Mn}x3+\\text{Nb}x5+{{\\text{O}}3} , accompanied by a monotonous increase of the lattice parameters, unit-cell volume, average Mn-O bond distance and a decrease in Mn-O-Mn bond angle, with increasing x. Low temperature magnetic ground state of CaMn1-x Nb x O3 has been found to be dependent on niobium doping level. The ground magnetic state evolves from mostly antiferromagnetic, with a weak ferromagnetic component for x = 0.02-0.08, to charge ordered C-type antiferromagnetic state at x = 0.1. Spontaneous magnetization increases sharply with increasing doping level, approaches a maximal value of 4.1 emu g-1 at T = 10 K for x = 0.08, and then decreases rapidly to reach a very small value of 0.2 emu g-1 for x = 0.1. Anomalous negative magnetization behavior below the magnetic transition temperature has been observed for the compound with x = 0.04 in the field cooled magnetization and remanent dc magnetization measurements. Vertical and horizontal shifts of the hysteresis loop of the field cooled sample have been observed for CaMn0.9Nb0.1O3 as possible signatures of the exchange bias effect. The effect of hydrostatic pressure on dc magnetization for the sample with x > 0.02 revealed a significant increase of the ferromagnetic phase volume under pressure, linked to progressive suppression of a negative magnetization in x = 0.04 sample.
Monoclinic structures of niobium trisulfide
NASA Astrophysics Data System (ADS)
Bloodgood, Matthew A.; Wei, Pingrong; Aytan, Ece; Bozhilov, Krassimir N.; Balandin, Alexander A.; Salguero, Tina T.
2018-02-01
Two new polymorphs of niobium trisulfide are established by single crystal x-ray diffraction. NbS3-iv crystallizes in the monoclinic space group P21/c with lattice parameters a = 6.7515(5) Å, b = 4.9736(4) Å, c = 18.1315(13) Å, and β = 90.116(2)°. Its structure is based on chains of [NbS6] trigonal prisms containing Nb-Nb pairs with a bond length of 3.0448(8) Å; this pairing causes the chains to corrugate slightly along their axis, a feature also present in triclinic NbS3-i that leads to semiconductor properties. The stacking arrangement of chains is different in these polymorphs, however, with NbS3-i having an ABCDE repeating sequence of chain bilayers and NbS3-iv having an AB repeating sequence. HRTEM studies show the presence of topotactically-oriented intergrown zones and numerous dislocations, which result in mosaic structuring. A second new polymorph, NbS3-v, crystallizes in the monoclinic space group P21/m with lattice parameters a = 4.950(5) Å, b = 3.358(4) Å, c = 9.079(10) Å, β = 97.35(2)°. In contrast to NbS3-iv, NbS3-v maintains fixed a Nb-Nb bond distance of 3.358(4) Å along the chains, and it has an ABCDE repeating sequence of chain bilayers similar to NbS3-i. High resolution scanning transmission electron microscopy (HR-STEM) imaging of an exfoliated NbS3-v nanoribbon shows the continuous [NbS6] chains oriented along the b-axis. These results provide the first firmly established structural data for monoclinic NbS3. In addition, SEM images show the formation of NbS3 rings and cylinders, and a combination of powder x-ray diffraction and Raman spectroscopy provides a way to distinguish between NbS3 polymorphs.
Wu, Wei; Zhang, Zhe; Zhuo, Lisha; Zhou, Lina; Liu, Ping; He, Yun; Gao, Yunhua; Li, Rui; Chen, Qinghai; Hua, Xing
2013-09-01
Acute rejection (AR) is one of the main obstacles of cardiac transplantation; however, a noninvasive diagnostic method, which reflects its pathologic nature, has not been developed yet. In this study, we prepared a specific nanobubbles targeting to the activated T cells and applied it in the ultrasound molecular imaging of AR in heart transplantation by myocardial contrast echocardiography (MCE). Nanobubbles loading anti-CD25 antibody (NB(specific)) or isotype control antibody (NB(nonspecific)) were prepared and then applied in the ultrasound molecular imaging by MCE in a rat model. MCE was performed in 24 allografts and 18 isografts that were divided into three groups, including days 2, 4, and 6 after transplantation. Confocal laser scanning microscopy was used to evaluate the binding of nanobubbles and T cells in four allografts and four isografts. MCE with NB(specific) in allograft showed a "delayed enhancement," and the time-intensity curve presented a second peak. The intensity and time of second peak were both positively correlated with the transplant time (P<0.01) and the pathologic grade of AR (P<0.01). Confocal laser scanning microscopy demonstrated the binding of nanobubbles and lymphocytes in myocardium post-MCE with NB(specific). Ultrasound molecular imaging of AR after heart transplantation can be achieved by using MCE with the nanobubbles targeted to T cells. The appearance of delayed enhancement indicates the occurrence of AR, and the intensity and time of the second peak in time-intensity curve provide potential quantitative indications for diagnosis and severity of AR.
Hassan, A N; Frank, J F
2004-10-01
This study investigated the effect of growth in tryptic soy broth (TSB) and nutrient broth (NB) on the ability Escherichia coli O157:H7 to attach to lettuce and apple surfaces. In addition, cell surface hydrophobicity, charge and capsule production were determined on cells grown in these media. Cells grown in NB attached less to lettuce and apple surfaces than did those grown in TSB. TSB, but not NB, supported capsule production by E. coli O157:H7. Cells grown in TSB were more hydrophilic than those grown in NB. No difference was found in the electrokinetic properties of cells grown in these media. Electrostatic and hydrophobic interactions and surface proteins did not appear to play an important role in the attachment of E. coli O157:H7 to these surfaces. Of the factors studied, only capsule production was associated with attachment ability. Copyright 2003 Elsevier B.V.
Spectrum and energy levels of kryptonlike ion Nb VI
DOE Office of Scientific and Technical Information (OSTI.GOV)
Reader, J.; Ekberg, J.O.
1993-05-01
The spectrum of five-times ionized niobium, Nb, VI, was observed from 238 to 2700 {angstrom} with sliding spark discharges on 10.7-m normal- and grazing-incidence spectrographs. Experimental energies were determined for all levels of the 4s{sup 2}4p{sup 6}, 4s{sup 2}4p{sup 6}, 4s{sup 2}4p{sup 5}4d, 4f, 5s, 5p, 5g, 6s, and 4s4p{sup 6}4d configurations as well as some levels of 4p{sup 5}6g. A total of 291 lines were classified as transitions between 88 observed levels. A previous analysis of this spectrum was found to be totally erroneous. Large hyperfine splittings were found for several levels of the 4p{sup 5}5s and 5p configurations.more » The observed configurations were theoretically interpreted by means of Hartree-Fock calculations and least squares fits of the energy parameters to the observed levels. A revised value of the ionization energy was obtained from the 4p{sup 5}5g and 6g configurations.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kejun, Z.; Zhanpeng, J.
There are three intermetallic compounds in the Ni{sub 3}Nb, Ni{sub 6}Nb{sub 7}, and Ni{sub 8}Nb. Several attempts have been made to describe the Ni-Nb phase diagram by means of a thermodynamic approach. Kaufman and Nesor modeled the intermetallic compounds as line compounds. The compound Ni{sub 6}Nb{sub 7} was predicted to melt congruently, contrary to experimental data. In the work of Chevalier the homogeneity ranges of the compound phases were not considered, and the calculated (Ni) solvus overestimated the solubility of Nb. Although Ni{sub 6}Nb{sub 7} phase was described with a sublattice model, its nonzero width has not been predicted. Thismore » paper reports that a stoichiometric phase can usually be regarded as composed of two or more sublattices, the sites of each one being occupied by a certain element. If the phase has a small range of homogeneity, different species, which are sufficiently similar in size, shape, electronegativity, etc., may form mixtures on several of the sublattices.« less
NASA Astrophysics Data System (ADS)
Ida, H.; Shinozaki, K.; Honma, T.; Oh-ishi, K.; Komatsu, T.
2012-12-01
Ba1-xRE2x/3Nb2O6 nanocrystals with a tetragonal tungsten bronze (TTB) structure are synthesized using a conventional glass crystallization technique in 2.3RE2O3-27.4BaO-34.3Nb2O5-36B2O3 (mol%) (RE=Sm, Eu, Gd, Dy, and Er) glasses. One sharp crystallization peak is observed at ∼670 °C in both powdered and bulk glasses, and the formation of Ba1-xRE2x/3Nb2O6 nanocrystals with unit cell parameters of a∼1.24 nm and c∼0.39 nm was confirmed. It is found from high resolution transmission electron microscope observations that the morphology of Ba1-xRE2x/3Nb2O6 nanocrystals is ellipsoidal. Their average particle size is in the range of 15-60 nm and decreases with decreasing ionic radius of RE3+ being present in the precursor glasses. The optical transparent crystallized glass (bulk) shows the total photoluminescence (PL) quantum yield of 53% in the visible region of Eu3+ ions, suggesting a high potential of Ba1-xRE2x/3Nb2O6 nanocrystals as PL materials.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, Wenqing; Beilhartz, Greg; Roy, Yvette
2010-04-15
1,25 Dihydroxyvitamin D{sub 3} (1,25D{sub 3}) primes NB4 promyelocytic leukemia cells to differentiate along the monocyte/macrophage lineage through a non-genomic mechanism. Here we show that NB4 cells express high levels of the recently identified membrane receptor for 1,25D{sub 3}, which is a distinct gene product from the classical nuclear vitamin D receptor. This 57 kDa protein, named 1,25D{sub 3}-MARRS (Membrane Activated Rapid Response to Steroids)/ERp57/PIA3 appears to associate in a complex with the transcription factor, nuclear factor kappa B (NF{kappa}B). In unstimulated cells, 1,25D{sub 3}-MARRS can be co-immunoprecipitated with antibodies directed at NF{kappa}B, and NF{kappa}B is co-precipitated when antibodies againstmore » 1,25D{sub 3}-MARRS or ERp57 are used. Confocal microscopy and subcellular fractionation studies demonstrate that both 1,25D{sub 3}-MARRS and NF{kappa}B begin translocating to the nucleus within minutes of co-stimulation with 1,25D{sub 3} and phorbol ester. The predominant nuclear localization of both proteins precedes the expression of the monocyte/macrophage phenotype and suggests that this event may be critical to the differentiation pathway. This suggests a role for 1,25D{sub 3}-MARRS in the nucleus as a regulator of gene expression. Here it may also regulate the activity of NF{kappa}B and other factors with which it may be interacting.« less
Chu, Z L; Pio, F; Xie, Z; Welsh, K; Krajewska, M; Krajewski, S; Godzik, A; Reed, J C
2001-03-23
Apaf1/CED4 family members play central roles in apoptosis regulation as activators of caspase family cell death proteases. These proteins contain a nucleotide-binding (NB) self-oligomerization domain and a caspase recruitment domain (CARD). A novel human protein was identified, NAC, that contains an NB domain and CARD. The CARD of NAC interacts selectively with the CARD domain of Apaf1, a caspase-activating protein that couples mitochondria-released cytochrome c (cyt-c) to activation of cytosolic caspases. Cyt-c-mediated activation of caspases in cytosolic extracts and in cells is enhanced by overexpressing NAC and inhibited by reducing NAC using antisense/DNAzymes. Furthermore, association of NAC with Apaf1 is cyt c-inducible, resulting in a mega-complex (>1 MDa) containing both NAC and Apaf1 and correlating with enhanced recruitment and proteolytic processing of pro-caspase-9. NAC also collaborates with Apaf1 in inducing caspase activation and apoptosis in intact cells, whereas fragments of NAC representing only the CARD or NB domain suppress Apaf1-dependent apoptosis induction. NAC expression in vivo is associated with terminal differentiation of short lived cells in epithelia and some other tissues. The ability of NAC to enhance Apaf1-apoptosome function reveals a novel paradigm for apoptosis regulation.
Influence of cluster–support interactions on reactivity of size-selected Nb xO y clusters
Nakayama, Miki; Xue, Meng; An, Wei; ...
2015-04-17
Size-selected niobium oxide nanoclusters (Nb 3O 5, Nb 3O 7, Nb 4O 7, and Nb 4O 10) were deposited at room temperature onto a Cu(111) surface and a thin film of Cu 2O on Cu(111), and their interfacial electronic interactions and reactivity toward water dissociation were examined. These clusters were specifically chosen to elucidate the effects of the oxidation state of the metal centers; Nb 3O 5 and Nb 4O 7 are the reduced counterparts of Nb 3O 7 and Nb 4O 10, respectively. From two-photon photoemission spectroscopy (2PPE) measurements, we found that the work function increases upon cluster adsorptionmore » in all cases, indicating a negative interfacial dipole moment with the positive end pointing into the surface. The amount of increase was greater for the clusters with more metal centers and higher oxidation state. Additional analysis with DFT calculations of the clusters on Cu(111) indicated that the reduced clusters donate electrons to the substrate, indicating that the intrinsic cluster dipole moment makes a larger contribution to the overall interfacial dipole moment than charge transfer. X-ray photoelectron spectroscopy (XPS) measurements showed that the Nb atoms of Nb 3O 7 and Nb 4O 10 are primarily Nb 5+ on Cu(111), while for the reduced Nb 3O 5 and Nb 4O 7 clusters, a mixture of oxidation states was observed on Cu(111). Temperature-programmed desorption (TPD) experiments with D 2O showed that water dissociation occurred on all systems except for the oxidized Nb 3O 7 and Nb 4O 10 clusters on the Cu 2O film. A comparison of our XPS and TPD results suggests that Nb 5+ cations associated with Nb=O terminal groups act as Lewis acid sites which are key for water binding and subsequent dissociation. TPD measurements of 2-propanol dehydration also show that the clusters active toward water dissociation are indeed acidic. DFT calculations of water dissociation on Nb 3O 7 support our TPD results, but the use of bulk Cu 2O(111) as a model for the Cu 2O film merits future scrutiny in terms of interfacial charge transfer. The combination of our experimental and theoretical results suggests that both Lewis acidity and metal reducibility are important for water dissociation.« less
Wideband Waveguide Acousto-Optic Bragg Cell.
The results of an effort to improve the performance specifications of acousto - optic Bragg cells are reported. Various configurations of multiple...would provide a 700 MHz acousto - optic bandwidth. Investigated were Bragg cells fabricated on Ti diffused LiNb03 waveguides as well as Ti diffused LiNb03
Oviductal epithelial cells selected boar sperm according to their functional characteristics
López-Úbeda, Rebeca; García-Vázquez, Francisco A; Gadea, Joaquín; Matás, Carmen
2017-01-01
The interaction of oviductal epithelial cells (OECs) with the spermatozoa has beneficial effects on the sperm functions. The aim of this study is to evaluate the in vitro fertilizing capacity of incubating spermatozoa previously selected by density gradient in OEC and determinate some sperm characteristics that could explain the results obtained. In this study, we assessed in vitro fertilization (IVF), tyrosine phosphorylation, phosphatidylserine translocation, nuclear DNA fragmentation, and chromatin decondensation. Three experimental sperm groups, previously selected by Percoll gradient, were established according to the origin of the sperm used for IVF: (i) W30 group: spermatozoa were incubated with oocytes in the absence of OEC; (ii) NB group: after sperm incubation in OEC, the unbound spermatozoa were incubated with oocytes, in the absence of OEC; and (iii) B group: after sperm incubation with OEC, the bound spermatozoa were incubated with oocytes in the OEC plates. The results showed that sperm from the NB group led to a lower IVF yield, accompanied by low penetration rates (NB: 19.6%, B: 94.9%, and W30: 62.9%; P < 0.001) and problems of nuclear decondensation. Moreover, higher levels of tyrosine phosphorylation were observed in the NB group compared with the W30 and B groups (NB: 58.7%, B: 2.5%, and W30: 4.5%; P < 0.01). A similar trend was observed in phosphatidylserine translocation (NB: 93.7%, B: 5.7%, and W30: 44.2%; P < 0.01). These results demonstrate that the OEC exerts a rigorous degree of sperm selection, even within an already highly selected population of spermatozoa, and can capture the best functional spermatozoa for fertilization. PMID:27232850
NASA Astrophysics Data System (ADS)
Lawriniang, B.; Ghosh, R.; Badwar, S.; Vansola, V.; Santhi Sheela, Y.; Suryanarayana, S. V.; Naik, H.; Naik, Y. P.; Jyrwa, B.
2018-05-01
Excitation functions of the 93Nb(p,n)93mMo and 93Nb(p,pn)92mNb reactions were measured from threshold energies to ∼ 20MeV by employing stacked foil activation technique in combination with the off-line γ-ray spectroscopy at the BARC-TIFR Pelletron facility, Mumbai. For the 20 MeV proton beam, the energy degradation along the stack was calculated using the computer code SRIM 2013. The proton beam intensity was determined via the natCu(p,x)62Zn monitor reaction. The experimental data obtained were compared with the theoretical results from TALYS-1.8 as well as with the literature data available in EXFOR. It was found that for the 93Nb(p,n)92mMo reaction, the present data are in close agreement with some of the recent literature data and the theoretical values based on TALYS-1.8 but are lower than the other literature data. In the case of 93Nb(p,pn)93mNb reaction, present data agree very well with the literature data and the theoretical values.
Liu, Jun; Elmore, James Mitch; Lin, Zuh-Jyh Daniel; Coaker, Gitta
2011-02-17
Plants have evolved sophisticated surveillance systems to recognize pathogen effectors delivered into host cells. RPM1 is an NB-LRR immune receptor that recognizes the Pseudomonas syringae effectors AvrB and AvrRpm1. Both effectors associate with and affect the phosphorylation of RIN4, an immune regulator. Although the kinase and the specific mechanisms involved are unclear, it has been hypothesized that RPM1 recognizes phosphorylated RIN4. Here, we identify RIPK as a RIN4-interacting receptor-like protein kinase that phosphorylates RIN4. In response to bacterial effectors, RIPK phosphorylates RIN4 at amino acid residues T21, S160, and T166. RIN4 phosphomimetic mutants display constitutive activation of RPM1-mediated defense responses and RIN4 phosphorylation is induced by AvrB and AvrRpm1 during P. syringae infection. RIPK knockout lines exhibit reduced RIN4 phosphorylation and blunted RPM1-mediated defense responses. Taken together, our results demonstrate that the RIPK kinase associates with and modifies an effector-targeted protein complex to initiate host immunity. Copyright © 2011 Elsevier Inc. All rights reserved.
QDENSITY—A Mathematica Quantum Computer simulation
NASA Astrophysics Data System (ADS)
Juliá-Díaz, Bruno; Burdis, Joseph M.; Tabakin, Frank
2006-06-01
This Mathematica 5.2 package is a simulation of a Quantum Computer. The program provides a modular, instructive approach for generating the basic elements that make up a quantum circuit. The main emphasis is on using the density matrix, although an approach using state vectors is also implemented in the package. The package commands are defined in Qdensity.m which contains the tools needed in quantum circuits, e.g., multiqubit kets, projectors, gates, etc. Selected examples of the basic commands are presented here and a tutorial notebook, Tutorial.nb is provided with the package (available on our website) that serves as a full guide to the package. Finally, application is made to a variety of relevant cases, including Teleportation, Quantum Fourier transform, Grover's search and Shor's algorithm, in separate notebooks: QFT.nb, Teleportation.nb, Grover.nb and Shor.nb where each algorithm is explained in detail. Finally, two examples of the construction and manipulation of cluster states, which are part of "one way computing" ideas, are included as an additional tool in the notebook Cluster.nb. A Mathematica palette containing most commands in QDENSITY is also included: QDENSpalette.nb. Program summaryTitle of program: QDENSITY Catalogue identifier: ADXH_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADXH_v1_0 Program available from: CPC Program Library, Queen's University of Belfast, N. Ireland Operating systems: Any which supports Mathematica; tested under Microsoft Windows XP, Macintosh OS X, and Linux FC4 Programming language used: Mathematica 5.2 No. of bytes in distributed program, including test data, etc.: 180 581 No. of lines in distributed program, including test data, etc.: 19 382 Distribution format: tar.gz Method of solution: A Mathematica package is provided which contains commands to create and analyze quantum circuits. Several Mathematica notebooks containing relevant examples: Teleportation, Shor's Algorithm and Grover's search are explained in detail. A tutorial, Tutorial.nb is also enclosed. QDENSITY is available at http://www.pitt.edu/~tabakin/QDENSITY.
Flux-line response in 2H-NbSe 2 investigated by means of the vibrating superconductor method
NASA Astrophysics Data System (ADS)
D'Anna, G.; André, M.-O.; Benoit, W.; Rodríguez, E.; Rodríguez, D. S.; Luzuriaga, J.; Wasczak, J. V.
1993-12-01
We measure transverse AC losses in the low- and high-amplitude regime of 2H-NbSe 2 single crystals using vibrating superconductor methods. The measurements are sensitive to small deviations of the critical state. The data constitute evidence for a peak effect of the critical current as a function of the temperature in this compound. We construct in the H- T phase diagram the “peak-effect” line which is supposed to mark an abrupt cross-over in the vortex-pinning regime.
REFAB: A Prototype Graphical Frontend for the RESA Naval Wargame
1990-06-01
knots (dB) NBN - 6 0:999999 Signature line frequencies (Hz) 0:500 NB noise (dB) HFDF - I alphanumeric HFDF name DECM 1 YESINO DECEPTION (RADAR...dB) BBD3 - 1 0:500 BB @300 Hz noise at 05/10/15120/25/30 knots (dB) NBD - 6 0:999999 Signature line frequencies (Hz) 0:500 Diesel NB noise (dB) 48...Number Range of Values Description LFREQ 1 10:20000 Low end of band frequency (Hz) HFREQ 1 10:20000 High end of band frequency (Hz) HZBW 1 0:360
2012-01-01
Background Esophageal squamous cell carcinoma (ESCC), the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB), normal differentiated squamous epithelium (ND), and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA) were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and molecular pathways mediating ESCC development and provide information potentially useful in designing novel therapeutic interventions for this tumor type. PMID:22280838
Jeong, Yong-Hoon; Choe, Han-Cheol
2015-01-01
The aim of this study was to investigate the electrochemical characteristics of nano crystallized Si-HA coating on Ti-Nb-Zr alloy after human osteoblast like (HOB) cell attachment. The Ti-Nb-Zr alloy was manufactured with 35 wt.% of Nb and 10 wt.% of Zr by arc melting furnace to appropriate physical properties as biomaterials. The HA and Si-substituted coatings were prepared by electron-beam physical vapor deposition method with 0.5, 0.8 and 1.2 wt.% of Si contents, and nano aging treatment was performed 500 degrees C for 1 h. The characteristics of coating surface were analyzed by field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction, respectively. To evaluate of cell attachment on cell cultured surface, the potentiodynamic test was performed on the surface using HOB cells. The results showed that the Si-HA coating surface showed higher tendency of cell attachment than that of single HA coating, corrosion resistance value was increased by dense of cell attachment.
Hynowska, A; Blanquer, A; Pellicer, E; Fornell, J; Suriñach, S; Baró, M D; Gebert, A; Calin, M; Eckert, J; Nogués, C; Ibáñez, E; Barrios, L; Sort, J
2015-11-01
The microstructure, mechanical behaviour, and biocompatibility (cell culture, morphology, and cell adhesion) of nanostructured Ti45 Zr15 Pd35- x Si5 Nbx with x = 0, 5 (at. %) alloys, synthesized by arc melting and subsequent Cu mould suction casting, in the form of rods with 3 mm in diameter, are investigated. Both Ti-Zr-Pd-Si-(Nb) materials show a multi-phase (composite-like) microstructure. The main phase is cubic β-Ti phase (Im3m) but hexagonal α-Ti (P63/mmc), cubic TiPd (Pm3m), cubic PdZr (Fm3m), and hexagonal (Ti, Zr)5 Si3 (P63/mmc) phases are also present. Nanoindentation experiments show that the Ti45 Zr15 Pd30 Si5 Nb5 sample exhibits lower Young's modulus than Ti45 Zr15 Pd35 Si5 . Conversely, Ti45 Zr15 Pd35 Si5 is mechanically harder. Actually, both alloys exhibit larger values of hardness when compared with commercial Ti-40Nb, (HTi-Zr-Pd-Si ≈ 14 GPa, HTi-Zr-Pd-Si-Nb ≈ 10 GPa and HTi-40Nb ≈ 2.7 GPa). Concerning the biological behaviour, preliminary results of cell viability performed on several Ti-Zr-Pd-Si-(Nb) discs indicate that the number of live cells is superior to 94% in both cases. The studied Ti-Zr-Pd-Si-(Nb) bulk metallic system is thus interesting for biomedical applications because of the outstanding mechanical properties (relatively low Young's modulus combined with large hardness), together with the excellent biocompatibility. © 2014 Wiley Periodicals, Inc.
Niobium in R And (S6, 6e) and HR 1105 (S5, 3). [S star abundance
NASA Technical Reports Server (NTRS)
Davis, D. N.
1985-01-01
Lines of the first multiplet of niobium are strong in R And and HR 1105. These lines are also present in other S stars: HR 8714, R Cam, V Cnc, R CMi, and T Sgr. They are also visible in the M stars, Beta-Peg and Mu-UMa. An approximation to the abundance ratio, Nb/Fe, has been deduced from pairs of lines having nearly equal intensity. In R And, the ratio is about 200 times the solar value. It is hoped that good plates will soon be obtained for the near infrared region, so that the significant Nb/Rb abundance ratio may be determined.
NASA Astrophysics Data System (ADS)
Mendonça Costa, Lucimara; Ribeiro, Emerson Schwingel; Segatelli, Mariana Gava; do Nascimento, Danielle Raphael; de Oliveira, Fernanda Midori; Tarley, César Ricardo Teixeira
2011-05-01
The present study describes the adsorption characteristic of Cd(II) onto Nb 2O 5/Al 2O 3 mixed oxide dispersed on silica matrix. The characterization of the adsorbent has been carried out by infrared spectroscopy (IR), scanning electronic microscopy (SEM), energy dispersive spectroscopy (EDS), energy dispersive X-ray fluorescence analysis (EDXRF) and specific surface area ( SBET). From batch experiments, adsorption kinetic of Cd(II) was described by a pseudo-second-order kinetic model. The Langmuir linear isotherm fitted to the experimental adsorption isotherm very well, and the maximum adsorption capacity was found to be 17.88 mg g -1. Using the effective material, a method for Cd(II) preconcentration at trace level was developed. The method was based on on-line adsorption of Cd(II) onto SiO 2/Al 2O 3/Nb 2O 5 at pH 8.64, in which the quantitative desorption occurs with 1.0 mol L -1 hydrochloric acid towards FAAS detector. The experimental parameters related to the system were studied by means of multivariate analysis, using 2 4 full factorial design and Doehlert matrix. The effect of SO 42-, Cu 2+, Zn 2+ and Ni 2+ foreign ions showed no interference at 1:100 analyte:interferent proportion. Under the most favorable experimental conditions, the preconcentration system provided a preconcentration factor of 18.4 times, consumption index of 1.08 mL, sample throughput of 14 h -1, concentration efficiency of 4.35 min -1, linear range from 5.0 up to 35.0 μg L -1 and limits of detection and quantification of 0.19 and 0.65 μg L -1 respectively. The feasibility of the proposed method for Cd(II) determination was assessed by analysis of water samples, cigarette sample and certified reference materials TORT-2 (Lobster hepatopancreas) and DOLT-4 (Dogfish liver).
Li, Mingkai; Sun, Yan; Tomiya, Noboru; Hsu, Yuchao; Chai, Toby C
2013-08-15
Increased polyamine signaling in bladder urothelial cells (BUC) may play a role in the pathophysiology of overactive bladder (OAB). We quantitated intracellular polyamine levels in cultured BUC from OAB and asymptomatic (NB) subjects. We assessed whether polyamines modulated rapid intracellular calcium ([Ca(2+)]i) changes and delayed acetylcholine (ACh) release evoked by oxotremorine (OXO, a muscarinic agonist). BUC were cultured from cystoscopic biopsies. High-performance liquid chromatography (HPLC) quantitated intracellular putrescine, spermidine, and spermine levels. Five-millimeter difluoromethylornithine (DFMO), and one-millimeter methylglyoxalbisguanylhydrazone (MGBG) treatments were used to deplete intracellular polyamines. Ten micrometers of OXO were used to increase [Ca(2+)]i levels (measured by fura 2 microfluorimetry) and trigger extracellular ACh release (measured by ELISA). Polyamine levels were elevated in OAB compared with NB BUC (0.5 ± 0.15 vs. 0.16 ± 0.03 nmol/mg for putrescine, 2.4 ± 0.21 vs. 1.01 ± 0.13 nmol/mg for spermidine, and 1.90 ± 0.27 vs. 0.86 ± 0.26 nmol/mg for spermine; P < 0.05 for all comparisons). OXO evoked greater [Ca(2+)]i rise in OAB (205.10 ± 18.82% increase over baseline) compared with in NB BUC (119.54 ± 13.01%; P < 0.05). After polyamine depletion, OXO evoked [Ca(2+)]i rise decreased in OAB and NB BUC to 43.40 ± 6.45 and 38.82 ± 3.5%, respectively. OXO tended to increase ACh release by OAB vs. NB BUC (9.02 ± 0.1 vs. 7.04 ± 0.09 μM, respectively; P < 0.05). Polyamine depletion reduced ACh release by both OAB and NB BUC. In conclusion, polyamine levels were elevated twofold in OAB BUC. OXO evoked greater increase in [Ca(2+)]i and ACh release in OAB BUC, although these two events may be unrelated. Depletion of polyamines caused OAB BUC to behave similarly to NB BUC.
Li, Mingkai; Sun, Yan; Tomiya, Noboru; Hsu, Yuchao
2013-01-01
Increased polyamine signaling in bladder urothelial cells (BUC) may play a role in the pathophysiology of overactive bladder (OAB). We quantitated intracellular polyamine levels in cultured BUC from OAB and asymptomatic (NB) subjects. We assessed whether polyamines modulated rapid intracellular calcium ([Ca2+]i) changes and delayed acetylcholine (ACh) release evoked by oxotremorine (OXO, a muscarinic agonist). BUC were cultured from cystoscopic biopsies. High-performance liquid chromatography (HPLC) quantitated intracellular putrescine, spermidine, and spermine levels. Five-millimeter difluoromethylornithine (DFMO), and one-millimeter methylglyoxalbisguanylhydrazone (MGBG) treatments were used to deplete intracellular polyamines. Ten micrometers of OXO were used to increase [Ca2+]i levels (measured by fura 2 microfluorimetry) and trigger extracellular ACh release (measured by ELISA). Polyamine levels were elevated in OAB compared with NB BUC (0.5 ± 0.15 vs. 0.16 ± 0.03 nmol/mg for putrescine, 2.4 ± 0.21 vs. 1.01 ± 0.13 nmol/mg for spermidine, and 1.90 ± 0.27 vs. 0.86 ± 0.26 nmol/mg for spermine; P < 0.05 for all comparisons). OXO evoked greater [Ca2+]i rise in OAB (205.10 ± 18.82% increase over baseline) compared with in NB BUC (119.54 ± 13.01%; P < 0.05). After polyamine depletion, OXO evoked [Ca2+]i rise decreased in OAB and NB BUC to 43.40 ± 6.45 and 38.82 ± 3.5%, respectively. OXO tended to increase ACh release by OAB vs. NB BUC (9.02 ± 0.1 vs. 7.04 ± 0.09 μM, respectively; P < 0.05). Polyamine depletion reduced ACh release by both OAB and NB BUC. In conclusion, polyamine levels were elevated twofold in OAB BUC. OXO evoked greater increase in [Ca2+]i and ACh release in OAB BUC, although these two events may be unrelated. Depletion of polyamines caused OAB BUC to behave similarly to NB BUC. PMID:23698115
Design and development of hot corrosion-resistant
NASA Astrophysics Data System (ADS)
Zhang, J. S.; Hu, Z. Q.; Murata, Y.; Morinaga, M.; Yukawa, N.
1993-11-01
A systematic study of the effects of refractory metals Ti, Ta, and Nb on the microstructures and properties was conducted with a hot corrosion-resistant alloy system Ni-16Cr-9Al-4Co-2W-lMo-(0~4)Ti-(0~4)Ta-(0~4)Nb (in atomic percent) which was selected based on the d-electrons alloy design theory and some basic considerations in alloying features of single-crystal nickel-base superalloys. The contour lines of solidification reaction temperatures and eutectic (γ + γ') volume fraction in the Ti-Ta-Nb compositional triangle were determined by differential thermal analysis (DTA) and imaging analyzer. Compared with the reference alloy IN738LC, in most of the compositional ranges studied, the designed alloys show very low amounts of eutectic (γ + γ') (⪯0.4 vol pct), narrow solidification ranges (⪯65 °C), and wide “heat-treatment windows” (>100 °C). This indicates that the alloys should have the promising microstructural stability, single-crystal castability, and be easier for complete solution treatment. In a wide compositional range, the designed alloys showed good hot corrosion resistance (weight loss less than 20 mg/cm2 after 24 hours kept in molten salt at 900 °C). By summarizing the results, the promising alloy compositional ranges of the alloys with balanced properties were determined for the final step of the alloy design, i.e., to grow single crystal and characterize mechanical properties of the alloys selected from the previously mentioned regions.
Zhu, Jun; Koken, Marcel H. M.; Quignon, Frédérique; Chelbi-Alix, Mounira K.; Degos, Laurent; Wang, Zhen Yi; Chen, Zhu; de Thé, Hugues
1997-01-01
Acute promyelocytic leukemia (APL) is associated with the t(15;17) translocation, which generates a PML/RARα fusion protein between PML, a growth suppressor localized on nuclear matrix-associated bodies, and RARα, a nuclear receptor for retinoic acid (RA). PML/RARα was proposed to block myeloid differentiation through inhibition of nuclear receptor response, as does a dominant negative RARα mutant. In addition, in APL cells, PML/RARα displaces PML and other nuclear body (NB) antigens onto nuclear microspeckles, likely resulting in the loss of PML and/or NB functions. RA leads to clinical remissions through induction of terminal differentiation, for which the respective contributions of RARα (or PML/RARα) activation, PML/RARα degradation, and restoration of NB antigens localization are poorly determined. Arsenic trioxide also leads to remissions in APL patients, presumably through induction of apoptosis. We demonstrate that in non-APL cells, arsenic recruits the nucleoplasmic form of several NB antigens onto NB, but induces the degradation of PML only, identifying a powerful tool to approach NB function. In APL cells, arsenic targets PML and PML/RARα onto NB and induces their degradation. Thus, RA and arsenic target RARα and PML, respectively, but both induce the degradation of the PML/RARα fusion protein, which should contribute to their therapeutic effects. The difference in the cellular events triggered by these two agents likely stems from RA-induced transcriptional activation and arsenic effects on NB proteins. PMID:9108090
Construction of Escherichia coli Strains for Conversion of Nitroacetophenones to ortho-Aminophenols
Kadiyala, Venkateswarlu; Nadeau, Lloyd J.; Spain, Jim C.
2003-01-01
The predominant bacterial pathway for nitrobenzene (NB) degradation uses an NB nitroreductase and hydroxylaminobenzene (HAB) mutase to form the ring-fission substrate ortho-aminophenol. We tested the hypothesis that constructed strains might accumulate the aminophenols from nitroacetophenones and other nitroaromatic compounds. We constructed a recombinant plasmid carrying NB nitroreductase (nbzA) and HAB mutase A (habA) genes, both from Pseudomonas pseudoalcaligenes JS45, and expressed the enzymes in Escherichia coli JS995. IPTG (isopropyl-β-d-thiogalactopyranoside)-induced cells of strain JS995 rapidly and stoichiometrically converted NB to 2-aminophenol, 2-nitroacetophenone (2NAP) to 2-amino-3-hydroxyacetophenone (2AHAP), and 3-nitroacetophenone (3NAP) to 3-amino-2-hydroxyacetophenone (3AHAP). We constructed another recombinant plasmid containing the nitroreductase gene (nfs1) from Enterobacter cloacae and habA from strain JS45 and expressed the enzymes in E. coli JS996. Strain JS996 converted NB to 2-aminophenol, 2-nitrotoluene to 2-amino-3-methylphenol, 3-nitrotoluene to 2-amino-4-methylphenol, 4-nitrobiphenyl ether to 4-amino-5-phenoxyphenol, and 1-nitronaphthalene to 2-amino-1-naphthol. In larger-scale biotransformations catalyzed by strain JS995, 75% of the 2NAP transformed was converted to 2AHAP, whereas 3AHAP was produced stoichiometrically from 3NAP. The final yields of the aminophenols after extraction and recovery were >64%. The biocatalytic synthesis of ortho-aminophenols from nitroacetophenones suggests that strain JS995 may be useful in the biocatalytic production of a variety of substituted ortho-aminophenols from the corresponding nitroaromatic compounds. PMID:14602609
Kaido, Masanori; Abe, Kazutomo; Mine, Akira; Hyodo, Kiwamu; Taniguchi, Takako; Taniguchi, Hisaaki; Mise, Kazuyuki; Okuno, Tetsuro
2014-01-01
The formation of virus movement protein (MP)-containing punctate structures on the cortical endoplasmic reticulum is required for efficient intercellular movement of Red clover necrotic mosaic virus (RCNMV), a bipartite positive-strand RNA plant virus. We found that these cortical punctate structures constitute a viral replication complex (VRC) in addition to the previously reported aggregate structures that formed adjacent to the nucleus. We identified host proteins that interacted with RCNMV MP in virus-infected Nicotiana benthamiana leaves using a tandem affinity purification method followed by mass spectrometry. One of these host proteins was glyceraldehyde 3-phosphate dehydrogenase-A (NbGAPDH-A), which is a component of the Calvin-Benson cycle in chloroplasts. Virus-induced gene silencing of NbGAPDH-A reduced RCNMV multiplication in the inoculated leaves, but not in the single cells, thereby suggesting that GAPDH-A plays a positive role in cell-to-cell movement of RCNMV. The fusion protein of NbGAPDH-A and green fluorescent protein localized exclusively to the chloroplasts. In the presence of RCNMV RNA1, however, the protein localized to the cortical VRC as well as the chloroplasts. Bimolecular fluorescence complementation assay and GST pulldown assay confirmed in vivo and in vitro interactions, respectively, between the MP and NbGAPDH-A. Furthermore, gene silencing of NbGAPDH-A inhibited MP localization to the cortical VRC. We discuss the possible roles of NbGAPDH-A in the RCNMV movement process. PMID:25411849
Transmembrane adaptor protein PAG1 is a novel tumor suppressor in neuroblastoma
Agarwal, Saurabh; Ghosh, Rajib; Chen, Zaowen; Lakoma, Anna; Gunaratne, Preethi H.; Kim, Eugene S.; Shohet, Jason M.
2016-01-01
(NB) is the most common extracranial pediatric solid tumor with high mortality rates. The tyrosine kinase c-Src has been known to play an important role in differentiation of NB cells, but the mechanism of c-Src regulation has not been defined. Here, we characterize PAG1 (Cbp, Csk binding protein), a central inhibitor of c-Src and other Src family kinases, as a novel tumor suppressor in NB. Clinical cohort analysis demonstrate that low expression of PAG1 is a significant prognostic factor for high stage disease, increased relapse, and worse overall survival for children with NB. PAG1 knockdown in NB cells promotes proliferation and anchorage-independent colony formation with increased activation of AKT and ERK downstream of c-Src, while PAG1 overexpression significantly rescues these effects. In vivo, PAG1 overexpression significantly inhibits NB tumorigenicity in an orthotopic xenograft model. Our results establish PAG1 as a potent tumor suppressor in NB by inhibiting c-Src and downstream effector pathways. Thus, reactivation of PAG1 and inhibition of c-Src kinase activity represents an important novel therapeutic approach for high-risk NB. PMID:26993602
Postma, Wiebe J; Slootweg, Erik J; Rehman, Sajid; Finkers-Tomczak, Anna; Tytgat, Tom O G; van Gelderen, Kasper; Lozano-Torres, Jose L; Roosien, Jan; Pomp, Rikus; van Schaik, Casper; Bakker, Jaap; Goverse, Aska; Smant, Geert
2012-10-01
The potato cyst nematode Globodera rostochiensis invades roots of host plants where it transforms cells near the vascular cylinder into a permanent feeding site. The host cell modifications are most likely induced by a complex mixture of proteins in the stylet secretions of the nematodes. Resistance to nematodes conferred by nucleotide-binding-leucine-rich repeat (NB-LRR) proteins usually results in a programmed cell death in and around the feeding site, and is most likely triggered by the recognition of effectors in stylet secretions. However, the actual role of these secretions in the activation and suppression of effector-triggered immunity is largely unknown. Here we demonstrate that the effector SPRYSEC-19 of G. rostochiensis physically associates in planta with the LRR domain of a member of the SW5 resistance gene cluster in tomato (Lycopersicon esculentum). Unexpectedly, this interaction did not trigger defense-related programmed cell death and resistance to G. rostochiensis. By contrast, agroinfiltration assays showed that the coexpression of SPRYSEC-19 in leaves of Nicotiana benthamiana suppresses programmed cell death mediated by several coiled-coil (CC)-NB-LRR immune receptors. Furthermore, SPRYSEC-19 abrogated resistance to Potato virus X mediated by the CC-NB-LRR resistance protein Rx1, and resistance to Verticillium dahliae mediated by an unidentified resistance in potato (Solanum tuberosum). The suppression of cell death and disease resistance did not require a physical association of SPRYSEC-19 and the LRR domains of the CC-NB-LRR resistance proteins. Altogether, our data demonstrated that potato cyst nematodes secrete effectors that enable the suppression of programmed cell death and disease resistance mediated by several CC-NB-LRR proteins in plants.
Postma, Wiebe J.; Slootweg, Erik J.; Rehman, Sajid; Finkers-Tomczak, Anna; Tytgat, Tom O.G.; van Gelderen, Kasper; Lozano-Torres, Jose L.; Roosien, Jan; Pomp, Rikus; van Schaik, Casper; Bakker, Jaap; Goverse, Aska; Smant, Geert
2012-01-01
The potato cyst nematode Globodera rostochiensis invades roots of host plants where it transforms cells near the vascular cylinder into a permanent feeding site. The host cell modifications are most likely induced by a complex mixture of proteins in the stylet secretions of the nematodes. Resistance to nematodes conferred by nucleotide-binding-leucine-rich repeat (NB-LRR) proteins usually results in a programmed cell death in and around the feeding site, and is most likely triggered by the recognition of effectors in stylet secretions. However, the actual role of these secretions in the activation and suppression of effector-triggered immunity is largely unknown. Here we demonstrate that the effector SPRYSEC-19 of G. rostochiensis physically associates in planta with the LRR domain of a member of the SW5 resistance gene cluster in tomato (Lycopersicon esculentum). Unexpectedly, this interaction did not trigger defense-related programmed cell death and resistance to G. rostochiensis. By contrast, agroinfiltration assays showed that the coexpression of SPRYSEC-19 in leaves of Nicotiana benthamiana suppresses programmed cell death mediated by several coiled-coil (CC)-NB-LRR immune receptors. Furthermore, SPRYSEC-19 abrogated resistance to Potato virus X mediated by the CC-NB-LRR resistance protein Rx1, and resistance to Verticillium dahliae mediated by an unidentified resistance in potato (Solanum tuberosum). The suppression of cell death and disease resistance did not require a physical association of SPRYSEC-19 and the LRR domains of the CC-NB-LRR resistance proteins. Altogether, our data demonstrated that potato cyst nematodes secrete effectors that enable the suppression of programmed cell death and disease resistance mediated by several CC-NB-LRR proteins in plants. PMID:22904163
NASA Astrophysics Data System (ADS)
Zhao, Dandan; Fang, Lihua; Tang, Dian; Zhang, Teng
2016-09-01
In solid oxide fuel cell (SOFC) stacks, the volatile boron species present in the sealing glass often react with the lanthanum-containing cathode, degrading the activity of the cathode (this phenomenon is known as boron poisoning). In this work, we report that this detrimental reaction can be effectively reduced by doping bismuth-containing borosilicate sealing glass-ceramic with a niobium dopant. The addition of Nb2O5 not only condenses the [SiO4] structural units in the glass network, but also promotes the conversion of [BO3] to [BO4]. Moreover, the Nb2O5 dopant enhances the formation of boron-containing phases (Ca3B2O6 and CaB2Si2O8), which significantly reduces the volatility of boron compounds in the sealing glass, suppressing the formation of LaBO3 in the reaction couple between the glass and the cathode. The reported results provide a new approach to solve the problem of boron poisoning.
Chevallier, Laure; Bauer, Alexander; Cavaliere, Sara; Hui, Rob; Rozière, Jacques; Jones, Deborah J
2012-03-01
Crystalline microspheres of Nb-doped TiO(2) with a high specific surface area were synthesized using a templating method exploiting ionic interactions between nascent inorganic components and an ionomer template. The microspheres exhibit a porosity gradient, with a meso-macroporous kernel, and a mesoporous shell. The material has been investigated as cathode electrocatalyst support for polymer electrolyte membrane (PEM) fuel cells. A uniform dispersion of Pt particles on the Nb-doped TiO(2) support was obtained using a microwave method, and the electrochemical properties assessed by cyclic voltammetry. Nb-TiO(2) supported Pt demonstrated very high stability, as after 1000 voltammetric cycles, 85% of the electroactive Pt area remained compared to 47% in the case of commercial Pt on carbon. For the oxygen reduction reaction (ORR), which takes place at the cathode, the highest stability was again obtained with the Nb-doped titania-based material even though the mass activity calculated at 0.9 V vs RHE was slightly lower. The microspherical structured and mesoporous Nb-doped TiO(2) is an alternative support to carbon for PEM fuel cells. © 2012 American Chemical Society
Cation deficient layered Ruddlesden-Popper-related oxysulfides La2LnMS2O5 (Ln=La, Y; M=Nb, Ta).
Cario, Laurent; Popa, Aurelian Florin; Lafond, Alain; Guillot-Deudon, Catherine; Kabbour, Houria; Meerschaut, A; Clarke, Simon J; Adamson, Paul
2007-11-12
The structures of the new oxysulfide Ruddlesden-Popper phases La2LnMS2O5 (Ln=La, Y; M=Nb, Ta) are reported together with an iodide-containing variant: La3-xNb1+xS2O5I2x (0
Performance of all-NbN superconductive tunnel junctions as mixers at 205 GHz
NASA Technical Reports Server (NTRS)
Mcgrath, W. R.; Leduc, H. G.; Stern, J. A.
1990-01-01
Small-area (1x1 sq micron) high-current-density NbN-MgO-NbN tunnel junctions with I-V characteristics suitable for high frequency mixers were fabricated. These junctions are integrated with superconducting microstrip lines designed to resonate out the large junction capacitance. The mixer gain and noise performance were studied near 205 GHz as a function of the inductance provided by the microstrip. This has yielded values of junction capacitance of 85 fF/sq microns and magnetic penetration depth of 3800 angstroms. Mixer noise as low as 133 K has been obtained for properly tuned junctions. This is the best noise performance ever reported for an NbN SIS mixer.
NASA Astrophysics Data System (ADS)
Choi, Yong; Hong, Sun I.
2014-12-01
Nano-tubes of titanium and zirconium alloys like Ti-6Al-4V-1Nb and Zr-1Nb were prepared by anodization followed by coating with hydroxylapatite (HA) and their bio-mineralization behaviors were compared to develop a bio-compatible material for implants in orthopedics, dentistry and cardiology. Ti-6Al-4V-1Nb weight gain in a simulated body solution increased gradually. The bigger tube diameter was, the heavier HA was deposited. Surface roughness of both alloys increased highly with the increasing diameter of nano-tube. Their surface roughness decreased by HA deposition due to the removal of the empty space of the nano-tubes. Zr-1Nb alloy had faster growth of nano-tubes layers more than Ti-6Al-4V-1Nb alloy.
Liu, D.; Heidbrink, W. W.; Tritz, K.; ...
2016-07-29
A compact and multi-view solid state neutral particle analyzer (SSNPA) diagnostic based on silicon photodiode arrays has been successfully tested on the National Spherical Torus Experiment-Upgrade. The SSNPA diagnostic provides spatially, temporally, and pitch-angle resolved measurements of fast-ion distribution by detecting fast neutral flux resulting from the charge exchange (CX) reactions. The system consists of three 16-channel subsystems: t-SSNPA viewing the plasma mid-radius and neutral beam (NB) line #2 tangentially, r-SSNPA viewing the plasma core and NB line #1 radially, and p-SSNPA with no intersection with any NB lines. Due to the setup geometry, the active CX signals of t-SSNPAmore » and r-SSNPA are mainly sensitive to passing and trapped particles, respectively. Additionally, both t-SSNPA and r-SSNPA utilize three vertically stacked arrays with different filter thicknesses to obtain coarse energy information. The experimental data show that all channels are operational. The signal to noise ratio is typically larger than 10, and the main noise is x-ray induced signal. The active and passive CX signals are clearly observed on t-SSNPA and r-SSNPA during NB modulation. The SSNPA data also indicate significant losses of passing particles during sawteeth, while trapped particles are weakly affected. Fluctuations up to 120 kHz have been observed on SSNPA, and they are strongly correlated with magnetohydrodynamics instabilities.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, D., E-mail: deyongl@uci.edu; Heidbrink, W. W.; Hao, G. Z.
A compact and multi-view solid state neutral particle analyzer (SSNPA) diagnostic based on silicon photodiode arrays has been successfully tested on the National Spherical Torus Experiment-Upgrade. The SSNPA diagnostic provides spatially, temporally, and pitch-angle resolved measurements of fast-ion distribution by detecting fast neutral flux resulting from the charge exchange (CX) reactions. The system consists of three 16-channel subsystems: t-SSNPA viewing the plasma mid-radius and neutral beam (NB) line #2 tangentially, r-SSNPA viewing the plasma core and NB line #1 radially, and p-SSNPA with no intersection with any NB lines. Due to the setup geometry, the active CX signals of t-SSNPAmore » and r-SSNPA are mainly sensitive to passing and trapped particles, respectively. In addition, both t-SSNPA and r-SSNPA utilize three vertically stacked arrays with different filter thicknesses to obtain coarse energy information. The experimental data show that all channels are operational. The signal to noise ratio is typically larger than 10, and the main noise is x-ray induced signal. The active and passive CX signals are clearly observed on t-SSNPA and r-SSNPA during NB modulation. The SSNPA data also indicate significant losses of passing particles during sawteeth, while trapped particles are weakly affected. Fluctuations up to 120 kHz have been observed on SSNPA, and they are strongly correlated with magnetohydrodynamics instabilities.« less
Dopant occupancy and exposure energy in Hf:Nd:LiNbO3 crystal as a function of [Li]/[Nb] ratios
NASA Astrophysics Data System (ADS)
Dai, Li; Liu, Chunrui; Han, Xianbo; Yan, Zhehua; Tan, Chao; Wang, Luping; Xu, Yuheng
2017-09-01
A series of Hf: Nd: LiNbO3 crystals with various [Li]/[Nb] ratios ([Li]/[Nb] = 0.94, 1.05, 1.20, 1.38) in the melt were grown by conventional Czochralski technique. The distribution coefficients of Hf4+ and Nd3+ ions were recorded by an inductively coupled plasma-atomic emission spectrometer (ICP-AES). The effective distribution coefficient of Hf4+ is reduced and that of Nd3+ is increased with the increase of [Li]/[Nb] ratio in the melts. In all cases, the effective distribution coefficients is less than 1. The IR transmission spectroscopy of the Hf: Nd: LiNbO3 crystals were measured, getting the results that Hf: Yb: Ho: LiNbO3 crystals with 1.05 [Li]/[Nb] ratios was the stoichiometric. The optical damage resistance ability of Hf:Nd:LiNbO3 crystals were studied by light-induced scattering exposure energy flux threshold method and it increases with the increasing of [Li]/[Nb] ratios. When the [Li]/[Nb] ratio is 1.38 in the melt (the sample 4#), the exposure energy achieves 687.35 J/cm2, approximately 441 folds than that of the sample 1# ([Li]/[Nb] = 0.94) in magnitude.
Yco, Lisette P; Geerts, Dirk; Mocz, Gabor; Koster, Jan; Bachmann, André S
2015-06-21
Neuroblastoma (NB) is an aggressive childhood malignancy in children up to 5 years of age. High-stage tumors frequently relapse even after aggressive multimodal treatment, and then show therapy resistance, typically resulting in patient death. New molecular-targeted compounds that effectively suppress tumor growth and prevent relapse with more efficacy are urgently needed. We and others previously showed that polyamines (PA) like spermidine and spermine are essential for NB tumorigenesis and that DFMO, an inhibitor of the key PA synthesis gene product ODC, is effective both in vitro and in vivo, securing its evaluation in NB clinical trials. To find additional compounds interfering with PA biosynthesis, we tested sulfasalazine (SSZ), an FDA-approved salicylate-based anti-inflammatory and immune-modulatory drug, recently identified to inhibit sepiapterin reductase (SPR). We earlier presented evidence for a physical interaction between ODC and SPR and we showed that RNAi-mediated knockdown of SPR expression significantly reduced native ODC enzyme activity and impeded NB cell proliferation. Human NB mRNA expression datasets in the public domain were analyzed using the R2 platform. Cell viability, isobologram, and combination index analyses as a result of SSZ treatment with our without DFMO were carried out in NB cell cultures. Molecular protein-ligand docking was achieved using the GRAMM algorithm. Statistical analyses were performed with the Kruskal-Wallis test, 2log Pearson test, and Student's t test. In this study, we show the clinical relevance of SPR in human NB tumors. We found that high SPR expression is significantly correlated to unfavorable NB characteristics like high age at diagnosis, MYCN amplification, and high INSS stage. SSZ inhibits the growth of NB cells in vitro, presumably due to the inhibition of SPR as predicted by computational docking of SSZ into SPR. Importantly, the combination of SSZ with DFMO produces synergistic antiproliferative effects in vitro. The results suggest the use of SSZ in combination with DFMO for further experiments, and possible prioritization as a novel therapy for the treatment of NB patients.
Lapauw, Thomas; Tytko, Darius; Vanmeensel, Kim; Huang, Shuigen; Choi, Pyuck-Pa; Raabe, Dierk; Caspi, El'ad N; Ozeri, Offir; To Baben, Moritz; Schneider, Jochen M; Lambrinou, Konstantina; Vleugels, Jozef
2016-06-06
The solubility of zirconium (Zr) in the Nb4AlC3 host lattice was investigated by combining the experimental synthesis of (Nbx, Zr1-x)4AlC3 solid solutions with density functional theory calculations. High-purity solid solutions were prepared by reactive hot pressing of NbH0.89, ZrH2, Al, and C starting powder mixtures. The crystal structure of the produced solid solutions was determined using X-ray and neutron diffraction. The limited Zr solubility (maximum of 18.5% of the Nb content in the host lattice) in Nb4AlC3 observed experimentally is consistent with the calculated minimum in the energy of mixing. The lattice parameters and microstructure were evaluated over the entire solubility range, while the chemical composition of (Nb0.85, Zr0.15)4AlC3 was mapped using atom probe tomography. The hardness, Young's modulus, and fracture toughness at room temperature as well as the high-temperature flexural strength and E-modulus of (Nb0.85, Zr0.15)4AlC3 were investigated and compared to those of pure Nb4AlC3. Quite remarkably, an appreciable increase in fracture toughness was observed from 6.6 ± 0.1 MPa/m(1/2) for pure Nb4AlC3 to 10.1 ± 0.3 MPa/m(1/2) for the (Nb0.85, Zr0.15)4AlC3 solid solution.
Outcomes in multifocal neuroblastoma as part of the neurocristopathy syndrome.
Williams, Phoebe; Wegner, Eva; Ziegler, David S
2014-08-01
The neurocristopathy syndrome occurs because of a germline mutation of the paired-like homeobox 2b (PHOX2B) gene at 4p12, a neurogenesis regulator gene. The result is abnormal neural crest cell development resulting in congenital central hypoventilation syndrome, Hirschsprung disease, and neuroblastoma (NB), which is often multifocal and disseminated in its presentation. Previously, such widespread disease was regarded as highly aggressive and treated either with palliative intent or, conversely, with very intense, high-dose chemotherapy. We now present a patient who had neurocristopathy syndrome who had multifocal NB associated with an underlying germline PHOX2B mutation. He was treated conservatively with surgery and low-dose chemotherapy. After treatment he had extensive residual disease that has continued to mature despite no further treatment. A literature review identified 26 similar patients presenting with multifocal NB as part of the neurocristopathy syndrome. In all cases the NB behaved in an indolent manner with no deaths from tumor reported when patients received appropriate treatment. These provocative findings suggest for the first time that children who have neurocristopathy-associated NB should be treated conservatively, despite the aggressive appearance of their disease. Copyright © 2014 by the American Academy of Pediatrics.
Di Pietro, Cinzia; Ragusa, Marco; Barbagallo, Davide; Duro, Laura R; Guglielmino, Maria R; Majorana, Alessandra; Giunta, Veronica; Rapisarda, Antonella; Tricarichi, Elisa; Miceli, Marco; Angelica, Rosario; Grillo, Agata; Banelli, Barbara; Defferari, Isabella; Forte, Stefano; Laganà, Alessandro; Bosco, Camillo; Giugno, Rosalba; Pulvirenti, Alfredo; Ferro, Alfredo; Grzeschik, Karl H; Di Cataldo, Andrea; Tonini, Gian P; Romani, Massimo; Purrello, Michele
2008-01-01
Background The General Transcription Apparatus (GTA) comprises more than one hundred proteins, including RNA Polymerases, GTFs, TAFs, Mediator, and cofactors such as heterodimeric NC2. This complexity contrasts with the simple mechanical role that these proteins are believed to perform and suggests a still uncharacterized participation to important biological functions, such as the control of cell proliferation. Results To verify our hypothesis, we analyzed the involvement in Neuroblastoma (NB) pathogenesis of GTA genes localized at 1p, one of NB critical regions: through RT-PCR of fifty eight NB biopsies, we demonstrated the statistically significant reduction of the mRNA for NC2β (localized at 1p22.1) in 74% of samples (p = 0.0039). Transcripts from TAF13 and TAF12 (mapping at 1p13.3 and 1p35.3, respectively) were also reduced, whereas we didn't detect any quantitative alteration of the mRNAs from GTF2B and NC2α (localized at 1p22-p21 and 11q13.3, respectively). We confirmed these data by comparing tumour and constitutional DNA: most NB samples with diminished levels of NC2β mRNA had also genomic deletions at the corresponding locus. Conclusion Our data show that NC2β is specifically involved in NB pathogenesis and may be considered a new NB biomarker: accordingly, we suggest that NC2β, and possibly other GTA members, are physiologically involved in the control of cell proliferation. Finally, our studies unearth complex selective mechanisms within NB cells. PMID:18538002
Di Pietro, Cinzia; Ragusa, Marco; Barbagallo, Davide; Duro, Laura R; Guglielmino, Maria R; Majorana, Alessandra; Giunta, Veronica; Rapisarda, Antonella; Tricarichi, Elisa; Miceli, Marco; Angelica, Rosario; Grillo, Agata; Banelli, Barbara; Defferari, Isabella; Forte, Stefano; Laganà, Alessandro; Bosco, Camillo; Giugno, Rosalba; Pulvirenti, Alfredo; Ferro, Alfredo; Grzeschik, Karl H; Di Cataldo, Andrea; Tonini, Gian P; Romani, Massimo; Purrello, Michele
2008-06-06
The General Transcription Apparatus (GTA) comprises more than one hundred proteins, including RNA Polymerases, GTFs, TAFs, Mediator, and cofactors such as heterodimeric NC2. This complexity contrasts with the simple mechanical role that these proteins are believed to perform and suggests a still uncharacterized participation to important biological functions, such as the control of cell proliferation. To verify our hypothesis, we analyzed the involvement in neuroblastoma (NB) pathogenesis of GTA genes localized at 1p, one of NB critical regions: through RT-PCR of fifty eight NB biopsies, we demonstrated the statistically significant reduction of the mRNA for NC2beta (localized at 1p22.1) in 74% of samples (p = 0.0039). Transcripts from TAF13 and TAF12 (mapping at 1p13.3 and 1p35.3, respectively) were also reduced, whereas we didn't detect any quantitative alteration of the mRNAs from GTF2B and NC2alpha (localized at 1p22-p21 and 11q13.3, respectively). We confirmed these data by comparing tumour and constitutional DNA: most NB samples with diminished levels of NC2beta mRNA had also genomic deletions at the corresponding locus. Our data show that NC2beta is specifically involved in NB pathogenesis and may be considered a new NB biomarker: accordingly, we suggest that NC2beta, and possibly other GTA members, are physiologically involved in the control of cell proliferation. Finally, our studies unearth complex selective mechanisms within NB cells.
Mechanical, Electronic and Optical Properties of Two Phases of NbB4: First-Principles Calculations
NASA Astrophysics Data System (ADS)
Yang, Ruike; Ma, Shaowei; Wei, Qun; Zhang, Dongyun
2018-05-01
As transition metal borides have been successfully synthesised, the study of the combination of transition metal and boron is another effective way to investigate the properties of boride. We have predicted the novel phase Amm2-NbB4. Using the Cambridge Serial Total Energy Package (CASTEP) code, we further researched on the mechanical, electronic and optical properties of C2/c- and Amm2-NbB4. It is found that both the phases of NbB4 are dynamically and mechanically stable at 0 and 100 GPa. Their Vickers hardness values are both 34 GPa, which indicate that they are hard materials. The band gap of C2/c-NbB4 is 0.145 eV, which indicates that it is a semiconductor (or metalloid) at 0 GPa. For the Amm2-NbB4, the band structure without band gap indicates it is a metal at 0 GPa. The optical properties of these two structures are similar. At 0 eV, the real part of dielectric function is 28.8 for C2/c-NbB4, and the real part value for Amm2-NbB4 is 43. We hope our work will provide some help to the experimental work about the technology of the material.
A Cryogenic Waveguide Mount for Microstrip Circuit and Material Characterization
NASA Technical Reports Server (NTRS)
U-yen, Kongpop; Brown, Ari D.; Moseley, Samuel H.; Noroozian, Omid; Wollack, Edward J.
2016-01-01
A waveguide split-block fixture used in the characterization of thin-film superconducting planar circuitry at millimeter wavelengths is described in detail. The test fixture is realized from a pair of mode converters, which transition from rectangular-waveguide to on-chip microstrip-line signal propagation via a stepped ridge-guide impedance transformer. The observed performance of the W-band package at 4.2K has a maximum in-band transmission ripple of 2dB between 1.53 and 1.89 times the waveguide cutoff frequency. This metrology approach enables the characterization of superconducting microstrip test structures as a function temperature and frequency. The limitations of the method are discussed and representative data for superconducting Nb and NbTiN thin film microstrip resonators on single-crystal Si dielectric substrates are presented.
NASA Astrophysics Data System (ADS)
Posen, S.; Liepe, M.; Hall, D. L.
2015-02-01
Many future particle accelerators require hundreds of superconducting radiofrequency (SRF) cavities operating with high duty factor. The large dynamic heat load of the cavities causes the cryogenic plant to make up a significant part of the overall cost of the facility. This contribution can be reduced by replacing standard niobium cavities with ones coated with a low-dissipation superconductor such as Nb3Sn. In this paper, we present results for single cell cavities coated with Nb3Sn at Cornell. Five coatings were carried out, showing that at 4.2 K, high Q0 out to medium fields was reproducible, resulting in an average quench field of 14 MV/m and an average 4.2 K Q0 at quench of 8 × 109. In each case, the peak surface magnetic field at quench was well above Hc1, showing that it is not a limiting field in these cavities. The coating with the best performance had a quench field of 17 MV/m, exceeding gradient requirements for state-of-the-art high duty factor SRF accelerators. It is also shown that—taking into account the thermodynamic efficiency of the cryogenic plant—the 4.2 K Q0 values obtained meet the AC power consumption requirements of state-of-the-art high duty factor accelerators, making this a proof-of-principle demonstration for Nb3Sn cavities in future applications.
Electronic Transport Behaviors due to Charge Density Waves in Ni-Nb-Zr-H Glassy Alloys
NASA Astrophysics Data System (ADS)
Fukuhara, Mikio; Umemori, Yoshimasa
2013-11-01
The amorphous Ni-Nb-Zr-H glassy alloy containing subnanometer-sized icosahedral Zr5 Nb5Ni3 clusters exhibited four types of electronic phenomena: a metal/insulator transition, an electric current-induced voltage oscillation (Coulomb oscillation), giant capacitor behavior and an electron avalanche with superior resistivity. These findings could be excluded by charge density waves that the low-dimensional component of clusters, in which the atoms are lined up in chains along the [130] direction, plays important roles in various electron transport phenomena.
Sputum colour can identify patients with neutrophilic inflammation in asthma
Gibson, Peter; Lochrin, Alyssa J; Wood, Lisa; Baines, Katherine J; Simpson, Jodie L
2017-01-01
Introduction Sputum colour is associated with neutrophilic inflammation in chronic bronchitis and chronic obstructive pulmonary disease (COPD). Neutrophilia and sputum expectoration is notable in asthma, but whether sputum colour is associated with and predicts the presence of neutrophilic inflammation in asthma is unknown. The objective of the study is to assess the ability of sputum colour in distinguishing asthma inflammatory phenotypes. Methods Induced sputum samples collected from 271 adults with stable asthma were retrospectively assessed. Sputum colour was determined using the BronkoTest sputum colour chart and correlated to differential cell counts and CXCL-8 concentration. Neutrophilic inflammation was defined as an age-corrected sputum neutrophil proportion (≥61.6% for age 20–40 years; ≥63.2% for age 40–60 and ≥67.2% for age >60 years), whereas neutrophilic bronchitis (NB) was defined as high total cell count (≥5.1×106 cells/mL) plus an increased age-corrected neutrophil proportion. The optimal cut-off for sputum colour to predict neutrophilic inflammation and NB was determined using receiver operator characteristic curve analysis. Results A sputum colour score of ≥3 represented and predicted neutrophilic inflammation with modest accuracy (area under the curve (AUC)=0.64; p<0.001, specificity=78.4%, sensitivity=49.2%). Participants with a sputum colour score of ≥3 had significantly (p<0.05) higher CXCL-8, total cells and neutrophil number and proportion. Sputum colour score was also positively correlated with these factors. Sputum colour score ≥3 predicted NB with reasonably good accuracy (AUC=0.79, p<0.001, specificity=79.3%, sensitivity=70.7%). Conclusions Visual gradation of sputum colour in asthma relates to high total cell count and neutrophilic inflammation. Assessment of sputum colour can identify adults with asthma who are likely to have NB without the need for sputum processing and differential cell count, which may facilitate asthma management. PMID:29071085
Jiang, Lei; You, Ting; Deng, Wei-Qiao
2013-10-18
In this work Nb-doped anatase TiO2 nanocrystals are used as the photoanode of quantum-dot-sensitized solar cells. A solar cell with CdS/CdSe quantum dots co-sensitized 2.5 mol% Nb-doped anatase TiO2 nanocrystals can achieve a photovoltaic conversion efficiency of 3.3%, which is almost twice as high as the 1.7% obtained by a cell based on undoped TiO2 nanocrystals. The incident photon-to-current conversion efficiency can reach as high as 91%, which is a record for all quantum-dot-sensitized solar cells. Detailed analysis shows that such an enhancement is due to improved lifetime and diffusion length of electrons in the solar cell.
Titanium-35niobium alloy as a potential material for biomedical implants: In vitro study.
de Andrade, Dennia Perez; de Vasconcellos, Luana Marotta Reis; Carvalho, Isabel Chaves Silva; Forte, Lilibeth Ferraz de Brito Penna; de Souza Santos, Evelyn Luzia; Prado, Renata Falchete do; Santos, Dalcy Roberto Dos; Cairo, Carlos Alberto Alves; Carvalho, Yasmin Rodarte
2015-11-01
Research on new titanium alloys and different surface topographies aims to improve osseointegration. The objective of this study is to analyze the behavior of osteogenic cells cultivated on porous and dense samples of titanium-niobium alloys, and to compare them with the behavior of such type of cells on commercial pure titanium. Samples prepared using powder metallurgy were characterized using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and metallographic and profilometer analyses. Osteogenic cells from newborn rat calvaria were plated over different groups: dense or porous samples composed of Ti or Ti-35niobium (Nb). Cell adhesion, cell proliferation, MTT assay, cell morphology, protein total content, alkaline phosphatase activity, and mineralization nodules were assessed. Results from XRD and EDS analysis confirmed the presence of Ti and Nb in the test alloy. Metallographic analysis revealed interconnected pores, with pore size ranging from 138 to 150μm. The profilometer analysis detected the greatest rugosity within the dense alloy samples. In vitro tests revealed similar biocompatibility between Ti-35Nb and Ti; furthermore, it was possible to verify that the association of porous surface topography and the Ti-35Nb alloy positively influenced mineralized matrix formation. We propose that the Ti-35Nb alloy with porous topography constitutes a biocompatible material with great potential for use in biomedical implants. Copyright © 2015 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Manivasagam, Geetha; Anbarasan, V.; Kamachi Mudali, U.; Raj, Baldev
2011-09-01
This article reports the development, microstructure, and corrosion behavior of two new alloys such as Ti-4Nb-4Zr and Ti-2Nb-2Zr in boiling nitric acid environment. The corrosion test was carried out in the liquid, vapor, and condensate phases of 11.5 M nitric acid, and the potentiodynamic anodic polarization studies were performed at room temperature for both alloys. The samples subjected to three-phase corrosion testing were characterized using scanning electron microscopy (SEM) and energy-dispersive X-ray microanalysis (EDAX). As Ti-2Nb-2Zr alloy exhibited inferior corrosion behavior in comparison to Ti-4Nb-4Zr in all three phases, weldability and heat treatment studies were carried out only on Ti-4Nb-4Zr alloy. The weldability of the new alloy was evaluated using tungsten inert gas (TIG) welding processes, and the welded specimen was thereafter tested for its corrosion behavior in all three phases. The results of the present investigation revealed that the newly developed near alpha Ti-4Nb-4Zr alloy possessed superior corrosion resistance in all three phases and excellent weldability compared to conventional alloys used for nitric acid application in spent nuclear reprocessing plants. Further, the corrosion resistance of the beta heat-treated Ti-4Nb-4Zr alloy was superior when compared to the sample heat treated in the alpha + beta phase.
Hedgehog signaling pathway in neuroblastoma differentiation.
Souzaki, Ryota; Tajiri, Tatsuro; Souzaki, Masae; Kinoshita, Yoshiaki; Tanaka, Sakura; Kohashi, Kenichi; Oda, Yoshinao; Katano, Mitsuo; Taguchi, Tomoaki
2010-12-01
The hedgehog (Hh) signaling pathway is activated in some adult cancers. On the other hand, the Hh signaling pathway plays an important role in the development of the neural crest in embryos. The aim of this study is to show the activation of Hh signaling pathway in neuroblastoma (NB), a pediatric malignancy arising from neural crest cells, and to reveal the meaning of the Hh signaling pathway in NB development. This study analyzed the expression of Sonic hedgehog (Shh), GLI1, and Patched 1 (Ptch1), transactivators of Hh signaling pathway, by immunohistochemistry in 82 NB and 10 ganglioneuroblastoma cases. All 92 cases were evaluated for the status of MYCN amplification. Of the 92 cases, 67 (73%) were positive for Shh, 62 cases (67%) were positive for GLI1, and 73 cases (79%) were positive for Ptch1. Only 2 (10%) of the 20 cases with MYCN amplification were positive for Shh and GLI1, and 4 cases (20%) were positive for Ptch1 (MYCN amplification vs no MYCN amplification, P ≦ .01). The percentage of GLI1-positive cells in the cases with INSS stage 1 without MYCN amplification was significantly higher than that with INSS stage 4. Of 72 cases without MYCN amplification, 60 were GLI1-positive. Twelve cases were GLI1-negative, and the prognosis of the GLI1-positive cases was significantly better than that of the GLI1-negative cases (P = .015). Most of NBs without MYCN amplification were positive for Shh, GLI1, and Ptch1. In the cases without MYCN amplification, the high expression of GLI1 was significantly associated with early clinical stage and a good prognosis of the patients. In contrast to adult cancers, the activation of the Hh signaling pathway in NB may be associated with the differentiation of the NB. Copyright © 2010 Elsevier Inc. All rights reserved.
Intratumoral diversity of telomere length in individual neuroblastoma tumors.
Pezzolo, Annalisa; Pistorio, Angela; Gambini, Claudio; Haupt, Riccardo; Ferraro, Manuela; Erminio, Giovanni; De Bernardi, Bruno; Garaventa, Alberto; Pistoia, Vito
2015-04-10
The purpose of the work was to investigate telomere length (TL) and mechanisms involved in TL maintenance in individual neuroblastoma (NB) tumors. Primary NB tumors from 102 patients, ninety Italian and twelve Spanish, diagnosed from 2000 to 2008 were studied. TL was investigated by quantitative fluorescence in situ hybridization (IQ-FISH) that allows to analyze individual cells in paraffin-embedded tissues. Fluorescence intensity of chromosome 2 centromere was used as internal control to normalize TL values to ploidy. Human telomerase reverse transcriptase (hTERT) expression was detected by immunofluorescence in 99/102 NB specimens.The main findings are the following: 1) two intratumoral subpopulations of cancer cells displaying telomeres of different length were identified in 32/102 tumors belonging to all stages. 2) hTERT expression was detected in 99/102 tumors, of which 31 displayed high expression and 68 low expression. Alternative lengthening of telomeres (ALT)-mechanism was present in 60/102 tumors, 20 of which showed high hTERT expression. Neither ALT-mechanism nor hTERT expression correlated with heterogeneous TL. 3) High hTERT expression and ALT positivity were associated with significantly reduced Overall Survival. 4) High hTERT expression predicted relapse irrespective of patient age. Intratumoral diversity in TL represents a novel feature in NB.In conclusion, diversity of TL in individual NB tumors was strongly associated with disease progression and death, suggesting that these findings are of translational relevance. The combination of high hTERT expression and ALT positivity may represent a novel biomarker of poor prognosis that deserves further investigation.
Evaluation of swabs and transport media for the recovery of Yersinia pestis.
Gilbert, Sarah E; Rose, Laura J; Howard, Michele; Bradley, Meranda D; Shah, Sanjiv; Silvestri, Erin; Schaefer, Frank W; Noble-Wang, Judith
2014-01-01
The Government Accountability Office report investigating the surface sampling methods used during the 2001 mail contamination with Bacillus anthracis brought to light certain knowledge gaps that existed regarding environmental sampling with biothreat agents. Should a contamination event occur that involves non-spore forming biological select agents, such as Yersinia pestis, surface sample collection and processing protocols specific for these organisms will be needed. Two Y. pestis strains (virulent and avirulent), four swab types (polyester, macrofoam, rayon, and cotton), two pre-moistening solutions, six transport media, three temperatures, two levels of organic load, and four processing methods (vortexing, sonicating, combined sonicating and vortexing, no agitation) were evaluated to determine the conditions that would yield the highest percent of cultivable Y. pestis cells after storage. The optimum pre-moistening agent/transport media combination varied with the Y. pestis strain and swab type. Directly inoculated macrofoam swabs released the highest percent of cells into solution (93.9% recovered by culture) and rayon swabs were considered the second best swab option (77.0% recovered by culture). Storage at 4°C was found to be optimum for all storage times and transport media. In a worst case scenario, where the Y. pestis strain is not known and sample processing and analyses could not occur until 72h after sampling, macrofoam swabs pre-moistened with PBS supplemented with 0.05% Triton X-100 (PBSTX), stored at 4°C in neutralizing buffer (NB) as a transport medium (PBSTX/NB) or pre-moistened with NB and stored in PBSTX as a transport medium (NB/PBSTX), then vortexed 3min in the transport medium, performed significantly better than all other conditions for macrofoam swabs, regardless of strain tested (mean 12 - 72h recovery of 85.9-105.1%, p<0.001). In the same scenario, two combinations of pre-moistening medium/transport medium were found to be optimal for rayon swabs stored at 4°C (p<0.001), then sonicated 3min in the transport medium; PBSTX/PBSTX and NB/PBSTX (mean 12-72h recovery of 83.7-110.1%). © 2013.
Bouchet, Sandrine; Tang, Ruoping; Fava, Fanny; Legrand, Ollivier; Bauvois, Brigitte
2016-01-01
The CD13 antigen's binding site for the Asn-Gly-Arg (NGR) motif enables NGR-containing chemotherapeutic drugs to be delivered to CD13-positive tumours. Human CD13-positive acute myeloid leukemia (AML) cells proliferate abnormally and escape death. Here, we show that the CNGRC-GG-D(KLAKLAK)2 peptide induces death in AML cell lines (U937, THP-1, NB4, HL-60) and primary blood cells from AML patients. Cell death was characterized as a caspase-independent mechanism, without DNA fragmentation, but phosphatidylserine externalization and membrane disruption. Our results demonstrate in U937 cells that (i) the NGR-peptide triggers the loss of mitochondrial potential(ΔΨm) and generates superoxide anion (O2−), (ii) N-acetyl-L-cysteine (NAC) and extra/intracellular Ca2+ chelators (BAPTA) prevent both O2− production and cell death, (iii) the Ca2+-channel blocker nifedipine prevents cell death (indicating that Ca2+ influx is the initial death trigger), and (iv) BAPTA, but not NAC, prevents ΔΨm loss (suggesting O2− is a mitochondrial downstream effector). AML cell lines and primary blasts responding to the lethal action of NGR-peptide express promatrix metalloproteinase-12 (proMMP-12) and its substrate progranulin (an 88 kDa cell survival factor). A cell-free assay highlighted proMMP-12 activation by O2−. Accordingly, NGR-peptide's downregulation of 88 kDa progranulin protein was prevented by BAPTA and NAC. Conversely, AML blast resistance to NGR-peptide is associated with the expression of a distinct, 105 kDa progranulin isoform. These results indicate that CNGRC-GG-D(KLAKLAK)2 induces death in AML cells through the Ca2+-mitochondria-O2.-pathway, and support the link between proMMP-12 activation and progranulin cleavage during cell death. Our findings may have implications for the understanding of tumour biology and treatment. PMID:26655501
Bouchet, Sandrine; Tang, Ruoping; Fava, Fanny; Legrand, Ollivier; Bauvois, Brigitte
2016-04-12
The CD13 antigen's binding site for the Asn-Gly-Arg (NGR) motif enables NGR-containing chemotherapeutic drugs to be delivered to CD13-positive tumours. Human CD13-positive acute myeloid leukemia (AML) cells proliferate abnormally and escape death. Here, we show that the CNGRC-GG-D(KLAKLAK)2 peptide induces death in AML cell lines (U937, THP-1, NB4, HL-60) and primary blood cells from AML patients. Cell death was characterized as a caspase-independent mechanism, without DNA fragmentation, but phosphatidylserine externalization and membrane disruption. Our results demonstrate in U937 cells that (i) the NGR-peptide triggers the loss of mitochondrial potential(ΔΨm) and generates superoxide anion (O2-), (ii) N-acetyl-L-cysteine (NAC) and extra/intracellular Ca2+ chelators (BAPTA) prevent both O2- production and cell death, (iii) the Ca2+-channel blocker nifedipine prevents cell death (indicating that Ca2+ influx is the initial death trigger), and (iv) BAPTA, but not NAC, prevents ΔΨm loss (suggesting O2- is a mitochondrial downstream effector). AML cell lines and primary blasts responding to the lethal action of NGR-peptide express promatrix metalloproteinase-12 (proMMP-12) and its substrate progranulin (an 88 kDa cell survival factor). A cell-free assay highlighted proMMP-12 activation by O2-. Accordingly, NGR-peptide's downregulation of 88 kDa progranulin protein was prevented by BAPTA and NAC. Conversely, AML blast resistance to NGR-peptide is associated with the expression of a distinct, 105 kDa progranulin isoform. These results indicate that CNGRC-GG-D(KLAKLAK)2 induces death in AML cells through the Ca2+-mitochondria-O2.-pathway, and support the link between proMMP-12 activation and progranulin cleavage during cell death. Our findings may have implications for the understanding of tumour biology and treatment.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ida, H.; Shinozaki, K.; Honma, T.
2012-12-15
Ba{sub 1-x}RE{sub 2x/3}Nb{sub 2}O{sub 6} nanocrystals with a tetragonal tungsten bronze (TTB) structure are synthesized using a conventional glass crystallization technique in 2.3RE{sub 2}O{sub 3}-27.4BaO-34.3Nb{sub 2}O{sub 5}-36B{sub 2}O{sub 3} (mol%) (RE=Sm, Eu, Gd, Dy, and Er) glasses. One sharp crystallization peak is observed at {approx}670 Degree-Sign C in both powdered and bulk glasses, and the formation of Ba{sub 1-x}RE{sub 2x/3}Nb{sub 2}O{sub 6} nanocrystals with unit cell parameters of a{approx}1.24 nm and c{approx}0.39 nm was confirmed. It is found from high resolution transmission electron microscope observations that the morphology of Ba{sub 1-x}RE{sub 2x/3}Nb{sub 2}O{sub 6} nanocrystals is ellipsoidal. Their average particlemore » size is in the range of 15-60 nm and decreases with decreasing ionic radius of RE{sup 3+} being present in the precursor glasses. The optical transparent crystallized glass (bulk) shows the total photoluminescence (PL) quantum yield of 53% in the visible region of Eu{sup 3+} ions, suggesting a high potential of Ba{sub 1-x}RE{sub 2x/3}Nb{sub 2}O{sub 6} nanocrystals as PL materials. - Graphical abstract: This figure shows a TEM photograph for the heat-treated (667 Degree-Sign C, 3 h) sample of 2.3Dy{sub 2}O{sub 3}-27.4BaO-34.3Nb{sub 2}O{sub 5}-36B{sub 2}O{sub 3}. An ellipsoidal-shaped Ba{sub 1-x}Dy{sub 2x/3}Nb{sub 2}O{sub 6} nanocrystal with diameters of 17 and 28 nm is observed. The ellipsoidal morphology is a common feature in Ba{sub 1-x}RE{sub 2x/3}Nb{sub 2}O{sub 6} nanocrystals synthesized by the crystallization of 2.3RE{sub 2}O{sub 3}-27.4BaO-34.3Nb{sub 2}O{sub 5}-36B{sub 2}O{sub 3} glasses. Highlights: Black-Right-Pointing-Pointer Ba{sub 1-x}RE{sub 2x/3}Nb{sub 2}O{sub 6} nanocrystals with a tetragonal tungsten bronze structure are synthesized. Black-Right-Pointing-Pointer A glass crystallization technique was applied. Black-Right-Pointing-Pointer The morphology of Ba{sub 1-x}RE{sub 2x/3}Nb{sub 2}O{sub 6} nanocrystals is ellipsoidal. Black-Right-Pointing-Pointer The average particle size with 15-60 nm decreases with decreasing ionic radius of RE{sup 3+}. Black-Right-Pointing-Pointer Ba{sub 1-x}RE{sub 2x/3}Nb{sub 2}O{sub 6} nanocrystals have a high potential as photoluminescence materials.« less
Ferroelasticity in the LnNbO/sub 4/-type rare earth niobates
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brixner, L.H.; Whitney, J.F.; Zumsteg, F.C.
1977-01-01
The previously reported phase transitions for the isostructural rare earth niobates between 500/sup 0/C and 850/sup 0/C correspond to a point group transformation 4/mF2/m, which is purely ferroelastic. The correct room temperature point group for all LnNbO/sub 4/ compounds is 2/m. Crystal growth and domain wall behavior is discussed for LaNbO/sub 4/. The high temperature phase transition is described for YbNbO/sub 4/.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bang, Hyunjin; Kim, Youngmee; Kim, Seri
We found new synthetic routes to obtain 1-D quaternary thiophosphate compounds and a 0-D molecular complex containing a Nb{sub 2}S{sub 4} core from a 2-D ternary thiophosphate, Nb{sub 4}P{sub 2}S{sub 21}. When Nb{sub 4}P{sub 2}S{sub 21} was reacted with alkali metal halides (ACl; A=Na, K, Rb, Cs) or TlCl at 500-700 deg. C, the -S-S-S- bridges in 2-D Nb{sub 2}PS{sub 10}-S-S{sub 10}PNb{sub 2} were excised to form a 1-D chain, and cations were inserted between the chains to form ANb{sub 2}PS{sub 10} (A=Na, K, Rb, Cs, Tl). We also found that thallium chloride (TlCl) is an excellent reagent for furthermore » excision, and it substitutes chloride ligands for the sulfur ligands of 2-D Nb{sub 4}P{sub 2}S{sub 21} to form the molecular complex Tl{sub 5}[Nb{sub 2}S{sub 4}Cl{sub 8}]Cl. Crystal data for TlNb{sub 2}PS{sub 10}: monoclinic, Pn, a=6.9452(11) A, b=7.3761(12) A, 12.873(2) A, {beta}=104.472(3){sup o}, and Z=2. Crystal data for Tl{sub 5}[Nb{sub 2}S{sub 4}Cl{sub 8}]Cl: orthorhombic, Immm, a=7.001(5) A, b=9.509(7) A, c=15.546(11) A, and Z=2. - Graphical abstract: We developed new synthetic routes to obtain 1-D quaternary thiophosphate compounds and a molecular complex containing a Nb{sub 2}S{sub 4} core from a 2-D ternary thiophosphate, Nb{sub 4}P{sub 2}S{sub 21}. When Nb{sub 4}P{sub 2}S{sub 21} was reacted with alkali metal halides or TlCl, the -S-S-S- bridges in 2-D Nb{sub 2}PS{sub 10}-S-S{sub 10}PNb{sub 2} were excised to form a 1-D chain, and cations were inserted between the chains.« less
Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions.
Balajthy, Zoltán; Csomós, Krisztián; Vámosi, György; Szántó, Attila; Lanotte, Michel; Fésüs, László
2006-09-15
Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2(-/-) mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2(-/-) mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract-induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil.
Jura, Marek; Levason, William; Reid, Gillian; Webster, Michael
2009-10-07
Two very unusual sulfonium salts, [{o-C(6)H(4)(CH(2)SMe)(2)}H][NbF(6)] and [{[9]aneS(3)}H][NbF(6)], obtained from reaction of the thioethers with NbF(5) in CH(2)Cl(2) solution, are reported and their structures described; the eight-coordinate tetrafluoro Nb(v) cation of the dithioether is obtained from the same reaction.
Fifteen years' review of advanced childhood neuroblastoma from a single institution in Hong Kong.
Leung, C K
1998-05-01
To assess the progress in the treatment of advanced childhood neuroblastoma. From 1981 to 1996, there were 32 children with neuroblastoma (NB) diagnosed, staged and treated in our institution. There were 4 patients with stage II NB (12%), 5 stage III (16%), 21 stage IV (66%) and 2 stage IV s (6%). The NBs were excised if CT scan indicated that the tumors were operable. For advanced NB, stages III and IV, multiple drug chemotherapy was started first and operability was assessed with serial CT scan examinations. Once the X-ray imaging indicated the tumors were operable, surgical interventions were done. The medical records of the advanced NB were reviewed. In the initial period of the study, 9 patients were treated using the VAC protocol [vincristine (vcr), adriamycin (adria) and cyclophosphamide (cyc)]. No patient was convertible to operable and all died with a mean survival of 10 months. OPEC [vcr, cyc, VM26, cisplatin (cis)], Rapid COJEC (carboplatin, VP16, vcr, cis and cyc) and more recently N6 protocol (cyc, adria, vcr, VP16, cis) was used for 17 patients. 80% of them were converted to operable. In 4 patients, surgical specimens showed only necrotic tissue without viable tumor tissue and 6 (35%) tumors were converted to ganglioneuroma or ganglioneuroblastoma. Although 2 (12%) patients died of fungal septicemia and 1 (6%) developed Fanconi's syndrome after chemotherapy, the mean survival period increased to 27 months. In the 10 survivors (60%), 4 had megatherapy with melphalan followed by autologous peripheral blood stem cell (PBSC) transplantation and 2 were waiting for transplantation. There is a high percentage of advanced NB on presentation in Hong Kong. With more potent multiple drug chemotherapy for advanced stage NB there are (1) improvement in the survival of these patients, (2) opportunities for more operations for tumor excision and (3) opportunities for autologous PBSC transplantation for better tumor eradication.
Biomechanical Evaluation of Ti-Nb-Sn Alloy Implants with a Low Young’s Modulus
Takahashi, Kenta; Shiraishi, Naru; Ishiko-Uzuka, Risa; Anada, Takahisa; Suzuki, Osamu; Masumoto, Hiroshi; Sasaki, Keiichi
2015-01-01
Dental implants are widely used and are a predictable treatment in various edentulous cases. Occlusal overload may be causally related to implant bone loss and a loss of integration. Stress concentrations may be diminished using a mechanobiologically integrated implant with bone tissue. The purpose of this study was to investigate the biomechanical behavior, biocompatibility and bioactivity of a Ti-Nb-Sn alloy as a dental implant material. It was compared with cpTi. Cell proliferation and alkaline phosphatase (ALP) activity were quantified. To assess the degree of osseointegration, a push-in test was carried out. Cell proliferation and ALP activity in the cells grown on prepared surfaces were similar for the Ti-Nb-Sn alloy and for cpTi in all the experiments. A comparison between the Ti-Nb-Sn alloy implant and the cpTi implant revealed that no significant difference was apparent for the push-in test values. These results suggest that implants fabricated using Ti-Nb-Sn have a similar biological potential as cpTi and are capable of excellent osseointegration. PMID:25775158
Conjoint corrosion and wear in titanium alloys.
Khan, M A; Williams, R L; Williams, D F
1999-04-01
When considering titanium alloys for orthopaedic applications it is important to examine the conjoint action of corrosion and wear. In this study we investigate the corrosion and wear behaviour of Ti-6Al-4V, Ti-6Al-7Nb and Ti-13Nb-13Zr in phosphate buffered saline (PBS), bovine albumin solutions in PBS and 10% foetal calf serum solutions in PBS. The tests were performed under four different conditions to evaluate the influence of wear on the corrosion and corrosion on the wear behaviour as follows: corrosion without wear, wear-accelerated corrosion, wear in a non-corrosive environment and wear in a corrosive environment. The corrosion behaviour was investigated using cyclic polarisation studies to measure the ability of the surface to repassivate following breakdown of the passive layer. The properties of the repassivated layer were evaluated by measuring changes in the surface hardness of the alloys. The amount of wear that had occurred was assessed from weight changes and measurement of the depth of the wear scar. It was found that in the presence of wear without corrosion the wear behaviour of Ti-13Nb-13Zr was greater than that of Ti-6Al-7Nb or Ti-6Al-4V and that in the presence of proteins the wear of all three alloys is reduced. In the presence of corrosion without wear Ti-13Nb-13Zr was more corrosion resistant than Ti-6Al-7Nb which was more corrosion resistant than Ti-6Al-4V without proteins whereas in the presence of protein the corrosion resistance of Ti-13Nb-13Zr and Ti-6Al-7Nb was reduced and that of Ti-6Al-4V increased. In the presence of corrosion and wear the corrosion resistance of Ti-13Nb-13Zr is higher than that of Ti-6Al-7Nb or Ti-6Al-4V in PBS but in the presence of proteins the corrosion resistance of Ti-13Nb-13Zr and Ti-6Al-7Nb are very similar but higher than that of Ti-6Al-4V. The wear of Ti-13Nb-13Zr is lower than that of Ti-6Al-7Nb and Ti-6Al-4V with or without the presence of proteins in a corrosive environment. Therefore the overall degradation when both corrosion and wear processes are occurring is lowest for Ti-13Nb-13Zr and highest for Ti-6Al-4V and the presence of proteins reduces the degradation of all three alloys.
In Vitro Biocompatibility of Si Alloyed Multi-Principal Element Carbide Coatings
Vladescu, Alina; Titorencu, Irina; Dekhtyar, Yuri; Jinga, Victor; Pruna, Vasile; Balaceanu, Mihai; Dinu, Mihaela; Pana, Iulian; Vendina, Viktorija
2016-01-01
In the current study, we have examined the possibility to improve the biocompatibility of the (TiZrNbTaHf)C through replacement of either Ti or Ta by Si. The coatings were deposited on Si and 316L stainless steel substrates by magnetron sputtering in an Ar+CH4 mixed atmosphere and were examined for elemental composition, chemical bonds, surface topography, surface electrical charge and biocompatible characteristics. The net surface charge was evaluated at nano and macroscopic scale by measuring the electrical potential and work function, respectively. The biocompatible tests comprised determination of cell viability and cell attachment to the coated surface. The deposited coatings had C/(metal+Si) ratios close to unity, while a mixture of metallic carbide, free-carbon and oxidized species formed on the film surface. The coatings’ surfaces were smooth and no influence of surface roughness on electrical charge or biocompatibility was found. The biocompatible characteristics correlated well with the electrical potential/work function, suggesting a significant role of surface charge in improving biocompatibility, particularly cell attachment to coating's surface. Replacement of either Ti or Ta by Si in the (TiZrNbTaHf)C coating led to an enhanced surface electrical charge, as well as to superior biocompatible properties, with best results for the (TiZrNbSiHf)C coating. PMID:27571361
Shashoua, V E; Adams, D; Boyer-Boiteau, A
2001-10-19
An 8-amino acid peptide fragment (CMX-8933) of Ependymin, a glycoprotein component of the extracellular fluid and cerebrospinal fluid of goldfish brain, was synthesized and tested for its capacity to activate AP-1 transcription factor in cell cultures. Dose-response and time-course studies of AP-1's binding to DNA were carried out in neuroblastoma (NB2a/dl) and primary rat brain cortical cultures using an electrophoretic mobility shift assay (EMSA). A 13-14-fold increase in AP-1's DNA binding was obtained when NB2a cells were incubated for 4 h with 6-10 microg/ml CMX-8933. Primary rat brain cortical cultures were much more sensitive to the effects of CMX-8933 than transformed (NB2a) cultures; here a 26.7+/-5.2-fold increase in binding was observed following a 3-h treatment with as little as 10 ng/ml peptide. These findings are consistent with an activation of this transcription factor, a characteristic that has been previously correlated with functional aspects of full-sized neurotrophic factors (nerve growth factor and brain-derived nerve growth factor) in neuronal differentiation and regeneration. Such data suggest a role for Ependymin in transcriptional control.
NASA Astrophysics Data System (ADS)
Okazaki, Yoshimitsu; Nagata, Hiroyuki
2012-12-01
Metal release from implantable metals and the properties of oxide films formed on alloy surfaces were analyzed, focusing on the highly biocompatible Ti-15Zr-4Nb-4Ta alloy. The thickness and electrical resistance (Rp) of the oxide film on such an alloy were compared with those of other implantable metals. The quantity of metal released during a 1-week immersion test was considerably smaller for the Ti-15Zr-4Nb-4Ta than the Ti-6Al-4V alloy. The potential (E10) indicating a current density of 10 μA cm-2 estimated from the anodic polarization curve was significantly higher for the Ti-15Zr-4Nb-4Ta than the Ti-6Al-4V alloy and other metals. Moreover, the oxide film (4-7 nm thickness) formed on the Ti-15Zr-4Nb-4Ta surface is electrochemically robust. The oxide film mainly consisted of TiO2 with small amounts of ZrO2, Nb2O5 and Ta2O5 that made the film electrochemically stable. The Rp of Ti-15Zr-4Nb-4Ta was higher than that of Ti-6Al-4V, i.e. 0.9 Ω cm2 in 0.9% NaCl and 1.3 Ω cm2 in Eagle's medium. This Rp was approximately five-fold higher than that of stainless steel, which has a history of more than 40 years of clinical use in the human body. Ti-15Zr-4Nb-4Ta is a potential implant material for long-term clinical use. Moreover, E10 and Rp were found to be useful parameters for assessing biological safety.
On-sky characterisation of the VISTA NB118 narrow-band filters at 1.19 μm
NASA Astrophysics Data System (ADS)
Milvang-Jensen, Bo; Freudling, Wolfram; Zabl, Johannes; Fynbo, Johan P. U.; Møller, Palle; Nilsson, Kim K.; McCracken, Henry Joy; Hjorth, Jens; Le Fèvre, Olivier; Tasca, Lidia; Dunlop, James S.; Sobral, David
2013-12-01
Observations of the high redshift Universe through narrow-band filters have proven very successful in the last decade. The 4-m VISTA telescope, equipped with the wide-field camera VIRCAM, offers a major step forward in wide-field near-infrared imaging, and in order to utilise VISTA's large field-of-view and sensitivity, the Dark Cosmology Centre provided a set of 16 narrow-band filters for VIRCAM. These NB118 filters are centered at a wavelength near 1.19 μm in a region with few airglow emission lines. The filters allow the detection of Hα emitters at z = 0.8, Hβ and [O iii] emitters at z ≈ 1.4, [O ii] emitters at z = 2.2, and Lyα emitters at z = 8.8. Based on guaranteed time observations of the COSMOS field we here present a detailed description and characterization of the filters and their performance. In particular we provide sky-brightness levels and depths for each of the 16 detector/filter sets and find that some of the filters show signs of some red-leak. We identify a sample of 2 × 103 candidate emission-line objects in the data. Cross-correlating this sample with a large set of galaxies with known spectroscopic redshifts we determine the "in situ" passbands of the filters and find that they are shifted by about 3.5 - 4 nm (corresponding to 30% of the filter width) to the red compared to the expectation based on the laboratory measurements. Finally, we present an algorithm to mask out persistence in VIRCAM data. Scientific results extracted from the data will be presented separately. Based on observations collected at the European Southern Observatory, Chile, as part of programme 284.A-5026 (VISTA NB118 GTO, PI Fynbo) and 179.A-2005 (UltraVISTA, PIs Dunlop, Franx, Fynbo, & Le Fèvre).
Hashemzadeh, Fatemeh; Gaffarinejad, Ali; Rahimi, Rahmatollah
2015-04-09
Porous NiO/Nb2O5 nanocomposites with Ni/Nb molar ratio of 0.4, 0.8 and 1.2 have been obtained via the EISA route using P123 copolymer as organic template, and are assigned as NiNb0.4, NiNb0.8 and NiNb1.2, respectively. For comparison, pure Nb2O5 sample assigned as NiNb0.0 was also synthesized by the same method. Structural and textural features of the as prepared samples were investigated by XRD, FTIR, FE-SEM, EDX, UV-vis DRS and BET techniques. The results indicated that the porous p-NiO/n-Nb2O5 junction nanocomposites were formed and coupling of NiO with Nb2O5 resulted a remarkable red shift in the optical response of the nanocomposite samples. The photocatalytic properties of the nanocomposite samples, and also synthesized pure Nb2O5 (NiNb0.0) and commercial Nb2O5 as reference catalysts were evaluated for the first time by simultaneous Cr(VI) reduction and MO decolorization in aqueous suspension under visible light irradiation at pH 2. NiNb0.4 was found to be the most active photocatalyst, which might be attributed to the extended absorption in the visible light region and the effective photogenerated electron-hole separation by the photosynergistic effects of the p-NiO/n-Nb2O5 composite powder. The photocatalytic efficiency of the most active photocatalyst, NiNb0.4, was found to be rather low for either single Cr(VI) solution or single MO solution. However, the photocatalytic reduction of Cr(VI) and photocatalytic decolorization of MO proceed more rapidly for the coexistence system of Cr(VI) and MO than for the single process, showing synergetic effect between the reduction and decolorization reactions. The effects of initial concentration of Cr(VI), MO and the initial pH value on the rate of simultaneous photoreactions over NiNb0.4 sample, were also investigated. The Cr(VI) and MO removal rates were further enhanced by increasing MO and Cr (VI) concentration to an optimal value, respectively, and/or decreasing solution pH. Copyright © 2014 Elsevier B.V. All rights reserved.
Growth and characterization of few unit-cell NbN superconducting films on 3C-SiC/Si substrate
NASA Astrophysics Data System (ADS)
Chang, H. W.; Wang, C. L.; Huang, Y. R.; Chen, T. J.; Wang, M. J.
2017-11-01
Superconducting δ-NbN ultrathin film has become a key element in extremely sensitive detector applications in recent decades because of its excellent electronic properties. We have realized the epitaxial growth of ultrathin δ-NbN films on (100)-oriented 3C-SiC/Si substrates by dc reactive magnetron sputtering at 760 °C with a deposition rate of 0.054 nm s-1. High-resolution transmission electron microscope images confirm the excellent epitaxy of these films. Even with a thickness of 1.3 nm (˜3 unit cells), the δ-NbN film shows a superconducting transition above 8 K. Furthermore, our ultrathin δ-NbN films demonstrate a long Ginzburg-Landau superconducting coherent length ({ξ }{{G}{{L}}}(0)> 5 {{nm}}) with a critical current density of about 2.2 MA cm-2, and good stability in an ambient environment.
Shue, Eveline; Wu, Jianfeng; Schecter, Samuel; Miniati, Doug
2013-06-01
Many infants develop a postsurgical chylothorax after diaphragmatic hernia repair. The pathogenesis remains elusive but may be owing to dysfunctional lymphatic development. This study characterizes pulmonary lymphatic development in the nitrofen mouse model of CDH. CD1 pregnant mice were fed nitrofen/bisdiamine (N/B) or olive oil at E8.5. At E14.5 and E15.5, lung buds were categorized by phenotype: normal, N/B without CDH (N/B - CDH), or N/B with CDH (N/B+CDH). Anti-CD31 was used to localize all endothelial cells, while anti-LYVE-1 was used to identify lymphatic endothelial cells in lung buds using immunofluorescence. Differential protein expression of lymphatic-specific markers was analyzed. Lymphatic endothelial cells localized to the mesenchyme surrounding the airway epithelium at E15.5. CD31 and LYVE-1 colocalization identified lymphatic endothelial cells. LYVE-1 expression was upregulated in N/B+CDH lung buds in comparison to N/B - CDH and normal lung buds by immunofluorescence. Western blotting shows that VEGF-D, LYVE-1, Prox-1, and VEGFR-3 expression was upregulated in N/B+CDH lung buds in comparison to N/B - CDH or control lung buds at E14.5. Lung lymphatics are hyperplastic in N/B+CDH. Upregulation of lymphatic-specific genes suggests that lymphatic hyperplasia plays an important role in dysfunctional lung lymphatic development in the nitrofen mouse model of CDH. Copyright © 2013 Elsevier Inc. All rights reserved.
Zhang, Hui; Hu, Tao; Wang, Xiaohui; Li, Zhaojin; Hu, Minmin; Wu, Erdong; Zhou, Yanchun
2015-01-01
The conventional wisdom to tailor the properties of binary transition metal carbides by order-disorder phase transformation has been inapplicable for the machinable ternary carbides (MTCs) due to the absence of ordered phase in bulk sample. Here, the presence of an ordered phase with structural carbon vacancies in Nb4AlC3–x (x ≈ 0.3) ternary carbide is predicted by first-principles calculations, and experimentally identified for the first time by transmission electron microscopy and micro-Raman spectroscopy. Consistent with the first-principles prediction, the ordered phase, o-Nb4AlC3, crystalizes in P63/mcm with a = 5.423 Å, c = 24.146 Å. Coexistence of ordered (o-Nb4AlC3) and disordered (Nb4AlC3–x) phase brings about abundant domains with irregular shape in the bulk sample. Both heating and electron irradiation can induce the transformation from o-Nb4AlC3 to Nb4AlC3–x. Our findings may offer substantial insights into the roles of carbon vacancies in the structure stability and order-disorder phase transformation in MTCs. PMID:26388153
NASA Astrophysics Data System (ADS)
Pan, Ke-Ji; Hussain, A. Mohammed; Wachsman, Eric D.
2017-04-01
Variants of SNNV (Sr0.2Na0.8Nb1-xVxO3, X = 0.1-0.3) ceramic oxides were synthesized via wet chemical method. SNNVs show high electronic conductivity of >100 S/cm when reduced in hydrogen at a relatively low temperature of 650 °C. In particular, 30% V-doped SNNV exhibited the highest conductivity of 300 S/cm at 450 °C. In order to investigate the fuel cell performance, Gd0.1Ce0.9O2-δ (GDC) based electrolyte-supported fuel cells were prepared to study the anode characteristics. Sr0.2Na0.8Nb0.9V0.1O3 (SNNV10)-GDC composite was used as an anode and La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF)-GDC as a cathode. Both electrodes were porous and sintered at 1050 °C for 2 h in air. The anode side of the fuel cell was infiltrated with 10 wt% GDC/Ni-GDC precursor to activate the anode for fuel oxidation. I-V characteristics were determined in gas conditions such as dry/humidified hydrogen and methane at 650 °C. With the infiltration Ni-GDC, peak power density (PPD) of 280 mW/cm2 and 220 mW/cm2 in dry H2 and CH4, respectively, were obtained at 650 °C, which is higher than GDC alone as infiltrate. The high resistances in the humidified conditions are attributed to the lower conductivity of SNNV10 in high PO2 atmospheres.
Hellriegel, Christian; Caiolfa, Valeria R.; Corti, Valeria; Sidenius, Nicolai; Zamai, Moreno
2011-01-01
We studied the molecular forms of the GPI-anchored urokinase plasminogen activator receptor (uPAR-mEGFP) in the human embryo kidney (HEK293) cell membrane and demonstrated that the binding of the amino-terminal fragment (ATF) of urokinase plasminogen activator is sufficient to induce the dimerization of the receptor. We followed the association kinetics and determined precisely the dimeric stoichiometry of uPAR-mEGFP complexes by applying number and brightness (N&B) image analysis. N&B is a novel fluctuation-based approach for measuring the molecular brightness of fluorophores in an image time sequence in live cells. Because N&B is very sensitive to long-term temporal fluctuations and photobleaching, we have introduced a filtering protocol that corrects for these important sources of error. Critical experimental parameters in N&B analysis are illustrated and analyzed by simulation studies. Control experiments are based on mEGFP-GPI, mEGFP-mEGFP-GPI, and mCherry-GPI, expressed in HEK293. This work provides a first direct demonstration of the dimerization of uPAR in live cells. We also provide the first methodological guide on N&B to discern minor changes in molecular composition such as those due to dimerization events, which are involved in fundamental cell signaling mechanisms.—Hellriegel, C., Caiolfa, V. R., Corti, V., Sidenius, N., Zamai, M. Number and brightness image analysis reveals ATF-induced dimerization kinetics of uPAR in the cell membrane. PMID:21602447
Choice of costimulatory domains and of cytokines determines CAR T-cell activity in neuroblastoma
Quintarelli, Concetta; Orlando, Domenico; Boffa, Iolanda; Guercio, Marika; Petretto, Andrea; Lavarello, Chiara; Sinibaldi, Matilde; Weber, Gerrit; Del Bufalo, Francesca; Giorda, Ezio; Scarsella, Marco; Petrini, Stefania; Pagliara, Daria; Locatelli, Franco
2018-01-01
ABSTRACT Chimeric antigen receptor (CAR) T-cell therapy has been shown to be dramatically effective in the treatment of B-cell malignancies. However, there are still substantial obstacles to overcome, before similar responses can be achieved in patients with solid tumors. We evaluated both in vitro and in a preclinical murine model the efficacy of different 2nd and 3rd generation CAR constructs targeting GD2, a disial-ganglioside expressed on the surface of neuroblastoma (NB) tumor cells. In order to address potential safety concerns regarding clinical application, an inducible safety switch, namely inducible Caspase-9 (iC9), was also included in the vector constructs. Our data indicate that a 3rd generation CAR incorporating CD28.4-1BB costimulatory domains is associated with improved anti-tumor efficacy as compared with a CAR incorporating the combination of CD28.OX40 domains. We demonstrate that the choice of 4-1BB signaling results into significant amelioration of several CAR T-cell characteristics, including: 1) T-cell exhaustion, 2) basal T-cell activation, 3) in vivo tumor control and 4) T-cell persistence. The fine-tuning of T-cell culture conditions obtained using IL7 and IL15 was found to be synergic with the CAR.GD2 design in increasing the anti-tumor activity of CAR T cells. We also demonstrate that activation of the suicide gene iC9, included in our construct without significantly impairing neither CAR expression nor anti-tumor activity, leads to a prompt induction of apoptosis of GD2.CAR T cells. Altogether, these findings are instrumental in optimizing the function of CAR T-cell products to be employed in the treatment of children with NB. PMID:29872565
DOE Office of Scientific and Technical Information (OSTI.GOV)
Woodward, S.; Curtis, M.D.; Rheingold, A.L.
1992-06-01
Cp{sub 2}Nb{sub 2}Cl{sub 2}({mu}-Cl{sub 2})(CO){sub 4} reacts with Cp{sub 2}Ni{sub 2}({mu}-SEt){sub 2} to yield paramagnetic CpNbCl{sub 2}({mu}-SEt){sub 2}NiCp: (g) = 2.004, A = 129 G; space group = P2{sub 1}/c,a = 7.466 (1) {Angstrom}, b = 28.427 (5) {Angstrom}, c = 8.620 (2) {Angstrom}, {beta} = 104.81 (1){degree}. CpNb(PhCCPh)({mu}-SPr{sup i}){sub 2}Mo(CO){sub 4} is synthesized by the addition of LiSPr{sup i} to CpNbCl{sub 2}PhCCPh resulting in formation of CpNb(SPr{sup i}){sub 2}(PhCCPh) followed by the reaction of the thiolate complex with Mo(MeCN){sub 3}(CO){sub 3} and CO (1 equiv). The crystal structure for CpNb(PhCCPh)({mu}-SPr{sup i}){sub 2}Mo(CO){sub 4} is reported and EHMO calculations ofmore » the bonding in CpNbCl{sub 2}({mu}-SEt{sub 2})NiCp were discussed. 27 refs., 5 figs., 5 tabs.« less
Xiao, Guoliang; Wang, Siwei; Lin, Ye; Zhang, Yanxiang; An, Ke; Chen, Fanglin
2014-11-26
Donor-doped perovskite-type SrTiO3 experiences stoichiometric changes at high temperatures in different Po2 involving the formation of Sr or Ti-rich impurities. NiO is incorporated into the stoichiometric strontium titanate, SrTi0.8Nb0.2O3-δ (STN), to form an A-site deficient perovskite material, (NiO)0.05-(SrTi0.8Nb0.2O3)0.95 (Ni-STN), for balancing the phase transition. Metallic Ni nanoparticles can be released upon reduction instead of forming undesired secondary phases. This material design introduces a simple catalytic modification method with good compositional control of the ceramic backbones, by which transport property and durability of solid oxide fuel cell anodes are largely determined. Using Ni-STN as anodes for solid oxide fuel cells, enhanced catalytic activity and remarkable stability in redox cycling have been achieved. Electrolyte-supported cells with the cell configuration of Ni-STN-SDC anode, La0.8Sr0.2Ga0.87Mg0.13O3 (LSGM) electrolyte, and La0.6Sr0.4Co0.2Fe0.8O3 (LSCF) cathode produce peak power densities of 612, 794, and 922 mW cm(-2) at 800, 850, and 900 °C, respectively, using H2 as the fuel and air as the oxidant. Minor degradation in fuel cell performance resulted from redox cycling can be recovered upon operating the fuel cells in H2. Such property makes Ni-STN a promising regenerative anode candidate for solid oxide fuel cells.
Preparation and crystal structure of K/sub 2/Nb/sub 2/As/sub 2/O/sub 11/
DOE Office of Scientific and Technical Information (OSTI.GOV)
Faouzi Zid, M.; Jouini, T.; Juoini, N.
1988-06-01
K/sup 2/Nb/sub 2/As/sub 2/O/sub 11/ crystallizes in the monoclinic system, space group P21/a, with a = 10.342(6), b = 10.446(5), c = 9.971(4) A, ..beta.. = 96.72(4)/sup 0/, M = 589.86, V = 1069.8(5) A/sup 3/, Z = 4, rho = 3.67 g cm/sup -1/. The crystal structure was refined (105 variables) from 1782 independent reflections collected on a Philips PW 1100 automatic diffractometer with AgK anti ..cap alpha.. radiation. The final R index and weighted R/sub w/ index are 0.058 and 0.056, respectively. The structure consists of NbO/sub 6/ octahedra and AsO/sub 4/ tetrahedra sharing vertices, forming infinite chainsmore » (NbO/sub 6/-AsO/sub 4/)infinity parallel to the a axis. Two chains are linked together by Nb-O-Nb and Nb-O-As bonds. These double chains are connected by vertices, forming a three-dimensional network. The potassium atoms are located in tunnels parallel to the a axis.« less
Characterization of NbN films and tunnel junctions
NASA Technical Reports Server (NTRS)
Stern, J. A.; Leduc, H. G.
1991-01-01
Properties of NbN films and NbN/MgO/NbN tunnel junctions are discussed. NbN junctions are being developed for use in high-frequency, SIS quasiparticle mixers. To properly design mixer circuits, junction and film properties need to be characterized. The specific capacitance of NbN/MgO/NbN junctions has been measured as a function of the product of the normal-state resistance and the junction area (RnA), and it is found to vary by more than a factor of two (35-85 fF/sq microns) over the range of RnA measured (1000-50 ohm sq microns). This variation is important because the specific capacitance determines the RC speed of the tunnel junction at a given RnA value. The magnetic penetration depth of NbN films deposited under different conditions is also measured. The magnetic penetration depth affects the design of microstrip line used in RF tuning circuits. Control of the magnetic penetration depth is necessary to fabricate reproducible tuning circuits. Additionally, the critical current uniformity for arrays of 100 junctions has been measured. Junction uniformity will affect the design of focal-plane arrays of SIS mixers. Finally, the relevance of these measurements to the design of Josephson electronics is discussed.
Development of Ti-Nb-Zr alloys with high elastic admissible strain for temporary orthopedic devices.
Ozan, Sertan; Lin, Jixing; Li, Yuncang; Ipek, Rasim; Wen, Cuie
2015-07-01
A new series of beta Ti-Nb-Zr (TNZ) alloys with considerable plastic deformation ability during compression test, high elastic admissible strain, and excellent cytocompatibility have been developed for removable bone tissue implant applications. TNZ alloys with nominal compositions of Ti-34Nb-25Zr, Ti-30Nb-32Zr, Ti-28Nb-35.4Zr and Ti-24.8Nb-40.7Zr (wt.% hereafter) were fabricated using the cold-crucible levitation technique, and the effects of alloying element content on their microstructures, mechanical properties (tensile strength, yield strength, compressive yield strength, Young's modulus, elastic energy, toughness, and micro-hardness), and cytocompatibilities were investigated and compared. Microstructural examinations revealed that the TNZ alloys consisted of β phase. The alloy samples displayed excellent ductility with no cracking, or fracturing during compression tests. Their tensile strength, Young's modulus, elongation at rupture, and elastic admissible strain were measured in the ranges of 704-839 MPa, 62-65 GPa, 9.9-14.8% and 1.08-1.31%, respectively. The tensile strength, Young's modulus and elongation at rupture of the Ti-34Nb-25Zr alloy were measured as 839 ± 31.8 MPa, 62 ± 3.6 GPa, and 14.8 ± 1.6%, respectively; this alloy exhibited the elastic admissible strain of approximately 1.31%. Cytocompatibility tests indicated that the cell viability ratios (CVR) of the alloys are greater than those of the control group; thus the TNZ alloys possess excellent cytocompatibility. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Rios, Paula; Bailey, Helen D; Orsi, Laurent; Lacour, Brigitte; Valteau-Couanet, Dominique; Levy, Dominique; Corradini, Nadège; Leverger, Guy; Defachelles, Anne-Sophie; Gambart, Marion; Sirvent, Nicolas; Thebaud, Estelle; Ducassou, Stéphane; Clavel, Jacqueline
2016-11-01
Neuroblastoma (NB), an embryonic tumour arising from neural crest cells, is the most common malignancy among infants. The aetiology of NB is largely unknown. We conducted a pooled analysis to explore whether there is an association between NB and preconception and perinatal factors using data from two French national population-based case-control studies. The mothers of 357 NB cases and 1783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on demographic, socioeconomic and perinatal characteristics, childhood environment, life-style and maternal reproductive history. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. After controlling for matching variables, study of origin and potential confounders, being born either small (OR 1.4 95% CI 1.0-2.0) or large (OR 1.5 95% CI 1.1-2.2) for gestational age and, among children younger than 18 months, having congenital malformations (OR 3.6 95% CI 1.3-8.9), were significantly associated with NB. Inverse associations were observed with breastfeeding (OR 0.7 95% CI 0.5-1.0) and maternal use of any supplements containing folic acid, vitamins or minerals (OR 0.5 95% CI 0.3-0.9) during the preconception period. Our findings reinforce the hypothesis that fetal growth anomalies and congenital malformations may be associated with an increased risk of NB. Further investigations are needed in order to clarify the role of folic acid supplementation and breastfeeding, given their potential importance in NB prevention. © 2016 UICC.
NASA Astrophysics Data System (ADS)
Moon, Keon Ho; Avdeev, Maxim; Kim, Young-Il
2017-10-01
Oxynitride type complex perovskites AM0.2Nb0.8O3-xNx (A = Sr, Ba; M = Li, Na, Mg) were newly synthesized by the solid state diffusion of Li+, Na+, or Mg2+ into the layered oxide, A5Nb4O15, with concurrent O/N substitution. Neutron and synchrotron X-ray Rietveld refinement showed that SrLi0.2Nb0.8O2.8N0.2, SrNa0.2Nb0.8O2.8N0.2, and SrMg0.2Nb0.8O2.6N0.4 had body-centered tetragonal symmetry (I4/mcm), while those with A = Ba had simple cubic symmetry (Pm 3 ̅ m). In the tetragonal Sr-compounds, the nitrogen atoms were localized on the c-axial 4a site. However, the octahedral cations, M/Nb (M = Li, Na, Mg) were distributed randomly in all six compounds. The lattice volume of AM0.2Nb0.8O3-xNx was dependent on various factors including the type of A and the electronegativity of M. Compared to the simple perovskites, ANbO2N (A = Sr, Ba), AM0.2Nb0.8O3-xNx had wider band gaps (1.76-2.15 eV for A = Sr and 1.65-2.10 eV for A = Ba), but significantly lower sub-gap absorption.
Cho, Sang-Yun; Cho, Won Kyong; Sohn, Seong-Han; Kim, Kook-Hyung
2012-01-06
Plant viruses must interact with host cellular components to replicate and move from cell to cell. In the case of Potato virus X (PVX), it carries stem-loop 1 (SL1) RNA essential for viral replication and movement. Using two-dimensional electrophoresis northwestern blot analysis, we previously identified several host proteins that bind to SL1 RNA. Of those, we further characterized a DnaJ-like protein from Nicotiana benthamiana named NbDnaJ. An electrophoretic mobility shift assay confirmed that NbDnaJ binds only to SL1 minus-strand RNA, and bimolecular fluorescence complementation (BiFC) indicated that NbDnaJ interacts with PVX capsid protein (CP). Using a series of deletion mutants, the C-terminal region of NbDnaJ was found to be essential for the interaction with PVX CP. The expression of NbDnaJ significantly changed upon infection with different plant viruses such as PVX, Tobacco mosaic virus, and Cucumber mosaic virus, but varied depending on the viral species. In transient experiments, both PVX replication and movement were inhibited in plants that over-expressed NbDnaJ but accelerated in plants in which NbDnaJ was silenced. In summary, we suggest that the newly identified NbDnaJ plays a role in PVX replication and movement by interacting with SL1(-) RNA and PVX CP. Copyright © 2011 Elsevier Inc. All rights reserved.
Laminated NbTi-on-Kapton Microstrip Cables for Flexible Sub-Kelvin RF Electronics
NASA Astrophysics Data System (ADS)
Walter, Alex B.; Bockstiegel, Clinton; Mazin, Benjamin A.; Daal, Miguel
2017-11-01
Large arrays of superconducting devices such as microwave kinetic inductance detectors require high density interconnects from higher temperatures with minimal heat load, low loss, and negligible crosstalk capable of carrying large and overlapping bandwidth signals. We report the fabrication of superconducting 53 wt% Nb-47 wt% Ti (Nb-47Ti) microstrip transmission lines laminated onto flexible polyimide substrates with lengths up to 40 cm and up to ten traces. The 50 Ω traces terminate in G3PO coaxial push-on connectors. We found transmission losses of 2.5 dB and a nearest-neighbor forward crosstalk of -25 dB at 8 GHz on a typical 5 trace, 1.8-cm-wide, 0.198-mm-thick, 22-cm-long flex cable at 30 mK. A simple two-port analytical model and subsequent Sonnet simulations indicate that this loss is mainly due to a complex impedance mismatch from wirebonds at the end connector without which the insertion loss would be < 2.7 dB/m. This is about six times worse than the transmission measured in Coax Company, Ltd.'s smallest ( 0.86 mm) Nb-47Ti coaxial cables, possibly from differences in the low temperature loss properties of polyimide laminates versus PTFE or from unaccounted resistive losses in the copper adapter coaxes of our tested device. Heat flow calculations from literature data show that the 0.198-mm-thick flex cables tested have roughly equivalent thermal conductance per trace below 4 K compared to the 0.86 mm Nb-47Ti coaxial cables.
Structural, microstructural and thermal analysis of U-(6-x)Zr-xNb alloys (x = 0, 2, 4, 6)
NASA Astrophysics Data System (ADS)
Kaity, Santu; Banerjee, Joydipta; Parida, S. C.; Bhasin, Vivek
2018-06-01
Uranium-rich U-Zr-Nb alloy is considered as a good alternative fuel for fast reactors from the perspective of excellent dimensional stability and desired thermo-physical properties to achieve higher burnup. Detailed investigations related to the structural and microstructural characterization, thermal expansion, phase transformation, microhardness were carried out on U-6Zr, U-4Zr-2Nb, U-2Zr-4Nb and U-6Nb alloys (composition in wt%) where the total amount of alloying elements was restricted to 6 wt%. Structural, microstructural and thermal analysis studies revealed that these alloys undergo a series of transformations from high temperature bcc γ-phase to a variety of equilibrium and intermediate phases depending upon alloy composition, cooling rate and quenching. The structural analysis was carried out by Rietveld refinement. The data of U-Nb and U-Zr-Nb alloys have been highlighted and compared with binary U-Zr alloy.
Niobium Nitride Nb4N5 as a New High‐Performance Electrode Material for Supercapacitors
Cui, Houlei; Zhu, Guilian; Liu, Xiangye; Liu, Fengxin; Xie, Yian; Yang, Chongyin; Lin, Tianquan; Gu, Hui
2015-01-01
Supercapacitors suffer either from low capacitance for carbon or derivate electrodes or from poor electrical conductivity and electrochemical stability for metal oxide or conducting polymer electrodes. Transition metal nitrides possess fair electrical conductivity but superior chemical stability, which may be desirable candidates for supercapacitors. Herein, niobium nitride, Nb4N5, is explored to be an excellent capacitive material for the first time. An areal capacitance of 225.8 mF cm−2, with a reasonable rate capability (60.8% retention from 0.5 to 10 mA cm−2) and cycling stability (70.9% retention after 2000 cycles), is achieved in Nb4N5 nanochannels electrode with prominent electrical conductivity and electrochemical activity. Faradaic pseudocapacitance is confirmed by the mechanistic studies, deriving from the proton incorporation/chemisorption reaction owing to the copious +5 valence Nb ions in Nb4N5. Moreover, this Nb4N5 nanochannels electrode with an ultrathin carbon coating exhibits nearly 100% capacitance retention after 2000 CV cycles, which is an excellent cycling stability for metal nitride materials. Thus, the Nb4N5 nanochannels are qualified for a candidate for supercapacitors and other energy storage applications. PMID:27980920
Niobium Nitride Nb4N5 as a New High-Performance Electrode Material for Supercapacitors.
Cui, Houlei; Zhu, Guilian; Liu, Xiangye; Liu, Fengxin; Xie, Yian; Yang, Chongyin; Lin, Tianquan; Gu, Hui; Huang, Fuqiang
2015-12-01
Supercapacitors suffer either from low capacitance for carbon or derivate electrodes or from poor electrical conductivity and electrochemical stability for metal oxide or conducting polymer electrodes. Transition metal nitrides possess fair electrical conductivity but superior chemical stability, which may be desirable candidates for supercapacitors. Herein, niobium nitride, Nb 4 N 5 , is explored to be an excellent capacitive material for the first time. An areal capacitance of 225.8 mF cm -2 , with a reasonable rate capability (60.8% retention from 0.5 to 10 mA cm -2 ) and cycling stability (70.9% retention after 2000 cycles), is achieved in Nb 4 N 5 nanochannels electrode with prominent electrical conductivity and electrochemical activity. Faradaic pseudocapacitance is confirmed by the mechanistic studies, deriving from the proton incorporation/chemisorption reaction owing to the copious +5 valence Nb ions in Nb 4 N 5 . Moreover, this Nb 4 N 5 nanochannels electrode with an ultrathin carbon coating exhibits nearly 100% capacitance retention after 2000 CV cycles, which is an excellent cycling stability for metal nitride materials. Thus, the Nb 4 N 5 nanochannels are qualified for a candidate for supercapacitors and other energy storage applications.
NASA Astrophysics Data System (ADS)
Bayot, Daisy; Degand, Matthieu; Devillers, Michel
2005-09-01
New water-soluble bimetallic peroxo complexes of niobium V and/or tantalum V with high-denticity polyaminocarboxylate ligands have been prepared, characterized from the spectroscopic point of view, and used as molecular precursors for Nb-Ta mixed oxides. Four new homobimetallic complexes, (gu) 3[Nb 2(O 2) 4(dtpaO 3)]·3H 2O 1, (gu) 3[Ta 2(O 2) 4(dtpaO 3)]·5H 2O 2, (gu) 3[Nb 2(O 2) 4(HtthaO 4)]·2H 2O 4 and (gu) 3[Ta 2(O 2) 4(HtthaO 4)]·3H 2O 5 and the corresponding heterometallic complexes, (gu) 3[NbTa(O 2) 4(dtpaO 3)]·2.5H 2O 3 and (gu) 3[NbTa(O 2) 4(HtthaO 4)]·2H 2O 6 have been obtained. In these compounds, the in situ oxidation of the nitrogen atoms of the PAC ligands into N-oxide groups has been evidenced by IR spectroscopy and mass spectrometry. The thermal treatment of the homonuclear complexes in air at 700 or 800 °C, depending on the Ta content, provided Nb 2O 5 or Ta 2O 5 while the heteronuclear compounds led to the solid solution TaNbO 5. BET and SEM measurements have been carried out and comparison of the morphology of the samples prepared from homo- and heterometallic precursors is discussed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cao, Yong; Duan, Nanqi; Yan, Dong, E-mail: yand@hust.edu.cn
Ca{sub 0.01}La{sub 0.99−x}Sm{sub x}NbO{sub 4−δ} (x=0, 0.1, 0.2, 0.4, 0.6, 0.8, 0.99) is prepared by using a solid reaction route, and single phase is achieved. Structural and phase transformation of Ca{sub 0.01}La{sub 0.99−x}Sm{sub x}NbO{sub 4−δ} have been characterized by high temperature X-ray diffraction. The lattice parameters a, b, c decrease and γ increases with increasing x, at both room and high temperature. The phase transformation temperature increases linearly with increasing x for Ca{sub 0.01}La{sub 0.99−x}Sm{sub x}NbO{sub 4−δ}. The electrical conductivity of Ca{sub 0.01}La{sub 0.99−x}Sm{sub x}NbO{sub 4−δ} is measured in wet air. A clear relationship between the structural, phase transformation andmore » electrical conductivity of Ca{sub 0.01}La{sub 0.99−x}Sm{sub x}NbO{sub 4−δ} is built, which will provide a guideline to tailor the electrical conductivity. - Graphical abstract: Structural and phase transformation of Ca{sub 0.01}La{sub 0.99−x}Sm{sub x}NbO{sub 4−δ} have been characterized by high temperature X-ray diffraction, as well as the conductivity of Ca{sub 0.01}La{sub 0.99−x}Sm{sub x}NbO{sub 4−δ} in wet air. A clear relationship between the structural, phase transformation and electrical conductivity of Ca{sub 0.01}La{sub 0.99−x}Sm{sub x}NbO{sub 4−δ} is built. - Highlights: • Ca{sub 0.01}La{sub 0.99−x}Sm{sub x}NbO{sub 4−δ} with various Sm contents was prepared. • Structure, phase transformation and electrical conductivity of Ca{sub 0.01}La{sub 0.99−x}Sm{sub x}NbO{sub 4−δ} were characterized. • A relationship between the structure, phase transformation and electrical conductivity was well established.« less
Cellular response of osteoblasts to low modulus Ti-24Nb-4Zr-8Sn alloy mesh structure.
Nune, K C; Misra, R D K; Li, S J; Hao, Y L; Yang, R
2017-03-01
Titanium alloys (Ti-6Al-4V and Ti-6Al-7Nb) are widely used for implants, which are characterized by high elastic modulus (∼110 GPa) with (α + β) structure and that may induce undesirable stress shielding effect and immune responses associated with the presence of toxic elements. In this regard, we have combined the attributes of a new alloy design and the concept of additive manufacturing to fabricate 3D scaffolds with an interconnected porous structure. The new alloy is a β-type Ti-24Nb-4Zr-8Sn (Ti2448) alloy with significantly reduced modulus. In the present study, we explore the biological response of electron beam melted low modulus Ti2448 alloy porous mesh structure through the elucidation of bioactivity and osteoblast functions. The cellular activity was explored in terms of cell-to-cell communication involving proliferation, spreading, synthesis of extracellular and intracellular proteins, differentiation, and mineralization. The formation of fine apatite-like crystals on the surface during immersion test in simulated body fluid confirmed the bioactivity of the scaffold surface, which provided the favorable osteogenic microenvironment for cell-material interaction. The combination of unique surface chemistry and interconnected porous architecture provided the desired pathway for supply of nutrients and oxygen to cells and a favorable osteogenic micro-environment for incorporation (on-growth and in-growth) of osteoblasts. The proliferation and differentiation of pre-osteoblasts and their ability to form a well mineralized bone-like extracellular matrix (ECM) by secreting bone markers (ALP, calcium, etc.) over the struts of the scaffold point toward the determining role of unique surface chemistry and 3D architecture of the Ti2448 alloy mesh structure in modulating osteoblasts functions. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 859-870, 2017. © 2016 Wiley Periodicals, Inc.
DOT National Transportation Integrated Search
2008-12-01
The appendix includes various ML speed-flow plots: OR-217 NB, 72nd MP 6.61; OR-217 NB, 99W-EB MP 5.9; OR-217 NB, 99W-WB MP 5.85; OR-217 NB, Greenburg MP 4.65; OR-217 NB, Scholls MP 3.85; OR-217 NB, Denney MP 2.68; OR-217 NB, Allen MP 2.16; OR-217 NB,...
Posen, S.; Liepe, M.; Hall, D. L.
2015-02-23
Many future particle accelerators require hundreds of superconducting radiofrequency (SRF) cavities operating with high duty factor. The large dynamic heat load of the cavities causes the cryogenic plant to make up a significant part of the overall cost of the facility. Our contribution can be reduced by replacing standard niobium cavities with ones coated with a low-dissipation superconductor such as Nb 3Sn. Here, we present results for single cell cavities coated with Nb 3Sn at Cornell. Five coatings were carried out, showing that at 4.2 K, high Q 0 out to medium fields was reproducible, resulting in an average quenchmore » field of 14 MV/m and an average 4.2 K Q 0 at quench of 8 x 10 9 . In each case, the peak surface magnetic field at quench was well above H c1, showing that it is not a limiting field in these cavities. Furthermore, the coating with the best performance had a quench field of 17 MV/m, exceeding gradient requirements for state-of-the-art high duty factor SRF accelerators. It is also shown that—taking into account the thermodynamic efficiency of the cryogenic plant—the 4.2 K Q 0 values obtained meet the AC power consumption requirements of state-of-the-art high duty factor accelerators, making this a proof-of-principle demonstration for Nb 3Sn cavities in future applications.« less
DOT National Transportation Integrated Search
2008-12-01
The appendix includes various ramp flow and ML speed-flow plots: OR-217 NB, 72nd MP 6.61; OR-217 NB, 99W-EB MP 5.9; OR-217 NB, 99W-WB MP 5.85; OR-217 NB, Greenburg MP 4.65; OR-217 NB, Scholls MP 3.85; OR-217 NB, Denney MP 2.68; OR-217 NB, Allen MP 2....
A review and prospects for Nb3Sn superconductor development
NASA Astrophysics Data System (ADS)
Xu, Xingchen
2017-09-01
Nb3Sn superconductors have significant applications in constructing high-field (>10 T) magnets. This article briefly reviews development of Nb3Sn superconductor and proposes prospects for further improvement. It is shown that significant improvement of critical current density (J c) is needed for future accelerator magnets. After a brief review of the development of Nb3Sn superconductors, the factors controlling J c are summarized and correlated with their microstructure and chemistry. The non-matrix J c of Nb3Sn conductors is mainly determined by three factors: the fraction of current-carrying Nb3Sn phase in the non-matrix area, the upper critical field B c2, and the flux line pinning capacity. Then prospects to improve the three factors are discussed respectively. An analytic model was developed to show how the ratios of precursors determine the phase fractions after heat treatment, based on which it is predicted that the limit of current-carrying Nb3Sn fraction in subelements is ∼65%. Then, since B c2 is largely determined by the Nb3Sn stoichiometry, a thermodynamic/kinetic theory is presented to show what essentially determines the Sn content of Nb3Sn conductors. This theory explains the influences of Sn sources and Ti addition on stoichiometry and growth rate of Nb3Sn layers. Next, to improve flux pinning, previous efforts in this community to introduce additional pinning centers to Nb3Sn wires are reviewed, and an internal oxidation technique is described. Finally, prospects for further improvement of non-matrix J c of Nb3Sn conductors are discussed, and it is seen that the only opportunity for further significantly improving J c lies in improving flux pinning.
A review and prospects for Nb 3Sn superconductor development
Xu, Xingchen
2017-08-03
Nb 3Sn superconductors have significant applications in constructing high-field (> 10 T) magnets. This article briefly reviews development of Nb 3Sn superconductor and proposes prospects for further improvement. It is shown that significant improvement of critical current density (J c) is needed for future accelerator magnets. After a brief review of the development of Nb 3Sn superconductors, the factors controlling J c are summarized and correlated with their microstructure and chemistry. The non-matrix J c of Nb 3Sn conductors is mainly determined by three factors: the fraction of current-carrying Nb 3Sn phase in the non-matrix area, the upper critical fieldmore » B c2, and the flux-line pinning capacity. Then prospects to improve the three factors are discussed respectively. An analytic model was developed to show how the ratios of precursors determine the phase fractions after heat treatment, based on which it is predicted that the limit of current-carrying Nb 3Sn fraction in subelements is ~65%. Then, since B c2 is largely determined by the Nb 3Sn stoichiometry, a thermodynamic/kinetic theory was presented to show what essentially determines the Sn content of Nb 3Sn conductors. This theory explains the influences of Sn sources and Ti addition on stoichiometry and growth rate of Nb 3Sn layers. Next, to improve flux pinning, previous efforts in this community to introduce additional pinning centers (APC) to Nb 3Sn wires are reviewed, and an internal oxidation technique is described. Lastly, prospects for further improvement of non-matrix J c of Nb 3Sn conductors are discussed, and it is seen that the only opportunity for further significantly improving J c lies in improving the flux pinning.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tanis, Elizabeth A.; Simon, Adam; Tschauner, Oliver
Rutile (TiO 2) is an important host phase for high field strength elements (HFSE) such as Nb in metamorphic and subduction zone environments. The observed depletion of Nb in arc rocks is often explained by the hypothesis that rutile sequesters HFSE in the subducted slab and overlying sediment, and is chemically inert with respect to aqueous fluids evolved during prograde metamorphism in the forearc to subarc environment. However, field observations of exhumed terranes, and experimental studies, indicate that HFSE may be soluble in complex aqueous fluids at high pressure (i.e., >0.5 GPa) and moderate to high temperature (i.e., >300 °C).more » In this study, we investigated experimentally the mobility of Nb in NaCl- and NaF-bearing aqueous fluids in equilibrium with Nb-bearing rutile at pressure-temperature conditions applicable to fluid evolution in arc environments. Niobium concentrations in aqueous fluid at rutile saturation were measured directly by using a hydrothermal diamond-anvil cell (HDAC) and synchrotron X-ray fluorescence (SXRF) at 2.1 to 6.5 GPa and 300-500 °C, and indirectly by performing mass loss experiments in a piston-cylinder (PC) apparatus at similar to 1 GPa and 700-800 °C. The concentration of Nb in a 10 wt% NaCl aqueous fluid increases from 6 to 11 mu g/g as temperature increases from 300 to 500 °C, over a pressure range from 2.1 to 2.8 GPa, consistent with a positive temperature dependence. The concentration of Nb in a 20 wt% NaCl aqueous fluid varies from 55 to 150 mu g/g at 300 to 500 °C, over a pressure range from 1.8 to 6.4 GPa; however, there is no discernible temperature or pressure dependence. Here, the Nb concentration in a 4 wt% NaF-bearing aqueous fluid increases from 180 to 910 mu g/g as temperature increases from 300 to 500 °C over the pressure range 2.1 to 6.5 GPa. The data for the F-bearing fluid indicate that the Nb content of the fluid exhibits a dependence on temperature between 300 and 500 °C at ≥ 2 GPa, but there is no observed dependence on pressure. Together, the data demonstrate that the hydrothermal mobility of Nb is strongly controlled by the composition of the fluid, consistent with published data for Ti. At all experimental conditions, however, the concentration of Nb in the fluid is always lower than coexisting rutile, consistent with a role for rutile in moderating the Nb budget of arc rocks.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tanis, Elizabeth A.; Simon, Adam; Tschauner, Oliver
Rutile (TiO₂) is an important host phase for high field strength elements (HFSE) such as Nb in metamorphic and subduction zone environments. The observed depletion of Nb in arc rocks is often explained by the hypothesis that rutile sequesters HFSE in the subducted slab and overlying sediment, and is chemically inert with respect to aqueous fluids evolved during prograde metamorphism in the forearc to subarc environment. However, field observations of exhumed terranes, and experimental studies, indicate that HFSE may be soluble in complex aqueous fluids at high pressure (i.e., >0.5 GPa) and moderate to high temperature (i.e., >300 °C). Inmore » this study, we investigated experimentally the mobility of Nb in NaCl- and NaF-bearing aqueous fluids in equilibrium with Nb-bearing rutile at pressure-temperature conditions applicable to fluid evolution in arc environments. Niobium concentrations in aqueous fluid at rutile saturation were measured directly by using a hydrothermal diamond-anvil cell (HDAC) and synchrotron X-ray fluorescence (SXRF) at 2.1 to 6.5 GPa and 300–500 °C, and indirectly by performing mass loss experiments in a piston-cylinder (PC) apparatus at ~1 GPa and 700–800 °C. The concentration of Nb in a 10 wt% NaCl aqueous fluid increases from 6 to 11 μg/g as temperature increases from 300 to 500 °C, over a pressure range from 2.1 to 2.8 GPa, consistent with a positive temperature dependence. The concentration of Nb in a 20 wt% NaCl aqueous fluid varies from 55 to 150 μg/g at 300 to 500 °C, over a pressure range from 1.8 to 6.4 GPa; however, there is no discernible temperature or pressure dependence. The Nb concentration in a 4 wt% NaF-bearing aqueous fluid increases from 180 to 910 μg/g as temperature increases from 300 to 500 °C over the pressure range 2.1 to 6.5 GPa. The data for the F-bearing fluid indicate that the Nb content of the fluid exhibits a dependence on temperature between 300 and 500 °C at ≥2 GPa, but there is no observed dependence on pressure. Together, the data demonstrate that the hydrothermal mobility of Nb is strongly controlled by the composition of the fluid, consistent with published data for Ti. At all experimental conditions, however, the concentration of Nb in the fluid is always lower than coexisting rutile, consistent with a role for rutile in moderating the Nb budget of arc rocks.« less
Tanis, Elizabeth A.; Simon, Adam; Tschauner, Oliver; ...
2015-07-01
Rutile (TiO 2) is an important host phase for high field strength elements (HFSE) such as Nb in metamorphic and subduction zone environments. The observed depletion of Nb in arc rocks is often explained by the hypothesis that rutile sequesters HFSE in the subducted slab and overlying sediment, and is chemically inert with respect to aqueous fluids evolved during prograde metamorphism in the forearc to subarc environment. However, field observations of exhumed terranes, and experimental studies, indicate that HFSE may be soluble in complex aqueous fluids at high pressure (i.e., >0.5 GPa) and moderate to high temperature (i.e., >300 °C).more » In this study, we investigated experimentally the mobility of Nb in NaCl- and NaF-bearing aqueous fluids in equilibrium with Nb-bearing rutile at pressure-temperature conditions applicable to fluid evolution in arc environments. Niobium concentrations in aqueous fluid at rutile saturation were measured directly by using a hydrothermal diamond-anvil cell (HDAC) and synchrotron X-ray fluorescence (SXRF) at 2.1 to 6.5 GPa and 300-500 °C, and indirectly by performing mass loss experiments in a piston-cylinder (PC) apparatus at similar to 1 GPa and 700-800 °C. The concentration of Nb in a 10 wt% NaCl aqueous fluid increases from 6 to 11 mu g/g as temperature increases from 300 to 500 °C, over a pressure range from 2.1 to 2.8 GPa, consistent with a positive temperature dependence. The concentration of Nb in a 20 wt% NaCl aqueous fluid varies from 55 to 150 mu g/g at 300 to 500 °C, over a pressure range from 1.8 to 6.4 GPa; however, there is no discernible temperature or pressure dependence. Here, the Nb concentration in a 4 wt% NaF-bearing aqueous fluid increases from 180 to 910 mu g/g as temperature increases from 300 to 500 °C over the pressure range 2.1 to 6.5 GPa. The data for the F-bearing fluid indicate that the Nb content of the fluid exhibits a dependence on temperature between 300 and 500 °C at ≥ 2 GPa, but there is no observed dependence on pressure. Together, the data demonstrate that the hydrothermal mobility of Nb is strongly controlled by the composition of the fluid, consistent with published data for Ti. At all experimental conditions, however, the concentration of Nb in the fluid is always lower than coexisting rutile, consistent with a role for rutile in moderating the Nb budget of arc rocks.« less
NASA Technical Reports Server (NTRS)
Spain, I. L.
1983-01-01
Diamond cells were constructed for use to 1 Mbar. A refrigerator for cooling diamond cells was adapted for studies between 15 and 300 K. A cryostat for superconductivity studies between 1.5 to 300 K was constructed. Optical equipment was constructed for fluorescence, transmission, and reflectance studies. X-ray equipment was adapted for use with diamond cells. Experimental techniques were developed for X-ray diffraction studies using synchrotron radiation. AC susceptibility techniques were developed for detecting superconducting transitions. The following materials were studied: compressed solidified gases (Xe, Ar), semiconductors (Ge, Si, GaAs), superconductors (Nb3Ge, Nb3Si, Nb3As, CuCl), molecular crystals (I).
Chemical Vapor Synthesis of Niobium Aluminides
1992-01-01
69 4.2.2 Deposition on Singly Supported Niobium Substrates ............ . . . ..... 72 4.3 DEPOSITION OF NbxSiy FROM H2, NbC15 , AND SICl4 ...direct CVD of NbxSiy from the hydrogen reduction of SiCl4 and NbCl5 is described by the overall reaction: xNbCl5 + ySiCl4 + (5x + 4y)/2 H2 - NbxSiy
Choi, Jaeyeon; Vaidyanathan, Ganesan; Koumarianou, Eftychia; McDougald, Darryl; Pruszynski, Marek; Osada, Takuya; Lahoutte, Tony; Lyerly, H. Kim; Zalutsky, Michael R.
2014-01-01
Introduction N-succinimidyl 4-guanidinomethyl-3-[*I]iodobenzoate ([*I]SGMIB) has shown promise for the radioiodination of monoclonal antibodies (mAbs) and other proteins that undergo extensive internalization after receptor binding, enhancing tumor targeting compared to direct electrophilic radioiodination. However, radiochemical yields for [131I]SGMIB synthesis are low, which we hypothesize is due to steric hindrance from the Boc-protected guanidinomethyl group ortho to the tin moiety. To overcome this, we developed the isomeric compound, N-succinimidyl 3-guanidinomethyl-5-[131I]iodobenzoate (iso-[131I]SGMIB) wherein this bulky group was moved from ortho to meta position. Methods Boc2-iso-SGMIB standard and its tin precursor, N-succinimidyl 3-((1,2-bis(tert-butoxycarbonyl)guanidino)methyl)-5-(trimethylstannyl)benzoate (Boc2-iso-SGMTB), were synthesized using two disparate routes, and iso-[*I]SGMIB synthesized from the tin precursor. Two HER2-targeted vectors — trastuzumab (Tras) and a nanobody 5F7 (Nb) — were labeled using iso-[*I]SGMIB and [*I]SGMIB. Paired-label internalization assays in vitro with both proteins, and biodistribution in vivo with trastuzumab, labeled using the two isomeric prosthetic agents were performed. Results When the reactions were performed under identical conditions, radioiodination yields for the synthesis of Boc2-iso-[131I]SGMIB were significantly higher than those for Boc2-[131I]SGMIB (70.7 ± 2.0% vs 56.5 ± 5.5%). With both Nb and trastuzumab, conjugation efficiency also was higher with iso-[131I]SGMIB than with [131I]SGMIB (Nb, 33.1 ± 7.1% vs 28.9 ± 13.0%; Tras, 45.1 ± 4.5% vs 34.8 ± 10.3%); however, the differences were not statistically significant. Internalization assays performed on BT474 cells with 5F7 Nb indicated similar residualizing capacity over 6 h; however, at 24 h, radioactivity retained intracellularly for iso-[131I]SGMIB-Nb was lower than for [125I]SGMIB-Nb (46.4 ± 1.3% vs 56.5 ± 2.5%); similar results were obtained using Tras. Likewise, a paired-label biodistribution of Tras labeled using iso-[125I]SGMIB and [131I]SGMIB indicated an up to 22% tumor uptake advantage at later time points for [131I]SGMIB-Tras. Conclusion Given the higher labeling efficiency obtained with iso-SGMIB, this residualizing agent might be of value for use with shorter half-life radiohalogens. PMID:25156548
Surface Nb-ALLOYING on 0.4C-13Cr Stainless Steel: Microstructure and Tribological Behavior
NASA Astrophysics Data System (ADS)
Yu, Shengwang; You, Kai; Liu, Xiaozhen; Zhang, Yihui; Wang, Zhenxia; Liu, Xiaoping
2016-02-01
0.4C-13Cr stainless steel was alloyed with niobium using double glow plasma surface alloying and tribological properties of Nb-alloyed steel such as hardness, friction and wear were measured. Effects of the alloying temperature on microstructure and the tribological behavior of the alloyed steel were investigated compared with untreated steel. Formation mechanisms of Nb-alloyed layers and increased wear resistance were also studied. The result shows that after surface Nb-alloying treatment, the 0.4C-13Cr steel exhibits a diffusion adhesion at the alloyed layer/substrate interface and improved tribological property. The friction coefficient of Nb-alloyed steel is decreased by about 0.3-0.45 and the wear rate after Nb-alloying is only 2-5% of untreated steel.
Superelasticity, corrosion resistance and biocompatibility of the Ti-19Zr-10Nb-1Fe alloy.
Xue, Pengfei; Li, Yan; Li, Kangming; Zhang, Deyuan; Zhou, Chungen
2015-05-01
Microstructure, mechanical properties, superelasticity and biocompatibility of a Ti-19Zr-10Nb-1Fe alloy are investigated. X-ray diffraction spectroscopy and transmission electron microscopy observations show that the as-cast Ti-19Zr-10Nb-1Fe alloy is composed of α' and β phases, but only the β phase exists in the as-rolled and as-quenched alloys. The tensile stress-strain tests indicate that the as-quenched alloy exhibits a good combination of mechanical properties with a large elongation of 25%, a low Young's modulus of 59 GPa and a high ultimate tensile stress of 723 MPa. Superelastic recovery behavior is found in the as-quenched alloy during tensile tests, and the corresponding maximum of superelastic strain is 4.7% at the pre-strain of 6%. A superelastic recovery of 4% with high stability is achieved after 10 cyclic loading-unloading training processes. Potentiodynamic polarization and ion release measurements indicate that the as-quenched alloy shows a lower corrosion rate in Hank's solution and a much less ion release rate in 0.9% NaCl solution than those of the NiTi alloys. Cell culture results indicate that the osteoblasts' adhesion and proliferation are similar on both the Ti-19Zr-10Nb-1Fe and NiTi alloys. A better hemocompatibility is confirmed for the as-quenched Ti-19Zr-10Nb-1Fe alloy, attributed to more stable platelet adhesion and small activation degree, and a much lower hemolysis rate compared with the NiTi alloy. Copyright © 2015 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Miura, Seiji; Hatabata, Toru; Okawa, Takuya; Mohri, Tetsuo
2014-03-01
To find a new route for microstructure control and to find additive elements beneficial for improving high-temperature strength, a systematic investigation is performed on hypoeutectic Nb-15 at. pct Si-X ternary alloys containing a transition element, Fe, Co, Ni, Cu, Ru, Rh, Pd, Re, Os, Ir, Pt, or Au. Information on phase equilibrium is classified in terms of phase stability of silicide phases, α Nb5Si3, Nb4SiX, and Nb3Si, and the relationship between microstructure and mechanical properties both at room temperature and high temperature is investigated. All the additive elements are found to stabilize either α Nb5Si3 or Nb4SiX but destabilize Nb3Si. A microstructure of Nbss/α Nb5Si3 alloy composed of spheroidized α Nb5Si3 phase embedded in the Nbss matrix is effective for toughening, regardless of the initial as-cast microstructure. Also the plastic deformation of Nbss dendrites may effectively suppress the propagation of longer cracks. High-temperature strength of alloys is governed by the deformation of Nbss phase and increases with higher melting point additives.
Nonequilibrium synthesis of NbAl3 and Nb-Al-V alloys by laser cladding. II - Oxidation behavior
NASA Technical Reports Server (NTRS)
Haasch, R. T.; Tewari, S. K.; Sircar, S.; Loxton, C. M.; Mazumder, J.
1992-01-01
Isothermal oxidation behaviors of NbAl3 alloy synthesized by laser cladding were investigated at temperatures between 800 and 1400 C, and the effect of vanadium microalloying on the oxidation of the laser-clad alloy was examined. The oxidation kinetics of the two alloys were monitored using thermal gravimetric weight gain data, and the bulk and surface chemistries were analyzed using XRD and XPS, respectively. It was found that NbAl3 did not form an exclusive layer of protective Al2O3. The oxidation products at 800 C were found to be a mixture of Nb2O5 and Al2O3. At 1200 C, a mixture of NbAlO4, Nb2O5, and Al2O3 formed; and at 1400 C, a mixture of NbAlO4, Al2O3, NbO2, NbO(2.432), and Nb2O5 formed. The addition of V led to a dramatic increase of the oxidation rate, which may be related to the formation of (Nb, V)2O5 and VO2, which grows in preference to protective Al2O3.
{Nb288O768(OH)48(CO3)12}: A Macromolecular Polyoxometalate with Niobium Atoms Close to 300.
Wu, Yan-Lan; Li, Xin-Xiong; Qi, Yan-Jie; Yu, Hao; Jin, Lu; Zheng, Shou-Tian
2018-05-29
A protein-sized (ca. 4.2 ᵡ 4.2 ᵡ 3.6 nm3) non-biologically derived molecule {Nb288O768(OH)48(CO3)12} (Nb288) containing up to 288 niobium atoms has been obtained, which is by far the largest and the highest nuclearity polyoxoniobate (PONb). Particularly, in terms of metal nuclearity number, Nb288 is the second largest cluster so far reported in classic polyoxometalate chemistry (V, Mo, W, Nb, and Ta). Nb288 can be described as a giant windmill-like cluster aggregate of six brand-new, nanoscale high-nuclearity PONb units {Nb47O128(OH)6(CO3)2} (Nb47) joined together by six additional Nb ions. Interestingly, the in situ generated 47-nuclearity Nb47 units can be isolated and bridged by copper complexes to form an inorganic-organic hybrid three-dimensional PONb framework, which exhibits effective catalytic activity for hydrolyzing nerve agent simulant of dimethyl methylphosphonate. The unique Nb47 cluster also provides a new type of topology to very limited family of Nb-O clusters. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
NASA Astrophysics Data System (ADS)
Xin, Deqiong; Chen, Qiang; Wu, Jiagang; Bao, Shaoming; Zhang, Wen; Xiao, Dingquan; Zhu, Jianguo
2016-07-01
Bismuth-layered structured ceramics Ca0.85(Li,Ce)0.075Bi4Ti4- x Nb x O15-0.01MnCO3 were prepared by the conventional solid-state reaction method. The evolution of microstructure and corresponding electrical properties were studied. All the samples presented a single bismuth layered-structural phase with m = 4, indicating that (Li, Ce)4+, Nb5+ and Mn2+ adequately enter into the pseudo-perovskite structure and form solid solutions. It was found that Ca0.85(Li,Ce)0.075Bi4Ti3.98Nb0.02O15-0.01MnCO3 (CBTLCM-0.02Nb) ceramics possess the optimum electrical properties. The piezoelectric coefficient d 33, dielectric constant ɛ r, loss tan δ, planar electromechanical coupling factor k p and Curie-temperature T C of CBTLCM-0.02Nb ceramics were found to be ˜19.6 pC/N, 160, 0.16%, 8.1% and 767°C, respectively. Furthermore, the thermal depoling behavior demonstrates that the d 33 value of x = 0.02 content remains at 16.8 pC/N after annealing at 500°C. These results suggest that the (Li, Ce)4+-, Nb5+- and Mn2+-doped CBT-based ceramics are promising candidates for high-temperature piezoelectric applications.
DOT National Transportation Integrated Search
2008-12-01
The appendix includes various flow-occupancy plots, including: I-205 NB, Gladstone MP 11.05; I-205 NB, Gladstone Hway MP 12.94; I-205 NB, Lawnfield MP 13.58; I-205 NB, Sunnybrook MP 14.32; I-205 NB, Sunnyside MP 14.7; I-205 NB, Johnson Creek MP 16.2;...
Okazaki, Yoshimitsu
2012-01-01
Zr, Nb, and Ta as alloying elements for Ti alloys are important for attaining superior corrosion resistance and biocompatibility in the long term. However, note that the addition of excess Nb and Ta to Ti alloys leads to higher manufacturing cost. To develop low-cost manufacturing processes, the effects of hot-forging and continuous-hot-rolling conditions on the microstructure, mechanical properties, hot forgeability, and fatigue strength of Ti-15Zr-4Nb-4Ta alloy were investigated. The temperature dependences with a temperature difference (ΔT) from β-transus temperature (Tβ) for the volume fraction of the α- and β-phases were almost the same for both Ti-15Zr-4Nb-4Ta and Ti-6Al-4V alloys. In the α-β-forged Ti-15Zr-4Nb-4Ta alloy, a fine granular α-phase structure containing a fine granular β-phase at grain boundaries of an equiaxed α-phase was observed. The Ti-15Zr-4Nb-4Ta alloy billet forged at Tβ-(30 to 50) °C exhibited high strength and excellent ductility. The effects of forging ratio on mechanical strength and ductility were small at a forging ratio of more than 3. The maximum strength (σmax) markedly increased with decreasing testing temperature below Tβ. The reduction in area (R.A.) value slowly decreased with decreasing testing temperature below Tβ. The temperature dependences of σmax for the Ti-15Zr-4Nb-4Ta and Ti-6Al-4V alloys show the same tendency and might be caused by the temperature difference (ΔT) from Tβ. It was clarified that Ti-15Zr-4Nb-4Ta alloy could be manufactured using the same manufacturing process as for previously approved Ti-6Al-4V alloy, taking into account the difference (ΔT) between Tβ and heat treatment temperature. Also, the manufacturing equivalency of Ti-15Zr-4Nb-4Ta alloy to obtain marketing approval of implants was established. Thus, it was concluded that continuous hot rolling is useful for manufacturing α-β-type Ti alloy.
Arsenic trioxide promoting ETosis in acute promyelocytic leukemia through mTOR-regulated autophagy.
Li, Tao; Ma, Ruishuang; Zhang, Yan; Mo, Hongdan; Yang, Xiaoyan; Hu, Shaoshan; Wang, Lixiu; Novakovic, Valerie A; Chen, He; Kou, Junjie; Bi, Yayan; Yu, Bo; Fang, Shaohong; Wang, Jinghua; Zhou, Jin; Shi, Jialan
2018-01-23
Despite the high efficacy and safety of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) and eradicating APL leukemia-initiating cells (LICs), the mechanism underlying its selective cytotoxicity remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, through autophagy. However, the role of ETosis in ATO-induced APL LIC eradication remains unclear. For this study, we evaluated the effects of ATO on ETosis and the contributions of drug-induced ETosis to APL LIC eradication. In NB4 cells, ATO primarily increased ETosis at moderate concentrations (0.5-0.75 μM) and stimulated apoptosis at higher doses (1.0-2.0 μM). Furthermore, ATO induced ETosis through mammalian target of rapamycin (mTOR)-dependent autophagy, which was partially regulated by reactive oxygen species. Additionally, rapamycin-enhanced ATO-induced ETosis in NB4 cells and APL cells from newly diagnosed and relapsed patients. In contrast, rapamycin had no effect on apoptosis in these cells. We also noted that PML/RARA oncoprotein was effectively cleared with this combination. Intriguingly, activation of autophagy with rapamycin-enhanced APL LIC eradication clearance by ATO in vitro and in a xenograft APL model, while inhibition of autophagy spared clonogenic cells. Our current results show that ATO exerts antileukemic effects at least partially through ETosis and targets LICs primarily through ETosis. Addition of drugs that target the ETotic pathway could be a promising therapeutic strategy to further eradicate LICs and reduce relapse.
Creep Testing of High-Temperature Cu-8 Cr-4 Nb Alloy Completed
NASA Technical Reports Server (NTRS)
1995-01-01
A Cu-8 at.% Cr-4 at.% Nb (Cu-8 Cr-4 Nb) alloy is under development for high-temperature, high heatflux applications, such as actively cooled, hypersonic vehicle heat exchangers and rocket engine combustion chambers. Cu-8 Cr-4 Nb offers a superior combination of strength and conductivity. It has also shown exceptional low-cycle fatigue properties. Following preliminary testing to determine the best processing route, a more detailed testing program was initiated to determine the creep lives and creep rates of Cu-8 Cr-4 Nb alloy specimens produced by extrusion. Testing was conducted at the NASA Lewis Research Center with constant-load vacuum creep units. Considering expected operating temperatures and mission lives, we developed a test matrix to accurately determine the creep properties of Cu-8 Cr-4 Nb between 500 and 800 C. Six bars of Cu-8 Cr-4 Nb were extruded. From these bars, 54 creep samples were machined and tested. The figure on the left shows the steady-state, or second-stage, creep rates for the samples. Comparison data for NARloy-Z (Cu-3 wt % Ag-0.5 wt % Zr), the alloy currently used in combustion chamber liners, were not unavailable. Therefore the steady-state creep rates for Cu at similar temperatures are presented. As expected, in comparison to pure Cu, the creep rates for Cu-8 Cr-4 Nb are much lower. The lives of the samples are presented in the figure on the right. As shown, Cu-8 Cr-4 Nb at 800 C is comparable to NARloy-Z at 648 C. At equivalent temperatures, Cu-8 Cr-4 Nb enjoys a 20 to 50 percent advantage in stress for a given life and 1 to 3 orders of magnitude greater life at a given stress. The improved properties allow for design tradeoffs and improvements in new and existing heat exchangers such as the next generation of combustion chamber liners. Average creep rates for Cu-8 Cr-4 Nb and pure Cu are shown. Average creep lives for Cu-8 Cr- 4 Nb and NARloy-Z are also shown. Currently, two companies are interested in the commercial usage of the Cu-8 Cr-4 Nb alloy. The Rocketdyne Division of Rockwell International is conducting independent testing to analyze the properties for their projected needs in advanced rocket engine applications. Metallamics, a company based in Traverse City, Michigan, is entering into a Space Act Agreement to evaluate and test Cu-Cr-Nb alloys as materials for welding electrodes that are used in robotic welding operations. Creep rate is one of the alloy properties that determines the degree to which a welding electrode will mushroom or expand at the tip. A material with a low creep rate will resist mushrooming and give the electrode a longer life, minimizing downtime. This application holds the potential for large-scale usage of the alloy in the automotive and other industries. Success here would dramatically decrease the cost of the alloy and increase availability for aerospace applications.
Vella, Serena; Penna, Ilaria; Longo, Luca; Pioggia, Giulia; Garbati, Patrizia; Florio, Tullio; Rossi, Fabio; Pagano, Aldo
2015-01-01
High Risk Neuroblastoma (HR-NB) is a pediatric cancer characterized by high malignancy and remarkable cell heterogeneity within the tumour nodules. In a recent study, we demonstrated that in vitro and in vivo over-expression of the non-coding RNA NDM29 (neuroblastoma differentiation marker 29) induces NB cell differentiation, dramatically reducing their malignancy. Among gene expression changes, differentiated phenotype induced by NDM29 is characterized by decrease of the expression of ABC transporters responsible for anticancer drug resistance. Thus, the pharmacological induction of NDM29, in principle, might represent a possible novel strategy to increase cytotoxic drug responses. In this work, we identify a small molecule able to induce the expression of NDM29 in NB cells, conferring to malignant cells increased susceptibility to cisplatin cytotoxic effects. We demonstrate that the pharmacological induction of NDM29 expression in vivo enhances the antitumoral effects of chemotherapy specifically on tumour initiating/cancer stem cells sub-population, usually refractory to therapies and responsible for tumour relapse. In summary, we suggest a novel therapeutical approach possibly useful to treat very aggressive NB cases with poor prognosis. This novel pharmacological strategy aims to promote differentiation of “stem-like” cells to render them more susceptible to the killing action of cytotoxic anticancer drugs. PMID:26674674
Vella, Serena; Penna, Ilaria; Longo, Luca; Pioggia, Giulia; Garbati, Patrizia; Florio, Tullio; Rossi, Fabio; Pagano, Aldo
2015-12-17
High Risk Neuroblastoma (HR-NB) is a pediatric cancer characterized by high malignancy and remarkable cell heterogeneity within the tumour nodules. In a recent study, we demonstrated that in vitro and in vivo over-expression of the non-coding RNA NDM29 (neuroblastoma differentiation marker 29) induces NB cell differentiation, dramatically reducing their malignancy. Among gene expression changes, differentiated phenotype induced by NDM29 is characterized by decrease of the expression of ABC transporters responsible for anticancer drug resistance. Thus, the pharmacological induction of NDM29, in principle, might represent a possible novel strategy to increase cytotoxic drug responses. In this work, we identify a small molecule able to induce the expression of NDM29 in NB cells, conferring to malignant cells increased susceptibility to cisplatin cytotoxic effects. We demonstrate that the pharmacological induction of NDM29 expression in vivo enhances the antitumoral effects of chemotherapy specifically on tumour initiating/cancer stem cells sub-population, usually refractory to therapies and responsible for tumour relapse. In summary, we suggest a novel therapeutical approach possibly useful to treat very aggressive NB cases with poor prognosis. This novel pharmacological strategy aims to promote differentiation of "stem-like" cells to render them more susceptible to the killing action of cytotoxic anticancer drugs.
Fe4Nb2O9 : A magnetoelectric antiferromagnet
NASA Astrophysics Data System (ADS)
Maignan, Antoine; Martin, Christine
2018-04-01
The structural, magnetic, and electrical properties of a Fe4Nb2O9 polycrystalline sample have been characterized. It is found that this compound crystallizes in the P 3 ¯c 1 space group of the α -A l2O3 structure and is thus isostructural to Co4Nb2O9 and Mn4Nb2O9 , two linear magnetoelectric oxides. But in marked contrast, its ɛ'(T ) curve reveals two broad transitions at TN 1≅90 K and TN 2≅77 K , the former corresponding to the antiferromagnetic ordering temperature. Below TN 1, the M(H ) magnetization curves reveal the existence of spin flop at about 6 T. In this temperature region, a H-induced electric polarization for μ0H >6 T is evidenced by both sets of Ip(T) H and P (H) T curves. All these results point towards Fe4Nb2O9 being a magnetoelectric member of the A4B2O9 family (A =Mn , Fe, Co and B =Nb , Ta).
Yang, Xinan Holly; Tang, Fangming; Shin, Jisu; Cunningham, John M
2017-10-03
Previous studies suggested that cancer cells possess traits reminiscent of the biological mechanisms ascribed to normal embryonic stem cells (ESCs) regulated by MYC and Polycomb repressive complex 2 (PRC2). Several poorly differentiated adult tumors showed preferentially high expression levels in targets of MYC, coincident with low expression levels in targets of PRC2. This paper will reveal this ESC-like cancer signature in high-risk neuroblastoma (HR-NB), the most common extracranial solid tumor in children. We systematically assembled genomic variants, gene expression changes, priori knowledge of gene functions, and clinical outcomes to identify prognostic multigene signatures. First, we assigned a new, individualized prognostic index using the relative expressions between the poor- and good-outcome signature genes. We then characterized HR-NB aggressiveness beyond these prognostic multigene signatures through the imbalanced effects of MYC and PRC2 signaling. We further analyzed Retinoic acid (RA)-induced HR-NB cells to model tumor cell differentiation. Finally, we performed in vitro validation on ZFHX3, a cell differentiation marker silenced by PRC2, and compared cell morphology changes before and after blocking PRC2 in HR-NB cells. A significant concurrence existed between exons with verified variants and genes showing MYCN-dependent expression in HR-NB. From these biomarker candidates, we identified two novel prognostic gene-set pairs with multi-scale oncogenic defects. Intriguingly, MYC targets over-represented an unfavorable component of the identified prognostic signatures while PRC2 targets over-represented a favorable component. The cell cycle arrest and neuronal differentiation marker ZFHX3 was identified as one of PRC2-silenced tumor suppressor candidates. Blocking PRC2 reduced tumor cell growth and increased the mRNA expression levels of ZFHX3 in an early treatment stage. This hypothesis-driven systems bioinformatics work offered novel insights into the PRC2-mediated tumor cell growth and differentiation in neuroblastoma, which may exert oncogenic effects together with MYC regulation. Our results propose a prognostic effect of imbalanced MYC and PRC2 moderations in pediatric HR-NB for the first time. This study demonstrates an incorporation of genomic landscapes and transcriptomic profiles into the hypothesis-driven precision prognosis and biomarker discovery. The application of this approach to neuroblastoma, as well as other cancer more broadly, could contribute to reduced relapse and mortality rates in the long term.
DOT National Transportation Integrated Search
2008-12-01
The appendix includes various ML speed-occupancy plots: OR-217 NB, 72nd MP 6.61; OR-217 NB, 99W-EB MP 5.9; OR-217 NB, 99W-WB MP 5.85; OR-217 NB, Greenburg MP 4.65; OR-217 NB, Scholls MP 3.85; OR-217 NB, Denney MP 2.68; OR-217 NB, Allen MP 2.16; OR-21...
DOT National Transportation Integrated Search
2008-12-01
The appendix includes various ML flow occupancy plots: OR-217 NB, 72nd MP 6.61; OR-217 NB, 99W-EB MP 5.9; OR-217 NB, 99W-WB MP 5.85; OR-217 NB, Greenburg MP 4.65; OR-217 NB, Scholls MP 3.85; OR-217 NB, Denney MP 2.68; OR-217 NB, Allen MP 2.16; OR-217...
NASA Astrophysics Data System (ADS)
Guo, Heng; Yang, Jian; Pu, Bingxue; Zhang, Haiyan; Niu, Xiaobin
2018-01-01
Organo-lead perovskites as light harvesters have represented a hot field of research on high-efficiency perovskite solar cells. Previous approaches to increasing the solar cell efficiency have focused on optimization of the morphology of perovskite film. In fact, the electron transporting layer (ETL) also has a significant impact on solar cell performance. Herein, we introduce a facile and low temperature solution-processing method to deposit Nb2O5 film as ETL for PSCs. Based on Nb2O5 ETL, we investigate the effect of the annealing time for the perovskite films via different solution processing, relating it to the perovskite film morphology and its influence on the device working mechanisms. These results shed light on the origin of photovoltaic performance voltage in perovskite solar cells, and provide a path to further increase their efficiency.
Oxidation Behavior of Copper Alloy Candidates for Rocket Engine Applications (Technical Poster)
NASA Technical Reports Server (NTRS)
Ogbuji, Linus U. J.; Humphrey, Donald H.; Barrett, Charles A.; Greenbauer-Seng, Leslie (Technical Monitor); Gray, Hugh R. (Technical Monitor)
2002-01-01
A rocket engine's combustion chamber is lined with material that is highly conductive to heat in order to dissipate the huge thermal load (evident in a white-hot exhaust plume). Because of its thermal conductivity copper is the best choice of liner material. However, the mechanical properties of pure copper are inadequate to withstand the high stresses, hence, copper alloys are needed in this application. But copper and its alloys are prone to oxidation and related damage, especially "blanching" (an oxidation-reduction mode of degradation). The space shuttle main engine combustion chamber is lined with a Cu-Ag-Zr alloy, "NARloy-Z", which exhibits blanching. A superior liner is being sought for the next generation of RLVs (Reusable Launch Vehicles) It should have improved mechanical properties and higher resistance to oxidation and blanching, but without substantial penalty in thermal conductivity. GRCop84, a Cu-8Cr-4Nb alloy (Cr2Nb in Cu matrix), developed by NASA Glenn Research Center (GRC) and Case Western Reserve University, is a prime contender for RLV liner material. In this study, the oxidation resistance of GRCop-84 and other related/candidate copper alloys are investigated and compared
Hernández-Bule, María Luisa; Cid, María Antonia; Trillo, María Angeles; Leal, Jocelyne; Ubeda, Alejandro
2010-12-01
The capacitive-resistive electric transfer (CRet) therapy is a non-invasive technique that applies electrical currents of 0.4-0.6 MHz to the treatment of musculoskeletal injuries. Although this therapy has proved effective in clinical studies, its interaction mechanisms at the cellular level still are insufficiently investigated. Results from previous studies have shown that the application of CRet currents at subthermal doses causes alterations in cell cycle progression and decreased proliferation in hepatocarcinoma (HepG2) and neuroblastoma (NB69) human cell lines. The aim of the present study was to investigate the antiproliferative response of HepG2 to CRet currents. The results showed that 24-h intermittent treatment with 50 µA/mm(2) current density induced in HepG2 statistically significant changes in expression and activation of cell cycle control proteins p27Kip1 and cyclins D1, A and B1. The chronology of these changes is coherent with that of the alterations reported in the cell cycle of HepG2 when exposed to the same electric treatment. We propose that the antiproliferative effect exerted by the electric stimulus would be primarily mediated by changes in the expression and activation of proteins intervening in cell cycle regulation, which are among the targets of emerging chemical therapies. The capability to arrest the cell cycle through electrically-induced changes in cell cycle control proteins might open new possibilities in the field of oncology.
Han, Xue; Liu, Hong-Chen; Wang, Dong-Sheng; Li, Shu-Jun; Yang, Rui
2011-01-01
To observe the efficacy of micro-arc oxidation and alkali-heat treatment (MAH) on Ti-24Nb-4Zr-8Sn (Ti2448). Disks (diameter of 14.5 mm, thickness of 1 mm) and cylinders (diameter of 3 mm, height of 10 mm) were fabricated from Ti2448 alloy. Samples were divided into three groups: polished (Ti2448), micro-arc oxidation(MAO-Ti2448), micro-arc oxidation and alkali-heat treatment (MAH-Ti2448). MC3T3-E1 osteoblastic cells were cultured on the disks and cell morphology was observed with scanning electron microscopy (SEM) aftre 3 days. The cylinder samples were implanted in the tibia of dogs and implant-bone interface was observed with SEM after 3 months. A rough and porous structure was shown in both MAO and MAH group. The MC3T3-E1 cells on the MAH-Ti2448 discs spread fully in intimate contact with the underlying coarse surface through active cytoskeletal extentions. Osseointegration was formed in the implant-bone interface in MAH samples. MAH treatment can provide a more advantageous Ti2448 surface to osteoblastic cells than MAO treatment does, and the former can improve the implant-bone integration.
Okazaki, Y; Rao, S; Ito, Y; Tateishi, T
1998-07-01
The effects of various metallic ions using various metallic powders on the relative growth ratio of fibroblasts L929 and osteoblasts MC3T3-E1 cells were carried out. Ti, Zr, Sn, Nb and Ta had evidently no effect on the relative growth ratios of cells. Otherwise, Al and V ions exhibit cytotoxicity from a concentration of > or = 0.2 ppm. This Al effect on cells tend to be stronger in medium containing small quantity of V ions (< or = 0.03 ppm). The new Ti-15%Zr-4%Nb-4%Ta-0.2%Pd alloy exhibited a higher corrosion resistance in physiological saline solution. The addition of 0.02%O and 0.05%N to Ti-Zr alloy improved the mechanical properties at room temperature and corrosion fatigue strength. The relative growth ratios for the new Ti alloy plate and the alloy block extraction were unity. Further, the relative growth ratios were almost unity for the new Ti alloy against apatite ceramic pins up to 10(5) wear cycles in Eagle's MEM solution. However, there was a sharp decrease for Ti-6%Al-4%V ELI alloy from 3 x 10(4) wear cycles as V ion was released during wear into the wear test solution since the pH of the Eagle's MEM increases with increasing wear cycles.
NASA Astrophysics Data System (ADS)
Kodre, A.; Tellier, J.; Arčon, I.; Malič, B.; Kosec, M.
2009-06-01
Following an x-ray diffraction study of phase transitions of the piezoelectric perovskite K0.5Na0.5NbO3 the structural changes of the material are studied using extended x-ray absorption fine structure analysis, whereby the neighborhood of Nb atom is determined in the temperature range of monoclinic, tetragonal, and cubic phases. Within the entire range Nb atom is displaced from the center of the octahedron of its immediate oxygen neighbors, as witnessed by the splitting of Nb-O distance. The model shows high prevalence of the displacement in the (111) crystallographic direction of the simple perovskite cell. The corresponding splitting of the Nb-Nb distance is negligible. There is no observable disalignment of the linear Nb-O-Nb bonds from the ideal cubic arrangement, judging from the intensity of the focusing of the photoelectron wave on the Nb-Nb scattering path by the interposed oxygen atom. As a general result, the phase transitions are found as an effect of the long-range order, while the placement of the atoms in the immediate vicinity remains largely unaffected.
NASA Astrophysics Data System (ADS)
Kito, Hijiri; Iyo, Akira; Wada, Toshimi
2011-01-01
Using a cubic-anvil high-pressure apparatus, ternary iridium phosphides MIrP (M=Ti, Zr, Nb, Mo) and MgRuP have been prepared by reaction of stoichiometric amounts of each metal and phosphide powders at around 2 Gpa and above 1523 K for the first time. The structure of these compounds prepared at high-pressure has been characterized by X-ray powder diffraction. Diffraction lines of these compounds are assigned by the index of the Co2Si-type structure. The electrical resistivity and the d.c magnetic susceptibility of MIrP (M=Ti, Zr, Nb, Mo) have measured at low temperatures. Unfortunately, no superconducting transition for MIrP (M=Ti, Zr, Nb, Mo) and MgRuP are observed down to 2 K.
NASA Astrophysics Data System (ADS)
Zhang, Lu; Yi, Shuangping; Hu, Xiaoxue; Liang, Boxin; Zhao, Weiren; Wang, Yinhai
2017-03-01
A color-tunable phosphor based on Tb3+/Eu3+ co-doped GdNbO4 were synthesized by a traditional solid-state reaction method. X-ray powder diffraction (XRD), diffuse reflectance spectra, photoluminescence spectra and decay curves were utilized to characterize the as-prepared phosphors. XRD result indicated that various concentrations Tb3+/Eu3+ single-doped and co-doped phosphors were well indexed to the pure GdNbO4 phase. The GdNbO4 host was proved to be a self-activated phosphor with broad absorption range from 200 nm to 325 nm. When Tb3+ ions were added into the host lattice, the energy transferring from host to Tb3+ was identified. And the broad absorption in the UV region was changed and enhanced. Therefore, we selected Tb3+ as the sensitizer ion, and adjusted red component from Eu3+ to control the emission color. The energy transfer from Tb3+ to Eu3+ was confirmed based on the luminescence spectra and decay curves. Furthermore, the energy transmission mechanism was deduced to be the dipole-quadrupole interaction. On the whole, the obtained GdNbO4, GdNbO4:Tb3+, and GdNbO4:Tb3+, Eu3+ phosphors may have potential application in the UV white-light-emitting diodes (w-LEDs) and display devices.
Tan, Dina; Zeng, Honghu; Liu, Jie; Yu, Xiaozhang; Liang, Yanpeng; Lu, Lanjing
2013-07-01
The kinetics of the degradation of trace nitrobenzene (NB) by a granular activated carbon (GAC) enhanced microwave (MW)/hydrogen peroxide (H202) system was studied. Effects of pH, NB initial concentration and tert-butyl alcohol on the removal efficiency were examined. It was found that the reaction rate fits well to first-order reaction kinetics in the MW/GAC/H202 process. Moreover, GAC greatly enhanced the degradation rate of NB in water. Under a given condition (MW power 300 W, H202 dosage 10 mg/L, pH 6.85 and temperature (60 +/- 5)degrees C), the degradation rate of NB was 0.05214 min-1when 4 g/L GAC was added. In general, alkaline pH was better for NB degradation; however, the optimum pH was 8.0 in the tested pH value range of 4.0-12.0. At H202 dosage of 10 mg/L and GAC dosage of 4 g/L, the removal of NB was decreased with increasing initial concentrations of NB, indicating that a low initial concentration was beneficial for the degradation of NB. These results indicated that the MW/GAC/H202 process was effective for trace NB degradation in water. Gas chromatography-mass spectrometry analysis indicated that a hydroxyl radical addition reaction and dehydrogenation reaction enhanced NB degradation.
Radiation and Thermally Hardened Switching Materials
1974-10-01
to make TiO/Ti-0 devices. The method used was exactly the same as for the standards NbO/NbOg spike suppressors, i.e., we have annealed chips of TiO...volt)] fig. 4 4.0 ■ - ■ - i --■-- - ~- - MJMit^fc-Miir’rä>fliti* J 1 Kma) NbO/WbO. 400 £00 I i -200 - 400 4 4 -^ E(volt
Temperature-dependent performance of all-NbN DC-SQUID magnetometers
NASA Astrophysics Data System (ADS)
Liu, Quansheng; Wang, Huiwu; Zhang, Qiyu; Wang, Hai; Peng, Wei; Wang, Zhen
2017-05-01
Integrated NbN direct current superconducting quantum interference device (DC-SQUID) magnetometers were developed based on high-quality epitaxial NbN/AlN/NbN Josephson junctions for SQUID applications operating at high temperatures. We report the current-voltage and voltage-flux characteristics and the noise performance of the NbN DC-SQUIDs for temperatures ranging from 4.2 to 9 K. The critical current and voltage swing of the DC-SQUIDs decreased by 15% and 25%, respectively, as the temperature was increased from 4.2 to 9 K. The white flux noise of the DC-SQUID magnetometer at 1 kHz increased from 3.9 μΦ0/Hz1/2 at 4.2 K to 4.8 μΦ0/Hz1/2 at 9 K with 23% increase, corresponding to the magnetic field noise of 6.6 and 8.1 fT/Hz1/2, respectively. The results show that NbN DC-SQUIDs improve the tolerance of the operating temperatures and temperature fluctuations in SQUID applications.
Veum, T L; Raboy, V
2016-03-01
A 35-d experiment was conducted using 63 crossbred pigs (35 barrows and 28 gilts) with an initial average BW of 7.0 kg and age of 28 d to evaluate the efficacy of the low-phytic acid (LPA) genetic trait in hulled or hull-less barley in isocaloric diets. Hulled barleys were the normal barley (NB) cultivar Harrington and the near-isogenic LPA mutant 955 (M955) with P availabilities of 36 and 95%, respectively. Hull-less lines were produced by crossing NB and the LPA mutant 422 line with a hull-less line, producing hull-less NB (HNB) and hull-less mutant 422 (HM422) with P availabilities of 41 and 66%, respectively. Pigs were in individual metabolism cages or pens for Phase 1 (d 0 to 14) and Phase 2 (d 14 to 35). Diets defined as NB, HNB, HM422, or M955 with no added inorganic P (iP) had available P (aP) concentrations of 0.27, 0.28, 0.35, and 0.40% for Phase 1 and 0.15, 0.17, 0.23, and 0.31% for Phase 2, respectively. Only diet M955 was adequate in aP. Therefore, iP was added to the P-deficient diets to make diets NB + iP, HNB + iP, and HM422 + iP with aP equal to that in diet M955. Overall (d 0 to 35), ADG and G:F were greater ( < 0.01) for pigs fed diet M955 or the diets with added iP than for pigs fed the NB diet. Serum tartrate-resistant acid phosphatase activity on d 34 was greater ( < 0.01) for pigs fed the NB or HNB diets than for pigs fed the other diets. Bone breaking strength and P absorption (g/d) were greater ( < 0.01) for pigs fed diet M955 or the diets with iP than for pigs fed the NB or HNB diets. Pigs fed diet M955 absorbed greater ( < 0.01) percentages of P and Ca and had less ( < 0.01) fecal excretion of P (g/d and %) and Ca (%) than pigs fed the other diets. In conclusion, the LPA genetic trait was effective in hulled and hull-less barley in isocaloric diets fed to young pigs. Pigs fed the diet with LPA M955 consumed 31% less P and excreted 78% less fecal P and 30% less fecal Ca than pigs fed the diet with NB + iP that was equal to diet M955 in aP. Therefore, LPA barley, especially M955 with 95% aP, will reduce the use of iP in swine diets, reduce P pollution from swine manure, and support the goal of achieving global P sustainability.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Woodward, S.; Riaz, U.; Curtis, M.D.
1990-10-01
Reaction of CpNbCl{sub 4} (Cp = {eta}-C{sub 5}H{sub 5}) with (Pr{sup i}O){sub 2}P(S)(SH) in the presence of NEt{sub 3} yields CpNbCl{sub 3}(S{sub 2}P(S{sub 2}Pr{sup i}){sub 2}) (1). Reduction of 1 with Na/Hg affords the Nb-Nb-bonded complex CpNbCl({mu}-Cl){sub 2}Nb(S{sub 2}P(OR){sub 2})Cp (2). In refluxing toluene, (Pr{sup i}O){sub 2}P(S)(SH) with (Cp{prime}Mo(CO){sub 3}){sub 2} (Cp{prime} = {eta}-C{sub 5}H{sub 4}Me) gives cis-Cp{prime}Mo(CO){sub 2}(S{sub 2}P(OPr{sup i}){sub 2}) (3). Oxidation of 3 with I{sub 2} affords Cp{prime}MoI{sub 2}(CO)(S{sub 2}P(OPr{sup i}){sub 2}) (4). The crystal structures of 1-3 are compared. For 1, triclinic, P{bar 1}, a = 7.122 (3) {angstrom}, b = 11.365 (4) {angstrom}, c =more » 12.532 (4) {angstrom}, {alpha} = 77.38 (3){degree}, {beta} = 89.08 (3){degree}, {gamma} = 72.87 (3){degree}, V = 944.5 (8) {angstrom}{sup 3}. For 2, triclinic, P{bar 1}, a = 7.251 (3) {angstrom}, b = 12.386 (5) {angstrom}, c = 13.988 (5) {angstrom}, {alpha} = 102.66 (3){degree}, {beta} = 103.56 (3){degree}, {gamma} = 94.66 (3){degree}, V = 1180.0 (8) {angstrom}{sup 3}, Z = 2. For 3, orthorhombic, Pbca, a = 12.703 (3) {angstrom}, b = 16.707 (4) {angstrom}, c = 18.398 (4) {angstrom}, V = 3904.4 (17) {angstrom}{sup 3}, Z = 8.« less
Aravindan, Sheeja; Natarajan, Mohan; Awasthi, Vibhudutta; Herman, Terence S; Aravindan, Natarajan
2013-01-01
Recently, we demonstrated that radiation (IR) instigates the occurrence of a NFκB-TNFα feedback cycle which sustains persistent NFκB activation in neuroblastoma (NB) cells and favors survival advantage and clonal expansion. Further, we reported that curcumin targets IR-induced survival signaling and NFκB dependent hTERT mediated clonal expansion in human NB cells. Herein, we investigated the efficacy of a novel synthetic monoketone, EF24, a curcumin analog in inhibiting persistent NFκB activation by disrupting the IR-induced NFκB-TNFα-NFκB feedback signaling in NB and subsequent mitigation of survival advantage and clonal expansion. EF24 profoundly suppressed the IR-induced NFκB-DNA binding activity/promoter activation and, maintained the NFκB repression by deterring NFκB-dependent TNFα transactivation/intercellular secretion in genetically varied human NB (SH-SY5Y, IMR-32, SK-PN-DW, MC-IXC and SK-N-MC) cell types. Further, EF24 completely suppressed IR-induced NFκB-TNFα cross-signaling dependent transactivation/translation of pro-survival IAP1, IAP2 and Survivin and subsequent cell survival. In corroboration, EF24 treatment maximally blocked IR-induced NFκB dependent hTERT transactivation/promoter activation, telomerase activation and consequent clonal expansion. EF24 displayed significant regulation of IR-induced feedback dependent NFκB and NFκB mediated survival signaling and complete regression of NB xenograft. Together, the results demonstrate for the first time that, novel synthetic monoketone EF24 potentiates radiotherapy and mitigates NB progression by selectively targeting IR-triggered NFκB-dependent TNFα-NFκB cross-signaling maintained NFκB mediated survival advantage and clonal expansion.
Aravindan, Sheeja; Natarajan, Mohan; Awasthi, Vibhudutta; Herman, Terence S.; Aravindan, Natarajan
2013-01-01
Recently, we demonstrated that radiation (IR) instigates the occurrence of a NFκB-TNFα feedback cycle which sustains persistent NFκB activation in neuroblastoma (NB) cells and favors survival advantage and clonal expansion. Further, we reported that curcumin targets IR-induced survival signaling and NFκB dependent hTERT mediated clonal expansion in human NB cells. Herein, we investigated the efficacy of a novel synthetic monoketone, EF24, a curcumin analog in inhibiting persistent NFκB activation by disrupting the IR-induced NFκB-TNFα-NFκB feedback signaling in NB and subsequent mitigation of survival advantage and clonal expansion. EF24 profoundly suppressed the IR-induced NFκB-DNA binding activity/promoter activation and, maintained the NFκB repression by deterring NFκB-dependent TNFα transactivation/intercellular secretion in genetically varied human NB (SH-SY5Y, IMR-32, SK–PN–DW, MC-IXC and SK–N-MC) cell types. Further, EF24 completely suppressed IR-induced NFκB-TNFα cross-signaling dependent transactivation/translation of pro-survival IAP1, IAP2 and Survivin and subsequent cell survival. In corroboration, EF24 treatment maximally blocked IR-induced NFκB dependent hTERT transactivation/promoter activation, telomerase activation and consequent clonal expansion. EF24 displayed significant regulation of IR-induced feedback dependent NFκB and NFκB mediated survival signaling and complete regression of NB xenograft. Together, the results demonstrate for the first time that, novel synthetic monoketone EF24 potentiates radiotherapy and mitigates NB progression by selectively targeting IR-triggered NFκB-dependent TNFα-NFκB cross-signaling maintained NFκB mediated survival advantage and clonal expansion. PMID:23967300
NASA Astrophysics Data System (ADS)
Srivastava, P.; Chaudhary, S.; Maurya, V.; Saha, J.; Kaushik, S. D.; Siruguri, V.; Patnaik, S.
2018-05-01
Synthesis and extensive structural, pyroelectric, magnetic, dielectric and magneto-electric characterizations are reported for polycrystalline Co4Nb2O9 towards unraveling the multiferroic ground state. Magnetic measurements confirm that Co4Nb2O9 becomes an anti-ferromagnet at around 28 K. Associated with the magnetic phase transition, a sharp peak in pyroelectric current indicates the appearance of strong magneto-electric coupling below Neel temperature (TN) along with large coupling constant upto 17.8 μC/m2T. Using temperature oscillation technique, we establish Co4Nb2O9 to be a genuine multiferroic with spontaneous electric polarization in the anti-ferromagnetic state in the absence of magnetic field poling. This is in agreement with our low temperature neutron diffraction studies that show the magnetic structure of Co4Nb2O9 to be that of a non-collinear anti-ferromagnet with ferroelectric ground state.
Defect Complex Effect in Nb Doped TiO2 Ceramics with Colossal Permittivity
NASA Astrophysics Data System (ADS)
Li, Fuchao; Shang, Baoqiang; Liang, Pengfei; Wei, Lingling; Yang, Zupei
2016-10-01
Donor-doped Nb x Ti1- x O2 ( x = 1%, 2%, 4%, 6%, and 8%) ceramics with giant permittivity (>104) and a very low dielectric loss (˜0.05) were sintered under flowing N2 at 1400°C for 10 h. By increasing Nb doping concentration, two different dielectric responses were evidenced in the frequency dependence of dielectric properties of Nb doped TiO2 ceramics, which corresponded to the space charge polarization and the electron-pinned defect-dipoles effect, respectively. Especially, combined with the x-ray photoelectron spectroscopy results, the electron-pinned defect-dipoles induced by the 2({Nb}^{5 + } )_{{Ti}}^{ bullet } to 4({Ti}^{3 + } )^'_{{Ti}} leftarrow {V}_{{o}}^{ bullet bullet } defect complex were further confirmed to give rise to both their high ɛr and low tan δ in the high frequency range for the Nb x Ti1- x O2 ceramics with x > 4%.
Dimerization of A-[alpha]-[SiNb3W9O40]7- by pH-controlled formation of individual Nb−µ-O−Nb linkages
Gyu-Shik Kim; Huadong Zeng; Wade A. Neiwert; Jennifer J. Cowan; Donald VanDerveer; Craig L. Hill; Ira A. Weinstock
2003-01-01
The reversible, stepwise formation of individual Nb−µ-O−Nb linkages during acid condensation of 2 equiv of A-[alpha]-[SiNb3W9O40]7- (1) to the tri-µ-oxo-bridged structure A-[alpha]-[Si2Nb6W18O77]8- (4) is demonstrated by a combination of X-ray crystallography and variable-pD solution 183W and 29Si NMR spectroscopy. Addition of DCl to a pD 8.4...
B7-H4 as a Target for Breast Cancer Immunotherapy
2012-06-01
lymphoma and leukemia cell lines. CEM, Karpas 299, and TLBR -1, cell lines derived from acute T-cell lymphoblastic leukemia, large cell anaplastic...Accomplishments Generation of human B7-H4-Fc fusion protein (antigen). Discovery of a B7-H4 receptor on CEM, Karpas 299, and TLBR -1 cell lines...CEM Karpas 299 TLBR -1 Jurkat B7-H4R Figure 3. B7-H4 binding to human T-cell lymphoma cell lines. Red
PPAR Gamma in Neuroblastoma: The Translational Perspectives of Hypoglycemic Drugs
Conaldi, Pier Giulio
2016-01-01
Neuroblastoma (NB) is the most common and aggressive pediatric cancer, characterized by a remarkable phenotypic diversity and high malignancy. The heterogeneous clinical behavior, ranging from spontaneous remission to fatal metastatic disease, is attributable to NB biology and genetics. Despite major advances in therapies, NB is still associated with a high morbidity and mortality. Thus, novel diagnostic, prognostic, and therapeutic approaches are required, mainly to improve treatment outcomes of high-risk NB patients. Among neuroepithelial cancers, NB is the most studied tumor as far as PPAR ligands are concerned. PPAR ligands are endowed with antitumoral effects, mainly acting on cancer stem cells, and constitute a possible add-on therapy to antiblastic drugs, in particular for NB with unfavourable prognosis. While discussing clinical background, this review will provide a synopsis of the major studies about PPAR expression in NB, focusing on the potential beneficial effects of hypoglycemic drugs, thiazolidinediones and metformin, to reduce the occurrence of relapses as well as tumor regrowth in NB patients. PMID:27799938
PPAR Gamma in Neuroblastoma: The Translational Perspectives of Hypoglycemic Drugs.
Vella, Serena; Conaldi, Pier Giulio; Florio, Tullio; Pagano, Aldo
2016-01-01
Neuroblastoma (NB) is the most common and aggressive pediatric cancer, characterized by a remarkable phenotypic diversity and high malignancy. The heterogeneous clinical behavior, ranging from spontaneous remission to fatal metastatic disease, is attributable to NB biology and genetics. Despite major advances in therapies, NB is still associated with a high morbidity and mortality. Thus, novel diagnostic, prognostic, and therapeutic approaches are required, mainly to improve treatment outcomes of high-risk NB patients. Among neuroepithelial cancers, NB is the most studied tumor as far as PPAR ligands are concerned. PPAR ligands are endowed with antitumoral effects, mainly acting on cancer stem cells, and constitute a possible add-on therapy to antiblastic drugs, in particular for NB with unfavourable prognosis. While discussing clinical background, this review will provide a synopsis of the major studies about PPAR expression in NB, focusing on the potential beneficial effects of hypoglycemic drugs, thiazolidinediones and metformin, to reduce the occurrence of relapses as well as tumor regrowth in NB patients.
Xi, Zhongnan; Ruan, Jieji; Li, Chen; Zheng, Chunyan; Wen, Zheng; Dai, Jiyan; Li, Aidong; Wu, Di
2017-01-01
Recently, ferroelectric tunnel junctions have attracted much attention due to their potential applications in non-destructive readout non-volatile memories. Using a semiconductor electrode has been proven effective to enhance the tunnelling electroresistance in ferroelectric tunnel junctions. Here we report a systematic investigation on electroresistance of Pt/BaTiO3/Nb:SrTiO3 metal/ferroelectric/semiconductor tunnel junctions by engineering the Schottky barrier on Nb:SrTiO3 surface via varying BaTiO3 thickness and Nb doping concentration. The optimum ON/OFF ratio as great as 6.0 × 106, comparable to that of commercial Flash memories, is achieved in a device with 0.1 wt% Nb concentration and a 4-unit-cell-thick BaTiO3 barrier. With this thinnest BaTiO3 barrier, which shows a negligible resistance to the tunnelling current but is still ferroelectric, the device is reduced to a polarization-modulated metal/semiconductor Schottky junction that exhibits a more efficient control on the tunnelling resistance to produce the giant electroresistance observed. These results may facilitate the design of high performance non-volatile resistive memories. PMID:28513590
Influence of La doping on structural and dielectric properties of SrBi2Nb2O9 ceramics
NASA Astrophysics Data System (ADS)
Verma, Maya; Sreenivas, K.; Gupta, Vinay
2009-01-01
Lanthanum doped SrBi2Nb2O9 ceramics with the chemical formula SrBi2-xLaxNb2O9 (SBLN) (x =0-0.5) have been prepared through conventional solid state route. X-ray diffraction reveals the shrinkage of unit cell of strontium bismuth niobate with incorporation of La3+ dopant, having no lone pair electrons. Shifting of Raman phonon modes indicates the reduced rattling space of NbO6 octahedra with increase in La doping concentration. Further, the softening of lowest frequency phonon mode with increasing x in SBLN shows the transition from ferroelectric to paraelectric at room temperature. The dielectric properties for all the compositions are studied as a function of temperature (25 to 500 °C) over the frequency range of 10 kHz-1 MHz. With increase in lanthanum doping concentration the phase transition becomes diffused and transition temperature gets shifted toward lower temperature. A phase transition from normal ferroelectric to paraelectric has been observed via relaxor-type ferroelectrics with increase in x. The frequency dependence of transition temperature was studied in terms of Vogel-Fulcher relation for SBLN (x =0.4).
NASA Astrophysics Data System (ADS)
Xi, Zhongnan; Ruan, Jieji; Li, Chen; Zheng, Chunyan; Wen, Zheng; Dai, Jiyan; Li, Aidong; Wu, Di
2017-05-01
Recently, ferroelectric tunnel junctions have attracted much attention due to their potential applications in non-destructive readout non-volatile memories. Using a semiconductor electrode has been proven effective to enhance the tunnelling electroresistance in ferroelectric tunnel junctions. Here we report a systematic investigation on electroresistance of Pt/BaTiO3/Nb:SrTiO3 metal/ferroelectric/semiconductor tunnel junctions by engineering the Schottky barrier on Nb:SrTiO3 surface via varying BaTiO3 thickness and Nb doping concentration. The optimum ON/OFF ratio as great as 6.0 × 106, comparable to that of commercial Flash memories, is achieved in a device with 0.1 wt% Nb concentration and a 4-unit-cell-thick BaTiO3 barrier. With this thinnest BaTiO3 barrier, which shows a negligible resistance to the tunnelling current but is still ferroelectric, the device is reduced to a polarization-modulated metal/semiconductor Schottky junction that exhibits a more efficient control on the tunnelling resistance to produce the giant electroresistance observed. These results may facilitate the design of high performance non-volatile resistive memories.
Studies on niobium triselenide cathode material for lithium rechargeable cells
NASA Technical Reports Server (NTRS)
Ratnakumar, B. V.; Ni, C. L.; Distefano, S.; Somoano, R. B.; Bankston, C. P.
1988-01-01
NbSe3 exhibits superior characteristics such as high capacity, high volumetric and gravimetric energy densities, and high discharge rate capability, as compared to other intercalating cathodes. This paper reports the preparation, characterization, and performance of NbSe3. Several electrochemical techniques, such as cyclic voltammetry, constant-current/constant-potential discharges, dc potentiodynamic scans, ac impedance, and ac voltammetry, have been used to give insight to the mechanisms of intercalation of three lithiums with NbSe3 and also into the rate determining process in the reduction of NbSe3.
Alemayehu, Matti B; Falmbigl, Matthias; Ta, Kim; Johnson, David C
2015-04-28
Inorganic isomers ([SnSe]1+δ)m(NbSe2)n([SnSe]1+δ)p(NbSe2)q([SnSe]1+δ)r(NbSe2)s where m, n, p, q, r, and s are integers and m + p + r = n + q + s = 4 were prepared using the modulated elemental reactant technique. This series of all six possible isomers provides an opportunity to study the influence of interface density on properties while maintaining the same unit cell size and composition. As expected, all six compounds were observed to have the same atomic compositions and an almost constant c-axis lattice parameter of ≈4.90(5) nm, with a slight trend in the c-axis lattice parameter correlated with the different number of interfaces in the isomers: two, four and six. The structures of the constituents in the ab-plane were independent of one another, confirming the nonepitaxial relationship between them. The temperature dependent electrical resistivities revealed metallic behavior for all the six compounds. Surprisingly, the electrical resistivity at room temperature decreases with increasing number of interfaces. Hall measurements suggest this results from changes in carrier concentration, which increases with increasing thickness of the thickest SnSe block in the isomer. Carrier mobility scales with the thickness of the thickest NbSe2 block due to increased interfacial scattering as the NbSe2 blocks become thinner. The observed behavior suggests that the two constituents serve different purposes with respect to electrical transport. SnSe acts as a charge donor and NbSe2 acts as the charge transport layer. This separation of function suggests that such heterostructures can be designed to optimize performance through choice of constituent, layer thickness, and layer sequence. A simplistic model, which predicts the properties of the complex isomers from a weighted sum of the properties of building blocks, was developed. A theoretical model is needed to predict the optimal compound for specific properties among the many potential compounds that can be prepared.
Xie, Xiangyang; Yang, Yanfang; Lin, Wen; Liu, Hui; Liu, Hong; Yang, Yang; Chen, Ying; Fu, Xudong; Deng, Jianping
2015-12-01
Due to the absence of effective in vivo delivery systems, the employment of small interference RNA (siRNA) in the clinic has been hindered. In this paper, a new siRNA targeting system for EphA2-positive tumors was developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, a CPP-siRNA conjugate (CPP-siRNA) was entrapped in an ephrin mimetic peptide (YSA peptide)-modified NB (CPP-siRNA/YSA-NB) and the penetration of the CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research demonstrated that the CPP-siRNA/YSA-NBs had particle sizes of approximately 200 nm and a siRNA entrapment efficiency of more than 85%. The in vitro release results showed that over 90% of the encapsulated CPP-siRNA released from the NBs in the presence of ultrasound, while less than 1.5% of that (30 min) released without ultrasound. Cell experiments showed a the higher CPP-siRNA cellular uptake of CPP-siRNA/YSA-NB among the various formulations in human breast adenocarcinoma cells (MCF-7, EphA2 positive cells). Additionally, after systemic administration in mice, CPP-siRNA/YSA-NB accumulated in the tumor, augmented c-Myc silencing and delayed tumor progression. In conclusion, the application of CPP-siRNA/YSA-NB with ultrasound may provide a strategy for the selective and efficient delivery of siRNA. Copyright © 2015 Elsevier B.V. All rights reserved.
Synthesis and characterization of InNbO₄ nanopowder for gas sensors.
Balamurugan, C; Vijayakumar, E; Subramania, A
2012-01-15
Indium niobate (InNbO(4)) nanopowder was prepared by a comparatively low temperature niobium citrate complex process. The prepared InNbO(4) was characterized by thermal analysis, X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy, diffuse reflectance spectroscopy (DRS), and impedance studies. It revealed that the well crystalline monoclinic InNbO(4) nanopowder was obtained at the calcination temperature of 600°C. The average particle diameter was 22nm. The optical band gap was found to be 2.66eV. The temperature dependent conductivity obeyed Arrhenius relation. The activation energy of the conductivity process was calculated to be 0.43eV. The gas sensing behaviour of the prepared InNbO(4) was studied by measuring the change in resistance of the sensor material as a function of various concentrations of the test gases such as liquid petroleum gas (LPG), ammonia (NH(3)) and ethanol (C(2)H(5)OH) at their optimized operating temperature. InNbO(4) had a better sensitivity to LPG (0.97) and NH(3) (0.70) gas than ethanol (0.46). The sensor responses of InNbO(4) as a function of gas concentrations and with recovery time were also studied in detail. Copyright © 2011 Elsevier B.V. All rights reserved.
PACAP and VIP regulate hypoxia-inducible factors in neuroblastoma cells exposed to hypoxia.
Maugeri, Grazia; D'Amico, Agata Grazia; Rasà, Daniela Maria; Saccone, Salvatore; Federico, Concetta; Cavallaro, Sebastiano; D'Agata, Velia
2018-06-01
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two related peptides acting as neurotransmitters/neuromodulators in central and peripheral nervous system. They are also involved in cancer showing a controversial role. Particulary, they are implicated in neuroblastoma differentiation (NB). This pediatric tumor can evolve to a malignant metastatic disease or spontaneously regress towards a benign form, known as ganglioneuroblastoma/ganglioneuroma. A negative hallmark of neoplasia progression is represented by hypoxic microenvironment. Low oxygen tension induces activation of hypoxia-inducible factors (HIFs) promoting cells proliferation and metastasis formation. Moreover, HIFs trigger vascular endothelial growth factor (VEGF) release favouring high-risk NB phenotype development. In the present work, we have investigated for the first time, if PACAP and VIP interfere with NB differentiation through modulation of hypoxic/angiogenic process. To this end, we analyzed their effect in malignant undifferentiated and all-trans retinoic acid (RA) differentiated SH-SY5Y cells, representing the benign form of this tumor. Our results have suggested tha both peptides, but predominantly VIP, induce NB differentiation into benign form by regulating HIFs, VEGF and VEGFRs expression and distribution. All these data give new insight regarding PACAP/VIP regulatory role in NB progression. Copyright © 2018 Elsevier Ltd. All rights reserved.
do Prado, Renata Falchete; Rabêlo, Sylvia Bicalho; de Andrade, Dennia Perez; Nascimento, Rodrigo Dias; Henriques, Vinicius André Rodrigues; Carvalho, Yasmin Rodarte; Cairo, Carlos Alberto Alves; de Vasconcellos, Luana Marotta Reis
2015-11-01
Tests on titanium alloys that possess low elastic modulus, corrosion resistance and minimal potential toxicity are ongoing. This study aimed to evaluate the behavior of human osteoblastic cells cultured on dense and porous Titanium (Ti) samples comparing to dense and porous Ti-35 Niobium (Ti-35Nb) samples, using gene expression analysis. Scanning electronic microscopy confirmed surface porosity and pore interconnectivity and X-ray diffraction showed titanium beta-phase stabilization in Ti-35Nb alloy. There were no differences in expression of transforming growth factor-β, integrin-β1, alkaline phosphatase, osteopontin, macrophage colony stimulating factor, prostaglandin E synthase, and apolipoprotein E regarding the type of alloy, porosity and experimental period. The experimental period was a significant factor for the markers: bone sialoprotein II and interleukin 6, with expression increasing over time. Porosity diminished Runt-related transcription factor-2 (Runx-2) expression. Cells adhering to the Ti-35Nb alloy showed statistically similar expression to those adhering to commercially pure Ti grade II, for all the markers tested. In conclusion, the molecular mechanisms of interaction between human osteoblasts and the Ti-35Nb alloy follow the principal routes of osseointegration of commercially pure Ti grade II. Porosity impaired the route of transcription factor Runx-2.
Experiments on the transportation of a magnetized plasma stream in the GOL-3 facility
DOE Office of Scientific and Technical Information (OSTI.GOV)
Postupaev, V. V., E-mail: V.V.Postupaev@inp.nsk.su; Batkin, V. I.; Burdakov, A. V.
2016-04-15
The program of the deep upgrade of the GOL-3 multiple-mirror trap is presented. The upgrade is aimed at creating a new GOL-NB open trap located at the GOL-3 site and intended to directly demonstrate the efficiency of using multiple-mirror magnetic cells to improve longitudinal plasma confinement in a gasdynamic open trap. The GOL-NB device will consist of a new central trap, adjoint cells with a multiple-mirror magnetic field, and end tanks (magnetic flux expanders). Plasma in the central trap will be heated by neutral beam injection with a power of up to 1.5 MW and duration of 1 ms. Atmore » present, physical experiments directed at developing plasma technologies that are novel for this facility are being carried out using the 6-m-long autonomous part of the GOL-3 solenoid. The aim of this work was to develop a method for filling the central trap with a low-temperature start plasma. Transportation of a plasma stream from an arc source over a distance of 3 m in a uniform magnetic field with an induction of 0.5–4.5 T is demonstrated. In these experiments, the axial plasma density was (1–4) × 10{sup 20} m{sup –3} and the mirror ratio varied from 5 to 60. In general, the experiments confirmed the correctness of the adopted decisions for the start plasma source of the GOL-NB device.« less
Bénard, Jean; Raguénez, Gilda; Kauffmann, Audrey; Valent, Alexander; Ripoche, Hugues; Joulin, Virginie; Job, Bastien; Danglot, Gisèle; Cantais, Sabrina; Robert, Thomas; Terrier-Lacombe, Marie-José; Chassevent, Agnès; Koscielny, Serge; Fischer, Matthias; Berthold, Frank; Lipinski, Marc; Tursz, Thomas; Dessen, Philippe; Lazar, Vladimir; Valteau-Couanet, Dominique
2008-10-01
Stage 4 neuroblastoma (NB) are heterogeneous regarding their clinical presentations and behavior. Indeed infants (stage 4S and non-stage 4S of age <365days at diagnosis) show regression contrasting with progression in children (>365days). Our study aimed at: (i) identifying age-based genomic and gene expression profiles of stage 4 NB supporting this clinical stratification; and (ii) finding a stage 4S NB signature. Differential genome and transcriptome analyses of a learning set of MYCN-non amplified stage 4 NB tumors at diagnosis (n=29 tumors including 12 stage 4S) were performed using 1Mb BAC microarrays and Agilent 22K probes oligo-microarrays. mRNA chips data following filtering yielded informative genes before supervised hierarchical clustering to identify relationship among tumor samples. After confirmation by quantitative RT-PCR, a stage 4S NB's gene cluster was obtained and submitted to a validation set (n=22 tumors). Genomic abnormalities of infant's tumors (whole chromosomes gains or loss) differ radically from that of children (intra-chromosomal rearrangements) but could not discriminate infants with 4S from those without this presentation. In contrast, differential gene expression by looking at both individual genes and whole biological pathways leads to a molecular stage 4S NB portrait which provides new biological clues about this fascinating entity.
NASA Astrophysics Data System (ADS)
Gu, Huimin; Lang, Junyu; Ma, Yuli; Gu, Huayu; Song, Yanyong; Chai, Zhanli; Li, Guangshe; Wang, Xiaojing
2018-05-01
In this investigation, phosphotungstic acid (H3PW12O40) was successfully self-assembly implanted into the interspace of K4Nb6O17 nanosheet via an impregnation method to form an adsorption-photocatalytic composite, in which n-type semiconductor K4Nb6O17 was selected as photo-electron emitter and H3PW12O40 was particularly used as an electronic transmitter. By characterizing with X-ray diffraction (XRD), transmission (TEM), scan electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and FT-IR spectrum (FT-IR), it confirmed that H3PW12O40 (HPW) was converted to the insoluble tiny particles of K3PW12O40 (KPW) with the remained primary Keggin group via an ion-exchanged H+ of HPW with K+ in K4Nb6O17 in the implanted process and was firmly bound to the surface of K4Nb6O17 to form well sandwich structure. UV-vis diffuse reflectance spectroscopy revealed that the band gap of K4Nb6O17-K3PW12O40 have a slight red shift compared with the single K4Nb6O17. Its adsorption-photocatalytic properties were evaluated with the removal of tetracycline as model reaction. Compared with pure K4Nb6O17, tetracycline removal rate can be significantly improved for the as-prepared sandwich. Importantly, the removal could still maintain 70% after five reuses in recycle tests at an acidic solution, inferring a good stability which was mainly ascribed to the formation of water-insoluble K3PW12O40. The separation and transfer process of photogenerated electrons were investigated by surface photovoltage spectroscopy (SPV). It proposed that the KPW anchored firmly on the interlayers of K4Nb6O17 through a O-K-O bridge plays a significantly role in promoting the separation of the photogenerated carriers and preventing the leakage and agglomeration of HPW. The present results showed that the strategy of the phosphotungstic acid binding in situ to K4Nb6O17 was favorable to promote the hetero-photocatalytic efficiency as well as reusability. [Figure not available: see fulltext.
Xie, Xiangyang; Lin, Wen; Liu, Hui; Deng, Jianping; Chen, Ying; Liu, Hong; Fu, Xudong; Yang, Yang
2016-10-01
To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP-camptothecin conjugate (CPP-CPT) into nanobubble (CPP-CPT NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP-CPT to the tumor cells. The mean particle size of the prepared CPP-CPT NB was ∼200 nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP-CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP-CPT NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP-CPT NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.
Transformation behavior of the γU(Zr,Nb) phase under continuous cooling conditions
NASA Astrophysics Data System (ADS)
Komar Varela, C. L.; Gribaudo, L. M.; González, R. O.; Aricó, S. F.
2014-10-01
The selected alloy for designing a high-density monolithic-type nuclear fuel with U-Zr-Nb alloy as meat and Zry-4 as cladding, has to remain in the γU(Zr,Nb) phase during the whole fabrication process. Therefore, it is necessary to define a range of concentrations in which the γU(Zr,Nb) phase does not decompose under the process conditions. In this work, several U alloys with concentrations between 28.2-66.9 at.% Zr and 0-13.3 at.% Nb were fabricated to study the possible transformations of the γU(Zr,Nb) phase under different continuous cooling conditions. The results of the electrical resistivity vs temperature experiments are presented. For a cooling rate of 4 °C/min a linear regression was determined by fitting the starting decomposition temperature as a function of Nb concentration. Under these conditions, a concentration of 45.3 at.% Nb would be enough to avoid any transformation of the γU(Zr,Nb) phase. In experiments that involve higher cooling conditions, it has been determined that this concentration can be halved.
Maman, Shelly; Edry-Botzer, Liat; Sagi-Assif, Orit; Meshel, Tsipi; Yuan, Weirong; Lu, Wuyuan; Witz, Isaac P
2013-11-15
Recent data suggest that the mechanisms determining whether a tumor cell reaching a secondary organ will enter a dormant state, progress toward metastasis, or go through apoptosis are regulated by the microenvironment of the distant organ. In neuroblastoma, 60-70% of children with high-risk disease will ultimately experience relapse due to the presence of micrometastases. The main goal of this study is to evaluate the role of the lung microenvironment in determining the fate of neuroblastoma lung metastases and micrometastases. Utilizing an orthotopic mouse model for human neuroblastoma metastasis, we were able to generate two neuroblastoma cell populations-lung micrometastatic (MicroNB) cells and lung macrometastatic (MacroNB) cells. These two types of cells share the same genetic background, invade the same distant organ, but differ in their ability to create metastasis in the lungs. We hypothesize that factors present in the lung microenvironment inhibit the propagation of MicroNB cells preventing them from forming overt lung metastasis. This study indeed shows that lung-derived factors significantly reduce the viability of MicroNB cells by up regulating the expression of pro-apoptotic genes, inducing cell cycle arrest and decreasing ERK and FAK phosphorylation. Lung-derived factors affected various additional progression-linked cellular characteristics of neuroblastoma cells, such as the expression of stem-cell markers, morphology, and migratory capacity. An insight into the microenvironmental effects governing neuroblastoma recurrence and progression would be of pivotal importance as they could have a therapeutic potential for the treatment of neuroblastoma residual disease. Copyright © 2013 UICC.
Growth inhibition mediated by PSP94 or CRISP-3 is prostate cancer cell line specific.
Pathak, Bhakti R; Breed, Ananya A; Nakhawa, Vaishali H; Jagtap, Dhanashree D; Mahale, Smita D
2010-09-01
The prostate secretory protein of 94 amino acids (PSP94) has been shown to interact with cysteine-rich secretory protein 3 (CRISP-3) in human seminal plasma. Interestingly, PSP94 expression is reduced or lost in the majority of the prostate tumours, whereas CRISP-3 expression is upregulated in prostate cancer compared with normal prostate tissue. To obtain a better understanding of the individual roles these proteins have in prostate tumourigenesis and the functional relevance of their interaction, we ectopically expressed either PSP94 or CRISP-3 alone or PSP94 along with CRISP-3 in three prostate cell lines (PC3, WPE1-NB26 and LNCaP) and performed growth inhibition assays. Reverse transcription-polymerase chain reaction and Western blot analysis were used to screen prostate cell lines for PSP94 and CRISP-3 expression. Mammalian expression constructs for human PSP94 and CRISP-3 were also generated and the expression, localization and secretion of recombinant protein were assayed by transfection followed by Western blot analysis and immunofluorescence assay. The effect that ectopic expression of PSP94 or CRISP-3 had on cell growth was studied by clonogenic survival assay following transfection. To evaluate the effects of co-expression of the two proteins, stable clones of PC3 that expressed PSP94 were generated. They were subsequently transfected with a CRISP-3 expression construct and subjected to clonogenic survival assay. Our results showed that PSP94 and CRISP-3 could each induce growth inhibition in a cell line specific manner. Although the growth of CRISP-3-positive cell lines was inhibited by PSP94, growth inhibition mediated by CRISP-3 was not affected by the presence or absence of PSP94. This suggests that CRISP-3 may participate in PSP94-independent activities during prostate tumourigenesis.
Wu, Zhen; Dong, Yu Bing; Xiong, Zheng Qin
2018-01-01
To evaluate the long-term effects of biochar amendment on greenhouse gas emissions (GHGs), a field experiment was conducted to examine the effects of 3-year field-aged biochar (B 3 ) and fresh biochar (B 0 ) on global warming potential (GWP) and greenhouse gas intensity (GHGI) of methane (CH 4 ) and nitrous oxide (N 2 O) in a typical rice-wheat rotation system. Four treatments were established as control without nitrogen fertilizer (CK), urea without biochar (N), urea with fresh biochar amended in 2015 (NB 0 ), and urea with 3-year field-aged biochar amended in 2012 (NB 3 ). Results showed that both the NB 0 and NB 3 treatments obviously increased soil pH, soil organic carbon (SOC), total nitrogen (TN) and influenced the potential activity of functional microorganisms related to GHGs compared to the N treatment. Relative to the N treatment, the NB 3 treatment significantly improved crop yield by 14.1% while reduced the CH 4 and N 2 O emissions by 9.0% and 34.0%, respectively. In addition, the NB 0 treatment significantly improved crop yield by 9.3%, while reduced the N 2 O emission by 38.6% though increased the CH 4 emissions by 4.7% relative to the N treatment. Moreover, both the NB 0 and NB 3 treatments could significantly reduce both GWP and GHGI, with NB 3 being more effective in simultaneously mitigating the GHGs emissions and enhancing crop yield. Since field-aged biochar showed obvious effects on GHGs mitigation and carbon sequestration after 3 years, biochar incorporations had long-term effect on GHGs mitigation and crop production in the rice-wheat rotation system.
Preparation of orthophosphate glasses in the MgO-CaO-SiO2-Nb2O5-P2O5 system.
Lee, Sungho; Ueda, Kyosuke; Narushima, Takayuki; Nakano, Takayoshi; Kasuga, Toshihiro
2017-01-01
Niobia/magnesia-containing orthophosphate invert glasses were successfully prepared in our earlier work. Orthophosphate groups in the glasses were cross-linked by tetrahedral niobia (NbO4) and magnesia. The aim of this work is to prepare calcium orthophosphate invert glasses containing magnesia and niobia, incorporating silica, and to evaluate their structures and releasing behaviors. The glasses were prepared by melt-quenching, and their structures and ion-releasing behaviors were evaluated. 31P solid-state nuclear magnetic resonance (NMR) and Raman spectroscopies showed the glasses consist of orthophosphate (PO4), orthosilicate (SiO4), and NbO4 tetrahedra. NbO4 and MgO in the glasses act as network formers. By incorporating SiO2 into the glasses, the chemical durability of the glasses was slightly improved. The glasses reheated at 800°C formed the orthophosphate crystalline phases, such as β-Ca3(PO4)2, Mg3(PO4)2 and Mg3Ca3(PO4)4 in the glasses. The chemical durability of the crystallized glasses was slightly improved. Orthosilicate groups and NbO4 in the glasses coordinated with each other to form Si-O-Nb bonds. The chemical durability of the glasses was slightly improved by addition of SiO2, since the field strength of Si is larger than that of Ca or Mg.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bayot, Daisy; Degand, Matthieu; Devillers, Michel
2005-09-15
New water-soluble bimetallic peroxo complexes of niobium{sup V} and/or tantalum{sup V} with high-denticity polyaminocarboxylate ligands have been prepared, characterized from the spectroscopic point of view, and used as molecular precursors for Nb-Ta mixed oxides. Four new homobimetallic complexes (gu){sub 3}[Nb{sub 2}(O{sub 2}){sub 4}(dtpaO{sub 3})].3H{sub 2}O 1 (gu){sub 3}[Ta{sub 2}(O{sub 2}){sub 4}(dtpaO{sub 3})].5H{sub 2}O 2 (gu){sub 3}[Nb{sub 2}(O{sub 2}){sub 4}(HtthaO{sub 4})].2H{sub 2}O 4 and (gu){sub 3}[Ta{sub 2}(O{sub 2}){sub 4}(HtthaO{sub 4})].3H{sub 2}O 5 and the corresponding heterometallic complexes (gu){sub 3}[NbTa(O{sub 2}){sub 4}(dtpaO{sub 3})].2.5H{sub 2}O 3 and (gu){sub 3}[NbTa(O{sub 2}){sub 4}(HtthaO{sub 4)}].2H{sub 2}O 6 have been obtained. In these compounds, the in situmore » oxidation of the nitrogen atoms of the PAC ligands into N-oxide groups has been evidenced by IR spectroscopy and mass spectrometry. The thermal treatment of the homonuclear complexes in air at 700 or 800 deg. C, depending on the Ta content, provided Nb{sub 2}O{sub 5} or Ta{sub 2}O{sub 5} while the heteronuclear compounds led to the solid solution TaNbO{sub 5}. BET and SEM measurements have been carried out and comparison of the morphology of the samples prepared from homo- and heterometallic precursors is discussed.« less
Shelake, Sagar; Eslin, Don; Sutphin, Robert M; Sankpal, Umesh T; Wadwani, Anmol; Kenyon, Laura E; Tabor-Simecka, Leslie; Bowman, W Paul; Vishwanatha, Jamboor K; Basha, Riyaz
2015-11-01
Chemotherapeutic regimens used for the treatment of Neuroblastoma (NB) cause long-term side effects in pediatric patients. NB arises in immature sympathetic nerve cells and primarily affects infants and children. A high rate of relapse in high-risk neuroblastoma (HRNB) necessitates the development of alternative strategies for effective treatment. This study investigated the efficacy of a small molecule, tolfenamic acid (TA), for enhancing the anti-proliferative effect of 13 cis-retinoic acid (RA) in HRNB cell lines. LA1-55n and SH-SY5Y cells were treated with TA (30μM) or RA (20μM) or both (optimized doses, derived from dose curves) for 48h and tested the effect on cell viability, apoptosis and selected molecular markers (Sp1, survivin, AKT and ERK1/2). Cell viability and caspase activity were measured using the CellTiter-Glo and Caspase-Glo kits. The apoptotic cell population was determined by flow cytometry with Annexin-V staining. The expression of Sp1, survivin, AKT, ERK1/2 and c-PARP was evaluated by Western blots. The combination therapy of TA and RA resulted in significant inhibition of cell viability (p<0.0001) when compared to individual agents. The anti-proliferative effect is accompanied by a decrease in Sp1 and survivin expression and an increase in apoptotic markers, Annexin-V positive cells, caspase 3/7 activity and c-PARP levels. Notably, TA+RA combination also caused down regulation of AKT and ERK1/2 suggesting a distinct impact on survival and proliferation pathways via signaling cascades. This study demonstrates that the TA mediated inhibition of Sp1 in combination with RA provides a novel therapeutic strategy for the effective treatment of HRNB in children. Copyright © 2015 Elsevier Ltd. All rights reserved.
Zhao, Dan; Liang, Peng; Su, Ling; Chang, Huan; Yan, Shi
2011-02-12
Single crystals of the title compound, aluminium niobium triphosphate, Al(0.5)Nb(1.5)(PO(4))(3), have been synthesized by a high-temperature reaction in a platinium crucible. The Al(III) and Nb(V) atoms occupy the same site on the axis, with disorder in the ratio of 1:3. The fundamental building units of the title structure are isolated Al/NbO(6) octa-hedra and PO(4) tetra-hedra (. 2 symmetry), which are further inter-locked by corner-sharing O atoms, leading to a three-dimensional framework structure with infinite channels along the a axis.
Cr3+ and Nb5+ co-doped Ti2Nb10O29 materials for high-performance lithium-ion storage
NASA Astrophysics Data System (ADS)
Yang, Chao; Yu, Shu; Ma, Yu; Lin, Chunfu; Xu, Zhihao; Zhao, Hua; Wu, Shunqing; Zheng, Peng; Zhu, Zi-Zhong; Li, Jianbao; Wang, Ning
2017-08-01
Ti2Nb10O29 is an advanced anode material for lithium-ion batteries due to its large specific capacity and high safety. However, its poor electronic/ionic conductivity significantly limits its rate capability. To tackle this issue, a Cr3+-Nb5+ co-doping is employed, and a series of CrxTi2-2xNb10+xO29 compounds are prepared. The co-doping does not change the Wadsley-Roth shear structure but increases the unit-cell volume and decreases the particle size. Due to the increased unit-cell volumes, the co-doped samples show increased Li+-ion diffusion coefficients. Experimental data and first-principle calculations reveal significantly increased electronic conductivities arising from the formation of impurity bands after the co-doping. The improvements of the electronic/ionic conductivities and the smaller particle sizes in the co-doped samples significantly contribute to improving their electrochemical properties. During the first cycle at 0.1 C, the optimized Cr0.6Ti0.8Nb10.6O29 sample delivers a large reversible capacity of 322 mAh g-1 with a large first-cycle Coulombic efficiency of 94.7%. At 10 C, it retains a large capacity of 206 mAh g-1, while that of Ti2Nb10O29 is only 80 mAh g-1. Furthermore, Cr0.6Ti0.8Nb10.6O29 shows high cyclic stability as demonstrated in over 500 cycles at 10 C with tiny capacity loss of only 0.01% per cycle.
Mycophenolate mofetil increases adhesion capacity of tumor cells in vitro.
Blaheta, Roman A; Bogossian, Harilaos; Beecken, Wolf-Dietrich; Jonas, Dietger; Hasenberg, Christoph; Makarevic, Jasmina; Ogbomo, Henry; Bechstein, Wolf O; Oppermann, Elsie; Leckel, Kerstin; Cinatl, Jindrich
2003-12-27
The immunosuppressive drug mycophenolate mofetil (MMF) reduces expression of the heterophilic binding elements intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and thereby prevents attachment of alloactivated leukocytes to donor endothelium. The authors speculated that MMF might further diminish receptors of the immunoglobulin superfamily which, however, act as homophilic binding elements. Because decrease of homophilic adhesion receptors correlates with tumor dissemination and metastasis, MMF could trigger development or recurrence of neoplastic tumors. The authors analyzed the influence of MMF on homotypic adhesion receptors and its consequence for tumor cell attachment to an endothelial cell monolayer. Neuroblastoma (NB) cells, which self-aggregate by means of the homophilic-binding element neural cell adhesion molecule (NCAM), were used. Effects of MMF on the 140- and 180-kDa NCAM isoforms were investigated quantitatively by flow cytometry, Western blot, and reverse-transcriptase (RT) polymerase chain reaction (PCR). The relevance of NCAM for tumor cell binding was proven by treating NB with NCAM antisense oligonucleotides. MMF profoundly increased the number of adherent NB cells, with a maximum effect at 0.1 microM, compared with controls. Decrease of NCAM on the cell surface was detected by flow cytometry. Western blot and RT-PCR demonstrated reduced protein and RNA levels of the 140- and 180-kDa isoforms. Treatment of NB cells with NCAM antisense oligonucleotides showed that reduced NCAM expression leads to enhanced tumor cell adhesion. MMF decreases NCAM receptors, which is associated with enhanced tumor cell invasiveness. The authors conclude that an MMF-based immunosuppressive regimen might increase the risk of tumor metastasis if this process is predominantly conveyed by means of homophilic adhesion proteins.
Structure of zinc and niobium tellurite glasses by neutron and x-ray diffraction
NASA Astrophysics Data System (ADS)
Hoppe, U.; Yousef, E.; Rüssel, C.; Neuefeind, J.; Hannon, A. C.
2004-03-01
Neutron and x-ray diffraction experiments of high resolving power with neutrons from a spallation source and high-energy photons from a synchrotron have been performed on compositional series of binary Zn, Nb and on mixed Zn/Nb tellurite glasses. The Te-O, Zn-O and Nb-O coordination numbers are determined by Gaussian fitting of the first-neighbour peaks in the neutron and x-ray data simultaneously. The transition of TeO4 to TeO3 units with increasing fraction of a second component is indicated by decreasing total Te-O coordination numbers. This transition appears different for glasses with ZnO or Nb2O5 additions. Details of the Te-O peaks suggest there are two species of Te-O bonds with lengths of {\\sim }0.19 and {\\sim }0.21 nm. The change of their fractions shows excellent agreement with the existence of TeO4 trigonal bipyramids and TeO3 trigonal pyramids. All oxygen atoms from ZnO and Nb2O5 are used for rupture of Te-O-Te bridges, which is accompanied with a change of nearly all participating TeO4 to TeO3 groups. The tendency for a {\\mathrm {TeO}}_{4} \\to {\\mathrm {TeO}}_{3} change decreases for glasses of higher second component content which is accompanied by the occurrence of TeO4 groups with non-bridging oxygens. The Nb tellurite glasses show transition to network-forming behaviour with the formation of Nb-O-Nb bridges. The fractions of TeO3 units of ternary Zn/Nb tellurite glasses agree with an additivity behaviour of the modifying effects of ZnO and Nb2O5 additions. Some of these results have already been presented in thesis work: Yousef E 2003 A study of some physical properties of tellurite glass (Al-Azhar University, Assiut Egypt).
NASA Astrophysics Data System (ADS)
Ohbayashi, Kazushige; Matsuoka, Takayuki; Kitamura, Kazuaki; Yamada, Hideto; Hishida, Tomoko; Yamazaki, Masato
2017-06-01
We developed a (K,Na)NbO3-based lead-free piezoelectric ceramic with a KTiNbO5 system, (K1- x Na x )0.86Ca0.04Li0.02Nb0.85O3-δ-K0.85Ti0.85Nb1.15O5-BaZrO3-Fe2O3-MgO (K1- x N x N-NTK-FM). K1- x N x N-NTK-FM ceramic exhibits a very dense microstructure and a coupling coefficient of k p = 0.59, which is almost comparable to that of conventional lead zirconate titanate (PZT). The (K,Na)NbO3-based ceramic has the Γ15 mode for a wide x range. The nanodomains of orthorhombic (K,Na)NbO3 with the M3 mode coexist within the tetragonal Γ15 mode (K,Na)NbO3 matrix. Successive phase transition cannot occur with increasing x. The maximum k p is observed at approximately the minimum x required to generate the M3 mode phase. Unlike the behavior at the morphotropic phase boundary (MPB) in PZT, the characteristics of K1- x N x N-NTK-FM ceramic in this region changed moderately. This gentle phase transition seems to be a relaxor, although the diffuseness degree is not in line with this hypothesis. Furthermore, piezoelectric properties change from “soft” to “hard” upon the M3 mode phase aggregation.
Prospect for a 60 GHz multicharged ECR ion source
NASA Astrophysics Data System (ADS)
Thuillier, T.; Bondoux, D.; Angot, J.; Baylac, M.; Froidefond, E.; Jacob, J.; Lamy, T.; Leduc, A.; Sole, P.; Debray, F.; Trophime, C.; Skalyga, V.; Izotov, I.
2018-05-01
The conceptual design of a fourth generation hybrid electron cyclotron resonance (ECR) ion source operated at 60 GHz is proposed. The axial magnetic mirror is generated with a set of three Nb3Sn coils, while the hexapole is made with room temperature (RT) copper coils. The motivations for such a hybrid development are to study further the ECR plasma physics and the intense multicharged ion beams' production and transport at a time when a superconducting (SC) hexapole appears unrealistic at 60 GHz. The RT hexapole coil designed is an evolution of the polyhelix technology developed at the French High Magnetic Field Facility. The axial magnetic field is generated by means of 3 Nb3Sn SC coils operated with a maximum current density of 350 A/mm2 and a maximum coil load line factor of 81%. The ECR plasma chamber resulting from the design features an inner radius of 94 mm and a length of 500 mm. The radial magnetic intensity is 4.1 T at the wall. Characteristic axial mirror peaks are 8 and 4.5 T, with 1.45 T minimum in between.
Wang, Xing; Zhang, Ligang; Guo, Ziyi; Jiang, Yun; Tao, Xiaoma; Liu, Libin
2016-09-01
CALPHAD-type modeling was used to describe the single-crystal elastic constants of the bcc solution phase in the ternary Ti-Nb-Zr system. The parameters in the model were evaluated based on the available experimental data and first-principle calculations. The composition-elastic properties of the full compositions were predicted and the results were in good agreement with the experimental data. It is found that the β phase can be divided into two regions which are separated by a critical dynamical stability composition line. The corresponding valence electron number per atom and the polycrystalline Young׳s modulus of the critical compositions are 4.04-4.17 and 30-40GPa respectively. Orientation dependencies of single-crystal Young׳s modulus show strong elastic anisotropy on the Ti-rich side. Alloys compositions with a Young׳s modulus along the <100> direction matching that of bone were found. The current results present an effective strategy for designing low modulus biomedical alloys using computational modeling. Copyright © 2016 Elsevier Ltd. All rights reserved.
Xia, Qineng; Zhuang, Xiaojing; Li, Molly Meng-Jung; Peng, Yung-Kang; Liu, Guoliang; Wu, Tai-Sing; Soo, Yun-Liang; Gong, Xue-Qing; Wang, Yanqin; Tsang, Shik Chi Edman
2016-04-14
Near quantitative carbon yields of diesel-range alkanes were achieved from the hydrodeoxygenation of triglycerides over Pd/NbOPO4 under mild conditions with no catalyst deactivation: catalyst characterization and theoretical calculations suggest that the high hydrodeoxygenation activity originated from the synergistic effect of Pd and strong Lewis acidity on the unique structure of NbOPO4.
Hydrometallurgical Separation of Niobium and Tantalum: A Fundamental Approach
NASA Astrophysics Data System (ADS)
Nete, Motlalepula; Purcell, Walter; Nel, Johann T.
2016-02-01
A mixture of pure Ta2O5 and Nb2O5 was dissolved using two different fluxes, namely NH4F·HF and Na2HPO4/NaH2PO4·H2O. Selective precipitation and ion exchange were used as separation techniques. Selective precipitation using p-phenylediamine in a fluoride matrix resulted in the isolation of 73(3)% tantalum accompanied by 23(5)% niobium. A separation factor of 11(4) was obtained. A single solvent extraction step using methyl-isobutyl ketone at a 4 M H2SO4 yielded excellent Ta and Nb separation in the fluoride solution with 80% of the Ta and only 2% Nb recovered in the organic layer. A two-step extraction recovered 100% Ta at 0.5-4 M H2SO4 with a separation factor of ~2000. A study of the extraction mechanism indicated that the stability of the protonated compounds such as H2TaF7/H2NbOF5 is in the extraction and separation determining steps in this process. A K' (double de-protonated constant) of approximately 0.2 was calculated for H2TaF7. Only 91.7% Nb and 73.4% Ta were recovered from anion separation using strong Amberlite resin and 96.1% Nb and 52.3% using the weak Dowex Marathon resin from fluoride dissolution.
Efficiency of Nb-Doped ZnO Nanoparticles Electrode for Dye-Sensitized Solar Cells Application
NASA Astrophysics Data System (ADS)
Anuntahirunrat, Jirapat; Sung, Youl-Moon; Pooyodying, Pattarapon
2017-09-01
The technological of Dye-sensitized solar cells (DSSCs) had been improved for several years. Due to its simplicity and low cost materials with belonging to the part of thin films solar cells. DSSCs have numerous advantages and benefits among the other types of solar cells. Many of the DSSC devices had use organic chemical that produce by specific method to use as thin film electrodes. The organic chemical that widely use to establish thin film electrodes are Zinc Oxide (ZnO), Titanium Dioxide (TiO2) and many other chemical substances. Zinc oxide (ZnO) nanoparticles had been used in DSSCs applications as thin film electrodes. Nanoparticles are a part of nanomaterials that are defined as a single particles 1-100 nm in diameter. From a few year ZnO widely used in DSSC applications because of its optical, electrical and many others properties. In particular, the unique properties and utility of ZnO structure. However the efficiency of ZnO nanoparticles based solar cells can be improved by doped various foreign impurity to change the structures and properties. Niobium (Nb) had been use as a dopant of metal oxide thin films. Using specification method to doped the ZnO nanoparticles thin film can improved the efficiencies of DSSCs. The efficiencies of Nb-doped ZnO can be compared by doping 0 at wt% to 5 at wt% in ZnO nanoparticles thin films that prepared by the spin coating method. The thin film electrodes doped with 3 at wt% represent a maximum efficiencies with the lowest resistivity of 8.95×10-4 Ω·cm.
Function of endoplasmic reticulum calcium ATPase in innate immunity-mediated programmed cell death
Zhu, Xiaohong; Caplan, Jeffrey; Mamillapalli, Padmavathi; Czymmek, Kirk; Dinesh-Kumar, Savithramma P
2010-01-01
Programmed cell death (PCD) initiated at the pathogen-infected sites during the plant innate immune response is thought to prevent the development of disease. Here, we describe the identification and characterization of an ER-localized type IIB Ca2+-ATPase (NbCA1) that function as a regulator of PCD. Silencing of NbCA1 accelerates viral immune receptor N- and fungal-immune receptor Cf9-mediated PCD, as well as non-host pathogen Pseudomonas syringae pv. tomato DC3000 and the general elicitor cryptogein-induced cell death. The accelerated PCD rescues loss-of-resistance phenotype of Rar1, HSP90-silenced plants, but not SGT1-silenced plants. Using a genetically encoded calcium sensor, we show that downregulation of NbCA1 results in the modulation of intracellular calcium signalling in response to cryptogein elicitor. We further show that NbCAM1 and NbrbohB function as downstream calcium decoders in N-immune receptor-mediated PCD. Our results indicate that ER-Ca2+-ATPase is a component of the calcium efflux pathway that controls PCD during an innate immune response. PMID:20075858
Savych, Iuliia; Subianto, Surya; Nabil, Yannick; Cavaliere, Sara; Jones, Deborah; Rozière, Jacques
2015-07-14
Novel platinum-catalysed, corrosion-resistant, loose-tube-structured electrocatalysts for proton exchange membrane fuel cells have been obtained using single-needle electrospinning associated with a microwave-assisted polyol method. Monodisperse platinum particles supported on Nb-SnO2 demonstrated higher electrochemical stability than conventional Pt/C electrodes during ex situ potential cycling and comparable activity in the oxygen reduction reaction. In situ fuel cell operation under accelerated stress test conditions of a membrane electrode assembly elaborated using a Pt/C anode and Pt/Nb-SnO2 cathode confirmed that the voltage loss is significantly lower for the novel cathode than for an MEA prepared using conventional Pt/C supported electrocatalysts. Furthermore, the Nb-SnO2 stabilised the supported platinum nanoparticles against dissolution, migration and reprecipitation in the membrane. Pt/Nb-SnO2 loose-tubes constitute a mitigation strategy for two known degradation mechanisms in PEMFC: corrosion of the carbon support at the cathode, and dissolution of Pt at high cell voltages.
2011 Final Report - Nano-Oxide Photocatalysis for Solar Energy Conversion
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eckstein, James N.; Suslick, Kenneth S.
2011-10-19
We have very recently discovered a new hydrogen-producing photocatalyst is BiNbO4. BiNbO4 powders prepared by solid state reaction were tested for photocatalytic activity in methanol solutions under UV irradiation. When the material is tested without the presence of a Pt co-catalyst, photocatalytic activity for H2 evolution is superior to that of TiO2. It was also found that BiNbO4 photodegrades into metallic Bi and reduced Nb oxides after use; materials were characterized by SEM, XRD, and XPS. Adding Pt to the surface of the photocatalyst increases photocatalytic activity and importantly, helps to prevent photodegradation of the oxide material. With 1 wt.more » % Pt loading, photodegradation is essentially absent. BiNbO4 photodegrades into metallic Bi and reduced Nb oxides after use; materials were characterized by SEM, XRD, and XPS. Adding Pt to the surface of the photocatalyst increases photocatalytic activity and importantly, helps to prevent photodegradation of the oxide material. With 1 wt. % Pt loading, photodegradation is essentially absent.« less
Silica passivated conjugated polymer nanoparticles for biological imaging applications
NASA Astrophysics Data System (ADS)
Bourke, Struan; Urbano, Laura; Olona, Antoni; Valderrama, Ferran; Dailey, Lea Ann; Green, Mark A.
2017-02-01
Colorectal and prostate cancers are major causes of cancer-related death, with early detection key to increased survival. However, as symptoms occur during advanced stages and current diagnostic methods have limitations, there is a need for new fluorescent probes that remain bright, are biocompatible and can be targeted. Conjugated polymer nanoparticles have shown great promise in biological imaging due to their unique optical properties. We have synthesised small, bright, photo-stable CN-PPV, nanoparticles encapsulated with poloxamer polymer and a thin silica shell. By incubating the CN-PPV silica shelled cross-linked (SSCL) nanoparticles in mammalian (HeLa) cells; we were able to show that cellular uptake occurred. Uptake was also shown by incubating the nanoparticles in RWPE-1, WPE1-NB26 and WPE1- NA22 prostate cancer cell lines. Finally, HEK cells were used to show the particles had limited cytotoxicity.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dunstan, Matthew T., E-mail: m.dunstan@chem.usyd.edu.au; Southon, Peter D.; Kepert, Cameron J.
Through the construction of the Ba{sub 4}Nb{sub 2-x}Ta{sub x}O{sub 9} phase diagram, it was discovered that the unique high-temperature {gamma} phase is a thermodynamic intermediate between the low-temperature {alpha} phase (Sr{sub 4}Ru{sub 2}O{sub 9}-type) and a 6H-perovskite. Refined site occupancies for the {gamma} phase across the Ba{sub 4}Nb{sub 2-x}Ta{sub x}O{sub 9} solid-solution indicate that Nb preferentially occupies the tetrahedral sites over the octahedral sites in the structure. When annealed in a CO{sub 2}-rich atmosphere, all of the phases studied absorb large amounts of CO{sub 2} at high temperatures between {approx}700 and 1300 K. In situ controlled-atmosphere diffraction studies show thatmore » this behaviour is linked to the formation of BaCO{sub 3} on the surface of the material, accompanied by a Ba{sub 5}(Nb,Ta){sub 4}O{sub 15} impurity phase. In situ diffraction in humid atmospheres also confirms that these materials hydrate below {approx}1273K, and that this plays a critical role in the various reconstructive phase transitions as well as giving rise to proton conduction. - Graphical abstract: Thermodynamic phase diagram of Ba{sub 4}Nb{sub 2-x}Ta{sub x}O{sub 9}. Highlights: > {gamma}-Ba{sub 4}Nb{sub 2}O{sub 9} phase is a structural intermediate between the {alpha} and 6H-perovskite phases. > Ba{sub 4}Nb{sub 2}O{sub 9} and Ba{sub 4}Ta{sub 2}O{sub 9} decompose at high temperatures in the presence of CO{sub 2}. > These materials all absorb between 5% and 6% of CO{sub 2} by mass between {approx}800 and 1200 K.« less
New red Y 0.85Bi 0.1Eu 0.05V 1-yM yO 4 (M=Nb, P) phosphors for light-emitting diodes
NASA Astrophysics Data System (ADS)
Wang, Yuhua; Sun, Yunkui; Zhang, Jiachi; Ci, Zhipeng; Zhang, Zhiya; Wang, Lei
2008-06-01
The Y 0.85Bi 0.1Eu 0.05V 1-yM yO 4 (M=Nb, P) as new near-ultraviolet excited phosphors were synthesized and their luminescence properties under 365 nm excitation were investigated in detail. It indicated that by doping small amount of P 5+ into V 5+ sites, the excitation intensity of charge transfer (CT) band of Bi-O (330-400 nm) was greatly improved. By substituting Nb 5+ for V 5+, both the CT bands of Bi-O and Eu-O (240-320 nm) were significantly enhanced. As a result, the emission intensity of Y 0.85Bi 0.1Eu 0.05V 1-yM yO 4 (M=Nb, P) could be improved about 90% by doping 5 mol% P 5+ and 110% by doping 5 mol% Nb 5+. Comparing with the commercial Y 2O 2S:Eu 3+ phosphors, the Y 0.85Bi 0.1Eu 0.05V 0.95M 0.05O 4 (M=Nb, P) phosphors exhibited excellent color purity and much higher brightness. The results showed that these Y 0.85Bi 0.1Eu 0.05V 1-yM yO 4 (M=Nb, P) phosphors could be considered as promising red phosphors for application in LED.
NASA Astrophysics Data System (ADS)
Apparao, K. Ch; Birru, Anil Kumar
2018-01-01
A novel Al-3.5FeNb-1.5C master alloy with uniform microstructure was prepared using a melt reaction process for this study. In the master alloy, basic intermetallic particles such as NbAl3, NbC act as heterogeneous nucleation substrates during the solidification of aluminium. The grain refining performance of the novel master alloy on Al-Si9.8-Cu3.4 alloy has also been investigated. It is observed that the addition of 0.1 wt.% of Al-3.5FeNb-1.5C master alloy can induce very effective grain refinement of the Al-Si9.8-Cu3.4 alloy. The average grain size of α-Al is reduced to 22.90 μm from about 61.22 μm and most importantly, the inoculation of Al-Si9.8-Cu3.4 alloy with FeNb-C is not characterised by any visible poisoning effect, which is the drawback of using commercial Al-Ti-B master alloys on aluminium cast alloys. Therefore, the mechanical properties of the Al-Si9.8-Cu3.4 alloy have been improved obviously by the addition of the 0.1 wt.% of Al-3.5FeNb-1.5C master alloy, including the yield strength and elongation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Devesa, S.; Graça, M.P.; Costa, L.C., E-mail: kady@ua.pt
2016-06-15
Highlights: • The thermal treatment at 1200 °C generates a non-stoichiometric secondary phase. • The secondary phase Bi{sub 3.54}Nb{sub 7.09}O{sub 22.7}, is responsible for the highest Q × f and density. • The samples with triclinic BiNbO{sub 4} have the highest ε′. - Abstract: BiNbO{sub 4} ceramic powders were prepared using the sol-gel method. The fine particles were pressed into cylinders and, then, they were treated at temperatures between 500 and 1150 °C. The structure was studied by X-ray diffraction and Raman spectroscopy and the morphology was observed by scanning electron microscopy. The measurements of the complex permittivity were mademore » in a resonant cavity operating at 2.7 GHz, using the small perturbation method. The reversible phase transformation between β-BiNbO{sub 4} and α-BiNbO{sub 4} was observed. The density, dielectric constant (ε') and the dielectric loss (tg δ) of the prepared powders increase with the sintering temperature, and the sample treated at 1150 °C shows the highest ε' and the highest Q × f.« less
Dielectric and Energy Storage Properties of Ba0.65Sr0.35TiO3 Ceramics Modified by BiNbO4
NASA Astrophysics Data System (ADS)
Zheng, Yi; Zhang, Jihua; Wei, Meng; Dong, Xiangxiang; Huang, Jiapeng; Wu, Kaituo; Chen, Hongwei
2018-02-01
(1 - x) (Ba0.65Sr0.35TiO3)-xBiNbO4 (x = 0.0-0.15) ceramic were prepared by solid-state reaction method. The phase composition, microstructure, dielectric properties, polarization-electric field, breakdown strength and energy storage behaviors for the BiNbO4-modified Ba0.65Sr0.35TiO3 ceramics were investigated. With the addition of BiNbO4, the remnant polarization and saturation polarization decreased and the nonlinearity was suppressed. When x = 0.07, the maximum recoverable energy storage achieved was 0.5 J/cm3, 1.5 times that of un-doped Ba0.65Sr0.35TiO3 ceramics, with an efficiency of 96.89% and a breakdown electric field reaching 15.3 kV/mm. Therefore, BiNbO4 doping could improve the energy storage properties of Ba0.65Sr0.35TiO3 for high-energy pulse capacitor application.
Zhang, Qingmeng; Luo, Jun; Tang, Qun; Han, Dongfang; Zhou, Yi; Du, Jun
2012-11-01
Nanocomposite dielectrics in 6PbO-4BaO-20Na2O-40Nb2O5-30SiO2 system were prepared via melt-quenching followed by controlled crystallization. X-ray diffraction studies reveal that Pb2Nb2O7, Ba,NaNb5O15, NaNbO3 and PbNb2O6 phases are formed from the as-quenched glass annealed in temperature range from 700 degrees C to 850 degrees C. Ba2NaNb5O15, Pb2Nb2O7 crystallizes at 700 degrees C and then Pb2Nb2O7 disappears at 850 degrees C, while PbNb2O6 and NaNbO3 are formed at 850 degrees C. Microstructural observation shows that the crystallized particles are nanometer-sized and randomly distributed with glass matrix being often found at grain boundaries. The dielectric constant of the nanocomposites formed at different crystallization temperatures shows good frequency and electric field stability. The breakdown strength is slightly decreased when the glass-ceramics thickness is varied from 1 mm to 4 mm. The corresponding energy density could reach 2.96 J/cm3 with a breakdown strength of 58 kV/mm for thickness of 1 mm.
NASA Astrophysics Data System (ADS)
Touzani, Rachid St.; Fokwa, Boniface P. T.
2014-03-01
The Nb2FeB2 phase (U3Si2-type, space group P4/mbm, no. 127) is known for almost 50 years, but until now its magnetic properties have not been investigated. While the synthesis of Nb2OsB2 (space group P4/mnc, no. 128, a twofold superstructure of U3Si2-type) with distorted Nb-layers and Os2-dumbbells was recently achieved, "Nb2RuB2" is still not synthesized and its crystal structure is yet to be revealed. Our first principles density functional theory (DFT) calculations have confirmed not only the experimental structures of Nb2FeB2 and Nb2OsB2, but also predict "Nb2RuB2" to crystalize with the Nb2OsB2 structure type. According to chemical bonding analysis, the homoatomic B-B interactions are optimized and very strong, but relatively strong heteroatomic M-B, B-Nb and M-Nb bonds (M=Fe, Ru, Os) are also found. These interactions, which together build a three-dimensional network, are mainly responsible for the structural stability of these ternary borides. The density-of-states at the Fermi level predicts metallic behavior, as expected, from metal-rich borides. Analysis of possible magnetic structures concluded preferred antiferromagnetic ordering for Nb2FeB2, originating from ferromagnetic interactions within iron chains and antiferromagnetic exchange interactions between them.
Opoku, Francis; Kuben Govender, Krishna; van Sittert, Cornelia Gertina Catharina Elizabeth; Poomani Govender, Penny
2017-10-25
In the 21st century, the growing demand of global energy is one of the key challenges. The photocatalytic generation of hydrogen has attracted extensive attention to discuss the increasing global demand for sustainable and clean energy. However, hydrogen evolution reactions normally use the economically expensive rare noble metals and the processes remain a challenge. Herein, low-cost BiNbO 4 /MWO 4 (010) heterostructures are studied for the first time to check their suitability towards photocatalytic hydrogen production. A theoretical study with the aid of density functional theory (DFT) is used to investigate the synergistic effect, ionisation energy, electron affinities, charge transfer, electronic properties and the underlying mechanism for hydrogen generation of BiNbO 4 /MWO 4 (010) heterostructures. The experimental band gaps of bulk ZnWO 4 , CdWO 4 and BiNbO 4 are well reproduced using the DFT+U method. The calculated band edge position shows a type-II staggered band alignment and the charge transfer between BiNbO 4 and MWO 4 monolayers results in a large interfacial built-in potential, which will favour the separation of charge carriers in the heterostructures. The effective mass of the photoinduced holes is higher compared to the electrons, making the heterostructures useful in hydrogen production. The relatively low ionisation energy and electron affinity for the heterostructures compared to the monolayers make them ideal for photocatalysis applications due to their small energy barrier for the injection of electrons and creation of holes. The BiNbO 4 /MWO 4 (010) heterostructures are more suitable for photocatalytic hydrogen production due to their strong reducing power relative to the H + /H 2 O potential. This study sheds light on the less known BiNbO 4 /ZnWO 4 (010) heterostructures and the fully explored electronic and optical properties will pave way for future photocatalytic water splitting applications.
Overcoming CRPC Treatment Resistance via Novel Dual AKR1C3 Targeting
2017-10-01
We therefore characterized another drug resistant line from C4-2B cells, C4-2B AbiR cells. C4-2B AbiR cells were resistant to Abi acetate in a...Testosterone level in C4-2B AbiR cell was 12 pg/50 million cells, similar to that in C4-2B MDVR or LNCaP-AKR1C3 cells. With the single drug resistant...cell lines on hand, we tested for their cross- resistance to Enza and Abi. While the parental line was sensitive to both drugs , the resistant lines
Hollingsworth, M A; Strawhecker, J M; Caffrey, T C; Mack, D R
1994-04-15
We examined the steady-state expression levels of mRNA for the MUC1, MUC2, MUC3 and MUC4 gene products in 12 pancreatic tumor cell lines, 6 colon tumor cell lines, and one ileocecal tumor cell line. The results showed that 10 of 12 pancreatic tumor cell lines expressed MUC1 mRNA and that 7 of these 12 lines also expressed relatively high levels of MUC4 mRNA. In contrast, MUC2 mRNA was expressed at only low levels and MUC3 was not detected in the pancreatic tumor cell lines. All 7 intestinal tumor cell lines examined expressed MUC2, and 5 of 7 expressed MUC3; however only one expressed significant levels of MUC1 and 2 expressed low levels of MUC4 mRNA. This report of high levels of MUC4 mRNA expression by pancreatic tumor cells raises the possibility that mucin carbohydrate epitopes defined by antibodies such as DuPan 2 may be expressed on a second mucin core protein produced by pancreatic tumor cells.
Velleman, Sandra G; Clark, Daniel L; Tonniges, Jeffrey R
2018-09-01
Posthatch skeletal muscle growth requires myogenic satellite cells and the dynamic expression of cell membrane-associated proteins. The membrane associated heparan sulfate proteoglycans, syndecan-4 and glypican-1, link the satellite cell niche to the intracellular environment. Sydnecan-4 and glypican-1 are differentially expressed with age in turkey satellite cells and their over-expression impacts both satellite cell proliferation and differentiation, but their effect on satellite cells from lines with different growth potentials is not known. The objective of the current study was to determine if syndecan-4 and glypican-1 regulation of satellite cell proliferation and differentiation is affected by age and growth selection. Pectoralis major satellite cells isolated at 1 d, 7 and 16-wk of age from a Randombred Control 2 (RBC2) line and a 16-wk body weight (F) line selected from the RBC2 line turkeys were studied. Syndecan-4 and glypican-1 expression was knocked down in both lines. The F-line cells proliferated faster than RBC2 line cells regardless of age, while differentiation tended to be greater in RBC2 line cells than F-line cells at each age. Syndecan-4 knockdown decreased proliferation at 7- and 16-wk but not 1 d cells, and increased differentiation at 1 d and 7 wk but not 16 wk cells. Glypican-1 knockdown differentially affected proliferation depending on cell age, whereas differentiation was decreased for 7- and 16-wk but not 1 d cells. These data suggest syndecan-4 and glypican-1 differentially affected satellite cell function in an age-dependent manner, but had little impact on differences in proliferation and differentiation due to growth selection. Copyright © 2018. Published by Elsevier Inc.
Long-term hepatic outcomes in survivors of stage 4S and 4 neuroblastoma in infancy.
French, Amy E; Irwin, Meredith S; Navarro, Oscar M; Greenberg, Mark; Nathan, Paul C
2012-02-01
Infants with stage 4 and 4S neuroblastoma (NB) have a superior prognosis to older children. However, they often require intensive therapy including abdominal radiation. We aimed to investigate the long-term hepatic outcomes in infants with stage 4S and 4 NB. We reviewed the charts of 38 infants diagnosed with stage 4S and 4 NB between 1984 and 2002. We included only those with available follow-up 5 years following diagnosis. We assessed hepatic imaging and function (transaminases, bilirubin, alkaline phosphatase) at all available time points from diagnosis. Abnormalities present at more than 5 years from diagnosis were considered persistent late changes. We identified 15 stage 4S and 12 stage 4 patients. Twelve of 15 stage 4S patients had hepatic involvement at diagnosis, 8 of whom required abdominal radiation. Five of eight demonstrated late imaging changes. Two of four with hepatic metastases but no radiation demonstrated late imaging changes. The late imaging changes resolved over time and without intervention in 3/7 survivors. The persistent lesions included liver fibrosis (1) and focal nodular hyperplasia (FNH) (3). Five of 12 stage 4 NB patients had hepatic involvement at diagnosis; none required radiation or had late hepatic imaging changes. In stage 4S NB, adverse hepatic effects are infrequent, may resolve over time, and occur with or without radiation. FNH should be considered in those with persistent late imaging changes. Adverse hepatic outcomes after liver involvement or radiation in infants with stage 4 NB rarely occur. Copyright © 2011 Wiley Periodicals, Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Woodward, David I., E-mail: d.i.woodward@warwick.ac.uk; Lees, Martin R.; Thomas, Pam A.
2012-08-15
The phase transitions between various structural modifications of the natrotantite-structured system xAg{sub 2}Nb{sub 4}O{sub 11}-(1-x)Na{sub 2}Nb{sub 4}O{sub 11} have been investigated and a phase diagram constructed as a function of temperature and composition. This shows three separate phase transition types: (1) paraelectric-ferroelectric, (2) rhombohedral-monoclinic and (3) a phase transition within the ferroelectric rhombohedral zone between space groups R3c and R3. The parent structure for the entire series has space group R3{sup Macron }c. Compositions with x>0.75 are rhombohedral at all temperatures whereas compositions with x<0.75 are all monoclinic at room temperature and below. At x=0.75, rhombohedral and monoclinic phases coexistmore » with the phase boundary below room temperature being virtually temperature-independent. The ferroelectric phase boundary extends into the monoclinic phase field. No evidence was found for the R3-R3c phase boundary extending into the monoclinic phase field and it is concluded that a triple point is formed. - Graphical abstract: Phase diagram for xAg{sub 2}Nb{sub 4}O{sub 11}-(1-x)Na{sub 2}Nb{sub 4}O{sub 11} solid solution showing changes in crystal symmetry as a function of temperature and composition. The crystal structure is depicted. Highlights: Black-Right-Pointing-Triangle Ferroelectric, rhombohedral Ag{sub 2}Nb{sub 4}O{sub 11} in solid solution with monoclinic Na{sub 2}Nb{sub 4}O{sub 11}. Black-Right-Pointing-Triangle Three phase boundaries were studied as a function of composition and temperature. Black-Right-Pointing-Triangle Both rhombohedral and monoclinic variants exhibit ferroelectricity. The parent phase of the series has space group R3{sup Macron }c.« less
NASA Astrophysics Data System (ADS)
Kim, Minjoong; Kwon, Chorong; Eom, Kwangsup; Kim, Jihyun; Cho, Eunae
2017-03-01
This study explores a facile method to prepare an efficient and durable support for Pt catalyst of polymer electrolyte membrane fuel cell (PEMFC). As a candidate, Nb-doped TiO2 (Nb-TiO2) nanofibers are simply fabricated using an electrospinning technique, followed by a heat treatment. Doping Nb into the TiO2 nanofibers leads to a drastic increase in electrical conductivity with doping level of up to 25 at. % (Nb0.25Ti0.75O2). Pt nanoparticles are synthesized on the prepared 25 at. % Nb-doped TiO2-nanofibers (Pt/Nb-TiO2) as well as on a commercial powdered carbon black (Pt/C). The Pt/Nb-TiO2 nanofiber catalyst exhibits similar oxygen reaction reduction (ORR) activity to that of the Pt/C catalyst. However, during an accelerated stress test (AST), the Pt/Nb-TiO2 nanofiber catalyst retained more than 60% of the initial ORR activity while the Pt/C catalyst lost 65% of the initial activity. The excellent durability of the Pt/Nb-TiO2 nanofiber catalyst can be attributed to high corrosion resistance of TiO2 and strong interaction between Pt and TiO2.
Kim, MinJoong; Kwon, ChoRong; Eom, KwangSup; Kim, JiHyun; Cho, EunAe
2017-03-14
This study explores a facile method to prepare an efficient and durable support for Pt catalyst of polymer electrolyte membrane fuel cell (PEMFC). As a candidate, Nb-doped TiO 2 (Nb-TiO 2 ) nanofibers are simply fabricated using an electrospinning technique, followed by a heat treatment. Doping Nb into the TiO 2 nanofibers leads to a drastic increase in electrical conductivity with doping level of up to 25 at. % (Nb 0.25 Ti 0.75 O 2 ). Pt nanoparticles are synthesized on the prepared 25 at. % Nb-doped TiO 2 -nanofibers (Pt/Nb-TiO 2 ) as well as on a commercial powdered carbon black (Pt/C). The Pt/Nb-TiO 2 nanofiber catalyst exhibits similar oxygen reaction reduction (ORR) activity to that of the Pt/C catalyst. However, during an accelerated stress test (AST), the Pt/Nb-TiO 2 nanofiber catalyst retained more than 60% of the initial ORR activity while the Pt/C catalyst lost 65% of the initial activity. The excellent durability of the Pt/Nb-TiO 2 nanofiber catalyst can be attributed to high corrosion resistance of TiO 2 and strong interaction between Pt and TiO 2 .
Kim, MinJoong; Kwon, ChoRong; Eom, KwangSup; Kim, JiHyun; Cho, EunAe
2017-01-01
This study explores a facile method to prepare an efficient and durable support for Pt catalyst of polymer electrolyte membrane fuel cell (PEMFC). As a candidate, Nb-doped TiO2 (Nb-TiO2) nanofibers are simply fabricated using an electrospinning technique, followed by a heat treatment. Doping Nb into the TiO2 nanofibers leads to a drastic increase in electrical conductivity with doping level of up to 25 at. % (Nb0.25Ti0.75O2). Pt nanoparticles are synthesized on the prepared 25 at. % Nb-doped TiO2-nanofibers (Pt/Nb-TiO2) as well as on a commercial powdered carbon black (Pt/C). The Pt/Nb-TiO2 nanofiber catalyst exhibits similar oxygen reaction reduction (ORR) activity to that of the Pt/C catalyst. However, during an accelerated stress test (AST), the Pt/Nb-TiO2 nanofiber catalyst retained more than 60% of the initial ORR activity while the Pt/C catalyst lost 65% of the initial activity. The excellent durability of the Pt/Nb-TiO2 nanofiber catalyst can be attributed to high corrosion resistance of TiO2 and strong interaction between Pt and TiO2. PMID:28290503
Malloy, Melanie Theodore; McIntosh, Deneshia J; Walters, Treniqka S; Flores, Andrea; Goodwin, J Shawn; Arinze, Ifeanyi J
2013-05-17
Ubiquitylation of Nrf2 by the Keap1-Cullin3/RING box1 (Cul3-Rbx1) E3 ubiquitin ligase complex targets Nrf2 for proteasomal degradation in the cytoplasm and is an extensively studied mechanism for regulating the cellular level of Nrf2. Although mechanistic details are lacking, reports abound that Nrf2 can also be degraded in the nucleus. Here, we demonstrate that Nrf2 is a target for sumoylation by both SUMO-1 and SUMO-2. HepG2 cells treated with As2O3, which enhances attachment of SUMO-2/3 to target proteins, increased SUMO-2/3-modification (polysumoylation) of Nrf2. We show that Nrf2 traffics, in part, to promyelocytic leukemia-nuclear bodies (PML-NBs). Cell fractions harboring key components of PML-NBs did not contain biologically active Keap1 but contained modified Nrf2 as well as RING finger protein 4 (RNF4), a poly-SUMO-specific E3 ubiquitin ligase. Overexpression of wild-type RNF4, but not the catalytically inactive mutant, decreased the steady-state levels of Nrf2, measured in the PML-NB-enriched cell fraction. The proteasome inhibitor MG-132 interfered with this decrease, resulting in elevated levels of polysumoylated Nrf2 that was also ubiquitylated. Wild-type RNF4 accelerated the half-life (t½) of Nrf2, measured in PML-NB-enriched cell fractions. These results suggest that RNF4 mediates polyubiquitylation of polysumoylated Nrf2, leading to its subsequent degradation in PML-NBs. Overall, this work identifies Nrf2 as a target for sumoylation and provides a novel mechanism for its degradation in the nucleus, independent of Keap1.
[The characters and specific features of new human embryonic stem cells lines].
Krylova, T A; Kol'tsova, A M; Zenin, V V; Gordeeva, O F; Musorina, A S; Goriachaia, T S; Shlykova, S A; Kamenetskaia, Iu K; Pinaev, G P; Polianskaia, G G
2009-01-01
Four continuous human embryonic stem cell lines (SC1, SC2, SC3 and SC4), derived from the blastocysts has been described. The cell lines were cultivated on mitotically inactivated human feeder cells. The cell lines SC1 and SC2 have passed through 150 population doublings and the cell lines SC3 and SC4 -- near 120 populations doublings, which exceeds Hayflick limit sufficiently. These cell lines maintain high activity of alkaline phosphatase, expression of transcription factor OCT-4 and cell surface antigens (SSEA-4, TRA-1-60 and TRA-1-81), confirming their ESC status and human specificity. Immunofluorescent detection of antigens, characteristic of ectoderm, endoderm and mesoderm confirms the ability of these cells to retain their pluripotency under in vitro condition. PCR analysis revealed expression of six genes specific for pluripotent cells (OCT-4, NANOG, DPPA3/STELLA, TDGF/CRIPTO and LEFTYA). Correlation between the level of proliferative activity and the character of DNA-bound fluorescent staining was found. Fluorescent dyes, Hoechst 33342 and PI, produced diffuse staining of the nuclei in slowly proliferating cells of the SC1 and SC2 lines. In contrast, in actively proliferating cells of the SC3 and SC4 lines, the clear staining of the nuclei was observed. Upon changing the cultivation condition, proliferative activity of SC3 and SC4 lines decreased and became similar to that of SC1 and SC2 lines. The character of the fluorescent staining of all these lines was also shown to be similar. These results show that quality of the fluorescent staining with Hoechst 33342 and PI reflects the level of proliferation. Possible causes and mechanisms of this feature of human ESC are discussed.
Suresh, S; Unni, Gautam E; Satyanarayana, M; Sreekumaran Nair, A; Mahadevan Pillai, V P
2018-08-15
Guiding and capturing photons at the nanoscale by means of metal nanoparticles and interfacial engineering for preventing back-electron transfer are well documented techniques for performance enhancement in excitonic solar cells. Drifting from the conventional route, we propose a simple one-step process to integrate both metal nanoparticles and surface passivation layer in the porous photoanode matrix of a dye-sensitized solar cell. Silver nanoparticles and Nb 2 O 5 surface passivation layer are simultaneously deposited on the surface of a highly porous nanocrystalline TiO 2 photoanode, facilitating an absorption enhancement in the 465 nm and 570 nm wavelength region and a reduction in back-electron transfer in the fabricated dye-sensitized solar cells together. The TiO 2 photoanodes were prepared by spray pyrolysis deposition method from a colloidal solution of TiO 2 nanoparticles. An impressive 43% enhancement in device performance was accomplished in photoanodes having an Ag-incorporated Nb 2 O 5 passivation layer as against a cell without Ag nanoparticles. By introducing this idea, we were able to record two benefits - the metal nanoparticles function as the absorption enhancement agent, and the Nb 2 O 5 layer as surface passivation for TiO 2 nanoparticles and as an energy barrier layer for preventing back-electron transfer - in a single step. Copyright © 2018 Elsevier Inc. All rights reserved.
Environment Mediated Drug Resistance in Neuroblastoma
2015-12-01
activate STAT3 and MYC in neuroblastomas independently of IL6). Figure 9: Effect of IL-6 knockout crossing with NB- Tag mice. (A) MRI of abdominal...production. (D) Representative MRI images of NB-Tag and NB- Tag/IL-6KO pre-chemotherapy, post 3 and 6 weeks of chemotherapy. Task 6. Contribution of bone...described (16). Cells were lysed in radioimmunoprecipitation assay (RIPA) buffer supplemented with 1 tablet of complete mini-EDTA protease inhibitor
NASA Astrophysics Data System (ADS)
Liu, Siyang; Chen, Xiang; Zhao, Jiayue; Su, Junming; Zhang, Congcong; Huang, Tao; Wu, Jianhua; Yu, Aishui
2018-01-01
Ni-rich cathode materials attract ongoing interest due to their high specific capacity (∼200 mAh g-1). However, these materials suffer rapid capacity fading when charged to a high voltage and cycled at elevated temperature. In this study, we propose a facile method to reconstruct the surface structure of LiNi0.6Co0.2Mn0.2O2 via Nb modification, which integrates the merits of partial Nb5+ doping in the pristine structure and surface Li3NbO4 coating. The obtained results from Rietveld refinement and high resolution transmission electron microscopy confirm that Nb5+ is partially doped into Li+ sites within the surface lattice. Further ex-situ powder X-ray diffraction and kinetic analysis using electrochemical impedance spectroscopy reveal that Nb modification stabilizes the layered structure and facilitates the charge transfer process. Owing to the robust surface structure, 1 mol% Nb modified LiNi0.6Co0.2Mn0.2O2 delivers a discharge capacity of 160.9 mAh g-1 with 91% capacity retention after 100 cycles at 3.0-4.5 V, whereas the discharge capacity of the pristine sample drops to 139.6 mAh g-1, corresponding to 78% of its initial value. The presence of Nb5+ in the Li layer exhibits positive effects on stability of layered structure, and the surface Li3NbO4 coating layer increases interfacial stability, which results in superior electrochemical performance.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Reeves-McLaren, Nik, E-mail: n.reeves@sheffield.ac.uk; Ferrarelli, Matthew C.; Tung, Yuan-Wei
2011-07-15
Subsolidus phase relations in the CuO{sub x}-TiO{sub 2}-Nb{sub 2}O{sub 5} system were determined at 935 deg. C. The phase diagram contains one new phase, Cu{sub 3.21}Ti{sub 1.16}Nb{sub 2.63}O{sub 12} (CTNO) and one rutile-structured solid solution series, Ti{sub 1-3x}Cu{sub x}Nb{sub 2x}O{sub 2}: 0
Thermoelectric properties of Nb3SbxTe7-x compounds
NASA Technical Reports Server (NTRS)
Snyder, J.; Wang, S.; Caillat, T.
2002-01-01
Niobium antimony telluride, Nb3Sbx,Te7-x, was synthesized and tested for thermoelectric properties in the Thermoelectrics group at the Jet Propulsion Laboratory. The forty atoms per unit cell of Nb3Sb2Te5 and its varied mixture of atoms yield acomplicated structure, suggesting that Nb3Sb2Te5 and related compounds may exhibit low thermal conductivity and hence a higher ZT value. Nb3SbxTe7-x, compounds were synthesized and subsequently analyzed for their Seebeck voltage, heat conduction, and electrical resistivity. Results indicate that Nb3Sb2Te5 is a heavily doped semiconductor whose thermoelectric properties are compromised by compensating n-type and p-type carriers. Attempts to dope in favor of either carrier by varying the Sb:Te ratio yielded samples containing secondary metallic phases that dominated the transport properties of the resulting compounds.
Synthesis and microwave dielectric behavior of (Bi1-xPbx)NbO4 ceramics
NASA Astrophysics Data System (ADS)
Butee, S. P.; Kambale, K. R.; Upadhyay, Shaishav; Bashaiah, S.; Raju, K. C. James; Panda, Himanshu
2016-03-01
Ceramic samples of (Bi1-xPbx)NbO4 (x=0, 0.025, 0.05, 0.10, 0.15, 0.20) with 0.75wt.% V2O5 addition sintered at 920∘C, 940∘C and 960∘C are investigated. Pb is selected as a substitute for Bi3+ in BiNbO4 ceramics as it exists in two stable valence states of +2 and +4 and the average valency matches to that of Bi3+. The average Shannon radius (for octahedral coordination) of Pb2+ (1.19Å) and Pb4+(0.775Å) cations is 0.9825Å, which is similar to that of Bi3+ ion (1.03Å). The dense (>94%) polycrystalline (Bi1-xPbx)NbO4 samples fabricated mostly reveal orthorhombic (Pnna) phase (α-BiNbO4, Sp. Gp. 52) by powder XRD. Presence of satellite Pb2Nb2O7 phase, the amount of which is increasing with increase in Pb content, is also noticed. The microwave dielectric constant (ɛr‧) values of the niobates are found to increase from 42 to 71, whereas the quality factor (Qu.f) values are found to decrease from 5400 to 550 GHz with increasing substitution of Pb. The compositions so synthesized are important as hardly there are any microwave dielectric ceramics available with 45<ɛr‧<75.
Mechanism of action of NB2001 and NB2030, novel antibacterial agents activated by beta-lactamases.
Stone, Geoffrey W; Zhang, Qin; Castillo, Rosario; Doppalapudi, V Ramana; Bueno, Analia R; Lee, Jean Y; Li, Qing; Sergeeva, Maria; Khambatta, Gody; Georgopapadakou, Nafsika H
2004-02-01
Two potent antibacterial agents designed to undergo enzyme-catalyzed therapeutic activation were evaluated for their mechanisms of action. The compounds, NB2001 and NB2030, contain a cephalosporin with a thienyl (NB2001) or a tetrazole (NB2030) ring at the C-7 position and are linked to the antibacterial triclosan at the C-3 position. The compounds exploit beta-lactamases to release triclosan through hydrolysis of the beta-lactam ring. Like cephalothin, NB2001 and NB2030 were hydrolyzed by class A beta-lactamases (Escherichia coli TEM-1 and, to a lesser degree, Staphylococcus aureus PC1) and class C beta-lactamases (Enterobacter cloacae P99 and E. coli AmpC) with comparable catalytic efficiencies (k(cat)/K(m)). They also bound to the penicillin-binding proteins of S. aureus and E. coli, but with reduced affinities relative to that of cephalothin. Accordingly, they produced a cell morphology in E. coli consistent with the toxophore rather than the beta-lactam being responsible for antibacterial activity. In biochemical assays, they inhibited the triclosan target enoyl reductase (FabI), with 50% inhibitory concentrations being markedly reduced relative to that of free triclosan. The transport of NB2001, NB2030, and triclosan was rapid, with significant accumulation of triclosan in both S. aureus and E. coli. Taken together, the results suggest that NB2001 and NB2030 act primarily as triclosan prodrugs in S. aureus and E. coli.
A comparative study on NbOx films reactively sputtered from sintered and cold gas sprayed targets
NASA Astrophysics Data System (ADS)
Lorenz, Roland; O'Sullivan, Michael; Fian, Alexander; Sprenger, Dietmar; Lang, Bernhard; Mitterer, Christian
2018-04-01
The aim of this work is to evaluate novel cold gas sprayed Nb targets in a reactive sputter deposition process of thin films with respect to the widely used sintered Nb targets. With the exception of a higher target discharge voltage of ∼100 V for the cold gas sprayed targets and the thus higher film growth rate compared to sintered targets, NbOx films with comparable microstructure and properties were obtained for both target variants. The amorphous films with thicknesses between 2.9 and 4.9 μm present an optical shift from dark and non-transparent towards transparent properties, as the oxygen partial pressure increases. X-ray photoelectron spectroscopy confirms the occurrence of the Nb5+ oxidation state for the highest oxygen partial pressure, while Nb4+ is additionally present at lower oxygen partial pressure settings. With a maximal transparency of ∼80% and a refractive index of ∼2.5, the transparent films show characteristics similar to Nb2O5.
Ti-Doped GaOx Resistive Switching Memory with Self-Rectifying Behavior by Using NbOx/Pt Bilayers.
Park, Ju Hyun; Jeon, Dong Su; Kim, Tae Geun
2017-12-13
Crossbar arrays (CBAs) with resistive random access memory (ReRAM) constitute an established architecture for high-density memory. However, sneak paths via unselected cells increase the total power consumption of these devices and limit the array size. To eliminate such sneak-path problems, we propose a Ti/GaO x /NbO x /Pt structure with a self-rectifying resistive-switching (RS) behavior. In this structure, to reduce the operating voltage, we used a Ti/GaO x stack to increase the number of trap sites in the RS GaO x layer through interfacial reactions between the Ti and GaO x layers. This increase enables easier carrier transport with reduced electric fields. We then adopted a NbO x /Pt stack to add rectifying behavior to the RS GaO x layer. This behavior is a result of the large Schottky barrier height between the NbO x and Pt layers. Finally, both the Ti/GaO x and NbO x /Pt stacks were combined to realize a self-rectifying ReRAM device, which exhibited excellent performance. Characteristics of the device include a low operating voltage range (-2.8 to 2.5 V), high on/off ratios (∼20), high selectivity (∼10 4 ), high operating speeds (200-500 ns), a very low forming voltage (∼3 V), stable operation, and excellent uniformity for high-density CBA-based ReRAM applications.
Effective passivation of silicon surfaces by ultrathin atomic-layer deposited niobium oxide
NASA Astrophysics Data System (ADS)
Macco, B.; Bivour, M.; Deijkers, J. H.; Basuvalingam, S. B.; Black, L. E.; Melskens, J.; van de Loo, B. W. H.; Berghuis, W. J. H.; Hermle, M.; Kessels, W. M. M. Erwin
2018-06-01
This letter reports on effective surface passivation of n-type crystalline silicon by ultrathin niobium oxide (Nb2O5) films prepared by atomic layer deposition (ALD) and subjected to a forming gas anneal at 300 °C. A champion recombination parameter J0 of 20 fA/cm2 and a surface recombination velocity Seff of 4.8 cm/s have been achieved for ultrathin films of 1 nm. The surface pretreatment was found to have a strong impact on the passivation. Good passivation can be achieved on both HF-treated c-Si surfaces and c-Si surfaces with a wet-chemically grown interfacial silicon oxide layer. On HF-treated surfaces, a minimum film thickness of 3 nm is required to achieve a high level of surface passivation, whereas the use of a wet chemically-grown interfacial oxide enables excellent passivation even for Nb2O5 films of only 1 nm. This discrepancy in passivation between both surface types is attributed to differences in the formation and stoichiometry of interfacial silicon oxide, resulting in different levels of chemical passivation. On both surface types, the high level of passivation of ALD Nb2O5 is aided by field-effect passivation originating from a high fixed negative charge density of 1-2 × 1012 cm-3. Furthermore, it is demonstrated that the passivation level provided by 1 nm of Nb2O5 can be further enhanced through light-soaking. Finally, initial explorations show that a low contact resistivity can be obtained using Nb2O5-based contacts. Together, these properties make ALD Nb2O5 a highly interesting building block for high-efficiency c-Si solar cells.
Microstructure and Mechanical Properties of Vacuum Plasma Sprayed Cu-8Cr-4Nb
NASA Technical Reports Server (NTRS)
Holmes, Richard; Ellis, David; McKechnie, Timothy; Hickman, Robert
1997-01-01
This paper compares the tensile properties of Cu-8Cr-4Nb material produced by VPS to material previously produced by extrusion. The microstructure of the VPS material is also presented. The combustion chamber liner of rocket motors represents an extreme materials application. The liner hot wall is exposed to a 2760 C (5000 F) flame while the cold side is exposed to cryogenic hydrogen liquid. Materials for use in the combustion chamber liner require a combination of high temperature strength, creep resistance, and low cycle fatigue resistance along with high thermal conductivity. The hot side is also subject to localized cycles between reducing and oxidizing environments that degrade the liner by a process called blanching. A new Cu-8 at.% Cr-4 at% Nb (Cu-8Cr-4Nb) alloy has been developed at NASA Lewis Research Center as a replacement for the currently used alloy, NARloy-z (Cu-3 wt.% Ag-0.5 wt.% Zr). The alloy is strengthened by a fine dispersion of Cr2Nb particles. The alloy has better mechanical properties than NARloy-Z while retaining most of the thermal conductivity of pure copper. The alloy has been successfully consolidated by extrusion and hot isostatic pressing (HIPing). However, vacuum plasma spraying (VPS) offers several advantages over prior consolidation methods. VPS can produce a near net shape piece with the profile of the liner. In addition, oxidation resistant and thermal barrier coatings can be incorporated as an integral part of the liner hot wall during the VPS deposition. The low oxygen VPS Cu-8Cr-4Nb exhibits a higher strength than Cu-8Cr-4Nb produced by extrusion at elevated temperatures and a comparable strength at room temperature. Moduli and ductility were not significantly different. However, the ability to produce parts to near-net shape and maintain the good elevated temperature tensile properties of the extruded Cu-8Cr-4Nb makes VPS an attractive processing method for fabricating rocket engine combustion liners.
Diffusion studies and critical current in superconducting Nb-Ti-Ta artificial pinning center wire
NASA Astrophysics Data System (ADS)
Bormio-Nunes, C.; Gomes, P. M. N.; Tirelli, M. A.; Ghivelder, L.
2005-08-01
The diffusion between Nb-20%Ta (wt %) and pure Ti is studied at temperatures of 973, 1023, and 1073K, for duration times among 25 and 121h in an artificial pinning center (APC) wire composed of a Ti core surrounded by a Nb-20%Ta layer. The produced diffusion layer is a ternary alloy with superconducting properties, such as critical field Bc2 and critical current density JC, which intrinsically depend on the layer composition. Measurements of layer morphology and composition were performed, and the results show a preferential diffusion of Nb and Ta into Ti. There is a slight diffusion of Ti into Nb through grain boundaries. The presence of Ta also slows down the diffusion of Nb in Ti if compared to the couple formed by pure Nb and Ti. Regarding the mechanical properties of the composite wire, the use of lower temperatures to form the ternary phase is desirable in order to avoid a larger portion of the diffusion layer rich in Ti that favorites α-Ti precipitations that are detrimental to the wire ductility. The best JC value was obtained for the sample heat treated at 973K. The improvement of the flux-line pinning was associated with a sharp change of the diffusion layer composition rather than pinning by normal layer interfaces, suggesting a new source of pinning in this kind of material. Nb-Ti-Ta ternary alloys have the potential to be used in superconducting magnets when fields above 12T are required.
Zimbabweite, a new alkali-lead arsenic tantalate from St Anns mine, Karoi district, Zimbabwe.
Foord, E.E.; Taggart, J.E.; Gaines, R.V.; Grubb, P.L.C.; Kristiansen, R.
1986-01-01
Zimbabweite occurs as honey yellow-brown crystals (= or 2.10, 2Vgamma approx 80o, dispersion very strong v > r; alpha (pale yellow brown) = c, beta (light reddish brown = b, gamma (reddish brown) = a. Mean reflectance in air for an (010) = alpha -gamma cleavage plate is 16.6% at 589 nm. Chemical analysis gave Ta2O5 46.5, As2O3 26.5, PbO 15.0, Nb2O5 4.8, Na2O 3.1 K2O 1.5, TiO2 1.4, BaO 0.4, UO2 0.3, Bi2O3 0.2, H2O 0.19, SnO2 0.1, F 0.04, SrO 0.02, less O = F 0.02, = 100.05, leading to the idealized formula (Na,K)2PbAs4(Ta,Nb,Ti)4O18. Indexed XRD powder data are tabulated; strongest lines 3.195(100), 2.990(70), 2.882(70), 3.033(60), 3.823(55), 2.548(50), 1.913(50) A; a 12.233, b 15.292, c 8.665; A; space group Ccma or Cc2a, Z = 4. The TG curve shows a rapid weight loss of approx 22.5% at 840-900oC, due to the loss of As2O5.-R.A.H.
Fabrication and Characterization of Novel Refractory Coatings Using Combinatorial Nanocalorimetry
2015-07-21
The report summarizes the results of solid-state reaction in Zr /B and Zr /B4C multilayers, oxidation of ZrB2, the effect of Nb and C doping on the...oxidation resistance of the coatings at temperatures below 1000 K, but the temperature-dependence of the diffusion rate constant suggests that Nb ...28 B4. Zr -B- Nb oxidation
Beneficial read-through of a USH1C nonsense mutation by designed aminoglycoside NB30 in the retina.
Goldmann, Tobias; Rebibo-Sabbah, Annie; Overlack, Nora; Nudelman, Igor; Belakhov, Valery; Baasov, Timor; Ben-Yosef, Tamar; Wolfrum, Uwe; Nagel-Wolfrum, Kerstin
2010-12-01
The human Usher syndrome (USH) is the most frequent cause of inherited combined deaf-blindness. USH is clinically and genetically heterogeneous, assigned to three clinical types. The most severe type is USH1, characterized by profound inner ear defects and retinitis pigmentosa. Thus far, no effective treatment for the ophthalmic component of USH exists. The p.R31X nonsense mutation in USH1C leads to a disease causing premature termination of gene translation. Here, we investigated the capability of the novel synthetic aminoglycoside NB30 for the translational read-through of the USH1C-p.R31X nonsense mutation as a retinal therapy option. Read-through of p.R31X by three commercial, clinically applied aminoglycosides and the synthetic derivative NB30 was validated in vitro, in cell culture, and in retinal explants. Restoration of harmonin functions was monitored in GST pull-downs (scaffold function) and by F-actin bundling analysis in HEK293T cells. Biocompatibility of aminoglycosides was determined in retinal explants by TUNEL assays. In vitro translation and analyses of transfected HEK293T cells revealed a dose-dependent read-through by all aminoglycosides. In addition, gentamicin, paromomycin, and NB30 induced read-through of p.R31X in mouse retinal explants. The read-through of p.R31X restored harmonin protein function. In contrast to all commercial aminoglycosides NB30 showed good biocompatibility. Commercial aminoglycosides and NB30 induced significant read-through of the USH1C-p.R31X nonsense mutation. However, the observed read-through efficiency, along with its significantly reduced toxicity and good biocompatibility, indicate that the novel derivate NB30 represents a better choice than commercial aminoglycosides in a read-through therapy of USH1C and other ocular diseases.
Comparison of metal release from various metallic biomaterials in vitro.
Okazaki, Yoshimitsu; Gotoh, Emiko
2005-01-01
To investigate the metal release of each base and alloying elements in vitro, SUS316L stainless steel, Co-Cr-Mo casting alloy, commercially pure Ti grade 2, and Ti-6Al-4V, V-free Ti-6Al-7Nb and Ti-15Zr-4Nb-4Ta alloys were immersed in various solutions, namely, alpha-medium, PBS(-), calf serum, 0.9% NaCl, artificial saliva, 1.2 mass% L-cysteine, 1 mass% lactic acid and 0.01 mass% HCl for 7d. The difference in the quantity of Co released from the Co-Cr-Mo casting alloy was relatively small in all the solutions. The quantities of Ti released into alpha-medium, PBS(-), calf serum, 0.9% NaCl and artificial saliva were much lower than those released into 1.2% L-cysteine, 1% lactic acid and 0.01% HCl. The quantity of Fe released from SUS316L stainless steel decreased linearly with increasing pH. On the other hand, the quantity of Ti released from Ti materials increased with decreasing pH, and it markedly attenuated at pHs of approximately 4 and higher. The quantity of Ni released from stainless steel gradually decreased with increasing pH. The quantities of Al released from the Ti-6Al-4V and Ti-6Al-7Nb alloys gradually decreased with increasing pH. A small V release was observed in calf serum, PBS(-), artificial saliva, 1% lactic acid, 1.2% l-cysteine and 0.01% HCl. The quantity of Ti released from the Ti-15Zr-4Nb-4Ta alloy was smaller than those released from the Ti-6Al-4V and Ti-6Al-7Nb alloys in all the solutions. In particular, it was approximately 30% or smaller in 1% lactic acid, 1.2% L-cysteine and 0.01% HCl. The quantity of (Zr + Nb + Ta) released was also considerably lower than that of (Al + Nb) or (Al + V) released. Therefore, the Ti-15Zr-4Nb-4Ta alloy with its low metal release in vitro is considered advantageous for long-term implants. Copyright 2004 Elsevier Ltd.
Intrinsic high electrical conductivity of stoichiometric SrNb O3 epitaxial thin films
NASA Astrophysics Data System (ADS)
Oka, Daichi; Hirose, Yasushi; Nakao, Shoichiro; Fukumura, Tomoteru; Hasegawa, Tetsuya
2015-11-01
SrV O3 and SrNb O3 are perovskite-type transition-metal oxides with the same d1 electronic configuration. Although SrNb O3 (4 d1 ) has a larger d orbital than SrV O3 (3 d1 ), the reported electrical resistivity of SrNb O3 is much higher than that of SrV O3 , probably owing to nonstoichiometry. In this paper, we grew epitaxial, high-conductivity stoichiometric SrNb O3 using pulsed laser deposition. The growth temperature strongly affected the Sr/Nb ratio and the oxygen content of the films, and we obtained stoichiometric SrNb O3 at a very narrow temperature window around 630 °C. The stoichiometric SrNb O3 epitaxial thin films grew coherently on KTa O3 (001) substrates with high crystallinity. The room-temperature resistivity of the stoichiometric film was 2.82 ×10-5Ω cm , one order of magnitude lower than the lowest reported value of SrNb O3 and comparable with that of SrV O3 . We observed a T -square dependence of resistivity below T*=180 K and non-Drude behavior in near-infrared absorption spectroscopy, attributable to the Fermi-liquid nature caused by electron correlation. Analysis of the T -square coefficient A of resistivity experimentally revealed that the 4 d orbital of Nb that is larger than the 3 d ones certainly contributes to the high electrical conduction of SrNb O3 .
2011-01-01
Background Plant lipoxygenases (LOXs) have been proposed to form biologically active compounds both during normal developmental stages such as germination or growth as well as during responses to environmental stress such as wounding or pathogen attack. In our previous study, we found that enzyme activity of endogenous 9-LOX in Nicotiana benthamiana was highly induced by agroinfiltration using a tobacco mosaic virus (TMV) based vector system. Results A LOX gene which is expressed after treatment of the viral vectors was isolated from Nicotiana benthamiana. As the encoded LOX has a high amino acid identity to other 9-LOX proteins, the gene was named as Nb-9-LOX. It was heterologously expressed in yeast cells and its enzymatic activity was characterized. The yeast cells expressed large quantities of stable 9-LOX (0.9 U ml-1 cell cultures) which can oxygenate linoleic acid resulting in high yields (18 μmol ml-1 cell cultures) of hydroperoxy fatty acid. The product specificity of Nb-9-LOX was examined by incubation of linoleic acid and Nb-9-LOX in combination with a 13-hydroperoxide lyase from watermelon (Cl-13-HPL) or a 9/13-hydroperoxide lyase from melon (Cm-9/13-HPL) and by LC-MS analysis. The result showed that Nb-9-LOX possesses both 9- and 13-LOX specificity, with high predominance for the 9-LOX function. The combination of recombinant Nb-9-LOX and recombinant Cm-9/13-HPL produced large amounts of C9-aldehydes (3.3 μmol mg-1 crude protein). The yield of C9-aldehydes from linoleic acid was 64%. Conclusion The yeast expressed Nb-9-LOX can be used to produce C9-aldehydes on a large scale in combination with a HPL gene with 9-HPL function, or to effectively produce 9-hydroxy-10(E),12(Z)-octadecadienoic acid in a biocatalytic process in combination with cysteine as a mild reducing agent. PMID:21450085
NASA Astrophysics Data System (ADS)
Zeng, H. J.; Zhang, L. Q.; Lin, J. P.; He, X. Y.; Zhang, Y. C.; Jia, P.
2012-12-01
Hot dip galvanizing has been extensively employed for corrosion protection of steel structures. However, during the process of galvanization, the corrosion in molten zinc brings many problems to galvanization industry. In this study, as a material of corrosion resistance to molten zinc intended for application in Hot-dip galvanization, HVOF Ti28.15Al63.4Nb8.25Y (at.%) coatings with different bond coats (NiCr5Al, NiCoCrAlY, CoCrAlYTaSi, and NiCr80/20) were deposited onto 316L stainless steel substrate, respectively. The influences of different bond coats on HVOF Ti28.15Al63.4Nb8.25Y coatings were investigated. The results showed that bond coat had an obvious influence on improving the mechanical properties of HVOF Ti28.15Al63.4Nb8.25Y coatings. HVOF Ti28.15Al63.4Nb8.25Y coatings with NiCoCrAlY bond coat displayed the best mechanical properties. However, bond coats had no obvious effects on the microstructure, porosity, and hardness of HVOF Ti28.15Al63.4Nb8.25Y top coatings. The effects of as-received powder morphology and grain size on the characteristics of coatings were also discussed.
NASA Astrophysics Data System (ADS)
Koo, Bon-Ryul; Oh, Dong-Hyeun; Ahn, Hyo-Jin
2018-03-01
Nb-doped TiO2 (Nb-TiO2) blocking layers (BLs) were developed using horizontal ultrasonic spray pyrolysis deposition (HUSPD). In order to improve the photovoltaic properties of the dye-sensitized solar cells (DSSCs), we optimized the Nb doping level of the Nb-TiO2 BLs by controlling the Nb/Ti molar ratio (0, 5, 6, and 7) of the precursor solution for HUSPD. Compared to bare TiO2 BLs, the Nb-TiO2 BLs formed a cascading band structure using the positive shift of the conduction band minimum of the Nb-TiO2 positioned between fluorine-doped tin oxide (FTO) and TiO2. This results in the increase of the potential current and the suppression of the electron recombination. Hence, it led to the improvement of the electrical conductivity, due to the increased electron concentration by the Nb doping into TiO2. Therefore, the DSSC fabricated with the Nb-TiO2 BLs at a Nb/Ti molar ratio of 6 showed superior photoconversion efficiency (∼7.50 ± 0.20%) as a result of the improved short-circuit current density. This is higher than those with the other Nb-TiO2 BLs and without BL. This improvement of the photovoltaic properties for the DSSCs can be attributed to the synergistic effects of uniform and compact BL relative to the prevention of the backward electron transport at the FTO/electrolyte interface, efficient electron transport at interfaces relative to a cascading band structure of FTO/Nb-TiO2/TiO2 multilayers and the facilitated electron transport at the BLs relative to the increased electrical conductivity of the optimized Nb-TiO2 BLs.
Comparison of Fatigue Properties and Fatigue Crack Growth Rates of Various Implantable Metals
Okazaki, Yoshimitsu
2012-01-01
The fatigue strength, effects of a notch on the fatigue strength, and fatigue crack growth rate of Ti-15Zr-4Nb-4Ta alloy were compared with those of other implantable metals. Zr, Nb, and Ta are important alloying elements for Ti alloys for attaining superior long-term corrosion resistance and biocompatibility. The highly biocompatible Ti-15Zr-4Nb-4Ta alloy exhibited an excellent balance between strength and ductility. Its notched tensile strength was much higher than that of a smooth specimen. The strength of 20% cold-worked commercially pure (C.P.) grade 4 Ti was close to that of Ti alloy. The tension-to-tension fatigue strength of an annealed Ti-15Zr-4Nb-4Ta rod at 107 cycles was approximately 740 MPa. The fatigue strength of this alloy was much improved by aging treatment after solution treatment. The fatigue strengths of C.P. grade 4 Ti and stainless steel were markedly improved by 20% cold working. The fatigue strength of Co-Cr-Mo alloy was markedly increased by hot forging. The notch fatigue strengths of 20% cold-worked C.P. grade 4 Ti, and annealed and aged Ti-15Zr-4Nb-4Ta, and annealed Ti-6Al-4V alloys were less than those of the smooth specimens. The fatigue crack growth rate of Ti-15Zr-4Nb-4Ta was the same as that of Ti-6Al-4V. The fatigue crack growth rate in 0.9% NaCl was the same as that in air. Stainless steel and Co-Cr-Mo-Ni-Fe alloy had a larger stress-intensity factor range (ΔK) than Ti alloy.
Kakinuma, Katsuyoshi; Kim, In-Tae; Senoo, Yuichi; Yano, Hiroshi; Watanabe, Masahiro; Uchida, Makoto
2014-12-24
We synthesized Pt and PtRu catalysts supported on Nb-doped SnO(2-δ) (Pt/Sn0.99Nb0.01O(2-δ), PtRu/Sn0.99Nb0.01O(2-δ)) for direct oxidation fuel cells (DOFCs) using poly oxymethylene-dimethyl ether (POMMn, n = 2, 3) as a fuel. The onset potential for the oxidation of simulated fuels of POMMn (methanol-formaldehyde mixtures; n = 2, 3) for Pt/Sn0.99Nb0.01O(2-δ) and PtRu/Sn0.99Nb0.01O(2-δ) was less than 0.3 V vs RHE, which was much lower than those of two commercial catalysts (PtRu black and Pt2Ru3/carbon black). In particular, the onset potential of the oxidation reaction of simulated fuels of POMMn (n = 2, 3) for PtRu/Sn0.99Nb0.01O(2-δ) sintered at 800 °C in nitrogen atmosphere was less than 0.1 V vs RHE and is thus considered to be a promising anode catalyst for DOFCs. The mass activity (MA) of PtRu/Sn0.99Nb0.01O(2-δ) sintered at 800 °C was more than five times larger than those of the commercial catalysts in the measurement temperature range from 25 to 80 °C. Even though the MA for the methanol oxidation reaction was of the same order as those of the commercial catalysts, the MA for the formaldehyde oxidation reaction was more than five times larger than those of the commercial catalysts. Sn from the Sn0.99Nb0.01O(2-δ) support was found to have diffused into the Pt catalyst during the sintering process. The Sn on the top surface of the Pt catalyst accelerated the oxidation of carbon monoxide by a bifunctional mechanism, similar to that for Pt-Ru catalysts.
Vacuum Plasma Spray of CuCrNb Alloy for Advanced Liquid - Fuel Combustion Chambers
NASA Technical Reports Server (NTRS)
Zimmerman, Frank
2000-01-01
The copper-8 atomic percent chromium-4 atomic percent niobium (CuCrNb) alloy was developed by Glenn Research Center (formally Lewis Research Center) as an improved alloy for combustion chamber liners. In comparison to NARloy-Z, the baseline (as in Space Shuttle Main Engine) alloy for such liners, CuCrNb demonstrates mechanical and thermophysical properties equivalent to NARloy-Z, but at temperatures 100 C to 150 C (180 F to 270 F) higher. Anticipated materials related benefits include decreasing the thrust cell liner weight 5% to 20%, increasing the service life at least two fold over current combustion chamber design, and increasing the safety margins available to designers. By adding an oxidation and thermal barrier coating to the liner, the combustion chamber can operate at even higher temperatures. For all these benefits, however, this alloy cannot be formed using conventional casting and forging methods because of the levels of chromium and niobium, which exceed their solubility limit in copper. Until recently, the only forming process that maintains the required microstructure of CrNb intermetallics is powder metallurgy formation of a billet from powder stock, followed by extrusion. This severely limits its usefulness in structural applications, particularly the complex shapes required for combustion chamber liners. Vacuum plasma spray (VPS) has been demonstrated as a method to form structural articles including small combustion chambers from the CuCrNb alloy. In addition, an oxidation and thermal barrier layer can be formed integrally on the hot wall of the liner that improve performance and extend service life. This paper discusses the metallurgy and thermomechanical properties of VPS formed CuCrNb versus the baseline powder metallurgy process, and the manufacturing of small combustion chamber liners at Marshall Space Flight Center using the VPS process. The benefits to advanced propulsion initiatives of using VPS to fabricate combustion chamber liners while maintaining the superior CuCrNb properties are also presented.
NASA Astrophysics Data System (ADS)
Reeves-McLaren, Nik; Ferrarelli, Matthew C.; Tung, Yuan-Wei; Sinclair, Derek C.; West, Anthony R.
2011-07-01
Subsolidus phase relations in the CuO x-TiO 2-Nb 2O 5 system were determined at 935 °C. The phase diagram contains one new phase, Cu 3.21Ti 1.16Nb 2.63O 12 (CTNO) and one rutile-structured solid solution series, Ti 1-3 xCu xNb 2 xO 2: 0< x<0.2335 (35). The crystal structure of CTNO is similar to that of CaCu 3Ti 4O 12 (CCTO) with square planar Cu 2+ but with A site vacancies and a disordered mixture of Cu +, Ti 4+ and Nb 5+ on the octahedral sites. It is a modest semiconductor with relative permittivity ˜63 and displays non-Arrhenius conductivity behavior that is essentially temperature-independent at the lowest temperatures.
Rapid Solidification in Bulk Ti-Nb Alloys by Single-Track Laser Melting
NASA Astrophysics Data System (ADS)
Roehling, John D.; Perron, Aurélien; Fattebert, Jean-Luc; Haxhimali, Tomorr; Guss, Gabe; Li, Tian T.; Bober, David; Stokes, Adam W.; Clarke, Amy J.; Turchi, Patrice E. A.; Matthews, Manyalibo J.; McKeown, Joseph T.
2018-05-01
Single-track laser melting experiments were performed on bulk Ti-Nb alloys to explore process parameters and the resultant macroscopic structure and microstructure. The microstructures in Ti-20Nb and Ti-50Nb (at.%) alloys exhibited cellular growth during rapid solidification, with average cell size of approximately 0.5 µm. Solidification velocities during cellular growth were calculated from images of melt tracks. Measurements of the composition in the cellular and intercellular regions revealed nonequilibrium partitioning and its dependence on velocity during rapid solidification. Experimental results were used to benchmark a phase-field model to describe rapid solidification under conditions relevant to additive manufacturing.
Silva, Guilherme F; Tanomaru-Filho, Mário; Bernardi, Maria I B; Guerreiro-Tanomaru, Juliane M; Cerri, Paulo S
2015-11-01
The physicochemical properties and the tissue reaction promoted by microparticulated or nanoparticulated niobium pentoxide (Nb2O5) added to calcium silicate-based cement (CS), compared to MTA-Angelus™, were evaluated. Materials were submitted to the tests of radiopacity, setting time, pH, and calcium ion release. Polyethylene tubes filled with the materials were implanted into rats subcutaneously. After 7, 15, 30, and 60 days, the specimens were fixed and embedded in paraffin. Hematoxylin & eosin (H&E)-stained sections were used to compute the number of inflammatory cells (IC). Interleukin-6 (IL-6) detection was performed, and the number of immunolabeled cells was obtained; von Kossa method was also carried out. Data were subjected to ANOVA and Tukey test (p ≤ 0.05). Nb2O5micro and Nb2O5nano provided to the CS radiopacity values (3.52 and 3.75 mm Al, respectively) superior to the minimum recommended. Groups containing Nb2O5 presented initial setting time significantly superior than mineral trioxide aggregate (MTA). All materials presented an alkaline pH and released calcium ions. The number of IC and IL-6 immunolabeled cells in the CS + Nb2O5 groups was significantly reduced in comparison to MTA in all periods. von Kossa-positive structures were observed adjacent to implanted materials in all periods. The addition of Nb2O5 to the CS resulted in a material biocompatible and with adequate characteristics regarding radiopacity and final setting time and provides an alkaline pH to the environment. Furthermore, the particle size did not significantly affect the physicochemical and biological properties of the calcium silicate-based cement. Niobium pentoxide can be used as radiopacifier for the development of calcium silicate-based materials.
NASA Astrophysics Data System (ADS)
Debnath, Tapas; Rüscher, Claus H.; Gesing, Thorsten M.; Koepke, Jürgen; Hussain, Altaf
2008-04-01
Series of compounds in the system Na xNb yW 1-yO 3 were prepared according to the appropriate molar ratio of Na 2WO 4, WO 3, WO 2 and Nb 2O 5 with x=0.80 and 0.0⩽ y⩽0.4 at 600 °C in evacuated silica glass tubes. These compounds were investigated by X-ray powder diffraction, optical microscopy, microprobe analysis, Raman and optical microspectroscopy. A y-dependent separation into three distinct coloured crystallites with cubic perovskite-type structures is observed: (i) red-orange crystallites with composition Na xWO 3 with slightly decreasing x (i.e. 0.8-0.72) with increasing nominal y, (ii) bluish solid solution of composition Na xNb yW 1-yO 3 and (iii) white crystallites of a new phase having defect perovskite-type structure with composition Na 0.5NbO 2.75.
NASA Astrophysics Data System (ADS)
Jimenez, K.; Gaballah, A. E. H.; Ahmed, Nadeem; Zuppella, P.; Nicolosi, P.
2017-05-01
High brilliance sources in the EUV spectral range such as Synchrotron and Free Electron Lasers (FEL) are widely used in multiple scientific and technological applications thanks to their peculiar characteristics. One main technical problem of FEL is related to the rejection of high harmonics, seed laser, first stage photons, and diffuse light; in order to improve the quality of the beam delivered by these sources, a suitable optical system acting as band-pass filters is necessary. In this paper we discuss the optical and structure characterization of Nb/Zr and Zr/Nb self-stand transmittance filters, designed for 4.5 nm-20 nm wavelength ranges. In order to understand the properties of these bilayers filters, a campaign of measurements has been planned to be performed on Zr and Nb films on Si3N4 membrane windows and silicon substrates, deposited with e- beam deposition technique. Comparison of the results has been planned too. IMD transmittance and reflectance simulations, together with preliminary AFM and reflectance measurements will be shown in this work.
NASA Astrophysics Data System (ADS)
Lu, M. F.; Zhou, C. P.; Li, Q. Q.; Zhang, C. L.; Shi, H. F.
2018-01-01
In order to improve the photocatalytic activity under visible-light irradiation, we adopted first principle calculations based on density functional theory (DFT) to calculate the electronic structures of B site transition metal element doped InNbO4. The results indicated that the complete hybridization of Nb 4d states and some Ti 3d states contributed to the new conduction band of Ti doped InNbO4, barely changing the position of band edge. For Cr doping, some localized Cr 3d states were introduced into the band gap. Nonetheless, the potential of localized levels was too positive to cause visible-light reaction. When it came to Cu doping, the band gap was almost same with that of InNbO4 as well as some localized Cu 3d states appeared above the top of VB. The introduction of localized energy levels benefited electrons to migrate from valence band (VB) to conduction band (CB) by absorbing lower energy photons, realizing visible-light response.
Method for preparing high transition temperature Nb.sub.3 Ge superconductors
Newkirk, Lawrence R.; Valencia, Flavio A.
1977-01-01
Bulk coatings of Nb.sub.3 Ge superconductors having transition temperatures in excess of 20 K are readily formed by a chemical vapor deposition technique involving the coreduction of NbCl.sub.5 and GeCl.sub.4 in the presence of hydrogen. The NbCl.sub.5 vapor may advantageously be formed quantitatively in the temperature range of about 250.degree. to 260.degree. C by the chlorination of Nb metal provided the partial pressure of the product NbCl.sub.5 vapor is maintained at or below about 0.1 atm.
Method for preparing high transition temperature Nb/sub 3/Ge superconductors. [Patent application
Newkirk, L.R.; Valencia, F.A.
1975-06-26
Bulk coatings of Nb/sub 3/Ge superconductors having transition temperatures in excess of 20/sup 0/K are readily formed by a chemical vapor deposition technique involving the coreduction of NbCl/sub 5/ and GeCl/sub 4/ in the presence of hydrogen. The NbCl/sub 5/ vapor may advantageously be formed quantitatively in the temperature range of about 250 to 260/sup 0/C by the chlorination of Nb metal provided the partial pressure of the product NbCl/sub 5/ vapor is maintained at or below about 0.1 atm.