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Sample records for ratio regulates osteoclastogenesis

  1. RANKL signaling and osteoclastogenesis is negatively regulated by cardamonin.

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    Bokyung Sung

    Full Text Available Bone loss/resorption or osteoporosis is a disease that is accelerated with aging and age-associated chronic diseases such as cancer. Bone loss has been linked with human multiple myeloma, breast cancer, and prostate cancer and is usually treated with bisphosphonates, and recently approved denosumab, an antibody against receptor activator of NF-κB ligand (RANKL. Because of the numerous side effects of the currently available drugs, the search continues for safe and effective therapies for bone loss. RANKL, a member of the TNF superfamily, has emerged as a major mediator of bone loss via activation of osteoclastogenesis. We have identified cardamonin, a chalcone isolated from Alpinia katsumadai Hayata that can affect osteoclastogenesis through modulation of RANKL. We found that treatment of monocytes with cardamonin suppressed RANKL-induced NF-κB activation and this suppression correlated with inhibition of IκBα kinase and of phosphorylation and degradation of IκBα, an inhibitor of NF-κB. Furthermore, cardamonin also downregulated RANKL-induced phosphorylation of MAPK including ERK and p38 MAPK. Cardamonin suppressed the RANKL-induced differentiation of monocytes to osteoclasts in a dose-dependent and time-dependent manner. We also found that an inhibitor of NF-κB essential modulator (NEMO blocked RANKL-induced osteoclastogenesis, indicating a direct link with NF-κB. Finally, osteoclastogenesis induced by human breast cancer cells or human multiple myeloma cells were completely suppressed by cardamonin. Collectively, our results indicate that cardamonin suppresses osteoclastogenesis induced by RANKL and tumor cells by suppressing activation of the NF-κB and MAPK pathway.

  2. Tetraspanin CD9 regulates osteoclastogenesis via regulation of p44/42 MAPK activity

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    Yi, TacGhee; Kim, Hye-Jin; Cho, Je-Yoel; Woo, Kyung Mi; Ryoo, Hyun-Mo; Kim, Gwan-Shik; Baek, Jeong-Hwa

    2006-01-01

    Tetraspanin CD9 has been shown to regulate cell-cell fusion in sperm-egg fusion and myotube formation. However, the role of CD9 in osteoclast, another multinucleated cell type, is not still clear. Therefore, we investigated the role of CD9 in osteoclast differentiation. CD9 was expressed in osteoclast lineage cells and its expression level increased during the progression of RANKL-induced osteoclastogenesis. KMC8, a neutralizing antibody specific to CD9, significantly suppressed RANKL-induced multinucleated osteoclast formation and the mRNA expression of osteoclast differentiation marker genes. To define CD9-regulated osteoclastogenic signaling pathway, MAPK pathways were examined. KMC8 induced long-term phosphorylation of p44/42 MAPK, but not of p38 MAPK. Constitutive activation of p44/42 MAPK by overexpressing constitutive-active mutant of MEK1 almost completely blocked osteoclast differentiation. Taken together, these results suggest that CD9 expressed on osteoclast lineage cells might positively regulate osteoclastogenesis via the regulation of p44/42 MAPK activity

  3. Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling

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    Oh, Se Jeong [Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Gu, Dong Ryun [Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Center for Metabolic Function Regulation (CMFR), School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Jin, Su Hyun [Center for Metabolic Function Regulation (CMFR), School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Park, Keun Ha [Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Center for Metabolic Function Regulation (CMFR), School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Lee, Seoung Hoon, E-mail: leesh2@wku.ac.kr [Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Center for Metabolic Function Regulation (CMFR), School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Wonkwang Institute of Biomaterials and Implant, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of)

    2016-06-17

    Cytosolic malate dehydrogenase (malate dehydrogenase 1, MDH1) plays pivotal roles in the malate/aspartate shuttle that might modulate metabolism between the cytosol and mitochondria. In this study, we investigated the role of MDH1 in osteoclast differentiation and formation. MDH1 expression was induced by receptor activator of nuclear factor kappa-B ligand (RANKL) treatment. Knockdown of MDH1 by infection with retrovirus containing MDH1-specific shRNA (shMDH1) reduced mature osteoclast formation and bone resorption activity. Moreover, the expression of marker genes associated with osteoclast differentiation was downregulated by shMDH1 treatment, suggesting a role of MDH1 in osteoclast differentiation. In addition, intracellular ATP production was reduced following the activation of adenosine 5′ monophosphate-activated protein kinase (AMPK), a cellular energy sensor and negative regulator of RANKL-induced osteoclast differentiation, in shMDH1-infected osteoclasts compared to control cells. In addition, the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a critical transcription factor of osteoclastogenesis, was decreased with MDH1 knockdown during RANKL-mediated osteoclast differentiation. These findings provide strong evidence that MDH1 plays a critical role in osteoclast differentiation and function via modulation of the intracellular energy status, which might affect AMPK activity and NFATc1 expression.

  4. Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling

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    Oh, Se Jeong; Gu, Dong Ryun; Jin, Su Hyun; Park, Keun Ha; Lee, Seoung Hoon

    2016-01-01

    Cytosolic malate dehydrogenase (malate dehydrogenase 1, MDH1) plays pivotal roles in the malate/aspartate shuttle that might modulate metabolism between the cytosol and mitochondria. In this study, we investigated the role of MDH1 in osteoclast differentiation and formation. MDH1 expression was induced by receptor activator of nuclear factor kappa-B ligand (RANKL) treatment. Knockdown of MDH1 by infection with retrovirus containing MDH1-specific shRNA (shMDH1) reduced mature osteoclast formation and bone resorption activity. Moreover, the expression of marker genes associated with osteoclast differentiation was downregulated by shMDH1 treatment, suggesting a role of MDH1 in osteoclast differentiation. In addition, intracellular ATP production was reduced following the activation of adenosine 5′ monophosphate-activated protein kinase (AMPK), a cellular energy sensor and negative regulator of RANKL-induced osteoclast differentiation, in shMDH1-infected osteoclasts compared to control cells. In addition, the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a critical transcription factor of osteoclastogenesis, was decreased with MDH1 knockdown during RANKL-mediated osteoclast differentiation. These findings provide strong evidence that MDH1 plays a critical role in osteoclast differentiation and function via modulation of the intracellular energy status, which might affect AMPK activity and NFATc1 expression.

  5. Mouse genome-wide association and systems genetics identify Asxl2 as a regulator of bone mineral density and osteoclastogenesis.

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    Charles R Farber

    2011-04-01

    Full Text Available Significant advances have been made in the discovery of genes affecting bone mineral density (BMD; however, our understanding of its genetic basis remains incomplete. In the current study, genome-wide association (GWA and co-expression network analysis were used in the recently described Hybrid Mouse Diversity Panel (HMDP to identify and functionally characterize novel BMD genes. In the HMDP, a GWA of total body, spinal, and femoral BMD revealed four significant associations (-log10P>5.39 affecting at least one BMD trait on chromosomes (Chrs. 7, 11, 12, and 17. The associations implicated a total of 163 genes with each association harboring between 14 and 112 genes. This list was reduced to 26 functional candidates by identifying those genes that were regulated by local eQTL in bone or harbored potentially functional non-synonymous (NS SNPs. This analysis revealed that the most significant BMD SNP on Chr. 12 was a NS SNP in the additional sex combs like-2 (Asxl2 gene that was predicted to be functional. The involvement of Asxl2 in the regulation of bone mass was confirmed by the observation that Asxl2 knockout mice had reduced BMD. To begin to unravel the mechanism through which Asxl2 influenced BMD, a gene co-expression network was created using cortical bone gene expression microarray data from the HMDP strains. Asxl2 was identified as a member of a co-expression module enriched for genes involved in the differentiation of myeloid cells. In bone, osteoclasts are bone-resorbing cells of myeloid origin, suggesting that Asxl2 may play a role in osteoclast differentiation. In agreement, the knockdown of Asxl2 in bone marrow macrophages impaired their ability to form osteoclasts. This study identifies a new regulator of BMD and osteoclastogenesis and highlights the power of GWA and systems genetics in the mouse for dissecting complex genetic traits.

  6. Echinocystic acid inhibits RANKL-induced osteoclastogenesis by regulating NF-κB and ERK signaling pathways

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    Yang, Jian-hui, E-mail: jianhui_yangxa@163.com [Rehabilitation Center, First Affiliated Hospital of Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi Province (China); Li, Bing [Department of Dermatology, the 451st Hospital of People’s Liberation Army, Xi’an 710054, Shaanxi Province (China); Wu, Qiong; Lv, Jian-guo; Nie, Hui-Yong [Rehabilitation Center, First Affiliated Hospital of Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi Province (China)

    2016-09-02

    Receptor activator of nuclear factor-κB ligand (RANKL) is a key factor in the differentiation and activation of osteoclasts. Echinocystic acid (EA), a pentacyclic triterpene isolated from the fruits of Gleditsia sinensis Lam, was reported to prevent reduction of bone mass and strength and improve the cancellous bone structure and biochemical properties in ovariectomy rats. However, the molecular mechanism of EA on the osteoclast formation has not been reported. The purpose of this study was to investigate the effects and mechanism of EA on RANKL-induced osteoclastogenesis. Our results showed that EA inhibited the formation of osteoclast, as well as the expression of osteoclastogenesis-related marker proteins in bone marrow macrophages (BMMs). At molecular levels, EA inhibited RANKL-induced NF-κB activation and ERK phosphorylation in BMMs. In conclusion, the present study demonstrated that EA can suppress osteoclastogenesis in vitro. Moreover, we clarified that these inhibitory effects of EA occur through suppression of NF-κB and ERK activation. Therefore, EA may be a potential agent in the treatment of osteoclast-related diseases such as osteoporosis. - Highlights: • EA inhibited the formation of osteoclast in BMMs. • EA inhibits the expression of osteoclastogenesis-related marker proteins in BMMs. • EA inhibits RANKL-induced NF-κB activation in BMMs. • EA inhibits RANKL-induced ERK phosphorylation in BMMs.

  7. Protective protein/cathepsin A down-regulates osteoclastogenesis by associating with and degrading NF-kappaB p50/p65.

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    Masuhara, Masaaki; Sato, Takuya; Hada, Naoto; Hakeda, Yoshiyuki

    2009-01-01

    Disruption of the cooperative function balance between osteoblasts and osteoclasts causes various bone disorders, some of which are attributed to abnormal osteoclast recruitment. Osteoclast differentiation is dependent on the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) as well as the macrophage colony-stimulating factor. The osteoclast formation induced by cytokines requires activation of NF-kappaB, AP-1 and nuclear factor of activated T cells c1. However, osteoclasts are not the only cell types that express these transcription factors, suggesting that some unknown molecules specific for osteoclasts may associate with the transcription factors. Here, we explored the possibility of molecules binding directly to NF-kappaB and cloned protective protein/cathepsin A (PPCA) by yeast two-hybrid screening using a cDNA library of osteoclast precursors. Forced expression of PPCA with p50/p65 in HEK293 cells decreased both the level of p50/p65 proteins and the transcriptional activity. Abundant PPCA was detected in the lysosomes of the transfected HEK293 cells, but a small amount of this enzyme was also present in the cytosolic fraction. In addition, over-expression of PPCA caused the disappearance of p50/p65 in both the lysosomal and cytosolic fractions. PPCA was expressed throughout osteoclastogenesis, and the expression was slightly up-regulated by RANKL signaling. Knockdown of PPCA in osteoclast precursors with PPCA siRNA stimulated binding of nuclear proteins to oligonucleotides containing an NF-kappaB binding motif and increased osteoclastogenesis. Our present results indicate a novel role for PPCA in osteoclastogenesis via down-regulation of NF-kappaB activity and suggest a new function for PPCA as an NF-kappaB-degrading enzyme in addition to its known multifunctional properties.

  8. Role of miR-222-3p in c-Src-Mediated Regulation of Osteoclastogenesis

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    Shinya Takigawa

    2016-02-01

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs that play a mostly post-transcriptional regulatory role in gene expression. Using RAW264.7 pre-osteoclast cells and genome-wide expression analysis, we identified a set of miRNAs that are involved in osteoclastogenesis. Based on in silico analysis, we specifically focused on miR-222-3p and evaluated its role in osteoclastogenesis. The results show that the inhibitor of miR-222-3p upregulated the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1 and tartrate-resistant acid phosphatase (TRAP, while its mimicking agent downregulated their mRNA levels. Western blot analysis showed that its inhibitor increased the protein levels of TRAP and cathepsin K, while its mimicking agent decreased their levels. Genome-wide mRNA expression analysis in the presence and absence of receptor activator of nuclear factor κ-B ligand (RANKL predicted c-Src as a potential regulatory target of miR-222-3p. Live cell imaging using a fluorescence resonance energy transfer (FRET technique revealed that miR-222-3p acted as an inhibitor of c-Src activity, and a partial silencing of c-Src suppressed RANKL-induced expression of TRAP and cathepsin K, as well as the number of multi-nucleated osteoclasts and their pit formation. Collectively, the study herein demonstrates that miR-222-3p serves as an inhibitor of osteoclastogenesis and c-Src mediates its inhibition of cathepsin K and TRAP.

  9. miR-218 is involved in the negative regulation of osteoclastogenesis and bone resorption by partial suppression of p38MAPK-c-Fos-NFATc1 signaling: Potential role for osteopenic diseases.

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    Qu, Bo; Xia, Xun; Yan, Ming; Gong, Kai; Deng, Shaolin; Huang, Gang; Ma, Zehui; Pan, Xianming

    2015-10-15

    The increased osteoclastic activity accounts for pathological bone loss in diseases including osteoporosis. MicroRNAs are widely accepted to be involved in the regulation of osteopenic diseases. Recently, the low expression of miR-218 was demonstrated in CD14(+) peripheral blood mononuclear cells (PBMCs) from patients with postmenopausal osteoporosis. However, its role and the underlying mechanism in osteoporosis are still undefined. Here, an obvious decrease in miR-218 expression was observed during osteoclastogenesis under receptor activator of nuclear factor κB ligand (RANKL) stimulation, in both osteoclast precursors of bone marrow macrophages (BMMs) and RAW 264.7. Further analysis confirmed that overexpression of miR-218 obviously attenuated the formation of multinuclear mature osteoclasts, concomitant with the decrease in Trap and Cathepsin K levels, both the master regulators of osteoclastogenesis. Moreover, miR-218 up-regulation dramatically inhibited osteoclast precursor migration, actin ring formation and bone resorption. Mechanism assay demonstrated that miR-218 overexpression attenuated the expression of p38MAPK, c-Fos and NFATc1 signaling molecules. Following preconditioning with P79350, an agonist of p38MAPK, the inhibitor effect of miR-218 on osteoclastogenesis and bone-resorbing activity was strikingly ameliorated. Together, this study revealed a crucial role of miR-218 as a negative regulator for osteoclastogenesis and bone resorption by suppressing the p38MAPK-c-Fos-NFATc1 pathway. Accordingly, this research will provide a promising therapeutic agent against osteopenic diseases including osteoporosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Regulation by Phloroglucinol of Nrf2/Maf-Mediated Expression of Antioxidant Enzymes and Inhibition of Osteoclastogenesis via the RANKL/RANK Signaling Pathway: In Silico study

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    Rahim, Agus Hadian; Setiawan, Bambang; Dewi, Firli Rahmah Primula; Noor, Zairin

    2015-01-01

    Introduction: Phloroglucinol is an antioxidant compound with many positive effects on health. The purpose of this study was to determine the role of phloroglucinol in osteoclastogenesis via the RANKL/RANK signaling pathway and the activity of the transcription factor Nrf2. Material and methods: Analysis was performed in silico using the primary method of docking by the use of Hex 8.0 software and Haddock web server. Analysis of interactions was then performed to determine interactions between the ligand and its receptors by using the software LigPlus and LigandScout 3.1. Results: Results indicated that phloroglucinol compound was thought to inhibit osteoclastogenesis via three mechanisms: inhibiting RANKL−RANK interaction, sustaining the RANKL−OPG bond, and increasing the activity of the transcription factor Nrf2. PMID:26483597

  11. Wedelolactone enhances osteoblastogenesis by regulating Wnt/β-catenin signaling pathway but suppresses osteoclastogenesis by NF-κB/c-fos/NFATc1 pathway.

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    Liu, Yan-Qiu; Hong, Zhi-Lai; Zhan, Li-Bin; Chu, Hui-Ying; Zhang, Xiao-Zhe; Li, Guo-Hui

    2016-08-25

    Bone homeostasis is maintained by formation and destruction of bone, which are two processes tightly coupled and controlled. Targeting both stimulation on bone formation and suppression on bone resorption becomes a promising strategy for treating osteoporosis. In this study, we examined the effect of wedelolactone, a natural product from Ecliptae herba, on osteoblastogenesis as well as osteoclastogenesis. In mouse bone marrow mesenchymal stem cells (BMSC), wedelolactone stimulated osteoblast differentiation and bone mineralization. At the molecular level, wedelolactone directly inhibited GSK3β activity and enhanced the phosphorylation of GSK3β, thereafter stimulated the nuclear translocation of β-catenin and runx2. The expression of osteoblastogenesis-related marker gene including osteorix, osteocalcin and runx2 increased. At the same concentration range, wedelolactone inhibited RANKL-induced preosteoclastic RAW264.7 actin-ring formation and bone resorption pits. Further, wedelolactone blocked NF-kB/p65 phosphorylation and abrogated the NFATc1 nuclear translocation. As a result, osteoclastogenesis-related marker gene expression decreased, including c-src, c-fos, and cathepsin K. In ovariectomized mice, administration of wedelolactone prevented ovariectomy-induced bone loss by enhancing osteoblast activity and inhibiting osteoclast activity. Together, these data demonstrated that wedelolactone facilitated osteoblastogenesis through Wnt/GSK3β/β-catenin signaling pathway and suppressed RANKL-induced osteoclastogenesis through NF-κB/c-fos/NFATc1 pathway. These results suggested that wedelolacone could be a novel dual functional therapeutic agent for osteoporosis.

  12. Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis.

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    Kim, Ji H; Gupta, Subash C; Park, Byoungduck; Yadav, Vivek R; Aggarwal, Bharat B

    2012-03-01

    The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Tenuigenin inhibits RANKL-induced osteoclastogenesis by down-regulating NF-κB activation and suppresses bone loss in vivo

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    Yang, Shuo [Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008 (China); Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410012 (China); Li, Xianan [Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410012 (China); Cheng, Liang [Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008 (China); Wu, Hongwei [Department of Orthopedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410012 (China); Zhang, Can [Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008 (China); Li, Kanghua, E-mail: lkh8738@sina.com [Department of Orthopedic Surgery, The Xiangya Hospital of Central South University, Changsha, Hunan 410008 (China)

    2015-10-30

    Tenuigenin, a major active component of polygala tenuifolia root, has been used to treat patients with insomnia, dementia, and neurosis. In this study, we aimed to investigate the effects of tenuigenin on osteoclastogenesis and clarify the possible mechanism. We showed that tenuigenin inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption without cytotoxicity, which was further demonstrated by reduced osteoclast specific gene expression such as TRAP, c-Src, ATP6v0d2, etc. Moreover, the inhibitory effect of tenuigenin was associated with impaired NF-κB activity owing to delayed degradation/regeneration of IkBa and inhibition of p65 nuclear translocation. Consistent with the in vitro results, micro-ct scanning and analysis data showed that tenuigenin suppressed RANKL-induced bone loss in an animal model. Taken together, our data demonstrate that tenuigenin inhibit osteoclast formation and bone resorption both in vitro and in vivo, and comprise a potential therapeutic alternative for osteoclast-related disorders such as osteoporosis and cancer-induced bone destruction. - Highlights: • Tenuigenin suppresses osteoclasts formation, survival and function in vitro. • Tenuigenin impairs NF-κB activation. • Tenuigenin suppresses RANKL-induced bone lose in vivo. • Tenuigenin may be used for treating osteoclast related diseases.

  14. Tenuigenin inhibits RANKL-induced osteoclastogenesis by down-regulating NF-κB activation and suppresses bone loss in vivo

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    Yang, Shuo; Li, Xianan; Cheng, Liang; Wu, Hongwei; Zhang, Can; Li, Kanghua

    2015-01-01

    Tenuigenin, a major active component of polygala tenuifolia root, has been used to treat patients with insomnia, dementia, and neurosis. In this study, we aimed to investigate the effects of tenuigenin on osteoclastogenesis and clarify the possible mechanism. We showed that tenuigenin inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption without cytotoxicity, which was further demonstrated by reduced osteoclast specific gene expression such as TRAP, c-Src, ATP6v0d2, etc. Moreover, the inhibitory effect of tenuigenin was associated with impaired NF-κB activity owing to delayed degradation/regeneration of IkBa and inhibition of p65 nuclear translocation. Consistent with the in vitro results, micro-ct scanning and analysis data showed that tenuigenin suppressed RANKL-induced bone loss in an animal model. Taken together, our data demonstrate that tenuigenin inhibit osteoclast formation and bone resorption both in vitro and in vivo, and comprise a potential therapeutic alternative for osteoclast-related disorders such as osteoporosis and cancer-induced bone destruction. - Highlights: • Tenuigenin suppresses osteoclasts formation, survival and function in vitro. • Tenuigenin impairs NF-κB activation. • Tenuigenin suppresses RANKL-induced bone lose in vivo. • Tenuigenin may be used for treating osteoclast related diseases.

  15. Impact of acetylcholine and nicotine on human osteoclastogenesis in vitro.

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    Ternes, Sebastian; Trinkaus, Katja; Bergen, Ivonne; Knaack, Sven; Gelinsky, Michael; Kilian, Olaf; Heiss, Christian; Lips, Katrin Susanne

    2015-11-01

    Recent studies showed that the non-neuronal cholinergic system (NNCS) is taking part in bone metabolism. Most studies investigated its role in osteoblasts, but up to now, the involvement of the NNCS in human osteoclastogenesis remains relatively unclear. Thus, aim of the present study was to determine whether the application of acetylcholine (ACh, 10(−4) M), nicotine (10(−6) M), mineralized collagen membranes or brain derived neurotrophic factor (BDNF, 40 ng/mL) influences the mRNA regulation of molecular components of the NNCS and the neurotrophin family during osteoclastogenesis. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of young healthy donors (n = 8) and incubated with bone fragments and osteoclast differentiation media for 21 days. All the results are based on the measurement of RNA. Real-time RT-PCR analysis demonstrated a down-regulation of nicotinic acetylcholine receptor (nAChR) subunit α2 and muscarinic acetylcholine receptor (mAChR) M3by osteoclastogenesis while BDNF mRNA expression was not regulated. Application of ACh, nicotine, BDNF or collagen membranes did not affect osteoclastic differentiation.No regulation was detected for nAChR subunit α7, tropomyosin-related kinase receptor B (TrkB), and cholineacetyl transferase (ChAT). Taken together, we assume that the transcriptional level of osteoclastogenesis of healthy young humans is not regulated by BDNF, ACh, and nicotine. Thus, these drugs do not seem to worsen bone degradation and might therefore be suitable as modulators of bone substitution materials if having a positive effect on bone formation.

  16. MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis

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    Guo, Li-Juan; Liao, Lan; Yang, Li; Li, Yu; Jiang, Tie-Jian

    2014-01-01

    MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. In the present study, we found that miR-125a was dramatically down-regulated during macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclastogenesis of circulating CD14+ peripheral blood mononuclear cells (PBMCs). Overexpression of miR-125a in CD14+ PBMCs inhibited osteoclastogenesis, while inhibition of miR-125a promoted osteoclastogenesis. TNF receptor-associated factor 6 (TRAF6), a transduction factor for RANKL/RANK/NFATc1 signal, was confirmed to be a target of miR-125a. EMSA and ChIP assays confirmed that NFATc1 bound to the promoter of the miR-125a. Overexpression of NFATc1 inhibited miR-125a transcription, and block of NFATc1 expression attenuated RANKL-regulated miR-125a transcription. Here, we reported that miR-125a played a biological function in osteoclastogenesis through a novel TRAF6/ NFATc1/miR-125a regulatory feedback loop. It suggests that regulation of miR-125a expression may be a potential strategy for ameliorating metabolic disease. - Highlights: • MiR-125a was significantly down-regulated in osteoclastogenesis of CD14+ PBMCs. • MiR-125a inhibited osteoclast differentiation by targeting TRAF6. • NFATc1 inhibited miR-125a transciption by binding to the promoter of miR-125a. • TRAF6/NFATc1 and miR-125a form a regulatory feedback loop in osteoclastogenesis

  17. Global epigenomic analysis indicates protocadherin-7 activates osteoclastogenesis by promoting cell–cell fusion

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    Nakamura, Haruhiko [Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan); Nakashima, Tomoki [Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan); Japan Science and Technology Agency, PRESTO, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan); Hayashi, Mikihito [Department of Cell Signaling, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan); Japan Science and Technology Agency, ERATO, Takayanagi Osteonetwork Project, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Izawa, Naohiro; Yasui, Tetsuro [Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Aburatani, Hiroyuki [Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8904 (Japan); Tanaka, Sakae [Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Takayanagi, Hiroshi, E-mail: takayana@m.u-tokyo.ac.jp [Japan Science and Technology Agency, ERATO, Takayanagi Osteonetwork Project, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2014-12-12

    Highlights: • Identification of epigenetically regulated genes during osteoclastogenesis. • Pcdh7 is regulated by H3K4me3 and H3K27me3 during osteoclastogenesis. • Pcdh7 expression is increased by RANKL during osteoclastogenesis. • Establishment of novel cell fusion analysis for osteoclasts by imaging cytometer. • Pcdh7 regulates osteoclastogenesis by promoting cell fusion related gene expressions. - Abstract: Gene expression is dependent not only on genomic sequences, but also epigenetic control, in which the regulation of chromatin by histone modification plays a crucial role. Histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3) are related to transcriptionally activated and silenced sequences, respectively. Osteoclasts, the multinucleated cells that resorb bone, are generated by the fusion of precursor cells of monocyte/macrophage lineage. To elucidate the molecular and epigenetic regulation of osteoclast differentiation, we performed a chromatin immunoprecipitation sequencing (ChIP-seq) analysis for H3K4me3 and H3K27me3 in combination with RNA sequencing. We focused on the histone modification change from H3K4me3(+)H3K27me3(+) to H3K4me3(+)H3K27me3(–) and identified the protocadherin-7 gene (Pcdh7) to be among the genes epigenetically regulated during osteoclastogenesis. Pcdh7 was induced by RANKL stimulation in an NFAT-dependent manner. The knockdown of Pcdh7 inhibited RANKL-induced osteoclast differentiation due to the impairment of cell–cell fusion, accompanied by a decreased expression of the fusion-related genes Dcstamp, Ocstamp and Atp6v0d2. This study demonstrates that Pcdh7 plays a key role in osteoclastogenesis by promoting cell–cell fusion.

  18. Global epigenomic analysis indicates protocadherin-7 activates osteoclastogenesis by promoting cell–cell fusion

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    Nakamura, Haruhiko; Nakashima, Tomoki; Hayashi, Mikihito; Izawa, Naohiro; Yasui, Tetsuro; Aburatani, Hiroyuki; Tanaka, Sakae; Takayanagi, Hiroshi

    2014-01-01

    Highlights: • Identification of epigenetically regulated genes during osteoclastogenesis. • Pcdh7 is regulated by H3K4me3 and H3K27me3 during osteoclastogenesis. • Pcdh7 expression is increased by RANKL during osteoclastogenesis. • Establishment of novel cell fusion analysis for osteoclasts by imaging cytometer. • Pcdh7 regulates osteoclastogenesis by promoting cell fusion related gene expressions. - Abstract: Gene expression is dependent not only on genomic sequences, but also epigenetic control, in which the regulation of chromatin by histone modification plays a crucial role. Histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3) are related to transcriptionally activated and silenced sequences, respectively. Osteoclasts, the multinucleated cells that resorb bone, are generated by the fusion of precursor cells of monocyte/macrophage lineage. To elucidate the molecular and epigenetic regulation of osteoclast differentiation, we performed a chromatin immunoprecipitation sequencing (ChIP-seq) analysis for H3K4me3 and H3K27me3 in combination with RNA sequencing. We focused on the histone modification change from H3K4me3(+)H3K27me3(+) to H3K4me3(+)H3K27me3(–) and identified the protocadherin-7 gene (Pcdh7) to be among the genes epigenetically regulated during osteoclastogenesis. Pcdh7 was induced by RANKL stimulation in an NFAT-dependent manner. The knockdown of Pcdh7 inhibited RANKL-induced osteoclast differentiation due to the impairment of cell–cell fusion, accompanied by a decreased expression of the fusion-related genes Dcstamp, Ocstamp and Atp6v0d2. This study demonstrates that Pcdh7 plays a key role in osteoclastogenesis by promoting cell–cell fusion

  19. RANKL downregulates cell surface CXCR6 expression through JAK2/STAT3 signaling pathway during osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Changhong; Zhao, Jinxia; Sun, Lin; Yao, Zhongqiang; Liu, Rui [Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191 (China); Huang, Jiansheng [Department of Pediatrics, Washington University School of Medicine, St. Louis, MO (United States); Liu, Xiangyuan, E-mail: liu-xiangyuan@263.net [Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191 (China)

    2012-12-14

    Highlights: Black-Right-Pointing-Pointer CXCR6 is down-regulated during RANKL-induced osteoclastogenesis in RAW264.7 cells. Black-Right-Pointing-Pointer CXCR6 reduction was nearly reversed by inhibition of JAK2/STAT3 signaling pathway. Black-Right-Pointing-Pointer CXCL16 alone does not positively regulate osteoclastogenesis. -- Abstract: The receptor activator of nuclear factor-{kappa}B ligand (RANKL), as a member of the tumor necrosis factor (TNF) family, plays an essential role in osteoclast differentiation and function. Chemokines and their receptors have recently been shown to play critical roles in osteoclastogenesis, however, whether CXCL16-CXCR6 plays role in RANKL-mediated osteoclastogenesis is unknown. In this study, we first reported that RANKL decreased CXCR6 in a dose-dependent manner, which may be through deactivation of Akt and STAT3 signaling induced by CXCL16. Interestingly, RANKL-mediated CXCR6 reduction may be associated to the activation of STAT3 by phosphorylation. When STAT3 activation was blocked by JAK2/STAT3 inhibitor AG490, RANKL failed to shut down CXCR6 expression during osteoclastogenesis. However, CXCL16 alone did not augment RANKL-mediated osteoclast differentiation and did not alter RANKL-receptor RANK mRNA expression. These results demonstrate that reduction of CXCL16-CXCR6 is critical in RANKL-mediated osteoclastogenesis, which is mainly through the activation of JAK2/STAT3 signaling. CXCL16-CXCR6 axis may become a novel target for the therapeutic intervention of bone resorbing diseases such as rheumatoid arthritis and osteoporosis.

  20. Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production.

    Science.gov (United States)

    Oshita, Koichi; Yamaoka, Kunihiro; Udagawa, Nobuyuki; Fukuyo, Shunsuke; Sonomoto, Koshiro; Maeshima, Keisuke; Kurihara, Ryuji; Nakano, Kazuhisa; Saito, Kazuyoshi; Okada, Yosuke; Chiba, Kenji; Tanaka, Yoshiya

    2011-06-01

    Mesenchymal stem cells (MSCs) have been proposed to be a useful tool for treatment of rheumatoid arthritis (RA), not only because of their multipotency but also because of their immunosuppressive effect on lymphocytes, dendritic cells, and other proinflammatory cells. Since bone destruction caused by activated osteoclasts occurs in RA, we undertook the present study to investigate the effect of MSCs on osteoclast function and differentiation in order to evaluate their potential use in RA therapy. Human MSCs and peripheral blood mononuclear cells were cultured under cell-cell contact-free conditions with osteoclast induction medium. Differentiation into osteoclast-like cells was determined by tartrate-resistant acid phosphatase staining and expression of osteoclast differentiation markers. The number of osteoclast-like cells was decreased and expression of cathepsin K and nuclear factor of activated T cells c1 (NF-ATc1) was down-regulated by the addition of either MSCs or a conditioned medium obtained from MSCs. Osteoprotegerin (OPG) was constitutively produced by MSCs and inhibited osteoclastogenesis. However, osteoclast differentiation was not fully recovered upon treatment with either anti-OPG antibody or OPG small interfering RNA, suggesting that OPG had only a partial role in the inhibitory effect of MSCs. Moreover, bone-resorbing activity of osteoclast-like cells was partially recovered by addition of anti-OPG antibody into the conditioned medium. The present results indicate that human MSCs constitutively produce OPG, resulting in inhibition of osteoclastogenesis and expression of NF-ATc1 and cathepsin K in the absence of cell-cell contact. Therefore, we conclude that human MSCs exert a suppressive effect on osteoclastogenesis, which may be beneficial in inhibition of joint damage in RA. Copyright © 2011 by the American College of Rheumatology.

  1. Mechanical loading prevents the stimulating effect of IL-1{beta} on osteocyte-modulated osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kulkarni, Rishikesh N.; Bakker, Astrid D.; Everts, Vincent [Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Amsterdam (Netherlands); Klein-Nulend, Jenneke, E-mail: j.kleinnulend@acta.nl [Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Amsterdam (Netherlands)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Osteocyte incubation with IL-1{beta} stimulated osteocyte-modulated osteoclastogenesis. Black-Right-Pointing-Pointer Conditioned medium from IL-1{beta}-treated osteocytes increased osteoclastogenesis. Black-Right-Pointing-Pointer IL-1{beta} upregulated RANKL and downregulated OPG gene expression by osteocytes. Black-Right-Pointing-Pointer CYR61 is upregulated in mechanically stimulated osteocytes. Black-Right-Pointing-Pointer Mechanical loading of osteocytes may abolish IL-1{beta}-induced osteoclastogenesis. -- Abstract: Inflammatory diseases such as rheumatoid arthritis are often accompanied by higher plasma and synovial fluid levels of interleukin-1{beta} (IL-1{beta}), and by increased bone resorption. Since osteocytes are known to regulate bone resorption in response to changes in mechanical stimuli, we investigated whether IL-1{beta} affects osteocyte-modulated osteoclastogenesis in the presence or absence of mechanical loading of osteocytes. MLO-Y4 osteocytes were pre-incubated with IL-1{beta} (0.1-1 ng/ml) for 24 h. Cells were either or not subjected to mechanical loading by 1 h pulsating fluid flow (PFF; 0.7 {+-} 0.3 Pa, 5 Hz) in the presence of IL-1{beta} (0.1-1 ng/ml). Conditioned medium was collected after 1 h PFF or static cultures. Subsequently mouse bone marrow cells were seeded on top of the IL-1{beta}-treated osteocytes to determine osteoclastogenesis. Conditioned medium from mechanically loaded or static IL-1{beta}-treated osteocytes was added to co-cultures of untreated osteocytes and mouse bone marrow cells. Gene expression of cysteine-rich protein 61 (CYR61/CCN1), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) by osteocytes was determined immediately after PFF. Incubation of osteocytes with IL-1{beta}, as well as conditioned medium from static IL-1{beta}-treated osteocytes increased the formation of osteoclasts. However, conditioned medium from mechanically loaded IL

  2. Mechanical loading prevents the stimulating effect of IL-1β on osteocyte-modulated osteoclastogenesis

    International Nuclear Information System (INIS)

    Kulkarni, Rishikesh N.; Bakker, Astrid D.; Everts, Vincent; Klein-Nulend, Jenneke

    2012-01-01

    Highlights: ► Osteocyte incubation with IL-1β stimulated osteocyte-modulated osteoclastogenesis. ► Conditioned medium from IL-1β-treated osteocytes increased osteoclastogenesis. ► IL-1β upregulated RANKL and downregulated OPG gene expression by osteocytes. ► CYR61 is upregulated in mechanically stimulated osteocytes. ► Mechanical loading of osteocytes may abolish IL-1β-induced osteoclastogenesis. -- Abstract: Inflammatory diseases such as rheumatoid arthritis are often accompanied by higher plasma and synovial fluid levels of interleukin-1β (IL-1β), and by increased bone resorption. Since osteocytes are known to regulate bone resorption in response to changes in mechanical stimuli, we investigated whether IL-1β affects osteocyte-modulated osteoclastogenesis in the presence or absence of mechanical loading of osteocytes. MLO-Y4 osteocytes were pre-incubated with IL-1β (0.1–1 ng/ml) for 24 h. Cells were either or not subjected to mechanical loading by 1 h pulsating fluid flow (PFF; 0.7 ± 0.3 Pa, 5 Hz) in the presence of IL-1β (0.1–1 ng/ml). Conditioned medium was collected after 1 h PFF or static cultures. Subsequently mouse bone marrow cells were seeded on top of the IL-1β-treated osteocytes to determine osteoclastogenesis. Conditioned medium from mechanically loaded or static IL-1β-treated osteocytes was added to co-cultures of untreated osteocytes and mouse bone marrow cells. Gene expression of cysteine-rich protein 61 (CYR61/CCN1), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) by osteocytes was determined immediately after PFF. Incubation of osteocytes with IL-1β, as well as conditioned medium from static IL-1β-treated osteocytes increased the formation of osteoclasts. However, conditioned medium from mechanically loaded IL-1β-treated osteocytes prevented osteoclast formation. Incubation with IL-1β upregulated RANKL and downregulated OPG gene expression by static osteocytes. PFF upregulated

  3. The polymethoxy flavonoid sudachitin suppresses inflammatory bone destruction by directly inhibiting osteoclastogenesis due to reduced ROS production and MAPK activation in osteoclast precursors.

    Directory of Open Access Journals (Sweden)

    Yoko Ohyama

    Full Text Available Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and peri-implantitis, are associated not only with the production of inflammatory cytokines but also with local oxidative status, which is defined by intracellular reactive oxygen species (ROS. Osteoclast differentiation has been reported to be related to increased intracellular ROS levels in osteoclast lineage cells. Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses antioxidant properties and regulates various functions in mammalian cells. However, the effects of sudachitin on inflammatory bone destruction and osteoclastogenesis remain unknown. In calvaria inflamed by a local lipopolysaccharide (LPS injection, inflammation-induced bone destruction and the accompanying elevated expression of osteoclastogenesis-related genes were reduced by the co-administration of sudachitin and LPS. Moreover, sudachitin inhibited osteoclast formation in cultures of isolated osteoblasts and osteoclast precursors. However, sudachitin rather increased the expression of receptor activator of NF-κB ligand (RANKL, which is an important molecule triggering osteoclast differentiation, and the mRNA ratio of RANKL/osteoprotegerin that is a decoy receptor for RANKL, in the isolated osteoblasts, suggesting the presence of additional target cells. When osteoclast formation was induced from osteoclast precursors derived from bone marrow cells in the presence of soluble RANKL and macrophage colony-stimulating factor, sudachitin inhibited osteoclastogenesis without influencing cell viability. Consistently, the expression of osteoclast differentiation-related molecules including c-fos, NFATc1, cathepsin K and osteoclast fusion proteins such as DC-STAMP and Atp6v0d2 was reduced by sudachitin. In addition, sudachitin decreased activation of MAPKs such as Erk and JNK and the ROS production evoked by RANKL in osteoclast lineage cells. Our findings suggest that sudachitin is a

  4. Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis.

    Science.gov (United States)

    Hwang, J K; Erkhembaatar, M; Gu, D R; Lee, S H; Lee, C H; Shin, D M; Lee, Y R; Kim, M S

    2014-07-01

    Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca(2+) ([Ca(2+)]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca(2+)]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow-derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca(2+)]i while suppressing RANKL-induced [Ca(2+)]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca(2+)]i was dependent on extracellular Ca(2+) and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca(2+) channels (VGCCs), but was independent of store-operated Ca(2+) channels. Notably, after transient [Ca(2+)] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKL-induced [Ca(2+)]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis. © International & American Associations for Dental Research.

  5. Inhibition of osteoclastogenesis by RNA interference targeting RANK

    Directory of Open Access Journals (Sweden)

    Ma Ruofan

    2012-08-01

    Full Text Available Abstract Background Osteoclasts and osteoblasts regulate bone resorption and formation to allow bone remodeling and homeostasis. The balance between bone resorption and formation is disturbed by abnormal recruitment of osteoclasts. Osteoclast differentiation is dependent on the receptor activator of nuclear factor NF-kappa B (RANK ligand (RANKL as well as the macrophage colony-stimulating factor (M-CSF. The RANKL/RANK system and RANK signaling induce osteoclast formation mediated by various cytokines. The RANK/RANKL pathway has been primarily implicated in metabolic, degenerative and neoplastic bone disorders or osteolysis. The central role of RANK/RANKL interaction in osteoclastogenesis makes RANK an attractive target for potential therapies in treatment of osteolysis. The purpose of this study was to assess the effect of inhibition of RANK expression in mouse bone marrow macrophages on osteoclast differentiation and bone resorption. Methods Three pairs of short hairpin RNAs (shRNA targeting RANK were designed and synthesized. The optimal shRNA was selected among three pairs of shRNAs by RANK expression analyzed by Western blot and Real-time PCR. We investigated suppression of osteoclastogenesis of mouse bone marrow macrophages (BMMs using the optimal shRNA by targeting RANK. Results Among the three shRANKs examined, shRANK-3 significantly suppressed [88.3%] the RANK expression (p Conclusions These findings suggest that retrovirus-mediated shRNA targeting RANK inhibits osteoclast differentiation and osteolysis. It may appear an attractive target for preventing osteolysis in humans with a potential clinical application.

  6. MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner

    International Nuclear Information System (INIS)

    Miyamoto, Kana; Ninomiya, Ken; Sonoda, Koh-Hei; Miyauchi, Yoshiteru; Hoshi, Hiroko; Iwasaki, Ryotaro; Miyamoto, Hiroya

    2009-01-01

    Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a critical role in the recruitment and activation of leukocytes. Here, we describe that multinuclear osteoclast formation was significantly inhibited in cells derived from MCP-1-deficient mice. MCP-1 has been implicated in the regulation of osteoclast cell-cell fusion; however defects of multinuclear osteoclast formation in the cells from mice deficient in DC-STAMP, a seven transmembrane receptor essential for osteoclast cell-cell fusion, was not rescued by recombinant MCP-1. The lack of MCP-1 in osteoclasts resulted in a down-regulation of DC-STAMP, NFATc1, and cathepsin K, all of which were highly expressed in normal osteoclasts, suggesting that osteoclast differentiation was inhibited in MCP-1-deficient cells. MCP-1 alone did not induce osteoclastogenesis, however, the inhibition of osteoclastogenesis in MCP-1-deficient cells was restored by addition of recombinant MCP-1, indicating that osteoclastogenesis was regulated in an autocrine/paracrine manner by MCP-1 under the stimulation of RANKL in osteoclasts.

  7. Gambogic acid inhibits multiple myeloma mediated osteoclastogenesis through suppression of chemokine receptor CXCR4 signaling pathways.

    Science.gov (United States)

    Pandey, Manoj K; Kale, Vijay P; Song, Chunhua; Sung, Shen-shu; Sharma, Arun K; Talamo, Giampaolo; Dovat, Sinisa; Amin, Shantu G

    2014-10-01

    Bone disease, characterized by the presence of lytic lesions and osteoporosis is the hallmark of multiple myeloma (MM). Stromal cell-derived factor 1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4), has been implicated as a regulator of bone resorption, suggesting that agents that can suppress SDF1α/CXCR4 signaling might inhibit osteoclastogenesis, a process closely linked to bone resorption. We, therefore, investigated whether gambogic acid (GA), a xanthone, could inhibit CXCR4 signaling and suppress osteoclastogenesis induced by MM cells. Through docking studies we predicted that GA directly interacts with CXCR4. This xanthone down-regulates the expression of CXCR4 on MM cells in a dose- and time-dependent manner. The down-regulation of CXCR4 was not due to proteolytic degradation, but rather GA suppresses CXCR4 mRNA expression by inhibiting nuclear factor-kappa B (NF-κB) DNA binding. This was further confirmed by quantitative chromatin immunoprecipitation assay, as GA inhibits p65 binding at the CXCR4 promoter. GA suppressed SDF-1α-induced chemotaxis of MM cells and downstream signaling of CXCR4 by inhibiting phosphorylation of Akt, p38, and Erk1/2 in MM cells. GA abrogated the RANKL-induced differentiation of macrophages to osteoclasts in a dose- and time-dependent manner. In addition, we found that MM cells induced differentiation of macrophages to osteoclasts, and that GA suppressed this process. Importantly, suppression of osteoclastogenesis by GA was mediated through IL-6 inhibition. Overall, our results show that GA is a novel inhibitor of CXCR4 expression and has a strong potential to suppress osteoclastogenesis mediated by MM cells. Published by Elsevier Inc.

  8. Interleukin-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Huixian [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China); Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Shi, Zhenqi [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Qiao, Ping [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Department of Pharmacology, Norman Bethune Medical College, Jilin University, Changchun, Jilin 130021 (China); Li, Hui [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); McCoy, Erin M. [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Mao, Ping [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China); Xu, Hui [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Feng, Xu [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Wang, Shunqing, E-mail: shqwang_cn@yahoo.com [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China)

    2013-11-01

    Highlights: •IL-3 treatment of bone marrow cells generates a population of hematopoietic cells. •IL-3-dependent hematopoietic cells are capable of differentiating into osteoclasts. •Osteoclasts derived from IL-3-dependent hematopoietic cells are functional. •IL-3 promotes the development of osteoclast progenitors. •IL-3 inhibits the osteoclastogenic process. -- Abstract: Interleukin (IL)-3, a multilineage hematopoietic growth factor, is implicated in the regulation of osteoclastogenesis. However, the role of IL-3 in osteoclastogenesis remains controversial; whereas early studies showed that IL-3 stimulates osteoclastogenesis, recent investigations demonstrated that IL-3 inhibits osteoclast formation. The objective of this work is to further address the role of IL-3 in osteoclastogenesis. We found that IL-3 treatment of bone marrow cells generated a population of cells capable of differentiating into osteoclasts in tissue culture dishes in response to the stimulation of the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of nuclear factor kappa B ligand (RANKL). The IL-3-dependent hematopoietic cells were able to further proliferate and differentiate in response to M-CSF stimulation and the resulting cells were also capable of forming osteoclasts with M-CSF and RANKL treatment. Interestingly, IL-3 inhibits M-CSF-/RANKL-induced differentiation of the IL-3-dependent hematopoietic cells into osteoclasts. The flow cytometry analysis indicates that while IL-3 treatment of bone marrow cells slightly affected the percentage of osteoclast precursors in the surviving populations, it considerably increased the percentage of osteoclast precursors in the populations after subsequent M-CSF treatment. Moreover, osteoclasts derived from IL-3-dependent hematopoietic cells were fully functional. Thus, we conclude that IL-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the

  9. MyD88 expression in the rat dental follicle: Implications for osteoclastogenesis and tooth eruption

    Science.gov (United States)

    Liu, Dawen; Yao, Shaomian; Wise, Gary E.

    2010-01-01

    Myeloid differentiation factor 88 (MyD88) is a key adaptor molecule in the interleukin-1 (IL-1) and IL-18 Toll-like receptor signaling pathway. Because it is present in dental follicle (DF) cells in vitro, the purpose of this study was to determine its chronological expression in vivo, as well as its possible role in osteoclastogenesis and tooth eruption. An oligo DNA microarray was used to determine gene expression of MyD88 in vivo in the DFs from the first mandibular molars of postnatal rats from days 1–11. The results showed that MyD88 was expressed maximally at day 3. Using siRNA to knock down MyD88 expression in the DF cells also reduced the gene expression of nuclear factor-kappa B-1 (NFKB1) and monocyte chemoattractant protein 1 (MCP-1). IL-1α up-regulated the expression of NFKB1, MCP-1 and receptor activator of nuclear factor kappa B ligand (RANKL), but knockdown of MyD88 nullified this IL-1α effect. Conditioned medium from DF cells with MyD88 knocked down reduced chemotactic activity for mononuclear cells and reduced osteoclastogenesis as opposed to controls. In conclusion, the maximal expression of MyD88 at day 3 in the DF may contribute to the major burst of osteoclastogenesis needed for eruption by up-regulating MCP-1 and RANKL expression. PMID:20662905

  10. The inhibitors of cyclin-dependent kinases and GSK-3β enhance osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Yosuke Akiba

    2016-03-01

    Full Text Available Osteoclasts are multinucleated cells with bone resorption activity that is crucial for bone remodeling. RANK‐RANKL (receptor activator of nuclear factor κB ligand signaling has been shown as a main signal pathway for osteoclast differentiation. However, the molecular mechanism and the factors regulating osteoclastogenesis remain to be fully understood. In this study, we performed a chemical genetic screen, and identified a Cdks/GSK-3β (cyclin-dependent kinases/glycogen synthase kinase 3β inhibitor, kenpaullone, and two Cdks inhibitors, olomoucine and roscovitine, all of which significantly enhance osteoclastogenesis of RAW264.7 cells by upregulating NFATc1 (nuclear factor of activated T cells, cytoplasmic 1 levels. We also determined that the all three compounds increase the number of osteoclast differentiated from murine bone marrow cells. Furthermore, the three inhibitors, especially kenpaullone, promoted maturation of cathepsin K, suggesting that the resorption activity of the resultant osteoclasts is also activated. Our findings indicate that inhibition of GSK-3β and/or Cdks enhance osteoclastogenesis by modulating the RANK–RANKL signaling pathway.

  11. Role of periodontal ligament fibroblasts in osteoclastogenesis: a review

    NARCIS (Netherlands)

    Sokos, D.; Everts, V.; de Vries, T.J.

    2015-01-01

    During the last decade it has become clear that periodontal ligament fibroblasts may contribute to the in vitro differentiation of osteoclasts. We surveyed the current findings regarding their osteoclastogenesis potential. Periodontal ligament fibroblasts have the capacity to select and attract

  12. cAMP/PKA regulates osteogenesis, adipogenesis and ratio of RANKL/OPG mRNA expression in mesenchymal stem cells by suppressing leptin.

    Directory of Open Access Journals (Sweden)

    Der-Chih Yang

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs are a pluripotent cell type that can differentiate into adipocytes, osteoblasts and other cells. The reciprocal relationship between adipogenesis and osteogenesis was previously demonstrated; however, the mechanisms remain largely unknown. METHODS AND FINDINGS: We report that activation of PKA by 3-isobutyl-1 methyl xanthine (IBMX and forskolin enhances adipogenesis, the gene expression of PPARgamma2 and LPL, and downregulates the gene expression of Runx2 and osteopontin, markers of osteogenesis. PKA activation also decreases the ratio of Receptor Activator of the NF-kappaB Ligand to Osteoprotegerin (RANKL/OPG gene expression - the key factors of osteoclastogenesis. All these effects are mediated by the cAMP/PKA/CREB pathway by suppressing leptin, and may contribute to PKA stimulators-induced in vivo bone loss in developing zebrafish. CONCLUSIONS: Using MSCs, the center of a newly proposed bone metabolic unit, we identified cAMP/PKA signaling, one of the many signaling pathways that regulate bone homeostasis via controlling cyto-differentiation of MSCs and altering RANKL/OPG gene expression.

  13. In vitro osteoclastogenesis on textile chitosan scaffold

    Directory of Open Access Journals (Sweden)

    C Heinemann

    2010-02-01

    Full Text Available Textile chitosan fibre scaffolds were evaluated in terms of interaction with osteoclast-like cells, derived from human primary monocytes. Part of the scaffolds was further modified by coating with fibrillar collagen type I in order to make the surface biocompatible. Monocytes were cultured directly on the scaffolds in the presence of macrophage colony stimulating factor (M-CSF and receptor activator of nuclear factor kappaB ligand (RANKL for up to 18 days. Confocal laser scanning microscopy (CLSM as well as scanning electron microscopy (SEM revealed the formation of multinuclear osteoclast-like cells on both the raw chitosan fibres and the collagen-coated scaffolds. The modified surface supported the osteoclastogenesis. Differentiation towards the osteoclastic lineage was confirmed by the microscopic detection of cathepsin K, tartrate resistant acid phosphatase (TRAP, acidic compartments using 3-(2,4-dinitroanillino-3’-amino-N-methyldipropylamine (DAMP, immunological detection of TRAP isoform 5b, and analysis of gene expression of the osteoclastic markers TRAP, cathepsin K, vitronectin receptor, and calcitonin receptor using reverse transcription-polymerase chain reaction (RT-PCR. The feature of the collagen-coated but also of the raw chitosan fibre scaffolds to support attachment and differentiation of human monocytes facilitates cell-induced material resorption – one main requirement for successful bone tissue engineering.

  14. IL-12 Inhibits Lipopolysaccharide Stimulated Osteoclastogenesis in Mice

    Directory of Open Access Journals (Sweden)

    Masako Yoshimatsu

    2015-01-01

    Full Text Available Lipopolysaccharide (LPS is related to osteoclastogenesis in osteolytic diseases. Interleukin- (IL- 12 is an inflammatory cytokine that plays a critical role in host defense. In this study, we investigated the effects of IL-12 on LPS-induced osteoclastogenesis. LPS was administered with or without IL-12 into the supracalvariae of mice, and alterations in the calvarial suture were evaluated histochemically. The number of osteoclasts in the calvarial suture and the mRNA level of tartrate-resistant acid phosphatase (TRAP, an osteoclast marker, were lower in mice administered LPS with IL-12 than in mice administered LPS alone. The serum level of tartrate-resistant acid phosphatase 5b (TRACP 5b, a bone resorption marker, was also lower in mice administered LPS with IL-12 than in mice administered LPS alone. These results revealed that IL-12 might inhibit LPS-induced osteoclastogenesis and bone resorption. In TdT-mediated dUTP-biotin nick end-labeling (TUNEL assays, apoptotic changes in cells were recognized in the calvarial suture in mice administered LPS with IL-12. Furthermore, the mRNA levels of both Fas and FasL were increased in mice administered LPS with IL-12. Taken together, the findings demonstrate that LPS-induced osteoclastogenesis is inhibited by IL-12 and that this might arise through apoptotic changes in osteoclastogenesis-related cells induced by Fas/FasL interactions.

  15. OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice

    DEFF Research Database (Denmark)

    Barrow, Alexander David; Raynal, Nicolas; Levin Andersen, Thomas

    2011-01-01

    by preosteoclasts in vitro, but OSCAR lacks a cognate ligand and its role in vivo has been unclear. Using samples from mice and patients deficient in various ITAM signaling pathways, we show here that OSCAR costimulates one of the major FcRγ-associated pathways required for osteoclastogenesis in vivo. Furthermore...... to signaling that increased numbers of osteoclasts in culture. Thus, our results suggest that ITAM-containing receptors can respond to exposed ligands in collagen, leading to the functional differentiation of leukocytes, which provides what we believe to be a new concept for ITAM regulation of cytokine...

  16. A DNA Microarray Analysis of Chemokine and Receptor Genes in the Rat Dental Follicle – Role of Secreted Frizzled-Related Protein-1 in Osteoclastogenesis

    Science.gov (United States)

    Liu, Dawen; Wise, Gary E.

    2007-01-01

    The dental follicle, a loose connective tissue sac that surrounds the unerupted tooth, appears to regulate the osteoclastogenesis needed for eruption; i.e., bone resorption to form an eruption pathway. Thus, DNA microarray studies were conducted to determine which chemokines and their receptors were expressed chronologically in the dental follicle, chemokines that might attract osteoclast precursors. In the rat first mandibular molar, a major burst of osteoclastogenesis occurs at day 3 with a minor burst at day 10. The results of the microarray confirmed our previous studies showing the gene expression of molecules such as CSF-1 and MCP-1 in the dental follicle cells. Other new genes also were detected, including secreted frizzled-related protein-1 (SFRP-1), which was found to be down-regulated at days 3 and 9. Using rat bone marrow cultures to conduct in vitro osteoclastogenic assays, it was demonstrated that SFRP-1 inhibited osteoclast formation in a concentration-dependent fashion. However, with increasing concentrations of SFRP-1, the number of TRAP-positive mononuclear cells increased suggesting that SFRP-1 inhibits osteoclast formation by inhibiting the fusion of mononuclear cells (osteoclast precursors). Co-culturing bone marrow mononuclear cells and dental follicle cells demonstrated that the dental follicle cells were secreting a product(s) that inhibited osteoclastogenesis, as measured by counting of TRAP-positive osteoclasts. Adding an antibody either to SFRP-1 or OPG partially restored osteoclastogenesis. Adding both anti-SFRP-1 and anti-OPG fully negated the inhibitory effect of the follicle cells upon osteoclastogenesis. These results strongly suggest that SFRP-1 and OPG, both secreted by the dental follicle cells, use different pathways to exert their inhibitory effect on osteoclastogenesis. Based on these in vitro studies of osteoclastogenesis, it is likely that the down-regulation of SFRP-1 gene expression in the dental follicle at days 3 and 9 is

  17. Expression and Function of Transmembrane-4 Superfamily (Tetraspanin Proteins in Osteoclasts: Reciprocal Roles of Tspan-5 and NET-6 during Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Kaori Iwai

    2007-01-01

    Conclusions: These data indicate that a diversity of tetraspanins is expressed in osteoclast precursors, and that cell fusion during osteoclastogenesis is regulated by cooperation of distinct tetraspanin family proteins such as Tspan-5 and NET-6. This study indicates that functional alterations of tetraspanin family proteins may have therapeutic potential in diseases where osteoclasts play a major role, such as rheumatoid arthritis and osteoporosis.

  18. Regulation of the Docosapentaenoic Acid/Docosahexaenoic Acid Ratio (DPA/DHA Ratio) in Schizochytrium limacinum B4D1.

    Science.gov (United States)

    Zhang, Ke; Li, Huidong; Chen, Wuxi; Zhao, Minli; Cui, Haiyang; Min, Qingsong; Wang, Haijun; Chen, Shulin; Li, Demao

    2017-05-01

    Docosapentaenoic acid/docosahexaenoic acid ratio (DPA/DHA ratio) in Schizochytrium was relatively stable. But ideally the ratio of DPA/DHA will vary according to the desired end use. This study reports several ways of modulating the DPA/DHA ratio. Incubation times changed the DPA/DHA ratio, and changes in this ratio were associated with the variations in the saturated fatty acid (SFAs) content. Propionic acid sharply increased the SFAs content in lipids, dramatically decreased the even-chain SFAs content, and reduced the DPA/DHA ratio. Pentanoic acid (C5:0) and heptanoic acid (C7:0) had similar effects as propionic acid, whereas butyric acid (C4:0), hexanoic acid (C6:0), and octanoic acid (C8:0) did not change the fatty acid profile and the DPA/DHA ratio. Transcription analyses show that β-oxidation might be responsible for this phenomenon. Iodoacetamide upregulated polyunsaturated fatty acid (PUFA) synthase genes, reduced the DHA content, and improved the DPA content, causing the DPA/DHA ratio to increase. These results present new insights into the regulation of the DPA/DHA ratio.

  19. Molecular Signaling Pathways Mediating Osteoclastogenesis Induced by Prostate Cancer Cells

    International Nuclear Information System (INIS)

    Rafiei, Shahrzad; Komarova, Svetlana V

    2013-01-01

    Advanced prostate cancer commonly metastasizes to bone leading to osteoblastic and osteolytic lesions. Although an osteolytic component governed by activation of bone resorbing osteoclasts is prominent in prostate cancer metastasis, the molecular mechanisms of prostate cancer-induced osteoclastogenesis are not well-understood. We studied the effect of soluble mediators released from human prostate carcinoma cells on osteoclast formation from mouse bone marrow and RAW 264.7 monocytes. Soluble factors released from human prostate carcinoma cells significantly increased viability of naïve bone marrow monocytes, as well as osteoclastogenesis from precursors primed with receptor activator of nuclear factor κ-B ligand (RANKL). The prostate cancer-induced osteoclastogenesis was not mediated by RANKL as it was not inhibited by osteoprotegerin (OPG). However inhibition of TGFβ receptor I (TβRI), or macrophage-colony stimulating factor (MCSF) resulted in attenuation of prostate cancer-induced osteoclastogenesis. We characterized the signaling pathways induced in osteoclast precursors by soluble mediators released from human prostate carcinoma cells. Prostate cancer factors increased basal calcium levels and calcium fluctuations, induced nuclear localization of nuclear factor of activated t-cells (NFAT)c1, and activated prolonged phosphorylation of ERK1/2 in RANKL-primed osteoclast precursors. Inhibition of calcium signaling, NFATc1 activation, and ERK1/2 phosphorylation significantly reduced the ability of prostate cancer mediators to stimulate osteoclastogenesis. This study reveals the molecular mechanisms underlying the direct osteoclastogenic effect of prostate cancer derived factors, which may be beneficial in developing novel osteoclast-targeting therapeutic approaches

  20. Brucella abortus-infected B cells induce osteoclastogenesis.

    Science.gov (United States)

    Pesce Viglietti, Ayelén Ivana; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán; Delpino, María Victoria

    2016-09-01

    Brucella abortus is an intracellular bacterium that establishes lifelong infections in livestock and humans although the mechanisms of its chronicity are poorly understood. Activated B cells have long lifespan and B. abortus infection activates B cells. Our results indicate that the direct infection of B cells with B. abortus induced matrix metalloproteinase-9 (MMP-9), receptor activator for NF κB ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion. In addition, supernatants from B. abortus-infected B cells induced bone marrow-derived monocytes to undergo osteoclastogenesis. Using osteoprotegerin, RANKL's decoy receptor, we determined that RANKL is involved in osteoclastogenesis induced by supernatants from B. abortus-infected B cells. The results presented here shed light on how the interactions of B. abortus with B cells may have a role in the pathogenesis of brucellar osteoarticular disease. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  1. The Modulatory Effects of Mesenchymal Stem Cells on Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Wessam E. Sharaf-Eldin

    2016-01-01

    Full Text Available The effect of mesenchymal stem cells (MSCs on bone formation has been extensively demonstrated through several in vitro and in vivo studies. However, few studies addressed the effect of MSCs on osteoclastogenesis and bone resorption. Under physiological conditions, MSCs support osteoclastogenesis through producing the main osteoclastogenic cytokines, RANKL and M-CSF. However, during inflammation, MSCs suppress osteoclast formation and activity, partly via secretion of the key anti-osteoclastogenic factor, osteoprotegerin (OPG. In vitro, co-culture of MSCs with osteoclasts in the presence of high concentrations of osteoclast-inducing factors might reflect the in vivo inflammatory pathology and prompt MSCs to exert an osteoclastogenic suppressive effect. MSCs thus seem to have a dual effect, by stimulating or inhibiting osteoclastogenesis, depending on the inflammatory milieu. This effect of MSCs on osteoclast formation seems to mirror the effect of MSCs on other immune cells, and may be exploited for the therapeutic potential of MSCs in bone loss associated inflammatory diseases.

  2. Staphylococcal enterotoxin C2 promotes osteogenesis and suppresses osteoclastogenesis of human mesenchymal stem cells.

    Science.gov (United States)

    Fu, Wei-ming; Zhu, Xiao; Wang, Hua; Wei-Mao Wang; Chen, Ju-yu; Liang, Yan; Zhang, Jin-fang; Kung, Hsiang-fu

    2014-03-10

    As a super-antigen, staphylococcal enterotoxin C2 (SEC2) stimulates the release of massive inflammatory cytokines such as interferon-gamma (IFN-γ), interleukin-1 (IL-1) and interleukin-2 (IL-2) which are documented to implicate osteoblast differentiation. In the present study, SEC2 was found to significantly improve the osteoblast differentiation by up-regulating BMP2 and Runx2/Cbfa1 expression. Interferon (IFN)-inducible gene IFI16, a co-activator of Runx2/Cbfa1, was also activated by SEC2 in the osteoblast differentiation. In addition, exogenous introduction of SEC2 stimulated OPG expression and suppressed RANKL, suggesting suppression of osteoclastogenesis in hMSCs. Therefore, our results displayed that SEC2 plays an important role in the commitment of MSC to the osteoblast and it might be a potential new therapeutic candidate for bone regeneration. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Effects of diclofenac and celecoxib on osteoclastogenesis during alveolar bone healing, in vivo

    Directory of Open Access Journals (Sweden)

    Parichehr Ghalayani

    2014-01-01

    Full Text Available Background: Osteoclastogenesis is coordinated by the interaction of members of the tumor necrosis factor (TNF superfamily: Receptor activator of nuclear factor- κB ligand (RANKL and Osteoprotegerin (OPG. The aim of this study was to compare the effect of two different types of non-steroidal anti-inflammatory drugs (NSAIDs on the RANKL/OPG balance during the healing of the alveolar process. Materials and Methods: This was an experimental study, carried on 45 male Wistar rats (200 ± 25 g, 8-10 weeks old. After extraction of the right maxillary first molar, 15 rats received 5 mg/kg/day of diclofenac and 15 rats received 15 mg/kg/day of celecoxib and 15 rats received normal saline. The animals were sacrificed 7, 14 and 21 days after tooth extraction. The number of osteoclasts, OPG and RANKL messenger ribonucleic acid expression were determined by tartrate-resistant acid phosphate (TRAP staining and polymerase chain reaction (PCR respectively. The data were analyzed by one-way ANOVA followed by Tukey′s post-hoc test. Values of P < 0.05 were considered significant. Results: On days 7, 14 and 21 the ratio of RANKL/OPG in the control group was higher than diclofenac and celecoxib groups. TRAP immunolabeling of the control group was more than diclofenac group on day 7 and was more than celecoxib group on day 14. On day 21, no significant differences were noted among the three studied groups. Conclusion: Both drugs affect RANKL/OPG gene expression and also osteoclastogenesis in alveolar socket during the experimental period of 21 days.

  4. Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Yoon-Hee [Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kim, Ju-Young [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Baek, Jong Min; Ahn, Sung-Jun [Department of Anatomy, School of Medicine, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Oh, Jaemin, E-mail: jmoh@wku.ac.kr [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Department of Anatomy, School of Medicine, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2016-02-05

    Niclosamide (5-chloro-salicyl-(2-chloro-4-nitro) anilide) is an oral anthelmintic drug used for treating intestinal infection of most tapeworms. Recently, niclosamide was shown to have considerable efficacy against some tumor cell lines, including colorectal, prostate, and breast cancers, and acute myelogenous leukemia. Specifically, the drug was identified as a potent inhibitor of signal transducer and activator of transcription 3 (STAT3), which is associated with osteoclast differentiation and function. In this study, we assessed the effect of niclosamide on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was inhibited by niclosamide, due to inhibition of serine–threonine protein kinase (Akt) phosphorylation, inhibitor of nuclear factor-kappaB (IκB), and STAT3 serine{sup 727}. Niclosamide decreased the expression of the major transcription factors c-Fos and NFATc1, and thereafter abrogated the mRNA expression of osteoclast-specific genes, including TRAP, OSCAR, αv/β3 integrin (integrin αv, integrin β3), and cathepsin K (CtsK). In an in vivo model, niclosamide prevented lipopolysaccharide-induced bone loss by diminishing osteoclast activity. Taken together, our results show that niclosamide is effective in suppressing osteoclastogenesis and may be considered as a new and safe therapeutic candidate for the clinical treatment of osteoclast-related diseases such as osteoporosis. - Highlights: • We first investigated the anti-osteoclastogenic effects of niclosamide in vitro and in vivo. • Niclosamide impairs the activation of the Akt-IκB-STAT3 ser{sup 727} signaling axis. • Niclosamide acts a negative regulator of actin ring formation during osteoclast differentiation. • Niclosamide suppresses LPS-induced bone loss in vivo. • Niclosamide deserves new evaluation as a potential treatment target in various bone diseases.

  5. Dual role of interleukin-17 in pannus growth and osteoclastogenesis in rheumatoid arthritis.

    Science.gov (United States)

    Ito, Hiroshi; Yamada, Hidehiro; Shibata, Toshiko N; Mitomi, Hirofumi; Nomoto, So; Ozaki, Shoichi

    2011-02-04

    In a murine model, interleukin (IL)-17 plays a critical role in the pathogenesis of arthritis. There are controversies, however, regarding whether IL-17 is a proinflammatory mediator in rheumatoid arthritis (RA). We previously established an ex vivo cellular model using synovial tissue (ST)-derived inflammatory cells, which reproduced pannus-like tissue growth and osteoclastic activity in vitro. Using this model, we investigated the effects of IL-17 on pannus growth and osteoclastogenesis in RA. Inflammatory cells that infiltrated synovial tissue from patients with RA were collected without enzyme digestion and designated as ST-derived inflammatory cells. ST-derived inflammatory cells were cultured in the presence or absence of IL-17 or indomethacin, and the morphologic changes were observed for 4 weeks. Cytokines produced in the culture supernatants were measured by using enzyme-linked immunosorbent assay kits. Osteoclastic activity was assessed by the development of resorption pits in calcium phosphate-coated slides. Exogenous addition of IL-17 dramatically enhanced the spontaneous production of IL-6 and prostaglandin E₂ (PGE₂) by the ST-derived inflammatory cells, while it had no effect on the production of tumor necrosis factor (TNF)-α and macrophage colony-stimulating factor (M-CSF). Furthermore, IL-17 did not affect the spontaneous development of pannus-like tissue growth and osteoclastic activity by the ST-derived inflammatory cells. On the other hand, IL-17 enhanced pannus-like tissue growth, the production of TNF-α and M-CSF and the development of osteoclastic activity in the presence of indomethacin, an inhibitor of endogenous prostanoid production, while exogenous addition of PGE₁ suppressed their activities. The present study suggests that IL-17 induces negative feedback regulation through the induction of PGE₂, while it stimulates proinflammatory pathways such as inflammatory cytokine production, pannus growth and osteoclastogenesis in RA.

  6. Down-regulation of tissue N:P ratios in terrestrial plants by elevated CO2.

    Science.gov (United States)

    Deng, Qi; Hui, Dafeng; Luo, Yiqi; Elser, James; Wang, Ying-ping; Loladze, Irakli; Zhang, Quanfa; Dennis, Sam

    2015-12-01

    Increasing atmospheric CO2 concentrations generally alter element stoichiometry in plants. However, a comprehensive evaluation of the elevated CO2 impact on plant nitrogen: phosphorus (N:P) ratios and the underlying mechanism has not been conducted. We synthesized the results from 112 previously published studies using meta-analysis to evaluate the effects of elevated CO2 on the N:P ratio of terrestrial plants and to explore the underlying mechanism based on plant growth and soil P dynamics. Our results show that terrestrial plants grown under elevated CO2 had lower N:P ratios in both above- and belowground biomass across different ecosystem types. The response ratio for plant N:P was negatively correlated with the response ratio for plant growth in croplands and grasslands, and showed a stronger relationship for P than for N. In addition, the CO2-induced down-regulation of plant N:P was accompanied by 19.3% and 4.2% increases in soil phosphatase activity and labile P, respectively, and a 10.1% decrease in total soil P. Our results show that down-regulation of plant N:P under elevated CO2 corresponds with accelerated soil P cycling. These findings should be useful for better understanding of terrestrial plant stoichiometry in response to elevated CO2 and of the underlying mechanisms affecting nutrient dynamics under climate change.

  7. G protein-coupled receptor 84 controls osteoclastogenesis through inhibition of NF-κB and MAPK signaling pathways.

    Science.gov (United States)

    Park, Ji-Wan; Yoon, Hye-Jin; Kang, Woo Youl; Cho, Seungil; Seong, Sook Jin; Lee, Hae Won; Yoon, Young-Ran; Kim, Hyun-Ju

    2018-02-01

    GPR84, a member of the G protein-coupled receptor family, is found predominantly in immune cells, such as macrophages, and functions as a pivotal modulator of inflammatory responses. In this study, we investigated the role of GPR84 in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. Our microarray data showed that GPR84 was significantly downregulated in osteoclasts compared to in their precursors, macrophages. The overexpression of GPR84 in bone marrow-derived macrophages suppressed the formation of multinucleated osteoclasts without affecting precursor proliferation. In addition, GPR84 overexpression attenuated the induction of c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), which are transcription factors that are critical for osteoclastogenesis. Furthermore, knockdown of GPR84 using a small hairpin RNA promoted RANKL-mediated osteoclast differentiation and gene expression of osteoclastogenic markers. Mechanistically, GPR84 overexpression blocked RANKL-stimulated phosphorylation of IκBα and three MAPKs, JNK, ERK, and p38. GPR84 also suppressed NF-κB transcriptional activity mediated by RANKL. Conversely, GPR84 knockdown enhanced RANKL-induced activation of IκBα and the three MAPKs. Collectively, our results revealed that GPR84 functions as a negative regulator of osteoclastogenesis, suggesting that it may be a potential therapeutic target for osteoclast-mediated bone-destructive diseases. © 2017 Wiley Periodicals, Inc.

  8. RANKL release from self-assembling nanofiber hydrogels for inducing osteoclastogenesis in vitro.

    Science.gov (United States)

    Xing, James Z; Lu, Lei; Unsworth, Larry D; Major, Paul W; Doschak, Michael R; Kaipatur, Neelambar R

    2017-02-01

    , facilitating the required changes in the surrounding alveolar bone through the process of bone remodelling. The RANKL system regulates alveolar bone remodelling and controls root resorption during OTM. The use of exogenous RANKL to accelerate OTM has not been attempted to date because large quantities of RANKL for systemic therapy may subsequently cause serious systemic loss of skeletal bone. The controlled and sustained local release of RANKL from a carrier matrix could maximize its therapeutic benefit whilst minimizing systemic side effects. In this study a NF-hydrogel was used for sustained and controlled release of RANKL and the release kinetics and biofunctionality of the released RANKL was characterized. Our results provide fundamental insight for further investigating the role of RANKL NF-hydrogel release systems for inducing osteoclastogenesis in vivo. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. Lipoxin A4 suppresses osteoclastogenesis in RAW264.7 cells and prevents ovariectomy-induced bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Changyu; Guan, Hanfeng; Cai, Cong; Li, Feng, E-mail: lifengmd@hust.edu.cn; Xiao, Jun, E-mail: jun_xiao@hust.edu.cn

    2017-03-15

    Lipoxin A4 (LXA4; 5S, 6R, 15Strihydroxy- 7,9,13-trans-11-eicosatetraenoic acid) is a metabolic product of arachidonic acid under the action of lipoxidase. This lipid molecule plays important roles in several biological functions, especially inflammatory processes. In vivo, LXA4 regulates the inflammatory response through several signaling pathways. Its mechanism suggests that it might have an effect on osteoclastogenesis and bone loss. Using both in vitro and in vivo studies, it was here observed that LXA4 could significantly inhibit the formation and function of osteoclasts and these effects could be blocked by Boc-2, the specific inhibitor of FPR2/ALX (the receptor of LXA4). Meanwhile, LXA4 reduce the amount of ovariectomy-induced bone loss. These protective effects was found to be associated with inhibition of nuclear factor-κB (NF-κB), activator protein-1 (AP-1), PI3K-AKT, and p-38, ERK, and JNK in MAPKs. The expression of the receptor activator of the NF-κB ligand RANKL:osteoprotegerin ratio and serum levels of TNF-α, IL-1β, and IL-6 were decreased by LXA4. Moreover, LXA4 prevented the production of reactive oxygen species (ROS), the expression of osteoclast-specific genes, including tartrate-resistant acid phosphatase (TRAP), cathepsin K (CK), matrix metalloproteinase (MMP)-9, RANK, and osteoclastic related transcription factors of c-Fos, NFATc1 could also be significantly inhibited by LXA4 in a dose-dependent manner. Studies have demonstrated that LXA4 can inhibit the formation and function of osteoclasts through modulation of several pathways both upstream and downstream of RANKL signaling and FPR2/ALX was involved in the procedures. This shows that LXA4 may be used as a new strategy for the treatment of osteoclast-related diseases. - Highlights: • Lipoxin A4 can significantly inhibit the formation and function of osteoclasts. • Several pathways both upstream and downstream of RANKL signaling can be inhibit by Lipoxin A4. • Lipoxin A4 can

  10. Modulation of human osteoclastogenesis and osteoblastogenesis by lycopene.

    Science.gov (United States)

    Costa-Rodrigues, João; Fernandes, Maria Helena; Pinho, Olívia; Monteiro, Pedro Ribeiro Rocha

    2018-03-15

    Lycopene is a lipid-soluble pigment that is mainly found in tomato. It is the carotenoid that presents the highest antioxidant potential, and due to that, it has been implicated in a decrease of the risk of several oxidative-stress-related disorders, such as cancer, inflammatory diseases and osteoporosis. Nevertheless, at the present, there is no detailed information about how lycopene affects bone metabolism. The aim of the present work was to characterize the cellular and molecular effects of lycopene on human osteoclast and osteoblast differentiation and function. It was observed that lycopene, at levels found in plasma after the ingestion of lycopene-containing products, decreased osteoclast differentiation but did not affect cell density/survival; calcium-phosphate resorbing ability was also decreased. On the other hand, osteoblast proliferation (via a decrease on apoptosis) and differentiation were increased in the presence of lycopene. The observed effects in both cell types appeared to be related to significant changes in MEK signaling pathway, but also in protein kinase C pathway in osteoclasts and NFkB signaling in osteoblasts. In conclusion, lycopene appears to promote an anabolic state of bone metabolism, stimulating osteoblastogenesis and inhibiting osteoclastogenesis, which may contribute to the promotion of a proper health status of bone tissue. This information might be relevant for the prevention and delay in the progression of osteolytic bone conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Kazuyo [Microscopy and Imaging Core Facility, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD (United States); Adhikari, Rewati [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); Yamada, Kenneth M. [National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Dhawan, Subhash, E-mail: subhash.dhawan@fda.hhs.gov [Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

    2015-08-14

    The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection.

  12. Hemin activation of innate cellular response blocks human immunodeficiency virus type-1-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    Takeda, Kazuyo; Adhikari, Rewati; Yamada, Kenneth M.; Dhawan, Subhash

    2015-01-01

    The normal skeletal developmental and homeostatic process termed osteoclastogenesis is exacerbated in numerous pathological conditions and causes excess bone loss. In cancer and HIV-1-infected patients, this disruption of homeostasis results in osteopenia and eventual osteoporesis. Counteracting the factors responsible for these metabolic disorders remains a challenge for preventing or minimizing this co-morbidity associated with these diseases. In this report, we demonstrate that a hemin-induced host protection mechanism not only suppresses HIV-1 associated osteoclastogenesis, but it also exhibits anti-osteoclastogenic activity for non-infected cells. Since the mode of action of hemin is both physiological and pharmacological through induction of heme oxygenase-1 (HO-1), an endogenous host protective response to an FDA-licensed therapeutic used to treat another disease, our study suggests an approach to developing novel, safe and effective therapeutic strategies for treating bone disorders, because hemin administration in humans has previously met required FDA safety standards. - Highlights: • HIV-1 infection induced osteoclastogenesis in primary human macrophages. • Heme oxygenase-1 (HO-1) induction inhibited HIV-1-induced osteoclastogenesis in macrophages. • HO-1 induction suppressed RANKL-enhanced osteoclastogenesis in HIV-1-infected macrophages. • This inverse relationship between HO-1 and HIV-1 pathogenesis may define a novel host defense response against HIV-1 infection

  13. Toll-Like Receptor 2 Stimulation of Osteoblasts Mediates Staphylococcus Aureus Induced Bone Resorption and Osteoclastogenesis through Enhanced RANKL

    Science.gov (United States)

    Kassem, Ali; Lindholm, Catharina; Lerner, Ulf H

    2016-01-01

    Severe Staphylococcus aureus (S. aureus) infections pose an immense threat to population health and constitute a great burden for the health care worldwide. Inter alia, S. aureus septic arthritis is a disease with high mortality and morbidity caused by destruction of the infected joints and systemic bone loss, osteoporosis. Toll-Like receptors (TLRs) are innate immune cell receptors recognizing a variety of microbial molecules and structures. S. aureus recognition via TLR2 initiates a signaling cascade resulting in production of various cytokines, but the mechanisms by which S. aureus causes rapid and excessive bone loss are still unclear. We, therefore, investigated how S. aureus regulates periosteal/endosteal osteoclast formation and bone resorption. S. aureus stimulation of neonatal mouse parietal bone induced ex vivo bone resorption and osteoclastic gene expression. This effect was associated with increased mRNA and protein expression of receptor activator of NF-kB ligand (RANKL) without significant change in osteoprotegerin (OPG) expression. Bone resorption induced by S. aureus was abolished by OPG. S. aureus increased the expression of osteoclastogenic cytokines and prostaglandins in the parietal bones but the stimulatory effect of S. aureus on bone resorption and Tnfsf11 mRNA expression was independent of these cytokines and prostaglandins. Stimulation of isolated periosteal osteoblasts with S. aureus also resulted in increased expression of Tnfsf11 mRNA, an effect lost in osteoblasts from Tlr2 knockout mice. S. aureus stimulated osteoclastogenesis in isolated periosteal cells without affecting RANKL-stimulated resorption. In contrast, S. aureus inhibited RANKL-induced osteoclast formation in bone marrow macrophages. These data show that S. aureus enhances bone resorption and periosteal osteoclast formation by increasing osteoblast RANKL production through TLR2. Our study indicates the importance of using different in vitro approaches for studies of how S

  14. Cofactor engineering to regulate NAD+/NADH ratio with its application to phytosterols biotransformation.

    Science.gov (United States)

    Su, Liqiu; Shen, Yanbing; Zhang, Wenkai; Gao, Tian; Shang, Zhihua; Wang, Min

    2017-10-30

    Cofactor engineering is involved in the modification of enzymes related to nicotinamide adenine dinucleotides (NADH and NAD + ) metabolism, which results in a significantly altered spectrum of metabolic products. Cofactor engineering plays an important role in metabolic engineering but is rarely reported in the sterols biotransformation process owing to its use of multi-catabolic enzymes, which promote multiple consecutive reactions. Androst-4-ene-3, 17-dione (AD) and androst-1, 4-diene-3, 17-dione (ADD) are important steroid medicine intermediates that are obtained via the nucleus oxidation and the side chain degradation of phytosterols by Mycobacterium. Given that the biotransformation from phytosterols to AD (D) is supposed to be a NAD + -dependent process, this work utilized cofactor engineering in Mycobacterium neoaurum and investigated the effect on cofactor and phytosterols metabolism. Through the addition of the coenzyme precursor of nicotinic acid in the phytosterols fermentation system, the intracellular NAD + /NADH ratio and the AD (D) production of M. neoaurum TCCC 11978 (MNR M3) were higher than in the control. Moreover, the NADH: flavin oxidoreductase was identified and was supposed to exert a positive effect on cofactor regulation and phytosterols metabolism pathways via comparative proteomic profiling of MNR cultured with and without phytosterols. In addition, the NADH: flavin oxidoreductase and a water-forming NADH oxidase from Lactobacillus brevis, were successfully overexpressed and heterologously expressed in MNR M3 to improve the intracellular ratio of NAD + /NADH. After 96 h of cultivation, the expression of these two enzymes in MNR M3 resulted in the decrease in intracellular NADH level (by 51 and 67%, respectively) and the increase in NAD + /NADH ratio (by 113 and 192%, respectively). Phytosterols bioconversion revealed that the conversion ratio of engineered stains was ultimately improved by 58 and 147%, respectively. The highest AD (D

  15. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei

    2015-01-01

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release

  16. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei, E-mail: chtw@sina.com

    2015-03-06

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release.

  17. Excavatolide B Attenuates Rheumatoid Arthritis through the Inhibition of Osteoclastogenesis.

    Science.gov (United States)

    Lin, Yen-You; Jean, Yen-Hsuan; Lee, Hsin-Pai; Lin, Sung-Chun; Pan, Chieh-Yu; Chen, Wu-Fu; Wu, Shu-Fen; Su, Jui-Hsin; Tsui, Kuan-Hao; Sheu, Jyh-Horng; Sung, Ping-Jyun; Wen, Zhi-Hong

    2017-01-06

    Osteoclasts are multinucleated giant cells of macrophage/monocyte lineage, and cell differentiation with the upregulation of osteoclast-related proteins is believed to play a major role in the destruction of the joints in the course of rheumatoid arthritis (RA). Pro-inflammatory cytokines, such as interleukin-17A (IL-17A) and macrophage colony-stimulating factor (M-CSF), can be overexpressed in RA and lead to osteoclastogenesis. In a previous study, we found that cultured-type soft coral-derived excavatolide B (Exc-B) exhibited anti-inflammatory properties. In the present study, we thus aimed to evaluate the anti-arthritic activity of Exc-B in in vitro and in vivo models. The results demonstrated that Exc-B inhibits LPS-induced multinucleated cell and actin ring formation, as well as TRAP, MMP-9, and cathepsin K expression. Additionally, Exc-B significantly attenuated the characteristics of RA in adjuvant (AIA) and type II collagen-induced arthritis (CIA) in rats. Moreover, Exc-B improved histopathological features, and reduced the number of TRAP-positive multinucleated cells in the in vivo AIA and CIA models. Immunohistochemical analysis showed that Exc-B attenuated the protein expression of cathepsin K, MMP-2, MMP-9, CD11b, and NFATc1 in ankle tissues of AIA and CIA rats. Level of interleukin-17A and macrophage colony-stimulating factor were also decreased by Exc-B. These findings strongly suggest that Exc-B could be of potential use as a therapeutic agent by inhibiting osteoclast differentiation in arthritis. Moreover, this study also illustrates the use of the anti-inflammatory marine compound, Exc-B, as a potential therapeutic strategy for RA.

  18. Excavatolide B Attenuates Rheumatoid Arthritis through the Inhibition of Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Yen-You Lin

    2017-01-01

    Full Text Available Osteoclasts are multinucleated giant cells of macrophage/monocyte lineage, and cell differentiation with the upregulation of osteoclast-related proteins is believed to play a major role in the destruction of the joints in the course of rheumatoid arthritis (RA. Pro-inflammatory cytokines, such as interleukin-17A (IL-17A and macrophage colony-stimulating factor (M-CSF, can be overexpressed in RA and lead to osteoclastogenesis. In a previous study, we found that cultured-type soft coral-derived excavatolide B (Exc-B exhibited anti-inflammatory properties. In the present study, we thus aimed to evaluate the anti-arthritic activity of Exc-B in in vitro and in vivo models. The results demonstrated that Exc-B inhibits LPS-induced multinucleated cell and actin ring formation, as well as TRAP, MMP-9, and cathepsin K expression. Additionally, Exc-B significantly attenuated the characteristics of RA in adjuvant (AIA and type II collagen-induced arthritis (CIA in rats. Moreover, Exc-B improved histopathological features, and reduced the number of TRAP-positive multinucleated cells in the in vivo AIA and CIA models. Immunohistochemical analysis showed that Exc-B attenuated the protein expression of cathepsin K, MMP-2, MMP-9, CD11b, and NFATc1 in ankle tissues of AIA and CIA rats. Level of interleukin-17A and macrophage colony-stimulating factor were also decreased by Exc-B. These findings strongly suggest that Exc-B could be of potential use as a therapeutic agent by inhibiting osteoclast differentiation in arthritis. Moreover, this study also illustrates the use of the anti-inflammatory marine compound, Exc-B, as a potential therapeutic strategy for RA.

  19. Abnormalities in osteoclastogenesis and decreased tumorigenesis in mice deficient for ovarian cancer G protein-coupled receptor 1.

    Directory of Open Access Journals (Sweden)

    Hui Li

    2009-05-01

    Full Text Available Ovarian cancer G protein-coupled receptor 1 (OGR1 has been shown to be a proton sensing receptor in vitro. We have shown that OGR1 functions as a tumor metastasis suppressor gene when it is over-expressed in human prostate cancer cells in vivo. To examine the physiological functions of OGR1, we generated conditional OGR1 deficient mice by homologous recombination. OGR1 deficient mice were viable and upon gross-inspection appeared normal. Consistent with in vitro studies showing that OGR1 is involved in osteoclastogenesis, reduced osteoclasts were detected in OGR1 deficient mice. A pH-dependent osteoclasts survival effect was also observed. However, overall abnormality in the bones of these animals was not observed. In addition, melanoma cell tumorigenesis was significantly inhibited in OGR1 deficient mice. OGR1 deficient mice in the mixed background produced significantly less peritoneal macrophages when stimulated with thioglycolate. These macrophages also showed altered extracellular signal-regulated kinases (ERK activation and nitric oxide (NO production in response to lipopolysaccharide. OGR1-dependent pH responses assessed by cAMP production and cell survival in macrophages or brown fat cells were not observed, presumably due to the presence of other proton sensing receptors in these cells. Our results indicate that OGR1's role in osteoclastogenesis is not strong enough to affect overall bone development and its role in tumorigenesis warrants further investigation. The mice generated can be potentially used for several disease models, including cancers or osteoclast-related diseases.

  20. Foxp3 regulates ratio of Treg and NKT cells in a mouse model of asthma.

    Science.gov (United States)

    Lu, Yanming; Guo, Yinshi; Xu, Linyun; Li, Yaqin; Cao, Lanfang

    2015-05-01

    Chronic inflammatory disorder of the airways causes asthma. Regulatory T cells (Treg cells) and Natural killer T cells (NKT cells) both play critical roles in the pathogenesis of asthma. Activation of Treg cells requires Foxp3, whereas whether Foxp3 may regulate the ratio of Treg and NKT cells to affect asthma is uncertain. In an ovalbumin (OVA)-induced mouse model of asthma, we either increased Treg cells by lentivirus-mediated forced expression of exogenous Foxp3, or increased NKT cells by stimulation with its activator α-GalCer. We found that the CD4+CD25+ Treg cells increased by forced Foxp3 expression, and decreased by α-GalCer, while the CD3+CD161+ NKT cells decreased by forced Foxp3 expression, and increased by α-GalCer. Moreover, forced Foxp3 expression, but not α-GalCer, significantly alleviated the hallmarks of asthma. Furthermore, forced Foxp3 increased levels of IL_10 and TGFβ1, and α-GalCer increased levels of IL_4 and INFγ in the OVA-treated lung. Taken together, our study suggests that Foxp3 may activate Treg cells and suppress NKT cells in asthma. Treg and NKT cells may antagonize the effects of each other in asthma.

  1. Impact of Docosahexaenoic Acid on Gene Expression during Osteoclastogenesis in Vitro—A Comprehensive Analysis

    Directory of Open Access Journals (Sweden)

    Ikuo Morita

    2013-08-01

    Full Text Available Polyunsaturated fatty acids (PUFAs, especially n-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA, are known to protect against inflammation-induced bone loss in chronic inflammatory diseases, such as rheumatoid arthritis, periodontitis and osteoporosis. We previously reported that DHA, not EPA, inhibited osteoclastogenesis induced by the receptor activator of nuclear factor-κB ligand (sRANKL in vitro. In this study, we performed gene expression analysis using microarrays to identify genes affected by the DHA treatment during osteoclastogenesis. DHA strongly inhibited osteoclastogenesis at the late stage. Among the genes upregulated by the sRANKL treatment, 4779 genes were downregulated by DHA and upregulated by the EPA treatment. Gene ontology analysis identified sets of genes related to cell motility, cell adhesion, cell-cell signaling and cell morphogenesis. Quantitative PCR analysis confirmed that DC-STAMP, an essential gene for the cell fusion process in osteoclastogenesis, and other osteoclast-related genes, such as Siglec-15, Tspan7 and Mst1r, were inhibited by DHA.

  2. Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Wani, Mohan R., E-mail: mohanwani@nccs.res.in [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India)

    2010-09-03

    Research highlights: {yields} IL-3 inhibits receptor activator of NF-{kappa}B ligand (RANKL)-induced osteoclastogenesis. {yields} IL-3 inhibits RANKL-induced JNK activation. {yields} IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. {yields} IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. {yields} IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-{kappa}B (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

  3. Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T.; Wani, Mohan R.

    2010-01-01

    Research highlights: → IL-3 inhibits receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. → IL-3 inhibits RANKL-induced JNK activation. → IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. → IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. → IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-κB (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

  4. BONE METABOLISM AND ITS REGULATION IN PATIENTS WITH ANKYLOSING SPONDYLITIS

    Directory of Open Access Journals (Sweden)

    O. V. Bugrova

    2016-01-01

    Full Text Available Osteoporosis in ankylosing spondylitis (AS may exacerbate pain and functional disorders and increases the risk of fractures. The mechanisms  of its development in AS have not been adequately studied.Objective: to study bone mineral density (BMD  and its regulation in patients with AS.Subjects and methods. 70 patients (mean age, 43.2±9.2 years with a documented diagnosis of AS (mean disease duration, 17.1±7.8 years and a control group of 30 healthy individuals were examined. All the patients underwent estimation of BMD and the serum concentrations of osteocalcin,  CrossLaps, and key regulators of osteoclastogenesis, such as osteoprotegerin (OPG  and a receptor activator of nuclear factor kappa-B ligand (RANKL by an enzyme immunoassay. Results and discussion. In patients with AS, bone metabolism was characterized  by a decrease in bone formation and by some increase in bone tissue degradation especially in high AS activity. These patients showed the elevated levels of the major blocker of osteoclastogenesis OPG and the OPG/RANKL ratio, which can cause the process of ossification characteristic  of AS.

  5. Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity in the Context of Collagen-Induced Arthritis

    Science.gov (United States)

    Muschter, Dominique; Schäfer, Nicole; Stangl, Hubert; Straub, Rainer H.; Grässel, Susanne

    2015-01-01

    Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA). Concomitantly, local synovial changes comprise neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze if collagen-induced arthritis (CIA) alters bone marrow-derived macrophage (BMM) osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters participate in this process. Therefore, BMMs from Dark Agouti rats at different CIA stages were differentiated into osteoclasts in vitro and osteoclast number, cathepsin K activity, matrix resorption and apoptosis were analyzed in the presence of acetylcholine (ACh), noradrenaline (NA) vasoactive intestinal peptide (VIP) and assay-dependent, adenylyl cyclase activator NKH477. We observed modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts without affecting protein level. CIA stage-dependently altered marker gene expression associated with osteoclast differentiation and activity without affecting osteoclast number or activity. Neurotransmitter stimulation modulated osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477, 10-6M NA) whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA alone does not affect metabolism of in vitro generated osteoclasts whereas stimulation with NA, VIP plus specific activation of adenylyl cyclase induced anti-resorptive effects probably mediated via cAMP signaling. Contrary, we suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via muscarinic receptors. PMID:26431344

  6. Relaxing technical regulations under the Landings Obligation – effects on the discard ratio

    DEFF Research Database (Denmark)

    Mortensen, Lars O.; Olesen, Hans Jakob; Qvist Eliasen, Søren

    to investigate differences in landings, discards, discard ratio, CPUE, VPUE and DPUE, between conventional (control) and new gears (test). The results showed a varying degree of success, depending both on area and on choices made by the individual fisher. The best results were observed in the Baltic Sea, where......, Skagerrak and the Baltic Sea. Fishers used test and control gears interchangeably or in pairs and were required to sort and weight all discard of seven common target species on a haul by haul basis. All vessels were equipped for Fully Documented Fisheries, including cameras. Collected data were analyzed...

  7. The endogenous plant hormones and ratios regulate sugar and dry matter accumulation in Jerusalem artichoke in salt-soil.

    Science.gov (United States)

    Li, Lingling; Shao, Tianyun; Yang, Hui; Chen, Manxia; Gao, Xiumei; Long, Xiaohua; Shao, Hongbo; Liu, Zhaopu; Rengel, Zed

    2017-02-01

    The changes in content of endogenous hormones in stolons and tubers of Jerusalem artichoke (Helianthus tuberosus L.) regulate tuber growth, but the specific knowledge about the importance of balance among the endogenous hormones is lacking. Two varieties of Jerusalem artichoke (NY-1 and QY-2) were tested for the endogenous zeatin (ZT), auxins (IAA), gibberellins (GA 3 ) and abscisic acid (ABA) in regulating sugar and dry matter accumulation in tubers. The dry matter content and sugar accumulation in tubers were correlated positively with endogenous ZT and negatively with GA 3 content and GA 3 /ABA and IAA/ABA content ratios. Throughout the tuber formation, ZT content was higher in NY-1 than QY-2 tubers, whereas ABA content was higher in QY-2 than NY-1 tubers. The content ratios GA 3 /ABA and IAA/ABA were greater in NY-1 than QY-2 before tuber initiation, but QY-2 surpassed NY-1 during the tuber growth stage. The GA 3 /ABA and IAA/ABA content ratios declined during tuber growth. The results suggested that a dynamic balance of endogenous hormones played an important role in tuber development. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Involvement of interleukin‑23 induced by Porphyromonas endodontalis lipopolysaccharide in osteoclastogenesis.

    Science.gov (United States)

    Ma, Nan; Yang, Di; Okamura, Hirohiko; Teramachi, Jumpei; Hasegawa, Tomokazu; Qiu, Lihong; Haneji, Tatsuji

    2017-02-01

    Periapical lesions are characterized by the destruction of periapical bone, and occur as a result of local inflammatory responses to root canal infection by microorganisms including Porphyromonas endodontalis (P. endodontalis). P. endodontalis and its primary virulence factor, lipopolysaccharide (LPS), are associated with the development of periapical lesions and alveolar bone loss. Interleukin‑23 (IL‑23) is critical in the initiation and progression of periodontal disease via effects on peripheral bone metabolism. The present study investigated the expression of IL‑23 in tissue where a periapical lesion was present, and the effect of P. endodontalis LPS on the expression of IL‑23 in periodontal ligament (PDL) cells. Reverse transcription‑ quantitative polymerase chain reaction and immunohistochemistry revealed increased levels of IL‑23 expression in tissue with periapical lesions compared with healthy PDL tissue. Treatment with P. endodontalis LPS increased the expression of IL‑23 in the SH‑9 human PDL cell line. BAY11‑7082, a nuclear factor κB inhibitor, suppressed P. endodontalis LPS‑induced IL‑23 expression in SH‑9 cells. Treatment of RAW264.7 cells with conditioned medium from P. endodontalis LPS‑treated SH‑9 cells promoted osteoclastogenesis. By contrast, RAW264.7 cells treated with conditioned medium from IL‑23‑knockdown SH‑9 cells underwent reduced levels of osteoclastogenesis. The results of the present study indicated that the expression of IL‑23 in PDL cells induced by P. endodontalis LPS treatment may be involved in the progression of periapical lesions via stimulation of the osteoclastogenesis process.

  9. Involvement of interleukin-23 induced by Porphyromonas endodontalis lipopolysaccharide in osteoclastogenesis

    Science.gov (United States)

    Ma, Nan; Yang, Di; Okamura, Hirohiko; Teramachi, Jumpei; Hasegawa, Tomokazu; Qiu, Lihong; Haneji, Tatsuji

    2017-01-01

    Periapical lesions are characterized by the destruction of periapical bone, and occur as a result of local inflammatory responses to root canal infection by microorganisms including Porphyromonas endodontalis (P. endodontalis). P. endodontalis and its primary virulence factor, lipopolysaccharide (LPS), are associated with the development of periapical lesions and alveolar bone loss. Interleukin-23 (IL-23) is critical in the initiation and progression of periodontal disease via effects on peripheral bone metabolism. The present study investigated the expression of IL-23 in tissue where a periapical lesion was present, and the effect of P. endodontalis LPS on the expression of IL-23 in periodontal ligament (PDL) cells. Reverse transcription- quantitative polymerase chain reaction and immunohistochemistry revealed increased levels of IL-23 expression in tissue with periapical lesions compared with healthy PDL tissue. Treatment with P. endodontalis LPS increased the expression of IL-23 in the SH-9 human PDL cell line. BAY11-7082, a nuclear factor κB inhibitor, suppressed P. endodontalis LPS-induced IL-23 expression in SH-9 cells. Treatment of RAW264.7 cells with conditioned medium from P. endodontalis LPS-treated SH-9 cells promoted osteoclastogenesis. By contrast, RAW264.7 cells treated with conditioned medium from IL-23-knockdown SH-9 cells underwent reduced levels of osteoclastogenesis. The results of the present study indicated that the expression of IL-23 in PDL cells induced by P. endodontalis LPS treatment may be involved in the progression of periapical lesions via stimulation of the osteoclastogenesis process. PMID:28000855

  10. M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Shoichi Fukui

    2018-01-01

    Full Text Available ObjectivesWe investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA.MethodsPeripheral blood mononuclear cells (PBMCs were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro.ResultsForty RA patients and 20 healthy donors were included. Twenty-two patients (55% were anticitrullinated protein antibody (ACPA positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range. There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001. The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028 and significantly greater numbers of OCs in vitro (p = 0.005 than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes.ConclusionM1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.

  11. A study about critical flow characteristics and the pipeline network modeling of a pressure regulator (II) : the influence of a opening ratio

    International Nuclear Information System (INIS)

    Shin, Chang Hoon; Ha, Jong Man; Lee, Cheol Gu; Her, Jae Young; Im, Ji Hyun; Joo, Won Gu

    2005-01-01

    The suitable pressure regulator modeling at each opening ratio and pressure ratio is very important to obtain reliable results, especially in small scale pipeline network analysis such as a pressure regulator system. And it is needed to confirm both whether temperature recovery is achieved after passing by the pressure regulator's narrow neck and how much amount of low temperature area that can cause condensate accumulation is distributed by various PCV models and driving conditions. In this research, the numerical model resembling P company pressure regulator that is used widely for high pressure range in commercial, is adopted as the base model of CFD analysis to investigate pressure regulator's flow characteristics at each pressure ratio and opening ratio. And it is also introduced to examine pressure regulator's critical flow characteristics and possibility of condensation or freezing at each pressure ratio and opening ratio. Additionally, the comparison between the results of CFD analysis and the results of analytic solution obtained by compressible fluid-dynamics theory is attempted to validate the results of CFD modeling in this study and to estimate the accuracy of theoretical approach at each pressure ratio and opening ratio too

  12. Is the medical loss ratio a good target measure for regulation in the individual market for health insurance?

    Science.gov (United States)

    Karaca-Mandic, Pinar; Abraham, Jean M; Simon, Kosali

    2015-01-01

    Effective January 1, 2011, individual market health insurers must meet a minimum medical loss ratio (MLR) of 80%. This law aims to encourage 'productive' forms of competition by increasing the proportion of premium dollars spent on clinical benefits. To date, very little is known about the performance of firms in the individual health insurance market, including how MLRs are related to insurer and market characteristics. The MLR comprises one component of the price-cost margin, a traditional gauge of market power; the other component is percent of premiums spent on administrative expenses. We use data from the National Association of Insurance Commissioners (2001-2009) to evaluate whether the MLR is a good target measure for regulation by comparing the two components of the price-cost margin between markets that are more competitive versus those that are not, accounting for firm and market characteristics. We find that insurers with monopoly power have lower MLRs. Moreover, we find no evidence suggesting that insurers' administrative expenses are lower in more concentrated insurance markets. Thus, our results are largely consistent with the interpretation that the MLR could serve as a target measure of market power in regulating the individual market for health insurance but with notable limited ability to capture product and firm heterogeneity. Copyright © 2013 John Wiley & Sons, Ltd.

  13. Technetium-99 conjugated with methylene diphosphonate inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis.

    Science.gov (United States)

    Gong, Wei; Dou, Huan; Liu, Xianqin; Sun, Lingyun; Hou, Yayi

    2012-10-01

    1. In the present study, we investigated the effects of technetium-99 conjugated with methylene diphosphonate ((99)Tc-MDP), an agent used in radionuclide therapy, on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and explored the underlying mechanisms. 2. The murine macrophage cell line RAW264.7 and bone marrow-derived-macrophages from C57BL/6 mice (BMM) were used as models for osteoclastogenesis in vitro. The expression of some key factors in RANKL (50 ng/mL)-induced osteoclastogenesis in RAW264.7 cells was investigated by flow cytometry and real-time reverse transcription-polymerase chain reaction (RT-PCR). To detect multinucleated osteoclast formation, RAW264.7 cells were induced with RANKL for 4 days, whereas BMM were induced by 50 ng/mL RANKL and 20 ng/mL macrophage colony-stimulating factor for 7 days, before being stained with tartrate-resistant acid phosphatase. 3. Osteoclastogenesis was evaluated using the osteoclast markers CD51, matrix metalloproteinase (MMP)-9 and cathepsin K. At 0.01 μg/mL, (99)Tc-MDP significantly inhibited RANKL-induced osteoclastogenesis without any cytotoxicity. In addition, (99)Tc-MDP abolished the appearance of multinucleated osteoclasts. 4. Real-time RT-PCR analysis of transcription factor expression revealed that (99)Tc-MDP inhibited the expression of c-Fos and nuclear factor of activated T cells. In addition, (99)Tc-MDP inhibited the expression of the inflammatory factors interleukin (IL)-6, tumour necrosis factor-α and IL-1β. Finally, (99)Tc-MDP inhibited the activation of mitogen-activated protein kinases in RAW264.7 cells following RANKL stimulation. 5. In conclusion, (99)Tc-MDP possesses anti-osteoclastogenic activity against RANKL-induced osteoclast formation. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.

  14. Caffeine may enhance orthodontic tooth movement through increasing osteoclastogenesis induced by periodontal ligament cells under compression.

    Science.gov (United States)

    Yi, Jianru; Yan, Boxi; Li, Meile; Wang, Yu; Zheng, Wei; Li, Yu; Zhao, Zhihe

    2016-04-01

    Caffeine is the kernel component of coffee and has multiple effects on bone metabolism. Here we aimed to investigate the effects of caffeine intake on orthodontic tooth movement (OTM). (1) In the in vivo study, two groups comprising 15 randomly assigned rats each underwent orthodontic treatment. One group ingested caffeine at 25mg/kg body weight per day and the other, plain water. After 3 weeks, the degree of tooth movement and effect on the periodontium were assessed. (2) In the in vitro study, we established a model mimicking the essential bioprocess of OTM, which contained a periodontal ligament tissue model (PDLtm), and a co-culture system of osteoblasts (OBs) and osteoclast precursors (pre-OCs). After being subjected to static compressive force with or without caffeine administration, the conditioned media from the PDLtm were used for the OB/pre-OC co-cultures to induce osteoclastogenesis. (1) In vivo, the caffeine group displayed a significantly greater rate of tooth movement than the control. The alveolar bone mineral density and bone volume fraction were similar between the two groups; however, immunohistochemical staining showed that the caffeine group had significantly more TRAP(+) osteoclasts and higher RANKL expression in the compressed periodontium. (2) In vitro, caffeine at 0.01mM significantly enhanced the compression-induced expression of RANKL and COX-2, as well as prostaglandin E2 production in the PDLtm. Furthermore, the "caffeine+compression"-conditioned media induced significantly more TRAP(+) OC formation when compared with compression alone. Daily intake of caffeine, at least at some specific dosage, may enhance OTM through increasing osteoclastogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Attenuated RANKL-induced cytotoxicity by Portulaca oleracea ethanol extract enhances RANKL-mediated osteoclastogenesis.

    Science.gov (United States)

    Erkhembaatar, Munkhsoyol; Choi, Eun-Joo; Lee, Hak-Yong; Lee, Choong Hun; Lee, Young-Rae; Kim, Min Seuk

    2015-07-14

    Portulaca oleracea (PO) has been widely used as traditional medicine because of its pharmacological activities. However, the effects of PO on osteoclasts that modulate bone homeostasis are still elusive. In this study, we examined the effects of PO ethanol extract (POEE) on receptor activator of nuclear factor-κB ligand (RANKL)-mediated Ca(2+) mobilization, nuclear factor of activated T-cell c1 (NFATc1) amplification, tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cell (MNC) formation, and cytotoxicity. Our results demonstrated that POEE suppressed RANKL-induced Ca(2+) oscillations by inhibition of Ca(2+) release from internal Ca(2+) stores, resulting in reduction of NFATc1 amplification. Notably, POEE attenuated RANKL-mediated cytotoxicity and cleavage of polyadenosine 5'-diphosphate-ribose polymerase (PARP), resulted in enhanced formation of TRAP+ MNCs. These results present in vitro effects of POEE on RANKL-mediated osteoclastogenesis and suggest the possible use of PO in treating bone disorders, such as osteopetrosis.

  16. The Inhibitory Effect of Alisol A 24-Acetate from Alisma canaliculatum on Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Kwang-Jin Kim

    2015-01-01

    Full Text Available Osteoporosis is a disease that decreases bone mass. The number of patients with osteoporosis has been increasing, including an increase in patients with bone fractures, which lead to higher medical costs. Osteoporosis treatment is all-important in preventing bone loss. One strategy for osteoporosis treatment is to inhibit osteoclastogenesis. Osteoclasts are bone-resorbing multinucleated cells, and overactive osteoclasts and/or their increased number are observed in bone disorders including osteoporosis and rheumatoid arthritis. Bioactivity-guided fractionations led to the isolation of alisol A 24-acetate from the dried tuber of Alisma canaliculatum. Alisol A 24-acetate inhibited RANKL-mediated osteoclast differentiation by downregulating NFATc1, which plays an essential role in osteoclast differentiation. Furthermore, it inhibited the expression of DC-STAMP and cathepsin K, which are related to cell-cell fusion of osteoclasts and bone resorption, respectively. Therefore, alisol A 24-acetate could be developed as a new structural scaffold for inhibitors of osteoclast differentiation in order to develop new drugs against osteoporosis.

  17. Regulation of phytoplankton carbon to chlorophyll ratio by light, nutrients and temperature in the Equatorial Pacific Ocean: a basin-scale model

    Directory of Open Access Journals (Sweden)

    X. J. Wang

    2009-03-01

    Full Text Available The complex effects of light, nutrients and temperature lead to a variable carbon to chlorophyll (C:Chl ratio in phytoplankton cells. Using field data collected in the Equatorial Pacific, we derived a new dynamic model with a non-steady C:Chl ratio as a function of irradiance, nitrate, iron, and temperature. The dynamic model is implemented into a basin-scale ocean circulation-biogeochemistry model and tested in the Equatorial Pacific Ocean. The model reproduces well the general features of phytoplankton dynamics in this region. For instance, the simulated deep chlorophyll maximum (DCM is much deeper in the western warm pool (~100 m than in the Eastern Equatorial Pacific (~50 m. The model also shows the ability to reproduce chlorophyll, including not only the zonal, meridional and vertical variations, but also the interannual variability. This modeling study demonstrates that combination of nitrate and iron regulates the spatial and temporal variations in the phytoplankton C:Chl ratio in the Equatorial Pacific. Sensitivity simulations suggest that nitrate is mainly responsible for the high C:Chl ratio in the western warm pool while iron is responsible for the frontal features in the C:Chl ratio between the warm pool and the upwelling region. In addition, iron plays a dominant role in regulating the spatial and temporal variations of the C:Chl ratio in the Central and Eastern Equatorial Pacific. While temperature has a relatively small effect on the C:Chl ratio, light is primarily responsible for the vertical decrease of phytoplankton C:Chl ratio in the euphotic zone.

  18. Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss.

    Directory of Open Access Journals (Sweden)

    Donatella Granchi

    Full Text Available The extracellular acidic milieu in bones results in activation of osteoclasts (OC and inhibition of osteoblasts (OB causing a net loss of calcium from the skeleton and the deterioration of bone microarchitecture. Alkalinization through supplementation with potassium citrate (K citrate has been proposed to limit the osteopenia progression, even though its pharmacological activity in bone microenvironment is not well defined. We evaluated if K citrate was able to prevent the adverse effects that acidic milieu induces on bone cells. OC and OB were maintained in neutral (pH 7.4 versus acidic (pH 6.9 culture medium, and treated with different K citrate concentrations. We evaluated the OC differentiation at seven days, by counting of multinucleated cells expressing tartrate-resistant acid phosphatase, and the activity of mature OC at 14 days, by quantifying of collagen degradation. To evaluate the effects on OB, we analyzed proliferation, mineralization, and expression of bone-related genes. We found that the low pH increased OC differentiation and activity and decreased OB function. The osteoclastogenesis was also promoted by RANKL concentrations ineffective at pH 7.4. Non-cytotoxic K citrate concentrations were not sufficient to steadily neutralize the acidic medium, but a inhibited the osteoclastogenesis, the collagen degradation, and the expression of genes involved in RANKL-mediated OC differentiation, b enhanced OB proliferation and alkaline phosphatase expression, whereas it did not affect the in vitro mineralization, and c were effective also in OC cultures resistant to alendronate, i.e. the positive control of osteoclastogenesis inhibition. In conclusion, K citrate prevents the increase in OC activity induced by the acidic microenvironment, and the effect does not depend exclusively on its alkalizing capacity. These data provide the biological basis for the use of K citrate in preventing the osteopenia progression resulting from low

  19. Influence of surface microstructure and chemistry on osteoinduction and osteoclastogenesis by biphasic calcium phosphate discs

    Directory of Open Access Journals (Sweden)

    NL Davison

    2015-06-01

    Full Text Available It has been reported that surface microstructural dimensions can influence the osteoinductivity of calcium phosphates (CaPs, and osteoclasts may play a role in this process. We hypothesised that surface structural dimensions of ≤ 1 μm trigger osteoinduction and osteoclast formation irrespective of macrostructure (e.g., concavities, interconnected macropores, interparticle space or surface chemistry. To test this, planar discs made of biphasic calcium phosphate (BCP: 80 % hydroxyapatite, 20 % tricalcium phosphate were prepared with different surface structural dimensions – either ~ 1 μm (BCP1150 or ~ 2-4 μm (BCP1300 – and no macropores or concavities. A third material was made by sputter coating BCP1150 with titanium (BCP1150Ti, thereby changing its surface chemistry but preserving its surface structure and chemical reactivity. After intramuscular implantation in 5 dogs for 12 weeks, BCP1150 formed ectopic bone in 4 out of 5 samples, BCP1150Ti formed ectopic bone in 3 out of 5 samples, and BCP1300 formed no ectopic bone in any of the 5 samples. In vivo, large multinucleated osteoclast-like cells densely colonised BCP1150, smaller osteoclast-like cells formed on BCP1150Ti, and osteoclast-like cells scarcely formed on BCP1300. In vitro, RAW264.7 cells cultured on the surface of BCP1150 and BCP1150Ti in the presence of osteoclast differentiation factor RANKL (receptor activator for NF-κB ligand proliferated then differentiated into multinucleated osteoclast-like cells with positive tartrate resistant acid phosphatase (TRAP activity. However, cell proliferation, fusion, and TRAP activity were all significantly inhibited on BCP1300. These results indicate that of the material parameters tested – namely, surface microstructure, macrostructure, and surface chemistry – microstructural dimensions are critical in promoting osteoclastogenesis and triggering ectopic bone formation.

  20. Regulation of gonadal sex ratios and pubertal development by the thyroid endocrine system in zebrafish (Danio rerio).

    Science.gov (United States)

    Sharma, Prakash; Patiño, Reynaldo

    2013-04-01

    We examined associations between thyroid condition, gonadal sex and pubertal development in zebrafish. Seventy-two-hour postfertilization larvae were reared in untreated medium or in the presence of goitrogens (sodium perchlorate, 0.82 mM; methimazole, 0.15 and 0.3 mM) or thyroxine (1 and 10 nM) for 30 days. Thyrocyte height, gonadal sex and gonadal development were histologically determined at 45 and 60 days postfertilization (dpf). Thyrocyte hypertrophy, an index of hypothyroidism, was observed at 45 and 60 dpf in perchlorate-treated but only at 45 dpf in methimazole-treated fish. Similarly, gonadal sex ratios were biased toward ovaries relative to control animals at 45 and 60 dpf in perchlorate-treated fish but only at 45 dpf in methimazole-treated fish. Gonadal sex ratios were biased toward testes at 45 and 60 dpf in thyroxine-treated fish. Spermatogenesis was delayed in testes from goitrogen-treated fish at 60 dpf relative to control values, but was unaffected in testes from thyroxine-treated individuals. Oogenesis seemed to be nonspecifically delayed in all treatments relative to control at 60 dpf. This study confirmed the previously reported association between hypothyroid condition and ovarian-skewed ratios, and hyperthyroid condition and testicular-skewed ratios, and also showed that male pubertal development is specifically delayed by experimental hypothyroidism. The simultaneous recovery from the hypothyroid and ovary-inducing effects of methimazole by 60 dpf (27 days post-treatment) suggests that the ovary-skewing effect of goitrogens is reversible when thyroid conditions return to basal levels before developmental commitment of gonadal sex. Conversely, the masculinizing effect of hyperthyroidism seems to be stable and perhaps permanent. Published by Elsevier Inc.

  1. Regulation of gonadal sex ratios and pubertal development by the thyroid endocrine system in zebrafish (Danio rerio)

    Science.gov (United States)

    Sharma, Prakash; Patino, Reynaldo

    2013-01-01

    We examined associations between thyroid condition, gonadal sex and pubertal development in zebrafish. Seventy-two-hour postfertilization larvae were reared in untreated medium or in the presence of goitrogens (sodium perchlorate, 0.82 mM; methimazole, 0.15 and 0.3 mM) or thyroxine (1 and 10 nM) for 30 days. Thyrocyte height, gonadal sex and gonadal development were histologically determined at 45 and 60 days postfertilization (dpf). Thyrocyte hypertrophy, an index of hypothyroidism, was observed at 45 and 60 dpf in perchlorate-treated but only at 45 dpf in methimazole-treated fish. Similarly, gonadal sex ratios were biased toward ovaries relative to control animals at 45 and 60 dpf in perchlorate-treated fish but only at 45 dpf in methimazole-treated fish. Gonadal sex ratios were biased toward testes at 45 and 60 dpf in thyroxine-treated fish. Spermatogenesis was delayed in testes from goitrogen-treated fish at 60 dpf relative to control values, but was unaffected in testes from thyroxine-treated individuals. Oogenesis seemed to be nonspecifically delayed in all treatments relative to control at 60 dpf. This study confirmed the previously reported association between hypothyroid condition and ovarian-skewed ratios, and hyperthyroid condition and testicular-skewed ratios, and also showed that male pubertal development is specifically delayed by experimental hypothyroidism. The simultaneous recovery from the hypothyroid and ovary-inducing effects of methimazole by 60 dpf (27 days post-treatment) suggests that the ovary-skewing effect of goitrogens is reversible when thyroid conditions return to basal levels before developmental commitment of gonadal sex. Conversely, the masculinizing effect of hyperthyroidism seems to be stable and perhaps permanent.

  2. A Low Input Current and Wide Conversion Ratio Buck Regulator with 75% Efficiency for High-Voltage Triboelectric Nanogenerators

    Science.gov (United States)

    Luo, Li-Chuan; Bao, De-Chun; Yu, Wu-Qi; Zhang, Zhao-Hua; Ren, Tian-Ling

    2016-01-01

    It is meaningful to research the Triboelectric Nanogenerators (TENG), which can create electricity anywhere and anytime. There are many researches on the structures and materials of TENG to explain the phenomenon that the maximum voltage is stable and the current is increasing. The output voltage of the TENG is high about 180-400 V, and the output current is small about 39 μA, which the electronic devices directly integration of TENG with Li-ion batteries will result in huge energy loss due to the ultrahigh TENG impedance. A novel interface circuit with the high-voltage buck regulator for TENG is introduced firstly in this paper. The interface circuit can transfer the output signal of the TENG into the signal fit to a lithium ion battery. Through the circuit of the buck regulator, the average output voltage is about 4.0 V and the average output current is about 1.12 mA. Further, the reliability and availability for the lithium ion battery and the circuit are discussed. The interface circuit is simulated using the Cadence software and verified through PCB experiment. The buck regulator can achieve 75% efficiency for the High-Voltage TENG. This will lead to a research hot and industrialization applications.

  3. Ellagic acid protects against neuron damage in ischemic stroke through regulating the ratio of Bcl-2/Bax expression.

    Science.gov (United States)

    Liu, Qing-Shan; Deng, Ran; Li, Shuran; Li, Xu; Li, Keqin; Kebaituli, Gulibanumu; Li, Xueli; Liu, Rui

    2017-08-01

    An oxygen-glucose deprivation and reoxygenation model in primary cultured rat cortical neurons was developed for this study to investigate the effects of ellagic acid (EA), a low-molecular-weight polyphenol, on neuron cells and their function, and to evaluate whether EA can be safely utilized by humans as a functional food or therapeutic agent. Administration of EA significantly decreased the volume of cerebrum infarction and the neurological deficit scores of the rats; EA treatment also increased the number of Bcl-2-positive cells and the ratio of Bcl-2-positive to Bax-positive neurons in the semidarkness zone near the brain ischemic focus in the photothrombotic cerebral ischemia model. Treatment of EA resulted in increased neuron viability, cell nuclear integrity, and the ratio of Bcl-2/Bax expression in the primary cultured neuron model; EA treatment also lead to a decrease in the number of apoptotic cells. Our results therefore suggest a specific mechanism for the beneficial effects of EA, providing new insights into how it provides neuroprotection. To the best of our knowledge, these results represent new insights on the mechanisms of the brain cell protective activity of EA. Thus, EA may be used in functional foods or medicines to help treat nerve dysfunction, neurodegenerative disease, and aging.

  4. A Comprehensive Mixture of Tobacco Smoke Components Retards Orthodontic Tooth Movement via the Inhibition of Osteoclastogenesis in a Rat Model

    Directory of Open Access Journals (Sweden)

    Maya Nagaie

    2014-10-01

    Full Text Available Tobacco smoke is a complex mixture of numerous components. Nevertheless, most experiments have examined the effects of individual chemicals in tobacco smoke. The comprehensive effects of components on tooth movement and bone resorption remain unexplored. Here, we have shown that a comprehensive mixture of tobacco smoke components (TSCs attenuated bone resorption through osteoclastogenesis inhibition, thereby retarding experimental tooth movement in a rat model. An elastic power chain (PC inserted between the first and second maxillary molars robustly yielded experimental tooth movement within 10 days. TSC administration effectively retarded tooth movement since day 4. Histological evaluation disclosed that tooth movement induced bone resorption at two sites: in the bone marrow and the peripheral bone near the root. TSC administration significantly reduced the number of tartrate-resistant acid phosphatase (TRAP-positive osteoclastic cells in the bone marrow cavity of the PC-treated dentition. An in vitro study indicated that the inhibitory effects of TSCs on osteoclastogenesis seemed directed more toward preosteoclasts than osteoblasts. These results indicate that the comprehensive mixture of TSCs might be a useful tool for detailed verification of the adverse effects of tobacco smoke, possibly contributing to the development of reliable treatments in various fields associated with bone resorption.

  5. Acute regulation of circulating parathyroid hormone (PTH) molecular forms by calcium: utility of PTH fragments/PTH(1-84) ratios derived from three generations of PTH assays.

    Science.gov (United States)

    D'Amour, Pierre; Räkel, Agnès; Brossard, Jean-Hugues; Rousseau, Louise; Albert, Caroline; Cantor, Tom

    2006-01-01

    The quantitative evaluation of circulating PTH peaks revealed by PTH assays after HPLC separation constitutes the best way to study the behavior of PTH molecular forms, but it is also impractical. The objective of the study was to investigate the regulation of circulating PTH molecular forms by calcium through the use of PTH fragments/PTH (1-84) ratios derived from PTH assays with different specificities before and after HPLC separation of circulating PTH. CaCl2 and Na citrate were infused in eight volunteers. PTH was measured in serum and HPLC fractions at different calcium concentrations in PTH assays reacting with regions 1-2 (CA), 12-18 (T), and 65-69 (C) of the PTH structure. From hypo- to hypercalcemia, the C/CA ratio had the highest range (1.92 to 9.75; P < 0.001), and the C/T ratio had a higher range (1.69 to 6.11; P < 0.01) than the T/CA ratio (1.15 to 1.86). Human (h) PTH (1-84) represented 32.7 and 4.3% of circulating PTH in hypo- and hypercalcemic HPLC profiles, respectively. These numbers were 5 and 0.9% for amino-terminal (N)-PTH, an amino-terminal form of PTH distinct from hPTH (1-84), 7.3 and 6.8% for non-(1-84) PTH or large C-PTH fragments with a partially preserved N structure, and 54.9 and 88.1% for C-PTH fragments missing a N structure. The HPLC C-PTH fragments to hPTH (1-84) ratio had the most extensive range (1.67 to 20.58). Despite their quantitative differences, all ratios identified identical behavior of PTH fragments relative to PTH (1-84). PTH assay ratios are an adequate tool to investigate the modulation of PTH molecular forms, even if all PTH assays show some undesirable cross-reactivity with certain circulating forms of PTH.

  6. Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma.

    Science.gov (United States)

    Morisawa, Ayaka; Okui, Tatsuo; Shimo, Tsuyoshi; Ibaragi, Soichiro; Okusha, Yuka; Ono, Mitsuaki; Nguyen, Thi Thu Ha; Hassan, Nur Mohammad Monsur; Sasaki, Akira

    2018-03-01

    Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically where one of the mechanisms responsible for the invasion into facial bones occurs via the activation of osteoclasts. Copper has been demonstrated to play a key role in skeletal remodeling. However, the role of copper in cancer-associated bone destruction is thus far unknown. Lysyl oxidase (LOX) is a copper-dependent enzyme that promotes osteoclastogenesis. In the present study, we investigated the effects of copper on HNSCC with bone invasion by the copper chelator, ammonium tetrathiomolybdate (TM) in vitro and in vivo. We demonstrate that TM blocks the proliferation of HNSCC cells, inhibits LOX activation and decreases the expression of the receptor activator of nuclear factor-κB ligand (RANKL) in osteoblasts and osteocytes, subsequently suppressing bone destruction. These findings suggest that copper is a potential target for the treatment of HNSCCs associated with bone destruction.

  7. Porphyromonas gingivalis GroEL induces osteoclastogenesis of periodontal ligament cells and enhances alveolar bone resorption in rats.

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    Feng-Yen Lin

    Full Text Available Porphyromonas gingivalis is a major periodontal pathogen that contains a variety of virulence factors. The antibody titer to P. gingivalis GroEL, a homologue of HSP60, is significantly higher in periodontitis patients than in healthy control subjects, suggesting that P. gingivalis GroEL is a potential stimulator of periodontal disease. However, the specific role of GroEL in periodontal disease remains unclear. Here, we investigated the effect of P. gingivalis GroEL on human periodontal ligament (PDL cells in vitro, as well as its effect on alveolar bone resorption in rats in vivo. First, we found that stimulation of PDL cells with recombinant GroEL increased the secretion of the bone resorption-associated cytokines interleukin (IL-6 and IL-8, potentially via NF-κB activation. Furthermore, GroEL could effectively stimulate PDL cell migration, possibly through activation of integrin α1 and α2 mRNA expression as well as cytoskeletal reorganization. Additionally, GroEL may be involved in osteoclastogenesis via receptor activator of nuclear factor κ-B ligand (RANKL activation and alkaline phosphatase (ALP mRNA inhibition in PDL cells. Finally, we inoculated GroEL into rat gingiva, and the results of microcomputed tomography (micro-CT and histomorphometric assays indicated that the administration of GroEL significantly increased inflammation and bone loss. In conclusion, P. gingivalis GroEL may act as a potent virulence factor, contributing to osteoclastogenesis of PDL cells and resulting in periodontal disease with alveolar bone resorption.

  8. MyD88 But Not TRIF Is Essential for Osteoclastogenesis Induced by Lipopolysaccharide, Diacyl Lipopeptide, and IL-1α

    Science.gov (United States)

    Sato, Nobuaki; Takahashi, Naoyuki; Suda, Koji; Nakamura, Midori; Yamaki, Mariko; Ninomiya, Tadashi; Kobayashi, Yasuhiro; Takada, Haruhiko; Shibata, Kenichiro; Yamamoto, Masahiro; Takeda, Kiyoshi; Akira, Shizuo; Noguchi, Toshihide; Udagawa, Nobuyuki

    2004-01-01

    Myeloid differentiation factor 88 (MyD88) plays essential roles in the signaling of the Toll/interleukin (IL)-1 receptor family. Toll–IL-1 receptor domain-containing adaptor inducing interferon-β (TRIF)-mediated signals are involved in lipopolysaccharide (LPS)-induced MyD88-independent pathways. Using MyD88-deficient (MyD88−/−) mice and TRIF-deficient (TRIF−/−) mice, we examined roles of MyD88 and TRIF in osteoclast differentiation and function. LPS, diacyl lipopeptide, and IL-1α stimulated osteoclastogenesis in cocultures of osteoblasts and hemopoietic cells obtained from TRIF−/− mice, but not MyD88−/− mice. These factors stimulated receptor activator of nuclear factor-κB ligand mRNA expression in TRIF−/− osteoblasts, but not MyD88−/− osteoblasts. LPS stimulated IL-6 production in TRIF−/− osteoblasts, but not TRIF−/− macrophages. LPS and IL-1α enhanced the survival of TRIF−/− osteoclasts, but not MyD88−/− osteoclasts. Diacyl lipopeptide did not support the survival of osteoclasts because of the lack of Toll-like receptor (TLR)6 in osteoclasts. Macrophages expressed both TRIF and TRIF-related adaptor molecule (TRAM) mRNA, whereas osteoblasts and osteoclasts expressed only TRIF mRNA. Bone histomorphometry showed that MyD88−/− mice exhibited osteopenia with reduced bone resorption and formation. These results suggest that the MyD88-mediated signal is essential for the osteoclastogenesis and function induced by IL-1 and TLR ligands, and that MyD88 is physiologically involved in bone turnover. PMID:15353553

  9. Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Fei; Zhai, Zanjing; Jiang, Chuan; Liu, Xuqiang; Li, Haowei; Qu, Xinhua [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Ouyang, Zhengxiao [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 (China); Fan, Qiming; Tang, Tingting [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Qin, An, E-mail: dr.qinan@gmail.com [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Gu, Dongyun, E-mail: dongyungu@gmail.com [Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Engineering Research Center of Digital Medicine and Clinical Translation, Ministry of Education of PR China (China); School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030 (China)

    2015-01-01

    Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure. - Highlights: • Geraniin suppresses osteoclasts formation and function in vitro. • Geraniin impairs RANKL-induced nuclear factor-κB and ERK signaling pathway. • Geraniin suppresses osteolysis in vivo. • Geraniin may be used for treating osteoclast related diseases.

  10. Cavin-1/PTRF alters prostate cancer cell-derived extracellular vesicle content and internalization to attenuate extracellular vesicle-mediated osteoclastogenesis and osteoblast proliferation

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    Kerry L. Inder

    2014-06-01

    Full Text Available Background: Tumour-derived extracellular vesicles (EVs play a role in tumour progression; however, the spectrum of molecular mechanisms regulating EV secretion and cargo selection remain to be fully elucidated. We have reported that cavin-1 expression in prostate cancer PC3 cells reduced the abundance of a subset of EV proteins, concomitant with reduced xenograft tumour growth and metastasis. Methods: We examined the functional outcomes and mechanisms of cavin-1 expression on PC3-derived EVs (PC3-EVs. Results: PC3-EVs were internalized by osteoclast precursor RAW264.7 cells and primary human osteoblasts (hOBs in vitro, stimulating osteoclastogenesis 37-fold and hOB proliferation 1.5-fold, respectively. Strikingly, EVs derived from cavin-1-expressing PC3 cells (cavin-1-PC3-EVs failed to induce multinucleate osteoblasts or hOB proliferation. Cavin-1 was not detected in EVs, indicating an indirect mechanism of action. EV morphology, size and quantity were also not affected by cavin-1 expression, suggesting that cavin-1 modulated EV cargo recruitment rather than release. While cavin-1-EVs had no osteoclastogenic function, they were internalized by RAW264.7 cells but at a reduced efficiency compared to control EVs. EV surface proteins are required for internalization of PC3-EVs by RAW264.7 cells, as proteinase K treatment abolished uptake of both control and cavin-1-PC3-EVs. Removal of sialic acid modifications by neuraminidase treatment increased the amount of control PC3-EVs internalized by RAW264.7 cells, without affecting cavin-1-PC3-EVs. This suggests that cavin-1 expression altered the glycosylation modifications on PC3-EV surface. Finally, cavin-1 expression did not affect EV in vivo tissue targeting as both control and cavin-1-PC3-EVs were predominantly retained in the lung and bone 24 hours after injection into mice. Discussion: Taken together, our results reveal a novel pathway for EV cargo sorting, and highlight the potential of utilizing

  11. Golden Ratio

    Indian Academy of Sciences (India)

    Our attraction to another body increases if the body is symmetricaland in proportion. If a face or a structure is in proportion,we are more likely to notice it and find it beautiful.The universal ratio of beauty is the 'Golden Ratio', found inmany structures. This ratio comes from Fibonacci numbers.In this article, we explore this ...

  12. Golden Ratio

    Indian Academy of Sciences (India)

    Keywords. Fibonacci numbers, golden ratio, Sanskrit prosody, solar panel. Abstract. Our attraction to another body increases if the body is symmetricaland in proportion. If a face or a structure is in proportion,we are more likely to notice it and find it beautiful.The universal ratio of beauty is the 'Golden Ratio', found inmany ...

  13. Golden Ratio

    Indian Academy of Sciences (India)

    Our attraction to another body increases if the body is sym- metrical and in proportion. If a face or a structure is in pro- portion, we are more likely to notice it and find it beautiful. The universal ratio of beauty is the 'Golden Ratio', found in many structures. This ratio comes from Fibonacci numbers. In this article, we explore this ...

  14. Picrasidine I from Picrasma Quassioides Suppresses Osteoclastogenesis via Inhibition of RANKL Induced Signaling Pathways and Attenuation of ROS Production

    Directory of Open Access Journals (Sweden)

    Lingbo Kong

    2017-10-01

    Full Text Available Background/Aims: Osteoporosis is a metabolic bone disorder that tortures about millions of people worldwide. Recent study demonstrated agents derived from picrasma quassioides is a promising drug for targets multiple signaling pathways. However its potential in treatment of bone loss has not been fully understood. Methods: The bone marrow macrophages (BMMs were cultured and induced with M-CSF and RANKL followed by picrasidine I (PI treatment. Then the effects of PI on osteoclast formation were evaluated by counting tartrate-resistant acid phosphatase (TRAP-positive multinucleated cells. Moreover, effects of PI on bone resorption activity of mature osteoclast were studied through bone resorption pit counting and actin ring structure analysis. Further, the involved potential signaling pathways cross-talking were investigated by performed Western blotting and quantitative real-time PCR examination. Results: Results demonstrated PI strongly inhibited RANKL induced osteoclast formation from its precursors. Mechanistically, the inhibitory effect of PI on osteoclast differentiation was due to the suppression of osteoclastogenic transcription factors, c-Fos and NFATc1. Moreover, PI markedly blocked the RANKL-induced osteoclastogenesis by attenuating MAPKs and NF-κB signaling pathways. In addition, PI decreased the ROS generation in osteoclast and osteoblast. Conclusion: Taken together our data demonstrate that PI has antiosteoclastogenic effect by inhibiting inflammation induced activation of MAPKs, NF-κB and ROS generation followed by suppressing the gene expression of c-Fos and NFATc1 in osteoclast precursors.

  15. Sex ratios

    OpenAIRE

    West, Stuart A; Reece, S E; Sheldon, Ben C

    2002-01-01

    Sex ratio theory attempts to explain variation at all levels (species, population, individual, brood) in the proportion of offspring that are male (the sex ratio). In many cases this work has been extremely successful, providing qualitative and even quantitative explanations of sex ratio variation. However, this is not always the situation, and one of the greatest remaining problems is explaining broad taxonomic patterns. Specifically, why do different organisms show so ...

  16. Allium cepa L. and Quercetin Inhibit RANKL/Porphyromonas gingivalis LPS-Induced Osteoclastogenesis by Downregulating NF-κB Signaling Pathway

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    Tatiane Oliveira

    2015-01-01

    Full Text Available Objectives. We evaluated the in vitro modulatory effects of Allium cepa L. extract (AcE and quercetin (Qt on osteoclastogenesis under inflammatory conditions (LPS-induced. Methods. RAW 264.7 cells were differentiated with 30 ng/mL of RANKL, costimulated with PgLPS (1 µg/mL, and treated with AcE (50–1000 µg/mL or Qt (1.25, 2.5, or 5 µM. Cell viability was determined by alamarBlue and protein assays. Nuclei morphology was analysed by DAPI staining. TRAP assays were performed as follows: p-nitrophenyl phosphate was used to determine the acid phosphatase activity of the osteoclasts and TRAP staining was used to evaluate the number and size of TRAP-positive multinucleated osteoclast cells. Von Kossa staining was used to measure osteoclast resorptive activity. Cytokine levels were measured on osteoclast precursor cell culture supernatants. Using western blot analysis, p-IκBα and IκBα degradation, inhibitor of NF-kappaB, were evaluated. Results. Both AcE and Qt did not affect cell viability and significantly reduced osteoclastogenesis compared to control. We observed lower production of IL-6 and IL-1α and an increased production of IL-3 and IL-4. AcE and Qt downregulated NF-κB pathway. Conclusion. AcE and Qt may be inhibitors of osteoclastogenesis under inflammatory conditions (LPS-induced via attenuation of RANKL/PgLPS-induced NF-κB activation.

  17. Interleukin-4 inhibits RANKL-induced expression of NFATc1 and c-Fos: A possible mechanism for downregulation of osteoclastogenesis

    International Nuclear Information System (INIS)

    Kamel Mohamed, Saad Gad; Sugiyama, Eiji; Shinoda, Kouichiro; Hounoki, Hiroyuki; Taki, Hirofumi; Maruyama, Muneharu; Miyahara, Tatsuro; Kobayashi, Masashi

    2005-01-01

    Interleukin-4 (IL-4), an anti-inflammatory cytokine, has been shown to inhibit osteoclast differentiation. Therefore, this cytokine is considered to be a promising therapeutic applicant for bone-resorbing diseases such as rheumatoid arthritis (RA). Recently NFATc1, a transcription factor, has been shown to play critical roles in osteoclastogenesis. The aim of this study was to clarify the role of IL-4 on the intracellular signaling of NFATc1. A RAW264.7 monocyte/macrophage cell line and murine bone marrow precursors were differentiated into osteoclasts in the presence of receptor activator of nuclear factor κB ligand (RANKL) and/or macrophage colony-stimulating factor. Tartrate-resistant acid phosphatase (TRAP) staining and a pit assay using dentine were used for the identification of activated osteoclasts. The protein expression of IL-4 receptor, NFATc1, and c-Fos was determined by Western blot analysis. In addition, the gene expression of NFATc1 and c-Fos was determined by reverse transcription and polymerase chain reaction. The IL-4 receptor was constitutively expressed in RAW264.7 cells. RANKL induced osteoclast generation, as determined by TRAP staining and pit assay. IL-4 inhibited RANKL-induced osteoclastogenesis at low concentrations of 10 ng/ml and more. Interestingly, IL-4 potently inhibited RANKL-induced expression of NFATc1 at mRNA level. Furthermore, IL-4 inhibited c-Fos expression, which is shown to be responsible for NFATc1 expression, in time- and dose-dependent manners. In addition, IL-4 inhibited the RANKL-induced expression of NFATc1 and c-Fos in murine bone marrow cells. Thus, we suggest that IL-4 may downregulate osteoclastogenesis in part through inhibition of the expression of transcription factors, NFATc1 and c-Fos. These findings provide new insight into development of new medication for osteoporosis and RA

  18. Hydrogen sulphide-releasing diclofenac derivatives inhibit breast cancer-induced osteoclastogenesis in vitro and prevent osteolysis ex vivo.

    Science.gov (United States)

    Frantzias, J; Logan, J G; Mollat, P; Sparatore, A; Del Soldato, P; Ralston, S H; Idris, A I

    2012-03-01

    Hydrogen sulphide (H(2)S) and prostaglandins are both involved in inflammation, cancer and bone turnover, and non-steroidal anti-inflammatory drugs (NSAIDs) and H(2)S donors exhibit anti-inflammatory and anti-tumour properties. H(2)S-releasing diclofenac (S-DCF) derivatives are a novel class of NSAIDs combining the properties of a H(2)S donor with those of a conventional NSAID. We studied the effects of the S-DCF derivatives ACS15 and ACS32 on osteoclast and osteoblast differentiation and activity in vitro, human and mouse breast cancer cells support for osteoclast formation and signalling in vitro, and osteolysis ex vivo. The S-diclofenac derivatives ACS15 and ACS32 inhibited the increase in osteoclast formation induced by human MDA-MB-231 and MCF-7 and mouse 4T1 breast cancer cells without affecting breast cancer cell viability. Conditioned media from human MDA-MB-231 cells enhanced IκB phosphorylation and osteoclast formation and these effects were significantly inhibited following treatment by ACS15 and ACS32, whereas the parent compound diclofenac had no effects. ACS15 and ACS32 inhibited receptor activator of NFκB ligand-induced osteoclast formation and resorption, and caused caspase-3 activation and apoptosis in mature osteoclasts via a mechanism dependent on IKK/NFκB inhibition. In calvaria organ culture, human MDA-MB-231 cells caused osteolysis, and this effect was completely prevented following treatment with ACS15 and ACS32. S-diclofenac derivatives inhibit osteoclast formation and activity, suppress breast cancer cell support for osteoclastogenesis and prevent osteolysis. This suggests that H(2)S-releasing diclofenac derivatives exhibit anti-resorptive properties, which might be of clinical value in the treatment of osteolytic bone disease. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  19. 25-hydroxycholesterol promotes RANKL-induced osteoclastogenesis through coordinating NFATc1 and Sp1 complex in the transcription of miR-139-5p

    International Nuclear Information System (INIS)

    Zhang, Lishan; Lv, Yinping; Xian, Guozhe; Lin, Yanliang

    2017-01-01

    25-hydroxycholesterol (25-HC) is implicated in many processes, including lipid metabolism and the immune response. However, the role of 25-HC in RANKL-induced osteoclastogenesis remains largely unknown. Our results showed that 25-HC inhibited miR-139-5p expression in mouse bone marrow macrophages (BMMs) cultured in receptor activator of NF-κB ligand (RANKL) and monocyte macrophage colony-stimulating factor (M-CSF). Further investigation suggested that 25-HC promoted the expression of nuclear factor of activated T cell cytoplasmic 1 (NFATc1) and Sp1, especially in the presence of RANKL and M-CSF. Meanwhile, 25-HC induced nuclear translocation of NFATc1, resulting in the interaction between NFATc1 and Sp1 that was confirmed by co-immunoprecipitation. Chromatin immunoprecipitation assay indicated that Sp1 could bind to miR-139-5p promoter, but NFATc1 had no binding capacity. Although forming NFATc1/Sp1 complex increased its binding to miR-139-5p promoter, the complex inhibited the transcriptional activity of Sp1. Inhibition of NFATc1 increase the expression of miR-139-5p, which might be due to the release of free Sp1 that could bind to the promoter of miR-139-5p. Enforced expression of miR-139-5p impaired osteoclastogenesis induced by co-treatment with 25-HC and RANKL. These results suggested that 25-HC induced the interaction between NFATc1 and Sp1, reducing the level of free Sp1 to inhibit miR-139-5p expression and promote osteoclastogenesis. - Highlights: • 25-hydroxycholesterol inhibited miR-139-5p expression in bone marrow macrophages. • 25-hydroxycholesterol promoted the expression of NFATc1 and Sp1. • 25-hydroxycholesterol induced the interaction between NFATc1 and Sp1. • NFATc1/Sp1 complex inhibited the transcription of miR-139-5p. • MiR-139-5p impaired osteoclastogenesis induced by 25-hydroxycholesterol and RANKL.

  20. Discovery of novel benzopyranyl tetracycles that act as inhibitors of osteoclastogenesis induced by receptor activator of NF-κB ligand.

    Science.gov (United States)

    Zhu, Mingyan; Kim, Myung Hee; Lee, Sanghee; Bae, Su Jung; Kim, Seong Hwan; Park, Seung Bum

    2010-12-23

    A novel benzopyran-fused molecular framework 7ai was discovered as a specific inhibitor of RANKL-induced osteoclastogenesis using a cell-based TRAP activity assay from drug-like small-molecule libraries constructed by diversity-oriented synthesis. Its inhibitory activity was confirmed by in vitro evaluations including specific inhibition of RANKL-induced ERK phosphorylation and NF-κB transcriptional activation. 7ai can serve as a specific small-molecule modulator for mechanistic studies of RANKL-induced osteoclast differentiation as well as a potential lead for the development of antiresorptive drugs.

  1. Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-κB activation.

    Science.gov (United States)

    Yamaguchi, Masayoshi; Weitzmann, M Neale

    2011-01-01

    Several bone protective factors are reported to exhibit stimulatory activities on bone formation coupled with inhibitory effects on bone resorption; one such factor is vitamin K2. Vitamin K species [K1 (phylloquinone) and K2 (menaquinone)] have long been associated with bone protective activities and are receiving intense interest as nutritional supplements for the prevention or amelioration of bone disease in humans. However, the mechanisms of vitamin K action on the skeleton are poorly defined. Activation of the nuclear factor κB (NF-κB) signal transduction pathway is essential for osteoclast formation and resorption. By contrast, NF-κB signaling potently antagonizes osteoblast differentiation and function, prompting us to speculate that NF-κB antagonists may represent a novel class of dual anti-catabolic and pro-anabolic agents. We now show that vitamin K2 action on osteoblast and osteoclast formation and activity is accomplished by down-regulating basal and cytokine-induced NF-κB activation, by increasing IκB mRNA, in a γ-carboxylation-independent manner. Furthermore, vitamin K2 prevented repression by tumor necrosis factor α (TNFα) of SMAD signaling induced by either transforming growth factor ß (TGFß) or bone morphogenetic protein-2 (BMP-2). Vitamin K2 further antagonized receptor activator of NF-κB (RANK) ligand (RANKL)-induced NF-κB activation in osteoclast precursors. Our data provide a novel mechanism to explain the dual pro-anabolic and anti-catabolic activities of vitamin K2, and may further support the concept that pharmacological modulation of NF-κB signal transduction may constitute an effective mechanism for ameliorating pathological bone loss and for promoting bone health.

  2. Macrolactin F inhibits RANKL-mediated osteoclastogenesis by suppressing Akt, MAPK and NFATc1 pathways and promotes osteoblastogenesis through a BMP-2/smad/Akt/Runx2 signaling pathway.

    Science.gov (United States)

    Li, Liang; Sapkota, Mahesh; Gao, Ming; Choi, Hyukjae; Soh, Yunjo

    2017-11-15

    The balance between bone formation and bone resorption is maintained by osteoblasts and osteoclasts. In the current study, macrolactin F (MF) was investigated for novel biological activity on the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages (BMMs). We found that RANKL-induced osteoclast formation and differentiation from BMMs was significantly inhibited by MF in a dose-dependent manner without cytotoxicity. RANKL-induced F-actin ring formation and bone resorption activity in BMMs which was attenuated by MF. In addition, MF suppressed the expression of osteoclast-related genes, including c-myc, RANK, tartrate-resistant acid phosphatase (TRAP), nuclear factor of activated T cells c1 (NFATc1), cathepsin K and matrix metalloproteinase 9 (MMP9). Furthermore, the protein expression NFATc1, c-Fos, MMP9, cathepsin K and phosphorylation of Jun N-terminal kinase (JNK), p38 and Akt were also down-regulated by MF treatment. Interestingly, MF promoted pre-osteoblast cell differentiation on Alizarin Red-mineralization activity, alkaline phosphatase (ALP) activity, and the expression of osteoblastogenic markers including Runx2, Osterix, Smad4, ALP, type I collagen alpha 1 (Col1α), osteopontin (OPN), and osteocalcin (OCN) via activation of the BMP-2/smad/Akt/Runx2 pathway on MC3T3-E1. Taken together, these results indicate that MF may be useful as a therapeutic agent to enhance bone health and treat osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  4. Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging.

    Science.gov (United States)

    Davis, Hannah M; Pacheco-Costa, Rafael; Atkinson, Emily G; Brun, Lucas R; Gortazar, Arancha R; Harris, Julia; Hiasa, Masahiro; Bolarinwa, Surajudeen A; Yoneda, Toshiyuki; Ivan, Mircea; Bruzzaniti, Angela; Bellido, Teresita; Plotkin, Lilian I

    2017-06-01

    Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency. Cx43-silenced MLO-Y4 osteocytic (Cx43 def ) cells undergo spontaneous cell death in culture through caspase-3 activation and exhibit increased levels of apoptosis-related genes, and only transfection of Cx43 constructs able to form gap junction channels reverses Cx43 def cell death. Cx43 def cells and bones from old mice exhibit reduced levels of the pro-survival microRNA miR21 and, consistently, increased levels of the miR21 target phosphatase and tensin homolog (PTEN) and reduced phosphorylated Akt, whereas PTEN inhibition reduces Cx43 def cell apoptosis. miR21 reduction is sufficient to induce apoptosis of Cx43-expressing cells and miR21 deletion in miR21 fl/fl bones increases apoptosis-related gene expression, whereas a miR21 mimic prevents Cx43 def cell apoptosis, demonstrating that miR21 lies downstream of Cx43. Cx43 def cells release more osteoclastogenic cytokines [receptor activator of NFκB ligand (RANKL)/high-mobility group box-1 (HMGB1)], and caspase-3 inhibition prevents RANKL/HMGB1 release and the increased osteoclastogenesis induced by conditioned media from Cx43 def cells, which is blocked by antagonizing HMGB1-RAGE interaction. These findings identify a novel Cx43/miR21/HMGB1/RANKL pathway involved in preventing osteocyte apoptosis that also controls osteoclast formation/recruitment and is impaired with aging. © 2017 The Authors. Aging Cell published by the Anatomical Society

  5. The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors

    International Nuclear Information System (INIS)

    Kwon, Oh Hyung; Lee, Chong-Kil; Lee, Young Ik; Paik, Sang-Gi; Lee, Hyun-Jun

    2005-01-01

    Osteoclasts are bone resorbing cells of hematopoietic origin. The hematopoietic transcription factor PU.1 is critical for osteoclastogenesis; however, the molecular mechanisms of PU.1-regulated osteoclastogenesis have not been explored. Here, we present evidence that the receptor activator of nuclear factor κB (RANK) gene that has been shown to be crucial for osteoclastogenesis is a transcriptional target of PU.1. The PU.1 -/- progenitor cells failed to express the RANK gene and reconstitution of PU.1 in these cells induced RANK expression. Treatment of the PU.1 reconstituted cells with M-CSF and RANKL further augmented the RANK gene expression. To explore the regulatory mechanism of the RANK gene expression by PU.1, we have cloned the human RANK promoter. Transient transfection assays have revealed that the 2.2-kb RANK promoter was functional in a monocyte line RAW264.7, whereas co-transfection of PU.1 transactivated the RANK promoter in HeLa cells. Taken together, these results suggest that PU.1 regulates the RANK gene transcription and this may represent one of the key roles of PU.1 in osteoclast differentiation

  6. Regulation of SFRP-1 expression in the rat dental follicle.

    Science.gov (United States)

    Liu, Dawen; Yao, Shaomian; Wise, Gary E

    2012-01-01

    Tooth eruption requires osteoclastogenesis and subsequent bone resorption. Secreted frizzled-related protein-1 (SFRP-1) negatively regulates osteoclastogenesis. Our previous studies indicated that SFRP-1 is expressed in the rat dental follicle (DF), with reduced expression at days 3 and 9 close to the times for the major and minor bursts of osteoclastogenesis, respectively; but it remains unclear as to what molecules contribute to its reduced expression at these critical times. Thus, it was the aim of this study to determine which molecules regulate the expression of SFRP-1 in the DF. To that end, the DF cells were treated with cytokines that are maximally expressed at days 3 or 9, and SFRP-1 expression was determined. Our study indicated that colony-stimulating factor-1 (CSF-1), a molecule maximally expressed in the DF at day 3, down-regulated SFRP-1 expression. As to endothelial monocyte-activating polypeptide II (EMAP-II), a highly expressed molecule in the DF at day 3, it had no effect on the expression of SFRP-1. However, when EMAP-II was knocked down by siRNA, the expression of SFRP-1 was elevated, and this elevated SFRP-1 expression could be reduced by adding recombinant EMAP-II protein. This suggests that EMAP-II maintained a lower level of SFRP-1 in the DF. TNF-α is a molecule maximally expressed at day 9, and this study indicated that it also down-regulated the expression of SFRP-1 in the DF cells. In conclusion, CSF-1 and EMAP-II may contribute to the reduced SFRP-1 expression seen on day 3, while TNF-α may contribute to the reduced SFRP-1 expression at day 9.

  7. TRAF Family Member-Associated NF-κB Activator (TANK) Induced by RANKL Negatively Regulates Osteoclasts Survival and Function

    OpenAIRE

    Mengrui Wu, Yiping Wang, Lianfu Deng, Wei Chen, Yi-Ping Li

    2012-01-01

    Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation...

  8. TRAF Family Member-Associated NF-κB Activator (TANK) Induced by RANKL Negatively Regulates Osteoclasts Survival and Function

    OpenAIRE

    Wu, Mengrui; Wang, Yiping; Deng, Lianfu; Chen, Wei; Li, Yi-Ping

    2012-01-01

    Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation, and...

  9. A Study of the Abundance and 13C/12C Ratio of Atmospheric Carbon Dioxide to Advance the Scientific Understanding of Terrestrial Processes Regulating the Global Carbon Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Stephen C. Piper

    2005-10-15

    The primary goal of our research program, consistent with the goals of the U.S. Climate Change Science Program and funded by the terrestrial carbon processes (TCP) program of DOE, has been to improve understanding of changes in the distribution and cycling of carbon among the active land, ocean and atmosphere reservoirs, with particular emphasis on terrestrial ecosystems. Our approach is to systematically measure atmospheric CO2 to produce time series data essential to reveal temporal and spatial patterns. Additional measurements of the 13C/12C isotopic ratio of CO2 provide a basis for distinguishing organic and inorganic processes. To pursue the significance of these patterns further, our research also involved interpretations of the observations by models, measurements of inorganic carbon in sea water, and of CO2 in air near growing land plants.

  10. The plant limonoid 7-oxo-deacetoxygedunin inhibits RANKL-induced osteoclastogenesis by suppressing activation of the NF-{kappa}B and MAPK pathways

    Energy Technology Data Exchange (ETDEWEB)

    Wisutsitthiwong, Chonnaree; Buranaruk, Chayanit [Graduate Program in Industrial Microbiology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Phayathai Road, Bangkok 10330 (Thailand); Pudhom, Khanitha [Department of Chemistry, Faculty of Science and Center for Petroleum, Petrochemicals and Advanced Materials, Chulalongkorn University, Phayathai Road, Bangkok 10330 (Thailand); Palaga, Tanapat, E-mail: tanapat.p@chula.ac.th [Graduate Program in Industrial Microbiology, Department of Microbiology, Faculty of Science, Chulalongkorn University, Phayathai Road, Bangkok 10330 (Thailand)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer A gedunin type limonoid from seeds of mangroves, 7-oxo-7-deacetoxygedunin, exhibits strong anti-osteoclastogenic activity. Black-Right-Pointing-Pointer Treatment with this limonoid results in significant decrease in expression of NFATc1 and osteoclast-related genes. Black-Right-Pointing-Pointer The mode of action of this limonoid is by inhibiting activation of the NF-{kappa}B and MAPK pathways which are activated by RANKL. -- Abstract: Osteoclasts together with osteoblasts play pivotal roles in bone remodeling. Aberrations in osteoclast differentiation and activity contribute to osteopenic disease. Osteoclasts differentiate from monocyte/macrophage progenitors, a process that is initiated by the interaction between receptor activator of NF-{kappa}B (RANK) and its ligand, RANKL. In this study, we identified 7-oxo-7-deacetoxygedunin (7-OG), a gedunin type limonoid from seeds of the mangrove Xylocarpus moluccensis, as a potent inhibitor of osteoclastogenesis. Additionally, 7-OG showed strong anti-osteoclastogenic activity with low cytotoxicity against the monocyte/macrophage progenitor cell line, RAW264.7. The IC50 for anti-osteoclastogenic activity was 4.14 {mu}M. Treatment with 7-OG completely abolished the appearance of multinucleated giant cells with tartrate-resistant acid phosphatase activity in RAW264.7 cells stimulated with RANKL. When the expression of genes related to osteoclastogenesis was investigated, a complete downregulation of NFATc1 and cathepsin K and a delayed downregulation of irf8 were observed upon 7-OG treatment in the presence of RANKL. Furthermore, treatment with this limonoid suppressed RANKL-induced activation of p38, MAPK and Erk and nuclear localization of NF-{kappa}B p65. Taken together, we present evidence indicating a plant limonoid as a novel osteoclastogenic inhibitor that could be used for osteoporosis and related conditions.

  11. The plant limonoid 7-oxo-deacetoxygedunin inhibits RANKL-induced osteoclastogenesis by suppressing activation of the NF-κB and MAPK pathways

    International Nuclear Information System (INIS)

    Wisutsitthiwong, Chonnaree; Buranaruk, Chayanit; Pudhom, Khanitha; Palaga, Tanapat

    2011-01-01

    Highlights: ► A gedunin type limonoid from seeds of mangroves, 7-oxo-7-deacetoxygedunin, exhibits strong anti-osteoclastogenic activity. ► Treatment with this limonoid results in significant decrease in expression of NFATc1 and osteoclast-related genes. ► The mode of action of this limonoid is by inhibiting activation of the NF-κB and MAPK pathways which are activated by RANKL. -- Abstract: Osteoclasts together with osteoblasts play pivotal roles in bone remodeling. Aberrations in osteoclast differentiation and activity contribute to osteopenic disease. Osteoclasts differentiate from monocyte/macrophage progenitors, a process that is initiated by the interaction between receptor activator of NF-κB (RANK) and its ligand, RANKL. In this study, we identified 7-oxo-7-deacetoxygedunin (7-OG), a gedunin type limonoid from seeds of the mangrove Xylocarpus moluccensis, as a potent inhibitor of osteoclastogenesis. Additionally, 7-OG showed strong anti-osteoclastogenic activity with low cytotoxicity against the monocyte/macrophage progenitor cell line, RAW264.7. The IC50 for anti-osteoclastogenic activity was 4.14 μM. Treatment with 7-OG completely abolished the appearance of multinucleated giant cells with tartrate-resistant acid phosphatase activity in RAW264.7 cells stimulated with RANKL. When the expression of genes related to osteoclastogenesis was investigated, a complete downregulation of NFATc1 and cathepsin K and a delayed downregulation of irf8 were observed upon 7-OG treatment in the presence of RANKL. Furthermore, treatment with this limonoid suppressed RANKL-induced activation of p38, MAPK and Erk and nuclear localization of NF-κB p65. Taken together, we present evidence indicating a plant limonoid as a novel osteoclastogenic inhibitor that could be used for osteoporosis and related conditions.

  12. Ménage-à-trois: The ratio of bicarbonate to CO2 and the pH regulate the capacity of neutrophils to form NETs

    Directory of Open Access Journals (Sweden)

    Christian Maueröder

    2016-12-01

    Full Text Available In this study we identified and characterized the potential of a high ratio of bicarbonate to CO2 and a moderately alkaline pH to render neutrophils prone to undergo neutrophil extracellular trap (NET formation. Both experimental settings increased the rate of spontaneous NET release and potentiated the NET-inducing capacity of phorbol esters (PMA, ionomycin, monosodium urate and LPS. In contrast, an acidic environment impaired neutrophil extracellular trap formation both spontaneous and induced. Our findings indicate that intracellular alkalinization of neutrophils in response to an alkaline environment leads to an increase of intracellular calcium and neutrophil activation. We further found that the anion channel blocker DIDS strongly reduced NET formation induced by bicarbonate. This finding suggests that the effects observed are due to a molecular program that renders neutrophils susceptible to neutrophil extracellular trap formation. Inflammatory foci are characterized by an acidic environment. Our data indicates that NET formation is favored by the higher pH at the border regions of inflamed areas. Moreover our findings highlight the necessity for strict pH control during assays of neutrophil extracellular trap formation.

  13. Ratios of colony mass to thermal conductance of tree and man-made nest enclosures of Apis mellifera: implications for survival, clustering, humidity regulation and Varroa destructor

    Science.gov (United States)

    Mitchell, Derek

    2016-05-01

    In the absence of human intervention, the honeybee ( Apis mellifera L.) usually constructs its nest in a tree within a tall, narrow, thick-walled cavity high above the ground (the enclosure); however, most research and apiculture is conducted in the thin-walled, squat wooden enclosures we know as hives. This experimental research, using various hives and thermal models of trees, has found that the heat transfer rate is approximately four to seven times greater in the hives in common use, compared to a typical tree enclosure in winter configuration. This gives a ratio of colony mass to lumped enclosure thermal conductance (MCR) of less than 0.8 kgW-1 K for wooden hives and greater than 5 kgW-1 K for tree enclosures. This result for tree enclosures implies higher levels of humidity in the nest, increased survival of smaller colonies and lower Varroa destructor breeding success. Many honeybee behaviours previously thought to be intrinsic may only be a coping mechanism for human intervention; for example, at an MCR of above 2 kgW-1 K, clustering in a tree enclosure may be an optional, rare, heat conservation behaviour for established colonies, rather than the compulsory, frequent, life-saving behaviour that is in the hives in common use. The implied improved survival in hives with thermal properties of tree nests may help to solve some of the problems honeybees are currently facing in apiculture.

  14. Adaptive Control Using Fully Online Sequential-Extreme Learning Machine and a Case Study on Engine Air-Fuel Ratio Regulation

    Directory of Open Access Journals (Sweden)

    Pak Kin Wong

    2014-01-01

    Full Text Available Most adaptive neural control schemes are based on stochastic gradient-descent backpropagation (SGBP, which suffers from local minima problem. Although the recently proposed regularized online sequential-extreme learning machine (ReOS-ELM can overcome this issue, it requires a batch of representative initial training data to construct a base model before online learning. The initial data is usually difficult to collect in adaptive control applications. Therefore, this paper proposes an improved version of ReOS-ELM, entitled fully online sequential-extreme learning machine (FOS-ELM. While retaining the advantages of ReOS-ELM, FOS-ELM discards the initial training phase, and hence becomes suitable for adaptive control applications. To demonstrate its effectiveness, FOS-ELM was applied to the adaptive control of engine air-fuel ratio based on a simulated engine model. Besides, controller parameters were also analyzed, in which it is found that large hidden node number with small regularization parameter leads to the best performance. A comparison among FOS-ELM and SGBP was also conducted. The result indicates that FOS-ELM achieves better tracking and convergence performance than SGBP, since FOS-ELM tends to learn the unknown engine model globally whereas SGBP tends to “forget” what it has learnt. This implies that FOS-ELM is more preferable for adaptive control applications.

  15. Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice

    Directory of Open Access Journals (Sweden)

    Jong Min Baek

    2014-08-01

    Full Text Available Aconitum pseudo-laeve var. erectum (APE has been widely shown in herbal medicine to have a therapeutic effect on inflammatory conditions. However, there has been no evidence on whether the extract of APE is involved in the biological bone metabolism process, particularly osteoclast-mediated bone resorption. In this study, we confirmed that the administration of APE could restore normal skeletal conditions in a murine model of lipopolysaccharide (LPS-induced bone loss via a decrease in the receptor activator of nuclear factor kappa-B ligand (RANKL/osteoprotegerin (OPG ratio and osteoclast number. We then investigated the effect of APE on the RANKL-induced formation and function of osteoclasts to elucidate its underlying molecular mechanisms. APE suppressed the formation of tartrate-resistant acid phosphatase (TRAP-positive cells, as well as the bone-resorbing activity of mature osteoclasts. Furthermore, APE attenuated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1 and c-Fos without affecting any early signal pathway of osteoclastogenesis. Subsequently, APE significantly downregulated the expression of various genes exclusively expressed in osteoclasts. These results demonstrate that APE restores LPS-induced bone loss through a decrease of the serum RANKL/OPG ratio, and inhibits osteoclast differentiation and function, suggesting the promise of APE as a potential cure for various osteoclast-associated bone diseases.

  16. Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jun-Oh; Lee, Yong Deok; Kim, Haemin; Kim, Min Kyung; Song, Min-Kyoung; Lee, Zang Hee; Kim, Hong-Hee, E-mail: hhbkim@snu.ac.kr

    2016-09-02

    Tetraspanin family proteins regulate morphology, motility, fusion, and signaling in various cell types. We investigated the role of the tetraspanin 7 (Tspan7) isoform in the differentiation and function of osteoclasts. Tspan7 was up-regulated during osteoclastogenesis. When Tspan7 expression was reduced in primary precursor cells by siRNA-mediated gene knock-down, the generation of multinuclear osteoclasts was not affected. However, a striking cytoskeletal abnormality was observed: the formation of the podosome belt structure was inhibited and the microtubular network were disrupted by Tspan7 knock-down. Decreases in acetylated microtubules and levels of phosphorylated Src and Pyk2 in Tspan7 knock-down cells supported the involvement of Tspan7 in cytoskeletal rearrangement signaling in osteoclasts. This cytoskeletal defect interfered with sealing zone formation and subsequently the bone-resorbing activity of mature osteoclasts on dentin surfaces. Our results suggest that Tspan7 plays an important role in cytoskeletal organization required for the bone-resorbing function of osteoclasts by regulating signaling to Src, Pyk2, and microtubules. - Highlights: • Tspan7 expression is up-regulated during osteoclastogenesis. • Tspan7 regulates podosome belt organization in osteoclasts. • Tspan7 is crucial for sealing zone formation and bone-resorption by osteoclasts. • Src and Pyk2 phosphorylation and microtubule acetylation mediate Tspan7 function.

  17. Bu-Shen-Ning-Xin decoction: inhibition of osteoclastogenesis by abrogation of the RANKL-induced NFATc1 and NF-κB signaling pathways via selective estrogen receptor α

    Directory of Open Access Journals (Sweden)

    Wang L

    2015-07-01

    Full Text Available Ling Wang,1,2,* Xue-Min Qiu,1,2,* Yu-Yan Gui,1,2 Ying-Ping Xu,1,2 Hans-Jürgen Gober,3 Da-Jin Li11Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, 2Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People’s Republic of China; 3Department of Pharmacy, Wagner Jauregg Hospital and Children’s Hospital, Wagner Jauregg Weg, Linz, Austria*These authors contributed equally to this workIntroduction: Bu-Shen-Ning-Xin decoction (BSNXD is a traditional Chinese medicinal composition that has been used as a remedy for postmenopausal osteoporosis, but the mechanisms affecting bone metabolism are not fully understood.Purpose: We investigated the molecular mechanism and signaling pathway underlying the effect of BSNXD on osteoclastogenesis.Materials and methods: A postmenopausal osteoporosis animal model generated by ovariectomy was administered BSNXD and drug-derived serum was prepared. An enzyme immunoassay was conducted to measure the 17-β-estradiol (E2 concentration in the drug-derived serum. Bone marrow-derived monocyte/macrophage precursor cells were treated with drug-derived serum, and tartrate-resistance acid phosphatase staining was conducted to observe osteoclastogenesis. A bone resorption assay was performed to analyze the effect on osteoclastic resorptive function. Real-time PCR, flow cytometry, Western blotting, transfection, and luciferase assays were conducted to explore the related mechanism.Results: E2 was not elevated in BSNXD-derived serum. BSNXD-derived serum suppressed receptor activation of nuclear factor κB ligand (RANKL-activated osteoclastogenesis in a dose-dependent manner; this effect could be reversed by estrogen receptor α antagonist methyl-piperidino-pyrazole. The serum suppressed RANKL-induced NF-κB transcription and inhibited the accumulation of nuclear factor of activated T-cells, cytoplasmic 1

  18. Ethyl acetate extract of Chinese medicinal herb Sarcandra glabra induces growth inhibition on human leukemic HL-60 cells, associated with cell cycle arrest and up-regulation of pro-apoptotic Bax/Bcl-2 ratio.

    Science.gov (United States)

    Li, W Y; Chiu, Lawrence C M; Lam, W S; Wong, W Y; Chan, Y T; Ho, Y P; Wong, Elaine Y L; Wong, Y S; Ooi, Vincent E C

    2007-02-01

    Sarcandra glabra (Thunb.) Nakai, colloquially known as Caoshanhu, is a Chinese medicinal herb with reported anti-tumor, anti-inflammatory, anti-viral and non-specific immunoenhancing properties. Although the plant has been clinically used for treating a variety of diseases, its bioactive ingredients are largely unknown and its mode of action has never been investigated. In this study, the anti-tumor property of ethyl acetate (EA) extract of S. glabra was investigated by determining its in vitro growth-inhibitory effects on a panel of human cancer cell lines of different histotypes. Growth inhibition of the EA extract on the cancer cells seemed to be selective, and the leukemic HL-60 was found to be the most responsive after 48 h of treatment (IC50=58 microg/ml). Flow cytometric studies further illustrated that the extract might interfere with DNA replication and thus arrested the cell cycle at S phase in the leukemic cells, followed by DNA fragmentation and loss of phospholipid asymmetry in the plasma membrane after 72 h of treatment. Concurrently, the pro-apoptotic Bax/Bcl-2 ratio was also up-regulated by more than 178% of the control level. All these findings suggested that the extract had initiated apoptosis to kill the leukemic cells. Results from this pioneer study help to establish a scientific foundation for future research and development of the bioactive ingredients in EA extract of S. glabra as efficacious anti-cancer agents.

  19. TRAF family member-associated NF-κB activator (TANK) induced by RANKL negatively regulates osteoclasts survival and function.

    Science.gov (United States)

    Wu, Mengrui; Wang, Yiping; Deng, Lianfu; Chen, Wei; Li, Yi-Ping

    2012-01-01

    Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation, and confirmed by western blot and quantitative RT-PCR. Bone marrow macrophages (BMMs) transduced with lentivirus carrying tank-shRNA were induced to form osteoclast in the presence of RANKL and M-CSF. Tank expression was downregulated by 90% by Tank-shRNA, which is confirmed by western blot. Compared with wild-type (WT) cells, osteoclastogenesis of Tank-silenced BMMs was increased, according to tartrate-resistant acid phosphatase (TRAP) stain on day 5 and day 7. Number of bone resorption pits by Tank-silenced osteoclasts was increased by 176% compared with WT cells, as shown by wheat germ agglutinin (WGA) stain and scanning electronic microscope (SEM) analysis. Survival rate of Tank-silenced mature osteoclast is also increased. However, acid production of Tank-knockdown cells was not changed compared with control cells. IκBα phosphorylation is increased in tank-silenced cells, indicating that TANK may negatively regulate NF-κB activity in osteoclast. In conclusion, Tank, whose expression is increased during osteoclastogenesis, inhibits osteoclast formation, activity and survival, by regulating NF-κB activity and c-FLIP expression. Tank enrolls itself in a negative feedback loop in bone resorption. These results may provide means for therapeutic intervention in diseases of excessive bone resorption.

  20. Fluctuation of Dof1/Dof2 expression ratio under the influence of varying nitrogen and light conditions: involvement in differential regulation of nitrogen metabolism in two genotypes of finger millet (Eleusine coracana L.).

    Science.gov (United States)

    Gupta, Supriya; Gupta, Sanjay Mohan; Gupta, Alok Kumar; Gaur, Vikram Singh; Kumar, Anil

    2014-08-10

    In order to gain insights into the mechanism of high nitrogen use efficiency (NUE) of finger millet (FM) the role of Dof2 transcription factor (TF), which is a repressor of genes involved in C/N metabolism was investigated. The partial cDNA fragment of EcDof2 (912-bp; GenBank acc. no. KF261117) was isolated and characterized from finger millet (FM) that showed 63% and 58% homology with Dof2 of Zea mays at nucleotide and protein level, respectively. Its expression studies were carried out along with the activator EcDof1 in two genotypes (GE3885, high protein genotype (HPG); GE1437, low protein genotype (LPG)) of FM differing in grain protein contents (13.8% and 6.2%) showed that EcDof2 is expressed in both shoot and root tissues with significantly (p≤0.05) higher expression in the roots. The diurnal expression of both EcDof1 and EcDof2 in shoots was differential having different time of peak expression indicating a differential response to diurnal condition. Under continuous dark conditions, expression of EcDof1 and EcDof2 oscillated in both the genotypes whereas on illumination, the fold expression of EcDof1 was higher as compared to EcDof2. Under increasing nitrate concentration, EcDof2 expression increases in roots and shoots of LPG while it remains unchanged in HPG. However, the EcDof1 expression was found to increase in both genotypes. Further, time kinetics studies under single nitrate concentration revealed that EcDof2 was repressed in the roots of both genotypes whereas EcDof1 oscillated with time. The EcDof1/EcDof2 ratio measured showed differential response under different light and nitrogen conditions. It was higher in the roots of HPG indicating higher activation of genes involved in N uptake and assimilation resulting in high grain protein accumulation. The results indicate that both light and nitrogen concentration influence Dof1 and Dof2 expression and suggests a complex pattern of regulation of genes influenced by these plant specific TFs. In

  1. A novel dual inhibitor of microtubule and Bruton's tyrosine kinase inhibits survival of multiple myeloma and osteoclastogenesis.

    Science.gov (United States)

    Pandey, Manoj K; Gowda, Krishne; Sung, Shen-Shu; Abraham, Thomas; Budak-Alpdogan, Tulin; Talamo, Giampolo; Dovat, Sinisa; Amin, Shantu

    2017-09-01

    Bruton's tyrosine kinase (BTK) regulates many vital signaling pathways and plays a critical role in cell proliferation, survival, migration, and resistance. Previously, we reported that a small molecule, KS99, is an inhibitor of tubulin polymerization. In the present study, we explored whether KS99 is a dual inhibitor of BTK and tubulin polymerization. Although it is known that BTK is required for clonogenic growth and resistance, and microtubules are essential for cancer cell growth, dual targeting of these two components has not been explored previously. Through docking studies, we predicted that KS99 interacts directly with the catalytic domain of BTK and inhibits phosphorylation at the Y223 residue and kinase activities. Treatment of KS99 reduces the cell viability of multiple myeloma (MM) and CD138 + cells, with an IC 50 of between 0.5 and 1.0 μmol/L. We found that KS99 is able to induce apoptosis in MM cells in a caspase-dependent manner. KS99 suppressed the receptor activator of NF-κB ligand (RANKL)-induced differentiation of macrophages to osteoclasts in a dose-dependent manner and, importantly, inhibited the expression of cytokines associated with bone loss. Finally, we found that KS99 inhibits the in vivo tumor growth of MM cells through the inhibition of BTK and tubulin. Overall, our results show that dual inhibition of BTK and tubulin polymerization by KS99 is a viable option in MM treatment, particularly in the inhibition of refraction and relapse. Copyright © 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  2. Financial Key Ratios

    OpenAIRE

    Tănase Alin-Eliodor

    2014-01-01

    This article focuses on computing techniques starting from trial balance data regarding financial key ratios. There are presented activity, liquidity, solvency and profitability financial key ratios. It is presented a computing methodology in three steps based on a trial balance.

  3. VVER-1000 dominance ratio

    International Nuclear Information System (INIS)

    Gorodkov, S.

    2009-01-01

    Dominance ratio, or more precisely, its closeness to unity, is important characteristic of large reactor. It allows evaluate beforehand the number of source iterations required in deterministic calculations of power spatial distribution. Or the minimal number of histories to be modeled for achievement of statistical error level desired in large core Monte Carlo calculations. In this work relatively simple approach for dominance ratio evaluation is proposed. It essentially uses core symmetry. Dependence of dominance ratio on neutron flux spatial distribution is demonstrated. (author)

  4. WWER-1000 dominance ratio

    International Nuclear Information System (INIS)

    Gorodkov, S.S.

    2009-01-01

    Dominance ratio, or more precisely, its closeness to unity, is important characteristic of large reactor. It allows evaluate beforehand the number of source iterations required in deterministic calculations of power spatial distribution. Or the minimal number of histories to be modeled for achievement of statistical error level desired in large core Monte Carlo calculations. In this work relatively simple approach for dominance ratio evaluation is proposed. It essentially uses core symmetry. Dependence of dominance ratio on neutron flux spatial distribution is demonstrated. (Authors)

  5. Sharpening Sharpe Ratios

    OpenAIRE

    William N. Goetzmann; Jonathan E. Ingersoll Jr.; Matthew I. Spiegel; Ivo Welch

    2002-01-01

    It is now well known that the Sharpe ratio and other related reward-to-risk measures may be manipulated with option-like strategies. In this paper we derive the general conditions for achieving the maximum expected Sharpe ratio. We derive static rules for achieving the maximum Sharpe ratio with two or more options, as well as a continuum of derivative contracts. The optimal strategy has a truncated right tail and a fat left tail. We also derive dynamic rules for increasing the Sharpe ratio. O...

  6. Detecting isotopic ratio outliers

    International Nuclear Information System (INIS)

    Bayne, C.K.; Smith, D.H.

    1985-01-01

    An alternative method is proposed for improving isotopic ratio estimates. This method mathematically models pulse-count data and uses iterative reweighted Poisson regression to estimate model parameters to calculate the isotopic ratios. This computer-oriented approach provides theoretically better methods than conventional techniques to establish error limits and to identify outliers. 6 refs., 3 figs., 3 tabs

  7. Detecting isotopic ratio outliers

    Science.gov (United States)

    Bayne, C. K.; Smith, D. H.

    An alternative method is proposed for improving isotopic ratio estimates. This method mathematically models pulse-count data and uses iterative reweighted Poisson regression to estimate model parameters to calculate the isotopic ratios. This computer-oriented approach provides theoretically better methods than conventional techniques to establish error limits and to identify outliers.

  8. Detecting isotopic ratio outliers

    International Nuclear Information System (INIS)

    Bayne, C.K.; Smith, D.H.

    1986-01-01

    An alternative method is proposed for improving isotopic ratio estimates. This method mathematically models pulse-count data and uses iterative reweighted Poisson regression to estimate model parameters to calculate the isotopic ratios. This computer-oriented approach provides theoretically better methods than conventional techniques to establish error limits and to identify outliers

  9. The transcription factor Jdp2 controls bone homeostasis and antibacterial immunity by regulating osteoclast and neutrophil differentiation.

    Science.gov (United States)

    Maruyama, Kenta; Fukasaka, Masahiro; Vandenbon, Alexis; Saitoh, Tatsuya; Kawasaki, Takumi; Kondo, Takeshi; Yokoyama, Kazunari K; Kidoya, Hiroyasu; Takakura, Nobuyuki; Standley, Daron; Takeuchi, Osamu; Akira, Shizuo

    2012-12-14

    Jdp2 is an AP-1 family transcription factor that regulates the epigenetic status of histones. Previous in vitro studies revealed that Jdp2 is involved in osteoclastogenesis. However, the roles of Jdp2 in vivo and its pleiotropic functions are largely unknown. Here we generated Jdp2(-/-) mice and discovered its crucial roles not only in bone metabolism but also in differentiation of neutrophils. Jdp2(-/-) mice exhibited osteopetrosis resulting from impaired osteoclastogenesis. Jdp2(-/-) neutrophils were morphologically normal but had impaired surface expression of Ly6G, bactericidal function, and apoptosis. We also found that ATF3 was an inhibitor of neutrophil differentiation and that Jdp2 directly suppresses its expression via inhibition of histone acetylation. Strikingly, Jdp2(-/-) mice were highly susceptible to Staphylococcus aureus and Candida albicans infection. Thus, Jdp2 plays pivotal roles in in vivo bone homeostasis and host defense by regulating osteoclast and neutrophil differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Difference and ratio plots

    DEFF Research Database (Denmark)

    Svendsen, Anders Jørgen; Holmskov, U; Bro, Peter

    1995-01-01

    and systemic lupus erythematosus from another previously published study (Macanovic, M. and Lachmann, P.J. (1979) Clin. Exp. Immunol. 38, 274) are also represented using ratio plots. Our observations indicate that analysis by regression analysis may often be misleading....... hitherto unnoted differences between controls and patients with either rheumatoid arthritis or systemic lupus erythematosus. For this we use simple, but unconventional, graphic representations of the data, based on difference plots and ratio plots. Differences between patients with Burkitt's lymphoma...

  11. The rectilinear Steiner ratio

    Directory of Open Access Journals (Sweden)

    PO de Wet

    2005-06-01

    Full Text Available The rectilinear Steiner ratio was shown to be 3/2 by Hwang [Hwang FK, 1976, On Steiner minimal trees with rectilinear distance, SIAM Journal on Applied Mathematics, 30, pp. 104– 114.]. We use continuity and introduce restricted point sets to obtain an alternative, short and self-contained proof of this result.

  12. C-Mpl Is Expressed on Osteoblasts and Osteoclasts and Is Important in Regulating Skeletal Homeostasis.

    Science.gov (United States)

    Meijome, Tomas E; Baughman, Jenna T; Hooker, R Adam; Cheng, Ying-Hua; Ciovacco, Wendy A; Balamohan, Sanjeev M; Srinivasan, Trishya L; Chitteti, Brahmananda R; Eleniste, Pierre P; Horowitz, Mark C; Srour, Edward F; Bruzzaniti, Angela; Fuchs, Robyn K; Kacena, Melissa A

    2016-04-01

    C-Mpl is the receptor for thrombopoietin (TPO), the main megakaryocyte (MK) growth factor, and c-Mpl is believed to be expressed on cells of the hematopoietic lineage. As MKs have been shown to enhance bone formation, it may be expected that mice in which c-Mpl was globally knocked out (c-Mpl(-/-) mice) would have decreased bone mass because they have fewer MKs. Instead, c-Mpl(-/-) mice have a higher bone mass than WT controls. Using c-Mpl(-/-) mice we investigated the basis for this discrepancy and discovered that c-Mpl is expressed on both osteoblasts (OBs) and osteoclasts (OCs), an unexpected finding that prompted us to examine further how c-Mpl regulates bone. Static and dynamic bone histomorphometry parameters suggest that c-Mpl deficiency results in a net gain in bone volume with increases in OBs and OCs. In vitro, a higher percentage of c-Mpl(-/-) OBs were in active phases of the cell cycle, leading to an increased number of OBs. No difference in OB differentiation was observed in vitro as examined by real-time PCR and functional assays. In co-culture systems, which allow for the interaction between OBs and OC progenitors, c-Mpl(-/-) OBs enhanced osteoclastogenesis. Two of the major signaling pathways by which OBs regulate osteoclastogenesis, MCSF/OPG/RANKL and EphrinB2-EphB2/B4, were unaffected in c-Mpl(-/-) OBs. These data provide new findings for the role of MKs and c-Mpl expression in bone and may provide insight into the homeostatic regulation of bone mass as well as bone loss diseases such as osteoporosis. © 2015 Wiley Periodicals, Inc.

  13. Transformer ratio enhancement experiment

    International Nuclear Information System (INIS)

    Gai, W.; Power, J. G.; Kanareykin, A.; Neasheva, E.; Altmark, A.

    2004-01-01

    Recently, a multibunch scheme for efficient acceleration based on dielectric wakefield accelerator technology was outlined in J.G. Power, W. Gai, A. Kanareykin, X. Sun. PAC 2001 Proceedings, pp. 114-116, 2002. In this paper we present an experimental program for the design, development and demonstration of an Enhanced Transformer Ratio Dielectric Wakefield Accelerator (ETR-DWA). The principal goal is to increase the transformer ratio R, the parameter that characterizes the energy transfer efficiency from the accelerating structure to the accelerated electron beam. We present here an experimental design of a 13.625 GHz dielectric loaded accelerating structure, a laser multisplitter producing a ramped bunch train, and simulations of the bunch train parameters required. Experimental results of the accelerating structure bench testing and ramped pulsed train generation with the laser multisplitter are shown as well. Using beam dynamic simulations, we also obtain the focusing FODO lattice parameters

  14. Intake to Production Ratio

    DEFF Research Database (Denmark)

    Nazaroff, William; Weschler, Charles J.; Little, John C.

    2012-01-01

    BACKGROUND: Limited data are available to assess human exposure to thousands of chemicals currently in commerce. Information that relates human intake of a chemical to its production and use can help inform understanding of mechanisms and pathways that control exposure and support efforts...... to protect public health.OBJECTIVES: We introduce the intake-to-production ratio (IPR) as an economy-wide quantitative indicator of the extent to which chemical production results in human exposure.METHODS: The IPR was evaluated as the ratio of two terms: aggregate rate of chemical uptake in a human......(n-butyl) phthalate, 1,040 ppm for para-dichlorobenzene, 6,800 ppm for di(isobutyl) phthalate, 7,700 ppm for diethyl phthalate, and 8,000-24,000 ppm (range) for triclosan.CONCLUSION: The IPR is well suited as an aggregate metric of exposure intensity for characterizing population-level exposure to synthesized...

  15. Osteocyte regulation of bone and blood.

    Science.gov (United States)

    Divieti Pajevic, Paola; Krause, Daniela S

    2018-02-16

    This past decade has witnessed a renewed interest in the function and biology of matrix-embedded osteocytes and these cells have emerged as master regulators of bone homeostasis. They secrete two very powerful proteins, sclerostin, a Wnt-inhibitor, that suppresses bone formation, and receptor-activator of NF-kB ligand (RANKL), a cytokine required for osteoclastogenesis. Neutralizing antibodies against these proteins are currently used for the treatment of osteoporosis. Recent studies however, ascribed yet another function to osteocytes: the control of hematopoiesis and the HSPC niche, directly and through secreted factors. In the absence of osteocytes there is an increase in HSC mobilization and abnormal lymphopoiesis whereas in the absence of G s α signaling in these cells there is an increase of myeloid cells. How exactly osteocytes control hematopoiesis or the HSPC niche is still not completely understood. In this review we summarize the actions of osteocytes in bone and then analyze the effects of these cells on hematopoiesis. Future directions and gaps in current knowledge are further discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. The Reference Return Ratio

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Faber Frandsen, Tove

    2008-01-01

    The paper introduces a new journal impact measure called The Reference Return Ratio (3R). Unlike the traditional Journal Impact Factor (JIF), which is based on calculations of publications and citations, the new measure is based on calculations of bibliographic investments (references) and returns...... (citations). A comparative study of the two measures shows a strong relationship between the 3R and the JIF. Yet, the 3R appears to correct for citation habits, citation dynamics, and composition of document types - problems that typically are raised against the JIF. In addition, contrary to traditional...

  17. Potential support ratios

    DEFF Research Database (Denmark)

    Kjærgaard, Søren; Canudas-Romo, Vladimir

    2017-01-01

    The ‘prospective potential support ratio’ has been proposed by researchers as a measure that accurately quantifies the burden of ageing, by identifying the fraction of a population that has passed a certain measure of longevity, for example, 17 years of life expectancy. Nevertheless......, the prospective potential support ratio usually focuses on the current mortality schedule, or period life expectancy. Instead, in this paper we look at the actual mortality experienced by cohorts in a population, using cohort life tables. We analyse differences between the two perspectives using mortality models...

  18. Tau hadronic branching ratios

    CERN Document Server

    Buskulic, Damir; De Bonis, I; Décamp, D; Ghez, P; Goy, C; Lees, J P; Lucotte, A; Minard, M N; Odier, P; Pietrzyk, B; Ariztizabal, F; Chmeissani, M; Crespo, J M; Efthymiopoulos, I; Fernández, E; Fernández-Bosman, M; Gaitan, V; Martínez, M; Orteu, S; Pacheco, A; Padilla, C; Palla, Fabrizio; Pascual, A; Perlas, J A; Sánchez, F; Teubert, F; Colaleo, A; Creanza, D; De Palma, M; Farilla, A; Gelao, G; Girone, M; Iaselli, Giuseppe; Maggi, G; Maggi, M; Marinelli, N; Natali, S; Nuzzo, S; Ranieri, A; Raso, G; Romano, F; Ruggieri, F; Selvaggi, G; Silvestris, L; Tempesta, P; Zito, G; Huang, X; Lin, J; Ouyang, Q; Wang, T; Xie, Y; Xu, R; Xue, S; Zhang, J; Zhang, L; Zhao, W; Bonvicini, G; Cattaneo, M; Comas, P; Coyle, P; Drevermann, H; Engelhardt, A; Forty, Roger W; Frank, M; Hagelberg, R; Harvey, J; Jacobsen, R; Janot, P; Jost, B; Kneringer, E; Knobloch, J; Lehraus, Ivan; Markou, C; Martin, E B; Mato, P; Minten, Adolf G; Miquel, R; Oest, T; Palazzi, P; Pater, J R; Pusztaszeri, J F; Ranjard, F; Rensing, P E; Rolandi, Luigi; Schlatter, W D; Schmelling, M; Schneider, O; Tejessy, W; Tomalin, I R; Venturi, A; Wachsmuth, H W; Wiedenmann, W; Wildish, T; Witzeling, W; Wotschack, J; Ajaltouni, Ziad J; Bardadin-Otwinowska, Maria; Barrès, A; Boyer, C; Falvard, A; Gay, P; Guicheney, C; Henrard, P; Jousset, J; Michel, B; Monteil, S; Pallin, D; Perret, P; Podlyski, F; Proriol, J; Rossignol, J M; Saadi, F; Fearnley, Tom; Hansen, J B; Hansen, J D; Hansen, J R; Hansen, P H; Nilsson, B S; Kyriakis, A; Simopoulou, Errietta; Siotis, I; Vayaki, Anna; Zachariadou, K; Blondel, A; Bonneaud, G R; Brient, J C; Bourdon, P; Passalacqua, L; Rougé, A; Rumpf, M; Tanaka, R; Valassi, Andrea; Verderi, M; Videau, H L; Candlin, D J; Parsons, M I; Focardi, E; Parrini, G; Corden, M; Delfino, M C; Georgiopoulos, C H; Jaffe, D E; Antonelli, A; Bencivenni, G; Bologna, G; Bossi, F; Campana, P; Capon, G; Chiarella, V; Felici, G; Laurelli, P; Mannocchi, G; Murtas, F; Murtas, G P; Pepé-Altarelli, M; Dorris, S J; Halley, A W; ten Have, I; Knowles, I G; Lynch, J G; Morton, W T; O'Shea, V; Raine, C; Reeves, P; Scarr, J M; Smith, K; Smith, M G; Thompson, A S; Thomson, F; Thorn, S; Turnbull, R M; Becker, U; Braun, O; Geweniger, C; Graefe, G; Hanke, P; Hepp, V; Kluge, E E; Putzer, A; Rensch, B; Schmidt, M; Sommer, J; Stenzel, H; Tittel, K; Werner, S; Wunsch, M; Beuselinck, R; Binnie, David M; Cameron, W; Colling, D J; Dornan, Peter J; Konstantinidis, N P; Moneta, L; Moutoussi, A; Nash, J; San Martin, G; Sedgbeer, J K; Stacey, A M; Dissertori, G; Girtler, P; Kuhn, D; Rudolph, G; Bowdery, C K; Brodbeck, T J; Colrain, P; Crawford, G; Finch, A J; Foster, F; Hughes, G; Sloan, Terence; Whelan, E P; Williams, M I; Galla, A; Greene, A M; Kleinknecht, K; Quast, G; Raab, J; Renk, B; Sander, H G; Wanke, R; Van Gemmeren, P; Zeitnitz, C; Aubert, Jean-Jacques; Bencheikh, A M; Benchouk, C; Bonissent, A; Bujosa, G; Calvet, D; Carr, J; Diaconu, C A; Etienne, F; Thulasidas, M; Nicod, D; Payre, P; Rousseau, D; Talby, M; Abt, I; Assmann, R W; Bauer, C; Blum, Walter; Brown, D; Dietl, H; Dydak, Friedrich; Ganis, G; Gotzhein, C; Jakobs, K; Kroha, H; Lütjens, G; Lutz, Gerhard; Männer, W; Moser, H G; Richter, R H; Rosado-Schlosser, A; Schael, S; Settles, Ronald; Seywerd, H C J; Saint-Denis, R; Wolf, G; Alemany, R; Boucrot, J; Callot, O; Cordier, A; Courault, F; Davier, M; Duflot, L; Grivaz, J F; Heusse, P; Jacquet, M; Kim, D W; Le Diberder, F R; Lefrançois, J; Lutz, A M; Musolino, G; Nikolic, I A; Park, H J; Park, I C; Schune, M H; Simion, S; Veillet, J J; Videau, I; Abbaneo, D; Azzurri, P; Bagliesi, G; Batignani, G; Bettarini, S; Bozzi, C; Calderini, G; Carpinelli, M; Ciocci, M A; Ciulli, V; Dell'Orso, R; Fantechi, R; Ferrante, I; Foà, L; Forti, F; Giassi, A; Giorgi, M A; Gregorio, A; Ligabue, F; Lusiani, A; Marrocchesi, P S; Messineo, A; Rizzo, G; Sanguinetti, G; Sciabà, A; Spagnolo, P; Steinberger, Jack; Tenchini, Roberto; Tonelli, G; Triggiani, G; Vannini, C; Verdini, P G; Walsh, J; Betteridge, A P; Blair, G A; Bryant, L M; Cerutti, F; Gao, Y; Green, M G; Johnson, D L; Medcalf, T; Mir, L M; Perrodo, P; Strong, J A; Bertin, V; Botterill, David R; Clifft, R W; Edgecock, T R; Haywood, S; Edwards, M; Maley, P; Norton, P R; Thompson, J C; Bloch-Devaux, B; Colas, P; Emery, S; Kozanecki, Witold; Lançon, E; Lemaire, M C; Locci, E; Marx, B; Pérez, P; Rander, J; Renardy, J F; Roussarie, A; Schuller, J P; Schwindling, J; Trabelsi, A; Vallage, B; Johnson, R P; Kim, H Y; Litke, A M; McNeil, M A; Taylor, G; Beddall, A; Booth, C N; Boswell, R; Cartwright, S L; Combley, F; Dawson, I; Köksal, A; Letho, M; Newton, W M; Rankin, C; Thompson, L F; Böhrer, A; Brandt, S; Cowan, G D; Feigl, E; Grupen, Claus; Lutters, G; Minguet-Rodríguez, J A; Rivera, F; Saraiva, P; Smolik, L; Stephan, F; Apollonio, M; Bosisio, L; Della Marina, R; Giannini, G; Gobbo, B; Ragusa, F; Rothberg, J E; Wasserbaech, S R; Armstrong, S R; Bellantoni, L; Elmer, P; Feng, Z; Ferguson, D P S; Gao, Y S; González, S; Grahl, J; Harton, J L; Hayes, O J; Hu, H; McNamara, P A; Nachtman, J M; Orejudos, W; Pan, Y B; Saadi, Y; Schmitt, M; Scott, I J; Sharma, V; Turk, J; Walsh, A M; Wu Sau Lan; Wu, X; Yamartino, J M; Zheng, M; Zobernig, G

    1996-01-01

    From 64492 selected \\tau-pair events, produced at the Z^0 resonance, the measurement of the tau decays into hadrons from a global analysis using 1991, 1992 and 1993 ALEPH data is presented. Special emphasis is given to the reconstruction of photons and \\pi^0's, and the removal of fake photons. A detailed study of the systematics entering the \\pi^0 reconstruction is also given. A complete and consistent set of tau hadronic branching ratios is presented for 18 exclusive modes. Most measurements are more precise than the present world average. The new level of precision reached allows a stringent test of \\tau-\\mu universality in hadronic decays, g_\\tau/g_\\mu \\ = \\ 1.0013 \\ \\pm \\ 0.0095, and the first measurement of the vector and axial-vector contributions to the non-strange hadronic \\tau decay width: R_{\\tau ,V} \\ = \\ 1.788 \\ \\pm \\ 0.025 and R_{\\tau ,A} \\ = \\ 1.694 \\ \\pm \\ 0.027. The ratio (R_{\\tau ,V} - R_{\\tau ,A}) / (R_{\\tau ,V} + R_{\\tau ,A}), equal to (2.7 \\pm 1.3) \\ \\%, is a measure of the importance of Q...

  19. IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kiyomiya, Hiroyasu [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Ariyoshi, Wataru; Okinaga, Toshinori [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Kaneuji, Takeshi [Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Mitsugi, Sho [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Sakurai, Takuma [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Habu, Manabu [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Yoshioka, Izumi [Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Tominaga, Kazuhiro [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); and others

    2015-05-01

    Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression. - Highlights: • IL-33 inhibits RANKL-induced osteoclast formation. • IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression. • IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8.

  20. IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression

    International Nuclear Information System (INIS)

    Kiyomiya, Hiroyasu; Ariyoshi, Wataru; Okinaga, Toshinori; Kaneuji, Takeshi; Mitsugi, Sho; Sakurai, Takuma; Habu, Manabu; Yoshioka, Izumi; Tominaga, Kazuhiro

    2015-01-01

    Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression. - Highlights: • IL-33 inhibits RANKL-induced osteoclast formation. • IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression. • IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8

  1. Peak power ratio generator

    Science.gov (United States)

    Moyer, R.D.

    A peak power ratio generator is described for measuring, in combination with a conventional power meter, the peak power level of extremely narrow pulses in the gigahertz radio frequency bands. The present invention in a preferred embodiment utilizes a tunnel diode and a back diode combination in a detector circuit as the only high speed elements. The high speed tunnel diode provides a bistable signal and serves as a memory device of the input pulses for the remaining, slower components. A hybrid digital and analog loop maintains the peak power level of a reference channel at a known amount. Thus, by measuring the average power levels of the reference signal and the source signal, the peak power level of the source signal can be determined.

  2. Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

    International Nuclear Information System (INIS)

    Kaneuji, Takeshi; Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro; Takahashi, Tetsu; Nishihara, Tatsuji

    2011-01-01

    Highlights: → Effect of compressive force on osteoblasts were examined. → Compressive force induced OPG expression and suppressed osteoclastogenesis. → This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm 2 ) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-κB ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of IκBα, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca 2+ pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-κB) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt/Ca 2+ pathway.

  3. Ly49Q, an ITIM-bearing NK receptor, positively regulates osteoclast differentiation

    International Nuclear Information System (INIS)

    Hayashi, Mikihito; Nakashima, Tomoki; Kodama, Tatsuhiko; Makrigiannis, Andrew P.; Toyama-Sorimachi, Noriko; Takayanagi, Hiroshi

    2010-01-01

    Osteoclasts, multinucleated cells that resorb bone, play a key role in bone remodeling. Although immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling is critical for osteoclast differentiation, the significance of immunoreceptor tyrosine-based inhibitory motif (ITIM) has not been well understood. Here we report the function of Ly49Q, an Ly49 family member possessing an ITIM motif, in osteoclastogenesis. Ly49Q is selectively induced by receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) stimulation in bone marrow-derived monocyte/macrophage precursor cells (BMMs) among the Ly49 family of NK receptors. The knockdown of Ly49Q resulted in a significant reduction in the RANKL-induced formation of tartrate-resistance acid phosphatase (TRAP)-positive multinucleated cells, accompanied by a decreased expression of osteoclast-specific genes such as Nfatc1, Tm7sf4, Oscar, Ctsk, and Acp5. Osteoclastogenesis was also significantly impaired in Ly49Q-deficient cells in vitro. The inhibitory effect of Ly49Q-deficiency may be explained by the finding that Ly49Q competed for the association of Src-homology domain-2 phosphatase-1 (SHP-1) with paired immunoglobulin-like receptor-B (PIR-B), an ITIM-bearing receptor which negatively regulates osteoclast differentiation. Unexpectedly, Ly49Q deficiency did not lead to impaired osteoclast formation in vivo, suggesting the existence of a compensatory mechanism. This study provides an example in which an ITIM-bearing receptor functions as a positive regulator of osteoclast differentiation.

  4. Down-regulation of Irf8 by Lyz2-cre/loxP accelerates osteoclast differentiation in vitro.

    Science.gov (United States)

    Saito, Emi; Suzuki, Dai; Kurotaki, Daisuke; Mochizuki, Ayako; Manome, Yoko; Suzawa, Tetsuo; Toyoshima, Yoichi; Ichikawa, Takahiro; Funatsu, Takahiro; Inoue, Tomio; Takami, Masamichi; Tamura, Tomohiko; Inagaki, Katsunori; Kamijo, Ryutaro

    2017-06-01

    Interferon regulatory factor 8 (Irf8) is a transcription factor that negatively regulates osteoclast differentiation and Irf8 global knockout (Irf8 -/- ) mice have been shown to have reduced bone volume resulting from increased osteoclast numbers. However, detailed analysis of the functions of Irf8 in osteoclast precursors with a monocyte/macrophage linage is difficult, because the population and properties of hematopoietic cells in Irf8 -/- mice are severely altered. Therefore, to clearly elucidate the functions of Irf8 during osteoclastogenesis, we established myeloid cell-specific Irf8 conditional knockout (Irf8 fl/fl ;Lyz2 cre/+ ) mice. We found that trabecular bone volume in the Irf8 fl/fl ;Lyz2 cre/+ mice was not significantly affected, while exposure to M-CSF and RANKL significantly increased TRAP activity in vitro in osteoclasts that underwent osteoclastogenesis from bone marrow-derived macrophages (BMMs) induced from bone marrow cells (BMCs) of those mice by addition of M-CSF. Our results also showed that expression of Irf8 mRNA and protein in BMMs obtained from Irf8 fl/fl ;Lyz2 cre/+ mice and cultured with M-CSF was reduced. These findings predicted that Lyz2/Lyz2-cre expression is induced when BMCs differentiate into BMMs in cultures with M-CSF. In osteoclast differentiation cultures, Lyz2 was gradually increased by M-CSF during the first 3 days of culture, then rapidly decreased by the addition of RANKL with M-CSF during the next 3 days. Furthermore, BMCs differentiated into osteoclasts while maintaining a low level of Lyz2 expression when cultured simultaneously with both M-CSF and RANKL from the initiation of culture. These findings suggest that Lyz2-cre expression is induced along with differentiation to BMMs by BMCs obtained from Irf8 fl/fl ;Lyz2 cre/+ mice and cultured with M-CSF. In addition, Irf8 was down-regulated by activation of the cre/loxP recombination system in BMMs and osteoclastogenesis was accelerated. Based on our results, we propose

  5. The Liquidity Coverage Ratio: the need for further complementary ratios?

    OpenAIRE

    Ojo, Marianne

    2013-01-01

    This paper considers components of the Liquidity Coverage Ratio – as well as certain prevailing gaps which may necessitate the introduction of a complementary liquidity ratio. The definitions and objectives accorded to the Liquidity Coverage Ratio (LCR) and Net Stable Funding Ratio (NSFR) highlight the focus which is accorded to time horizons for funding bank operations. A ratio which would focus on the rate of liquidity transformations and which could also serve as a complementary metric gi...

  6. Energy Profit Ratio Compared

    International Nuclear Information System (INIS)

    Amano, Osamu

    2007-01-01

    We need more oil energy to take out oil under the ground. Limit resources make us consider other candidates of energy source instead of oil. Electricity shall be the main role more and more like electric vehicles and air conditioners so we should consider electricity generation ways. When we consider what kind of electric power generation is the best or suitable, we should not only power generation plant but whole process from mining to power generation. It is good way to use EPR, Energy Profit Ratio, to analysis which type is more efficient and which part is to do research and development when you see the input breakdown analysis. Electricity by the light water nuclear power plant, the hydrogen power plant and the geothermal power plant are better candidates from EPR analysis. Forecasting the world primly energy supply in 2050, it is said that the demand will be double of the demand in 2000 and the supply will not be able to satisfy the demand in 2050. We should save 30% of the demand and increase nuclear power plants 3.5 times more and recyclable energy like hydropower plants 3 times more. When the nuclear power plants are 3.5 times more then uranium peak will come and we will need breed uranium. I will analysis the EPR of FBR. Conclusion: A) the EPR of NPS in Japan is 17.4 and it is the best of all. B) Many countries will introduce new nuclear power plants rapidly may be 3.5 times in 2050. C) Uranium peak will happen around 2050. (author)

  7. IGFBP-4 regulates adult skeletal growth in a sex-specific manner.

    Science.gov (United States)

    Maridas, David E; DeMambro, Victoria E; Le, Phuong T; Nagano, Kenichi; Baron, Roland; Mohan, Subburaman; Rosen, Clifford J

    2017-04-01

    Insulin-like growth factor-1 (IGF-1) and its binding proteins are critical mediators of skeletal growth. Insulin-like growth factor-binding protein 4 (IGFBP-4) is highly expressed in osteoblasts and inhibits IGF-1 actions in vitro Yet, in vivo studies suggest that it could potentiate IGF-1 and IGF-2 actions. In this study, we hypothesized that IGFBP-4 might potentiate the actions of IGF-1 on the skeleton. To test this, we comprehensively studied 8- and 16-week-old Igfbp4 -/- mice. Both male and female adult Igfbp4 -/- mice had marked growth retardation with reductions in body weight, body and femur lengths, fat proportion and lean mass at 8 and 16 weeks. Marked reductions in aBMD and aBMC were observed in 16-week-old Igfbp4 -/- females, but not in males. Femoral trabecular BV/TV and thickness, cortical fraction and thickness in 16-week-old Igfbp4 -/- females were significantly reduced. However, surprisingly, males had significantly more trabeculae with higher connectivity density than controls. Concordantly, histomorphometry revealed higher bone resorption and lower bone formation in Igfbp4 -/- females. In contrast, Igfbp4 -/- males had lower mineralized surface/bone surface. Femoral expression of Sost and circulating levels of sclerostin were reduced but only in Igfbp4 -/- males. Bone marrow stromal cultures from mutants showed increased osteogenesis, whereas osteoclastogenesis was markedly increased in cells from Igfbp4 -/- females but decreased in males. In sum, our results indicate that loss of Igfbp4 affects mesenchymal stromal cell differentiation, regulates osteoclastogenesis and influences both skeletal development and adult bone maintenance. Thus, IGFBP-4 modulates the skeleton in a gender-specific manner, acting as both a cell autonomous and cell non-autonomous factor. © 2017 The authors.

  8. Down-regulation of mTOR leads to up-regulation of osteoprotegerin in bone marrow cells

    International Nuclear Information System (INIS)

    Mogi, Makio; Kondo, Ayami

    2009-01-01

    Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor regulates bone mass by inhibiting osteoclastic bone resorption. mTOR, which is the mammalian target of rapamycin, is a kinase and central regulator of cell growth, proliferation, and survival. By using Rapamycin, we studied whether mTOR pathway is associated with OPG protein production in the mouse bone marrow-derived stromal cell line ST2. Rapamycin markedly increased the level of soluble OPG in ST2 cells. This antibiotic treatment resulted in the suppression of phosphorylation of mTOR. Rapamycin had no effects on the proliferation, differentiation, or apoptosis of the cells. Treatment with bone morphogenetic protein-4, which can induce OPG protein in ST2 cells, also resulted in a decrease in the density of the phospho-mTOR-band, suggesting that the suppression of the phospho-mTOR pathway is necessary for OPG production in ST2 cells. Thus, suitable suppression of mTOR phosphorylation is a necessary requirement for OPG production in bone marrow stromal cells.

  9. DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss in mice

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Ditzel, Nicholas; Mahmood, Amer

    2011-01-01

    . In a number of in vitro culture systems, Dlk1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of proinflammatory bone-resorbing cytokines (eg, Il7, Tnfa, and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of Dlk1...... in the bone marrow by activated T cells. Interestingly, Dlk1(-/-) mice were significantly protected from ovx-induced bone loss compared with wild-type mice. Thus we identified Dlk1 as a novel regulator of bone mass that functions to inhibit bone formation and to stimulate bone resorption. Increasing DLK1...... production by T cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss....

  10. Voltage regulator for generator

    Energy Technology Data Exchange (ETDEWEB)

    Naoi, K

    1989-01-17

    It is an object of this invention to provide a voltage regulator for a generator charging a battery, wherein even if the ambient temperature at the voltage regulator rises abnormally high, possible thermal breakage of the semiconductor elements constituting the voltage regulator can be avoided. A feature of this invention is that the semiconductor elements can be protected from thermal breakage, even at an abnormal ambient temperature rise at the voltage regulator for the battery charging generator, by controlling a maximum conduction ratio of a power transistor in the voltage regulator in accordance with the temperature at the voltage regulator. This is achieved through a switching device connected in series to the field coil of the generator and adapted to be controlled in accordance with an output voltage of the generator and the ambient temperature at the voltage regulator. 6 figs.

  11. Large Aspect Ratio Tokamak Study

    International Nuclear Information System (INIS)

    Reid, R.L.; Holmes, J.A.; Houlberg, W.A.; Peng, Y.K.M.; Strickler, D.J.; Brown, T.G.; Wiseman, G.W.

    1980-06-01

    The Large Aspect Ratio Tokamak Study (LARTS) at Oak Ridge National Laboratory (ORNL) investigated the potential for producing a viable longburn tokamak reactor by enhancing the volt-second capability of the ohmic heating transformer through the use of high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were assessed in the context of extended burn operation. Using a one-dimensional transport code plasma startup and burn parameters were addressed. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the startup and shutdown portions of the tokamak cycle. A representative large aspect ratio tokamak with an aspect ratio of 8 was found to achieve a burn time of 3.5 h at capital cost only approx. 25% greater than that of a moderate aspect ratio design tokamak

  12. Sex Ratio Elasticity Influences the Selection of Sex Ratio Strategy

    Science.gov (United States)

    Wang, Yaqiang; Wang, Ruiwu; Li, Yaotang; (Sam) Ma, Zhanshan

    2016-12-01

    There are three sex ratio strategies (SRS) in nature—male-biased sex ratio, female-biased sex ratio and, equal sex ratio. It was R. A. Fisher who first explained why most species in nature display a sex ratio of ½. Consequent SRS theories such as Hamilton’s local mate competition (LMC) and Clark’s local resource competition (LRC) separately explained the observed deviations from the seemingly universal 1:1 ratio. However, to the best of our knowledge, there is not yet a unified theory that accounts for the mechanisms of the three SRS. Here, we introduce the price elasticity theory in economics to define sex ratio elasticity (SRE), and present an analytical model that derives three SRSs based on the following assumption: simultaneously existing competitions for both resources A and resources B influence the level of SRE in both sexes differently. Consequently, it is the difference (between two sexes) in the level of their sex ratio elasticity that leads to three different SRS. Our analytical results demonstrate that the elasticity-based model not only reveals a highly plausible mechanism that explains the evolution of SRS in nature, but also offers a novel framework for unifying two major classical theories (i.e., LMC & LRC) in the field of SRS research.

  13. Bone mass regulation of leptin and postmenopausal osteoporosis with obesity.

    Science.gov (United States)

    Legiran, Siswo; Brandi, Maria Luisa

    2012-09-01

    Leptin has been known to play a role in weight regulation through food intake and energy expenditure. Leptin also has an important role in bone metabolism. The role of leptin is determined by leptin receptors, either central or peripheral to the bones. We discuss the role of leptin on bone and molecular genetics of osteoporosis in postmenopausal obese women. The role of leptin in bone preserves bone mineral density (BMD) through increased OPG levels leading to bind RANKL, resulting in reducing osteoclast activity. The estrogen role on bone is also mediated by RANKL and OPG. In postmenopausal women who have estrogen deficiency, it increases the rate of RANKL, which increases osteoclastogenesis. Obese individuals who have a high level of leptin will be effected by bone protection. There are similarities in the mechanism between estrogen and leptin in influencing the process of bone remodeling. It may be considered that the role of estrogen can be replaced by leptin. Molecular genetic aspects that play a role in bone remodeling, such as leptin, leptin receptors, cytokines (e.g. RANK, RANKL, and OPG), require further study to be useful, especially regarding osteoporosis therapy based on genetic analysis.

  14. Regulating the Regulator

    Energy Technology Data Exchange (ETDEWEB)

    1992-08-26

    The article reports on a challenge to the UK electricity regulator to defend his record by the Coalition for Fair Electricity Regulation (COFFER). The challenge centres on whether the obligation for the regional electric companies (REC) to purchase power from the cheapest source is being enforced. This is related to the wider issue of whether the REC's support of combined-cycle gas turbine (CCGT) is economic. COFFER considers that uneconomic gas-fired power plants are being allowed to displace economic coal-fired stations. Aspects discussed include the background to the dispute and the costs of CCGT and coal fired power generation. 1 fig., 1 tab.

  15. Holes at High Blowing Ratios

    Directory of Open Access Journals (Sweden)

    Phillip M. Ligrani

    1996-01-01

    Full Text Available Experimental results are presented which describe the development and structure of flow downstream of a single row of holes with compound angle orientations producing film cooling at high blowing ratios. This film cooling configuration is important because similar arrangements are frequently employed on the first stage of rotating blades of operating gas turbine engines. With this configuration, holes are spaced 6d apart in the spanwise direction, with inclination angles of 24 degrees, and angles of orientation of 50.5 degrees. Blowing ratios range from 1.5 to 4.0 and the ratio of injectant to freestream density is near 1.0. Results show that spanwise averaged adiabatic effectiveness, spanwise-averaged iso-energetic Stanton number ratios, surveys of streamwise mean velocity, and surveys of injectant distributions change by important amounts as the blowing ratio increases. This is due to injectant lift-off from the test surface just downstream of the holes.

  16. Deriving aerosol scattering ratio using range-resolved lidar ratio

    Indian Academy of Sciences (India)

    2014-02-13

    Feb 13, 2014 ... ratio (LDR) are used to suggest the type of aerosols. The altitude-dependent ... to the station and the experimentally measured lidar data. The 'model ... The integrated aerosol extinction profile with altitude-dependent S and k.

  17. RATIO_TOOL - SOFTWARE FOR COMPUTING IMAGE RATIOS

    Science.gov (United States)

    Yates, G. L.

    1994-01-01

    Geological studies analyze spectral data in order to gain information on surface materials. RATIO_TOOL is an interactive program for viewing and analyzing large multispectral image data sets that have been created by an imaging spectrometer. While the standard approach to classification of multispectral data is to match the spectrum for each input pixel against a library of known mineral spectra, RATIO_TOOL uses ratios of spectral bands in order to spot significant areas of interest within a multispectral image. Each image band can be viewed iteratively, or a selected image band of the data set can be requested and displayed. When the image ratios are computed, the result is displayed as a gray scale image. At this point a histogram option helps in viewing the distribution of values. A thresholding option can then be used to segment the ratio image result into two to four classes. The segmented image is then color coded to indicate threshold classes and displayed alongside the gray scale image. RATIO_TOOL is written in C language for Sun series computers running SunOS 4.0 and later. It requires the XView toolkit and the OpenWindows window manager (version 2.0 or 3.0). The XView toolkit is distributed with Open Windows. A color monitor is also required. The standard distribution medium for RATIO_TOOL is a .25 inch streaming magnetic tape cartridge in UNIX tar format. An electronic copy of the documentation is included on the program media. RATIO_TOOL was developed in 1992 and is a copyrighted work with all copyright vested in NASA. Sun, SunOS, and OpenWindows are trademarks of Sun Microsystems, Inc. UNIX is a registered trademark of AT&T Bell Laboratories.

  18. High ratio recirculating gas compressor

    Science.gov (United States)

    Weinbrecht, J.F.

    1989-08-22

    A high ratio positive displacement recirculating rotary compressor is disclosed. The compressor includes an integral heat exchanger and recirculation conduits for returning cooled, high pressure discharge gas to the compressor housing to reducing heating of the compressor and enable higher pressure ratios to be sustained. The compressor features a recirculation system which results in continuous and uninterrupted flow of recirculation gas to the compressor with no direct leakage to either the discharge port or the intake port of the compressor, resulting in a capability of higher sustained pressure ratios without overheating of the compressor. 10 figs.

  19. Output factors and scatter ratios

    Energy Technology Data Exchange (ETDEWEB)

    Shrivastava, P N; Summers, R E; Samulski, T V; Baird, L C [Allegheny General Hospital, Pittsburgh, PA (USA); Ahuja, A S; Dubuque, G L; Hendee, W R; Chhabra, A S

    1979-07-01

    Reference is made to a previous publication on output factors and scatter ratios for radiotherapy units in which it was suggested that the output factor should be included in the definitions of scatter-air ratio and tissue-maximum ratio. In the present correspondence from other authors and from the authors of the previous publication, the original definitions and the proposed changes are discussed. Radiation scatter from source and collimator degradation of beam energy and calculation of dose in tissue are considered in relation to the objective of accurate dosimetry.

  20. Large aspect ratio tokamak study

    International Nuclear Information System (INIS)

    Reid, R.L.; Holmes, J.A.; Houlberg, W.A.; Peng, Y.K.M.; Strickler, D.J.; Brown, T.G.; Sardella, C.; Wiseman, G.W.

    1979-01-01

    The Large Aspect Ratio Tokamak Study (LARTS) investigated the potential for producing a viable long burn tokamak reactor through enhanced volt-second capability of the ohmic heating transformer by employing high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were accessed in the context of extended burn operation. Plasma startup and burn parameters were addressed using a one-dimensional transport code. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the field in the ohmic heating coil and the wave shape of the ohmic heating discharge. A high aspect ratio reference reactor was chosen and configured

  1. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had......This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  2. Arcjet nozzle area ratio effects

    Science.gov (United States)

    Curran, Francis M.; Sarmiento, Charles J.; Birkner, Bjorn W.; Kwasny, James

    1990-01-01

    An experimental investigation was conducted to determine the effect of nozzle area ratio on the operating characteristics and performance of a low power dc arcjet thruster. Conical thoriated tungsten nozzle inserts were tested in a modular laboratory arcjet thruster run on hydrogen/nitrogen mixtures simulating the decomposition products of hydrazine. The converging and diverging sides of the inserts had half angles of 30 and 20 degrees, respectively, similar to a flight type unit currently under development. The length of the diverging side was varied to change the area ratio. The nozzle inserts were run over a wide range of specific power. Current, voltage, mass flow rate, and thrust were monitored to provide accurate comparisons between tests. While small differences in performance were observed between the two nozzle inserts, it was determined that for each nozzle insert, arcjet performance improved with increasing nozzle area ratio to the highest area ratio tested and that the losses become very pronounced for area ratios below 50. These trends are somewhat different than those obtained in previous experimental and analytical studies of low Re number nozzles. It appears that arcjet performance can be enhanced via area ratio optimization.

  3. Arcjet Nozzle Area Ratio Effects

    Science.gov (United States)

    Curran, Francis M.; Sarmiento, Charles J.; Birkner, Bjorn W.; Kwasny, James

    1990-01-01

    An experimental investigation was conducted to determine the effect of nozzle area ratio on the operating characteristics and performance of a low power dc arcjet thruster. Conical thoriated tungsten nozzle inserts were tested in a modular laboratory arcjet thruster run on hydrogen/nitrogen mixtures simulating the decomposition products of hydrazine. The converging and diverging sides of the inserts had half angles of 30 and 20 degrees, respectively, similar to a flight type unit currently under development. The length of the diverging side was varied to change the area ratio. The nozzle inserts were run over a wide range of specific power. Current, voltage, mass flow rate, and thrust were monitored to provide accurate comparisons between tests. While small differences in performance were observed between the two nozzle inserts, it was determined that for each nozzle insert, arcjet performance improved with increasing nozzle area ratio to the highest area ratio tested and that the losses become very pronounced for area ratios below 50. These trends are somewhat different than those obtained in previous experimental and analytical studies of low Re number nozzles. It appears that arcjet performance can be enhanced via area ratio optimization.

  4. Incentive Ratios of Fisher Markets

    DEFF Research Database (Denmark)

    Chen, Ning; Deng, Xuaitue; Zhang, Hongyang

    2012-01-01

    In a Fisher market, a market maker sells m items to n potential buyers. The buyers submit their utility functions and money endowments to the market maker, who, upon receiving submitted information, derives market equilibrium prices and allocations of its items. While agents may benefit...... by misreporting their private information, we show that the percentage of improvement by a unilateral strategic play, called incentive ratio, is rather limited—it is less than 2 for linear markets and at most $e^{1/e}\\thickapprox 1.445$ for Cobb-Douglas markets. We further prove that both ratios are tight....

  5. EFSA ND A Panel ( EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013. Scientific Opinion on the substantiation of a health claim related to eicosapentanoic acid (EPA) and “ reduces the AA/EPA ratio in blood. A high AA/EPA level is a risk factor in the d evelopment of attention, difficulties in children with ADHD - like symptoms ” pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following an application from Minami Nutrition Health BVBA, submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation...... of a health claim related to eicosapentaenoic acid (EPA) and “reduces the AA/EPA ratio in blood. A high AA/EPA level is a risk factor in the development of attention difficulties in children with attention deficit hyperactivity disorder (ADHD)-like symptoms”. The food constituent, EPA, which is the subject...... of the health claim, is sufficiently characterised. The claimed effect proposed by the applicant is “reduces the AA/EPA ratio in blood. A high AA/EPA level is a risk factor in the development of attention difficulties in children with ADHD-like symptoms. These children are also characterised by less...

  6. Ratio Bias and Policy Preferences

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2016-01-01

    Numbers permeate modern political communication. While current scholarship on framing effects has focused on the persuasive effects of words and arguments, this article shows that framing of numbers can also substantially affect policy preferences. Such effects are caused by ratio bias, which...

  7. Avoiding mandatory hospital nurse staffing ratios: an economic commentary.

    Science.gov (United States)

    Buerhaus, Peter I

    2009-01-01

    The imposition of mandatory hospital nurse staffing ratios is among the more visible public policy initiatives affecting the nursing profession. Although the practice is intended to address problems in hospital nurse staffing and quality of patient care, this commentary argues that staffing ratios will lead to negative consequences for nurses involving the equity, efficiency, and costs of producing nursing care in hospitals. Rather than spend time and effort attempting to regulate nurse staffing, this commentary offers alternatives strategies that are directed at fixing the problems that motivate the advocates of staffing ratios.

  8. Global Carbon Reservoir Oxidative Ratios

    Science.gov (United States)

    Masiello, C. A.; Gallagher, M. E.; Hockaday, W. C.

    2010-12-01

    Photosynthesis and respiration move carbon and oxygen between the atmosphere and the biosphere at a ratio that is characteristic of the biogeochemical processes involved. This ratio is called the oxidative ratio (OR) of photosynthesis and respiration, and is defined as the ratio of moles of O2 per moles of CO2. This O2/CO2 ratio is a characteristic of biosphere-atmosphere gas fluxes, much like the 13C signature of CO2 transferred between the biosphere and the atmosphere has a characteristic signature. OR values vary on a scale of 0 (CO2) to 2 (CH4), with most ecosystem values clustered between 0.9 and 1.2. Just as 13C can be measured for both carbon fluxes and carbon pools, OR can also be measured for fluxes and pools and can provide information about the processes involved in carbon and oxygen cycling. OR values also provide information about reservoir organic geochemistry because pool OR values are proportional to the oxidation state of carbon (Cox) in the reservoir. OR may prove to be a particularly valuable biogeochemical tracer because of its ability to couple information about ecosystem gas fluxes with ecosystem organic geochemistry. We have developed 3 methods to measure the OR of ecosystem carbon reservoirs and intercalibrated them to assure that they yield accurate, intercomparable data. Using these tools we have built a large enough database of biomass and soil OR values that it is now possible to consider the implications of global patterns in ecosystem OR values. Here we present a map of the natural range in ecosystem OR values and begin to consider its implications. One striking pattern is an apparent offset between soil and biospheric OR values: soil OR values are frequently higher than that of their source biomass. We discuss this trend in the context of soil organic geochemistry and gas fluxes.

  9. GUT Scale Fermion Mass Ratios

    International Nuclear Information System (INIS)

    Spinrath, Martin

    2014-01-01

    We present a series of recent works related to group theoretical factors from GUT symmetry breaking which lead to predictions for the ratios of quark and lepton Yukawa couplings at the unification scale. New predictions for the GUT scale ratios y μ /y s , y τ /y b and y t /y b in particular are shown and compared to experimental data. For this comparison it is important to include possibly large supersymmetric threshold corrections. Due to this reason the structure of the fermion masses at the GUT scale depends on TeV scale physics and makes GUT scale physics testable at the LHC. We also discuss how this new predictions might lead to predictions for mixing angles by discussing the example of the recently measured last missing leptonic mixing angle θ 13 making this new class of GUT models also testable in neutrino experiments

  10. Ratio Bias and Policy Preferences

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2017-01-01

    Numbers permeate modern political communication. While current scholarship on framing effects has focused on the persuasive effects of words and arguments, this article shows that framing of numbers can also substantially affect policy preferences. Such effects are caused by ratio bias, which...... is a general tendency to focus on numerators and pay insufficient attention to denominators in ratios. Using a population-based survey experiment, I demonstrate how differently framed but logically equivalent representations of the exact same numerical value can have large effects on citizens’ preferences...... regarding salient political issues such as education and taxes. Furthermore, the effects of numerical framing are found across most groups of the population, largely regardless of their political predisposition and their general ability to understand and use numerical information. These findings have...

  11. High aspect ratio spheromak experiments

    International Nuclear Information System (INIS)

    Robertson, S.; Schmid, P.

    1987-05-01

    The Reversatron RFP (R/a = 50cm/8cm) has been operated as an ohmically heated spheromak of high aspect ratio. We find that the dynamo can drive the toroidal field upward at rates as high as 10 6 G/sec. Discharges can be initiated and ramped upward from seed fields as low as 50 G. Small toroidal bias fields of either polarity (-0.2 < F < 0.2) do not significantly affect operation. 5 refs., 3 figs

  12. Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Kaneuji, Takeshi [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Takahashi, Tetsu [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan)

    2011-04-29

    Highlights: {yields} Effect of compressive force on osteoblasts were examined. {yields} Compressive force induced OPG expression and suppressed osteoclastogenesis. {yields} This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm{sup 2}) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-{kappa}B ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of I{kappa}B{alpha}, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca{sup 2+} pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-{kappa}B) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt

  13. BIOCHEMICAL MARKERS OF BONE RESORPTION AND HORMONAL REGULATION OF BONE METABOLISM FOLLOWING LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    V. P. Buzulina

    2013-01-01

    Full Text Available Aim. Comparative evaluation of two biochemical markers of bone resorption and hormonal regulation of bone metabolism in liver recipients. Methods and results. Bоne densitometry of L2–L4 and neck of femur, serum level of some hormones (PTH, vitamin D3, estradiol, testosterone regulating osteoclastogenesis as well as com- parative analyses of two bone resorption markers β-crosslaps and tartrate-resistant acid phosphatase type 5b (TRAP-5b were fulfilled in patients after orthotopic liver transplantation (OLT. In 1 month after OLT bone density reduction of L2–L4 and neck of femur; decrease of vitamin D3, estradiol in women, testosterone in men and increase levels of bone resorption markers were observed. In 1 and 2 years after OLT the rise of bone density, increased levels of PTH, estradiol, testosterone and decreased β-crosslaps levels were revealed, while vitamin D3 and TRAP-5b levels remained stable. Conclusion. TRAP-5b was found to be a more speciffic marker of bone resorption, independent from collagen metabolism in liver. Osteoporosis defined in long-term period after OLT was associated with higher TRAP-5b and revialed in women with low estradiol level. 

  14. Envera Variable Compression Ratio Engine

    Energy Technology Data Exchange (ETDEWEB)

    Charles Mendler

    2011-03-15

    Aggressive engine downsizing, variable compression ratio and use of the Atkinson cycle are being combined to improve fuel economy by up to 40 percent relative to port fuel injected gasoline engines, while maintaining full engine power. Approach Engine downsizing is viewed by US and foreign automobile manufacturers as one of the best options for improving fuel economy. While this strategy has already demonstrated a degree of success, downsizing and fuel economy gains are currently limited. With new variable compression ratio technology however, the degree of engine downsizing and fuel economy improvement can be greatly increased. A small variable compression ratio (VCR) engine has the potential to return significantly higher vehicle fuel economy while also providing high power. Affordability and potential for near term commercialization are key attributes of the Envera VCR engine. VCR Technology To meet torque and power requirements, a smaller engine needs to do more work per stroke. This is typically accomplished by boosting the incoming charge with either a turbo or supercharger so that more energy is present in the cylinder per stroke to do the work. With current production engines the degree of engine boosting (which correlates to downsizing) is limited by detonation (combustion knock) at high boost levels. Additionally, the turbo or supercharger needs to be responsive and efficient while providing the needed boost. VCR technology eliminates the limitation of engine knock at high load levels by reducing compression ratio to {approx}9:1 (or whatever level is appropriate) when high boost pressures are needed. By reducing the compression ratio during high load demand periods there is increased volume in the cylinder at top dead center (TDC) which allows more charge (or energy) to be present in the cylinder without increasing the peak pressure. Cylinder pressure is thus kept below the level at which the engine would begin to knock. When loads on the engine are low

  15. Reproducibility of isotope ratio measurements

    International Nuclear Information System (INIS)

    Elmore, D.

    1981-01-01

    The use of an accelerator as part of a mass spectrometer has improved the sensitivity for measuring low levels of long-lived radionuclides by several orders of magnitude. However, the complexity of a large tandem accelerator and beam transport system has made it difficult to match the precision of low energy mass spectrometry. Although uncertainties for accelerator measured isotope ratios as low as 1% have been obtained under favorable conditions, most errors quoted in the literature for natural samples are in the 5 to 20% range. These errors are dominated by statistics and generally the reproducibility is unknown since the samples are only measured once

  16. GOLD and the fixed ratio

    Directory of Open Access Journals (Sweden)

    Vestbo J

    2012-09-01

    Full Text Available Jørgen VestboUniversity of Manchester, Manchester, UKI read with interest the paper entitled "Diagnosis of airway obstruction in the elderly: contribution of the SARA study" by Sorino et al in a recent issue of this journal.1 Being involved in the Global Initiative for Obstructive Lung Diseases (GOLD, it is nice to see the interest sparked by the GOLD strategy document. However, in the paper by Sorino et al, there are a few misunderstandings around GOLD and the fixed ratio (forced expiratory volume in 1 second/forced volume vital capacity < 0.70 that need clarification.View original paper by Sorino and colleagues.

  17. Using Ratio Analysis to Evaluate Financial Performance.

    Science.gov (United States)

    Minter, John; And Others

    1982-01-01

    The ways in which ratio analysis can help in long-range planning, budgeting, and asset management to strengthen financial performance and help avoid financial difficulties are explained. Types of ratios considered include balance sheet ratios, net operating ratios, and contribution and demand ratios. (MSE)

  18. Radiation regulation

    International Nuclear Information System (INIS)

    Braithwaite, J.; Grabosky, P.

    1985-01-01

    The five main areas of radiation regulation considered are radiation exposure in the mining of uranium and other minerals, exposure in the use of uranium in nuclear reactors, risks in the transport of radioactive materials and hazards associated with the disposal of used materials. In Australia these problems are regulated by mines departments, the Australian Atomic Energy Commission and radiation control branches in state health departments. Each of these instutional areas of regulation is examined

  19. Isokinetic Hamstrings: Quadriceps Ratios in Intercollegiate Athletes.

    Science.gov (United States)

    Rosene, John M.; Fogarty, Tracey D.; Mahaffey, Brian L.

    2001-01-01

    Compared the differences in the concentric hamstrings to quadriceps (H:Q) ratio among athletes in different sports at three velocities. Measurement of H:Q ratio of both knees among male and female college athletes indicated that the H:Q ratio increased as velocity increased. No differences existed for the H:Q ratio for sport or side of body. (SM)

  20. Regulative environmental policy. Regulative Umweltpolitik

    Energy Technology Data Exchange (ETDEWEB)

    Goerlitz, A; Voigt, R [Universitaet der Bundeswehr Muenchen, Neubiberg (Germany, F.R.). Fakultaet fuer Sozialwissenschaften; eds.

    1991-01-01

    Regulative policy means those governmental attempts to steer the course of things which can fall back on a certain repertoire of instruments for actions in order to warrant the causal and temporal connection between the making available and the employment of means. The fact that environmental protection needs regulative policy is substantiated by the thesis that the market has failed; consequently only government can manage the public goods 'environment' in a suitable way, and it is a matter of fact that environmental protection at present is operated preferably via regulative policy. The problems of regulative enviromental policy are manifold. Its implementation often miscarries because of limited administrative resources on the one hand - making sufficient control impossible for instance -, and because of poor quality regulative instruments on the other hand. One way out would be to increase the efficiency of regulative policy by sophisticating judicial techniques. Other ways out point to the executing level and aim at improving implementation strategies or are concerned with post-regulative law. The latter refers to a new legal quality which demonstrates itself already in corporatistical crisis regulation or in induction programs such as pollution limits. A final way out favours deregulation strategies which includes the introduction of environmental levies or the allocation of environmental licences. An interdisciplinary discourse is to find out what would happen if these ways were taken. Pointers to solutions from varying scientific disciplines resulting from this discourse are to be found in this volume. (orig./HSCH).

  1. Myostatin is a direct regulator of osteoclast differentiation and its inhibition reduces inflammatory joint destruction in mice.

    Science.gov (United States)

    Dankbar, Berno; Fennen, Michelle; Brunert, Daniela; Hayer, Silvia; Frank, Svetlana; Wehmeyer, Corinna; Beckmann, Denise; Paruzel, Peter; Bertrand, Jessica; Redlich, Kurt; Koers-Wunrau, Christina; Stratis, Athanasios; Korb-Pap, Adelheid; Pap, Thomas

    2015-09-01

    Myostatin (also known as growth and differentiation factor 8) is a secreted member of the transforming growth factor-β (TGF-β) family that is mainly expressed in skeletal muscle, which is also its primary target tissue. Deletion of the myostatin gene (Mstn) in mice leads to muscle hypertrophy, and animal studies support the concept that myostatin is a negative regulator of muscle growth and regeneration. However, myostatin deficiency also increases bone formation, mainly through loading-associated effects on bone. Here we report a previously unknown direct role for myostatin in osteoclastogenesis and in the progressive loss of articular bone in rheumatoid arthritis (RA). We demonstrate that myostatin is highly expressed in the synovial tissues of RA subjects and of human tumor necrosis factor (TNF)-α transgenic (hTNFtg) mice, a model for human RA. Myostatin strongly accelerates receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast formation in vitro through transcription factor SMAD2-dependent regulation of nuclear factor of activated T-cells (NFATC1). Myostatin deficiency or antibody-mediated inhibition leads to an amelioration of arthritis severity in hTNFtg mice, chiefly reflected by less bone destruction. Consistent with these effects in hTNFtg mice, the lack of myostatin leads to increased grip strength and less bone erosion in the K/BxN serum-induced arthritis model in mice. The results strongly suggest that myostatin is a potent therapeutic target for interfering with osteoclast formation and joint destruction in RA.

  2. A fixed carbohydrate:protein ratio ≤ 1.8 on an energy basis consumed in the context of an energy-restricted diet and reduction of body weight: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Sjödin, Anders Mikael

    2017-01-01

    Following an application from Marks and Spencer PLC, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the United Kingdom, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver...

  3. A Librarian's Primer on Financial Ratios.

    Science.gov (United States)

    Kerbel, Sandra Sandor

    1982-01-01

    Explains in simple terms the nature and function of a number of basic types of business and industrial financial ratios. An annotated list of five basic sources for ratios is included and a reference list and bibliography are attached. (JL)

  4. Contribution to the problem of liquidity ratios

    OpenAIRE

    Dvoøáèek Jaroslav

    1997-01-01

    The article is based on the importance of the financial analysis in mining industry. The author pays attention to liquidity ratios given in literature from the standpoint of their number, content, units and recommended quantity value of single ratios. For the application in practice two liquidity ratios are suggested and the methodology of their recommended values determination is given.

  5. Relationships between breath ratios, spirituality and health ...

    African Journals Online (AJOL)

    The aim of this retrospective, quantitative study was to investigate relationships between breath ratios, spirituality perceptions and health perceptions, with special reference to breath ratios that best predict optimal health and spirituality. Significant negative correlations were found between breath ratios and spirituality ...

  6. Contribution to the problem of liquidity ratios

    Directory of Open Access Journals (Sweden)

    Dvoøáèek Jaroslav

    1997-03-01

    Full Text Available The article is based on the importance of the financial analysis in mining industry. The author pays attention to liquidity ratios given in literature from the standpoint of their number, content, units and recommended quantity value of single ratios. For the application in practice two liquidity ratios are suggested and the methodology of their recommended values determination is given.

  7. Hygienic regulation of ionizing radiations

    International Nuclear Information System (INIS)

    Saurov, M.M.

    1984-01-01

    Modern state of the problem on hygienic regulation of ionizing radiations is considered. Concepts and principles of the regulation based on risk concept are presented according to ICRP 26 and 27. Two types of risk are designated: ''absolute'' and ''relative'' ones. The concept of acceptable risk on the basis of cost - benefit ratio is substantiated. Special attention is paid to the principle of accounting the complex of health signs, when determining radiation hazard. To determine the level of permissible risk and permissible dose to population the concept of ''inadmissibility of s-tatistically significant risk'' has been developed. Standards, regulating population doses in the USSR, which are valid nowadays, are considered

  8. Retinoic acid receptor signalling directly regulates osteoblast and adipocyte differentiation from mesenchymal progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Green, A.C. [St Vincent' s Institute, Fitzroy, Victoria 3065 (Australia); Department of Medicine at St. Vincent' s Hospital, The University of Melbourne, Victoria 3065 (Australia); Kocovski, P.; Jovic, T.; Walia, M.K. [St Vincent' s Institute, Fitzroy, Victoria 3065 (Australia); Chandraratna, R.A.S. [IO Therapeutics, Inc., Santa Ana, CA 92705 (United States); Martin, T.J.; Baker, E.K. [St Vincent' s Institute, Fitzroy, Victoria 3065 (Australia); Department of Medicine at St. Vincent' s Hospital, The University of Melbourne, Victoria 3065 (Australia); Purton, L.E., E-mail: lpurton@svi.edu.au [St Vincent' s Institute, Fitzroy, Victoria 3065 (Australia); Department of Medicine at St. Vincent' s Hospital, The University of Melbourne, Victoria 3065 (Australia)

    2017-01-01

    Low and high serum retinol levels are associated with increased fracture risk and poor bone health. We recently showed retinoic acid receptors (RARs) are negative regulators of osteoclastogenesis. Here we show RARs are also negative regulators of osteoblast and adipocyte differentiation. The pan-RAR agonist, all-trans retinoic acid (ATRA), directly inhibited differentiation and mineralisation of early osteoprogenitors and impaired the differentiation of more mature osteoblast populations. In contrast, the pan-RAR antagonist, IRX4310, accelerated differentiation of early osteoprogenitors. These effects predominantly occurred via RARγ and were further enhanced by an RARα agonist or antagonist, respectively. RAR agonists similarly impaired adipogenesis in osteogenic cultures. RAR agonist treatment resulted in significant upregulation of the Wnt antagonist, Sfrp4. This accompanied reduced nuclear and cytosolic β-catenin protein and reduced expression of the Wnt target gene Axin2, suggesting impaired Wnt/β-catenin signalling. To determine the effect of RAR inhibition in post-natal mice, IRX4310 was administered to male mice for 10 days and bones were assessed by µCT. No change to trabecular bone volume was observed, however, radial bone growth was impaired. These studies show RARs directly influence osteoblast and adipocyte formation from mesenchymal cells, and inhibition of RAR signalling in vivo impairs radial bone growth in post-natal mice. - Graphical abstract: Schematic shows RAR ligand regulation of osteoblast differentiation in vitro. RARγ antagonists±RARα antagonists promote osteoblast differentiation. RARγ and RARα agonists alone or in combination block osteoblast differentiation, which correlates with upregulation of Sfrp4, and downregulation of nuclear and cytosolic β-catenin and reduced expression of the Wnt target gene Axin2. Red arrows indicate effects of RAR agonists on mediators of Wnt signalling.

  9. The HNC/HCN ratio in star-forming regions

    International Nuclear Information System (INIS)

    Graninger, Dawn M.; Öberg, Karin I.; Herbst, Eric; Vasyunin, Anton I.

    2014-01-01

    HNC and HCN, typically used as dense gas tracers in molecular clouds, are a pair of isomers that have great potential as a temperature probe because of temperature dependent, isomer-specific formation and destruction pathways. Previous observations of the HNC/HCN abundance ratio show that the ratio decreases with increasing temperature, something that standard astrochemical models cannot reproduce. We have undertaken a detailed parameter study on which environmental characteristics and chemical reactions affect the HNC/HCN ratio and can thus contribute to the observed dependence. Using existing gas and gas-grain models updated with new reactions and reaction barriers, we find that in static models the H + HNC gas-phase reaction regulates the HNC/HCN ratio under all conditions, except for very early times. We quantitatively constrain the combinations of H abundance and H + HNC reaction barrier that can explain the observed HNC/HCN temperature dependence and discuss the implications in light of new quantum chemical calculations. In warm-up models, gas-grain chemistry contributes significantly to the predicted HNC/HCN ratio and understanding the dynamics of star formation is therefore key to model the HNC/HCN system.

  10. NORM regulations

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

    The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

  11. Fisheries regulation

    DEFF Research Database (Denmark)

    Jensen, Frank; Frost, Hans Staby; Abildtrup, Jens

    2017-01-01

    Economists normally claim that a stock externality arises within fisheries because each individual fisherman does not take the effect on stock size into account when making harvest decisions. Due to the stock externality, it is commonly argued that fisheries regulation is necessary, but regulatory...... decisions are complicated by a tremendous amount of uncertainty and asymmetric information. This paper provides an overview of selected parts of the literature on the regulation of fisheries under uncertainty and asymmetric information, and possible areas for future research are identified. Specifically...

  12. Application of Performance Ratios in Portfolio Optimization

    Directory of Open Access Journals (Sweden)

    Aleš Kresta

    2015-01-01

    Full Text Available The cornerstone of modern portfolio theory was established by pioneer work of Harry Markowitz. Based on his mean-variance framework, Sharpe formulated his well-known Sharpe ratio aiming to measure the performance of mutual funds. The contemporary development in computer’s computational power allowed to apply more complex performance ratios, which take into account also higher moments of return probability distribution. Although these ratios were proposed to help the investors to improve the results of portfolio optimization, we empirically demonstrated in our paper that this may not necessarily be true. On the historical dataset of DJIA components we empirically showed that both Sharpe ratio and MAD ratio outperformed Rachev ratio. However, for Rachev ratio we assumed only one level of parameters value. Different set-ups of parameters may provide different results and thus further analysis is certainly required.

  13. Poisson's ratio of fiber-reinforced composites

    Science.gov (United States)

    Christiansson, Henrik; Helsing, Johan

    1996-05-01

    Poisson's ratio flow diagrams, that is, the Poisson's ratio versus the fiber fraction, are obtained numerically for hexagonal arrays of elastic circular fibers in an elastic matrix. High numerical accuracy is achieved through the use of an interface integral equation method. Questions concerning fixed point theorems and the validity of existing asymptotic relations are investigated and partially resolved. Our findings for the transverse effective Poisson's ratio, together with earlier results for random systems by other authors, make it possible to formulate a general statement for Poisson's ratio flow diagrams: For composites with circular fibers and where the phase Poisson's ratios are equal to 1/3, the system with the lowest stiffness ratio has the highest Poisson's ratio. For other choices of the elastic moduli for the phases, no simple statement can be made.

  14. PENGARUH PERUBAHAN RETURN ON ASSETS, PERUBAHAN DEBT TO EQUITY RATIO DAN PERUBAHAN CASH RATIO TERHADAP PERUBAHAN DIVIDEND PAYOUT RATIO

    Directory of Open Access Journals (Sweden)

    Yuli Soesetio

    2008-02-01

    Full Text Available Dividend Payout Ratio used to calculate all of revenue that will be accepted by stockholders as cash dividend, usually explained as percentage. This research was conducted to know several factors that affected change of Dividend Payout Ratio and to know the significance level and the correlation between dependent and independent variable. Analysis instrument used was parametric statistic. Based on the result of statistic test,  The Change of Return on Asset (X1, The Change of Debt to Equity Ratio (X2,  were able to explain dependent variable of the change Dividend Payout Ratio, and The Change of CashRatio can’t explain dependent variable of the change Dividend Payout Ratio

  15. French regulations

    International Nuclear Information System (INIS)

    Ballereau, P.

    1998-01-01

    In this issue are given the new French regulations relative to radiation protection of temporary personnel, the licensing to release gaseous and liquid wastes and the licensing granted to thirty two laboratories using beta and gamma decay radioisotopes. (N.C.)

  16. Hubungan Analisis Ratio Keuangan dengan Kesehatan Perusahaan

    Directory of Open Access Journals (Sweden)

    Soekarso Soekarso

    2009-09-01

    Full Text Available In the business world, companies develop a vision and mission to improve welfare in the future. The work program the company is to achieve productivity and profitability. Finance in the company is one of the strategic functions that includes wealth management and transformation of added value (added value and also the control of corporate health. The financial statements such as balance sheet (balance sheet, profit and loss statement (income statement, and financial ratio (financial ratios, reflects the company's performance and health. Financial ratio analysis relates to the health of the company through a ratio of effectiveness, efficiency, productivity, profitability, liquidity, and solvability. Analysis shows that whenever actual value of financial ratios is above standard it means the company is healthy, and when the actual value of financial ratios is below the standard, it reversely means that companies are not healthy.

  17. Eccentric crank variable compression ratio mechanism

    Science.gov (United States)

    Lawrence, Keith Edward [Kobe, JP; Moser, William Elliott [Peoria, IL; Roozenboom, Stephan Donald [Washington, IL; Knox, Kevin Jay [Peoria, IL

    2008-05-13

    A variable compression ratio mechanism for an internal combustion engine that has an engine block and a crankshaft is disclosed. The variable compression ratio mechanism has a plurality of eccentric disks configured to support the crankshaft. Each of the plurality of eccentric disks has at least one cylindrical portion annularly surrounded by the engine block. The variable compression ratio mechanism also has at least one actuator configured to rotate the plurality of eccentric disks.

  18. NHE10, a novel osteoclast-specific member of the Na+/H+ exchanger family, regulates osteoclast differentiation and survival

    International Nuclear Information System (INIS)

    Lee, Seoung Hoon; Kim, Taesoo; Park, Eui-Soon; Yang, Sujeong; Jeong, Daewon; Choi, Yongwon; Rho, Jaerang

    2008-01-01

    Bone homeostasis is tightly regulated by the balanced actions of osteoblasts (OBs) and osteoclasts (OCs). We previously analyzed the gene expression profile of OC differentiation using a cDNA microarray, and identified a novel osteoclastogenic gene candidate, clone OCL-1-E7 [J. Rho, C.R. Altmann, N.D. Socci, L. Merkov, N. Kim, H. So, O. Lee, M. Takami, A.H. Brivanlou, Y. Choi, Gene expression profiling of osteoclast differentiation by combined suppression subtractive hybridization (SSH) and cDNA microarray analysis, DNA Cell Biol. 21 (2002) 541-549]. In this study, we have isolated full-length cDNAs corresponding to this clone from mice and humans to determine the functional roles of this gene in osteoclastogenesis. The full-length cDNA of OCL-1-E7 encodes 12 membrane-spanning domains that are typical of isoforms of the Na + /H + exchangers (NHEs), indicating that this clone is a novel member of the NHE family (hereafter referred to as NHE10). Here, we show that NHE10 is highly expressed in OCs in response to receptor activator of nuclear factor-κB ligand signaling and is required for OC differentiation and survival

  19. Regulating Internalities

    OpenAIRE

    Sunstein, Cass Robert; Allcott, Hunt

    2015-01-01

    This paper offers a framework for regulating internalities. Using a simple economic model, we provide four principles for designing and evaluating behaviorally-motivated policy. We then outline rules for determining which contexts reliably reflect true preferences and discuss empirical strategies for measuring internalities. As a case study, we focus on energy efficiency policy, including Corporate Average Fuel Economy (CAFE) standards and appliance and lighting energy efficiency standards.

  20. Extraordinary sex ratios: cultural effects on ecological consequences.

    Directory of Open Access Journals (Sweden)

    Ferenc Molnár

    Full Text Available We model sex-structured population dynamics to analyze pairwise competition between groups differing both genetically and culturally. A sex-ratio allele is expressed in the heterogametic sex only, so that assumptions of Fisher's analysis do not apply. Sex-ratio evolution drives cultural evolution of a group-associated trait governing mortality in the homogametic sex. The two-sex dynamics under resource limitation induces a strong Allee effect that depends on both sex ratio and cultural trait values. We describe the resulting threshold, separating extinction from positive growth, as a function of female and male densities. When initial conditions avoid extinction due to the Allee effect, different sex ratios cannot coexist; in our model, greater female allocation always invades and excludes a lesser allocation. But the culturally transmitted trait interacts with the sex ratio to determine the ecological consequences of successful invasion. The invading female allocation may permit population persistence at self-regulated equilibrium. For this case, the resident culture may be excluded, or may coexist with the invader culture. That is, a single sex-ratio allele in females and a cultural dimorphism in male mortality can persist; a low-mortality resident trait is maintained by father-to-son cultural transmission. Otherwise, the successfully invading female allocation excludes the resident allele and culture and then drives the population to extinction via a shortage of males. Finally, we show that the results obtained under homogeneous mixing hold, with caveats, in a spatially explicit model with local mating and diffusive dispersal in both sexes.

  1. Selective breeding for a behavioral trait changes digit ratio.

    Directory of Open Access Journals (Sweden)

    Reginia H Y Yan

    Full Text Available The ratio of the length of the second digit (index finger divided by the fourth digit (ring finger tends to be lower in men than in women. This 2D:4D digit ratio is often used as a proxy for prenatal androgen exposure in studies of human health and behavior. For example, 2D:4D ratio is lower (i.e. more "masculinized" in both men and women of greater physical fitness and/or sporting ability. Lab mice have also shown variation in 2D:4D as a function of uterine environment, and mouse digit ratios seem also to correlate with behavioral traits, including daily activity levels. Selective breeding for increased rates of voluntary exercise (wheel running in four lines of mice has caused correlated increases in aerobic exercise capacity, circulating corticosterone level, and predatory aggression. Here, we show that this selection regime has also increased 2D:4D. This apparent "feminization" in mice is opposite to the relationship seen between 2D:4D and physical fitness in human beings. The present results are difficult to reconcile with the notion that 2D:4D is an effective proxy for prenatal androgen exposure; instead, it may more accurately reflect effects of glucocorticoids, or other factors that regulate any of many genes.

  2. Corporate prediction models, ratios or regression analysis?

    NARCIS (Netherlands)

    Bijnen, E.J.; Wijn, M.F.C.M.

    1994-01-01

    The models developed in the literature with respect to the prediction of a company s failure are based on ratios. It has been shown before that these models should be rejected on theoretical grounds. Our study of industrial companies in the Netherlands shows that the ratios which are used in

  3. Maternal preconception diet and the sex ratio

    NARCIS (Netherlands)

    Cramer, J.S.; Lumey, L.H.

    2009-01-01

    Temporal variations in the sex ratio or the ratio of boys over girls at birth have been widely studied and variously attributed to social changes, conditions of war, and environmental changes. Recently, Mathews, Johnson and Neil (2008) studied the direct evidence of individual pregnancies and

  4. The Golden Ratio--A Contrary Viewpoint

    Science.gov (United States)

    Falbo, Clement

    2005-01-01

    Many assertions about the occurrence of the golden ratio phi in art, architecture, and nature have been shown to be false, unsupported, or misleading. For instance, we show that the spirals found in sea shells, in particular the "Nautilus pompilius," are not in the shape of the golden ratio, as is often claimed. Some of the most interesting…

  5. Osmosis and Surface Area to Volume Ratio.

    Science.gov (United States)

    Barrett, D. R. B.

    1984-01-01

    Describes an experiment designed to help students understand the concepts of osmosis and surface area to volume ratio (SA:VOL). The task for students is to compare water uptake in different sizes of potato cubes and relate differences to their SA:VOL ratios. (JN)

  6. Key financial ratios can foretell hospital closures.

    Science.gov (United States)

    Lynn, M L; Wertheim, P

    1993-11-01

    An analysis of various financial ratios sampled from open and closed hospitals shows that certain leverage, liquidity, capital efficiency, and resource availability ratios can predict hospital closure up to two years in advance of the closure with an accuracy of nearly 75 percent.

  7. Charge ratio of muons from atmospheric neutrinos

    Energy Technology Data Exchange (ETDEWEB)

    Gaisser, T.K.; Stanev, Todor

    2003-05-22

    We calculate the intensities and angular distributions of positive and negative muons produced by atmospheric neutrinos. We comment on some sources of uncertainty in the charge ratio. We also draw attention to a potentially interesting signature of neutrino oscillations in the muon charge ratio, and we discuss the prospects for its observation (which are not quite within the reach of currently planned magnetized detectors)

  8. Maternal preconception diet and the sex ratio

    NARCIS (Netherlands)

    Cramer, J.S.; Lumey, L.H.

    2010-01-01

    Temporal variations in the sex ratio, or the ratio of boys to girls at birth, have been widely studied and variously attributed to social changes, conditions of war, and environmental changes. Recently, Mathews et al. ["You are what your mother eats: Evidence for maternal preconception diet

  9. Financial Ratio Analysis Comes to Nonprofits.

    Science.gov (United States)

    Chabotar, Kent John

    1989-01-01

    To evaluate their financial health, a growing number of colleges, universities, and other nonprofit organizations are using financial ratio analysis, a technique used in business. The strengths and weaknesses of ratio analysis are assessed and suggestions are made on how nonprofits can use it most effectively. (Author/MLW)

  10. Curious Sex Ratios and Cytoplasmic Genes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 6. Curious Sex Ratios and Cytoplasmic Genes Microbes Can Distort the Sex Ratio of Populations. Stephen J Freeland Laurence D Hurst. General Article Volume 2 Issue 6 June 1997 pp 68-78 ...

  11. Geometrical scaling in charm structure function ratios

    International Nuclear Information System (INIS)

    Boroun, G.R.; Rezaei, B.

    2014-01-01

    By using a Laplace-transform technique, we solve the next-to-leading-order master equation for charm production and derive a compact formula for the ratio R c =F L cc ¯ /F 2 cc ¯ , which is useful for extracting the charm structure function from the reduced charm cross section, in particular, at DESY HERA, at small x. Our results show that this ratio is independent of x at small x. In this method of determining the ratios, we apply geometrical scaling in charm production in deep inelastic scattering (DIS). Our analysis shows that the renormalization scales have a sizable impact on the ratio R c at high Q 2 . Our results for the ratio of the charm structure functions are in a good agreement with some phenomenological models

  12. Equity Theory Ratios as Causal Schemas

    Directory of Open Access Journals (Sweden)

    Alexios Arvanitis

    2016-08-01

    Full Text Available Equity theory approaches justice evaluations based on ratios of exchange inputs to exchange outcomes. Situations are evaluated as just if ratios are equal and unjust if unequal. We suggest that equity ratios serve a more fundamental cognitive function than the evaluation of justice. More particularly, we propose that they serve as causal schemas for exchange outcomes, that is, they assist in determining whether certain outcomes are caused by inputs of other people in the context of an exchange process. Equality or inequality of ratios in this sense points to an exchange process. Indeed, Study 1 shows that different exchange situations, such as disproportional or balanced proportional situations, create perceptions of give-and-take on the basis of equity ratios. Study 2 shows that perceptions of justice are based more on communicatively accepted rules of interaction than equity-based evaluations, thereby offering a distinction between an attribution and an evaluation cognitive process for exchange outcomes.

  13. Equity Theory Ratios as Causal Schemas.

    Science.gov (United States)

    Arvanitis, Alexios; Hantzi, Alexandra

    2016-01-01

    Equity theory approaches justice evaluations based on ratios of exchange inputs to exchange outcomes. Situations are evaluated as just if ratios are equal and unjust if unequal. We suggest that equity ratios serve a more fundamental cognitive function than the evaluation of justice. More particularly, we propose that they serve as causal schemas for exchange outcomes, that is, they assist in determining whether certain outcomes are caused by inputs of other people in the context of an exchange process. Equality or inequality of ratios in this sense points to an exchange process. Indeed, Study 1 shows that different exchange situations, such as disproportional or balanced proportional situations, create perceptions of give-and-take on the basis of equity ratios. Study 2 shows that perceptions of justice are based more on communicatively accepted rules of interaction than equity-based evaluations, thereby offering a distinction between an attribution and an evaluation cognitive process for exchange outcomes.

  14. Independent isomer yield ratio of 90Rb

    International Nuclear Information System (INIS)

    Reeder, P.L.; Warner, R.A.; Ford, G.P.; Willmes, H.

    1985-05-01

    The independent isomer yield ratio for 90 Rb from thermal neutron fission of 235 U has been measured by use of a new technique involving a pulsed reactor and an on-line mass spectrometer facility. The apparent isomer yield ratio was measured for different ion collection time intervals and extrapolated to zero collection time to eliminate interference from 90 Kr decay. The observed isomer yield ratio of 8.7 +- 1.0 is one of the largest ratios measured for a low energy fission process. However, a statistical model analysis shows that the average angular momentum ( = 4.5) deduced from this isomer yield ratio is consistent with average angular momentum for other products from low energy fission. 7 refs

  15. Development of air fuel ratio sensor; A/F sensor no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    Sakawa, T; Hori, M [Denso Corp., Aichi (Japan); Nakamura, Y [Toyota Motor Corp., Aichi (Japan)

    1997-10-01

    The Air Fuel Ratio Sensor (A/F sensor), which is applied to a 1997 model year Low Emission Vehicle (LEV) was developed. This sensor enables the detection of the exhaust gas air fuel ratio, both lean and rich of stoichiometric. It has an effective air fuel ratio range from 12 to 18 as required for LEV regulation. It has the fast light off, - within 20 seconds - to minimize exhaust hydrocarbon content. Further, it has fast response time, less than 200 msec, to improve the air fuel ratio controllability. 3 refs., 7 figs.

  16. Energy ratios in Finnish agricultural production

    Directory of Open Access Journals (Sweden)

    H. J. MIKKOLA

    2008-12-01

    Full Text Available The objective of this study was to assess energy ratios and net energy in plant production and energy ratios in animal production in Finland. Energy ratios and net energy were determined on the basis of plant- and animal-specific energy analyses. In plant production, energy ratios and net energy were assessed as a function of nitrogen fertilization, because indirect energy input in the form of agrochemicals was 54—73% from the total energy input and nitrogen was responsible for the major part of this. The highest energy ratio was 18.6 for reed canary grass. As a whole reed canary grass was superior to the other crops, which were barley, spring wheat, spring turnip rape, ley for silage, potato and sugar beet. Reed canary grass and sugar beet gained the highest net energy yields of 111–115 GJ ha-1. The optimum energy ratio was gained in general with less nitrogen fertilization intensity than farmers use. The energy ratios in pork production varied between 0.14–1.28 depending on what was included or excluded in the analysis and for milk production between 0.15–1.85. Ratios of 1.28 in pork production and 1.85 in milk production are unrealistic as they do not give any shelter to the animals, although they can be approached in very low-input production systems. If the ratio is calculated with feed energy content then the ratio is low, 0.14–0.22 for pork and 0.15 for milk. This shows that animals can convert 14–22 percent of the input energy to usable products. In pork production, the largest portion of the energy input was the ventilation of the building. In milk production milking and cooling consumes a lot of energy and for this reason the electricity consumption is high.;

  17. Comparing computing formulas for estimating concentration ratios

    International Nuclear Information System (INIS)

    Gilbert, R.O.; Simpson, J.C.

    1984-03-01

    This paper provides guidance on the choice of computing formulas (estimators) for estimating concentration ratios and other ratio-type measures of radionuclides and other environmental contaminant transfers between ecosystem components. Mathematical expressions for the expected value of three commonly used estimators (arithmetic mean of ratios, geometric mean of ratios, and the ratio of means) are obtained when the multivariate lognormal distribution is assumed. These expressions are used to explain why these estimators will not in general give the same estimate of the average concentration ratio. They illustrate that the magnitude of the discrepancies depends on the magnitude of measurement biases, and on the variances and correlations associated with spatial heterogeneity and measurement errors. This paper also reports on a computer simulation study that compares the accuracy of eight computing formulas for estimating a ratio relationship that is constant over time and/or space. Statistical models appropriate for both controlled spiking experiments and observational field studies for either normal or lognormal distributions are considered. 24 references, 15 figures, 7 tables

  18. Introducing optional reserve ratios in Hungary

    OpenAIRE

    Lóránt Varga

    2010-01-01

    As of the reserve maintenance period commencing in November 2010, Hungarian credit institutions will be free to decide whether to apply the previously valid 2% reserve ratio, or to apply a higher mandatory reserve ratio. Credit institutions required to hold reserves may select from reserve ratios of 2, 3, 4 and 5%, and may change their decision on a semi-annual basis. In line with the international best practice, the purpose of the MNB’s reserve requirement system is to support credit institu...

  19. Transcription and the aspect ratio of DNA

    DEFF Research Database (Denmark)

    Olsen, Kasper Wibeck; Bohr, Jakob

    2013-01-01

    analysis of transcription. It is shown that under certain reasonable assumptions transcription is only possible if the aspect ratio is in the regime corresponding to further twisting. We find this constraint to be in agreement with long-established crystallographic studies of DNA.......Two separate regimes exist for the aspect ratio of DNA. A low aspect regime where DNA will twist further under strain and a high aspect regime where DNA will untwist under strain. The question of the overall geometry, i.e. the aspect ratio, of DNA is revisited from the perspective of a geometrical...

  20. Financial Ratios and Perceived Household Financial Satisfaction

    Directory of Open Access Journals (Sweden)

    Scott Garrett

    2013-08-01

    Full Text Available This paper tests the relative strength of three objective measures of financial health (using the solvency, liquidity, and investment asset ratio in predicting a household’s subjective feeling of current financial satisfaction. Using a sample of 6,923 respondents in the 2008 Health and Retirement Study this paper presents evidence of two main findings: 1 the solvency ratio is most strongly associated with financial satisfaction levels based on a cross-sectional design and 2 changes in the investment asset ratio are most strongly associated with changes in financial satisfaction over time.

  1. Curious Sex Ratios and Cytoplasmic Genes

    Indian Academy of Sciences (India)

    instances of curious sex ratios exemplify an important principle: the fitness ..... markable transition - the whole means of sex determination has changed. No longer ... to the cytoplasmic symbiont is self-evident; the symbionts simply increase the.

  2. Asthma Medication Ratio Predicts Emergency Depart...

    Data.gov (United States)

    U.S. Department of Health & Human Services — According to findings reported in Asthma Medication Ratio Predicts Emergency Department Visits and Hospitalizations in Children with Asthma, published in Volume 3,...

  3. Anomalous Enantiomer Ratios in Meteoritic Sugar Derivatives

    Science.gov (United States)

    Cooper, G.; Sant, M.; Asiyo, C.

    2009-03-01

    The enantiomer (mirror-image) ratios of sugar acids in carbonaceous meteorites have been measured. D-enantiomer excesses are found in all acids measured thus far. This includes rare as well as common compounds.

  4. Recent development in isotope ratio mass spectrometry

    International Nuclear Information System (INIS)

    Platzner, I.

    1992-01-01

    Within the limited of this review the following topics will be briefly discussed: a) Accuracy, precision, internal relative standard deviation (RISD) and external relative standard deviation (RESD) of isotope ratio measurements. With advanced instrumentation and use of standard reference materials, high accuracy and RESD = 0.002% (or better) may be achieved; b) The advantages of modern automatic isotope ratio mass spectrometer are briefly described. Computer controlled operation and data acquisition, and multiple ion collection are the recent important improvement; c) The isotopic fractionation during the course of isotope ratio measurement is considered as a major source of errors in thermal ionization of metallic elements. The phenomenon in strontium, neodymium, uranium, lead and calcium and methods to correct the measured data are discussed; d) Applications of isotope ratio mass spectrometry in atomic weight determinations, the isotope dilution technique, isotope geology, and isotope effects in biological systems are described together with specific applications in various research and technology area. (author)

  5. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... between preoperatively measured neutrophil-lymphocyte ratio (NLR) – as an inflammation ... analgesic (tenoxicam – as the first drug of choice, paracetamol, tramadol, or pethidine) usage ... fracture fixation). Age, sex, type of ...

  6. Urine Albumin and Albumin/ Creatinine Ratio

    Science.gov (United States)

    ... it used? The urine albumin test or albumin/creatinine ratio (ACR) is used to screen people with chronic conditions, such as diabetes and high blood pressure ( hypertension ) that put them at an ...

  7. Temperature diagnostic line ratios of Fe XVII

    International Nuclear Information System (INIS)

    Raymond, J.C.; Smith, B.W.; Los Alamos National Lab., NM)

    1986-01-01

    Based on extensive calculations of the excitation rates of Fe XVII, four temperature-sensitive line ratios are investigated, paying special attention to the contribution of resonances to the excitation rates and to the contributions of dielectronic recombination satellites to the observed line intensities. The predictions are compared to FPCS observations of Puppis A and to Solar Maximum Mission (SMM) and SOLEX observations of the sun. Temperature-sensitive line ratios are also computed for emitting gas covering a broad temperature range. It is found that each ratio yields a differently weighted average for the temperature and that this accounts for some apparent discrepancies between the theoretical ratios and solar observations. The effects of this weighting on the Fe XVII temperature diagnostics and on the analogous Fe XXIV/Fe XXV satellite line temperature diagnostics are discussed. 27 references

  8. Ratio Analysis: Where Investments Meet Mathematics.

    Science.gov (United States)

    Barton, Susan D.; Woodbury, Denise

    2002-01-01

    Discusses ratio analysis by which investments may be evaluated. Requires the use of fundamental mathematics, problem solving, and a comparison of the mathematical results within the framework of industry. (Author/NB)

  9. Isotopic ratios in the solar system

    International Nuclear Information System (INIS)

    1985-01-01

    This colloquium is aimed at presentation of isotope ratio measurements in different objects of solar system and surrounding interstellar space and evaluation of what information on composition and structure of primitive solar nebula and on chemical evolution of interstellar space in this part of the galaxy can be deduced from it. Isotope ratio in solar system got from laboratory study of extraterrestrial materials is a subject of this colloquium. Then isotope ratio measured in solar wind, planets and comets. Measurements either are made in-situ by mass spectrometry of ions in solar wind or planetery atmosphere gases either are remote measurements of spectra emitted by giant planets and comets. At last, planetology and astrophysics implications are presented and reviewed. Consraints for solar system formation model can be deduced from isotope ratio measurement. Particularly, isotope anomalies are marks of the processes, which have influenced the primitive solar nebula contraction [fr

  10. From Fibonacci Sequence to the Golden Ratio

    Directory of Open Access Journals (Sweden)

    Alberto Fiorenza

    2013-01-01

    Full Text Available We consider the well-known characterization of the Golden ratio as limit of the ratio of consecutive terms of the Fibonacci sequence, and we give an explanation of this property in the framework of the Difference Equations Theory. We show that the Golden ratio coincides with this limit not because it is the root with maximum modulus and multiplicity of the characteristic polynomial, but, from a more general point of view, because it is the root with maximum modulus and multiplicity of a restricted set of roots, which in this special case coincides with the two roots of the characteristic polynomial. This new perspective is the heart of the characterization of the limit of ratio of consecutive terms of all linear homogeneous recurrences with constant coefficients, without any assumption on the roots of the characteristic polynomial, which may be, in particular, also complex and not real.

  11. Determining sex ratios of turtle hatchlings

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Previous status assessments of marine turtles have assumed that the natural sex ratio of a marine turtle population is 1:1 (e.g. Conant et al. 2009). However, this...

  12. Minsky and dynamic macroprudential regulation

    Directory of Open Access Journals (Sweden)

    Jan Kregel

    2014-06-01

    Full Text Available In the context of current debates about the proper form of prudential regulation and proposals for the imposition of liquidity and capital ratios, the paper examines Hyman Minsky’s work as a consultant to government agencies exploring financial regulatory reform in the 1960s. As the author explains, this often-overlooked early work, a precursor to Minsky’s “financial instability hypothesis”, serves as yet another useful guide to explaining why regulation and supervision in the lead-up to the 2008 financial crisis were flawed, and why the approach to reregulation after the crisis has been incomplete.

  13. Three-dimensional stereo by photometric ratios

    International Nuclear Information System (INIS)

    Wolff, L.B.; Angelopoulou, E.

    1994-01-01

    We present a methodology for corresponding a dense set of points on an object surface from photometric values for three-dimensional stereo computation of depth. The methodology utilizes multiple stereo pairs of images, with each stereo pair being taken of the identical scene but under different illumination. With just two stereo pairs of images taken under two different illumination conditions, a stereo pair of ratio images can be produced, one for the ratio of left-hand images and one for the ratio of right-hand images. We demonstrate how the photometric ratios composing these images can be used for accurate correspondence of object points. Object points having the same photometric ratio with respect to two different illumination conditions constitute a well-defined equivalence class of physical constraints defined by local surface orientation relative to illumination conditions. We formally show that for diffuse reflection the photometric ratio is invariant to varying camera characteristics, surface albedo, and viewpoint and that therefore the same photometric ratio in both images of a stereo pair implies the same equivalence class of physical constraints. The correspondence of photometric ratios along epipolar lines in a stereo pair of images under different illumination conditions is a correspondence of equivalent physical constraints, and the determination of depth from stereo can be performed. Whereas illumination planning is required, our photometric-based stereo methodology does not require knowledge of illumination conditions in the actual computation of three-dimensional depth and is applicable to perspective views. This technique extends the stereo determination of three-dimensional depth to smooth featureless surfaces without the use of precisely calibrated lighting. We demonstrate experimental depth maps from a dense set of points on smooth objects of known ground-truth shape, determined to within 1% depth accuracy

  14. The Laplace Likelihood Ratio Test for Heteroscedasticity

    Directory of Open Access Journals (Sweden)

    J. Martin van Zyl

    2011-01-01

    Full Text Available It is shown that the likelihood ratio test for heteroscedasticity, assuming the Laplace distribution, gives good results for Gaussian and fat-tailed data. The likelihood ratio test, assuming normality, is very sensitive to any deviation from normality, especially when the observations are from a distribution with fat tails. Such a likelihood test can also be used as a robust test for a constant variance in residuals or a time series if the data is partitioned into groups.

  15. A note on trader Sharpe Ratios.

    Science.gov (United States)

    Coates, John M; Page, Lionel

    2009-11-25

    Traders in the financial world are assessed by the amount of money they make and, increasingly, by the amount of money they make per unit of risk taken, a measure known as the Sharpe Ratio. Little is known about the average Sharpe Ratio among traders, but the Efficient Market Hypothesis suggests that traders, like asset managers, should not outperform the broad market. Here we report the findings of a study conducted in the City of London which shows that a population of experienced traders attain Sharpe Ratios significantly higher than the broad market. To explain this anomaly we examine a surrogate marker of prenatal androgen exposure, the second-to-fourth finger length ratio (2D:4D), which has previously been identified as predicting a trader's long term profitability. We find that it predicts the amount of risk taken by traders but not their Sharpe Ratios. We do, however, find that the traders' Sharpe Ratios increase markedly with the number of years they have traded, a result suggesting that learning plays a role in increasing the returns of traders. Our findings present anomalous data for the Efficient Markets Hypothesis.

  16. A note on trader Sharpe Ratios.

    Directory of Open Access Journals (Sweden)

    John M Coates

    Full Text Available Traders in the financial world are assessed by the amount of money they make and, increasingly, by the amount of money they make per unit of risk taken, a measure known as the Sharpe Ratio. Little is known about the average Sharpe Ratio among traders, but the Efficient Market Hypothesis suggests that traders, like asset managers, should not outperform the broad market. Here we report the findings of a study conducted in the City of London which shows that a population of experienced traders attain Sharpe Ratios significantly higher than the broad market. To explain this anomaly we examine a surrogate marker of prenatal androgen exposure, the second-to-fourth finger length ratio (2D:4D, which has previously been identified as predicting a trader's long term profitability. We find that it predicts the amount of risk taken by traders but not their Sharpe Ratios. We do, however, find that the traders' Sharpe Ratios increase markedly with the number of years they have traded, a result suggesting that learning plays a role in increasing the returns of traders. Our findings present anomalous data for the Efficient Markets Hypothesis.

  17. INFLUENCE OF SCALE RATIO, ASPECT RATIO, AND PLANFORM ON THE PERFORMANCE OF SUPERCAVITATING HYDROFOILS.

    Science.gov (United States)

    performance of supercavitating hydrofoils. No appreciable scale effect was found for scale ratios up to 3 in the fully-cavitating flow region. The...overall performance of the hydrofoil by increasing the aspect ratio above 3, and (2) moderate taper ratio seems to be advantageous in view of the overall performance of supercavitating hydrofoils. (Author)

  18. Sex ratios at birth after induced abortion.

    Science.gov (United States)

    Urquia, Marcelo L; Moineddin, Rahim; Jha, Prabhat; O'Campo, Patricia J; McKenzie, Kwame; Glazier, Richard H; Henry, David A; Ray, Joel G

    2016-06-14

    Skewed male:female ratios at birth have been observed among certain immigrant groups. Data on abortion practices that might help to explain these findings are lacking. We examined 1 220 933 births to women with up to 3 consecutive singleton live births between 1993 and 2012 in Ontario. Records of live births, and induced and spontaneous abortions were linked to Canadian immigration records. We determined associations of male:female infant ratios with maternal birthplace, sex of the previous living sibling(s) and prior spontaneous or induced abortions. Male:female infant ratios did not appreciably depart from the normal range among Canadian-born women and most women born outside of Canada, irrespective of the sex of previous children or the characteristics of prior abortions. However, among infants of women who immigrated from India and had previously given birth to 2 girls, the overall male:female ratio was 1.96 (95% confidence interval [CI] 1.75-2.21) for the third live birth. The male:female infant ratio after 2 girls was 1.77 (95% CI 1.26-2.47) times higher if the current birth was preceded by 1 induced abortion, 2.38 (95% CI 1.44-3.94) times higher if preceded by 2 or more induced abortions and 3.88 (95% CI 2.02-7.50) times higher if the induced abortion was performed at 15 weeks or more gestation relative to no preceding abortion. Spontaneous abortions were not associated with male-biased sex ratios in subsequent births. High male:female ratios observed among infants born to women who immigrated from India are associated with induced abortions, especially in the second trimester of pregnancy. © 2016 Canadian Medical Association or its licensors.

  19. Serial binary interval ratios improve rhythm reproduction.

    Science.gov (United States)

    Wu, Xiang; Westanmo, Anders; Zhou, Liang; Pan, Junhao

    2013-01-01

    Musical rhythm perception is a natural human ability that involves complex cognitive processes. Rhythm refers to the organization of events in time, and musical rhythms have an underlying hierarchical metrical structure. The metrical structure induces the feeling of a beat and the extent to which a rhythm induces the feeling of a beat is referred to as its metrical strength. Binary ratios are the most frequent interval ratio in musical rhythms. Rhythms with hierarchical binary ratios are better discriminated and reproduced than rhythms with hierarchical non-binary ratios. However, it remains unclear whether a superiority of serial binary over non-binary ratios in rhythm perception and reproduction exists. In addition, how different types of serial ratios influence the metrical strength of rhythms remains to be elucidated. The present study investigated serial binary vs. non-binary ratios in a reproduction task. Rhythms formed with exclusively binary (1:2:4:8), non-binary integer (1:3:5:6), and non-integer (1:2.3:5.3:6.4) ratios were examined within a constant meter. The results showed that the 1:2:4:8 rhythm type was more accurately reproduced than the 1:3:5:6 and 1:2.3:5.3:6.4 rhythm types, and the 1:2.3:5.3:6.4 rhythm type was more accurately reproduced than the 1:3:5:6 rhythm type. Further analyses showed that reproduction performance was better predicted by the distribution pattern of event occurrences within an inter-beat interval, than by the coincidence of events with beats, or the magnitude and complexity of interval ratios. Whereas rhythm theories and empirical data emphasize the role of the coincidence of events with beats in determining metrical strength and predicting rhythm performance, the present results suggest that rhythm processing may be better understood when the distribution pattern of event occurrences is taken into account. These results provide new insights into the mechanisms underlining musical rhythm perception.

  20. Serial binary interval ratios improve rhythm reproduction

    Directory of Open Access Journals (Sweden)

    Xiang eWu

    2013-08-01

    Full Text Available Musical rhythm perception is a natural human ability that involves complex cognitive processes. Rhythm refers to the organization of events in time, and musical rhythms have an underlying hierarchical metrical structure. The metrical structure induces the feeling of a beat and the extent to which a rhythm induces the feeling of a beat is referred to as its metrical strength. Binary ratios are the most frequent interval ratio in musical rhythms. Rhythms with hierarchical binary ratios are better discriminated and reproduced than rhythms with hierarchical non-binary ratios. However, it remains unclear whether a superiority of serial binary over non-binary ratios in rhythm perception and reproduction exists. In addition, how different types of serial ratios influence the metrical strength of rhythms remains to be elucidated. The present study investigated serial binary vs. non-binary ratios in a reproduction task. Rhythms formed with exclusively binary (1:2:4:8, non-binary integer (1:3:5:6, and non-integer (1:2.3:5.3:6.4 ratios were examined within a constant meter. The results showed that the 1:2:4:8 rhythm type was more accurately reproduced than the 1:3:5:6 and 1:2.3:5.3:6.4 rhythm types, and the 1:2.3:5.3:6.4 rhythm type was more accurately reproduced than the 1:3:5:6 rhythm type. Further analyses showed that reproduction performance was better predicted by the distribution pattern of event occurrences within an inter-beat interval, than by the coincidence of events with beats, or the magnitude and complexity of interval ratios. Whereas rhythm theories and empirical data emphasize the role of the coincidence of events with beats in determining metrical strength and predicting rhythm performance, the present results suggest that rhythm processing may be better understood when the distribution pattern of event occurrences is taken into account. These results provide new insights into the mechanisms underlining musical rhythm perception.

  1. Novel bacterial ratio for predicting fecal age

    Energy Technology Data Exchange (ETDEWEB)

    Nieman, J.; Brion, G.M. [Univ. of Kentucky, Dept. of Civil Engineering, Lexington, Kentucky (United States)]. E-mail: gbrion@engr.uky.edu

    2002-06-15

    This study presents an extension of ongoing research into the utility of the ratio of bacterial colonies isolated on membrane filters during the total coliform test using m-Endo broth media for the prediction of fecal age. Analysis of the relative shifts in concentrations of indicator bacterial populations in Kentucky River water quality data collected from the inlet of a local water treatment plant showed a correlation between raw concentrations of atypical colonies (AC) and total coliform colonies (TC) formed on m-Endo membrane filter tests, and fecal age. Visual analysis of plant treatment records showed that low values of the AC/TC ratio were related to periods of high flow, when runoff added fresh fecal material to the river. A more detailed analysis of 2 years of Kentucky River water quality data showed the average AC/TC ratio during months with high river flow (rain) to be 3.4, rising to an average of 27.6 during months with low flow. The average AC/TC ratio during high flow months compared to that found in other studies for raw human sewage (3.9) and the ratio increased to values associated with animal impacted urban runoff (18.9) during low flow months. (author)

  2. Mixing ratio sensor for alcohol mixed fuel

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Shigeru; Matsubara, Yoshihiro

    1987-08-24

    In order to improve the combustion efficiency of an internal combustion engine using gasoline-alcohol mixed fuel and to reduce harmful substance in its exhaust gas, it is necessary to control strictly the air-fuel ratio to be supplied and the ignition timing. In order to detect the mixing ratio of the mixed fuel, a mixing ratio sensor has so far been proposed to detect the above mixing ratio by casting a ray of light to the mixed fuel and utilizing a change of critical angle associated with the change of the composition of the fluid of the mixed fuel. However, because of the arrangement of its transparent substance in the fuel passage with the sealing material in between, this sensor invited the leakage of the fluid due to deterioration of the sealing material, etc. and its cost became high because of too many parts to be assembled. In view of the above, in order to reduce the number of parts, to lower the cost of parts and the assembling cost and to secure no fluid leakage from the fuel passage, this invention formed the above fuel passage and the above transparent substance both concerning the above mixing ratio sensor in an integrated manner using light transmitting resin. (3 figs)

  3. Mixing ratio sensor of alcohol mixed fuel

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Shigeru; Matsubara, Yoshihiro

    1987-08-07

    In order to improve combustion efficiency of an internal combustion engine using gasoline-alcohol mixed fuel and to reduce harmful substance in its exhaust gas, it is necessary to control strictly the air-fuel ratio to be supplied and the ignition timing and change the condition of control depending upon the mixing ratio of the mixed fuel. In order to detect the mixing ratio of the mixed fuel, the above mixing ratio has so far been detected by casting a ray of light to the mixed fuel and utilizing a change of critical angle associated with the change of the composition of the fluid of the mixed fuel. However, in case when a light emitting diode is used for the light source above, two kinds of sensors are further needed. Concerning the two kinds of sensors above, this invention offers a mixing ratio sensor for the alcohol mixed fuel which can abolish a temperature sensor to detect the environmental temperature by making a single compensatory light receiving element deal with the compensation of the amount of light emission of the light emitting element due to the temperature change and the compensation of the critical angle caused by the temperature change. (6 figs)

  4. Novel bacterial ratio for predicting fecal age

    International Nuclear Information System (INIS)

    Nieman, J.; Brion, G.M.

    2002-01-01

    This study presents an extension of ongoing research into the utility of the ratio of bacterial colonies isolated on membrane filters during the total coliform test using m-Endo broth media for the prediction of fecal age. Analysis of the relative shifts in concentrations of indicator bacterial populations in Kentucky River water quality data collected from the inlet of a local water treatment plant showed a correlation between raw concentrations of atypical colonies (AC) and total coliform colonies (TC) formed on m-Endo membrane filter tests, and fecal age. Visual analysis of plant treatment records showed that low values of the AC/TC ratio were related to periods of high flow, when runoff added fresh fecal material to the river. A more detailed analysis of 2 years of Kentucky River water quality data showed the average AC/TC ratio during months with high river flow (rain) to be 3.4, rising to an average of 27.6 during months with low flow. The average AC/TC ratio during high flow months compared to that found in other studies for raw human sewage (3.9) and the ratio increased to values associated with animal impacted urban runoff (18.9) during low flow months. (author)

  5. Golden ratio beauty as scientific function

    Directory of Open Access Journals (Sweden)

    Scott A. Olsen

    2018-01-01

    Full Text Available Normally when one is considering the golden ratio in the history of ideas, one is often looking at it as an aesthetic principle – usually associated with Greek art, sculpture and mathematics. However, in recent years the prevalence of the golden ratio within a broad range of scientific disciplines has brought its role in the perfection of science to the forefront. I would like to collapse these two areas by proposing a somewhat novel way of looking at the aesthetics of the golden ratio: its pervasive expression in scientific form and function is the basis of the aesthetics in the world. Therefore, science contains the same mathematical beauty as found in artistic expression. The golden ratio guides the Chaos Border of Kolmogorov, Arnold, and Moser (KAM theorem and it can be found hidden in all elementary particles, and even in the proportions of dark matter and energy relative to visible matter and energy. It is evident in the structure and growth functions of plants and animals and it can be found in the physiological functions of humans. It now appears that without the golden ratio, we would not have the form or function of the proton, cell, athlete, horse, species, planet, solar system or galaxy.

  6. D/H ratio for Jupiter

    International Nuclear Information System (INIS)

    Smith, H.; Schempp, W.V.; Baines, K.H.

    1989-01-01

    Observations of Jupiter's spectrum near the R5(0) HD line at 6063.88 A are reported. A feature with an equivalent width of 0.065 + or - 0.021 mA is coincident with the expected line. This feature is compared with HD profiles computed for inhomogeneous scattering models for Jupiter to yield a range for the Jovian D/H ratio of 1.0-2.9 x 10 to the -5th. This D/H ratio is in the lower range of previously reported D/H values for Jupiter and corresponds to an essentially solar D/H ratio for Jupiter. The detection of HD features in the presence of probable blends with spectral features of minor atmospheric hydrocarbon molecules is discussed. Such blends may make unambiguous identification of HD features difficult. 26 references

  7. Odor concentration invariance by chemical ratio coding

    Directory of Open Access Journals (Sweden)

    Naoshige Uchida

    2008-08-01

    Full Text Available Many animal species rely on chemical signals to extract ecologically important information from the environment. Yet in natural conditions chemical signals will frequently undergo concentration changes that produce differences in both level and pattern of activation of olfactory receptor neurons. Thus, a central problem in olfactory processing is how the system is able to recognize the same stimulus across different concentrations. To signal species identity for mate recognition, some insects use the ratio of two components in a binary chemical mixture to produce a code that is invariant to dilution. Here, using psychophysical methods, we show that rats also classify binary odor mixtures according to the molar ratios of their components, spontaneously generalizing over at least a tenfold concentration range. These results indicate that extracting chemical ratio information is not restricted to pheromone signaling and suggest a general solution for concentration-invariant odor recognition by the mammalian olfactory system.

  8. Isotope ratio in stellar atmospheres and nucleosynthesis

    International Nuclear Information System (INIS)

    Barbuy, B.L.S.

    1987-01-01

    The determination of isotopic ratios in stellar atmospheres is studied. The isotopic shift of atomic and molecular lines of different species of a certain element is examined. CH and MgH lines are observed in order to obtain the 12 C: 13 C and 24 Mg: 25 Mg: 26 Mg isotpic ratios. The formation of lines in stellar atmospheres is computed and the resulting synthetic spectra are employed to determine the isotopic abundances. The results obtained for the isotopic ratios are compared to predictions of nucleosynthesis theories. Finally, the concept of primary and secondary element is discussed, and these definitions are applied to the observed variations in the abundance of elements as a function of metallicity. (author) [pt

  9. Transport in a small aspect ratio torus

    International Nuclear Information System (INIS)

    White, R.B.; Gates, D.A.; Mynick, H.E.

    2005-01-01

    Transport theory in toroidal devices often assumes large aspect ratio and also assumes the poloidal field is small compared to the toroidal field. These assumptions result in transport which in the low collision rate limit is dominated by banana orbits, giving the largest collisionless excursion of a particle from an initial flux surface. However in a small aspect ratio device the gyro radius may be larger than the banana excursion, resulting in significant deviations from the standard neoclassical predictions. In this paper we report numerical simulation of diffusion in low and high beta low aspect ratio equilibria. We also sketch an analytic theory. The diffusion, which we refer to as omniclassical, is a combination of neoclassical and properly averaged classical effects, and can be two or three times the neoclassical value. Good agreement of the analytic theory with numerical simulations is obtained. (author)

  10. Maternal serum ratio of ghrelin to obestatin decreased in preeclampsia.

    Science.gov (United States)

    Wu, Weiguang; Fan, Xiaobin; Yu, Yuecheng; Wang, Yingchun

    2015-10-01

    Ghrelin, an endogenous for the growth hormone secretagogue receptor, has been shown to participate in blood pressure regulation. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. We hypothesized that ghrelin/obestatin imbalance played a role in the pathogenesis. This study was designed to determine the alterations of ghrelin and obestatin concentrations and ghrelin/obestatin ratio in maternal serum in preeclampsia. This retrospective case-control study included 31 preeclampsia and 31 gestational week-matched normal pregnancies. Ghrelin and obestatin concentrations in maternal serum were determined by radioimmunoassay, and the ghrelin/obestatin ratio was calculated. The ghrelin concentration and ghrelin/obestatin ratio in maternal serum were significantly lower in preeclampsia than in normal pregnancies (214.34±14.27pg/mL vs 251.49±16.15pg/mL, P=0.041, 1.07±0.09 vs 0.82±0.08, P=0.023). The obestatin concentration in maternal serum was significantly higher in preeclampsia than in normal pregnancies (276.35±15.38pg/mL vs 223.53±18.61pg/mL, P=0.019). The systolic blood pressure in preeclampsia was negatively correlated with ghrelin concentration and ghrelin/obestatin ratio (r=-0.549, P=0.003; r=-0.491, P=0.004) and was positively correlated with obestatin concentrations in preeclampsia (r=0.388, P=0.013). The findings of this study suggested disturbance of ghrelin and obestatin in maternal serum in preeclampsia, and ghrelin/obestatin imbalance might play a role in the pathogenesis of preeclampsia. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  11. The reaction index and positivity ratio revisited

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Andersen, Flemming

    2008-01-01

    BACKGROUND AND OBJECTIVES: Assessing the quality of patch test preparations continues to be a challenge. 2 parameters, the reaction index (RI) and positivity ratio (PR), have been proposed as quality indicators by the Information Network of Departments of Dermatology (IVDK). The value of these st......BACKGROUND AND OBJECTIVES: Assessing the quality of patch test preparations continues to be a challenge. 2 parameters, the reaction index (RI) and positivity ratio (PR), have been proposed as quality indicators by the Information Network of Departments of Dermatology (IVDK). The value...

  12. Uranium isotope ratio measurements in field settings

    International Nuclear Information System (INIS)

    Shaw, R.W.; Barshick, C.M.; Young, J.P.; Ramsey, J.M.

    1997-01-01

    The authors have developed a technique for uranium isotope ratio measurements of powder samples in field settings. Such a method will be invaluable for environmental studies, radioactive waste operations, and decommissioning and decontamination operations. Immediate field data can help guide an ongoing sampling campaign. The measurement encompasses glow discharge sputtering from pressed sample hollow cathodes, high resolution laser spectroscopy using conveniently tunable diode lasers, and optogalvanic detection. At 10% 235 U enrichment and above, the measurement precision for 235 U/( 235 U+ 238 U) isotope ratios was ±3%; it declined to ±15% for 0.3% (i.e., depleted) samples. A prototype instrument was constructed and is described

  13. Ultima Ratio as a Constitutional Principle

    Directory of Open Access Journals (Sweden)

    Kaarlo Tuori

    2013-01-01

    Full Text Available The paper argues the criminal law notion of ultima ratio is an instance of a broader constitutional law principle of proportionality. However, ultima ratio is not the only principle relevant in a constitutional assessment of criminalization. The role of ultima ratio is to impose limitations on criminalization. But constitutional doctrines also exist which call for criminalization and might even be seen as establishing a criminalization obligation. The paper examines three constitutional counter weights to ultima ratio. The first of these is discussed in the context of state constitutions. This is the cluster of the interrelated constitutional doctrines of the horizontal effect of fundamental rights and the protective duty of the state, as well as the understanding of collective security as a basic right. These doctrines are analysed in the light of the praxis of the German Constitutional Court and the Finnish Constitutional Law Committee. The two other constitutional counterweights are discussed at the level of the transnational, European constitution. These are the principles of precaution and effectiveness. Este artículo defiende que el concepto de ultima ratio es una instancia más amplia del principio de proporcionalidad dentro del derecho constitucional. Sin embargo, el ultima ratio no es el único principio relevante en la valoración constitucional de la criminalización. El papel del ultima ratio es imponer límites a la criminalización. Pero también existen doctrinas constitucionales que exigen la criminalización e incluso dan pie a entender que obligan a establecer una pena. El documento examina tres contrapesos constitucionales al ultima ratio. En primer lugar, se analiza en el contexto de las constituciones estatales. Este es el conjunto de las doctrinas constitucionales interrelacionadas entre el efecto horizontal de los derechos fundamentales y el deber de protección del Estado, así como la asunción de la seguridad colectiva

  14. Radioactive anomaly discrimination from spectral ratios

    Science.gov (United States)

    Maniscalco, James; Sjoden, Glenn; Chapman, Mac Clements

    2013-08-20

    A method for discriminating a radioactive anomaly from naturally occurring radioactive materials includes detecting a first number of gamma photons having energies in a first range of energy values within a predetermined period of time and detecting a second number of gamma photons having energies in a second range of energy values within the predetermined period of time. The method further includes determining, in a controller, a ratio of the first number of gamma photons having energies in the first range and the second number of gamma photons having energies in the second range, and determining that a radioactive anomaly is present when the ratio exceeds a threshold value.

  15. Ratio method of measuring W boson mass

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Feng [Stony Brook Univ., NY (United States)

    2010-08-01

    This dissertation describes an alternative method of measuring the W boson mass in DØ experiment. Instead of extracting MW from the fitting of W → ev fast Monte Carlo simulations to W → ev data as in the standard method, we make the direct fit of transverse mass between W → ev data and Z → ee data. One of the two electrons from Z boson is treated as a neutrino in the calculation of transverse mass. In ratio method, the best fitted scale factor corresponds to the ratio of W and Z boson mass (MW/MZ). Given the precisely measured Z boson mass, W mass is directly fitted from W → ev and Z → ee data. This dissertation demonstrates that ratio method is a plausible method of measuring the W boson mass. With the 1 fb-1 DØ Run IIa dataset, ratio method gives MW = 80435 ± 43(stat) ± 26(sys) MeV.

  16. Decay ratio for third order Brownian oscillators

    International Nuclear Information System (INIS)

    Konno, H.; Kanemoto, S.

    1998-01-01

    We have obtained the analytical expressions of the decay ratios for two types of third order Brownian oscillators which are generalizations of the second order Brownian oscillator driven by the Gaussian-white noise. The resulting expressions will provide us useful baseline information for more complicated practical problems and their applications

  17. Bowen ratio over the Norway spruce stand

    Czech Academy of Sciences Publication Activity Database

    Taufarová, Klára; Dvořáková, Marcela; Czerný, Radek; Pokorný, Radek; Janouš, Dalibor

    2007-01-01

    Roč. 20, č. 1 (2007), s. 131-136 ISSN 1803-1013 R&D Projects: GA ČR GD526/03/H036; GA MŽP SM/640/18/03 Institutional research plan: CEZ:AV0Z60870520 Keywords : Bowen ratio * evapotranspiration * transpiration * eddy covariance technique Subject RIV: DG - Athmosphere Sciences, Meteorology

  18. Crown ratio influences allometric scaling in trees

    Science.gov (United States)

    Annikki Makela; Harry T. Valentine

    2006-01-01

    Allometric theories suggest that the size and shape of organisms follow universal rules, with a tendency toward quarter-power scaling. In woody plants, however, structure is influenced by branch death and shedding, which leads to decreasing crown ratios, accumulation of heartwood, and stem and branch tapering. This paper examines the impacts on allometric scaling of...

  19. Measuring Poisson Ratios at Low Temperatures

    Science.gov (United States)

    Boozon, R. S.; Shepic, J. A.

    1987-01-01

    Simple extensometer ring measures bulges of specimens in compression. New method of measuring Poisson's ratio used on brittle ceramic materials at cryogenic temperatures. Extensometer ring encircles cylindrical specimen. Four strain gauges connected in fully active Wheatstone bridge self-temperature-compensating. Used at temperatures as low as liquid helium.

  20. Multipole mixing ratios in /sup 154/Gd

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Won Mo; Song, Choong Sik; Joo, Koan Sik

    1985-06-01

    We have measured gamma-gamma angular correlations to determine the mixing ratios of several gamma transitions in /sup 154/Gd. The results are compared with those derived from the pairing-plus-quadrupole model and from the interacting boson model.

  1. Factors affecting egg ratios in planktonic rotifers

    NARCIS (Netherlands)

    Sarma, S.S.S.; Gulati, R.D.; Nandini, S.

    2005-01-01

    Edmondson’s egg ratio (number of amictic eggs per female) is an important life history variable, which has been in wide use to understand and predict patterns of population growth in planktonic rotifers under field conditions. It is also useful as an indicator of the health of rotifers under culture

  2. 34 CFR 668.172 - Financial ratios.

    Science.gov (United States)

    2010-07-01

    ... effect of changes in accounting principles, and the effect of changes in accounting estimates; (2) May... intangible assets defined as intangible in accordance with generally accepted accounting principles; and (5... 34 Education 3 2010-07-01 2010-07-01 false Financial ratios. 668.172 Section 668.172 Education...

  3. Abundance Ratios in Dwarf Elliptical Galaxies

    NARCIS (Netherlands)

    Sen, Seyda; Peletier, Reynier F.; Toloba, Elisa; Mentz, Jaco J.

    The aim of this study is to determine abundance ratios and star formation histories (SFH) of dwarf ellipticals in the nearby Virgo cluster. We perform a stellar population analysis of 39 dEs and study them using index-index and scaling relations. We find an unusual behaviour where [Na/Fe] is

  4. Asymptotics for ratios with applications to reinsurance

    NARCIS (Netherlands)

    Ladoucette, S.A.; Teugels, J.L.

    2007-01-01

    This paper provides an overview of results pertaining to moment convergence for certain ratios of random variables involving sums, order statistics and extreme terms in the sense of modulus. Most of the literature on this matter originates from Darling (1952) who gave a criterion for the convergence

  5. Influence of pollution of boron chlorinity ratio

    Digital Repository Service at National Institute of Oceanography (India)

    Narvekar, P.V.; Zingde, M.D.

    Presence of boron in domestic wastewater has resulted in high B/CI ratio at some locations in the coastal water around Bombay. A widest range (0.215-0.281) of B/CI was observed at a location with high influence of wastewater release. The mean B...

  6. 12 CFR 567.8 - Leverage ratio.

    Science.gov (United States)

    2010-01-01

    ... anticipating or experiencing significant growth and have well-diversified risks, including no undue interest rate risk exposure, excellent asset quality, high liquidity, and good earnings. (b) For all savings... capital ratios may be required if warranted by the particular circumstances or risk profiles of an...

  7. Likelihood-ratio-based biometric verification

    NARCIS (Netherlands)

    Bazen, A.M.; Veldhuis, Raymond N.J.

    2002-01-01

    This paper presents results on optimal similarity measures for biometric verification based on fixed-length feature vectors. First, we show that the verification of a single user is equivalent to the detection problem, which implies that for single-user verification the likelihood ratio is optimal.

  8. Likelihood Ratio-Based Biometric Verification

    NARCIS (Netherlands)

    Bazen, A.M.; Veldhuis, Raymond N.J.

    The paper presents results on optimal similarity measures for biometric verification based on fixed-length feature vectors. First, we show that the verification of a single user is equivalent to the detection problem, which implies that, for single-user verification, the likelihood ratio is optimal.

  9. Neutrophil Lymphocyte Ratio Predicts Postoperative Pain after ...

    African Journals Online (AJOL)

    Background and Aim: Postoperative pain is well known and usually disturbing complication of surgery. Inflammation plays an important role in the development and progression of postoperative pain. We aimed to investigate possible relationship between preoperatively measured neutrophil‑lymphocyte ratio (NLR) – as an ...

  10. The European Stability Pact and the Effect of Uncertainty on the Debt and Deficit Ratios

    DEFF Research Database (Denmark)

    Rubin, Jonathan

    to pecuniary sanctions. To provide a framework for an economic analysis of this proposed "stability and growth pact", this paper examines the dynamics of these interdependent ratios. The model demonstrates that the time path for the debt/GDP ratio is highly sensitive to the assumptions made about economic......Proposed regulations aimed at promoting fiscal discipline among states participating in the Economic and Monetary Union (EMU) employ dept-to-GDP and deficit-to-GDP ratios as criteria for fiscal performance. Countries participating in EMU are expected to maintain these criteria or be subject...

  11. Mother's occupation and sex ratio at birth

    Directory of Open Access Journals (Sweden)

    Amiot Volodymyr

    2010-05-01

    Full Text Available Abstract Background Many women are working outside of the home, occupying a multitude of jobs with varying degrees of responsibilities and levels of psychological stress. We investigated whether different job types in women are associated with child sex at birth, with the hypothesis that women in job types, which are categorized as "high psychological stress" jobs, would be more likely to give birth to a daughter than a son, as females are less vulnerable to unfavourable conditions during conception, pregnancy and after parturition, and are less costly to carry to term. Methods We investigated the effects of mother's age, maternal and paternal job type (and associated psychological stress levels and paternal income on sex ratio at birth. Our analyses were based on 16,384 incidences of birth from a six-year (2000 to 2005 inclusive childbirth dataset from Addenbrooke's Hospital in Cambridge, UK. We obtained a restricted data set from Addenbrooke's hospital with: maternal age, maternal and paternal occupations, and whether or not the child was first-born. Results Women in job types that were categorized as "high stress" were more likely to give birth to daughters, whereas women in job types that were categorized as "low stress" had equal sex ratios or a slight male bias in offspring. We also investigated whether maternal age, and her partner's income could be associated with reversed offspring sex ratio. We found no association between mother's age, her partner's job stress category or partner income on child sex. However, there was an important interaction between job stress category and partner income in some of the analyses. Partner income appears to attenuate the association between maternal job stress and sex ratios at moderate-income levels, and reverse it at high-income levels. Conclusions To our knowledge this is the first report on the association between women's job type stress categories and offspring sex ratio in humans, and the

  12. Variable Ratio Hydrostatic Transmission Simulator for Optimal Wind Power Drivetrains

    Directory of Open Access Journals (Sweden)

    Jose M. Garcia-Bravo

    2017-01-01

    Full Text Available This work presents a hydromechanical transmission coupled to an electric AC motor and DC generator to simulate a wind power turbine drive train. The goal of this project was to demonstrate and simulate the ability of a hydrostatic variable ratio system to produce constant electric power at varying wind speeds. The experimental results show that the system can maintain a constant voltage when a 40% variation in input speed is produced. An accompanying computer simulation of the system was built and experimentally validated showing a discrete error no larger than 12%. Both the simulation and the experimental results show that the electrical power output can be regulated further if an energy storage device is used to absorb voltage spikes produced by abrupt changes in wind speed or wind direction.

  13. Characterizing gamma fields using isomeric activation ratios

    Science.gov (United States)

    Venkataraman, Ramkumar; Fleming, Ronald F.

    1994-12-01

    Isomeric activities were induced in indium by gamma irradiation in three different gamma fields, through the reactions 115In(γ, γ') 115mIn and 113In(γ, γ') 113mIn. The irradiation fields were (i) the 15 kCi 60Co source available in the University, (ii) the spent fuel gamma irradiator in the pool of the University's Ford Nuclear Reactor (FNR) and (iii) south face of the core of the FNR during routine shut downs. Isomeric activation ratios can serve to characterize gamma fields, provided the response functions of the two (γ, γ') reactions sample different energy regimes of the gamma spectrum present in the irradiation fields. The response of an isomeric activation detector, in turn, depends on the number of activation energy levels of the nuclide and the probabilities with which the activation levels de-populate to the isomeric level. The reaction rate ratio RIn115m/ RIn113m was measured in the three gamma fields. The measured ratios were (i) 1.210 ± 0.011 in the 60Co source, (ii) 1.314 ± 0.060 in the spent fuel gamma irradiator and (iii) 1.298 ± 0.039 in a location alongside the FNR core during routine shut downs. The measured reaction rate ratios are not only close to each other, but close to unity as well. This indicates that the excitation functions for the reactions 115In(γ, γ') 115mIn and 113In(γ, γ') 113mIn have similar shapes and that for the nuclides 115In and 113In, the number of activation energy levels and the probabilities with which they populate the isomeric levels are very similar to each other. Thus, the ratio RIn115m/ RIn113m will not yield any information regarding the shape of gamma spectrum in the field of measurement. However by choosing (γ, γ') reactions with different shapes for the excitation functions one can measure a set of isomeric activation ratios that characterize a given gamma field.

  14. PRELP (proline/arginine-rich end leucine-rich repeat protein) promotes osteoblastic differentiation of preosteoblastic MC3T3-E1 cells by regulating the β-catenin pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Haiying; Cui, Yazhou; Luan, Jing [School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Science, Ji' nan, Shandong (China); Key Laboratory for Rare Disease Research of Shandong Province, Key Laboratory for Biotech Drugs of the Ministry of Health, Shandong Medical Biotechnological Center, Shandong Academy of Medical Sciences, Ji' nan, Shandong (China); Zhang, Xiumei [School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Science, Ji' nan, Shandong (China); Li, Chengzhi; Zhou, Xiaoyan; Shi, Liang [School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Science, Ji' nan, Shandong (China); Key Laboratory for Rare Disease Research of Shandong Province, Key Laboratory for Biotech Drugs of the Ministry of Health, Shandong Medical Biotechnological Center, Shandong Academy of Medical Sciences, Ji' nan, Shandong (China); Wang, Huaxin [Shandong University of Traditional Chinese Medicine, Ji' an, Shandong (China); Han, Jinxiang, E-mail: jxhan9888@aliyun.com [School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Science, Ji' nan, Shandong (China); Key Laboratory for Rare Disease Research of Shandong Province, Key Laboratory for Biotech Drugs of the Ministry of Health, Shandong Medical Biotechnological Center, Shandong Academy of Medical Sciences, Ji' nan, Shandong (China)

    2016-02-12

    Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a collagen-binding proteoglycan highly expressed in the developing bones. Recent studies indicated that PRELP could inhibit osteoclastogenesis as a NF-κB inhibitor. However, its role during osteoblast differentiation is still unclear. In this study, we confirmed that the expression of PRELP increased with the osteogenesis induction of preosteoblastic MC3T3-E1 cells. Down-regulation of PRELP expression by shRNA reduced ALP activity, mineralization and expression of osteogenic marker gene Runx2. Our microarray analysis data suggested that β-catenin may act as a hub gene in the PRELP-mediated gene network. We validated furtherly that PRELP knockdown could inhibit the level of connexin43, a key regulator of osteoblast differentiation by affecting β-catenin protein expression, and its nuclear translocation in MC3T3-E1 preosteoblasts. Therefore, this study established a new role of PRELP in modulating β-catenin/connexin43 pathway and osteoblast differentiation.

  15. Econometric models for predicting confusion crop ratios

    Science.gov (United States)

    Umberger, D. E.; Proctor, M. H.; Clark, J. E.; Eisgruber, L. M.; Braschler, C. B. (Principal Investigator)

    1979-01-01

    Results for both the United States and Canada show that econometric models can provide estimates of confusion crop ratios that are more accurate than historical ratios. Whether these models can support the LACIE 90/90 accuracy criterion is uncertain. In the United States, experimenting with additional model formulations could provide improved methods models in some CRD's, particularly in winter wheat. Improved models may also be possible for the Canadian CD's. The more aggressive province/state models outperformed individual CD/CRD models. This result was expected partly because acreage statistics are based on sampling procedures, and the sampling precision declines from the province/state to the CD/CRD level. Declining sampling precision and the need to substitute province/state data for the CD/CRD data introduced measurement error into the CD/CRD models.

  16. True gender ratios and stereotype rating norms

    Directory of Open Access Journals (Sweden)

    Alan eGarnham

    2015-07-01

    Full Text Available We present a study comparing, in English, perceived distributions of men and women in 422 named occupations with actual real world distributions. The first set of data was obtained from previous a large-scale norming study, whereas the second set was mostly drawn from UK governmental sources. In total, real world ratios for 290 occupations were obtained for our perceive vs. real world comparison, of which 205 were deemed to be unproblematic. The means for the two sources were similar and the correlation between them was high, suggesting that people are generally accurate at judging real gender ratios, though there were some notable exceptions. Beside this correlation, some interesting patterns emerged from the two sources, suggesting some response strategies when people complete norming studies. We discuss these patterns in terms of the way real world data might complement norming studies in determining gender stereotypicality.

  17. Influence of forest disturbance on stable nitrogen isotope ratios in soil and vegetation profiles

    Science.gov (United States)

    Jennifer D. Knoepp; Scott R. Taylor; Lindsay R. Boring; Chelcy F. Miniat

    2015-01-01

    Soil and plant stable nitrogen isotope ratios (15 N) are influenced by atmospheric nitrogen (N) inputs and processes that regulate organic matter (OM) transformation and N cycling. The resulting 15N patterns may be useful for discerning ecosystem differences in N cycling. We studied two ecosystems; longleaf pine wiregrass (...

  18. 34 CFR Appendix A to Subpart L of... - Ratio Methodology for Proprietary Institutions

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Ratio Methodology for Proprietary Institutions A Appendix A to Subpart L of Part 668 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STUDENT ASSISTANCE GENERAL PROVISIONS...

  19. 34 CFR Appendix B to Subpart L of... - Ratio Methodology for Private Non-Profit Institutions

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Ratio Methodology for Private Non-Profit Institutions B Appendix B to Subpart L of Part 668 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STUDENT ASSISTANCE GENERAL PROVISIONS...

  20. Adjusted Money's Worth Ratios in Life Annuities

    OpenAIRE

    Jaime Casassus; Eduardo Walker

    2013-01-01

    The Money's Worth Ratio (MWR) measures an annuity's actuarial fairness. It is calculated as the discounted present value of expected future payments divided by its cost. We argue that from the perspective of annuitants, this measure may overestimate the value-for-money obtained, since it does not adjust for liquidity or risk factors. Measuring these factors is challenging, requiring detailed knowledge of assets, liabilities, and of the stochastic processes followed by them. Using a multi-fact...

  1. Modelling the liquidity ratio as macroprudential instrument

    OpenAIRE

    Jan Willem van den End; Mark Kruidhof

    2012-01-01

    The Basel III Liquidity Coverage Ratio (LCR) is a microprudential instrument to strengthen the liquidity position of banks. However, if in extreme scenarios the LCR becomes a binding constraint, the interaction of bank behaviour with the regulatory rule can have negative externalities. We simulate the systemic implications of the LCR by a liquidity stress-testing model, which takes into account the impact of bank reactions on second round feedback effects. We show that a flexible approach of ...

  2. Realisation Ratios in the Capital Expenditure Survey

    OpenAIRE

    Leon Berkelmans; Gareth Spence

    2013-01-01

    The Australian Bureau of Statistics capital expenditure survey is one of the inputs into the Reserve Bank’s forecasts for private business investment. This article considers several methods for interpreting the expectations data from this survey and evaluates these methods using out-of-sample forecasts. Forecasts based on long-run average realisation ratios are found to be the most accurate of the options considered, although the use of these forecasts for predicting investment in the nationa...

  3. Production ratio of pseudoscalar to vector mesons

    International Nuclear Information System (INIS)

    Chliapnikov, P.V.; Uvarov, V.A.

    1990-01-01

    The P/V ratio of directly produced pseudoscalar (P) to vector (V) mesons is analysed using the data on the K S 0 and K * (892) total inclusive cross sections in pp, π + p and K ± p reactions. The indication for a change of P/V from a value of about 1 at low energies, where the fragmentation processes dominate, to a value of 1/3, suggested by spin-statistics, at high energies is discussed. (orig.)

  4. MARKETING MIX BY BED OCCUPANCY RATIO (BOR

    Directory of Open Access Journals (Sweden)

    Abdul Muhith

    2017-04-01

    Full Text Available Introduction: Bed Occupancy Ratio (BOR in RSI Arafah Mojosari during the last three years are at under ideal rate and the lowest of the three existing hospitals in the area of Mojosari. The purpose of this study was to determine the relationship marketing mix with Bed Occupancy Ratio in RSI Arafah Mojosari. Methods: This research uses analytic methods with crossectional approach. Variables in the study is marketing mix and Bed Occupancy Ratio (BOR. The population in this study were all patients hospitalized in the RSI Arafah Mojosari. Samples amounted 44 respondents taken by the Stratified random sampling technique. Data were collected using the questionnaire and analyzed using Fisher's Exact test. Result: The results obtained more than 50% of respondents (59.1% rate well against the marketing mix is developed by the hospital management and the majority of respondents (79.5% are in the treatment room that has a number BOR is not ideal. Fisher Exact test test results obtained probabililty value=0.02<0.05 so that H0 is rejected, which means there is a relationship marketing mix with the Bed Occupancy Ratio in RSI Arafah Mojosari. Discussion: Hospitals which able to develop the marketing mix very well, can attract consumers to use inpatient services at the hospital, with that BOR value will increase as the increased use of inpatient services. Hospital management must be able to formulate a good marketing mix strategy that hospital marketing objectives can be achieved. Conformity between service quality and service rates must be addressed, otherwise it extent of media promotions can attract patients to inpatient services.

  5. Implications of Fast Reactor Transuranic Conversion Ratio

    International Nuclear Information System (INIS)

    Piet, Steven J.; Hoffman, Edward A.; Bays, Samuel E.

    2010-01-01

    Theoretically, the transuranic conversion ratio (CR), i.e. the transuranic production divided by transuranic destruction, in a fast reactor can range from near zero to about 1.9, which is the average neutron yield from Pu239 minus 1. In practice, the possible range will be somewhat less. We have studied the implications of transuranic conversion ratio of 0.0 to 1.7 using the fresh and discharge fuel compositions calculated elsewhere. The corresponding fissile breeding ratio ranges from 0.2 to 1.6. The cases below CR=1 ('burners') do not have blankets; the cases above CR=1 ('breeders') have breeding blankets. The burnup was allowed to float while holding the maximum fluence to the cladding constant. We graph the fuel burnup and composition change. As a function of transuranic conversion ratio, we calculate and graph the heat, gamma, and neutron emission of fresh fuel; whether the material is 'attractive' for direct weapon use using published criteria; the uranium utilization and rate of consumption of natural uranium; and the long-term radiotoxicity after fuel discharge. For context, other cases and analyses are included, primarily once-through light water reactor (LWR) uranium oxide fuel at 51 MWth-day/kg-iHM burnup (UOX-51). For CR 1, heat, gamma, and neutron emission decrease with recycling. The uranium utilization exceeds 1%, especially as all the transuranic elements are recycled. exceeds 1%, especially as all the transuranic elements are recycled. At the system equilibrium, heat and gamma vary by somewhat over an order of magnitude as a function of CR. Isotopes that dominate heat and gamma emission are scattered throughout the actinide chain, so the modest impact of CR is unsurprising. Neutron emitters are preferentially found among the higher actinides, so the neutron emission varies much stronger with CR, about three orders of magnitude.

  6. Surface area-volume ratios in insects.

    Science.gov (United States)

    Kühsel, Sara; Brückner, Adrian; Schmelzle, Sebastian; Heethoff, Michael; Blüthgen, Nico

    2017-10-01

    Body mass, volume and surface area are important for many aspects of the physiology and performance of species. Whereas body mass scaling received a lot of attention in the literature, surface areas of animals have not been measured explicitly in this context. We quantified surface area-volume (SA/V) ratios for the first time using 3D surface models based on a structured light scanning method for 126 species of pollinating insects from 4 orders (Diptera, Hymenoptera, Lepidoptera, and Coleoptera). Water loss of 67 species was measured gravimetrically at very dry conditions for 2 h at 15 and 30 °C to demonstrate the applicability of the new 3D surface measurements and relevance for predicting the performance of insects. Quantified SA/V ratios significantly explained the variation in water loss across species, both directly or after accounting for isometric scaling (residuals of the SA/V ∼ mass 2/3 relationship). Small insects with a proportionally larger surface area had the highest water loss rates. Surface scans of insects to quantify allometric SA/V ratios thus provide a promising method to predict physiological responses, improving the potential of body mass isometry alone that assume geometric similarity. © 2016 Institute of Zoology, Chinese Academy of Sciences.

  7. Bankruptcy Prediction Based on the Autonomy Ratio

    Directory of Open Access Journals (Sweden)

    Daniel Brîndescu Olariu

    2016-11-01

    Full Text Available The theory and practice of the financial ratio analysis suggest the existence of a negative correlation between the autonomy ratio and the bankruptcy risk. Previous studies conducted on a sample of companies from Timis County (largest county in Romania confirm this hypothesis and recommend the autonomy ratio as a useful tool for measuring the bankruptcy risk two years in advance. The objective of the current research was to develop a methodology for measuring the bankruptcy risk that would be applicable for the companies from the Timis County (specific methodologies are considered necessary for each region. The target population consisted of all the companies from Timis County with annual sales of over 10,000 lei (aprox. 2,200 Euros. The research was performed over all the target population. The study has thus included 53,252 yearly financial statements from the period 2007 – 2010. The results of the study allow for the setting of benchmarks, as well as the configuration of a methodology of analysis. The proposed methodology cannot predict with perfect accuracy the state of the company, but it allows for a valuation of the risk level to which the company is subjected.

  8. Cold versus hot fusion deuterium branching ratios

    International Nuclear Information System (INIS)

    Fox, H.; Bass, R.

    1995-01-01

    A major source of misunderstanding of the nature of cold nuclear fusion has been the expectation that the deuterium branching ratios occurring within a palladium lattice would be consistent with the gas-plasma branching ratios. This misunderstanding has led to the concept of the dead graduate student, the 1989's feverish but fruitless search for neutron emissions from cold fusion reactors, and the follow-on condemnation of the new science of cold fusion. The experimental facts are that in a properly loaded palladium lattice, the deuterium fusion produces neutrons at little above background, a greatly less-than-expected production of tritium (the tritium desert), and substantially more helium-4 than is observed in hot plasma physics. The experimental evidence is now compelling (800 reports of success from 30 countries) that cold nuclear fusion is a reality, that the branching ratios are unexpected, and that a new science is struggling to be recognized. Commercialization of some types of cold fusion devices has already begun

  9. Statistical moments of the Strehl ratio

    Science.gov (United States)

    Yaitskova, Natalia; Esselborn, Michael; Gladysz, Szymon

    2012-07-01

    Knowledge of the statistical characteristics of the Strehl ratio is essential for the performance assessment of the existing and future adaptive optics systems. For full assessment not only the mean value of the Strehl ratio but also higher statistical moments are important. Variance is related to the stability of an image and skewness reflects the chance to have in a set of short exposure images more or less images with the quality exceeding the mean. Skewness is a central parameter in the domain of lucky imaging. We present a rigorous theory for the calculation of the mean value, the variance and the skewness of the Strehl ratio. In our approach we represent the residual wavefront as being formed by independent cells. The level of the adaptive optics correction defines the number of the cells and the variance of the cells, which are the two main parameters of our theory. The deliverables are the values of the three moments as the functions of the correction level. We make no further assumptions except for the statistical independence of the cells.

  10. Omniclassical Diffusion in Low Aspect Ratio Tokamaks

    International Nuclear Information System (INIS)

    Mynick, H.E.; White, R.B.; Gates, D.A.

    2004-01-01

    Recently reported numerical results for axisymmetric devices with low aspect ratio A found radial transport enhanced over the expected neoclassical value by a factor of 2 to 3. In this paper, we provide an explanation for this enhancement. Transport theory in toroidal devices usually assumes large A, and that the ratio B p /B t of the poloidal to the toroidal magnetic field is small. These assumptions result in transport which, in the low collision limit, is dominated by banana orbits, giving the largest collisionless excursion of a particle from an initial flux surface. However in a small aspect ratio device one may have B p /B t ∼ 1, and the gyroradius may be larger than the banana excursion. Here, we develop an approximate analytic transport theory valid for devices with arbitrary A. For low A, we find that the enhanced transport, referred to as omniclassical, is a combination of neoclassical and properly generalized classical effects, which become dominant in the low-A, B p /B t ∼ 1 regime. Good agreement of the analytic theory with numerical simulations is obtained

  11. KERMA ratios in pediatric CT dosimetry

    International Nuclear Information System (INIS)

    Huda, Walter; Ogden, Kent M.; Lavallee, Robert L.; Roskopf, Marsha L.; Scalzetti, Ernest M.

    2012-01-01

    Patient organ doses may be estimated from CTDI values. More accurate estimates may be obtained by measuring KERMA (Kinetic Energy Released in Matter) in anthropomorphic phantoms and referencing these values to free-in-air X-ray intensity. To measure KERMA ratios (R K ) in pediatric phantoms at CT. CT scans produce an air KERMA K in a phantom and an air KERMA K CT at isocenter. KERMA ratios (R K ) are defined as (K/K CT ), measured using TLD chips in phantoms representing newborns to 10-year-olds. R K in the newborn is approximately constant. For the other phantoms, there is a peak R K value in the neck. The median R K values for the GE scanner at 120 kV were 0.92, 0.83, 0.77 and 0.76 for newborns, 1-year-olds, 5-year-olds and 10-year-olds, respectively. Organ R K values were 0.91 ± 0.04, 0.84 ± 0.07, 0.74 ± 0.09 and 0.72 ± 0.10 in newborns, 1-year-olds, 5-year-olds and 10-year-olds, respectively. At 120 kV, a Siemens Sensation 16 scanner had R K values 5% higher than those of the GE LightSpeed Ultra. KERMA ratios may be combined with air KERMA measurements at the isocenter to estimate organ doses in pediatric CT patients. (orig.)

  12. Physical Conditions Regulate the Fungal to Bacterial Ratios of a Tropical Suspended Soil

    Directory of Open Access Journals (Sweden)

    Julian Donald

    2017-12-01

    Full Text Available As a source of ‘suspended soils’, epiphytes contribute large amounts of organic matter to the canopy of tropical rain forests. Microbes associated with epiphytes are responsible for much of the nutrient cycling taking place in rain forest canopies. However, soils suspended far above the ground in living organisms differ from soil on the forest floor, and traditional predictors of soil microbial community composition and functioning (nutrient availability and the activity of soil organisms are likely to be less important. We conducted an experiment in the rain forest biome at the Eden Project in the U.K. to explore how biotic and abiotic conditions determine microbial community composition and functioning in a suspended soil. To simulate their natural epiphytic lifestyle, bird’s nest ferns (Asplenium nidus were placed on a custom-built canopy platform suspended 8 m above the ground. Ammonium nitrate and earthworm treatments were applied to ferns in a factorial design. Extracellular enzyme activity and Phospholipid Fatty Acid (PLFA profiles were determined at zero, three and six months. We observed no significant differences in either enzyme activity or PLFA profiles between any of the treatments. Instead, we observed decreases in β-glucosidase and N-acetyl-glucosaminidase activity, and an increase in phenol oxidase activity across all treatments and controls over time. An increase in the relative abundance of fungi during the experiment meant that the microbial communities in the Eden Project ferns after six months were comparable with ferns sampled from primary tropical rain forest in Borneo.

  13. Circulating Follistatin Is Liver-Derived and Regulated by the Glucagon-to-Insulin Ratio

    DEFF Research Database (Denmark)

    Hansen, Jakob S; Rutti, Sabine; Arous, Caroline

    2016-01-01

    CONTEXT: Follistatin is a plasma protein recently reported to increase under conditions with negative energy balance, such as exercise and fasting in humans. Currently, the perception is that circulating follistatin is a result of para/autocrine actions from various tissues. The large and acute i...

  14. Building Coverage Ratio at the Eastern Corridor of Jalan Ir. H. Djuanda Bandung

    Science.gov (United States)

    Megayanti, T.; Widaningsih, L.; Minggra, R.; Dewi, N. I. K.

    2018-01-01

    Historically in the Colonial period, the Corridor of Jalan Ir. H. Juanda or better known as Jalan Dago was designed as a residential area. As the high development of commercial activity along of Bandung City, almost all of buildings in this area are turned its’ function to supported commercial activity. The change is shown in many aspects from the shape of the building and even occur in changing the old building into a new one due to a high intensity of this commercial activity. This paper investigates the use of Building Coverage Ratio regulation related to functional change in the Corridor of Jalan Ir. H. Juanda Bandung. The aim is to what extent the regulations related to Building Coverage area are implemented. This study used a descriptive qualitative method by conducting observation to identify buildings on the Corridor by dividing it into three segments. The results show quantitatively there is a lot of irrelevancies to Building Coverage Ratio regulation which is shown in the second and third segment. Most of the building in the first segment has in compliance with the regulation. However, to build a harmony in characters of City corridor is not only created by Building Coverage Ratio but also others parameters such as the land use, the shape of buildings, façade, and design concept. Thus, it is highly recommended to create a detail regulation regarding those parameters.

  15. Invited review: sex ratio and rheumatic disease.

    Science.gov (United States)

    Lockshin, M D

    2001-11-01

    Human illnesses affect men and women differently. In some cases (diseases of sex organs, diseases resulting from X or Y chromosome mutations), reasons for sex discrepancy are obvious, but in other cases no reason is apparent. Explanations for sex discrepancy of illness occur at different biological levels: molecular (e.g., imprinting, X-inactivation), cellular (sex-specific receptor activity), organ (endocrine influences), whole organism (size, age), and environmental-behavioral, including intrauterine influences. Autoimmunity represents a prototypical class of illness that has high female-to-male (F/M) ratios. Although the F/M ratios in autoimmune diseases are usually attributed to the influence of estrogenic hormones, evidence demonstrates that the attributed ratios are imprecise and that definitions and classifications of autoimmune diseases vary, rendering at least part of the counting imprecise. In addition, many studies on sex discrepancy of human disease fail to distinguish between disease incidence and disease severity. In April 2001, the Institute of Medicine of the National Academy of Sciences published Exploring the Biological Contributions to Human Health: Does Sex Matter? (Wizemann T and Pardue M-L, editors). This minireview summarizes the section of that report that concerns autoimmune and infectious disease. Some thyroid, rheumatic, and hepatic autoimmune diseases have high F/M ratios, whereas others have low. Those that have high ratios occur primarily in young adulthood. Gonadal hormones, if they play a role, likely do so through a threshold or permissive mechanism. Examples of sex differences that could be caused by environmental exposure, X inactivation, imprinting, X or Y chromosome genetic modulators, and intrauterine influences are presented as alternate, theoretical, and largely unexplored explanations for sex differences of incidence. The epidemiology of autoimmune diseases (young, female) suggests that an explanation for sex discrepancy of

  16. Identifying Malignant Pleural Effusion by A Cancer Ratio (Serum LDH: Pleural Fluid ADA Ratio).

    Science.gov (United States)

    Verma, Akash; Abisheganaden, John; Light, R W

    2016-02-01

    We studied the diagnostic potential of serum lactate dehydrogenase (LDH) in malignant pleural effusion. Retrospective analysis of patients hospitalized with exudative pleural effusion in 2013. Serum LDH and serum LDH: pleural fluid ADA ratio was significantly higher in cancer patients presenting with exudative pleural effusion. In multivariate logistic regression analysis, pleural fluid ADA was negatively correlated 0.62 (0.45-0.85, p = 0.003) with malignancy, whereas serum LDH 1.02 (1.0-1.03, p = 0.004) and serum LDH: pleural fluid ADA ratio 0.94 (0.99-1.0, p = 0.04) was correlated positively with malignant pleural effusion. For serum LDH: pleural fluid ADA ratio, a cut-off level of >20 showed sensitivity, specificity of 0.98 (95 % CI 0.92-0.99) and 0.94 (95 % CI 0.83-0.98), respectively. The positive likelihood ratio was 32.6 (95 % CI 10.7-99.6), while the negative likelihood ratio at this cut-off was 0.03 (95 % CI 0.01-0.15). Higher serum LDH and serum LDH: pleural fluid ADA ratio in patients presenting with exudative pleural effusion can distinguish between malignant and non-malignant effusion on the first day of hospitalization. The cut-off level for serum LDH: pleural fluid ADA ratio of >20 is highly predictive of malignancy in patients with exudative pleural effusion (whether lymphocytic or neutrophilic) with high sensitivity and specificity.

  17. FINANCIAL RATIOS – REVEAL HOW A BUSINESS IS DOING?

    OpenAIRE

    MIRELA MONEA

    2009-01-01

    The paper aims to present the main financial ratios which provide a picture about company’s profitability, its financial position, use of its assets efficiency, its long-term debt financing. Discussion is focused on: profitability ratios, short-term financial ratios, activity ratios, long-term debt ratios or dividend policy ratios. Also, will try to answer at the following main questions: What financial ratios analysis tells us? What the users of these needs to know?

  18. Word Class Ratios and Genres in Written Japanese: Revisiting the Modifier Verb Ratio

    Directory of Open Access Journals (Sweden)

    Bor HODOŠČEK

    2011-10-01

    Full Text Available This paper explores the variability of genres in the Balanced Corpus of Contemporary Written Japanese using the modifier-verb ratio proposed by Kabashima and Jukaku (1965. Using bagplots to quantifying the relation between noun and modifier-verb ratios, as well as some summary statistics obtain from them, we attempt to classify genres according to Kabashima and Jugaku (1965. Our initial analysis confirms previous research results, while at the same time uncovering some contradictions in the ratios of the genre of magazines.

  19. Do banks differently set their liquidity ratios based on their network characteristics? Do banks differently set their liquidity ratios based on their network characteristics?

    OpenAIRE

    Distinguin, Isabelle; Mahdavi-Ardekani, Aref; Tarazi, Amine

    2017-01-01

    This paper investigates the impact of interbank network topology on bank liquidity ratios. Whereas more emphasis has been put on liquidity requirements by regulators since the global financial crisis of 2007-2008, how differently shaped interbank networks impact individual bank liquidity behavior remains an open issue. We look at how bank interconnectedness within interbank loan and deposit networks affects their decision to hold more or less liquidity during normal times and distress times a...

  20. Colloid normalizes resuscitation ratio in pediatric burns.

    Science.gov (United States)

    Faraklas, Iris; Lam, Uyen; Cochran, Amalia; Stoddard, Gregory; Saffle, Jeffrey

    2011-01-01

    Fluid resuscitation of burned children is challenging because of their small size and intolerance to over- or underresuscitation. Our American Burn Association-verified regional burn center has used colloid "rescue" as part of our pediatric resuscitation protocol. With Institutional Review Board approval, the authors reviewed children with ≥15% TBSA burns admitted from January 1, 2004, to May 1, 2009. Resuscitation was based on the Parkland formula, which was adjusted to maintain urine output. Patients requiring progressive increases in crystalloid were placed on a colloid protocol. Results were expressed as an hourly resuscitation ratio (I/O ratio) of fluid infusion (ml/kg/%TBSA/hr) to urine output (ml/kg/hr). We reviewed 53 patients; 29 completed resuscitation using crystalloid alone (lactated Ringer's solution [LR]), and 24 received colloid supplementation albumin (ALB). Groups were comparable in age, gender, weight, and time from injury to admission. ALB patients had more inhalation injuries and larger total and full-thickness burns. LR patients maintained a median I/O of 0.17 (range, 0.08-0.31), whereas ALB patients demonstrated escalating ratios until the institution of albumin produced a precipitous return of I/O comparable with that of the LR group. Hospital stay was lower for LR patients than ALB patients (0.59 vs 1.06 days/%TBSA, P = .033). Twelve patients required extremity or torso escharotomy, but this did not differ between groups. There were no decompressive laparotomies. The median resuscitation volume for ALB group was greater than LR group (9.7 vs 6.2 ml/kg/%TBSA, P = .004). Measuring hourly I/O is a helpful means of evaluating fluid demands during burn shock resuscitation. The addition of colloid restores normal I/O in pediatric patients.

  1. Stopping-power ratios for dosimetry

    International Nuclear Information System (INIS)

    Andreo, P.

    1988-01-01

    The determination of the absorbed dose at a specified location in a medium irradiated with an electron or photon beam normally consists of two steps: (1) the determination of the mean absorbed dose to a detector by using a calibration factor or performing an absolute measurement, (2) the determination of the absorbed dose to the medium at the point of interest by calculations based on the knowledge of the absorbed dose to the detector and the different stopping and scattering properties of the medium and the detector material. When the influence of the detector is so small that the electron fluence in the medium is not modified, the ratio of the mass collision stopping power of the two materials accounts for the differences in energy deposition, and provides a conversion factor to relate the absorbed dose in both materials. Today, all national and international dosimetry protocols and codes of practice are based on such procedures, and the user easily can carry out these steps using tabulated data to convert a measured quantity to absorbed dose in the irradiated medium at the location of interest. Effects due to the spatial extension of the detector are taken into account using perturbation correction factors. The Monte Carlo method has become the most common and powerful calculational technique for determining the electron fluence (energy spectra) under different irradiation conditions. Cavity theory is then used to calculate stopping-power ratios. In this chapter, the different steps needed to evaluate s-ratios will be considered, emphasizing the different types of cavity-theory integrals and the Monte Carlo techniques used to derive the necessary electron spectra in the range of energies commonly used in radiation dosimetry, i.e., photon and electron beams with energies up to 50 MeV

  2. On the universality of knot probability ratios

    Energy Technology Data Exchange (ETDEWEB)

    Janse van Rensburg, E J [Department of Mathematics and Statistics, York University, Toronto, Ontario M3J 1P3 (Canada); Rechnitzer, A, E-mail: rensburg@yorku.ca, E-mail: andrewr@math.ubc.ca [Department of Mathematics, University of British Columbia, 1984 Mathematics Road, Vancouver, BC V6T 1Z2 (Canada)

    2011-04-22

    Let p{sub n} denote the number of self-avoiding polygons of length n on a regular three-dimensional lattice, and let p{sub n}(K) be the number which have knot type K. The probability that a random polygon of length n has knot type K is p{sub n}(K)/p{sub n} and is known to decay exponentially with length (Sumners and Whittington 1988 J. Phys. A: Math. Gen. 21 1689-94, Pippenger 1989 Discrete Appl. Math. 25 273-8). Little is known rigorously about the asymptotics of p{sub n}(K), but there is substantial numerical evidence. It is believed that the entropic exponent, {alpha}, is universal, while the exponential growth rate is independent of the knot type but varies with the lattice. The amplitude, C{sub K}, depends on both the lattice and the knot type. The above asymptotic form implies that the relative probability of a random polygon of length n having prime knot type K over prime knot type L. In the thermodynamic limit this probability ratio becomes an amplitude ratio; it should be universal and depend only on the knot types K and L. In this communication we examine the universality of these probability ratios for polygons in the simple cubic, face-centred cubic and body-centred cubic lattices. Our results support the hypothesis that these are universal quantities. For example, we estimate that a long random polygon is approximately 28 times more likely to be a trefoil than be a figure-eight, independent of the underlying lattice, giving an estimate of the intrinsic entropy associated with knot types in closed curves. (fast track communication)

  3. The transverse Poisson's ratio of composites.

    Science.gov (United States)

    Foye, R. L.

    1972-01-01

    An expression is developed that makes possible the prediction of Poisson's ratio for unidirectional composites with reference to any pair of orthogonal axes that are normal to the direction of the reinforcing fibers. This prediction appears to be a reasonable one in that it follows the trends of the finite element analysis and the bounding estimates, and has the correct limiting value for zero fiber content. It can only be expected to apply to composites containing stiff, circular, isotropic fibers bonded to a soft matrix material.

  4. Flutter analysis of low aspect ratio wings

    Science.gov (United States)

    Parnell, L. A.

    1986-01-01

    Several very low aspect ratio flat plate wing configurations are analyzed for their aerodynamic instability (flutter) characteristics. All of the wings investigated are delta planforms with clipped tips, made of aluminum alloy plate and cantilevered from the supporting vehicle body. Results of both subsonic and supersonic NASTRAN aeroelastic analyses as well as those from another version of the program implementing the supersonic linearized aerodynamic theory are presented. Results are selectively compared with the experimental data; however, supersonic predictions of the Mach Box method in NASTRAN are found to be erratic and erroneous, requiring the use of a separate program.

  5. High aspect ratio, remote controlled pumping assembly

    Science.gov (United States)

    Brown, Steve B.; Milanovich, Fred P.

    1995-01-01

    A miniature dual syringe-type pump assembly which has a high aspect ratio and which is remotely controlled, for use such as in a small diameter penetrometer cone or well packer used in water contamination applications. The pump assembly may be used to supply and remove a reagent to a water contamination sensor, for example, and includes a motor, gearhead and motor encoder assembly for turning a drive screw for an actuator which provides pushing on one syringe and pulling on the other syringe for injecting new reagent and withdrawing used reagent from an associated sensor.

  6. Aspect Ratio Dependence of Impact Fragmentation

    International Nuclear Information System (INIS)

    Inaoka, H.; Toyosawa, E.; Takayasu, H.; Inaoka, H.

    1997-01-01

    A numerical model of three-dimensional impact fragmentation produces a power-law cumulative fragment mass distribution followed by a flat tail. The result is consistent with an experimental result in a recent paper by Meibom and Balslev [Phys. Rev. Lett. 76, 2492 (1996)]. Our numerical simulation also implies that the fragment mass distribution changes from a power law with a flat tail to a power law with a sudden cutoff, depending on the aspect ratio of the fractured object. copyright 1997 The American Physical Society

  7. Electronic branching ratio of the τ lepton

    International Nuclear Information System (INIS)

    Ammar, R.; Baringer, P.; Coppage, D.; Davis, R.; Kelly, M.; Kwak, N.; Lam, H.; Ro, S.; Kubota, Y.; Lattery, M.; Nelson, J.K.; Perticone, D.; Poling, R.; Schrenk, S.; Wang, R.; Alam, M.S.; Kim, I.J.; Nemati, B.; Romero, V.; Sun, C.R.; Wang, P.; Zoeller, M.M.; Crawford, G.; Fulton, R.; Gan, K.K.; Kagan, H.; Kass, R.; Lee, J.; Malchow, R.; Morrow, F.; Sung, M.K.; Whitmore, J.; Wilson, P.; Butler, F.; Fu, X.; Kalbfleisch, G.; Lambrecht, M.; Skubic, P.; Snow, J.; Wang, P.; Bortoletto, D.; Brown, D.N.; Dominick, J.; McIlwain, R.L.; Miller, D.H.; Modesitt, M.; Shibata, E.I.; Schaffner, S.F.; Shipsey, I.P.J.; Battle, M.; Ernst, J.; Kroha, H.; Roberts, S.; Sparks, K.; Thorndike, E.H.; Wang, C.; Stroynowski, R.; Artuso, M.; Goldberg, M.; Haupt, T.; Horwitz, N.; Kennett, R.; Moneti, G.C.; Playfer, S.; Rozen, Y.; Rubin, P.; Skwarnicki, T.; Stone, S.; Thulasidas, M.; Yao, W.; Zhu, G.; Barnes, A.V.; Bartelt, J.; Csorna, S.E.; Jain, V.; Letson, T.; Mestayer, M.D.; Akerib, D.S.; Barish, B.; Chadha, M.; Cowen, D.F.; Eigen, G.; Miller, J.S.; Urheim, J.; Weinstein, A.J.; Morrison, R.J.; Tajima, H.; Schmidt, D.; Sperka, D.; Procario, M.; Daoudi, M.; Ford, W.T.; Johnson, D.R.; Lingel, K.; Lohner, M.; Rankin, P.; Smith, J.G.; Alexander, J.; Bebek, C.; Berkelman, K.; Besson, D.; Browder, T.E.; Cassel, D.G.; Cheu, E.; Coffman, D.M.; Drell, P.S.; Ehrlich, R.; Galik, R.S.; Garcia-Sciveres, M.; Geiser, B.; Gittelman, B.; Gray, S.W.; Hartill, D.L.; Heltsley, B.K.; Honscheid, K.; Jones, C.; Kandaswamy, J.; Katayama, N.; Kim, P.C.; Kreinick, D.L.; Ludwig, G.S.; Masui, J.; Mevissen, J.; Mistry, N.B.; Nandi, S.; Ng, C.R.; Nordberg, E.; O'Grady, C.; Patterson, J.R.; Peterson, D.; Riley, D.; Sapper, M.; Selen, M.; Worden, H.; Worris, M.; Wuerthwein, F.; Avery, P.; Freyberger, A.; Rodriguez, J.; Yelton, J.; Henderson, S.; Kinoshita, K.; Pipkin, F.; Saulnier, M.; Wilson, R.; Wolinski, J.; Xiao, D.; Yamamoto, H.; Sadoff, A.J.

    1992-01-01

    Using data accumulated by the CLEO I detector operating at the Cornell Electron Storage Ring, we have measured the ratio R=Γ(τ→e bar ν e ν τ )/Γ 1 , where Γ 1 is the τ decay rate to final states with one charged particle. We find R=0.2231±0.0044±0.0073 where the first error is statistical and the second is systematic. Together with the measured topological one-charged-particle branching fraction, this yields the branching fraction of the τ lepton to electrons, B e =0.192±0.004±0.006

  8. Decay ratio estimation in pressurized water reactor

    International Nuclear Information System (INIS)

    Por, G.; Runkel, J.

    1990-11-01

    The well known decay ratio (DR) from stability analysis of boiling water reactors (BWR) is estimated from the impulse response function which was evaluated using a simplified univariate autoregression method. This simplified DR called modified DR (mDR) was applied on neutron noise measurements carried out during five fuel cycles of a 1300 MWe PWR. Results show that this fast evaluation method can be used for monitoring of the growing oscillation of the neutron flux during the fuel cycles which is a major concern of utilities in PWRs, thus it can be used for estimating safety margins. (author) 17 refs.; 10 figs

  9. Abundance ratios in dwarf elliptical galaxies

    Science.gov (United States)

    Şen, Ş.; Peletier, R. F.; Boselli, A.; den Brok, M.; Falcón-Barroso, J.; Hensler, G.; Janz, J.; Laurikainen, E.; Lisker, T.; Mentz, J. J.; Paudel, S.; Salo, H.; Sybilska, A.; Toloba, E.; van de Ven, G.; Vazdekis, A.; Yesilyaprak, C.

    2018-04-01

    We determine abundance ratios of 37 dwarf ellipticals (dEs) in the nearby Virgo cluster. This sample is representative of the early-type population of galaxies in the absolute magnitude range -19.0 originate from late-type dwarfs or small spirals. Na-yields appear to be very metal-dependent, in agreement with studies of giant ellipticals, probably due to the large dependence on the neutron-excess in stars. We conclude that dEs have undergone a considerable amount of chemical evolution, they are therefore not uniformly old, but have extended SFH, similar to many of the Local Group galaxies.

  10. Isotopic ratio method for determining uranium contamination

    International Nuclear Information System (INIS)

    Miles, R.E.; Sieben, A.K.

    1994-01-01

    The presence of high concentrations of uranium in the subsurface can be attributed either to contamination from uranium processing activities or to naturally occurring uranium. A mathematical method has been employed to evaluate the isotope ratios from subsurface soils at the Rocky Flats Nuclear Weapons Plant (RFP) and demonstrates conclusively that the soil contains uranium from a natural source and has not been contaminated with enriched uranium resulting from RFP releases. This paper describes the method used in this determination which has widespread application in site characterizations and can be adapted to other radioisotopes used in manufacturing industries. The determination of radioisotope source can lead to a reduction of the remediation effort

  11. Energy Balance Bowen Ratio (EBBR) Handbook

    Energy Technology Data Exchange (ETDEWEB)

    Cook, D. R. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2016-01-01

    The Energy Balance Bowen Ratio (EBBR) system produces 30-minute estimates of the vertical fluxes of sensible and latent heat at the local surface. Flux estimates are calculated from observations of net radiation, soil surface heat flux, and the vertical gradients of temperature and relative humidity (RH). Meteorological data collected by the EBBR are used to calculate bulk aerodynamic fluxes, which are used in the Bulk Aerodynamic Technique (BA) EBBR value-added product (VAP) to replace sunrise and sunset spikes in the flux data. A unique aspect of the system is the automatic exchange mechanism (AEM), which helps to reduce errors from instrument offset drift.

  12. DPOAE generation dependence on primary frequencies ratio

    Science.gov (United States)

    Botti, Teresa; Sisto, Renata; Moleti, Arturo; D'Amato, Luisa; Sanjust, Filippo

    2015-12-01

    Two different mechanisms are responsible for the DPOAE generation. The nonlinear distortion wave-fixed mechanism generates the DPOAE Zero-Latency (ZL) component, as a backward traveling wave from the "overlap" region. Linear reflection of the forward DP wave (IDP) generates the DPOAE Long-Latency (LL) component through a place-fixed mechanism. ZL and LL components add up vectorially to generate the DPOAE recorded in the ear canal. The 2f1 - f2 and 2f2 - f1 DPOAE intensity depends on the stimulus level and on the primary frequency ratio r = f2/f1, where f1 and f2 are the primary stimuli frequencies. Here we study the behavior of the ZL and LL DPOAE components as a function of r by both numerical and laboratory experiments, measuring DPAOEs with an equal primary levels (L1 = L2) paradigm in the range [35, 75] dB SPL, with r ranging in [1.1, 1.45]. Numerical simulations of a nonlocal nonlinear model have been performed without cochlear roughness, to suppress the linear reflection mechanism. In this way the model solution at the base represents the DPOAE ZL component, and the solution at the corresponding DPOAE tonotopic place corresponds to the IDP. This technique has been not effectual to study the 2f2 - f1 DPOAE, as a consequence of its generation mechanism. While the 2f1 - f2 generation place is known to be the tonotopic place x(f2), the 2f2 - f1 DPOAE one has to be assumed basal to its corresponding reflection place. That is because ZL components generated in x(f2) cannot significantly pass through their resonant place. Moreover increasing the ratio r, 2f2 - f1 ZL and LL generation place approach each other, because the overlap region of primary tones decreases. Consequently, the distinction between the two places becomes complicated. DPOAEs have been measured in six young normal-hearing subjects. DPOAE ZL and LL components have been separated by a time-frequency filtering method based on the wavelet transform 1. due to their different phase gradient delay

  13. effect of effect of blend ratio on blend ratio on characteristics

    African Journals Online (AJOL)

    User

    properties, cassava-soybean composite, wheat, bread, blend ratio ... dily growing population, an in eating and ... thermodynamic variables can produce an effect on .... these conditions. ..... Ragaee, S. et al., Pasting properties of starch and.

  14. Hilar height ratio in normal Korea

    International Nuclear Information System (INIS)

    Yoo, Kyung Ho; Lee, Nam Joon; Seol, Hae Young; Chung, Kyoo Byung

    1979-01-01

    Hilar displacement is one of the significant sign of pulmonary volume change. The hilar height ratio (HHR) is a value that express the normal position of hilum in its hemithorax, and it is calculated by dividing the distance from the hilum to the lung apex by the distance from the hilum to the diaphragm. Displacement of one hilum is usually easy to detect but both are displaced in the same direction especially, recognition is more difficult. Knowledge of normal HHR allows evaluation of hilar positional change even when the relative hilar position are not altered. Normal chest PA views of 275 cases taken at Korea University Hospital during the period of April 1978 to Jun 1979 were analyzed. The right hilum is positioned in lower half of the right hemithorax, while the left hilum is situated in the upper half of left hemithorax. The difference of hilar ratio according to age group is slight, but there is significant difference between right-HHR and left-HHR. The value of right-HHR is 1.28 ± 0.14, the value of left-HHR is 0.88 ± 0.09.

  15. Carbon isotope ratios of atmospheric carbon dioxide

    International Nuclear Information System (INIS)

    Sakai, Hitoshi; Kishima, Noriaki; Tsutaki, Yasuhiro.

    1982-01-01

    The delta 13 C values relative to PDB were measured for carbon dioxide in air samples collected at various parts of Japan and at Mauna Loa Observatory, Hawaii in the periods of 1977 and 1978. The delta 13 C values of the ''clean air'' are -7.6 % at Hawaii and -8.1 per mille Oki and Hachijo-jima islands. These values are definitely lighter than the carbon isotope ratios (-6.9 per mille) obtained by Keeling for clean airs collected at Southern California in 1955 to 1956. The increase in 12 C in atmospheric carbon dioxide is attributed to the input of the anthropogenic light carbon dioxides (combustion of fossil fuels etc.) Taking -7.6 per mille to be the isotope ratio of CO 2 in the present clean air, a simple three box model predicts that the biosphere has decreased rather than increased since 1955, implying that it is acting as the doner of carbon rather than the sink. (author)

  16. Flexible Conversion Ratio Fast Reactor Systems Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Neil Todreas; Pavel Hejzlar

    2008-06-30

    Conceptual designs of lead-cooled and liquid salt-cooled fast flexible conversion ratio reactors were developed. Both concepts have cores reated at 2400 MWt placed in a large-pool-type vessel with dual-free level, which also contains four intermediate heat exchanges coupling a primary coolant to a compact and efficient supercritical CO2 Brayton cycle power conversion system. Decay heat is removed passively using an enhanced Reactor Vessel Auxiliary Cooling System and a Passive Secondary Auxiliary Cooling System. The most important findings were that (1) it is feasible to design the lead-cooled and salt-cooled reactor with the flexible conversion ratio (CR) in the range of CR=0 and CR=1 n a manner that achieves inherent reactor shutdown in unprotected accidents, (2) the salt-cooled reactor requires Lithium thermal Expansion Modules to overcme the inherent salt coolant's large positive coolant temperature reactivity coefficient, (3) the preferable salt for fast spectrum high power density cores is NaCl-Kcl-MgCl2 as opposed to fluoride salts due to its better themal-hydraulic and neutronic characteristics, and (4) both reactor, but attain power density 3 times smaller than that of the sodium-cooled reactor.

  17. Validation of the Rotation Ratios Method

    International Nuclear Information System (INIS)

    Foss, O.A.; Klaksvik, J.; Benum, P.; Anda, S.

    2007-01-01

    Background: The rotation ratios method describes rotations between pairs of sequential pelvic radiographs. The method seems promising but has not been validated. Purpose: To validate the accuracy of the rotation ratios method. Material and Methods: Known pelvic rotations between 165 radiographs obtained from five skeletal pelvises in an experimental material were compared with the corresponding calculated rotations to describe the accuracy of the method. The results from a clinical material of 262 pelvic radiographs from 46 patients defined the ranges of rotational differences compared. Repeated analyses, both on the experimental and the clinical material, were performed using the selected reference points to describe the robustness and the repeatability of the method. Results: The reference points were easy to identify and barely influenced by pelvic rotations. The mean differences between calculated and real pelvic rotations were 0.0 deg (SD 0.6) for vertical rotations and 0.1 deg (SD 0.7) for transversal rotations in the experimental material. The intra- and interobserver repeatability of the method was good. Conclusion: The accuracy of the method was reasonably high, and the method may prove to be clinically useful

  18. Flexible Conversion Ratio Fast Reactor Systems Evaluation

    International Nuclear Information System (INIS)

    Neil Todreas; Pavel Hejzlar

    2008-01-01

    Conceptual designs of lead-cooled and liquid salt-cooled fast flexible conversion ratio reactors were developed. Both concepts have cores treated at 2400 MWt placed in a large-pool-type vessel with dual-free level, which also contains four intermediate heat exchanges coupling a primary coolant to a compact and efficient supercritical CO2 Brayton cycle power conversion system. Decay heat is removed passively using an enhanced Reactor Vessel Auxiliary Cooling System and a Passive Secondary Auxiliary Cooling System. The most important findings were that (1) it is feasible to design the lead-cooled and salt-cooled reactor with the flexible conversion ratio (CR) in the range of CR=0 and CR=1 n a manner that achieves inherent reactor shutdown in unprotected accidents, (2) the salt-cooled reactor requires Lithium thermal Expansion Modules to overcome the inherent salt coolant's large positive coolant temperature reactivity coefficient, (3) the preferable salt for fast spectrum high power density cores is NaCl-Kcl-MgCl2 as opposed to fluoride salts due to its better thermal-hydraulic and neutronic characteristics, and (4) both reactor, but attain power density 3 times smaller than that of the sodium-cooled reactor

  19. Fast fission ratio and relative conversion ratio measurements in gadolinium poisoned water moderated UO2 lattices

    International Nuclear Information System (INIS)

    Murphy, M.F.

    1984-01-01

    A programme of criticality experiments has been carried out for BNFL by the Battelle reactor facility at Pacific Northwest Laboratories in Washington State, USA. A series of water moderated lattices of 4.3% enriched, 12.7 mm diameter, UO 2 fuel rods was studied, the fuel pitch was varied and the effects of gadolinium poison were measured. This report deals with the measurement of Fast Fission Ratios and Relative Conversion Ratios at the centre of five of the critical lattices. The Fast Fission Ratio (FFR) is defined here as the ratio of the fission rate per atom of U238, to the fission rate per atom of U235. The Relative Conversion Ratio (RCR) is defined as the ratio of the capture rate per ,atom of U238, to the fission rate per atom of U235, in the reactor fuel, relative to the corresponding ratio in a well thermalised neutron spectrum. A major aspect of these measurements was that the packs of foils were prepared at AEEW Winfrith, despatched to the USA for irradiation and returned to Winfrith for counting. This resulted in a considerable logistics problem but by good planning and the co-operation and diligence of all concerned this problem was overcome. However, the long distance involved inevitably meant that samples were not available for measurement until about 28 hours after the irradiation. It was therefore necessary to modify the techniques that are normally used in the Reactor Physics Division Counting Laboratory, where samples are normally available about two hours after shut-down. The techniques used and the results obtained are given below

  20. Oxygen enhancement ratio for negative pi mesons

    International Nuclear Information System (INIS)

    Hall, E.J.; Astor, M.

    1979-01-01

    Experiments were performed at the Los Alamos Meson Physics Facility (LAMPF) to determine the oxygen enhancement ratio (OER) for the clinically used beam of negative pi mesons. V79 Chinese hamster cells, cultured in vitro, were used as the biological test system; hypoxia was produced by metabolic depletion as a result of sealing 2 million cells in 1 ml glass ampules. The Bragg peak of the pion depth dose curve was spread out to cover 10 cm by using a dynamic range shifter. Cells were irradiated at the center of the spead out Bragg peak, where the dose/rate was 0.1 Gy/min over a 6 x 6 cm field. The OER obtained was 2.2, compared with 3.8 obtained for γ rays under the same conditions

  1. Ratio-Based Gradual Aggregation of Data

    DEFF Research Database (Denmark)

    Iftikhar, Nadeem

    2012-01-01

    cause data management and data storage issues. However, non-flexible and ineffective means of data aggregation not only reduce performance of database queries but also lead to erroneous reporting. This paper presents flexible and effective ratio-based methods for gradual data aggregation in databases....... Gradual data aggregation is a process that reduces data volume by converting the detailed data into multiple levels of summarized data as the data gets older. This paper also describes implementation strategies of the proposed methods based on standard database technology.......Majority of databases contain large amounts of data, gathered over long intervals of time. In most cases, the data is aggregated so that it can be used for analysis and reporting purposes. The other reason of data aggregation is to reduce data volume in order to avoid over-sized databases that may...

  2. Ventilation and ventilation/perfusion ratios

    International Nuclear Information System (INIS)

    Valind, S.O.

    1989-01-01

    The thesis is based on five different papers. The labelling of specific tracer compounds with positron emitting radionuclides enables a range of structural, physiological and biochemical parameters in the lung to be measured non-invasively, using positron emission tomography. This concept affords a unique opportunity for in vivo studies of different expressions of pulmonary pathophysiology at the regional level. The present thesis describes the application of positron emission tomography to the measurements of ventilation and ventilation/perfusion ratios using inert gas tracers, neon-19 and nitrogen-13 respectively. The validity of the methods applied was investigated with respect to the transport of inert gas tracers in the human lung. Both ventilation and the ventilation/perfusion ratio may be obtained with errors less than 10 % in the normal lung. In disease, however, errors may increase in those instances where the regional ventilation is very low or the intra-regional gas flow distribution is markedly nonuniform. A 2-3 fold increase in ventilation was demonstrated in normal nonsmoking subjects going from ventral to dorsal regions in the supine posture. These large regional differences could be well explained by the intrinsic elastic properties of lung tissue, considering the gravitational gradient in transpulmonary pressure. In asymptomatic smokers substantial regional ventilatroy abnormalities were found whilst the regional gas volume was similar in smokers and nonsmokers. The uncoupling between ventilation and gas volume probably reflects inflammatory changes in the airways. The regional differences in dV/dt/dQ/dt were relatively small and blood flow was largely matched to ventilation in the supine posture. However, small regions of lung with very low ventilation, unmatched by blood flow commonly exists in the most dependent parts of the lung in both smokers and nonsmokers. (29 illustrations, 7 tables, 113 references)

  3. Oxygen isotope ratios of the Icelandic crust

    International Nuclear Information System (INIS)

    Hattori, K.; Muehlenbachs, K.

    1982-01-01

    Oxygen isotope ratios of hydrothermally altered basalts from depth of up to approx.3 km are reported from three localities in Iceland: International Research Drilling Project (IRDP) core at Reydarfjordur, eastern Iceland (Tertiary age); drill cuttings from Reykjavik (Plio-Pleistocene age); and Halocene drill cuttings from the active Krafla central volcano. Whole rock samples from these three localities have delta 18 O values averaging +3.9 +- 1.3, +2.4 +- 1.1, and -7.7 +- 2.4%, respectively. The observed values in the deeper samples from Krafla are as low as the values for any rocks previously reported. There seems to be a slight negative gradient in delta 18 O with depth at the former two localities and a more pronounced one at Krafla. Oxygen isotope fractionations between epidote and quartz and those between calcite and fluid suggests that the basalts were altered at temperatures of 300 0 --400 0 C. Low deltaD and delta 18 O of epidote and low delta 34 S of anhydrite indicate that the altering fluids in all three areas originated as meteoric waters and have undergone varied 'oxygen shifts'. Differences in the 18 O shift of the fluids are attributed to differences in hydrothermal systems; low water/rock ratios ( 5) at Krafla. The convective hydrothermal activity, which is probably driven by silicic magma beneath the central volcanoes, has caused strong subsolidus depletion of 18 O in the rocks. The primary-magnetic delta 18 O value of the rocks in the Tertiary IRDP core was about +3.9%, which is lower than that obtained for fresh basalt from other places. Such exceptionally low delta 18 O magmas are common in Iceland and may occur as the result of oxygen isotope exchange with or assimilation of altered rocks that form a thick sequence beneath the island due to isostatic subsidence

  4. Qubit-qutrit separability-probability ratios

    International Nuclear Information System (INIS)

    Slater, Paul B.

    2005-01-01

    Paralleling our recent computationally intensive (quasi-Monte Carlo) work for the case N=4 (e-print quant-ph/0308037), we undertake the task for N=6 of computing to high numerical accuracy, the formulas of Sommers and Zyczkowski (e-print quant-ph/0304041) for the (N 2 -1)-dimensional volume and (N 2 -2)-dimensional hyperarea of the (separable and nonseparable) NxN density matrices, based on the Bures (minimal monotone) metric--and also their analogous formulas (e-print quant-ph/0302197) for the (nonmonotone) flat Hilbert-Schmidt metric. With the same seven 10 9 well-distributed ('low-discrepancy') sample points, we estimate the unknown volumes and hyperareas based on five additional (monotone) metrics of interest, including the Kubo-Mori and Wigner-Yanase. Further, we estimate all of these seven volume and seven hyperarea (unknown) quantities when restricted to the separable density matrices. The ratios of separable volumes (hyperareas) to separable plus nonseparable volumes (hyperareas) yield estimates of the separability probabilities of generically rank-6 (rank-5) density matrices. The (rank-6) separability probabilities obtained based on the 35-dimensional volumes appear to be--independently of the metric (each of the seven inducing Haar measure) employed--twice as large as those (rank-5 ones) based on the 34-dimensional hyperareas. (An additional estimate--33.9982--of the ratio of the rank-6 Hilbert-Schmidt separability probability to the rank-4 one is quite clearly close to integral too.) The doubling relationship also appears to hold for the N=4 case for the Hilbert-Schmidt metric, but not the others. We fit simple exact formulas to our estimates of the Hilbert-Schmidt separable volumes and hyperareas in both the N=4 and N=6 cases

  5. Competition between bank regulators

    OpenAIRE

    Schindler, Dirk; Eggert, Wolfgang

    2004-01-01

    This paper examines competition between bank regulators in open economies. We use a model where credit demand of firms is endogenous and show any tendency for downward competition in regulation policy is limited by the effect of regulation on profits of nonfinancial firms. Moreover, perfect mobility on loans and deposit markets fully eliminates the incentives of regulators to set bank regulation at ine±cient low levels.

  6. Pengaruh Likuiditas, Profitabilitas, Leverage, dan Market Ratio terhadap Dividend Payout Ratio pada Perusahaan Manufaktur

    Directory of Open Access Journals (Sweden)

    Erna Puspita

    2017-04-01

    Full Text Available Dividend policy is concerned with financial policies regarding what amount cash dividend paid to shareholders and re-invested as retained earnings. The recent research aimed to test empirically various factors is considered to affect dividend policy. The independent variables in his research included Current Ratio (CR, Return on Equity (ROE, Debt to Equity Ratio (DER, and Earning Per Share (EPS. Meanwhile, the dependent variable was Dividend Payout Ratio (DPR. Quantitative research was used as the research design and the data was secondary data. Furthermore, purposive sampling was selected to get the sample. The result was 14 companies that pay dividend continuously during this research conducted on 2012 - 2014 were selected as the sample of this research. Multiple linier regression was used to analyze the data. The results showed that ROE and EPS has a contribution to the DPR, and then CR and DER has no contribution to the DPR.

  7. Combined slope ratio analysis and linear-subtraction: An extension of the Pearce ratio method

    Science.gov (United States)

    De Waal, Sybrand A.

    1996-07-01

    A new technique, called combined slope ratio analysis, has been developed by extending the Pearce element ratio or conserved-denominator method (Pearce, 1968) to its logical conclusions. If two stoichiometric substances are mixed and certain chemical components are uniquely contained in either one of the two mixing substances, then by treating these unique components as conserved, the composition of the substance not containing the relevant component can be accurately calculated within the limits allowed by analytical and geological error. The calculated composition can then be subjected to rigorous statistical testing using the linear-subtraction method recently advanced by Woronow (1994). Application of combined slope ratio analysis to the rocks of the Uwekahuna Laccolith, Hawaii, USA, and the lavas of the 1959-summit eruption of Kilauea Volcano, Hawaii, USA, yields results that are consistent with field observations.

  8. Cereal Production Ratio and NDVI in Spain

    Science.gov (United States)

    Saa-Requejo, Antonio; Recuero, Laura; Palacios, Alicia; Díaz-Ambrona, Carlos G. H.; Tarquis, Ana M.

    2014-05-01

    Droughts are long-term phenomena affecting large regions causing significant damages both in human lives and economic losses. The use of remote sensing has proved to be very important in monitoring the growth of agricultural crops and trying to asses weather impact on crop loss. Several indices has been developed based in remote sensing data being one of them the normalized difference vegetation index (NDVI). In this study we have focus to know the correlation between NDVI data and the looses of rain fed cereal in the Spanish area where this crop is majority. For this propose data from drought damage in cereal come from the pool of agricultural insurance in Spain (AGROSEGURO) including 2007/2008 to 2011/2012 (five agricultural campaigns). This data is given as a ratio between drought party claims against the insured value of production aggregated at the agrarian region level. Medium resolution (500x500 m2) MODIS images were used during the same campaigns to estimate the eight-day composites NDVI at these locations. The NDVI values are accumulated following the normal cycle of the cereal taking in account the sowing date at different sites. At the same time, CORINE Land Cover (2006) was used to classify the pixels belonging to rain fed cereal use including a set of conditions such as pixels showing dry during summer, area in which there has been no change of use. Fallow presence is studied with particular attention as it imposes an inter annual variation between crop and bare soil and causes decreases in greenness in a pixel and mix both situations. This is more complex in the situation in which the avoid fallow and a continuous monoculture is performed. The results shown that around 40% of the area is subject to the regime of fallow while 60% have growing every year. In addition, another variation is detected if the year is humid (decrease of fallow) or dry (increase of fallow). The level of correlation between the drought damage ratios and cumulative NDVI for the

  9. Concentration ratio of radon progeny in air

    International Nuclear Information System (INIS)

    Kobayashi, Tsuneo

    2000-01-01

    Investigations have been made on the concentration ratio of radon progeny in air. Data have been acquired intermittently since 1988 using alpha spectroscopic method around the author's office that is located in the northeastern part of Japan. Clarifying the behavior of radon progeny is an issue of wide importance to radiation protection, predicting earthquakes, etc. Let Rabc=ECRn(RaA)/{ECRn(RaB) + ECRn(RaC)}; the concentration ratio, Rabc, is relevant to the stability of the air. Statistical and time series analyses indicated several interesting results. To examine the log-normal distribution, Lilliefors test was made for logarithm of outdoor data every one year. Rabc passed the test 6 times for 9 years, while Radon progeny passed 8 times. Outdoor data indicated that the value of Rabc was lower in the morning, in other world, the air was more stable in the morning than in the afternoon. To see the seasonal variation, one-way layout analysis was made for four groups of data, i.e., spring (March to May), summer (June to August), autumn (September to November), and winter (December to February). Rabc indicated significantly higher level in spring and winter, in other word, air was stable in summer and autumn. Time series analysis was made for various variables; power spectra were estimated with autoregressive model that is equivalent to maximum entropy method. Power spectrum for Rabc was most similar to that of wind speed. One-year period, that is always remarkable for radon progeny, was not significant for Rabc. Three- to nine-day periods were often seen for Rabc, radon progeny, wind speed, and atmospheric pressure. These several-day periods are probably attributed to the passage of air masses. Twenty-day to thirty-day peak may be attributed to meteorological phenomena corresponding to the rotation period of the sun. Temperature indicated no significant periodicity except overwhelming one-year period. Wind speed is well known to affect the radon progeny concentration

  10. Regulating through leverage: Civil regulation in China

    NARCIS (Netherlands)

    Fürst, K.

    2016-01-01

    The overarching goal of this study is to examine the efforts of Chinese NGOs to prevent and/or control industrial pollution risks and then use the findings of this research to study the nature of civil regulation in, and beyond, China’s authoritarian setting. It first argues that 'regulation through

  11. Diffusion piecewise homogenization via flux discontinuity ratios

    International Nuclear Information System (INIS)

    Sanchez, Richard; Dante, Giorgio; Zmijarevic, Igor

    2013-01-01

    We analyze piecewise homogenization with flux-weighted cross sections and preservation of averaged currents at the boundary of the homogenized domain. Introduction of a set of flux discontinuity ratios (FDR) that preserve reference interface currents leads to preservation of averaged region reaction rates and fluxes. We consider the class of numerical discretizations with one degree of freedom per volume and per surface and prove that when the homogenization and computing meshes are equal there is a unique solution for the FDRs which exactly preserve interface currents. For diffusion sub-meshing we introduce a Jacobian-Free Newton-Krylov method and for all cases considered obtain an 'exact' numerical solution (eight digits for the interface currents). The homogenization is completed by extending the familiar full assembly homogenization via flux discontinuity factors to the sides of regions laying on the boundary of the piecewise homogenized domain. Finally, for the familiar nodal discretization we numerically find that the FDRs obtained with no sub-mesh (nearly at no cost) can be effectively used for whole-core diffusion calculations with sub-mesh. This is not the case, however, for cell-centered finite differences. (authors)

  12. Detection strategies for extreme mass ratio inspirals

    International Nuclear Information System (INIS)

    Cornish, Neil J

    2011-01-01

    The capture of compact stellar remnants by galactic black holes provides a unique laboratory for exploring the near-horizon geometry of the Kerr spacetime, or possible departures from general relativity if the central cores prove not to be black holes. The gravitational radiation produced by these extreme mass ratio inspirals (EMRIs) encodes a detailed map of the black hole geometry, and the detection and characterization of these signals is a major scientific goal for the LISA mission. The waveforms produced are very complex, and the signals need to be coherently tracked for tens of thousands of cycles to produce a detection, making EMRI signals one of the most challenging data analysis problems in all of gravitational wave astronomy. Estimates for the number of templates required to perform an exhaustive grid-based matched-filter search for these signals are astronomically large, and far out of reach of current computational resources. Here I describe an alternative approach that employs a hybrid between genetic algorithms and Markov chain Monte Carlo techniques, along with several time-saving techniques for computing the likelihood function. This approach has proven effective at the blind extraction of relatively weak EMRI signals from simulated LISA data sets.

  13. A ratio scale for brightness perception derived from difference and ratio judgments

    NARCIS (Netherlands)

    Ridder, de H.; Sabourin, M.

    1992-01-01

    The often observed nonlinearity between magnitude estimations and category ratings has raised the question whether subjects can judge sensation differences as well as sensation ratios when instructed to do so. For brightness this will be shown to be the case; the rank order of difference judgments

  14. 26 CFR 26.2642-5 - Finality of inclusion ratio.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Finality of inclusion ratio. 26.2642-5 Section...-5 Finality of inclusion ratio. (a) Direct skips. The inclusion ratio applicable to a direct skip...) Other GSTs. With respect to taxable distributions and taxable terminations, the inclusion ratio for a...

  15. The adenoid-nasopharynx ratio. Its clinical value in children

    International Nuclear Information System (INIS)

    Zou Mingshun

    1997-01-01

    To evaluate the clinical usefulness of adenoid-nasopharynx ratio (A/N ratio) measured on nasopharyngeal lateral plain film, 106 clinical cases of secretory otitis media were selected to measure the A/N ratio before treatment. For patients with A/N ratio of 0.50-0.70, the symptoms improved distinctly after conservative treatment, but one half of patients with A/N ratio ≥ 0.71 required adenoidectomy. A/N ratio is a practical and convenient method for evaluation of the adenoid. A/N ratio ≥ 0.71 indicates pathological enlarged adenoid

  16. Reserves to production ratios and present value relationships

    International Nuclear Information System (INIS)

    Hayhow, I. G.; Lemee, J. A.

    2000-01-01

    It is shown that reserves to production ratio, R/P, which optimizes development and maximizes present value, can be estimated using an equation containing the four variables of well initial production; rate, well costs, netback prices and discount rate. A sensitivity analysis of the optimization equation indicates that well costs and well productivity have the most influence on the optimum R/P. Improvements in technology beneficially affect well productivity and reduce costs, hence reducing capital requirements and producing an economic incentive to produce at low R/Ps. The influence of gas prices is considered less significant, but the expected increases in gas prices in the Western Canadian Sedimentary Basin will also act an an incentive to produce at low R/Ps. Recent gas discoveries in the Basin have been single well pools with high productivity and limited areal extent, which produce at low R/Ps. Continuation of this trend will cause further decrease in R/Ps. While this study assumed maximizing present value as the most likely objective, it is possible that regulators and producers have other objectives. It would be reasonable to expect that these alternative objectives will also favour producing at high rates and at low R/Ps. 2 tabs., 13 figs

  17. Plutonium isotope ratios in polychaete worms

    International Nuclear Information System (INIS)

    Beasley, T.M.; Fowler, S.W.

    1976-01-01

    Reference is made to recent reports that suggest that terrestrial and aquatic organisms may preferentially take up 238 Pu compared with sup(239+240)Pu. It is stated that although kinetic isotope effects are known to occur in biological systems for low mass number elements, such as H, C and N, such effects are generally discounted with higher mass numbers, and differences in the biological 'uptake' of isotopes of high mass number elements, such as those of Pu, are normally attributable to differences in the chemical or physical forms of the isotopes or to different quantities of isotopes available to organisms. This has been applied to explain differential Pu isotope behaviour in animals under controlled laboratory conditions, but it is not certain that it can be applied to explain anomalies of Pu isotope behaviour in organisms contaminated by nuclear test debris or by wastes from nuclear fuel reprocessing plants. Geochemical weathering may also have an effect. Described here are experiments in which it was found that deposit feeding marine worms living in sediments contaminated in different ways with Pu isotopes did not show preferential accumulation of 238 Pu. The worms had been exposed to different chemical and physical forms of the isotopes, including exposure to laboratory-labelled sediment, sediment collected from a former weapons test site, and sediment contaminated by wastes from a nuclear fuel reprocessing plant. The worms were allowed to accumulate Pu for times of 5 to 40 days. Isotope ratios were determined by α-spectrometric techniques. It is considered that the results are important for environmental samples where Pu activity levels are low. (U.K.)

  18. Do banks differently set their liquidity ratios based on their network characteristics?

    OpenAIRE

    Distinguin, Isabelle; Mahdavi-Ardekani, Aref; Tarazi, Amine

    2016-01-01

    This paper investigates the impact of interbank network topology on bank liquidity ratios. Whereas more emphasis has been put on liquidity requirements by regulators since the global financial crisis of 2007-2008, how differently shaped interbank networks impact individual bank liquidity behavior remains an open issue. We look at how bank interconnectedness within interbank loan and deposit networks affects their decision to hold more or less liquidity during normal times and distress times a...

  19. Do banks differently set their liquidity ratios based on their network characteristics?

    OpenAIRE

    Distinguin , Isabelle; Mahdavi-Ardekani , Aref; Tarazi , Amine

    2017-01-01

    This paper investigates the impact of interbank network topology on bank liquidity ratios. Whereas more emphasis has been put on liquidity requirements by regulators since the global financial crisis of 2007-2008, how differently shaped interbank networks impact individual bank liquidity behavior remains an open issue. We look at how bank interconnectedness within interbank loan and deposit networks affects their decision to hold more or less liquidity during normal times and distress times a...

  20. Atomic Energy Control Regulations

    International Nuclear Information System (INIS)

    1992-01-01

    This is the consolidated text of the Atomic Energy Control Regulations of 17 March 1960, with amendments to 27 August 1992. The Regulations cover the licensing of nuclear facilities, radiation sources, including uranium mining, radiation protection questions, etc. (NEA)

  1. Environmental regulation and competitiveness

    NARCIS (Netherlands)

    Mulatu, A.; Florax, R.J.G.M.; Withagen, C.A.A.M.

    2001-01-01

    The potential relationship between domestic environmental regulation and international competitiveness has evoked various speculations. The common neoclassical train of thought is that strict environmental regulation is detrimental to the competitiveness of industry, and that it induces phenomena

  2. Ocean Dumping Control Regulations

    International Nuclear Information System (INIS)

    1978-01-01

    These Regulations were made further to the Ocean Dumping Control Act which provides for restrictions in dumping operations. The Regulations contain model applications for permits to dump or load a series of materials. (NEA)

  3. Regulation of Genetic Tests

    Science.gov (United States)

    ... for Genomics Research Intellectual Property Issues in Genetics Archive Online Bioethics Resources Privacy in Genomics Regulation of ... are not regulated, meaning that they go to market without any independent analysis to verify the claims ...

  4. Trout Stream Special Regulations

    Data.gov (United States)

    Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

  5. The Role of ATP in Sleep Regulation

    Directory of Open Access Journals (Sweden)

    Sachiko eChikahisa

    2011-12-01

    Full Text Available One of the functions of sleep is to maintain energy balance in the brain. There are a variety of hypotheses related to how metabolic pathways interact with sleep/wake regulation. A major finding that demonstrates an interaction between sleep and metabolic homeostasis is the involvement of adenosine in sleep homeostasis. An accumulation of adenosine is supplied from ATP, which can act as an energy currency in the cell. Extracellularly, ATP can act as an activity-dependent signaling molecule, especially in regard to communication between neurons and glia, including astrocytes. Furthermore, the intracellular AMP/ATP ratio controls the activity of AMP-activated protein kinase (AMPK, which is a potent energy regulator and is recently reported to play a role in the regulation of sleep homeostasis. Brain ATP may support multiple functions in the regulation of the sleep/wake cycle and sleep homeostasis.

  6. Enantiomer Ratios of Meteoritic Sugar Derivatives

    Science.gov (United States)

    Cooper, George

    2012-01-01

    Carbonaceous meteorites contain a diverse suite of soluble organic compounds. Studies of these compounds reveal the Solar System's earliest organic chemistry. Among the classes of organic compounds found in meteorites are keto acids (pyruvic acid, etc.), hydroxy tricarboxylic acids (1), amino acids, amides, purines and pyrimidines. The Murchison and Murray meteorites are the most studied for soluble and insoluble organic compounds and organic carbon phases. The majority of (indigenous) meteoritic compounds are racemic, (i.e., their D/L enantiomer ratios are 50:50). However, some of the more unusual (non-protein) amino acids contain slightly more of one enantiomer (usually the L) than the other. This presentation focuses on the enantiomer analyses of three to six-carbon (3C to 6C) meteoritic sugar acids. The molecular and enantiomer analysis of corresponding sugar alcohols will also be discussed. Detailed analytical procedures for sugar-acid enantiomers have been described. Results of several meteorite analyses show that glyceric acid is consistently racemic (or nearly so) as expected of non-biological mechanisms of synthesis. Also racemic are 4-C deoxy sugar acids: 2-methyl glyceric acid; 2,4-dihydroxybutyric acid; 2,3-dihydroxybutyric acid (two diastereomers); and 3,4-dihydroxybutyric acid. However, a 4C acid, threonic acid, has never been observed as racemic, i.e., it possesses a large D excess. In several samples of Murchison and one of GRA 95229 (possibly the most pristine carbonaceous meteorite yet analyzed) threonic acid has nearly the same D enrichment. In Murchison, preliminary isotopic measurements of individual threonic acid enantiomers point towards extraterrestrial sources of the D enrichment. Enantiomer analyses of the 5C mono-sugar acids, ribonic, arabinonic, xylonic, and lyxonic also show large D excesses. It is worth noting that all four of these acids (all of the possible straight-chained 5C sugar acids) are present in meteorites, including the

  7. Minimum short-circuit ratios for grid interconnection of wind farms with induction generators

    Energy Technology Data Exchange (ETDEWEB)

    Reginatto, Romeu; Rocha, Carlos [Western Parana State University (UNIOESTE), Foz do Iguacu, PR (Brazil). Center for Engineering and Exact Sciences], Emails: romeu@unioeste.br, croberto@unioeste.br

    2009-07-01

    This paper concerns the problem of determining the minimum value for the short-circuit ratio which is adequate for the interconnection of a given wind farms to a given grid point. First, a set of 3 criteria is defined in order to characterize the quality/safety of the interconnection: acceptable terminal voltage variations, a minimum active power margin, and an acceptable range for the internal voltage angle. Then, the minimum short circuit ratio requirement is determined for 6 different induction generator based wind turbines, both fixed-speed (with and without reactive power compensation) and variable-speed (with the following control policies: reactive power, power factor, and terminal voltage regulation). The minimum short-circuit ratio is determined and shown in graphical results for the 6 wind turbines considered, for X/R in the range 0-15, also analyzing the effect of more/less stringent tolerances for the interconnection criteria. It is observed that the tighter the tolerances the larger the minimum short-circuit ratio required. For the same tolerances in the interconnection criteria, a comparison of the minimum short circuit ratio required for the interconnection of both squirrel-cage and doubly-fed induction generators is presented, showing that the last requires much smaller values for the short-circuit ratio. (author)

  8. Tau mRNA 3'UTR-to-CDS ratio is increased in Alzheimer disease.

    Science.gov (United States)

    García-Escudero, Vega; Gargini, Ricardo; Martín-Maestro, Patricia; García, Esther; García-Escudero, Ramón; Avila, Jesús

    2017-08-10

    Neurons frequently show an imbalance in expression of the 3' untranslated region (3'UTR) relative to the coding DNA sequence (CDS) region of mature messenger RNAs (mRNA). The ratio varies among different cells or parts of the brain. The Map2 protein levels per cell depend on the 3'UTR-to-CDS ratio rather than the total mRNA amount, which suggests powerful regulation of protein expression by 3'UTR sequences. Here we found that MAPT (the microtubule-associated protein tau gene) 3'UTR levels are particularly high with respect to other genes; indeed, the 3'UTR-to-CDS ratio of MAPT is balanced in healthy brain in mouse and human. The tau protein accumulates in Alzheimer diseased brain. We nonetheless observed that the levels of RNA encoding MAPT/tau were diminished in these patients' brains. To explain this apparently contradictory result, we studied MAPT mRNA stoichiometry in coding and non-coding regions, and found that the 3'UTR-to-CDS ratio was higher in the hippocampus of Alzheimer disease patients, with higher tau protein but lower total mRNA levels. Our data indicate that changes in the 3'UTR-to-CDS ratio have a regulatory role in the disease. Future research should thus consider not only mRNA levels, but also the ratios between coding and non-coding regions. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Disinflation in a DSGE Perspective: Sacrifice Ratio or Welfare Gain Ratio?

    OpenAIRE

    Guido Ascari; Tiziano Ropele

    2009-01-01

    When used to examine disinflation monetary policies, the current workhorse dynamic stochastic general equilibrium model of business cycle fluctuations is able to quantitatively account for the main stylized facts in terms of recessionary effects and sacrifice ratio. We complement the transitional analysis of the short-run costs with a rigorous welfare evaluation and show that, despite the long-lasting economic downturn, disinflation entails non-zero overall welfare gains.

  10. Survey of literature on dispersion ratio and collection ratio of radioisotopes in animal study using radioisotopes

    International Nuclear Information System (INIS)

    Tozuka, Zenzaburo; Doi, Masahiro; Miyazawa, Eiji; Kawakami, Takeo

    1998-01-01

    A survey of literature in the title was performed to know the actual status of the dispersion from excretion and expiration studies of radioisotopes since, at present, the probable dispersion ratio is assumed to be 100% in calculation for legally permitted use of radioisotopes which conceivably being far from the real status and being incompatible with the guideline for pharmacokinetic studies requiring the recovery of >95% of dosed radioactivity in balance study. There are two interpretations for the dispersion; it is the expiration ratio and it is the fraction unrecovered. Survey was done on 11 Japanese and foreign journals in 1985-1996 publishing most of pharmacokinetic studies and on 650 compounds in 358 facilities with 1,975 experiments in total. In those experiments, the total recovery of radioactivity was 95% in average, unrecovered fraction, 5% and expiration ratio, 2%. As for unclide, 14 C, 3 H, 125 I and 35 S were surveyed since they occupied 99.4% of the experiments and their dispersion was <5%. Rats were used in 70% of the experiments and the dispersion in all animal experiments was about 5%. Administration route was regardless of the dispersion. (K.H.)

  11. Why is digit ratio correlated to sports performance?

    Science.gov (United States)

    Kim, Tae Beom; Kim, Khae Hawn

    2016-12-01

    Second to fourth digit ratio is the ratio of second to fourth digit length. It has been known that digit ratio is sexually dimorphic in humans, such that males tend to have lower digit ratio (longer fourth digits relative to second digits) than females. Digit ratio is thought to be a biomarker of the balance between fetal testosterone (FT) and fetal estrogen (FE) in a relatively narrow developmental window at the end of the first trimester of pregnancy. On the contrary, the relationships between digit ratio and levels of sex steroids in adults are not clear. Most correlational studies between digit ratio and adult sex steroids have revealed that this association is statistically not significant. However, for many years, a lot of researches showed negative relationships between digit ratio and sports performance such as rugby, surfing, rowing, sprinting, endurance, and hand grip strength. Here, we discuss possible mechanisms about the relationships between digit ratio and sports performance.

  12. MCA Vmean and the arterial lactate-to-pyruvate ratio correlate during rhythmic handgrip

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Plomgaard, Peter; Krogh-Madsen, Rikke

    2006-01-01

    /P ratio at two plasma lactate levels. MCA Vmean was determined by ultrasound Doppler sonography at rest, during 10 min of rhythmic handgrip exercise at approximately 65% of maximal voluntary contraction force, and during 20 min of recovery in seven healthy male volunteers during control...... and a approximately 15 mmol/l hyperglycemic clamp. Cerebral arteriovenous differences for metabolites were obtained by brachial artery and retrograde jugular venous catheterization. Control resting arterial lactate was 0.78 +/- 0.09 mmol/l (mean +/- SE) and pyruvate 55.7 +/- 12.0 micromol/l (L/P ratio 16.4 +/- 1......Regulation of cerebral blood flow during physiological activation including exercise remains unknown but may be related to the arterial lactate-to-pyruvate (L/P) ratio. We evaluated whether an exercise-induced increase in middle cerebral artery mean velocity (MCA Vmean) relates to the arterial L...

  13. Simulation Analysis of Computer-Controlled pressurization for Mixture Ratio Control

    Science.gov (United States)

    Alexander, Leslie A.; Bishop-Behel, Karen; Benfield, Michael P. J.; Kelley, Anthony; Woodcock, Gordon R.

    2005-01-01

    A procedural code (C++) simulation was developed to investigate potentials for mixture ratio control of pressure-fed spacecraft rocket propulsion systems by measuring propellant flows, tank liquid quantities, or both, and using feedback from these measurements to adjust propellant tank pressures to set the correct operating mixture ratio for minimum propellant residuals. The pressurization system eliminated mechanical regulators in favor of a computer-controlled, servo- driven throttling valve. We found that a quasi-steady state simulation (pressure and flow transients in the pressurization systems resulting from changes in flow control valve position are ignored) is adequate for this purpose. Monte-Carlo methods are used to obtain simulated statistics on propellant depletion. Mixture ratio control algorithms based on proportional-integral-differential (PID) controller methods were developed. These algorithms actually set target tank pressures; the tank pressures are controlled by another PID controller. Simulation indicates this approach can provide reductions in residual propellants.

  14. Compost feedstock characteristics and ratio modelling for organic waste materials co-composting in Malaysia.

    Science.gov (United States)

    Chai, E W; H'ng, P S; Peng, S H; Wan-Azha, W M; Chin, K L; Chow, M J; Wong, W Z

    2013-01-01

    In Malaysia, large amounts of organic materials, which lead to disposal problems, are generated from agricultural residues especially from palm oil industries. Increasing landfill costs and regulations, which limit many types of waste accepted at landfills, have increased the interest in composting as a component of waste management. The objectives of this study were to characterize compost feedstock properties of common organic waste materials available in Malaysia. Thus, a ratio modelling of matching ingredients for empty fruit bunches (EFBs) co-composting using different organic materials in Malaysia was done. Organic waste materials with a C/N ratio of composting. The outcome of this study suggested that the percentage of EFB ranged between 50% and 60%, which is considered as the ideal mixing ratio in EFB co-composting. Conclusively, EFB can be utilized in composting if appropriate feedstock in term of physical and chemical characteristics is coordinated in the co-composting process.

  15. Impaired imprinted X chromosome inactivation is responsible for the skewed sex ratio following in vitro fertilization

    Science.gov (United States)

    Tan, Kun; An, Lei; Miao, Kai; Ren, Likun; Hou, Zhuocheng; Tao, Li; Zhang, Zhenni; Wang, Xiaodong; Xia, Wei; Liu, Jinghao; Wang, Zhuqing; Xi, Guangyin; Gao, Shuai; Sui, Linlin; Zhu, De-Sheng; Wang, Shumin; Wu, Zhonghong; Bach, Ingolf; Chen, Dong-bao; Tian, Jianhui

    2016-01-01

    Dynamic epigenetic reprogramming occurs during normal embryonic development at the preimplantation stage. Erroneous epigenetic modifications due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF) are linked to various short- or long-term consequences. Among these, the skewed sex ratio, an indicator of reproductive hazards, was reported in bovine and porcine embryos and even human IVF newborns. However, since the first case of sex skewing reported in 1991, the underlying mechanisms remain unclear. We reported herein that sex ratio is skewed in mouse IVF offspring, and this was a result of female-biased peri-implantation developmental defects that were originated from impaired imprinted X chromosome inactivation (iXCI) through reduced ring finger protein 12 (Rnf12)/X-inactive specific transcript (Xist) expression. Compensation of impaired iXCI by overexpression of Rnf12 to up-regulate Xist significantly rescued female-biased developmental defects and corrected sex ratio in IVF offspring. Moreover, supplementation of an epigenetic modulator retinoic acid in embryo culture medium up-regulated Rnf12/Xist expression, improved iXCI, and successfully redeemed the skewed sex ratio to nearly 50% in mouse IVF offspring. Thus, our data show that iXCI is one of the major epigenetic barriers for the developmental competence of female embryos during preimplantation stage, and targeting erroneous epigenetic modifications may provide a potential approach for preventing IVF-associated complications. PMID:26951653

  16. Global budgets in Maryland: early evidence on revenues, expenses, and margins in regulated and unregulated services

    DEFF Research Database (Denmark)

    Malmmose, Margit; Mortensen, Karoline; Holm, Claus

    2018-01-01

    suggest that regulated profit ratios for treatment hospitals increased (from 5% in2007 to 8% in 2013) and regulated expense-to-gross patient revenue ratios decreased (75%in 2007 and 68% in 2013) relative to the controls. Simultaneously, the profit margins fortreatment hospitals’ unregulated services...

  17. Culture and emotion regulation.

    Science.gov (United States)

    Ford, Brett Q; Mauss, Iris B

    2015-06-01

    While anthropological research has long emphasized cultural differences in whether emotions are viewed as beneficial versus harmful, psychological science has only recently begun to systematically examine those differences and their implications for emotion regulation and well-being. Underscoring the pervasive role of culture in people's emotions, we summarize research that has examined links between culture, emotion regulation, and well-being. Specifically, we focus on two questions. First, how does culture lead individuals to regulate their emotions? And second, how does culture modulate the link between emotion regulation and well-being? We finish by suggesting directions for future research to advance the study of culture and emotion regulation.

  18. Radiation Control Regulation 1993

    International Nuclear Information System (INIS)

    1993-01-01

    This Regulation (No. 434-1993) was made in pursuance of the Radiation Control Act 1990 and replaces the Active Substances Regulations 1959 repealed by the Act. It entered into force on 1 September 1993. The Regulation specifies that the technical radiation protection definitions have the same meaning as in the 1990 recommendations. The Regulation provides for the licensing of persons to use radioactive substances and radiation apparatus. It prescribes activities which may only be carried out by an accredited radiation expert and regulates the use of radiation apparatus and radioactive substances as well as the disposal and transport of radiation apparatus and radioactive substances. (NEA)

  19. Load regulating expansion fixture

    International Nuclear Information System (INIS)

    Wagner, L.M.; Strum, M.J.

    1998-01-01

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located there between. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig

  20. Volume regulation in epithelia

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Hoffmann, Else Kay

    2016-01-01

    to amphibian skin and mammalian cortical collecting tubule of low and intermediate osmotic permeability. Crosstalk between entrance and exit mechanisms interferes with volume regulation both at aniso-osmotic and iso-osmotic volume perturbations. It has been proposed that cell volume regulation is an intrinsic...... regulation are cloned. The volume-regulated anion channel (VRAC) exhibiting specific electrophysiological characteristics seems exclusive to serve cell volume regulation. This is contrary to K+ channels as well as cotransporters and exchange mechanisms that may serve both transepithelial transport and cell...... volume regulation. In the same cell, these functions may be maintained by different ion pathways that are separately regulated. RVD is often preceded by increase in cytosolic free Ca2+, probably via influx through TRP channels, but Ca2+ release from intracellular stores has also been observed. Cell...

  1. Reevaluation of the Pavlov ratio in patients with cervical myelopathy.

    Science.gov (United States)

    Suk, Kyung-Soo; Kim, Ki-Tack; Lee, Jung-Hee; Lee, Sang-Hun; Kim, Jin-Soo; Kim, Jin-Young

    2009-03-01

    This study was designed to reevaluate the effectiveness of the Pavlov ratio in patients with cervical myelopathy. We studied 107 patients who underwent open door laminoplasty for the treatment of cervical myelopathy between the C3 to C7 levels. We determined the Pavlov ratio on preoperative and postoperative cervical spine lateral radiographs, the vertebral body-to-canal ratio on sagittal reconstruction CT scans, and the vertebral body-to-cerebrospinal fluid (CSF) column ratio on T2-weighted sagittal MR images from C3 to C6. The severity of myelopathy was determined using the JOA score on both preoperative and postoperative images. The recovery rate was also calculated. The Pavlov ratio in plain radiographs from patients with myelopathy was compared with the ratio of the vertebral body to the spinal canal on CT and MRI. The average Pavlov ratio between C3 and C6 ranged from 0.71 to 0.76. On CT scan, the average vertebral body-to-canal ratio between C3 and C6 ranged from 0.62 to 0.66. On MRI, the vertebral body-to-CSF column ratio between C3 and C6 ranged between 0.53 and 0.57. A positive correlation was noted between the Pavlov ratio and the vertebral body-to-canal ratio on sagittal-reconstruction CT (correlation coefficient = 0.497-0.627, p = 0.000) and between the Pavlov ratio and the vertebral body-to-CSF column ratio on MRI (correlation coefficient = 0.511-0.649, p = 0.000). We demonstrated a good correlation between the Pavlov ratio and both the vertebral body-to-canal ratio on CT and the vertebral body-to-CSF column ratio on MRI. Therefore, the Pavlov ratio can be relied upon to predict narrowing of the cervical spinal canal in the sagittal plane.

  2. Particle ratios, quarks, and Chao-Yang statistics

    Energy Technology Data Exchange (ETDEWEB)

    Chew, C K; Low, G B; Lo, S Y [Nanyang Univ. (Singapore). Dept. of Physics; Phua, K K [Argonne National Lab., IL (USA)

    1980-01-01

    By introducing quarks into Chao-Yang statistics for 'violent' collisions, particle ratios are obtained which are consistent with the Chao-Yang results. The present method can also be extended to baryon-meson and baryon-antibaryon ratios.

  3. Amplitude ratios in ρ0 leptoproductions and GPDs

    Directory of Open Access Journals (Sweden)

    Goloskokov S.V.

    2017-01-01

    Using the model results we calculate the ratio of different helicity amplitudes for a transversely polarized proton target to the leading twist longitudinal amplitude. Our results are close to the amplitude ratios measured by HERMES.

  4. A Hybrid Joint Moment Ratio Test for Financial Time Series

    NARCIS (Netherlands)

    Groenendijk, Patrick A.; Lucas, André; Vries, de Casper G.

    1998-01-01

    We advocate the use of absolute moment ratio statistics in conjunctionwith standard variance ratio statistics in order to disentangle lineardependence, non-linear dependence, and leptokurtosis in financial timeseries. Both statistics are computed for multiple return horizonssimultaneously, and the

  5. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis.

    Science.gov (United States)

    Mazza, Mario Gennaro; Lucchi, Sara; Tringali, Agnese Grazia Maria; Rossetti, Aurora; Botti, Eugenia Rossana; Clerici, Massimo

    2018-06-08

    The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Effect of the Th-232/U-238 ratio on the conversion ratio of PWR's

    International Nuclear Information System (INIS)

    Correa, F.

    1977-01-01

    The conversion ratio, the consumption of natural uranium and separative work for current PWR lattice designs are studied as function of: the initial fraction of thorium in the fuel, the type of fuel recycling employed, and the growth rate of the system of reactors. The incentive to utilize thorium is maximum when: thorium is used together with fully enriched uranium (93%); if only uranium can be recycled; and the system of reactors is at equilibrium. Under these conditions, the comsumption of natural uranium and separative work are lower than the all-uranium-fuel case by 41% and 18%,respectively [pt

  7. 10 CFR 436.21 - Savings-to-investment ratio.

    Science.gov (United States)

    2010-01-01

    ... is the ratio of the present value savings to the present value costs of an energy or water conservation measure. The numerator of the ratio is the present value of net savings in energy or water and non... conservation measure. The denominator of the ratio is the present value of the net increase in investment and...

  8. The Improved Estimation of Ratio of Two Population Proportions

    Science.gov (United States)

    Solanki, Ramkrishna S.; Singh, Housila P.

    2016-01-01

    In this article, first we obtained the correct mean square error expression of Gupta and Shabbir's linear weighted estimator of the ratio of two population proportions. Later we suggested the general class of ratio estimators of two population proportions. The usual ratio estimator, Wynn-type estimator, Singh, Singh, and Kaur difference-type…

  9. 7 CFR 1425.10 - Financial ratio requirement.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Financial ratio requirement. 1425.10 Section 1425.10... Financial ratio requirement. To be financially able to make advances to their members and to market their commodities, CMA's shall have a current ratio of at least 1 dollar of current assets for each 1 dollar of...

  10. 41 CFR 109-27.5002 - Stores inventory turnover ratio.

    Science.gov (United States)

    2010-07-01

    ... turnover ratio. 109-27.5002 Section 109-27.5002 Public Contracts and Property Management Federal Property....5002 Stores inventory turnover ratio. Comparison of investment in stores inventories to annual issues... comparison may be expressed either as a turnover ratio (dollar value of issues divided by dollar value of...

  11. DC-to-AC inverter ratio failure detector

    Science.gov (United States)

    Ebersole, T. J.; Andrews, R. E.

    1975-01-01

    Failure detection technique is based upon input-output ratios, which is independent of inverter loading. Since inverter has fixed relationship between V-in/V-out and I-in/I-out, failure detection criteria are based on this ratio, which is simply inverter transformer turns ratio, K, equal to primary turns divided by secondary turns.

  12. Lagoa Real design. Cachoeira mine. Uranium ratio from gamma profile

    International Nuclear Information System (INIS)

    Juliao, B.

    1984-06-01

    This paper presents the satisfactory accuracy of uranium ratio from gamma profile, using an equation from simple regression. The comparative study between radiometric ratios calculated from gamma data in boreholes and uranium ratio determined by Delayed Neutron Analysis shows a good measure of correlation in Cachoeira Mines. (author)

  13. [Operation directions by comparing financial ratio of 22 provincial hospitals].

    Science.gov (United States)

    Wang, J Y; Ko, Y C; Wang, J W; Jan, L C; Chang, F M; Lin, K C

    1996-12-01

    Even more restrictive regulations and reimbursement limits seem to be a very heavy burden and stress for most provincial hospitals, especially after the National Health Insurance System has been introduced. The purpose of this project to find a better, universal direction for these hospitals through three steps: 1) Using different financial and accounting ratio indexes to evaluate the general business performance of each hospital. 2) Taking a comprehensive questionnaire with senior managers of each hospital to know their concepts and attitudes concerning external environment and internal operation. 3) Comparing data's correlation and differentiation to ascertain better trends for future operation for all hospitals. The database for this project comes from two resources: 1) Government finance and budget reports of 22 provincial hospitals for the 1994 accounting calendar year. 2) The results of questionnaires returned by 274 senior managers of hospitals, and analysis of these by chi-square test. Through statistical comparison, a number of conclusions can be made: 1) Most hospitals have better operation efficiency if any professional hospital administrator is working for them. 2) The hospital with more comprehensive personnel system shows better business performance. 3) The hospital with routine and formal financial analysis reports always has better business performance. 4) The hospital with poor operational efficiency tends to get rid of restriction or limitation from government's system. 5) The hospital with good operational efficiency has more confidence and desire to improve and change. 6) The hospital with poor operational efficiency is more dependent on outside support from government. 7) The hospital with better business performance has more concern about the impact of malpractice around the hospital. In short, a hospital with poor business efficiency always has more pessimistic attitude and tends to rely on outside resource support. On the other hand, a

  14. Optimal ratio of cash and non-cash payments

    Directory of Open Access Journals (Sweden)

    Galina S. Panova

    2014-01-01

    Full Text Available Analysis of the present condition and prospects of development of the monetary sector of the Russian economy. Quantitative parameters of aggregate turnover, including the value of cash and non-cash it. Researched issues restricting cash advance industry in Russia and other countries; the problems encountered by foreign States in imposing administrative limits on cash payments; provides specific recommendations and identified risks imposing such restrictions in Russia. The article deals with topical issues of optimization of structure of aggregate turnover. Analyzing the development of money turnover, the role and the place of cash in the economy, the author explored the basic approaches to the determination and regulation of money turnover, proposed a new approach to ensure transparency in money flows. Particularly promising cash flow optimization are: a measures aimed at improving the cash turnover (including maintaining the stability of the national currency, improving the procedures for issuing and withdrawing money from circulation, determine the optimal structure of monetary aggregates, etc. and b development of cashless money turnover. The author's position is presented on the future of the scientific basis and practical realization of the optimal ratio of cash and cashless money turnover in Russia and other countries. In particular, felt the need to increase information transparency, openness international information exchange in order to improve monetary policy by countries at the national and international level. To develop common approaches (models of the analysis and forecasting of financial markets, as well as the establishment of an international coordination centre responsible for the collection, verification and access to public information databases for the cross-country studies of banking and financial and monetary sphere.

  15. How the oxygen isotope ratio of rain water influences the isotope ratio of chicken eggshell carbonate

    Science.gov (United States)

    Price, Gregory; Grimes, Stephen

    2015-04-01

    The stable oxygen isotope ratio of chicken eggshell carbonate was analysed from chicken eggs laid under free range, and organic farming regimes from across the UK. The eggshell carbonate oxygen isotope data shows a clear depletion in delta18O distribution from the southwest to the northeast. Although consistently offset by around 1 permil, the same isotopic distribution as that seen in eggshell carbonate is observed in the delta18O ratio of rainfall and groundwater from across the UK. This distribution is related to the Rayleigh distillation of rainfall driven by westerly winds across the UK landmass. The clear relationship observed between eggshell delta18O values and that of rainwater presumably reflects the nature of free range chickens which must be drinking locally derived rainwater and supplementing their diet and water intake with locally derived food. These results suggest that the oxygen isotope value of chicken eggshells can be used as a forensic tool to identify the locality that free range and organic eggs were laid within the UK. Furthermore, if suitable material is preserved in the archaeological and geological record then such a relationship can potentially be used to establish the oxygen isotope value of rainwater from which ancient and / or ancestral birds lived.

  16. Mean platelet volume, neutrophil to lyphocyte ratio and platelet to lymphocyte ratio in psoriasis

    Directory of Open Access Journals (Sweden)

    Mehmet Ünal

    2015-06-01

    Full Text Available Background and Design: It has been demonstrated that ratio of neutrophil and platelet count systemic inflammation and is associated with prognosis of many cardiovascular diseases, malignates and chronic inflammatory diseases.As far as it is known, there are no studies investigating neutrophil/lymphocyeratio(NLR, platelet/lymphocyte ratio(PLR and mean platelet volume(MPV values together within the context of psoriasis, a chronic and systemic inflammatory disease. Materials and Methods: 320 patients followed up in our polyclinic with psoriasis vulgaris and 200 healthy persons were evaluated in the study. Results: Leukocyte, neutrophil, platelet, MPV, NLR and PLR values in patients with psoriasis were significantly higher, and lymphocyte count, on the other hand, was significantly lower than those of the control group. No significant difference was found between MPV, NLR and PLR values of patients with or without a family history, nail and joint involvement. Conclusions: These parameters may be made use of as cheap and easily applicable methods in predicting which psoriasis patients are under the risk of cardiovascular disease. PLR is a better inflammation marker than MPV and NLR in patients with psoriasis. We did not observe a significant relationship between MPV, NLR and PLR values and such disease characteristics as severity of disease, joint involvement, nail involvement and duration of disease in patients with psoriasis. So, we believe that there is little information on the extent to which MPV,NLR and PLR might be useful regarding these characteristics.

  17. TOWARD MORE EFFECTIVE REGULATION

    Energy Technology Data Exchange (ETDEWEB)

    J. GRAF

    2000-06-01

    This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

  18. The development of regulations

    International Nuclear Information System (INIS)

    Slokan Dusic, D.; Levstek, M.F.; Stritar, A.

    2003-01-01

    In October 2002, The Act on Protection Against Ionising Radiation and Nuclear Safety which regulates all aspects of protection against ionising radiation and nuclear safety entered into force in Slovenia. The Slovenian government and its responsible ministries shall issue several governmental and ministerial regulations to support the above - mentioned act. The Slovenian Nuclear Safety Administration (SNSA) which acts within the Ministry of the Environment, Spatial Planing and Energy takes an active part in drafting the regulations which are defined in the act. Due to a very comprehensive and pretentious task, that is to be completed in a relatively short period of time, taking into consideration the involvement of stakeholders and all competent ministries, the SNSA within the Quality Management System developed a special procedure that insures the systematic approach to the preparation of regulations. The article will briefly represent the process that: defines the preparation, development, harmonisation, review, approval and issue of regulations and uniforms the format of developed regulations. (author)

  19. Investigation of Pockels Cells Crystal Contrast Ratio Distribution

    Directory of Open Access Journals (Sweden)

    Giedrius Sinkevičius

    2017-07-01

    Full Text Available The BBO Pockel’s cell has been investigated. The investigation results of optimal operating area on the surface of the crystal dependent of intrinsic contrast ratio (ICR and voltage contrast ratio (VCR for Pockel’s cell are presented. The block diagram of Pockel’s cells contrast measurement stand and measurement methodology are introduced and discussed. The graphs of intrinsic contrast ratio distribution on crystal surface, contrast ratio with voltage dependency and voltage contrast ratio distribution on crystal surface with half-wave voltage are presented.

  20. Elevated sacroilac joint uptake ratios in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    De Smet, A.A.; Mahmood, T.; Robinson, R.G.; Lindsley, H.B.

    1984-01-01

    Sacroiliac joint radiographs and radionuclide sacroiliac joint uptake ratios were obtained on 14 patients with active systemic lupus erythematosus. Elevated joint ratios were found unilaterally in two patients and bilaterally in seven patients when their lupus was active. In patients whose disease became quiescent, the uptake ratios returned to normal. Two patients had persistently elevated ratios with continued clinical and laboratory evidence of active lupus. Mild sacroiliac joint sclerosis and erosions were detected on pelvic radiographs in these same two patients. Elevated quantitative sacroiliac joint uptake ratios may occur as a manifestation of active systemic lupus erythematosus

  1. Effect of ceramic calcium-phosphorus ratio on chondrocyte-mediated biosynthesis and mineralization.

    Science.gov (United States)

    Boushell, Margaret K; Khanarian, Nora T; LeGeros, Raquel Z; Lu, Helen H

    2017-10-01

    The osteochondral interface functions as a structural barrier between cartilage and bone, maintaining tissue integrity postinjury and during homeostasis. Regeneration of this calcified cartilage region is thus essential for integrative cartilage healing, and hydrogel-ceramic composite scaffolds have been explored for calcified cartilage formation. The objective of this study is to test the hypothesis that Ca/P ratio of the ceramic phase of the composite scaffold regulates chondrocyte biosynthesis and mineralization potential. Specifically, the response of deep zone chondrocytes to two bioactive ceramics with different calcium-phosphorus ratios (1.35 ± 0.01 and 1.41 ± 0.02) was evaluated in agarose hydrogel scaffolds over two weeks in vitro. It was observed that the ceramic with higher calcium-phosphorus ratio enhanced chondrocyte proliferation, glycosaminoglycan production, and induced an early onset of alkaline phosphorus activity, while the ceramic with lower calcium-phosphorus ratio performed similarly to the ceramic-free control. These results underscore the importance of ceramic bioactivity in directing chondrocyte response, and demonstrate that Ca/P ratio is a key parameter to be considered in osteochondral scaffold design. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2694-2702, 2017. © 2017 Wiley Periodicals, Inc.

  2. Liquidity Analysis Using Cash Flow Ratios as Compared to Traditional Ratios in the Pharmaceutical Sector in Jordan

    OpenAIRE

    Sulayman H. Atieh

    2014-01-01

    The purpose of this study is to examine the liquidity position of the Jordanian pharmaceutical sector using the traditional ratios as compared to the more recently developed cash flow ratios. The research involved the comparison between traditional ratios and cash flow ratios of the big seven companies of the pharmaceutical industry in Jordan over six years period (2007¨C2012). The companies were all from the same sector, and the data was obtained from the annual reports of these companies. T...

  3. Regulating hedge funds.

    OpenAIRE

    Daníelsson, J.; Zigrand, JP.

    2007-01-01

    Due to the ever-increasing amounts under management and their unregulated and opaque nature, hedge funds have emerged as a key concern for policymakers. While until now, hedge funds have been left essentially unregulated, we are seeing increasing calls for regulation for both microprudential and macroprudential reasons. In our view, most calls for the regulation of hedge funds are based on a misperception of the effectiveness of financial regulations, perhaps coupled with a lack of understand...

  4. A Study on the Effects of Compression Ratio, Engine Speed and Equivalence Ratio on HCCI Combustion of DME

    DEFF Research Database (Denmark)

    Pedersen, Troels Dyhr; Schramm, Jesper

    2007-01-01

    An experimental study has been carried out on the homogeneous charge compression ignition (HCCI) combustion of Dimethyl Ether (DME). The study was performed as a parameter variation of engine speed and compression ratio on excess air ratios of approximately 2.5, 3 and 4. The compression ratio was...

  5. Regulating household financial advice

    Directory of Open Access Journals (Sweden)

    Benjamin F. Cummings

    2012-08-01

    Full Text Available This paper reviews economic theory related to investment advice. This theory explains 1 why financial advisors need to be carefully regulated for the benefit of both the investment advice industry and for consumers, 2 why principles-based regulation (e.g., a fiduciary standard is more efficient than rules-based regulation, 3 why dual regulation of financial professionals providing investment or insurance advice is inefficient and inequitable policy, and 4 why the application of a universal and uniform fiduciary standard will be difficult to implement.

  6. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank

    Within hunting, wildlife populations are estimated to be too high in many countries which is assumed to be due to the market failure, that each hunter harvests too little compared to what the regulator wants. This may be due to the existing regulation which, among other things, requires knowledge...... by an individual, variable tax rate. The variable tax rate is, among other things, based on the difference in marginal value of the population between the hunter and the regulator. The paper shows that the population tax/subsidy secures a first-best optimum. Thus, the population tax is a good alternative...... to the existing regulation....

  7. Nuclear safety and regulation

    International Nuclear Information System (INIS)

    Kim, Hho Jung

    2000-03-01

    This book contains 12 chapters, which are atom and radiation, nuclear reactor and kinds of nuclear power plant, safeguard actuation system and stability evaluation for rock foundation of nuclear power plant, nuclear safety and principle, safety analysis and classification of incident, probabilistic safety assessment and major incident, nuclear safety regulation, system of nuclear safety regulation, main function and subject of safety regulation in nuclear facilities, regulation of fuel cycle and a nuclear dump site, protection of radiation and, safety supervision and, safety supervision and measurement of environmental radioactivity.

  8. Impact of Inflation Accounting Application on Key Financial Ratios

    Directory of Open Access Journals (Sweden)

    Aydın KARAPINAR

    2012-03-01

    Full Text Available This paper investigates the impact of inflation accounting on key financal ratios. To this end, the financial statements of 132 companies listed in the Istanbul Stock Exchange (ISE are studied. An analyis of paired samples t test has been conducted on the financial ratios of the companies. The results show that a significant difference between adjusted cost based financial ratios and historical cost based financial ratios occurs only for current, ratios, equity ratios and noncurrent turnover ratios. The study does not cover companies operating in the financial sector. The companies reporting in accordance with IFRS for the studied periods that spans 2001-2004 are not included in the study either. The study offers valuable information as to analysing companies operating in hiper inflation economies.

  9. Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation

    DEFF Research Database (Denmark)

    Nicolaï, Niels; Leersnyder, Fien De; Copot, Dana

    2018-01-01

    for the dynamic behavior of the granule liquid‐to‐solid ratio (w) at the end of the granulation unit of a commercial ConsiGmaTM‐25 production line. Near‐infrared spectroscopy was used to monitor the granule composition in‐line. The outcome for both the tracking and regulator problem using either conventional...

  10. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-κB ligand (RANKL) expression in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Takeshita, Harunori; Kitano, Masayasu; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto; Miyazawa, Keiji; Hla, Timothy; Sano, Hajime

    2012-01-01

    Highlights: ► MH7A cells and CD4 + T cells expressed S1P1 and RANKL. ► S1P increased RANKL expression in MH7A cells and CD4 + T cells. ► The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-κB ligand (RANKL) in RA synoviocytes and CD4 + T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4 + T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4 + T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-α in MH7A cells and CD4 + T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4 + T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  11. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, Harunori [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitano, Masayasu, E-mail: mkitano6@hyo-med.ac.jp [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi [Department of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima Kobe, Hyogo 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Miyazawa, Keiji [Discovery Research III, Research and Development, Kissei Pharmaceutical Company, 4365-1 Hodakakashiwara, Azumino, Nagano 399-8304 (Japan); Hla, Timothy [Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Box 69, NY 10065 (United States); Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  12. A Study on the Effects of Compression Ratio, Engine Speed and Equivalence Ratio on HCCI Combustion of DME

    DEFF Research Database (Denmark)

    Pedersen, Troels Dyhr; Schramm, Jesper

    2007-01-01

    An experimental study has been carried out on the homogeneous charge compression ignition (HCCI) combustion of Dimethyl Ether (DME). The study was performed as a parameter variation of engine speed and compression ratio on excess air ratios of approximately 2.5, 3 and 4. The compression ratio...... was adjusted in steps to find suitable regions of operation, and the effect of engine speed was studied at 1000, 2000 and 3000 RPM. It was found that leaner excess air ratios require higher compression ratios to achieve satisfactory combustion. Engine speed also affects operation significantly....

  13. PAH diagnostic ratios for the identification of pollution emission sources

    International Nuclear Information System (INIS)

    Tobiszewski, Marek; Namieśnik, Jacek

    2012-01-01

    Polycyclic aromatic hydrocarbon (PAH) diagnostic ratios have recently come into common use as a tool for identifying and assessing pollution emission sources. Some diagnostic ratios are based on parent PAHs, others on the proportions of alkyl-substituted to non-substituted molecules. The ratios are applicable to PAHs determined in different environmental media: air (gas + particle phase), water, sediment, soil, as well as biomonitor organisms such as leaves or coniferous needles, and mussels. These ratios distinguish PAH pollution originating from petroleum products, petroleum combustion and biomass or coal burning. The compounds involved in each ratio have the same molar mass, so it is assumed they have similar physicochemical properties. Numerous studies show that diagnostic ratios change in value to different extents during phase transfers and environmental degradation. The paper reviews applications of diagnostic ratios, comments on their use and specifies their limitations. - Highlights: ► PAH diagnostic ratios may identify pollution coming from petroleum spills, fuel combustion and coal or biomass burning. ► They are sensitive to changes during PAHs environmental fate processes. ► Some diagnostic ratios are of limited value due to fast photodegradation of one of the compounds. - The paper reviews PAH diagnostic ratios that are applied to identify pollution emission originating from petroleum products, fuel combustion or coal and biomass burning.

  14. Sex ratios of Mountain Plovers from egg production to fledging

    Directory of Open Access Journals (Sweden)

    Margaret M. Riordan

    2015-12-01

    Full Text Available Skewed sex ratios can have negative implications for population growth if they do not match a species' life history. A skewed tertiary sex ratio has been detected in a population of Mountain Plover (Charadrius montanus, a grassland shorebird experiencing population declines. To study the cause of the observed male skew, we examined three early life stages between egg and fledgling in eastern Colorado from 2010 to 2012. This allows us to distinguish between egg production and chick survival as an explanation for the observed skew. We examined the primary sex ratio in eggs produced and the secondary sex ratio in hatched chicks to see if the sex ratio bias occurs before hatching. We also determined the sex ratio at fledging to reveal sex-specific mortality of nestlings. The primary sex ratio was 1.01 (± 0.01 males per female. The secondary sex ratio consisted of 1.10 (± 0.02 males per female. The probability of a chick surviving to fledging differed between males (0.55 ± 0.13 and females (0.47 ± 0.15, but the precision of these survival estimates was low. Sex ratios in early life stages of the Mountain Plover do not explain the skewed sex ratio observed in adults in this breeding population.

  15. [Using log-binomial model for estimating the prevalence ratio].

    Science.gov (United States)

    Ye, Rong; Gao, Yan-hui; Yang, Yi; Chen, Yue

    2010-05-01

    To estimate the prevalence ratios, using a log-binomial model with or without continuous covariates. Prevalence ratios for individuals' attitude towards smoking-ban legislation associated with smoking status, estimated by using a log-binomial model were compared with odds ratios estimated by logistic regression model. In the log-binomial modeling, maximum likelihood method was used when there were no continuous covariates and COPY approach was used if the model did not converge, for example due to the existence of continuous covariates. We examined the association between individuals' attitude towards smoking-ban legislation and smoking status in men and women. Prevalence ratio and odds ratio estimation provided similar results for the association in women since smoking was not common. In men however, the odds ratio estimates were markedly larger than the prevalence ratios due to a higher prevalence of outcome. The log-binomial model did not converge when age was included as a continuous covariate and COPY method was used to deal with the situation. All analysis was performed by SAS. Prevalence ratio seemed to better measure the association than odds ratio when prevalence is high. SAS programs were provided to calculate the prevalence ratios with or without continuous covariates in the log-binomial regression analysis.

  16. General applicability of synthetic gene-overexpression for cell-type ratio control via reprogramming.

    Science.gov (United States)

    Ishimatsu, Kana; Hata, Takashi; Mochizuki, Atsushi; Sekine, Ryoji; Yamamura, Masayuki; Kiga, Daisuke

    2014-09-19

    Control of the cell-type ratio in multistable systems requires wide-range control of the initial states of cells. Here, using a synthetic circuit in E. coli, we describe the use of a simple gene-overexpression system combined with a bistable toggle switch, for the purposes of enabling the wide-range control of cellular states and thus generating arbitrary cell-type ratios. Theoretically, overexpression induction temporarily alters the bistable system to a monostable system, in which the location of the single steady state of cells can be manipulated over a wide range by regulating the overexpression levels. This induced cellular state becomes the initial state of the basal bistable system upon overexpression cessation, which restores the original bistable system. We experimentally demonstrated that the overexpression induced a monomodal cell distribution, and subsequent overexpression withdrawal generated a bimodal distribution. Furthermore, as designed theoretically, regulating the overexpression levels by adjusting the concentrations of small molecules generated arbitrary cell-type ratios.

  17. Temperature and air-fuel ratio dependent specific heat ratio functions for lean burned and unburned mixture

    International Nuclear Information System (INIS)

    Ceviz, M.A.; Kaymaz, I.

    2005-01-01

    The most important thermodynamic property used in heat release calculations for engines is the specific heat ratio. The functions proposed in the literature for the specific heat ratio are temperature dependent and apply at or near stoichiometric air-fuel ratios. However, the specific heat ratio is also influenced by the gas composition in the engine cylinder and especially becomes important for lean combustion engines. In this study, temperature and air-fuel ratio dependent specific heat ratio functions were derived to minimize the error by using an equilibrium combustion model for burned and unburned mixtures separately. After the error analysis between the equilibrium combustion model and the derived functions is presented, the results of the global specific heat ratio function, as varying with mass fraction burned, were compared with the proposed functions in the literature. The results of the study showed that the derived functions are more feasible at lean operating conditions of a spark ignition engine

  18. QUASARS ARE NOT LIGHT BULBS: TESTING MODELS OF QUASAR LIFETIMES WITH THE OBSERVED EDDINGTON RATIO DISTRIBUTION

    International Nuclear Information System (INIS)

    Hopkins, Philip F.; Hernquist, Lars

    2009-01-01

    We use the observed distribution of Eddington ratios as a function of supermassive black hole (BH) mass to constrain models of quasar/active galactic nucleus (AGN) lifetimes and light curves. Given the observed (well constrained) AGN luminosity function, a particular model for AGN light curves L(t) or, equivalently, the distribution of AGN lifetimes (time above a given luminosity t(>L)) translates directly and uniquely (without further assumptions) to a predicted distribution of Eddington ratios at each BH mass. Models for self-regulated BH growth, in which feedback produces a self-regulating 'decay' or 'blowout' phase after the AGN reaches some peak luminosity/BH mass and begins to expel gas and shut down accretion, make specific predictions for the light curves/lifetimes, distinct from, e.g., the expected distribution if AGN simply shut down by gas starvation (without feedback) and very different from the prediction of simple phenomenological 'light bulb' scenarios. We show that the present observations of the Eddington ratio distribution, spanning nearly 5 orders of magnitude in Eddington ratio, 3 orders of magnitude in BH mass, and redshifts z = 0-1, agree well with the predictions of self-regulated models, and rule out phenomenological 'light bulb' or pure exponential models, as well as gas starvation models, at high significance (∼5σ). We also compare with observations of the distribution of Eddington ratios at a given AGN luminosity, and find similar good agreement (but show that these observations are much less constraining). We fit the functional form of the quasar lifetime distribution and provide these fits for use, and show how the Eddington ratio distributions place precise, tight limits on the AGN lifetimes at various luminosities, in agreement with model predictions. We compare with independent estimates of episodic lifetimes and use this to constrain the shape of the typical AGN light curve, and provide simple analytic fits to these for use in

  19. Peak regulation right

    International Nuclear Information System (INIS)

    Gao, Z. |; Ren, Z.; Li, Z.; Zhu, R.

    2005-01-01

    A peak regulation right concept and corresponding transaction mechanism for an electricity market was presented. The market was based on a power pool and independent system operator (ISO) model. Peak regulation right (PRR) was defined as a downward regulation capacity purchase option which allowed PRR owners to buy certain quantities of peak regulation capacity (PRC) at a specific price during a specified period from suppliers. The PRR owner also had the right to decide whether or not they would buy PRC from suppliers. It was the power pool's responsibility to provide competitive and fair peak regulation trading markets to participants. The introduction of PRR allowed for unit capacity regulation. The PRR and PRC were rated by the supplier, and transactions proceeded through a bidding process. PRR suppliers obtained profits by selling PRR and PRC, and obtained downward regulation fees regardless of whether purchases are made. It was concluded that the peak regulation mechanism reduced the total cost of the generating system and increased the social surplus. 6 refs., 1 tab., 3 figs

  20. Soft Regulators, though judges

    NARCIS (Netherlands)

    de Geest, G.G.A.; Dari Mattiacci, G.

    Judges have a tendency to be more demanding than regulators. In the United States, a majority of the courts has adopted the rule that the unexcused violation of a statutory standard is negligence per se. However, the converse does not hold: compliance with regulation does not relieve the injurer of

  1. Mortgage market regulation: Europe

    NARCIS (Netherlands)

    Aalbers, M.B.; Smith, S.J.

    2012-01-01

    Despite several European Union (EU) initiatives, there is only limited pan-European mortgage market regulation. The EU strategy can be characterised as one of parallel liberalisation and consolidation. This article highlights the key differences in regulation among European mortgage markets.

  2. Regulation as Rhetoric

    DEFF Research Database (Denmark)

    Boll, Karen; Györy, Csaba

    This paper analyses the way regulatory agencies strategically use public ‘rhetoric’ and ‘management of appearance’ to strengthen their regulation. It reports a comparative study of the Securities and Exchange Commission (SEC) which is the US federal securities regulator and the Danish Tax...... and Customs Administration (SKAT) which is the national tax regulator in Denmark. SEC operates in a US context where the agency fights to get trust, while SKAT operates in a context where high trust in public agencies is a basic condition. We argue, however, that despite the radically different institutional...... engage reflectively in image promotion which serves two purposes: establishing and maintaining legitimacy in a particular social and political environment and producing compliance. Further, we argue that this regulation is a form of ‘post-bureaucratic’ regulation in which compliance is achieved...

  3. Reconceptualizing Civil Regulation

    DEFF Research Database (Denmark)

    Galang, Roberto Martin; Castello, Itziar

    2011-01-01

    This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility litera....... Finally, we argue that, in Asia, governments act as a structuration mechanism which challenges the current understanding of CSR.......This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility...... and environmental standards; but also that local, small and medium companies play a key role in the development of Asian civil regulation. We call this second finding the “CSR importation trap”. Our findings are supported by evidence on the limitations in the interchangeable properties of business and governments...

  4. The impact of tissue Doppler index E/e' ratio on instantaneous wave-free ratio.

    Science.gov (United States)

    Arashi, Hiroyuki; Yamaguchi, Junichi; Ri, Tonre; Otsuki, Hisao; Nakao, Masashi; Kamishima, Kazuho; Jujo, Kentaro; Minami, Yuichiro; Ogawa, Hiroshi; Hagiwara, Nobuhisa

    2018-03-01

    The instantaneous wave-free ratio (iFR) is a vasodilator-free, invasive pressure wire index of the functional severity of coronary stenosis and is calculated under resting conditions. In a recent study, iFR was found to be more closely linked to coronary flow reserve (CFR) than fractional flow reserve (FFR). E/e' is a surrogate marker of left ventricular (LV) filling pressure and LV diastolic dysfunction. Coronary resting flow was found to be increased in patients with elevated E/e', and higher coronary resting flow was associated with lower CFR. Higher baseline coronary flow induces a greater loss of translesional pressure and may affect iFR. However, no reports have examined the impact of E/e' on iFR. The purpose of this study was to assess the relationship between iFR and E/e' compared with FFR. We retrospectively examined 103 consecutive patients (142 with stenosis) whose iFR, FFR, and E/e' were measured simultaneously. The mean age, LV mass index, and systolic blood pressure of patients with elevated E/e' were higher than those of patients with normal E/e'. Although no significant differences were observed in mean FFR values and % diameter stenosis, the mean iFR value in patients with elevated E/e' was significantly lower than that in patients with normal E/e'. The iFR was negatively correlated with E/e', while there was no correlation between FFR and E/e'. Multivariate analysis showed that E/e' and % diameter stenosis were independent determinants of iFR. E/e' ratio affects iFR values. Our results suggest that FFR mainly reflects the functional severity of the epicardial stenosis whereas iFR could potentially be influenced by not only epicardial stenosis but also other factors related to LV filling pressure or LV diastolic dysfunction. Further research is needed to understand the underlying mechanisms that influence the evaluation of iFR in patients with elevated E/e'. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights

  5. Financial Ratio and Its Influence to Profitability in Islamic Banks.

    Directory of Open Access Journals (Sweden)

    Erika Amelia

    2015-10-01

    Full Text Available This research aims to analyze the influence of the Capital Adequacy Ratio (CAR, Non Performing Financing (NPF, Financing to Deposit Ratio (FDR and Biaya Operasional Pendapatan Operasional (BOPO to Return on Asset (ROA in Bank Muamalat Indonesia and Bank Syariah Mega. The data analysis method used in this research is multiple regression analysis. From the test results show that the Capital Adequacy Ratio (CAR, Non Performing Financing (NPF, Financing to Deposit Ratio (FDR and Biaya Operasional Pendapatan Operasional (BOPO simultaneously effect to Return on Asset (ROA. Based on the test results of the t statistic was concluded that the Capital Adequacy Ratio (CAR, Non Performing Financing (NPF and the Financing to Deposit Ratio (FDR partially no significant effect to Return on Asset (ROA, while Biaya Operasional Pendapatan Operasional (BOPO partially significant effect to Return on Asset (ROADOI: 10.15408/aiq.v7i2.1700

  6. Rotator Cuff Strength Ratio and Injury in Glovebox Workers

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, Amelia M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-01-30

    Rotator cuff integrity is critical to shoulder health. Due to the high workload imposed upon the shoulder while working in an industrial glovebox, this study investigated the strength ratio of the rotator cuff muscles in glovebox workers and compared this ratio to the healthy norm. Descriptive statistics were collected using a short questionnaire. Handheld dynamometry was used to quantify the ratio of forces produced in the motions of shoulder internal and external rotation. Results showed this population to have shoulder strength ratios that were significantly different from the healthy norm. The deviation from the normal ratio demonstrates the need for solutions designed to reduce the workload on the rotator cuff musculature of glovebox workers in order to improve health and safety. Assessment of strength ratios can be used to screen for risk of symptom development.

  7. Explorations in statistics: the analysis of ratios and normalized data.

    Science.gov (United States)

    Curran-Everett, Douglas

    2013-09-01

    Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This ninth installment of Explorations in Statistics explores the analysis of ratios and normalized-or standardized-data. As researchers, we compute a ratio-a numerator divided by a denominator-to compute a proportion for some biological response or to derive some standardized variable. In each situation, we want to control for differences in the denominator when the thing we really care about is the numerator. But there is peril lurking in a ratio: only if the relationship between numerator and denominator is a straight line through the origin will the ratio be meaningful. If not, the ratio will misrepresent the true relationship between numerator and denominator. In contrast, regression techniques-these include analysis of covariance-are versatile: they can accommodate an analysis of the relationship between numerator and denominator when a ratio is useless.

  8. Evaluation of miR-182/miR-100 Ratio for Diagnosis and Survival Prediction in Bladder Cancer.

    Science.gov (United States)

    Chen, Zhanguo; Wu, Lili; Lin, Qi; Shi, Jing; Lin, Xiangyang; Shi, Liang

    2016-09-01

    Abnormal expression of microRNAs (miRNAs) plays an important role in development of several cancer types, including bladder cancer (BCa). However, the relationship between the ratio of miR-181/miR-100 and the prognosis of BCa has not been studied yet. The aim of this study was to evaluate the expression of miR-182, miR-100 and their clinical significance in BCa. Upregulation of miR-182 and down-regulation of miR-100 were validated in tissue specimens of 134 BCa cases compared with 148 normal bladder epithelia (NBE) specimens  using TaqMan-based real-time reverse transcription quantitative PCR (RT-qPCR). The diagnostic and prognostic evaluation of miR-182, miR-100, and miR-182/miR-100 ratio was also performed. miR-182 was upregulated in BCa and miR-100 was down-regulated in BCa compared with NBE (P ratio increased the diagnostic performance, yielding an AUC of 0.981 (97.01% sensitivity and 90.54% specificity). Moreover, miR-182/miR-100 ratio was associated with pT-stage, histological grade, BCa recurrence and carcinoma in situ (P analysis indicated that miR-182/miR-100 ratio was an independent prognostic factor for overall survival (Hazard ratio: 7.142; 95% CI: 2.106 - 9.891; P analysis revealed that high-level of miR-182/miR-100 ratio was significantly correlated with shortened survival time for BCa patients (P ratio may serve as a novel promising biomarker for diagnosis and survival prediction in BCa. Further studies are needed to elucidate the role of miR-182/miR-100 ratio as a non‑invasive diagnostic tool for BCa.

  9. A father effect explains sex-ratio bias.

    Science.gov (United States)

    Malo, Aurelio F; Martinez-Pastor, Felipe; Garcia-Gonzalez, Francisco; Garde, Julián; Ballou, Jonathan D; Lacy, Robert C

    2017-08-30

    Sex ratio allocation has important fitness consequences, and theory predicts that parents should adjust offspring sex ratio in cases where the fitness returns of producing male and female offspring vary. The ability of fathers to bias offspring sex ratios has traditionally been dismissed given the expectation of an equal proportion of X- and Y-chromosome-bearing sperm (CBS) in ejaculates due to segregation of sex chromosomes at meiosis. This expectation has been recently refuted. Here we used Peromyscus leucopus to demonstrate that sex ratio is explained by an exclusive effect of the father, and suggest a likely mechanism by which male-driven sex-ratio bias is attained. We identified a male sperm morphological marker that is associated with the mechanism leading to sex ratio bias; differences among males in the sperm nucleus area (a proxy for the sex chromosome that the sperm contains) explain 22% variation in litter sex ratio. We further show the role played by the sperm nucleus area as a mediator in the relationship between individual genetic variation and sex-ratio bias. Fathers with high levels of genetic variation had ejaculates with a higher proportion of sperm with small nuclei area. This, in turn, led to siring a higher proportion of sons (25% increase in sons per 0.1 decrease in the inbreeding coefficient). Our results reveal a plausible mechanism underlying unexplored male-driven sex-ratio biases. We also discuss why this pattern of paternal bias can be adaptive. This research puts to rest the idea that father contribution to sex ratio variation should be disregarded in vertebrates, and will stimulate research on evolutionary constraints to sex ratios-for example, whether fathers and mothers have divergent, coinciding, or neutral sex allocation interests. Finally, these results offer a potential explanation for those intriguing cases in which there are sex ratio biases, such as in humans. © 2017 The Author(s).

  10. Method of Poisson's ratio imaging within a material part

    Science.gov (United States)

    Roth, Don J. (Inventor)

    1996-01-01

    The present invention is directed to a method of displaying the Poisson's ratio image of a material part. In the present invention longitudinal data is produced using a longitudinal wave transducer and shear wave data is produced using a shear wave transducer. The respective data is then used to calculate the Poisson's ratio for the entire material part. The Poisson's ratio approximations are then used to displayed the image.

  11. Effect of H/C ratio on coal ignition

    Energy Technology Data Exchange (ETDEWEB)

    Furimsky, E.

    1988-09-01

    The Cahn balance technique was found to be suitable for estimating ignition temperature and its dependence on the H/C ratio of the coal. This temperature decreased with increasing H/C ratio of coals. For coals a linear correlation between H/C ratio and the temperature was established. Chars derived from the coals deviated from the linear correlation established on coals. 17 refs., 4 figs.

  12. SM Higgs decay branching ratios and total Higgs width

    CERN Multimedia

    Daniel Denegri

    2001-01-01

    Upper: Higgs decay ratios as a function of Higgs mass. The largest branching ratio is not necessarily the most usefull one. The most usefull ones are gamma gamma bbar ZZ and WW as in those modes latter signal to background ratios can be achieved. Lower: Total Higgs decay width versus Higgs mass. At low masses the natural width is extremely small, thus observability depends on instrumental resolution primarily.

  13. BENEFITS AND CHALLENGES OF VARIABLE COMPRESSION RATIO AT DIESEL ENGINES

    OpenAIRE

    Radivoje B Pešić; Saša T Milojević; Stevan P Veinović

    2010-01-01

    The compression ratio strongly affects the working process and provides an exceptional degree of control over engine performance. In conventional internal combustion engines, the compression ratio is fixed and their performance is therefore a compromise between conflicting requirements. One fundamental problem is that drive units in the vehicles must successfully operate at variable speeds and loads and in different ambient conditions. If a diesel engine has a fixed compression ratio, a minim...

  14. The behavior of the likelihood ratio test for testing missingness

    OpenAIRE

    Hens, Niel; Aerts, Marc; Molenberghs, Geert; Thijs, Herbert

    2003-01-01

    To asses the sensitivity of conclusions to model choices in the context of selection models for non-random dropout, one can oppose the different missing mechanisms to each other; e.g. by the likelihood ratio tests. The finite sample behavior of the null distribution and the power of the likelihood ratio test is studied under a variety of missingness mechanisms. missing data; sensitivity analysis; likelihood ratio test; missing mechanisms

  15. Concentration ratios for BIOPATH: selection of the soil-to-plant concentration ratio database

    International Nuclear Information System (INIS)

    Grogan, H.A.

    1985-01-01

    In Switzerland, high-level radioactive waste is planned to be deposited in deep crystalline formations. 'BIOPATH' is the computer code which has been used to simulate the movement of radionuclides in the biosphere, in order to calculate the doses to man. The key parameter used in the model on which the code is based is the concentration ratio (CR). This specifies the transfer of individual radionuclides via the various foodchains, ultimately to man. Five types of CR are required for the model, namely soil to plant, intake by cattle to milk, intake by cattle to meat, intake by poultry to eggs and from water to fish. Each of these CR are discussed in turn; it is shown that soil to plant CR exhibit a variability that greatly exceeds that observed in the other types of CR and for this reason the report goes on to consider these in much closer detail. The different methods and experimental techniques used to derive soil to plant CR are examined and assessed, to allow evaluation of a meaningful data base for use in BIOPATH. The report concludes by examining the data available for each radionuclide in turn and listing a recommended CR for it, to input into the BIOPATH model. (author)

  16. Limiting density ratios in piston-driven compressions

    International Nuclear Information System (INIS)

    Lee, S.

    1985-07-01

    By using global energy and pressure balance applied to a shock model it is shown that for a piston-driven fast compression, the maximum compression ratio is not dependent on the absolute magnitude of the piston power, but rather on the power pulse shape. Specific cases are considered and a maximum density compression ratio of 27 is obtained for a square-pulse power compressing a spherical pellet with specific heat ratio of 5/3. Double pulsing enhances the density compression ratio to 1750 in the case of linearly rising compression pulses. Using this method further enhancement by multiple pulsing becomes obvious. (author)

  17. Accurate isotope ratio mass spectrometry. Some problems and possibilities

    International Nuclear Information System (INIS)

    Bievre, P. de

    1978-01-01

    The review includes reference to 190 papers, mainly published during the last 10 years. It covers the following: important factors in accurate isotope ratio measurements (precision and accuracy of isotope ratio measurements -exemplified by determinations of 235 U/ 238 U and of other elements including 239 Pu/ 240 Pu; isotope fractionation -exemplified by curves for Rb, U); applications (atomic weights); the Oklo natural nuclear reactor (discovered by UF 6 mass spectrometry at Pierrelatte); nuclear and other constants; isotope ratio measurements in nuclear geology and isotope cosmology - accurate age determination; isotope ratio measurements on very small samples - archaeometry; isotope dilution; miscellaneous applications; and future prospects. (U.K.)

  18. Do Workplace Sex Ratios Affect Partnership Formation and Dissolution?

    DEFF Research Database (Denmark)

    Svarer, Michael

    In this paper, I analyse the association between workplace sex ratios and partnership formation and dissolution. I find that the risk of dissolution increases with the fraction of coworkers of the opposite sex at both the female and male workplace. On the other hand, workplace sex ratios are not ......In this paper, I analyse the association between workplace sex ratios and partnership formation and dissolution. I find that the risk of dissolution increases with the fraction of coworkers of the opposite sex at both the female and male workplace. On the other hand, workplace sex ratios...

  19. Risk-informed regulation

    International Nuclear Information System (INIS)

    Hoffman, D.R.

    2003-01-01

    In assessing safety for nuclear facilities, regulators have traditionally used a deterministic approach. New techniques for assessing nuclear or radiological risks make it possible for regulators to incorporate risk insights into their regulations. By 'risk-informing' the regulatory processes, independent bodies tasked with protecting the health and safety of the public can focus on those design and operational issues most important to safety. Such an approach is a move away from prescriptive regulations that were based on conservative engineering judgments toward regulations focused on issues that contribute significantly to safety. Despite the availability of probabilistic risk assessment (PRA) tools, organisations often struggle with how to best use this capability. Most international regulations are still based largely on deterministic analyses that were developed without the benefit of quantitative or measurable estimates of risk. PRA considers issues of risk in a more comprehensive manner by examining a wider spectrum of initiating events and their frequency, and considers the likelihood of events in a rigorous and comprehensive manner. In some countries, nuclear regulators are actively moving toward increasing the use of risk insights in a variety of strategic arenas, including risk-informed technical specifications (operating limits and conditions), in-service inspection and testing, programs, and assessment and enforcement actions. A risk-informed approach enhances the traditional deterministic approach by explicitly considering a broader range of safety challenges, focusing resources on the basis of risk significance, considering a broader range of counter measures to mitigate challenges, and explicitly identifying and quantifying uncertainties in analyses. (author)

  20. Epigenetic Regulation of Adipokines

    Directory of Open Access Journals (Sweden)

    Tho X. Pham

    2017-08-01

    Full Text Available Adipose tissue expansion in obesity leads to changes in the expression of adipokines, adipocyte-specific hormones that can regulate whole body energy metabolism. Epigenetic regulation of gene expression is a mechanism by which cells can alter gene expression through the modifications of DNA and histones. Epigenetic mechanisms, such as DNA methylation and histone modifications, are intimately tied to energy metabolism due to their dependence on metabolic intermediates such as S-adenosylmethionine and acetyl-CoA. Altered expression of adipokines in obesity may be due to epigenetic changes. The goal of this review is to highlight current knowledge of epigenetic regulation of adipokines.

  1. The power of regulation

    International Nuclear Information System (INIS)

    Lewis, M.G.

    1995-01-01

    Slides accompanying a presentation at The Power of Change Conference in Vancouver, BC in April 1995 about regulations affecting the power industry were presented. Issues addressed included customer choice, incentive regulation changes (price-caps, revenue sharing and pricing flexibility), the reactions of Canadian industry to regulatory changes, and anticipated reactions of the financial markets to changes in regulations. The potential effects of competition and changes that will create competition were discussed. The level of readiness of Canadian financial, ownership and regulatory bodies was discussed. The needs and expectations of investors from a new regulatory regime were quesstimated. Possible alternatives to the present regulatory framework were suggested

  2. Electrical installations and regulations

    CERN Document Server

    Whitfield, J F

    1966-01-01

    Electrical Installations and Regulations focuses on the regulations that apply to electrical installations and the reasons for them. Topics covered range from electrical science to alternating and direct current supplies, as well as equipment for providing protection against excess current. Cables, wiring systems, and final subcircuits are also considered, along with earthing, discharge lighting, and testing and inspection.Comprised of 12 chapters, this book begins with an overview of electrical installation work, traits of a good electrician, and the regulations governing installations. The r

  3. Determination of the Geographical Origin of All Commercial Hake Species by Stable Isotope Ratio (SIR) Analysis.

    Science.gov (United States)

    Carrera, Mónica; Gallardo, José M

    2017-02-08

    The determination of the geographical origin of food products is relevant to comply with the legal regulations of traceability, to avoid food fraud, and to guarantee food quality and safety to the consumers. For these reasons, stable isotope ratio (SIR) analysis using an isotope ratio mass spectrometry (IRMS) instrument is one of the most useful techniques for evaluating food traceability and authenticity. The present study was aimed to determine, for the first time, the geographical origin for all commercial fish species belonging to the Merlucciidae family using SIR analysis of carbon (δ 13 C) and nitrogen (δ 15 N). The specific results enabled their clear classification according to the FAO (Food and Agriculture Organization of the United Nations) fishing areas, latitude, and geographical origin in the following six different clusters: European, North African, South African, North American, South American, and Australian hake species.

  4. Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo

    DEFF Research Database (Denmark)

    Bülow, J; Madsen, J; Astrup, A

    1985-01-01

    Subcutaneous or perirenal adipose tissue blood flow was measured with the 133Xe-washout technique before and after intravenous injection or infusion of Intralipid in six anesthetized, otherwise intact mongrel dogs. In four anesthetized mongrel puppies adipose tissue blood flow was measured...... as well as in young dogs after this treatment. The administration of Intralipid did not per se induce the vasoconstriction. The vasoconstriction took place simultaneously with increasing FFA/albumin molar ratios. The results support our previous findings in perfused fat pads that high molar FFA....../albumin ratios increase vascular resistance in adipose tissue and they give further support to our suggestion that this vasoconstriction may be a link in a negative-feedback mechanism regulating FFA-mobilization in relation to FFA utilization....

  5. Sex ratios in fetuses and liveborn infants with autosomal aneuploidy

    Energy Technology Data Exchange (ETDEWEB)

    Heuther, C.A.; Martin, R.L.M.; Stoppelman, S.M. [Univ. of Cincinnati, OH (United States)] [and others

    1996-06-14

    Ten data sources were used substantially to increase the available data for estimating fetal and livebirth sex ratios for Patau (trisomy 13), Edwards (trisomy 18), and Down (trisomy 21) syndromes and controls. The fetal sex ratio estimate was 0.88 (N = 584) for trisomy 13, 0.90 (N = 1702) for trisomy 18, and 1.16 (N = 3154) for trisomy 21. All were significantly different from prenatal controls (1.07). The estimated ratios in prenatal controls were 1.28 (N = 1409) for CVSs and 1.06 (N = 49427) for amniocenteses, indicating a clear differential selection against males, mostly during the first half of fetal development. By contrast, there were no sex ratio differences for any of the trisomies when comparing gestational ages <16 and >16 weeks. The livebirth sex ratio estimate was 0.90 (N = 293) for trisomy 13, 0.63 (N = 497) for trisomy 18, and 1.15 (N = 6424) for trisomy 21, the latter two being statistically different than controls (1.05) (N = 3660707). These ratios for trisomies 13 and 18 were also statistically different than the ratio for trisomy 21. Only in trisomy 18 did the sex ratios in fetuses and livebirths differ, indicating a prenatal selection against males >16 weeks. No effects of maternal age or race were found on these estimates for any of the fetal or livebirth trisomies. Sex ratios for translocations and mosaics were also estimated for these aneuploids. Compared to previous estimates, these results are less extreme, most likely because of larger sample sizes and less sample bias. They support the hypothesis that these trisomy sex ratios are skewed at conception, or become so during embryonic development through differential intrauterine selection. The estimate for Down syndrome livebirths is also consistent with the hypothesis that its higher sex ratio is associated with paternal nondisjunction. 36 refs., 5 tabs.

  6. Ratio superior, ratio inferior y el agustinismo de Tomás de Aquino

    Directory of Open Access Journals (Sweden)

    Moya Cañas, Patricia

    2013-12-01

    Full Text Available This article discusses Aquinas’ reception of the Augustinian distinction between ratio inferior and superior. Though not a central aspect of Aquinas’ thought, it is a signifi cant pointer to the presence of Augustinian patterns of thought in a non-theological part of his work. After a general survey of the presence of this distinction in the opera omnia of Aquinas, his use of this topic in some specific instances is discussed: the distinction between contemplative and active life, the division of human faculties, and the moral problem of peevish delight.El artículo discute la recepción que hace Tomás de Aquino de la distinción agustiniana entre razón superior e inferior. Si bien no se trata de uno de los tópicos centrales de la doctrina tomasiana, es un elemento significativo a la hora de considerar dentro de la obra de Tomás la presencia de patrones agustinianos de pensamiento que no sean primordialmente teológicos. Tras discutir de modo general la presencia de esta distinción en la obra del aquinate, y los estudios previos sobre este binomio, se procede a discutir su uso por parte de Tomás de Aquino ante tres problemas específicos: la distinción entre géneros de vida, la división de las facultades humanas, y el problema moral de la delectación morosa.

  7. Cortisol/cortisone ratio and matrix metalloproteinase-9 activity are associated with pediatric primary hypertension.

    Science.gov (United States)

    Martinez-Aguayo, Alejandro; Campino, Carmen; Baudrand, Rene; Carvajal, Cristian A; García, Hernán; Aglony, Marlene; Bancalari, Rodrigo; García, Lorena; Loureiro, Carolina; Vecchiola, Andrea; Tapia-Castillo, Alejandra; Valdivia, Carolina; Sanhueza, Sebastian; Fuentes, Cristobal A; Lagos, Carlos F; Solari, Sandra; Allende, Fidel; Kalergis, Alexis M; Fardella, Carlos E

    2016-09-01

    To identify novel biomarkers associated with pediatric primary hypertension. We recruited 350 participants (4-16 years). Anthropometric parameters and aldosterone, plasma renin activity, cortisol, cortisone, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), high-sensitivity C-reactive protein, adiponectin, IL-6, plasminogen activator inhibitor type 1 levels and matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9 and MMP-2) activities were measured. Genomic DNA was isolated. Patients with altered glucose metabolism, severe obesity [BMI-SD score (BMI-SDS) > 2.5], renovascular disease, primary aldosteronism and apparent mineralocorticoid excess syndrome were excluded. In selected participants (n = 320), SBP was positively correlated with BMI-SDS (r = 0.382, P cortisol/cortisone ratio (r = 0.231, P cortisol/cortisone ratio (P cortisol/cortisone ratio (OR = 3.92; 95% CI = 1.98-7.71) and increased MMP-9 activity (OR = 4.23; 95% CI = 2.15-8.32). We report that MMP-9 activity and the cortisol/cortisone ratio were higher in pediatric primary hypertensive patients, and these associations were independent of the effect of obesity. The potential role of these novel biomarkers in predicting hypertension risk and blood pressure regulation warrants further investigation.

  8. Glutamate/GABA+ ratio is associated with the psychosocial domain of autistic and schizotypal traits.

    Science.gov (United States)

    Ford, Talitha C; Nibbs, Richard; Crewther, David P

    2017-01-01

    The autism and schizophrenia spectra overlap to a large degree in the social and interpersonal domains. Similarly, abnormal excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) neurotransmitter concentrations have been reported for both spectra, with the interplay of these neurotransmitters important for cortical excitation to inhibition regulation. This study investigates whether these neurotransmitter abnormalities are specific to the shared symptomatology, and whether the degree of abnormality increases with increasing symptom severity. Hence, the relationship between the glutamate/GABA ratio and autism and schizophrenia spectrum traits in an unmedicated, subclinical population was investigated. A total of 37 adults (19 female, 18 male) aged 18-38 years completed the Autism Spectrum Quotient (AQ) and Schizotypal Personality Questionnaire (SPQ), and participated in the resting state proton magnetic resonance spectroscopy study in which sequences specific for quantification of glutamate and GABA+ concentration were applied to a right and left superior temporal voxel. There were significant, moderate, positive relationships between right superior temporal glutamate/GABA+ ratio and AQ, SPQ and AQ+SPQ total scores (pGABA+ coinciding with higher scores on these subscales. Only the relationships between glutamate/GABA+ ratio and Social Anxiety, Constricted Affect, Social Skills and Communication survived multiple comparison correction (pGABA+ ratio reduced with increasing restricted imagination (pschizophrenia spectra.

  9. Sustainable industrial estate by managing the building coverage ratio in Cibitung Industrial Town, Indonesia

    Science.gov (United States)

    Budiyanto, T. M. T.; Prajitno, I. S.; Hasibuan, H. S.

    2018-03-01

    The problem faced in the management of the industrial estate is the development of industrial buildings which are not in accordance with the existing environmental regulations, especially the building coverage ratio (BCR). This violation is due to the limitation of industrial land owned, and the tenant’s desire to maximize building area. This research conducted at Cibitung Industrial Town, Indonesia, to assess the compliance of industrial building in complying with environmental regulations, and efforts by industrial estate manager together with industrial communities to meet building regulations. The compliance is shown from the conformity of the tenant’s BCR to the building provisions contained in the regulation within the industrial estate; which is maximum 60% from land owned. And whether the rest of green open space (GOS) area can still be maintained at a minimum 10%. This study found tenant’s building density (BCR) at 24.55% population was 84.77%, and the rest of green open space at 21.56% population was only 2.49%. Excessive building development and expansion by the industrial communities, led to a continued reduction in green open space as a rainwater absorption area. It is resulting the rainfall runoff directly into the environmental drainage system, and causing flooding in the region.

  10. The evolution of sex ratios and sex-determining systems

    NARCIS (Netherlands)

    Uller, Tobias; Pen, Ido; Wapstra, Erik; Beukeboom, Leo W.; Komdeur, Jan

    Sex determination is a fundamental process governed by diverse mechanisms. Sex ratio selection is commonly implicated in the evolution of sex-determining systems, although formal models are rare. Here, we argue that, although sex ratio selection can induce shifts in sex determination, genomic

  11. Sex ratio variation and sex determination in Urtica dioica

    NARCIS (Netherlands)

    Glawe, Grit Anja

    2006-01-01

    This thesis will first document on variation in progeny sex ratios among individual female plants of Urtica dioica at our field site in Meijendel (Chapter 2). Next, we show that there is also considerable sex ratio variation among male and female flowering shoots in 26 natural populations studied

  12. The golden ratio in Schwarzschild-Kottler black holes

    Energy Technology Data Exchange (ETDEWEB)

    Cruz, Norman [Universidad de Santiago de Chile, Departamento de Fisica, Facultad de Ciencia, Santiago 2 (Chile); Olivares, Marco [Universidad Diego Portales, Facultad de Ingenieria, Santiago (Chile); Villanueva, J.R. [Universidad de Valparaiso, Instituto de Fisica y Astronomia, Valparaiso (Chile)

    2017-02-15

    In this paper we show that the golden ratio is present in the Schwarzschild-Kottler metric. For null geodesics with maximal radial acceleration, the turning points of the orbits are in the golden ratio Φ = (√(5)-1)/2. This is a general result which is independent of the value and sign of the cosmological constant Λ. (orig.)

  13. Worldwide lead-isotope ratio in bivalves and sediments

    DEFF Research Database (Denmark)

    Larsen, Martin Mørk; Jacobsen, Gitte; Strand, Jakob

    The lead-isotope ratio have been used to assess and identify impact of leaded gasoline, coal combustion and  mineral activities[ref 1] due to the difference in 206Pb (~52%), 207Pb (~24%) and 208Pb (~23%) isotope ratios. The source of these differences is the decaying of the parent isotopes of 238U...

  14. Determination of Optimum Compression Ratio: A Tribological Aspect

    Directory of Open Access Journals (Sweden)

    L. Yüksek

    2013-12-01

    Full Text Available Internal combustion engines are the primary energy conversion machines both in industry and transportation. Modern technologies are being implemented to engines to fulfill today's low fuel consumption demand. Friction energy consumed by the rubbing parts of the engines are becoming an important parameter for higher fuel efficiency. Rate of friction loss is primarily affected by sliding speed and the load acting upon rubbing surfaces. Compression ratio is the main parameter that increases the peak cylinder pressure and hence normal load on components. Aim of this study is to investigate the effect of compression ratio on total friction loss of a diesel engine. A variable compression ratio diesel engine was operated at four different compression ratios which were "12.96", "15:59", "18:03", "20:17". Brake power and speed was kept constant at predefined value while measuring the in- cylinder pressure. Friction mean effective pressure ( FMEP data were obtained from the in cylinder pressure curves for each compression ratio. Ratio of friction power to indicated power of the engine was increased from 22.83% to 37.06% with varying compression ratio from 12.96 to 20:17. Considering the thermal efficiency , FMEP and maximum in- cylinder pressure optimum compression ratio interval of the test engine was determined as 18.8 ÷ 19.6.

  15. Diagnosis of childhood hypertension: is blood pressure height ratio ...

    African Journals Online (AJOL)

    Blood pressure was also recorded according to the standard method. Systolic and diastolic blood pressure to height ratio were then calculated. Receiver operating curves was used to assess the ability of systolic blood and diastolic blood pressure height ratio to discriminate childhood prehypertension and hypertension.

  16. Optimal Fisher Discriminant Ratio for an Arbitrary Spatial Light Modulator

    Science.gov (United States)

    Juday, Richard D.

    1999-01-01

    Optimizing the Fisher ratio is well established in statistical pattern recognition as a means of discriminating between classes. I show how to optimize that ratio for optical correlation intensity by choice of filter on an arbitrary spatial light modulator (SLM). I include the case of additive noise of known power spectral density.

  17. Explorations in Statistics: The Analysis of Ratios and Normalized Data

    Science.gov (United States)

    Curran-Everett, Douglas

    2013-01-01

    Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This ninth installment of "Explorations in Statistics" explores the analysis of ratios and normalized--or standardized--data. As researchers, we compute a ratio--a numerator divided by a denominator--to compute a…

  18. Effect of sodium adsorption ratio and electric conductivity of the ...

    African Journals Online (AJOL)

    of the water and its sodium content relative to calcium and magnesium content. ... calcium and magnesium is the sodium adsorption ratio (SAR). It is a measure of the ..... comparison of ANN and geo statistics methods for estimating spatial distribution of sodium adsorption ratio (SAR) in groundwater. Int. J. Agric. Crop Sci.

  19. Pupil – Teacher Ratio: Implication for Quality Education in Nigeria ...

    African Journals Online (AJOL)

    Significantly, pupil-teacher ratios are very essential to quality of education. They perhaps rank alongside professional knowledge, skill, as well as strategies, in genuinely determining educational success and performance. This paper discusses pupil-teacher ratio and relevance that pupils seem to have a greater impact on ...

  20. Human sex ratio at amniocentesis and at birth in Taiwan

    Directory of Open Access Journals (Sweden)

    I-Wen Lee

    2012-12-01

    Conclusions: The results showed that sex ratio was already skewed toward male at midtrimester. Our data imply that artificial sex selection, if it were present, might have already emerged prior to the timing of amniocentesis. However, more large nationwide studies on sex ratios in Taiwan are warranted.

  1. Distribution of Bowen ratio over the north Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Rao, G.R.L.; Rao, M.V.; Prasad, P.H.; Reddy, K.G.

    The monthly averages of Bowen ratio over the north Indian Ocean have been computed Three typical situations in the months of January May and September are taken for the present study Month to month differences in the Bowen ratio over the study...

  2. Inequalities in mortality: study rates, not standardised mortality ratios [Letter

    NARCIS (Netherlands)

    Bonneux, L.G.A.

    2010-01-01

    In their study from 1921 to 2007 Thomas and colleagues conclude on the basis of standardised mortality ratios that inequalities in mortality continue to rise and are now almost as high as in the 1930s. Relative ratios are, however, misleading when absolute rates change strongly. I calculated the

  3. Introducing errors in progress ratios determined from experience curves

    NARCIS (Netherlands)

    van Sark, W.G.J.H.M.

    2008-01-01

    Progress ratios (PRs) derived from historical data in experience curves are used for forecasting development of many technologies as a means to model endogenous technical change in for instance climate–economy models. These forecasts are highly sensitive to uncertainties in the progress ratio. As a

  4. Digit ratios, the menstrual cycle and social preferences

    NARCIS (Netherlands)

    Buser, T.

    2012-01-01

    We examine whether social preferences are partially determined by biological factors. We do this by investigating whether digit ratios (2D:4D) and menstrual cycle information are correlated with choices in ultimatum, trust, public good and dictator games. Digit ratios are thought to be a proxy for

  5. On the product and ratio of Bessel random variables

    Directory of Open Access Journals (Sweden)

    Saralees Nadarajah

    2005-01-01

    Full Text Available The distributions of products and ratios of random variables are of interest in many areas of the sciences. In this paper, the exact distributions of the product |XY| and the ratio |X/Y| are derived when X and Y are independent Bessel function random variables. An application of the results is provided by tabulating the associated percentage points.

  6. Concept of planetary gear system to control fluid mixture ratio

    Science.gov (United States)

    Mcgroarty, J. D.

    1966-01-01

    Mechanical device senses and corrects for fluid flow departures from the selected flow ratio of two fluids. This system has been considered for control of rocket engine propellant mixture control but could find use wherever control of the flow ratio of any two fluids is desired.

  7. 12 CFR 3.6 - Minimum capital ratios.

    Science.gov (United States)

    2010-01-01

    ... should have well-diversified risks, including no undue interest rate risk exposure; excellent control... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Minimum capital ratios. 3.6 Section 3.6 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MINIMUM CAPITAL RATIOS; ISSUANCE...

  8. Updating Financial Ratios: Seeking Greater Understanding, Precision, and Practicality.

    Science.gov (United States)

    Jenny, Hans H.; Minter, W. John

    1993-01-01

    Modifications to current methods of calculating and reporting financial ratios are outlined for college managers. The modified ratios, felt to be more realistic, are illustrated with applications in three areas: (1) student revenues; (2) endowment and other investment income; and (3) public and private gifts, grants, and contracts revenue. (MSE)

  9. A Hybrid Joint Moment Ratio Test for Financial Time Series

    NARCIS (Netherlands)

    P.A. Groenendijk (Patrick); A. Lucas (André); C.G. de Vries (Casper)

    1998-01-01

    textabstractWe advocate the use of absolute moment ratio statistics in conjunction with standard variance ratio statistics in order to disentangle linear dependence, non-linear dependence, and leptokurtosis in financial time series. Both statistics are computed for multiple return horizons

  10. Statistical validity of using ratio variables in human kinetics research.

    Science.gov (United States)

    Liu, Yuanlong; Schutz, Robert W

    2003-09-01

    The purposes of this study were to investigate the validity of the simple ratio and three alternative deflation models and examine how the variation of the numerator and denominator variables affects the reliability of a ratio variable. A simple ratio and three alternative deflation models were fitted to four empirical data sets, and common criteria were applied to determine the best model for deflation. Intraclass correlation was used to examine the component effect on the reliability of a ratio variable. The results indicate that the validity, of a deflation model depends on the statistical characteristics of the particular component variables used, and an optimal deflation model for all ratio variables may not exist. Therefore, it is recommended that different models be fitted to each empirical data set to determine the best deflation model. It was found that the reliability of a simple ratio is affected by the coefficients of variation and the within- and between-trial correlations between the numerator and denominator variables. It was recommended that researchers should compute the reliability of the derived ratio scores and not assume that strong reliabilities in the numerator and denominator measures automatically lead to high reliability in the ratio measures.

  11. Risk aversion vs. the Omega ratio : Consistency results

    NARCIS (Netherlands)

    Balder, Sven; Schweizer, Nikolaus

    This paper clarifies when the Omega ratio and related performance measures are consistent with second order stochastic dominance and when they are not. To avoid consistency problems, the threshold parameter in the ratio should be chosen as the expected return of some benchmark – as is commonly done

  12. Parental correlates of offspring sex ratio in Eurasian Oystercatchers

    NARCIS (Netherlands)

    Heg, D.; Dingemanse, NJ; Lessells, CM; Mateman, AC

    2000-01-01

    We investigated hatchling and fledgling sex ratios in Eurasian Oystercatchers (Haematopus ostralegus) using random amplified polymorphic DNA markers. The overall hatchling (53% males, n = 374 hatchlings from 177 broods) and fledgling (49% males, n = 51) sex ratio did not differ significantly from

  13. Riparian Sediment Delivery Ratio: Stiff Diagrams and Artifical Neural Networks

    Science.gov (United States)

    Various methods are used to estimate sediment transport through riparian buffers and grass jilters with the sediment delivery ratio having been the most widely applied. The U.S. Forest Service developed a sediment delivery ratio using the stiff diagram and a logistic curve to int...

  14. On efficiency of some ratio estimators in double sampling design ...

    African Journals Online (AJOL)

    In this paper, three sampling ratio estimators in double sampling design were proposed with the intention of finding an alternative double sampling design estimator to the conventional ratio estimator in double sampling design discussed by Cochran (1997), Okafor (2002) , Raj (1972) and Raj and Chandhok (1999).

  15. Deep Reactive Ion Etching for High Aspect Ratio Microelectromechanical Components

    DEFF Research Database (Denmark)

    Jensen, Søren; Yalcinkaya, Arda Deniz; Jacobsen, S.

    2004-01-01

    A deep reactive ion etch (DRIE) process for fabrication of high aspect ratio trenches has been developed. Trenches with aspect ratios exceeding 20 and vertical sidewalls with low roughness have been demonstrated. The process has successfully been used in the fabrication of silicon-on-insulator (SOI...

  16. Sex Dimorphism of the Heart Diameters and Cardiothoracic Ratios ...

    African Journals Online (AJOL)

    Objective: To determine gender associated differences in the cardiothoracic ratio (CTR) and heart diameters in a normal Nigerian population. Subject and Method: The normal heart diameters and cardiothoracic ratios were measured from posteroanterior (PA) chest radiographs of healthy 510 male and 508 female ...

  17. Sex ratio, gonadal development and fecundity of the grunt ...

    African Journals Online (AJOL)

    The sex ratio, gonadosomatic index, stages of gonadal development and fecundity of the grunt, Pomadasys jubelini in the New Calabar-Bonny River were investigated. P. jubelini had a sex ratio of 1: 2.1 (male to female). Gonadosomatic index ranged from 0.33 to 7.29% with a mean of 2.89+0.08%. High gonadosomatic ...

  18. Sex ratio and Wolbachia infection in the ant Formica exsecta.

    Science.gov (United States)

    Keller, L; Liautard, C; Reuter, M; Brown, W D; Sundström, L; Chapuisat, M

    2001-08-01

    Sex allocation data in social Hymenoptera provide some of the best tests of kin selection, parent-offspring conflict and sex ratio theories. However, these studies critically depend on controlling for confounding ecological factors and on identifying all parties that potentially manipulate colony sex ratio. It has been suggested that maternally inherited parasites may influence sex allocation in social Hymenoptera. If the parasites can influence sex allocation, infected colonies are predicted to invest more resources in females than non-infected colonies, because the parasites are transmitted through females but not males. Prime candidates for such sex ratio manipulation are Wolbachia, because these cytoplasmically transmitted bacteria have been shown to affect the sex ratio of host arthropods by cytoplasmic incompatibility, parthenogenesis, male-killing and feminization. In this study, we tested whether Wolbachia infection is associated with colony sex ratio in two populations of the ant Formica exsecta that have been the subject of extensive sex ratio studies. In these populations colonies specialize in the production of one sex or the other. We found that almost all F. exsecta colonies in both populations are infected with Wolbachia. However, in neither population did we find a significant association in the predicted direction between the prevalence of Wolbachia and colony sex ratio. In particular, colonies with a higher proportion of infected workers did not produce more females. Hence, we conclude that Wolbachia does not seem to alter the sex ratio of its hosts as a means to increase transmission rate in these two populations of ants.

  19. Measurements of K/Π ratio in cosmic radiation

    International Nuclear Information System (INIS)

    Mahon, J.R.P.

    1986-01-01

    Measurements of k/Π ratio in cosmic radiation by its half lives and its fluxes, were carried out. The kaon flux was obtained using the Cherenkov detector, and for pion flux scintillation detectors were used. The final results of K/Π ratio ∼ 0.2 was obtained. (M.C.K.) [pt

  20. The Steiner ratio for points on a triangular lattice

    African Journals Online (AJOL)

    design of integrated circuit boards, communication networks, power networks and pipelines of minimum cost. In such applications the Steiner ratio is an indication of how badly a minimum spanning tree performs compared to a Steiner minimal tree. In this paper a short proof is presented for the Steiner ratio for points on a ...

  1. Legislation and regulation

    International Nuclear Information System (INIS)

    1998-01-01

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the nuclear and environmental licensing, and emergency preparedness legislation

  2. Benchmarking and Regulation

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    . The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  3. Legislation and regulation

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the nuclear and environmental licensing, and emergency preparedness legislation.

  4. The Effects of Liquidity Regulation on Bank Assets and Liabilities

    OpenAIRE

    Patty Duijm; Peter Wierts

    2014-01-01

    Under Basel III rules, banks become subject to a liquidity coverage ratio (LCR) from 2015 onwards, to promote short-term resilience. We investigate the effects of such liquidity regulation on bank liquid assets and liabilities. Results indicate co-integration of liquid assets and liabilities, to maintain a minimum short-term liquidity buffer. Still, microprudential regulation has not prevented an aggregate liquidity cycle characterised by a pro-cyclical pattern in the size of balance sheets a...

  5. Liquidity regulation and the implementation of monetary policy

    OpenAIRE

    Morten L. Bech; Todd Keister

    2013-01-01

    In addition to revamping existing rules for bank capital, Basel III introduces a new global framework for liquidity regulation. One part of this framework is the liquidity coverage ratio (LCR), which requires banks to hold sufficient high-quality liquid assets to survive a 30-day period of market stress. As monetary policy typically involves targeting the interest rate on loans of one of these assets — central bank reserves — it is important to understand how this regulation may impact the ef...

  6. Exploring the possibilities for stabilizing the sex ratio in India

    Directory of Open Access Journals (Sweden)

    Saurabh RamBihariLal Shrivastava

    2015-12-01

    Full Text Available The sex ratio is an important demographic indicator for a nation. A wide range of adverse social consequences have been observed because of a skewed sex ratio in India. If India as a nation is to achieve the Millennium Development Goal – 3 (which promotes gender equality and ensures the empowerment of women, the primary target should be involve all those involved, so that a collective and comprehensive approach can be developed to counter the public health menace of an asymmetrical sex ratio. In conclusion, the nation’s program managers should prioritize the issue of a skewed sex ratio and work towards developing a coordinated response.Key Words: Sex ratio, policy makers, India.

  7. A note on Youden's J and its cost ratio

    Directory of Open Access Journals (Sweden)

    Smits Niels

    2010-09-01

    Full Text Available Abstract Background The Youden index, the sum of sensitivity and specificity minus one, is an index used for setting optimal thresholds on medical tests. Discussion When using this index, one implicitly uses decision theory with a ratio of misclassification costs which is equal to one minus the prevalence proportion of the disease. It is doubtful whether this cost ratio truly represents the decision maker's preferences. Moreover, in populations with a different prevalence, a selected threshold is optimal with reference to a different cost ratio. Summary The Youden index is not a truly optimal decision rule for setting thresholds because its cost ratio varies with prevalence. Researchers should look into their cost ratio and employ it in a decision theoretic framework to obtain genuinely optimal thresholds.

  8. SOLVENCY RATIO AS A TOOL FOR BANKRUPTCY PREDICTION

    Directory of Open Access Journals (Sweden)

    Daniel BRÎNDESCU–OLARIU

    2016-08-01

    Full Text Available The current study evaluates the potential of the solvency ratio in predicting corporate bankruptcy. The research is focused on Romania and, in particular, on Timis County. The interest for the solvency ratio was based on the recommendations of the scientific literature, as well as on the availability of information concerning its values to all stakeholders. The event on which the research was focused was represented by the manifestation of bankruptcy 2 years after the date of the financial statements of reference. All tests were performed over 2 paired samples of 1176 companies in total. The methodology employed in evaluating the potential of the solvency ratio was based on the Area Under the ROC Curve (0.646 and the general accuracy ensured by the ratio (64.5% out-of-sample accuracy. The results confirm the practical utility of the solvency ratio in the prediction of bankruptcy.

  9. Psychological distress during early gestation and offspring sex ratio

    DEFF Research Database (Denmark)

    Obel, C; Henriksen, TB; Secher, Niels Jørgen

    2007-01-01

    BACKGROUND: Exposure to severe stress in early pregnancy is associated with a lower male to female ratio (sex ratio), but whether more moderate levels of psychological discomfort have the same kind of effect is unknown. In a population based follow-up study, we aimed to test whether psychological...... suggest that not only severe stress, but also more moderate and common levels of psychological distress, may decrease the sex ratio in the offspring. Stress during pregnancy is a likely candidate involved in the decreasing sex ratio observed in many countries....... distress was associated with the sex ratio in the offspring. METHODS: From 1989 to 1992, a cohort of 8,719 Danish-speaking pregnant women were followed until delivery. Questionnaires were administered to the women in early pregnancy and 6,629 (76%) completed the 30-item version of the General Health...

  10. Psychological distress during early gestation and offspring sex ratio

    DEFF Research Database (Denmark)

    Obel, Carsten; Henriksen, Tine Brink; Secher, Niels Jørgen

    2007-01-01

    BACKGROUND: Exposure to severe stress in early pregnancy is associated with a lower male to female ratio (sex ratio), but whether more moderate levels of psychological discomfort have the same kind of effect is unknown. In a population based follow-up study, we aimed to test whether psychological...... suggest that not only severe stress, but also more moderate and common levels of psychological distress, may decrease the sex ratio in the offspring. Stress during pregnancy is a likely candidate involved in the decreasing sex ratio observed in many countries. Udgivelsesdato: 2007-Nov...... distress was associated with the sex ratio in the offspring. METHODS: From 1989 to 1992, a cohort of 8,719 Danish-speaking pregnant women were followed until delivery. Questionnaires were administered to the women in early pregnancy and 6,629 (76%) completed the 30-item version of the General Health...

  11. Equivalence ratio and constriction effects on RBCC thrust augmentation

    Science.gov (United States)

    Koupriyanov, M.; Etele, J.

    2011-06-01

    A theoretical analysis of a variable area rocket based combined cycle engine with and without simultaneous mixing and combustion is presented. The flowfield is solved using a steady, quasi-one-dimensional, inviscid control volume formulation with combustion effects included via a generalized equilibrium calculation. Compression augmentation is shown to be sensitive to the equivalence ratio within the primary rocket chamber, where ejector section performance is greatest at both low and high equivalence ratios but near a minimum at stoichiometric conditions. The thrust generated by the RBCC engine compared to that generated by the same rocket in isolation can be increased by as much as 12% at constriction ratios of between 45% and 50%. Thrust augmentation is also shown to vary with equivalence ratio, where for a fixed geometry the maximum thrust is generated at equivalence ratios slightly below unity.

  12. Achieving high aspect ratio wrinkles by modifying material network stress.

    Science.gov (United States)

    Chen, Yu-Cheng; Wang, Yan; McCarthy, Thomas J; Crosby, Alfred J

    2017-06-07

    Wrinkle aspect ratio, or the amplitude divided by the wavelength, is hindered by strain localization transitions when an increasing global compressive stress is applied to synthetic material systems. However, many examples from living organisms show extremely high aspect ratios, such as gut villi and flower petals. We use three experimental approaches to demonstrate that these high aspect ratio structures can be achieved by modifying the network stress in the wrinkle substrate. We modify the wrinkle stress and effectively delay the strain localization transition, such as folding, to larger aspect ratios by using a zero-stress initial wavy substrate, creating a secondary network with post-curing, or using chemical stress relaxation materials. A wrinkle aspect ratio as high as 0.85, almost three times higher than common values of synthetic wrinkles, is achieved, and a quantitative framework is presented to provide understanding the different strategies and predictions for future investigations.

  13. The regulation of appetite

    OpenAIRE

    Druce, M; Bloom, S R

    2006-01-01

    The worsening global obesity epidemic, particularly the increase in childhood obesity, has prompted research into the mechanisms of appetite regulation. Complex pathways modulate energy balance, involving appetite centres in the hypothalamus and brain stem, and hormonal signals of energy status released by the gut and by the periphery. Better understanding of appetite regulation improves understanding of the aetiology of obesity. Manipulation of this homoeostatic system offers potentially use...

  14. Corruption, Institutions and Regulation

    OpenAIRE

    Michael Breen; Robert Gillanders

    2011-01-01

    We analyze the effects of corruption and institutional quality on the quality of business regulation. Our key findings indicate that corruption negatively aspects the quality of regulation and that general institutional quality is insignificant once corruption is controlled for. These findings hold over a number of specifications which include additional exogenous historical and geographic controls. The findings imply that policy-makers should focus on curbing corruption to improve regulat...

  15. Regulating deregulated energy markets

    International Nuclear Information System (INIS)

    Jackson, M.

    2002-01-01

    The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

  16. Interpersonal emotion regulation.

    Science.gov (United States)

    Zaki, Jamil; Williams, W Craig

    2013-10-01

    Contemporary emotion regulation research emphasizes intrapersonal processes such as cognitive reappraisal and expressive suppression, but people experiencing affect commonly choose not to go it alone. Instead, individuals often turn to others for help in shaping their affective lives. How and under what circumstances does such interpersonal regulation modulate emotional experience? Although scientists have examined allied phenomena such as social sharing, empathy, social support, and prosocial behavior for decades, there have been surprisingly few attempts to integrate these data into a single conceptual framework of interpersonal regulation. Here we propose such a framework. We first map a "space" differentiating classes of interpersonal regulation according to whether an individual uses an interpersonal regulatory episode to alter their own or another person's emotion. We then identify 2 types of processes--response-dependent and response-independent--that could support interpersonal regulation. This framework classifies an array of processes through which interpersonal contact fulfills regulatory goals. More broadly, it organizes diffuse, heretofore independent data on "pieces" of interpersonal regulation, and identifies growth points for this young and exciting research domain.

  17. Nondestructive measurement of the grid ratio using a single image

    International Nuclear Information System (INIS)

    Pasciak, A. S.; Jones, A. Kyle

    2009-01-01

    The antiscatter grid is an essential part of modern radiographic systems. Since the introduction of the antiscatter grid, however, there have been few methods proposed for acceptance testing and verification of manufacturer-supplied grid specifications. The grid ratio (r) is an important parameter describing the antiscatter grid because it affects many other grid quality metrics, such as the contrast improvement ratio (K), primary transmission (T p ), and scatter transmission (T s ). Also, the grid ratio in large part determines the primary clinical use of the grid. To this end, the authors present a technique for the nondestructive measurement of the grid ratio of antiscatter grids. They derived an equation that can be used to calculate the grid ratio from a single off-focus flat field image by exploiting the relationship between grid cutoff and off-focus distance. The calculation can be performed by hand or with included analysis software. They calculated the grid ratios of several different grids throughout the institution, and afterward they destructively measured the grid ratio of a nominal r8 grid previously evaluated with the method. They also studied the sensitivity of the method to technical factors and choice of parameters. With one exception, the results for the grids found in the institution were in agreement with the manufacturer's specifications and international standards. The nondestructive evaluation of the r8 grid indicated a ratio of 7.3, while the destructive measurement indicated a ratio of 7.53±0.28. Repeated evaluations of the same grid yielded consistent results. The technique provides the medical physicist with a new tool for quantitative evaluation of the grid ratio, an important grid performance criterion. The method is robust and repeatable when appropriate choices of technical factors and other parameters are made.

  18. Estimating 24-h urinary sodium/potassium ratio from casual ('spot') urinary sodium/potassium ratio: the INTERSALT Study.

    Science.gov (United States)

    Iwahori, Toshiyuki; Miura, Katsuyuki; Ueshima, Hirotsugu; Chan, Queenie; Dyer, Alan R; Elliott, Paul; Stamler, Jeremiah

    2017-10-01

    Association between casual and 24-h urinary sodium-to-potassium (Na/K) ratio is well recognized, although it has not been validated in diverse demographic groups. Our aim was to assess utility across and within populations of casual urine to estimate 24-h urinary Na/K ratio using data from the INTERSALT Study. The INTERSALT Study collected cross-sectional standardized data on casual urinary sodium and potassium and also on timed 24-h urinary sodium and potassium for 10 065 individuals from 52 population samples in 32 countries (1985-87). Pearson correlation coefficients and agreement were computed for Na/K ratio of casual urine against 24-h urinary Na/K ratio both at population and individual levels. Pearson correlation coefficients relating means of 24-h urine and casual urine Na/K ratio were r = 0.96 and r = 0.69 in analyses across populations and individuals, respectively. Correlations of casual urine Na/creatinine and K/creatinine ratios with 24-h urinary Na and K excretion, respectively, were lower than correlation of casual and 24-h urinary Na/K ratio in analyses across populations and individuals. The bias estimate with the Bland-Altman method, defined as the difference between Na/K ratio of 24-h urine and casual urine, was approximately 0.4 across both populations and individuals. Spread around, the mean bias was higher for individuals than populations. With appropriate bias correction, casual urine Na/K ratio may be a useful, low-burden alternative method to 24-h urine for estimation of population urinary Na/K ratio. It may also be applicable for assessment of the urinary Na/K ratio of individuals, with use of repeated measurements to reduce measurement error and increase precision. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association

  19. Federal Aviation Regulations - National Aviation Regulations of Russia

    Science.gov (United States)

    Chernykh, O.; Bakiiev, M.

    2018-03-01

    Chinese Aerospace Engineering is currently developing cooperation with Russia on a wide-body airplane project that has directed the work towards better understanding of Russian airworthiness management system. The paper introduces national Aviation regulations of Russia, presents a comparison of them with worldwide recognized regulations, and highlights typical differences. They have been found to be: two general types of regulations used in Russia (Aviation Regulations and Federal Aviation Regulations), non-unified structure of regulations on Aircraft Operation management, various separate agencies responsible for regulation issuance instead of one national aviation authority, typical confusions in references. The paper also gives a list of effective Russian Regulations of both types.

  20. The ATP/DNA Ratio Is a Better Indicator of Islet Cell Viability Than the ADP/ATP Ratio

    Science.gov (United States)

    Suszynski, T.M.; Wildey, G.M.; Falde, E.J.; Cline, G.W.; Maynard, K. Stewart; Ko, N.; Sotiris, J.; Naji, A.; Hering, B.J.; Papas, K.K.

    2009-01-01

    Real-time, accurate assessment of islet viability is critical for avoiding transplantation of nontherapeutic preparations. Measurements of the intracellular ADP/ATP ratio have been recently proposed as useful prospective estimates of islet cell viability and potency. However, dead cells may be rapidly depleted of both ATP and ADP, which would render the ratio incapable of accounting for dead cells. Since the DNA of dead cells is expected to remain stable over prolonged periods of time (days), we hypothesized that use of the ATP/DNA ratio would take into account dead cells and may be a better indicator of islet cell viability than the ADP/ATP ratio. We tested this hypothesis using mixtures of healthy and lethally heat-treated (HT) rat insulinoma cells and human islets. Measurements of ATP/DNA and ADP/ATP from the known mixtures of healthy and HT cells and islets were used to evaluate how well these parameters correlated with viability. The results indicated that ATP and ADP were rapidly (within 1 hour) depleted in HT cells. The fraction of HT cells in a mixture correlated linearly with the ATP/DNA ratio, whereas the ADP/ADP ratio was highly scattered, remaining effectively unchanged. Despite similar limitations in both ADP/ADP and ATP/DNA ratios, in that ATP levels may fluctuate significantly and reversibly with metabolic stress, the results indicated that ATP/DNA was a better measure of islet viability than the ADP/ATP ratio. PMID:18374063

  1. Stable isotope ratio determination of the origin of vanillin in vanilla extracts and its relationship to vanillin/potassium ratios

    International Nuclear Information System (INIS)

    Martin, G.E.; Alfonso, F.C.; Figert, D.M.; Burggraff, J.M.

    1981-01-01

    A method is described for isolating vanillin from vanilla extract, followed by stable isotope ratio analysis to determine the amount of natural vanillin contained in adulterated vanilla extracts. After the potassium content is determined, the percent Madagascar and/or Java vanilla beans incorporated into the extract may then be approximated from the vanillin/potassium ratio

  2. Patterns of Family Formation in Response to Sex Ratio Variation.

    Science.gov (United States)

    Schacht, Ryan; Kramer, Karen L

    2016-01-01

    The impact that unbalanced sex ratios have on health and societal outcomes is of mounting contemporary concern. However, it is increasingly unclear whether it is male- or female-biased sex ratios that are associated with family and social instability. From a socio-demographic perspective, male-biased sex ratios leave many men unable to find a mate, elevating competition among males, disrupting family formation and negatively affecting social stability. In contrast, from a mating-market perspective, males are expected to be less willing to marry and commit to a family when the sex ratio is female-biased and males are rare. Here we use U.S. data to evaluate predictions from these competing frameworks by testing the relationship between the adult sex ratio and measures of family formation. We find that when women are rare men are more likely to marry, be part of a family and be sexually committed to a single partner. Our results do not support claims that male-biased sex ratios lead to negative family outcomes due to a surplus of unmarried men. Rather, our results highlight the need to pay increased attention to female-biased sex ratios.

  3. Correlation Between Cometary Gas/Dust Ratios and Heliocentric Distance

    Science.gov (United States)

    Harrington, Olga; Womack, Maria; Lastra, Nathan

    2017-10-01

    We compiled CO-based gas/dust ratios for several comets out to heliocentric distances, rh, of 8 au to probe whether there is a noticeable change in comet behavior over the range that water-ice sublimation starts. Previously, gas/dust ratios were calculated for an ensemble of comets using Q(CO2)/efp values derived from infrared measurements, which showed that the gas/dust ratio follows a rh-2 within 4 AU, but is flat at greater distances (Bauer et al. 2015). Our project focuses on gas/dust ratios for which CO is assumed to be the dominant gas, in order to test whether similar breaks in slope occur for CO. The gas/dust ratios were calculated from measurements of CO production rates (mostly from millimeter-wavelength spectroscopy) and reflected sunlight of comets (mostly via reported visual magnitudes of dusty comets). We present our new CO-based gas/dust ratios at different heliocentric distances, compare them to existing CO2-based gas/dust ratios, and discuss implications for CO-driven and CO2-driven activity. We discuss O.H. acknowledges support from the Hartmann Student Travel Grant program. M.W. acknowledges support from NSF grant AST-1615917.

  4. Determinants of capital adequacy ratio in Kuwaiti banks

    Directory of Open Access Journals (Sweden)

    Moeidh Alajmi

    2015-10-01

    Full Text Available The aim of this study is to identify the effects of seven internal factors of five conventional Kuwaiti banks on capital adequacy ratio (CAR. The five factors are: Loans to Assets, Loans to Deposits, Non-Performing Loans to Total Loans, Return on Assets, Return on Equity, Dividend Payout and Total Liability to Total Assets. The study covers the period from 2005 to 2013. The study shows that under fixed effect model, variables DIVIEDEND, LAR, LDR, NPLLR, and ROE do not have any impact on capital adequacy ratio. However, SIZE has a significant and negative relationship with capital adequacy ratio. Also, ROA shows a significant and negative relationship with capital adequacy ratio. Under random effect model, results indicate that CAR is adversely affected by bank’s SIZE (total liability to assets, and ROA has a significant and negative relationship with capital adequacy ratio, However, Loan to Deposit Ratio (LDR showed a significant and positive relationship with capital adequacy ratio. On the other hand, dividend payout, loans to assets, Non-Performing Loans to Total Loans and Return on equity do not have significant effect on CAR under random effect model.

  5. Elevated Neutrophil Lymphocyte Ratio in Recurrent Optic Neuritis

    Directory of Open Access Journals (Sweden)

    Hande Guclu

    2015-01-01

    Full Text Available Purpose. To demonstrate the relation between optic neuritis (ON and systemic inflammation markers as neutrophil lymphocyte ratio (N/L ratio, platelet count, mean platelet volume (MPV, and red cell distribution width (RDW and furthermore to evaluate the utilization of these markers to predict the frequency of the ON episodes. Methods. Forty-two patients with acute ON and forty healthy subjects were enrolled into the study. The medical records were reviewed for age, sex, hemoglobin (Hb, Haematocrit (Htc, RDW, platelet count, MPV, white blood cell count (WBC, neutrophil and lymphocyte count, and neutrophil lymphocyte ratio (N/L ratio. Results. The mean N/L ratio, platelet counts, and RDW were significantly higher in ON group (p=0.000, p=0.048, and p=0.002. There was a significant relation between N/L ratio and number of episodes (r=0.492, p=0.001. There was a statistically significant difference for MPV between one episode group and recurrent ON group (p=0.035. Conclusions. Simple and inexpensive laboratory methods could help us show systemic inflammation and monitor ON patients. Higher N/L ratio can be a useful marker for predicting recurrent attacks.

  6. Nuclear regulation in transition

    International Nuclear Information System (INIS)

    Tomain, J.P.

    1986-01-01

    The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed. (author)

  7. Nuclear regulation in transition

    Energy Technology Data Exchange (ETDEWEB)

    Tomain, J.P. (Cincinnati Univ., OH, US. Coll. of Law)

    1986-01-01

    The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed.

  8. The human heart: application of the golden ratio and angle.

    Science.gov (United States)

    Henein, Michael Y; Zhao, Ying; Nicoll, Rachel; Sun, Lin; Khir, Ashraf W; Franklin, Karl; Lindqvist, Per

    2011-08-04

    The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Inhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo

    International Nuclear Information System (INIS)

    Franco, Gilson C.N.; Kajiya, Mikihito; Nakanishi, Tadashi; Ohta, Kouji; Rosalen, Pedro L.; Groppo, Francisco C.; Ernst, Cory W.O.; Boyesen, Janie L.; Bartlett, John D.; Stashenko, Philip; Taubman, Martin A.; Kawai, Toshihisa

    2011-01-01

    Tetracycline antibiotics, including doxycycli/e (DOX), have been used to treat bone resorptive diseases, partially because of their activity to suppress osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand (RANKL). However, their precise inhibitory mechanism remains unclear. Therefore, the present study examined the effect of Dox on osteoclastogenesis signaling induced by RANKL, both in vitro and in vivo. Although Dox inhibited RANKL-induced osteoclastogenesis and down-modulated the mRNA expression of functional osteoclast markers, including tartrate-resistant acid phosphatase (TRAP) and cathepsin K, Dox neither affected RANKL-induced MAPKs phosphorylation nor NFATc1 gene expression in RAW264.7 murine monocytic cells. Gelatin zymography and Western blot analyses showed that Dox down-regulated the enzyme activity of RANKL-induced MMP-9, but without affecting its protein expression. Furthermore, MMP-9 enzyme inhibitor also attenuated both RANKL-induced osteoclastogenesis and up-regulation of TRAP and cathepsin K mRNA expression, indicating that MMP-9 enzyme action is engaged in the promotion of RANKL-induced osteoclastogenesis. Finally, Dox treatment abrogated RANKL-induced osteoclastogenesis and TRAP activity in mouse calvaria along with the suppression of MMP9 enzyme activity, again without affecting the expression of MMP9 protein. These findings suggested that Dox inhibits RANKL-induced osteoclastogenesis by its inhibitory effect on MMP-9 enzyme activity independent of the MAPK-NFATc1 signaling cascade.

  10. Inhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Franco, Gilson C.N. [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Pharmacology, FOP/UNICAMP, Piracicaba, SP (Brazil); Kajiya, Mikihito [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA (United States); Nakanishi, Tadashi [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Ohta, Kouji [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA (United States); Rosalen, Pedro L.; Groppo, Francisco C. [Department of Pharmacology, FOP/UNICAMP, Piracicaba, SP (Brazil); Ernst, Cory W.O.; Boyesen, Janie L. [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Bartlett, John D.; Stashenko, Philip [Department of Cytokine Biology, Forsyth Institute, Cambridge, MA (United States); Taubman, Martin A. [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Kawai, Toshihisa, E-mail: tkawai@forsyth.org [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA (United States)

    2011-06-10

    Tetracycline antibiotics, including doxycycli/e (DOX), have been used to treat bone resorptive diseases, partially because of their activity to suppress osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand (RANKL). However, their precise inhibitory mechanism remains unclear. Therefore, the present study examined the effect of Dox on osteoclastogenesis signaling induced by RANKL, both in vitro and in vivo. Although Dox inhibited RANKL-induced osteoclastogenesis and down-modulated the mRNA expression of functional osteoclast markers, including tartrate-resistant acid phosphatase (TRAP) and cathepsin K, Dox neither affected RANKL-induced MAPKs phosphorylation nor NFATc1 gene expression in RAW264.7 murine monocytic cells. Gelatin zymography and Western blot analyses showed that Dox down-regulated the enzyme activity of RANKL-induced MMP-9, but without affecting its protein expression. Furthermore, MMP-9 enzyme inhibitor also attenuated both RANKL-induced osteoclastogenesis and up-regulation of TRAP and cathepsin K mRNA expression, indicating that MMP-9 enzyme action is engaged in the promotion of RANKL-induced osteoclastogenesis. Finally, Dox treatment abrogated RANKL-induced osteoclastogenesis and TRAP activity in mouse calvaria along with the suppression of MMP9 enzyme activity, again without affecting the expression of MMP9 protein. These findings suggested that Dox inhibits RANKL-induced osteoclastogenesis by its inhibitory effect on MMP-9 enzyme activity independent of the MAPK-NFATc1 signaling cascade.

  11. How required reserve ratio affects distribution and velocity of money

    Science.gov (United States)

    Xi, Ning; Ding, Ning; Wang, Yougui

    2005-11-01

    In this paper the dependence of wealth distribution and the velocity of money on the required reserve ratio is examined based on a random transfer model of money and computer simulations. A fractional reserve banking system is introduced to the model where money creation can be achieved by bank loans and the monetary aggregate is determined by the monetary base and the required reserve ratio. It is shown that monetary wealth follows asymmetric Laplace distribution and latency time of money follows exponential distribution. The expression of monetary wealth distribution and that of the velocity of money in terms of the required reserve ratio are presented in a good agreement with simulation results.

  12. High extinction ratio integrated optical modulator for quantum telecommunication systems

    Science.gov (United States)

    Tronev, A.; Parfenov, M.; Agruzov, P.; Ilichev, I.; Shamray, A.

    2018-01-01

    A method for increasing the extinction ratio of integrated optical Mach-Zehnder modulators based on LiNbO3 via the photorefractive effect is proposed. The influence of the photorefractive effect on the X- and Y-splitters of intensity modulators is experimentally studied. An increase in the modulator extinction ratio by 17 dB (from 30 to 47 dB) is obtained. It is shown that fabricated modulators with a high extinction ratio are important for quantum key distribution systems.

  13. An improved data acquisition system for isotopic ratio mass spectrometers

    International Nuclear Information System (INIS)

    Saha, T.K.; Reddy, B.; Nazare, C.K.; Handu, V.K.

    1999-01-01

    Isotopic ratio mass spectrometers designed and fabricated to measure the isotopic ratios with a precision of better than 0.05%. In order to achieve this precision, the measurement system consisting of ion signal to voltage converters, analog to digital converters, and data acquisition electronics should be at least one order better than the overall precision of measurement. Using state of the art components and techniques, a data acquisition system, which is an improved version of the earlier system, has been designed and developed for use with multi-collector isotopic ratio mass spectrometers

  14. Ratios of charmed and bottom meson decay constants

    International Nuclear Information System (INIS)

    Oakes, R.J.

    1994-01-01

    It is shown that general features of the standard theory require the double ratio (f Bs /f Bd )/(f Ds /f Dd ) to be very nearly unity with only very small corrections. The ratios f Bs /f Bd and f Ds /f Dd are both also near unity, within small corrections which partially cancel in the double ratio. A precise measurement of f Ds /f Dd therefore provides a sensitive test of some generally accepted features of the standard Lagrangian, as well as determines the value of f Bs /f Bd , which is important for calculating the relative strengths of B s- bar B s and B d- bar B d mixing

  15. K0/K+ ratio in relativistic heavy-ion collisions

    International Nuclear Information System (INIS)

    Ivanov, Yu.B.; Russkikh, V.N.

    1996-11-01

    It is shown that ratio of production yields of K 0 and K + mesons in collisions of isotopically asymmetric nuclei at incident energies ∼ 1 GeV/nucleon is related directly enough to temperature of nuclear matter at the initial stage of the collision. Sensitivity of the K 0 /K + ratio to the temperature variation is analyzed. Ambiguities, associated with interpretation of this quantity as a probe of nuclear temperature, are discussed. It is argued that the K 0 /K + ratio is a fairly model-independent quantity, provided channels with Δ isobars dominate the kaon production. (orig.)

  16. Measurement of the temperature coefficient of ratio transformers

    Science.gov (United States)

    Briggs, Matthew E.; Gammon, Robert W.; Shaumeyer, J. N.

    1993-01-01

    We have measured the temperature coefficient of the output of several ratio transformers at ratios near 0.500,000 using an ac bridge and a dual-phase, lock-in amplifier. The two orthogonal output components were each resolved to +/- ppb of the bridge drive signal. The results for three commercial ratio transformers between 20 and 50 C range from 0.5 to 100 ppb/K for the signal component in phase with the bridge drive, and from 4 to 300 ppb/K for the quadrature component.

  17. Ratio of νe/νμ in atmospheric neutrinos

    International Nuclear Information System (INIS)

    Barr, S.; Gaisser, T.K.; Tilav, S.

    1988-01-01

    When the effect of muon polarization is included, the calculated ratio ν e /ν μ for atmospheric neutrinos with energies above ≅ 200 MeV is increased by 10-20% compared to the result when polarization is neglected. We give an analytic derivation of this ratio for the artificial case of a power law differential spectrum of parent pions propagating in an atmosphere in which all pions and muons decay. This is sufficient to estimate the effect on the calculated ratio of electron-like to muon-like events induced by neutrino interactions in large underground detectors. (orig.)

  18. To regulate or not to regulate?

    Energy Technology Data Exchange (ETDEWEB)

    Mason, G.; Wrixon, A. [IAEA, Vienna (Austria)

    2006-07-01

    Full text of publication follows: In Hamlet famous soliloquy to be or not to be, he wrestles with the perennial human problem of choosing the right course of action in difficult circumstances. In recent years, we have witnessed a cast of thousands playing out a long-running scene that seems to echo Hamlet dilemma on a rather more prosaic level. When is it necessary to apply regulations to the control of exposure to ionizing radiation and when is regulatory control not warranted? This seemingly straightforward question has brought out the philosopher, ethician, lawyer, pragmatist, orator in simple radiation protection folk and has led to passionate debate on numerous occasions. This paper attempts an answer based on a review of recent developments. For deciding when to apply regulatory controls, several concepts have evolved over time, including exemption of practices and sources, exclusion of exposures and clearance of materials. These have different origins, purposes and characteristics. Exemption and clearance have often been associated with triviality of risk, while exclusion has been related to un-amenability of control. For each concept, criteria have been developed to assist the regulator in reaching a decision, but there has much disputation over numerical values. This paper briefly reviews and analyses recent developments and attempts to clarify the problem from first principles. The conclusion is that the underlying issue in each case is to determine when regulatory controls become unwarranted: that is, when the societal resources expended in applying them and complying with them would be disproportionate to any benefit they might bring. This is a natural extension of the principle of optimization of protection to the regulatory control of protection, in the context of exposure to radiation at very low levels. It also reflects common expectations of good governance: wise management of finite societal resources and avoidance of unwarranted controls on

  19. To regulate or not to regulate?

    International Nuclear Information System (INIS)

    Mason, G.; Wrixon, A.

    2006-01-01

    Full text of publication follows: In Hamlet famous soliloquy to be or not to be, he wrestles with the perennial human problem of choosing the right course of action in difficult circumstances. In recent years, we have witnessed a cast of thousands playing out a long-running scene that seems to echo Hamlet dilemma on a rather more prosaic level. When is it necessary to apply regulations to the control of exposure to ionizing radiation and when is regulatory control not warranted? This seemingly straightforward question has brought out the philosopher, ethician, lawyer, pragmatist, orator in simple radiation protection folk and has led to passionate debate on numerous occasions. This paper attempts an answer based on a review of recent developments. For deciding when to apply regulatory controls, several concepts have evolved over time, including exemption of practices and sources, exclusion of exposures and clearance of materials. These have different origins, purposes and characteristics. Exemption and clearance have often been associated with triviality of risk, while exclusion has been related to un-amenability of control. For each concept, criteria have been developed to assist the regulator in reaching a decision, but there has much disputation over numerical values. This paper briefly reviews and analyses recent developments and attempts to clarify the problem from first principles. The conclusion is that the underlying issue in each case is to determine when regulatory controls become unwarranted: that is, when the societal resources expended in applying them and complying with them would be disproportionate to any benefit they might bring. This is a natural extension of the principle of optimization of protection to the regulatory control of protection, in the context of exposure to radiation at very low levels. It also reflects common expectations of good governance: wise management of finite societal resources and avoidance of unwarranted controls on

  20. Further comments on the sequential probability ratio testing methods

    Energy Technology Data Exchange (ETDEWEB)

    Kulacsy, K. [Hungarian Academy of Sciences, Budapest (Hungary). Central Research Inst. for Physics

    1997-05-23

    The Bayesian method for belief updating proposed in Racz (1996) is examined. The interpretation of the belief function introduced therein is found, and the method is compared to the classical binary Sequential Probability Ratio Testing method (SPRT). (author).