Relation of soluble RANKL and osteoprotegerin levels in blood and gingival crevicular fluid to the degree of root resorption after orthodontic tooth movement

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Tyrovola, J.B.; Halazonetis, D.J.; Makou, M.; Perrea, D.; Dontas, I.; Vlachos, I.S.

2010-01-01

The aim of the present study was the determination of the levels of osteoprotegerin and soluble receptor activator of nuclear factor-(KB) ligand (RANKL) in blood serum and in gingival crevicular fluid relative to the degree of orthodontic root resorption in a rat model. Blood samples and gingival crevicular fluid were collected from fourteen 6-month-old male Wistar rats weighing 350-500 g. A 25-g closed orthodontic coil spring was inserted between each upper right first molar and the upper incisors. After 21 days of loading, both upper first molars (treated and control) were extracted and studied under microcomputed tomography scanning. Statistical analysis demonstrated a positive linear correlation between the initial concentration of RANKL in blood serum and the degree of root resorption. The ratio of the initial concentrations of osteoprotegerin to RANKL in blood serum proved to be an independent prognostic factor of the degree of root resorption. The initial concentration of RANKL in gingival crevicular fluid showed a negative correlation to the initial concentration of RANKL in blood serum and for a finite range of initial concentrations of osteoprotegerin in gingival crevicular fluid, the dental root seemed protected against extreme external root resorption. Finally, the concentration of osteoprotegerin in blood serum decreased significantly in cases of severe root resorption. (author)

 Dehydroepiandrosterone sulfate, osteoprotegerin and its soluble ligand sRANKL and bone metabolism in girls with anorexia nervosa

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Zofia Ostrowska

2012-09-01

Full Text Available  Background:Only scarce data exist concerning the relationship between dehydroepiandrosterone (DHEA and/or its sulfate form DHEAS and bone status in adolescents with anorexia nervosa (AN.Aim:We investigated whether a relationship existed between DHEAS and bone metabolism (as assessed based on serum osteocalcin [OC], and collagen type I cross-linked carboxy-terminal telopeptide [CTx]. We also aimed to establish whether the above mentioned relationship might be affected by osteoprotegerin (OPG and its soluble ligand sRANKL.Material/Methods:Fifty-six female patients with AN and 21 healthy female subjects aged 13 to 16 years participated in the study. Serum DHEAS, OC, CTx, OPG and sRANKL were measured by ELISA.Results:Our female patients with AN demonstrated significant suppression of DHEAS and bone markers, an increase in OPG and sRANKL levels, and a reduction of the OPG/sRANKL ratio. DHEAS, CTx and the OPG/sRANKL ratio correlated positively with BMI. A significant positive correlation was also observed between DHEAS and the OPG/sRANKL ratio, OC and the OPG/sRANKL ratio, and CTx and sRANKL. The correlation was negative in the case of DHEAS and CTx, DHEAS and sRANKL, CTx and the OPG/sRANKL ratio, and sRANKL and the OPG/sRANKL ratio.Discussion/DHEAS suppression in girls with anorexia nervosa was associated with a decrease in the levels of bone markers, an increase in OPG and sRANKL concentrations and a significant decrease in the OPG/sRANKL ratio. DHEAS suppression in girls with anorexia nervosa might have a harmful effect on their bone tissue, probably via a shift in the OPG/RANKL ratio toward a functional excess of sRANKL.

Imbalanced expression of RANKL and osteoprotegerin mRNA in pannus tissue of rheumatoid arthritis.

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Ainola, M; Mandelin, J; Liljeström, M; Konttinen, Y T; Salo, J

2008-01-01

To test if the pannus tissue is characterized by a high receptor activator of nuclear factor kappaB ligand to osteoprotegerin (RANKL:OPG) ratio, which could explain local osteoclastogenesis and formation of bony erosions. Messenger RNA and protein expressions of RANKL and OPG in rheumatoid and osteoarthritic tissue samples were measured using quantitative real-time RT-PCR and Western blot/densitometry. Pannus and synovitis fibroblasts explanted from tissue samples were cultured in vitro without and with TNF-alpha, IL-1Beta or IL-17 and analyzed quantitatively for RANKL expression. The ability of pannus fibroblasts to induce formation of multinuclear osteoclast-like cells from human monocytes, with macrophage-colony stimulating factor (M-CSF) but without RANKL added, was tested. Histochemical staining was used to assess the eventual presence of RANKL and tartrate resistant acid phosphatase positive osteoclast-like cells at the pannus-bone interface. RANKL:OPG ratios of messenger RNA (ppannus (2.06+/-0.73 and 2.2+/-0.65) compared to rheumatoid (0.62+/-0.13 and 1.31+/-0.69) and osteoarthritis (0.62+/-0.32 and 0.52+/-0.16) synovial membranes. Resting and stimulated (p dependent on the cytokine used) pannus fibroblasts produced RANKL in excess (p=0.0005) and unstimulated pannus fibroblasts also effectively induced osteoclast-like cell formation from monocytes in vitro without any exogenous RANKL added. Compatible with these findings, multinuclear osteoclasts-like cells were frequent in the fibroblast- and macrophage-rich pannus tissue at the soft tissue-to-bone interface. The high RANKL:OPG ratio, together with close fibroblast-to-monocyte contacts in pannus tissue, probably favor local generation of bone resorbing osteoclasts at the site of erosion in rheumatoid arthritis.

Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease.

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Kajiya, Mikihito; Giro, Gabriela; Taubman, Martin A; Han, Xiaozhe; Mayer, Marcia P A; Kawai, Toshihisa

2010-11-08

Accumulated lines of evidence suggest that hyperimmune responses to periodontal bacteria result in the destruction of periodontal connective tissue and alveolar bone. The etiological roles of periodontal bacteria in the onset and progression of periodontal disease (PD) are well documented. However, the mechanism underlying the engagement of periodontal bacteria in RANKL-mediated alveolar bone resorption remains unclear. Therefore, this review article addresses three critical subjects. First, we discuss earlier studies of immune intervention, ultimately leading to the identification of bacteria-reactive lymphocytes as the cellular source of osteoclast-induction factor lymphokine (now called RANKL) in the context of periodontal bone resorption. Next, we consider (1) the effects of periodontal bacteria on RANKL production from a variety of adaptive immune effector cells, as well as fibroblasts, in inflamed periodontal tissue and (2) the bifunctional roles (upregulation vs. downregulation) of LPS produced from periodontal bacteria in a RANKL-induced osteoclast-signal pathway. Future studies in these two areas could lead to new therapeutic approaches for the management of PD by down-modulating RANKL production and/or RANKL-mediated osteoclastogenesis in the context of host immune responses against periodontal pathogenic bacteria.

Effects of a Mikania laevigata extract on bone resorption and RANKL expression during experimental periodontitis in rats

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Bruno B. Benatti

2012-06-01

Full Text Available OBJECTIVES: The Mikania laevigata extract (MLE (popularly known in Brazil as "guaco" possesses anti-inflammatory properties. In the present study we tested the effects of MLE in a periodontitis experimental model in rats. We also investigated possible mechanisms underlying such effects. MATERIAL AND METHODS: Periodontal disease was induced by a ligature placed around the mandibular first molars of each animal. Male Wistar rats were divided into 4 groups: non-ligated animals treated with vehicle; non-ligated animals treated with MLE (10 mg/kg, daily; ligature-induced animals treated with vehicle and ligature-induced animals treated with MLE (10 mg/kg, daily. Thirty days after the induction of periodontal disease, the animals were euthanized and mandibles and gingival tissues removed for further analysis. RESULTS: Morphometric analysis of alveolar bone loss demonstrated that MLE-treated animals presented a decreased alveolar bone loss and a lower expression of the activator of nuclear factor-κB ligand (RANKL measured by immunohistochemistry. Moreover, gingival tissues from the MLE-treated group showed decreased neutrophil migration myeloperoxidase (MPO assay. CONCLUSIONS: These results indicate that MLE may be useful to control bone resorption during progression of experimental periodontitis in rats.

Isoproterenol Increases RANKL Expression in a ATF4/NFATc1-Dependent Manner in Mouse Osteoblastic Cells

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Kyunghwa Baek

2017-10-01

Full Text Available Sympathetic nervous system stimulation-induced β-adrenergic signal transduction is known to induce bone loss and increase of osteoclast activity. Although isoproterenol, a nonspecific β-adrenergic receptor agonist, has been shown to increase receptor activator of NF-κB ligand (RANKL, the details of the regulatory mechanisms remain unclear. In the present study, we investigated the role of the nuclear factor of activated T-cells (NFAT in isoproterenol-induced RANKL expression in C2C12 and in primary cultured mouse calvarial cells. Isoproterenol increased nuclear factor of activated T-cells cytoplasmic 1 (NFATc1 and RANKL expressions at both mRNA and protein levels and increased NFAT reporter activity. NFATc1 knockdown blocked isoproterenol-mediated RANKL expression. Isoproterenol also promoted cAMP response element-binding protein 1 (CREB1 and activating transcription factor 4 (ATF4 phosphorylation. Isoproterenol-mediated transcriptional activation of NFAT was blocked by protein kinase A (PKA inhibitor H89. Isoproterenol-induced CREB1, ATF4, NFATc1, and RANKL expressions were suppressed by H89. Mutations in cAMP response element-like or NFAT-binding element suppressed isoproterenol-induced RANKL promoter activity. Chromatin immunoprecipitation analysis demonstrated that isoproterenol increased NFAT-binding and ATF4-binding activities on the mouse RANKL promoter, but did not increase CREB1-binding activity. Association of NFATc1 and ATF4 was not observed in a co-immunoprecipitation study. ATF4 knockdown suppressed isoproterenol-induced NFAT binding to the RANKL promoter, whereas NFATc1 knockdown did not suppress isoproterenol-induced ATF4 binding to the RANKL promoter. ATF4 knockdown suppressed isoproterenol-induced expressions of NFATc1 and RANKL. These results suggest that isoproterenol increases RANKL expression in an ATF4/NFATc1-dependent manner.

Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

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Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

2009-11-01

Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis.

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Ota, Yuri; Niiro, Hiroaki; Ota, Shun-Ichiro; Ueki, Naoko; Tsuzuki, Hirofumi; Nakayama, Tsuyoshi; Mishima, Koji; Higashioka, Kazuhiko; Jabbarzadeh-Tabrizi, Siamak; Mitoma, Hiroki; Akahoshi, Mitsuteru; Arinobu, Yojiro; Kukita, Akiko; Yamada, Hisakata; Tsukamoto, Hiroshi; Akashi, Koichi

2016-03-16

The efficacy of B cell-depleting therapies for rheumatoid arthritis underscores antibody-independent functions of effector B cells such as cognate T-B interactions and production of pro-inflammatory cytokines. Receptor activator of nuclear factor κB ligand (RANKL) is a key cytokine involved in bone destruction and is highly expressed in synovial fluid B cells in patients with rheumatoid arthritis. In this study we sought to clarify the generation mechanism of RANKL(+) effector B cells and their impacts on osteoclast differentiation. Peripheral blood and synovial fluid B cells from healthy controls and patients with rheumatoid arthritis were isolated using cell sorter. mRNA expression of RANKL, osteoprotegerin, tumor necrosis factor (TNF)-α, and Blimp-1 was analyzed by quantitative real-time polymerase chain reaction. Levels of RANKL, CD80, CD86, and CXCR3 were analyzed using flow cytometry. Functional analysis of osteoclastogenesis was carried out in the co-culture system using macrophage RAW264 reporter cells. RANKL expression was accentuated in CD80(+)CD86(+) B cells, a highly activated B-cell subset more abundantly observed in patients with rheumatoid arthritis. Upon activation via B-cell receptor and CD40, switched-memory B cells predominantly expressed RANKL, which was further augmented by interferon-γ (IFN-γ) but suppressed by interleukin-21. Strikingly, IFN-γ also enhanced TNF-α expression, while it strongly suppressed osteoprotegerin expression in B cells. IFN-γ increased the generation of CXCR3(+)RANKL(+) effector B cells, mimicking the synovial B cell phenotype in patients with rheumatoid arthritis. Finally, RANKL(+) effector B cells in concert with TNF-α facilitated osteoclast differentiation in vitro. Our current findings have shed light on the generation mechanism of pathogenic RANKL(+) effector B cells that would be an ideal therapeutic target for rheumatoid arthritis in the future.

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

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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.

Evaluation of the osteoclastogenic process associated with RANK / RANK-L / OPG in odontogenic myxomas

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González-Galván, María del Carmen; Mosqueda-Taylor, Adalberto; Bologna-Molina, Ronell; Setien-Olarra, Amaia; Marichalar-Mendia, Xabier; Aguirre-Urizar, José-Manuel

2018-01-01

Background Odontogenic myxoma (OM) is a benign intraosseous neoplasm that exhibits local aggressiveness and high recurrence rates. Osteoclastogenesis is an important phenomenon in the tumor growth of maxillary neoplasms. RANK (Receptor Activator of Nuclear Factor κappa B) is the signaling receptor of RANK-L (Receptor activator of nuclear factor kappa-Β ligand) that activates the osteoclasts. OPG (osteoprotegerin) is a decoy receptor for RANK-L that inhibits pro-osteoclastogenesis. The RANK / RANKL / OPG system participates in the regulation of osteolytic activity under normal conditions, and its alteration has been associated with greater bone destruction, and also with tumor growth. Objectives To analyze the immunohistochemical expression of OPG, RANK and RANK-L proteins in odontogenic myxomas (OMs) and their relationship with the tumor size. Material and Methods Eighteen OMs, 4 small ( 3cm) and 18 dental follicles (DF) that were included as control were studied by means of standard immunohistochemical procedure with RANK, RANKL and OPG antibodies. For the evaluation, 5 fields (40x) of representative areas of OM and DF were selected where the expression of each antibody was determined. Descriptive and comparative statistical analyses were performed with the obtained data. Results There are significant differences in the expression of RANK in OM samples as compared to DF (p = 0.022) and among the OMSs and OMLs (p = 0.032). Also a strong association is recognized in the expression of RANK-L and OPG in OM samples. Conclusions Activation of the RANK / RANK-L / OPG triad seems to be involved in the mechanisms of bone balance and destruction, as well as associated with tumor growth in odontogenic myxomas. Key words:Odontogenic myxoma, dental follicle, RANK, RANK-L, OPG, osteoclastogenesis. PMID:29680857

Safflower bud inhibits RANKL-induced osteoclast differentiation and prevents bone loss in ovariectomized mice.

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Choi, Joo-Hee; Lim, Seul-Ki; Kim, Dong-Il; Park, Min-Jung; Kim, Young-Kuk; Lee, An-Chul; Kim, Young-Min; Yang, Soo-Jin; Park, Jong-Hwan

2017-10-15

The powder and extract of safflower seeds are known to be effective in the prevention of bone loss in ovariectomized animals. However, the inhibitory effect and molecular mechanisms of safflower bud (SB), the germinated safflower, on bone destruction is unclear. The present study was designed to investigate the inhibitory effect and molecular mechanism of SB on osteoclastic differentiation and on bone loss in ovarietomized (OVX) mice. Osteoclastogenesis was determined by TRAP staining, F-actin ring formation, and bone resorption assay. NF-κB and MAPKs activation was analyzed by transfection assay and Western blot, respectively. Real-time PCR was performed to examine the expression of osteoclastogenesis-related genes. Histological changes, increases in TRAP-positive cells, and cathepsin K expression were examined in the metaphysis of OVX mice. Density of bone marrow was evaluated by µCT. SB inhibited the RANKL-induced differentiation of BMDMs into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by SB in RANKL-treated BMDMs. In addition, SB decreased the activation of NF-κB and MAPKs and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. Feeding of SB-included diet prevented bone loss in OVX mice. The number of TRAP-positive cells and level of protein expression of cathepsin K was reduced and bone mineral density was increased in the metaphysis of mice fed SB compared with OVX mice. These findings suggest that SB can be a preventive and therapeutic candidate for destructive bone diseases. Copyright © 2017. Published by Elsevier GmbH.

Involvement of the G-protein-coupled receptor 4 in RANKL expression by osteoblasts in an acidic environment

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Okito, Asuka [Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Tokyo (Japan); Department of Orthodontic Science, Tokyo Medical and Dental University, Tokyo (Japan); Nakahama, Ken-ichi, E-mail: nakacell@tmd.ac.jp [Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Tokyo (Japan); Akiyama, Masako [Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Tokyo (Japan); Ono, Takashi [Department of Orthodontic Science, Tokyo Medical and Dental University, Tokyo (Japan); Morita, Ikuo [Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Tokyo (Japan)

2015-03-06

Osteoclast activity is enhanced in acidic environments following systemic or local inflammation. However, the regulatory mechanism of receptor activator of NF-κB ligand (RANKL) expression in osteoblasts under acidic conditions is not fully understood. In the present paper, we detected the mRNA expression of the G-protein-coupled receptor (GPR) proton sensors GPR4 and GPR65 (T-cell death-associated gene 8, TDAG8), in osteoblasts. RANKL expression and the cyclic AMP (cAMP) level in osteoblasts were up-regulated under acidic culture conditions. Acidosis-induced up-regulation of RANKL was abolished by the protein kinase A inhibitor H89. To clarify the role of GPR4 in RANKL expression, GPR4 gain and loss of function experiments were performed. Gene knockdown and forced expression of GPR4 caused reduction and induction of RANKL expression, respectively. These results suggested that, at least in part, RANKL expression by osteoblasts in an acidic environment was mediated by cAMP/PKA signaling resulting from GPR4 activation. A comprehensive microarray analysis of gene expression of osteoblasts revealed that, under acidic conditions, the phenotype of osteoblasts was that of an osteoclast supporting cell rather than that of a mineralizing cell. These findings will contribute to a molecular understanding of bone disruption in an acidic environment. - Highlights: • RANKL expression was increased in osteoblasts under acidosis via cAMP/PKA pathway. • GRP4 knockdown resulted in decrease of RANKL expression. • GRP4 overexpression resulted in increase of RANKL expression. • Osteoblast mineralization was reduced under acidic condition.

Schisantherin A suppresses osteoclast formation and wear particle-induced osteolysis via modulating RANKL signaling pathways

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He, Yi; Zhang, Qing; Shen, Yi; Chen, Xia; Zhou, Feng; Peng, Dan, E-mail: xyeypd@163.com

2014-07-04

Highlights: • Schisantherin A suppresses osteoclasts formation and function in vitro. • Schisantherin A impairs RANKL signaling pathway. • Schisantherin A suppresses osteolysis in vivo. • Schisantherin A may be used for treating osteoclast related diseases. - Abstract: Receptor activator of NF-κB ligand (RANKL) plays critical role in osteoclastogenesis. Targeting RANKL signaling pathways has been a promising strategy for treating osteoclast related bone diseases such as osteoporosis and aseptic prosthetic loosening. Schisantherin A (SA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent, but its effect on osteoclasts has been hitherto unknown. In the present study, SA was found to inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, SA inhibited OSCAR, cathepsin K and TRAP in a dose dependent manner. Further signal transduction studies revealed that SA down-regulate RANKL-induced nuclear factor-kappaB (NF-κB) signaling activation by suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the NF-κB transcriptional activity. Moreover, SA also decreased the RANKL-induced MAPKs signaling pathway, including JNK and ERK1/2 posphorylation while had no obvious effects on p38 activation. Finally, SA suppressed the NF-κB and MAPKs subsequent gene expression of NFATc1 and c-Fos. In vivo studies, SA inhibited osteoclast function and exhibited bone protection effect in wear-particle-induced bone erosion model. Taken together, SA could attenuate osteoclast formation and wear particle-induced osteolysis by mediating RANKL signaling pathways. These data indicated that SA is a promising therapeutic natural compound for the treatment of osteoclast-related prosthesis loosening.

Expression profile of osteoprotegerin, RANK and RANKL genes in the femoral head of patients with avascular necrosis.

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Samara, Stavroula; Dailiana, Zoe; Chassanidis, Christos; Koromila, Theodora; Papatheodorou, Loukia; Malizos, Konstantinos N; Kollia, Panagoula

2014-02-01

Femoral head avascular necrosis (AVN) is a recalcitrant disease of the hip that leads to joint destruction. Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B (RANK) and RANK ligand (RANKL) regulate the balance between osteoclasts-osteoblasts. The expression of these genes affects the maturation and function of osteoblasts-osteoclasts and bone remodeling. In this study, we investigated the molecular pathways leading to AVN by studying the expression profile of OPG, RANK and RANKL genes. Quantitative Real Time-PCR was performed for evaluation of OPG, RANK and RANKL expression. Analysis was based on parallel evaluation of mRNA and protein levels in normal/necrotic sites of 42 osteonecrotic femoral heads (FHs). OPG and RANKL protein levels were estimated by western blotting. The OPG mRNA levels were higher (insignificantly) in the necrotic than the normal site (p > 0.05). Although the expression of RANK and RANKL was significantly lower than OPG in both sites, RANK and RANKL mRNA levels were higher in the necrotic part than the normal (p < 0.05). Protein levels of OPG and RANKL showed no remarkable divergence. Our results indicate that differential expression mechanisms for OPG, RANK and RANKL that could play an important role in the progress of bone remodeling in the necrotic area, disturbing bone homeostasis. This finding may have an effect on the resulting bone destruction and the subsequent collapse of the hip joint. Copyright © 2013. Published by Elsevier Inc.

Clinical prognostic significance and pro-metastatic activity of RANK/RANKL via the AKT pathway in endometrial cancer.

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Wang, Jing; Liu, Yao; Wang, Lihua; Sun, Xiao; Wang, Yudong

2016-02-02

RANK/RANKL plays a key role in metastasis of certain malignant tumors, which makes it a promising target for developing novel therapeutic strategies for cancer. However, the prognostic value and pro-metastatic activity of RANK in endometrial cancer (EC) remain to be determined. Thus, the present study investigated the effect of RANK on the prognosis of EC patients, as well as the pro-metastatic activity of EC cells. The results indicated that those with high expression of RANK showed decreased overall survival and progression-free survival. Statistical analysis revealed the positive correlations between RANK/RANKL expression and metastasis-related factors. Additionally, RANK/RANKL significantly promoted cell migration/invasion via activating AKT/β-catenin/Snail pathway in vitro. However, RANK/RANKL-induced AKT activation could be suppressed after osteoprotegerin (OPG) treatment. Furthermore, the combination of medroxyprogesterone acetate (MPA) and RANKL could in turn attenuate the effect of RANKL alone. Similarly, MPA could partially inhibit the RANK-induced metastasis in an orthotopic mouse model via suppressing AKT/β-catenin/Snail pathway. Therefore, therapeutic inhibition of MPA in RANK/RANKL-induced metastasis was mediated by AKT/β-catenin/Snail pathway both in vitro and in vivo, suggesting a potential target of RANK for gene-based therapy for EC.

Monosodium Urate in the Presence of RANKL Promotes Osteoclast Formation through Activation of c-Jun N-Terminal Kinase

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Jung-Yoon Choe

2015-01-01

Full Text Available The aim of this study was to clarify the role of monosodium urate (MSU crystals in receptor activator of nuclear factor kB ligand- (RANKL- RANK-induced osteoclast formation. RAW 264.7 murine macrophage cells were incubated with MSU crystals or RANKL and differentiated into osteoclast-like cells as confirmed by staining for tartrate-resistant acid phosphatase (TRAP and actin ring, pit formation assay, and TRAP activity assay. MSU crystals in the presence of RANKL augmented osteoclast differentiation, with enhanced mRNA expression of NFATc1, cathepsin K, carbonic anhydrase II, and matrix metalloproteinase-9 (MMP-9, in comparison to RAW 264.7 macrophages incubated in the presence of RANKL alone. Treatment with both MSU crystals and RANKL induced osteoclast differentiation by activating downstream molecules in the RANKL-RANK pathway including tumor necrosis factor receptor-associated factor 6 (TRAF-6, JNK, c-Jun, and NFATc1. IL-1b produced in response to treatment with both MSU and RANKL is involved in osteoclast differentiation in part through the induction of TRAF-6 downstream of the IL-1b pathway. This study revealed that MSU crystals contribute to enhanced osteoclast formation through activation of RANKL-mediated pathways and recruitment of IL-1b. These findings suggest that MSU crystals might be a pathologic causative agent of bone destruction in gout.

Expression of osteoprotegerin, RNAK and RANKL genes in femoral head avascular necrosis and related signaling pathway.

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Miao, Qingtang; Hao, Sibin; Li, Hongmei; Sun, Fang; Wang, Xueling

2015-01-01

Femoral head avascular necrosis (AVN) causes the damage of hip joint and related dysfunctions, thus consisting of a clinical challenge. Osteoprotegerin (OPG), receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) all regulate the formation of bones via gene transcriptional regulation for the balance between osteoblasts and osteoclasts. This study thus investigated the expressional profiles of OPG, RANK and RANKL genes in AVN patients, and explored related molecular mediating pathways. Real-time qPCR was used to measure the gene expression of OPG, RANK and RANKL genes in AVN femoral head tissue samples from 42 patients, along with normal tissues. Western blotting analysis was performed to quantify protein levels of OPG and RANKL. There was a trend but not statistically significant elevation of mRNA levels of OPG in femoral head AVN tissues compared to normal tissues (P>0.05). The expression of RNAK and RNAKL, however, was significantly elevated in necrotic tissues (P<0.05). No significant difference in protein levels of OPG or RANKL between groups. The expression of OPG, RANK and RANKL genes exert a crucial role in the progression of AVN, suggesting their roles in mediating bone homeostasis and potential effects on bone destruction.

Fisetin antagonizes cell fusion, cytoskeletal organization and bone resorption in RANKL-differentiated murine macrophages.

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Kim, Yun-Ho; Kim, Jung-Lye; Lee, Eun-Jung; Park, Sin-Hye; Han, Seon-Young; Kang, Soon Ah; Kang, Young-Hee

2014-03-01

Osteoclastogenesis is comprised of several stage s including progenitor survival, differentiation to mononuclear preosteoclasts, cell fusion to multinuclear mature osteoclasts, and activation to osteoclasts with bone resorbing activity. Botanical antioxidants are now being increasingly investigated for their health-promoting effects on bone. This study investigated that fisetin, a flavonol found naturally in many fruits and vegetables, suppressed osteoclastogenesis by disturbing receptor activator of nuclear factor (NF)-κB ligand (RANKL)-mediated signaling pathway and demoting osteoclastogenic protein induction. Nontoxic fisetin at ≤10 μM inhibited the induction of RANK, tumor necrosis factor receptor associated factor 6 (TRAF6) and the activation of NF-κB in RANKL-stimulated RAW 264.7 macrophages. In RANKL-differentiated osteoclasts cell fusion protein of E-cadherin was induced, which was dampened by fisetin. The formation of tartrate-resistance acid phosphatase-positive multinucleated osteoclasts was suppressed by adding fisetin to RANKL-exposed macrophages. It was also found that fisetin reduced actin ring formation and gelsolin induction of osteclasts enhanced by RANKL through disturbing c-Src-proline-rich tyrosine kinase 2 signaling. Fisetin deterred preosteoclasts from the cell-cell fusion and the organization of the cytoskeleton to seal the resorbing area and to secret protons for bone resorption. Consistently, the 5 day-treatment of fisetin diminished RANKL-induced cellular expression of carbonic anhydrase II and integrin β3 concurrently with a reduction of osteoclast bone-resorbing activity. Therefore, fisetin was a natural therapeutic agent retarding osteoclast fusion and cytoskeletal organization such as actin rings and ruffled boarder, which is a property of mature osteoclasts and is required for osteoclasts to resorb bone. Copyright © 2014 Elsevier Inc. All rights reserved.

RANKL-Targeted Therapies: The Next Frontier in the Treatment of Male Osteoporosis

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Alicia K. Morgans

2011-01-01

Full Text Available Male osteoporosis is an increasingly recognized problem in aging men. A common cause of male osteoporosis is hypogonadism. Thousands of men with prostate cancer are treated with androgen deprivation therapy, a treatment that dramatically reduces serum testosterone and causes severe hypogonadism. Men treated with androgen deprivation therapy experience a decline in bone mineral density and have an increased rate of fracture. This paper describes prostate cancer survivors as a model of hypogonadal osteoporosis and discusses the use of RANKL-targeted therapies in osteoporosis. Denosumab, the only RANKL-targeted therapy currently available, increases bone mineral density and decreases fracture rate in men with prostate cancer. Denosumab is also associated with delayed time to first skeletal-related event and an increase in bone metastasis-free survival in these men. It is reasonable to investigate the use of RANKL-targeted therapy in male osteoporosis in the general population.

Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults

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Mathiesen, Inger Hee Mabuza; Salem, Mohammad; Gerstoft, Jan

2017-01-01

accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery. METHODS: We used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation. RESULTS......: Soluble RANKL changed significantly over time (overall p = 0.02) with 25% decrease (95% CI: -42 to -5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD...... and changes in sRANKL. CONCLUSION: In this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART. TRIAL REGISTRATION: Clinical...

Curcumol suppresses RANKL-induced osteoclast formation by attenuating the JNK signaling pathway

International Nuclear Information System (INIS)

Yu, Mingxiang; Chen, Xianying; Lv, Chaoyang; Yi, Xilu; Zhang, Yao; Xue, Mengjuan; He, Shunmei; Zhu, Guoying; Wang, Hongfu

2014-01-01

Highlights: • Curcumol suppresses osteoclasts differentiation in vitro. • Curcumol impairs JNK/AP-1 signaling pathway. • Curcumol may be used for treating osteoclast related diseases. - Abstract: Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases

Curcumol suppresses RANKL-induced osteoclast formation by attenuating the JNK signaling pathway

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Yu, Mingxiang, E-mail: yu.mingxiang@zs-hospital.sh.cn [Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Xianying [Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan (China); Lv, Chaoyang [Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai (China); Yi, Xilu [Department of Endocrinology and Metabolism, Shanghai Songjiang District Central Hospital, Shanghai (China); Zhang, Yao; Xue, Mengjuan; He, Shunmei [Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai (China); Zhu, Guoying [Institute of Radiation Medicine, Fudan University, Shanghai (China); Wang, Hongfu, E-mail: hfwang@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, Shanghai (China)

2014-05-02

Highlights: • Curcumol suppresses osteoclasts differentiation in vitro. • Curcumol impairs JNK/AP-1 signaling pathway. • Curcumol may be used for treating osteoclast related diseases. - Abstract: Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases.

RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

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Konca Degertekin, Ceyla; Turhan Iyidir, Ozlem; Aktas Yılmaz, Banu; Elbeg, Sehri; Pasaoglu, Ozge Tugce; Pasaoglu, Hatice; Cakır, Nuri; Arslan, Metin

2016-10-01

Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.

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.

The inhibitory effect of vitamin K on RANKL-induced osteoclast differentiation and bone resorption.

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Wu, Wei-Jie; Kim, Min Seuk; Ahn, Byung-Yong

2015-10-01

To further understand the correlation between vitamin K and bone metabolism, the effects of vitamins K1, menaquinone-4 (MK-4), and menaquinone-7 (MK-7) on RANKL-induced osteoclast differentiation and bone resorption were comparatively investigated. Vitamin K2 groups (MK-4 and MK-7) were found to significantly inhibit RANKL-medicated osteoclast cell formation of bone marrow macrophages (BMMs) in a dose-dependent manner, without any evidence of cytotoxicity. The mRNA expression of specific osteoclast differentiation markers, such as c-Fos, NFATc1, OSCAR, and TRAP, as well as NFATc1 protein expression and TRAP activity in RANKL-treated BMMs were inhibited by vitamin K2, although MK-4 exhibited a significantly greater efficiency compared to MK-7. In contrast, the same dose of vitamin K1 had no inhibitory effect on RANKL-induced osteoclast cell formation, but increased the expression of major osteoclastogenic genes. Interestingly, vitamins K1, MK-4 and MK-7 all strongly inhibited osteoclastic bone resorption (p vitamins K1, MK-4 and MK-7 have anti-osteoporotic properties, while their regulation effects on osteoclastogenesis are somewhat different.

Periapical fluid RANKL and IL-8 are differentially regulated in pulpitis and apical periodontitis.

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Rechenberg, Dan-K; Bostanci, Nagihan; Zehnder, Matthias; Belibasakis, Georgios N

2014-09-01

The dental pulp space can become infected due to a breach in the surrounding hard tissues. This leads to inflammation of the pulp (pulpitis), soft tissue breakdown, and finally to bone loss around the root apex (apical periodontitis). The succession of the molecular events leading to apical periodontitis is currently not known. The main inflammatory mediator associated with neutrophil chemotaxis is interleukin-8 (IL-8), and with bone resorption the dyad of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). The levels of RANKL, OPG and IL-8 were studied in periapical tissue fluid of human teeth (n = 48) diagnosed with symptomatic irreversible pulpitis (SIP) and asymptomatic apical periodontitis (AAP). SIP represents the starting point, and AAP an established steady state of the disease. Periapical tissue fluid samples were collected using paper points and then evaluated using enzyme-linked immunosorbent assays (ELISAs). Target protein levels per case were calibrated against the corresponding total protein content, as determined fluorometrically. RANKL was expressed at significantly higher levels in SIP compared to AAP (P apical periodontitis, periapical bone resorption signaling, as determined by RANKL, occurs prior to inflammatory cell recruitment signaling, as determined by IL-8. Copyright © 2014 Elsevier Ltd. All rights reserved.

Constitutive expression of TNF-related activation-induced cytokine (TRANCE/receptor activating NF-κB ligand (RANK-L by rat plasmacytoid dendritic cells.

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Thomas Anjubault

Full Text Available Plasmacytoid dendritic cells (pDCs are a subset of DCs whose major function relies on their capacity to produce large amount of type I IFN upon stimulation via TLR 7 and 9. This function is evolutionary conserved and place pDC in critical position in the innate immune response to virus. Here we show that rat pDC constitutively express TNF-related activation-induced cytokine (TRANCE also known as Receptor-activating NF-κB ligand (RANKL. TRANCE/RANKL is a member of the TNF superfamily which plays a central role in osteoclastogenesis through its interaction with its receptor RANK. TRANCE/RANK interaction are also involved in lymphoid organogenesis as well as T cell/DC cross talk. Unlike conventional DC, rat CD4(high pDC were shown to constitutively express TRANCE/RANKL both at the mRNA and the surface protein level. TRANCE/RANKL was also induced on the CD4(low subsets of pDC following activation by CpG. The secreted form of TRANCE/RANKL was also produced by rat pDC. Of note, levels of mRNA, surface and secreted TRANCE/RANKL expression were similar to that observed for activated T cells. TRANCE/RANKL expression was found on pDC in all lymphoid organs as well blood and BM with a maximum expression in mesenteric lymph nodes. Despite this TRANCE/RANKL expression, we were unable to demonstrate in vitro osteoclastogenesis activity for rat pDC. Taken together, these data identifies pDC as novel source of TRANCE/RANKL in the immune system.

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

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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.

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

Histomorphometric analysis and immunolocalization of RANKL and OPG during the alveolar healing process in female ovariectomized rats treated with oestrogen or raloxifene.

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Luvizuto, Eloá Rodrigues; Queiroz, Thallita Pereira; Dias, Sheila Mônica Damásio; Okamoto, Tetuo; Dornelles, Rita Cássia Menegati; Garcia, Idelmo Rangel; Okamoto, Roberta

2010-01-01

To investigate the effects of bone-resorption inhibitors (oestrogen and raloxifene) on the RANKL/OPG balance during the chronology of the alveolar healing process in ovariectomized (OVX) rats by means of immunocolocalization and histomorphometric analysis. One hundred sixty female Wistar rats at 70 days of age were either OVX or sham-operated and divided into four groups: sham, OVX/Oil, OVX with E(2) replacement (17beta-estradiol, 400 microg/month), OVX with RLX treatment (1mg/kg bw/day). The 60-day treatment started 8 days after ovariectomy. The incisors were extracted to allow analysis of 7, 14, 21, 28 and 42 days of wound healing. After obtaining the histological samples, slides were stained with hematoxylin and eosin or subjected to immunocolocalization reaction for RANKL and OPG. Results were quantitatively evaluated. Histomorphometric analysis showed that the sham group presented the highest and OVX/Oil group the lowest mean bone formation value in the post-extraction period. The immunocolocalization analysis showed a larger increase in bone turnover at 7 postoperative days in OVX/Oil and sham groups and decreasing bone turnover in the other periods. The OVX/Oil group showed a large decrease in bone turnover at 14 postoperative days, a period demonstrated by mild cellular activity. OVX/E(2) and sham groups showed a decreased bone turnover at 28 postoperative days while OVX/RLX group showed a decreased bone turnover at 21 postoperative days. On the 42nd postoperative day, sham and OVX/RLX groups showed an established alveolar bone healing process. Ovariectomy delays the alveolar healing process and interferes with bone turnover through the balance between RANKL and OPG. Oestrogen replacement or raloxifene treatment did not totally recover the oestrogen-deficient state. However raloxifene treatment showed more satisfactory results than oestrogen replacement. Copyright 2009 Elsevier Ltd. All rights reserved.

Parallel Assessment of Bone Mineral Density and RANKL/OPG Ratio in Saudi Females

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AI Hassan

2016-02-01

Full Text Available Background: Osteoporosis is a significant risk factor for morbidity, and its high prevalence among Saudi women should be considered to be a public health problem. Quantitative ultrasound was recommended for bone mineral density (BMD screening. Receptor activator of nuclear factor kappa-B ligand (RANKL and osteoprotegerin (OPG and their ratio are critical for physiological bone remodelling, and related abnormalities may lead to several osteopathies. Methods: The BMD of 499 Saudi females aged 20 to 65 years was measured using quantitative ultrasound from the beginning of October 2013 to the end of March 2014 at the female medical unit of Taibah University, Madinah, KSA. Possible associated risk factors for low BMD were studied. Blood RANKL and OPG were measured by enzyme-linked immunosorbent assay (ELISA. Results: No significant differences were found between participants with normal and low BMD regarding the studied risk factors. However, there was a significant association (p < 0.05 between BMD and regular physical activity among participants aged 20 years to less than 35 years, and women aged 35–50 years with higher body mass index (BMI had higher BMD. The RANKL/OPG ratio was inversely associated (p = 0.04 with BMD. Conclusions: Regular physical activity is crucial for maximizing BMD in young females and decreasing the possibility of developing osteoporosis with ageing. The RANKL/OPG ratio might be considered a useful and easy-to-use tool for the prediction of low BMD.

[Correlation of RANKL/OPG, dickkopf-1 and bone marrow edema in rheumatoid arthritis with the complaint of knee pain].

Science.gov (United States)

Li, Min; Wu, Xiao-hui; Yin, Geng; Xie, Qi-bing

2015-03-01

To investigate the correlation of the receptor activator of nuclear factor kappa-B ligand (RANKL)/serum osteoprotegerin (OPG) system, Dickkopf-1 (DKK-1) and bone marrow edema (BME) in rheumatoid arthritis (RA) with the complaint of knee pain. The clinical data of 50 cases of RA with the complaint of knee pain were collected. According to MRI finding, half of them (25 cases) had bone marrow edema (BME). Each patient received the measurement of serum OPG, RANKL, DKK-1, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti cyclic citrullinated peptide antibody (CCP), rheumatoid factort(RF). The clinical symptoms, disease activity score 28 (DAS28), were compared between BME and non-BME griups, and the correlation between RANKL/OPG system, DKK-1 and BME of RA was analyzed. Compared with non BME group, BME group had shorter course (P=0.000), higher DAS28 score (P=0.009), CRP (P=0:000), RF (P=0.033) and CCP (P=0.012). lower level of serum OPG (P=0.000), higher level of RANKL (P=0.000), RANKL/OPG (P=0.000), and DKK-1 (P=0.001). The severity of bone marrow edema was correlated with the serum RANKL (volume r(s)=0.31, P=0.027; degree r(s)=0.33, P=0.022), RANKL/OPG (volume r(s)=0.29, P=0.039; degree r(s)=0.28, P=0.043), DKK-1 (volume r(s)=0.33, P=0.021; degree r(s)=0.34, P=0.019). BME is one of the early signs of bone erosion in RA, there were more active inflammation, autoantibodies, and osteocasts in RA patients with BME.

Biotechnological approach for systemic delivery of membrane Receptor Activator of NF-κB Ligand (RANKL) active domain into the circulation

Science.gov (United States)

Cappariello, Alfredo; Paone, Riccardo; Maurizi, Antonio; Capulli, Mattia; Rucci, Nadia; Muraca, Maurizio; Teti, Anna

2015-01-01

Deficiency of Receptor Activator of NF-κB Ligand (RANKL) prevents osteoclast formation causing osteopetrosis. RANKL is a membrane-bound protein cleaved into active soluble (s)RANKL by metalloproteinase 14 (MMP14). We created a bio-device that harbors primary osteoblasts, cultured on 3D hydroxyapatite scaffolds carrying immobilized MMP14 catalytic domain. Scaffolds were sealed in diffusion chambers and implanted in RANKL-deficient mice. Mice received 1 or 2 diffusion chambers, once or twice and were sacrificed after 1 or 2 months from implants. A progressive increase of body weight was observed in the implanted groups. Histological sections of tibias of non-implanted mice were negative for the osteoclast marker Tartrate-Resistant Acid Phosphatase (TRAcP), consistent with the lack of osteoclasts. In contrast, tibias excised from implanted mice showed TRAcP-positive cells in the bone marrow and on the bone surface, these latter morphologically similar to mature osteoclasts. In mice implanted with 4 diffusion chambers total, we noted the highest number and size of TRAcP-positive cells, with quantifiable eroded bone surface and significant reduction of trabecular bone volume. These data demonstrate that our bio-device delivers effective sRANKL, inducing osteoclastogenesis in RANKL-deficient mice, supporting the feasibility of an innovative experimental strategy to treat systemic cytokine deficiencies. PMID:25678116

Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats

International Nuclear Information System (INIS)

Brzóska, Malgorzata M.; Rogalska, Joanna

2013-01-01

It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system. - Highlights: • Cd induces oxidative stress in the bone tissue. • Cd disturbs bone metabolism via disorder of the RANK/RANKL/OPG system balance. • Zn supplementation protects from Cd-induced oxidative stress in the bone tissue. • Zn protects from the RANK/RANKL/OPG system imbalance caused by Cd in the bone tissue. • Enhanced Zn intake protects from Cd

Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats

Energy Technology Data Exchange (ETDEWEB)

Brzóska, Malgorzata M., E-mail: Malgorzata.Brzoska@umb.edu.pl; Rogalska, Joanna

2013-10-01

It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system. - Highlights: • Cd induces oxidative stress in the bone tissue. • Cd disturbs bone metabolism via disorder of the RANK/RANKL/OPG system balance. • Zn supplementation protects from Cd-induced oxidative stress in the bone tissue. • Zn protects from the RANK/RANKL/OPG system imbalance caused by Cd in the bone tissue. • Enhanced Zn intake protects from Cd

Immunolocalization of RANK and RANKL along the root surface and in the periodontal membrane of human primary and permanent teeth

DEFF Research Database (Denmark)

Bille, Marie-Louise Bastholm; Thomsen, Bjarke; Andersen, Thomas Levin

2012-01-01

Abstract Objective. Root resorption, impaired tooth eruption and early tooth loss have been described in relation to diseases that involve defects in the RANK-RANKL-OPG-expression. The aim of the present immunhistochemical study was to localize and compare the reactions for RANK and membrane...... in odontoblasts and in cells along denticles in one primary tooth. RANK was located in mononuclear cells in the pulp and in multinucleated odontoclasts along resorbed root surfaces and along resorbed dentin surfaces in the pulp in primary teeth and one permanent tooth. Conclusions. This study demonstrated RANK...... positivity in resorption areas in primary and permanent teeth. RANKL was positive in the pulp of one primary tooth. RANK expression in odontoclasts and RANKL expression in the pulp may indicate that RANK/RANKL play a role during resorption....

Low-magnitude high-frequency vibration inhibits RANKL-induced osteoclast differentiation of RAW264.7 cells.

Science.gov (United States)

Wu, Song-Hui; Zhong, Zhao-Ming; Chen, Jian-Ting

2012-01-01

Osteoclasts are the key participants in regulation of bone mass. Low-magnitude high-frequency vibration (LMHFV) has been found to be anabolic to bone in vivo. This study aimed to investigate the effect of LMHFV on osteoclast differentiation in vitro. Murine monocyte cell line RAW264.7 cells in the presence of receptor activator of nuclear factor-kappaB ligand (RANKL) were treated with or without LMHFV at 45 Hz (0.3 g) for 15 min day(-1). Tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) and actin ring formation were evaluated. Expression of the osteoclast-specific genes, such as cathepsin K, matrix metallopeptidase-9 (MMP-9) and TRAP, were analyzed using real time-PCR. c-Fos, an osteoclast-specific transcription factor, was determined using Western blot. We found that LMHFV significantly decreased the number of RANKL-induced TRAP-positive MNCs (P<0.01), and inhibited the actin ring formation. The mRNA expression of the cathepsin K, MMP-9 and TRAP were down-regulated by LMHFV intervention (all P<0.001). Furthermore, LMHFV also inhibited the expression of c-Fos protein in the RANKL-treated RAW264.7 cells (P<0.05). Our results suggest that LMHFV can inhibit the RANKL-induced osteoclast differentiation of RAW264.7 cells, which give some new insight into the anabolic effects of LMHFV on bone.

Nitrogen-containing bisphosphonate, YM529/ONO-5920 (a novel minodronic acid), inhibits RANKL expression in a cultured bone marrow stromal cell line ST2

International Nuclear Information System (INIS)

Nishida, Shozo; Tsubaki, Masanobu; Hoshino, Mayumi; Namimatsu, Ayumi; Uji, Hiromi; Yoshioka, Shohei; Tanimori, Yoshihiro; Yanae, Masashi; Iwaki, Masahiro; Irimajiri, Kiyohiro

2005-01-01

Increase in bone resorption by osteoclasts can cause metabolic bone diseases, such as osteoporosis. Recent attention has been paid to the receptor activator of the NF-κB ligand (RANKL), an accelerator of osteoclast differentiation. RANKL is expressed on the bone marrow-derived stromal cell membrane and induces the differentiation of osteoclasts by binding to RANK expressed on the osteoclast precursor cell membrane. Since the inhibition of RANKL expression can lead to the inhibition of osteoclastic bone resorption, the clinical application of RANKL inhibition could be expected to have a major effect on metabolic bone disease therapy. In this study, we investigated whether or not YM529/ONO-5920, a nitrogen-containing bisphosphonate (a novel minodronic acid), inhibits RANKL expression in a bone marrow-derived stromal cell line (ST2 cells). Reverse transcription-polymerase chain reaction revealed that the administration of YM529/ONO-5920 to ST2 cells inhibited RANKL mRNA expression and reduced RANKL proteins as assessed by Western blot analysis. The inhibition of RANKL mRNA expression was reversed when geranylgeranyl pyrophosphate (GGPP), an intermediate in the mevalonate pathway, was used in combination. Furthermore, YM529/ONO-5920 reduced phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), and similarly, U0126, a mitogen-activated protein kinase kinase 1/2 inhibitor, inhibited RANKL expression. Pretreatment with GGPP reversed the YM529/ONO-5920-induced decrease in phosphorylation of ERK. Furthermore, YM529/ONO-5920 decreased TRAP-positive cells in co-culture of ST2 cells and an osteoclast cell line, C7 cells, and this decrease was inhibited by pretreatment with GGPP. This indicates that YM529/ONO-5920 inhibits GGPP biosynthesis in the mevalonate pathway and then signal transduction in the Ras-mitogen-activated protein kinase pathway, thereby inhibiting RANKL expression on ST2 cells. These results suggest a newly elucidated action of bisphosphonates in

Involvement of Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-induced Incomplete Cytokinesis in the Polyploidization of Osteoclasts*

Science.gov (United States)

Takegahara, Noriko; Kim, Hyunsoo; Mizuno, Hiroki; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Tomura, Michio; Kanagawa, Osami; Ishii, Masaru; Choi, Yongwon

2016-01-01

Osteoclasts are specialized polyploid cells that resorb bone. Upon stimulation with receptor activator of nuclear factor-κB ligand (RANKL), myeloid precursors commit to becoming polyploid, largely via cell fusion. Polyploidization of osteoclasts is necessary for their bone-resorbing activity, but the mechanisms by which polyploidization is controlled remain to be determined. Here, we demonstrated that in addition to cell fusion, incomplete cytokinesis also plays a role in osteoclast polyploidization. In in vitro cultured osteoclasts derived from mice expressing the fluorescent ubiquitin-based cell cycle indicator (Fucci), RANKL induced polyploidy by incomplete cytokinesis as well as cell fusion. Polyploid cells generated by incomplete cytokinesis had the potential to subsequently undergo cell fusion. Nuclear polyploidy was also observed in osteoclasts in vivo, suggesting the involvement of incomplete cytokinesis in physiological polyploidization. Furthermore, RANKL-induced incomplete cytokinesis was reduced by inhibition of Akt, resulting in impaired multinucleated osteoclast formation. Taken together, these results reveal that RANKL-induced incomplete cytokinesis contributes to polyploidization of osteoclasts via Akt activation. PMID:26670608

1,25-Dihydroxyvitamin D3 Inhibits the RANKL Pathway and Impacts on the Production of Pathway-Associated Cytokines in Early Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Jing Luo

2013-01-01

Full Text Available Objectives. To study effects of 1,25-dihydroxyvitamin D3 (1,25(OH2D3 on RANKL signaling pathway and pathway-associated cytokines in patients with rheumatoid arthritis (RA. Methods. Receptor activator of nuclear factor-kappa B ligand (RANKL, osteoprotegerin (OPG, IFN-γ, IL-6, TNF-α, IL-17, and IL-4 were examined in 54 patients with incipient RA using a cytometric bead array (CBA or an enzyme-linked immunosorbent assay (ELISA. Results. After 72 hours of incubation of peripheral blood mononuclear cells (PBMCs with 1,25(OH2D3 in RA patients, the levels of RANKL, TNF-α, IL-17 and IL-6 significantly decreased compared to those of the control. 1,25(OH2D3 had no significantly impact on the levels of OPG, RANKL/OPG, and IL-4. Conclusions. The present study demonstrated that 1,25(OH2D3 reduced the production of RANKL and the secretion of TNF-α, IL-17, and IL-6 in PBMCs of RA patients, which indicated that 1,25(OH2D3 might be able to decrease damage of cartilage and bone in RA patients by regulating the expression of RANKL signaling pathway and pathway-associated cytokines.

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

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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.

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.

Involvement of Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-induced Incomplete Cytokinesis in the Polyploidization of Osteoclasts.

Science.gov (United States)

Takegahara, Noriko; Kim, Hyunsoo; Mizuno, Hiroki; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Tomura, Michio; Kanagawa, Osami; Ishii, Masaru; Choi, Yongwon

2016-02-12

Osteoclasts are specialized polyploid cells that resorb bone. Upon stimulation with receptor activator of nuclear factor-κB ligand (RANKL), myeloid precursors commit to becoming polyploid, largely via cell fusion. Polyploidization of osteoclasts is necessary for their bone-resorbing activity, but the mechanisms by which polyploidization is controlled remain to be determined. Here, we demonstrated that in addition to cell fusion, incomplete cytokinesis also plays a role in osteoclast polyploidization. In in vitro cultured osteoclasts derived from mice expressing the fluorescent ubiquitin-based cell cycle indicator (Fucci), RANKL induced polyploidy by incomplete cytokinesis as well as cell fusion. Polyploid cells generated by incomplete cytokinesis had the potential to subsequently undergo cell fusion. Nuclear polyploidy was also observed in osteoclasts in vivo, suggesting the involvement of incomplete cytokinesis in physiological polyploidization. Furthermore, RANKL-induced incomplete cytokinesis was reduced by inhibition of Akt, resulting in impaired multinucleated osteoclast formation. Taken together, these results reveal that RANKL-induced incomplete cytokinesis contributes to polyploidization of osteoclasts via Akt activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Genetic deletion of muscle RANK or selective inhibition of RANKL is not as effective as full-length OPG-fc in mitigating muscular dystrophy.

Science.gov (United States)

Dufresne, Sébastien S; Boulanger-Piette, Antoine; Bossé, Sabrina; Argaw, Anteneh; Hamoudi, Dounia; Marcadet, Laetitia; Gamu, Daniel; Fajardo, Val A; Yagita, Hideo; Penninger, Josef M; Russell Tupling, A; Frenette, Jérôme

2018-04-24

Although there is a strong association between osteoporosis and skeletal muscle atrophy/dysfunction, the functional relevance of a particular biological pathway that regulates synchronously bone and skeletal muscle physiopathology is still elusive. Receptor-activator of nuclear factor κB (RANK), its ligand RANKL and the soluble decoy receptor osteoprotegerin (OPG) are the key regulators of osteoclast differentiation and bone remodelling. We thus hypothesized that RANK/RANKL/OPG, which is a key pathway for bone regulation, is involved in Duchenne muscular dystrophy (DMD) physiopathology. Our results show that muscle-specific RANK deletion (mdx-RANK mko ) in dystrophin deficient mdx mice improves significantly specific force [54% gain in force] of EDL muscles with no protective effect against eccentric contraction-induced muscle dysfunction. In contrast, full-length OPG-Fc injections restore the force of dystrophic EDL muscles [162% gain in force], protect against eccentric contraction-induced muscle dysfunction ex vivo and significantly improve functional performance on downhill treadmill and post-exercise physical activity. Since OPG serves a soluble receptor for RANKL and as a decoy receptor for TRAIL, mdx mice were injected with anti-RANKL and anti-TRAIL antibodies to decipher the dual function of OPG. Injections of anti-RANKL and/or anti-TRAIL increase significantly the force of dystrophic EDL muscle [45% and 17% gains in force, respectively]. In agreement, truncated OPG-Fc that contains only RANKL domains produces similar gains, in terms of force production, than anti-RANKL treatments. To corroborate that full-length OPG-Fc also acts independently of RANK/RANKL pathway, dystrophin/RANK double-deficient mice were treated with full-length OPG-Fc for 10 days. Dystrophic EDL muscles exhibited a significant gain in force relative to untreated dystrophin/RANK double-deficient mice, indicating that the effect of full-length OPG-Fc is in part independent of the RANKL

Effect of Bisphosphonates on the Levels of Rankl and Opg in Gingival Crevicular Fluid of Patients With Periodontal Disease and Post-menopausal Osteoporosis.

Science.gov (United States)

Verde, María E; Bermejo, Daniela; Gruppi, Adriana; Grenón, Miriam

2015-12-01

The Receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/Osteoprotegerine (OPG) system has been proposed as essential for osteoclast biology and identified as key part in regulating the physiology and pathology of the skeletal system. The study of the RANKL/RANK/OPG system has increased the understanding of the mechanisms involved in the bone remodeling process, especially in postmenopausal osteoporosis and periodontal disease. Bisphosphonates have become the mainstay of the treatment and prevention of post-menopausal osteoporosis. They inhibit the formation and dissolution of calcium phosphate crystals in bone and also osteoclasts, thus reducing bone turnover.Current investigations relate osteoporosis with the appearance and progression of periodontal disease. Although the etiology of both is different, the bone loss present in both shares several characteristics. Thus, therapy used for osteoporosis can be considered of value in the treatment of periodontal disease. The aim of this study was to evaluate the levels of RANKL, OPG and their relationship in gingival crevicular fluid (GCF) in patients with periodontal disease and postmenopausal osteoporosis/ osteopenia in relation to consumption of bisphosphonates. We studied 66 periodontal active sites obtained from 17 post- menopausal women patients aged between 45-70 years old with osteoporosis/osteopenia and periodontal disease. GCF samples were collected using sterile filter paper strips. To determine the concentration of RANKL and OPG, a commercial ELISA assay was used. The values of RANKL, OPG and their ratio (RANKL/ OPG) were compared with Mann-Whitney U Test. The values of RANKL, OPG and their ratio obtained in patients with osteoporosis/osteopenia and periodontal disease with or without bisphosphonates treatment showed no differences. Bisphosphonates do not alter the concentration of RANKL and OPG and their ratio in the GCF of patients with osteoporosis/ osteopenia and periodontal disease

Osteoprotegerin inhibits bone resorption and prevents tumor development in a xenogenic model of Ewing's sarcoma by inhibiting RANKL

Science.gov (United States)

Picarda, Gaëlle; Matous, Etienne; Amiaud, Jérôme; Charrier, Céline; Lamoureux, François; Heymann, Marie-Françoise; Tirode, Franck; Pitard, Bruno; Trichet, Valérie; Heymann, Dominique; Redini, Françoise

2013-01-01

Ewing's sarcoma (ES) associated with high osyeolytic lesions typically arises in the bones of children and adolescents. The development of multi-disciplinary therapy has increased current long-term survival rates to greater than 50% but only 20% for high risk group patients (relapse, metastases, etc.). Among new therapeutic approaches, osteoprotegerin (OPG), an anti-bone resorption molecule may represent a promising candidate to inhibit RANKL-mediated osteolytic component of ES and consequently to limit the tumor development. Xenogenic orthotopic models of Ewing's sarcoma were induced by intra-osseous injection of human TC-71 ES cells. OPG was administered in vivo by non-viral gene transfer using an amphiphilic non ionic block copolymer. ES bearing mice were assigned to controls (no treatment, synthetic vector alone or F68/empty pcDNA3.1 plasmid) and hOPG treated groups. A substantial but not significant inhibition of tumor development was observed in the hOPG group as compared to control groups. Marked bone lesions were revealed by micro-computed tomography analyses in control groups whereas a normal bone micro-architecture was preserved in the hOPG treated group. RANKL over-expressed in ES animal model was expressed by tumor cells rather than by host cells. However, TRAIL present in the tumor microenvironment may interfere with OPG effect on tumor development and bone remodeling via RANKL inhibition. In conclusion, the use of a xenogenic model of Ewing's sarcoma allowed discriminating between the tumor and host cells responsible for the elevation of RANKL production observed in this tumor and demonstrated the relevance of blocking RANKL by OPG as a promising therapy in ES. PMID:26909278

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.

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

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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.

Porphyromonas endodontalis lipopolysaccharides induce RANKL by mouse osteoblast in a way different from that of Escherichia coli lipopolysaccharide.

Science.gov (United States)

Tang, Yin; Sun, Feifei; Li, Xiaoting; Zhou, Yuan; Yin, Shihai; Zhou, Xuedong

2011-12-01

Porphyromonas endodontalis lipopolysaccharide (LPS) has been shown to have a high positive rate in infected root canals and symptomatic apical periodontitis. It may play an integral role as a potent stimulator of inflammatory cytokines involved in apical lesions. The receptor activator of nuclear factor-κB ligand (RANKL) has been proven to be the key regulator of bone remodeling. This study investigated P. endodontalis LPS-induced RANKL production and LPS signaling in mouse osteoblasts. LPS-induced RANKL production in mouse osteoblast MC3T3-E1 cells was measured by Western blot and real-time polymerase chain reaction, and the Toll-like receptors (TLRs) were determined by the blocking test using anti-TLRs antibodies. In addition, specific inhibitors were used to analyze the intracellular signaling pathways. Escherichia coli LPS was used as the control. Both of the anti-TLR2 and anti-TLR4 antibodies significantly (P endodontalis LPS; only anti-TLR2 antibody had a significant (P endodontalis LPS-infected osteoblasts (P endodontalis LPS has the ability to promote the expression of RANKL in mouse osteoblasts, and this induction was mainly through the TLR2/4-JNK signaling pathway, a situation quite different from that of typical bacterial endotoxin (E. coli LPS). Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Assessment of the relationship between melatonin, hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes, and osteoprotegerin and its ligand sRANKL in girls with anorexia nervosa

Directory of Open Access Journals (Sweden)

Zofia Ostrowska

2013-05-01

Full Text Available Background: It has been suggested that disturbances in melatonin (MEL secretion might play a role in osteoporosis development in females with anorexia nervosa (AN. It might be hypothesized that changes in the levels of hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes might mediate the potential relationship between MEL and bone tissue.Aim: We investigated whether a relationship existed between MEL and LH, FSH-E2, TSH-FT3, FT4 and ACTH-cortisol axes in girls with AN. We also aimed to establish whether such a relationship might adversely affect the balance of the OPG/sRANKL system.Material/Methods: Eighty-six girls with AN and 21 healthy subjects aged 12.6 to 18.2 years participated in the study. The serum levels of hormones as well as OPG and sRANKL were determined by radioimmunoassay (RIA, immunoradiometric assay (IRMA or enzyme-linked immunosorbent assay (ELISA methods.Discussion: Our study participants with AN showed a significant reduction in body mass and body mass index (BMI, a decrease in LH, E2 and FT3 concentrations, increased MEL concentration at 02.00 hours and increased amplitude between its nocturnal and morning levels (Δ MEL2.00/9.00 as well as an increase in cortisol concentration. These changes were associated with a significant increase of OPG and sRANKL levels and a decrease in the OPG/sRANKL ratio. BMI values correlated positively with LH, FSH, E2, FT3 and the OPG/sRANKL ratio while the correlation between BMI and cortisol was negative. Δ MEL2.00/9.00 correlated positively with cortisol and negatively with LH, FSH, E2, FT3 concentrations and the OPG/sRANKL ratio. A positive correlation was observed between LH, E2 and the OPG/sRANKL ratio as well as between cortisol and sRANKL while the correlation between LH and OPG as well as between cortisol and the OPG/sRANKL ratio was negative. E2 and LH were shown to be significant and independent predictors of Δ MEL2.00/9.00. LH turned out to be a

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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.

Systems principles of planning the net cost of oil and gas extraction

Energy Technology Data Exchange (ETDEWEB)

Ryazanova, N I

1979-01-01

The automated system of calculation of ASPC ''oil extraction'' is developed in order to improve the existing system of planning of the oil extracting sector. The most complete expression of the systems construction of the plan is found in the section ''net cost and profit.'' Unity of the production process advances definite requirements for construction of the plan for net cost of oil and gas extraction as the model of this unified process. According to these requirements, the plan for net cost must be developed on the basis of interrelationship of the indicators of the plan for net cost within the section and with indicators of other sections of the plan, methodological unity and continuity of the methods of planning net cost by elements of outlays, articles of calculation and technical-economic factors, methodological continuity of regimes and stages of planning, as well as based on methodological continuity of the control levels. The listed requirements are principles for systems planning of the net cost of oil and gas extraction. These principles guarantee improvement in planning of net cost of oil and gas extraction according to the requirements made for the national economic planning.

EFFECT OF INFLIXIMAB ON PARAMETERS OF REMODELING OF ARTERIAL BLOODSTREAM, RANKL AND OSTEOPROTEGERIN LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS

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Larisa Aleksandrovna Knyazeva

2013-01-01

Full Text Available Objective. To study the effect of infliximab (INF on serum levels of RANKL and osteoprotegerin (OPG, as well as on structural and functional properties of the vascular wall in patients with rheumatoid arthritis (RA.Material and Methods. A total of 79 RA patients who corresponded to the classification criteria ACR (1987 or ACR/EULAR (2010 and were seronegative for IgM rheumatoid factor (RF were examined. The mean age of patients was 43.6±8.5 years. The serum levels of OPG and RANKL were determined by ELISA (Biomedica, Austria; the common carotid arteries (CCAs were visualized using an Acuson X/10 ultrasonic complex equipped with a 7 MHz linear sensor in the β-mode prior to therapy and after 12-month therapy with INF.Results and Discussion. An increased OPG level was observed mostly in patients with RA duration up to 1 year; an increase in RANKL level was pronounced stronger in patients with PA duration over 2 years. The disturbance of structural and functional properties of the arterial bloodstream was revealed, manifesting itself as an increase in the intimamedia complex thickness, diameter and rigidity index of CCA that were stronger pronounced in patients with late onset RA. A correlation analysis showed the presence of reliable relationship between the RANKL and OPG levels and CCA remodeling parameters. INF therapy showed high clinical effectiveness and correction effect on the RANKL/OPG system. In addition, it was accompanied by a reduction of signs of CCA remodeling, which was stronger pronounced in patients with early RA.Conclusion. The results prove the reasonability of using INF at early stages of RA in order to optimize the therapy and achieve more efficient control of cardiovascular complications.

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

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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

Arctigenin suppresses receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow-derived macrophages.

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Kim, A-Ram; Kim, Hyuk Soon; Lee, Jeong Min; Choi, Jung Ho; Kim, Se Na; Kim, Do Kyun; Kim, Ji Hyung; Mun, Se Hwan; Kim, Jie Wan; Jeon, Hyun Soo; Kim, Young Mi; Choi, Wahn Soo

2012-05-05

Osteoclasts, multinucleated bone-resorbing cells, are closely associated with bone diseases such as rheumatoid arthritis and osteoporosis. Osteoclasts are derived from hematopoietic precursor cells, and their differentiation is mediated by two cytokines, including macrophage colony stimulating factor and receptor activator of nuclear factor κB ligand (RANKL). Previous studies have shown that arctigenin exhibits an anti-inflammatory effect. However, the effect of arctigenin on osteoclast differentiation is yet to be elucidated. In this study, we found that arctigenin inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages in a dose-dependent manner and suppressed RANKL-mediated bone resorption. Additionally, the expression of typical marker proteins, such as NFATc1, c-Fos, TRAF6, c-Src, and cathepsin K, were significantly inhibited. Arctigenin inhibited the phosphorylation of Erk1/2, but not p38 and JNK, in a dose-dependent manner. Arctigenin also dramatically suppressed immunoreceptor tyrosine-based activation motif-mediated costimulatory signaling molecules, including Syk and PLCγ2, and Gab2. Notably, arctigenin inhibited the activation of Syk through RANKL stimulation. Furthermore, arctigenin prevented osteoclast differentiation in the calvarial bone of mice following stimulation with lipopolysaccharide. Our results show that arctigenin inhibits osteoclast differentiation in vitro and in vivo. Therefore, arctigenin may be useful for treating rheumatoid arthritis and osteoporosis. Copyright © 2012 Elsevier B.V. All rights reserved.

Bone metabolism and RANKL/RANK/OPG trail in periodontal disease

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Czupkallo Lukasz

2016-12-01

Full Text Available Periodontal disease is an inflammatory disease of multifactorial etiology. In order for it to appear there must come to an imbalance between the effects of pathogens and host defense mechanisms. As a result of its course the destruction of structures supporting the teeth appears (periodontium, cement, bone, and consequently leads to teeth loosening and loss. In recent years, the participation of RANKL/RANK/OPG in bone remodeling process was highligted.

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.

Water extract of Acer tegmentosum reduces bone destruction by inhibiting osteoclast differentiation and function.

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Ha, Hyunil; Shim, Ki-Shuk; Kim, Taesoo; An, Hyosun; Lee, Chung-Jo; Lee, Kwang Jin; Ma, Jin Yeul

2014-04-01

The stem of Acer tegmentosum has been widely used in Korea for the treatment of hepatic disorders. In this study, we investigated the bone protective effect of water extract of the stem of Acer tegmentosum (WEAT). We found that WEAT inhibits osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclast differentiation. In osteoclast precursor cells, WEAT inhibited RANKL-induced activation of JNK, NF-κB, and cAMP response element-binding protein, leading to suppression of the induction of c-Fos and nuclear factor of activated T cells cytoplasmic 1, key transcription factors for osteoclast differentiation. In addition, WEAT inhibited bone resorbing activity of mature osteoclasts. Furthermore, the oral administration of WEAT reduced RANKL-induced bone resorption and trabecular bone loss in mice. Taken together, our study demonstrates that WEAT possesses a protective effect on bone destruction by inhibiting osteoclast differentiation and function.

Ethanol Extract of Atractylodes macrocephala Protects Bone Loss by Inhibiting Osteoclast Differentiation

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Youn-Hwan Hwang

2013-06-01

Full Text Available The rhizome of Atractylodes macrocephala has been used mainly in Traditional Chinese Medicine for invigorating the functions of the stomach and spleen. In the present study, we investigated the inhibitory effect of the 70% ethanol extract of the rhizome of Atractylodes macrocephala (AMEE on osteoclast differentiation. We found that AMEE inhibits osteoclast differentiation from its precursors induced by receptor activator of nuclear factor-κB ligand (RANKL, an essential cytokine required for osteoclast differentiation. AMEE attenuated RANKL-induced activation of NF-κB signaling pathway, subsequently inhibiting the induction of osteoclastogenic transcription factors, c-Fos and nuclear factor of activated T cells cytoplasmic 1. Consistent with the in vitro results, administration of AMEE protected RANKL-induced bone loss in mice. We also identified atractylenolide I and II as active constituents contributing to the anti-osteoclastogenic effect of AMEE. Taken together, our results demonstrate that AMEE has a protective effect on bone loss via inhibiting osteoclast differentiation and suggest that AMEE may be useful in preventing and treating various bone diseases associated with excessive bone resorption.

Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model.

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Zhao, Rong; Chen, Ni-Nan; Zhou, Xiao-Wei; Miao, Ping; Hu, Chao-Ying; Qian, Liu; Yu, Qi-Wen; Zhang, Ji-Ying; Nie, Hong; Chen, Xue-hua; Li, Pu; Xu, Rong; Xiao, Lian-Bo; Zhang, Xin; Liu, Jian-Ren; Zhang, Dong-Qing

2014-12-10

Although a variety of drugs have been used to treat the symptoms of rheumatoid arthritis (RA), none of them are able to cure the disease. Interferon β (IFN-β) has pleiotropic effects on RA, but whether it can be used to treat RA remains globally controversial. Thus, in this study we tested the effects of IFN-β on RA patients and on collagen antibody-induced arthritis (CAIA) model mice. The cytokine and auto-antibody expression profiles in the serum and synovial fluid (SF) from RA patients were assessed using enzyme-linked immunosorbent assay (ELISA) and compared with the results from osteoarthritis (OA) patients. Exogenous IFN-β was administered to RA patients and CAIA model mice, and the therapeutic effects were evaluated. Endogenous IFN-β expression in the joint bones of CAIA model mice was evaluated by quantitative real-time PCR (qRT-PCR). The effects of exogenous IFN-β on CAIA model mice were assessed using a clinical scoring system, hematoxylin eosin and safranin-O with fast green counterstain histology, molybdenum target X-ray, and tartrate-resistant acid phosphatase (TRAP) staining. The RANKL-RANK signaling pathway was analyzed using qRT-PCR. The RAW 264.7 cell line was differentiated into osteoclasts with RANKL stimulation and then treated with exogenous IFN-β. The expression of inflammatory cytokines (IFN-γ, IL-17, MMP-3, and RANKL) and auto-antibodies (CII antibodies, RF-IgM, and anti-CCP/GPI) were significantly higher in RA compared with OA patients. After IFN-β intervention, some clinical symptoms in RA patients were partially alleviated, and the expression of IFN-γ, IL-17, MMP-3, and OPG) returned to normal levels. In the CAIA model, the expression of endogenous IFN-β in the joint bones was decreased. After IFN-β administration, the arthritis scores were decreased; synovial inflammation, cartilage, and bone destruction were clearly attenuated; and the expression of c-Fos and NFATc1 were reduced, while RANKL and TRAF6 expression was

RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT).

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Mutoh, Mami; Kimura, Shunsuke; Takahashi-Iwanaga, Hiromi; Hisamoto, Meri; Iwanaga, Toshihiko; Iida, Junichiro

2016-04-01

Murine nasopharynx-associated lymphoid tissue (NALT), located at the base of the nasal cavity, serves as a major site for the induction of mucosal immune responses against airway antigens. The follicle-associated epithelium (FAE) covering the luminal surface of NALT is characterized by the presence of microfold cells (M cells), which take up and transport luminal antigens to lymphocytes. Glycoprotein 2 (GP2) has recently been identified as a reliable marker for M cells in Peyer's patches of the intestine. However, the expression of GP2 and other functional molecules in the M cells of NALT has not yet been examined. We have immunohistochemically detected GP2-expressing cells in the FAE of NALT and the simultaneous expression of other intestinal M-cell markers, namely Tnfaip2, CCL9, and Spi-B. These cells have been further identified as M cells because of their higher uptake capacity of luminal microbeads. Electron microscopic observations have shown that GP2-expressing cells on the FAE display morphological features typical of M cells: they possess short microvilli and microfolds on the luminal surface and are closely associated with intraepithelial lymphocytes. We have also found that the receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed by stromal cells underneath the FAE, which provides its receptor RANK. The administration of RANKL markedly increases the number of GP2(+)Tnfaip2(+) cells on the NALT FAE and that of intestinal M cells. These results suggest that GP2(+)Tnfaip2(+) cells in NALT are equivalent to intestinal M cells, and that RANKL-RANK signaling induces their differentiation.

The effect of leptin replacement on parathyroid hormone, RANKL-osteoprotegerin axis, and Wnt inhibitors in young women with hypothalamic amenorrhea.

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Foo, Joo-Pin; Polyzos, Stergios A; Anastasilakis, Athanasios D; Chou, Sharon; Mantzoros, Christos S

2014-11-01

Recombinant leptin (metreleptin) treatment restores bone mineral density in women with hypothalamic amenorrhea (HA), a condition characterized by hypoleptinemia, which has adverse impact on bone health. The objective of the study was to investigate how metreleptin exerts its positive effect on bone metabolism in humans. This was a randomized, double-blinded, placebo-controlled study. The study was conducted at Beth Israel Deaconess Medical Center (Boston, Massachusetts). Women (n = 18) with HA and hypoleptinemia for at least 6 months were randomized to receive either metreleptin or placebo for 36 weeks. Serum samples were obtained at baseline and 12, 24, and 36 weeks of treatment. Circulating levels of leptin, intact PTH (iPTH), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), sclerostin, dickkopf-1, and fibroblast growth factor-23. Metreleptin administration significantly increased leptin levels throughout the treatment period (P = .001). iPTH decreased over the 36 weeks of treatment (P = .01). There was a trend toward a decrease in serum RANKL and increase in serum OPG in the metreleptin-treated group. The RANKL to OPG ratio was significantly decreased within the metreleptin (P = .04) but not the placebo group. Metreleptin had no effect on serum sclerostin, dickkopf-1, and fibroblast growth factor-23. Metreleptin treatment over 36 weeks decreases iPTH and RANKL to OPG ratio levels in hypoleptinemic women with HA.

The Effect of RANKL/OPG Balance on Reducing Implant Complications

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Elizabeth R. Kapasa

2017-09-01

Full Text Available Despite the phenomenal success of implants particularly in the realms of dentistry and orthopaedics, there are still challenges to overcome. The failure of implants resulting from infection, prosthetic loosening, and non-union continue to be the most notorious examples. The cascade of fracture healing and bone repair, especially with the presence of an implant, is complex because it involves a multifaceted immune response alongside the intricate process of bone formation and remodelling. Bone loss is a serious clinical problem that is frequently accompanied by chronic inflammation, illustrating that there is a convoluted relationship between inflammation and bone erosion. The effects of pro-inflammatory factors play a significant role in initiating and maintaining osteoclastogenesis that results in bone resorption by osteoclasts. This is because there is a disruption of the relative ratio between Receptor Activator of Nuclear Factor κB-Ligand (RANKL and osteoprotegerin (OPG, which is central to modulating bone repair and remodelling. This review aims to provide a background to the bone remodelling process, the bone repair cascade post-implantation, and the associated complications. Furthermore, current clinical solutions that can influence bone formation via either internal or extrinsic mechanisms will be described. These efficacious treatments for osteolysis via targeting the RANKL/OPG ratio may be crucial to reducing the incidence of related implant failures in the future.

Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice

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Naoto Tokuyama

2015-06-01

Full Text Available We examined the individual and combined effects of teriparatide and anti-RANKL (receptor activator of nuclear factor κB ligand monoclonal antibody in ovariectomized mice. Three-month-old female C57BL/6 mice were ovariectomized (OVX or sham operated. Four weeks after OVX, they were assigned to 3 different groups to receive anti-RANKL monoclonal antibody (Ab alone (5 mg/kg single injection at 4 weeks after OVX, Ab group, teriparatide alone (80 μg/kg daily injection for 4 weeks from 4 weeks after OVX, PTH group, or mAb plus teriparatide (Ab + PTH group. Mice were sacrificed 8 weeks after OVX. Bone mineral density (BMD was measured at the femur and lumbar spine. Hind limbs were subjected to histological and histomorphometric analysis. Serum osteocalcin and CTX-I levels were measured to investigate the bone turnover. Compared with Ab group, Ab + PTH group showed a significant increase in BMD at distal femur and femoral shaft. Cortical bone volume was significantly increased in PTH and Ab + PTH groups compared with Ab group. Bone turnover in Ab + PTH group was suppressed to the same degree as in Ab group. The number of TRAP-positive multinucleated cells was markedly reduced in Ab and Ab + PTH groups. These results suggest that combined treatment of teriparatide with anti-RANKL antibody has additive effects on BMD in OVX mice compared with individual treatment.

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

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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.

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.

STAT6 silencing induces hepatocellular carcinoma-derived cell apoptosis and growth inhibition by decreasing the RANKL expression.

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Qing, Tian; Yamin, Zhang; Guijie, Wang; Yan, Jin; Zhongyang, Shen

2017-08-01

Signal transducer and activator of transcription-6 (STAT6) is highly expressed in various human cancers and considered a regulator of multiple biological processes in cancers, including cell apoptosis. Evidence has indicated that STAT6 predicts a worse prognosis in hepatocellular carcinoma (HCC) patients. The objective of this study was to investigate the effects and mechanism of STAT6 in human HCC cells. We found that STAT6 silencing significantly inhibited HepG2 and Hep3B cell survival and proliferation. We observed that depletion of STAT6 increased HepG2 and Hep3B cell apoptosis by using a histone DNA ELISA detection kit. STAT6 silencing induced expression of apoptosis-associated genes Bax and caspase-3/7 and inhibited anti-apoptosis gene Bcl-2 levels. We also observed that STAT6 silencing downregulated the expression of receptor activator of NF-κB ligand (RANKL). Our results demonstrated that treatment with pcDNA3.1-RANKL abolished STAT6 depletion-induced HepG2 and Hep3B cell apoptosis and growth inhibition. Based on these findings, we believe that RANKL plays a major role in STAT6-induced HCC cell apoptosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Feeding blueberry diets to young rats dose-dependently inhibits bone resorption through suppression of RANKL in stromal cells.

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Jian Zhang

Full Text Available Previous studies have demonstrated that weanling rats fed AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB powder for two weeks beginning on postnatal day 21 (PND21 significantly increased bone formation at PND35. However, the minimal level of dietary BB needed to produce these effects is, as yet, unknown. The current study examined the effects of three different levels of BB diet supplementation (1, 3, and 5% for 35 days beginning on PND25 on bone quality, and osteoclastic bone resorption in female rats. Peripheral quantitative CT scan (pQCT of tibia, demonstrated that bone mineral density (BMD and content (BMC were dose-dependently increased in BB-fed rats compared to controls (P<0.05. Significantly increased bone mass after feeding 5% BB extracts was also observed in a TEN (total enteral nutrition rat model in which daily caloric and food intake was precisely controlled. Expression of RANKL (receptor activator of nuclear factor-κB ligand a protein essential for osteoclast formation was dose-dependently decreased in the femur of BB animals. In addition, expression of PPARγ (peroxisome proliferator-activated receptor γ which regulates bone marrow adipogenesis was suppressed in BB diet rats compared to non-BB diet controls. Finally, a set of in vitro cell cultures revealed that the inhibitory effect of BB diet rat serum on RANKL expression was more profound in mesenchymal stromal cells compared to its effect on mature osteoblasts, pre-adipocytes and osteocytes. These results suggest that inhibition of bone resorption may contribute to increased bone mass during early development after BB consumption.

Effects of interleukin-7/interleukin-7 receptor on RANKL-mediated osteoclast differentiation and ovariectomy-induced bone loss by regulating c-Fos/c-Jun pathway.

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Zhao, Ji-Jun; Wu, Zhao-Feng; Yu, Ying-Hao; Wang, Ling; Cheng, Li

2018-09-01

To explore the effects of IL-7/IL-7R on the RANKL-mediated osteoclast differentiation in vitro and OVX-induced bone loss in vivo. BMMs and RAW264.7 were transfected with IL-7, IL-7R siRNA, c-Fos siRNA, and c-jun siRNA and later stimulated by RANKL. TRAP and toluidine blue staining were used to observe osteoclast formation and bone resorption, respectively. HE and TRAP staining were used to detect trabecular bone microstructure and osteoclasts of mice, respectively. qRT-PCR and Western blot analysis were used to examine expression. IL-7 unregulated the expression of CTSK, NFATc1, MMP9, and the phosphorylation of p38 and Akt by activating the c-Fos/c-Jun pathway, which increased osteoclast numbers and bone resorption in RANKL-stimulated macrophages. While IL-7R siRNA and c-Fos siRNA decreased the expression, as well as and the phosphorylation of p38 and Akt.IL-7 decreased the BMD and OPG expression in OVX-induced mice and increased the TRAP positive cells, the mRNA expression of c-fos, c-jun, and RANKL, which was contradictory to IL-7R siRNA, and c-Fos siRNA. Furthermore, IL-7R siRNA and c-Fos siRNA caused thicker trabeculae, increased trabecular number, and decreased osteolysis in OVX mice. IL-7/IL-7R can promote RANKL-mediated osteoclast formation and bone resorption by activating the c-Fos/c-Jun pathway, as well as inducing bone loss in OVX mice. © 2018 Wiley Periodicals, Inc.

Polymorphisms in the RANK/RANKL Genes and Their Effect on Bone Specific Prognosis in Breast Cancer Patients

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Alexander Hein

2014-01-01

Full Text Available The receptor activator of NF-κB (RANK pathway is involved in bone health as well as breast cancer (BC pathogenesis and progression. Whereas the therapeutic implication of this pathway is established for the treatment of osteoporosis and bone metastases, the application in adjuvant BC is currently investigated. As genetic variants in this pathway have been described to influence bone health, aim of this study was the prognostic relevance of genetic variants in RANK and RANKL. Single nucleotide polymorphisms in RANK(L (rs1054016/rs1805034/rs35211496 were genotyped and analyzed with regard to bone metastasis-free survival (BMFS, disease-free survival, and overall survival for a retrospective cohort of 1251 patients. Cox proportional hazard models were built to examine the prognostic influence in addition to commonly established prognostic factors. The SNP rs1054016 seems to influence BMFS. Patients with two minor alleles had a more favorable prognosis than patients with at least one common allele (HR 0.37 (95% CI: 0.17, 0.84, whereas other outcome parameters remained unaffected. rs1805034 and rs35211496 had no prognostic relevance. The effect of rs1054016(RANKL adds to the evidence that the RANK pathway plays a role in BC pathogenesis and progression with respect to BMFS, emphasizing the connection between BC and bone health.

Inhibitory effects of methyl-3,5-di-O-caffeoyl-epi-quinate on RANKL-induced osteoclast differentiation.

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Kim, Tae Hoon; Ihn, Hye Jung; Kim, Kiryeong; Cho, Hye-Sung; Shin, Hong-In; Bae, Yong Chul; Park, Eui Kyun

2018-04-09

In this study, we have shown that methyl-3,5-di-O-caffeoyl-epi-quinate, a naturally occurring compound isolated from Ainsliaea acerifolia, inhibits receptor activator of nuclear factor-κB ligand (RANKL)-induced formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and the expression of osteoclast marker genes. Methyl-3,5-di-O-caffeoyl-epi-quinate also inhibited RANKL-induced activation of p38, Akt and extracellular signal-regulated kinase (ERK) as well as the expression of nuclear factor of activated T-cell (NFATc1), the key regulator of osteoclast differentiation. Negative regulators for osteoclast differentiation was upregulated by methyl-3,5-di-O-caffeoyl-epi-quinate. Collectively, our results suggested that methyl-3,5-di-O-caffeoyl-epi-quinate suppresses osteoclast differentiation via downregulation of RANK signaling pathways and NFATc1. Copyright © 2018 Elsevier Ltd. All rights reserved.

Scoparone attenuates RANKL-induced osteoclastic differentiation through controlling reactive oxygen species production and scavenging

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Lee, Sang-Hyun; Jang, Hae-Dong, E-mail: haedong@hnu.kr

2015-02-15

Scoparone, one of the bioactive components of Artemisia capillaris Thunb, has various biological properties including immunosuppressive, hepatoprotective, anti-allergic, anti-inflammatory, and antioxidant effects. This study aims at evaluating the anti-osteoporotic effect of scoparone and its underlying mechanism in vitro. Scoparone demonstrated potent cellular antioxidant capacity. It was also found that scoparone inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and suppressed cathepsin K and tartrate-resistant acid phosphatase (TRAP) expression via c-jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)/p38-mediated c-Fos–nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway. During osteoclast differentiation, the production of general reactive oxygen species (ROS) and superoxide anions was dose-dependently attenuated by scoparone. In addition, scoparone diminished NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 1 (Nox1) expression and activation via the tumor necrosis factor receptor-associated factor 6 (TRAF6)–cSrc–phosphatidylinositol 3-kinase (PI3k) signaling pathway and prevented the disruption of mitochondrial electron transport chain system. Furthermore, scoparone augmented the expression of superoxide dismutase 1 (SOD1) and catalase (CAT). The overall results indicate that the inhibitory effect of scoparone on RANKL-induced osteoclast differentiation is attributed to the suppressive effect on ROS and superoxide anion production by inhibiting Nox1 expression and activation and protecting the mitochondrial electron transport chain system and the scavenging effect of ROS resulting from elevated SOD1 and CAT expression. - Highlights: • Scoparone dose-dependently inhibited RANKL-induced osteoclast differentiation. • Scoparone diminished general ROS and superoxide anions in a dose-dependent manner. • Scoparone inhibited Nox1 expression and

Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages.

Science.gov (United States)

Choe, Jung-Yoon; Kim, Seong-Kyu

2017-03-01

Melittin is a major toxic component of bee venom (Apis mellifera). It is not known whether melittin is involved in bone metabolism and osteoclastogenesis. The aim of this study was to determine the role of melittin in the regulation of osteoclastogenesis. In vitro osteoclastogenesis assays were performed using mouse RAW 264.7 cells and bone marrow-derived macrophages (BMMs) treated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Morphologic and functional analyses for osteoclast-like multinucleated cells (MNCs) were performed by tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and pit formation methods. The gene expression of TRAP, cathepsin K, matrix metalloproteinase-9 (MMP-9) and carbonic anhydrase II was measured by reverse transcription-quantitative PCR. The protein expression levels of mitogen-activated protein kinases (MAPKs), the p65 subunit of nuclear factor-κB (NF-κB), c-Fos, c-Jun, nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), TNF receptor-associated factor-6 (TRAF6), and interleukin-1β (IL-1β) were assessed by western blot analysis. Melittin inhibited the mRNA expression of TRAP, cathepsin K, MMP-9 and carbonic anhydrase II in RANKL-stimulated RAW 264.7 cells. The increased protein expression of TRAF6, p-extracellular signal-regulated kinase (ERK), p-JNK, p-p65, p-c-Fos and NFATc1 induced by RANKL was significantly suppressed in the RAW 264.7 cells treated with melittin. A synergistic effect of IL-1β on the formation of RANKL-induced osteoclast-like MNCs was found in two experimental cells. The increased expression of IL-1β following the stimulation of RAW 264.7 cells with RANKL activated TRAF6, p-ERK, p-JNK, p-p65, p-c-Fos and NFATc1. These effects were attenuated by the downregulation of IL-1β using siRNA against IL-1β, and also by treatment with melittin. On the whole, the findings of this study demonstrate that melittin

Combined Inhibition of the BMP pathway and the RANK-RANKL axis in a Mixed Lytic/blastic Prostate Cancer Lesion

Science.gov (United States)

Virk, Mandeep S.; Alaee, Farhang; Petrigliano, Frank A.; Sugiyama, Osamu; Chatziioannou, Arion F.; Stout, David; Dougall, William C.; Lieberman, Jay R.

2010-01-01

The purpose of this study was to investigate the influence of combined inhibition of RANKL (receptor activator of nuclear factor kappa-B ligand) and bone morphogenetic protein (BMP) activity in a mixed lytic/blastic prostate cancer lesion in bone. Human prostate cancer cells (C4 2b) were injected into immunocompromised mice using an intratibial injection model to create mixed lytic/blastic lesions. RANK-Fc, a recombinant RANKL antagonist, was injected subcutaneously three times a week (10mg/kg) to inhibit RANKL and subsequent formation, function and survival of osteoclasts. Inhibition of BMP activity was achieved by transducing prostate cancer cells ex vivo with a retroviral vector expressing noggin (retronoggin; RN). There were three treatment groups (RANK-Fc treatment, RN treatment and combined RN and RANK-Fc treatment) and two control groups (untreated control and empty vector control for the RN treatment group). The progression of bone lesion and tumor growth was evaluated using plain radiographs, hind limb tumor size, 18F-Fluorodeoxyglucose and 18F-fluoride micro PET-CT, histology and histomorphometry. Treatment with RANK-Fc alone inhibited osteolysis and transformed a mixed lytic/blastic lesion into an osteoblastic phenotype. Treatment with RN alone inhibited the osteoblastic component in a mixed lytic/blastic lesion and resulted in formation of smaller osteolytic bone lesion with smaller soft tissue size. The animals treated with both RN and RANK-Fc demonstrated delayed development of bone lesions, inhibition of osteolysis, small soft tissue tumors and preservation of bone architecture with less tumor induced new bone formation. This study suggests that combined inhibition of the RANKL and the BMP pathway may be an effective biologic therapy to inhibit the progression of established mixed lytic/blastic prostate cancer lesions in bone. PMID:21073986

Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease

OpenAIRE

Mikihito Kajiya; Gabriela Giro; Martin A. Taubman; Xiaozhe Han; Marcia P.A. Mayer; Toshihisa Kawai

2010-01-01

Accumulated lines of evidence suggest that hyperimmune responses to periodontal bacteria result in the destruction of periodontal connective tissue and alveolar bone. The etiological roles of periodontal bacteria in the onset and progression of periodontal disease (PD) are well documented. However, the mechanism underlying the engagement of periodontal bacteria in RANKL-mediated alveolar bone resorption remains unclear. Therefore, this review article addresses three critical subjects. First, ...

ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency.

Science.gov (United States)

Sauer, Aisha V; Mrak, Emanuela; Hernandez, Raisa Jofra; Zacchi, Elena; Cavani, Francesco; Casiraghi, Miriam; Grunebaum, Eyal; Roifman, Chaim M; Cervi, Maria C; Ambrosi, Alessandro; Carlucci, Filippo; Roncarolo, Maria Grazia; Villa, Anna; Rubinacci, Alessandro; Aiuti, Alessandro

2009-10-08

Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanical competence. These alterations are the combined result of an imbalanced receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin axis, causing decreased osteoclastogenesis and an intrinsic defect of osteoblast function with subsequent low bone formation. In vitro, osteoblasts lacking ADA displayed an altered transcriptional profile and growth reduction. Furthermore, the bone marrow microenvironment of ADA-deficient mice showed a reduced capacity to support in vitro and in vivo hematopoiesis. Treatment of ADA-deficient neonatal mice with enzyme replacement therapy, bone marrow transplantation, or gene therapy resulted in full recovery of the altered bone parameters. Remarkably, untreated ADA-severe combined immunodeficiency patients showed a similar imbalance in RANKL/osteoprotegerin levels alongside severe growth retardation. Gene therapy with ADA-transduced hematopoietic stem cells increased serum RANKL levels and children's growth. Our results indicate that the ADA metabolism represents a crucial modulatory factor of bone cell activities and remodeling.

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.

Etude de l'influence du TNFSF11 (RANKL) sur le développment et homéostasie des organes lymphoïdes secondaires

OpenAIRE

Cordeiro , Olga

2015-01-01

RANKL and RANK are members of the TNF-superfamily and TNF-receptor superfamily, respectively. They are known to play an important role in the regulation of bone mass and in the development and the function of the immune system. However questions still remain. We have used genetically modified mice to address some of these questions, in particular by using a mouse whose lymph node marginal reticular stromal cells lack RANKL. The results obtained during this PhD provide important new insights i...

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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.

Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Ken-ichiro, E-mail: ken1nai@med.shimane-u.ac.jp; Yamaguchi, Toru, E-mail: yamaguch@med.shimane-u.ac.jp; Kanazawa, Ippei, E-mail: ippei.k@med.shimane-u.ac.jp; Sugimoto, Toshitsugu, E-mail: sugimoto@med.shimane-u.ac.jp

2015-05-29

In diabetes mellitus (DM), high glucose (HG) and advanced glycation end products (AGEs) are involved in bone quality deterioration. Osteocytes produce sclerostin and receptor activator of nuclear factor-kB ligand (RANKL) and regulate osteoblast and osteoclast function. However, whether HG or AGEs directly affect osteocytes and regulate sclerostin and RANKL production is unknown. Here, we examined the effects of HG, AGE2, and AGE3 on the expression of sclerostin and RANKL and on apoptosis in osteocyte-like MLO-Y4-A2 cells. Treatment of the cells with 22 mM glucose, 100 μg/mL either AGE2 or AGE3 significantly increased the expression of sclerostin protein and mRNA; however, both AGEs, but not glucose, significantly decreased the expression of RANKL protein and mRNA. Moreover, treatment of the cells with HG, AGE2, or AGE3 for 72 h induced significant apoptosis. These detrimental effects of HG, AGE2, and AGE3 on sclerostin and RANKL expressions and on apoptosis were antagonized by pretreatment of the cells with 10{sup −8} M human parathyroid hormone (PTH)-(1–34). Thus, HG and AGEs likely suppress bone formation by increasing sclerostin expression in osteocytes, whereas AGEs suppress bone resorption by decreasing RANKL expression. Together, these processes may cause low bone turnover in DM. In addition, HG and AGEs may cause cortical bone deterioration by inducing osteocyte apoptosis. PTH may effectively treat these pathological processes and improve osteocyte function. - Highlights: • AGEs are involved in bone quality deterioration in diabetes mellitus (DM). • AGEs increased sclerostin as well as apoptosis, and decreased RANKL in osteocytes. • The effects of AGEs on osteocyte function were antagonized by human PTH-(1–34). • AGEs may cause low bone turnover and cortical porosity in DM. • PTH may be effective in bone quality deterioration by improving osteocyte function.

Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α.

Science.gov (United States)

Brunetti, G; Papadia, F; Tummolo, A; Fischetto, R; Nicastro, F; Piacente, L; Ventura, A; Mori, G; Oranger, A; Gigante, I; Colucci, S; Ciccarelli, M; Grano, M; Cavallo, L; Delvecchio, M; Faienza, M F

2016-07-01

In this study, we investigated the bone cell activity in patients with osteogenesis imperfecta (OI) treated and untreated with neridronate. We demonstrated the key role of Dickkopf-1 (DKK1), receptor activator of nuclear factor-κB ligand (RANKL), and tumor necrosis factor alpha (TNF-α) in regulating bone cell of untreated and treated OI subjects. These cytokines could represent new pharmacological targets for OI. Bisphosphonates are widely used in the treatment of children with osteogenesis imperfecta (OI) with the objective of reducing the risk of fractures. Although bisphosphonates increase bone mineral density in OI subjects, the effects on fracture incidence are conflicting. The aim of this study was to investigate the mechanisms underlying bone cell activity in subjects with mild untreated forms of OI and in a group of subjects with severe OI treated with cycles of intravenous neridronate. Sclerostin, DKK1, TNF-α, RANKL, osteoprotegerin (OPG), and bone turnover markers were quantified in serum of 18 OI patients (12 females, mean age 8.86 ± 3.90), 8 of which were receiving cyclic intravenous neridronate, and 21 sex- and age-matched controls. The effects on osteoblastogenesis and OPG expression of media conditioned by the serum of OI patients and anti-DKK1 neutralizing antibody were evaluated. Osteoclastogenesis was assessed in cultures from patients and controls. DKK1 and RANKL levels were significantly increased both in untreated and in treated OI subjects with respect to controls. The serum from patients with high DKK1 levels inhibited both osteoblast differentiation and OPG expression in vitro. High RANKL and low OPG messenger RNA (mRNA) levels were found in lymphomonocytes from patients. High amounts of TNF-α were expressed by monocytes, and an elevated percentage of circulating CD11b-CD51/CD61+ osteoclast precursors was observed in patients. Our study demonstrated the key role of DKK1, RANKL, and TNF-α in regulating bone cell activity of subjects

Effects of Wenyangbushen formula on the expression of VEGF, OPG, RANK and RANKL in rabbits with steroid-induced femoral head avascular necrosis.

Science.gov (United States)

Song, Hong-Mei; Wei, Ying-Chen; Li, Nan; Wu, Bin; Xie, Na; Zhang, Kun-Mu; Wang, Shi-Zhong; Wang, He-Ming

2015-12-01

The present study aimed to investigate the effects of Wenyangbushen formula on the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), osteoprotegerin (OPG), receptor activator of nuclear factor (NF)‑κβ ligand (RANK), and RANK ligand (RANKL) in a rabbit model of steroid‑induced avascular necrosis of the femoral head (SANFH). The present study also aimed to examine the potential mechanism underlying the effect of this formula on the treatment of SANFH. A total of 136 New Zealand rabbits were randomly divided into five groups: Normal group, model group, and three groups treated with the traditional Chinese medicine (TCM), Wenyangbushen decoction, at a low, moderate and high dose, respectively. The normal group and positive control group were intragastrically administered with saline. The TCM groups were treated with Wenyangbushen decoction at the indicated dosage. Following treatment for 8 weeks, the mRNA and protein expression levels of VEGF, OPG, RANK and RANKL in the femoral head tissues were determined using reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. The data revealed that Wenyangbushen decoction effectively promoted the growth of bone cells, osteoblasts and chondrocytes, and prevented cell apoptosis in the SANFH. The mRNA and protein expression levels of OPG and VEGF were increased, while the levels of RANK and RANKL were reduced in the necrotic tissue of the model group, compared with those in the normal rabbits. Wenyangbushen treatment prevented these changes, manifested by an upregulation in the expression levels of VEGF and OPG, and downregulation in the expression levels of RANK and RANKL in a dose‑dependent manner. It was concluded that treatment with Wenyangbushen formula alleviated necrosis of the femoral head induced by steroids. It was observed to promote bone cell, osteoblast and chondrocyte growth, as well as prevent cell apoptosis. In addition, it

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

Parallel Assessment of Bone Mineral Density and RANKL/OPG Ratio in Saudi Females

OpenAIRE

AI Hassan; SA Eltarhouny; HE Hashem; SA Algaidi; AR Abdallah; AM Sandokji

2016-01-01

Background: Osteoporosis is a significant risk factor for morbidity, and its high prevalence among Saudi women should be considered to be a public health problem. Quantitative ultrasound was recommended for bone mineral density (BMD) screening. Receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) and their ratio are critical for physiological bone remodelling, and related abnormalities may lead to several osteopathies. Methods: The BMD of 499 Saudi female...

The key role of proinflammatory cytokines, matrix proteins, RANKL/OPG and Wnt/β-catenin in bone healing of hip arthroplasty patients.

Science.gov (United States)

Cassuto, Jean; Folestad, Agnetha; Göthlin, Jan; Malchau, Henrik; Kärrholm, Johan

2018-02-01

We still lack understanding of why some implants fail while most remain stable after decades of use. Proinflammatory cytokines, matrix proteins and bone regulating cytokines of the RANKL/OPG (receptor activator of nuclear factor kappa B ligand/osteoprotegerin) and Wnt/β-catenin pathways are mandatory for normal bone repair but their spatial and temporal role in the healing of primary total hip arthroplasties (THA) has not been previously shown. Twenty-four osteoarthritis patients with one-sided well-fixed primary THA were prospectively monitored during 18years (18Y) with repeated blood samples, clinical variables and radiographs. Eighty-one healthy donors divided in three age- and gender-matched groups and twenty osteoarthritis patients awaiting THA and serving as control of the validity of stored plasma in THA patients, were included. Plasma was analyzed for C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-1β, tumor necrosis factor (TNF)-α, osteopontin (OPN), secreted protein acidic and rich in cysteine (SPARC/osteonectin), osteocalcin (OC), bone specific alkaline phosphatase (BALP), N-terminal propeptide of collagen type I (P1NP), RANKL, OPG, the Wnt agonistic ligands (Wnt)-1 and Wnt-3a, and the Wnt antagonists sclerostin, Dickkopf (Dkk)-1, Dkk-3, Dkk-4, secreted frizzled related protein (sFRP)-1, sFRP-3 and Wnt inhibitory factor-1 (Wif-1). Inflammatory mediators in arthroplasty patients (CRP, IL-6, OPN) increased significantly on day one after surgery vs preoperative value (PR) and healthy subjects and returned to baseline at 6W. TNF-α did not change relative preoperative level or healthy subjects. SPARC and OC increased in a biphasic fashion with the primary phase beginning shortly after surgery and lasting 3M (SPARC) and 2Y (OC) while the secondary phase peaked at 1Y (SPARC) and 13Y (OC), with both returning to basal level at 15Y. BALP peaked at 3M after surgery with a return to basal level at 2Y followed by a continuous increase from 5Y until 18Y. P

Osteocytes, not Osteoblasts or Lining Cells, are the Main Source of the RANKL Required for Osteoclast Formation in Remodeling Bone.

Directory of Open Access Journals (Sweden)

Jinhu Xiong

Full Text Available The cytokine receptor activator of nuclear factor kappa B ligand (RANKL, encoded by the Tnfsf11 gene, is essential for osteoclastogenesis and previous studies have shown that deletion of the Tnfsf11 gene using a Dmp1-Cre transgene reduces osteoclast formation in cancellous bone by more than 70%. However, the Dmp1-Cre transgene used in those studies leads to recombination in osteocytes, osteoblasts, and lining cells making it unclear whether one or more of these cell types produce the RANKL required for osteoclast formation in cancellous bone. Because osteoblasts, osteocytes, and lining cells have distinct locations and functions, distinguishing which of these cell types are sources of RANKL is essential for understanding the orchestration of bone remodeling. To distinguish between these possibilities, we have now created transgenic mice expressing the Cre recombinase under the control of regulatory elements of the Sost gene, which is expressed in osteocytes but not osteoblasts or lining cells in murine bone. Activity of the Sost-Cre transgene in osteocytes, but not osteoblast or lining cells, was confirmed by crossing Sost-Cre transgenic mice with tdTomato and R26R Cre-reporter mice, which express tdTomato fluorescent protein or LacZ, respectively, only in cells expressing the Cre recombinase or their descendants. Deletion of the Tnfsf11 gene in Sost-Cre mice led to a threefold decrease in osteoclast number in cancellous bone and increased cancellous bone mass, mimicking the skeletal phenotype of mice in which the Tnfsf11 gene was deleted using the Dmp1-Cre transgene. These results demonstrate that osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling cancellous bone.

RANK/RANKL/OPG Signalization Implication in Periodontitis: New Evidence from a RANK Transgenic Mouse Model

Directory of Open Access Journals (Sweden)

Bouchra Sojod

2017-05-01

Full Text Available Periodontitis is based on a complex inflammatory over-response combined with possible genetic predisposition factors. The RANKL/RANK/OPG signaling pathway is implicated in bone resorption through its key function in osteoclast differentiation and activation, as well as in the inflammatory response. This central element of osteo-immunology has been suggested to be perturbed in several diseases, including periodontitis, as it is a predisposing factor for this disease. The aim of the present study was to validate this hypothesis using a transgenic mouse line, which over-expresses RANK (RTg and develops a periodontitis-like phenotype at 5 months of age. RTg mice exhibited severe alveolar bone loss, an increased number of TRAP positive cells, and disorganization of periodontal ligaments. This phenotype was more pronounced in females. We also observed dental root resorption lacunas. Hyperplasia of the gingival epithelium, including Malassez epithelial rests, was visible as early as 25 days, preceding any other symptoms. These results demonstrate that perturbations of the RANKL/RANK/OPG system constitute a core element of periodontitis, and more globally, osteo-immune diseases.

RANK/RANKL/OPG Signalization Implication in Periodontitis: New Evidence from a RANK Transgenic Mouse Model

Science.gov (United States)

Sojod, Bouchra; Chateau, Danielle; Mueller, Christopher G.; Babajko, Sylvie; Berdal, Ariane; Lézot, Frédéric; Castaneda, Beatriz

2017-01-01

Periodontitis is based on a complex inflammatory over-response combined with possible genetic predisposition factors. The RANKL/RANK/OPG signaling pathway is implicated in bone resorption through its key function in osteoclast differentiation and activation, as well as in the inflammatory response. This central element of osteo-immunology has been suggested to be perturbed in several diseases, including periodontitis, as it is a predisposing factor for this disease. The aim of the present study was to validate this hypothesis using a transgenic mouse line, which over-expresses RANK (RTg) and develops a periodontitis-like phenotype at 5 months of age. RTg mice exhibited severe alveolar bone loss, an increased number of TRAP positive cells, and disorganization of periodontal ligaments. This phenotype was more pronounced in females. We also observed dental root resorption lacunas. Hyperplasia of the gingival epithelium, including Malassez epithelial rests, was visible as early as 25 days, preceding any other symptoms. These results demonstrate that perturbations of the RANKL/RANK/OPG system constitute a core element of periodontitis, and more globally, osteo-immune diseases. PMID:28596739

Paracrine-mediated osteoclastogenesis by the osteosarcoma MG63 cell line: is RANKL/RANK signalling really important?

Science.gov (United States)

Costa-Rodrigues, J; Teixeira, C A; Fernandes, M H

2011-08-01

Although in the past little attention has been paid to the influence of osteosarcoma cells in osteoclast function, recent studies suggest a close relationship between osteosarcoma aggressiveness and osteoclastic activity. The present study addresses the paracrine effects of MG63 cells, a human osteosarcoma-derived cell line, on the differentiation of peripheral blood osteoclast precursor cells (PBMC). PBMC were cultured for 21 days in the presence of conditioned media from MG63 cell cultures (CM) collected at 48 h (CM_MG1), 7 days (CM_MG2) and 14 days (CM_MG3). MG63 cell cultures displayed the expression of ALP and BMP-2 and, also, the osteoclastogenic genes M-CSF and RANKL, although with a low expression of RANKL. PBMC cultures supplemented with CM presented an evident osteoclastogenic behavior, which was dependent on the culture period of the MG63 cells. The inductive effect appeared to be more relevant for the differentiation and activation genes, c-myc and c-src, and lower for genes associated with osteoclast function. In addition, PBMC cultures displayed increased functional parameters, including calcium phosphate resorbing activity. Assessment of the PBMC cultures in the presence of U0126, PDTC, and indomethacin suggested that in addition to MEK and NFkB pathways, other signaling mechanisms, probably not involving RANKL/RANK interaction, might be activated in the presence of conditioned medium from MG63. In conclusion, MG63 cell line appears to induce a significant paracrine-mediated osteoclastogenic response. Understanding the mechanisms underlying the interaction of osteosarcoma cells and osteoclasts may contribute to the development of new potential approaches in the treatment of such bone metabolic diseases.

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.

Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model

DEFF Research Database (Denmark)

Atkinson, Sara Marie; Bleil, Janine; Maier, Rene

2016-01-01

. Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling...... and bone formation were analyzed by mRNA deep sequencing. Serum concentrations of tartrate-resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were determined by enzyme-linked immunosorbent assay. Anti......-RANKL monoclonal antibody treatment was initiated at the time of immunization. Results: Bone destruction (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after arthritis induction, followed by a peak in cartilage destruction and bone erosion on day 5 after arthritis induction...

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

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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.

Treatment with Rhizoma Dioscoreae Extract Has Protective Effect on Osteopenia in Ovariectomized Rats

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Zhiguo Zhang

2014-01-01

Full Text Available The aims of this study were to evaluate the osteoprotective effect of aqueous extract from Rhizoma Dioscoreae (RDE on rats with ovariectomy- (OVX- induced osteopenia. Our results show that RDE could inhibit bone loss of OVX rats after a 12-week treatment. The microarray analysis showed that 68 genes were upregulated and that 100 genes were downregulated in femurs of the RDE group rats compared to those in the OVX group. The Ingenuity Pathway Analysis (IPA showed that several downregulated genes had the potential to code for proteins that were involved in the Wnt/β-catenin signaling pathway (Sost, Lrp6, Tcf7l2, and Alpl and the RANKL/RANK signaling pathway (Map2k6 and Nfatc4. These results revealed that the mechanism for an antiosteopenic effect of RDE might lie in the synchronous inhibitory effects on both the bone formation and the bone resorption, which is associated with modulating the Wnt/β-catenin signaling and the RANKL/RANK signaling.

Treatment with Rhizoma Dioscoreae extract has protective effect on osteopenia in ovariectomized rats.

Science.gov (United States)

Zhang, Zhiguo; Xiang, Lihua; Bai, Dong; Fu, Xiaowei; Wang, Wenlai; Li, Yan; Liu, Hong; Pan, Jinghua; Li, Ya'nan; Xiao, Gary Guishan; Ju, Dahong

2014-01-01

The aims of this study were to evaluate the osteoprotective effect of aqueous extract from Rhizoma Dioscoreae (RDE) on rats with ovariectomy- (OVX-) induced osteopenia. Our results show that RDE could inhibit bone loss of OVX rats after a 12-week treatment. The microarray analysis showed that 68 genes were upregulated and that 100 genes were downregulated in femurs of the RDE group rats compared to those in the OVX group. The Ingenuity Pathway Analysis (IPA) showed that several downregulated genes had the potential to code for proteins that were involved in the Wnt/ β -catenin signaling pathway (Sost, Lrp6, Tcf7l2, and Alpl) and the RANKL/RANK signaling pathway (Map2k6 and Nfatc4). These results revealed that the mechanism for an antiosteopenic effect of RDE might lie in the synchronous inhibitory effects on both the bone formation and the bone resorption, which is associated with modulating the Wnt/ β -catenin signaling and the RANKL/RANK signaling.

Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways

Science.gov (United States)

Wang, Tao; Liu, Qian; Zhou, Lin; Yuan, Jin Bo; Lin, Xixi; Zeng, Rong; Liang, Xiaonan; Zhao, Jinmin; Xu, Jiake

2015-01-01

Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP), a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect on osteoporosis is unknown. In this study, an ovariectomy (OVX) mouse model was used to evaluate the therapeutic effects of AP on post-menopausal osteoporosis by using micro-computed tomography (micro-CT). Bone marrow-derived osteoclast culture was used to examine the inhibitory effect of AP on osteoclastogenesis. Real time PCR was employed to examine the effect of AP on the expression of osteoclast marker genes. The activities of transcriptional factors NF-κB and NFATc1 were evaluated using a luciferase reporter assay, and the IκBα protein level was analyzed by Western blot. We found that OVX mice treated with AP have greater bone volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) compared to vehicle-treated OVX mice. AP inhibited RANKL-induced osteoclastogenesis, the expression of osteoclast marker genes including cathepsin K (Ctsk), TRACP (Acp5), and NFATc1, as well as the transcriptional activities of NF-κB and NFATc1. In conclusion, our results suggest that AP inhibits estrogen deficiency-induced bone loss in mice via the suppression of RANKL-induced osteoclastogensis and NF-κB and NFATc1 activities and, thus, might have therapeutic potential for osteoporosis. PMID:26593901

Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways.

Science.gov (United States)

Wang, Tao; Liu, Qian; Zhou, Lin; Yuan, Jin Bo; Lin, Xixi; Zeng, Rong; Liang, Xiaonan; Zhao, Jinmin; Xu, Jiake

2015-11-17

Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP), a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect on osteoporosis is unknown. In this study, an ovariectomy (OVX) mouse model was used to evaluate the therapeutic effects of AP on post-menopausal osteoporosis by using micro-computed tomography (micro-CT). Bone marrow-derived osteoclast culture was used to examine the inhibitory effect of AP on osteoclastogenesis. Real time PCR was employed to examine the effect of AP on the expression of osteoclast marker genes. The activities of transcriptional factors NF-κB and NFATc1 were evaluated using a luciferase reporter assay, and the IκBα protein level was analyzed by Western blot. We found that OVX mice treated with AP have greater bone volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) compared to vehicle-treated OVX mice. AP inhibited RANKL-induced osteoclastogenesis, the expression of osteoclast marker genes including cathepsin K (Ctsk), TRACP (Acp5), and NFATc1, as well as the transcriptional activities of NF-κB and NFATc1. In conclusion, our results suggest that AP inhibits estrogen deficiency-induced bone loss in mice via the suppression of RANKL-induced osteoclastogensis and NF-κB and NFATc1 activities and, thus, might have therapeutic potential for osteoporosis.

Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways

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Tao Wang

2015-11-01

Full Text Available Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP, a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect on osteoporosis is unknown. In this study, an ovariectomy (OVX mouse model was used to evaluate the therapeutic effects of AP on post-menopausal osteoporosis by using micro-computed tomography (micro-CT. Bone marrow-derived osteoclast culture was used to examine the inhibitory effect of AP on osteoclastogenesis. Real time PCR was employed to examine the effect of AP on the expression of osteoclast marker genes. The activities of transcriptional factors NF-κB and NFATc1 were evaluated using a luciferase reporter assay, and the IκBα protein level was analyzed by Western blot. We found that OVX mice treated with AP have greater bone volume (BV/TV, trabecular thickness (Tb.Th, and trabecular number (Tb.N compared to vehicle-treated OVX mice. AP inhibited RANKL-induced osteoclastogenesis, the expression of osteoclast marker genes including cathepsin K (Ctsk, TRACP (Acp5, and NFATc1, as well as the transcriptional activities of NF-κB and NFATc1. In conclusion, our results suggest that AP inhibits estrogen deficiency-induced bone loss in mice via the suppression of RANKL-induced osteoclastogensis and NF-κB and NFATc1 activities and, thus, might have therapeutic potential for osteoporosis.

Target costing as an element of the hard coal extraction cost planning process

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Katarzyna Segeth-Boniecka

2017-09-01

Full Text Available Target costing as an element of the hard coal extraction cost planning process Striving for the efficiency of activities is of great significance in the management of hard coal extractive enterprises, which are constantly subjected to the process of restructuring. Effective cost management is an important condition of the increase in the efficiency of the researched business entities’ activity. One of the tools whose basic objective is conscious influencing cost levels is target costing. The aim of this article is to analyse the conditions of implementing target costing in the planning of hard coal extraction costs in hard coal mines in Poland. The subject area raises a topical and important problem of the scope of solutions concerning cost analysis in hard coal mines in Poland, which has not been thoroughly researched yet. To achieve the abovementioned aim, the theoretical works of the subject area have been referenced. The mine management process is difficult and requires the application of best suited and most modern tools, including those used in the planning process of hard coal extraction costs in order to support the economic efficiency of mining operations. The use of the target costing concept in the planning of hard coal mine operations aims to support the decision-making process, so as to achieve a specified level of economic efficiency of the operations carried out in a territorially designated site of hard coal extraction.

Influence of Simultaneous Targeting of the Bone Morphogenetic Protein Pathway and RANK-RANKL Axis in Osteolytic Prostate Cancer Lesion in Bone

Science.gov (United States)

Virk, Mandeep S.; Petrigliano, Frank A.; Liu, Nancy Q.; Chatziioannou, Arion F.; Stout, David; Kang, Christine O.; Dougall, William C.; Lieberman, Jay R.

2009-01-01

Metastasis to bone is the leading cause of morbidity and mortality in advanced prostate cancer patients. Considering the complex reciprocal interactions between the tumor cells and the bone microenvironment, there is increasing interest in developing combination therapies targeting both the tumor growth and the bone microenvironment. In this study, we investigated the effect of simultaneous blockade of BMP pathway and RANK-RANKL axis in an osteolytic prostate cancer lesion in bone. We used a retroviral vector encoding noggin (Retronoggin) to antagonize the effect of BMPs and RANK: Fc, which is a recombinant RANKL antagonist was used to inhibit RANK-RANKL axis. The tumor growth and bone loss were evaluated using plain radiographs, hind limb tumor measurements, micro PET-CT (18F- fluorodeoxyglucose [FDG] and 18F-fluoride tracer), and histology. Tibias implanted with PC-3 cells developed pure osteolytic lesions at 2 weeks with progressive increase in cortical bone destruction at successive time points. Tibias implanted with PC-3 cells over expressing noggin (Retronoggin) resulted in reduced tumor size and decreased bone loss compared to the implanted tibias in untreated control animals. RANK: Fc administration inhibited the formation of osteoclasts, delayed the development of osteolytic lesions, decreased bone loss and reduced tumor size in tibias implanted with PC-3 cells. The combination therapy with RANK: Fc and noggin over expression effectively delayed the radiographic development of osteolytic lesions, and decreased the bone loss and tumor burden compared to implanted tibias treated with noggin over expression alone. Furthermore, the animals treated with the combination strategy exhibited decreased bone loss (micro CT) and lower tumor burden (FDG micro PET) compared to animals treated with RANK: Fc alone. Combined blockade of RANK-RANKL axis and BMP pathway resulted in reduced tumor burden and decreased bone loss compared to inhibition of either individual

Planning wood extraction in a forest coppice

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Civitarese V

2006-01-01

Full Text Available A series of cartographic models of analysis have been elaborated through the softwares ArcView GIS (ESRI 2002 and Surfer 8 (Golden software 2002 to find optimal work systems for the wood extraction in an oak coppice, located on the Monti della Tolfa, near Rome, Italy. The main factors analyzed were the morphology of the territory and the roads characteristics. The methodological procedure followed was applied on the different classes of slope, the direction of water outflow, the presence of ditches and channels, the principal and secondary roads, the wood cover and the clearings. The possibility to employ tractors with cages, polyethylene chutes, mules and cable cranes has been examined, also identifying the fittest areas to their use. This first analytical phase was followed by a second phase dedicated to the evaluation of the technical feasibility. The proposed method contributes to a rational planning of the work site. The advantage could be the planning of extraction operations on the map, but it will be necessary to verify the method in field studies. Although this method has been developed on limited extensions of territories, it could be applicable to situations of greater complexity, representing the base for the creation of a tool that may be employed in ampler territorial contexts, such as Comunità Montane and hydrographic basins.

Using cone beam computed thomography in planning the extraction of impacted third molars

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Vlahović Zoran

2016-01-01

Full Text Available The panoramic radiography is the most used diagnostic imaging method in planning impacted lower third molar extractions. However, often panoramic radiography does not provide enough information in treatment planning for performing safely surgical extraction of impacted third molars. CBCT (Cone beam computed tomography provides more precise information in diagnostic analysis especially for planning surgical procedures where complications can be expected due to close relationship between mandibular canal and lower impacted third molars. The aim of this study is comparative analysis of panoramic radiography and CBCT in evaluating the topographic relationship between mandibular canal and impacted third molars. The study included 50 patients with close relationship between mandibular canal and impacted third molars detected using panoramic radiography. After panoramic radiography analysis CBCT was performed in order to diagnose, plan and prevent complications during the surgical tooth extraction. CBCT examination considered comparative analysis with panoramic radiography, marking, volume rendering and assessment of mandibular canal in buccolingual direction. Out of total patients where suprimposition of mandibular canal and impacted third molar on panoramic radiography was detected, in 32 patients mandibular chanal was localised on lingual side. Mandibular canal was positioned at bucal side in 18 of 50 patients. Results of this research indicate that panoramic radiography can be useful in everyday practice for diagnosis, planning and preparing lower third molar extractions, but in cases where close relationship between mandibular canal and lower third molars is detected CBCT is recommended as more precise radiographic imaging method in order to prevent complications.

Caffeic acid phenethyl ester protects against glucocorticoid-induced osteoporosis in vivo: Impact on oxidative stress and RANKL/OPG signals

International Nuclear Information System (INIS)

Tolba, Mai F.; El-Serafi, Ahmed T.; Omar, Hany A.

2017-01-01

Glucocorticoid-induced osteoporosis (GIO) is one of the most common causes of secondary osteoporosis. Given that glucocorticoids are considered as a main component of the treatment protocols for a variety of inflammation and immune-mediated diseases besides its use as adjuvant to several chemotherapeutic agents, it is crucial to find ways to overcome this critical adverse effect. Caffeic acid phenethyl ester (CAPE), which is a natural compound derived from honeybee propolis displayed promising antiosteoporotic effects against mechanical bone injury in various studies. The current work aimed at investigating the potential protective effect of CAPE against GIO in vivo with emphasis on the modulation of oxidative status and receptor activator of NF-kB ligand (RANKL)/osteoprotegrin (OPG) signaling. The results showed that CAPE opposed dexamethasone (DEX)-mediated alterations in bone histology and tartarate-resistant acid phosphatase (TRAP) activity. In addition, CAPE restored oxidative balance, Runt-related transcription factor 2 (RunX2) expression and reduced caspase-3 activity in femur tissues. Co-administration of CAPE with DEX normalized RANKL/OPG ratio and Akt activation indicating a reduction in DEX-osteoclastogenesis. In conclusion, concurrent treatment of CAPE with DEX exhibited promising effects in the protection against DEX-induced osteoporosis through opposing osteoclastogenesis and protecting osteoblasts. The potent antioxidant activity of CAPE is, at least in part, involved in its anti-apoptotic effects and modulation of RunX2 and RANKL/OPG signals. The use of CAPE-enriched propolis formulas is strongly recommended for patients on chronic glucocorticoid therapy to help in the attenuation of GIO. - Highlights: • Caffeic acid phenethyl ester (CAPE) counteracts DEX-induced osteoporosis. • CAPE hinders DEX-induced alterations in oxidation parameters as GSH, SOD and MDA. • CAPE opposes osteoclastogenesis via suppressing RANL/OPG ratio and Akt signals. �

Caffeic acid phenethyl ester protects against glucocorticoid-induced osteoporosis in vivo: Impact on oxidative stress and RANKL/OPG signals

Energy Technology Data Exchange (ETDEWEB)

Tolba, Mai F. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566 (Egypt); Chapman University, Irvine 92618, CA (United States); El-Serafi, Ahmed T. [Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272 (United Arab Emirates); Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia (Egypt); Omar, Hany A., E-mail: hanyomar@sharjah.ac.ae [Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272 (United Arab Emirates); Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt)

2017-06-01

Glucocorticoid-induced osteoporosis (GIO) is one of the most common causes of secondary osteoporosis. Given that glucocorticoids are considered as a main component of the treatment protocols for a variety of inflammation and immune-mediated diseases besides its use as adjuvant to several chemotherapeutic agents, it is crucial to find ways to overcome this critical adverse effect. Caffeic acid phenethyl ester (CAPE), which is a natural compound derived from honeybee propolis displayed promising antiosteoporotic effects against mechanical bone injury in various studies. The current work aimed at investigating the potential protective effect of CAPE against GIO in vivo with emphasis on the modulation of oxidative status and receptor activator of NF-kB ligand (RANKL)/osteoprotegrin (OPG) signaling. The results showed that CAPE opposed dexamethasone (DEX)-mediated alterations in bone histology and tartarate-resistant acid phosphatase (TRAP) activity. In addition, CAPE restored oxidative balance, Runt-related transcription factor 2 (RunX2) expression and reduced caspase-3 activity in femur tissues. Co-administration of CAPE with DEX normalized RANKL/OPG ratio and Akt activation indicating a reduction in DEX-osteoclastogenesis. In conclusion, concurrent treatment of CAPE with DEX exhibited promising effects in the protection against DEX-induced osteoporosis through opposing osteoclastogenesis and protecting osteoblasts. The potent antioxidant activity of CAPE is, at least in part, involved in its anti-apoptotic effects and modulation of RunX2 and RANKL/OPG signals. The use of CAPE-enriched propolis formulas is strongly recommended for patients on chronic glucocorticoid therapy to help in the attenuation of GIO. - Highlights: • Caffeic acid phenethyl ester (CAPE) counteracts DEX-induced osteoporosis. • CAPE hinders DEX-induced alterations in oxidation parameters as GSH, SOD and MDA. • CAPE opposes osteoclastogenesis via suppressing RANL/OPG ratio and Akt signals. �

Comparison of low-intensity pulsed ultrasound and pulsed electromagnetic field treatments on OPG and RANKL expression in human osteoblast-like cells

NARCIS (Netherlands)

Borsje, Manon A.; Ren, Yijin; de Haan-Visser, H. Willy; Kuijer, Roel

OBJECTIVE: To compare two clinically applied treatments to stimulate bone healing-low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF)-for their effects on RANKL and OPG expression in osteoblast-like cells in vitro. MATERIALS AND METHODS: LIPUS or PEMF was applied to

[Automatic Extraction and Analysis of Dosimetry Data in Radiotherapy Plans].

Science.gov (United States)

Song, Wei; Zhao, Di; Lu, Hong; Zhang, Biyun; Ma, Jun; Yu, Dahai

To improve the efficiency and accuracy of extraction and analysis of dosimetry data in radiotherapy plans for a batch of patients. With the interface function provided in Matlab platform, a program was written to extract the dosimetry data exported from treatment planning system in DICOM RT format and exported the dose-volume data to an Excel file with the SPSS compatible format. This method was compared with manual operation for 14 gastric carcinoma patients to validate the efficiency and accuracy. The output Excel data were compatible with SPSS in format, the dosimetry data error for PTV dose interval of 90%-98%, PTV dose interval of 99%-106% and all OARs were -3.48E-5 ± 3.01E-5, -1.11E-3 ± 7.68E-4, -7.85E-5 ± 9.91E-5 respectively. Compared with manual operation, the time required was reduced from 5.3 h to 0.19 h and input error was reduced from 0.002 to 0. The automatic extraction of dosimetry data in DICOM RT format for batch patients, the SPSS compatible data exportation, quick analysis were achieved in this paper. The efficiency of clinical researches based on dosimetry data analysis of large number of patients will be improved with this methods.

RANKL/RANK/OPG cytokine receptor system: mRNA expression pattern in BPH, primary and metastatic prostate cancer disease.

Science.gov (United States)

Christoph, Frank; König, Frank; Lebentrau, Steffen; Jandrig, Burkhard; Krause, Hans; Strenziok, Romy; Schostak, Martin

2018-02-01

The cytokine system RANKL (receptor activator of NF-κB ligand), its receptor RANK and the antagonist OPG (osteoprotegerin) play a critical role in bone turnover. Our investigation was conducted to describe the gene expression at primary tumour site in prostate cancer patients and correlate the results with Gleason Score and PSA level. Seventy-one samples were obtained from prostate cancer patients at the time of radical prostatectomy and palliative prostate resection (n = 71). Patients with benign prostate hyperplasia served as controls (n = 60). We performed real-time RT-PCR after microdissection of the samples. The mRNA expression of RANK was highest in tumour tissue from patients with bone metastases (p BPH or locally confined tumours, also shown in clinical subgroups distinguished by Gleason Score (BPH tissue but did not exceed as much as in the tumour tissue. We demonstrated that RANK, RANKL and OPG are directly expressed by prostate cancer cells at the primary tumour site and showed a clear correlation with Gleason Score, serum PSA level and advanced disease. In BPH, mRNA expression is also detectable, but RANK expression does not exceed as much as compared to tumour tissue.

Porphyromonas gingivalis decreases osteoblast proliferation through IL-6-RANKL/OPG and MMP-9/TIMPs pathways

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Le Xuan

2009-01-01

Full Text Available Background: Porphyromonas gingivalis, an important periodontal pathogen, is closely associated with inflammatory alveolar bone resorption. This bacterium exerts its pathogenic effect indirectly through multiple virulence factors, such as lipopolysaccharides, fimbriae, and proteases. Another possible pathogenic path may be through a direct interaction with the host′s soft and hard tissues (e.g., alveolar bone, which could lead to periodontitis. Aims and Objectives: The aim of the present study was to investigate the direct effect of live and heat-inactivated P gingivalis on bone resorption, using an in vitro osteoblast culture model. Results: Optical microscopy and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide MTT assay revealed that live P gingivalis induced osteoblast detachment and reduced their proliferation. This effect was specific to live bacteria and was dependent on their concentration. Live P gingivalis increased IL-6 mRNA expression and protein production and downregulated RANKL and OPG mRNA expression. The effect of live P gingivalis on bone resorption was strengthened by an increase in MMP-9 expression and its activity. This increase was accompanied by an increase in TIMP-1 and TIMP-2 mRNA expression and protein production by osteoblasts infected with live P gingivalis. Conclusion: Overall, the results suggest that direct contact of P gingivalis with osteoblasts induces bone resorption through an inflammatory pathway that involves IL-6, RANKL/OPG, and MMP-9/TIMPs.

Azilsartan increases levels of IL-10, down-regulates MMP-2, MMP-9, RANKL/RANK, Cathepsin K and up-regulates OPG in an experimental periodontitis model.

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Aurigena Antunes de Araújo

Full Text Available AIMS: The aim of this study was to evaluate the effects of azilsartan (AZT on bone loss, inflammation, and the expression of matrix metallo proteinases (MMPs, receptor activator of nuclear factor κB ligand (RANKL, receptor activator of nuclear factor κB (RANK, osteoprotegerin (OPG, cyclooxygenase-2 (COX-2, and cathepsin K in periodontal tissue in a rat model of ligature-induced periodontitis. MATERIALS AND METHODS: Male Wistar albino rats were randomly divided into 5 groups of 10 rats each: (1 nonligated, water; (2 ligated, water; (3 ligated, 1 mg/kg AZT; (4 ligated, 5 mg/kg AZT; and (5 ligated, 10 mg/kg AZT. All groups were treated with saline or AZT for 10 days. Periodontal tissues were analyzed by histopathology and immunohistochemical detection of MMP-2, MMP-9, COX-2, RANKL, RANK, OPG, and cathepsin K. Levels of IL-1β, IL-10, TNF-α, myeloperoxidase (MPO, and glutathione (GSH were determined by ELISA. RESULTS: Treatment with 5 mg/kg AZT resulted in reduced MPO (p<0.05 and IL-1β (p<0.05, increased levels of IL-10 (p<0.05, and reduced expression of MMP-2, MMP-9, COX-2, RANK, RANKL, cathepsin K, and increased expression of OPG. CONCLUSIONS: These findings reveal that AZT increases anti-inflammatory cytokines and GSH and decreases bone loss in ligature-induced periodontitis in rats.

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

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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.

Analysis Methods for Extracting Knowledge from Large-Scale WiFi Monitoring to Inform Building Facility Planning

DEFF Research Database (Denmark)

Ruiz-Ruiz, Antonio; Blunck, Henrik; Prentow, Thor Siiger

2014-01-01

realistic data to inform facility planning. In this paper, we propose analysis methods to extract knowledge from large sets of network collected WiFi traces to better inform facility management and planning in large building complexes. The analysis methods, which build on a rich set of temporal and spatial......The optimization of logistics in large building com- plexes with many resources, such as hospitals, require realistic facility management and planning. Current planning practices rely foremost on manual observations or coarse unverified as- sumptions and therefore do not properly scale or provide....... Spatio-temporal visualization tools built on top of these methods enable planners to inspect and explore extracted information to inform facility-planning activities. To evaluate the methods, we present results for a large hospital complex covering more than 10 hectares. The evaluation is based on Wi...

Statistical model of planning technological indicators for oil extraction

Energy Technology Data Exchange (ETDEWEB)

Galeyev, R G; Lavushchenko, V P; Sheshnev, A S

1979-01-01

The efficiency of the process of oil extraction is determined by the effect of a number of interrelated technological indicators. Analytical expression of the interrelationships of the indicators was represented by an econometric model consisting of a system of linear regression equations. The basic advantage of these models is the possibility of calculating in them different, significantly important interrelationships. This makes it possible to correlate all calculations into a single logically noncontradictory balanced system. The developed model of the technological process of oil extraction makes it possible to significantly facilitate calculation and planning of its basic indicators with regard for system and balance requirements, makes it possible to purposefully generate new variants. In this case because of the optimal distribution of the volumes of geological-technical measures, a decrease in the total outlays for their implementation is achieved. Thus for the Berezovskiy field, this saving was R 150,000.

Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and function through inhibition of MAP kinase activation and actin ring formation

International Nuclear Information System (INIS)

Park, Eui Kyun; Kim, Myung Sunny; Lee, Seung Ho; Kim, Kyung Hee; Park, Ju-Young; Kim, Tae-Ho; Lee, In-Seon; Woo, Je-Tae; Jung, Jae-Chang; Shin, Hong-In; Choi, Je-Yong; Kim, Shin-Yoon

2004-01-01

Phenolic compounds including tannins and flavonoids have been implicated in suppression of osteoclast differentiation/function and prevention of bone diseases. However, the effects of hydrolysable tannins on bone metabolism remain to be elucidated. In this study, we found that furosin, a hydrolysable tannin, markedly decreased the differentiation of both murine bone marrow mononuclear cells and Raw264.7 cells into osteoclasts, as revealed by the reduced number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells and decreased TRAP activity. Furosin appears to target at the early stage of osteoclastic differentiation while having no cytotoxic effect on osteoclast precursors. Analysis of the inhibitory mechanisms of furosin revealed that it inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK)/activating protein-1 (AP-1). Furthermore, furosin reduced resorption pit formation in osteoclasts, which was accompanied by disruption of the actin rings. Taken together, these results demonstrate that naturally occurring furosin has an inhibitory activity on both osteoclast differentiation and function through mechanisms involving inhibition of the RANKL-induced p38MAPK and JNK/AP-1 activation as well as actin ring formation

Stability, structure and scale: improvements in multi-modal vessel extraction for SEEG trajectory planning.

Science.gov (United States)

Zuluaga, Maria A; Rodionov, Roman; Nowell, Mark; Achhala, Sufyan; Zombori, Gergely; Mendelson, Alex F; Cardoso, M Jorge; Miserocchi, Anna; McEvoy, Andrew W; Duncan, John S; Ourselin, Sébastien

2015-08-01

Brain vessels are among the most critical landmarks that need to be assessed for mitigating surgical risks in stereo-electroencephalography (SEEG) implantation. Intracranial haemorrhage is the most common complication associated with implantation, carrying significantly associated morbidity. SEEG planning is done pre-operatively to identify avascular trajectories for the electrodes. In current practice, neurosurgeons have no assistance in the planning of electrode trajectories. There is great interest in developing computer-assisted planning systems that can optimise the safety profile of electrode trajectories, maximising the distance to critical structures. This paper presents a method that integrates the concepts of scale, neighbourhood structure and feature stability with the aim of improving robustness and accuracy of vessel extraction within a SEEG planning system. The developed method accounts for scale and vicinity of a voxel by formulating the problem within a multi-scale tensor voting framework. Feature stability is achieved through a similarity measure that evaluates the multi-modal consistency in vesselness responses. The proposed measurement allows the combination of multiple images modalities into a single image that is used within the planning system to visualise critical vessels. Twelve paired data sets from two image modalities available within the planning system were used for evaluation. The mean Dice similarity coefficient was 0.89 ± 0.04, representing a statistically significantly improvement when compared to a semi-automated single human rater, single-modality segmentation protocol used in clinical practice (0.80 ± 0.03). Multi-modal vessel extraction is superior to semi-automated single-modality segmentation, indicating the possibility of safer SEEG planning, with reduced patient morbidity.

FIELD IMPLEMENTATION PLAN FOR A WILLISTON BASIN BRINE EXTRACTION AND STORAGE TEST

Energy Technology Data Exchange (ETDEWEB)

Hamling, John; Klapperich, Ryan; Stepan, Daniel; Sorensen, James; Pekot, Lawrence; Peck, Wesley; Jacobson, Lonny; Bosshart, Nicholas; Hurley, John; Wilson, William; Kurz, Marc; Burnison, Shaughn; Salako, Olarinre; Musich, Mark; Botnen, Barry; Kalenze, Nicholas; Ayash, Scott; Ge, Jun; Jiang, Tao; Dalkhaa, Chantsalmaa; Oster, Benjamin; Peterson, Kyle; Feole, Ian; Gorecki, Charles; Steadman, Edward

2016-03-31

The Energy & Environmental Research Center (EERC) successfully completed all technical work of Phase I, including development of a field implementation plan (FIP) for a brine extraction and storage test (BEST) in the North Dakota portion of the Williston Basin. This implementation plan was commissioned by the U.S. Department of Energy (DOE) National Energy Technology Laboratory (NETL) as a proxy for managing formation pressure plumes and measuring/monitoring the movement of differential pressure and CO2 plumes in the subsurface for future saline CO2 storage projects. BEST comprises the demonstration and validation of active reservoir management (ARM) strategies and extracted brine treatment technologies. Two prospective commercial brine injection sites were evaluated for BEST to satisfy DOE’s goals. Ultimately, an active saltwater disposal (SWD) site, Johnsons Corner, was selected because it possesses an ideal combination of key factors making it uniquely suited to host BEST. This site is located in western North Dakota and operated by Nuverra Environmental Solutions (Nuverra), a national leader in brine handling, treatment, and injection. An integrated management approach was used to incorporate local and regional geologic characterization activities with geologic and simulation models, inform a monitoring, verification, and accounting (MVA) plan, and to conduct a risk assessment. This approach was used to design a FIP for an ARM schema and an extracted brine treatment technology test bed facility. The FIP leverages an existing pressure plume generated by two commercial SWD wells. These wells, in conjunction with a new brine extraction well, will be used to conduct the ARM schema. Results of these tests will be quantified based on their impact on the performance of the existing SWD wells and the surrounding reservoir system. Extracted brine will be injected into an underlying deep saline formation through a new injection well. The locations of proposed

Development and planning of plant for the high-pressure extraction of natural products

Energy Technology Data Exchange (ETDEWEB)

Eggers, R; Tschiersch, R [Thyssen Industrie A.G., Witten (Germany, F.R.)

1978-11-01

Important criteria in the designing of plant for the recovery of carrier or extract are reviewed, especially for the extraction of natural products with supercritical CO/sub 2/. The quantities to be determined in the planning of a large-scale plant are outlined and a typical process, the extraction of spices, is discussed in detail. The plant components and assemblies are presented together with their particular process engineering and construction characteristics. Finally, the thermodynamic aspects are dealt with in more detail and ways of optimizing a large-scale plant and reducing the power consumption are outlined. Particular attention is paid to the question of optimization regarding the most economic method of operation of such a plant in the future.

Substance P Promotes the Proliferation, but Inhibits Differentiation and Mineralization of Osteoblasts from Rats with Spinal Cord Injury via RANKL/OPG System.

Directory of Open Access Journals (Sweden)

Hai-Juan Liu

Full Text Available Spinal cord injury (SCI causes a significant amount of bone loss, which results in osteoporosis (OP. The neuropeptide substance P (SP and SP receptors may play important roles in the pathogenesis of OP after SCI. To identify the roles of SP in the bone marrow mesenchymal stem cell derived osteoblasts (BMSC-OB in SCI rats, we investigated the expression of neurokinin-1 receptors (NK1R in BMSC-OB and the effects of SP on bone formation by development of BMSC-OB cultures. Sixty young male Sprague-Dawley rats were randomized into two groups: SHAM and SCI. The expression of NK1R protein in BMSC-OB was observed using immunohistochemistry and Western blot analysis. The dose- and time-dependent effects of SP on the proliferation, differentiation and mineralization of BMSC-OB and the expression of osteoblastic markers by in vitro experiments. The expression of NK1R in BMSC-OB was observed on plasma membranes and in cytoplasm. One week after osteogenic differentiation, the expression of NK1R was significantly increased after SCI at mRNA and protein levels. However, this difference was gradually attenuated at 2 or 3 weeks later. SP have the function to enhance cell proliferation, inhibite cell differentiation and mineralization at a proper concentration and incubation time, and this effect would be inhibited by adding SP or NK1R antagonist. The expression of RANKL/OPG was significantly increased in tibiae after SCI. Similarly, the RANKL/OPG expression in SCI rats was significantly increased when treating with 10-8 M SP. SP plays a very important role in the pathogenesis of OP after SCI. The direct effect of SP may lead to increased bone resorption through the RANKL/OPG axis after SCI. In addition, high expression of SP also results in the suppression of osteogenesis in SCI rats. Then, the balance between bone resorption and bone formation was broken and finally osteoporosis occurred.

Combined treatment with Dendrobium candidum and black tea extract promotes osteoprotective activity in ovariectomized estrogen deficient rats and osteoclast formation.

Science.gov (United States)

Wang, Ming-Yue; Shen, Chang; An, Meng-Fei; Xie, Chuan-Qi; Wu, Xin; Zhu, Qiang-Qiang; Sun, Bin; Huang, Yan-Ping; Zhao, Yun-Li; Wang, Xuan-Jun; Sheng, Jun

2018-05-01

Dendrobium candidum (DC) and black tea, are traditional chinese drinks, which contain multiple active ingredients. However, whether or not the combination of these two ingredients can improve osteoporosis remains unknown. This study therefore aimed to examine the effects of the combination of DC and black tea extract (BTE) on osteoporosis. Ovariectomy (OVX)-induced osteoporosis in vivo as well as receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in vitro was selected. Results showed that OVX rats that were treated orally with a DC and BTE combination for 12 weeks maintained their calcium (Ca) and phosphorus (P) homeostasis and exhibited significantly enhanced estradiol (E 2 ) and OPG levels. This combination treatment also simultaneously reduced levels of interleukin (IL)-1β, IL-6 and improved the organ coefficients of the uterus and femur as well as BMD and BMC in OVX rats. In addition, this DC and BTE combination suppressed osteoclast differentiation in the RANKL-stimulated osteoclastogenesis of RAW 264.7 cells and effectively inhibited the expression of osteoclast-associated genes and proteins. The results of this study further highlight the fact that a combination of DC and BTE improved ovariectomy-induced osteoporosis in rats and suppressed RANKL-stimulated osteoclastogenesis in RAW 264.7 cells. This combination also significantly alleviated osteoporosis when compared to the alternative sole treatments above, due to synergistic effects among components. One partial mechanism of this combination might be the inhibition of osteoclast proliferation and the regulation of NFATC1/c-Fos expression. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Osteoprotective effects of Fructus Ligustri Lucidi aqueous extract in aged ovariectomized rats

Directory of Open Access Journals (Sweden)

Fung Kwok

2010-11-01

Full Text Available Abstract Background Fructus Ligustri Lucidi (FLL is a commonly used herb for treating bone disorders in Chinese medicine. The present study investigates the anti-osteoporotic activity of FLL aqueous extract in the model of postmenopausal bone loss in aged ovariectomized (OVX female rats. Methods After eight weeks of treatment of FLL or water, the lumbar spine was scanned by peripheral quantitative computed tomography (pQCT. Effects of FLL water extract on osteogenic and adipogenic differentiations in rat mesenchymal stem cells (MSCs were assessed by biochemical methods and staining. Results FLL aqueous extract significantly inhibited bone mineral density (BMD loss in total, trabecular and cortical bones without affecting body weight and uterus wet weight. FLL extract significantly promoted osteogenesis and suppressed adipogenesis in MSCs as indicated by the elevated alkaline phosphatase activity, calcium deposition levels and decreased adipocyte number in a dose-dependent manner without cytotoxic effects. Real-time PCR analysis revealed significant increase of osteoprotegerin (OPG-to-receptor activator for nuclear factor-κB ligand (RANKL mRNA, indicating a decrease in osteoclastogenesis. Conclusion The present study demonstrates the osteoprotective effects of FLL aqueous extract on aged OVX rats, stimulation of osteogenesis, inhibition of adipogenesis and osteoclastogenesis in MSCs.

The Anti-Periodontitis Effects of Ethanol Extract Prepared Using Lactobacillus paracasei subsp. paracasei NTU 101

Directory of Open Access Journals (Sweden)

Te-Hua Liu

2018-04-01

Full Text Available Poor oral health and related diseases, including caries, periodontal disease, and oral cancer, are highly prevalent across the world, particularly in the elderly. This study aimed to investigate the anti-periodontitis activity of fermented skim milk produced using the promising probiotic Lactobacillus paracasei subsp. paracasei NTU 101 (NTU101FM. An initial analysis found that an ethanol extract of NTU101FM displayed anti-oxidative activities. Further investigation of pathogen growth inhibition zones, minimum inhibitory concentrations (MICs, and minimum bactericidal concentrations (MBCs revealed that the NTU101FM ethanol extract also had anti-periodontal pathogen activities. In addition, the NTU101FM ethanol extract significantly decreased the release of pro-inflammatory cytokines induced by lipopolysaccharide (LPS in RAW 264.7 macrophage cells. Finally, the NTU101FM ethanol extract was found to inhibit receptor activator of nuclear factor-κB ligand (RANKL-induced osteoclast differentiation by reducing tartrate-resistant acid phosphatase (TRAP activity and the number of TRAP-positive multinucleated osteoclasts. In summary, our study demonstrated that ethanol extract prepared from NTU101FM has potential use as an anti-periodontitis agent.

Soil Vapor Extraction and Bioventing Test Work Plan for the MOGAS Site, Myrtle Beach Air Force Base, South Carolina

National Research Council Canada - National Science Library

1995-01-01

This work plan presents an evaluation of soil vapor extraction (SVE) and bioventing, and describes the SVE pilot scale and bioventing activities to be conducted to extract and treat soil gas at Installation Restoration Program (IRP...

Surveillance and Maintenance Plan for the Plutonium Uranium Extraction (PUREX) Facility

International Nuclear Information System (INIS)

Woods, P.J.

1998-05-01

This document provides a plan for implementing surveillance and maintenance (S ampersand M) activities to ensure the Plutonium Uranium Extraction (PUREX) Facility is maintained in a safe, environmentally secure, and cost-effective manner until subsequent closure during the final disposition phase of decommissioning. This plan has been prepared in accordance with the guidelines provided in the U.S. Department of Energy (DOE), Office of Environmental Management (EM) Decommissioning Resource Manual (DOE/EM-0246) (DOE 1995), and Section 8.6 of TPA change form P-08-97-01 to the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) (Ecology, et al. 1996). Specific objectives of the S ampersand M program are: Ensure adequate containment of remaining radioactive and hazardous material. Provide security control for access into the facility and physical safety to surveillance personnel. Maintain the facility in a manner that will minimize potential hazards to the public, the environment, and surveillance personnel. Provide a plan for the identification and compliance with applicable environmental, safety, health, safeguards, and security requirements

Alveolar bone healing in rats: micro-CT, immunohistochemical and molecular analysis

Directory of Open Access Journals (Sweden)

Jaqueline Suemi HASSUMI

2018-06-01

Full Text Available Abstract Alveolar bone healing after upper incisor extraction in rats is a classical model of preclinical studies. The underlying morphometric, cellular and molecular mechanism, however, remains imprecise in a unique study. Objectives The aim of this study was therefore to characterize the alveolar bone healing after upper incisor extraction in rats by micro computed tomographic (Micro-CT, immunohistochemical and real-time polymerase chain reaction (RT-PCR analysis. Material and Methods Thirty animals (Rattus norvegicus, Albinus Wistar were divided into three groups after upper incisors extraction at 7, 14, and 28 days. Micro-CT was evaluated based on the morphometric parameters. Subsequently, the histological analyses and immunostaining of osteoprotegerin (OPG, receptor activator of nuclear kappa B ligand (RANKL and tartrate resistant acid phosphate (TRAP was performed. In addition, RT-PCR analyses of OPG, RANKL, the runt-related transcription factor 2 (RUNX2, osteocalcin (OC, osteopontin (OPN, osterix (OST and receptor activator of nuclear kappa B (RANK were performed to determine the expression of these proteins in the alveolar bone healing. Results Micro-CT: The morphometric parameters of bone volume and trabecular thickness progressively increased over time. Consequently, a gradual decrease in trabecular separation, trabecular space and total bone porosity was observed. Immunohistochemical: There were no differences statistically significant between the positive labeling for OPG, RANKL and TRAP in the different periods. RT-PCR: At 28 days, there was a significant increase in OPG expression, while RANKL expression and the RANKL/OPG ratio both decreased over time. Conclusion Micro-CT showed the newly formed bone had favorable morphometric characteristics of quality and quantity. Beyond the RUNX2, OC, OPN, OST, and RANK proteins expressed in the alveolar bone healing, OPG and RANKL activity showed to be essential for activation of basic

Mate tea (Ilex paraguariensis) improves bone formation in the alveolar socket healing after tooth extraction in rats.

Science.gov (United States)

Brasilino, Matheus da Silva; Stringhetta-Garcia, Camila Tami; Pereira, Camila Scacco; Pereira, Ariana Aparecida Ferreira; Stringhetta, Karina; Leopoldino, Andréia Machado; Crivelini, Marcelo Macedo; Ervolino, Edilson; Dornelles, Rita Cássia Menegati; de Melo Stevanato Nakamune, Ana Cláudia; Chaves-Neto, Antonio Hernandes

2018-04-01

The objective of this study was to investigate the effects of mate tea (MT) [Ilex paraguariensis] on alveolar socket healing after tooth extraction. Sixteen male rats were divided into MT and control groups. MT was administered by intragastric gavage at a dose of 20 mg/kg/day for 28 days before and 28 days after right maxillary incisor extraction. The control group received an equal volume of water. Histopathological and histometric analysis of the neoformed bone area and osteocyte density were performed, as well as immunohistochemical analysis of osteocalcin (OCN), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and manganese superoxide dismutase (MnSOD) in the alveolar socket. Calcium, phosphorus, alkaline phosphatase (ALP) activity, total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in plasma, whereas TRAP activity was determined in serum. Histometry evidenced an increase in bone area (P alveolar socket healing on day 28 after tooth extraction. Regular MT ingestion improves the antioxidant defenses and bone formation, which is beneficial for alveolar socket bone healing after tooth extraction.

Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver.

Science.gov (United States)

Nagashima, Kazuki; Sawa, Shinichiro; Nitta, Takeshi; Prados, Alejandro; Koliaraki, Vasiliki; Kollias, George; Nakashima, Tomoki; Takayanagi, Hiroshi

2017-11-04

The gut-associated lymphoid tissues (GALTs), including Peyer's patches (PPs), cryptopatches (CPs) and isolated lymphoid follicles (ILFs), establish a host-microbe symbiosis by the promotion of immune reactions against gut microbes. Microfold cell inducer (MCi) cells in GALTs are the recently identified mesenchymal cells that express the cytokine RANKL and initiate bacteria-specific immunoglobulin A (IgA) production via induction of microfold (M) cell differentiation. In the previous study, the Twist2-Cre driver was utilized for gene deletion in mesenchymal cells including MCi cells. In order to investigate MCi cells more extensively, it will be necessary to develop experimental tools in addition to the Twist2-Cre driver mice and characterize such drivers in specificity and efficiency. Here we show that M cell differentiation and IgA production are impaired in the targeted deletion of RANKL by the Col6a1-Cre driver. We compared Col6a1-Cre with Twist2-Cre in terms of the specificity for mesenchymal cells in GALTs. Col6a1-Cre CAG-CAT-EGFP mice exhibited EGFP expression in podoplanin + CD31 - cells including MCi cells, while Twist2-Cre mice were shown to target endothelial cells and podoplanin + CD31 - cells. Tnfsf11 fl/Δ Col6a1-Cre mice exhibited the absence of M cells and severe IgA reduction together with an alteration in gut microbial composition. Moreover, we analyzed germ free mice to test whether changes in the microbiota are the cause of M cell deficiency. M cell differentiation was normal in the CPs/ILFs of germ free mice, indicating that MCi cells induce M cells independently of microbial colonization. This study demonstrates that Col6a1-Cre driver mice are as useful as Twist2-Cre driver mice for functional analyses of GALT-resident mesenchymal cells, including MCi cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone resorptive activity in symptomatic and asymptomatic apical lesions of endodontic origin

OpenAIRE

Salinas-Muñoz, M.; Garrido-Flores, M.; Baeza, M.; Huamán-Chipana, P.; García-Sesnich, J.; Bologna, R.; Vernal, R.; Hernández, M.

2017-01-01

Objectives The aim of this study is to assess the levels and diagnostic accuracy of a set of bone resorption biomarkers, including TRAP-5, RANKL, and OPG in symptomatic and asymptomatic apical lesions and controls. Materials and methods Apical tissues from symptomatic and asymptomatic apical periodontitis patients and periodontal ligaments from healthy teeth extracted for orthodontic reasons were processed for tissue homogenization and the levels of TRAP-5, RANKL, and OPG were determined by m...

Planning maximum extraction of a safety pillar in the Most surface mine

Energy Technology Data Exchange (ETDEWEB)

Helis, P; Hess, L; Kubiznak, K [SHR - Banske Projekty, Teplice (Czechoslovakia)

1990-11-01

Discusses planned coal surface mining in the Most mine in the area of the Hnevin safety pillar with coal reserves amounting to about 7.5 Mt. The following aspects are evaluated: coal reserves and their distribution in the pillar, coal seam thickness and dip angles, water conditions, water influx rates, mechanical properties of the overburden and strata situated in the seam floor, slope stability and hazards of landslides, effects of water influx on landslide hazards, types of bucket wheel excavators used for overburden removal and mining, types of belt conveyors used for mine haulage, stackers, position of mining equipment in the mine. A scheme developed by Banske Projekty Teplice for partial extraction of the safety pillar would result in extraction of 4.5 Mt coal. About 1.7 Mt coal would be left in a safety coal layer about 10.0 m thick situated in the floor in zones with landslide hazards. KU 300 bucket wheel excavators, belt conveyors 1,200 mm wide and ZP 2,500 stackers would be used. 4 refs.

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.

Program support of the automated system of planned calculations of the Oil and Gas Extracting Administration

Energy Technology Data Exchange (ETDEWEB)

Ashkinuze, V G; Reznikovskiy, P T

1978-01-01

An examination is made of the program support of the Automated System of Planned Calculations (ASPC) of the oil and Gas Extracting Administration (OGEA). Specific requirements for the ASPC of the OGEA are indicated and features of its program realization. In developing the program support of the system, an approach of parametric programming was used. A formal model of the ASPC OGEA is described in detail. It was formed in a theoretical-multiple language. Sets with structure of a tree are examined. They illustrate the production and administrative hierarchical structure of the planning objects in the oil region. The top of the tree corresponds to the OGEA as a whole. In the simplest realization, the tree has two levels of hierarchy: association and field. In general features, a procedure is described for possible use of the system by the planning workers. A plan is presented for program support of the ASPC OGEA, in light of whose specific nature a large part of the programs which realize this system are written in a language ASSEMBLER.

Test plan for the FY 1997 rebound study at the carbon tetrachloride soil vapor extraction site

International Nuclear Information System (INIS)

Rohay, V.J.; Tranbarger, R.K.

1996-11-01

This test plan describes the strategy and field measurements designed to evaluate the potential rebound of carbon tetrachloride vapor concentrations following cessation of soil vapor extraction (SVE) operations at the 200-ZP-2 Operable Unit in the 200 West Area of the Hanford Site. Soil vapor extraction was initiated in February 1992 as the preferred remedial alternative of the Carbon Tetrachloride Expedited Response Action for removal of carbon tetrachloride from the unsaturated zone beneath the primary carbon tetrachloride disposal sites. The magnitude, extent, and rate of rebound in carbon tetrachloride vapor concentrations will help determine the availability of additional carbon tetrachloride for removal using SVE. At the conclusion of the field measurements, a report will be completed to evaluate the results of the rebound study

A-Type Cranberry Proanthocyanidins Inhibit the RANKL-Dependent Differentiation and Function of Human Osteoclasts

Directory of Open Access Journals (Sweden)

Amy B. Howell

2011-03-01

Full Text Available This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP staining, while the secretion of interleukin-8 (IL-8 and matrix metalloproteinases (MMPs was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 µg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 µg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 µg/ml affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.

A SCHEMA FOR EXTRACTION OF INDOOR PEDESTRIAN NAVIGATION GRID NETWORK FROM FLOOR PLANS

Directory of Open Access Journals (Sweden)

L. Niu

2016-06-01

Full Text Available The requirement of the indoor navigation related tasks such emergency evacuation calls for efficient solutions for handling data sources. Therefore, the navigation grid extraction from existing floor plans draws attentions. To this, we have to thoroughly analyse the source data, such as Autocad dxf files. Then, we could establish a sounding navigation solution, which firstly complements the basic navigation rectangle boundaries, secondly subdivides these rectangles and finally generates accessible networks with these refined rectangles. Test files are introduced to validate the whole workflow and evaluate the solution performance. In conclusion, we have achieved the preliminary step of forming up accessible network from the navigation grids.

a Schema for Extraction of Indoor Pedestrian Navigation Grid Network from Floor Plans

Science.gov (United States)

Niu, Lei; Song, Yiquan

2016-06-01

The requirement of the indoor navigation related tasks such emergency evacuation calls for efficient solutions for handling data sources. Therefore, the navigation grid extraction from existing floor plans draws attentions. To this, we have to thoroughly analyse the source data, such as Autocad dxf files. Then, we could establish a sounding navigation solution, which firstly complements the basic navigation rectangle boundaries, secondly subdivides these rectangles and finally generates accessible networks with these refined rectangles. Test files are introduced to validate the whole workflow and evaluate the solution performance. In conclusion, we have achieved the preliminary step of forming up accessible network from the navigation grids.

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

Bone resorptive activity in symptomatic and asymptomatic apical lesions of endodontic origin.

Science.gov (United States)

Salinas-Muñoz, M; Garrido-Flores, M; Baeza, M; Huamán-Chipana, P; García-Sesnich, J; Bologna, R; Vernal, R; Hernández, M

2017-11-01

The aim of this study is to assess the levels and diagnostic accuracy of a set of bone resorption biomarkers, including TRAP-5, RANKL, and OPG in symptomatic and asymptomatic apical lesions and controls. Apical tissues from symptomatic and asymptomatic apical periodontitis patients and periodontal ligaments from healthy teeth extracted for orthodontic reasons were processed for tissue homogenization and the levels of TRAP-5, RANKL, and OPG were determined by multiplex assay. Marker levels were analyzed by Kruskal Wallis test, and diagnostic accuracy was analyzed with ROC curves. Higher levels of RANKL, OPG, and RANKL/OPG ratio were determined in both types of apical lesions compared to healthy periodontal ligament, whereas higher TRAP-5 levels were found only in symptomatic apical lesions (p apical lesions versus healthy controls (AUC = 0.69, p asymptomatic apical periodontitis (AUC = 0.71, p Apical lesions showed higher RANKL and OPG levels than healthy tissues. TRAP-5 levels were the highest in symptomatic apical lesions, suggesting that these represent a progressive state, and showed diagnostic potential. Clinically symptomatic apical periodontitis might represent biologically progressive apical lesions based on TRAP5 levels. TRAP5 has diagnostic potential to identify these lesions, representing a candidate prognostic biomarker.

Acute effects of dietary fatty acids on osteclastogenesis via RANKL/RANK/OPG system.

Science.gov (United States)

Naranjo, M Carmen; Garcia, Indara; Bermudez, Beatriz; Lopez, Sergio; Cardelo, Magdalena P; Abia, Rocio; Muriana, Francisco J G; Montserrat-de la Paz, Sergio

2016-11-01

Postprandial state is directly linked with chronic diseases. We hypothesized that dietary fats may have acute effects on health status by modulating osteoclast differentiation and activation in a fatty acid-dependent manner. In healthy subjects, a fat-enriched meal increased plasma levels of the RANKL (receptor activator of nuclear factor κB ligand)/OPG (osteoprotegerin) ratio (SFAs > MUFAs = PUFAs) in the postprandial state. Postprandial TRL-SFAs enhanced tartrate-resistant acid phosphatase (TRAP) activity and the expression of osteoclast marker genes (TRAP, OSCAR, RANK, and CATHK) while downregulated the expression of OPG gene in human monocyte-derived osteoclasts. These effects were not observed with monounsaturated fatty acid (MUFA)-enriched postprandial triglyceride-rich lipoproteins (TRLs). Moreover, postprandial TRL-SFAs increased the release of osteoclastogenic cytokines (TNF-α, IL-1β, and IL-6) meanwhile TRL-MUFAs and TRL-PUFAs increased the release of anti-osteoclastogenic cytokines (IL-4 and IL-10) in the medium of human monocyte-derived osteoclasts. For the first time, we show that postprandial TRLs are metabolic entities with osteoclastogenic activity and that this property is related to the type of dietary fatty acid in the meal. The osteoclastogenic potency was as follows: SFAs > MUFAs = PUFAs. These exciting findings open opportunities for developing nutritional strategies with olive oil as the principal dietary source of MUFAs, notably oleic acid, to prevent development and progression of osteoclast-related diseases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Development of 1-Amino-4-(phenylamino)anthraquinone-2-sulfonate Sodium Derivatives as a New Class of Inhibitors of RANKL-Induced Osteoclastogenesis.

Science.gov (United States)

Lee, Chia-Chung; Chen, Chun-Liang; Liu, Fei-Lan; Chiou, Chung-Yu; Chen, Tsung-Chih; Wu, Cheng-Chi; Sun, Wei-Hsin; Chang, Deh-Ming; Huang, Hsu-Shan

2016-05-01

A series of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium derivatives was synthesized and evaluated for osteoclast inhibition using a TRAP-staining assay. Among them, two compounds, LCCY-13 and LCCY-15, dose-dependently suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Moreover, the cytotoxicity assay on RAW264.7 cells suggested that the inhibition of osteoclastic bone resorption by these compounds was not a result of their cytotoxicity. Further, the inhibitory activities of compounds LCCY-13 and LCCY-15 were further confirmed by including specific inhibition of NFATc1 expression levels in nuclei using an immunofluorescent analysis. In addition, LCCY-13 and LCCY-15 also significantly attenuated the bone resorption activity of osteoclasts according to a pit formation assay. Thus, a new class of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium compounds might be considered as an essential lead structure for the further development of anti-resorptive agents. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of a signal-extraction scheme for resonant sideband extraction

International Nuclear Information System (INIS)

Kokeyama, K; Kawazoe, F; Sugamoto, A; Somiya, K; Sato, S; Kawamura, S

2008-01-01

As a future plan, an advanced gravitational-wave detector will employ an optical configuration of resonant sideband extraction (RSE), achieved with an additional mirror at the signal-detection port of the power-recycled Fabry-Perot Michelson interferometer. To control the complex coupled cavity system, one of the most important design issues is how to extract the longitudinal control signals of the cavities. We have developed a new signal-extraction scheme which provides an appropriate sensing matrix. The new method uses two sets of sidebands: one of the sideband components satisfies the critical coupling condition for the RSE interferometer and reaches the signal-extraction port, and the other sideband is completely reflected by the Michelson interferometer. They provide a diagonalized sensing matrix and enable the RSE control to be robust

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

Science.gov (United States)

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

Facility effluent monitoring plan for the plutonium-uranium extraction facility

International Nuclear Information System (INIS)

Nickels, J.M.; Geiger, J.L.

1992-11-01

A facility effluent monitoring plan is required by the US Department of Energy in DOE Order 5400.1 for any operations that involve hazardous materials and radioactive substances that could impact employee or public safety or the environment. A facility effluent monitoring plan determination was performed during Calendar Year 1991 and the evaluation requires the need for a facility effluent monitoring plan. This document is prepared using the specific guidelines identified. in. A Guide for Preparing Hanford Site Facility Effluent Monitoring Plans, WHC-EP-0438. This facility effluent monitoring plan assesses effluent monitoring systems and evaluates whether they are adequate to ensure the public health and safety as specified in applicable federal, state, and local requirements

Extraction of Thyme Oil: Comparison between Hydrodistillation and Supercritical CO2 Extraction

Czech Academy of Sciences Publication Activity Database

Aleksovski, S. A.; Sovová, Helena; Poposka, F. A.

2001-01-01

Roč. 51, č. 4 (2001), s. 305-310 ISSN 1330-0075 Institutional research plan: CEZ:AV0Z4072921 Keywords : thymus serpyllum * supercritical fluid extraction * assential oil Subject RIV: CI - Industrial Chemistry, Chemical Engineering

Approach to novel functional foods for stress control 4. Regulation of serotonin transporter by food factors.

Science.gov (United States)

Ito, Mikiko; Haito, Sakiko; Furumoto, Mari; Kawai, Yoshichika; Terao, Junji; Miyamoto, Ken-ichi

2005-11-01

Serotonin transporters (SERTs) are pre-synaptic proteins specialized for the clearance of serotonin following vesicular release at central nervous system (CNS) and enteric nervous system synapses. SERTs are high affinity targets in vivo for antidepressants such as serotonin selective reuptake inhibitors (SSRIs). These include 'medical' psychopharmacological agents such as analgesics and antihistamines, a plant extract called St John's Wort (Hypericum). Osteoclasts are the primary cells responsible for bone resorption. They arise by the differentiation of osteoclast precursors of the monocyte/macrophage lineage. The expression of SERTs was increased in RANKL-induced osteoclast-like cells. Using RANKL stimulation of RAW264.7 cells as a model system for osteoclast differentiation, we studied the direct effects of food factor on serotonin uptake. The SSRIs (fluoxetine and fluvoxamine) inhibited markedly (approximately 95%) in serotonin transport in differentiated osteoclast cells. The major components of St. John's Wort, hyperforin and hypericine were significantly decreased in serotonin transport activity. Thus, a new in vitro model using RANKL-induced osteoclast-like cells may be useful to analyze the regulation of SERT by food factors and SSRIs.

New plan of strategy and organization. Annual report 1995; Ny strategisk plan og organisasjon. Aarsberetning 1995

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-10-01

The annual report from EFI (Norwegian Research Institute for Electricity) relates to an new strategic plan and organization of the institute. An example of this is the Research Council of Norway`s new R and D programme EFFEKT, which will be a major locomotive for research up to the year 2000. Topics are: EFI`s new strategic plan and organization; extracts from the Board`s annual report; extract from the accounts; diagnostic testing of circuit-breakers; breakdown and interruption statistics from the grid; power system reliability

Osteoporosis Recovery by Antrodia camphorata Alcohol Extracts through Bone Regeneration in SAMP8 Mice

Directory of Open Access Journals (Sweden)

Hen-Yu Liu

2016-01-01

Full Text Available Antrodia camphorata has previously demonstrated the efficacy in treating cancer and anti-inflammation. In this study, we are the first to evaluate Antrodia camphorata alcohol extract (ACAE for osteoporosis recovery in vitro with preosteoblast cells (MC3T3-E1 and in vivo with an osteoporosis mouse model established in our previous studies, ovariectomized senescence accelerated mice (OVX-SAMP8. Our results demonstrated that ACAE treatment was slightly cytotoxic to preosteoblast at 25 μg/mL, by which the osteogenic gene expression (RUNX2, OPN, and OCN was significantly upregulated with an increased ratio of OPG to RANKL, indicating maintenance of the bone matrix through inhibition of osteoclastic pathway. Additionally, evaluation by Alizarin Red S staining showed increased mineralization in ACAE-treated preosteoblasts. For in vivo study, our results indicated that ACAE inhibits bone loss and significantly increases percentage bone volume, trabecular bone number, and bone mineral density in OVX-SAMP8 mice treated with ACAE. Collectively, in vitro and in vivo results showed that ACAE could promote osteogenesis and prevent bone loss and should be considered an evidence-based complementary and alternative medicine for osteoporosis therapy through the maintenance of bone health.

Transcriptional regulation of human RANK ligand gene expression by E2F1

International Nuclear Information System (INIS)

Hu Yan; Sun Meng; Nadiminty, Nagalakshmi; Lou Wei; Pinder, Elaine; Gao, Allen C.

2008-01-01

Receptor activator of nuclear factor kappa B ligand (RANKL) is a critical osteoclastogenic factor involved in the regulation of bone resorption, immune function, the development of mammary gland and cardiovascular system. To understand the transcriptional regulation of RANKL, we amplified and characterized a 1890 bp 5'-flanking sequence of human RANKL gene (-1782 bp to +108 bp relative to the transcription start site). Using a series of deletion mutations of the 1890 bp RANKL promoter, we identified a 72 bp region (-172 to -100 bp) mediating RANKL basal transcriptional activity. Sequence analysis revealed a putative E2F binding site within this 72 bp region in the human RANKL promoter. Overexpression of E2F1 increased RANKL promoter activity, while down-regulation of E2F1 expression by small interfering RNA decreased RANKL promoter activity. RT-PCR and enzyme linked immunosorbent assays (ELISA) further demonstrated that E2F1 induced the expression of RANKL. Electrophoretic gel mobility shift assays (EMSA) and antibody competition assays confirmed that E2F1 proteins bind to the consensus E2F binding site in the RANKL promoter. Mutation of the E2F consensus binding site in the RANKL promoter profoundly reduced the basal promoter activity and abolished the transcriptional modulation of RANKL by E2F1. These results suggest that E2F1 plays an important role in regulating RANKL transcription through binding to the E2F consensus binding site

Citizen-Centric Urban Planning through Extracting Emotion Information from Twitter in an Interdisciplinary Space-Time-Linguistics Algorithm

Directory of Open Access Journals (Sweden)

Bernd Resch

2016-07-01

Full Text Available Traditional urban planning processes typically happen in offices and behind desks. Modern types of civic participation can enhance those processes by acquiring citizens’ ideas and feedback in participatory sensing approaches like “People as Sensors”. As such, citizen-centric planning can be achieved by analysing Volunteered Geographic Information (VGI data such as Twitter tweets and posts from other social media channels. These user-generated data comprise several information dimensions, such as spatial and temporal information, and textual content. However, in previous research, these dimensions were generally examined separately in single-disciplinary approaches, which does not allow for holistic conclusions in urban planning. This paper introduces TwEmLab, an interdisciplinary approach towards extracting citizens’ emotions in different locations within a city. More concretely, we analyse tweets in three dimensions (space, time, and linguistics, based on similarities between each pair of tweets as defined by a specific set of functional relationships in each dimension. We use a graph-based semi-supervised learning algorithm to classify the data into discrete emotions (happiness, sadness, fear, anger/disgust, none. Our proposed solution allows tweets to be classified into emotion classes in a multi-parametric approach. Additionally, we created a manually annotated gold standard that can be used to evaluate TwEmLab’s performance. Our experimental results show that we are able to identify tweets carrying emotions and that our approach bears extensive potential to reveal new insights into citizens’ perceptions of the city.

RANKL inhibition with denosumab does not influence 3-year progression of aortic calcification or incidence of adverse cardiovascular events in postmenopausal women with osteoporosis and high cardiovascular risk.

Science.gov (United States)

Samelson, Elizabeth J; Miller, Paul D; Christiansen, Claus; Daizadeh, Nadia S; Grazette, Luanda; Anthony, Mary S; Egbuna, Ogo; Wang, Andrea; Siddhanti, Suresh R; Cheung, Angela M; Franchimont, Nathalie; Kiel, Douglas P

2014-02-01

Atherosclerosis and osteoporosis are chronic diseases that progress with age, and studies suggest aortic calcification, an indicator of atherosclerosis, is inversely associated with bone mineral density (BMD). The osteoprotegerin (OPG)/receptor activator of NF-κB (RANK)/RANK ligand (RANKL) system has been proposed as a shared regulatory system for bone and vasculature. Denosumab (DMAb), a monoclonal antibody against RANKL, improved BMD and reduced fracture risk in the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. We evaluated whether or not treatment with DMAb influenced progression of aortic calcification (AC) and incidence of cardiovascular (CV) adverse events. We included 2363 postmenopausal women with osteoporosis (1142 placebo, 1221 DMAb), selected from 7808 participants in the FREEDOM trial (3906 placebo, 3902 DMAb), at high risk of CV events according to modified Raloxifene Use for the Heart (RUTH) criteria. CV adverse events were reported by participants. AC scores were assessed using a semiquantitative method from lateral spine X-rays. Change in AC score from baseline to 12 (n = 1377), 24 (n = 1231), and 36 months (n = 1045) was calculated as AC score at follow-up minus AC score at baseline. AC progression was defined as change in AC score >0. Baseline characteristics, CV risk factors, and AC scores were similar between treatment groups. Mean age of participants was 74 years (range, 60-90), 88% were white, and 77% had AC score >0 at baseline. Frequency of AC progression over 3 years did not differ between women in placebo (22%) and DMAb (22%) groups (p = 0.98). AC progression did not differ between treatment groups when analyzed by baseline estimated glomerular filtration rate or by baseline AC scores. Frequency of CV adverse events did not differ between placebo (40%) and DMAb (38%) groups (p = 0.26). In conclusion, DMAb treatment had no effect on progression of AC or incidence of CV

Skeletal changes in osteoprotegerin and receptor activator of nuclear factor-κb ligand mRNA levels in primary hyperparathyroidism

DEFF Research Database (Denmark)

Stilgren, L.S.; Rettmer, E.; Eriksen, E. F.

2004-01-01

, and treatment of PHPT were included. A transiliac bone biopsy was done before (n = 24) and 12 months after parathyroidectomy (PTX) (n = 21). Biopsies were frozen in liquid nitrogen and RNA extracted using Trizol. A competitive RT-PCR assay for RANKL and OPG mRNA using artificial cDNA standards was developed...

Automatic Planning of External Search Engine Optimization

Directory of Open Access Journals (Sweden)

Vita Jasevičiūtė

2015-07-01

Full Text Available This paper describes an investigation of the external search engine optimization (SEO action planning tool, dedicated to automatically extract a small set of most important keywords for each month during whole year period. The keywords in the set are extracted accordingly to external measured parameters, such as average number of searches during the year and for every month individually. Additionally the position of the optimized web site for each keyword is taken into account. The generated optimization plan is similar to the optimization plans prepared manually by the SEO professionals and can be successfully used as a support tool for web site search engine optimization.

Facility effluent monitoring plan for the plutonium-uranium extraction facility

International Nuclear Information System (INIS)

Lohrasbi, J.; Johnson, D.L.; De Lorenzo, D.S.

1993-12-01

A facility effluent monitoring plan is required by the US Department of Energy in DOE Order 5400.1 for any operations that involve hazardous materials and radioactive substances that could impact employee or public safety or the environment. This document is prepared using the specific guidelines identified in A Guide for Preparing Hanford Site Facility Effluent Monitoring Plans, WHC-EP-0438-01. This facility effluent monitoring plan assesses effluent monitoring systems and evaluates whether they are adequate to ensure the public health and safety as specified in applicable federal, state, and local requirements. This facility effluent monitoring plan shall ensure long-range integrity of the effluent monitoring systems by requiring an update whenever a new process or operation introduces new hazardous materials or significant radioactive materials. This document must be reviewed annually even if there are no operational changes, and it must be updated at a minimum of every three years

Facility effluent monitoring plan for the plutonium uranium extraction facility

Energy Technology Data Exchange (ETDEWEB)

Wiegand, D.L.

1994-09-01

A facility effluent monitoring plan is required by the US Department of Energy in DOE Order 5400.1 for any operations that involve hazardous materials and radioactive substances that could impact employee or public safety or the environment. This document is prepared using the specific guidelines identified in A Guide for Preparing Hanford Site Facility Effluent Monitoring Plans, WHC-EP-0438-01. This facility effluent monitoring plan assesses effluent monitoring systems and evaluates whether they are adequate to ensure the public health and safety as specified in applicable federal, state, and local requirements. This facility effluent monitoring plan shall ensure long-range integrity of the effluent monitoring systems by requiring an update whenever a new process or operation introduces new hazardous materials or significant radioactive materials. This document must be reviewed annually even if there are no operational changes, and it must be updated at a minimum of every three years.

Facility effluent monitoring plan for the plutonium uranium extraction facility

International Nuclear Information System (INIS)

Wiegand, D.L.

1994-09-01

A facility effluent monitoring plan is required by the US Department of Energy in DOE Order 5400.1 for any operations that involve hazardous materials and radioactive substances that could impact employee or public safety or the environment. This document is prepared using the specific guidelines identified in A Guide for Preparing Hanford Site Facility Effluent Monitoring Plans, WHC-EP-0438-01. This facility effluent monitoring plan assesses effluent monitoring systems and evaluates whether they are adequate to ensure the public health and safety as specified in applicable federal, state, and local requirements. This facility effluent monitoring plan shall ensure long-range integrity of the effluent monitoring systems by requiring an update whenever a new process or operation introduces new hazardous materials or significant radioactive materials. This document must be reviewed annually even if there are no operational changes, and it must be updated at a minimum of every three years

Facility effluent monitoring plan for the Plutonium Uranium Extraction Facility

International Nuclear Information System (INIS)

Greager, E.M.

1997-01-01

A facility effluent monitoring plan is required by the US Department of Energy in DOE Order 5400.1 for any operations that involve hazardous materials and radioactive substances that could impact employee or public safety or the environment. This document is prepared using the specific guidelines identified in A Guide for Preparing Hanford Site Facility Effluent Monitoring Plans, WHC-EP-0438-01. This facility effluent monitoring plan assesses effluent monitoring systems and evaluates whether these systems are adequate to ensure the public health and safety as specified in applicable federal, state, and local requirements. This facility effluent monitoring plan will ensure long-range integrity of the effluent monitoring systems by requiring an update whenever a new process or operation introduces new hazardous materials or significant radioactive materials. This document must be reviewed annually even if there are no operational changes, and it must be updated, at a minimum, every 3 years

Facility effluent monitoring plan for the plutonium-uranium extraction facility

Energy Technology Data Exchange (ETDEWEB)

Lohrasbi, J.; Johnson, D.L. [Westinghouse Hanford Co., Richland, WA (United States); De Lorenzo, D.S. [Los Alamos Technical Associates, NM (United States)

1993-12-01

A facility effluent monitoring plan is required by the US Department of Energy in DOE Order 5400.1 for any operations that involve hazardous materials and radioactive substances that could impact employee or public safety or the environment. This document is prepared using the specific guidelines identified in A Guide for Preparing Hanford Site Facility Effluent Monitoring Plans, WHC-EP-0438-01. This facility effluent monitoring plan assesses effluent monitoring systems and evaluates whether they are adequate to ensure the public health and safety as specified in applicable federal, state, and local requirements. This facility effluent monitoring plan shall ensure long-range integrity of the effluent monitoring systems by requiring an update whenever a new process or operation introduces new hazardous materials or significant radioactive materials. This document must be reviewed annually even if there are no operational changes, and it must be updated at a minimum of every three years.

NRPB corporate plan

International Nuclear Information System (INIS)

Clarke, Roger

1995-01-01

As with all non-departmental public bodies, the National Radiological Protection Board is required to prepare a Corporate Plan each year. The Plan for 1995/1996 to 1999/2000 is now available as a Board report; extracts from the introductory section are given here. They deal with the Board's statutory duty to provide advice and conduct research and with its power to provide services, all in relation to ionising and non-ionising radiations. (author)

Facility effluent monitoring plan for the plutonium-uranium extraction facility

International Nuclear Information System (INIS)

Thompson, R.J.; Sontage, S.

1991-11-01

A facility effluent monitoring plan is required by the US Department of Energy in DOE Order 5400.1 for any operations that involve hazardous materials and radioactive substances that could impact employee or public safety or the environment. This document is prepared using the specific guidelines identified in A Guide for Preparing Hanford Site Facility Effluent Monitoring Plans, WHC-EP-0438. This facility effluent monitoring plan assesses effluent monitoring systems and evaluates whether they are adequate to ensure the public health and safety as specified in applicable federal, state, and local requirements. This facility effluent monitoring plan is the first annual report. It shall ensure long-range integrity of the effluent monitoring systems by requiring an update whenever a new process or operation introduces new hazardous materials or significant radioactive materials. This document must be reviewed annually even if there are no operational changes, and it must be updated as a minimum every three years

Diluent effects in solvent extraction. The Effects of Diluents in Solvent Extraction - a literature study

International Nuclear Information System (INIS)

Loefstroem-Engdahl, Elin; Aneheim, Emma; Ekberg, Christian; Foreman, Mark; Skarnemark, Gunnar

2010-01-01

The fact that the choice of organic diluent is important for a solvent extraction process goes without saying. Several factors, such as e.g. price, flash point, viscosity, polarity etc. each have their place in the planning of a solvent extraction system. This high number of variables makes the lack of compilations concerning diluent effects to an interesting topic. Often the interest for the research concerning a specific extraction system focuses on the extractant used and the complexes built up during an extraction. The diluents used are often classical ones, even if it has been shown that choice of diluent can affect extraction as well as separation in an extraction system. An attempt to point out important steps in the understanding of diluent effects in solvent extraction is here presented. This large field is, of course, not summarized in this article, but an attempt is made to present important steps in the understanding of diluents effects in solvent extraction. Trying to make the information concerning diluent effects and applications more easily accessible this review offers a selected summarizing of literature concerning diluents effects in solvent extraction. (authors)

Automation model of sewerage rehabilitation planning.

Science.gov (United States)

Yang, M D; Su, T C

2006-01-01

The major steps of sewerage rehabilitation include inspection of sewerage, assessment of structural conditions, computation of structural condition grades, and determination of rehabilitation methods and materials. Conventionally, sewerage rehabilitation planning relies on experts with professional background that is tedious and time-consuming. This paper proposes an automation model of planning optimal sewerage rehabilitation strategies for the sewer system by integrating image process, clustering technology, optimization, and visualization display. Firstly, image processing techniques, such as wavelet transformation and co-occurrence features extraction, were employed to extract various characteristics of structural failures from CCTV inspection images. Secondly, a classification neural network was established to automatically interpret the structural conditions by comparing the extracted features with the typical failures in a databank. Then, to achieve optimal rehabilitation efficiency, a genetic algorithm was used to determine appropriate rehabilitation methods and substitution materials for the pipe sections with a risk of mal-function and even collapse. Finally, the result from the automation model can be visualized in a geographic information system in which essential information of the sewer system and sewerage rehabilitation plans are graphically displayed. For demonstration, the automation model of optimal sewerage rehabilitation planning was applied to a sewer system in east Taichung, Chinese Taiwan.

Automatic Knowledge Extraction and Knowledge Structuring for a National Term Bank

DEFF Research Database (Denmark)

Lassen, Tine; Madsen, Bodil Nistrup; Erdman Thomsen, Hanne

2011-01-01

This paper gives an introduction to the plans and ongoing work in a project, the aim of which is to develop methods for automatic knowledge extraction and automatic construction and updating of ontologies. The project also aims at developing methods for automatic merging of terminological data fr...... various existing sources, as well as methods for target group oriented knowledge dissemination. In this paper, we mainly focus on the plans for automatic knowledge extraction and knowledge structuring that will result in ontologies for a national term bank.......This paper gives an introduction to the plans and ongoing work in a project, the aim of which is to develop methods for automatic knowledge extraction and automatic construction and updating of ontologies. The project also aims at developing methods for automatic merging of terminological data from...

Use of ethanol extracts of Terminalia chebula to prevent periodontal disease induced by dental plaque bacteria.

Science.gov (United States)

Lee, Jongsung; Nho, Youn Hwa; Yun, Seok Kyun; Hwang, Young Sun

2017-02-16

The fruit of the Terminalia chebula tree has been widely used for the treatment of various disorders. Its anti-diabetic, anti-mutagenic, anti-oxidant, anti-bacterial, anti-fungal, and anti-viral effects have been studied. Dental plaque bacteria (DPB) are intimately associated with gingivitis and periodontitis. In the quest for materials that will prove useful in the treatment and prevention of periodontal disease, we investigated the preventive effects of an ethanol extract of Terminalia chebula (EETC) on DPB-induced inflammation and bone resorption. The anti-bacterial effect of EETC was analyzed using the disc diffusion method. The anti-inflammatory effect of EETC was determined by molecular biological analysis of the DPB-mediated culture cells. Prevention of osteoclastic bone resorption by EETC was explored using osteoclast formation and pit formation assays. EETC suppressed the growth of oral bacteria and reduced the induction of inflammatory cytokines and proteases, abolishing the expression of PGE2 and COX-2 and inhibiting matrix damage. By stimulating the DPB-derived lipopolysaccharides, EETC inhibited both osteoclast formation in osteoclast precursors and RANKL expression in osteoblasts, thereby contributing to the prevention of bone resorption. EETC may be a beneficial supplement to help prevent DPB-mediated periodontal disease.

Comparative analysis of extracted heights from topographic maps ...

African Journals Online (AJOL)

Topographic maps represent the three-dimensional landscape by providing relief information in the form of contours in addition to plan information on which natural and man-made landmarks are quite accurately represented. Height information, extractible from topographic maps, comes in handy for most land use planning.

Bone remodeling after hip joint replacement. Numerical Modeling and Comparism with Clinical Observation

Czech Academy of Sciences Publication Activity Database

Klika, Václav; Maršík, František; Landor, I.

2007-01-01

Roč. 14, 3-4 (2007), s. 340-343 ISSN 1212-4575. [Prague-Sydney-Lublin Symposium /9./, Kubát's Podiatric Day /12./. Prague, 19.10.2007-20.10.2007] Institutional research plan: CEZ:AV0Z20760514 Keywords : bone remodeling * prosthesis * RANKL/RANK/OPG pathway Subject RIV: BO - Biophysics

Vznik kortikális jako důsledek mechanické zátěže-osteoporóza jako důsledek biochemické nerovnováhy

Czech Academy of Sciences Publication Activity Database

Klika, V.; Maršík, František; Mařík, I.

2007-01-01

Roč. 12, 1-2 (2007), s. 17-18 ISSN 1212-4575 R&D Projects: GA ČR GA106/03/1073; GA MŠk(CZ) 1M06031 Institutional research plan: CEZ:AV0Z20760514 Keywords : bone remodelling * cortical bone * RANKL-RANK-OPG chain Subject RIV: BO - Biophysics

Multicriteria optimization informed VMAT planning

Energy Technology Data Exchange (ETDEWEB)

Chen, Huixiao; Craft, David L.; Gierga, David P., E-mail: dgierga@partners.org

2014-04-01

We developed a patient-specific volumetric-modulated arc therapy (VMAT) optimization procedure using dose-volume histogram (DVH) information from multicriteria optimization (MCO) of intensity-modulated radiotherapy (IMRT) plans. The study included 10 patients with prostate cancer undergoing standard fractionation treatment, 10 patients with prostate cancer undergoing hypofractionation treatment, and 5 patients with head/neck cancer. MCO-IMRT plans using 20 and 7 treatment fields were generated for each patient on the RayStation treatment planning system (clinical version 2.5, RaySearch Laboratories, Stockholm, Sweden). The resulting DVH of the 20-field MCO-IMRT plan for each patient was used as the reference DVH, and the extracted point values of the resulting DVH of the MCO-IMRT plan were used as objectives and constraints for VMAT optimization. Weights of objectives or constraints of VMAT optimization or both were further tuned to generate the best match with the reference DVH of the MCO-IMRT plan. The final optimal VMAT plan quality was evaluated by comparison with MCO-IMRT plans based on homogeneity index, conformity number of planning target volume, and organ at risk sparing. The influence of gantry spacing, arc number, and delivery time on VMAT plan quality for different tumor sites was also evaluated. The resulting VMAT plan quality essentially matched the 20-field MCO-IMRT plan but with a shorter delivery time and less monitor units. VMAT plan quality of head/neck cancer cases improved using dual arcs whereas prostate cases did not. VMAT plan quality was improved by fine gantry spacing of 2 for the head/neck cancer cases and the hypofractionation-treated prostate cancer cases but not for the standard fractionation–treated prostate cancer cases. MCO-informed VMAT optimization is a useful and valuable way to generate patient-specific optimal VMAT plans, though modification of the weights of objectives or constraints extracted from resulting DVH of MCO

Gingival Crevicular Fluid Turnover Markers in Premenopausal vs Postmenopausal Women receiving Orthodontic Treatment.

Science.gov (United States)

Bitra, Anusha; Rani, B Jhansi; Agarkar, Sanket S; Parihar, Anuj S; Vynath, Gopinath P; Grover, Shekhar

2017-10-01

Orthodontic treatment is one of the commonly used dental treatments. Orthodontic forces act on the bone by modulating the biomolecules, chiefly the osteoprotegerin (OPG), osteopontin (OPN), receptor activator of nuclear factor kappa-B (RANK), and RANK ligand (RANKL) (OPG ligand). Hormonal changes are known to cause marked alteration in the levels of these biomolecules. Hence, we planned this study to evaluate the response of bone biomarkers in the gingival crevicular fluid (GCF) in postmenopausal women undergoing fixed orthodontic therapy. This study included assessment of 50 subjects who underwent orthodontic treatment from June 2012 to July 2016. All the patients were divided into two study groups with 25 patients in each group: premenopausal group and postmenopausal group. Similar orthodontic wires were used for controlling the forces applied in subjects of both the study groups and their GCF levels of RANKL, and OPN was assessed at baseline and 24 hours after the activation of orthodontic forces. All the results were compiled, assessed, and analyzed by Statistical Package for the Social Sciences software version 16.0. Chi-square test, Student's t-test, and Mann-Whitney U test were used for the assessment of the level of significance. The mean values of RANKL and OPN in the premenopausal and postmenopausal groups were found to be 241.52 and 317.15 pg/μL respectively. The mean values of RANKL at baseline in the premenopausal and postmenopausal groups were found to be 7.15 and 3.84 pg/μL respectively. Nonsignificant results were obtained while comparing mean OPN and RANKL level alteration in between the two study groups. The mean alterations in the GCF levels of bone biomarkers are similar for both premenopausal and postmeno-pausal women. For women with either premenopausal or postmenopausal status, orthodontic treatment appears to be equally safer.

Passive vapor extraction feasibility study

International Nuclear Information System (INIS)

Rohay, V.J.

1994-01-01

Demonstration of a passive vapor extraction remediation system is planned for sites in the 200 West Area used in the past for the disposal of waste liquids containing carbon tetrachloride. The passive vapor extraction units will consist of a 4-in.-diameter pipe, a check valve, a canister filled with granular activated carbon, and a wind turbine. The check valve will prevent inflow of air that otherwise would dilute the soil gas and make its subsequent extraction less efficient. The granular activated carbon is used to adsorb the carbon tetrachloride from the air. The wind turbine enhances extraction rates on windy days. Passive vapor extraction units will be designed and operated to meet all applicable or relevant and appropriate requirements. Based on a cost analysis, passive vapor extraction was found to be a cost-effective method for remediation of soils containing lower concentrations of volatile contaminants. Passive vapor extraction used on wells that average 10-stdft 3 /min air flow rates was found to be more cost effective than active vapor extraction for concentrations below 500 parts per million by volume (ppm) of carbon tetrachloride. For wells that average 5-stdft 3 /min air flow rates, passive vapor extraction is more cost effective below 100 ppm

Osteoprotegerin in bone metastases: mathematical solution to the puzzle.

Directory of Open Access Journals (Sweden)

Marc D Ryser

Full Text Available Bone is a common site for cancer metastasis. To create space for their growth, cancer cells stimulate bone resorbing osteoclasts. Cytokine RANKL is a key osteoclast activator, while osteoprotegerin (OPG is a RANKL decoy receptor and an inhibitor of osteoclastogenesis. Consistently, systemic application of OPG decreases metastatic tumor burden in bone. However, OPG produced locally by cancer cells was shown to enhance osteolysis and tumor growth. We propose that OPG produced by cancer cells causes a local reduction in RANKL levels, inducing a steeper RANKL gradient away from the tumor and towards the bone tissue, resulting in faster resorption and tumor expansion. We tested this hypothesis using a mathematical model of nonlinear partial differential equations describing the spatial dynamics of OPG, RANKL, PTHrP, osteoclasts, tumor and bone mass. We demonstrate that at lower expression rates, tumor-derived OPG enhances the chemotactic RANKL gradient and osteolysis, whereas at higher expression rates OPG broadly inhibits RANKL and decreases osteolysis and tumor burden. Moreover, tumor expression of a soluble mediator inducing RANKL in the host tissue, such as PTHrP, is important for correct orientation of the RANKL gradient. A meta-analysis of OPG, RANKL and PTHrP expression in normal prostate, carcinoma and metastatic tissues demonstrated an increase in expression of OPG, but not RANKL, in metastatic prostate cancer, and positive correlation between OPG and PTHrP in metastatic prostate cancer. The proposed mechanism highlights the importance of the spatial distribution of receptors, decoys and ligands, and can be applied to other systems involving regulation of spatially anisotropic processes.

SORPTION OF CO2-EXTRACTS OF SPICES TO THE TOMATO PASTE

Directory of Open Access Journals (Sweden)

A. M. Gadzhieva

2014-01-01

Full Text Available The possibility of the production of products without the preservatives, the fillers, the chemical, undesirable aromatic substances and other additives is one of the prime advantages of technologies, based on the use of СO2- extraction. There is great theoretical and practical interest in the study of the absorption of СO2- extracts on the tomato carriers with the production of ketchup. There are examined the principles of the optimization of the process of absorbing the СO2- extracts of anise, ginger and amaranth on the tomato paste with the production of ketchup. There are examined the principles of the optimization of the process of absorbing the СO2- extracts of anise, ginger and amaranth on the tomato paste with the production of ketchup. The miscella of the extracts of spices is brought to the tomato paste. This was reached by the selection of СO2- miscella from the extractor under the pressure to 6 MPa. Then solvent due to a pressure decrease in the apparatus to the atmospheric instantly was moved away from the obtained material. The degrees of the absorption of the СO2- extracts of anise, ginger, amaranth and sea buckthorn are determined. Calculations were performed through the program of that composed in medium of the mathematical packet “Of mathCAD 14”. As a result conducted investigations are obtained the equations of regression for absorbing of anise, amaranth and ginger on the tomato paste depending on the concentration of individual extracts in the miscella. The possibilities of the method of complete factor experiment are shown. In the utilized method of the mathematical planning of experiment adapt the dimensionless coded composition factors x1 and x2. In the experiment is realized plan 23. Was used the central composition plan, which corresponds to the requirement of rotatable, i.e., the plan, which makes it possible to obtain the model, capable of predicting the value of the parameter of optimization with the

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.

RANK and RANK ligand expression in primary human osteosarcoma

Directory of Open Access Journals (Sweden)

Daniel Branstetter

2015-09-01

Our results demonstrate RANKL expression was observed in the tumor element in 68% of human OS using IHC. However, the staining intensity was relatively low and only 37% (29/79 of samples exhibited≥10% RANKL positive tumor cells. RANK expression was not observed in OS tumor cells. In contrast, RANK expression was clearly observed in other cells within OS samples, including the myeloid osteoclast precursor compartment, osteoclasts and in giant osteoclast cells. The intensity and frequency of RANKL and RANK staining in OS samples were substantially less than that observed in GCTB samples. The observation that RANKL is expressed in OS cells themselves suggests that these tumors may mediate an osteoclastic response, and anti-RANKL therapy may potentially be protective against bone pathologies in OS. However, the absence of RANK expression in primary human OS cells suggests that any autocrine RANKL/RANK signaling in human OS tumor cells is not operative, and anti-RANKL therapy would not directly affect the tumor.

Extraction from TEV-range accelerators using bent crystal channeling

International Nuclear Information System (INIS)

Carrigan, R.A. Jr.; Jackson, G.; Murphy, C.T.; Newberger, B.

1993-01-01

Plans and first results from Fermilab Experiment 853 are presented. E853 is an experiment to test the feasibility and efficiency of extracting a low-intensity beam from the halo of the Tevatron using channeling in a bent silicon crystal. The motivation of the experiment is to apply crystal extraction to trans-TeV accelerators like the SSC. Channeling developments related to crystal extraction and some early results from accelerator studies at the Tevatron are presented

Extraction of bitter acids from hops and hop products using pressurized solvent extraction (PSE)

Czech Academy of Sciences Publication Activity Database

Čulík, J.; Jurková, M.; Horák, T.; Čejka, P.; Kellner, V.; Dvořák, J.; Karásek, Pavel; Roth, Michal

2009-01-01

Roč. 115, č. 3 (2009), s. 220-225 ISSN 0046-9750 R&D Projects: GA ČR GA203/08/1536; GA MŠk 1M0570 Institutional research plan: CEZ:AV0Z40310501 Keywords : hops * bitter acids * pressurized solvent extraction Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 1.000, year: 2009

Effects of extracellular magnesium extract on the proliferation and differentiation of human osteoblasts and osteoclasts in coculture.

Science.gov (United States)

Wu, Lili; Feyerabend, Frank; Schilling, Arndt F; Willumeit-Römer, Regine; Luthringer, Bérengère J C

2015-11-01

Coculture of osteoblasts and osteoclasts is a subject of interest in the understanding of how magnesium (Mg)-based implants influence the bone metabolism and remodeling upon degradation. Human telomerase reverse transcriptase (hTERT) transduced mesenchymal stem cells (SCP-1) were first differentiated into osteoblasts with osteogenic supplements and then further cocultured with peripheral blood mononucleated cells (PBMC) without the addition of osteoclastogenesis promoting factors. Concomitantly, the cultures were exposed to variable Mg extract dilutions (0, 30×, 10×, 5×, 3×, 2× and 1×). Phenotype characterization documented that while 2× dilution of Mg extract was extremely toxic to osteoclast monoculture, monocytes in coculture with osteoblasts exhibited a greater tolerance to higher Mg extract concentration. The dense growth of osteoblasts in cultures with 1× dilution of Mg extract suggested that high concentration of Mg extract promoted osteoblast proliferation/differentiation behavior. The results of intracellular alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activities as well as protein and gene expressions of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and osteoclast-associated receptor (OSCAR) revealed significantly enhanced formation of osteoblasts whereas decreased osteoclastogenesis in the cultures with high concentrations of Mg extract (2× and 1× dilutions). In conclusion, while an increased osteoinductivity has been demonstrated, the impact of potentially decreased osteoclastogenesis around the Mg-based implants should be also taken into account. Cocultures containing both bone-forming osteoblasts and bone-resorbing osteoclasts should be preferentially performed for in vitro cytocompatibility assessment of Mg-based implants as they more closely mimic the in vivo environment. An attractive human osteoblasts and osteoclasts cocultivation regime was

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.

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.

Vulnerability mapping as a tool to manage the environmental impacts of oil and gas extraction.

Science.gov (United States)

Esterhuyse, Surina; Sokolic, Frank; Redelinghuys, Nola; Avenant, Marinda; Kijko, Andrzej; Glazewski, Jan; Plit, Lisa; Kemp, Marthie; Smit, Ansie; Vos, A Tascha; von Maltitz, Michael J

2017-11-01

Various biophysical and socio-economic impacts may be associated with unconventional oil and gas (UOG) extraction. A vulnerability map may assist governments during environmental assessments, spatial planning and the regulation of UOG extraction, as well as decision-making around UOG extraction in fragile areas. A regional interactive vulnerability map was developed for UOG extraction in South Africa. This map covers groundwater, surface water, vegetation, socio-economics and seismicity as mapping themes, based on impacts that may emanate from UOG extraction. The mapping themes were developed using a normative approach, where expert input during the identification and classification of vulnerability indicators may increase the acceptability of the resultant map. This article describes the development of the interactive vulnerability map for South Africa, where UOG extraction is not yet allowed and where regulations are still being developed to manage this activity. The importance and policy implications of using vulnerability maps for managing UOG extraction impacts in countries where UOG extraction is planned are highlighted in this article.

Total glucosides of paeony prevents juxta-articular bone loss in experimental arthritis.

Science.gov (United States)

Wei, Chen Chao; You, Fan Tian; Mei, Li Yu; Jian, Sun; Qiang, Chen Yong

2013-07-21

Total glucosides of paeony (TGP) is a biologically active compound extracted from Paeony root. TGP has been used in rheumatoid arthritis therapy for many years. However, the mechanism by which TGP prevents bone loss has been less explored. TGP was orally administered for 3 months to New Zealand rabbits with antigen-induced arthritis (AIA). Digital x-ray knee images and bone mineral density (BMD) measurements of the subchondral knee bone were performed before sacrifice. Chondrocytes were observed using transmission electron microscopy (TEM). Histological analysis and mRNA expression of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) were evaluated in joint tissues. The BMD value in TGP rabbits was significantly higher compared with that seen in the AIA model rabbits. In addition, the subchondral bone plate was almost completely preserved by TGP treatment, while there was a decrease in bone plate integrity in AIA rabbits. There was less damage to the chondrocytes of the TGP treated group. Immunohistochemical examination of the TGP group showed that a higher percentage of TGP treated chondrocytes expressed OPG as compared to the chondrocytes isolated from AIA treated animals. In contrast, RANKL expression was significantly decreased in the TGP treated group compared to the AIA group. In support of the immunohistochemistry data, the expression of RANKL mRNA was decreased and OPG mRNA expression was enhanced in the TGP group when compared to that of the AIA model group. These results reveal that TGP suppresses juxta-articular osteoporosis and prevents subchondral bone loss. The decreased RANKL and increased OPG expression seen in TGP treated animals could explain how administration of TGP maintains higher BMD.

Novel Approaches to Breast Cancer Prevention and Inhibition of Metastases

Science.gov (United States)

2016-10-01

Using mouse genetics, we showed that RANKL and its receptor RANK are critical regulators of sex hormone and BRCA1 mutation-driven breast cancer...into breast cancer patients and controls due to self reporting and histological examination. We have tested differences in RANKL, OPG and RANKL/OPG...cohort, we determined RANKL and OPG serum levels of participants from the Bruneck study [28, 29], that allowed us to analyse matched patient samples

Du-Zhong (Eucommia ulmoides Oliv.) Cortex Extract Alleviates Lead Acetate-Induced Bone Loss in Rats.

Science.gov (United States)

Qi, Shanshan; Zheng, Hongxing; Chen, Chen; Jiang, Hai

2018-05-09

The purpose of this study was to evaluate the protective effect of Du-Zhong cortex extract (DZCE) on lead acetate-induced bone loss in rats. Forty female Sprague-Dawley rats were randomly divided into four groups: group I (control) was provided with distilled water. Group II (PbAc) received 500 ppm lead acetate in drinking water for 60 days. Group III (PbAc+DZCE) received 500 ppm lead acetate in drinking water, and given intragastric DZCE (100 mg/kg body weight) for 60 days. Group IV (DZCE) was given intragastric DZCE (100 mg/kg body weight) for 60 days. The bone mineral density, serum biochemical markers, bone histomorphology, and bone marrow adipocyte parameters were analyzed using dual-energy X-ray absorptiometry, biochemistry, histomorphometry, and histopathology, respectively. The results showed that the lumbar spine and femur bone mineral density was significantly decreased in PbAc group compared with the control (P  0.05, vs. control and DZCE group). Serum calcium and serum phosphorus in the PbAc+DZCE group were greater than that in the PbAc group (P control group (P control, and DZCE groups (P > 0.05). Serum OPG and OPG/RANKL ration were significantly higher in the PbAc+DZCE group than that in the PbAc group (P control group, but those were restored in the PbAc+DZCE groups. The bone marrow adipocyte number, percent adipocyte volume per tissue volume (AV/TV), and mean adipocyte diameter were significantly increased in the PbAc group compared to the control (P control group were not significant. The results above indicate that the Du-Zhong cortex extract has protective effects on both stimulation of bone formation and suppression of bone resorption in lead-exposed rats, therefore, Du-Zhong cortex extract has the potential to prevent or treat osteoporosis resulting from lead expose.

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.

A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts

DEFF Research Database (Denmark)

Henriksen, Kim; Andreassen, Kim V; Thudium, Christian S

2012-01-01

Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium wa...... dependent and independent of their resorptive activity, secrete factors stimulating osteoblastic bone formation.......Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium...... release. The osteoblastic cell line 2T3 was treated with 50% of CM or non-CM for 12days. Bone formation was assessed by Alizarin Red extraction. CM from mature osteoclasts induced bone formation, while CM from macrophages did not. Non-resorbing osteoclasts generated from osteopetrosis patients showed...

RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation

International Nuclear Information System (INIS)

Sundaram, Kumaran; Nishimura, Riko; Senn, Joseph; Youssef, Rimon F.; London, Steven D.; Reddy, Sakamuri V.

2007-01-01

Osteoclast differentiation is tightly regulated by receptor activator of NF-κB ligand (RANKL) signaling. Matrix metalloproteinase-9 (MMP-9), a type IV collagenase is highly expressed in osteoclast cells and plays an important role in degradation of extracellular matrix; however, the molecular mechanisms that regulate MMP-9 gene expression are unknown. In this study, we demonstrate that RANKL signaling induces MMP-9 gene expression in osteoclast precursor cells. We further show that RANKL regulates MMP-9 gene expression through TRAF6 but not TRAF2. Interestingly, blockade of p38 MAPK activity by pharmacological inhibitor, SB203580 increases MMP-9 activity whereas ERK1/2 inhibitor, PD98059 decreases RANKL induced MMP-9 activity in RAW264.7 cells. These data suggest that RANKL differentially regulates MMP-9 expression through p38 and ERK signaling pathways during osteoclast differentiation. Transient expression of MMP-9 gene (+ 1 to - 1174 bp relative to ATG start codon) promoter-luciferase reporter plasmids in RAW264.7 cells and RANKL stimulation showed significant increase (20-fold) of MMP-9 gene promoter activity; however, there is no significant change with respect to + 1 bp to - 446 bp promoter region and empty vector transfected cells. These results indicated that MMP-9 promoter sequence from - 446 bp to - 1174 bp relative to start codon is responsive to RANKL stimulation. Sequence analysis of the mouse MMP-9 gene promoter region further identified the presence of binding motif (- 1123 bp to - 1153 bp) for the nuclear factor of activated T cells 1 (NFATc1) transcription factor. Inhibition of NFATc1 using siRNA and VIVIT peptide inhibitor significantly decreased RANKL stimulation of MMP-9 activity. We further confirm by oligonucleotide pull-down assay that RANKL stimuli enhanced NFATc1 binding to MMP-9 gene promoter element. In addition, over-expression of constitutively active NFAT in RAW264.7 cells markedly increased (5-fold) MMP-9 gene promoter activity in

Dual Effect of Chrysanthemum indicum Extract to Stimulate Osteoblast Differentiation and Inhibit Osteoclast Formation and Resorption In Vitro

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Jong Min Baek

2014-01-01

Full Text Available The risk of bone-related diseases increases due to the imbalance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively. The goal in the development of antiosteoporotic treatments is an agent that will improve bone through simultaneous osteoblast stimulation and osteoclast inhibition without undesirable side effects. To achieve this goal, numerous studies have been performed to identify novel approaches using natural oriental herbs to treat bone metabolic diseases. In the present study, we investigated the effect of Chrysanthemum indicum extract (CIE on the differentiation of osteoclastic and osteoblastic cells. CIE inhibited the formation of TRAP-positive mature osteoclasts and of filamentous-actin rings and disrupted the bone-resorbing activity of mature osteoclasts in a dose-dependent manner. CIE strongly inhibited Akt, GSK3β, and IκB phosphorylation in RANKL-stimulated bone marrow macrophages and did not show any effects on MAP kinases, including p38, ERK, and JNK. Interestingly, CIE also enhanced primary osteoblast differentiation via upregulation of the expression of alkaline phosphatase and the level of extracellular calcium concentrations during the early and terminal stages of differentiation, respectively. Our results revealed that CIE could have a potential therapeutic role in bone-related disorders through its dual effects on osteoclast and osteoblast differentiation.

Computer aided planning of orthopaedic surgeries: the definition of generic planning steps for bone removal procedures.

Science.gov (United States)

Putzer, David; Moctezuma, Jose Luis; Nogler, Michael

2017-11-01

An increasing number of orthopaedic surgeons are using computer aided planning tools for bone removal applications. The aim of the study was to consolidate a set of generic functions to be used for a 3D computer assisted planning or simulation. A limited subset of 30 surgical procedures was analyzed and verified in 243 surgical procedures of a surgical atlas. Fourteen generic functions to be used in 3D computer assisted planning and simulations were extracted. Our results showed that the average procedure comprises 14 ± 10 (SD) steps with ten different generic planning steps and four generic bone removal steps. In conclusion, the study shows that with a limited number of 14 planning functions it is possible to perform 243 surgical procedures out of Campbell's Operative Orthopedics atlas. The results may be used as a basis for versatile generic intraoperative planning software.

Super/Subcritical Fluid Extractions for Preparation of the Crystalline Titania

Czech Academy of Sciences Publication Activity Database

Matějová, Lenka; Cajthaml, Tomáš; Matěj, Z.; Benada, Oldřich; Klusoň, Petr; Šolcová, Olga

2010-01-01

Roč. 52, č. 2 (2010), s. 215-221 ISSN 0896-8446 R&D Projects: GA ČR GP104/09/P290; GA ČR GA104/09/0694 Institutional research plan: CEZ:AV0Z40720504; CEZ:AV0Z50200510 Keywords : titania * supercritical fluid extraction * pressurised fluid extraction Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.986, year: 2010

Remote Sensing Image in the Application of Agricultural Tourism Planning

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Guojing Fan

2013-06-01

Full Text Available This paper introduces the processing technology of high resolution remote sensing image, the specific making process of tourism map and different remote sensing data in the key application of tourism planning and so on. Remote sensing extracts agricultural tourism planning information, improving the scientificalness and operability of agricultural tourism planning. Therefore remote sensing image in the application of agricultural tourism planning will be the inevitable trend of tourism development.

SigmaPlot 2000, Version 6.00, SPSS Inc. Computer Software Test Plan

Energy Technology Data Exchange (ETDEWEB)

HURLBUT, S.T.

2000-10-24

SigmaPlot is a vendor software product used in conjunction with the supercritical fluid extraction Fourier transform infrared spectrometer (SFE-FTIR) system. This product converts the raw spectral data to useful area numbers. SigmaPlot will be used in conjunction with procedure ZA-565-301, ''Determination of Moisture by Supercritical Fluid Extraction and Infrared Detection.'' This test plan will be performed in conjunction with or prior to HNF-6936, ''HA-53 Supercritical Fluid Extraction System Acceptance Test Plan'', to perform analyses for water. The test will ensure that the software can be installed properly and will manipulate the analytical data correctly.

OSM-ORIENTED METHOD OF MULTIMODAL ROUTE PLANNING

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X. Li

2015-07-01

Full Text Available With the increasing pervasiveness of basic facilitate of transportation and information, the need of multimodal route planning is becoming more essential in the fields of communication and transportation, urban planning, logistics management, etc. This article mainly described an OSM-oriented method of multimodal route planning. Firstly, it introduced how to extract the information we need from OSM data and build proper network model and storage model; then it analysed the accustomed cost standard adopted by most travellers; finally, we used shortest path algorithm to calculate the best route with multiple traffic means.

The potential of chitosan combined with chicken shank collagen as scaffold on bone defect regeneration process in Rattus norvegicus

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Fitria Rahmitasari

2016-12-01

Full Text Available Background: In the field of dentistry, alveolar bone damage can be caused by periodontal disease, traumatic injury due to tooth extraction, cyst enucleation, and tumor surgery. One of the ways to regenerate the bone defect is using graft scaffold. Thus, combination of chitosan and collagen can stimulate osteogenesis. Purpose: The aim of this study was to examine the potential of chitosan combined with chicken shank collagen on bone defect regeneration process. Method: Twelve Rattus norvegicus were prepared as animal models in this research. A bone defect was intentionally created at both of the right and left femoral bones of the models. Next, 24 samples were divided into four groups, namely Group 1 using chitosan – collagen scaffold (50:50, Group 2 using chitosan collagen-scaffold (80:20, Group 3 using chitosan scaffold only, and Control Group using 3% CMC-Na. On 14th day, those animals were sacrificed, and histopathological anatomy examination was conducted to observe osteoclast cells. In addition, immunohistochemistry examination was also performed to observe RANKL expressions. Result: There was a significant difference in RANKL expressions among the groups, except between Group 3 using chitosan scaffold only and control group (p value > 0.05. The highest expression of RANKL was found in Group 1 with chitosan – collagen scaffold (50:50, followed by Group 2 with chitosan-collagen scaffold (80:20. Moreover, there was also a significant difference in osteoclast generation, except between Group 1 using chitosan – collagen scaffold (50:50 and Group 2 using chitosan-collagen scaffold (80:20, p value 0.05. Less osteoclast was found in the groups using chitosan – collagen scaffold (Group 1 and Group 2. Conclusion: Combination of chitosan and chicken shank collagen scaffold can improve regeneration process of bone defect in Rattus novergicus animals through increasing of RANKL expressions, and decreasing of osteoclast.

Electromembrane extraction using stabilized constant d.c. electric current — A simple tool for improvement of extraction performance

Czech Academy of Sciences Publication Activity Database

Šlampová, Andrea; Kubáň, Pavel; Boček, Petr

2012-01-01

Roč. 1234, APR 20 (2012), s. 32-37 ISSN 0021-9673 R&D Projects: GA ČR GAP206/10/1219 Institutional research plan: CEZ:AV0Z40310501 Keywords : electromembrane extraction * sample pretreatment * supported liquid membranes Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.612, year: 2012

Optimizing Conditions for Ultrasound Extraction of Fullerenes from Coal Matrices

Czech Academy of Sciences Publication Activity Database

Vítek, P.; Jehlička, J.; Frank, Otakar; Hamplová, Věra; Pokorná, Zdeňka; Juha, Libor; Boháček, J.

2009-01-01

Roč. 17, č. 2 (2009), s. 109-122 ISSN 1536-383X R&D Projects: GA ČR GA205/07/0772; GA ČR GA205/03/1468 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z10100520 Keywords : fullerene C60 * Ultrasound -assisted extraction * Extraction yield * Fullerene decomposition Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.710, year: 2009

Solid-phase extraction of berries’ anthocyanins and evaluation of their antioxidative properties

Czech Academy of Sciences Publication Activity Database

Denev, P.; Číž, Milan; Ambrožová, Gabriela; Lojek, Antonín; Yanakieva, I.; Kratchanova, M.

2010-01-01

Roč. 123, č. 4 (2010), s. 1055-1061 ISSN 0308-8146 R&D Projects: GA MŠk(CZ) OC08058 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : anthocyanins * solid-phase extraction * berry extracts Subject RIV: BO - Biophysics Impact factor: 3.458, year: 2010

Feature-based plan adaptation for fast treatment planning in scanned ion beam therapy

International Nuclear Information System (INIS)

Chen Wenjing; Gemmel, Alexander; Rietzel, Eike

2013-01-01

We propose a plan adaptation method for fast treatment plan generation in scanned ion beam therapy. Analysis of optimized treatment plans with carbon ions indicates that the particle number modulation of consecutive rasterspots in depth shows little variation throughout target volumes with convex shape. Thus, we extract a depth-modulation curve (DMC) from existing reference plans and adapt it for creation of new plans in similar treatment situations. The proposed method is tested with seven CT serials of prostate patients and three digital phantom datasets generated with the MATLAB code. Plans are generated with a treatment planning software developed by GSI using single-field uniform dose optimization for all the CT datasets to serve as reference plans and ‘gold standard’. The adapted plans are generated based on the DMC derived from the reference plans of the same patient (intra-patient), different patient (inter-patient) and phantoms (phantom-patient). They are compared with the reference plans and a re-positioning strategy. Generally, in 1 min on a standard PC, either a physical plan or a biological plan can be generated with the adaptive method provided that the new target contour is available. In all the cases, the V95 values of the adapted plans can achieve 97% for either physical or biological plans. V107 is always 0 indicating no overdosage, and target dose homogeneity is above 0.98 in all cases. The dose received by the organs at risk is comparable to the optimized plans. The plan adaptation method has the potential for on-line adaptation to deal with inter-fractional motion, as well as fast off-line treatment planning, with either the prescribed physical dose or the RBE-weighted dose. (paper)

Sitagliptin, An Anti-diabetic Drug, Suppresses Estrogen Deficiency-Induced OsteoporosisIn Vivo and Inhibits RANKL-Induced Osteoclast Formation and Bone Resorption In Vitro

Directory of Open Access Journals (Sweden)

Chuandong Wang

2017-06-01

Full Text Available Postmenopausal osteoporosis is a disease characterized by excessive osteoclastic bone resorption. Some anti-diabetic drugs were demonstrated for anti-osteoclastic bone-loss effects. The present study investigated the skeletal effects of chronic administration of sitagliptin, a dipeptidyl peptidase IV (DPP IV inhibitor that is increasingly used for type 2 diabetes treatments, in an estrogen deficiency-induced osteoporosis and elucidated the associated mechanisms. This study indicated that sitagliptin effectively prevented ovariectomy-induced bone loss and reduced osteoclast numbers in vivo. It was also indicated that sitagliptin suppressed receptor activator of nuclear factor-κB ligand (RANKL-mediated osteoclast differentiation, bone resorption, and F-actin ring formation in a manner of dose-dependence. In addition, sitagliptin significantly reduced the expression of osteoclast-specific markers in mouse bone-marrow-derived macrophages, including calcitonin receptor (Calcr, dendrite cell-specific transmembrane protein (Dc-stamp, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 (Nfatc1. Further study indicated that sitagliptin inhibited osteoclastogenesis by suppressing AKT and ERK signaling pathways, scavenging ROS activity, and suppressing the Ca2+ oscillation that consequently affects the expression and/or activity of the osteoclast-specific transcription factors, c-Fos and NFATc1. Collectively, these findings suggest that sitagliptin possesses beneficial effects on bone and the suppression of osteoclast number implies that the effect is exerted directly on osteoclastogenesis.

Immunohistochemical detection of receptor activator nuclear κB ligand and osteoprotegerin in odontogenic cysts and tumors.

Science.gov (United States)

de Matos, Felipe Rodrigues; de Moraes, Maiara; das Neves Silva, Emília Beatriz; Galvão, Hébel Cavalcanti; de Almeida Freitas, Roseana

2013-11-01

The aim of the present study was to compare the immunohistochemical detection of receptor activator nuclear κB ligand (RANKL) and osteoprotegerin (OPG) in radicular cysts (RCs), dentigerous cysts (DCs), solid ameloblastomas (SAs), and keratocystic odontogenic tumors (KOTs). A total of 20 RCs, 20 DCs, 20 KOTs, 14 dental follicles (DFs), and 18 SAs were evaluated by immunohistochemistry using anti-RANKL and anti-OPG antibodies. The analysis was quantitative, and the number of positive cells was counted in 10 microscopic high-power fields (400×). The DFs, KOTs, and SAs showed higher expression of RANKL than did the RCs and DCs in the epithelium (P < .05). The epithelial expression of OPG was higher in the DFs, KOTs, RCs, and DCs than in the SAs (P < .05). The ratio of OPG less than RANKL was more frequent in SAs and OPG greater than RANKL in DCs (P < .05). Our results have shown differences in RANKL and OPG detection in the odontogenic cysts and tumors studied. The higher RANKL and lower OPG detection in SA could play a role in bone resorption, compatible with the tumor's biologic behavior. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Die Rolle von RANK-Ligand und Osteoprotegerin bei Osteoporose

Directory of Open Access Journals (Sweden)

Hofbauer LC

2004-01-01

Full Text Available Receptor activator of nuclear factor (NF- κB ligand (RANKL, sein zellulärer Rezeptor RANK und der Decoy-Rezeptor Osteoprotegerin (OPG stellen ein essentielles Zytokinsystem für die Zellbiologie von Osteoklasten dar. Verschiedene Untersuchungen belegen die Bedeutung von Störungen des OPG/RANKL/RANK-Systems bei der Pathogenese metabolischer Knochenerkrankungen. In dieser Arbeit werden die wichtigsten Störungen des OPG/RANKL/RANK-Systems bei verschiedenen Osteoporoseformen dargestellt. Östrogenrezeptor- (ER- Agonisten wie 17 β-Östradiol, Raloxifen und Genistein stimulieren die osteoblastäre Produktion von OPG durch Aktivierung von ER- α in vitro, während Lymphozyten von Patientinnen mit Östrogenmangel RANKL überexprimieren. Die parenterale Gabe von OPG vermag den mit Östrogenmangel assoziierten Knochenverlust im Tiermodell und in einer kleineren klinischen Studie zu verhindern. Glukokortikoide und Immunsuppressiva steigern gleichzeitig die RANKL-Expression und hemmen die OPG-Produktion in osteoblastären Zellen in vitro. Glukokortikoide sind auch in vivo imstande, die OPG-Serumspiegel deutlich zu reduzieren. Dagegen hemmen biomechanische Reize in vitro die RANKL-Produktion und steigern die OPG-Produktion. Ein Fehlen dieser biomechanischen Reize bei längerer Immobilisierung kann daher den RANKL/OPG-Quotienten steigern, während die tierexperimentelle Immobilisierungs-Osteoporose durch die parenterale Gabe von OPG gemildert werden kann.

The Relationship Between Vitamin D Levels and Receptor Activator of Nuclear Factor Ligand in Hashimoto’s Thyroiditis

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Hakan Yavuzer

2017-12-01

Full Text Available Aim: In order to analyze the relationship of Hashimoto’s thyroiditis with vitamin D and osteoclastogenic markers, we investigated vitamin D, osteoprotegerin (OPG and receptor activator of nuclear factor ligand (RANKL levels in patients over 60 years with and without Hashimoto’s thyroiditis. Methods: Eighty three female patients (49 with and 34 without Hashimoto’s thyroiditis, who attended the endocrinology and geriatrics departments between May 2013 and October 2013 were included in the study. Results: There was no statistically significant difference in the levels of vitamin D, OPG and RANKL between the groups. Vitamin D was significantly correlated with OPG and RANKL in patients with Hashimoto’s thyroiditis. In addition, a significant relationship was found between OPG and RANKL levels. Of the patients with Hashimoto’s thyroiditis, 33 were autoantibody-positive and 16 were negative. Vitamin D, OPG and RANKL levels were significantly lower in antibody-positive patients than in negative subjects. Conclucion: There were no differences in vitamin D, OPG and RANKL levels between patients with and without Hashimoto’s thyroidits. Autoantibody-positive Hashimoto’s thyroiditis group had statistically significantly lower vitamin D, OPG and RANKL levels. This reverse correlation suggests that autoantibodies may have an effect on osteoclastogenesis.

The upregulation of receptor activator NF-kappaB ligand expression by interleukin-1alpha and Porphyromonas endodontalis in human osteoblastic cells.

Science.gov (United States)

Chen, S-C; Huang, F-M; Lee, S-S; Li, M-Z; Chang, Y-C

2009-04-01

To investigate the receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL) in osteoblastic cells stimulated with inflammatory mediators. The expression of RANKL in human osteoblastic cell line U2OS stimulated by pro-inflammatory cytokine interleukin (IL)-1alpha and black-pigmented bacteria Porphyromonas endodontalis was investigated by Western blot and enzyme-linked immunosorbent assay (ELISA). The significance of the results obtained from control and treated groups was statistically analysed by the paired Student's t-test. IL-1alpha was found to upregulate RANKL production in U2OS cells (P endodontalis also increased RANKL expression in U2OS cells after 4-h incubation period demonstrated by Western blot and ELISA (P endodontalis may be involved in developing apical periodontitis through the stimulation of RANKL production.

Relationship between circulating serum osteoprotegerin and total receptor activator of nuclear κ-B ligand levels, triglycerides, and coronary calcification in postmenopausal women.

Science.gov (United States)

Poornima, Indu G; Mackey, Rachel H; Buhari, Alhaji M; Cauley, Jane A; Matthews, Karen A; Kuller, Lewis H

2014-07-01

This study evaluates the relationship of blood osteoprotegerin (OPG) and receptor activator of nuclear κ-B ligand (RANKL) levels with coronary artery calcium (CAC) and cardiovascular risk factors in two studies of postmenopausal women. OPG, a marker of bone turnover, and its ligand, RANKL, may contribute to cardiovascular disease risk. We tested the hypothesis that serum OPG and RANKL levels were associated with CAC and cardiovascular disease risk factors among postmenopausal women in the Women On the Move through Activity and Nutrition Study (WOMAN Study; n = 86; mean [SD], age 58 [2.9] y) and replicated our findings in the Healthy Women Study (HWS; n = 205; mean [SD] age, 61 [2.3] y). Serum OPG, total RANKL, and CAC were measured at baseline and 48 months in the WOMAN Study and on the eighth postmenopausal visit in the HWS. In the WOMAN Study, higher OPG was associated with higher CAC, and higher total RANKL was associated with lower CAC and triglycerides. In the HWS, higher total RANKL was also associated with lower CAC and triglycerides. In logistic regression models adjusted for body mass index and triglycerides, the odds ratios (95% CIs) for CAC per unit increase in OPG were 1.78 (1.17-2.73) for the WOMAN Study and 1.02 (0.84-1.24) for the HWS, and the odds ratios (95% CIs) for CAC per unit increase in log total RANKL were 0.86 (0.64-1.17) for the WOMAN Study and 0.83 (0.72-0.96) for the HWS. The inverse association of total RANKL with CAC and triglycerides is a new finding and may have important implications given the increasing use of drugs that modify total RANKL and its receptor, receptor activator of nuclear κ-B.

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

Directory of Open Access Journals (Sweden)

Schlegel Karl A

2010-10-01

Full Text Available Abstract Background Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL; however, osteonecrosis of the jaw (ONJ is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP-related and denosumab (anti-RANKL antibody-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL in ONJ-altered and healthy periodontal tissue. Methods Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment. Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Results Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Conclusions These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to

Computer-Assisted Technique for Surgical Tooth Extraction

Directory of Open Access Journals (Sweden)

Hosamuddin Hamza

2016-01-01

Full Text Available Introduction. Surgical tooth extraction is a common procedure in dentistry. However, numerous extraction cases show a high level of difficulty in practice. This difficulty is usually related to inadequate visualization, improper instrumentation, or other factors related to the targeted tooth (e.g., ankyloses or presence of bony undercut. Methods. In this work, the author presents a new technique for surgical tooth extraction based on 3D imaging, computer planning, and a new concept of computer-assisted manufacturing. Results. The outcome of this work is a surgical guide made by 3D printing of plastics and CNC of metals (hybrid outcome. In addition, the conventional surgical cutting tools (surgical burs are modified with a number of stoppers adjusted to avoid any excessive drilling that could harm bone or other vital structures. Conclusion. The present outcome could provide a minimally invasive technique to overcome the routine complications facing dental surgeons in surgical extraction procedures.

Simulation of solvent extraction in reprocessing

Energy Technology Data Exchange (ETDEWEB)

Kumar, Shekhar; Koganti, S B [Reprocessing Group, Indira Gandhi Centre for Atomic Research, Kalpakkam (India)

1994-06-01

A SIMulation Program for Solvent EXtraction (SIMPSEX) has been developed for simulation of PUREX process used in nuclear fuel reprocessing. This computer program is written in double precision structured FORTRAN77 and at present it is used in DOS environment on a PC386. There is a plan to port it to ND supermini computers in future. (author). 5 refs., 3 figs.

Life Cycle Assessment in Spatial Planning

DEFF Research Database (Denmark)

Bidstrup, Morten; Pizzol, Massimo; Schmidt, Jannick Højrup

2015-01-01

Spatial planning establishes conditions for societal patterns of production and consumption. However, the assigned Strategic Environmental Assessments (SEA) tend to have a too narrow focus. In particular, there is a need for applying a system perspective in SEA, extending assessment beyond...... towards operationalising LCA in SEA by adjusting LCA methodology to focus on the ways planners and planning processes can influence the environmental impacts of interconnected activities. The proposed procedure was tested on a case study of Danish extraction planning, and it was found to generate new...... knowledge for decision support. The procedure enabled identification of key systemic impacts, as well as it enabled formulation of recommendations for how to address these impacts in planning processes. On a more general level, this article demonstrates an application of LCA which until now has received...

Synovial tissue rank ligand expression and radiographic progression in rheumatoid arthritis: observations from a proof-of-concept randomized clinical trial of cytokine blockade.

LENUS (Irish Health Repository)

Rooney, Terence

2012-02-01

The objective of the study was to evaluate synovial tissue receptor activator of nuclear factor-kappabeta ligand (RANKL) and osteoprotegerin (OPG) as biomarkers of disease activity, progressive joint damage, and therapeutic response, during cytokine blockade in rheumatoid arthritis (RA). Patients with active RA entered a randomized open-label 12-month study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 mug\\/kg twice weekly. Arthroscopic synovial tissue biopsies were obtained at baseline, at 4 weeks and at the final time point. Following immunohistochemical staining, RANKL and OPG expression was quantified using digital image analysis. Radiographic damage was evaluated using the van der Heijde modification of the Sharp scoring system. Twenty-two patients were randomized. Baseline expression of RANKL, but not OPG, correlated significantly with baseline CRP levels (r = 0.61, P < 0.01). While a significant reduction in OPG expression following treatment was observed in clinical responders at the final time point (P < 0.05 vs. baseline), RANKL levels did not change, and the RANKL:OPG ratio remained unaltered, even at the highest levels of clinical response. When potential predictors of radiographic outcome were evaluated, baseline RANKL expression correlated with erosive progression at 1 year (r = 0.71, P < 0.01). Distinct, though related, pathophysiologic processes mediate joint inflammation and destruction in RA. Elevated synovial tissue RANKL expression is associated with progressive joint erosion, and may be independent of the clinical response to targeted therapy. The potential therapeutic importance of modulating RANKL in RA is highlighted, if radiographic arrest is to be achieved.

Advanced integrated solvent extraction systems

Energy Technology Data Exchange (ETDEWEB)

Horwitz, E.P.; Dietz, M.L.; Leonard, R.A. [Argonne National Lab., IL (United States)

1997-10-01

Advanced integrated solvent extraction systems are a series of novel solvent extraction (SX) processes that will remove and recover all of the major radioisotopes from acidic-dissolved sludge or other acidic high-level wastes. The major focus of this effort during the last 2 years has been the development of a combined cesium-strontium extraction/recovery process, the Combined CSEX-SREX Process. The Combined CSEX-SREX Process relies on a mixture of a strontium-selective macrocyclic polyether and a novel cesium-selective extractant based on dibenzo 18-crown-6. The process offers several potential advantages over possible alternatives in a chemical processing scheme for high-level waste treatment. First, if the process is applied as the first step in chemical pretreatment, the radiation level for all subsequent processing steps (e.g., transuranic extraction/recovery, or TRUEX) will be significantly reduced. Thus, less costly shielding would be required. The second advantage of the Combined CSEX-SREX Process is that the recovered Cs-Sr fraction is non-transuranic, and therefore will decay to low-level waste after only a few hundred years. Finally, combining individual processes into a single process will reduce the amount of equipment required to pretreat the waste and therefore reduce the size and cost of the waste processing facility. In an ongoing collaboration with Lockheed Martin Idaho Technology Company (LMITCO), the authors have successfully tested various segments of the Advanced Integrated Solvent Extraction Systems. Eichrom Industries, Inc. (Darien, IL) synthesizes and markets the Sr extractant and can supply the Cs extractant on a limited basis. Plans are under way to perform a test of the Combined CSEX-SREX Process with real waste at LMITCO in the near future.

Field Test Design Simulations of Pore-Water Extraction for the SX Tank Farm

Energy Technology Data Exchange (ETDEWEB)

Truex, Michael J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Oostrom, Martinus [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2013-09-01

A proof of principle test of pore water extraction is being performed by Washington River Protection Solutions for the U.S. Department of Energy, Office of River Protection. This test is being conducted to meet the requirements of Hanford Federal Facility Agreement and Consent Order (HFFACO) (Ecology et al. 1989) Milestone M 045-20, and is described in RPP-PLAN-53808, 200 West Area Tank Farms Interim Measures Investigation Work Plan. To support design of this test, numerical simulations were conducted to help define equipment and operational parameters. The modeling effort builds from information collected in laboratory studies and from field characterization information collected at the test site near the Hanford Site 241-SX Tank Farm. Numerical simulations were used to evaluate pore-water extraction performance as a function of the test site properties and for the type of extraction well configuration that can be constructed using the direct-push installation technique. Output of simulations included rates of water and soil-gas production as a function of operational conditions for use in supporting field equipment design. The simulations also investigated the impact of subsurface heterogeneities in sediment properties and moisture distribution on pore-water extraction performance. Phenomena near the extraction well were also investigated because of their importance for pore-water extraction performance.

Climate protection in the spatial planning. Strategic options of the regional planning and land-use planning. Short documentation of the case studies; Klimaschutz in der raeumlichen Planung. Gestaltungsmoeglichkeiten der Raumordnung und Bauleitplanung. Kurzdokumentation der Fallstudien

Energy Technology Data Exchange (ETDEWEB)

Ahlhelm, Inge; Bula, Andreas; Frerichs, Stefan; Hinzen, Ajo [BKR Aachen Castro und Hinzen, Aachen (Germany); Madry, Thomas; Schuele, Ralf [Wuppertal Institut fuer Klima, Umwelt, Energie GmbH, Wuppertal (Germany); Groth, Klaus-Martin; Kerstan, Susann [Kanzlei Gassner, Groth, Siederer und Collegen, Berlin (Germany)

2013-02-15

As the basis for the practical help 'Climate protection in the spatial planning', the Federal Environment Agency (Dessau-Rosslau, Federal Republic of Germany) investigated a lot of plans, concepts and programs at regional level and provincial level. The essential principles and extracts from case studies are summarized in brief dossiers which are presented in the contribution under consideration. This contribution shall present an overview on the state of the art of the application of instruments at the geospatial climate protection at different planning levels.

Test plan for demonstrating plutonium extraction from 10-L solutions using EIChrom extraction chromatographic resins

International Nuclear Information System (INIS)

Barney, G.S.

1994-01-01

Corrosive plutonium solutions stored in 10-L containers at the Plutonium Finishing Plant must be treated to convert the plutonium to a safe, solid form for storage and to remove the americium so that radiation exposure can be reduced. Extraction chromatographic resins will be tested for separating plutonium from these solutions in the laboratory. Separation parameters will be developed during the testing for large scale processing of the 10-L solutions and solutions of similar composition. Use of chromatographic resins will allow plutonium separation with minimum of chemical addition to the feed and without the need for plutonium valence adjustment. The separated plutonium will be calcined to plutonium oxide by direct solution calcination

Hazardous waste operational plan for site 300

International Nuclear Information System (INIS)

Roberts, R.S.

1982-01-01

This plan outlines the procedures and operations used at LLNL's Site 300 for the management of the hazardous waste generated. This waste consists primarily of depleted uranium (a by-product of U-235 enrichment), beryllium, small quantities of analytical chemicals, industrial type waste such as solvents, cleaning acids, photographic chemicals, etc., and explosives. This plan details the operations generating this waste, the proper handling of this material and the procedures used to treat or dispose of the hazardous waste. A considerable amount of information found in this plan was extracted from the Site 300 Safety and Operational Manual written by Site 300 Facility personnel and the Hazards Control Department

Extraction of urban vegetation with Pleiades multiangular images

Science.gov (United States)

Lefebvre, Antoine; Nabucet, Jean; Corpetti, Thomas; Courty, Nicolas; Hubert-Moy, Laurence

2016-10-01

Vegetation is essential in urban environments since it provides significant services in terms of health, heat, property value, ecology ... As part of the European Union Biodiversity Strategy Plan for 2020, the protection and development of green-infrastructures is strengthened in urban areas. In order to evaluate and monitor the quality of the green infra-structures, this article investigates contributions of Pléiades multi-angular images to extract and characterize low and high urban vegetation. From such images one can extract both spectral and elevation information from optical images. Our method is composed of 3 main steps : (1) the computation of a normalized Digital Surface Model from the multi-angular images ; (2) Extraction of spectral and contextual features ; (3) a classification of vegetation classes (tree and grass) performed with a random forest classifier. Results performed in the city of Rennes in France show the ability of multi-angular images to extract DEM in urban area despite building height. It also highlights its importance and its complementarity with contextual information to extract urban vegetation.

Offline combination of pressurized fluid extraction and electron paramagnetic resonance spectroscopy for antioxidant activity of grape skin extracts assessment

Czech Academy of Sciences Publication Activity Database

Polovka, M.; Šťavíková, Lenka; Hohnová, Barbora; Karásek, Pavel; Roth, Michal

2010-01-01

Roč. 1217, č. 51 (2010), s. 7990-8000 ISSN 0021-9673 R&D Projects: GA ČR GA203/08/1536; GA MŠk LC06023 Institutional research plan: CEZ:AV0Z40310501 Keywords : pressurized fluid extraction * electron paramagnetic resonance spectroscopy * antioxidant activity Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.194, year: 2010

Consequences of early extraction of compromised first permanent molar: a systematic review.

Science.gov (United States)

Saber, Afnan M; Altoukhi, Doua H; Horaib, Mariam F; El-Housseiny, Azza A; Alamoudi, Najlaa M; Sabbagh, Heba J

2018-04-05

The aim of this study was to systematically review the literature to determine the sequelae of early extraction of compromised first permanent molars (FPMs) with regard to the skeletal and dental development of 5- to 15-year-old children. Meta-analysis was conducted when applicable. Our research protocol included a search strategy, inclusion/exclusion criteria, and a data extraction plan. The search engines used were PubMed, Scopus, and Science Direct. Study selection was performed independently by three reviewers. Articles published from 1960 to 2017 were reviewed based on inclusion and exclusion criteria. Meta-analysis was performed to compare space closure between upper and lower arches. Eleven studies fulfilled the inclusion criteria. The consequences were decrease in post extraction space, accelerated development and eruption of second permanents molars (SPMs) and third molars, a decrease in caries and/or fillings on the proximal surfaces of adjacent teeth, lingual tipping and retrusion of incisors, and counter clockwise rotation of the occlusal plane. There were several consequences of early extraction of FPMs, which were related to skeletal and dental development. Our systematic review suggests that comprehensive evaluation of the compromised FPMs should be performed before planning an extraction. The ideal time for FPM extraction is when the SPM is at the early bifurcation stage in order to achieve complete closure of the extraction space by the SPM. Benefits should be weighed over the risks to decrease the risk of unfavorable outcomes as much as possible. However, due to the limited evidence on the outcomes and variables that influence them, high-quality prospective studies are needed.

[Effect of medicinal plant extracts on the growth of microorganisms].

Science.gov (United States)

Baronets, N G; Adlova, G P; Mel'nikova, V A

2001-01-01

Extracts obtained from sweatweed and licorice roots, flax seeds, milfoil, bur-marigold, plantain, coltsfoot, nettle, Indian corn stigmas, laminaria produced a stimulating effect on the growth of Candida albicans test strain and Streptococcus pyogenes test strain Dick 1. Sweatweed, licorice, Aerva lanata and violet extracts influenced the growth of Corynebacterium xerosis 1911, while sweatweed, violet, horse-tail, bur-marigold, camomile, plantain, and nettle extracts influenced the growth of shigellae. The stimulating effect could be supposedly produced by biologically active substances contained in medicinal plants (organic acids, alkaloids, carotinoids, vitamins, microelements). Further studies aimed at the identification of substances producing the stimulating effect are planned.

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features.

Science.gov (United States)

Wehrhan, Falk; Hyckel, Peter; Ries, Jutta; Stockmann, Phillip; Nkenke, Emeka; Schlegel, Karl A; Neukam, Friedrich W; Amann, Kerstin

2010-10-13

Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p Msx-1 (p Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue.

International benchmark and best practices on national infrastructure plans. Application to Spanish strategic planning

Energy Technology Data Exchange (ETDEWEB)

Pino Hernandez, E.M.; Delgado Quiralte, C.

2016-07-01

The need for planning regarding investment in infrastructures is recognised and supported by most governments around the world. Planning helps to take effective and correct decisions, provides a basis for monitoring its impacts and also facilitates further developments. However it requires a high level of organization, coordination among stakeholders and anticipation of transport needs. There are some different methodological approaches for strategic planning. This paper examines the importance of infrastructure planning and how it is undertaken in different countries from Europe and other continents. It is based on a benchmarking about planning procedures of 7 reference countries (UK, France, the Netherlands, Poland, Germany, Japan and USA), in addition to others whose strategic plans are being developed at the present moment such as Croatia or Romania. This benchmarking aims to extract and compare best practices carried out in this field and to define the optimal formulation of strategic planning. In this regard, the benchmarking is focused on some key aspects: firstly, on the plan structure and its main contents. There are a lot of differences about how each country defines the future needs for transport and how it establishes the objectives and the strategies to be followed. Secondly, on the characterisation of the authorities which are responsible of the plan development (level of dependence from the government, know-how…) along with the time frame and final validity of the plans. And finally, the level of detail of the proposed actions and budgetary commitments provided by the strategic plans. Throughout the comparative analysis, the knowledge generated by this benchmarking has allowed setting a series of specific recommendations in strategic planning which can be applied as innovative solutions and best practices in future planning processes in Spain. (Author)

Molten salt/metal extractions for recovery of transuranic elements

International Nuclear Information System (INIS)

Chow, L.S.; Basco, J.K.; Ackerman, J.P.; Johnson, T.R.

1992-01-01

The integral fast reactor (EFR) is an advanced reactor concept that incorporates metallic driver and blanket fuels, an inherently safe, liquid-sodium-cooled, pool-type, reactor design, and on-site pyrochemical reprocessing (including electrorefining) of spent fuels and wastes. This paper describes a pyrochemical method that is being developed at Argonne National Laboratory to recover transuranic elements from the EFR electrorefiner process salt. The method uses multistage extractions between molten chloride salts and cadmium metal at high temperatures. The chemical basis of the salt extraction method, the test equipment, and a test plan are discussed

Shielding calculation of slow extracted beam facility at KEK proton synchrotron

International Nuclear Information System (INIS)

Hirabayashi, Hiromi; Katoh, Kazuaki

1978-01-01

The KEK proton synchrotron has two external beam lines, i.e. a fast extracted beam line for a bubble chamber and a slow extracted beam line for counter experiments. The maximum total intensity of the slow beam is estimated as 5 x 10 12 protons per sec. For beam losses along the line, shielding calculation was made, and on the basis of these results, adequacy of the current shielding construction plans was discussed. (Mori, K.)

Logistic Principles Application for Managing the Extraction and Transportation of Solid Minerals

Directory of Open Access Journals (Sweden)

Tyurin Alexey

2017-01-01

Full Text Available Reducing the cost of resources in solid mineral extraction is an urgent task. For its solution the article proposes logistic approach use to management of mining company all resources, including extraction processes, transport, mineral handling and storage. The account of the uneven operation of mining, transport units and complexes for processing and loading coal into railroad cars allows you to identify the shortcomings in the work of the entire enterprise and reduce resources use at the planned production level. In the article the mining planning model taking into account the dynamics of the production, transport stations and export coal to consumers rail transport on example of Krasnoyarsk region Nazarovo JSC «Razrez Sereul'skiy». Rolling planning methods use and data aggregation allows you to split the planning horizon (month on equal periods and to use of dynamic programming method for building mining optimal production programme for the month. Coal mining production program definition technique will help align the work of all enterprise units, to optimize resources of all areas, to establish a flexible relationship between manufacturer and consumer, to take into account the irregularity of rail transport.

Logistic Principles Application for Managing the Extraction and Transportation of Solid Minerals

Science.gov (United States)

Tyurin, Alexey

2017-11-01

Reducing the cost of resources in solid mineral extraction is an urgent task. For its solution the article proposes logistic approach use to management of mining company all resources, including extraction processes, transport, mineral handling and storage. The account of the uneven operation of mining, transport units and complexes for processing and loading coal into railroad cars allows you to identify the shortcomings in the work of the entire enterprise and reduce resources use at the planned production level. In the article the mining planning model taking into account the dynamics of the production, transport stations and export coal to consumers rail transport on example of Krasnoyarsk region Nazarovo JSC «Razrez Sereul'skiy». Rolling planning methods use and data aggregation allows you to split the planning horizon (month) on equal periods and to use of dynamic programming method for building mining optimal production programme for the month. Coal mining production program definition technique will help align the work of all enterprise units, to optimize resources of all areas, to establish a flexible relationship between manufacturer and consumer, to take into account the irregularity of rail transport.

Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment.

Science.gov (United States)

Wehrhan, F; Hyckel, P; Amann, K; Ries, J; Stockmann, P; Schlegel, Ka; Neukam, Fw; Nkenke, E

2011-05-01

Bone-destructive disease treatments include bisphosphonates and antibodies against receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis of the jaw (ONJ) is a side-effect. Aetiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx-1 is expressed constitutively only in mature jaw bone. Msx-1 expression might be impaired in bisphosphonate-related ONJ. This study compared the expression of Msx-1, Bone Morphogenetic Protein (BMP)-2 and RANKL, in ONJ-affected and healthy jaw bone. An automated immunohistochemistry-based alkaline phosphatase-anti-alkaline phosphatase method was used on ONJ-affected and healthy jaw bone samples (n = 20 each): cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed to quantitatively compare Msx-1, BMP-2, RANKL and GAPDH mRNA levels. Labelling indices were significantly lower for Msx-1 (P Msx-1, 22-fold lower (P Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible explanation of the exclusivity of ONJ in jaw bone. Functional analyses of Msx-1- RANKL interaction during bone remodelling should be performed in the future. © 2011 John Wiley & Sons A/S.

[The expression and significance of receptor activator of nuclear factor kappaB ligand and osteoprotegerin in periapical cyst and periapical granuloma].

Science.gov (United States)

Zhang, Meihua; Yu, Yunzhi; Miao, Yu

2012-08-01

To investigate the expression of receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) in periapical cyst and periapical granuloma by comparison with the expression in the normal periodontal tissue as control, and to identify their functional mechanism in the bone destruction of periapical cyst and granuloma. 20 periapical cyst tissues (cyst group), 20 periapical granuloma tissues (granuloma group), and 20 normal periodontal tissues (control group) were collected respectively. Immunohistochemical technology was performed to detect the expression of RANKL and OPG in above three groups. In cyst group, granuloma group and control group, the expression of RANKL were 75.00 +/- 7.54, 68.40 +/- 6.74 and 29.40 +/- 2.46, respectively. The expression of OPG were 38.10 +/- 7.09, 47.65 +/- 13.85 and 58.60 +/- 5.88, respectively. The differences among the three groups were statistically significant (Pcysts group were negatively correlated (r=-0.56, P=0.01) and were not correlated with granuloma and control group (P>0.05). RANKL and OPG play roles in the bone absorption of periapical disease. In periapical disease, abnormal expression of RANKL and OPG are detected, RANKL significantly increase, OPG decrease, bone absorption accelerate and osteolytic lesion are observed. In periapical cyst, the bone absorption is more active compared with periapical granuloma.

SU-E-T-357: Semi-Automated Knowledge-Based Radiation Therapy (KBRT) Planning for Head-And-Neck Cancer (HNC): Can KBRT Plans Achieve Better Results Than Manual Planning?

International Nuclear Information System (INIS)

Lutzky, C; Grzetic, S; Lo, J; Das, S

2014-01-01

Purpose: Knowledge Based Radiation Therapy Treatment (KBRT) planning can be used to semi-automatically generate IMRT plans for new patients using constraints derived from previously manually-planned, geometrically similar patients. We investigate whether KBRT plans can achieve greater dose sparing than manual plans using optimized, organspecific constraint weighting factors. Methods: KBRT planning of HNC radiotherapy cases geometrically matched each new (query) case to one of the 105 clinically approved plans in our database. The dose distribution of the planned match was morphed to fit the querys geometry. Dose-volume constraints extracted from the morphed dose distribution were used to run the IMRT optimization with no user input. In the first version, all constraints were multiplied by a weighting factor of 0.7. The weighting factors were then systematically optimized (in order of OARs with increasing separation from the target) to maximize sparing to each OAR without compromising other OARs. The optimized, second version plans were compared against the first version plans and the clinically approved plans for 45 unilateral/bilateral target cases using the dose metrics: mean, median and maximum (brainstem and cord) doses. Results: Compared to the first version, the second version significantly reduced mean/median contralateral parotid doses (>2Gy) for bilateral cases. Other changes between the two versions were not clinically meaningful. Compared to the original clinical plans, both bilateral and unilateral plans in the second version had lower average dose metrics for 5 of the 6 OARs. Compared to the original plans, the second version achieved dose sparing that was at least as good for all OARs and better for the ipsilateral parotid (bilateral) and oral cavity (bilateral/unilateral). Differences in planning target volume coverage metrics were not clinically significant. Conclusion: HNC-KBRT planning generated IMRT plans with at least equivalent dose sparing to

SU-E-T-357: Semi-Automated Knowledge-Based Radiation Therapy (KBRT) Planning for Head-And-Neck Cancer (HNC): Can KBRT Plans Achieve Better Results Than Manual Planning?

Energy Technology Data Exchange (ETDEWEB)

Lutzky, C; Grzetic, S; Lo, J; Das, S [Duke University Medical Center, Durham, NC (United States)

2014-06-01

Purpose: Knowledge Based Radiation Therapy Treatment (KBRT) planning can be used to semi-automatically generate IMRT plans for new patients using constraints derived from previously manually-planned, geometrically similar patients. We investigate whether KBRT plans can achieve greater dose sparing than manual plans using optimized, organspecific constraint weighting factors. Methods: KBRT planning of HNC radiotherapy cases geometrically matched each new (query) case to one of the 105 clinically approved plans in our database. The dose distribution of the planned match was morphed to fit the querys geometry. Dose-volume constraints extracted from the morphed dose distribution were used to run the IMRT optimization with no user input. In the first version, all constraints were multiplied by a weighting factor of 0.7. The weighting factors were then systematically optimized (in order of OARs with increasing separation from the target) to maximize sparing to each OAR without compromising other OARs. The optimized, second version plans were compared against the first version plans and the clinically approved plans for 45 unilateral/bilateral target cases using the dose metrics: mean, median and maximum (brainstem and cord) doses. Results: Compared to the first version, the second version significantly reduced mean/median contralateral parotid doses (>2Gy) for bilateral cases. Other changes between the two versions were not clinically meaningful. Compared to the original clinical plans, both bilateral and unilateral plans in the second version had lower average dose metrics for 5 of the 6 OARs. Compared to the original plans, the second version achieved dose sparing that was at least as good for all OARs and better for the ipsilateral parotid (bilateral) and oral cavity (bilateral/unilateral). Differences in planning target volume coverage metrics were not clinically significant. Conclusion: HNC-KBRT planning generated IMRT plans with at least equivalent dose sparing to

CMP(O) tripodands: synthesis, potentiometric studies and extractions

Czech Academy of Sciences Publication Activity Database

Reinoso-García, M.M.; Janczewski, D.; Reinhoudt, D.N.; Verboom, W.; Malinowska, E.; Pietrzak, M.; Hill, C.; Báča, Jiří; Grüner, Bohumír; Selucký, P.; Grűttner, C.

2006-01-01

Roč. 30, č. 10 (2006), s. 1480-1492 ISSN 1144-0546 Grant - others:EEC(PL) FIKW-CT-2000-00088; EEC(PL) F16W-CT-2003-508854 Institutional research plan: CEZ:AV0Z40320502 Keywords : assisted chemical-separation * complex-formation constants * solvent-extraction Subject RIV: CA - Inorganic Chemistry Impact factor: 2.647, year: 2006

Supercritical CO2 Extraction of Salvia officinalis L

Czech Academy of Sciences Publication Activity Database

Aleksovski, S.A.; Sovová, Helena

2007-01-01

Roč. 40, č. 2 (2007), s. 239-245 ISSN 0896-8446 R&D Projects: GA AV ČR(CZ) IAA4072102 Grant - others:GA_(MK) 40108601/0 Institutional research plan: CEZ:AV0Z40720504 Keywords : supercritical fluid extraction * essential oil * collection efficiency Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 2.189, year: 2007

Emprego de planejamento fatorial no desenvolvimento de uma metodologia para extração de zinco de resíduos galvânicos Use of factorial planning in developing a methodology for galvanic zinc residue extraction

Directory of Open Access Journals (Sweden)

Samantha Olivier

2007-01-01

Full Text Available The plating process generates solid waste rich in heavy metals and aiming to reduce environmental impact of such waste, this work suggests a methodology for zinc reduction, through a 2(4 factorial planning, studying the influence of the following variables: acid concentration (15, 20 or 30% v/v, acid type (sulfuric or hydrochloric, acid volume (15, 20 or 25 mL and extraction time (12, 24 or 36 h. Through this methodology it is possible to establish the optimal conditions (15 mL of a 30% hydrochloric acid concentration during 12 h to get a 100% efficiency in zinc extraction.

State planning policy 2/07: protection of extractive resources results in certainty of materials supply

Energy Technology Data Exchange (ETDEWEB)

NONE

2007-09-15

Extractive resources are primary source materials used for building infrastructure such as roads, ports, airports, bridges, railways, factories, hospitals, schools and homes. The Policy seeks to protect those essential and finite construction materials for future and existing extraction purposes. Population increases in south-east Queensland the upgrading of rail and port facilities to export coal and other minerals will form a major part in the expansion of extractive industry. Over $4 billion has been committed by the Government and industry to coal infrastructure developments such as upgrades at RG Tanna, Barney Point and the proposed Wiggins Island coal terminals at Gladstone, the Dalryample Bay and Hay Point terminals near Mackay and the Abbot Point coal terminal near Bower. The new Bauhinia regional railway will service the Rolleston coal mines.

CT images and radiotherapy treatment planning of patients with breast cancer: A dataset

Directory of Open Access Journals (Sweden)

Mohammad Rezaei

2017-08-01

Full Text Available The data presented here were originally collected for the research project “CT-Scan processing and analysis in patient with breast cancer after radiotherapy”. Also, it reported in our study “Prediction of Lung Tissue Damage by Evaluating Clinical and Dosimetric Parameters in Breast Cancer Patients” (Hasanabdali et al., 2016 [1]. This article describes and directly links to 52 subjects referred to Mahdieh Oncology and Radiotherapy Center from February to August 2015. Treatment planning was done for delivering 50 Gy dose to PTV in 25 fractions. the lungs and heart objects were extracted from CT images along with compliance Dose plan. Dose-volume histogram (DVH and Dose-mass histogram (DMH extracted using CT images and dose plan matrix. Moreover, the complete clinical and dosimetric specifications of subjects is attached.

A System with Intelligent Editing for Extracting Ridge and Ravine Terrain Features

National Research Council Canada - National Science Library

Schmidt, Greg; Swan, J. E., II; Rosenblum, Lawrence; Tomlin, Erik B; Overby, Derek

2005-01-01

We describe a system for extracting ridges and ravines from elevation data. The application context is a map-based military planning tool, which allows users to select ridges and ravines by simple mouse clicks...

Manufacture of electrostatic septum for extracting particle beam

International Nuclear Information System (INIS)

Tokumoto, Shuichi

1979-01-01

In the main ring of National Laboratory for High Energy Physics, fast and slow extractions of accelerated proton beam are carried out by using electrostatic septa. The electrostatic septum is an apparatus to deflect beam by an electrostatic field, basically composed of a couple of parallel plate electrodes installed in a vacuum chamber. The electrostatic septum is required to satisfy the following two conditions: it must be very thin and flat to reduce the loss of extracted beam, and sufficiently high electric field must be generated to deflect beam in a limited length. The structure and manufacture of electrostatic septa are described. The manufacturing is explained by dividing a septum into an anode and a cathode, terminals introducing high voltage, a vacuum chamber, and high voltage circuit. The performance is also described on the experiments for no-beam condition and beam extraction. Beam extraction has been carried out over 1500 hours thus far, the average beam intensity being 1 x 10 12 ppp, and extraction efficiency more than 90%. There have been no serious failure to affect the performance nor metal wire breakage. They have satisfied their purposes, being used for both fast and slow extractions. Presently, lengthening of the electrostatic field region is being planned to increase the length of the septa to 1.5 m per unit. (Wakatsuki, Y.)

Isolation of quaternary benzo[c]phenanthridine alkaloids from Macleaya microcarpa (MAXIM.) FEDDE: Comparison of maceration, Soxhlet extraction and pressurized liquid extraction

Czech Academy of Sciences Publication Activity Database

Urbanová, J.; Pěnčíková, K.; Gregorová, J.; Hohnová, Barbora; Šťavíková, Lenka; Karásek, Pavel; Roth, Michal; Táborská, E.

2012-01-01

Roč. 23, č. 5 (2012), s. 477-482 ISSN 0958-0344 R&D Projects: GA ČR(CZ) GAP206/11/0138; GA ČR(CZ) GPP503/11/P523 Institutional research plan: CEZ:AV0Z40310501 Keywords : benzo[c]phenanthridine alkaloids * extraction methods * Macleaya microcarpa Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.480, year: 2012

Reserves reporting for decision-making planning and control

International Nuclear Information System (INIS)

Higgins, G.

1992-01-01

This paper shows how the established Monte Carlo simulation approach to estimating hydrocarbon reserves can be expanded to provide the basis of a comprehensive valuation, planning and control system meeting all the reserve reporting requirements of an oil exploration and production company. The approach presented is also appropriate for other mining and extractive industries. The paper demonstrates how individual expectation curves can be modified to reflect both technically and commercially recoverable reserves and how these are in turn combined into the economic valuation, planning and control processes of an enterprise. Estimates across the full range of risk and reserves can be aggregated to provide a powerful planning tool that can be used to set corporate, divisional and individual objectives

[Immunoexpression and clinical significance of interleukin-21 and receptor activator of nuclear factor κB ligand in human periapical granulomas and radicular cysts].

Science.gov (United States)

Hu, Juhua; Li, Qian; Wang, Yanqing; Li, Song

2015-06-01

This study aimed to detect the immunoexpression of interleukin-21 (IL-21) and receptor activator. of nuclear factor KB ligand (RANKL) in periapical granulomas (PGs) and radicular cysts (RCs). The interaction of IL-21 with RANKL and its role in periapical pathogenesis were also speculated. A total of 32 PGs and 23 RCs were selected as experimental samples. Lesion size and occurrence of tenderness were recorded. Up to 10 healthy gingival tissues were collected as normal control samples. All tissues were subjected to immunohistocheincal analysis with anti-human IL-21 and RANKL polyclonal antibodies. The correlations of IL-21 with RANKL, lesion size, and the occurrence of tenderness of the PGs and RCs were evaluated. IL-21-positive cells were detected in all periapical lesion tissues but not in normal tissues. In the cyst group and granuloma group, the corresponding expression levels of IL-21 were 59.92±6.57 and 36.80± 6.81, whereas those of RANKL were 68.81±18.59 and 36.12±14.87, respectively. Moreover, t-test revealed a significantly higher expression of IL-21 and RANKL in RCs than in PGs (P<0.05). IL-21 and RANKL were positively correlated in both PGs and RCs (P<0.05). Furthermore, IL-21 was correlated with lesion size (P<0.05). This study demonstrated that IL-21 is potentially involved in the pathogenesis of apical periodontitis lesions. A role in the exacerbation of chronic inflammation, as well as in bone resorption, is suspected. Further studies are required to elucidate the specific functions of IL-21 in periradicular inflammatory processes.

A method for efficient extraction of rotifers (Rotifera) from soils

Czech Academy of Sciences Publication Activity Database

Devetter, Miloslav

2010-01-01

Roč. 53, č. 2 (2010), s. 115-118 ISSN 0031-4056 R&D Projects: GA ČR(CZ) GP206/06/P405 Institutional research plan: CEZ:AV0Z60660521 Keywords : soil rotifers * Bdelloids * quantitative extraction Subject RIV: EH - Ecology, Behaviour Impact factor: 1.474, year: 2010

Tick salivary gland extract-activated transmission of Borrelia afzelii spirochaetes

Czech Academy of Sciences Publication Activity Database

Pechová, Jitka; Tresová, Gabriela; Kovář, Lubomír; Kopecký, Jan

2002-01-01

Roč. 49, č. 2 (2002), s. 153ů159 ISSN 0015-5683 R&D Projects: GA ČR GA524/02/0901 Institutional research plan: CEZ:AV0Z6022909 Keywords : Ixodes ricinus * salivary gland extract * Borrelia afzelii Subject RIV: EC - Immunology Impact factor: 0.515, year: 2002

Technique of calculating specific capital investments in the fuel extracting sectors of industry

Energy Technology Data Exchange (ETDEWEB)

Bugrov, V.A.; Filey, I.A.

1980-01-01

An analysis is made of the existing methods of calculating specific capital investments in the fuel extracting sectors of industry. Their shortcomings are shown. It is suggested that specific capital investments for extraction of coal and gas be defined as the ratio of capital investments to the conditional increase in extraction. Coal extraction should take int consideration all the capital investments associated with the input of new facilities, and the maintenance of the attained level of extraction and reconstruction of the enterprise, as well as all the newly introduced facilities both at the new and at the active enterprises associated with an increase in coal extraction and with maintenance of the facilities. The suggested technique completely corresponds to the ''Standard Technique for Developing a Technical-Industrial-Financial Plan,'' which stipulates determination of specific capital investments per unit of introduced facilities with only the difference that it takes into consideration the specific features of the fuel extracting sectors of industry.

SU-D-BRD-03: Improving Plan Quality with Automation of Treatment Plan Checks

International Nuclear Information System (INIS)

Covington, E; Younge, K; Chen, X; Lee, C; Matuszak, M; Kessler, M; Acosta, E; Orow, A; Filpansick, S; Moran, J; Keranen, W

2015-01-01

Purpose: To evaluate the effectiveness of an automated plan check tool to improve first-time plan quality as well as standardize and document performance of physics plan checks. Methods: The Plan Checker Tool (PCT) uses the Eclipse Scripting API to check and compare data from the treatment planning system (TPS) and treatment management system (TMS). PCT was created to improve first-time plan quality, reduce patient delays, increase efficiency of our electronic workflow, and to standardize and partially automate plan checks in the TPS. A framework was developed which can be configured with different reference values and types of checks. One example is the prescribed dose check where PCT flags the user when the planned dose and the prescribed dose disagree. PCT includes a comprehensive checklist of automated and manual checks that are documented when performed by the user. A PDF report is created and automatically uploaded into the TMS. Prior to and during PCT development, errors caught during plan checks and also patient delays were tracked in order to prioritize which checks should be automated. The most common and significant errors were determined. Results: Nineteen of 33 checklist items were automated with data extracted with the PCT. These include checks for prescription, reference point and machine scheduling errors which are three of the top six causes of patient delays related to physics and dosimetry. Since the clinical roll-out, no delays have been due to errors that are automatically flagged by the PCT. Development continues to automate the remaining checks. Conclusion: With PCT, 57% of the physics plan checklist has been partially or fully automated. Treatment delays have declined since release of the PCT for clinical use. By tracking delays and errors, we have been able to measure the effectiveness of automating checks and are using this information to prioritize future development. This project was supported in part by P01CA059827

SU-D-BRD-03: Improving Plan Quality with Automation of Treatment Plan Checks

Energy Technology Data Exchange (ETDEWEB)

Covington, E; Younge, K; Chen, X; Lee, C; Matuszak, M; Kessler, M; Acosta, E; Orow, A; Filpansick, S; Moran, J [University of Michigan Hospital and Health System, Ann Arbor, MI (United States); Keranen, W [Varian Medical Systems, Palo Alto, CA (United States)

2015-06-15

Purpose: To evaluate the effectiveness of an automated plan check tool to improve first-time plan quality as well as standardize and document performance of physics plan checks. Methods: The Plan Checker Tool (PCT) uses the Eclipse Scripting API to check and compare data from the treatment planning system (TPS) and treatment management system (TMS). PCT was created to improve first-time plan quality, reduce patient delays, increase efficiency of our electronic workflow, and to standardize and partially automate plan checks in the TPS. A framework was developed which can be configured with different reference values and types of checks. One example is the prescribed dose check where PCT flags the user when the planned dose and the prescribed dose disagree. PCT includes a comprehensive checklist of automated and manual checks that are documented when performed by the user. A PDF report is created and automatically uploaded into the TMS. Prior to and during PCT development, errors caught during plan checks and also patient delays were tracked in order to prioritize which checks should be automated. The most common and significant errors were determined. Results: Nineteen of 33 checklist items were automated with data extracted with the PCT. These include checks for prescription, reference point and machine scheduling errors which are three of the top six causes of patient delays related to physics and dosimetry. Since the clinical roll-out, no delays have been due to errors that are automatically flagged by the PCT. Development continues to automate the remaining checks. Conclusion: With PCT, 57% of the physics plan checklist has been partially or fully automated. Treatment delays have declined since release of the PCT for clinical use. By tracking delays and errors, we have been able to measure the effectiveness of automating checks and are using this information to prioritize future development. This project was supported in part by P01CA059827.

Measures of Ruleset Quality for General Rules Extraction Methods

Czech Academy of Sciences Publication Activity Database

Holeňa, Martin

2009-01-01

Roč. 50, č. 6 (2009), s. 867-879 ISSN 0888-613X R&D Projects: GA ČR GA201/08/0802 Institutional research plan: CEZ:AV0Z10300504 Keywords : rules extraction from data * quality measures * ruleset measures * ROC curves * observational logic * fuzzy logic Subject RIV: IN - Informatics, Computer Science Impact factor: 2.090, year: 2009

Tritium extraction technologies and DEMO requirements

Energy Technology Data Exchange (ETDEWEB)

Demange, D., E-mail: david.demange@kit.edu [Karlsruhe Institute of Technology, Institute for Technical Physics, Tritium Laboratory Karlsruhe, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Antunes, R.; Borisevich, O.; Frances, L. [Karlsruhe Institute of Technology, Institute for Technical Physics, Tritium Laboratory Karlsruhe, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Rapisarda, D. [Laboratorio Nacional de Fusión, EURATOM-CIEMAT, 28040 Madrid (Spain); Santucci, A. [ENEA for EUROfusion, Via E. Fermi 45, 00044 Frascati, Roma (Italy); Utili, M. [ENEA CR Brasimone, 40032 Camugnano, BO (Italy)

2016-11-01

Highlights: • We detail the R&D plan for tritium technology of the European DEMO breeding blanket. • We study advanced and efficient extraction techniques to improve tritium management. • We consider inorganic membranes and catalytic membrane reactor for solid blankets. • We consider permeator against vacuum and vacuum sieve tray for liquid blankets. - Abstract: The conceptual design of the tritium extraction system (TES) for the European DEMO reactor is worked out in parallel for four different breeding blankets (BB) retained by EUROfusion. The TES design has to be tackled in an integrated manner optimizing the synergy with the directly interfacing inner fuel cycle, while minimizing the tritium permeation into the coolant. Considering DEMO requirements, it is most likely that only advanced technologies will be suitable for the tritium extraction systems of the BB. This paper overviews the European work programme for R&D on tritium technology for the DEMO BB, summaries the general first outcomes, and details the specific and comprehensive R&D program to study experimentally immature but promising technologies such as vacuum sieve tray or permeator against vacuum for tritium extraction from PbLi, and advanced inorganic membranes and catalytic membrane reactor for tritium extraction from He. These techniques are simple, fully continuous, likely compact with contained energy consumption. Several European Laboratories are joining their efforts to deploy several new experimental setups to accommodate the tests campaigns that will cover small scale experiments with tritium and inactive medium scale tests so as to improve the technology readiness level of these advanced processes.

Growth rate of bacteria is affected by soil texture and extraction procedure

Czech Academy of Sciences Publication Activity Database

Uhlířová, Eva; Šantrůčková, Hana

2003-01-01

Roč. 35, - (2003), s. 217-224 ISSN 0038-0717 Institutional research plan: CEZ:AV0Z6066911 Keywords : soil texture * extraction of bacteria * biosynthetic activity of bacteria Subject RIV: EH - Ecology, Behaviour Impact factor: 1.915, year: 2003

Rent extraction by large shareholders: evidence using dividend policy in the Czech Republic

Czech Academy of Sciences Publication Activity Database

Hanousek, Jan; Bena, Jan

-, č. 556 (2006), s. 1-38 R&D Projects: GA ČR GA402/06/1293 Institutional research plan: CEZ:AV0Z70850503 Keywords : rent extraction * large shareholders * dividend policy Subject RIV: AH - Economics

Beam optics of the AmPS extraction line

International Nuclear Information System (INIS)

Hoekstra, R.

1991-01-01

The design of the Amsterdam Pulse Stretcher includes a feasibility study of part of the extraction trajectory. The latter includes some proposed curves projected through the hall of the beam switch yard. Since extraction is performed in the north line of the ring and the connection to the trajectory of the spectrometers is planned in a trajectory parallel to the east line of the ring the curves contain bending magnets for bending 90 degrees either by only two magnets or by making use of ring bending magnets in the same way as the ring curves are constructed. The bending through 90 degrees has optimal imaging properties of a unit cell much the same as the curves in the ring. This one-to-one (or one-to-minus-one) property is intended to shift the known required beam dimensions stream upwards from a defined point in the trajectory of the spectrometers to be able to create the dimensions at this shifted point by means of a so called beam transformer, placed in between the extraction point and this position. This report deals with the further developments with respect to the extraction trajectory. (author). 5 refs.; 9 figs.; 3 tabs

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.

Ghrelin attenuates vascular calcification in diabetic patients with amputation.

Science.gov (United States)

Xu, Suining; Ye, Fei; Li, Lihua; Yan, Jinchuan; Bao, Zhengyang; Sun, Zhen; Xu, Liangjie; Zhu, Jie; Wang, Zhongqun

2017-07-01

Vascular calcification is established to be a critical factor in diabetes mellitus, which causes cardiovascular and amputation complication of diabetic patients. OPG/RANKL/RANK axis serves as a regulatory role in vascular calcification. Ghrelin, an endogenous ligand of growth hormone secretagogue receptor (GHSR), has been reported to exhibit potent cardiovascular protective effects. However, the role of ghrelin in the regulation of diabetic vascular calcification is still elusive. Here, we reported the role of ghrelin and its relationship with OPG/RANKL/RANK system in patients with diabetic foot amputation. In vivo and in vitro investigations were performed. Sixty type 2 diabetic patients with foot amputation were enrolled in vivo investigation, and they were divided into three groups through Doppler ultrasound: mild stenosis group (n=20), moderate stenosis group (n=20), and severe stenosis/occlusion group (n=20). Morphological analysis results showed diffused calcium depositions in the anterior tibial artery of diabetic amputees. Compared with the mild and moderate stenosis group, the severe stenosis/occlusion group had more spotty calcium depositions in atherosclerotic plaques. Western blot analysis indicated the expressions of osteoprotegerin (OPG) and ghrelin were downregulated, while the expression of receptor activator of nuclear factor kappa B ligand (RANKL) was upregulated with the vascular stenosis aggravation. Pearson correlation analysis revealed a negative correlation between calcium content and ghrelin levels (r=-0.58, Pghrelin levels and sRANKL levels (r=-0.57, Pghrelin levels (r=0.63, PGhrelin blunted calcification in a dose-dependent manner. In addition, ghrelin upregulated OPG expression and downregulated RANKL expression in VSMC calcification when anti-OPG antibody and RANKL were performed. Collectively, we therefore conclude serum ghrelin level may be a predictor of diabetic vascular calcification. The possible mechanism may be related with OPG/RANKL

Facility effluent monitoring plan determinations for the 200 Area facilities

International Nuclear Information System (INIS)

Nickels, J.M.

1991-11-01

The following facility effluent monitoring plan determinations document the evaluations conducted for the Westinghouse Hanford Company 200 Area facilities (chemical processing, waste management, 222-S Laboratory, and laundry) on the Hanford Site in south central Washington State. These evaluations determined the need for facility effluent monitoring plans for the 200 Area facilities. The facility effluent monitoring plan determinations have been prepared in accordance with A Guide for Preparing Hanford Site Facility Effluent Monitoring Plans, WHC-EP-0438 (WHC 1991). The Plutonium/Uranium Extraction Plant and UO 3 facility effluent monitoring plan determinations were prepared by Los Alamos Technical Associates, Richland, Washington. The Plutonium Finishing Plant, Transuranic Waste Storage and Assay Facility, T Plant, Tank Farms, Low Level Burial Grounds, and 222-S Laboratory determinations were prepared by Science Applications International Corporation of Richland, Washington. The B Plant Facility Effluent Monitoring Plan Determination was prepared by ERCE Environmental Services of Richland, Washington

Plan and present status of synchrotron radiation applications at HESYRL

International Nuclear Information System (INIS)

Zhang, Y.; Su, Y.; Qian, S.; Xu, X.; Jiang, D.; Xu, C.

1985-01-01

An 800 MeV electron storage ring is being constructed at Hefei, China. It is a dedicated UV synchrotron light source from which 27 beam lines could be extracted to accommodate about 50 experimental stations. Four beam lines and five stations are planned and some instruments have been designed and are under construction for the first five-year plan. The proposed experiments include x-ray lithography, soft x-ray microscopy, photoelectron spectroscopy, time-resolved spectroscopy and photochemistry

Receptor activator NFkappaB-ligand and osteoprotegerin protein expression in human periapical cysts and granulomas.

Science.gov (United States)

Menezes, Renato; Bramante, Clóvis Monteiro; da Silva Paiva, Katiúcia Batista; Letra, Ariadne; Carneiro, Everdan; Fernando Zambuzzi, Willian; Granjeiro, José Mauro

2006-09-01

The purpose of this study was to determine the expression of receptor activator of NFkappaB ligand (RANKL) and osteoprotegerin (OPG) associated with bone destruction in periapical cysts and granulomas. Forty human dental chronic periapical lesions were collected after periapical surgery. The lesions collected were fixed in 10% buffered formalin and histologically processed. At least 2 sections of each specimen were stained with hematoxylin and eosin for microscopic diagnosis. After that, 10 human periapical granulomas and 10 cysts were selected for immunohistochemical analysis for RANKL, OPG, and CD68+. Polymorphonuclear neutrophils, macrophages, endothelial cells, and lymphocytes were stained for RANKL and OPG in both lesions. Epithelial cells were also stained for RANKL and OPG in periapical cysts. Quantitative analysis was conducted and the results were expressed as a ratio of the number of immunostained cells over the total number of cells in the field (n = 100). The ratio of RANKL+/total cells was higher than OPG+/total cells in periapical granulomas (0.553 +/- 0.153 and 0.483 +/- 0.189, respectively; P cysts (0.519 +/- 0.09 and 0.339 +/- 0.117, respectively; P cysts. However, the ratio RANKL+/OPG+ in granulomas (1.336 +/- 0.723) and cysts (1.404 +/- 0.385) was not significantly different. The ratio of CD68+/total cells was significantly higher in granulomas (0.381 +/- 0.040) than in cysts (0.307 +/- 0.068) (P cysts and granulomas, strongly suggesting the involvement of these gene products in the development of periapical lesions.

Improved efficacy of soluble human receptor activator of nuclear factor kappa B (RANK) fusion protein by site-directed mutagenesis.

Science.gov (United States)

Son, Young Jun; Han, Jihye; Lee, Jae Yeon; Kim, HaHyung; Chun, Taehoon

2015-06-01

Soluble human receptor activator of nuclear factor kappa B fusion immunoglobulin (hRANK-Ig) has been considered as one of the therapeutic agents to treat osteoporosis or diseases associated with bone destruction by blocking the interaction between RANK and the receptor activator of nuclear factor kappa B ligand (RANKL). However, no scientific record showing critical amino acid residues within the structural interface between the human RANKL and RANK complex is yet available. In this study, we produced several mutants of hRANK-Ig by replacement of amino acid residue(s) and tested whether the mutants had increased binding affinity to human RANKL. Based on the results from flow cytometry and surface plasmon resonance analyses, the replacement of E(125) with D(125), or E(125) and C(127) with D(125) and F(127) within loop 3 of cysteine-rich domain 3 of hRANK-Ig increases binding affinity to human RANKL over the wild-type hRANK-Ig. This result may provide the first example of improvement in the efficacy of hRANK-Ig by protein engineering and may give additional information to understand a more defined structural interface between hRANK and RANKL.

Supercritical CO2 Extraction of Essential Oil from Yarrow.

Czech Academy of Sciences Publication Activity Database

Bocevska, M.; Sovová, Helena

2007-01-01

Roč. 40, 3 (2007) , s. 360-367 ISSN 0896-8446 R&D Projects: GA AV ČR(CZ) KSK4040110 Grant - others:BEMUSAC(XE) G1MA/CT/2002/04019 Institutional research plan: CEZ:AV0Z40720504 Keywords : supercritical CO2 * essential oil * extraction curves Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 2.189, year: 2007

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.

Evaluation of the biological activity of sunflower hull extracts

Energy Technology Data Exchange (ETDEWEB)

Taha, F. S.; Wagdy, S. M.; Hassanein, M. M. M.; Hamed, S. F.

2012-11-01

This work was planned with the aim of adding value to sunflower seed hulls, a waste product of the oil industry by preparing a sunflower hull phenolic extract rich in chlorogenic acid (CGA). In order to fulfill this goal, the optimization for the extraction of a phenolic extract from the hulls was investigated. The parameters studied were: type of solvent, solvent to water ratio and hull to solvent ratio. In addition, the solvent mixtures were also studied. The resulting phenolic extracts were evaluated for their biological activities. This included phenolic content determination, evaluation of the antioxidant and antimicrobial activities. Chlorogenic acid was determined in two chosen hull extracts using the UV spectrophotometric method and HPLC analysis. The anti carcinogenic activity of the two chosen extracts was tested on seven different cell line carcinomas. The results revealed that all the phenolic extracts of sunflower hull studied contain between 190-312.5 mg phenolics/ 100 g hulls. The highest phenolic extraction was achieved with 80% methanol (1:30, hull to solvent, w/v ratio) and methanol to ethanol to water (7:7:6 v/v/v) mixture with values of 312.5 and 306.5 mg phenolics/100 g hulls, respectively. The free radical scavenging activity and antioxidant activity of all the samples ranged from 33.6-72.6%. The highest antioxidant activity and free radical scavenging activity were achieved by the same extracts that possessed the highest phenolic content, namely methanol to ethanol to water extract and 80% methanol with values 71.8 and 72.6%, 68.2 and 70.9% respectively, compared to 77.9 and 76.9% respectively for TBHQ. All the phenolic extracts possessed antimicrobial activity but to different levels against different pathogenic bacteria. The two chosen extracts also possessed anti carcinogenic activity, which differed among varying cell line carcinomas. The HPLC analysis indicated that chlorogenic acid was the main phenolic acid in the extract. Thus it can

AMATCHMETHOD BASED ON LATENT SEMANTIC ANALYSIS FOR EARTHQUAKEHAZARD EMERGENCY PLAN

Directory of Open Access Journals (Sweden)

D. Sun

2017-09-01

Full Text Available The structure of the emergency plan on earthquake is complex, and it’s difficult for decision maker to make a decision in a short time. To solve the problem, this paper presents a match method based on Latent Semantic Analysis (LSA. After the word segmentation preprocessing of emergency plan, we carry out keywords extraction according to the part-of-speech and the frequency of words. Then through LSA, we map the documents and query information to the semantic space, and calculate the correlation of documents and queries by the relation between vectors. The experiments results indicate that the LSA can improve the accuracy of emergency plan retrieval efficiently.

Amatchmethod Based on Latent Semantic Analysis for Earthquakehazard Emergency Plan

Science.gov (United States)

Sun, D.; Zhao, S.; Zhang, Z.; Shi, X.

2017-09-01

The structure of the emergency plan on earthquake is complex, and it's difficult for decision maker to make a decision in a short time. To solve the problem, this paper presents a match method based on Latent Semantic Analysis (LSA). After the word segmentation preprocessing of emergency plan, we carry out keywords extraction according to the part-of-speech and the frequency of words. Then through LSA, we map the documents and query information to the semantic space, and calculate the correlation of documents and queries by the relation between vectors. The experiments results indicate that the LSA can improve the accuracy of emergency plan retrieval efficiently.

Chicle harvesting and extractive reserves in the Maya Biosphere b: Reserve

Energy Technology Data Exchange (ETDEWEB)

Dugelby, B.L.

1995-12-31

Chicle latex has been extracted from the forests of northern Guatemala for over 100 years and is a key element in the extractive reserve component of the Maya Biosphere Reserve. The carrying capacity of the reserve for chicle extraction can be estimated from a model incorporating ecological data (such as latex yields per tree and population structure of chicle trees, Manilkara zapota, Sapot.) with socio-ecological and political information concerning camp and chicle resource availability, harvester tapping behavior, and historical and present-day institutional organization. I estimate that chicle harvestors currently utilize and area larger than the multiple use zone of the reserve in a unsustainable manner. Simple reduction of harvestors numbers will not ensure sustainability; institutional reforms are also in order. Extractive reserves can play an important role in preserving tropical forests. However, their effectiveness is highly dependent on prevailing ecological, socio-economic, and political conditions. Wise planning and management of extractive reserves demands an understanding of the system`s carrying capacity. In addition, a strong institutional foundation is necessary to assure effective monitoring and enforcement of harvesting regulations.

Supercritical Fluid Extraction of Minor Components of Vegetable Oils: beta-Sitosterol

Czech Academy of Sciences Publication Activity Database

Sovová, Helena; Galushko, A.A.; Stateva, R.P.; Rochová, Kristina; Sajfrtová, Marie; Bártlová, Milena

2010-01-01

Roč. 101, č. 2 (2010), s. 201-209 ISSN 0260-8774 R&D Projects: GA MŠk 2B06024 Institutional research plan: CEZ:AV0Z40720504 Keywords : supercritical fluid extraction * sea buckthorn oil * beta-sitosterol Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 2.168, year: 2010

The effects of three different grinding methods in DNA extraction of ...

African Journals Online (AJOL)

uwerhiavwe

2013-04-17

Apr 17, 2013 ... The effects of three different grinding methods in DNA extraction of cowpea .... 100 mg of the leaf tissues were weighed in an electronic balance. CTAB method .... The primers were synthesized by Life Technologies (AB & Invitrogen). .... This work was supported by 'Shuang-Zhi Plan' of Sichuan. Agricultural ...

Energy-Aware Path Planning for UAS Persistent Sampling and Surveillance

Science.gov (United States)

Shaw-Cortez, Wenceslao

The focus of this work is to develop an energy-aware path planning algorithm that maximizes UAS endurance, while performing sampling and surveillance missions in a known, stationary wind environment. The energy-aware aspect is specifically tailored to extract energy from the wind to reduce thrust use, thereby increasing aircraft endurance. Wind energy extraction is performed by static soaring and dynamic soaring. Static soaring involves using upward wind currents to increase altitude and potential energy. Dynamic soaring involves taking advantage of wind gradients to exchange potential and kinetic energy. The path planning algorithm developed in this work uses optimization to combine these soaring trajectories with the overarching sampling and surveillance mission. The path planning algorithm uses a simplified aircraft model to tractably optimize soaring trajectories. This aircraft model is presented and along with the derivation of the equations of motion. A nonlinear program is used to create the soaring trajectories based on a given optimization problem. This optimization problem is defined using a heuristic decision tree, which defines appropriate problems given a sampling and surveillance mission and a wind model. Simulations are performed to assess the path planning algorithm. The results are used to identify properties of soaring trajectories as well as to determine what wind conditions support minimal thrust soaring. Additional results show how the path planning algorithm can be tuned between maximizing aircraft endurance and performing the sampling and surveillance mission. A means of trajectory stitching is demonstrated to show how the periodic soaring segments can be combined together to provide a full solution to an infinite/long horizon problem.

Knochenstoffwechsel bei malignen Erkrankungen

Directory of Open Access Journals (Sweden)

Keck A-V

2003-01-01

Full Text Available Bei malignen Erkrankungen, wie dem Mammakarzinom, dem Prostatakarzinom, dem Bronchialkarzinom oder dem multiplen Myelom ist der Knochen eines der am häufigsten von Metastasen betroffenen Organe. Das klinische Beschwerdebild ist durch das Auftreten pathologischer Frakturen, Schmerzen und Hyperkalzämien gekennzeichnet. Eine erhöhte Knochenresorptionsrate und Verlust an Knochenmasse im Sinne von osteoporoseartigen Veränderungen bedingt durch eine inadäquat überschießende Osteoklastendifferenzierung und -aktivierung sind ursächlich dafür verantwortlich. Durch jüngst publizierte Ergebnisse diverser Studien und Untersuchungen konnten die genauen Mechanismen der Rekrutierung und Aktivierung von Osteoklasten weiter aufgeklärt werden. Receptor activator of nuclear factor-kappa-B ligand (RANKL, ein Mitglied der Tumor necrosis factor (TNF Superfamilie konnte als entscheidender Faktor in der Osteoklastengenese identifiziert werden. Die Interaktion von RANKL mit seinem Rezeptor RANK (receptor activator of nuclear factor-kappa-B induziert die Entwicklung der osteoklastären Reihe aus dem hämatopoetischen Kompartment und fördert weiters die Differenzierung zu Osteoklastenvorstufen und die Aktivierung reifer Osteoklasten, ebenso wird eine verzögert einsetzende Apoptose bewirkt. Neben RANK und RANKL ist Osteoprotegerin (OPG als dritte Komponente in der Regulation der Knochenresorption involviert. Als Mitglied der TNF-Superfamilie bindet OPG an RANKL und blockiert somit alle stimulierenden Effekte von RANK auf die Osteoklastenentwicklung und neutralisiert so alle biologischen Effekte von RANKL. Diverse Hormone und Zytokine üben durch die Modifikation der Ratio von RANKL zu OPG einen regulatorischen Effekt auf die Knochenresorption aus. Diese ist bei osteolytischen Knochenmetastasen, beim multiplen Myelom und bei der malignen Hyperkalzämie erhöht. Das Gleichgewicht knochenaufbauender wie -abbauender Mechanismen scheint somit durch die Ratio von

Mathematical Modelling of Supercritical CO2 Extraction of Volatile Oils from Aromatic Plants

Czech Academy of Sciences Publication Activity Database

Grosso, C.; Coelho, J.P.; Pessoa, F.L.P.; Fareleira, J.M.N.A.; Barroso, J.G.; Urieta, J.S.; Palavra, A.F.; Sovová, Helena

2010-01-01

Roč. 65, č. 11 (2010), s. 3579-3590 ISSN 0009-2509 Institutional research plan: CEZ:AV0Z40720504 Keywords : supercritical fluid extraction * modelling * volatile oils Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 2.379, year: 2010

Denosumab for bone diseases: translating bone biology into targeted therapy.

Science.gov (United States)

Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

2011-12-01

Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

Novel Weed-Extracted Silver Nanoparticles and Their Antibacterial Appraisal against a Rare Bacterium from River and Sewage Treatment Plan

Directory of Open Access Journals (Sweden)

Achmad Syafiuddin

2017-12-01

Full Text Available This is the first investigation to demonstrate the use of biochemical contents present within Cyperus rotundus, Eleusin indica, Euphorbia hirta, Melastoma malabathricum, Clidemia hirta and Pachyrhizus erosus extracts for the reduction of silver ion to silver nanoparticles (AgNPs form. In addition, the antibacterial capability of the synthesized AgNPs and plant extracts alone against a rare bacterium, Chromobacterium haemolyticum (C. haemolyticum, was examined. Moreover, ultraviolet-visible spectroscopy (UV-vis, Fourier transform infrared spectroscopy (FTIR, field emission scanning electron microscopy (FESEM, energy-dispersive X-ray spectroscopy (EDX and inductively coupled plasma atomic emission spectroscopy (ICPOES of the synthesized AgNPs were characterized. The smallest AgNPs can be produced when Cyperus rotundus extracts were utilized. In addition, this study has found that the synthesis efficiencies using all plant extracts are in the range of 72% to 91% with the highest percentage achieved when Eleusin indica extract was employed. All synthesized AgNPs have antibacterial capability against all examined bacteria depending on their size and bacteria types. Interestingly, Melastoma malabathricum and Clidemia hirta extracts have demonstrated an antibacterial ability against C. haemolyticum.

Creating Esthetic Harmony with Nonloading, Fixed Provisional Restoration using Extracted Teeth after Immediate Implant Placement.

Science.gov (United States)

Satwalekar, Parth; Satwalekar, Tanushree; Bondugula, Vasanthi; Bhuvaneshwari, B; Harshavardhan, K V; Pasula, Kiran

2016-04-01

To make use of fiber-reinforced composite and the patient's own extracted teeth in fabricating a provisional restoration following immediate implant placement. Fiber-reinforced composites offer various possibilities in temporization of osseointegrating implants in the esthetic zone. In this chairside technique, the patient's own extracted teeth with fiber-reinforced composite were used to fabricate a provisional restoration after immediate implant placement. A putty index was made before extracting the teeth and placing the implants as planned. The index and crowns of the extracted teeth were used to make a nonloading, esthetic, chair-side provisional restoration after immediate implant placement. By using the patient's own teeth for pro-visionalization immediately after implant placement, acceptance is greatly enhanced.

Advanced Recovery and Integrated Extraction System (ARIES) program plan. Rev. 1

International Nuclear Information System (INIS)

Nelson, T.O.; Massey, P.W.; Cremers, T.L.

1996-01-01

The Advanced Recovery and Integrated Extraction System (ARIES) demonstration combines various technologies, some of which were/are being developed under previous/other Department of Energy (DOE) funded programs. ARIES is an overall processing system for the dismantlement of nuclear weapon primaries. The program will demonstrate dismantlement of nuclear weapons and retrieval of the plutonium into a form that is compatible with long term storage and that is inspectable in an unclassified form appropriate for the application of traditional international safeguards. The success of the ARIES demonstration would lead to the development of a transportable modular or other facility type systems for weapons dismantlement to be used at other DOE sites as well as in other countries

Angle Class I malocclusion treated with lower incisor extraction.

Science.gov (United States)

Barbosa, Vanessa Leal Tavares

2013-01-01

In planning orthodontic cases that include extractions as an alternative to solve the problem of negative space discrepancy, the critical decision is to determine which teeth will be extracted. Several aspects must be considered, such as periodontal health, orthodontic mechanics, functional and esthetic alterations, and treatment stability. Despite controversies, extraction of teeth to solve dental crowding is a therapy that has been used for decades. Premolar extractions are the most common, but there are situations in which atypical extractions facilitate mechanics, preserve periodontal health and favor maintenance of the facial profile, which tends to unfavorably change due to facial changes with age. The extraction of a lower incisor, in selected cases, is an effective approach, and literature describes greater post-treatment stability when compared with premolar extractions. This article reports the clinical case of a patient with Angle Class I malocclusion and upper and lower anterior crowding, a balanced face and harmonious facial profile. The presence of gingival and bone recession limited large orthodontic movements. The molars and premolars were well occluded, and the discrepancy was mainly concentrated in the anterior region of the lower dental arch. The extraction of a lower incisor in the most ectopic position and with compromised periodontium, associated with interproximal stripping in the upper and lower arches, was the alternative of choice for this treatment, which restored function, providing improved periodontal health, maintained facial esthetics and allowed finishing with a stable and balanced occlusion. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO), as part of the requirements for obtaining the BBO Diplomate title.

Prospective study establishing a management plan for impacted third molar in patients undergoing hematopoietic stem cell transplantation

OpenAIRE

Yamagata, Kenji; Onizawa, Kojiro; Yanagawa, Toru; Takeuchi, Yasutoshi; Hasegawa, Yuichi; Chiba, Shigeru; Bukawa, Hiroki

2011-01-01

ObjectiveAlthough dental treatment before hematopoietic stem cell transplantation (HSCT) is essential to prevent serious infections from oral sources, the best management plan for impacted third molar (ITM) is unclear.Study designThis study was planned to establish a management plan for ITM. Eighty-four candidates for HSCT therapy were consecutively enrolled in the prospective trial. The management plan, which was evidence based and prospectively decided, was to extract the symptomatic ITMs a...

Development and design of plants for high-pressure extraction of natural products

Energy Technology Data Exchange (ETDEWEB)

Eggers, R; Tschiersch, R [Thyssen Industrie A.G., Witten (Germany, F.R.)

1979-06-01

Criteria underlying the design of plant for recovery of carrier material or extract are reviewed, particularly in relation to the extraction of natural products with supercritical CO/sub 2/. The parameters to be determined in the planning of a large-scale plant are outlined and as an example of a typical process, the extraction of spices is discussed in detail. The plant components and equipment are presented together with their particular process and construction characteristics. Finally, the thermodynamic aspects are analyzed and methods of optimizing a large-scale plant and of reducing the power consumption are outlined. Particular attention is paid to the question of optimization with regard to the most economic method of operation of such a plant to be applied in the future.

Targeting Integrin-β1 Impedes Cytokine-Induced Osteoclast ...

African Journals Online (AJOL)

but not in RANKL pathway. Given that, inflammatory cytokine secretions such as TNF-α are progressively implicated in pathological osteolysis, targeting this pathway may .... RANKL or TNF-alpha treated culture systems ... universal PCR Master Mix (Life Technologies,. USA). ... and developed using Super Signal West Dura.

Extraction and Separation of Cobalt and Nickel with Extractants Cyanex 302, Cyanex 272 and Their Mixture

Directory of Open Access Journals (Sweden)

Lenhard, Z.

2008-09-01

-nickel separation, which is obvious from the distributionratios for cobalt (Figs. 1 and 2 and nickel (Figs. 3 and 4 as well as from the cobalt-nickel separation factors (Table 1.In the extraction of cobalt and nickel with different mixtures of Cyanex 302 and Cyanex 272, no evidence for any synergistic effects were found, as indicated by the obtained synergistic coefficients (Table 2 and 3 and separation factors for cobalt and nickel (Table 4.In the follow-up work to this study, we plan to investigate new mixtures of extractants for their ability to separate cobalt from nickel in solutions with properties similar to those encountered in the extraction industry.

Sampling and Analysis Plan for PUREX canyon vessel flushing

International Nuclear Information System (INIS)

Villalobos, C.N.

1995-01-01

A sampling and analysis plan is necessary to provide direction for the sampling and analytical activities determined by the data quality objectives. This document defines the sampling and analysis necessary to support the deactivation of the Plutonium-Uranium Extraction (PUREX) facility vessels that are regulated pursuant to Washington Administrative Code 173-303

Planning Schools for the Future. Publication No. BM-1.

Science.gov (United States)

Weinberger, JoAnn

In a three-year study, Research for Better Schools (RBS) was asked by the National Institute of Education to identify, analyze, and verify definitive social changes forecast for the decades ahead, and to project their implications for schools of the future. RBS reviewed the literature to extract future planning needs relevant to educational…

A Tale of Two Regions: Landscape Ecological Planning for Shale Gas Energy Futures

Science.gov (United States)

Murtha, T., Jr.; Schroth, O.; Orland, B.; Goldberg, L.; Mazurczyk, T.

2015-12-01

As we increasingly embrace deep shale gas deposits to meet global energy demands new and dispersed local and regional policy and planning challenges emerge. Even in regions with long histories of energy extraction, such as coal, shale gas and the infrastructure needed to produce the gas and transport it to market offers uniquely complex transformations in land use and landcover not previously experienced. These transformations are fast paced, dispersed and can overwhelm local and regional planning and regulatory processes. Coupled to these transformations is a structural confounding factor. While extraction and testing are carried out locally, regulation and decision-making is multilayered, often influenced by national and international factors. Using a geodesign framework, this paper applies a set of geospatial landscape ecological planning tools in two shale gas settings. First, we describe and detail a series of ongoing studies and tools that we have developed for communities in the Marcellus Shale region of the eastern United States, specifically the northern tier of Pennsylvania. Second, we apply a subset of these tools to potential gas development areas of the Fylde region in Lancashire, United Kingdom. For the past five years we have tested, applied and refined a set of place based and data driven geospatial models for forecasting, envisioning, analyzing and evaluating shale gas activities in northern Pennsylvania. These models are continuously compared to important landscape ecological planning challenges and priorities in the region, e.g. visual and cultural resource preservation. Adapting and applying these tools to a different landscape allow us to not only isolate and define important regulatory and policy exigencies in each specific setting, but also to develop and refine these models for broader application. As we continue to explore increasingly complex energy solutions globally, we need an equally complex comparative set of landscape ecological

Prospective study establishing a management plan for impacted third molar in patients undergoing hematopoietic stem cell transplantation.

Science.gov (United States)

Yamagata, Kenji; Onizawa, Kojiro; Yanagawa, Toru; Takeuchi, Yasutoshi; Hasegawa, Yuichi; Chiba, Shigeru; Bukawa, Hiroki

2011-02-01

Although dental treatment before hematopoietic stem cell transplantation (HSCT) is essential to prevent serious infections from oral sources, the best management plan for impacted third molar (ITM) is unclear. This study was planned to establish a management plan for ITM. Eighty-four candidates for HSCT therapy were consecutively enrolled in the prospective trial. The management plan, which was evidence based and prospectively decided, was to extract the symptomatic ITMs and to leave the asymptomatic ones untreated, regardless of their impacted position. Eighty-seven ITMs were observed in 35 patients. The ITMs were in the maxilla of 25 patients and the mandible of 28 patients. Dental extraction of 7 teeth was performed in 6 patients without complications. All of the patients received the scheduled HSCT therapy and none experienced odontogenic infection while myelosuppressed. This management plan for ITM appears to be appropriate for pre-HSCT patients. Moreover, the experienced dental provider is suggested as a necessary and valuable part of the HSCT team. Crown Copyright © 2011. Published by Mosby, Inc. All rights reserved.

Bone status in patients with epilepsy: relationship to markers of bone remodeling

Directory of Open Access Journals (Sweden)

Sherifa Ahmed Hamed

2014-08-01

Full Text Available Patients with epilepsy and treated with antiepileptic drugs (AEDs may develop metabolic bone disease, however, the exact pathogenesis of bone loss with AEDs is still unclear. Included were 75 adults with epilepsy (mean age: 31.90±5.62years; duration of treatment with AEDs: 10.57±3.55years and 40 matched healthy controls. Bone mineral content (BMC and densities (BMD of the femoral neck and lumbar spine were measured using dual energy X-ray absorptiometry (DEXA. Blood samples were analyzed for calcium, magnesium, phosphate, alkaline phosphatase (ALP, 25-hydroxy vitamin D (25OHD, soluble receptor activator of nuclear factor kB ligand (sRANKL, osteoprotegerin (OPG and OPG/RANKL ratio (markers of bone remodeling. Compared to controls, patients had lower BMD, BMC, Z-score and T-score at the femoral neck and lumbar spine (all p<0.001. 72% and 29.33% of patients had osteoporosis of the lumbar spine and femoral neck. Patients had significantly lower serum calcium, 25(OHD and OPG and higher ALP, sRANKL levels and sRANKL/OPG (all p<0.001. 52% of patients had hypocalcemia, 93% had hypovitaminosis D, 31% had high levels of sRANKL and 49% had low levels of OPG. No differences were identified between DEXA and laboratory results in relation to the type, dose or serum levels of AEDs. BMD at the femoral neck and lumbar spine were found to be correlated with the duration of illness (p=0.043; p=0.010, duration of treatment with AEDs (p<0.001; p=0.012 and serum levels of 25(OHD (p<0.042; p=0.010, sRANKLs (p=0.005; p=0.01 and OPG (p<0.006; p<0.01. In linear regression analysis and after adjusting for gender, age, weight, duration and number of AEDs, we observed an association between BMD, 25(OHD (p=0.04 and sRANKL (p=0.03 concentrations. We conclude that AEDs may compromise bone health through disturbance of mineral metabolism and acceleration of bone turnover mechanisms.

Tick salivary gland extract accelerates proliferation of Francisella tularensis in the host

Czech Academy of Sciences Publication Activity Database

Kročová, Z.; Macela, A.; Hernychová, L.; Kroča, M.; Pechová, Jitka; Kopecký, Jan

2003-01-01

Roč. 89, č. 1 (2003), s. 14-20 ISSN 0022-3395 R&D Projects: GA ČR GA524/02/0901; GA MZd NI4700 Institutional research plan: CEZ:AV0Z6022909 Keywords : salivary gland extract * tick * Francisella tularensis Subject RIV: EC - Immunology Impact factor: 1.137, year: 2003

Environmental sensitive road planning and transportation techniques in forest engineering

Directory of Open Access Journals (Sweden)

H. Hulusi Acar

2016-07-01

Full Text Available Forestry management has activities dealing with technical, economic, social and environmental services. Forestry operations which are carried out on forest areas , an important part of the ecosistem are materialized in open space. This forestry activities on large areas and high sloping generally, include many different techniques. It is needed primarily to the forest road network in terms of forest management. Determining the approriate route in the natural environment, planning and road construction affairs for forest roads which are necessary accessing in forest areas, is also of great importance from an environmental viewpoint as well as technical and economic manner. Forest road planning which can not be changed later and left a permanent mark on the natural environment carries much more importance to the environment especially on sloping land. This is because, it is important choosing correct type of roaf structure, and doing periodic maintenance of the roads. Skidding activities, after wood production, is important in terms of its impact on forest soil and by means of effects on saplings and trees on the releated forest areas.The development of environmental sensitive techniques is difficult, limited or expensive for this wood extraction works which are made more difficult conditons in the sloping terrain. Therefore, especially in using some silvicultural methods wood extraction damages are even greater. In this study; some road planning, road construction and wood extraction techniques which performed by me have been made to examine the environmental aspects. Environment-friendly forest roads and primary transport techniques on the forest ecosystem are briefly explained and discussed in the frame of the environmental aspects.

Oil program implementation plan FY 1996--2000

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-04-01

This document reaffirms the US Department of Energy (DOE) Office of Fossil Energy commitment to implement the National Oil Research Program in a way to maximize assurance of energy security, economic growth, environmental protection, jobs, improved economic competitiveness, and improved US balance of trade. There are two sections and an appendix in this document. Section 1 is background information that guided its formulation and a summary of the Oil Program Implementation Plan. This summary includes mission statements, major program drivers, oil issues and trends, budget issues, customers/stakeholders, technology transfer, measures of program effectiveness, and benefits. Section 2 contains more detailed program descriptions for the eight technical areas and the NIPER infrastructure. The eight technical areas are reservoir characterization; extraction research; exploration, drilling, and risk-based decision management; analysis and planning; technology transfer; field demonstration projects; oil downstream operations; and environmental research. Each description contains an overview of the program, descriptions on main areas, a discussion of stakeholders, impacts, planned budget projections, projected schedules with Gantt charts, and measures of effectiveness. The appendix is a summary of comments from industry on an earlier draft of the plan. Although changes were made in response to the comments, many of the suggestions will be used as guidance for the FY 1997--2001 plan.

Retirement Planning: Young Professionals in Private Sector

Directory of Open Access Journals (Sweden)

Ahmad Zazili Ainol Sarin

2017-01-01

Full Text Available The purpose of this study is to determine the factors influencing retirement planning among young professionals in private sector. There are three factors identified in this research which includes financial literacy, job satisfaction and savings behavior. Data used for this study are primary and secondary data such as from journal articles, periodicals and textbooks. A questionnaire is distributed and administered to extract data from the respondents consist of executives, non-executives and managers around Klang Valley, aged between 20 - 34 years old. The data is analyzed using frequency analysis, reliability test and Pearson correlation in order to obtain a clear findings and results. The findings show that financial literacy, job satisfaction and savings behavior has a positive association towards retirement planning. Furthermore, it is shown that financial literacy and saving behavior have a significant relationship with retirement planning. It is hope that this study will inform and encourage the young professionals to save and invest for the retirement.

Study on the extraction kinetics of U(IV) extraction with neutral phosphoric extractant

International Nuclear Information System (INIS)

Lin Zhou; Liao Shishu; Li Zhou

1995-04-01

The extraction kinetics of U(IV) in the diisooctyl isobutylphosphonate system has been studied by using the single drop method. The effects of the concentrations of U(IV), HCl and extractant on the extraction rate have been examined. In a certain HCl concentration, the extraction rate equation has been acquired and in the condition of various HCl concentration the extraction rate of U(IV) is proportional to [HCl 1.51 . The effect of operation temperature was also examined, and the calculated apparent activation energy is equal to 23.24 kJ/mol. From the experimental results, the extraction reaction process and the rate-controlling step have been deduced. (4 figs., 5 tabs.)

Excavation-drier method of energy-peat extraction reduces long-term climatic impact

Energy Technology Data Exchange (ETDEWEB)

Silvan, N.; Silvan, K.; Laine, J. [Finnish Forest Research Inst., Parkano (Finland)], e-mail: niko.silvan@metla.fi; Vaisanen, S.; Soukka, R. [Lappeenranta Univ.of Techology (Finland)

2012-11-01

Climatic impacts of energy-peat extraction are of increasing concern due to EU emissions trading requirements. A new excavation-drier peat extraction method has been developed to reduce the climatic impact and increase the efficiency of peat extraction. To quantify and compare the soil GHG fluxes of the excavation drier and the traditional milling methods, as well as the areas from which the energy peat is planned to be extracted in the future (extraction reserve area types), soil CO{sub 2}, CH{sub 4} and N{sub 2}O fluxes were measured during 2006-2007 at three sites in Finland. Within each site, fluxes were measured from drained extraction reserve areas, extraction fields and stockpiles of both methods and additionally from the biomass driers of the excavation-drier method. The Life Cycle Assessment (LCA), described at a principal level in ISO Standards 14040:2006 and 14044:2006, was used to assess the long-term (100 years) climatic impact from peatland utilisation with respect to land use and energy production chains where utilisation of coal was replaced with peat. Coal was used as a reference since in many cases peat and coal can replace each other in same power plants. According to this study, the peat extraction method used was of lesser significance than the extraction reserve area type in regards to the climatic impact. However, the excavation-drier method seems to cause a slightly reduced climatic impact as compared with the prevailing milling method. (orig.)

Assessment of the BCR sequential extraction procedure for thallium fractionation using synthetic mineral mixtures

Czech Academy of Sciences Publication Activity Database

Vaněk, A.; Grygar, Tomáš; Chrastný, V.; Tejnecký, V.; Drahota, Petr; Komárek, M.

2010-01-01

Roč. 176, 1-3 (2010), s. 913-918 ISSN 0304-3894 Institutional research plan: CEZ:AV0Z4032918; CEZ:AV0Z30130516 Keywords : Metal * Sequential extraction * Goethite * Ferrihydrite * Birnessite * Illite Subject RIV: DD - Geochemistry Impact factor: 3.723, year: 2010

Records needed for orthodontic diagnosis and treatment planning: a systematic review.

Directory of Open Access Journals (Sweden)

Robine J Rischen

Full Text Available BACKGROUND: Traditionally, dental models, facial and intra-oral photographs and a set of two-dimensional radiographs are used for orthodontic diagnosis and treatment planning. As evidence is lacking, the discussion is ongoing which specific records are needed for the process of making an orthodontic treatment plan. OBJECTIVE: To estimate the contribution and importance of different diagnostic records for making an orthodontic diagnosis and treatment plan. DATA SOURCES: An electronic search in PubMed (1948-July 2012, EMBASE Excerpta Medica (1980-July 2012, CINAHL (1982-July 2012, Web of Science (1945-July 2012, Scopus (1996-July 2012, and Cochrane Library (1993-July 2012 was performed. Additionally, a hand search of the reference lists of included studies was performed to identify potentially eligible studies. There was no language restriction. STUDY SELECTION: The patient, intervention, comparator, outcome (pico question formulated for this study was as follows: for patients who need orthodontic treatment (P, will the use of record set X (I compared with record set Y (C change the treatment plan (O? Only primary publications were included. DATA EXTRACTION: Independent extraction of data and quality assessment was performed by two observers. RESULTS: Of the 1041 publications retrieved, 17 met the inclusion criteria. Of these, 4 studies were of high quality. Because of the limited number of high quality studies and the differences in study designs, patient characteristics, and reference standard or index test, a meta-analysis was not possible. CONCLUSION: Cephalograms are not routinely needed for orthodontic treatment planning in Class II malocclusions, digital models can be used to replace plaster casts, and cone-beam computed tomography radiographs can be indicated for impacted canines. Based on the findings of this review, the minimum record set required for orthodontic diagnosis and treatment planning could not be defined. SYSTEMATIC REVIEW

Rent extraction by large shareholders: evidence using dividend policy in the Czech Republic

Czech Academy of Sciences Publication Activity Database

Bena, Jan; Hanousek, Jan

-, č. 291 (2006), s. 1-45 ISSN 1211-3298 R&D Projects: GA ČR GA402/06/1293 Institutional research plan: CEZ:AV0Z70850503 Keywords : rent extraction * large shareholders * corporate governance Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp291.pdf

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.

Th17-cells in atopic dermatitis stimulate orthodontic root resorption.

Science.gov (United States)

Yamada, K; Yamaguchi, M; Asano, M; Fujita, S; Kobayashi, R; Kasai, K

2013-10-01

The aim of this study was to investigate how atopic dermatitis (AD) contributes to root resorption during orthodontic tooth movement. Atopic dermatitis model mice and wild-type mice were subjected to an excessive orthodontic force (OF) to induce movement of the upper first molars. The expression levels of the tartrate-resistant acid phosphatase (TRAP), IL-17, IL-6, and RANKL proteins were determined in the periodontal ligament (PDL) by an immunohistochemical analysis. Furthermore, the effects of the compression force on co-cultures of CD4(+) cells from AD patients or healthy individuals and human PDL cells were investigated with regard to the levels of secretion and mRNA expression of IL-17, IL-6, RANKL, and osteoprotegerin. The immunoreactivities for TRAP, IL-17, IL-6, and RANKL in the AD group were found to be significantly increased. The double immunofluorescence analysis for IL-17/CD4 detected immunoreaction. The secretion of IL-17, IL-6, and RANKL, and the mRNA levels of IL-6 and RANKL in the AD patients were increased compared with those in healthy individuals. Th17 cells may therefore be associated with the deterioration of root resorption of AD mice, and may explain why AD patients are more susceptible to root resorption than healthy individuals when an excessive OF is applied. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Do Groundwater Management Plans Work? A statistical evaluation of the effectiveness of groundwater management plans towards achieving water supply and environmental objectives under a changing climate.

Science.gov (United States)

White, E.; Peterson, T. J.; Costelloe, J. F.; Western, A. W.; Carrara, E.

2017-12-01

Regulation of groundwater through the use of management plans is becoming increasingly prevalent as global groundwater levels decline. But plans are seldom systematically and quantitatively assessed for effectiveness. Instead, the state of an aquifer is commonly considered a proxy for plan effectiveness despite a lack of casaulity. Groundwater managers face myraid challenges such as finite resources, conflicting uses and the uncertainty inherent in any groundwater investigation. Groundwater models have been used to provide insights into what may happen to the aquifer under various levels of stress. Generally, these models simulate the impact of predefined stresses for a certain time-span. However, this is not how management occurs in reality. Managers only see a fraction of the aquifer and use this limited knowledgeto make aquifer-wide decisions. Also, management changes over time in response to aquifer state, and groundwater management plans commonly contain trigger levels in monitoring wells that prompt management intervention. In this way there is a feedback between the aquifer state and management that is rarely captured by groundwater management models. To capture this management/aquifer feedback, groundwater management was structured as a systems control problem, and using this framework, a testability assessment rubric developed. The rubric was applied to 15 Australian groundwater management plans and 47% of plans were found to be testable. To numerically quantify the effectiveness of groundwater managment, the impact of extraction restrictions was probabilistically assessed by simulating "the act of management" of a simple unconfined groundwater system using MODFLOW and Flopy. Water managers were privy only to head levels in a varying number of grid cells assigned as monitoring wells, and used that limited information to make allocation decisions at each time step. Extraction rates for each simulated management period were determined based upon the observed

Supercritical Fluid Extraction of Lignans and Cinnamic Acid from Schizandra chinensis.

Czech Academy of Sciences Publication Activity Database

Sovová, Helena; Opletal, L.; Bártlová, Milena; Sajfrtová, Marie; Křenková, M.

2007-01-01

Roč. 42, 1 (2007) , s. 88-95 ISSN 0896-8446 R&D Projects: GA ČR(CZ) GA203/01/0550; GA AV ČR IAA4072102; GA AV ČR KSK4040110 Institutional research plan: CEZ:AV0Z40720504 Keywords : supercritical extraction * solubility * lignans Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 2.189, year: 2007

A research of road centerline extraction algorithm from high resolution remote sensing images

Science.gov (United States)

Zhang, Yushan; Xu, Tingfa

2017-09-01

Satellite remote sensing technology has become one of the most effective methods for land surface monitoring in recent years, due to its advantages such as short period, large scale and rich information. Meanwhile, road extraction is an important field in the applications of high resolution remote sensing images. An intelligent and automatic road extraction algorithm with high precision has great significance for transportation, road network updating and urban planning. The fuzzy c-means (FCM) clustering segmentation algorithms have been used in road extraction, but the traditional algorithms did not consider spatial information. An improved fuzzy C-means clustering algorithm combined with spatial information (SFCM) is proposed in this paper, which is proved to be effective for noisy image segmentation. Firstly, the image is segmented using the SFCM. Secondly, the segmentation result is processed by mathematical morphology to remover the joint region. Thirdly, the road centerlines are extracted by morphology thinning and burr trimming. The average integrity of the centerline extraction algorithm is 97.98%, the average accuracy is 95.36% and the average quality is 93.59%. Experimental results show that the proposed method in this paper is effective for road centerline extraction.

Improving treatment plan evaluation with automation

Science.gov (United States)

Covington, Elizabeth L.; Chen, Xiaoping; Younge, Kelly C.; Lee, Choonik; Matuszak, Martha M.; Kessler, Marc L.; Keranen, Wayne; Acosta, Eduardo; Dougherty, Ashley M.; Filpansick, Stephanie E.

2016-01-01

The goal of this work is to evaluate the effectiveness of Plan‐Checker Tool (PCT) which was created to improve first‐time plan quality, reduce patient delays, increase the efficiency of our electronic workflow, and standardize and automate the physics plan review in the treatment planning system (TPS). PCT uses an application programming interface to check and compare data from the TPS and treatment management system (TMS). PCT includes a comprehensive checklist of automated and manual checks that are documented when performed by the user as part of a plan readiness check for treatment. Prior to and during PCT development, errors identified during the physics review and causes of patient treatment start delays were tracked to prioritize which checks should be automated. Nineteen of 33 checklist items were automated, with data extracted with PCT. There was a 60% reduction in the number of patient delays in the six months after PCT release. PCT was successfully implemented for use on all external beam treatment plans in our clinic. While the number of errors found during the physics check did not decrease, automation of checks increased visibility of errors during the physics check, which led to decreased patient delays. The methods used here can be applied to any TMS and TPS that allows queries of the database. PACS number(s): 87.55.‐x, 87.55.N‐, 87.55.Qr, 87.55.tm, 89.20.Bb PMID:27929478

Comparison of mentha extracts obtained by different extraction methods

Directory of Open Access Journals (Sweden)

Milić Slavica

2006-01-01

Full Text Available The different methods of mentha extraction, such as steam distillation, extraction by methylene chloride (Soxhlet extraction and supercritical fluid extraction (SFE by carbon dioxide (CO J were investigated. SFE by CO, was performed at pressure of 100 bar and temperature of40°C. The extraction yield, as well as qualitative and quantitative composition of obtained extracts, determined by GC-MS method, were compared.

CURB-BASED STREET FLOOR EXTRACTION FROM MOBILE TERRESTRIAL LIDAR POINT CLOUD

Directory of Open Access Journals (Sweden)

S. Ibrahim

2012-07-01

Full Text Available Mobile terrestrial laser scanners (MTLS produce huge 3D point clouds describing the terrestrial surface, from which objects like different street furniture can be generated. Extraction and modelling of the street curb and the street floor from MTLS point clouds is important for many applications such as right-of-way asset inventory, road maintenance and city planning. The proposed pipeline for the curb and street floor extraction consists of a sequence of five steps: organizing the 3D point cloud and nearest neighbour search; 3D density-based segmentation to segment the ground; morphological analysis to refine out the ground segment; derivative of Gaussian filtering to detect the curb; solving the travelling salesman problem to form a closed polygon of the curb and point-inpolygon test to extract the street floor. Two mobile laser scanning datasets of different scenes are tested with the proposed pipeline. The results of the extracted curb and street floor are evaluated based on a truth data. The obtained detection rates for the extracted street floor for the datasets are 95% and 96.53%. This study presents a novel approach to the detection and extraction of the road curb and the street floor from unorganized 3D point clouds captured by MTLS. It utilizes only the 3D coordinates of the point cloud.

Angle Class II malocclusion treated with extraction of permanent teeth

Directory of Open Access Journals (Sweden)

Gustavo Mattos Barreto

2013-08-01

Full Text Available Angle Class II malocclusion associated with anterior open bite in adult patients demands a carefully elaborated orthodontic planning, aiming at restoring not only harmonious dental and facial esthetics, but also a balanced masticatory function. Orthognathic surgery or permanent teeth extraction are often the choice of treatment, therefore, treatment decision is related to all dental, skeletal and functional aspects. The present report discusses orthodontic compensation carried out by means of upper premolar extraction performed to correct the Class II canine relationship and, consequently, the anterior open bite, accepting that the upper incisors be retroclined. This clinical case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as part of the requirements for obtaining the BBO Certification.

Vector-model-supported approach in prostate plan optimization

International Nuclear Information System (INIS)

Liu, Eva Sau Fan; Wu, Vincent Wing Cheung; Harris, Benjamin; Lehman, Margot; Pryor, David; Chan, Lawrence Wing Chi

2017-01-01

Lengthy time consumed in traditional manual plan optimization can limit the use of step-and-shoot intensity-modulated radiotherapy/volumetric-modulated radiotherapy (S&S IMRT/VMAT). A vector model base, retrieving similar radiotherapy cases, was developed with respect to the structural and physiologic features extracted from the Digital Imaging and Communications in Medicine (DICOM) files. Planning parameters were retrieved from the selected similar reference case and applied to the test case to bypass the gradual adjustment of planning parameters. Therefore, the planning time spent on the traditional trial-and-error manual optimization approach in the beginning of optimization could be reduced. Each S&S IMRT/VMAT prostate reference database comprised 100 previously treated cases. Prostate cases were replanned with both traditional optimization and vector-model-supported optimization based on the oncologists' clinical dose prescriptions. A total of 360 plans, which consisted of 30 cases of S&S IMRT, 30 cases of 1-arc VMAT, and 30 cases of 2-arc VMAT plans including first optimization and final optimization with/without vector-model-supported optimization, were compared using the 2-sided t-test and paired Wilcoxon signed rank test, with a significance level of 0.05 and a false discovery rate of less than 0.05. For S&S IMRT, 1-arc VMAT, and 2-arc VMAT prostate plans, there was a significant reduction in the planning time and iteration with vector-model-supported optimization by almost 50%. When the first optimization plans were compared, 2-arc VMAT prostate plans had better plan quality than 1-arc VMAT plans. The volume receiving 35 Gy in the femoral head for 2-arc VMAT plans was reduced with the vector-model-supported optimization compared with the traditional manual optimization approach. Otherwise, the quality of plans from both approaches was comparable. Vector-model-supported optimization was shown to offer much shortened planning time and iteration

Vector-model-supported approach in prostate plan optimization

Energy Technology Data Exchange (ETDEWEB)

Liu, Eva Sau Fan [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); Department of Health Technology and Informatics, The Hong Kong Polytechnic University (Hong Kong); Wu, Vincent Wing Cheung [Department of Health Technology and Informatics, The Hong Kong Polytechnic University (Hong Kong); Harris, Benjamin [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); Lehman, Margot; Pryor, David [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); School of Medicine, University of Queensland (Australia); Chan, Lawrence Wing Chi, E-mail: wing.chi.chan@polyu.edu.hk [Department of Health Technology and Informatics, The Hong Kong Polytechnic University (Hong Kong)

2017-07-01

Lengthy time consumed in traditional manual plan optimization can limit the use of step-and-shoot intensity-modulated radiotherapy/volumetric-modulated radiotherapy (S&S IMRT/VMAT). A vector model base, retrieving similar radiotherapy cases, was developed with respect to the structural and physiologic features extracted from the Digital Imaging and Communications in Medicine (DICOM) files. Planning parameters were retrieved from the selected similar reference case and applied to the test case to bypass the gradual adjustment of planning parameters. Therefore, the planning time spent on the traditional trial-and-error manual optimization approach in the beginning of optimization could be reduced. Each S&S IMRT/VMAT prostate reference database comprised 100 previously treated cases. Prostate cases were replanned with both traditional optimization and vector-model-supported optimization based on the oncologists' clinical dose prescriptions. A total of 360 plans, which consisted of 30 cases of S&S IMRT, 30 cases of 1-arc VMAT, and 30 cases of 2-arc VMAT plans including first optimization and final optimization with/without vector-model-supported optimization, were compared using the 2-sided t-test and paired Wilcoxon signed rank test, with a significance level of 0.05 and a false discovery rate of less than 0.05. For S&S IMRT, 1-arc VMAT, and 2-arc VMAT prostate plans, there was a significant reduction in the planning time and iteration with vector-model-supported optimization by almost 50%. When the first optimization plans were compared, 2-arc VMAT prostate plans had better plan quality than 1-arc VMAT plans. The volume receiving 35 Gy in the femoral head for 2-arc VMAT plans was reduced with the vector-model-supported optimization compared with the traditional manual optimization approach. Otherwise, the quality of plans from both approaches was comparable. Vector-model-supported optimization was shown to offer much shortened planning time and iteration

A New Approach to Urban Road Extraction Using High-Resolution Aerial Image

Directory of Open Access Journals (Sweden)

Jianhua Wang

2016-07-01

Full Text Available Road information is fundamental not only in the military field but also common daily living. Automatic road extraction from a remote sensing images can provide references for city planning as well as transportation database and map updating. However, owing to the spectral similarity between roads and impervious structures, the current methods solely using spectral characteristics are often ineffective. By contrast, the detailed information discernible from the high-resolution aerial images enables road extraction with spatial texture features. In this study, a knowledge-based method is established and proposed; this method incorporates the spatial texture feature into urban road extraction. The spatial texture feature is initially extracted by the local Moran’s I, and the derived texture is added to the spectral bands of image for image segmentation. Subsequently, features like brightness, standard deviation, rectangularity, aspect ratio, and area are selected to form the hypothesis and verification model based on road knowledge. Finally, roads are extracted by applying the hypothesis and verification model and are post-processed based on the mathematical morphology. The newly proposed method is evaluated by conducting two experiments. Results show that the completeness, correctness, and quality of the results could reach approximately 94%, 90% and 86% respectively, indicating that the proposed method is effective for urban road extraction.

Internet plan and planning

Directory of Open Access Journals (Sweden)

Kahriman Emina

2008-01-01

Full Text Available Paper discuss specific features of internet plan as well as planning as management process in general in the contemporary environment. No need to stress out that marketing plan and marketing planning is core activity in approaching to market. At the same time, there are a lot specific c request in preparing marketing plan comparing to business planning due to marketing plan is an essential part. The importance of internet plan and planning rely on specific features of the internet network but as a part of general corporate as well as marketing strategy.

Efficient authentication scheme based on near-ring root extraction problem

Science.gov (United States)

Muthukumaran, V.; Ezhilmaran, D.

2017-11-01

An authentication protocolis the type of computer communication protocol or cryptography protocol specifically designed for transfer of authentication data between two entities. We have planned a two new entity authentication scheme on the basis of root extraction problem near-ring in this article. We suggest that this problem is suitably difficult to serve as a cryptographic assumption over the platform of near-ring N. The security issues also discussed.

A study on the total phenols content and antioxidant activity of essential oil and different solvent extracts of endemic plant Merremia borneensis

Directory of Open Access Journals (Sweden)

M. Amzad Hossain

2015-01-01

Full Text Available This study is planned to determine the antioxidant activity and total phenols content of the essential oil and different solvent extracts of the endemic plant Merremia borneensis. The antioxidant activities of the extracts were examined by three different methods, DPPH, β-carotene and reducing power assays. In all methods, aqueous ethanol extract exhibited a higher activity potential than that of other extracts (hexane, chloroform, ethyl acetate and butanol and the essential oil. As assumed, the amount of total phenolics was very high in this extract. Chloroform extract has been found to be rich in flavonoids. A positive result was observed between the antioxidant activity potential and total flavonoid levels of the extracts.

A New Method of Chinese Address Extraction Based on Address Tree Model

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KANG Mengjun

2015-01-01

Full Text Available Address is a spatial location encoding method of individual geographical area. In China, address planning is relatively backward due to the rapid development of the city, resulting in the presence of large number of non-standard address. The space constrain relationship of standard address model is analyzed in this paper and a new method of standard address extraction based on the tree model is proposed, which regards topological relationship as consistent criteria of space constraints. With this method, standard address can be extracted and errors can be excluded from non-standard address. Results indicate that higher math rate can be obtained with this method.

The inhibitory effect of strontium-doped calcium polyphosphate particles on cytokines from macrophages and osteoblasts leading to aseptic loosening in vitro

International Nuclear Information System (INIS)

Huang, Chengcheng; Yu, Xixun; Gu, Zhipeng; Li, Li; Zhang, Xu

2014-01-01

Aseptic loosening is a common cause of joint implant failure in humans. In order to enhance implant stability, we need to develop a new material that not only promotes the wear resistance of components of an artificial joint, but also possesses the pharmaceutical efficacy of protecting patients against aseptic loosening. Strontium-doped calcium polyphosphate (SCPP) has been found to have this potential ability. The goal of this study is to respectively quantify the levels of TNF-α (for macrophages), receptor activator of NF- k B ligand (RANKL) and osteoprotegerin (OPG) (for osteoblasts) when osteoblasts and macrophages are challenged with various particles (including SCPP). In this study, the osteoblasts ROS 17/2.8 and macrophages RAW 264.7 were challenged with various wear particles (8% SCPP, the molar percentage of Sr in SCPP is 8%, UHMWPE, hydroxyapatite (HA) and CPP). The secretion of TNF-α (from RAW 264.7), OPG and RANKL protein (from ROS 17/2.8) was analyzed by ELISA. The OPG and RANKL mRNA from ROS 17/2.8 was detected by RT-PCR. The data of ELISA indicated that the amount of TNF-α challenged with 8% SCPP particles was more than three-fold lower than that of all other test groups. The ratio of OPG/RANKL in the 8% SCPP group was significantly increased compared to that of all other test groups. The results of OPG and RANKL mRNA expression showed the same tendency as the ELISA results. In general, this study showed that 8% SCPP particles can inhibit the expression of TNF-α and RANKL, promote the expression of OPG so that SCPP can inhibit bone resorption and promote bone formation, and then inhibit aseptic loosening. Thus SCPP could be a promising material for the construction of artificial joints. (paper)

216-A-36B Crib supplemental information to the Hanford Facility Contingency Plan (DOE/RL-93-75)

International Nuclear Information System (INIS)

Ingle, S.J.

1996-05-01

This document is a unit-specific contingency plan for the 216-A-36B Crib and is intended to be used as a supplement to DOE/RL-93-75, Hanford Facility Contingency Plan (DOE-RL 1993). This unit-specific plan is to be used to demonstrate compliance with the contingency plan requirements of the Washington Administrative Code, Chapter 173- 303 for certain Resource Conservation and Recovery Act of 1976 waste management units. The 216-A-36B Crib is a landfill that received ammonia scrubber waste from the 202-A Building (Plutonium/Uranium Extraction Plant) between 1966 and 1972. In 1982, the unit was reactivated to receive additional waste from Plutonium/Uranium Extraction operations. Discharges ceased in 1987, and the crib will be closed under final facility standards. Because the crib is not receiving discharges, waste management activities are no longer required. The crib does not present a significant hazard to adjacent units, personnel, or the environment. There is little likelihood that any incidents presenting hazards to public health or the environment would occur at the 216-A-36B Crib

Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo.

Science.gov (United States)

Baek, Jong Min; Kim, Ju-Young; Ahn, Sung-Jun; Cheon, Yoon-Hee; Yang, Miyoung; Oh, Jaemin; Choi, Min Kyu

2016-03-01

Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects of DM on bone diseases such as osteoporosis. Thus, we investigated the relationship between DM and osteoclasts, cells that function in bone resorption. We found that DM significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation; DM directly induced the down-regulation of c-Fos and nuclear factor of activated T cells c1 (NFATc1) without affecting other RANKL-dependent transduction pathways. In the later stages of osteoclast maturation, DM negatively regulated the organization of filamentous actin (F-actin), resulting in impaired bone-resorbing activity by the mature osteoclasts. In addition, micro-computed tomography (μ-CT) analysis of the murine model revealed that DM had a beneficial effect on lipopolysaccharide (LPS)-mediated bone erosion. Histological analysis showed that DM attenuated the degradation of trabecular bone matrix and formation of TRAP-positive osteoclasts in bone tissues. These results suggest that DM is a potential candidate for the treatment of metabolic bone disorders such as osteoporosis.

Characterization of two types of osteoclasts from human peripheral blood monocytes

International Nuclear Information System (INIS)

Yuasa, Kimitaka; Mori, Kouki; Ishikawa, Hitoshi; Sudo, Akihiro; Uchida, Atsumasa; Ito, Yasuhiko

2007-01-01

The two osteoclastogenesis pathways, receptor activator nuclear factor (NF)-κB ligand (RANKL)-mediated and fusion regulatory protein-1 (FRP-1)-mediated osteoclastogenesis, have recently been reported. There were significant differences in differentiation and activation mechanisms between the two pathways. When monocytes were cultured with FRP-1 without adding M-CSF, essential for the RANKL system, TRAP-positive polykaryocyte formation occurred. FRP-1-mediated osteoclasts formed larger pits on mineralized calcium phosphate plates than RANKL+M-CSF-mediated osteoclasts did. Lacunae on dentin surfaces induced by FRP-1-mediated osteoclasts were inclined to be single and isolated. However, osteoclasts induced by RANKL+M-CSF made many connected pits on dentin surfaces as if they crawled on there. Interestingly, FRP-1 osteoclastogenesis was enhanced by M-CSF/IL-1α, while chemotactic behavior to the dentin slices was not effected. There were differences in pH and concentration of HCO3- at culture endpoint and in adherent feature to dentin surfaces. Our findings indicate there are two types of osteoclasts with distinct properties

Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate.

Science.gov (United States)

Fan, Yi; Hanai, Jun-Ichi; Le, Phuong T; Bi, Ruiye; Maridas, David; DeMambro, Victoria; Figueroa, Carolina A; Kir, Serkan; Zhou, Xuedong; Mannstadt, Michael; Baron, Roland; Bronson, Roderick T; Horowitz, Mark C; Wu, Joy Y; Bilezikian, John P; Dempster, David W; Rosen, Clifford J; Lanske, Beate

2017-03-07

Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1 + RANKL + marrow progenitors were twice as great in mutant versus control marrow. Intermittent PTH administration to control mice reduced BMAT significantly. A similar finding was noted in male osteoporotic patients. Thus, marrow adipocytes exhibit osteogenic and adipogenic characteristics, are uniquely responsive to PTH, and secrete RANKL. These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

Osteoclast formation is strongly reduced both in vivo and in vitro in the absence of CD47/SIRPα-interaction

International Nuclear Information System (INIS)

Lundberg, Pernilla; Koskinen, Cecilia; Baldock, Paul A.; Loethgren, Hanna; Stenberg, Asa; Lerner, Ulf H.; Oldenborg, Per-Arne

2007-01-01

Physical interaction between the cell surface receptors CD47 and signal regulatory protein alpha (SIRPα) was reported to regulate cell migration, phagocytosis, cytokine production, and macrophage fusion. However, it is unclear if the CD47/SIRPα-interaction can also regulate macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-κB ligand (RANKL)-stimulated formation of osteoclasts. Here, we show that functional blocking antibodies to either CD47 or SIRPα strongly reduced formation of multinucleated tartrate-resistant acid phosphatase (TRAP) + osteoclasts in cultures of murine hematopoietic cells, stimulated in vitro by M-CSF and RANKL. In addition, the numbers of osteoclasts formed in M-CSF/RANKL-stimulated bone marrow macrophage cultures from CD47 -/- mice were strongly reduced, and bones of CD47 -/- mice exhibited significantly reduced osteoclast numbers, as compared with wild-type controls. We conclude that the CD47/SIRPα interaction is important for M-CSF/RANKL-stimulated osteoclast formation both in vivo and in vitro, and that absence of CD47 results in decreased numbers of osteoclasts in CD47 -/- mice

Topical Treatment with Xiaozheng Zhitong Paste (XZP Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

Directory of Open Access Journals (Sweden)

Yanju Bao

2015-01-01

Full Text Available To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05. Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P<0.05 for all. Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

Plan of development of ZrC-TRISO coated fuel particle and construction of ZrC coater

Energy Technology Data Exchange (ETDEWEB)

Ueta, Shohei; Ino, Hiroichi; Sawa, Kazuhiro [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment; Tobita, Tsutomu [Nuclear Engineering Company, Ltd., Tokai, Ibaraki (Japan); Takahashi, Masashi [Nuclear Fuel Industries, Ltd., Tokyo (Japan)

2002-11-01

In order to use coated fuel particle under higher temperature condition, more refractory coating material, which is more refractory than conventional silicon carbide (SiC), should be applied. Zirconium carbide (ZrC) is considered to be one of the promising materials, which is proposed as candidate for VHTR fuel material in GENERATION-IV, because of its intactness under high temperature of around 2000degC and its higher stability against kernel migration (amoeba effect) and fission product corrosion under normal operating condition. In order to develop ZrC coated particle for commercial use, research and development items were extracted based on review of the previous works. Research and development plan was determined. Based on the plan, a new ZrC coater of 100g batch size, which applies bromine process, was constructed. This report describes the review of precious works, extracted research and develop items and plan, and specifications of the ZrC coater. (author)

Extraction of Phytosterols from Tall Oil Soap Using Selected Organic Solvents

Czech Academy of Sciences Publication Activity Database

Rousková, Milena; Heyberger, Aleš; Tříska, Jan; Krtička, M.

2011-01-01

Roč. 65, č. 6 (2011), s. 805-812 ISSN 0366-6352 R&D Projects: GA AV ČR 1QS400720504; GA MŠk(CZ) ED1.1.00/02.0073 Institutional research plan: CEZ:AV0Z40720504; CEZ:AV0Z60870520 Keywords : liquid - liquid extraction * tall oil soap * phytosterols Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 1.096, year: 2011

Autogenous tooth transplantation: an alternative to replace extracted tooth

Directory of Open Access Journals (Sweden)

David B. Kamadjaja

2015-09-01

Full Text Available Background: The gold standard treatment to replace missing tooth is dental implants, however, in certain cases, such as in young patients its placement is contraindicated. Autogenous tooth transplantation, which has been widely done in Scandinavian countries for many years, may become a good alternative to overcome this problem. Purpose: This article attempted to provide information about the indication, treatment planning, surgical technique and the successful result of autogenous tooth transplantation. Case: A fifteen year old male patient presented with large caries and periapical disease of his lower left first molar, which was partially erupted and the roots was not fully formed in radiograph. Case management: Autogenous tooth transplantation procedure was performed consisting of extraction of #36, odontectomy of #38 followed by its implantation to socket #36 and fixation of the transplanted tooth to the adjacent teeth. Post operative evaluation was done on regular basis within 18 months period. There was no complaint, the tooth was clinically stable and no evidence of periodontal problem. Serial radiographs showed healing of alveolar bone and periodontal tissue, and the complete root formation was evident by 18 months post operatively. Conclusion: Autogenous tooth transplantation is a potential alternative to replace extracted tooth. Provided that the case be properly planned and operation carefully performed, successful result of this treatment can be achieved.

Feasibility studies on supercritical fluid extraction of uranium from phosphoric acid

International Nuclear Information System (INIS)

Dubey, B.P.; Agarwal, A.K.

2014-01-01

Supercritical fluid extraction (SFE) is a promising novel technology for extraction of many materials. Work has been carried out worldwide on SFE of uranium from various matrices. However, there are no references indicating the R and D on uranium extraction from phosphoric acid using this technology. Heavy Water Board is involved in technology development for recovery of uranium from secondary source, hence it was considered prudent to investigate the technology of SFE for this purpose. Various experiments were carried out with both WPA (P 2 O 5 content 28%) and MGPA (P 2 O 5 content 54%) using bench scale facility available with one of the private party. Extraction experiments were carried out using several chelating agents including TBP, D2EHPA, D2EHPA+TBP/TOPO, TTA, TTA+TBP etc. Feasibility studies revealed the hydrodynamics of operation indicating liquid expansion by about three times during flow of super critical (SC) CO 2 . No flooding was observed when the extraction column filled 20% of its volume capacity, no carryover of entrained/extracted liquid with SC CO 2 with MGPA, material balance of inputs and outputs established i.e. 100% recovery of MGPA and chelating agent, No operational problems with raw MGPA (untreated). No significant extraction of impurities from phosphoric acid to SC CO 2 , 40℃ temperature and 160 bar pressure found ideal for extraction experiments since no other materials found extracted at these conditions and no apparent change/deterioration in PA and chelating agents. Experiments established feasibility of SCE with CO 2 , proper recovery of PA and chelating agents, no need for pretreatment/gunk removal from PA; however, extraction of uranium was found inadequate even though ORP of feed acid was boosted by H 2 O 2 addition. Investigations revealed that SCE column created reducing environment in phosphoric acid, which was not favourable for uranium extraction, which resulted in difficulty in extraction of Uranium. HWB has now designed

Using the method of mathematical-logical modeling in compiling an engineering plan for development of a mine

Energy Technology Data Exchange (ETDEWEB)

Fajkos, A.; Klimek, M.

1980-01-01

A possibility of using a mathematical-logical modeling to improve the quality of mine shaft operation planning in Czechloslovakia based on the example of the Sverma mine in Ostrova with complex mining-geological conditions is studied. For the basic criteria we assumed: extraction plant, number of shifts in the long walls, time period for beginning and ending long wall operation, processing of reserves with consideration of existing conditions, output and dip angle of a formation, quality of extracted coal, and also: time intervals for processing separate formations, limitation of extraction load in a long wall in connection with gas emission, timbering, the necessity of insuring normal operating conditions, concentration of extraction, time relationship of preparatory and extraction operations.

Development of a procedure for the sequential extraction of substances binding trace elements in plant biomass

Czech Academy of Sciences Publication Activity Database

Pavlíková, D.; Pavlík, Milan; Vašíčková, Soňa; Száková, J.; Vokáč, Karel; Balík, J.; Tlustoš, P.

2005-01-01

Roč. 381, - (2005), s. 863-872 ISSN 1618-2642 Institutional research plan: CEZ:AV0Z4055905 Keywords : organic compounds binding trace elements * spinach plant * sequential extraction Subject RIV: EI - Biotechnology ; Bionics Impact factor: 2.695, year: 2005

[Caesarean section with vacuum extraction of the head].

Science.gov (United States)

Dimitrov, A; Pavlova, E; Krŭsteva, K; Nikolov, A

2008-01-01

The aim of the study is to investigate the benefits and the limits in using the soft cup vacuum extractor on the fetal scalp during the caesarean section. The prospective study includes 19 cases of caesarean sections (group A), with vacuum assisted delivery using the soft cup vacuum extractor on the fetal scalp (diameter 6 cm) and 25 cases (group B) of caesarean sections with usual, manual extraction of the head assisted by fundal compression. All of the patients had undergone a planned caesarean section on term in absence of uterine activity and preserved amniotic membranes. Our results doesn't show differences in the Apgar score on the first and 5-th minute in the newborns of the two groups. The duration of the scalp traction was significantly shorter (30 +/- 4 sec) in comparison to the classical manual extraction (53 +/- 21 sec). The mean duration for applying the vacuum cup was 10 sec and 25 sec for tractions. The total blood loose and total duration of the caesarean sections were shorter than in the control group. The applied traction with the vacuum cup was sufficient for head extraction and there was no need for additional fundal compression. In conclusion we consider that the extraction of the fetal head in high position in caesarean section with vacuum extractor is an easy, non traumatic and rapid method which can put away the need of rough and prolonged fundal compression and its consequences.

[Extraction of buildings three-dimensional information from high-resolution satellite imagery based on Barista software].

Science.gov (United States)

Zhang, Pei-feng; Hu, Yuan-man; He, Hong-shi

2010-05-01

The demand for accurate and up-to-date spatial information of urban buildings is becoming more and more important for urban planning, environmental protection, and other vocations. Today's commercial high-resolution satellite imagery offers the potential to extract the three-dimensional information of urban buildings. This paper extracted the three-dimensional information of urban buildings from QuickBird imagery, and validated the precision of the extraction based on Barista software. It was shown that the extraction of three-dimensional information of the buildings from high-resolution satellite imagery based on Barista software had the advantages of low professional level demand, powerful universality, simple operation, and high precision. One pixel level of point positioning and height determination accuracy could be achieved if the digital elevation model (DEM) and sensor orientation model had higher precision and the off-Nadir View Angle was relatively perfect.

Modelos ridge em planejamentos de misturas: uma aplicação na extração da polpa de pequi Ridge models in mixture planning: an application in the extraction of pequi pulp

Directory of Open Access Journals (Sweden)

Tania Miranda Nepomucena

2013-01-01

Full Text Available Mixture Models can be used in experimental situations involving areas related to food science and chemistry. Some problems of a statistical nature can be found, such as effects of multicollinearity that result in uncertainty in the optimization of a dependent variable. This study proposes the application of the ridge model adapted for mixture planning considering the Kronecker (K-model and Scheffe (S-Model methods applied to response surfaces. The method determined the proportions of hexane, acetone and alcohol proportions that resulted in the maximum response of percentage of extracted pequi (Caryocar brasiliense pulp oil.

Solvent extraction

Energy Technology Data Exchange (ETDEWEB)

Coombs, D.M.; Latimer, E.G.

1988-01-05

It is an object of this invention to provide for the demetallization and general upgrading of heavy oil via a solvent extracton process, and to improve the efficiency of solvent extraction operations. The yield and demetallization of product oil form heavy high-metal content oil is maximized by solvent extractions which employ either or all of the following techniques: premixing of a minor amount of the solvent with feed and using countercurrent flow for the remaining solvent; use of certain solvent/free ratios; use of segmental baffle tray extraction column internals and the proper extraction column residence time. The solvent premix/countercurrent flow feature of the invention substantially improves extractions where temperatures and pressures above the critical point of the solvent are used. By using this technique, a greater yield of extract oil can be obtained at the same metals content or a lower metals-containing extract oil product can be obtained at the same yield. Furthermore, the premixing of part of the solvent with the feed before countercurrent extraction gives high extract oil yields and high quality demetallization. The solvent/feed ratio features of the invention substanially lower the captial and operating costs for such processes while not suffering a loss in selectivity for metals rejection. The column internals and rsidence time features of the invention further improve the extractor metals rejection at a constant yield or allow for an increase in extract oil yield at a constant extract oil metals content. 13 figs., 3 tabs.

The method for simultaneous extraction and back extraction in liquid three-phase system and equipment for simultaneous extraction and back extraction in liquid three-phase system

International Nuclear Information System (INIS)

Palyska, W.; Chmielewski, A.G.

1992-01-01

The method for simultaneous extraction and back extraction in liquid three-phase system has been worked out. The equipment designed for that process has been also subject of the patent. The interesting component is extracted first to intermediate phase consists of magnetic solvent keeping two extracting phases separately. The intermediate magnetic liquid has been kept in its position using a stable magnet maintained on the surface of the extraction vessel. Then the component pass from intermediate phase to the third phase as a result of back extraction. Mixing in the extraction and back extraction zones is organized by means of rotating shaft going along the whole apparatus. The extraction and back extraction processes occur simultaneously as a result of continuous flow of solvent in their zones. The single extraction back extraction facilities can be joined in larger batteries. 3 figs

PUREX/UO3 deactivation project management plan

International Nuclear Information System (INIS)

Washenfelder, D.J.

1993-12-01

From 1955 through 1990, the Plutonium-Uranium Extraction Plant (PUREX) provided the United States Department of Energy Hanford Site with nuclear fuel reprocessing capability. It operated in sequence with the Uranium Trioxide (UO 3 ) Plant, which converted the PUREX liquid uranium nitrate product to solid UO 3 powder. Final UO 3 Plant operation ended in 1993. In December 1992, planning was initiated for the deactivation of PUREX and UO 3 Plant. The objective of deactivation planning was to identify the activities needed to establish a passively safe, environmentally secure configuration at both plants, and ensure that the configuration could be retained during the post-deactivation period. The PUREX/UO 3 Deactivation Project management plan represents completion of the planning efforts. It presents the deactivation approach to be used for the two plants, and the supporting technical, cost, and schedule baselines. Deactivation activities concentrate on removal, reduction, and stabilization of the radioactive and chemical materials remaining at the plants, and the shutdown of the utilities and effluents. When deactivation is completed, the two plants will be left unoccupied and locked, pending eventual decontamination and decommissioning. Deactivation is expected to cost $233.8 million, require 5 years to complete, and yield $36 million in annual surveillance and maintenance cost savings

Extraction of Urban Water Bodies from High-Resolution Remote-Sensing Imagery Using Deep Learning

Directory of Open Access Journals (Sweden)

Yang Chen

2018-05-01

Full Text Available Accurate information on urban surface water is important for assessing the role it plays in urban ecosystem services in the context of human survival and climate change. The precise extraction of urban water bodies from images is of great significance for urban planning and socioeconomic development. In this paper, a novel deep-learning architecture is proposed for the extraction of urban water bodies from high-resolution remote sensing (HRRS imagery. First, an adaptive simple linear iterative clustering algorithm is applied for segmentation of the remote-sensing image into high-quality superpixels. Then, a new convolutional neural network (CNN architecture is designed that can extract useful high-level features of water bodies from input data in a complex urban background and mark the superpixel as one of two classes: an including water or no-water pixel. Finally, a high-resolution image of water-extracted superpixels is generated. Experimental results show that the proposed method achieved higher accuracy for water extraction from the high-resolution remote-sensing images than traditional approaches, and the average overall accuracy is 99.14%.

Receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in gingival crevicular fluid

Science.gov (United States)

Sarlati, Fatemeh; Sattari, Mandana; Razzaghi, Shilan; Nasiri, Malihe

2012-01-01

Background: Osteoclastogenesis is coordinated by the interaction of three members of the tumor necrosis factor (TNF) superfamily: Osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK). The aim of this study was to investigate RANKL and OPG levels, and their relative ratio in gingival crevicular fluid (GCF) of patients with chronic and aggressive periodontitis, as well as healthy controls. Materials and Methods: In this analytical study, GCF was obtained from healthy (n = 10), mild chronic periodontitis (n = 18), moderate chronic periodontitis (n = 18), severe chronic periodontitis (n = 20), and generalized aggressive periodontitis (n = 20) subjects. RANKL and OPG concentrations were measured by enzyme-linked immunosorbent assay. Statistical tests used were Kruskal–Wallis test, Mann–Whitney U rank sum test, and Spearman's rank correlation analysis. The level of statistical significance was set at P chronic periodontitis (mild, moderate, severe), and aggressive periodontitis (P = 0.41). There was statistically significant correlation between the concentration of sRANKL and Clinical Attachment Level (CAL) in moderate chronic periodontitis patients (R = 0.48, P = 0.04). There was also negative correlation between OPG concentration and CAL in moderate chronic periodontitis patients, although not significant (R = −0.13). Conclusion: RANKL was prominent in periodontitis sites, especially in moderate periodontitis patients, whereas OPG was not detectable in some diseased sites with bleeding on probing, supporting the role of these two molecules in the bone loss developed in this disease. PMID:23559954

Technical progress review of extraction of uranium from fly ash

International Nuclear Information System (INIS)

Gao Renxi; Gao Junning; Wu Qingming; Chen Gang; Wan Hongjin; Zhang Ziyue

2014-01-01

The increasing of fly ash in coal-fired power plants at home and abroad year by year and the potential impacts to the environment attracted media attention. Although the extraction of uranium from the fly ash in coal-fired power plants had optional process from technique aspect and sufficient preliminary researches, but considering the low grade of the uranium in fly ash and particularity of the mineral composition, it is easy to have a high cost of extraction. As a consequence, it is not included in the development plan of uranium mining and metallurgy. The present applications of fly ash are only building materials, building roads and pit valley backfill, the resource utilization rate was low and was still in its early stages of development and application. In view of this, the research advances and the latest development trends of extraction of uranium from fly ash at home and abroad were introduced from the technical aspect, and the beneficial analyzes of the prospect and advices to this industry were given. (authors)

Analysis of plant extracts antimutagenicity using the Ames test and the cytogenetic analysis of peripheral blood lymphocytes

Czech Academy of Sciences Publication Activity Database

Buňková, R.; Marová, I.; Pokorná, Z.; Lojek, Antonín

2005-01-01

Roč. 11, č. 2 (2005), s. 107-112 ISSN 1082-0132 Institutional research plan: CEZ:AV0Z50040507 Keywords : plant extracts * antioxidative activity * Ames test Subject RIV: BO - Biophysics Impact factor: 0.724, year: 2005

A Method of Generating Indoor Map Spatial Data Automatically from Architectural Plans

Directory of Open Access Journals (Sweden)

SUN Weixin

2016-06-01

Full Text Available Taking architectural plans as data source, we proposed a method which can automatically generate indoor map spatial data. Firstly, referring to the spatial data demands of indoor map, we analyzed the basic characteristics of architectural plans, and introduced concepts of wall segment, adjoining node and adjoining wall segment, based on which basic flow of indoor map spatial data automatic generation was further established. Then, according to the adjoining relation between wall lines at the intersection with column, we constructed a repair method for wall connectivity in relation to the column. Utilizing the method of gradual expansibility and graphic reasoning to judge wall symbol local feature type at both sides of door or window, through update the enclosing rectangle of door or window, we developed a repair method for wall connectivity in relation to the door or window and a method for transform door or window into indoor map point feature. Finally, on the basis of geometric relation between adjoining wall segment median lines, a wall center-line extraction algorithm was presented. Taking one exhibition hall's architectural plan as example, we performed experiment and results show that the proposed methods have preferable applicability to deal with various complex situations, and realized indoor map spatial data automatic extraction effectively.

Ultrasound-Assisted Extraction: Effect of Extraction Time and Solvent ...

African Journals Online (AJOL)

Purpose: To investigate the influence of extraction conditions assisted by ultrasound on the quality of extracts obtained from Mesembryanthemum edule shoots. Methods: The extraction procedure was carried out in an ultrasonic bath. The effect of two solvents (methanol and ethanol) and two extraction times (5 and 10 min) ...

In vitro antioxidant and antiproliferative activities of methanolic plant part extracts of Theobroma cacao.

Science.gov (United States)

Baharum, Zainal; Akim, Abdah Md; Taufiq-Yap, Yun Hin; Hamid, Roslida Abdul; Kasran, Rosmin

2014-11-10

The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid-reactive substances (TBARS), and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC50) was 358.3±7.0 µg/mL and total phenolic content was 22.0±1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4%±1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC50)=41.4±3.3 µg/mL]. Given the overall high IC50 for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts.

In Vitro Antioxidant and Antiproliferative Activities of Methanolic Plant Part Extracts of Theobroma cacao

Directory of Open Access Journals (Sweden)

Zainal Baharum

2014-11-01

Full Text Available The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH, thiobarbituric acid-reactive substances (TBARS, and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC50 was 358.3 ± 7.0 µg/mL and total phenolic content was 22.0 ± 1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4% ± 1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC50 = 41.4 ± 3.3 µg/mL]. Given the overall high IC50 for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts.

Extraction method

International Nuclear Information System (INIS)

Stary, J.; Kyrs, M.; Navratil, J.; Havelka, S.; Hala, J.

1975-01-01

Definitions of the basic terms and of relations are given and the knowledge is described of the possibilities of the extraction of elements, oxides, covalent-bound halogenides and heteropolyacids. Greatest attention is devoted to the detailed analysis of the extraction of chelates and ion associates using diverse agents. For both types of compounds detailed conditions are given of the separation and the effects of the individual factors are listed. Attention is also devoted to extractions using mixtures of organic agents, the synergic effects thereof, and to extractions in non-aqueous solvents. The effects of radiation on extraction and the main types of apparatus used for extractions carried out in the laboratory are described. (L.K.)

Accelerated Solvent Extraction: An Innovative Sample Extraction Technique for Natural Products

International Nuclear Information System (INIS)

Hazlina Ahmad Hassali; Azfar Hanif Abd Aziz; Rosniza Razali

2015-01-01

Accelerated solvent extraction (ASE) is one of the novel techniques that have been developed for the extraction of phytochemicals from plants in order to shorten the extraction time, decrease the solvent consumption, increase the extraction yield and enhance the quality of extracts. This technique combines elevated temperatures and pressure with liquid solvents. This paper gives a brief overview of accelerated solvent extraction technique for sample preparation and its application to the extraction of natural products. Through practical examples, the effects of operational parameters such as temperature, volume of solvent used, extraction time and extraction yields on the performance of ASE are discussed. It is demonstrated that ASE technique allows reduced solvent consumption and shorter extraction time, while the extraction yields are even higher than those obtained with conventional methods. (author)

Extraction process

International Nuclear Information System (INIS)

Rendall, J.S.; Cahalan, M.J.

1979-01-01

A process is described for extracting at least two desired constituents from a mineral, using a liquid reagent which produces the constituents, or compounds thereof, in separable form and independently extracting those constituents, or compounds. The process is especially valuable for the extraction of phosphoric acid and metal values from acidulated phosphate rock, the slurry being contacted with selective extractants for phosphoric acid and metal (e.g. uranium) values. In an example, uranium values are oxidized to uranyl form and extracted using an ion exchange resin. (U.K.)

Quantification of total and water extractable essential elements in medicinal plants used for stomach problems

International Nuclear Information System (INIS)

Sahito, S.R.; Kazi, T.G.; Shar, G.Q.; Mangrio, A.M; Shaikh, M.S.

2004-01-01

The role of elements particularly trace elements in health and disease is well known. Present study has been undertaken in our laboratories to quantify the commonly occurring elements in three medicinal plans. Peganum harmala Linn, Phyllanthus emblica Linn, Tamarix dioca used for stomach problems using atomic absorption spectrophotometer. Wet digestion method has been used to extract the acid extractable metals. Samples were boiled in water to obtain water extractable metals. The validation of the method was checked with the NBS-1570 (Spinach) as Standard Reference Material. Levels of essential elements were found high as compared to concentration of toxic elements. The considerable amounts of essential such as calcium, magnesium, potassium, zinc and iron were found in all these plant samples. (author)

Comparison of seven DNA extraction and ampliffication protocols in historical herbarium specimens of Juncaceae

Czech Academy of Sciences Publication Activity Database

Drábková, Lenka; Kirschner, Jan; Vlček, Čestmír

2002-01-01

Roč. 20, - (2002), s. 161-175 ISSN 0735-9640 R&D Projects: GA MŠk LN00A079; GA ČR GA206/02/0355 Institutional research plan: CEZ:AV0Z6005908 Keywords : cpDNA * DNA extraction * herbarium specimens Subject RIV: EF - Botanics Impact factor: 0.803, year: 2002

Adult orthodontic therapy: extraction versus non-extraction.

Science.gov (United States)

Baumrind, S

1998-11-01

This study addresses the problem of randomization of subjects with respect to an irreversible aspect of treatment strategy, namely, the extraction of teeth. The investigation includes both prospective and retrospective components. The data presented focus on clinician decision-making. Of the 1321 potential subjects for whom records were taken, 250 met the inclusion criteria. Of these subjects, 82 declined to participate and 20 were dropped because of difficulty in obtaining five independent evaluations of their records within a reasonable time frame. Thus, the final sample contained 148 subjects. Approximately one-third of the subjects in the sample are adult, somewhat more than half are female, and Class I malocclusions outnumber Class II malocclusions by a count of 95 to 53. Patterns of agreement and disagreement among five clinicians include: a) agreement/disagreement on the primary decision whether or not to extract: the data reveal a strong tendency towards consensus among the clinicians; b) agreement/disagreement on extraction pattern in patients in whom the clinician believes that extraction is indicated: the clinicians tended strongly to agree on extraction pattern; c) agreement/disagreement on the need for adjunctive orthognathic surgery: decisions favoring surgery were more common and more 'definite' than 'probable' in the adult cohort than in the adolescent cohort but this tendency was not as strong as had been anticipated; d) agreement/disagreement concerning Angle classification: disagreements were more common than had been anticipated; and e) differences among the individual clinicians as to their ratios of extraction/non-extraction decisions: overall, clinicians opted for extraction less frequently in the adolescent cohort than in the adult cohort (55 vs. 66%). Because the data are drawn from actual clinical experience, the conclusions involve a number of assumptions and their generalizability should be evaluated.

Separation of yttrium from strontium in the aqueous phase of the water/nitrobenzene extraction system

Czech Academy of Sciences Publication Activity Database

Vaňura, P.; Makrlík, E.; Vobecký, Miloslav

2003-01-01

Roč. 256, č. 1 (2003), s. 171-172 ISSN 0236-5731 R&D Projects: GA MŠk LN00B084 Institutional research plan: CEZ:AV0Z4031919; CEZ:MSM 230000009 Keywords : extraction * strontium * yttrium Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.472, year: 2003

Decision-support tools for climate change mitigation planning

DEFF Research Database (Denmark)

Puig, Daniel; Aparcana Robles, Sandra Roxana

. For example, in the case of life-cycle analysis, the evaluation criterion entails that the impacts of interest are examined across the entire life-cycle of the product under study, from extraction of raw materials, to product disposal. Effectively, then, the choice of decision-support tool directs......This document describes three decision-support tools that can aid the process of planning climate change mitigation actions. The phrase ‘decision-support tools’ refers to science-based analytical procedures that facilitate the evaluation of planning options (individually or compared to alternative...... options) against a particular evaluation criterion or set of criteria. Most often decision-support tools are applied with the help of purpose-designed software packages and drawing on specialised databases.The evaluation criteria alluded to above define and characterise each decision-support tool...

Advanced scale conditioning agent and consolidated deposit extraction planning, application experience, and results at Comanche Peak Unit 2 and industrial super critical water oxidation waste reduction

Energy Technology Data Exchange (ETDEWEB)

Forney, M.; Ramaley, D. [Westinghouse Electric Company, Cranberry Township, PA (United States); Bryant, W. [Luminant Energy, Comanche Peak Nuclear Power Plant, Dallas, TX (United States)

2015-07-01

Advance Scale Conditioning Agent (ASCA) technology has been applied more than forty times worldwide since its inception in 2000. This technology has continually grown in popularity since its development due to the combination of several process benefits and minimal outage impacts. Comanche Peak Unit 2 applied a Top of Tubesheet (TTS) ASCA in 2014 for partial dissolution and softening of consolidated TTS collars. In addition to the ASCA application, a Consolidated Deposit Extraction (CODE) step was applied to the TTS. CODE is a chemical treatment technology that effectively targets and dissolves 'binding species' such as those containing aluminum and silicon from steam generator deposits. Since magnetite dissolution technologies are not wholly effective in removing consolidated TTS 'collars' CODE technology was developed to address this need in the industry. This paper will discuss both the Westinghouse and utility perspective on TTS ASCA/CODE application planning, site execution, and process results. (author)

Tracer gas diffusion sampling test plan

International Nuclear Information System (INIS)

Rohay, V.J.

1993-01-01

Efforts are under way to employ active and passive vapor extraction to remove carbon tetrachloride from the soil in the 200 West Area an the Hanford Site as part of the 200 West Area Carbon Tetrachloride Expedited Response Action. In the active approach, a vacuum is applied to a well, which causes soil gas surrounding the well to be drawn up to the surface. The contaminated air is cleaned by passage through a granular activated carbon bed. There are questions concerning the radius of influence associated with application of the vacuum system and related uncertainties about the soil-gas diffusion rates with and without the vacuum system present. To address these questions, a series of tracer gas diffusion sampling tests is proposed in which an inert, nontoxic tracer gas, sulfur hexafluoride (SF 6 ), will be injected into a well, and the rates of SF 6 diffusion through the surrounding soil horizon will be measured by sampling in nearby wells. Tracer gas tests will be conducted at sites very near the active vacuum extraction system and also at sites beyond the radius of influence of the active vacuum system. In the passive vapor extraction approach, barometric pressure fluctuations cause soil gas to be drawn to the surface through the well. At the passive sites, the effects of barometric ''pumping'' due to changes in atmospheric pressure will be investigated. Application of tracer gas testing to both the active and passive vapor extraction methods is described in the wellfield enhancement work plan (Rohay and Cameron 1993)

Quality Parameters of Curcuma Longa L. Extracts by Supercritical Fluid Extraction (SFE) and Ultrasonic Assisted Extraction (UAE)

International Nuclear Information System (INIS)

Zaibunnisa Abdul Haiyee; Siti Hafsah Mohd Shah; Khudzir Ismail; Nooraain Hashim; Wan Iryani Wan Ismail

2016-01-01

Turmeric is one of the prominently use herbal plants due to its diverse beneficial effects especially in Indian medicine. The rhizome part of the turmeric contains valuable compounds which have been said to owe its antimicrobial effects, anti-cancer, anti-inflammatory and enhance wound healing. Due to its short-life span and perishable properties, the conversion of the rhizome into turmeric extract is desirable. Several methods have been used for extraction such as Soxhlet extraction and pressurized liquid extraction (PLE). However, these techniques are tedious, laborious, time consuming and involves the usage of toxic organic solvent, of which safeness of the end product is doubtful. In this study, a rapid, reliable and green extraction method of supercritical fluid extraction (SFE) and ultrasonic assisted extraction (UAE) were used. SFE without modifier has resulted in 0.0006 mg/ 100 g of curcuminoids concentration and 5.62 % of yield (dry weight basis). UAE using ethanol was able to produce significantly the highest yield (6.40 %, dry weight basis) and the highest curcuminoids concentration (0.1020 mg/ 100 g). However, SFE was able to produce extract that contain significantly higher major volatile compounds; tumerone, ar-turmerone and curlone. Therefore, this study proves that both extraction methods were able to produce high quality turmeric extract. (author)

Extractive distillation of nitric acid using the two-pot concept

International Nuclear Information System (INIS)

Counce, R.M.; Groenier, W.S.; Holland, W.D.; Jubin, R.T.; North, E.D.; Thompson, L.E. Jr.; Hebble, T.L.

1982-12-01

Experiments have confirmed the validity of a novel design for a nitric acid concentration system for use in shielded nuclear fuel reprocessing plants. Current plans for producing the scrub solution for the IODOX process require the concentration and recycle of low strength ( 3 ) 2 as the solvent and features two pots: an extractive distillation pot in which a concentrated acid product is obtained by contacting the acid feed with the solvent and a solvent recovery pot in which the solvent is dehydrated and recovered for recycle. In these experiments, a concentrated product of 89 wt % nitric acid was produced from azeotropic feed. The available vapor-liquid equilibria data for the Mg(NO 3 ) 2 -HNO 3 -H 2 O system has been empirically correlated, and a design methodology has been developed for the two-pot extractive distillation process

Statin Treatment Is Associated with Reduction in Serum Levels of Receptor Activator of NF-κB Ligand and Neutrophil Activation in Patients with Severe Carotid Stenosis

Directory of Open Access Journals (Sweden)

Sébastien Lenglet

2014-01-01

Full Text Available Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN, RANKL/osteoprotegerin (OPG ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.

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.

Skeletal class III camouflage by mandibular incisor extraction: A case report

OpenAIRE

Janardhanan Kumaresan; Tamizharasi Senthil Kumar; Senthil Kumar

2014-01-01

Treatment planning in orthodontics plays a key role in determining the successful treatment of any kind of malocclusion. Skeletal class III malocclusions are generally difficult to treat because of the complex nature of the skeletal and dental manifestations they produce. Mild to moderate skeletal class III malocclusions sometimes have an acceptable facial profile where orthodontic camouflage is possible. In this case report, camouflage of a mild skeletal class III is done by the extraction o...

Rent extraction by large shareholders: evidence using dividend policy in the Czech Republic

Czech Academy of Sciences Publication Activity Database

Bena, J.; Hanousek, Jan

2008-01-01

Roč. 58, 3-4 (2008), s. 106-130 ISSN 0015-1920 R&D Projects: GA ČR GA402/06/1293; GA MŠk LC542 Institutional research plan: CEZ:MSM0021620846 Keywords : rent extraction * large shareholders * dividend policy Subject RIV: AH - Economics Impact factor: 0.275, year: 2008 http://journal.fsv.cuni.cz/storage/1125_str_106_130--bena-hanousek.pdf

Extraction of Fuzzy Logic Rules from Data by Means of Artificial Neural Networks

Czech Academy of Sciences Publication Activity Database

Holeňa, Martin

2005-01-01

Roč. 41, č. 3 (2005), s. 297-314 ISSN 0023-5954 R&D Projects: GA AV ČR IAA1030004 Institutional research plan: CEZ:AV0Z10300504 Keywords : knowledge extraction from data * artificial neural networks * fuzzy logic * Lukasiewicz logic * disjunctive normal form Subject RIV: BA - General Mathematics Impact factor: 0.343, year: 2005 http://dml.cz/handle/10338.dmlcz/135657

[Effect of tumour necrosis factor α blockade on bone metabolism in chronic inflammatory joint diseases].

Science.gov (United States)

Aguilar Del Rey, Francisco Javier; García Portales, Rosa; Haro Liger, Manuel; Rodríguez Andreu, José; Casals Sánchez, José Luis; Pérez González, Rita

2016-07-15

To evaluate the effect of anti-TNF treatments on bone mineral density (BMD), bone remodelling markers (BRM) and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) in patients with chronic inflammatory joint diseases. A longitudinal prospective study was performed under clinical practice conditions on 31 patients diagnosed of rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis who had received treatment with anti-TNF alpha drugs for one year. BMD, OPG and RANKL soluble form (sRANKL) were studied at the onset and end of the study. During the study (0, 3, 6, 9 and 12 month), disease activity (SDAI, BASDAI and CRP), functional capacity (HAQ, BASFI), BRM and vitamin D were studied. BMD was not modified after one year of treatment. The patients who took corticosteroids had a mean bone mass loss of 3% in the lumbar spine (±1.6, P=.02). In regards to the BRM, did not experience significant changes over the course of the study. Disease activity, both SDAI (P=.002) and BASDAI (P=.002), decreased. OPG was maintained without changes during the year of treatment while both the sRANKL (0.28±0.22, P=.013) and sRANKL/OPG ratio significantly decreased (0.04±0.03, P=.031). The patients being treated with anti-TNF did not present with a significant loss of DMO during the study (one year), at the same time experiencing an improvement in disease activity. This protection has been clearer in the responding patients. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

A FAST AND ROBUST ALGORITHM FOR ROAD EDGES EXTRACTION FROM LIDAR DATA

Directory of Open Access Journals (Sweden)

K. Qiu

2016-06-01

Full Text Available Fast mapping of roads plays an important role in many geospatial applications, such as infrastructure planning, traffic monitoring, and driver assistance. How to extract various road edges fast and robustly is a challenging task. In this paper, we present a fast and robust algorithm for the automatic road edges extraction from terrestrial mobile LiDAR data. The algorithm is based on a key observation: most roads around edges have difference in elevation and road edges with pavement are seen in two different planes. In our algorithm, we firstly extract a rough plane based on RANSAC algorithm, and then multiple refined planes which only contains pavement are extracted from the rough plane. The road edges are extracted based on these refined planes. In practice, there is a serious problem that the rough and refined planes usually extracted badly due to rough roads and different density of point cloud. To eliminate the influence of rough roads, the technology which is similar with the difference of DSM (digital surface model and DTM (digital terrain model is used, and we also propose a method which adjust the point clouds to a similar density to eliminate the influence of different density. Experiments show the validities of the proposed method with multiple datasets (e.g. urban road, highway, and some rural road. We use the same parameters through the experiments and our algorithm can achieve real-time processing speeds.

The redevelopment of the Copenhagen harbourfront and recent planning strategies

DEFF Research Database (Denmark)

Khani, Roudaina Al

2001-01-01

development principles has been attached to the planning of the redevelopment of the harborfront areas. Nevertheless, this paper shortly presents an evaluation of the urban conversion of the Copenhagen harborfront sites and of their redevelopment strategies with regards to their contribution to sustainable...... strategies of the late 1990s and highlights their potentials for drawing up new paths towards sustainability. The aspects of the recent strategies demonstrate that a better reconciliation of the conflicting interests between the actors involved (the State, the Municipality and the Port Authority) is more...... the implementation of a coordinated redevelopment strategy. Finally, this paper culminates by extracting some conclusions that should be taken into account when making both planning and political choices....

Plutonium and americium extraction studies with bifunctional organophosphorus extractants

International Nuclear Information System (INIS)

Navratil, J.D.

1985-01-01

Neutral bifunctional organophosphorus extractants, such as octylphenyl-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO) and dihexyl-N,N-diethylcarbamoylmethylphosphonate (CMP), are under study at the Rocky Flats Plant (RFP) to remove plutonium and americium from the 7M nitric acid waste. These compounds extract trivalent actinides from strong nitric acid, a property which distinguishes them from monofunctional organiphosphorus reagents. Furthermore, the reagents extract hydroytic plutonium (IV) polymer which is present in the acid waste stream. The compounds extract trivalent actinides with a 3:1 stoichiometry, whereas tetra- and hexavalent actinides extract with a stoichiometry of 2:1. Preliminary studies indicate that the extracted plutonium polymer complex contains one to two molecules of CMP per plutonium ion and the plutonium(IV) maintains a polymeric structure. Recent studies by Horwitz and co-workers conclude that the CMPO and CMP reagents behave as monodentate ligands. At RFP, three techniques are being tested for using CMP and CMPO to remove plutonium and americium from nitric acid waste streams. The different techniques are liquid-liquid extraction, extraction chromatography, and solid-supported liquid membranes. Recent tests of the last two techniques will be briefly described. In all the experiments, CMP was an 84% pure material from Bray Oil Co. and CMPO was 98% pure from M and T Chemicals

Separation of uranium, molibdenum and vanadium in sulphuric solutions by extraction with alamine 336

International Nuclear Information System (INIS)

Floh, B.

1976-01-01

Alamine 336 - varsol - sulphuric acid-water system used for uranium, molibdenum and vanadium extraction, from sulphuric leaching and an appropriate plan for fractioning those elements are investigated. The behavior of cited elements in pure solutions followed by interaction that occurs in both bynary and tertiary systems are studied. Distribution coefficient is regarded for measuring such effects [pt

Rapid extraction of PCDD/Fs from soil and fly ash samples. Pressurized fluid extraction (PFE) and microwave-assisted extraction (MAE)

Energy Technology Data Exchange (ETDEWEB)

Sanz, P.; Fabrellas, B. [Centro de Investigaciones Energeticas Medioambientales y Tecnologicas (CIEMAT), Madrid (Spain)

2004-09-15

The main reference extraction method in the analysis of polychlorinated dibenzop- dioxins and dibenzofurans (PCDD/Fs) is still the Soxhlet extraction. But it requires long extraction times (up to 24 hs), large volumes of hazardous organic solvents (100-300 ml) and its automation is limited. Pressurized Fluid Extraction (PFE) and Microwave-Assisted Extraction (MAE) are two relatively new extraction techniques that reduce the time and the volume of solvent required for extraction. However, very different PFE extraction conditions are found for the same enviromental matrices in the literature. MAE is not a extraction technique very applied for the analysis of PCDD/Fs yet, although it is used for the determination of other organic compounds, such as PCBs and PAHs. In this study, PFE and MAE extraction conditions were optimized to determine PCDDs y PCDFs in fly ash and soil/sediment samples. Conventional Soxhlet extraction with toluene was used to compare the extraction efficiency of both techniques.

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.

Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

International Nuclear Information System (INIS)

Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun; Chung, Won-Yoon

2014-01-01

Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

Energy Technology Data Exchange (ETDEWEB)

Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun, E-mail: biochelab@yuhs.ac; Chung, Won-Yoon, E-mail: wychung@yuhs.ac

2014-03-01

Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

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

3D Power Line Extraction from Multiple Aerial Images

Directory of Open Access Journals (Sweden)

Jaehong Oh

2017-09-01

Full Text Available Power lines are cables that carry electrical power from a power plant to an electrical substation. They must be connected between the tower structures in such a way that ensures minimum tension and sufficient clearance from the ground. Power lines can stretch and sag with the changing weather, eventually exceeding the planned tolerances. The excessive sags can then cause serious accidents, while hindering the durability of the power lines. We used photogrammetric techniques with a low-cost drone to achieve efficient 3D mapping of power lines that are often difficult to approach. Unlike the conventional image-to-object space approach, we used the object-to-image space approach using cubic grid points. We processed four strips of aerial images to automatically extract the power line points in the object space. Experimental results showed that the approach could successfully extract the positions of the power line points for power line generation and sag measurement with the elevation accuracy of a few centimeters.

Individual Building Extraction from TerraSAR-X Images Based on Ontological Semantic Analysis

Directory of Open Access Journals (Sweden)

Rong Gui

2016-08-01

Full Text Available Accurate building information plays a crucial role for urban planning, human settlements and environmental management. Synthetic aperture radar (SAR images, which deliver images with metric resolution, allow for analyzing and extracting detailed information on urban areas. In this paper, we consider the problem of extracting individual buildings from SAR images based on domain ontology. By analyzing a building scattering model with different orientations and structures, the building ontology model is set up to express multiple characteristics of individual buildings. Under this semantic expression framework, an object-based SAR image segmentation method is adopted to provide homogeneous image objects, and three categories of image object features are extracted. Semantic rules are implemented by organizing image object features, and the individual building objects expression based on an ontological semantic description is formed. Finally, the building primitives are used to detect buildings among the available image objects. Experiments on TerraSAR-X images of Foshan city, China, with a spatial resolution of 1.25 m × 1.25 m, have shown the total extraction rates are above 84%. The results indicate the ontological semantic method can exactly extract flat-roof and gable-roof buildings larger than 250 pixels with different orientations.

Evaluation of a commercial biologically based IMRT treatment planning system

International Nuclear Information System (INIS)

Semenenko, Vladimir A.; Reitz, Bodo; Day, Ellen; Qi, X. Sharon; Miften, Moyed; Li, X. Allen

2008-01-01

A new inverse treatment planning system (TPS) for external beam radiation therapy with high energy photons is commercially available that utilizes both dose-volume-based cost functions and a selection of cost functions which are based on biological models. The purpose of this work is to evaluate quality of intensity-modulated radiation therapy (IMRT) plans resulting from the use of biological cost functions in comparison to plans designed using a traditional TPS employing dose-volume-based optimization. Treatment planning was performed independently at two institutions. For six cancer patients, including head and neck (one case from each institution), prostate, brain, liver, and rectal cases, segmental multileaf collimator IMRT plans were designed using biological cost functions and compared with clinically used dose-based plans for the same patients. Dose-volume histograms and dosimetric indices, such as minimum, maximum, and mean dose, were extracted and compared between the two types of treatment plans. Comparisons of the generalized equivalent uniform dose (EUD), a previously proposed plan quality index (fEUD), target conformity and heterogeneity indices, and the number of segments and monitor units were also performed. The most prominent feature of the biologically based plans was better sparing of organs at risk (OARs). When all plans from both institutions were combined, the biologically based plans resulted in smaller EUD values for 26 out of 33 OARs by an average of 5.6 Gy (range 0.24 to 15 Gy). Owing to more efficient beam segmentation and leaf sequencing tools implemented in the biologically based TPS compared to the dose-based TPS, an estimated treatment delivery time was shorter in most (five out of six) cases with some plans showing up to 50% reduction. The biologically based plans were generally characterized by a smaller conformity index, but greater heterogeneity index compared to the dose-based plans. Overall, compared to plans based on dose

Extraction efficiency of hydrophilic and lipophilic antioxidants from lyophilized foods using pressurized liquid extraction and manual extraction.

Science.gov (United States)

Watanabe, Jun; Oki, Tomoyuki; Takebayashi, Jun; Takano-Ishikawa, Yuko

2014-09-01

The efficient extraction of antioxidants from food samples is necessary in order to accurately measure their antioxidant capacities. α-Tocopherol and gallic acid were spiked into samples of 5 lyophilized and pulverized vegetables and fruits (onion, cabbage, Satsuma mandarin orange, pumpkin, and spinach). The lipophilic and hydrophilic antioxidants in the samples were sequentially extracted with a mixed solvent of n-hexane and dichloromethane, and then with acetic acid-acidified aqueous methanol. Duplicate samples were extracted: one set was extracted using an automated pressurized liquid extraction apparatus, and the other set was extracted manually. Spiked α-tocopherol and gallic acid were recovered almost quantitatively in the extracted lipophilic and hydrophilic fractions, respectively, especially when pressurized liquid extraction was used. The expected increase in lipophilic oxygen radical absorbance capacity (L-ORAC) due to spiking with α-tocopherol, and the expected increase in 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities and total polyphenol content due to spiking with gallic acid, were all recovered in high yield. Relatively low recoveries, as reflected in the hydrophilic ORAC (H-ORAC) value, were obtained following spiking with gallic acid, suggesting an interaction between gallic acid and endogenous antioxidants. The H-ORAC values of gallic acid-spiked samples were almost the same as those of postadded (spiked) samples. These results clearly indicate that lipophilic and hydrophilic antioxidants are effectively extracted from lyophilized food, especially when pressurized liquid extraction is used. © 2014 Institute of Food Technologists®

Supercritical fluid extraction of positron-emitting radioisotopes from solid target matrices

International Nuclear Information System (INIS)

Schlyer, D.

2000-01-01

Supercritical fluids are attractive as media for both chemical reactions, as well as process extraction, since their physical properties can be manipulated by small changes in pressure and temperature near the critical point of the fluid. Such changes can result in drastic effects on density-dependent properties such as solubility, refractive index, dielectric constant, viscosity and diffusivity of the fluid. This suggests that pressure tuning of a pure supercritical fluid may be a useful means to manipulate chemical reactions on the basis of a thermodynamic solvent effect. It also means that the solvation properties of the fluid can be precisely controlled to enable selective component extraction from a matrix. In recent years there has been a growing interest in applying supercritical fluid extraction to the selective removal of trace metals from solid samples. Much of the work has been done on simple systems comprised of inert matrices such as silica or cellulose. Recently, this process as been expanded to environmental samples as well. However, very little is understood about the exact mechanism of the extraction process. Of course, the widespread application of this technology is highly dependent on the ability of scientists to model and predict accurate phase equilibria in complex systems. In this project, we plan to explore the feasibility of utilizing supercritical fluids as solvents for reaction and extraction of radioisotopes produced from solid enriched targets. The reason for this work is that many of these enriched target materials used for radioisotope production are expensive

Solvent extraction of strontium into nitrobenzene using hydrogen dicarbollylcobaltate in the presence of 12-crown-4

Czech Academy of Sciences Publication Activity Database

Vaňura, P.; Makrlík, E.; Vobecký, Miloslav

2003-01-01

Roč. 257, č. 2 (2003), s. 437-440 ISSN 0236-5731 R&D Projects: GA MŠk LN00B084 Institutional research plan: CEZ:AV0Z4031919; CEZ:MSM 230000009 Keywords : strontium * extraction Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.472, year: 2003

Lanthanide and actinide extractions with cobalt bis(dicarbollide) ion derivatives covalently bonded to diglycolyl diamide platform

Czech Academy of Sciences Publication Activity Database

Lučaníková, M.; Selucký, P.; Rais, J.; Grüner, Bohumír; Kvíčalová, Magdalena

2011-01-01

Roč. 1, č. 1 (2011), s. 89-95 ISSN 2193-2875 R&D Projects: GA ČR GA104/09/0668; GA MŠk LC523 Institutional research plan: CEZ:AV0Z40320502 Keywords : Dicarbollides derivatives * TODGA * Liquid-liquid extraction * Lanthanides * Actinides Subject RIV: CA - Inorganic Chemistry

Criteria adopted by dentists to indicate the extraction of periodontally involved teeth

Directory of Open Access Journals (Sweden)

Carlos Heitor Cunha Moreira

2007-10-01

Full Text Available When dealing with patients with periodontal disease of variable severities, dentists must often choose between treating and restoring the involved tooth or indicating its extraction. Different criteria have been adopted in this decision-making process. The purpose of this study was to evaluate the criteria adopted by dentists to indicate the extraction of teeth with periodontitis. Dentists were interviewed at their private practices in three cities of the state of Rio Grande do Sul, Brazil. The evaluated criteria included severity of attachment loss, tooth mobility, furcation involvement, prosthetic planning, periodontal-endodontic lesion, possible systemic involvement due to the presence of periodontitis, referral to a periodontist for evaluation, radiographic bone loss greater than 50%, presence of extensive caries, socio-economic and cultural status of the patient, among others. The most often adopted criteria to indicate the extraction of periodontally affected teeth were the presence of mobility (37.5%, severity of attachment loss (24.3% and radiographic bone loss greater than 50% (21.2%. The results of the present study demonstrated the difficulties faced by dentists to indicate the extraction of teeth with severe attachment loss, in addition to the establishment of an adequate prognosis. Aspects associated with the past disease were still the most often reported to indicate the extraction of teeth for periodontal reasons.

Approach and practices of district energy planning to achieve low carbon outcomes in China

International Nuclear Information System (INIS)

Xu, Baoping; Zhou, Shaoxiang; Hao, Lin

2015-01-01

District energy planning is an important methodology to assist in realizing a lower carbon target. However, district energy planning has not yet been incorporated into the statutory planning system in China, primarily because there are no clear standards and specifications for these plans. In this paper, we propose a general framework and low carbon estimation method for district energy planning, which is based on evaluating the low carbon energy planning practices of several new districts in China. In addition, several key points of concern in the planning process are extracted and discussed: overall infrastructure planning; co-operation between city planning and other special low carbon eco-planning; investment, financing and profitable operation; planning management mechanisms; and the management of the construction of the energy system to coincide with the project schedule. We carried out a case study of a low carbon energy plan for a new district of Beijing to evaluate our framework. Finally, we conclude that to realize the low carbon target, regional energy planning covering technologies, the market and management should be standardized as soon as possible. -- Highlights: •A general framework for district energy planning is proposed. •A case study of a low carbon energy plan for a new district is carried out. •District energy planning should be standardized as soon as possible. •The most suitable spatial scale for energy planning is at the municipal level

EXTRACTION OF BUILIDNG SHAPE FROM TANDEM-X DATA

Directory of Open Access Journals (Sweden)

A. Thiele

2013-05-01

Full Text Available Large scale mapping and modeling of urban areas is requested in many fields, especially in planning of energy supply and for change detection. For this purpose, SAR systems are highly attractive due to their independency of daytime and weather. The new satellite configuration of TerraSAR-X and TanDEM-X provides single-pass 3D mapping of the earth with unprecedented geometric resolution, allowing for improved detection and extraction of building positions and shapes. In this paper, single-pass interferograms of the TanDEM-X mission are utilized to automatically reconstruct buildings. To this purpose, first an interferogram is calculated from a TanDEM pair. Then, a new detector is applied that analyses phase ramps in the interferogram. Phase ramps being a pattern typically observable in layover areas of buildings, the detector is able to indicate building locations. Afterwards, the detected building areas are analyzed in more detail to extract width, length, and height of the buildings. Last, an edge detector is applied to deduce the building shapes. The reconstruction results are compared with reference data.

Toward Personalized Pressure Ulcer Care Planning: Development of a Bioinformatics System for Individualized Prioritization of Clinical Pratice Guideline

Science.gov (United States)

2016-10-01

AWARD NUMBER: W81XWH-15-1-0342 TITLE: Toward Personalized Pressure Ulcer Care Planning: Development of a Bioinformatics System for Individualized...Planning: Development of a Bioinformatics System for Individualized Prioritization of Clinical Pratice Guideline 5a. CONTRACT NUMBER 5b. GRANT...recommendations of CPG has been identified by experts in the field. We will use bioinformatics to enable data extraction, storage, and analysis to support

Novel Fluorinated Tensioactive Extractant Combined with Flotation for Decontamination of Extractant Residual during Solvent Extraction

Science.gov (United States)

Wu, Xue; Chang, Zhidong; Liu, Yao; Choe, Chol Ryong

2017-12-01

Solvent-extraction is widely used in chemical industry. Due to the amphiphilic character, a large amount of extractant remains in water phase, which causes not only loss of reagent, but also secondary contamination in water phase. Novel fluorinated extractants with ultra-low solubility in water were regarded as effective choice to reduce extractant loss in aqueous phase. However, trace amount of extractant still remained in water. Based on the high tensioactive aptitude of fluorinated solvent, flotation was applied to separate fluorinated extractant remaining in raffinate. According to the data of surface tension measurement, the surface tension of solution was obviously decreased with the addition of fluorinated extractant tris(2,2,3,3,4,4,5,5-octafluoropentyl) phosphate (FTAP). After flotation, the FTAP dissolved in water can be removed as much as 70%, which proved the feasibility of this key idea. The effects of operation time, gas velocity, pH and salinity of bulk solution on flotation performance were discussed. The optimum operating parameters were determined as gas velocity of 12ml/min, operating time of 15min, pH of 8.7, and NaCl volume concentration of 1.5%, respectively. Moreover, adsorption process of FTAP on bubble surface was simulated by ANSYS VOF model using SIMPLE algorithm. The dynamic mechanism of flotation was also theoretically investigated, which can be considered as supplement to the experimental results.

Employee choice of a high-deductible health plan across multiple employers.

Science.gov (United States)

Lave, Judith R; Men, Aiju; Day, Brian T; Wang, Wei; Zhang, Yuting

2011-02-01

To determine factors associated with selecting a high-deductible health plan (HDHP) rather than a preferred provider plan (PPO) and to examine switching and market segmentation after initial selection. Claims and benefit information for 2005-2007 from nine employers in western Pennsylvania first offering HDHP in 2006. We examined plan growth over time, used logistic regression to determine factors associated with choosing an HDHP, and examined the distribution of healthy and sick members across plan types. We linked employees with their dependents to determine family-level variables. We extracted risk scores, covered charges, employee age, and employee gender from claims data. We determined census-level race, education, and income information. Health status, gender, race, and education influenced the type of individual and family policies chosen. In the second year the HDHP was offered, few employees changed plans. Risk segmentation between HDHPs and PPOs existed, but it did not increase. When given a choice, those who are healthier are more likely to select an HDHP leading to risk segmentation. Risk segmentation did not increase in the second year that HDHPs were offered. © Health Research and Educational Trust.

Novel Approaches to Breast Cancer Prevention and Inhibition of Metastases

Science.gov (United States)

2014-10-01

that women with BRCA1 mutations exhibit deregulated RANKL and reduced OPG (the natural inhibitor of RANKL) levels during their menstrual cycle...and kidney cancer cell lines. Light blue indicates a copy number decrease; dark blue indicates a loss of the indicated regions; shades of yellow...indicate increased copy numbers; black indicates normal diploid DNA content. For the presented copy number analysis, 50 and 100k Affymetrix SNP chips

[My humble opinion on teaching of acupoints: discussion on The Channels, Collaterals and Acupoints Science, a national plan teaching material of "the tenth five-year plan"].

Science.gov (United States)

Hou, Shu-Wei

2008-10-01

Analyze and probe a part of contents in The Channels, Collaterals and Acupoints Science, a national plan teaching material of "the tenth five-year plan", and put forward own opinion on compilation of the teaching materials. Various concepts of acupoints should strive to be strict and terse; location of acupoints should be accurate and conform to clinical practice and reduce errors; the new edition The Channels, Collaterals and Acupoints Science should reasonably select and supplement for extra-ordinary points; increase explanation of the point name, function of acupoints, and association of acupoints; enrich the contents of acupuncture manipulation; reasonably increase and reduce extracts of ancient and modern reports to conform to development of the new age.

Groundwater well services site safety and health plan

International Nuclear Information System (INIS)

Tuttle, B.G.

1996-08-01

This Site Specific Health and Safety Plan covers well servicing in support of the Environmental Restoration Contractor Groundwater Project. Well servicing is an important part of environmental restoration activities supporting several pump and treat facilities and assisting in evaluation and servicing of various groundwater wells throughout the Hanford Site. Remediation of contaminated groundwater is a major part of the ERC project. Well services tasks help enhance groundwater extraction/injection as well as maintain groundwater wells for sampling and other hydrologic testing and information gathering

Binary solvent extraction system and extraction time effects on phenolic antioxidants from kenaf seeds (Hibiscus cannabinus L.) extracted by a pulsed ultrasonic-assisted extraction.

Science.gov (United States)

Wong, Yu Hua; Lau, Hwee Wen; Tan, Chin Ping; Long, Kamariah; Nyam, Kar Lin

2014-01-01

The aim of this study was to determine the best parameter for extracting phenolic-enriched kenaf (Hibiscus cannabinus L.) seeds by a pulsed ultrasonic-assisted extraction. The antioxidant activities of ultrasonic-assisted kenaf seed extracts (KSE) were determined by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging assay, β -carotene bleaching inhibition assay, and ferric reducing antioxidant power (FRAP) assay. Total phenolic content (TPC) and total flavonoid content (TFC) evaluations were carried out to determine the phenolic and flavonoid contents in KSE. The KSE from the best extraction parameter was then subjected to high performance liquid chromatography (HPLC) to quantify the phenolic compounds. The optimised extraction condition employed 80% ethanol for 15 min, with the highest values determined for the DPPH, ABTS, and FRAP assay. KSE contained mainly tannic acid (2302.20 mg/100 g extract) and sinapic acid (1198.22 mg/100 g extract), which can be used as alternative antioxidants in the food industry.

Binary Solvent Extraction System and Extraction Time Effects on Phenolic Antioxidants from Kenaf Seeds (Hibiscus cannabinus L.) Extracted by a Pulsed Ultrasonic-Assisted Extraction

Science.gov (United States)

Lau, Hwee Wen; Nyam, Kar Lin

2014-01-01

The aim of this study was to determine the best parameter for extracting phenolic-enriched kenaf (Hibiscus cannabinus L.) seeds by a pulsed ultrasonic-assisted extraction. The antioxidant activities of ultrasonic-assisted kenaf seed extracts (KSE) were determined by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity assay, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging assay, β-carotene bleaching inhibition assay, and ferric reducing antioxidant power (FRAP) assay. Total phenolic content (TPC) and total flavonoid content (TFC) evaluations were carried out to determine the phenolic and flavonoid contents in KSE. The KSE from the best extraction parameter was then subjected to high performance liquid chromatography (HPLC) to quantify the phenolic compounds. The optimised extraction condition employed 80% ethanol for 15 min, with the highest values determined for the DPPH, ABTS, and FRAP assay. KSE contained mainly tannic acid (2302.20 mg/100 g extract) and sinapic acid (1198.22 mg/100 g extract), which can be used as alternative antioxidants in the food industry. PMID:24592184

Binary Solvent Extraction System and Extraction Time Effects on Phenolic Antioxidants from Kenaf Seeds (Hibiscus cannabinus L. Extracted by a Pulsed Ultrasonic-Assisted Extraction

Directory of Open Access Journals (Sweden)

Yu Hua Wong

2014-01-01

Full Text Available The aim of this study was to determine the best parameter for extracting phenolic-enriched kenaf (Hibiscus cannabinus L. seeds by a pulsed ultrasonic-assisted extraction. The antioxidant activities of ultrasonic-assisted kenaf seed extracts (KSE were determined by a 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging capacity assay, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS radical scavenging assay, β-carotene bleaching inhibition assay, and ferric reducing antioxidant power (FRAP assay. Total phenolic content (TPC and total flavonoid content (TFC evaluations were carried out to determine the phenolic and flavonoid contents in KSE. The KSE from the best extraction parameter was then subjected to high performance liquid chromatography (HPLC to quantify the phenolic compounds. The optimised extraction condition employed 80% ethanol for 15 min, with the highest values determined for the DPPH, ABTS, and FRAP assay. KSE contained mainly tannic acid (2302.20 mg/100 g extract and sinapic acid (1198.22 mg/100 g extract, which can be used as alternative antioxidants in the food industry.

Oil sands mine planning and waste management using goal programming

Energy Technology Data Exchange (ETDEWEB)

Ben-Awuah, E.; Askari-Nasab, H. [Alberta Univ., Edmonton, AB (Canada). Dept. of Civil and Environmental Engineering; Alberta Univ., Edmonton, AB (Canada). Mining Optimization Laboratory

2010-07-01

A goal programming method was used to plan waste management processes at an oil sands mine. This method requires the decision maker (DM) to set goals. Mine planning is used to determine a block extraction schedule that maximizes net present value (NPV). Due to land restrictions, tailings facilities are sited within the pit area and dykes are used to contain the tailings. Many of the materials used to construct the dykes come from the mining operation. The mine plan scheduled both ore and dyke material concurrently. Dykes were constructed simultaneously as the mine phase advanced. A model was used to classify an oil sands block model into different material types. A mixed integer goal programming (MIGP) method was used to generate a strategic schedule. Block clustering techniques were used to large-scale mine planning projects. The method was used to verify and validate synthetic and real case data related to the cost of mining all material as waste, and the extra cost of mining dyke material. A case study of an oil sands project was used to demonstrate the method. The study showed that the developed model generates a smooth and uniform strategic schedule for large-scale mine planning projects. tabs., figs.

Oil sands mine planning and waste management using goal programming

International Nuclear Information System (INIS)

Ben-Awuah, E.; Askari-Nasab, H.; Alberta Univ., Edmonton, AB

2010-01-01

A goal programming method was used to plan waste management processes at an oil sands mine. This method requires the decision maker (DM) to set goals. Mine planning is used to determine a block extraction schedule that maximizes net present value (NPV). Due to land restrictions, tailings facilities are sited within the pit area and dykes are used to contain the tailings. Many of the materials used to construct the dykes come from the mining operation. The mine plan scheduled both ore and dyke material concurrently. Dykes were constructed simultaneously as the mine phase advanced. A model was used to classify an oil sands block model into different material types. A mixed integer goal programming (MIGP) method was used to generate a strategic schedule. Block clustering techniques were used to large-scale mine planning projects. The method was used to verify and validate synthetic and real case data related to the cost of mining all material as waste, and the extra cost of mining dyke material. A case study of an oil sands project was used to demonstrate the method. The study showed that the developed model generates a smooth and uniform strategic schedule for large-scale mine planning projects. tabs., figs.

77 FR 58955 - Approval and Promulgation of Air Quality Implementation Plans; Commonwealth of Pennsylvania...

Science.gov (United States)

2012-09-25

... than 100 HP or gas extraction wells at landfills. However, the Commenter has not provided, and EPA is... processing of natural gas from the Marcellus Shale'' and asserts that these alleged monitoring or reporting... Marcellus Shale industry and therefore the ambient air quality monitoring plan is inadequate to monitor...

Determination of the coal extraction plan with reduction to a minimum of the outlays for extraction and storage with simultaneous fulfillment of the consumer's orders

Energy Technology Data Exchange (ETDEWEB)

Lacheta, A; Stangiewicz, T

1979-01-01

The use of dynamic programming of monthly extraction and storage of coal at mines was examined in order to reduce the annual outlays for these operations. In addition, realization of the model simultaneously satisfies the orders of the consumers, despite the seasonal fluctuations in the demand of the customers and the coal shipment capabilities of the mining enterprise.

Unsymmetrical phosphate as extractant for the extraction of nitric acid

International Nuclear Information System (INIS)

Gaikwad, R.H.; Jayaram, R.V.

2016-01-01

Tri-n-butyl phosphate (TBP) was first used as an extractant in 1944, during Manhattan project for the separation of actinides and further explored by Warf in 1949 for the extraction of Ce(IV) from aqueous nitric acid. TBP was further used as an extractant in the Plutonium Uranium Recovery by Extraction (PUREX) process. To meet the stringent requirements of the nuclear industry TBP has been extensively investigated. In spite of its wide applicability, TBP suffers from various disadvantages such as high aqueous solubility, third phase formation, chemical and radiation degradation leading to the formation of undesired products. It also suffers from incomplete decontamination of the actinides from fission products. Various attempts have been made to overcome the problems associated with TBP by way of using higher homologues of TBP such as Tri-iso amyl phosphate (TiAP), Tri-secondary butyl phosphate (TsBP), Tri amyl phosphate (TAP). It was found that in some cases the results were considerably better than those obtained with TBP for uranium/thorium extraction. The extraction of nitric acid by TBP and its higher homologues which are symmetrical are well documented. However, no solvent has emerged clearly superior than TBP. Here in we report the extraction of nitric acid with neutral unsymmetrical phosphates and study them as extractants for the extraction of nitric acid. Dibutyl secbutyl phosphate, dibutyl pentyl phosphate and dibutyl heptyl phosphate were synthesised for this purpose and the extraction of nitric acid was studied in n-dodecane. The results indicate that the substitution of one of the alkyl groups of the symmetrical phosphate adjacent to the phosphoryl (P=O) group of the phosphate does not have any pronounced effect on the extraction capacity of nitric acid. (author)

Effective extraction of photoluminescence from a diamond layer with a photonic crystal

Czech Academy of Sciences Publication Activity Database

Ondič, Lukáš; Dohnalová, Kateřina; Ledinský, Martin; Kromka, Alexander; Babchenko, Oleg; Rezek, Bohuslav

2011-01-01

Roč. 5, č. 1 (2011), s. 346-350 ISSN 1936-0851 R&D Projects: GA AV ČR KAN400100701; GA MŠk LC510; GA AV ČR KJB100100903 Grant - others:AV ČR(CZ) M100100902 Institutional research plan: CEZ:AV0Z10100521 Keywords : photonic crystals * spontaneous emission * light extraction * diffraction * nanocrystalline diamond films Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 10.774, year: 2011

Isolation of proteins from ejaculated and capacitated sperms by various extraction approaches

Czech Academy of Sciences Publication Activity Database

Zigo, Michal; Jonáková, Věra; Postlerová, Pavla

2010-01-01

Roč. 33, Supplement 1 (2010), s. 68-68 ISSN 0105-6263. [6th European Congress of And rology. 29.09.2010-01.10.2010, Athens] R&D Projects: GA ČR(CZ) GA303/09/1285; GA MŠk(CZ) 1M06011; GA MZd NS10009-4/2008 Institutional research plan: CEZ:AV0Z50520701 Keywords : spermatozoa * protein extraction * 2D electrophoresis * zona pellucida * glycoproteins Subject RIV: CE - Biochemistry

A comparison of accelerated solvent extraction, Soxhlet extraction, and ultrasonic-assisted extraction for analysis of terpenoids and sterols in tobacco.

Science.gov (United States)

Shen, Jinchao; Shao, Xueguang

2005-11-01

The performance of accelerated solvent extraction in the analysis of terpenoids and sterols in tobacco samples was investigated and compared with those of Soxhlet extraction and ultrasonically assisted extraction with respect to yield, extraction time, reproducibility and solvent consumption. The results indicate that although the highest yield was achieved by Soxhlet extraction, ASE appears to be a promising alternative to classical methods since it is faster and uses less solvent, especially when applied to the investigation of large batch tobacco samples. However, Soxhlet extraction is still the preferred method for analyzing sterols since it gives a higher extraction efficiency than other methods.

Expression levels of the receptor activator of NF-κB ligand and osteoprotegerin and the number of gram-negative bacteria in symptomatic and asymptomatic periapical lesions.

Science.gov (United States)

Carneiro, E; Parolin, A B; Wichnieski, C; Rosa, E A R; Silva Neto, U X; Westphalen, V P D; Fariniuk, L F; Johann, A C B R

2017-01-01

The study aimed to verify the potential correlation between the detected amount of gram-negative bacteria and the radiographic sizes of the lesions in patients with symptomatic and asymptomatic apical periodontitis. Furthermore, to evaluate whether the expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) and the RANKL/OPG ratio are differentially regulated in both groups. Twenty patients with periapical lesions were divided into two groups: symptomatic (SYM) n=10 and asymptomatic (ASYM) n=10. After periapical surgery, the lesions were collected and processed for histological examination, and immunohistochemistry. The percentage of RANKL- and OPG-immunopositive areas relative to the total area of the microscopic field was calculated. For gram staining, the number of gram-negative cells per microscopic field was assessed. The radiographs of each patient were processed and measured. The Student's t-test and the Pearson correlation coefficient were performed. The SYM group showed a significantly higher number of gram-negative cells (p=0.007) when compared to the ASYM group. A higher number of gram-negative bacteria occurred more frequently in larger periapical lesions and the SYM group (p=0.03). The expression for RANKL and OPG and the RANKL/OPG ratio were not significantly different between the groups. There was a significant positive correlation between the number of bacteria and OPG levels in the SYM group (p=0.01). The number of bacteria seems to influence the symptoms and the radiographic size of a periapical lesion. Gram-negative bacteria may play an important role in OPG activity in the SYM group. Copyright © 2016 Elsevier Ltd. All rights reserved.

Image-based path planning for automated virtual colonoscopy navigation

Science.gov (United States)

Hong, Wei

2008-03-01

Virtual colonoscopy (VC) is a noninvasive method for colonic polyp screening, by reconstructing three-dimensional models of the colon using computerized tomography (CT). In virtual colonoscopy fly-through navigation, it is crucial to generate an optimal camera path for efficient clinical examination. In conventional methods, the centerline of the colon lumen is usually used as the camera path. In order to extract colon centerline, some time consuming pre-processing algorithms must be performed before the fly-through navigation, such as colon segmentation, distance transformation, or topological thinning. In this paper, we present an efficient image-based path planning algorithm for automated virtual colonoscopy fly-through navigation without the requirement of any pre-processing. Our algorithm only needs the physician to provide a seed point as the starting camera position using 2D axial CT images. A wide angle fisheye camera model is used to generate a depth image from the current camera position. Two types of navigational landmarks, safe regions and target regions are extracted from the depth images. Camera position and its corresponding view direction are then determined using these landmarks. The experimental results show that the generated paths are accurate and increase the user comfort during the fly-through navigation. Moreover, because of the efficiency of our path planning algorithm and rendering algorithm, our VC fly-through navigation system can still guarantee 30 FPS.

Understanding extractive bleed : wood extractives: distribution, properties, and classes

Science.gov (United States)

Edward Burke; Norm Slavik; Tony Bonura; Dennis Connelly; Tom Faris; Arnie Nebelsick; Brent Stuart; Sam Williams; Alex C. Wiedenhoeft

2010-01-01

Color, odor, and natural durability of heartwood are characteristics imparted by a class of chemicals in wood known collectively extractives. Wood is converted by the tree from sapwood to heartwood by the deposition of extractives, typically many years after the growth ring undergoing this change was formed by the tree. Extractives are thus not a part of the wood...

Salicortin inhibits osteoclast differentiation and bone resorption by down-regulating JNK and NF-κB/NFATc1 signaling pathways

Energy Technology Data Exchange (ETDEWEB)

Nie, Shaobo [Department of Orthopaedics, PLA General Hospital, Beijing 100853 (China); Xu, Jiawei [Department of Orthopaedics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Zhang, Chenghua [Department of Orthopaedics, Changle County Hospital of Traditional Chinese Medicine, Weifang 262400 (China); Xu, Chen [Department of Orthopaedics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Liu, Ming, E-mail: ming_li4717@sina.com [Department of Orthopaedics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Yu, Degang, E-mail: ydg163@126.com [Department of Orthopaedics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China)

2016-01-29

Receptor activator of nuclear factor (NF)-κB ligand (RANKL)-activated signaling is essential for osteoclast differentiation, activation, and survival. Salicortin is a phenolic glycoside that has been isolated from many plants such as Populus and Salix species, and has been shown to have anti-amnesic and anti-adipogenic effects. In this study, we investigated the effect of salicortin on RANKL-induced osteoclasts formation, bone resorption, and activation of osteoclast-related signaling pathways. Salicortin suppressed RANKL-induced osteoclastogenesis in bone marrow macrophage cultures in a dose-dependent manner, and inhibited osteoclastic bone resorption activity without any cytotoxicity. Salicortin inhibited RANKL-induced c-Jun N-terminal kinase and NF-κB activation, concomitant with retarded IκBα phosphorylation and inhibition of p65 nuclear translocation, leading to impaired transcription of nuclear factor of activated T cells c1 (NFATc1) and expression of osteoclastic-specific genes. Taken together, our findings demonstrate that salicortin inhibits NF-κB and NFATc1 activation, leading to attenuation of osteoclastogenesis and bone resorption. Thus, salicortin may be of interest in developments of treatment for osteoclast related diseases. - Highlights: • Salicortin suppresses osteoclastogenesis in vitro. • Salicortin impairs the JNK and NF-κB/NFATc1 signaling pathway. • Salicortin may be of interest in developments of osteoporosis treatment.

Salicortin inhibits osteoclast differentiation and bone resorption by down-regulating JNK and NF-κB/NFATc1 signaling pathways

International Nuclear Information System (INIS)

Nie, Shaobo; Xu, Jiawei; Zhang, Chenghua; Xu, Chen; Liu, Ming; Yu, Degang

2016-01-01

Receptor activator of nuclear factor (NF)-κB ligand (RANKL)-activated signaling is essential for osteoclast differentiation, activation, and survival. Salicortin is a phenolic glycoside that has been isolated from many plants such as Populus and Salix species, and has been shown to have anti-amnesic and anti-adipogenic effects. In this study, we investigated the effect of salicortin on RANKL-induced osteoclasts formation, bone resorption, and activation of osteoclast-related signaling pathways. Salicortin suppressed RANKL-induced osteoclastogenesis in bone marrow macrophage cultures in a dose-dependent manner, and inhibited osteoclastic bone resorption activity without any cytotoxicity. Salicortin inhibited RANKL-induced c-Jun N-terminal kinase and NF-κB activation, concomitant with retarded IκBα phosphorylation and inhibition of p65 nuclear translocation, leading to impaired transcription of nuclear factor of activated T cells c1 (NFATc1) and expression of osteoclastic-specific genes. Taken together, our findings demonstrate that salicortin inhibits NF-κB and NFATc1 activation, leading to attenuation of osteoclastogenesis and bone resorption. Thus, salicortin may be of interest in developments of treatment for osteoclast related diseases. - Highlights: • Salicortin suppresses osteoclastogenesis in vitro. • Salicortin impairs the JNK and NF-κB/NFATc1 signaling pathway. • Salicortin may be of interest in developments of osteoporosis treatment.

Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment?

Directory of Open Access Journals (Sweden)

Roger von Moos

2013-08-01

Full Text Available Breast cancer cells preferentially metastasise to the skeleton, owing, in part, to the fertile environment provided by bone. Increased bone turnover releases growth factors that promote tumour cell growth. In turn, tumour cells release factors that stimulate further bone turnover, resulting in a vicious cycle of metastasis growth and bone destruction. The RANK-RANK ligand (RANKL pathway plays a key role in this cycle, and inhibition of RANKL using the fully-human monoclonal antibody denosumab, has demonstrated efficacy in delaying skeletal complications associated with bone metastases in three phase 3 trials. Preclinical studies suggest that the RANKL pathway also plays a role in breast cancer tumourigenesis and migration to bone. In a subgroup analysis of the negative Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE trial, the bisphosphonate zoledronic acid showed potential for improving survival in patients who were postmenopausal; however, a prospective study in this patient population is required to validate this observation. Ongoing trials are examining whether adjuvant blockade of the RANKL pathway using denosumab can prevent disease recurrence in patients with high-risk breast cancer. These are building on analogous studies that have shown that denosumab improves bone metastasis-free survival in prostate cancer and suggested that it confers an overall survival benefit in non-small-cell lung cancer.

In vitro comparison of the biological activity of alumina ceramic and titanium particles associated with aseptic loosening

International Nuclear Information System (INIS)

Ding Yue; Qin Chuqiang; Xu Jie; Huang Dongsheng; Fu Yuru

2012-01-01

Prosthetic wear particles are thought to play a central role in the initiation and development of periprosthetic osteolysis, leading to aseptic loosening of prostheses. This study aimed to compare the biological activity of ceramic and titanium particles that are associated with particle-induced, aseptic joint loosening. Different sizes of alumina-ceramic particles and titanium particles were prepared to stimulate murine macrophage cells RAW 264.7, of which the expressions of tumor necrosis factor alpha (TNF-alpha) and receptor activator of nuclear factor-κB ligand (RANKL) were measured by qPCR and ELISA at various time points. In the presence of all particles, the expression of TNF-alpha increased in a time-dependent manner, whereas the expression of RANKL showed no regular expression patterns. Notably, particles of smaller sizes provoked significantly higher levels of TNF-alpha and RANKL than those of larger sizes. Compared to the titanium particles, the ceramic particles provoked a significantly lower production of TNF-alpha. Thus, the bioactivities of titanium and alumina ceramic particles were inversely proportional to the sizes of the particles, and the expression of RANKL was not parallel to that of TNF-alpha. The successful outcome of ceramic-on-ceramic artificial joint prostheses may be attributed to the low biological activity of ceramic particles, as evidenced here. (paper)

Effects of different magnitudes of mechanical strain on Osteoblasts in vitro

International Nuclear Information System (INIS)

Tang Lin; Lin Zhu; Li Yongming

2006-01-01

In addition to systemic and local factors, mechanical strain plays a crucial role in bone remodeling during growth, development, and fracture healing, and especially in orthodontic tooth movement. Although many papers have been published on the effects of mechanical stress on osteoblasts or osteoblastic cells, little is known about the effects of different magnitudes of mechanical strain on such cells. In the present study, we investigated how different magnitudes of cyclic tensile strain affected osteoblasts. MC3T3-E1 osteoblastic cells were subjected to 0%, 6%, 12% or 18% elongation for 24 h using a Flexercell Strain Unit, and then the mRNA and protein expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were examined. The results showed that cyclic tensile strain induced a magnitude-dependent increase (0%, 6%, 12%, and 18%) in OPG synthesis and a concomitant decrease in RANKL mRNA expression and sRANKL release from the osteoblasts. Furthermore, the induction of OPG mRNA expression by stretching was inhibited by indomethacin or genistein, and the stretch-induced reduction of RANKL mRNA was inhibited by PD098059. These results indicate that different magnitudes of cyclic tensile strain influence the biological behavior of osteoblasts, which profoundly affects bone remodeling

Supercritical CO2 extraction of raw propolis and its dry ethanolic extract

Directory of Open Access Journals (Sweden)

L. C. Paviani

2012-06-01

Full Text Available Three types of propolis extract were prepared and analyzed with respect to their global extraction yields and with respect to the concentration of the following markers: 3,5-diprenyl-4-hydroxycinnamic acid; 3-prenyl-4-hydroxycinnamic acid; 4-hydroxycinnamic acid and 4-methoxy-3,5,7-trihydroxyflavone. The extract EEP (ethanolic extract of propolis was obtained by the conventional method from raw propolis using ethanol as solvent. The extracts (SFE were obtained by supercritical solvent extraction from the raw propolis using supercritical carbon dioxide (sc-CO2, with and without the addition of ethanol as a co-solvent. The fractionated supercritical extracts (FSCE were obtained by fractionation (extract and raffinate of the dry EEP with sc-CO2. EEP yields of 39.5% were obtained and maximum global extraction yields were 7.3% for SFE with no co-solvent, 51% for SFE with 15% ethanol and 18% for the FSCE extract fraction. The concentrations of the markers in the different extracts differed as a function of the operational parameters, indicating that the addition of co-solvent and the selectivity of sc-CO2 could be manipulated so as to obtain extracts with the yields and concentrations of interest.

Comparison of chemical composition and antibacterial activity of Nigella sativa seed essential oils obtained by different extraction methods

Czech Academy of Sciences Publication Activity Database

Kokoška, L.; Havlík, J.; Valterová, Irena; Sovová, Helena; Sajfrtová, Marie; Jankovská, I.

2008-01-01

Roč. 71, č. 12 (2008), s. 2475-2480 ISSN 0362-028X Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z40720504 Keywords : Nigella * essential oil * supercritical fluid extraction Subject RIV: CC - Organic Chemistry Impact factor: 1.763, year: 2008

Comparative analysis of proposals for the planning of the aggregate industry on the island of Tenerife

Energy Technology Data Exchange (ETDEWEB)

HernAndez-Duran, G.; Arranz-Gonzalez, C.; Vega-Panizo, R. de la

2016-07-01

The island of Tenerife is a territory with numerous protected natural areas and other areas which also deserve environmental protection, due to their ecological and landscape richness and values. According to current planning regulations, the aggregate mining industry is limited to a number of areas called extractive zones. The delimitation of such areas has some flaws and inconsistencies from the environmental point of view and from the consideration of the productive capacity of mining resources. This paper shows two models for environmental planning applied to the extractive activity for aggregates for the island of Tenerife, which could serve as alternatives to the current planning model: a model called zoned and another designated as zone- concentrated. These models provide improvements as far as respect for environmental values are concerned and are based on knowledge of the spatial distribution of geological materials. The conclusion is that this knowledge of the distribution of the potential mineral resources in the territory is the key to achieving the effective integration of mining in land-use planning, and to safeguard in the best possible way the mineral resources from the activities that may compromise their future availability. The applied methods could be extended to other territories, particularly islands, where it is very possible that there are similar problems to those that are occurring in Tenerife. (Author)

Modulation of ionizing radiation induced oxidative imbalance by semi-fractionated extract of Piper betle

Science.gov (United States)

Verma, Savita; Dutta, Ajaswrata; Sankhwar, Sanghmitra; Shukla, Sandeep Kumar

2010-01-01

The study was planned to evaluate modulatory effect of aqueous extract of Piper betle leaf (PBL) on ionizing radiation mediated oxidative stress leading to normal tissues damage during radiotherapy and other radiation exposures. The total polyphenols and flavonoids known as free radical scavenger (chelators) were measured in the extract. To ascertain antioxidant potential of PBL extract, we studied free radical scavenging, metal chelation, reducing power, lipid peroxidation inhibition and ferric reducing antioxidant properties (FRAP ) using in vitro assays. Mice were exposed to varied radiation doses administered with the same extract prior to irradiation to confirm its oxidative stress minimizing efficacy by evaluating ferric reducing ability of plasma, reduced glutathione, lipid peroxidation and micro-nuclei frequency. PBL extract was effective in scavenging DPPH (up to 92% at 100 µg/ml) and superoxide radicals (up to 95% at 80 µg/ml), chelated metal ions (up to 83% at 50 µg/ml) and inhibited lipid peroxidation (up to 45.65% at 500 µg/ml) in a dose dependant manner using in vitro model. Oral administration of PBL extract (225 mg/kg body weight) 1 hr before irradiation in mice significantly enhanced (p < 0.01) radiation abated antioxidant potential of plasma and GSH level in all the observed organs. The treatment with extract effectively lowered the radiation induced lipid peroxidation at 24 hrs in all the selected organs with maximum inhibition in thymus (p < 0.01). After 48 hrs, lipid peroxidation was maximally inhibited in the group treated with the extract. Frequency of radiation induced micronucleated cells declined significantly (34.78%, p < 0.01) at 24 hrs post-irradiation interval by PBL extract administration. The results suggest that PBL extract has high antioxidant potential and relatively non-toxic and thus could be assertively used to mitigate radiotherapy inflicted normal tissues damage and also injuries caused by moderate doses of radiation

Organization of extracting molecules of the diamide type: link with the extracting properties?

International Nuclear Information System (INIS)

Meridiano, Y.

2009-02-01

The aim of these studies is to establish a link between the different organizations of diamide extractants (used in the DIAMEX process) and their extracting properties. The effects of the key parameters leading the liquid-liquid extraction (concentration of extractant, nature of solute, activity of the aqueous phase, nature of the diluent and temperature) are studied: 1) at the supramolecular scale, with the characterization of the extractant organizations by vapor-pressure osmometry (VPO) and small angle neutron and X-ray scattering (SANS/SAXS) experiments; 2) at the molecular scale, with the quantification of the extracted solutes (water, nitric acid, metal nitrate) and the determination of extracted complexes stoichiometries by electro-spray mass spectrometry (ESI-MS) experiments. The DMDOHEMA molecule acts as a classical surfactant and forms aggregates of the reverse micelle type. Taking into account the established supramolecular diagrams, a quantitative link between the extractants structures and their extracting properties has been brought to light. To model the europium nitrate extraction, two approaches have been developed: - an approach based on mass action laws. Extractions equilibria have been proposed taking into account the supramolecular speciation; - an innovative approach considering the extracted ions as adsorbed on a specific surface of the extractant molecule which depends on the extractant organization state. The ion extraction can be considered as a sum of isotherms corresponding to the different states of organization. This approach allows to compare the extraction efficiency of an extracting molecule as a function of its organization state. (author)

EXTRACTION OF MONOAZO DYES BY HYDROPHILIC EXTRACTANTS FROM AQUEOUS SOLUTIONS

Directory of Open Access Journals (Sweden)

Y. I. Korenman

2012-01-01

Full Text Available The extraction of mono azo dyes E102, E122, E110, E124, E129 from aqueous solutions with hydrophilic solvents (alcohols, esters, ketones and polymers (poly-N-vinylamides, polyethylene glycol was studied. The main regularities of extraction are established. The distribution coefficients and degree of extraction of dyes was estimate. The influence of the nature of solvents and polymers on the extraction of dyes from aqueous solutions are established.

The decision to extract: Part 1--Interclinician agreement.

Science.gov (United States)

Baumrind, S; Korn, E L; Boyd, R L; Maxwell, R

1996-03-01

As part of an ongoing prospective clinical trial of conventional orthodontic treatment, the decision making patterns of a representative group of orthodontic clinicians were examined. Data were available for 148 subjects (100 adolescents and 48 adults) who had presented at the University of California San Francisco Graduate Orthodontic Clinic requesting treatment for correction of a Class I or Class II malocclusion. The records for each subject were evaluated independently by each of five members of the clinical faculty, making available a total of 740 independent patient evaluations. With regard to the primary decision as to whether extraction or nonextraction treatment was to be preferred, agreement among clinicians was higher than had been anticipated. In almost two thirds of the cases, the decisions of all five clinicians were in agreement as to whether extraction or nonextraction was the preferred treatment modality. (This figure included 59 cases of complete agreement for extraction therapy (40%) and 38 cases of complete agreement for nonextraction therapy (26%)). In only 51 cases (34%), did the reviewing clinicians disagree as to whether extraction or nonextraction was the preferred modality of treatment. The clinicians were also asked to indicate their opinions as to whether orthognathic surgery was likely to be a part of the ultimate treatment course for each individual subject. Nine percent of the 740 patient evaluations contained a clinician judgement that surgery would be a probable or definite component of the orthodontic treatment plan. For 29% of the adult subjects (14 cases) and 23% of the adolescent subjects (23 cases), one or more of the five examining clinicians believed that adjunctive surgical intervention would probably or definitely be appropriate. These high values were unexpected, particularly because the sample had been prescreened by a single clinician to exclude subjects who might require orthognathic surgery. Clinician agreement of

Antioxidant activities of extracts from five edible mushrooms using different extractants

Directory of Open Access Journals (Sweden)

Suphaphit Boonsong

2016-03-01

Full Text Available Extractions were performed of the total phenolic and flavonoid contents and antioxidant properties of five edible mushroom samples—Lentinus edodes, Volvariella volvacea, Pleurotus eous, Pleurotus sajor-caju and Auricularia auricular—using three different extractants. Among the three different extractants, 50% (volume per volume; v/v ethanol was the most suitable for antioxidant extraction from the mushroom samples. The 50% (v/v ethanolic extract of dried L. edodes contained higher total phenolic and flavonoid contents than in the other mushroom extract samples. The antioxidant activities of 50% (v/v ethanolic extract of dried L. edodes showed the strongest 2,2-diphenyl-1-picrylhydrazyl radical-scavenging assay (64.34% compared to butylated hydroxyanisole (BHA and α-tocopherol at 500 μg/mL. The ethanolic extract showed a lower reducing power of 0.10 compared to BHA and α-tocopherol at 500 μg/mL. Moreover, the L. edodes ethanolic extract also had the highest chelating ability (66.28% which was lower than for ethylenediaminetetraacetic acid at 500 μg/mL and showed the strongest superoxide radical-scavenging activity (64.17% compared to BHA and α-tocopherol. Therefore, the 50% (v/v ethanolic extract of L. edodes could be used as a potential natural antioxidative source or as an ingredient in the fish and fishery product industries.

Orthodontic treatment plan changed by 3D images

International Nuclear Information System (INIS)

Yordanova, G.; Stanimirov, P.

2014-01-01

Clinical application of CBCT is most often enforced in dental phenomenon of impacted teeth, hyperodontia, transposition, ankyloses or root resorption and other pathologies in the maxillofacial area. The goal, we put ourselves, is to show how the information from 3D images changes the protocol of the orthodontic treatment. The material, we presented six our clinical cases and the change in the plan of the treatment, which has used after analyzing the information carried on the three planes of CBCT. These cases are casuistic in the orthodontic practice and require individual approach to each of them during their analysis and decision taken. The discussion made by us is in line with reveal of the impacted teeth, where we need to evaluate their vertical depth and mediodistal ratios with the bond structures. At patients with hyperodontia, the assessment is of outmost importance to decide which of the teeth to be extracted and which one to be arranged into the dental arch. The conclusion we make is that diagnostic information is essential for decisions about treatment plan. The exact graphs will lead to better treatment plan and more predictable results. (authors) Key words: CBCT. IMPACTED CANINES. HYPERODONTIA. TRANSPOSITION

DOE-owned spent nuclear fuel program plan

International Nuclear Information System (INIS)

1995-11-01

The Department of Energy (DOE) has produced spent nuclear fuel (SNF) for many years as part of its various missions and programs. The historical process for managing this SNF was to reprocess it whereby valuable material such as uranium or plutonium was chemically separated from the wastes. These fuels were not intended for long-term storage. As the need for uranium and plutonium decreased, it became necessary to store the SNF for extended lengths of time. This necessity resulted from a 1992 DOE decision to discontinue reprocessing SNF to recover strategic materials (although limited processing of SNF to meet repository acceptance criteria remains under consideration, no plutonium or uranium extraction for other uses is planned). Both the facilities used for storage, and the fuel itself, began experiencing aging from this extended storage. New efforts are now necessary to assure suitable fuel and facility management until long-term decisions for spent fuel disposition are made and implemented. The Program Plan consists of 14 sections as follows: Sections 2--6 describe objectives, management, the work plan, the work breakdown structure, and the responsibility assignment matrix. Sections 7--9 describe the program summary schedules, site logic diagram, SNF Program resource and support requirements. Sections 10--14 present various supplemental management requirements and quality assurance guidelines

DOE-owned spent nuclear fuel program plan

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-11-01

The Department of Energy (DOE) has produced spent nuclear fuel (SNF) for many years as part of its various missions and programs. The historical process for managing this SNF was to reprocess it whereby valuable material such as uranium or plutonium was chemically separated from the wastes. These fuels were not intended for long-term storage. As the need for uranium and plutonium decreased, it became necessary to store the SNF for extended lengths of time. This necessity resulted from a 1992 DOE decision to discontinue reprocessing SNF to recover strategic materials (although limited processing of SNF to meet repository acceptance criteria remains under consideration, no plutonium or uranium extraction for other uses is planned). Both the facilities used for storage, and the fuel itself, began experiencing aging from this extended storage. New efforts are now necessary to assure suitable fuel and facility management until long-term decisions for spent fuel disposition are made and implemented. The Program Plan consists of 14 sections as follows: Sections 2--6 describe objectives, management, the work plan, the work breakdown structure, and the responsibility assignment matrix. Sections 7--9 describe the program summary schedules, site logic diagram, SNF Program resource and support requirements. Sections 10--14 present various supplemental management requirements and quality assurance guidelines.

Dependence of Achievable Plan Quality on Treatment Technique and Planning Goal Refinement: A Head-and-Neck Intensity Modulated Radiation Therapy Application

International Nuclear Information System (INIS)

Qi, X. Sharon; Ruan, Dan; Lee, Steve P.; Pham, Andrew; Kupelian, Patrick; Low, Daniel A.; Steinberg, Michael; Demarco, John

2015-01-01

Purpose: To develop a practical workflow for retrospectively analyzing target and normal tissue dose–volume endpoints for various intensity modulated radiation therapy (IMRT) delivery techniques; to develop technique-specific planning goals to improve plan consistency and quality when feasible. Methods and Materials: A total of 165 consecutive head-and-neck patients from our patient registry were selected and retrospectively analyzed. All IMRT plans were generated using the same dose–volume guidelines for TomoTherapy (Tomo, Accuray), TrueBeam (TB, Varian) using fixed-field IMRT (TB-IMRT) or RAPIDARC (TB-RAPIDARC), or Siemens Oncor (Siemens-IMRT, Siemens). A MATLAB-based dose–volume extraction and analysis tool was developed to export dosimetric endpoints for each patient. With a fair stratification of patient cohort, the variation of achieved dosimetric endpoints was analyzed among different treatment techniques. Upon identification of statistically significant variations, technique-specific planning goals were derived from dynamically accumulated institutional data. Results: Retrospective analysis showed that although all techniques yielded comparable target coverage, the doses to the critical structures differed. The maximum cord doses were 34.1 ± 2.6, 42.7 ± 2.1, 43.3 ± 2.0, and 45.1 ± 1.6 Gy for Tomo, TB-IMRT, TB-RAPIDARC, and Siemens-IMRT plans, respectively. Analyses of variance showed significant differences for the maximum cord doses but no significant differences for other selected structures among the investigated IMRT delivery techniques. Subsequently, a refined technique-specific dose–volume guideline for maximum cord dose was derived at a confidence level of 95%. The dosimetric plans that failed the refined technique-specific planning goals were reoptimized according to the refined constraints. We observed better cord sparing with minimal variations for the target coverage and other organ at risk sparing for the Tomo cases, and higher

Influence of Extraction Parameters on Hydroalcohol Extracts of the ...

African Journals Online (AJOL)

... the influence of alcohol concentration (50, 70 and 90 % v/v), extraction time (2, 6 and 10 h), and particle size of the herbal drug (0.25, 0.5 and 1.0 mm) on the pH, dry residue and myrsinoic acid B (MAB) content of hydroalcoholic extracts by high performance liquid chromatography (HPLC) method. Results: For the extracts, ...

Facility Effluent Monitoring Plan for the 222-S Laboratory

International Nuclear Information System (INIS)

Robinson, A.V.

1991-11-01

A facility effluent monitoring plan is required by the US Department of Energy in DOE Order 5400.1 for any operations that involve hazardous materials and radioactive substances that could impact employee or public safety or the environment. This document is prepared using the specific guidelines identified in A Guide for Preparing Hanford Site Facility Effluent Monitoring Plans, WHC-EP-0438. This facility effluent monitoring plan assesses effluent monitoring systems against applicable federal, state, and local requirements. This facility effluent monitoring plan is the first annual report. It shall ensure long-range integrity of the effluent monitoring systems by requiring an update whenever a new process or operation introduces new hazardous materials or significant radioactive materials. The current operation of the 222-S facilities includes the provision of analytical and radiological chemistry services in support of Hanford Site processing plants. The emphasis is on waste management, chemical processing, environmental monitoring effluent programs at B Plant, the Uranium Oxide Plant, Tank Farms, the 242-A Evaporator, the Waste Encapsulation and Storage Facility, the Plutonium-Uranium Extraction Facility, the Plutonium Finishing Plant, process development/impact activities, and essential materials. The laboratory also supplies analytical services in support of ongoing waste tank characterization

Design, Results and Plans for Power Beaming Competitive Challenge

International Nuclear Information System (INIS)

Shelef, Ben

2008-01-01

In our context, Power Beaming refers to the extraction of useable electrical power from a directed electromagnetic beam. In order to promote interest in this technology, the Spaceward Foundation proposed and is managing a technology prize challenge based on a Space Elevator design scenario. The challenge has a prize purse of $2M, provided by NASA's Centennial Challenges office. This paper covers the considerations that went into the design of the challenge, a brief chronology of past results, and plans for the future

A novel airport extraction model based on saliency region detection for high spatial resolution remote sensing images

Science.gov (United States)

Lv, Wen; Zhang, Libao; Zhu, Yongchun

2017-06-01

The airport is one of the most crucial traffic facilities in military and civil fields. Automatic airport extraction in high spatial resolution remote sensing images has many applications such as regional planning and military reconnaissance. Traditional airport extraction strategies usually base on prior knowledge and locate the airport target by template matching and classification, which will cause high computation complexity and large costs of computing resources for high spatial resolution remote sensing images. In this paper, we propose a novel automatic airport extraction model based on saliency region detection, airport runway extraction and adaptive threshold segmentation. In saliency region detection, we choose frequency-tuned (FT) model for computing airport saliency using low level features of color and luminance that is easy and fast to implement and can provide full-resolution saliency maps. In airport runway extraction, Hough transform is adopted to count the number of parallel line segments. In adaptive threshold segmentation, the Otsu threshold segmentation algorithm is proposed to obtain more accurate airport regions. The experimental results demonstrate that the proposed model outperforms existing saliency analysis models and shows good performance in the extraction of the airport.

Central Tolerance Blockade to Augment Checkpoint Immunotherapy in Melanoma

Science.gov (United States)

2017-09-01

expressed at higher levels in medullary thymic epithelial cells (mTECs) than in cortical thymic epithelial cells (cTECs), addition of anti-RANKL antibody...relative Aire expression by quantitative RT-PCR in cultured thymic tissue . 12-15 90% Subtask 3. Culture human thymus sections with OPG-Fc or vehicle...PCR in cultured thymic tissue . 15-18 90% ACURO approval 13-14 100% Major Task 1. Effect of concurrent anti-RANKL and checkpoint inhibitor

EXTRACT

DEFF Research Database (Denmark)

Pafilis, Evangelos; Buttigieg, Pier Luigi; Ferrell, Barbra

2016-01-01

The microbial and molecular ecology research communities have made substantial progress on developing standards for annotating samples with environment metadata. However, sample manual annotation is a highly labor intensive process and requires familiarity with the terminologies used. We have the...... and text-mining-assisted curation revealed that EXTRACT speeds up annotation by 15-25% and helps curators to detect terms that would otherwise have been missed.Database URL: https://extract.hcmr.gr/......., organism, tissue and disease terms. The evaluators in the BioCreative V Interactive Annotation Task found the system to be intuitive, useful, well documented and sufficiently accurate to be helpful in spotting relevant text passages and extracting organism and environment terms. Comparison of fully manual...

Region-Based Building Rooftop Extraction and Change Detection

Science.gov (United States)

Tian, J.; Metzlaff, L.; d'Angelo, P.; Reinartz, P.

2017-09-01

Automatic extraction of building changes is important for many applications like disaster monitoring and city planning. Although a lot of research work is available based on 2D as well as 3D data, an improvement in accuracy and efficiency is still needed. The introducing of digital surface models (DSMs) to building change detection has strongly improved the resulting accuracy. In this paper, a post-classification approach is proposed for building change detection using satellite stereo imagery. Firstly, DSMs are generated from satellite stereo imagery and further refined by using a segmentation result obtained from the Sobel gradients of the panchromatic image. Besides the refined DSMs, the panchromatic image and the pansharpened multispectral image are used as input features for mean-shift segmentation. The DSM is used to calculate the nDSM, out of which the initial building candidate regions are extracted. The candidate mask is further refined by morphological filtering and by excluding shadow regions. Following this, all segments that overlap with a building candidate region are determined. A building oriented segments merging procedure is introduced to generate a final building rooftop mask. As the last step, object based change detection is performed by directly comparing the building rooftops extracted from the pre- and after-event imagery and by fusing the change indicators with the roof-top region map. A quantitative and qualitative assessment of the proposed approach is provided by using WorldView-2 satellite data from Istanbul, Turkey.

REGION-BASED BUILDING ROOFTOP EXTRACTION AND CHANGE DETECTION

Directory of Open Access Journals (Sweden)

J. Tian

2017-09-01

Full Text Available Automatic extraction of building changes is important for many applications like disaster monitoring and city planning. Although a lot of research work is available based on 2D as well as 3D data, an improvement in accuracy and efficiency is still needed. The introducing of digital surface models (DSMs to building change detection has strongly improved the resulting accuracy. In this paper, a post-classification approach is proposed for building change detection using satellite stereo imagery. Firstly, DSMs are generated from satellite stereo imagery and further refined by using a segmentation result obtained from the Sobel gradients of the panchromatic image. Besides the refined DSMs, the panchromatic image and the pansharpened multispectral image are used as input features for mean-shift segmentation. The DSM is used to calculate the nDSM, out of which the initial building candidate regions are extracted. The candidate mask is further refined by morphological filtering and by excluding shadow regions. Following this, all segments that overlap with a building candidate region are determined. A building oriented segments merging procedure is introduced to generate a final building rooftop mask. As the last step, object based change detection is performed by directly comparing the building rooftops extracted from the pre- and after-event imagery and by fusing the change indicators with the roof-top region map. A quantitative and qualitative assessment of the proposed approach is provided by using WorldView-2 satellite data from Istanbul, Turkey.

Effect of soybean extract after tooth extraction on osteoblast numbers

Directory of Open Access Journals (Sweden)

Rosa Sharon Suhono

2011-06-01

Full Text Available Background: Many researches were done to find natural materials that may increase and promote bone healing processes after trauma and surgery. One of natural material that had been studied was soybean extract which contains phytoestrogen, a non-steroidal compounds found in plants that may binds to estrogen receptors and have estrogen-like activity. Purpose: The aim of this study was to investigate the effect of soybean extract feeding on the number of osteoblast cells in alveolar bone socket after mandibular tooth extraction. Methods: This study was studied on male Rattus norvegicus strain Wistar. Seventeen rats divided into three groups were used in this study. Group 1 fed with carboxy methyl cellulose (CMC solution 0,2% for seven days, and the left mandibular central incisivus was extracted; group 2 fed with soybean extract for seven days and the left mandibular central incisives was extracted; group 3 received the left mandibular central incisives extraction followed by soybean extract feeding for seven days after the extraction. All groups were sacrificed on the seventh day post-extraction, and the alveolar bone sockets were taken for histopathological observation. The tissues were processed and stained using hematoxylin and eosin to identify the amount of osteoblast cells. The number of osteoblast cells was counted using an Image Tool program. The data was analyzed statistically using the One-Way ANOVA test. Results: Significant differences were found on the number of osteoblast cells in alveolar bone after tooth extraction between groups. Group 2 (fed with soybean extract is higher than group 1 (fed with CMC and group 3 (fed with soybean extract after extraction. Conclusion: Soybean extract feeding that given for seven days pre-tooth extraction can increase the number of osteoblast cells compared with the group that were not given soybean extract feeding and also with the group that were given soybean extract feeding for seven days post

Bevalac extraction

International Nuclear Information System (INIS)

Kalnins, J.G.; Krebs, G.; Tekawa, M.; Cowles, D.; Byrne, T.

1992-02-01

This report will describe some of the general features of the Bevatron extraction system, primarily the dependence of the beam parameters and extraction magnet currents on the Bevalac field. The extraction magnets considered are: PFW, XPl, XP2, XS1, XS2, XM1, XM2, XM3, XQ3A and X03B. This study is based on 84 past tunes (from 1987 to the present) of various ions (p,He,O,Ne,Si,S,Ar,Ca,Ti,Fe,Nb,La,Au and U), for Bevalac fields from 1.749 to 12.575 kG, where all tunes included a complete set of beam line wire chamber pictures. The circulating beam intensity inside the Bevalac is measured with Beam Induction Electrodes (BIE) in the South Tangent Tank. The extracted beam intensity is usually measured with the Secondary Emission Monitor (SEM) in the F1-Box. For most of the tunes the extraction efficiency, as given by the SEM/BIE ratio, was not recorded in the MCR Log Book, but plotting the available Log Book data as a function of the Bevalac field, see Fig.9, we find that the extraction efficiency is typically between 30->60% with feedback spill

Planning documents: a business planning strategy.

Science.gov (United States)

Kaehrle, P A

2000-06-01

Strategic planning and business plan development are essential nursing management skills in today's competitive, fast paced, continually changing health care environment. Even in times of great uncertainty, nurse managers need to plan and forecast for the future. A well-written business plan allows nurse managers to communicate their expertise and proactively contribute to the programmatic decisions and changes occurring within their patient population or service area. This article presents the use of planning documents as a practical, strategic business planning strategy. Although the model addresses orthopedic services specifically, nurse managers can gain an understanding and working knowledge of planning concepts that can be applied to all patient populations.

Moringa oleifera leaf extract: An innovative priming tool for rangeland grasses

OpenAIRE

NOUMAN, Wasif; SIDDIQUI, Muhammad Tahir; BASRA, Shahzad Maqsood Ahmed

2012-01-01

Moringa oleifera leaf extract (MLE) is rich in amino acids, ascorbate, zeatin, minerals, and many other compounds known for their growth-promoting potential. This study was planned to explore the potential of MLE as a seed priming agent to increase the germination rate and plant vigor of 3 range grasses, i.e. Cenchrus ciliaris, Panicum antidotale, and Echinochloa crusgalli. The priming strategies used were hydropriming, CaCl2, PEG-8000 (-1.1 M Pa), MLE (concentrate; 1:10, 1:20, 1:30, and 1:40...

QUANTITATIVE DETERMINATION OF CHIRAL DICHLORPROP AND MECOPROP ENANTIOMERS IN DRINKING AND SURFACE WATERS BY SOLID-PHASE EXTRACTION AND CAPILLARY ELECTROPHORESIS

Czech Academy of Sciences Publication Activity Database

Tříska, Jan; Vrchotová, Naděžda

2002-01-01

Roč. 11, č. 7 (2002), s. 332-336 ISSN 1018-4619 Institutional research plan: CEZ:AV0Z6087904 Keywords : capillary electrophoresis * solid-phase extraction * chiral herbicides Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.309, year: 2002

A BIM-based system for demolition and renovation waste estimation and planning.

Science.gov (United States)

Cheng, Jack C P; Ma, Lauren Y H

2013-06-01

Due to the rising worldwide awareness of green environment, both government and contractors have to consider effective construction and demolition (C&D) waste management practices. The last two decades have witnessed the growing importance of demolition and renovation (D&R) works and the growing amount of D&R waste disposed to landfills every day, especially in developed cities like Hong Kong. Quantitative waste prediction is crucial for waste management. It can enable contractors to pinpoint critical waste generation processes and to plan waste control strategies. In addition, waste estimation could also facilitate some government waste management policies, such as the waste disposal charging scheme in Hong Kong. Currently, tools that can accurately and conveniently estimate the amount of waste from construction, renovation, and demolition projects are lacking. In the light of this research gap, this paper presents a building information modeling (BIM) based system that we have developed for estimation and planning of D&R waste. BIM allows multi-disciplinary information to be superimposed within one digital building model. Our system can extract material and volume information through the BIM model and integrate the information for detailed waste estimation and planning. Waste recycling and reuse are also considered in our system. Extracted material information can be provided to recyclers before demolition or renovation to make recycling stage more cooperative and more efficient. Pick-up truck requirements and waste disposal charging fee for different waste facilities will also be predicted through our system. The results could provide alerts to contractors ahead of time at project planning stage. This paper also presents an example scenario with a 47-floor residential building in Hong Kong to demonstrate our D&R waste estimation and planning system. As the BIM technology has been increasingly adopted in the architectural, engineering and construction industry

Extracting natural dyes from wool--an evaluation of extraction methods.

Science.gov (United States)

Manhita, Ana; Ferreira, Teresa; Candeias, António; Dias, Cristina Barrocas

2011-05-01

The efficiency of eight different procedures used for the extraction of natural dyes was evaluated using contemporary wool samples dyed with cochineal, madder, woad, weld, brazilwood and logwood. Comparison was made based on the LC-DAD peak areas of the natural dye's main components which had been extracted from the wool samples. Among the tested methods, an extraction procedure with Na(2)EDTA in water/DMF (1:1, v/v) proved to be the most suitable for the extraction of the studied dyes, which presented a wide range of chemical structures. The identification of the natural dyes used in the making of an eighteenth century Arraiolos carpet was possible using the Na(2)EDTA/DMF extraction of the wool embroidery samples and an LC-DAD-MS methodology. The effectiveness of the Na(2)EDTA/DMF extraction method was particularly observed in the extraction of weld dye components. Nine flavone derivatives previously identified in weld extracts could be identified in a single historical sample, confirming the use of this natural dye in the making of Arraiolos carpets. Indigo and brazilwood were also identified in the samples, and despite the fact that these natural dyes were referred in the historical recipes of Arraiolos dyeing, it is the first time that the use of brazilwood is confirmed. Mordant analysis by ICP-MS identified the widespread use of alum in the dyeing process, but in some samples with darker hues, high amounts of iron were found instead.

Wind turbine extraction from high spatial resolution remote sensing images based on saliency detection

Science.gov (United States)

Chen, Jingbo; Yue, Anzhi; Wang, Chengyi; Huang, Qingqing; Chen, Jiansheng; Meng, Yu; He, Dongxu

2018-01-01

The wind turbine is a device that converts the wind's kinetic energy into electrical power. Accurate and automatic extraction of wind turbine is instructive for government departments to plan wind power plant projects. A hybrid and practical framework based on saliency detection for wind turbine extraction, using Google Earth image at spatial resolution of 1 m, is proposed. It can be viewed as a two-phase procedure: coarsely detection and fine extraction. In the first stage, we introduced a frequency-tuned saliency detection approach for initially detecting the area of interest of the wind turbines. This method exploited features of color and luminance, was simple to implement, and was computationally efficient. Taking into account the complexity of remote sensing images, in the second stage, we proposed a fast method for fine-tuning results in frequency domain and then extracted wind turbines from these salient objects by removing the irrelevant salient areas according to the special properties of the wind turbines. Experiments demonstrated that our approach consistently obtains higher precision and better recall rates. Our method was also compared with other techniques from the literature and proves that it is more applicable and robust.

Comparative analysis of essential oil composition of Iranian and Indian Nigella sativa L. extracted using supercritical fluid extraction and solvent extraction.

Science.gov (United States)

Ghahramanloo, Kourosh Hasanzadeh; Kamalidehghan, Behnam; Akbari Javar, Hamid; Teguh Widodo, Riyanto; Majidzadeh, Keivan; Noordin, Mohamed Ibrahim

2017-01-01

The objective of this study was to compare the oil extraction yield and essential oil composition of Indian and Iranian Nigella sativa L. extracted by using Supercritical Fluid Extraction (SFE) and solvent extraction methods. In this study, a gas chromatography equipped with a mass spectrophotometer detector was employed for qualitative analysis of the essential oil composition of Indian and Iranian N. sativa L. The results indicated that the main fatty acid composition identified in the essential oils extracted by using SFE and solvent extraction were linoleic acid (22.4%-61.85%) and oleic acid (1.64%-18.97%). Thymoquinone (0.72%-21.03%) was found to be the major volatile compound in the extracted N. sativa oil. It was observed that the oil extraction efficiency obtained from SFE was significantly ( P essential oil, which is composed of higher linoleic acid and thymoquinone contents compared to the essential oil obtained by the solvent extraction technique.

Evaluation and scoring of radiotherapy treatment plans using an artificial neural network

International Nuclear Information System (INIS)

Willoughby, Twyla R.; Starkschall, George; Janjan, Nora A.; Rosen, Isaac I.

1996-01-01

Purpose: The objective of this work was to demonstrate the feasibility of using an artificial neural network to predict the clinical evaluation of radiotherapy treatment plans. Methods and Materials: Approximately 150 treatment plans were developed for 16 patients who received external-beam radiotherapy for soft-tissue sarcomas of the lower extremity. Plans were assigned a figure of merit by a radiation oncologist using a five-point rating scale. Plan scoring was performed by a single physician to ensure consistency in rating. Dose-volume information extracted from a training set of 511 treatment plans on 14 patients was correlated to the physician-generated figure of merit using an artificial neural network. The neural network was tested with a test set of 19 treatment plans on two patients whose plans were not used in the training of the neural net. Results: Physician scoring of treatment plans was consistent to within one point on the rating scale 88% of the time. The neural net reproduced the physician scores in the training set to within one point approximately 90% of the time. It reproduced the physician scores in the test set to within one point approximately 83% of the time. Conclusions: An artificial neural network can be trained to generate a score for a treatment plan that can be correlated to a clinically-based figure of merit. The accuracy of the neural net in scoring plans compares well with the reproducibility of the clinical scoring. The system of radiotherapy treatment plan evaluation using an artificial neural network demonstrates promise as a method for generating a clinically relevant figure of merit

Electromembrane extraction of amino acids from body fluids followed by capillary electrophoresis with capacitively coupled contactless conductivity detection

Czech Academy of Sciences Publication Activity Database

Strieglerová, Lenka; Kubáň, Pavel; Boček, Petr

2011-01-01

Roč. 1218, č. 37 (2011), s. 6248-6255 ISSN 0021-9673 R&D Projects: GA ČR GAP206/10/1219 Institutional research plan: CEZ:AV0Z40310501 Keywords : electromembrane extraction * biological samples * capillary electrophoresis Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.531, year: 2011

Locally accumulated extractable compounds in mycorrhizal parts of maize roots suppress the growth of hyphae of glomus intraradices

Czech Academy of Sciences Publication Activity Database

Gryndler, Milan; Hršelová, Hana; Malcová, Radka; Cajthaml, Tomáš; Halada, Petr

2003-01-01

Roč. 38, - (2003), s. 125-138 ISSN 0015-5551 R&D Projects: GA ČR GA526/97/0595 Institutional research plan: CEZ:AV0Z6005908; CEZ:AV0Z5020903 Keywords : fractions * patassium * root extract Subject RIV: EE - Microbiology, Virology Impact factor: 1.057, year: 2003

Extraction of liver volumetry based on blood vessel from the portal phase CT dataset

Science.gov (United States)

Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Utsunomiya, Tohru; Shimada, Mitsuo

2012-02-01

At liver surgery planning stage, the liver volumetry would be essential for surgeons. Main problem at liver extraction is the wide variability of livers in shapes and sizes. Since, hepatic blood vessels structure varies from a person to another and covers liver region, the present method uses that information for extraction of liver in two stages. The first stage is to extract abdominal blood vessels in the form of hepatic and nonhepatic blood vessels. At the second stage, extracted vessels are used to control extraction of liver region automatically. Contrast enhanced CT datasets at only the portal phase of 50 cases is used. Those data include 30 abnormal livers. A reference for all cases is done through a comparison of two experts labeling results and correction of their inter-reader variability. Results of the proposed method agree with the reference at an average rate of 97.8%. Through application of different metrics mentioned at MICCAI workshop for liver segmentation, it is found that: volume overlap error is 4.4%, volume difference is 0.3%, average symmetric distance is 0.7 mm, Root mean square symmetric distance is 0.8 mm, and maximum distance is 15.8 mm. These results represent the average of overall data and show an improved accuracy compared to current liver segmentation methods. It seems to be a promising method for extraction of liver volumetry of various shapes and sizes.

Comparative analysis of essential oil composition of Iranian and Indian Nigella sativa L. extracted using supercritical fluid extraction and solvent extraction

Directory of Open Access Journals (Sweden)

Ghahramanloo KH

2017-07-01

Full Text Available Kourosh Hasanzadeh Ghahramanloo,1 Behnam Kamalidehghan,2 Hamid Akbari Javar,3 Riyanto Teguh Widodo,1 Keivan Majidzadeh,4 Mohamed Ibrahim Noordin1 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Medical Genetics Department, National Institute of Genetic Engineering and Biotechnology (NIGEB, 3Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS, 4Breast Cancer Research Center (BCRC Academic Center for Education, Culture and Research, Tehran, Iran Abstract: The objective of this study was to compare the oil extraction yield and essential oil composition of Indian and Iranian Nigella sativa L. extracted by using Supercritical Fluid Extraction (SFE and solvent extraction methods. In this study, a gas chromatography equipped with a mass spectrophotometer detector was employed for qualitative analysis of the essential oil composition of Indian and Iranian N. sativa L. The results indicated that the main fatty acid composition identified in the essential oils extracted by using SFE and solvent extraction were linoleic acid (22.4%–61.85% and oleic acid (1.64%–18.97%. Thymoquinone (0.72%–21.03% was found to be the major volatile compound in the extracted N. sativa oil. It was observed that the oil extraction efficiency obtained from SFE was significantly (P<0.05 higher than that achieved by the solvent extraction technique. The present study showed that SFE can be used as a more efficient technique for extraction of N. Sativa L. essential oil, which is composed of higher linoleic acid and thymoquinone contents compared to the essential oil obtained by the solvent extraction technique. Keywords: Nigella sativa L., essential oil extraction, supercritical fluid extraction, solvent extraction, fatty acid composition, thymoquinone, linoleic acid

Research cooperation project on environmentally friendly technology for highly efficient mineral resources extraction and treatment. Detail design for pilot plant (Mechanical fabrication)

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-03-01

The paper prepared plans of the mechanical equipment in the detailed design of a pilot plant in the joint research project on the environmental protection technology for highly efficient mineral resource extraction and treatment. (NEDO)

Extraction of Tetravalent Uranium by Certain Acidic Organophosphorus Extractants from Phosphate Medium

International Nuclear Information System (INIS)

Daoud, J.A.; Zeid, M.M.; Aly, H.F.

1998-01-01

The extraction of U(IV) by octylphenyl acid phosphate (OPAP) or di-2-ethylhexyl phosphoric acid (HDEHP) in kerosene from phosphoric acid was carried out. The effect of extractant, phosphoric acid, uranium, Fe(II) and Fe(III) concentration on the extraction process was separately investigated. The effect of different reagents and temperature on the stripping of U(IV) was also investigated. The results obtained for the extraction of U(IV) by HDEHP showed that the extraction with the increase in HDEHP and Fe(III) concentration while it decreases with the increase in phosphoric acid, uranium and Fe(II) concentration. In case of extraction with OPAP, the extraction of U(IV) was found to decrease with the phosphoric acid, Fe(II) and initial uranium concentration while the increase in OPAP concentration slightly affected the extraction. The use of high phosphoric acid concentration as stripper at low temperature was found to give the best stripping results

Information extraction system

Science.gov (United States)

Lemmond, Tracy D; Hanley, William G; Guensche, Joseph Wendell; Perry, Nathan C; Nitao, John J; Kidwell, Paul Brandon; Boakye, Kofi Agyeman; Glaser, Ron E; Prenger, Ryan James

2014-05-13

An information extraction system and methods of operating the system are provided. In particular, an information extraction system for performing meta-extraction of named entities of people, organizations, and locations as well as relationships and events from text documents are described herein.

COMPARISONS OF SOXHLET EXTRACTION, PRESSURIZED LIQUID EXTRACTION, SUPERCRITICAL FLUID EXTRACTION, AND SUBCRITICAL WATER EXTRACTION FOR ENVIRONMENTAL SOLIDS: RECOVERY, SELECTIVITY, AND EFFECTS ON SAMPLE MATRIX. (R825394)

Science.gov (United States)

Extractions of a polycyclic aromatic hydrocarbon (PAH)-contaminated soil from a former manufactured gas plant site were performed with a Soxhlet apparatus (18 h), by pressurized liquid extraction (PLE) (50 min at 100°C), supercritical fluid extraction (SFE) (1 h at 150°...

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

RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.

Science.gov (United States)

Nolan, Emma; Vaillant, François; Branstetter, Daniel; Pal, Bhupinder; Giner, Göknur; Whitehead, Lachlan; Lok, Sheau W; Mann, Gregory B; Rohrbach, Kathy; Huang, Li-Ya; Soriano, Rosalia; Smyth, Gordon K; Dougall, William C; Visvader, Jane E; Lindeman, Geoffrey J

2016-08-01

Individuals who have mutations in the breast-cancer-susceptibility gene BRCA1 (hereafter referred to as BRCA1-mutation carriers) frequently undergo prophylactic mastectomy to minimize their risk of breast cancer. The identification of an effective prevention therapy therefore remains a 'holy grail' for the field. Precancerous BRCA1(mut/+) tissue harbors an aberrant population of luminal progenitor cells, and deregulated progesterone signaling has been implicated in BRCA1-associated oncogenesis. Coupled with the findings that tumor necrosis factor superfamily member 11 (TNFSF11; also known as RANKL) is a key paracrine effector of progesterone signaling and that RANKL and its receptor TNFRSF11A (also known as RANK) contribute to mammary tumorigenesis, we investigated a role for this pathway in the pre-neoplastic phase of BRCA1-mutation carriers. We identified two subsets of luminal progenitors (RANK(+) and RANK(-)) in histologically normal tissue of BRCA1-mutation carriers and showed that RANK(+) cells are highly proliferative, have grossly aberrant DNA repair and bear a molecular signature similar to that of basal-like breast cancer. These data suggest that RANK(+) and not RANK(-) progenitors are a key target population in these women. Inhibition of RANKL signaling by treatment with denosumab in three-dimensional breast organoids derived from pre-neoplastic BRCA1(mut/+) tissue attenuated progesterone-induced proliferation. Notably, proliferation was markedly reduced in breast biopsies from BRCA1-mutation carriers who were treated with denosumab. Furthermore, inhibition of RANKL in a Brca1-deficient mouse model substantially curtailed mammary tumorigenesis. Taken together, these findings identify a targetable pathway in a putative cell-of-origin population in BRCA1-mutation carriers and implicate RANKL blockade as a promising strategy in the prevention of breast cancer.

Extraction and determination of total flavonoids in jujube by alcohol extraction

Science.gov (United States)

Ji, Y. B.; Ru, X.; Yu, M.; Wang, S. W.; Lu, L.; Qiao, A. N.; Guo, A. Z.

2017-12-01

Jujube is a ripe fruit of Rhamnaceae. Its main active component is flavonoids, so the extraction and determination of total flavonoids in jujube will help to develop and utilize the medicinal value of jujube. In this study, the total flavonoids were extracted from jujube by alcohol extraction method. Through single factor investigation and orthogonal test, it was found that the total flavonoids content in jujube was the highest under the condition of 70°C, material ratio of 1:40, and extraction of 30 min by 70% ethanol. The content of total flavonoids in the extract of jujube was 1.57% at the wavelength of 510 nm by UV and rutin as the standard. The method was evaluated by methodological study, and it was determined that this method could be used as the detection of total flavonoids in jujube extraction.

Numerical modeling of the Linac4 negative ion source extraction region by 3D PIC-MCC code ONIX

CERN Document Server

Mochalskyy, S; Minea, T; Lifschitz, AF; Schmitzer, C; Midttun, O; Steyaert, D

2013-01-01

At CERN, a high performance negative ion (NI) source is required for the 160 MeV H- linear accelerator Linac4. The source is planned to produce 80 mA of H- with an emittance of 0.25 mm mradN-RMS which is technically and scientifically very challenging. The optimization of the NI source requires a deep understanding of the underling physics concerning the production and extraction of the negative ions. The extraction mechanism from the negative ion source is complex involving a magnetic filter in order to cool down electrons’ temperature. The ONIX (Orsay Negative Ion eXtraction) code is used to address this problem. The ONIX is a selfconsistent 3D electrostatic code using Particles-in-Cell Monte Carlo Collisions (PIC-MCC) approach. It was written to handle the complex boundary conditions between plasma, source walls, and beam formation at the extraction hole. Both, the positive extraction potential (25kV) and the magnetic field map are taken from the experimental set-up, in construction at CERN. This contrib...

A comparative study in disaster planning in selected countries

Directory of Open Access Journals (Sweden)

Mahmode M

2007-11-01

Full Text Available Background: Assessment of different strategic in disaster planning in selected countries. According to the international report indicating that IRAN is among the seven countries most susceptible to disaster, experiencing 31 known disasters out of 40 in the world, occurrence of 1536 moderate to severe earthquake, during 1370-80 and 712 other disasters at the same period it seems necessary to design a disaster plan."nMethods: This research is a comparative-descriptive and case based study in which the researcher used random sampling process in selecting the statistical society from both developed and developing countries. In this goal oriented research the necessary information are extracted from valid global reports, articles and many questionnaires which were subjected to scientific analysis."nResults: Studying different countries (which includes: Canada, Japan, India, USA, Turkey, Pakistan and Iran shows that there is a direct relationship between the level of countries development and their success in disaster planning and management (including preventive measures and confrontation. In most of the studied countries, decentralized planning caused many professional planners participate in different levels of disaster management which ultimately led to development of efficient and realistic plans which in turn decreased the catastrophic effects of disasters dramatically. The results of the aforementioned countries showed that a balanced approach to disaster plan with investment in prophylactic area is very important."nConclusion: As our country uses a centralized strategy for disaster management which has proven its ineffectiveness, the researcher suggests that we should change our approach in disaster management and let our planners participate from all levels include: provincial, rural and etc. This will led to a reality based planning and using all potential capacities in disaster management. According to this study it will be possible to use

Idaho Chemical Processing Plant and Plutonium-Uranium Extraction Plant phaseout/deactivation study

International Nuclear Information System (INIS)

Patterson, M.W.; Thompson, R.J.

1994-01-01

The decision to cease all US Department of Energy (DOE) reprocessing of nuclear fuels was made on April 28, 1992. This study provides insight into and a comparison of the management, technical, compliance, and safety strategies for deactivating the Idaho Chemical Processing Plant (ICPP) at Westinghouse Idaho Nuclear Company (WINCO) and the Westinghouse Hanford Company (WHC) Plutonium-Uranium Extraction (PUREX) Plant. The purpose of this study is to ensure that lessons-learned and future plans are coordinated between the two facilities

Membrane extraction instead of solvent extraction - what does it give

International Nuclear Information System (INIS)

Macasek, F.

1989-01-01

Membrane extraction, i.e. separation in double-emulsion systems, is analyzed theoretically as a three-phase distribution process. Its efficiency is evaluated from the point of view of chemical equilibria and diffusion transport kinetics. The main advantages of membrane extraction as compared with solvent extraction are in higher yields (for preconcentration) and higher capacity for recovery of solutes. A pertraction factor and multiplication factor were defined. They are convenient parameters for numerical characterization of solute distribution, system capacity, process economics, and separation kinetics (both at a linear and non-linear extraction isotherm). 17 refs.; 4 figs

Extraction of microamounts of calcium and strontium into nitrobenzene using synergistic mixture of hydrogen dicarbollylcobaltate and 2,3-naphtho-15-crown-5

Czech Academy of Sciences Publication Activity Database

Makrlík, E.; Vaňura, P.; Selucký, P.; Kašička, Václav

2010-01-01

Roč. 283, č. 1 (2010), s. 95-100 ISSN 0236-5731 Institutional research plan: CEZ:AV0Z40550506 Keywords : calcium * stroncium * extraction Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.777, year: 2010

Extraction of bioactive carbohydrates from artichoke (Cynara scolymus L.) external bracts using microwave assisted extraction and pressurized liquid extraction.

Science.gov (United States)

Ruiz-Aceituno, Laura; García-Sarrió, M Jesús; Alonso-Rodriguez, Belén; Ramos, Lourdes; Sanz, M Luz

2016-04-01

Microwave assisted extraction (MAE) and pressurized liquid extraction (PLE) methods using water as solvent have been optimized by means of a Box-Behnken and 3(2) composite experimental designs, respectively, for the effective extraction of bioactive carbohydrates (inositols and inulin) from artichoke (Cynara scolymus L.) external bracts. MAE at 60 °C for 3 min of 0.3 g of sample allowed the extraction of slightly higher concentrations of inositol than PLE at 75 °C for 26.7 min (11.6 mg/g dry sample vs. 7.6 mg/g dry sample). On the contrary, under these conditions, higher concentrations of inulin were extracted with the latter technique (185.4 mg/g vs. 96.4 mg/g dry sample), considering two successive extraction cycles for both techniques. Both methodologies can be considered appropriate for the simultaneous extraction of these bioactive carbohydrates from this particular industrial by-product. To the best of our knowledge this is the first time that these techniques are applied for this purpose. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of DVH data from multiple radiotherapy treatment planning systems

International Nuclear Information System (INIS)

Ebert, M A; Kearvell, R; Hooton, B; Spry, N A; Bydder, S A; Joseph, D J; Haworth, A; Hug, B

2010-01-01

This study examined the variation of dose-volume histogram (DVH) data sourced from multiple radiotherapy treatment planning systems (TPSs). Treatment plan exports were obtained from 33 Australian and New Zealand centres during a dosimetry study. Plan information, including DVH data, was exported from the TPS at each centre and reviewed in a digital review system (SWAN). The review system was then used to produce an independent calculation of DVH information for each delineated structure. The relationships between DVHs extracted from each TPS and independently calculated were examined, particularly in terms of the influence of CT scan slice and pixel widths, the resolution of dose calculation grids and the TPS manufacturer. Calculation of total volume and DVH data was consistent between SWAN and each TPS, with the small discrepancies found tending to increase with decreasing structure size. This was significantly influenced by the TPS model used to derive the data. For target structures covered with relatively uniform dose distributions, there was a significant difference between the minimum dose in each TPS-exported DVH and that calculated independently. (note)

Comparative exergy analyses of Jatropha curcas oil extraction methods: Solvent and mechanical extraction processes

International Nuclear Information System (INIS)

Ofori-Boateng, Cynthia; Keat Teong, Lee; JitKang, Lim

2012-01-01

Highlights: ► Exergy analysis detects locations of resource degradation within a process. ► Solvent extraction is six times exergetically destructive than mechanical extraction. ► Mechanical extraction of jatropha oil is 95.93% exergetically efficient. ► Solvent extraction of jatropha oil is 79.35% exergetically efficient. ► Exergy analysis of oil extraction processes allow room for improvements. - Abstract: Vegetable oil extraction processes are found to be energy intensive. Thermodynamically, any energy intensive process is considered to degrade the most useful part of energy that is available to produce work. This study uses literature values to compare the efficiencies and degradation of the useful energy within Jatropha curcas oil during oil extraction taking into account solvent and mechanical extraction methods. According to this study, J. curcas seeds on processing into J. curcas oil is upgraded with mechanical extraction but degraded with solvent extraction processes. For mechanical extraction, the total internal exergy destroyed is 3006 MJ which is about six times less than that for solvent extraction (18,072 MJ) for 1 ton J. curcas oil produced. The pretreatment processes of the J. curcas seeds recorded a total internal exergy destructions of 5768 MJ accounting for 24% of the total internal exergy destroyed for solvent extraction processes and 66% for mechanical extraction. The exergetic efficiencies recorded are 79.35% and 95.93% for solvent and mechanical extraction processes of J. curcas oil respectively. Hence, mechanical oil extraction processes are exergetically efficient than solvent extraction processes. Possible improvement methods are also elaborated in this study.