Sample records for sponsored project de-fgf22-95pc95229
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Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers FGF22 and FGF7.
Terauchi, Akiko; Timmons, Kendall M; Kikuma, Koto; Pechmann, Yvonne; Kneussel, Matthias; Umemori, Hisashi
2015-01-15
Specific formation of excitatory and inhibitory synapses is crucial for proper functioning of the brain. Fibroblast growth factor 22 (FGF22) and FGF7 are postsynaptic-cell-derived presynaptic organizers necessary for excitatory and inhibitory presynaptic differentiation, respectively, in the hippocampus. For the establishment of specific synaptic networks, these FGFs must localize to appropriate synaptic locations - FGF22 to excitatory and FGF7 to inhibitory postsynaptic sites. Here, we show that distinct motor and adaptor proteins contribute to intracellular microtubule transport of FGF22 and FGF7. Excitatory synaptic targeting of FGF22 requires the motor proteins KIF3A and KIF17 and the adaptor protein SAP102 (also known as DLG3). By contrast, inhibitory synaptic targeting of FGF7 requires the motor KIF5 and the adaptor gephyrin. Time-lapse imaging shows that FGF22 moves with SAP102, whereas FGF7 moves with gephyrin. These results reveal the basis of selective targeting of the excitatory and inhibitory presynaptic organizers that supports their different synaptogenic functions. Finally, we found that knockdown of SAP102 or PSD95 (also known as DLG4), which impairs the differentiation of excitatory synapses, alters FGF7 localization, suggesting that signals from excitatory synapses might regulate inhibitory synapse formation by controlling the distribution of the inhibitory presynaptic organizer. © 2015. Published by The Company of Biologists Ltd.
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Sulfur Speciation in Graves Nunataks GRA 95229 and Murchison: Similarities and Differences
Bose, M.; Root, R.
2017-07-01
We identified cysteine, a sulfur bearing amino acid in situ of Murchison and a large (120 × 150 µm2) phosphorus-bearing domain in GRA 95229 using XRF and u-XANES. Elemental sulfur, abundant in GRA 95229, is always co-located with sulfate.
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Deletion of fibroblast growth factor 22 (FGF22) causes a depression-like phenotype in adult mice.
Williams, Aislinn J; Yee, Patricia; Smith, Mitchell C; Murphy, Geoffrey G; Umemori, Hisashi
2016-07-01
Specific growth factors induce formation and differentiation of excitatory and inhibitory synapses, and are essential for brain development and function. Fibroblast growth factor 22 (FGF22) is important for specifying excitatory synapses during development, including in the hippocampus. Mice with a genetic deletion of FGF22 (FGF22KO) during development subsequently have fewer hippocampal excitatory synapses in adulthood. As a result, FGF22KO mice are resistant to epileptic seizure induction. In addition to playing a key role in learning, the hippocampus is known to mediate mood and anxiety. Here, we explored whether loss of FGF22 alters affective, anxiety or social cognitive behaviors in mice. We found that relative to control mice, FGF22KO mice display longer duration of floating and decreased latency to float in the forced swim test, increased immobility in the tail suspension test, and decreased preference for sucrose in the sucrose preference test, which are all suggestive of a depressive-like phenotype. No differences were observed between control and FGF22KO mice in other behavioral assays, including motor, anxiety, or social cognitive tests. These results suggest a novel role for FGF22 specifically in affective behaviors. Copyright © 2016 Elsevier B.V. All rights reserved.
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Ratzka, Andreas; Baron, Olga; Grothe, Claudia
2011-01-01
Secreted proteins of the fibroblast growth factor (FGF) family play important roles during development of various organ systems. A detailed knowledge of their temporal and spatial expression profiles, especially of closely related FGF family members, are essential to further identification of specific functions in distinct tissues. In the central nervous system dopaminergic neurons of the substantia nigra and their axonal projections into the striatum progressively degenerate in Parkinson's disease. In contrast, FGF-2 deficient mice display increased numbers of dopaminergic neurons. In this study, we determined the expression profiles of all 22 FGF-ligands and 10 FGF-receptor isoforms, in order to clarify, if FGF-2 deficiency leads to compensatory up-regulation of other FGFs in the nigrostriatal system. Three tissues, ventral mesencephalon (VM), striatum (STR) and as reference tissue spinal cord (SC) of wild-type and FGF-2 deficient mice at four developmental stages E14.5, P0, P28, and adult were comparatively analyzed by quantitative RT-PCR. As no differences between the genotypes were observed, a compensatory up-regulation can be excluded. Moreover, this analysis revealed that the majority of FGF-ligands (18/22) and FGF-receptors (9/10) are expressed during normal development of the nigrostriatal system and identified dynamic changes for some family members. By comparing relative expression level changes to SC reference tissue, general alterations in all 3 tissues, such as increased expression of FGF-1, -2, -22, FgfR-2c, -3c and decreased expression of FGF-13 during postnatal development were identified. Further, specific changes affecting only one tissue, such as increased FGF-16 (STR) or decreased FGF-17 (VM) expression, or two tissues, such as decreased expression of FGF-8 (VM, STR) and FGF-15 (SC, VM) were found. Moreover, 3 developmentally down-regulated FGFs (FGF-8b, FGF-15, FGF-17a) were functionally characterized by plasmid-based over-expression in
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22 CFR 62.3 - Sponsor eligibility.
2010-04-01
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Sponsor eligibility. 62.3 Section 62.3 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM General Provisions... visitor program are: (1) United States local, state and federal government agencies; (2) International...
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21 CFR 316.22 - Permanent-resident agent for foreign sponsor.
2010-04-01
... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.22 Permanent-resident agent for foreign sponsor. Every foreign sponsor that seeks orphan-drug designation shall name a permanent resident of the United States as the sponsor's agent upon whom service of all processes, notices...
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22 CFR 42.31 - Family-sponsored immigrants.
2010-04-01
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Family-sponsored immigrants. 42.31 Section 42.31 Foreign Relations DEPARTMENT OF STATE VISAS VISAS: DOCUMENTATION OF IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Immigrants Subject to Numerical Limitations § 42.31 Family...
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International Nuclear Information System (INIS)
Tuomela, Johanna; Solin, Olof; Minn, Heikki; Härkönen, Pirkko L; Grönroos, Tove J; Valta, Maija P; Sandholm, Jouko; Schrey, Aleksi; Seppänen, Jani; Marjamäki, Päivi; Forsback, Sarita; Kinnunen, Ilpo
2010-01-01
Prostate tumours are commonly poorly oxygenated which is associated with tumour progression and development of resistance to chemotherapeutic drugs and radiotherapy. Fibroblast growth factor 8b (FGF8b) is a mitogenic and angiogenic factor, which is expressed at an increased level in human prostate tumours and is associated with a poor prognosis. We studied the effect of FGF8b on tumour oxygenation and growth parameters in xenografts in comparison with vascular endothelial growth factor (VEGF)-expressing xenografts, representing another fast growing and angiogenic tumour model. Subcutaneous tumours of PC-3 cells transfected with FGF8b, VEGF or empty (mock) vectors were produced and studied for vascularity, cell proliferation, glucose metabolism and oxygenation. Tumours were evaluated by immunohistochemistry (IHC), flow cytometry, use of radiolabelled markers of energy metabolism ([ 18 F]FDG) and hypoxia ([ 18 F]EF5), and intratumoral polarographic measurements of pO 2 . Both FGF8b and VEGF tumours grew rapidly in nude mice and showed highly vascularised morphology. Perfusion studies, pO 2 measurements, [ 18 F]EF5 and [ 18 F]FDG uptake as well as IHC staining for glucose transport protein (GLUT1) and hypoxia inducible factor (HIF) 1 showed that VEGF xenografts were well-perfused and oxygenised, as expected, whereas FGF8b tumours were as hypoxic as mock tumours. These results suggest that FGF8b-induced tumour capillaries are defective. Nevertheless, the growth rate of hypoxic FGF8b tumours was highly increased, as that of well-oxygenised VEGF tumours, when compared with hypoxic mock tumour controls. FGF8b is able to induce fast growth in strongly hypoxic tumour microenvironment whereas VEGF-stimulated growth advantage is associated with improved perfusion and oxygenation of prostate tumour xenografts
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National Research Council Canada - National Science Library
Patton, Nanette; Shechet, Allan
2007-01-01
.... This article discusses conventional roles and responsibilities of the project sponsor and then discusses strategies a project manager can employ to define boundaries to reduce role confusion and promote partnership to facilitate project success.
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Osteomalacia por tumor secretor de FGF-23 Ostemalacia due to a tumor secreting FGF-23
Directory of Open Access Journals (Sweden)
Ariel Sánchez
2013-02-01
Full Text Available Se presenta un caso de osteomalacia oncogénica en un varón de 50 años, con fuertes dolores óseos y gran debilidad muscular durante 4 años. Tenía varias deformidades vertebrales dorsales en cuña, fracturas en ambas ramas iliopubianas y en una rama isquiopubiana, y una zona de Looser en la meseta tibial derecha. Se localizó un tumor de 2 cm de diámetro en el hueco poplíteo derecho mediante centellograma con octreótido marcado con tecnecio. El tumor fue extirpado quirúrgicamente. La microscopía mostró un tumor mesenquimático fosfatúrico, de tejido conectivo mixto. La inmunotinción demostró FGF-23. Hubo rápida mejoría, con consolidación de las fracturas pelvianas y de la pseudofractura tibial y normalización de las alteraciones bioquímicas.A case of oncogenic osteomalacia in a 50-year-old male is here presented. He suffered severe bone pain and marked muscular weakness of 4 years' duration. There were several vertebral deformities in the thoracic spine, bilateral fractures of the iliopubic branches, another fracture in the left ischiopubic branch, and a Looser's zone in the right proximal tibia. An octreotide-Tc scan allowed to identify a small tumor in the posterior aspect of the right knee. It was surgically removed. Microscopically, it was a phosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT. Expression of FGF-23 was documented by immune-peroxidase staining. There was rapid improvement, with consolidation of the pelvic fractures and the tibial pseudo-fracture. The laboratory values returned to normal.
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Pirou, Caroline; Montazer-Torbati, Fatemeh; Jah, Nadège; Delmas, Elisabeth; Lasbleiz, Christelle; Mignotte, Bernard; Renaud, Flore
2017-01-01
Neuroblastoma, a sympathetic nervous system tumor, accounts for 15% of cancer deaths in children. In contrast to most human tumors, p53 is rarely mutated in human primary neuroblastoma, suggesting impaired p53 activation in neuroblastoma. Various studies have shown correlations between fgf1 expression levels and both prognosis severity and tumor chemoresistance. As we previously showed that fibroblast growth factor 1 (FGF1) inhibited p53-dependent apoptosis in neuron-like PC12 cells, we initiated the study of the interaction between the FGF1 and p53 pathways in neuroblastoma. We focused on the activity of either extracellular FGF1 by adding recombinant rFGF1 in media, or of intracellular FGF1 by overexpression in human SH-SY5Y and mouse N2a neuroblastoma cell lines. In both cell lines, the genotoxic drug etoposide induced a classical mitochondrial p53-dependent apoptosis. FGF1 was able to inhibit p53-dependent apoptosis upstream of mitochondrial events in SH-SY5Y cells by both extracellular and intracellular pathways. Both rFGF1 addition and etoposide treatment increased fgf1 expression in SH-SY5Y cells. Conversely, rFGF1 or overexpressed FGF1 had no effect on p53-dependent apoptosis and fgf1 expression in neuroblastoma N2a cells. Using different FGF1 mutants (that is, FGF1K132E, FGF1S130A and FGF1S130D), we further showed that the C-terminal domain and phosphorylation of FGF1 regulate its intracrine anti-apoptotic activity in neuroblastoma SH-SY5Y cells. This study provides the first evidence for a role of an intracrine growth factor pathway on p53-dependent apoptosis in neuroblastoma, and could lead to the identification of key regulators involved in neuroblastoma tumor progression and chemoresistance. PMID:29048426
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Osteomalacia por tumor secretor de FGF-23
Directory of Open Access Journals (Sweden)
Ariel Sánchez
2013-02-01
Full Text Available Se presenta un caso de osteomalacia oncogénica en un varón de 50 años, con fuertes dolores óseos y gran debilidad muscular durante 4 años. Tenía varias deformidades vertebrales dorsales en cuña, fracturas en ambas ramas iliopubianas y en una rama isquiopubiana, y una zona de Looser en la meseta tibial derecha. Se localizó un tumor de 2 cm de diámetro en el hueco poplíteo derecho mediante centellograma con octreótido marcado con tecnecio. El tumor fue extirpado quirúrgicamente. La microscopía mostró un tumor mesenquimático fosfatúrico, de tejido conectivo mixto. La inmunotinción demostró FGF-23. Hubo rápida mejoría, con consolidación de las fracturas pelvianas y de la pseudofractura tibial y normalización de las alteraciones bioquímicas.
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Directory of Open Access Journals (Sweden)
Revista Chasqui
2015-01-01
Full Text Available La navegación en Internet y la consiguiente conexión a una red expone a una computadora a un sinfín de riesgos y peligros. Una PC que no sea utilizada para navegar en Internet o que no esté conectada a una red puede,incluso, ser también afectada por virus, por la utilización de disquetes contaminados que la contaminen con un virus. Para enfrentar esos problemas, la industria informática ha previsto una serie de protecciones y recaudos, de cuyo uso y utilización deben estar plenamente informados los usuarios de una PC.
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2010-04-01
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Procedures. 95.3 Section 95.3 Foreign Relations... torture are made or the issue is otherwise brought to the Department's attention, appropriate policy and... Secretary as to whether or not to sign the surrender warrant. (b) Based on the resulting analysis of...
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Allelic heterogeneity of FGF5 mutations causes the long-hair phenotype in dogs.
Dierks, C; Mömke, S; Philipp, U; Distl, O
2013-08-01
Hitherto, the only known mutant gene leading to the long-hair phenotype in mammals is the fibroblast growth factor 5 (FGF5). In many dog breeds, the previously discovered FGF5:p.Cys95Phe mutation appeared completely concordant with the long-hair phenotype, but for some breeds, the long-hair phenotype could not be resolved. First, we studied the role of the FGF5:p.Cys95Phe and FGF5:g.145_150dupACCAGC mutations in 268 dogs descending from 27 breeds and seven wolves. As these mutations did not explain all the long-hair phenotypes, all exons and their neighbouring regions of FGF5 were re-sequenced. We detected three novel mutations in the coding sequence and one novel non-coding splice-site mutation in FGF5 associated with the long-hair phenotype. The FGF5:p.Ala193Val polymorphism was perfectly consistent with long hair in Akitas and probably in Siberian huskies, too. Dogs of the long-hair breed Samoyed were either homozygous or compound heterozygous for the FGF5:p.Ala193Val or the FGF5:p.Cys95Phe polymorphisms respectively. The two newly detected polymorphisms FGF5:c.559_560dupGG and FGF5:g.8193T>A and the known mutation FGF5:p.Cys95Phe explained the long-hair phenotype of all Afghan hounds analysed. An FGF5:c.556_571del16 mutation was found in one longhaired Eurasier. All long-hair-associated mutations follow a recessive mode of inheritance, and allelic heterogeneity was a common finding in breeds other than Akita. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.
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De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy
Guella, Ilaria; Huh, Linda; McKenzie, Marna B.; Toyota, Eric B.; Bebin, E. Martina; Thompson, Michelle L.; Cooper, Gregory M.; Evans, Daniel M.; Buerki, Sarah E.; Adam, Shelin; Van Allen, Margot I.; Nelson, Tanya N.; Connolly, Mary B.; Farrer, Matthew J.
2016-01-01
Objective: We describe 2 additional patients with early-onset epilepsy with a de novo FGF12 mutation. Methods: Whole-exome sequencing was performed in 2 unrelated patients with early-onset epilepsy and their unaffected parents. Genetic variants were assessed by comparative trio analysis. Clinical evolution, EEG, and neuroimaging are described. The phenotype and response to treatment was reviewed and compared to affected siblings in the original report. Results: We identified the same FGF12 de novo mutation reported previously (c.G155A, p.R52H) in 2 additional patients with early-onset epilepsy. Similar to the original brothers described, both presented with tonic seizures in the first month of life. In the first patient, seizures responded to sodium channel blockers and her development was normal at 11 months. Patient 2 is a 15-year-old girl with treatment-resistant focal epilepsy, moderate intellectual disability, and autism. Carbamazepine (sodium channel blocker) was tried later in her course but not continued due to an allergic reaction. Conclusions: The identification of a recurrent de novo mutation in 2 additional unrelated probands with early-onset epilepsy supports the role of FGF12 p.R52H in disease pathogenesis. Affected carriers presented with similar early clinical phenotypes; however, this report expands the phenotype associated with this mutation which contrasts with the progressive course and early mortality of the siblings in the original report. PMID:27872899
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Dimerization effect of sucrose octasulfate on rat FGF1
International Nuclear Information System (INIS)
Kulahin, N.; Kiselyov, V.; Kochoyan, A.; Kristensen, O.; Kastrup, Jette S.; Berezin, V.; Bock, E.; Gajhede, M.
2008-01-01
The work describes the sucrose octasulfate-mediated dimerization of rat FGF1 by gel-filtration experiments and crystal structure determination. Fibroblast growth factors (FGFs) constitute a family of at least 23 structurally related heparin-binding proteins that are involved in regulation of cell growth, survival, differentiation and migration. Sucrose octasulfate (SOS), a chemical analogue of heparin, has been demonstrated to activate FGF signalling pathways. The structure of rat FGF1 crystallized in the presence of SOS has been determined at 2.2 Å resolution. SOS-mediated dimerization of FGF1 was observed, which was further supported by gel-filtration experiments. The major contributors to the sulfate-binding sites in rat FGF1 are Lys113, Lys118, Arg122 and Lys128. An arginine at position 116 is a consensus residue in mammalian FGF molecules; however, it is a serine in rat FGF1. This difference may be important for SOS-mediated FGF1 dimerization in rat
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Project-based fieldwork: perspectives of graduate entry students and project sponsors.
Fortune, Tracy; McKinstry, Carol
2012-08-01
This article builds on an earlier viewpoint regarding the need for project-focussed fieldwork. It presents the findings of an evaluative study into the value of project placements undertaken by final year graduate entry master's students as part of a capstone subject. The authors argue that provision of project placements enable impending graduates to develop and implement macro level strategies to develop prevention, resource and service development skills often required of contemporary occupational therapy practitioners. A qualitative approach is adopted. Student cohorts from 2005 and 2006 completed open-ended, written questionnaires, and agency project sponsors were interviewed to obtain their perspectives of the project placement experience. Despite some concern that project placements might be undertaken at the expense of 'clinical' placements these findings reveal that projects managed by students were perceived by services to add great value enabling them to advance important priorities. Students and sponsors highlighted a range of positive learning outcomes, including the ability to work collaboratively with supervisors and develop advanced communication skills and political acumen. The success of such placements depends on supportive supervision from academic staff. CONCLUSIONS AND SIGNIFICANCE OF THE STUDY: The findings promote project placements as a highly authentic aspect of work integrated learning enabling learners to draw together a range of attributes that support the ability to manage complex issues that have occupational relevance at a macro level. In addition, such experiences help learners to develop agency and political acumen both increasingly important capabilities for the contemporary workplace. © 2012 The Authors Australian Occupational Therapy Journal © 2012 Occupational Therapy Australia.
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[Analysis of projects of schistosomiasis sponsored by National Science Foundation of China].
Wen-di, Zhou; Liang, Shi; Xue-Dan, Ke; Jie, Wang
2017-07-27
To summarize the present development by analysis of projects in schistosomiasis funded by National Science Foundation of China (NSFC). Based on the ISIS database of NFSC, the projects in the studies of schistosomiasis from 2005 to 2016 were analyzed. The distributions of sponsored numbers, amounts, types, agencies, disciplines and changes in research topics by means of network profiles were described. During the study period, 198 projects were funded by NSFC totally with 76.05 million yuan in which the general and youth projects were main types. The main sponsored agencies were research institutes and medical colleges. The top three fields sponsored were medical pathogenic microbes and infection, veterinary and medical immunology. The funding on schistosomiasis researches has a downward trend, but studies are continuing in depth. In this situation, innovative and interdisciplinary researches need to be encouraged to promote the development of schistosomiasis.
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Directory of Open Access Journals (Sweden)
Huang Yadong
2010-02-01
Full Text Available Abstract Background Fibroblast growth factor 21 (FGF21 is a promising drug candidate to combat metabolic diseases. However, high-level expression and purification of recombinant FGF21 (rFGF21 in Escherichia coli (E. coli is difficult because rFGF21 forms inclusion bodies in the bacteria making it difficult to purify and obtain high concentrations of bioactive rFGF21. To overcome this problem, we fused the FGF21 with SUMO (Small ubiquitin-related modifier by polymerase chain reaction (PCR, and expressed the fused gene in E. coli BL21(DE3. Results By inducing with IPTG, SUMO-FGF21 was expressed at a high level. Its concentration reached 30% of total protein, and exceeded 95% of all soluble proteins. The fused protein was purified by DEAE sepharose FF and Ni-NTA affinity chromatography. Once cleaved by the SUMO protease, the purity of rFGF21 by high performance liquid chromatography (HPLC was shown to be higher than 96% with low endotoxin level (in vivo animal experiments showed that rFGF21 produced by using this method, could decrease the concentration of plasma glucose in diabetic rats by streptozotocin (STZ injection. Conclusions This study demonstrated that SUMO, when fused with FGF21, was able to promote its soluble expression of the latter in E. coli, making it more convenient to purify rFGF21 than previously. This may be a better method to produce rFGF21 for pharmaceutical research and development.
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Meng, Xiangqi; Vander Ark, Alexandra; Daft, Paul; Woodford, Erica; Wang, Jie; Madaj, Zachary; Li, Xiaohong
2018-04-01
TGF-β plays a central role in prostate cancer (PCa) bone metastasis, and it is crucial to understand the bone cell-specific role of TGF-β signaling in this process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2 gene specifically in osteoblasts (Tgfbr2 Col1CreERT KO) or in osteoclasts (Tgfbr2 LysMCre KO). We found that PCa-induced bone lesion development was promoted in the Tgfbr2 Col1CreERT KO mice, but was inhibited in the Tgfbr2 LysMCre KO mice, relative to their respective control Tgfbr2 FloxE2 littermates. Since metastatic PCa cells attach to osteoblasts when colonized in the bone microenvironment, we focused on the mechanistic studies using the Tgfbr2 Col1CreERT KO mouse model. We found that bFGF was upregulated in osteoblasts from PC3-injected tibiae of Tgfbr2 Col1CreERT KO mice and correlated with increased tumor cell proliferation, angiogenesis, amounts of cancer-associated fibroblasts and osteoclasts. In vitro studies showed that osteoblastogenesis was inhibited, osteoclastogenesis was stimulated, but PC3 viability was not affected, by bFGF treatments. Lastly, the increased PC3-induced bone lesions in Tgfbr2 Col1CreERT KO mice were significantly attenuated by blocking bFGF using neutralizing antibody, suggesting bFGF is a promising target inhibiting bone metastasis. Copyright © 2018 Elsevier B.V. All rights reserved.
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Directory of Open Access Journals (Sweden)
Fernanda de Almeida Fin de Lima
2010-01-01
Full Text Available O objetivo deste trabalho foi estudar a impregnação do corante fotocromático Reversacol Graphit® em filmes do compósito de policarbonato (PC e sílica-gel (Si, com a finalidade de obter aplicações em lentes fotocrômicas. Filmes de PC puros também foramimpregnados nas mesmas condições, para verificar o efeito da adição de sílica-gel. Os filmes do compósito foram produzidos em proporções de Si:PC de 1:40 e 1:80 (m m-1, pelo método casting. Para a impregnação do corante Reversacol Graphit nos filmes obtidos foiutilizado o processo supercrítico, pela sua eficiência e benefícios. A impregnação foi feita nos tempos de 15, 30, 45, 60, 90, 120, 150 e 180 min. A temperatura e a pressão adotadas foram de 60ºC e 120 bar. A quantidade de pigmento impregnado nos filmes de Si:PC – 1:40e 1:80 (m m-1 foi de 29 e 23% de massa de corante por massa de compósito, respectivamente, e para o filme de PC puro foi de apenas 2,2% massa de corante por massa de compósito. Pelas análises térmicas, verificou-se que os filmes do compósito apresentarammaior estabilidade térmica. Pela técnica de microscopia eletrônica, observou-se que os filmes de PC puro e dos compósitos Si:PC – 1:40 e 1:80 (m m-1 apresentaram uma superfície lisa e homogênea.The aim of this work was to study the impregnation of the photochromic dye Reversacol Graphit® in composite films ofpolycarbonate (PC and silica gel, with the purpose of finding applications in photochromic lenses. Pure PC films were also impregnated in the same conditions, to verify the effect of the silica-gel addition. The composites films were produced in Si:PC ratios of 1:40 and 1:80 (m m-1, using the casting method . For the impregnation of the dye Reversacol Graphit in the obtained films, the supercritical process was used due to its efficiency and benefits. The impregnation was made in the times of 15, 30, 45, 60, 90, 120, 150 and 180 minutes. The adopted temperature and pressure
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Comportamiento térmico y mecánico de mezclas de PC/PET con altos contenidos de PC
Cornement, Frédéric
2006-01-01
Las mezclas de polímeros tienen un interés científico e industrial considerable. Mezclar es una manera muy eficaz para adaptar las propiedades de los polímeros a diferentes circunstancias. El Poli(Etilén Tereftalato) (PET) y el PoliCarbonato (PC) son dos termoplásticos muy importantes. PC tiene una elevada resistencia al impacto y su resistencia a los solventes se mejora cuando se mezcla con PET. Los dos son poliésteres y pueden reaccionar mediante transesterificación en el fundido p...
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Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome
Directory of Open Access Journals (Sweden)
Griffith Andrew J
2011-02-01
Full Text Available Abstract Background Recessive mutations of fibroblast growth factor 3 (FGF3 can cause LAMM syndrome (OMIM 610706, characterized by fully penetrant complete labyrinthine aplasia, microtia and microdontia. Methods We performed a prospective molecular genetic and clinical study of families segregating hearing loss linked to FGF3 mutations. Ten affected individuals from three large Pakistani families segregating FGF3 mutations were imaged with CT, MRI, or both to detect inner ear abnormalities. We also modeled the three dimensional structure of FGF3 to better understand the structural consequences of the three missense mutations. Results Two families segregated reported mutations (p.R104X and p.R95W and one family segregated a novel mutation (p.R132GfsX26 of FGF3. All individuals homozygous for p.R104X or p.R132GfsX26 had fully penetrant features of LAMM syndrome. However, recessive p.R95W mutations were associated with nearly normal looking auricles and variable inner ear structural phenotypes, similar to that reported for a Somali family also segregating p.R95W. This suggests that the mild phenotype is not entirely due to genetic background. Molecular modeling result suggests a less drastic effect of p.R95W on FGF3 function compared with known missense mutations detected in fully penetrant LAMM syndrome. Since we detected significant intrafamilial variability of the inner ear structural phenotype in the family segregating p.R95W, we also sequenced FGF10 as a likely candidate for a modifier. However, we did not find any sequence variation, pointing out that a larger sample size will be needed to map and identify a modifier. We also observed a mild to moderate bilateral conductive hearing loss in three carriers of p.R95W, suggesting either a semi-dominant effect of this mutant allele of FGF3, otitis media, or a consequence of genetic background in these three family members. Conclusions We noted a less prominent dental and external ear phenotype in
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22 CFR 9.5 - Original classification authority.
2010-04-01
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Original classification authority. 9.5 Section 9.5 Foreign Relations DEPARTMENT OF STATE GENERAL SECURITY INFORMATION REGULATIONS § 9.5 Original classification authority. (a) Authority for original classification of information as Top Secret may be exercised...
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The USL NASA PC R and D project: General specifications of objectives
Dominick, Wayne D. (Editor)
1984-01-01
Given here are the general specifications of the objectives of the University of Southwestern Louisiana Data Base Management System (USL/DBMS) NASA PC R and D Project, a project initiated to address future R and D issues related to PC-based processing environments acquired pursuant to the NASA contract work; namely, the IBM PC/XT systems.
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Jian-Ming, Wang; Yan-Kai, Xia; Hui-Juan, Zhu; Feng, Chen; Hong-Bing, Shen
2016-05-10
To analyze the projects on the infectious disease epidemiology sponsored by the National Natural Science Foundation of China (NSFC), explore the hotspot and development trend, and offer a reference for researchers in this field. Based on the NSFC database, the projects on the infectious disease epidemiology (H2609) sponsored from 1987 to 2014 were analyzed. The changes of fund numbers, amounts and research fields were described. During the study period, NSFC sponsored 373 projects, including 228 general projects (61.1%), 78 youth projects (20.9%) and 67 other projects (18.0%). The average amount of the grant was 358.2 thousand Yuan (20 thousand-8 million). The main sponsored research fields were mechanisms of pathogen and immunity (36.2%) and population-based epidemiological studies (33.0%). The top three diseases were hepatitis, HIV/AIDS and tuberculosis. The amount of funding on researches of infectious disease epidemiology has increased continuously, which has played an important role in training scientific talents in the field of prevention and control of infectious diseases.
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Directory of Open Access Journals (Sweden)
Bee K Tan
Full Text Available OBJECTIVES: Circulating Fibroblast Growth Factor 21 (FGF21 levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM. In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants. DESIGN: CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26-47 years, BMI: 24.3-36.3 kg/m(2 and 12 controls (age: 22-40 years, BMI: 30.1-37.0 kg/m(2]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA. RESULTS: Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2-352.7 vs. 115.5 (60.5-188.7 pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3-0.6 vs. 0.8 (0.5-1.6; P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05. CONCLUSIONS: The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points.
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Industrial Sponsor Perspective on Leveraging Capstone Design Projects to Enhance Their Business
Weissbach, Robert S.; Snyder, Joseph W.; Evans, Edward R., Jr.; Carucci, James R., Jr.
2017-01-01
Capstone design projects have become commonplace among engineering and engineering technology programs. These projects are valuable tools when assessing students, as they require students to work in teams, communicate effectively, and demonstrate technical competency. The use of industrial sponsors enhances these projects by giving these projects…
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Bove, Liliana L.; Davies, W. Martin
2009-01-01
This case study outlines the use of client-sponsored research projects in a quantitative postgraduate marketing research subject conducted in a 12-week semester in a research-intensive Australian university. The case study attempts to address the dearth of recent literature on client-sponsored research projects in the discipline of marketing.…
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A FGF3 mutation associated with differential inner ear malformation, microtia, and microdontia.
Ramsebner, Reinhard; Ludwig, Martin; Parzefall, Thomas; Lucas, Trevor; Baumgartner, Wolf-Dieter; Bodamer, Olaf; Cengiz, Filiz Basak; Schoefer, Christian; Tekin, Mustafa; Frei, Klemens
2010-02-01
Analysis of association between genotype and phenotype. Prospective genetic study in a family. Auditory investigations, computer tomography, and genetic sequencing of the fibroblast growth factor 3 (FGF3) gene were performed on a Somali family presenting with autosomal recessive, hearing impairment, microdontia, and outer ear morphologies ranging from normal auricle development to microtia assessed as type 1 Weerda dysplasia in affected individuals. Computed tomography imaging identified differential inter- and intraindividual malformations of the inner ear including labyrinth aplasia, development of a common cavity to the presence of a cochlear with 1.5 windings (Mondini malformation) in affected individuals, symptoms similar to those described as labyrinth aplasia, microtia, and microdontia (LAMM) syndrome, caused by mutations in FGF3. Genetic sequencing revealed the presence of a novel p.R95W missense mutation in FGF3 segregating with pathology. The p.R95W mutation substitutes a positively charged arginine for a polar tryptophan in the highly conserved RYLAM consensus of the beta 6 sheet of FGF3 that interacts with FGFR2. These findings describe, for the first time, variable inner ear malformations and outer ear dysplasia in the presence of constant microdontia, associated with homozygous inheritance of the p.R95W mutation in FGF3, mirroring phenotypes observed in mouse models ablating FGF3/FGFR2 signaling.
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Andreucci, Elena; Bianchini, Francesca; Biagioni, Alessio; Del Rosso, Mario; Papucci, Laura; Schiavone, Nicola; Magnelli, Lucia
2017-01-01
Fibroblast growth factor 2 (FGF2) is involved in many physiological and pathological processes. Fgf2 deregulation contributes to the acquisition of malignant features of melanoma and other cancers. FGF2 is an alternative translation product expressed as five isoforms, a low-molecular-weight (18 KDa) and four high-molecular-weight (22, 22.5, 24, 34 KDa) isoforms, with different subcellular distributions. An internal ribosomal entry site (IRES) in its mRNA controls the translation of all the isoforms with the exception for the cap-dependent 34 KDa. The 18-KDa isoform has been extensively studied, while very few is known about the roles of high molecular weight isoforms. FGF2 is known to promote melanoma development and progression. To disclose the differential contribution of FGF2 isoforms in melanoma, we forced the expression of IRES-dependent low-molecular-weight (LMW, 18 KDa) and high-molecular-weight (HMW, 22, 22.5, 24 KDa) isoforms in a human metastatic melanoma cell line. This comparative study highlights that, while LMW isoform confers stem-like features to melanoma cells and promotes angiogenesis, HMW isoforms induce higher migratory ability and contribute to tumor perfusion by promoting vasculogenic mimicry (VM) when endothelial cell-driven angiogenesis is lacking. To conclude, FGF2 isoforms mainly behave in specific, antithetical manners, but can cooperate in different steps of tumor progression, providing melanoma cells with major malignant features. FGF2 is an alternative translation product expressed as different isoforms termed LMW and HMW. FGF2 is involved in melanoma development and progression. HMW FGF2 isoforms enhance in vitro motility of melanoma cells. LMW FGF2 confers stem-like features and increases in vivo metastasization. LMW FGF2 promotes angiogenesis while HMW FGF2 induces vasculogenic mimicry.
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Northcraft, Terry G.
2017-01-01
This qualitative study examined the effect the level of project management maturity a banking IT project sponsor has on project success. Project management maturity is gauged by the amount of modern project management training, knowledge and organizational skills an individual or organization has and applies to their project lifecycle experiences.…
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The USL NASA PC R and D project: Detailed specifications of objects
Dominick, Wayne D. (Editor); Chum, Frank Y.; Hall, Philip P.; Moreau, Dennis R.; Triantafyllopoulos, Spiros
1984-01-01
The specifications for a number of projects which are to be implemented within the University of Southwestern Louisiana NASA PC R and D Project are discussed. The goals and objectives of the PC development project and the interrelationships of the various components are discussed. Six projects are described. They are a NASA/RECON simulator, a user interface to multiple remote information systems, evaluation of various personal computer systems, statistical analysis software development, interactive presentation system development, and the development of a distributed processing environment. The relationships of these projects to one another and to the goals and objectives of the overall project are discussed.
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FGF-21: promising biomarker for detecting ketosis in dairy cows.
Xu, Chuang; Xu, Qiushi; Chen, Yuanyuan; Yang, Wei; Xia, Cheng; Yu, Hongjiang; Zhu, Kuilin; Shen, Taiyu; Zhang, Ziyang
2016-03-01
The objective of this study was to investigate the measurement of serum fibroblast growth factor-21 (FGF-21), a protein mainly synthesized by the liver, as a sensitive biomarker for diagnosis of ketosis in dairy cows. Ninety Holstein-Friesian dairy cows (60 healthy and 30 ketosis cases) were selected and divided into a Ketosis group (K), and a Control group (C). We measured serum FGF-21 and other biochemical parameters by commercial ELISA kits. In a combined population of all 90 cows, we found that serum FGF-21 level was lower (P ketosis. When the β-hydroxybutyric acid (BHBA) level increased over 1.2 mmol/L, the FGF-21 level tended to decline below 300.85 pg/ml. The area under the receiver operating characteristic curve (AUC-ROC) for serum FGF-21 for diagnosis of fatty liver was 0.952-0.025 [95% confidence interval (CI) 0.904, 1.000] which was higher than the AUC-ROC for glucose (Glc) and other tested parameters. We concluded that FGF-21 could be a diagnostic parameter in the evaluation and auxiliary diagnosis of changes in the energy metabolism state, and serum FGF-21 measurement would have a considerable clinical impact and lead to greater profitability in the dairy industry.
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African Journals Online (AJOL)
jenny
2006-02-22
Feb 22, 2006 ... Exploring Educators' Expectations and. Experiences of ... project and is sponsored by major corporate bodies. The project aims ... To explore participants' expectations and experiences of INSET the following research strategy.
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Jointly Sponsored Research Program
Energy Technology Data Exchange (ETDEWEB)
Everett A. Sondreal; John G. Hendrikson; Thomas A. Erickson
2009-03-31
U.S. Department of Energy (DOE) Cooperative Agreement DE-FC26-98FT40321 funded through the Office of Fossil Energy and administered at the National Energy Technology Laboratory (NETL) supported the performance of a Jointly Sponsored Research Program (JSRP) at the Energy & Environmental Research Center (EERC) with a minimum 50% nonfederal cost share to assist industry in commercializing and effectively applying highly efficient, nonpolluting energy systems that meet the nation's requirements for clean fuels, chemicals, and electricity in the 21st century. The EERC in partnership with its nonfederal partners jointly performed 131 JSRP projects for which the total DOE cost share was $22,716,634 (38%) and the nonfederal share was $36,776,573 (62%). Summaries of these projects are presented in this report for six program areas: (1) resource characterization and waste management, (2) air quality assessment and control, (3) advanced power systems, (4) advanced fuel forms, (5) value-added coproducts, and (6) advanced materials. The work performed under this agreement addressed DOE goals for reductions in CO{sub 2} emissions through efficiency, capture, and sequestration; near-zero emissions from highly efficient coal-fired power plants; environmental control capabilities for SO{sub 2}, NO{sub x}, fine respirable particulate (PM{sub 2.5}), and mercury; alternative transportation fuels including liquid synfuels and hydrogen; and synergistic integration of fossil and renewable resources.
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Directory of Open Access Journals (Sweden)
Giulia Donadel
2017-10-01
Full Text Available Background: Diabetes mellitus (DM is a multifactorial disease orphan of a cure. Regenerative medicine has been proposed as novel strategy for DM therapy. Human fibroblast growth factor (FGF-2b controls β-cell clusters via autocrine action, and human placental lactogen (hPL-A increases functional β-cells. We hypothesized whether FGF-2b/hPL-A treatment induces β-cell differentiation from ductal/non-endocrine precursor(s by modulating specific genes expression. Methods: Human pancreatic ductal-cells (PANC-1 and non-endocrine pancreatic cells were treated with FGF-2b plus hPL-A at 500 ng/mL. Cytofluorimetry and Immunofluorescence have been performed to detect expression of endocrine, ductal and acinar markers. Bromodeoxyuridine incorporation and annexin-V quantified cells proliferation and apoptosis. Insulin secretion was assessed by RIA kit, and electron microscopy analyzed islet-like clusters. Results: Increase in PANC-1 duct cells de-differentiation into islet-like aggregates was observed after FGF-2b/hPL-A treatment showing ultrastructure typical of islets-aggregates. These clusters, after stimulation with FGF-2b/hPL-A, had significant (p < 0.05 increase in insulin, C-peptide, pancreatic and duodenal homeobox 1 (PDX-1, Nkx2.2, Nkx6.1, somatostatin, glucagon, and glucose transporter 2 (Glut-2, compared with control cells. Markers of PANC-1 (Cytokeratin-19, MUC-1, CA19-9 were decreased (p < 0.05. These aggregates after treatment with FGF-2b/hPL-A significantly reduced levels of apoptosis. Conclusions: FGF-2b and hPL-A are promising candidates for regenerative therapy in DM by inducing de-differentiation of stem cells modulating pivotal endocrine genes.
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Clinical efficacy of basic fibroblast growth factor (bFGF) for diabetic ulcer.
UCHI, Hiroshi; IGARASHI, Atsuyuki; URABE, Kazunori; KOGA, Tetsuya; NAKAYAMA, Juichiro; KAWAMORI, Ryuzo; TAMAKI, Kunihiko; HIRAKATA, Hideki; OHURA, Takehiko; FURUE, Masutaka
2009-01-01
Basic fibroblast growth factor (bFGF) has been shown to promote wound healing. The present trial evaluated the clinical efficacy of bFGF for diabetic ulcer, a type of refractory skin ulcer, and the dose-response relationship. This was designed as a randomized, double-blind, dose-ranging, placebo-controlled trial. A total of 150 patients with non-ischaemic diabetic ulcers measuring 900 mm2 or less were randomized into a placebo group (n = 51), a 0.001% bFGF group (n = 49) and a 0.01% bFGF group (n = 50), and 148 of these patients received treatment for 8 weeks or less. The efficacy evaluation was carried out on 139 patients who met the protocol in this trial. The primary outcome was the percentage of patients showing 75% or greater reductions in the area of ulcer. The area of ulcer decreased by 75% or more in 57.5% (27/47), 72.3% (34/47), and 82.2% (37/45) in the placebo, 0.001% bFGF and 0.01% bFGF groups, respectively, and differences were significant between the 0.01% bFGF and placebo groups (p = 0.025). The cure rate was 46.8% (22/47), 57.4% (27/47), and 66.7% (30/45) in the placebo, 0.001% bFGF and 0.01% bFGF groups, respectively. The findings obtained in this trial showed wound healing accelerating effects of bFGF on diabetic ulcers.
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Endostatin competes with bFGF for binding to heparin-like glycosaminoglycans
International Nuclear Information System (INIS)
Reis, Renata C.M.; Schuppan, Detlef; Barreto, Aline C.; Bauer, Michael; Bork, Jens P.; Hassler, Gerda; Coelho-Sampaio, Tatiana
2005-01-01
Endostatin is a potent inhibitor of angiogenesis and tumor growth. Here, we used human endothelial cells from lung capillaries to investigate if endostatin competes with the proangiogenic growth factors, bFGF and VEGF, for binding to costimulatory heparan sulfate molecules. Endostatin inhibited 79% and 95% of the increase in proliferation induced by bFGF and VEGF 165 , respectively. The stimulatory effect of VEGF 165 was not affected by the presence of exogenous heparin, while that of bFGF was further enhanced in the presence of up to 0.1 μg/ml heparin. The heparin-binding protein protamine completely blocked bFGF-stimulated proliferation, while it did not affect the response to VEGF 165 . Simultaneous addition of endostatin and protamine led to additive effects both in inhibition of proliferation and induction of apoptosis. Although bFGF was found to bind more strongly to heparin-Sepharose than endostatin, the latter, but not the former, displaced protamine from heparin in solution, which supports the notion that endostatin can compete with bFGF for binding to heparan sulfate in vivo. Taken as a whole, our results demonstrate that there is a direct connection between the dependence of endostatin activity on heparin-like glycosaminoglycans and its ability to antagonize bFGF
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Itoh, Nobuyuki
2016-04-01
The FGF family comprises 22 members with diverse functions in development and health. FGF10 specifically activates FGFR2b in a paracrine manner with heparan sulfate as a co-factor. FGF10and FGFR2b are preferentially expressed in the mesenchyme and epithelium, respectively. FGF10 is a mesenchymal signaling molecule in the epithelium. FGF10 knockout mice die shortly after birth due to the complete absence of lungs as well as fore- and hindlimbs. FGF10 is also essential for the development of multiple organs. The phenotypes of Fgf10 knockout mice are very similar to those of FGFR2b knockout mice, indicating that FGF10 acts as a ligand that is specific to FGFR2b in mouse multi-organ development. FGF10 also plays roles in epithelial-mesenchymal transition, the repair of tissue injury, and embryonic stem cell differentiation. In humans, FGF10 loss-of-function mutations result in inherited diseases including aplasia of lacrimal and salivary gland, lacrimo-auriculo-dento-digital syndrome, and chronic obstructive pulmonary disease. FGF10 is also involved in the oncogenicity of pancreatic and breast cancers. Single nucleotide polymorphisms in FGF10 are also potential risk factors for limb deficiencies, cleft lip and palate, and extreme myopia. These findings indicate that FGF10 is a crucial paracrine signal from the mesenchyme to epithelium for development, health, and disease. Copyright © 2015. Published by Elsevier Ltd.
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International Nuclear Information System (INIS)
Sui, Lina; Mfopou, Josué K.; Geens, Mieke; Sermon, Karen; Bouwens, Luc
2012-01-01
Highlights: ► Deep study the FGF signaling role during DE specification in the context of hESCs. ► DE differentiation from hESCs has an early dependence on FGF signaling. ► A serum-free DE protocol is developed based on the findings. ► The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.
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USL/DBMS NASA/PC R and D project C programming standards
Dominick, Wayne D. (Editor); Moreau, Dennis R.
1984-01-01
A set of programming standards intended to promote reliability, readability, and portability of C programs written for PC research and development projects is established. These standards must be adhered to except where reasons for deviation are clearly identified and approved by the PC team. Any approved deviation from these standards must also be clearly documented in the pertinent source code.
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Directory of Open Access Journals (Sweden)
Kimble Matos
2008-08-01
Full Text Available PURPOSE: To investigate the immunohistochemical expression (IGF-1, EGFr, EGF, c-erbB-2/HER-2/neu, PDGF-A, PDGF-B, FGF and VEGF in patients with Graves' ophthalmopathy. METHODS: Twenty-four samples (Graves' ophthalmopathy patients underwent lateral rectus muscle and surrounding fibrous and adipose tissue biopsy. The control group was obtained by strabismus surgery. Correlation between clinical- ophthalmologic, endocrinological, ultrasonographic findings, and immunohistochemical expression was performed. RESULTS: IGF-1: There were 7 positive cases (29.2%. There was a direct relation with higher CAS (clinical activity score in all of them and if only CAS equal or higher than 5 was considered, this was 54.5%. FGF: There was expression in 5 cases (20.8% with a direct relation in all those with higher CAS (>5 (45.4%. VEGF: There were two positive cases (8.3% for VEGF in endothelial cells, in these cases the patients also presented CAS higher than 5. There was no expressions of all growth factors in the control group. CONCLUSIONS: All patients, except one, with positive expression of FGF, IGF-1 and VEGF showed CAS greater than 5, suggesting in this way an important role of these growth factors in the pathogenesis and severity of Graves' ophthalmopathy. However, statistical analysis revealed only significant association between IGF-1 and male sex (P=0.034. Low ultrasound reflectivity and endocrine status may not correlate directly with disease activity or with immunoexpression of growth factors and c-erbB-2/HER-2/neu.OBJETIVO: Investigar a expressão imuno-histoquímica de IGF-1, EGFr, EGF, c-erbB-2/HER-2/neu, PDGF-A, PDGF-B, FGF e VEGF na oftalmopatia de Graves. MÉTODOS: Vinte e dois pacientes (oftalmopatia de Graves foram submetidos à biópsia do músculo reto lateral e tecido fibroso e adiposo adjacente. O grupo controle foi de pacientes de cirurgia de estrabismo. Foi feita correlação entre achados clínico-oftalmológicos, endocrinol
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Directory of Open Access Journals (Sweden)
Singh Ravindra
2009-01-01
Full Text Available Background: Platelet rich plasma-platelet concentrate (PRP-PC, buffy coat poor-platelet concentrate (BC-PC, and apheresis-PC were prepared and their quality parameters were assessed. Study Design: In this study, the following platelet products were prepared: from random donor platelets (i platelet rich plasma - platelet concentrate (PRP-PC, and (ii buffy coat poor- platelet concentrate (BC-PC and (iii single donor platelets (apheresis-PC by different methods. Their quality was assessed using the following parameters: swirling, volume of the platelet concentrate, platelet count, WBC count and pH. Results: A total of 146 platelet concentrates (64 of PRP-PC, 62 of BC-PC and 20 of apheresis-PC were enrolled in this study. The mean volume of PRP-PC, BC-PC and apheresis-PC was 62.30±22.68 ml, 68.81±22.95 ml and 214.05±9.91 ml and ranged from 22-135 ml, 32-133 ml and 200-251 ml respectively. The mean platelet count of PRP-PC, BC-PC and apheresis-PC was 7.6±2.97 x 1010/unit, 7.3±2.98 x 1010/unit and 4.13±1.32 x 1011/unit and ranged from 3.2-16.2 x 1010/unit, 0.6-16.4 x 1010/unit and 1.22-8.9 x 1011/unit respectively. The mean WBC count in PRP-PC (n = 10, BC-PC (n = 10 and apheresis-PC (n = 6 units was 4.05±0.48 x 107/unit, 2.08±0.39 x 107/unit and 4.8±0.8 x 106/unit and ranged from 3.4 -4.77 x 107/unit, 1.6-2.7 x 107/unit and 3.2 - 5.2 x 106/unit respectively. A total of 26 units were analyzed for pH changes. Out of these units, 10 each were PRP-PC and BC-PC and 6 units were apheresis-PC. Their mean pH was 6.7±0.26 (mean±SD and ranged from 6.5 - 7.0 and no difference was observed among all three types of platelet concentrate. Conclusion: PRP-PC and BC-PC units were comparable in terms of swirling, platelet count per unit and pH. As expected, we found WBC contamination to be less in BC-PC than PRP-PC units. Variation in volume was more in BC-PC than PRP-PC units and this suggests that further standardization is required for preparation of BC-PC
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Energy Technology Data Exchange (ETDEWEB)
Sui, Lina, E-mail: linasui@vub.ac.be [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Mfopou, Josue K. [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Geens, Mieke; Sermon, Karen [Department of Embryology and Genetics, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Bouwens, Luc [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)
2012-09-28
Highlights: Black-Right-Pointing-Pointer Deep study the FGF signaling role during DE specification in the context of hESCs. Black-Right-Pointing-Pointer DE differentiation from hESCs has an early dependence on FGF signaling. Black-Right-Pointing-Pointer A serum-free DE protocol is developed based on the findings. Black-Right-Pointing-Pointer The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.
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Sistema de detección de fallos basado en PC en calderas pirotubulares
Rivas Pérez, R.; Feliu Batlle, V.; Sotomayor Moriano, J.
2005-01-01
Se ofrece un sistema basado en PC para la detección de fallos en calderas pirotubulares. Se presentan los algoritmos que posibilitan la detección rápida de fallos abruptos en esta clase de plantas, los cuales se basan en la detección de cambios en los
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Photogate de baixo custo com a porta de jogos do PC
Dionisio,Guilherme; Magno,Wictor C.
2007-01-01
Apresentamos neste trabalho um dispositivo de baixo custo para medidas de intervalos de tempo, velocidades e acelerações, bastante útil no problema de queda livre e em outros experimentos de mecânica. Construímos uma photogate usando a porta de jogos do PC para fazer aquisição de dados e para obter a aceleração da gravidade. Obtemos boa concordância dos dados experimentais com um modelo teórico de um corpo em queda livre. Nosso trabalho ressalta uma forma de medir com precisão curtos interval...
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Directory of Open Access Journals (Sweden)
Fernanda de Almeida Fin de Lima
2009-12-01
Full Text Available O objetivo deste trabalho foi estudar a impregnação do corante fotocromático Reversacol Graphit® em filmes do compósito de policarbonato (PC e sílica-gel (Si, com a finalidade de obter aplicações em lentes fotocrômicas. Filmes de PC puros também foram impregnados nas mesmas condições, para verificar o efeito da adição de sílica-gel. Os filmes do compósito foram produzidos em proporções de Si:PC de 1:40 e 1:80 (m m-1, pelo método casting. Para a impregnação do corante Reversacol Graphit® nos filmes obtidos foi utilizado o processo supercrítico, pela sua eficiência e benefícios. A impregnação foi feita nos tempos de 15, 30, 45, 60, 90, 120, 150 e 180 min. A temperatura e a pressão adotadas foram de 60ºC e 120 bar. A quantidade de pigmento impregnado nos filmes de Si:PC – 1:40 e 1:80 (m m-1 foi de 29 e 23% de massa de corante por massa de compósito, respectivamente, e para o filme de PC puro foi de apenas 2,2% massa de corante por massa de compósito. Pelas análises térmicas, verificou-se que os filmes do compósito apresentaram maior estabilidade térmica. Pela técnica de microscopia eletrônica, observou-se que os filmes de PC puro e dos compósitos Si:PC – 1:40 e 1:80 (m m-1 apresentaram uma superfície lisa e homogênea.
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Overview of the projects sponsored within th EU-R and D framework programme
International Nuclear Information System (INIS)
Zurita, A.; Goethem, G. van; Bermejo, J.M.
1999-01-01
Assuming that preventive measures to avoid reactor pressure vessel (RPV) failure under core degradation scenarios have failed, the stabilisation of the core melts after its release from the RPV is a key issue. Adequate cooling of the ex-vessel corium and the control of its interactions with the coolant and structures are the main challenges to mitigate and stabilise the situation preserving the containment integrity. In this regard, the on-going Fourth Euratom Framework Programme (4 th EFP) contributes with experimental and theoretical research activities aimed at responding to the main challenges mentioned, by satisfying three objectives: - To improve the understanding of the basic physics related to ex-vessel corium behaviour from the phenomenological and technological viewpoints, as well as to provide a methodology for investigating it and setting up joint multi-partner projects to be co-sponsored and co-ordinated by the EC; - to quantify and reduce the uncertainties associated with the risk issues by conducting experimental and numerical investigations and eventually to achieve a European consensus on the phenomenology and on accident mitigation strategies; - to provide a technological response to the risk issues by developing engineered safety systems (e.g. core-catchers) and severe accident management strategies (e.g. guidelines), and to discuss such a technological response with the end users of these technologies, i.e. designers and licensers. To fulfil these objectives, the 4 th EFP co-sponsors a total of five projects within the cluster 'Ex-Vessel Corium Behaviour and Coolability' of the Nuclear Fission Safety Programme. The research undertaken addresses the main different aspects such as the determination of the composition and thermodynamic data of the melt; experiments on spreading behaviour on various types of surfaces, as well as on corium coolability by flooding or water injection; investigation of corium stratification, crust and heat transfer
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Léger, Sophie; Brand, Michael
2002-11-01
The vertebrate inner ear develops from initially 'simple' ectodermal placode and vesicle stages into the complex three-dimensional structure which is necessary for the senses of hearing and equilibrium. Although the main morphological events in vertebrate inner ear development are known, the genetic mechanisms controlling them are scarcely understood. Previous studies have suggested that the otic placode is induced by signals from the chordamesoderm and the hindbrain, notably by fibroblast growth factors (Fgfs) and Wnt proteins. Here we study the role of Fgf8 as a bona-fide hindbrain-derived signal that acts in conjunction with Fgf3 during placode induction, maintenance and otic vesicle patterning. Acerebellar (ace) is a mutant in the fgf8 gene that results in a non-functional Fgf8 product. Homozygous mutants for acerebellar (ace) have smaller ears that typically have only one otolith, abnormal semi-circular canals, and behavioral defects. Using gene expression markers for the otic placode, we find that ace/fgf8 and Fgf-signaling are required for normal otic placode formation and maintenance. Conversely, misexpression of fgf8 or Fgf8-coated beads implanted into the vicinity of the otic placode can increase ear size and marker gene expression, although competence to respond to the induction appears restricted. Cell transplantation experiments and expression analysis suggest that Fgf8 is required in the hindbrain in the rhombomere 4-6 area to restore normal placode development in ace mutants, in close neighbourhood to the forming placode, but not in mesodermal tissues. Fgf3 and Fgf8 are expressed in hindbrain rhombomere 4 during the stages that are critical for placode induction. Joint inactivation of Fgf3 and Fgf8 by mutation or antisense-morpholino injection causes failure of placode formation and results in ear-less embryos, mimicking the phenotype we observe after pharmacological inhibition of Fgf-signaling. Fgf8 and Fgf3 together therefore act during induction
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Fourth natural analogue working group meeting and Pocos de Caldas project final workshop
International Nuclear Information System (INIS)
Come, B.; Chapman, N.A.
1991-01-01
The fourth meeting of the CEC-sponsored natural analogue working group (NAWG) was held in Pitlochry, Scotland, from 18 to 22 June 1990, and also included the final workshop of the Pocos de Caldas (Brazil) natural analogue project, sponsored by Nagra (CH), SKB (S) UK-DOE and US-DOE. About 80 specialists attended this meeting, originating from EC Member States and also Australia, Brazil, Canada, Finland, Japan, Sweden, Switzerland and the USA. The IAEA and OCDE-NEA were also represented. This plenary meeting was the opportunity to review and discuss five years of progress and activities of natural analogues in central areas of performance assessment: waste forms and engineered barriers, geochemistry and radionuclide speciation, radionuclide migration and the overall geological context of radwaste disposal. In addition, a feedback session provided the opportunity for regulators and those individuals who had advisory roles to give their views and impressions on the significance of natural analogue research. These proceedings, divided into two sessions, contain 32 technical papers and 14 abstracts of published papers
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Directory of Open Access Journals (Sweden)
Juan P. Cerliani
2010-12-01
Full Text Available We have previously demonstrated a crosstalk between fibroblast growth factor 2 (FGF2 and progestins inducing experimental breast cancer growth. The aim of the present study was to compare the effects of FGF2 and of medroxyprogesterone acetate (MPA on the mouse mammary glands and to investigate whether the antiprogestin RU486 was able to reverse the MPA- or FGF2-induced effects on both, mammary gland and tumor growth. We demonstrate that FGF2 administered locally induced an intraductal hyperplasia that was not reverted by RU486, suggesting that FGF2-induced effects are progesterone receptor (PR-independent. However, MPA-induced paraductal hyperplasia was reverted by RU486 and a partial agonistic effect was observed in RU486-treated glands. Using C4-HD tumors which only grow in the presence of MPA, we showed that FGF2 administered intratumorally was able to stimulate tumor growth as MPA. The histology of FGF2-treated tumors showed different degrees of gland differentiation. RU486 inhibited both, MPA or FGF2 induced tumor growth. However, only complete regression was observed in MPA-treated tumors. Our results support the hypothesis that stromal FGF2 activates PR inducing hormone independent tumor growth.
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International Nuclear Information System (INIS)
1979-03-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the Research Program Reactor Safety (RS - Projects) are sponsored by the BMFT (Federal Minister for Research and Technology), Bundesminister fuer Forschung und Technologie. Objective of this program is to investigate in greater detail the safety margins of nuclear power plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks first projects on the safety of FBR type reactors are sponsored by the BMFT. The GRS (Reactor Safety Association), Gesellschaft fuer Reaktorsicherheit mbH, by order of the BMFT, informs continuously of the status of such investigations by means of quarterly and annually publication of progress reports within the series GRS - F - Fortschrittsberichte (GRS - F - Progress Reports). Each progress report represents a compilation of individual reports about objectives, the work performed, the results, the next steps of the work etc. The individual reports are prepared in a standard form by the contractors themselves as a documentation of their progress in work. The individual reports are arranged according to the amended LWR Safety Research Program of the BMFT. Another table contents uses the same classification system as applied in the Nuclear Safety Index of the CEC European Communities and the OECD. (orig./HP) [de
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Propuesta de tipología básica de los videojuegos de PC y consola
Directory of Open Access Journals (Sweden)
Rafael Carrasco Polaino
2012-04-01
Full Text Available Identificar de forma sencilla los principales tipos de videojuegos tanto en soporte PC como videoconsola es importante para poder, a partir de ahí, estudiar cómo se acercan los usuarios a este sector de entretenimiento y cómo es su relación con cada uno de los tipos de juegos. Sólo de esta forma se podrá conocer cuáles son las consecuencias positivas o negativas que pueden ejercer esta actividad sobre los usuarios.
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Uebanso, Takashi; Taketani, Yutaka; Yamamoto, Hironori; Amo, Kikuko; Ominami, Hirokazu; Arai, Hidekazu; Takei, Yuichiro; Masuda, Masashi; Tanimura, Ayako; Harada, Nagakatsu; Yamanaka-Okumura, Hisami; Takeda, Eiji
2011-01-01
Fibroblast growth factor 21 (FGF21) has recently emerged as a metabolic hormone involved in regulating glucose and lipid metabolism in mouse, but the regulatory mechanisms and actions of FGF21 in humans remain unclear. Here we have investigated the regulatory mechanisms of the human FGF21 gene at the transcriptional level. A deletion study of the human FGF21 promoter (−1672 to +230 bp) revealed two fasting signals, including peroxisome proliferator-activated receptor α (PPARα) and glucagon signals, that independently induced human FGF21 gene transcription in mouse primary hepatocytes. In addition, two feeding signals, glucose and xylitol, also dose-dependently induced human FGF21 gene transcription and mRNA expression in both human HepG2 cells and mouse primary hepatocytes. FGF21 protein expression and secretion were also induced by high glucose stimulation. The human FGF21 promoter (−1672 to +230 bp) was found to have a carbohydrate-responsive element at −380 to −366 bp, which is distinct from the PPAR response element (PPRE). Knock-down of the carbohydrate response element binding protein by RNAi diminished glucose-induced human FGF21 transcription. Moreover, we found that a region from −555 to −443 bp of the human FGF21 promoter region exerts an important role in the activation of basic transcription. In conclusion, human FGF21 gene expression is paradoxically and independently regulated by both fasting and feeding signals. These regulatory mechanisms suggest that human FGF21 is increased with nutritional crisis, including starvation and overfeeding. PMID:21829679
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USL/DBMS NASA/PC R and D project system design standards
Dominick, Wayne D. (Editor); Moreau, Dennis R.
1984-01-01
A set of system design standards intended to assure the completeness and quality of designs developed for PC research and development projects is established. The standards presented address the areas of problem definition, initial design plan, design specification, and re-evaluation.
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Lu, L.; Annerén, C.; Reedquist, K. A.; Bos, J. L.; Welsh, M.
2000-01-01
The Src homology 2 (SH2) domain adaptor protein Shb has been shown to transmit NGF- and FGF-2-dependent differentiation signals in PC12 cells. To study if this involves signaling through the small GTPase Rap1, Rap1 activity was assessed in Shb-overexpressing PC12 cells. We demonstrate that NGF and
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International Nuclear Information System (INIS)
1978-09-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the Research Program Reactor Safety (RS - Projects) are sponsored by the BMFT (Federal Minister for Research and Technology), Bundesminister fuer Forschung und Technologie. Objective of this program is to investigate in greater detail the safety margins of nuclear power plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks first projects on the safety of FBR type reactors are sponsored by the BMFT. The GRS (Reactor Safety Association), Gesellschaft fuer Reaktorsicherheit mbH, by order of the BMFT, informs continuously of the status of such investigations by means of quarterly and annually publication of progress reports within the series GRS - F -Fortschrittsberichte (GRS - F - Progress Reports). Each progress report represents a compilation of individual reports about objectives, the work performed, the results, the next steps of the work etc. The individual reports are prepared in a standard form by the contractors themselves as a documentation of their progress in work, The individual reports are arranged according to the amended LWR Safety Research Program of the BMFT. Another table contents uses the same classification system as applied in the Nuclear Safety Index of the CEC Communities and the OECD. (orig./HP) 891 HP [de
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International Nuclear Information System (INIS)
1978-09-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the Research Program Reactor Safety (RS - Projects) are sponsored by the BMFT (Federal Minister for Research and Technology), der Bundesminister fuer Forschung und Technologie. Objective of this program is to investigate in greater detail the safety margins of nuclear power plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks first projects on the safety of FBR type reactors are sponsored by the BMFT. The GRS (Reactor Safety Association), Gesellschaft fuer Reaktorsicherheit mbH, by order of the BMFT, informs continuously of the status of such investigations by means of quarterly and annually publication of progress reports within the series GRS - F Fortschrittsberichte (GRS - F - Progress Reports). Each progress report represents a compilation of individual reports about objectives, the work performed, the results, the next steps of the work etc. The individual reports are prepared in a standard form by the contractors themselves as a documentation of their progress in work. The individual reports are arranged according to the amended LWR Safety Research Program of the BMFT. Another table contents uses the same classification system as applied in the Nuclear Safety Index of the CEC Communities and the OECD. (orig./HP) 891 HP [de
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International Nuclear Information System (INIS)
1979-09-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the Research Program Reactor Safety (RS - Projects) are sponsored by the BMFT (Federal Minister for Research and Technology), Bundesminister fuer Forschung und Technologie. Objective of this program is to investigate in greater detail the safety margins of nuclear power-plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks first projects on the safety of FBR type reactors are sponsored by the BMFT. The GRS (Reactor Safety Association), Gesellschaft fuer Reaktorsicherheit mbH, by order of the BMFT, informs continuously of the status of such investigations by means of quarterly and annually publication of progress reports within the series GRS - F - Fortschrittsberichte (GRS - F - Progress Reports). Each progress report represents a compilation of individual reports about objectives, the work performed, the results, the next steps of the work etc. The individual reports are prepared in a standard form by the contractors themselves as a documentation of their progress in work. The individual reports are arranged according to the amended LWR Safety Research Program of the BMFT in the near future. Another table contents uses the same classification system as applied in the Nuclear Safety Index of the CEC Communities and the OECD. (orig.) [de
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DeLucca named project director in Guatemala.
1984-01-01
Mike Delucca, a social marketing specialist since 1978, has been named director of a new contraceptive social marketing effort in Guatemala. The project is sponsored by Importadora de Productos Farmaceuticos (IPROFA), S.A., a group of private-sector community leaders who came together specifically to set up the project. IPROFA plan to being marketing 1 brand of oral contraceptive, condom, and foaming tablet in early 1985. Efforts will first be targeted at economically and socially disadvantaged fertile couples between the ages of 18-44 in large urban areas. By the end of 1985 marketing will begin in rural and small urban areas. DeLucca is on assignment IPROFA from Juarez and Associates, a marketing and research firm in Los Angeles. He was formerly with Development Associates of Arlington, Virginia, and served as project director for the social marketing project in El Salvador. He joined the Guatemala project in May 1984, overseeing prelaunch activities that included development of the marketing plan. After the product launch he will coordinate sales and follow-up marketing studies. The project is the result of a cooperative agreement between IPROFA and US Agency for International Development (USAID) signed in April 1982. full text
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Leptin as a Potential Regulator of FGF21
Directory of Open Access Journals (Sweden)
Mohamed Asrih
2016-03-01
Full Text Available Background/Aims: Fibroblast growth factor 21 (FGF21, a potent metabolic regulator, has been shown to improve insulin sensitivity in animal models of insulin resistance. Several studies have focused on identifying mediators of FGF21 effects. However, the identification of factors involved in FGF21 regulation is far from complete. As leptin is a potent metabolic modulator as well, we aimed at characterizing whether leptin may regulate FGF21. Methods: We investigated a potential regulation of FGF21 by leptin in vivo in Wistar rats and in vitro using human derived hepatocarcinoma HepG2 cells. This model was chosen as the liver is considered the main FGF21 expression site. Results: We found that leptin injections increased plasma FGF21 levels in adult Wistar rats. This was confirmed in vitro, as leptin increased FGF21 expression in HepG2 cells. We also showed that the leptin effect on FGF21 expression was mediated by STAT3 activation in HepG2 cells. Conclusion: New findings regarding a leptin-STAT3-FGF21 axis were provided in this study, although investigating the exact mechanisms linking leptin and FGF21 are still needed. These results are of great interest in the context of identifying potential new clinical approaches to treat metabolic diseases associated with insulin resistance, such as obesity and type 2 diabetes.
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Directory of Open Access Journals (Sweden)
Luis Espinosa-Chaurand
2012-12-01
Full Text Available Objetivo. Evaluar el efecto de cinco niveles de proteína cruda (PC en alimentos balanceados sobre el crecimiento, sobrevivencia y tasa de conversión alimenticia (FCA en juveniles de Macrobrachium tenellum. Materiales y métodos. Se alimentó por 60 días a juveniles de M. tenellum (0.31±0.01 g y 32.62±1.10 mm con niveles de 20, 25, 30, 35 y 40% de PC en el alimento. Los organismos fueron distribuidos al azar en 15 tinas experimentales de 64 L (15 org./tina bajo condiciones controladas (5.95±0.41 ppm de oxígeno, 29.89±0.72ºC, y pH 8.44±0.15 y alimentados con el 10% de su peso vivo. Resultados. El porcentaje de sobrevivencia fue del 98.22±3.96% sin diferencias significativas entre los tratamientos (p>0.05. Los organismos alimentados con un 40% de PC tuvieron un peso significativamente mayor (p<0.05 respecto a los demás tratamientos (cambio de peso de 0.54±0.02g; incremento de peso de 173.60±12.99%; y tasa de crecimiento específico de 1.68±0.08. El FCA fue significativamente mejor (p<0.05 en los organismos alimentados con 35 y 40% de PC (2.85±0.18 y 2.40±0.05, respectivamente que los demás tratamientos. Conclusiones. Los organismos juveniles de M. tenellum alimentados con niveles altos de proteína (40%, se desarrollaron más rápido que organismos que recibieron una menor concentración de proteína bajo las condiciones experimentales establecidas en este estudio.
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The use of PC based VR in clinical medicine: the VREPAR projects.
Riva, G; Bacchetta, M; Baruffi, M; Borgomainerio, E; Defrance, C; Gatti, F; Galimberti, C; Fontaneto, S; Marchi, S; Molinari, E; Nugues, P; Rinaldi, S; Rovetta, A; Ferretti, G S; Tonci, A; Wann, J; Vincelli, F
1999-01-01
Virtual reality (VR) is an emerging technology that alters the way individuals interact with computers: a 3D computer-generated environment in which a person can move about and interact as if he actually was inside it. Given to the high computational power required to create virtual environments, these are usually developed on expensive high-end workstations. However, the significant advances in PC hardware that have been made over the last three years, are making PC-based VR a possible solution for clinical assessment and therapy. VREPAR - Virtual Reality Environments for Psychoneurophysiological Assessment and Rehabilitation - are two European Community funded projects (Telematics for health - HC 1053/HC 1055 - http://www.psicologia.net) that are trying to develop a modular PC-based virtual reality system for the medical market. The paper describes the rationale of the developed modules and the preliminary results obtained.
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DEFF Research Database (Denmark)
Mace, Maria L; Gravesen, Eva; Nordholm, Anders
2018-01-01
hypocalcemia. We demonstrated that FGF23 rapidly inhibited PTH secretion and that this effect was completely blocked by inhibition of the FGF receptor. Furthermore, inhibition of the FGF receptor by itself significantly increased PTH levels, indicating that FGF23 has a suppressive tonus on the parathyroid...... gland's PTH secretion. In acute hypocalcemia, there was no effect of either recombinant FGF23 or FGF receptor inhibition on the physiological response to the low ionized calcium levels. In conclusion, FGF23 has an inhibitory tonus on PTH secretion in normocalcemia and signals through the FGF receptor....... In acute hypocalcemia, when increased PTH secretion is needed to restore the calcium homeostasis, this inhibitory effect of FGF23 is abolished....
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International Nuclear Information System (INIS)
1979-12-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the Research Program Reactor Safety (RS - Projects) are sponsored by the BMFT (Federal Minister for Research and Technology), Bundesminister fuer Forschung und Technologie. Objective of this program is to investigate in greater detail the safety margins of nuclear power plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks first projects on the safety of FBR type reactors are sponsored by the BMFT. The CRS (Reactor Safety Association), Gesellschaft fuer Reaktorsicherheit mbH, by order of the BMFT, informs continuously of the status of such investigations by means of quarterly and annually publication of progress reports within the series GRS - F - Fortschrittsberichte (GRS - F - Progress Reports). Each progress report represents a compilation of individual reports about objectives, the work performed, the results, the next steps of the work etc. The individual reports are prepared in a standard form by the contractors themselves as a documentation of their progress in work. The individual reports are arranged according to the amended LWR Safety Research Program of the BMFT in the near future. Another table contents uses the same classification system as applied in the Nuclear Safety Index of the CEC Communities and the OECD.(orig./HP) [de
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International Nuclear Information System (INIS)
1980-06-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the Research Program Reactor Safety (RS-Projects) are sponsored by the BMFT (Federal Minister for Research and Technology), Bundesminister fuer Forschung und Technologie. Objective of this program is to investigate in greater detail the safety margins of nuclear power plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks first projects on the safety of FBR type reactors are sponsored by the BMFT. The GRS (Reactor Safety Association), Gesellschaft fuer Reaktorsicherheit mbH, by order of the BMFT, informs continuously of the status of such investigations by means of quarterly and annually publication of progress reports within the series GRS-F-Fortschrittsberichte (GRS-F-progress reports). Each progress report represents a compilation of individual reports about objectives, the work performed, the results, the next steps of the work etc. The individual reports are prepared in a standard form by the contractors themselves as a documentation of their progress in work. The individual reports are arranged according to the amended LWR Safety Research Program of the BMFT, which will appear in the near future. Another table contents uses the same classification system as applied in the Nuclear Safety Index of the CEC and the OECD. (orig./HP) [de
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50 CFR 253.22 - State projects.
2010-10-01
... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false State projects. 253.22 Section 253.22... State projects. (a) General—(1) Designation of state agency. The Governor of each state shall notify the... participation under the Act, to sign project documents, and to receive payments. (2) States that choose to...
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PPARα is a key regulator of hepatic FGF21
International Nuclear Information System (INIS)
Lundasen, Thomas; Hunt, Mary C.; Nilsson, Lisa-Mari; Sanyal, Sabyasachi; Angelin, Bo; Alexson, Stefan E.H.; Rudling, Mats
2007-01-01
The metabolic regulator fibroblast growth factor 21 (FGF21) has antidiabetic properties in animal models of diabetes and obesity. Using quantitative RT-PCR, we here show that the hepatic gene expression of FGF21 is regulated by the peroxisome proliferator-activated receptor alpha (PPARα). Fasting or treatment of mice with the PPARα agonist Wy-14,643 induced FGF21 mRNA by 10-fold and 8-fold, respectively. In contrast, FGF21 mRNA was low in PPARα deficient mice, and fasting or treatment with Wy-14,643 did not induce FGF21. Obese ob/ob mice, known to have increased PPARα levels, displayed 12-fold increased hepatic FGF21 mRNA levels. The potential importance of PPARα for FGF21 expression also in human liver was shown by Wy-14,643 induction of FGF21 mRNA in human primary hepatocytes, and PPARα response elements were identified in both the human and mouse FGF21 promoters. Further studies on the mechanisms of regulation of FGF21 by PPARα in humans will be of great interest
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Blauwe ogen schieten tekort. Lessen voor sponsoring van landschap
Overbeek, M.M.M.; Graaff, de R.P.M.
2010-01-01
Literatuuronderzoek en gesprekken met (ervarings)deskundigen en vertegenwoordigers van bedrijven in Amstelland en in Het Groene Woud over het proces en de voorwaarden van bedrijven om sponsoring van landschap te realiseren. Sponsoring gebeurt meestal in het kader van mvo, waarbij bedrijven de
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International Nuclear Information System (INIS)
1978-12-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the Research Program Reactor Safety (RS - Projects) are sponsored by the BMFT (Federal Minister for Research and Technology), Bundesminister fuer Forschung und Technologie. Objective of this program is to investigate in greater detail the safety margins of nuclear power-plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks first projects on the safety of advanced reactors are sponsored by the BMFT. The GRS (Reactor Safety Association), Gesellschaft fuer Reaktorsicherheit mbH, by order of the BMFT, informs continuously of the status of such investigations by means of quarterly and annually publication of progress reports within the series GRS - F - Fortschrittsberichte (GRS - F - Progress Reports). Each progress report represents a compilation of individual reports about objectives, the work performed, the results, the next steps of the work etc. The individual reports are prepared in a standard form by the contractors themselves as a documentation of their progress in work and published by the FB (Research Coordination Department), Forschungsbetreuung at the GRS, within the framework of general information of the progress in reactor safety research. The individual reports are arranged according to the amended LWR Safety Research Program of the BMFT which will appear in the near future. Another table contents uses the same classification system as applied in the Nuclear Safety Index of the CEC and the OECD. (orig./HP) [de
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Directory of Open Access Journals (Sweden)
Laura García-Pupo
2013-03-01
Full Text Available Introducción: la diosgenina y sus derivados se han descrito como potentes inhibidores de la proliferación en varias líneas tumorales. Sin embargo otras moléculas relacionadas estructuralmente con dichos derivados, se han reportado como candidatos terapéuticos y otras de ellas se incluyen en alimentos de consumo humano. Objetivo: el presente trabajo evalúa el efecto sobre la viabilidad celular de una nueva serie de espiroesteroides sintéticos derivados de la diosgenina, en células tipo neurales PC12. Métodos: la viabilidad de los cultivos de PC12 se determinó mediante el ensayo de MTT y se calcularon descriptores moleculares teóricos como la lipofilicidad (logP virtual y la superficie de área polar (SAP, con el objetivo de establecer relaciones estructura-actividad. Resultados: nuestros resultados demuestran que solo el acido taurodesoxicólico disminuye de manera significativa la viabilidad celular. Más aun, dicha molécula presenta valores menores y mayores de logP virtual y SAP, respectivamente, respecto al resto de los esteroides de la serie. Conclusiones: los resultados anteriores avalan el estudio del acido taurodesoxicólico como potencial inhibidor de la proliferación celular y al resto de las moléculas de la serie como candidatos neuroprotectores a evaluar en esta misma línea celular y dosis de tratamiento.Introduction: diosgenin and its derivatives have been described as potent anti-proliferative compounds in several tumor cell lines. However, other structurally-related compounds are reported to exert neuroprotective activity and are also included in food for human consumption. Objective: to evaluate the effect of a novel series of diogesin-derived synthetic spirosteroids on cellular viability of neuron-like PC12 cell line. Methods: cellular viability was determined by the MTT assay along with some theorical molecular descriptors, such as lipophilicity and polar surface area, in order to establish the structure
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Wu, Song; Wu, Xiaoqiong; Zhu, Wu; Cai, Wei-Jun; Schaper, Jutta; Schaper, Wolfgang
2010-10-01
Growth factors are viewed as main arteriogenic stimulators for collateral vessel growth. However, the information about their native expression and distribution in collateral vessels is still limited. This study was designed to profile expression of acidic and basic FGF, platelet-derived growth factor (PDGF-AB) and vascular endothelial growth factor (VEGF-A) and its receptor, fetal liver kinase-1 (Flk-1) during arteriogenesis by confocal immunofluorescence in both dog ameroid constrictor model and rabbit arteriovenous shunt model of arteriogenesis. We found that: (1) in normal arteries (NA) in dog heart, aFGF, bFGF, and PDGF-AB all were mainly expressed in endothelial cells (EC) and media smooth muscle cells (SMC), but the expression of aFGF was very weak, with those of the other two being moderate; (2) in collateral arteries (CAs), aFGF, bFGF, and PDGF-AB all were significantly upregulated (P growth factors, aFGF, bFGF, and PDGF-AB are significantly upregulated in collateral vessels in dog heart, and enhanced VEGF-A and its receptor, Flk-1, are associated with rapid and lasting increased shear stress. These findings suggest that endogenous production of growth factors could be an important factor promoting collateral vessel growth.
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USL/DBMS NASA/PC R and D project system testing standards
Dominick, Wayne D. (Editor); Kavi, Srinu; Moreau, Dennis R.; Yan, Lin
1984-01-01
A set of system testing standards to be used in the development of all C software within the NASA/PC Research and Development Project is established. Testing will be considered in two phases: the program testing phase and the system testing phase. The objective of these standards is to provide guidelines for the planning and conduct of program and software system testing.
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Directory of Open Access Journals (Sweden)
Isabela Annunziato Ramos Mazaro
2011-12-01
Full Text Available OBJETIVO: Verificar a prevalência de obesidade, hipertensão arterial sistêmica (HAS, aumento de cintura e acanthosis nigricans em estudantes da cidade paulistana de Sorocaba em 2009, associando aos fatores de risco. MÉTODOS: Amostra probabilística com 680 crianças (7-11 anos de 13 escolas municipais de Sorocaba. Um questionário avaliou a prática de atividade física, tempo com televisão, videogame e computador (TV/VG/PC, antecedentes do aluno e dos pais para hipertensão arterial, doença renal e cardíaca e nível econômico. Foram realizadas medidas de peso, altura, cintura, pressão arterial (PA e verificado acanthosis nigricans. Determinou-se a prevalência de alteração nutricional, HAS, aumento da cintura e acanthosis nigricans. Para a associação do índice de massa corpórea (IMC IMC > P85 e da PA > P90 com outras variáveis, empregou-se o teste do qui-quadrado ou exato de Fisher (p P85 foi 22,1% [IC 95%: 19,0-25,3%], de PA > P90 10,9% [IC 95%: 8,6-13,5%], aumento da cintura 15,4% [IC 95%: 12,9-17,9%] e acanthosis nigricans 3,8% [IC 95%: 2,6-5,6%]. Foi encontrada associação do excesso de peso com antecedentes do pai (RCP: 1,76; IC 95%:1,05-2,95; p = 0,02 em ambas as análises. A elevação de PA associou-se ao sexo feminino (RCP: 1,90; IC 95%:1,12-3,23; p = 0,010, ao maior tempo na TV/VG/PC (RCP: 1,82; IC 95%:1,00-3,36; p = 0,030, à presença de acanthosis nigricans (RCP: 8,18; IC 95%:3,37-19,80; p OBJECTIVE: To verify the prevalence of obesity, systemic arterial hypertension (SAH, waist circumference and acanthosis nigricans (AN in school children from Sorocaba, in 2009 and associate them with risk factors. METHODS: A probabilistic sample study was carried out with 680 children (7-11 years from 13 public schools from the city of Sorocaba, SP. A questionnaire containing questions on physical activity, time spent watching television, playing with videogames and computers (TV/VG/PC, student and parental antecedents of
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Crespo-Enriquez, Ivan; Partanen, Juha; Martinez, Salvador; Echevarria, Diego
2012-01-01
Early brain patterning depends on proper arrangement of positional information. This information is given by gradients of secreted signaling molecules (morphogens) detected by individual cells within the responding tissue, leading to specific fate decisions. Here we report that the morphogen FGF8 exerts initially a differential signal activity along the E9.5 mouse neural tube. We demonstrate that this polarizing activity codes by RAS-regulated ERK1/2 signaling and depends on the topographical location of the secondary organizers: the isthmic organizer (IsO) and the anterior neural ridge (anr) but not on zona limitans intrathalamica (zli). Our results suggest that Sprouty2, a negative modulator of RAS/ERK pathway, is important for regulating Fgf8 morphogenetic signal activity by controlling Fgf8-induced signaling pathways and positional information during early brain development.
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EU-sponsored photovoltaic systems for rural electrification
Energy Technology Data Exchange (ETDEWEB)
Riesch, Gerhard [Joint Research Centre of the European Union, JRC, Ispra (Italy)
1995-12-31
Development and proliferation of renewable energies are sponsored since 1983 by the European Union, normally up to 40% of the cost. (Programme THERMIE and predecessors). In the frame of this programme for more than one hundred projects of all kinds with thousands of photovoltaic energy supply systems have been implemented in Europe, 29 of these projects with 939 single pv-systems concern electrification of rural sites (e.g. agriculture) or isolated sites (e.g. mountain huts). Most of the single systems are of small size, 50 to 1000 Wp. A few of the systems are larger, up to 25 kWp, and supply local isolated mini-grids. In this paper the main features of the systems in six european countries are presented: The technical, economical and social results as well as the contributions of the Electric Power Utility (EPU`s) to these electrification are discussed. [Espanol] Desde 1983 la Union Europea ha auspiciado normalmente hasta el 40% del costo del desarrollo y proliferacion de las energias renovables. (Programa THERMIE y predecesores). En el marco de este programa con mas de cien proyectos de todos tipos, con miles de sistemas fotovoltaicos de suministro de energia, han sido implantados en Europa, 29 de estos proyectos con 929 sistemas fotovoltaicos sencillos se relacionan con la electrificacion de sitios rurales (por ejemplo agricultura) o de sitios aislados (por ejemplo cabanas en la montana). La mayoria de los sistemas sencillos son de pequeno tamano, 50 a 1000 Wp. Unos pocos de los sistemas son mas grandes, hasta de 25 kWp y alimentan mini-redes locales aisladas. En este articulo se presentan las caracteristicas principales de los sistemas en seis paises europeos: se analizan los resultados tecnicos, economicos y sociales, asi como las contribuciones de las empresas electricas.
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EU-sponsored photovoltaic systems for rural electrification
Energy Technology Data Exchange (ETDEWEB)
Riesch, Gerhard [Joint Research Centre of the European Union, JRC, Ispra (Italy)
1996-12-31
Development and proliferation of renewable energies are sponsored since 1983 by the European Union, normally up to 40% of the cost. (Programme THERMIE and predecessors). In the frame of this programme for more than one hundred projects of all kinds with thousands of photovoltaic energy supply systems have been implemented in Europe, 29 of these projects with 939 single pv-systems concern electrification of rural sites (e.g. agriculture) or isolated sites (e.g. mountain huts). Most of the single systems are of small size, 50 to 1000 Wp. A few of the systems are larger, up to 25 kWp, and supply local isolated mini-grids. In this paper the main features of the systems in six european countries are presented: The technical, economical and social results as well as the contributions of the Electric Power Utility (EPU`s) to these electrification are discussed. [Espanol] Desde 1983 la Union Europea ha auspiciado normalmente hasta el 40% del costo del desarrollo y proliferacion de las energias renovables. (Programa THERMIE y predecesores). En el marco de este programa con mas de cien proyectos de todos tipos, con miles de sistemas fotovoltaicos de suministro de energia, han sido implantados en Europa, 29 de estos proyectos con 929 sistemas fotovoltaicos sencillos se relacionan con la electrificacion de sitios rurales (por ejemplo agricultura) o de sitios aislados (por ejemplo cabanas en la montana). La mayoria de los sistemas sencillos son de pequeno tamano, 50 a 1000 Wp. Unos pocos de los sistemas son mas grandes, hasta de 25 kWp y alimentan mini-redes locales aisladas. En este articulo se presentan las caracteristicas principales de los sistemas en seis paises europeos: se analizan los resultados tecnicos, economicos y sociales, asi como las contribuciones de las empresas electricas.
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PC/104 Embedded IOCs at Jefferson Lab
International Nuclear Information System (INIS)
Yan, Jianxun; Allison, Trent; Witherspoon, Sue; Cuffe, Anthony
2009-01-01
Jefferson Lab has developed embedded IOCs based on PC/104 single board computers (SBC) for low level control systems. The PC/104 IOCs run EPICS on top of the RTEMS operating system. Two types of control system configurations are used in different applications, PC/104 SBC with commercial PC/104 I/O cards and PC/104 SBC with custom designed FPGA-based boards. RTEMS was built with CEXP shell to run on the PC/104 SBC. CEXP shell provides the function of dynamic object loading, which is similar to the widely used VxWorks operating system. Standard software configurations were setup for PC/104 IOC application development to provide a familiar format for new projects as well as ease the conversion of applications from VME based IOCs to PC/104 IOCs. Many new projects at Jefferson Lab are going to employ PC/104 SBCs as IOCs and some applications have already been running them for accelerator operations. The PC/104 - RTEMS IOC provides a free open source Real-Time Operating System (RTOS), low cost/maintenance, easily installed/ configured, flexible, and reliable solution for accelerator control and 12GeV Upgrade projects.
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NASA Exercise Physiology and Countermeasures Project Overview
Loerch, Linda; Ploutz-Snyder, Lori
2009-01-01
Efficient exercise countermeasures are necessary to offset or minimize spaceflight-induced deconditioning and to maximize crew performance of mission tasks. These countermeasure protocols should use the fewest crew and vehicle resources. NASA s Exercise Physiology and Countermeasures (ExPC) Project works to identify, collect, interpret, and summarize evidence that results in effective exercise countermeasure protocols which protect crew health and performance during International Space Station (ISS) and future exploration-class missions. The ExPC and NASA s Human Research Program are sponsoring multiple studies to evaluate and improve the efficacy of spaceflight exercise countermeasures. First, the Project will measure maximal aerobic capacity (VO2max) during cycle ergometry before, during, and after ISS missions. Second, the Project is sponsoring an evaluation of a new prototype harness that offers improved comfort and increased loading during treadmill operations. Third, the Functional Tasks Test protocol will map performance of anticipated lunar mission tasks with physiologic systems before and after short and long-duration spaceflight, to target system contributions and the tailoring of exercise protocols to maximize performance. In addition to these studies that are actively enrolling crewmember participants, the ExPC is planning new studies that include an evaluation of a higher-intensity/lower-volume exercise countermeasure protocol aboard the ISS using the Advanced Resistive Exercise Device and second-generation treadmill, studies that evaluate bone loading during spaceflight exercise, and ground-based studies that focus on fitness for duty standards required to complete lunar mission tasks and for which exercise protocols need to protect. Summaries of these current and future studies and strategies will be provided to international colleagues for knowledge sharing and possible collaboration.
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Physiological and Pharmacological Roles of FGF21 in Cardiovascular Diseases
Directory of Open Access Journals (Sweden)
Peng Cheng
2016-01-01
Full Text Available Cardiovascular disease (CVD is one of the most severe diseases in clinics. Fibroblast growth factor 21 (FGF21 is regarded as an important metabolic regulator playing a therapeutic role in diabetes and its complications. The heart is a key target as well as a source of FGF21 which is involved in heart development and also induces beneficial effects in CVDs. Our review is to clarify the roles of FGF21 in CVDs. Strong evidence showed that the development of CVDs including atherosclerosis, coronary heart disease, myocardial ischemia, cardiac hypertrophy, and diabetic cardiomyopathy is associated with serum FGF21 levels increase which was regarded as a compensatory response to induced cardiac protection. Furthermore, administration of FGF21 suppressed the above CVDs. Mechanistic studies revealed that FGF21 induced cardiac protection likely by preventing cardiac lipotoxicity and the associated oxidative stress, inflammation, and apoptosis. Normally, FGF21 induced therapeutic effects against CVDs via activation of the above kinases-mediated pathways by directly binding to the FGF receptors of the heart in the presence of β-klotho. However, recently, growing evidence showed that FGF21 induced beneficial effects on peripheral organs through an indirect way mediated by adiponectin. Therefore whether adiponectin is also involved in FGF21-induced cardiac protection still needs further investigation.
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FGF21 and the late adaptive response to starvation in humans.
Fazeli, Pouneh K; Lun, Mingyue; Kim, Soo M; Bredella, Miriam A; Wright, Spenser; Zhang, Yang; Lee, Hang; Catana, Ciprian; Klibanski, Anne; Patwari, Parth; Steinhauser, Matthew L
2015-11-03
In mice, FGF21 is rapidly induced by fasting, mediates critical aspects of the adaptive starvation response, and displays a number of positive metabolic properties when administered pharmacologically. In humans, however, fasting does not consistently increase FGF21, suggesting a possible evolutionary divergence in FGF21 function. Moreover, many key aspects of FGF21 function in mice have been identified in the context of transgenic overexpression or administration of supraphysiologic doses, rather than in a physiologic setting. Here, we explored the dynamics and function of FGF21 in human volunteers during a 10-day fast. Unlike mice, which show an increase in circulating FGF21 after only 6 hours, human subjects did not have a notable surge in FGF21 until 7 to 10 days of fasting. Moreover, we determined that FGF21 induction was associated with decreased thermogenesis and adiponectin, an observation that directly contrasts with previous reports based on supraphysiologic dosing. Additionally, FGF21 levels increased after ketone induction, demonstrating that endogenous FGF21 does not drive starvation-mediated ketogenesis in humans. Instead, a longitudinal analysis of biologically relevant variables identified serum transaminases--markers of tissue breakdown--as predictors of FGF21. These data establish FGF21 as a fasting-induced hormone in humans and indicate that FGF21 contributes to the late stages of adaptive starvation, when it may regulate the utilization of fuel derived from tissue breakdown.
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2011-10-01
International Advisory Committee Richard F CastenYale, USA Luiz Carlos ChamonSão Paulo, Brazil Osvaldo CivitareseLa Plata, Argentina Jozsef CsehATOMKI, Hungary Jerry P DraayerLSU, USA Alfredo Galindo-UribarriORNL & UT, USA James J KolataNotre Dame, USA Jorge López UTEP, USA Joseph B NatowitzTexas A & M, USA Ma Esther Ortiz IF-UNAM Stuart PittelDelaware, USA Andrés SandovalIF-UNAM Adam SzczepaniakIndiana, USA Piet Van IsackerGANIL, France Michael WiescherNotre Dame, USA Organizing Committee Libertad Barrón-Palos (Chair)IF-UNAM Roelof BijkerICN-UNAM Ruben FossionICN-UNAM David LizcanoININ Sponsors Instituto de Ciencias Nucleares, UNAMInstituto de Física, UNAMInstituto Nacional de Investigaciones NuclearesDivisión de Física Nuclear de la SMFCentro Latinoamericano de Física
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Raubenolt, Amy
2016-01-01
In May 2016, the office of Finance and Sponsored Projects at The Research Institute at Nationwide Children's Hospital conducted a 5-day design sprint session to re-evaluate and redesign a flawed final reporting process within the department. The department sprint was modeled after the design sprint sessions that occur routinely in software…
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Metabolic actions of FGF21: molecular mechanisms and therapeutic implications
Directory of Open Access Journals (Sweden)
Xuan Ge
2012-08-01
Full Text Available Fibroblast growth factor 21 (FGF21 is an atypical member of the FGF family that functions as an endocrine factor. In obese animals, elevation of plasma FGF21 levels by either pharmacological or genetic approaches reduces body weight, decreases hyperglycemia and hyperlipidemia, alleviates fatty liver and increases insulin sensitivity. FGF21 exerts its pleiotropic metabolic effects through its actions on multiple targets, including adipose tissue, liver, brain and pancreas. The expression of FGF21 is under the control of both peroxisome proliferator-activated receptor gamma (PPARγ and peroxisome proliferator-activated receptor alpha (PPARα. A growing body of evidence suggests that the metabolic benefits of these two nuclear receptors are mediated in part by induction of FGF21. In humans, plasma levels of FGF21 are elevated in obese subjects and patients with type 2 diabetes, but are reduced in patients with autoimmune diabetes. This review summarizes recent advances in understanding the physiological roles of FGF21 and the molecular pathways underlying its actions, and also discusses the future prospective of developing FGF21 or its agonists as therapeutic agents for obesity-related medical complications.
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Energy Technology Data Exchange (ETDEWEB)
Picasso B, Cuitlahuac [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico); Astorga Q, Clemente [Luz y Fuerza del Centro (Mexico)
2003-07-01
In order to increase the services quality in the electrical energy, to improve the process of identification of energy losses, to increase the equipment efficiency, to count on more complete statistics of profiles of load consumptions, among other applications, the Compania de Luz y Fuerza del Centro (LyFC) carries out the modernization in automatization of substations and regional operation centers of distribution networks. The technological base to make these programs requires automating the operative schemes of the substation and distribution centers that supervise the events of the electrical process. In this article the main results of the development and integration of master stations based on PC, that were made in the Instituto de Investigaciones Electricas (IIE) and that have been integrated in the electrical company LyFC are presented. [Spanish] Con el proposito de incrementar la calidad de los servicios en la energia electrica, mejorar el proceso de identificacion de perdidas de energia, aumentar la eficiencia de los equipos, contar con estadisticas mas completas de perfiles de consumos de carga, entre otras aplicaciones, la Compania de Luz y Fuerza del Centro (LyFC) lleva a cabo la modernizacion en automatizacion de subestaciones y centros de operacion regional de redes electricas de distribucion. La base tecnologica para realizar estos programas, requiere de automatizar los esquemas operativos de la subestacion y centros de distribucion que supervisan los eventos del proceso electrico. En este articulo se presentan los principales resultados del desarrollo e integracion de estaciones maestras basadas en PC, que se realizaron en el Instituto de Investigaciones Electricas (IIE) y que se han integrado en la compania electrica LyFC.
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Directory of Open Access Journals (Sweden)
Javier Jesús Suárez Rivera
2004-04-01
Full Text Available Se realizó un estudio prospectivo y descriptivo del universo de escolares desde preescolar hasta 6to. grado de la Escuela Primaria "Jesús Menéndez," de la localidad de Alamar, en el período comprendido desde septiembre de 2000 hasta febrero de 2001, con el objetivo de estimar el comportamiento de los percentiles (pc de tensión arterial, según edad y sexo, así como los factores de riesgo asociados. La muestra quedó constituida por 743 alumnos, a los cuales se les realizó un examen físico que incluyó peso, talla, toma de tensión arterial y una encuesta abierta. Con los datos obtenidos se dividió la población en 4 grupos de estudio según percentiles de tensión arterial: grupo I ( 95 pc, según la literatura extranjera consultada, y se relacionaron con factores de riesgo. El mayor número de escolares estudiados se encontraban con cifras de tensión arterial ubicadas en canales menores al 50 pc (88,83 %, y el factor de riesgo que se encontró con mayor frecuencia fue el antecedente familiar de hipertensión arterial. Solo 6 escolares presentaron cifras de tensión arterial superiores al 95 pc.A prospective descriptive study of students from kindergarten to 6th grade in "Jesús Menendez" elementary school located in Alamar was performed from September 2000 to February 2001 to find out the performance of blood pressure percentiles by age and sex as well as the associated risk factors. The sample was comprised by 743 students who were physically examined, taking into account weight, height, blood pressure and an open survey. The obtained data allowed us to divide the population into 4 groups by blood pressure percentiles; group 1(95 pc according to the reviewed foreign literature and they were related to risk factors. The blood pressure values of the highest number of studied students were under 50 pc (88,83 % and the most frequent risk factors was family history of blood hypertension. Only 6 students had blood pressure value over 95 %.
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2. status colloquium of the project 'Applied ecology' (PAOe). Proceedings
International Nuclear Information System (INIS)
Breitenstein, A.; Scholz, W.; Waitzmann, M.; Zelesny, H.
1994-01-01
The 'Applied ecology' programme sponsors research on major subjects concerning application-oriented bases of nature conservation and environmental protection in the following sectors: 1. nature and landscape (succession research, scientific accompanying of measures restoring the natural condition of a landscape, nature conservation concepts and development of ecological paradigms); 2. ecotoxicology (further development and standardization of biological indication methods within the framework of the ecotoxicological register of effects of Baden-Wuertemberg, design of exposure models for forcasting long-term changes in Baden-Wuertemberg); 3. risk assessments and risk evaluations in environmental protection (selected ecological balances and development of ecological evaluation criteria).- On March 22nd and 23rd, 1994, the second status colloquium of the project ''Applied Ecology (PAOe)'' was held at Ettlingen. During this annual event, the results of 39 research projects in the above-mentioned major subject areas were presented and debated by 600 experts from science, administration and economy. This volume sums up the results of the research and demonstrates, at the same time, the range of the research projects sponsored under this scheme. (orig./VHE) [de
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METHANE de-NOX for Utility PC Boilers
Energy Technology Data Exchange (ETDEWEB)
Bruce Bryan; Serguei Nester; Joseph Rabovitser; Stan Wohadlo
2005-09-30
The overall project objective is the development and validation of an innovative combustion system, based on a novel coal preheating concept prior to combustion, that can reduce NO{sub x} emissions to 0.15 lb/million Btu or less on utility pulverized coal (PC) boilers. This NO{sub x} reduction should be achieved without loss of boiler efficiency or operating stability, and at more than 25% lower levelized cost than state-of-the-art SCR technology. A further objective is to ready technology for full-scale commercial deployment to meet the market demand for NO{sub x} reduction technologies. Over half of the electric power generated in the U.S. is produced by coal combustion, and more than 80% of these units utilize PC combustion technology. Conventional measures for NOx reduction in PC combustion processes rely on combustion and post-combustion modifications. A variety of combustion-based NO{sub x} reduction technologies are in use today, including low-NO{sub x} burners (LNBs), flue gas recirculation (FGR), air staging, and natural gas or other fuel reburning. Selective non-catalytic reduction (SNCR) and selective catalytic reduction (SCR) are post-combustion techniques. NO{sub x} reduction effectiveness from these technologies ranges from 30 to 60% and up to 90-93% for SCR. Typically, older wall-fired PC burner units produce NO{sub x} emissions in the range of 0.8-1.6 lb/million Btu. Low-NO{sub x} burner systems, using combinations of fuel staging within the burner and air staging by introduction of overfire air in the boiler, can reduce NO{sub x} emissions by 50-60%. This approach alone is not sufficient to meet the desired 0.15 lb/million Btu NO{sub x} standard with a range of coals and boiler loads. Furthermore, the heavy reliance on overfire air can lead to increased slagging and corrosion in furnaces, particularly with higher-sulfur coals, when LNBs are operated at sub-stoichiometric conditions to reduce fuel-derived NOx in the flame. Therefore, it is desirable
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Directory of Open Access Journals (Sweden)
Moriyama Mariko
2012-08-01
Full Text Available Abstract Background Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12. Results We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO, resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2 and fibroblast growth factor 2 (FGF2 transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK. Conclusions Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson’s disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.
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14 CFR 151.51 - Performance of construction work: Sponsor force account.
2010-01-01
... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Performance of construction work: Sponsor... Development Projects § 151.51 Performance of construction work: Sponsor force account. (a) Before undertaking any force account construction work, the sponsor (or any public agency acting as agent for the sponsor...
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bFGF influences human articular chondrocyte differentiation
DEFF Research Database (Denmark)
Schmal, H; Zwingmann, J; Fehrenbach, M
2007-01-01
BACKGROUND: The possible functional role of basic fibroblast growth factor (bFGF) in regulating the mitotic and metabolic activity of primary human articular chondrocytes was investigated. METHODS: [EF1]Chondrocytes were enzymatically isolated from femoral head cartilage, and were cultured in vitro......FGF concentrations in supernatants of primary human articular chondrocytes peaked immediately after isolation and then declined. In a dose-dependent manner, bFGF enhanced cell amplification and viability. BFGF induced a decrease in the apoptotic cell population, while the number of proliferating cells remained...... by 53%, which was correlated with diminished mRNA production. Monolayer cultured chondrocytes secreted significant amounts of aggrecan that decreased over time. Secretion of this cartilage-specific marker was further reduced by the addition of bFGF. DISCUSSION: These findings highlight the potential...
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Fgf16 is essential for pectoral fin bud formation in zebrafish
International Nuclear Information System (INIS)
Nomura, Ryohei; Kamei, Eriko; Hotta, Yuuhei; Konishi, Morichika; Miyake, Ayumi; Itoh, Nobuyuki
2006-01-01
Zebrafish pectoral fin bud formation is an excellent model for studying morphogenesis. Fibroblast growth factors (Fgfs) and sonic hedgehog (shh) are essential for pectoral fin bud formation. We found that Fgf16 was expressed in the apical ectodermal ridge (AER) of fin buds. A knockdown of Fgf16 function resulted in no fin bud outgrowth. Fgf16 is required for cell proliferation and differentiation in the mesenchyme and the AER of the fin buds, respectively. Fgf16 functions downstream of Fgf10, a mesenchymal factor, signaling to induce the expression of Fgf4 and Fgf8 in the AER. Fgf16 in the AER and shh in the zone of polarizing activity (ZPA) interact to induce and/or maintain each other's expression. These findings have revealed that Fgf16, a newly identified AER factor, plays a crucial role in pectoral fin bud outgrowth by mediating the interactions of AER-mesenchyme and AER-ZPA
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Mapping of FGF1 in the Medulla Oblongata of Macaca fascicularis.
Bisem, Naomi J; Takeuchi, Shigeko; Imamura, Toru; Abdelalim, Essam M; Tooyama, Ikuo
2012-12-26
FGF1 is highly expressed in neurons and it has been proposed to play a role in the neuroprotection and in regeneration. Low FGF1 expression in neurons has been linked to increased vulnerability in cholinergic neurons. Previous reports have shown that the expression of FGF1 in rat brain is localized to the cholinergic nuclei of the medulla oblongata, with low ratio of neurons positive for FGF1 in the dorsal motor nucleus of the vagus (DMNV). The role of FGF1 in the primate brain has yet to be clarified. In this study, we mapped FGF1 immunoreactivity in the medulla oblongata of cynomolgus monkey brainstems. Our results demonstrated that FGF1 immunoreactivity follows the pattern of distribution of cholinergic nuclei in the medulla oblongata; with strong localization of FGF1 to cholinergic neurons of the hypoglossal nucleus, the facial nucleus and the nucleus ambiguus. In contrast, the DMNV shows markedly lower FGF1 immunoreactivity. Localization of FGF1 to cholinergic neurons was only observed in the lateral region of the DMNV, with higher immunoreactivity in the rostral ventral-lateral region of the DMNV. These findings are consistent with the distribution of FGF1 immunoreactivity in previous studies of the rat brain.
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Mapping of FGF1 in the Medulla Oblongata of Macaca fascicularis
International Nuclear Information System (INIS)
Bisem, Naomi J.; Takeuchi, Shigeko; Imamura, Toru; Abdelalim, Essam M.; Tooyama, Ikuo
2012-01-01
FGF1 is highly expressed in neurons and it has been proposed to play a role in the neuroprotection and in regeneration. Low FGF1 expression in neurons has been linked to increased vulnerability in cholinergic neurons. Previous reports have shown that the expression of FGF1 in rat brain is localized to the cholinergic nuclei of the medulla oblongata, with low ratio of neurons positive for FGF1 in the dorsal motor nucleus of the vagus (DMNV). The role of FGF1 in the primate brain has yet to be clarified. In this study, we mapped FGF1 immunoreactivity in the medulla oblongata of cynomolgus monkey brainstems. Our results demonstrated that FGF1 immunoreactivity follows the pattern of distribution of cholinergic nuclei in the medulla oblongata; with strong localization of FGF1 to cholinergic neurons of the hypoglossal nucleus, the facial nucleus and the nucleus ambiguus. In contrast, the DMNV shows markedly lower FGF1 immunoreactivity. Localization of FGF1 to cholinergic neurons was only observed in the lateral region of the DMNV, with higher immunoreactivity in the rostral ventral-lateral region of the DMNV. These findings are consistent with the distribution of FGF1 immunoreactivity in previous studies of the rat brain
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FGF signaling refines Wnt gradients to regulate the patterning of taste papillae
Czech Academy of Sciences Publication Activity Database
Procházková, Michaela; Hakkinen, T.J.; Procházka, Jan; Špoutil, František; Jheon, A.H.; Ahn, Y.; Krumlauf, R.; Jernvall, J.; Klein, O. D.
2017-01-01
Roč. 144, č. 12 (2017), s. 2212-2221 ISSN 0950-1991 R&D Projects: GA MŠk(CZ) LM2015040 Institutional support: RVO:68378050 Keywords : FGF * Wnt * Tongue * Taste papilla Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Developmental biology Impact factor: 5.843, year: 2016
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IHH and FGF8 coregulate elongation of digit primordia.
Zhou, Jian; Meng, Junwei; Guo, Shengzhen; Gao, Bo; Ma, Gang; Zhu, Xuming; Hu, Jianxin; Xiao, Yue; Lin, Chuwen; Wang, Hongsheng; Ding, Lusheng; Feng, Guoyin; Guo, Xizhi; He, Lin
2007-11-23
In the developing limb bud, digit pattern arises from anterior-posterior (A-P) positional information which is provided by the concentration gradient of SHH. However, the mechanisms of translating early asymmetry into morphological form are still unclear. Here, we examined the ability of IHH and FGF8 signaling to regulate digital chondrogenesis, by implanting protein-loaded beads in the interdigital space singly and in combination. We found that IHH protein induced an elongated digit and that FGF8 protein blocked the terminal phalange formation. Molecular marker analysis showed that IHH expanded Sox9 expression in mesenchymal cells possibly through up-regulated FGF8 expression. Application of both IHH and FGF8 protein induced a large terminal phalange. These results suggest that both enhanced IHH and FGF8 signaling are required for the development of additional cartilage element in limbs. IHH and FGF8 maybe play different roles and act synergistically to promote chondrogenesis during digit primordia elongation.
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Directory of Open Access Journals (Sweden)
Fernando José Barbin Laurindo
2003-12-01
Full Text Available Apesar de o conceito de computador pessoal (personal computer - PC ter surgido nos anos 70, essa indústria realmente deslanchou somente após o lançamento do IBM PC, em 1981. Por meio de uma agressiva estratégia de outsourcing, a IBM rapidamente conquistou o mercado, mas esta estratégia também causou perda de competências internas para seus principais parceiros, Intel e Microsoft, bem como outros revendedores autônomos. No Brasil, atualmente, a indústria de PCs está relegada à montagem de kits importados e também à manufatura das etapas finais do processo de produção de componentes, com pouco valor agregado localmente. Após o término da reserva de mercado, marcado pela súbita abertura aos concorrentes externos, houve desmantelamento da indústria brasileira de PCs e de semicondutores, nos elos de maior valor agregado dessa cadeia. Para obter inserção nas cadeias globais, as empresas brasileiras precisam atingir qualificação nos critérios de desempenho, a fim de participar dos processos de outsourcing. Este artigo visa, por meio de um aparato teórico que relaciona aspectos de outsourcing, inovação, valor e evolução da indústria de PCs, a investigar os impactos desses aspectos na competitividade da indústria de PCs do Brasil e as repercussões para seu crescimento e inserção no mercado global. A abordagem metodológica adotada foi estudo de múltiplos casos, com os seguintes critérios de seleção: diferentes papéis na cadeia de valor, grau de verticalização, principal mercado visado e tamanho da empresa.Although the personal computer (PC appeared in the seventies, this industry really boomed only after IBM launched its PC, in 1981. Through an aggressive outsourcing strategy, IBM rapidly conquered the market, but this strategy also caused lost of internal competences to its main partners, Intel and Microsoft and also to autonomous vendors. Many PC manufacturers have appeared since then. In Brazil, nowadays, PC
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Ichikawa, Shoji; Sorenson, Andrea H; Austin, Anthony M; Mackenzie, Donald S; Fritz, Timothy A; Moh, Akira; Hui, Siu L; Econs, Michael J
2009-06-01
Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia. The disease is caused by inactivating mutations in fibroblast growth factor 23 (FGF23), Klotho (KL), and uridine diphosphate-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). In vitro studies indicate that GALNT3 O-glycosylates a phosphaturic hormone, FGF23, and prevents its proteolytic processing, thereby allowing secretion of intact FGF23. In this study we generated mice lacking the Galnt3 gene, which developed hyperphosphatemia without apparent calcifications. In response to hyperphosphatemia, Galnt3-deficient mice had markedly increased Fgf23 expression in bone. However, compared with wild-type and heterozygous littermates, homozygous mice had only about half of circulating intact Fgf23 levels and higher levels of C-terminal Fgf23 fragments in bone. Galnt3-deficient mice also exhibited an inappropriately normal 1,25-dihydroxyvitamin D level and decreased alkaline phosphatase activity. Furthermore, renal expression of sodium-phosphate cotransporters and Kl were elevated in Galnt3-deficient mice. Interestingly, there were sex-specific phenotypes; only Galnt3-deficient males showed growth retardation, infertility, and significantly increased bone mineral density. In summary, ablation of Galnt3 impaired secretion of intact Fgf23, leading to decreased circulating Fgf23 and hyperphosphatemia, despite increased Fgf23 expression. Our findings indicate that Galnt3-deficient mice have a biochemical phenotype of tumoral calcinosis and provide in vivo evidence that Galnt3 plays an essential role in proper secretion of Fgf23 in mice.
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Energy Technology Data Exchange (ETDEWEB)
Katoh-Semba, R.; Oohira, A.; Sano, M.; Watanabe, K.; Kitajima, S.; Kashiwamata, S.
1989-03-01
PC12D cells, a new subline of conventional PC12 cells, respond not only to nerve growth factor but also to cyclic AMP by extending their neurites. These cells are flat in shape and are similar in appearance to PC12 cells that have been treated with nerve growth factor for a few days. In both cell lines, we have characterized the glycosaminoglycans, the polysaccharide moieties of proteoglycans, which are believed to play an important role in cell adhesion and in cell morphology. Under the present culture conditions, only chondroitin sulfate was detected in the media from PC12 and PC12D cells, whereas both chondroitin sulfate and heparan sulfate were found in the cell layers. The levels of cell-associated heparan sulfate and chondroitin sulfate were about twofold and fourfold higher in PC12D cells than in PC12 cells, respectively. Compared to PC12 cells, the amounts of (/sup 35/S)sulfate incorporated for 48 h into chondroitin sulfate were twofold lower but those into heparan sulfate were 35% higher in PC12D cells. The amount of chondroitin sulfate released by PC12D cells into the medium was about a half of that released by PC12 cells. The ratio of (/sup 35/S)sulfate-labeled heparan sulfate to chondroitin sulfate was 6.2 in PC12D cells and 2.2 in PC12 cells. These results suggest that there may be some correlation between the increase in content of glycosaminoglycans and the change in cell morphology, which is followed by neurite outgrowth.
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Directory of Open Access Journals (Sweden)
Janette Brunstein
Full Text Available O objetivo nesta pesquisa é entender os significados atribuídos às experiências de inclusão de gestores e PcDs (Pessoas com Deficiência a eles subordinadas nas relações de trabalho cotidianas em grandes organizações. Seguindo a proposta dos estudos qualitativos básicos ou genéricos de Merriam, conduziu-se um estudo em cinco empresas paulistas que adotam políticas formais de diversidade e inclusão: três instituições do setor financeiro (um banco nacional privado, um banco multinacional e um banco nacional público, uma empresa do mercado editorial e uma organização pública do setor de transporte. Embora os resultados apontem que, a despeito de todos os avanços, o discurso e a prática da inclusão nas organizações nem sempre conciliam o respeito à diferença com igualdade de oportunidades, e que as experiências se concentram no paradigma de suporte e serviços, muito mais do que no paradigma de empoderamento da PcD, o estudo contribui para o entendimento do que é inclusão e quais suas implicações para PcDs, gestores e para a própria organização.
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Expression, Purification and Characterization of Recombinant Canine FGF21 in Escherichia coli.
Zheng, Zhong; Yang, Chengjun; Yin, Ruofeng; Jiang, Jinxi; He, Haiting; Wang, Xinxin; Kan, Mujie; Xiao, Yechen
2016-01-01
The canine metabolic diseases, such as obesity and diabetes, have become a worldwide problem. Fibroblast growth factor 21 (FGF21) is a potent regulator which has many biological functions relative to metabolism regulation. It suggests that FGF21 plays important roles in regulating canine metabolic diseases. To acquire the recombinant canine FGF21 (rcFGF21) in Escherichia coli, the recombinant bacteria were induced by 0.5 mM IPTG for 16 hours at 16 °C, and the rcFGF21 protein was purified by Ni-NTA. 8 mg rcFGF21 was acquired from one liter bacteria. The rcFGF21 protein has specific immunoblot reactivity against anti-FGF21 and anti-His antibody. The in vivo experimental result showed that rcFGF21 can significantly reduce plasma glucose of STZ-induced diabetic mice.
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FGF21 as a hepatokine, adipokine, and myokine in metabolism and diseases
Directory of Open Access Journals (Sweden)
Nobuyuki eItoh
2014-07-01
Full Text Available Fibroblast growth factor (FGF family members are mostly secreted as signaling proteins with diverse functions in development and metabolism. FGF21 is a unique FGF with metabolic, but not proliferative activities. FGF21 is mostly induced by different kinds of stress and acts though FGF receptor 1c with β−Klotho as a cofactor in an endocrine or, in parts, autocirne/paracrine manner. Hepatic FGF21 directly acts on white adipocytes to inhibit lipolysis and acts through the brain to increase systemic glucocorticoid levels and suppress physical activity in response to starvation. It also protects against dioxin toxicity. Adipocytic FGF21 induces the browning of white adipose tissue (WAT and activates brown adipocytes in response to cold exposure. It also acts as an upstream effector of adiponectin in white adipocytes. Myocytic FGF21 protects against diet-induced obesity and insulin resistance, induces the browning of WAT, and protects against cardiac hypertrophy. In addition, Fgf21 polymorphisms are possibly related with metabolic diseases and FGF21 are biomarker of metabolic diseases. These findings indicate that FGF21 plays roles as a hepatokine, adipokine, and myokine in metabolism, injury protection, and diseases.
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Alvarez-Sola, Gloria; Uriarte, Iker; Latasa, M Ujue; Fernandez-Barrena, Maite G; Urtasun, Raquel; Elizalde, Maria; Barcena-Varela, Marina; Jiménez, Maddalen; Chang, Haisul C; Barbero, Roberto; Catalán, Victoria; Rodríguez, Amaia; Frühbeck, Gema; Gallego-Escuredo, José M; Gavaldà-Navarro, Aleix; Villarroya, Francesc; Rodriguez-Ortigosa, Carlos M; Corrales, Fernando J; Prieto, Jesus; Berraondo, Pedro; Berasain, Carmen; Avila, Matias A
2017-10-01
Fibroblast growth factor 15/19 (FGF15/19), an enterokine that regulates synthesis of hepatic bile acids (BA), has been proposed to influence fat metabolism. Without FGF15/19, mouse liver regeneration after partial hepatectomy (PH) is severely impaired. We studied the role of FGF15/19 in response to a high fat diet (HFD) and its regulation by saturated fatty acids. We developed a fusion molecule encompassing FGF19 and apolipoprotein A-I, termed Fibapo, and evaluated its pharmacological properties in fatty liver regeneration. Fgf15 -/- mice were fed a HFD. Liver fat and the expression of fat metabolism and endoplasmic reticulum (ER) stress-related genes were measured. Influence of palmitic acid (PA) on FGF15/19 expression was determined in mice and in human liver cell lines. In vivo half-life and biological activity of Fibapo and FGF19 were compared. Hepatoprotective and proregenerative activities of Fibapo were evaluated in obese db/db mice undergoing PH. Hepatosteatosis and ER stress were exacerbated in HFD-fed Fgf15 -/- mice. Hepatic expression of Pparγ2 was elevated in Fgf15 -/- mice, being reversed by FGF19 treatment. PA induced FGF15/19 expression in mouse ileum and human liver cells, and FGF19 protected from PA-mediated ER stress and cytotoxicity. Fibapo reduced liver BA and lipid accumulation, inhibited ER stress and showed enhanced half-life. Fibapo provided increased db/db mice survival and improved regeneration upon PH. FGF15/19 is essential for hepatic metabolic adaptation to dietary fat being a physiological regulator of Pparγ2 expression . Perioperative administration of Fibapo improves fatty liver regeneration. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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FAP finds FGF21 easy to digest
DEFF Research Database (Denmark)
Gillum, Matthew P; Potthoff, Matthew J
2016-01-01
Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates carbohydrate and lipid metabolism. In humans, circulating FGF21 is inactivated by proteolytic cleavage of its C-terminus, thereby preventing signalling through a receptor complex. The mechanism for this cleavage event and ...
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FGF-dependent metabolic control of vascular development
Yu, Pengchun; Alves, Tiago C.; Fang, Jennifer S.; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G.; Hirschi, Karen K.; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W.; Eichmann, Anne; Potente, Michael; Simons, Michael
2017-01-01
Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are of importance to these processes1. While much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signaling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signaling inputs results in decreased glycolysis leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/r3 double mutant mice while HK2 overexpression partially rescues the defects caused by suppression of FGF signaling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. PMID:28467822
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Genetic rescue of glycosylation-deficient Fgf23 in the Galnt3 knockout mouse.
Ichikawa, Shoji; Gray, Amie K; Padgett, Leah R; Allen, Matthew R; Clinkenbeard, Erica L; Sarpa, Nicole M; White, Kenneth E; Econs, Michael J
2014-10-01
Fibroblast growth factor 23 (FGF23) is a hormone that inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D biosynthesis. The FGF23 subtilisin-like proprotein convertase recognition sequence ((176)RHTR(179)↓) is protected by O-glycosylation through ppGalNAc-T3 (GALNT3) activity. Thus, inactivating GALNT3 mutations render FGF23 susceptible to proteolysis, thereby reducing circulating intact hormone levels and leading to hyperphosphatemic familial tumoral calcinosis. To further delineate the role of glycosylation in the Fgf23 function, we generated an inducible FGF23 transgenic mouse expressing human mutant FGF23 (R176Q and R179Q) found in patients with autosomal dominant hypophosphatemic rickets (ADHR) and bred this animal to Galnt3 knockout mice, a model of familial tumoral calcinosis. Due to the low intact Fgf23 level, Galnt3 knockout mice with wild-type Fgf23 alleles were hyperphosphatemic. In contrast, carriers of the mutant FGF23 transgene, regardless of Galnt3 mutation status, had significantly higher serum intact FGF23, resulting in severe hypophosphatemia. Importantly, serum phosphorus and FGF23 were comparable between transgenic mice with or without normal Galnt3 alleles. To determine whether the presence of the ADHR mutation could improve biochemical and skeletal abnormalities in Galnt3-null mice, these mice were also mated to Fgf23 knock-in mice, carrying heterozygous or homozygous R176Q ADHR Fgf23 mutations. The knock-in mice with functional Galnt3 had normal Fgf23 but were slightly hypophosphatemic. The stabilized Fgf23 ADHR allele reversed the Galnt3-null phenotype and normalized total Fgf23, serum phosphorus, and bone Fgf23 mRNA. However, the skeletal phenotype was unaffected. In summary, these data demonstrate that O-glycosylation by ppGaINAc-T3 is only necessary for proper secretion of intact Fgf23 and, once secreted, does not affect Fgf23 function. Furthermore, the more stable Fgf23 ADHR mutant protein could normalize serum phosphorus
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Directory of Open Access Journals (Sweden)
José Humberto Vilar da Silva
2001-12-01
Full Text Available Níveis de energia metabolizável (EM de 2900, 3100 e 3300 kcal e relações energia: proteína (EM: PB de 128, 148, 168 e 188 kcal/%PB foram avaliados em frangos de corte machos de 22 a 42 dias de idade, distribuídos ao acaso em um esquema fatorial 3 x 4, com quatro repetições de 18 aves por tratamento. O aumento da relação EM: PB apresentou efeito linear decrescente sobre consumo de ração, peso vivo aos 42 dias, ganho de peso, consumo de proteína, consumo de energia metabolizável, peso da carcaça, peso da carne de peito, peso de pernas (coxa+sobrecoxa e elevou linearmente a porcentagem de gordura abdominal na carcaça em todos os níveis de energia. A relação EM: PB de 148 (20,95% PB dentro do nível de EM de 3100 kcal atende às exigências de ótimo crescimento de frangos de corte de 22 a 42 dias de idade, enquanto a relação EM: PB de 188 dentro de todos os níveis de energia estudados se mostrou inadequada. Em virtude do aumento do custo da ração, a redução da relação EM: PB, em rações práticas, deve ser avaliada para otimizar o modelo de produção em que a qualidade da carcaça também deve ser considerada.Levels of metabolizable energy (ME of 2,900, 3,100 and 3,300 kcal and energy to protein ratio (EM: PB of 128, 148, 168 and 188 kcal/%CP were evaluated with male broiler chicks from 22 to 42 days of age, assigned to a completely randomized 3 x 4 factorial design, where each treatment had four replications of 18 birds. Increasing the ME: CP ratio resulted in linear decreasing effect on feed intake, live weight, weight gain, crude protein intake, energy intake, carcass weight, breast meat weight, drumsticks weight and linearly increased abdominal fat percentage within each level of energy. The 148 ME:CP ratio (20,95% CP in the level of 3100 kcal ME met the broilers requirements to optimum growth from 22 to 42 days of age, while 188 ME:CP ratio was inadequate. Because of the high costs, decreasing EM: PB ratio must be
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Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates
Directory of Open Access Journals (Sweden)
Anne-Marie Lundsgaard
2017-01-01
plasma marker of hepatic de novo lipogenesis C16:1 n−7 FA (p < 0.01 was observed together with 101% increased plasma TG concentration (p < 0.001 in association with CHO intake and increased plasma FGF21 concentration. Conclusion: Excess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais. Keywords: FGF21, Diet, Carbohydrates, Lipolysis, Liver
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Validación de la causa básica de defunción en las muertes que requieren intervención medicolegal
Directory of Open Access Journals (Sweden)
Mercè Gotsens
2011-01-01
Full Text Available Fundamento, Las defunciones por causas externas requieren exámenes complementarios para determinar la causa demuerte. Si no se incorporan estos resultados a los registros de mortalidad estas causas pueden quedar mal clasificadas. El objetivo del estudio es validar la causa básica de defunción del Registro de Mortalidad con la obtenida de las fuentes forenses,en Barcelona entre los años 2004 y 2006. Métodos, Diseño transversal. La población de estudio son los fallecidos residentes en Barcelona con intervención medicolegal entre 2004 y 2006. Las fuentes de información son el Registro de Mortalidad y el archivo de patología forense delInstituto de Medicina Legal de Catalunya (IMLC (estándar de comparación. Las variables son la causa de defunción, el sexoy la edad. Se calcula la sensibilidad, el porcentaje de confirmación (PC y sus intervalos de confianza al 95% (IC95%. Resultados, La sensibilidad de las causas externas es 59,7% (IC95%,56,5-62,9 y el PC 96,7% (IC95%,94,8-98,0. Las lesiones por tráfico, las intoxicaciones y los suicidios estánsubnotificados en el Registro de Mortalidad siendo la sensibilidad inferior al 45% y el PC superior al 80%. Las causas maldefinidas están sobrenotificadas siendo la sensibilidad de 89,2% (IC95%,83,4-93,4 y el PC de 28,0% (IC95%,24,232,1. No hay diferencias por sexo y edad. Conclusiones, La validez de las causas externas del Registro de Mortalidad es escasa por la subnotificación y el elevadoporcentaje de causas mal definidas. Según los resultados, incorporar la información de las fuentes forenses al Registro deMortalidad aumenta la calidad de las estadísticas de mortalidad.
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BMP4 and FGF3 haplotypes increase the risk of tendinopathy in volleyball athletes.
Salles, José Inácio; Amaral, Marcus Vinícius; Aguiar, Diego Pinheiro; Lira, Daisy Anne; Quinelato, Valquiria; Bonato, Letícia Ladeira; Duarte, Maria Eugenia Leite; Vieira, Alexandre Rezende; Casado, Priscila Ladeira
2015-03-01
To investigate whether genetic variants can be correlated with tendinopathy in elite male volleyball athletes. Case-control study. Fifteen single nucleotide polymorphisms within BMP4, FGF3, FGF10, FGFR1 genes were investigated in 138 elite volleyball athletes, aged between 18 and 35 years, who undergo 4-5h of training per day: 52 with tendinopathy and 86 with no history of pain suggestive of tendinopathy in patellar, Achilles, shoulder, and hip abductors tendons. The clinical diagnostic criterion was progressive pain during training, confirmed by magnetic resonance image. Genomic DNA was obtained from saliva samples. Genetic markers were genotyped using TaqMan real-time PCR. Chi-square test compared genotypes and haplotype differences between groups. Multivariate logistic regression analyzed the significance of covariates and incidence of tendinopathy. Statistical analysis revealed participant age (p=0.005) and years of practice (p=0.004) were risk factors for tendinopathy. A significant association between BMP4 rs2761884 (p=0.03) and tendinopathy was observed. Athletes with a polymorphic genotype have 2.4 times more susceptibility to tendinopathy (OR=2.39; 95%CI=1.10-5.19). Also, association between disease and haplotype TTGGA in BMP4 (p=0.01) was observed. The FGF3 TGGTA haplotype showed a tendency of association with tendinopathy (p=0.05), and so did FGF10 rs900379. FGFR1 showed no association with disease. These findings indicate that haplotypes in BMP4 and FGF3 genes may contribute to the tendon disease process in elite volleyball athletes. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.
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Sanchez, Julio
2003-01-01
Part I - Graphics Fundamentals PC GRAPHICS OVERVIEW History and Evolution Short History of PC Video PS/2 Video Systems SuperVGA Graphics Coprocessors and Accelerators Graphics Applications State-of-the-Art in PC Graphics 3D Application Programming Interfaces POLYGONAL MODELING Vector and Raster Data Coordinate Systems Modeling with Polygons IMAGE TRANSFORMATIONS Matrix-based Representations Matrix Arithmetic 3D Transformations PROGRAMMING MATRIX TRANSFORMATIONS Numeric Data in Matrix Form Array Processing PROJECTIONS AND RENDERING Perspective The Rendering Pipeline LIGHTING AND SHADING Lightin
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FY95 software project management plan: TMACS, CASS computer systems
International Nuclear Information System (INIS)
Spurling, D.G.
1994-01-01
The FY95 Work Plan for TMACS and CASS Software Projects describes the activities planned for the current fiscal year. This plan replaces WHC-SD-WM-SDP-008. The TMACS project schedule is included in the TWRS Integrated Schedule
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Directory of Open Access Journals (Sweden)
Phillip A. Sanger
2011-07-01
Full Text Available
Abstract ¾ Many students are uncomfortable with real world engineering problems where needs and requirements must be concretely defined and the selection of design solutions is not black and white. This paper describes a two semester, multi-disciplinary senior capstone project for students from three Engineering and Technology Department programs (electrical engineering, electrical and computer engineering technology, and engineering technology that brings together the tools of project management and the creative product development process into industry sponsored projects. The projects are fully integrated with the Center for Rapid Product Realization with its dual goals of economic development and enhanced learning. The stage/gate development process is used with six formal reviews covering the development of the proposal through to the fabrication and testing of the project’s output. Over the past four years thirty five (35 projects have been undertaken with students getting an exciting
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FGF2 mediates DNA repair in epidermoid carcinoma cells exposed to ionizing radiation
International Nuclear Information System (INIS)
Marie, Melanie; Hafner, Sophie; Moratille, Sandra; Vaigot, Pierre; Rigaud, Odile; Martin, Michele T.; Mine, Solene
2012-01-01
Fibroblast growth factor 2 (FGF2) is a well-known survival factor. However, its role in DNA repair is poorly documented. The present study was designed to investigate in epidermoid carcinoma cells the potential role of FGF2 in DNA repair. The side population (SP) with cancer stem cell-like properties and the main population (MP) were isolated from human A431 squamous carcinoma cells. Radiation-induced DNA damage and repair were assessed using the alkaline comet assay. FGF2 expression was quantified by enzyme linked immunosorbent assay (ELISA). SP cells exhibited rapid repair of radiation induced DNA damage and a high constitutive level of nuclear FGF2. Blocking FGF2 signaling abrogated the rapid DNA repair. In contrast, in MP cells, a slower repair of damage was associated with low basal expression of FGF2. Moreover, the addition of exogenous FGF2 accelerated DNA repair in MP cells. When irradiated, SP cells secreted FGF2, whereas MP cells did not. FGF2 was found to mediate DNA repair in epidermoid carcinoma cells. We postulate that carcinoma stem cells would be intrinsically primed to rapidly repair DNA damage by a high constitutive level of nuclear FGF2. In contrast, the main population with a low FGF2 content exhibits a lower repair rate which can be increased by exogenous FGF2. (authors)
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Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses.
Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu
2017-08-01
Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses. Recent studies have revealed that FGF21 treatment can alleviate many age-related metabolic disorders, e.g. atherosclerosis, obesity, type 2 diabetes, and some cardiovascular diseases. In addition, transgenic mice overexpressing FGF21 have an extended lifespan. However, chronic metabolic and stress-related disorders involving inflammatory responses can provoke FGF21 resistance and thus disturb healthy aging process. First, we will describe the role of FGF21 in interorgan energy metabolism and explain how its functions as a stress hormone can improve healthspan. Next, we will examine both the induction of FGF21 expression via the integrated stress response and the molecular mechanism through which FGF21 enhances healthy aging. Finally, we postulate that FGF21 resistance, similarly to insulin resistance, jeopardizes human healthspan and accelerates the aging process. Copyright © 2017 Elsevier B.V. All rights reserved.
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Chalvon-Demersay, Tristan; Even, Patrick C; Tomé, Daniel; Chaumontet, Catherine; Piedcoq, Julien; Gaudichon, Claire; Azzout-Marniche, Dalila
2016-10-01
Fibroblast growth factor 21 (FGF21) is a polypeptide secreted by the liver and involved in several metabolic processes such as thermogenesis and lipid oxidation. The nutritional mechanisms controlling FGF21 production are poorly understood. This study aimed to investigate how dietary carbohydrates and proteins impact FGF21 production and how in turn, FGF21 is involved in the metabolic adaptation to changes in the carbohydrate and protein contents of the diet. For that purpose, we fed 25 male C57BL/6 mice diets composed of different protein and carbohydrate contents (normal-protein and carbohydrate diet (N=9, NPNC), low-protein high-carbohydrate diet (N=8, LPHC), high-protein low-carbohydrate diet (N=8, HPLC) for 3 weeks. We measured liver Fgf21 gene expression, synthesis and secretion as well as different parameters related to energy and glucose metabolism. We also investigated the direct role of amino acids and glucose in the control of Fgf21 gene expression in hepatocyte primary cultures (n=6). In vivo, FGF21 responds acutely to LPHC intake whereas under an HPLC diet, plasma FGF21 circulating levels are low in the fasted and refed states. In hepatocytes, Fgf21 expression was controlled by glucose but not amino acids. Both diets increased the thermic effect of feeding (TEF) and ketogenesis was increased in fasted HPLC mice. The results presented suggest that dietary glucose, rather than amino acids, directly controls FGF21 secretion, and that FGF21 may be involved in the increased TEF response to LPHC. The effects of the HPLC diet on ketogenesis and TEF are probably controlled by other metabolic pathways. Copyright © 2016 Elsevier Inc. All rights reserved.
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Energy Technology Data Exchange (ETDEWEB)
Casaravilla, G.; Chaer, R. [Instituto de Ingenieria Electrica, Facultad de Ingenieria, Universidad de la Republica, Montevideo (Uruguay)
1997-12-31
This paper describes the software Hybrid 95 and how it is used for the design of hybrid systems. As an application example some of the design stages are looked over (determination of the wind resource, simulations for sizing generation/storage and topology) of the Potrerillo installation. Taking into account the site clear ecological connotations, during the design consideration is made of the visual impact that represents the possible wind-generator, therefore several locations and wind-generator heights are studied, even arriving to the wind-generation elimination. [Espanol] Este trabajo describe el software Hybrid 95 y como se utiliza a los efectos del diseno de sistemas hibridos. Como ejemplo de aplicacion se recorren algunas de las etapas del diseno (determinacion del recurso eolico, simulaciones para el dimensionado de generacion/acumulacion y topologia) de la instalacion de Potrerillo. Teniendo en cuenta las claras connotaciones ecologistas del lugar, durante el diseno se tiene presente el impacto visual que representa el eventual aerogenerador por lo que se estudian diversas ubicaciones y alturas de aerogenerador, llegandose incluso a estudiar la eliminacion de la generacion eolica.
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Energy Technology Data Exchange (ETDEWEB)
Casaravilla, G; Chaer, R [Instituto de Ingenieria Electrica, Facultad de Ingenieria, Universidad de la Republica, Montevideo (Uruguay)
1998-12-31
This paper describes the software Hybrid 95 and how it is used for the design of hybrid systems. As an application example some of the design stages are looked over (determination of the wind resource, simulations for sizing generation/storage and topology) of the Potrerillo installation. Taking into account the site clear ecological connotations, during the design consideration is made of the visual impact that represents the possible wind-generator, therefore several locations and wind-generator heights are studied, even arriving to the wind-generation elimination. [Espanol] Este trabajo describe el software Hybrid 95 y como se utiliza a los efectos del diseno de sistemas hibridos. Como ejemplo de aplicacion se recorren algunas de las etapas del diseno (determinacion del recurso eolico, simulaciones para el dimensionado de generacion/acumulacion y topologia) de la instalacion de Potrerillo. Teniendo en cuenta las claras connotaciones ecologistas del lugar, durante el diseno se tiene presente el impacto visual que representa el eventual aerogenerador por lo que se estudian diversas ubicaciones y alturas de aerogenerador, llegandose incluso a estudiar la eliminacion de la generacion eolica.
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Efecto sobre la viabilidad celular de una nueva serie de espirosteroides sintéticos en células PC12
Directory of Open Access Journals (Sweden)
Laura García-Pupo
2013-03-01
Full Text Available Introducción: la diosgenina y sus derivados se han descrito como potentes inhibidores de la proliferación en varias líneas tumorales. Sin embargo otras moléculas relacionadas estructuralmente con dichos derivados, se han reportado como candidatos terapéuticos y otras de ellas se incluyen en alimentos de consumo humano. Objetivo: el presente trabajo evalúa el efecto sobre la viabilidad celular de una nueva serie de espiroesteroides sintéticos derivados de la diosgenina, en células tipo neurales PC12. Métodos: la viabilidad de los cultivos de PC12 se determinó mediante el ensayo de MTT y se calcularon descriptores moleculares teóricos como la lipofilicidad (logP virtual y la superficie de área polar (SAP, con el objetivo de establecer relaciones estructura-actividad. Resultados: nuestros resultados demuestran que solo el acido taurodesoxicólico disminuye de manera significativa la viabilidad celular. Más aun, dicha molécula presenta valores menores y mayores de logP virtual y SAP, respectivamente, respecto al resto de los esteroides de la serie. Conclusiones: los resultados anteriores avalan el estudio del acido taurodesoxicólico como potencial inhibidor de la proliferación celular y al resto de las moléculas de la serie como candidatos neuroprotectores a evaluar en esta misma línea celular y dosis de tratamiento.
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Incorporation of the KERN ECDS-PC software into a project oriented software environment
International Nuclear Information System (INIS)
Oren, W.; Pushor, R.; Ruland, R.
1986-11-01
The Stanford Linear Accelerator Center (SLAC) is in the process of building a new particle collider, the Stanford Linear Collider (SLC). The tunnel which houses the SLC is about 3 km long and contains approximately 1000 magnets. Besides a very precise absolute positioning of these magnets, the alignment of adjacent magnet ends is of particular importance to the success of the whole project. Because of this and the limited time frame, a survey method which was not only reliable and self-checking but also fast had to be developed. Therefore, the concept of MAS (Magnet Alignment System) was developed. This system utilizes the on-line data collection and the rigorous least-squares bundle adjustment of the KERN ECDS-PC system to fulfill these requirements. The ECDS software is embedded in a project tailored software system with modules which take care of: fixture and magnet calibration corrections, the calculation of ideal coordinates and their comparison to measured coordinates, the translation of detected misalignments into the coordinate system of the mechanical adjustments and the control of the adjustments with on-line electronic dial-gauges. This paper gives a brief introduction to the SLC project and some of the survey problems which are unique to this machine. The basic ideas of the KERN ECDS-PC system are explained and a discussion of the practical aspects, such as targeting and set-ups, are given. MAS and its modules are explained in detail
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IBM PC/IX operating system evaluation plan
Dominick, Wayne D. (Editor); Granier, Martin; Hall, Philip P.; Triantafyllopoulos, Spiros
1984-01-01
An evaluation plan for the IBM PC/IX Operating System designed for IBM PC/XT computers is discussed. The evaluation plan covers the areas of performance measurement and evaluation, software facilities available, man-machine interface considerations, networking, and the suitability of PC/IX as a development environment within the University of Southwestern Louisiana NASA PC Research and Development project. In order to compare and evaluate the PC/IX system, comparisons with other available UNIX-based systems are also included.
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METHANE de-NOX FOR UTILITY PC BOILERS
Energy Technology Data Exchange (ETDEWEB)
Joseph Rabovitser
2000-07-05
The overall project objective is the development and validation of an innovative combustion system, based on a novel coal preheating concept prior to combustion, that can reduce NO{sub x} emissions to 0.15 lb/million Btu or less on utility pulverized coal (PC) boilers. This NO{sub x} reduction should be achieved without loss of boiler efficiency or operating stability, and at more than 25% lower levelized cost than state-of-the-art SCR technology. A further objective is to make this technology ready for full-scale commercial deployment by 2002-2003 in order to meet an anticipated market demand for NO{sub x} reduction technologies resulting from the EPA's NO{sub x} SIP call.
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DOE-EERC jointly sponsored research program
Energy Technology Data Exchange (ETDEWEB)
Hendrikson, J.G.; Sondreal, E.A.
1999-09-01
U.S. Department of Energy (DOE) Cooperative Agreement DE-FC21-93MC30098 funded through the Office of Fossil Energy and administered at the Federal Energy Technology Center (FETC) supported the performance of a Jointly Sponsored Research Program (JSRP) at the Energy and Environmental Research Center (EERC) with a minimum 50% nonfederal cost share to assist industry in commercializing and effectively applying efficient, nonpolluting energy technologies that can compete effectively in meeting market demands for clean fuels, chemical feedstocks, and electricity in the 21st century. The objective of the JSRP was to advance the deployment of advanced technologies for improving energy efficiency and environmental performance through jointly sponsored research on topics that would not be adequately addressed by the private sector alone. Examples of such topics include the barriers to hot-gas cleaning impeding the deployment of high-efficiency power systems and the search for practical means for sequestering CO{sub 2} generated by fossil fuel combustion. The selection of particular research projects was guided by a combination of DOE priorities and market needs, as provided by the requirement for joint venture funding approved both by DOE and the private sector sponsor. The research addressed many different energy resource and related environmental problems, with emphasis directed toward the EERC's historic lead mission in low-rank coals (LRCs), which represent approximately half of the U.S. coal resources in the conterminous states, much larger potential resources in Alaska, and a major part of the energy base in the former U.S.S.R., East Central Europe, and the Pacific Rim. The Base and JSRP agreements were tailored to the growing awareness of critical environmental issues, including water supply and quality, air toxics (e.g., mercury), fine respirable particulate matter (PM{sub 2.5}), and the goal of zero net CO{sub 2} emissions.
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Fibroblast Growth Factor 23 (FGF23 and Disorders of Phosphate Metabolism
Directory of Open Access Journals (Sweden)
Tasuku Saito
2009-01-01
Full Text Available Derangements in serum phosphate level result in rickets/osteomalacia or ectopic calcification indicating that healthy people without these abnormalities maintain serum phosphate within certain ranges. These results indicate that there must be a regulatory mechanism of serum phosphate level. Fibroblast growth factor 23 (FGF23 was identified as the last member of FGF family. FGF23 is produced by bone and reduces serum phosphate level by suppressing phosphate reabsorption in proximal tubules and intestinal phosphate absorption through lowering 1,25-dihydroxyvitamin D level. It has been shown that excess and deficient actions of FGF23 result in hypophosphatemic rickets/osteomalacia and hyperphosphatemic tumoral calcinosis, respectively. These results indicate that FGF23 works as a hormone, and several disorders of phosphate metabolism can be viewed as endocrine diseases. It may become possible to treat patients with abnormal phosphate metabolism by pharmacologically modifying the activity of FGF23.
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Peacock, Munro; Gray, Amie K.; Padgett, Leah R.; Hui, Siu L.; Econs, Michael J.
2011-01-01
Context: In autosomal dominant hypophosphatemic rickets (ADHR), fibroblast growth factor 23 (FGF23) resists cleavage, causing increased plasma FGF23 levels. The clinical phenotype includes variable onset during childhood or adulthood and waxing/waning of hypophosphatemia. Delayed onset after puberty in females suggests iron status may be important. Objective: Studies were performed to test the hypothesis that plasma C-terminal and intact FGF23 concentrations are related to serum iron concentrations in ADHR. Design and Setting: Cross-sectional and longitudinal studies of ADHR and a cross-sectional study in healthy subjects were conducted at an academic medical center. Participants: Participants included 37 subjects with ADHR mutations from four kindreds and 158 healthy adult controls. Main Outcome Measure: The relationships of serum iron concentrations with plasma C-terminal and intact FGF23 concentrations were evaluated. Results: Serum phosphate and 1,25-dihydroxyvitamin D correlated negatively with C-terminal FGF23 and intact FGF23 in ADHR but not in controls. Serum iron was negatively correlated to both C-terminal FGF23 (r = −0.386; P < 0.05) and intact FGF23 (r = −0.602; P < 0.0001) in ADHR. However, control subjects also demonstrated a negative relationship of serum iron with C-terminal FGF23 (r = −0.276; P < 0.001) but no relationship with intact FGF23. Longitudinally in ADHR subjects, C-terminal FGF23 and intact FGF23 concentrations changed negatively with iron concentrations (P < 0.001 and P = 0.055, respectively), serum phosphate changed negatively with C-terminal FGF23 and intact FGF23 (P < 0.001), and there was a positive relationship between serum iron and phosphate (P < 0.001). Conclusions: Low serum iron is associated with elevated FGF23 in ADHR. However, in controls, low serum iron was also associated with elevated C-terminal FGF23, but not intact FGF23, suggesting cleavage maintains homeostasis despite increased FGF23 expression. PMID:21880793
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Energy Technology Data Exchange (ETDEWEB)
Jaimot Jimenez, J. J.; Imbert, J. J.
2013-07-01
This paper describes the project of changing units of air conditioning in the Asco NPP currently used R22 as coolant. The project has a powerful, affecting 37 units, of which more than half are Clase1E. The document describes the process of sizing, scope of change and solutions adopted for this change of design.
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Hepatic Fgf21 Expression Is Repressed after Simvastatin Treatment in Mice.
Directory of Open Access Journals (Sweden)
Panos Ziros
Full Text Available Fibroblast growth factor 21 (Fgf21 is a hormone with emerging beneficial roles in glucose and lipid homeostasis. The interest in Fgf21 as a potential antidiabetic drug and the factors that regulate its production and secretion is growing. Statins are the most widely prescribed drug for the treatment of dyslipidemia. However, the function of statins is not limited to the lowering of cholesterol as they are associated with pleiotropic actions such as antioxidant, anti-inflammatory and cytoprotective effects. The recently described effect of statins on mitochondrial function and the induction of Fgf21 by mitochondrial stress prompted us to investigate the effect of statin treatment on Fgf21 expression in the liver. To this end, C57BL6J male mice and primary mouse hepatocytes were treated with simvastatin, and Fgf21 expression was subsequently assessed by immunoblotting and quantitative real-time PCR. Hepatic Fgf21 protein and mRNA and circulating levels of FGF21significantly decreased in mice that had received simvastatin in their food (0.1% w/w for 1 week. This effect was also observed with simvastatin doses as low as 0.01% w/w for 1 week or following 2 intraperitoneal injections within a single day. The reduction in Fgf21 mRNA levels was further verified in primary mouse hepatocytes, indicating that the effect of simvastatin is cell autonomous. In conclusion, simvastatin treatment reduced the circulating and hepatic Fgf21 levels and this effect warrants further investigation with reference to its role in metabolism.
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International Nuclear Information System (INIS)
1986-11-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the research program on reactor safety (RS-projects) are sponsored by the Federal Ministry for Research and Technology (BMFT). Objective of this program is to investigate in greater detail the safety margins of nuclear power plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks also projects on the safety of advanced reactors are sponsored by the BMFT. The individual reports are classified according to the research program on the safety of LWRs 1977-1980 of the BMFT. Another table of contents uses the same classification system as applied in the nuclear safety index of the CEC (Commission of the European Communities) and the OECD (Organization for Economic Cooperation and Development). The reports are arranged in the sequence of their project numbers. (orig./HP) [de
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International Nuclear Information System (INIS)
1986-06-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of his research program on reactor safety (RS-projects) are sponsored by the Federal Ministry for Research and Technology (BMFT). Objective of this program is to investigate in greater detail the safety margins of nuclear power plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks also projects on the safety of advanced reactors are sponsored by the BMFT. The individual reports are classified according to the research program on the safety of LWRs 1977-1980 of the BMFT. Another table of contents uses the same classification system as applied in the nuclear safety index of the CEC (Commission of the European Communities) and the OECD (Organization for Economic Cooperation and Development). The reports are arranged in the sequence of their project numbers. (orig./HP) [de
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Directory of Open Access Journals (Sweden)
João Batista Silva Junior
2014-05-01
Full Text Available O artigo descreve o método de avaliação de risco potencial em serviços de hemoterapia (MARPSH aplicado pela Vigilância Sanitária (VISA no Brasil. Esse instrumento permite a identificação de riscos potenciais por meio do mapeamento dos multicritérios de controle e modelação das preferências para tomada de decisão, inserindo-o no âmbito da gestão proativa do risco. O MARPSH estrutura-se em 471 itens de controle, sendo 50% relacionados a riscos ao produto, 25% ao paciente, 17% ao doador e 8% ao trabalhador do serviço. Cada risco identificado é categorizado quanto à severidade, sua probabilidade e sua possibilidade de dano. Os sistemas analíticos utilizam a atribuição de duas ponderações, uma na valoração dos itens de controle e outra se refere à complexidade dos procedimentos. A relação entre a pontuação alcançada e a pontuação máxima possível origina o indicador Proporção de Controle (PC, pelo qual o risco potencial é classificado em Baixo (PC ≥ 95%, Médio-Baixo (80% ≤ PC < 95%, Médio (70% ≤ PC < 80%, Médio-Alto (60% ≤ PC < 70% e Alto (PC < 60%. A utilização do MARPSH permite o monitoramento e o controle da redução dos riscos e, consequentemente, o incremento da segurança transfusional. ----------------------------------------------------------------------- This article describes the method for the evaluation of potential risks in hemotherapy services (MARPSH applied by the Brazilian Health Surveillance Agency. It allows the identification of potential risks by mapping them for advanced control and modeling the preferences for decision making as a proactive risk management activity. The MARPSH structure is composed by 471 control items, being 50% related to risks for the product, 25% for the patient, 17% for the donor and 8% for the worker. Each identified inadequacy is categorized by its severity, its probability and relatively of a possibility of a hazard. For its analysis, the system adopted
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[Anti-FGF23 antibody therapy for patients with tumor-induced osteomalacia].
Kinoshita, Yuka; Fukumoto, Seiji
2014-08-01
Tumor-induced osteomalacia (TIO) is a disease caused by fibroblast growth factor 23 (FGF23) secreted from the causative tumor. This disease is cured by complete surgical removal of the tumor. However, there are several difficult cases in which the responsible tumors cannot be found, are incompletely removed, or relapse after the surgery. Anti-FGF23 antibody is being studied as a novel therapy for FGF23-related hypophosphatemic diseases. The efficacy of anti-FGF23 antibodies were confirmed using a murine model of X-linked hypophosphatemic rickets (XLHR) , which is the most common heritable form of FGF23-related hypophosphatemic disease. In addition, results of phase I study of single injection of humanized anti-FGF23 antibody for adult patients with XLHR were recently published and the safety and effectiveness of this antibody was shown. This antibody therapy may be useful for patients with TIO with similar pathogenesis to that of XLHR.
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Zhou, Mei; Learned, R. Marc; Rossi, Stephen J.; DePaoli, Alex M.; Tian, Hui
2017-01-01
Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease for which no approved therapies are available. Despite intensive research, the cellular mechanisms that mediate NAFLD pathogenesis and progression are poorly understood. Although obesity, diabetes, insulin resistance, and related metabolic syndrome, all consequences of a Western diet lifestyle, are well‐recognized risk factors for NAFLD development, dysregulated bile acid metabolism is emerging as a novel mechanism contributing to NAFLD pathogenesis. Notably, NAFLD patients exhibit a deficiency in fibroblast growth factor 19 (FGF19), an endocrine hormone in the gut–liver axis that controls de novo bile acid synthesis, lipogenesis, and energy homeostasis. Using a mouse model that reproduces the clinical progression of human NAFLD, including the development of simple steatosis, nonalcoholic steatohepatitis (NASH), and advanced “burnt‐out” NASH with hepatocellular carcinoma, we demonstrate that FGF19 as well as an engineered nontumorigenic FGF19 analogue, M70, ameliorate bile acid toxicity and lipotoxicity to restore liver health. Mass spectrometry‐based lipidomics analysis of livers from mice treated with FGF19 or M70 revealed significant reductions in the levels of toxic lipid species (i.e., diacylglycerols, ceramides and free cholesterol) and an increase in levels of unoxidized cardiolipins, an important component of the inner mitochondrial membrane. Furthermore, treatment with FGF19 or M70 rapidly and profoundly reduced levels of liver enzymes, resolved the histologic features of NASH, and enhanced insulin sensitivity, energy homeostasis, and lipid metabolism. Whereas FGF19 induced hepatocellular carcinoma formation following prolonged exposure in these mice, animals expressing M70 showed no evidence of liver tumorigenesis in this model. Conclusion: We have engineered an FGF19 hormone that is capable of regulating multiple pathways to deliver antisteatotic
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[Updates on rickets and osteomalacia: FGF23-mediated hypophosphatemic rickets/osteomalacia].
Michigami, Toshimi
2013-10-01
Some of the hypophosphatemic rickets/osteomalacia are caused by the increased bioactivity of FGF23, and classified into FGF23-mediated hypophosphatemic rickets/osteomalacia. This group includes various disorders such as X-linked, autosomal dominant and autosomal recessive hypophosphatemic rickets/osteomalacia, tumor-induced osteomalacia, and rickets/osteomalacia caused by the administration of iron polymaltose or saccharated ferric oxide. Measurement of serum levels of FGF23 is useful for diagnosis of these conditions. In the adult patients with FGF23-mediated hypophosphatemic rickets/osteomalacia, mineralizing enthesoopathy is an often observed complication.
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14 CFR 152.105 - Sponsors and planning agencies: Airport planning.
2010-01-01
... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Sponsors and planning agencies: Airport planning. 152.105 Section 152.105 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF....105 Sponsors and planning agencies: Airport planning. (a) To be eligible to apply for a project for...
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45 CFR 2551.25 - What are a sponsor's administrative responsibilities?
2010-10-01
... the sponsor organization and/or project service area. (f) Establish risk management policies and... project and carry out its project management responsibilities. (c) Employ a full-time project director to... responsibility for securing maximum and continuing community financial and in-kind support to operate the project...
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A report on the USL NASA/RECON project. Part 2: PC-based R and D in support of IS and R applications
Dominick, Wayne D. (Editor); Chum, Frank Y.; Hall, Philip P.; Moreau, Dennis R.; Triantafyllopoulos, Spiros
1984-01-01
This Working Paper Series entry describes the PC R and D development effort initiated as part of the NASA/RECON Project at the University of Southwestern Louisiana. This effort involves the development of a PC-based environment for the prototyping and evaluation of various tools designed to enhance the interaction between scientists and engineers and remote information systems. The design of PC-based tools for the enhancement of the NASA/RECON university-level courses is described as well as the design of a multi-functional PC-based workstation to support access to and processing of information from local, distributed, and remote sources. Course preparation activities are described in a companion report entitled A Report on the USL NASA/RECON Project: Part 1, the Development of a Transportable, University-Level, IS and R Educational Program, by Suzy Gallagher and Martin Granier, USL/DBMS NASA/RECON Working Paper Series report number DBMS.NASA/RECON-7.
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Kan brugerne finde hvad de leder efter - på både PC og mobil?
DEFF Research Database (Denmark)
Jacobsen, Peter; Skolnik, Karin
nyttigt eller nødvendigt i bestemte situationer. Fælles for den type informationsbehov er, at de i stigende grad søges dækket her-og-nu, på den medie-platform der nu er tilgængelig. Hvor opgaven tidligere typisk blev udskudt, til man kunne sidde stille og roligt om aftenen ved pc´en, søges den nu løst...
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Circulating FGF23 levels in response to acute changes in plasma Ca(2+)
DEFF Research Database (Denmark)
Gravesen, E; Mace, M.L.; Hofman-Bang, J.
2014-01-01
The regulation of fibroblast growth factor 23 (FGF23) synthesis and secretion is still incompletely understood. FGF23 is an important regulator of renal phosphate excretion and has regulatory effects on the calciotropic hormones calcitriol and parathyroid hormone (PTH). Calcium (Ca) and phosphate...... FGF23 levels and whether a close relationship, similar that known for Ca and PTH, exists between Ca and FGF23. Thus, the aim of the present study was to examine whether acute hypercalcemia and hypocalcemia regulate FGF23 levels in the rat. Acute hypercalcemia was induced by an intravenous Ca infusion...... and hypocalcemia by infusion of ethylene glycol tetraacetic acid (EGTA) in normal and acutely parathyroidectomized rats. Intact plasma FGF23 and intact plasma PTH and plasma Ca(2+) and phosphate were measured. Acute hypercalcemia and hypocalcemia resulted as expected in adequate PTH secretory responses. Plasma FGF...
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International Nuclear Information System (INIS)
1977-06-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the Research Program Reactor Safety (RS-projects) are sponsored by the BMFT (Federal Minister for Research and Technology), Bundesminister fuer Forschung und Technologie. Objective of this program is to investigate in greater detail the safety margins of nuclear energy plants and their systems and the further development of safety technology. The GRS (Reactor Safety Association), Gesellschaft fuer Reaktorsicherheit mbH, by order of the BMFT, informs continuously of the status of these investigations within the series 'GRS-F-Forschrittsberichte' (GRS-F-Progress Reports). Each progress report represents a compilation of individual reports about the different projects of the search program. The individual reports are prepared by the contractors themselves as a documentation of their progress in work and published by the GRS-FB (Research Coordination Department), Forschungsbetreuung at the GRS, within the framework of general information of the progress in reactor safety research. Each report describes the work performed, the results and the next steps of the work. The individual reports are attached to the classification system established by the CEC (Commission of the European Communities). The GRS-F-Progress Reports also include a list of the current investigations arranged according to the projects of the BMFT-Research Program Reactor Safety. This compilation, in addition to the LWR-investigations, also contains first contributions on the safety of advanced reactors. (orig.) [de
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International Nuclear Information System (INIS)
1977-11-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the Research Program Reactor Safety (RS-projects) are sponsored by the BMFT (Federal Minister for Research and Technology), Bundesminister fuer Forschung und Technologie. Objective of this program is to investigate in greater detail the safety margins of nuclear energy plants and their systems and the further development of safety technology. The GRS (Reactor Safety Association), Gesellschaft fuer Reaktorsicherheit mbH, by order of BMFT, informs continuously of the status of these investigations within the series 'GRS-F-Fortschrittsberichte' (GRS-F-Progress Reports). Each progress report represents a compilation of individual reports about the different projects of the search program. The individual reports are prepared by the contractors themselves as a documentation of their progress in work and published by the GRS-FB (Research Coordination Department), Forschungsbetreuung at the GRS, within the framework of general information of the progress in reactor safety research. Each report describes the work performed, the results and the next steps of the work. The individual reports are attached to the classification system established by the CEC (Commission of the European Communities). The GRS-F-Progress Reports also include a list of the current investigations arranged according to the projects of the BMFT-Research Program Reactor Safety. This compilation, in addition to the LWR-investigations, also contains first contributions on the safety of advanced reactors. (orig.) [de
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International Nuclear Information System (INIS)
1977-12-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the Research Program Reactor Safety (RS-projects) are sponsored by the BMFT (Federal Minister for Research and Technology), Bundesminister fuer Forschung und Technologie. Objective of this program is to investigate in greater detail the safety margins of nuclear energy plants and their systems and the further development of safety technology. The GRS (Reactor Safety Association), Gesellschaft fuer Reaktorsicherheit mbH, by order of the BMFT, informs continuously of the status of these investigations within the series 'GRS-F-Fortschrittsberichte' (GRS-F-Progress Reports). Each progress report represents a compilation of individual reports about the different projects of the search program. The individual reports are prepared by the contractors themselves as a documentation of their progress in work and published by the GRS-FB (Research Coordination Department), Forschungsbetreuung at the GRS, within the framework of general information of the progress in reactor safety research. Each report describes the work performed, the results and the next steps of the work. The individual reports are attached to the classification system established by the CEC (Commission of the European Communities). The GRS-F-Progress Reports also include a list of the current investigations arranged according to the projects of the BMFT-Research Program Reactor Safety. This compilation, in addition to the LWR-investigations, also contains first contributions on the safety of advanced reactors. (orig.) [de
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Ichikawa, Shoji; Sorenson, Andrea H.; Austin, Anthony M.; Mackenzie, Donald S.; Fritz, Timothy A.; Moh, Akira; Hui, Siu L.; Econs, Michael J.
2009-01-01
Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia. The disease is caused by inactivating mutations in fibroblast growth factor 23 (FGF23), Klotho (KL), and uridine diphosphate-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). In vitro studies indicate that GALNT3 O-glycosylates a phosphaturic hormone, FGF23, and prevents its proteolytic processing, thereby allowing secretion of intact FGF23. In this study we generat...
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Takashi, Yuichi; Kinoshita, Yuka; Hori, Michiko; Ito, Nobuaki; Taguchi, Manabu; Fukumoto, Seiji
2017-05-01
Fibroblast growth factor 23 (FGF23) is a hormone regulating phosphate metabolism. Excessive actions of FGF23 cause several types of FGF23-related hypophosphatemic rickets/osteomalacia. Recently, it was reported that FGF23 levels were independently correlated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD). In addition, FGF23 was also shown to cause cardiac hypertrophy directly acting on cardiomyocytes. However, there is no study indicating the correlation between FGF23 and LVH in adult patients with FGF23-related hypophosphatemic rickets/osteomalacia. Therefore, we examined the existence of LVH in these patients. We recruited consecutive 24 patients with FGF23-related hypophosphatemic diseases. Their serum intact FGF23 levels and the parameters associated with LVH, including left ventricular mass index (LVMI), relative wall thickness (RWT), Sokolow-Lyon voltage, and Cornell product, were measured. The correlations between FGF23 and these parameters were examined. The participants did not show LVH on the whole. In addition, no significant correlation was observed by these examinations. It seems unlikely that FGF23 levels are the apparent determinant of the cardiac mass in patients with FGF23-related hypophosphatemic rickets/osteomalacia.
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ATF4- and CHOP-Dependent Induction of FGF21 through Endoplasmic Reticulum Stress
Directory of Open Access Journals (Sweden)
Xiao-shan Wan
2014-01-01
Full Text Available Fibroblast growth factor 21 (FGF21 is an important endogenous regulator involved in the regulation of glucose and lipid metabolism. FGF21 expression is strongly induced in animal and human subjects with metabolic diseases, but little is known about the molecular mechanism. Endoplasmic reticulum (ER stress plays an essential role in metabolic homeostasis and is observed in numerous pathological processes, including type 2 diabetes, overweight, nonalcoholic fatty liver disease (NAFLD. In this study, we investigate the correlation between the expression of FGF21 and ER stress. We demonstrated that TG-induced ER stress directly regulated the expression and secretion of FGF21 in a dose- and time-dependent manner. FGF21 is the target gene for activating transcription factor 4 (ATF4 and CCAAT enhancer binding protein homologous protein (CHOP. Suppression of CHOP impaired the transcriptional activation of FGF21 by TG-induced ER stress in CHOP−/− mouse primary hepatocytes (MPH, and overexpression of ATF4 and CHOP resulted in FGF21 promoter activation to initiate the transcriptional programme. In mRNA stability assay, we indicated that ER stress increased the half-life of mRNA of FGF21 significantly. In conclusion, FGF21 expression is regulated by ER stress via ATF- and CHOP-dependent transcriptional mechanism and posttranscriptional mechanism, respectively.
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DEFF Research Database (Denmark)
Sørensen, Jens Otto
1996-01-01
Mange virksomheder der bruger pc'er står netop nu over for valget: Skal vi fortsætte med DOS/Windows 3.x som operativsystem, eller skal vi skifte til efterfølgeren Windows 95? Skal vi/kan vi skifte successivt, eller skal det være en "alt eller intet beslutning". Hvornår er det rigtige tidspunkt...... at skifte? Denne artikel vil forsøge at give en baggrundsviden om Windows 95, der kan hjælpe virksomhederne igennem denne beslutningsfase....
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Thrombin induces rapid PAR1-mediated non-classical FGF1 release
International Nuclear Information System (INIS)
Duarte, Maria; Kolev, Vihren; Soldi, Raffaella; Kirov, Alexander; Graziani, Irene; Oliveira, Silvia Marta; Kacer, Doreen; Friesel, Robert; Maciag, Thomas; Prudovsky, Igor
2006-01-01
Thrombin induces cell proliferation and migration during vascular injury. We report that thrombin rapidly stimulated expression and release of the pro-angiogenic polypeptide fibroblast growth factor 1 (FGF1). Thrombin failed to induce FGF1 release from protease-activated receptor 1 (PAR1) null fibroblasts, indicating that this effect was dependent on PAR1. Similarly to thrombin, FGF1 expression and release were induced by TRAP, a specific oligopeptide agonist of PAR1. These results identify a novel aspect of the crosstalk between FGF and thrombin signaling pathways which both play important roles in tissue repair and angiogenesis
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Are results from pharmaceutical-company-sponsored studies available to the public?
Dal-Ré, Rafael; Pedromingo, Alejandro; García-Losa, Manuel; Lahuerta, Juan; Ortega, Rafael
2010-11-01
Only 53% and 63% of studies and clinical trials results presented at congresses are published. Company-sponsored trial results are being posted on publicly accessible Web sites. We analyzed the public availability (publication or posting on a Web site) rate, time to publication, and factors predicting public availability of results of studies sponsored by a pharmaceutical company. This was a retrospective cohort study analyzing all studies conducted by GlaxoSmithKline in Spain between 2001 and 2006. Initiation and completion were defined as first participant/first visit and last participant/last visit (or their equivalents). Papers published up to 31 March 2009 were considered. Logistic regression models were used to identify factors predicting public availability of results. The cohort comprised 143 studies (94 clinical trials; of these, 87 were included in international products clinical development plans). Public availability rate was 80% (114/143) for all studies and 78% (73/94) for clinical trials; publication rates were 68% and 61%, respectively. The median time to publication for all studies and trials was 27.3 and 28.4 months, respectively. Study associated to a cancelled project was the only significant factor associated with lower publication rate for all studies [odds ratio (OR) 0.069; 95% confidence interval (CI) 0.02-024; p public availability rate (OR 0.052; 95% CI 0.007-0.382; p = 0.004) for trial results. Therapy area, sample size, positive trial results, duration of experimental phase, and being a clinical trial did not predict publication or public availability. Eighty percent of studies included in this analysis are publicly available. Web site posting increases public availability rate of clinical trial results from 61% to 78%. Cancellation of projects is the single factor negatively influencing publication and public availability rates.
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Klotho expression in long bones regulates FGF23 production during renal failure.
Kaludjerovic, Jovana; Komaba, Hirotaka; Sato, Tadatoshi; Erben, Reinhold G; Baron, Roland; Olauson, Hannes; Larsson, Tobias E; Lanske, Beate
2017-05-01
Circulating levels of bone-derived fibroblast growth factor 23 (FGF23) increase early during acute and chronic kidney disease and are associated with adverse outcomes. Membrane-bound Klotho acts as a permissive coreceptor for FGF23, and its expression was recently found in osteoblasts/osteocytes. We hypothesized that Klotho in bone cells is part of an autocrine feedback loop that regulates FGF23 expression during renal failure. Thus, we induced renal failure in mice with targeted deletion of Klotho in long bones. Uremic wild-type ( KL fl/fl ) and knockout ( Prx1-Cre;KL fl/fl ) mice both responded with reduced body weight, kidney atrophy, hyperphosphatemia, and increased bone turnover. Importantly, long bones of Prx1-Cre;KL fl/fl mice but not their axial skeleton failed to increase FGF23 expression as observed in uremic KL fl/fl mice. Consequently, Prx1-Cre;KL fl/fl mice had significantly lower serum FGF23 and parathyroid hormone levels, and higher renal 1-α-hydroxylase expression, serum 1,25-dihydroxyvitamin D, and calcium levels than KL fl/fl mice. These results were confirmed in two independent models of renal failure, adenine diet induced and 5/6 nephrectomy. Moreover, FGF23-treated bone cells required Klotho to increase FGF23 mRNA and ERK phosphorylation. In summary, our novel findings show that Klotho in bone is crucial for inducing FGF23 production upon renal failure. We propose the presence of an autocrine feedback loop in which Klotho senses the need for FGF23.-Kaludjerovic, J., Komaba, H., Sato, T., Erben, R. G., Baron, R., Olauson, H., Larsson, T. E., Lanske, B. Klotho expression in long bones regulates FGF23 production during renal failure. © FASEB.
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FGF-23 dysregulates calcium homeostasis and electrophysiological properties in HL-1 atrial cells.
Kao, Yu-Hsun; Chen, Yao-Chang; Lin, Yung-Kuo; Shiu, Rong-Jie; Chao, Tze-Fan; Chen, Shih-Ann; Chen, Yi-Jen
2014-08-01
Fibroblast growth factor (FGF)-23 is a key regulator of phosphate homeostasis. Higher FGF-23 levels are correlated with poor outcomes in cardiovascular diseases. FGF-23 can produce cardiac hypertrophy and increase intracellular calcium, which can change cardiac electrical activity. However, it is not clear whether FGF-23 possesses arrhythmogenic potential through calcium dysregulation. Therefore, the purposes of this study were to evaluate the electrophysiological effects of FGF-23 and identify the underlying mechanisms. Patch clamp, confocal microscope with Fluo-4 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, calcium homeostasis and calcium regulatory proteins in HL-1 atrial myocytes with and without FGF-23 (10 and 25 ng/mL) incubation for 24 h. FGF-23 (25 ng/mL) increased L-type calcium currents, calcium transient and sarcoplasmic reticulum Ca(2+) contents in HL-1 cells. FGF-23 (25 ng/mL)-treated cells (n = 14) had greater incidences (57%, 17% and 15%, P calcium/calmodulin-dependent protein kinase IIδ and phospholamban (PLB) at threonine 17 but had similar phosphorylation extents of PLB at serine 16, total PLB and sarcoplasmic reticulum Ca(2+) -ATPase protein. Moreover, the FGF receptor inhibitor (PD173074, 10 nM), calmodulin inhibitor (W7, 5 μM) and phospholipase C inhibitor (U73122, 1 μM) attenuated the effects of FGF-23 on calcium/calmodulin-dependent protein kinase II phosphorylation. FGF-23 increases HL-1 cells arrhythmogenesis with calcium dysregulation through modulating calcium-handling proteins. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.
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Physiological role of FGF signaling in growth and remodeling of developing cardiovascular system
Czech Academy of Sciences Publication Activity Database
Krejčí, Eliška; Peševski, Živorad; Naňka, O.; Sedmera, David
2016-01-01
Roč. 65, č. 3 (2016), s. 425-435 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP302/11/1308; GA ČR(CZ) GA16-02972S Institutional support: RVO:67985823 Keywords : chick embryo * vasculogenesis * FGF2 * FGFR1 * myocyte proliferation * conotruncal banding * SU5402 Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.461, year: 2016
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FGF-2 promotes osteocyte differentiation through increased E11/podoplanin expression.
Ikpegbu, Ekele; Basta, Lena; Clements, Dylan N; Fleming, Robert; Vincent, Tonia L; Buttle, David J; Pitsillides, Andrew A; Staines, Katherine A; Farquharson, Colin
2018-07-01
E11/podoplanin is critical in the early stages of osteoblast-to-osteocyte transitions (osteocytogenesis), however, the upstream events which regulate E11 expression are unknown. The aim of this study was to examine the effects of FGF-2 on E11-mediated osteocytogenesis and to reveal the nature of the underlying signaling pathways regulating this process. Exposure of MC3T3 osteoblast-like cells and murine primary osteoblasts to FGF-2 (10 ng/ml) increased E11 mRNA and protein expression (p 70% reduction of basal E11 mRNA expression (p < 0.05) and effectively abrogated FGF-2-related changes in E11 expression and dendrite formation. FGF-2 strongly activated the ERK signaling pathway in osteoblast-like cells but inhibition of this pathway did not block the ability of FGF-2 to enhance E11 expression or to promote acquisition of the osteocyte phenotype. The results of this study highlight a novel mechanism by which FGF-2 can regulate osteoblast differentiation and osteocyte formation. Specifically, the data suggests that FGF-2 promotes osteocytogenesis through increased E11 expression and further studies will identify if this regulatory pathway is essential for bone development and maintenance in health and disease. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
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National Research Council Canada - National Science Library
Stylianou, Dora
2004-01-01
...) to study the expression of FGF-BP in mammary tumorigenesis progression of the APC/+ mouse and 2) to determine the mechanism of regulation of FGF-BP b the APC/beta-catenin signaling pathway in breast cancer...
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National Research Council Canada - National Science Library
Stylianou, Dora
2003-01-01
...) to study the expression of FGF-BP in mammary tumorigenesis% progression of the APC/+ mouse and 2) to determine the mechanism of regulation of FGF-BP by the APC/beta- catenin signaling pathway in breast cancer...
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Polyguluronate sulfate and its oligosaccharides but not heparin promotes FGF19/FGFR1c signaling
Lan, Ying; Zeng, Xuan; Guo, Zhihua; Zeng, Pengjiao; Hao, Cui; Zhao, Xia; Yu, Guangli; Zhang, Lijuan
2017-06-01
Fibroblast growth factor 19(FGF19) functions as a hormone by affecting glucose metabolism. FGF19 improves glucose tolerance when overexpressed in mice with impaired glucose tolerance or diabetes. A functional cellular FGF19 receptor consists of FGF receptor (FGFR) and glycosaminoglycan complexed with either α Klotho or β Klotho. Interestingly, in mice with diet-induced diabetes, a single injection of FGF1 is enough to restore blood sugar levels to a healthy range. FGF1 binds heparin with high affinity whereas FGF19 does not, indicating that polysaccharides other than heparin might enhance FGF19/FGFR signaling. Using a FGFs/FGFR1c signaling-dependent BaF3 cell proliferation assay, we discovered that polyguluronate sulfate (PGS) and its oligosaccharides, PGS12 and PGS25, but not polyguluronate (PG), a natural marine polysaccharide, enhanced FGF19/FGFR1c signaling better than that of heparin based on 3H-thymidine incorporation. Interestingly, PGS6, PGS8, PGS10, PGS12, PGS25, and PGS, but not PG, had comparable FGF1/FGFR1c signal-stimulating activity compared to that of heparin. These results indicated that PGS and its oligosaccharides were excellent FGF1/FGFR1c and FGF19/FGFR1c signaling enhancers at cellular level. Since the inexpensive PGS and PGS oligosaccharides can be absorbed through oral route, these seaweed-derived compounds merit further investigation as novel agents for the treatment of type 2 diabetes through enhancing FGF1/FGFR1c and FGF19/FGFR1c signaling in future.
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International Nuclear Information System (INIS)
1975-12-01
Investigations on the safety of Light Water Reactors (LWR) being performed in the framework of the safety program 'Reactor Safety' are sponsored by the Bundesminister fuer Forschung und Technologie (BMFT - Secretary of State for Research and Technology). Objective of this program is to continue improving the safety of LWR, in order to minimize the risk for the environment. With grant assistance from the Bundesminister des Innern (BMI - Secretary of State for Home Affairs) research contracts in the field of reactor safety are being performed. Results of these projects should contribute to resolve questions arising nuclear licensing procedures. The Forschungsbetreuung (FB - research supervision department) at the Institute for Reactor Safety (IRS), as consultants to BMFT and BMI, provides information about the progress of investigations. Individual reports will be prepared and put into standard forms by the research contractors. Each report gives information on: 1) the work accomplished, 2) the results obtained, 3) the work planned to be continued. Initial reports of research projects describe in addition the purpose of the work. A BMFT-research program on the safety of Fast Breeders (Schneller Brutreaktor - SBR) is presently under discussion. In order to define several problems, investigations included in the present compilation (RS 139, 140, 143, 162) will be previously performed. (orig.) [de
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International Nuclear Information System (INIS)
1976-12-01
Investigations on the safety of light water reactors (LWR) being performed in the framework of the safety program 'Reactor Safety' are sponsored by the Bundesminister fuer Forschung und Technologie (BMFT - Secretary of State for Research and Technology). Objective of this program is to continue improving the safety of LWR, in order to minimize the risk for the environment. With grant assistance from the Bundesminister des Innern (BMI - Secretary of State for Home Affairs) research contrcts in the field of reactor safety are being performed. Results of these projects should contribute to resolve questions arising nuclear licensing procedures. The Forschungsbetreuung (FB - research supervision department) at the Institute for Reactor Safety (IRS), as consultants to BMFT and BMI, provides information about the progress of investigations. Individual reports will be prepared and put into standard forms by the research contractors. Each report gives information on: 1) the work accomplished, 2) the results obtained, 3) the work planned to be continued. Initial reports of research projects describe in addition the purpose of the work. A BMFT-research program on the safety of Fast Breeders (Schneller Brutreaktor - SRB) is presently under discussion. In order to define several problems, investigations included in the present compilation (RS 139, 140, 143, 162) will be previously performed. (orig.) [de
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Energy Technology Data Exchange (ETDEWEB)
Alonso A, D. [CPHR, Calle 20 No. 4113 e/41 y 47. Playa C.P. 11300, La Habana (Cuba); Arista R, E. [CEADEN, A.P. 6195, C.P. 10600, La Habana (Cuba); Alonso A, A. [Hasselt University, Building D, 3590 Diepenbeek (Belgium)]. e-mail: lola@cphr.edu.cu
2006-07-01
A comparative study whose main objective is the evaluation of the diagnoses capacity of the DETEC - PC, a detection-measurement system for the reception of iodine in thyroid, with it presumptive diagnostic is presented. To such effect a clinical essay was designed in which all the patients included in the study were evaluated using the new equipment (DETEC - PC) and the standard diagnoses procedure well-known for the initials RIA. The sample size was calculated in a such way that the percent of gross coincidence among both methods could be estimate with a precision of 1% at a trust level of 95%. In total 110 patients were included in the essay. For the analysis of the agreement in the diagnostic it was used the Kappa statistician. The obtained results showed a high grade of gross agreement and an agreement level among moderate and substantial when it was corrected by possible random agreement among both procedures. (Author)
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Diverse FGF receptor signaling controls astrocyte specification and proliferation
Energy Technology Data Exchange (ETDEWEB)
Kang, Kyungjun [School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of); Song, Mi-Ryoung, E-mail: msong@gist.ac.kr [School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of); Bioimaging Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of)
2010-05-07
During CNS development, pluripotency neuronal progenitor cells give rise in succession to neurons and glia. Fibroblast growth factor-2 (FGF-2), a major signal that maintains neural progenitors in the undifferentiated state, is also thought to influence the transition from neurogenesis to gliogenesis. Here we present evidence that FGF receptors and underlying signaling pathways transmit the FGF-2 signals that regulate astrocyte specification aside from its mitogenic activity. Application of FGF-2 to cortical progenitors suppressed neurogenesis whereas treatment with an FGFR antagonist in vitro promoted neurogenesis. Introduction of chimeric FGFRs with mutated tyrosine residues into cortical progenitors and drug treatments to specifically block individual downstream signaling pathways revealed that the overall activity of FGFR rather than individual autophosphorylation sites is important for delivering signals for glial specification. In contrast, a signal for cell proliferation by FGFR was mainly delivered by MAPK pathway. Together our findings indicate that FGFR activity promotes astrocyte specification in the developing CNS.
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Diverse FGF receptor signaling controls astrocyte specification and proliferation
International Nuclear Information System (INIS)
Kang, Kyungjun; Song, Mi-Ryoung
2010-01-01
During CNS development, pluripotency neuronal progenitor cells give rise in succession to neurons and glia. Fibroblast growth factor-2 (FGF-2), a major signal that maintains neural progenitors in the undifferentiated state, is also thought to influence the transition from neurogenesis to gliogenesis. Here we present evidence that FGF receptors and underlying signaling pathways transmit the FGF-2 signals that regulate astrocyte specification aside from its mitogenic activity. Application of FGF-2 to cortical progenitors suppressed neurogenesis whereas treatment with an FGFR antagonist in vitro promoted neurogenesis. Introduction of chimeric FGFRs with mutated tyrosine residues into cortical progenitors and drug treatments to specifically block individual downstream signaling pathways revealed that the overall activity of FGFR rather than individual autophosphorylation sites is important for delivering signals for glial specification. In contrast, a signal for cell proliferation by FGFR was mainly delivered by MAPK pathway. Together our findings indicate that FGFR activity promotes astrocyte specification in the developing CNS.
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Directory of Open Access Journals (Sweden)
Yusuke Murata
2011-01-01
Full Text Available The FGF family comprises twenty-two structurally related proteins with functions in development and metabolism. The Fgf21 gene was generated early in vertebrate evolution. FGF21 acts as an endocrine regulator in lipid metabolism. Hepatic Fgf21 expression is markedly induced in mice by fasting or a ketogenic diet. Experiments with Fgf21 transgenic mice and cultured cells indicate that FGF21 exerts pharmacological effects on glucose and lipid metabolism in hepatocytes and adipocytes via cell surface FGF receptors. However, experiments with Fgf21 knockout mice indicate that FGF21 inhibits lipolysis in adipocytes during fasting and attenuates torpor induced by a ketogenic diet but maybe not a physiological regulator for these hepatic functions. These findings suggest the pharmacological effects to be distinct from the physiological roles. Serum FGF21 levels are increased in patients with metabolic diseases having insulin resistance, indicating that FGF21 is a metabolic regulator and a biomarker for these diseases.
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Case study: I-95 Landfill gas recovery project Fairfax County, Virginia
International Nuclear Information System (INIS)
McGuigan, M.J.; Peterson, E.R.; Smithberger, J.M.; Owen, W.L.
1993-01-01
This paper presents a case study of the landfill gas (LFG) recovery project at the I-95 Landfill in Fairfax County, Virginia. The project originally was conceived more than 10 years ago and has overcome numerous obstacles enroute to its present success. The efforts of the landfill owner (Fairfax County) and the project developer (Michigan Cogeneration Systems, Inc.) to surmount these obstacles are presented
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Czech Academy of Sciences Publication Activity Database
Wells, K. L.; Gaete, M.; Matalová, Eva; Deutsch, D.; Rice, D.; Tucker, A. S.
2013-01-01
Roč. 2, č. 10 (2013), s. 981-989 ISSN 2046-6390 R&D Projects: GA ČR GAP304/11/1418 Grant - others:AV ČR(CZ) M200451201 Institutional support: RVO:67985904 Keywords : salivary gland * Fgf10 * epithelial-mesenchymal interactions Subject RIV: EI - Biotechnology ; Bionics
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Rottman, G. J.; Cebula, R. P.; Gillotay, D.; Simon, P. A.
1996-01-01
This report summarizes the activities of Working Group 2 and Working Group 3 of the SOLax Electromagnetic Radiation Study for Solar Cycle 22 (SOLERS22) Program. The international (SOLERS22) is Project 1.2 of the Solar-Terrestrial Energy Program (STEP) sponsored by SCOSTEP, a committee of the International Council of Scientific Unions). SOLERS22 is comprised of five Working Groups, each concentrating on a specific wave-length range: WG-1 - visible and infrared, WG-2 - mid-ultraviolet (200 solar irradiance values in the specified wavelength ranges, 2) consider the evolving solar structures as the cause of temporal variations, and 3) understand the underlying physical processes driving these changes.
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FGF signaling is required for brain left-right asymmetry and brain midline formation.
Neugebauer, Judith M; Yost, H Joseph
2014-02-01
Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expressions, and a midline barrier structure. Copyright © 2013 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Takeshi eInagaki
2015-09-01
Full Text Available Fibroblast growth factor 21 (FGF21 is a metabolic hormone primarily secreted from the liver and functions in multiple tissues. Various transcription factors induce FGF21 expression in the liver, which indicates that FGF21 is a mediator of multiple environmental cues. FGF21 alters metabolism under starvation conditions, protects the body from energy depletion, and extends life span. Pharmacological administration of FGF21 alleviates dyslipidemia and induces weight loss in obese animals. In addition to the well-studied functions of FG21, several lines of recent evidence indicate a possible link between FGF21 and nonalcoholic fatty liver disease (NAFLD. High serum levels of FGF21 are associated with NAFLD and its risk factors such as endoplasmic reticulum stress and chronic inflammation. In addition, FGF21 alleviates the major risk factors of NAFLD including obesity, dyslipidemia and insulin insensitivity. Thus, FGF21 is a potential drug candidate for diseases such as NAFLD, dyslipidemia, and type 2 diabetes. In this review, the research perspectives of FGF21 and therapeutic potencies of FGF21 as a modulator of NAFLD are summarized.
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FGF23 modulates the effects of erythropoietin on gene expression in renal epithelial cells
Directory of Open Access Journals (Sweden)
Yashiro M
2018-04-01
Full Text Available Mitsuru Yashiro,1 Masaki Ohya,1 Toru Mima,1 Yumi Ueda,2 Yuri Nakashima,1 Kazuki Kawakami,1 Yohei Ishizawa,2 Shuto Yamamoto,1 Sou Kobayashi,1 Takurou Yano,1 Yusuke Tanaka,1 Kouji Okuda,1 Tomohiro Sonou,1 Tomohiro Shoshihara,1 Yuko Iwashita,1 Yu Iwashita,1 Kouichi Tatsuta,1 Ryo Matoba,2 Shigeo Negi,1 Takashi Shigematsu1 1Department of Nephrology, Wakayama Medical University, Wakayama, Japan; 2DNA Chip Research Inc., Minato, Japan Background: FGF23 plays an important role in calcium–phosphorus metabolism. Other roles of FGF23 have recently been reported, such as commitment to myocardium enlargement and immunological roles in the spleen. In this study, we aimed to identify the roles of FGF23 in the kidneys other than calcium–phosphorus metabolism. Methods: DNA microarrays and bioinformatics tools were used to analyze gene expression in mIMCD3 mouse renal tubule cells following treatment with FGF23, erythropoietin and/or an inhibitor of ERK. Results: Three protein-coding genes were upregulated and 12 were downregulated in response to FGF23. Following bioinformatics analysis of these genes, PPARγ and STAT3 were identified as candidate transcript factors for mediating their upregulation, and STAT1 as a candidate for mediating their downregulation. Because STAT1 and STAT3 also mediate erythropoietin signaling, we investigated whether FGF23 and erythropoietin might show interactive effects in these cells. Of the 15 genes regulated by FGF23, 11 were upregulated by erythropoietin; 10 of these were downregulated following cotreatment with FGF23. Inhibition of ERK, an intracellular mediator of FGF23, reversed the effects of FGF23. However, FGF23 did not influence STAT1 phosphorylation, suggesting that it impinges on erythropoietin signaling through other mechanisms. Conclusion: Our results suggest cross talk between erythropoietin and FGF23 signaling in the regulation of renal epithelial cells. Keywords: FGF23, STAT1, PPARγ, DNA microarray
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The readout performance evaluation of PowerPC
International Nuclear Information System (INIS)
Chu Yuanping; Zhang Hongyu; Zhao Jingwei; Ye Mei; Tao Ning; Zhu Kejun; Tang Suqiu; Guo Yanan
2003-01-01
PowerPC, as a powerful low-cost embedded computer, is one of the very important research objects in recent years in the project of BESIII data acquisition system. The researches on the embedded system and embedded computer have achieved many important results in the field of High Energy Physics especially in the data acquisition system. The one of the key points to design an acquisition system using PowerPC is to evaluate the readout ability of PowerPC correctly. The paper introduce some tests for the PowerPC readout performance. (authors)
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Guia de gestors de projectes, setembre 2012
Morante Milla, Antoni
2012-01-01
¿Qué es un proyecto?, la gestión de proyectos, aspectos clave en la definición y gestión de un proyecto, planificación de un proyecto herramientas informáticas para la planificación y gestión de proyectos y guía de uso del software de gestión de proyectos ClockingIT. What is a project?, project management, key issues in definition and project management, project planning tools for planning and managing projects and guide on how to use ClockingIT, project management software. Què és un p...
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Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates
DEFF Research Database (Denmark)
Lundsgaard, Annemarie; Fritzen, Andreas Mæchel; Sjøberg, Kim Anker
2017-01-01
OBJECTIVE: Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must...... concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml(-1), p FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p ... intake and increased plasma FGF21 concentration. CONCLUSION: Excess dietary carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais....
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Vitamin D treatment attenuates cardiac FGF23/FGFR4 signaling and hypertrophy in uremic rats.
Leifheit-Nestler, Maren; Grabner, Alexander; Hermann, Laura; Richter, Beatrice; Schmitz, Karin; Fischer, Dagmar-Christiane; Yanucil, Christopher; Faul, Christian; Haffner, Dieter
2017-09-01
Vitamin D deficiency and excess of circulating fibroblast growth factor 23 (FGF23) contribute to cardiovascular mortality in patients with chronic kidney disease (CKD). FGF23 activates FGF receptor 4 and (FGFR4) calcineurin/nuclear factor of activated T cells (NFAT) signaling in cardiac myocytes, thereby causing left ventricular hypertrophy (LVH). Here, we determined if 1,25-dihydroxyvitamin D (calcitriol) inhibits FGF23-induced cardiac signaling and LVH. 5/6 nephrectomized (5/6 Nx) rats were treated with different doses of calcitriol for 4 or 10 weeks and cardiac expression of FGF23/FGFR4 and activation of calcineurin/NFAT as well as LVH were analyzed. FGFR4 activation and hypertrophic cell growth were studied in cultured cardiac myocytes that were co-treated with FGF23 and calcitriol. In 5/6Nx rats with LVH, we detected elevated FGF23 expression in bone and myocardium, increased cardiac expression of FGFR4 and elevated cardiac activation of calcineurin/NFAT signaling. Cardiac expression levels of FGF23 and FGFR4 significantly correlated with the presence of LVH in uremic rats. Treatment with calcitriol reduced LVH as well as cardiac FGFR4 expression and calcineurin/NFAT activation. Bone and cardiac FGF23 expression were further stimulated by calcitriol in a dose-dependent manner, but levels of intact cardiac FGF23 protein were suppressed by high-dose calcitriol. In cultured cardiac myocytes, co-treatment with calcitriol blocked FGF23-induced activation of FGFR4 and hypertrophic cell growth. Our data suggest that in CKD, cardioprotective effects of calcitriol stem from its inhibitory actions on the cardiac FGF23/FGFR4 system, and based on their counterbalancing effects on cardiac myocytes, high FGF23 and low calcitriol synergistically contribute to cardiac hypertrophy. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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Differentiation of stem cells upon deprivation of exogenous FGF2
DEFF Research Database (Denmark)
Kjartansdóttir, Kristín Rós; Gabrielsen, Anette; Reda, Ahmed
2012-01-01
Establishing a model for in vitro differentiation of human embryonic stem cells (hESCs) towards the germ cell lineage could be used to identify molecular mechanisms behind germ cell differentiation that may help in understanding human infertility. Here, we evaluate whether a lack of exogenous...... fibroblast growth factor 2 (FGF2) is supporting spontaneous differentiation of hESCs cultured on human foreskin fibroblast (hFF) monolayers towards germ cell lineage. Additionally to depriving the hESCs of exogenous FGF2, cells were stimulated with all-trans retinoic acid (ATRA). To get a more comprehensive...... impression on effects of removal of FGF2 and stimulation with ATRA, we combined the results of three cell lines for each experimental setting. When combining gene expression profiles of three cell lines for 96 genes, only 6 genes showed a significant up-regulation in all cell lines, when no FGF2 was added...
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mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes
Directory of Open Access Journals (Sweden)
Annabel Y. Minard
2016-09-01
Full Text Available FGF21 improves the metabolic profile of obese animals through its actions on adipocytes. To elucidate the signaling network responsible for mediating these effects, we quantified dynamic changes in the adipocyte phosphoproteome following acute exposure to FGF21. FGF21 regulated a network of 821 phosphosites on 542 proteins. A major FGF21-regulated signaling node was mTORC1/S6K. In contrast to insulin, FGF21 activated mTORC1 via MAPK rather than through the canonical PI3K/AKT pathway. Activation of mTORC1/S6K by FGF21 was surprising because this is thought to contribute to deleterious metabolic effects such as obesity and insulin resistance. Rather, mTORC1 mediated many of the beneficial actions of FGF21 in vitro, including UCP1 and FGF21 induction, increased adiponectin secretion, and enhanced glucose uptake without any adverse effects on insulin action. This study provides a global view of FGF21 signaling and suggests that mTORC1 may act to facilitate FGF21-mediated health benefits in vivo.
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Directory of Open Access Journals (Sweden)
Luciano Carlos Gomes de Miranda
2008-06-01
Full Text Available JUSTIFICATIVA E OBJETIVOS: Os bloqueadores neuromusculares (BNM são fármacos utilizados para produzir relaxamento da musculatura esquelética e facilitar a intubação traqueal (IT. A literatura descreve como sendo necessárias duas doses efetivas (DE95 o ideal para a IT. O rocurônio é um BNM não-despolarizante do tipo esteróide, sintético e de duração intermediária. O objetivo desse estudo foi avaliar e comparar as condições de intubação traqueal (IT, utilizando uma e duas doses efetivas (DE95 do rocurônio, seguindo os critérios da Conferência de Consenso de Copenhague. MÉTODO: Foram avaliados 60 pacientes divididos aleatoriamente em dois grupos de 30, de ambos os sexos, idades entre 20 e 60 anos, estado físico ASA I e II, Mallampati 1 e 2, índice de massa corporal (IMC JUSTIFICATIVA Y OBJETIVOS: Los bloqueadores neuromusculares (BNM son fármacos utilizados para producir el relajamiento de la musculatura esquelética y facilitar la intubación traqueal (IT. La literatura describe que son necesarias de los dosis efectivas (DE95 lo ideal para la IT. El rocuronio es un BNM no despolarizador del tipo esteroide, sintético y de duración intermedia. El objetivo de este estudio fue evaluar y comparar las condiciones de intubación traqueal (IT, utilizando una y de los dosis efectivas (DE95 del rocuronio, secundando los criterios de la Conferencia de Consenso de Copenhague. MÉTODO: Se estudiaron 60 pacientes divididos aleatoriamente en 2 grupos de 30, de ambos sexos, edades entre 20 y 60 años, estado físico ASA I y II, Mallampati 1 y 2, índice de masa corporal (IMC BACKGROUND AND OBJECTIVES: Neuromuscular blockers (NMB are used to induce relaxation of skeletal muscles and facilitate tracheal intubation (TI. According to the literature, two effective doses (ED95 of NMB are ideal for TI. Rocuronium is a steroid-type, synthetic, non-depolarizing neuromuscular blocker of medium duration. The objective of this study was to evaluate
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TGF-β2 inhibits AKT activation and FGF-2-induced corneal endothelial cell proliferation
International Nuclear Information System (INIS)
Lu Jiawei; Lu Zhenyu; Reinach, Peter
2006-01-01
The corneal endothelial cells form a boundary layer between anterior chamber and cornea. This single cell layer is important to maintain cornea transparency by eliciting net fluid transport into the anterior chamber. Injuries of the corneal endothelial layer in humans lead to corneal swelling and translucence. This hindrance is thought to be due to limited proliferative capacity of the endothelial layer. Fibroblast growth factor 2 (FGF-2) and transforming growth factor-beta 2 (TGF-β2) are both found in aqueous humor, and these two cytokines promote and inhibit cell growth, respectively. The intracellular signaling mechanisms by which TGF-β2 suppresses the mitogenic response to FGF-2, however, remain unclear. We have addressed this question by investigating potential crosstalk between FGF-2-induced and TGF-β2-regulated intracellular signaling events in cultured bovine corneal endothelial (BCE) cells. We found that TGF-β2 and FGF-2 oppositely affect BCE cell proliferation and TGF-β2 can override the stimulating effects of FGF-2 by increasing COX-2 expression in these cells. Consistent with these findings, overexpression of COX-2 significantly reduced FGF-2-induced cell proliferation whereas a COX-2 specific inhibitor NS398 reversed the effect of TGF-β2 on FGF-2-induced cell proliferation. The COX-2 product prostaglandin E2 (PGE-2) blocks FGF-2-induced cell proliferation. Whereas FGF-2 stimulates cell proliferation by activating the AKT pathway, TGF-β2 and PGE-2 both inhibit this pathway. In accordance with the effect of PGE-2, cAMP also inhibits FGF-2-induced AKT activation. These findings suggest that the mitogenic response to FGF-2 in vivo in the corneal endothelial layer may be inhibited by TGF-β2-induced suppression of the PI3-kinase/AKT signaling pathway
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International Nuclear Information System (INIS)
Kim, Kook Hwan; Jeong, Yeon Taek; Kim, Seong Hun; Jung, Hye Seung; Park, Kyong Soo; Lee, Hae-Youn; Lee, Myung-Shik
2013-01-01
Highlights: •Metformin induces FGF21 expression in an AMPK independent manner. •Metformin enhances FGF21 expression by inhibiting mitochondrial complex I activity. •The PERK-eIF2α-ATF4 axis is required for metformin-induced FGF21 expression. •Metformin activates the ATF4-FGF21 axis in the liver of mouse. •Metformin increases serum FGF21 level in diabetic human subjects. -- Abstract: Fibroblast growth factor 21 (FGF21) is an endocrine hormone that exhibits anti-obesity and anti-diabetes effects. Because metformin is widely used as a glucose-lowering agent in patients with type 2 diabetes (T2D), we investigated whether metformin modulates FGF21 expression in cell lines, and in mice or human subjects. We found that metformin increased the expression and release of FGF21 in a diverse set of cell types, including rat hepatoma FaO, primary mouse hepatocytes, and mouse embryonic fibroblasts (MEFs). Intriguingly, AMP-activated protein kinase (AMPK) was dispensable for the induction of FGF21 by metformin. Mammalian target of rapamycin complex 1 (mTORC1) and peroxisome proliferator-activated receptor α (PPARα), which are additional targets of metformin, were not involved in metformin-induced FGF21 expression. Importantly, inhibition of mitochondrial complex I activity by metformin resulted in FGF21 induction through PKR-like ER kinase (PERK)-eukaryotic translation factor 2α (eIF2α)-activating transcription factor 4 (ATF4). We showed that metformin activated ATF4 and increased FGF21 expression in the livers of mice, which led to increased serum levels of FGF21. We also found that serum FGF21 level was increased in human subjects with T2D after metformin therapy for 6 months. In conclusion, our results indicate that metformin induced expression of FGF21 through an ATF4-dependent mechanism by inhibiting mitochondrial respiration independently of AMPK. Therefore, FGF21 induction by metformin might explain a portion of the beneficial metabolic effects of metformin
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Energy Technology Data Exchange (ETDEWEB)
Kim, Kook Hwan [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Jeong, Yeon Taek [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Kim, Seong Hun [Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Jung, Hye Seung; Park, Kyong Soo [Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744 (Korea, Republic of); Lee, Hae-Youn [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Lee, Myung-Shik, E-mail: mslee0923@skku.edu [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of); Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710 (Korea, Republic of)
2013-10-11
Highlights: •Metformin induces FGF21 expression in an AMPK independent manner. •Metformin enhances FGF21 expression by inhibiting mitochondrial complex I activity. •The PERK-eIF2α-ATF4 axis is required for metformin-induced FGF21 expression. •Metformin activates the ATF4-FGF21 axis in the liver of mouse. •Metformin increases serum FGF21 level in diabetic human subjects. -- Abstract: Fibroblast growth factor 21 (FGF21) is an endocrine hormone that exhibits anti-obesity and anti-diabetes effects. Because metformin is widely used as a glucose-lowering agent in patients with type 2 diabetes (T2D), we investigated whether metformin modulates FGF21 expression in cell lines, and in mice or human subjects. We found that metformin increased the expression and release of FGF21 in a diverse set of cell types, including rat hepatoma FaO, primary mouse hepatocytes, and mouse embryonic fibroblasts (MEFs). Intriguingly, AMP-activated protein kinase (AMPK) was dispensable for the induction of FGF21 by metformin. Mammalian target of rapamycin complex 1 (mTORC1) and peroxisome proliferator-activated receptor α (PPARα), which are additional targets of metformin, were not involved in metformin-induced FGF21 expression. Importantly, inhibition of mitochondrial complex I activity by metformin resulted in FGF21 induction through PKR-like ER kinase (PERK)-eukaryotic translation factor 2α (eIF2α)-activating transcription factor 4 (ATF4). We showed that metformin activated ATF4 and increased FGF21 expression in the livers of mice, which led to increased serum levels of FGF21. We also found that serum FGF21 level was increased in human subjects with T2D after metformin therapy for 6 months. In conclusion, our results indicate that metformin induced expression of FGF21 through an ATF4-dependent mechanism by inhibiting mitochondrial respiration independently of AMPK. Therefore, FGF21 induction by metformin might explain a portion of the beneficial metabolic effects of metformin.
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PILOTSTUDY TO EVALUATE THE EFFECT OF PHOSPHORUSBINDERS ON FGF23
Directory of Open Access Journals (Sweden)
A.Bouma de Krijger
2012-06-01
Results are as follows; phosphorus binding by sevelamer significantly lowered urinary phosphate excretion, from a median of 26.25 mmol/24 h to 17.5 mmol/l. Other parameters showed no sgnificant association with urinary phosphate excretion. The serum phosphate was unchanged during treatment. Creatinin clearance was significantly associated with FGF23 (p0.03. FGF23 did not change significant following phosphorus binding therapy. In conclusion; although 8 weeks sevelamer treatment significantly lowered 24 h urinary phosphate excretion, there was no reduction in FGF23 levels in this group of CKD stage 3 patients.
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Development of a PC code package for the analysis of research and power reactors
International Nuclear Information System (INIS)
Urli, N.
1992-06-01
Computer codes available for performing reactor physics calculations for nuclear research reactors and power reactors are normally suited for running on mainframe computers. With the fast development in speed and memory of the PCs and affordable prices it became feasible to develop PC versions of commonly used codes. The present work performed under an IAEA sponsored research contract has successfully developed a code package for running on a PC. This package includes a cross-section generating code PSU-LEOPARD and 2D and 1D spatial diffusion codes, MCRAC and MCYC 1D. For adapting PSU-LEOPARD for a PC, the binary library has been reorganized to decimal form, upgraded to FORTRAN-77 standard and arrays and subroutines reorganized to conform to PC compiler. Similarly PC version of MCRAC for FORTRAN-77 and 1D code MCYC 1D have been developed. Tests, verification and bench mark results show excellent agreement with the results obtained from mainframe calculations. The execution speeds are also very satisfactory. 12 refs, 4 figs, 3 tabs
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Slotkin, Theodore A.; Card, Jennifer; Infante, Alice; Seidler, Frederic J.
2013-01-01
Early-life exposures to brominated diphenyl ethers (BDEs) lead to neurobehavioral abnormalities later in life. Although these agents are thyroid disruptors, it is not clear whether this mechanism alone accounts for the adverse effects. We evaluated the impact of 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99) on PC12 cells undergoing neurodifferentiation, contrasting the effects with chlorpyrifos, a known developmental neurotoxicant. BDE99 elicited decrements in the number of cells, evidenced by...
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Association of Fibroblast Growth Factor (Fgf-21) as a Screening ...
African Journals Online (AJOL)
24 control samples by enzyme-linked immunosorbent assay (ELISA) and determined the deletion of mitochondrial genome by multiplex polymerase chain reaction (PCR). Results: FGF-21 concentration in 50 % of CPEO patients showed notable differences from that in control subjects. FGF-21 concentration ratio in patient ...
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2011-04-27
... DEPARTMENT OF STATE [Public Notice: 7433] Culturally Significant Objects Imported for Exhibition Determinations: ``Projects 95: Runa Islam'' SUMMARY: Notice is hereby given of the following determinations... the exhibition ``Projects 95: Runa Islam'' imported from abroad for temporary exhibition within the...
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Stage-specific effects of FGF2 on the differentiation of dental pulp cells
Sagomonyants, Karen; Mina, Mina
2015-01-01
Dentinogenesis is a complex and multistep process, which is regulated by various growth factors, including members of the Fibroblast Growth Factor (FGF) family. Both positive and negative effects of FGFs on dentinogenesis have been reported but the underlying mechanisms of these conflicting results are still unclear. To gain better insight into the role of FGF2 in dentinogenesis, we used dental pulp cells from various transgenic mice, in which fluorescent protein expression identifies cells at different stages of odontoblast differentiation. Our results showed that continuous exposure of pulp cells to FGF2 inhibited mineralization and revealed both stimulatory and inhibitory effects of FGF2 on expression of markers of dentinogenesis and various transgenes. During the proliferation phase of in vitro growth FGF2 increased expression of markers of dentinogenesis and the percentages of DMP1-GFP+ functional odontoblasts and DSPP-Cerulean+ odontoblasts. Additional exposure to FGF2 during the differentiation/mineralization phase of in vitro growth decreased the extent of mineralization, expression of markers of dentinogenesis, and expression of DMP1-GFP and DSPP-Cerulean transgenes. Recovery experiments showed that the inhibitory effects of FGF2 on dentinogenesis were related to the blocking of differentiation of cells into mature odontoblasts. These observations together showed stage-specific effects of FGF2 on dentinogenesis by dental pulp cells and provide critical information for the development of improved treatments for vital pulp therapy and dentin regeneration. PMID:25823776
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International Nuclear Information System (INIS)
Xiang Yingsong; Yang Rujun; Cai Jianming; Li Bailong
1999-01-01
Objective: To develop a new method of bone marrow scheduled transplantation (BMST) by making use of the effects of acidic fibroblast growth factor (aFGF) on improving hematopoiesis. Methods: The scheduled transplantation of bone marrow cells preincubated with aFGF (aFGF-BMST) was carried out to study the effects of aFGF on hematopoietic reconstitution and reducing acute graft versus host disease (GVHD) in acute radiation disease model of Kunming mice. Results: The survival rate of the group of aFGF-BMST mice with 4 x 10 6 BMXs was 40%, which was higher than the survival of the group of BMT with 1 x 10 7 BMCs alone (30%), but was lower than the survival of the group of BMST with 4 x 10 6 BMCs. On the other hand, the recovery rates in numbers of leucocytes, nucleated cells and CFU-E, CFU-GM, CFU-S were faster than those in the group of BMT with 1 x 10 7 BMCs alone and in the group of BMST with 4 x 10 6 BMCs. In addition, the severity of GVHD in the group of aFGF-BMST mice with 4 x 10 6 BMCs was lower than that in the group of BMT with 1 x 10 7 BMCs alone but was higher than that in the group of BMST with 4 x 10 6 BMCs. Conclusion: Although aFGF can activate heterogeneous T cells to cause GVHD, there is prospect of making full use of the effects of aFGF on improving hematopoiesis and reducing the side effects of aFGF leading to GVHD through scheduled transplantation of bone marrow cells preincubated with aFGF
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FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting
Riminucci, Mara; Collins, Michael T.; Fedarko, Neal S.; Cherman, Natasha; Corsi, Alessandro; White, Kenneth E.; Waguespack, Steven; Gupta, Anurag; Hannon, Tamara; Econs, Michael J.; Bianco, Paolo; Gehron Robey, Pamela
2003-01-01
FGF-23, a novel member of the FGF family, is the product of the gene mutated in autosomal dominant hypophosphatemic rickets (ADHR). FGF-23 has been proposed as a circulating factor causing renal phosphate wasting not only in ADHR (as a result of inadequate degradation), but also in tumor-induced osteomalacia (as a result of excess synthesis by tumor cells). Renal phosphate wasting occurs in approximately 50% of patients with McCune-Albright syndrome (MAS) and fibrous dysplasia of bone (FD), which result from postzygotic mutations of the GNAS1 gene. We found that FGF-23 is produced by normal and FD osteoprogenitors and bone-forming cells in vivo and in vitro. In situ hybridization analysis of FGF-23 mRNA expression identified “fibrous” cells, osteogenic cells, and cells associated with microvascular walls as specific cellular sources of FGF-23 in FD. Serum levels of FGF-23 were increased in FD/MAS patients compared with normal age-matched controls and significantly higher in FD/MAS patients with renal phosphate wasting compared with those without, and correlated with disease burden bone turnover markers commonly used to assess disease activity. Production of FGF-23 by FD tissue may play an important role in the renal phosphate–wasting syndrome associated with FD/MAS. PMID:12952917
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Annual report of the project CIS-03-95, `evaluation of actinide nuclear data`
Energy Technology Data Exchange (ETDEWEB)
Maslov, V.M. [Radiation Physics and Chemistry Problems Inst., Minsk-Sosny (Belarus)
1997-03-01
The evaluation of neutron data for {sup 243}Cm, {sup 245}Cm and {sup 246}Cm is made in the energy region from 10-5 eV up to 20 MeV. The results of the evaluation are compiled in the ENDF/B-VI format. This work is performed under the Project Agreement CIS-03-95 with the International Science and Technology Center (Moscow). This is the annual report of the project CIS-03-95. (author)
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DEFF Research Database (Denmark)
Hansbøl, Mikala; Mathiasen, Helle
udviklingsprojekt med forsøg med DANSK IT's Junior PC-kørekort® som metode og redskab til at evaluere og dokumentere elevernes IT-kompetencer. Projektet blev gennemført i perioden fra 2002-2003 og afsluttet i foråret 2003. Rapporten er baseret på kvalitative case studier af elever og læreres arbejde med Junior PC......-kørekort® prøverne. DANSK IT's Junior PC-kørekort® kan betragtes som et forsøg på at etablere en bestemt fælleskulturel tilgang til elevernes IT-kompetencer i folkeskolen. Ud fra et situeret læringsperspektiv problematiserer rapporten anvendelsen af de standardiserede prøver som metode til at dokumentere og evaluere...... elevernes IT-kompetencer. Rapporten (2MB) fylder 80 sider ekskl. bilag. Bemærk, at forskningsrapporten handler om Dansk IT's Junior PC-kørekort - ikke at forveksle med det IT-bevis for folkeskolens elever, som Undevisningsministeriet har udviklet. Dette IT-bevis koncept skiftede navn i januar 2004, hvor...
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Functions and Mechanisms of Fibroblast Growth Factor (FGF Signalling in Drosophila melanogaster
Directory of Open Access Journals (Sweden)
Hans-Arno J. Müller
2013-03-01
Full Text Available Intercellular signalling via growth factors plays an important role in controlling cell differentiation and cell movements during the development of multicellular animals. Fibroblast Growth Factor (FGF signalling induces changes in cellular behaviour allowing cells in the embryo to move, to survive, to divide or to differentiate. Several examples argue that FGF signalling is used in multi-step morphogenetic processes to achieve and maintain a transitional state of the cells required for the control of cell fate. In the genetic model Drosophila melanogaster, FGF signalling via the receptor tyrosine kinases Heartless (Htl and Breathless (Btl is particularly well studied. These FGF receptors affect gene expression, cell shape and cell–cell interactions during mesoderm layer formation, caudal visceral muscle (CVM formation, tracheal morphogenesis and glia differentiation. Here, we will address the current knowledge of the biological functions of FGF signalling in the fly on the tissue, at a cellular and molecular level.
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What's So Special about FGF19-Unique Effects Reported on Skeletal Muscle Mass and Function.
Glass, David J
2017-08-01
In a recent study published in Nature Medicine, Benoit et al. (2017) reported unique effects of FGF19 on mouse skeletal muscle: FGF19 induced skeletal muscle hypertrophy and blocked muscle atrophy, acting via FGF receptors and ßKlotho, while a related FGF21 hormone was ineffective. Copyright © 2017 Elsevier Inc. All rights reserved.
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Relationship between family history of type 2 diabetes and serum FGF21.
Davis, Greggory R; Deville, Tiffany; Guillory, Joshua; Bellar, David; Nelson, Arnold G
2017-11-01
Determining predictive markers for the development of type 2 diabetes (T2D), particularly in young individuals, offers immense potential benefits in preventative medicine. Previous research examining serum fibroblast growth factor 21 (FGF21) in humans has revealed equivocal relationships with clinical markers of metabolic dysfunction. However, it is unknown to what extent, if any, first-degree family history of T2D (mother or father of the participant diagnosed with T2D) level affects serum FGF21 levels. The aim of this study was to determine whether in healthy individuals with FH+ (n = 18) and without FH- (n = 17) a family history of T2D affects serum FGF21. Fasting serum and clinical, metabolic and anthropometric measures were determined using a cross-sectional design. Differences between groups for FGF21 were not significant (FH+ = 266 pg/mL ± 51·4, FH = 180 pg/mL ± 29; Z = 0·97, P = 0·33). Adiponectin values were lower in FH+ (8·81 μg/mL ± 2·14) compared to FH- (10·65 μg/mL ± 1·44; F = 8·83, P = 0·01). Resistin was negatively correlated with FGF21 for all participants (r = -0·38, P = 0·03), but no other clinical, metabolic, or serum markers were predictive for serum FGF21 in FH+ or FH-. Serum FGF21 is not significantly different between FH+ and FH- in young, healthy individuals. Based upon the data of this pilot study, it is unclear whether serum FGF21 can be used as a stand-alone predictive marker for T2D in healthy subjects. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.
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JEF-PC 2.0. A PC program for viewing evaluated and experimental data
International Nuclear Information System (INIS)
Konieczny, M.
1997-01-01
In an attempt to make nuclear data more easily accessible to a wider user community, as well as providing a useful tool for experienced users, the NEA has supported the development of PC software for accessing and displaying nuclear data in a user-friendly and intuitive manner. The data contained in JEF-PC version 2.0 is predominantly taken from the Joint Evaluated File (JEF-2.2). The JEF-2.2 library comprises sets of evaluated nuclear data, mainly for fission reactor applications; it contains a number of different types of data, including neutron interaction data, radioactive decay data and fission yield data. The package consists of a central 'driver' program displaying an electronic representation of the Chart of the Nuclides, from which a target nuclide is selected. Through this interface a number of peripheral database modules, containing different categories of basic nuclear data, can be accessed. Cross section data, radioactive decay data, and fission yield data are available in separate modules named CROSS, DECAY and FISSION respectively. (K.A.)
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Energy Technology Data Exchange (ETDEWEB)
Wu, Zong-Sian, E-mail: gary810426@hotmail.com [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Liu, Che Fu, E-mail: s9823002@m98.nthu.edu.tw [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Fu, Brian, E-mail: brianfu9@gmail.com [Northwood High School, Irvine, CA (United States); Chou, Ruey-Hwang, E-mail: rhchou@mail.cmu.edu.tw [Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan (China); Department of Biotechnology, Asia University, Taiwan (China); Yu, Chin, E-mail: cyu.nthu@gmail.com [Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan (China)
2016-09-02
The extracellular portion of the human fibroblast growth factor receptor2 D2 domain (FGFR2 D2) interacts with human fibroblast growth factor 1 (hFGF1) to activate a downstream signaling cascade that ultimately affects mitosis and differentiation. Suramin is an antiparasiticdrug and a potent inhibitor of FGF-induced angiogenesis. Suramin has been shown to bind to hFGF1, and might block the interaction between hFGF1 and FGFR2 D2. Here, we titrated hFGF1 with FGFR2 D2 and suramin to elucidate their interactions using the detection of NMR. The docking results of both hFGF1-FGFR2 D2 domain and hFGF1-suramin complex were superimposed. The results indicate that suramin blocks the interaction between hFGF1 and FGFR2 D2. We used the PyMOL software to show the hydrophobic interaction of hFGF1-suramin. In addition, we used a Water-soluble Tetrazolium salts assay (WST1) to assess hFGF1 bioactivity. The results will be useful for the development of new antimitogenic activity drugs. - Highlights: • The interfacial residues on hFGF1-FGFR2 D2 and hFGF1-Suramin contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • hFGF1-FGFR2 D2 and hFGF1-Suramin complex models were generated from NMR restraints by using HADDOCK program. • We analyzed hFGF1-Suramin complex models and found the interaction between hFGF1-Suramin is hydrophobic. • The bioactivity of the hFGF1-FGFR2 D2 and hFGF1-Suramin complex was studied by using WST1 assay.
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International Nuclear Information System (INIS)
Wu, Zong-Sian; Liu, Che Fu; Fu, Brian; Chou, Ruey-Hwang; Yu, Chin
2016-01-01
The extracellular portion of the human fibroblast growth factor receptor2 D2 domain (FGFR2 D2) interacts with human fibroblast growth factor 1 (hFGF1) to activate a downstream signaling cascade that ultimately affects mitosis and differentiation. Suramin is an antiparasiticdrug and a potent inhibitor of FGF-induced angiogenesis. Suramin has been shown to bind to hFGF1, and might block the interaction between hFGF1 and FGFR2 D2. Here, we titrated hFGF1 with FGFR2 D2 and suramin to elucidate their interactions using the detection of NMR. The docking results of both hFGF1-FGFR2 D2 domain and hFGF1-suramin complex were superimposed. The results indicate that suramin blocks the interaction between hFGF1 and FGFR2 D2. We used the PyMOL software to show the hydrophobic interaction of hFGF1-suramin. In addition, we used a Water-soluble Tetrazolium salts assay (WST1) to assess hFGF1 bioactivity. The results will be useful for the development of new antimitogenic activity drugs. - Highlights: • The interfacial residues on hFGF1-FGFR2 D2 and hFGF1-Suramin contact surface were mapped by "1H-"1"5N HSQC experiments. • hFGF1-FGFR2 D2 and hFGF1-Suramin complex models were generated from NMR restraints by using HADDOCK program. • We analyzed hFGF1-Suramin complex models and found the interaction between hFGF1-Suramin is hydrophobic. • The bioactivity of the hFGF1-FGFR2 D2 and hFGF1-Suramin complex was studied by using WST1 assay.
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Directory of Open Access Journals (Sweden)
Ai-Luen Wu
Full Text Available Fibroblast growth factor 19 (FGF19 is a hormone-like protein that regulates carbohydrate, lipid and bile acid metabolism. At supra-physiological doses, FGF19 also increases hepatocyte proliferation and induces hepatocellular carcinogenesis in mice. Much of FGF19 activity is attributed to the activation of the liver enriched FGF Receptor 4 (FGFR4, although FGF19 can activate other FGFRs in vitro in the presence of the coreceptor βKlotho (KLB. In this report, we investigate the role of FGFR4 in mediating FGF19 activity by using Fgfr4 deficient mice as well as a variant of FGF19 protein (FGF19v which is specifically impaired in activating FGFR4. Our results demonstrate that FGFR4 activation mediates the induction of hepatocyte proliferation and the suppression of bile acid biosynthesis by FGF19, but is not essential for FGF19 to improve glucose and lipid metabolism in high fat diet fed mice as well as in leptin-deficient ob/ob mice. Thus, FGF19 acts through multiple receptor pathways to elicit pleiotropic effects in regulating nutrient metabolism and cell proliferation.
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Diagnostic Modalities for FGF23-Producing Tumors in Patients with Tumor-Induced Osteomalacia
Directory of Open Access Journals (Sweden)
Seiji Fukumoto
2014-06-01
Full Text Available Fibroblast growth factor 23 (FGF23 is a hormone that is produced by osteocytes and regulates phosphate and vitamin D metabolism through binding to the Klotho-FGF receptor complex. Excessive actions of FGF23 cause several kinds of hypophosphatemic rickets/osteomalacia. Tumor-induced rickets/osteomalacia (TIO is a paraneoplastic syndrome caused by overproduction of FGF23 from the responsible tumors. Because TIO is cured by complete resection of the causative tumors, it is of great clinical importance to locate these tumors. Several imaging methods including skeletal survey by magnetic resonance imaging and octreotide scintigraphy have been used to identify the tumors that cause TIO. However, none of these imaging studies indicate that the detected tumors are actually producing FGF23. Recently, systemic venous sampling was conducted for locating FGF23-producing tumor in suspected patients with TIO and demonstrated that this test might be beneficial to a subset of patient. Further studies with more patients are necessary to establish the clinical utility of venous sampling in patients with TIO.
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Impact of Annexin A 7 Deficiency on FGF23 Plasma Concentrations
Directory of Open Access Journals (Sweden)
Anja T. Umbach
2016-11-01
Full Text Available Background/Aims: The release of fibroblast growth factor FGF23, a powerful regulator of 1,25(OH2D3 formation and mineral metabolism, is stimulated by store-operated Ca2+ entry (SOCE, which is accomplished by the pore forming Ca2+ release activated channel protein Orai1. Regulators of Orai1 and thus FGF23 release include serum & glucocorticoid inducible kinase SGK1, a kinase up-regulated by glucocorticosteroids. Some effects of glucocorticoids require the presence of annexin A7, such as suppression of prostaglandin E2 in gastric glands. The present study thus explored whether annexin A7 impacts on FGF23 plasma levels. Methods: Comparisons were made between gene targeted mice lacking functional annexin A7 (Anx7-/- and their wild type littermates (Anx7+/+. Serum C-terminal-FGF23, intact FGF23, 1,25(OH2D3 and PTH concentrations were measured by ELISA or EIA. The serum and urinary phosphate concentrations were measured by colorimetry, the serum Ca2+ concentration and the urinary Ca2+ concentration by flame photometry. Results: Serum C-terminal FGF23 levels and corticosterone levels were significantly higher and serum 1,25(OH2 D3 and PTH levels were significantly lower in Anx7-/- than in Anx7+/+ mice. Water intake was slightly but significantly higher in Anx7-/- mice than in Anx7+/+ mice. No significant difference was observed between Anx7-/- and Anx7+/+ mice in urinary fluid excretion, plasma Ca2+ concentration, plasma phosphate concentration and urinary Ca2+ output. The urinary phosphate output was significantly lower in Anx7-/- mice than in Anx7+/+ mice. Conclusion: Annexin A7 deficiency upregulates FGF23 plasma levels, an effect paralleled by increased corticosterone plasma levels, as well as decreased 1,25(OH2 D3 and PTH plasma levels.
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Masuda, Yuki; Ohta, Hiroya; Morita, Yumiko; Nakayama, Yoshiaki; Miyake, Ayumi; Itoh, Nobuyuki; Konishi, Morichika
2015-01-01
Fibroblast growth factors (Fgfs) are polypeptide growth factors with diverse biological activities. While several studies have revealed that Fgf23 plays important roles in the regulation of phosphate and vitamin D metabolism, the additional physiological roles of Fgf23 remain unclear. Although it is believed that osteoblasts/osteocytes are the main sources of Fgf23, we previously found that Fgf23 mRNA is also expressed in the mouse thymus, suggesting that it might be involved in the immune system. In this study we examined the potential roles of Fgf23 in immunological responses. Mouse serum Fgf23 levels were significantly increased following inoculation with Escherichia coli or Staphylococcus aureus or intraperitoneal injection of lipopolysaccharide. We also identified activated dendritic cells and macrophages that potentially contributed to increased serum Fgf23 levels. Nuclear factor-kappa B (NF-κB) signaling was essential for the induction of Fgf23 expression in dendritic cells in response to immunological stimuli. Moreover, we examined the effects of recombinant Fgf23 protein on immune cells in vitro. Fgfr1c, a potential receptor for Fgf23, was abundantly expressed in macrophages, suggesting that Fgf23 might be involved in signal transduction in these cells. Our data suggest that Fgf23 potentially increases the number in macrophages and induces expression of tumor necrosis factor-α (TNF-α), a proinflammatory cytokine. Collectively, these data suggest that Fgf23 might be intimately involved in inflammatory processes.
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Directory of Open Access Journals (Sweden)
Zhifeng Huang
Full Text Available As one of fibroblast growth factor (FGF family members, FGF21 has been extensively investigated for its potential as a drug candidate to combat metabolic diseases. In the present study, recombinant human FGF21 (rhFGF21 was modified with polyethylene glycol (PEGylation in order to increase its in vivo biostabilities and therapeutic potency. At N-terminal residue rhFGF21 was site-selectively PEGylated with mPEG20 kDa-butyraldehyde. The PEGylated rhFGF21 was purified to near homogeneity by Q Sepharose anion-exchange chromatography. The general structural and biochemical features as well as anti-diabetic effects of PEGylated rhFGF21 in a type 2 diabetic rat model were evaluated. By N-terminal sequencing and MALDI-TOF mass spectrometry, we confirmed that PEG molecule was conjugated only to the N-terminus of rhFGF21. The mono-PEGylated rhFGF21 retained the secondary structure, consistent with the native rhFGF21, but its biostabilities, including the resistance to physiological temperature and trypsinization, were significantly enhanced. The in vivo immunogenicity of PEGylated rhFGF21 was significantly decreased, and in vivo half-life time was significantly elongated. Compared to the native form, the PEGylated rhFGF21 had a similar capacity of stimulating glucose uptake in 3T3-L1 cells in vitro, but afforded a significantly long effect on reducing blood glucose and triglyceride levels in the type 2 diabetic animals. These results suggest that the PEGylated rhFGF21 is a better and more effective anti-diabetic drug candidate than the native rhFGF21 currently available. Therefore, the PEGylated rhFGF21 may be potentially applied in clinics to improve the metabolic syndrome for type 2 diabetic patients.
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Recycling: Establishing a Citizen-Sponsored Reclamation Center.
Keep America Beautiful, Inc., New York, NY.
This booklet applies the Clean Community System (CCS) of Keep America Beautiful, Inc. to the development of citizen-sponsored recycling projects. Six initial steps in establishing a reclamation center are given and include information gathering, market analysis, legal requirements, and site location. Suggestions are included for recruiting staff…
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Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis
DEFF Research Database (Denmark)
Cao, Renhai; Ji, Hong; Feng, Ninghan
2012-01-01
Interplay between various lymphangiogenic factors in promoting lymphangiogenesis and lymphatic metastasis remains poorly understood. Here we show that FGF-2 and VEGF-C, two lymphangiogenic factors, collaboratively promote angiogenesis and lymphangiogenesis in the tumor microenvironment, leading...... endothelial cell tip cell formation is a prerequisite for FGF-2-stimulated lymphangiogenesis. In the tumor microenvironment, the reciprocal interplay between FGF-2 and VEGF-C collaboratively stimulated tumor growth, angiogenesis, intratumoral lymphangiogenesis, and metastasis. Thus, intervention and targeting...
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The effects of de-humidification and O{sub 2} direct injection in oxy-PC combustion
Energy Technology Data Exchange (ETDEWEB)
Choi, C.G.; Na, I.H.; Lee, J.W.; Chae, T.Y.; Yang, W. [Korea Insitute of Industrial Technology, Seoul (Korea, Republic of). Energy System R and D Dept.
2013-07-01
This study is aimed to derive effects of de-humidification and O{sub 2} direct injection in oxy-PC combustion system. Temperature distribution and flue gas composition were observed for various air and oxy-fuel conditions such as effect of various O{sub 2} concentration of total oxidant, O{sub 2} concentration of primary stream and O{sub 2} direct injection through 0-D heat and mass balance calculation and experiments in the oxy-PC combustion system of 0.3 MW scale in KITECH (Korea Institute of Industrial Technology). Flame attachment characteristic related to O{sub 2} direct injection was also observed experimentally. We found that FEGT (furnace exit gas temperature) of 100% de-humidification to oxidizer is lower than humidification condition; difference between two conditions is lower than 20 C in all cases. The efficiency changing of combustion was negligible in O{sub 2} direct injection. But O{sub 2} direct injection should be carefully designed to produce a stable flame.
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International Nuclear Information System (INIS)
Xu Zengyu; Chen Jiming; Liu Xiang
2001-01-01
15 year's achievements of Southwestern Institute of Physics, China, in fusion technology and materials research sponsored by National '863' Engineering Projects are summarized. Many scientific and technical achievements are obtained in the researches on tritium production and recovery, doped carbon basic materials, V-alloys, 316L SS irradiation performance, B 4 C and TiC coatings, etc. Some facilities were built and some were improved for materials research. 108 references are annexed
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Sustained levels of FGF2 maintain undifferentiated stem cell cultures with biweekly feeding.
Directory of Open Access Journals (Sweden)
Steven Lotz
Full Text Available An essential aspect of stem cell culture is the successful maintenance of the undifferentiated state. Many types of stem cells are FGF2 dependent, and pluripotent stem cells are maintained by replacing FGF2-containing media daily, while tissue-specific stem cells are typically fed every 3rd day. Frequent feeding, however, results in significant variation in growth factor levels due to FGF2 instability, which limits effective maintenance due to spontaneous differentiation. We report that stabilization of FGF2 levels using controlled release PLGA microspheres improves expression of stem cell markers, increases stem cell numbers and decreases spontaneous differentiation. The controlled release FGF2 additive reduces the frequency of media changes needed to maintain stem cell cultures, so that human embryonic stem cells and induced pluripotent stem cells can be maintained successfully with biweekly feedings.
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Balasis, G.; Daglis, I. A.; Mann, I. R.; Papadimitriou, C.; Zesta, E.; Georgiou, M.; Haagmans, R.; Tsinganos, K.
2015-10-01
We use multi-satellite and ground-based magnetic data to investigate the concurrent characteristics of Pc3 (22-100 mHz) and Pc4-5 (1-22 mHz) ultra-low-frequency (ULF) waves on the 31 October 2003 during the Halloween magnetic superstorm. ULF waves are seen in the Earth's magnetosphere, topside ionosphere, and Earth's surface, enabling an examination of their propagation characteristics. We employ a time-frequency analysis technique and examine data from when the Cluster and CHAMP spacecraft were in good local time (LT) conjunction near the dayside noon-midnight meridian. We find clear evidence of the excitation of both Pc3 and Pc4-5 waves, but more significantly we find a clear separation in the L shell of occurrence of the Pc4-5 and Pc3 waves in the equatorial inner magnetosphere, separated by the density gradients at the plasmapause boundary layer. A key finding of the wavelet spectral analysis of data collected from the Geotail, Cluster, and CHAMP spacecraft and the CARISMA and GIMA magnetometer networks was a remarkably clear transition of the waves' frequency into dominance in a higher-frequency regime within the Pc3 range. Analysis of the local field line resonance frequency suggests that the separation of the Pc4-5 and Pc3 emissions across the plasmapause is consistent with the structure of the inhomogeneous field line resonance Alfvén continuum. The Pc4-5 waves are consistent with direct excitation by the solar wind in the plasma trough, as well as Pc3 wave absorption in the plasmasphere following excitation by upstream waves originating at the bow shock in the local noon sector. However, despite good solar wind coverage, our study was not able to unambiguously identify a clear explanation for the sharp universal time (UT) onset of the discrete frequency and large-amplitude Pc3 wave power.
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ORPLOT.PC: a graphic utility for ORMGEN.PC and ORVIRT.PC
International Nuclear Information System (INIS)
Inversini, C.; Bryson, J.W.
1986-06-01
ORPLOT.PC is an interactive graphic utility for ORMGEN.PC and ORVIRT.PC. It executes on an IBM PC/XT or PC/AT equipped with hard disk, graphic card, and 512K minimum memory. The program is capable of: (1) displaying finite-element meshes generated by ORMGEN.PC complete with node numbers, element numbers, and boundary conditions; and (2) generating deformed mesh plots, contour plots, line (X-Y) plots, and developed surface plots of ORVIRT.PC output. A zooming feature allows detailed inspection of any subregion. Because simplicity and ease of use were important objectives during program development, all commands are entered interactively using free format. The option of automatic or user-defined scaling for most plots is another convenience. Plot files may be created and written to hard disk for subsequent hardcopy to printer or plotter. 2 refs., 7 figs
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Directory of Open Access Journals (Sweden)
Karina Ferreira Duarte
2012-01-01
Full Text Available Um experimento foi realizado com o objetivo de estabelecer critérios de avaliação das exigências de treonina digestível para frangos de corte de 22 a 42 dias de idade utilizando-se diferentes modelos de regressão (quadrático, exponencial e de retas segmentadas ou Linear Response Plateau. Foram utilizados 1.920 frangos de corte machos com 22 dias de idade, distribuídos em delineamento inteiramente ao acaso, com seis tratamentos (seis níveis de treonina digestível: 0,5904; 0,6441; 0,6977; 0,7514; 0,8051 e 0,8588% e oito repetições de 40 aves. Utilizou-se como padrão o nível de 0,6977% de treonina digestível. Foram avaliados dados de desempenho e características de carcaça. Com base nos dados, o nível de 0,7642% de treonina digestível, correspondente às relação treonina:lisina digestível de 71,19%, promoveu o melhor resultado de conversão alimentar de acordo com o modelo Linear Response Plateau.The objective of this experiment was to establish different criteria for evaluation of the requirements of digestible threonine for broilers from 22 to 42 d of age, using different regression models (quadratic, exponential, and Linear Response Plateau. A total of 1,920 22-day-old male Cobb broilers were distributed in randomized experimental design, with six treatments (six threonine levels: 0.5904, 0.6441, 0.6977, 0.7514, 0.8051, and 0.8588% and 8 replications containing 40 broilers each one. The level of 0.6977% digestible threonine was used as standard. Data on performance and carcass characteristics were evaluated. Based on the data, the threonine level of 0.7642%, corresponding to the threonine:digestible lysine ratio of 71.19% had the best result for feed conversion, according to the Linear Response Plateau model.
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Generation of FGF reporter transgenic zebrafish and their utility in chemical screens
Directory of Open Access Journals (Sweden)
Tsang Michael
2007-06-01
Full Text Available Abstract Background Fibroblast Growth Factors (FGFs represent a large family of secreted proteins that are required for proper development and physiological processes. Mutations in mouse and zebrafish FGFs result in abnormal embryogenesis and lethality. A key to understanding the precise role for these factors is to determine their spatial and temporal activity during embryogenesis. Results Expression of Dual Specificity Phosphatase 6 (dusp6, also known as Mkp3 is controlled by FGF signalling throughout development. The Dusp6 promoter was isolated from zebrafish and used to drive expression of destabilized green fluorescent protein (d2EGFP in transgenic embryos (Tg(Dusp6:d2EGFP. Expression of d2EGFP is initiated as early as 4 hours post-fertilization (hpf within the future dorsal region of the embryo, where fgf3 and fgf8 are initially expressed. At later stages, d2EGFP is detected within structures that correlate with the expression of Fgf ligands and their receptors. This includes the mid-hindbrain boundary (MHB, pharyngeal endoderm, otic vesicle, hindbrain, and Kupffer's vesicle. The expression of d2EGFP is under the control of FGF signalling as treatment with FGF Receptor (FGFR inhibitors results in the suppression of d2EGFP expression. In a pilot screen of commercially available small molecules we have evaluated the effectiveness of the transgenic lines to identify specific FGF inhibitors within the class of indolinones. These compounds were counter screened with the transgenic line Tg(Fli1:EGFPy1, that serves as an indirect read-out for Vascular Endothelial Growth Factor (VEGF signalling in order to determine the specificity between related receptor tyrosine kinases (RTKs. From these assays it is possible to determine the specificity of these indolinones towards specific RTK signalling pathways. This has enabled the identification of compounds that can block specifically the VEGFR or the FGFR signalling pathway. Conclusion The generation of
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PREPS2 - a PC-based computer program for performing economic analysis of capital projects
International Nuclear Information System (INIS)
Blake, M.W.; Brand, D.O.; Chastain, E.T.; Johnson, E.D.
1990-01-01
In these times of increased spending to finance new capacity and to meet clean air act legislation, many electric utilities are giving a high priority to controlling capital expenditures at existing generating facilities. Determining the level of capital expenditures which are economically justified is very difficult; units which have higher capacity factors are worth more to the utility. Therefore, the utility can more readily justify higher capital expenditures to improve or maintain reliability and heat rate than on units with lower capacity factors. This paper describes a PC-based computer program (PREPS2) which performs an economic analysis of individual capital projects. The program incorporates tables which describe the worth to the system of making improvements in each unit. This computer program is currently being used by the six Southern Company operating companies to evaluate all production capital projects over $50,000. Approximately 500 projects representing about $300 million are being analyzed each year
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VEGF and bFGF Gene Polymorphisms in Patients with Non-Hodgkin's Lymphoma
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Tomasz Wróbel
2013-01-01
Full Text Available Angiogenesis and lymphangiogenesis are important in the proliferation and survival of the malignant hematopoietic neoplasms, including non-Hodgkin’s lymphomas (NHLs. Vascular endothelial growth factor (VEGF and basic fibroblast growth factor (bFGF play an important role in the initiation of angiogenesis. Both VEGF and bFGF have been reported to have prognostic significance in NHL. The present study aimed to determine an association between the VEGF and bFGF gene polymorphisms and disease susceptibility and progression. VEGF (rs3025039; 936 C>T and bFGF (rs308395, −921 G>C variants were determined in 78 NHL patients and 122 healthy individuals by PCR-RFLP technique. The presence of the VEGF 936T allele was found to significantly associate with worse prognosis of the disease (expressed by the highest International Prognostic Index (IPI (0.41 versus 0.20, for IPI 4 among patients having and lacking the T allele. The VEGF 936T variant was also more frequent among patients with IPI 4 than in controls (OR = 3.37, . The bFGF −921G variant was more frequently detected among patients with aggressive as compared to those with indolent histological subtype (0.37 versus 0.18, and healthy individuals (0.37 versus 0.19, OR = 2.51, . These results imply that VEGF and bFGF gene polymorphisms have prognostic significance in patients with NHL.
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Oncogenic osteomalacia due to FGF23-expressing colon adenocarcinoma.
Leaf, David E; Pereira, Renata C; Bazari, Hasan; Jüppner, Harald
2013-03-01
Oncogenic osteomalacia, a paraneoplastic syndrome associated with hypophosphatemia due to increased urinary phosphate excretion, is caused by excessive synthesis and secretion of fibroblast growth factor 23 (FGF23), a phosphaturic hormone that is normally produced by osteocytes. Most cases of oncogenic osteomalacia have been associated with benign tumors of bone or soft tissue; however, whether malignant neoplasms can also produce and secrete FGF23 is currently unknown. The aim was to determine whether a malignant neoplasm could cause oncogenic osteomalacia through excessive production and secretion of FGF23. We describe an 80-year-old woman with stage IV colon adenocarcinoma who presented with severe hypophosphatemia (0.4 mg/dL; reference, 2.6-4.5 mg/dL). Fractional excretion of phosphate was 34% (reference, osteomalacia should be considered in the differential diagnosis for patients with a malignant tumor who present with hypophosphatemia.
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Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR)
Energy Technology Data Exchange (ETDEWEB)
Cheng, Xingguo, E-mail: chengx@stjohns.edu [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Queens, NY 11439 (United States); Vispute, Saurabh G. [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Queens, NY 11439 (United States); Liu, Jie [Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Cheng, Christine; Kharitonenkov, Alexei [Lilly Research Laboratories, Division of Eli Lilly and Co., Indianapolis, IN 46285 (United States); Klaassen, Curtis D., E-mail: curtisklaassenphd@gmail.com [Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States)
2014-07-01
The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (− 105/+ 1 base pair). Fgf21-null mice administered 200 μg/kg of TCDD died within 20 days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver. - Highlights: • TCDD induced Fgf21 expression at both mRNA and protein levels. • Fgf21 induction by TCDD is AhR-dependent. • DEHP attenuated TCDD-induced Fgf21 expression.
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Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR)
International Nuclear Information System (INIS)
Cheng, Xingguo; Vispute, Saurabh G.; Liu, Jie; Cheng, Christine; Kharitonenkov, Alexei; Klaassen, Curtis D.
2014-01-01
The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (− 105/+ 1 base pair). Fgf21-null mice administered 200 μg/kg of TCDD died within 20 days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver. - Highlights: • TCDD induced Fgf21 expression at both mRNA and protein levels. • Fgf21 induction by TCDD is AhR-dependent. • DEHP attenuated TCDD-induced Fgf21 expression
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Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination.
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Yuna Kim
2006-06-01
Full Text Available The genes encoding members of the wingless-related MMTV integration site (WNT and fibroblast growth factor (FGF families coordinate growth, morphogenesis, and differentiation in many fields of cells during development. In the mouse, Fgf9 and Wnt4 are expressed in gonads of both sexes prior to sex determination. Loss of Fgf9 leads to XY sex reversal, whereas loss of Wnt4 results in partial testis development in XX gonads. However, the relationship between these signals and the male sex-determining gene, Sry, was unknown. We show through gain- and loss-of-function experiments that fibroblast growth factor 9 (FGF9 and WNT4 act as opposing signals to regulate sex determination. In the mouse XY gonad, Sry normally initiates a feed-forward loop between Sox9 and Fgf9, which up-regulates Fgf9 and represses Wnt4 to establish the testis pathway. Surprisingly, loss of Wnt4 in XX gonads is sufficient to up-regulate Fgf9 and Sox9 in the absence of Sry. These data suggest that the fate of the gonad is controlled by antagonism between Fgf9 and Wnt4. The role of the male sex-determining switch--Sry in the case of mammals--is to tip the balance between these underlying patterning signals. In principle, sex determination in other vertebrates may operate through any switch that introduces an imbalance between these two signaling pathways.
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Mohammadi, M; Dionne, C A; Li, W; Li, N; Spivak, T; Honegger, A M; Jaye, M; Schlessinger, J
1992-08-20
Stimulation of growth factor receptors with tyrosine kinase activity is followed by rapid receptor dimerization, tyrosine autophosphorylation and phosphorylation of signalling molecules such as phospholipase C gamma (PLC gamma) and the ras GTPase-activating protein. PLC gamma and GTPase-activating protein bind to specific tyrosine-phosphorylated regions in growth factor receptors through their src-homologous SH2 domains. Growth factor-induced tyrosine phosphorylation of PLC gamma is essential for stimulation of phosphatidylinositol hydrolysis in vitro and in vivo. We have shown that a short phosphorylated peptide containing tyrosine at position 766 from a conserved region of the fibroblast growth factor (FGF) receptor is a binding site for the SH2 domain of PLC gamma (ref. 8). Here we show that an FGF receptor point mutant in which Tyr 766 is replaced by a phenylalanine residue (Y766F) is unable to associate with and tyrosine-phosphorylate PLC gamma or to stimulate hydrolysis of phosphatidylinositol. Nevertheless, the Y766F FGF receptor mutant can be autophosphorylated, and can phosphorylate several cellular proteins and stimulate DNA synthesis. Our data show that phosphorylation of the conserved Tyr 766 of the FGF receptor is essential for phosphorylation of PLC gamma and for hydrolysis of phosphatidylinositol, but that elimination of this hydrolysis does not affect FGF-induced mitogenesis.
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Directory of Open Access Journals (Sweden)
Randy Hecht
Full Text Available Fibroblast growth factor 21 (FGF21 is a promising drug candidate for the treatment of type 2 diabetes. However, the use of wild type native FGF21 is challenging due to several limitations. Among these are its short half-life, its susceptibility to in vivo proteolytic degradation and its propensity to in vitro aggregation. We here describe a rationale-based protein engineering approach to generate a potent long-acting FGF21 analog with improved resistance to proteolysis and aggregation. A recombinant Fc-FGF21 fusion protein was constructed by fusing the Fc domain of human IgG1 to the N-terminus of human mature FGF21 via a linker peptide. The Fc positioned at the N-terminus was determined to be superior to the C-terminus as the N-terminal Fc fusion retained the βKlotho binding affinity and the in vitro and in vivo potency similar to native FGF21. Two specific point mutations were introduced into FGF21. The leucine to arginine substitution at position 98 (L98R suppressed FGF21 aggregation at high concentrations and elevated temperatures. The proline to glycine replacement at position 171 (P171G eliminated a site-specific proteolytic cleavage of FGF21 identified in mice and cynomolgus monkeys. The derived Fc-FGF21(RG molecule demonstrated a significantly improved circulating half-life while maintaining the in vitro activity similar to that of wild type protein. The half-life of Fc-FGF21(RG was 11 h in mice and 30 h in monkeys as compared to 1-2 h for native FGF21 or Fc-FGF21 wild type. A single administration of Fc-FGF21(RG in diabetic mice resulted in a sustained reduction in blood glucose levels and body weight gains up to 5-7 days, whereas the efficacy of FGF21 or Fc-FGF21 lasted only for 1 day. In summary, we engineered a potent and efficacious long-acting FGF21 analog with a favorable pharmaceutical property for potential clinical development.
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Directory of Open Access Journals (Sweden)
Elizabeth Ortega-Soto
2012-01-01
Full Text Available Las encefalopatías espongiformes transmisibles (EETs son enfermedades neurodegenerativas fatales que afectan a humanos y ciertas especies animales. La hipótesis más aceptada indica que el agente infeccioso, denotado como prion y compuesto principalmente por la Proteína Priónica Scrapie (PrPSc, corresponde a una conformación anormal de una proteína codificada por el huésped denominada Proteína Priónica Celular (PrPC, cuya función es aún desconocida; sin embargo, la expresión ubicua de PrPC así como su elevado grado de conservación entre especies, sugieren un papel importante para esta proteína. En este trabajo se detectó a la PrPC en diferentes tipos celulares incluyendo un cultivo primario de células de peces (Tilapia, Oreochromis spp.. Además, basándonos en la secuencia de la PrPC humana, se diseñó un RNA de interferencia (siRNA con el fin de silenciar el gen PRNP en células neuronales SK-SY5Y. El siRNA diseñado inhibió la expresión de PrPC a lo largo de las 96 h post-transfección y las células silenciadas fueron menos susceptibles a la infección por HSV-1 y HSV-2, en comparación con células no transfectadas con el siRNA.
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Directory of Open Access Journals (Sweden)
Wientjes M Guillaume
2008-01-01
Full Text Available Abstract Background The role of basic fibroblast growth factor (bFGF in chemoresistance is controversial; some studies showed a relationship between higher bFGF level and chemoresistance while other studies showed the opposite finding. The goal of the present study was to quantify bFGF levels in archived tumor tissues, and to determine its relationship with chemosensitivity. Methods We established an image analysis-based method to quantify and convert the immunostaining intensity of intra-tumor bFGF to concentrations; this was accomplished by generating standard curves using human xenograft tumors as the renewable tissue source for simultaneous image analysis and ELISA. The relationships between bFGF concentrations and tumor chemosensitivity of patient tumors (n = 87 to paclitaxel were evaluated using linear regression analysis. Results The image analysis results were compared to our previous results obtained using a conventional, semi-quantitative visual scoring method. While both analyses indicated an inverse relationship between bFGF level and tumor sensitivity to paclitaxel, the image analysis method, by providing bFGF levels in individual tumors and therefore more data points (87 numerical values as opposed to four groups of staining intensities, further enabled the quantitative analysis of the relationship in subgroups of tumors with different pathobiological properties. The results show significant correlation between bFGF level and tumor sensitivity to the antiproliferation effect, but not the apoptotic effect, of paclitaxel. We further found stronger correlations of bFGF level and paclitaxel sensitivity in four tumor subgroups (high stage, positive p53 staining, negative aFGF staining, containing higher-than-median bFGF level, compared to all other groups. These findings suggest that the relationship between intra-tumoral bFGF level and paclitaxel sensitivity was context-dependent, which may explain the previous contradictory findings
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Direct effects of FGF21 on glucose uptake in human skeletal muscle
DEFF Research Database (Denmark)
Mashili, Fredirick L; Austin, Reginald L; Deshmukh, Atul S
2011-01-01
21 were determined in normal glucose tolerant (n = 40) and type 2 diabetic (T2D; n = 40) subjects. We determined whether FGF21 has direct effects on glucose metabolism in cultured myotubes (n = 8) and extensor digitorum longus skeletal muscle. RESULTS: Serum FGF21 levels increased 20% in T2D versus...... normal glucose tolerant subjects (p muscle mRNA expression was unaltered. Fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), waist circumference, and body mass index (BMI) significantly correlated with serum FGF21 levels in T2D (p ... and insulin-stimulated glucose uptake in human myotubes, coincident with increased glucose transporter 1 mRNA, and enhanced glucose transporter 1 abundance at the plasma membrane. In isolated extensor digitorum longus muscle, FGF21 potentiated insulin-stimulated glucose transport, without altering...
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2010-04-01
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Employment. 62.16 Section 62.16 Foreign... § 62.16 Employment. (a) An exchange visitor may receive compensation from the sponsor or the sponsor's appropriate designee for employment when such activities are part of the exchange visitor's program. (b) An...
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Directory of Open Access Journals (Sweden)
José Américo Bonatti
2008-04-01
Full Text Available PURPOSE: To develop in an interdisciplinary approach between ophthalmology and design areas an ergonomic +22-diopter 50-mm aspheric hand magnifier for low vision. METHODS: An aluminum cylinder was cut, processed using a lathe and carved to produce a ring that accommodated a 50-mm aspheric lens, with an external depression not to slide from the holder's fingers. A cylindrical steel bar was cut, processed using a lathe and carved in order to form an externally turned ring to be screwed into the internal thread of the aluminum ring, to maintain the lens in a steady position. Both rings were submitted to electrostatic painting with a dull black electrostatic Epoxi ink, except the lower border of the external ring, to indicate the correct side of the magnifier to face the material to be read. RESULTS: A 22-diopter 50-mm diameter aspheric lens magnifier with a black ring to be hold at its external circular depression was obtained in order to safely search the adequate reading focus with an inferior aluminum colored ring to face the object to be read and allow a less distorted reading. This is the first Brazilian high-magnification great-diameter magnifier for low vision that permits basically the focusing on an entire word, not only syllables, in order to allow a faster and more comfortable reading. CONCLUSIONS: By an interdisciplinary approach a 22-diopter 50-mm aspheric lens magnifier was developed with image and ergonomic characteristics such as to permit comfortable and adequate reading performance in cases of low vision.OBJETIVO: Desenvolver de modo interdisciplinar entre as áreas de oftalmologia e design uma lupa de mão ergonômica de +22 dioptrias de 50 mm de diâmetro asférica para baixa visão. MÉTODOS: Um cilindro de alumínio foi cortado, torneado e teve feita internamente uma rosca a fim de produzir um anel para acomodar uma lente asférica de 50 mm de diâmetro com uma depressão externa para não escorregar dos dedos do portador. Uma
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Energy Technology Data Exchange (ETDEWEB)
Juliachs, M
2004-07-01
In this state of the art on parallel scientific visualization applications on PC clusters, we deal with both surface and volume rendering approaches. We first analyze available PC cluster configurations and existing parallel rendering software components for parallel graphics rendering. CEA/DIF has been studying cluster visualization since 2001. This report is part of a study to set up a new visualization research platform. This platform consisting of an eight-node PC cluster under Linux and a tiled display was installed in collaboration with Versailles-Saint-Quentin University in August 2003. (author)
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A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response
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Alison Iroz
2017-10-01
Full Text Available While the physiological benefits of the fibroblast growth factor 21 (FGF21 hepatokine are documented in response to fasting, little information is available on Fgf21 regulation in a glucose-overload context. We report that peroxisome-proliferator-activated receptor α (PPARα, a nuclear receptor of the fasting response, is required with the carbohydrate-sensitive transcription factor carbohydrate-responsive element-binding protein (ChREBP to balance FGF21 glucose response. Microarray analysis indicated that only a few hepatic genes respond to fasting and glucose similarly to Fgf21. Glucose-challenged Chrebp−/− mice exhibit a marked reduction in FGF21 production, a decrease that was rescued by re-expression of an active ChREBP isoform in the liver of Chrebp−/− mice. Unexpectedly, carbohydrate challenge of hepatic Pparα knockout mice also demonstrated a PPARα-dependent glucose response for Fgf21 that was associated with an increased sucrose preference. This blunted response was due to decreased Fgf21 promoter accessibility and diminished ChREBP binding onto Fgf21 carbohydrate-responsive element (ChoRE in hepatocytes lacking PPARα. Our study reports that PPARα is required for the ChREBP-induced glucose response of FGF21.
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Genetic Rescue of Glycosylation-deficient Fgf23 in the Galnt3 Knockout Mouse
Ichikawa, Shoji; Gray, Amie K.; Padgett, Leah R.; Allen, Matthew R.; Clinkenbeard, Erica L.; Sarpa, Nicole M.; White, Kenneth E.; Econs, Michael J.
2014-01-01
Fibroblast growth factor 23 (FGF23) is a hormone that inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D biosynthesis. The FGF23 subtilisin-like proprotein convertase recognition sequence (176RHTR179↓) is protected by O-glycosylation through ppGalNAc-T3 (GALNT3) activity. Thus, inactivating GALNT3 mutations render FGF23 susceptible to proteolysis, thereby reducing circulating intact hormone levels and leading to hyperphosphatemic familial tumoral calcinosis. To further delineat...
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Directory of Open Access Journals (Sweden)
Jia-Xin Xie
Full Text Available Effective therapy for visual loss caused by optic nerve injury or diseases has not been achieved even though the optic nerve has the regeneration potential after injury. This study was designed to modify amniotic epithelial cells (AECs with basic fibroblast growth factor (bFGF gene, preliminarily investigating its effect on transected optic nerve.A human bFGF gene segment was delivered into rat AECs (AECs/hbFGF by lentiviral vector, and the gene expression was examined by RT-PCR and ELISA. The AECs/hbFGF and untransfected rat AECs were transplanted into the transected site of the rat optic nerve. At 28 days post transplantation, the survival and migration of the transplanted cells was observed by tracking labeled cells; meanwhile retinal ganglion cells (RGCs were observed and counted by employing biotin dextran amine (BDA and Nissl staining. Furthermore, the expression of growth associated protein 43 (GAP-43 within the injury site was examined with immunohistochemical staining.The AECs/hbFGF was proven to express bFGF gene and secrete bFGF peptide. Both AECs/hbFGF and AECs could survive and migrate after transplantation. RGCs counting implicated that RGCs numbers of the cell transplantation groups were significantly higher than that of the control group, and the AECs/hbFGF group was significantly higher than that of the AECs group. Moreover GAP-43 integral optical density value in the control group was significantly lower than that of the cell transplantation groups, and the value in the AECs/hbFGF group was significantly higher than that of the AECs group.AECs modified with bFGF could reduce RGCs loss and promote expression of GAP-43 in the rat optic nerve transected model, facilitating the process of neural restoration following injury.
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Directory of Open Access Journals (Sweden)
G. Balasis
2015-10-01
Full Text Available We use multi-satellite and ground-based magnetic data to investigate the concurrent characteristics of Pc3 (22–100 mHz and Pc4-5 (1–22 mHz ultra-low-frequency (ULF waves on the 31 October 2003 during the Halloween magnetic superstorm. ULF waves are seen in the Earth's magnetosphere, topside ionosphere, and Earth's surface, enabling an examination of their propagation characteristics. We employ a time–frequency analysis technique and examine data from when the Cluster and CHAMP spacecraft were in good local time (LT conjunction near the dayside noon–midnight meridian. We find clear evidence of the excitation of both Pc3 and Pc4-5 waves, but more significantly we find a clear separation in the L shell of occurrence of the Pc4-5 and Pc3 waves in the equatorial inner magnetosphere, separated by the density gradients at the plasmapause boundary layer. A key finding of the wavelet spectral analysis of data collected from the Geotail, Cluster, and CHAMP spacecraft and the CARISMA and GIMA magnetometer networks was a remarkably clear transition of the waves' frequency into dominance in a higher-frequency regime within the Pc3 range. Analysis of the local field line resonance frequency suggests that the separation of the Pc4-5 and Pc3 emissions across the plasmapause is consistent with the structure of the inhomogeneous field line resonance Alfvén continuum. The Pc4-5 waves are consistent with direct excitation by the solar wind in the plasma trough, as well as Pc3 wave absorption in the plasmasphere following excitation by upstream waves originating at the bow shock in the local noon sector. However, despite good solar wind coverage, our study was not able to unambiguously identify a clear explanation for the sharp universal time (UT onset of the discrete frequency and large-amplitude Pc3 wave power.
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Directory of Open Access Journals (Sweden)
Kayla A Boortz
Full Text Available Elevated fasting blood glucose (FBG has been associated with increased risk for development of type 2 diabetes. Single nucleotide polymorphisms (SNPs in G6PC2 are the most important common determinants of variations in FBG in humans. Studies using G6pc2 knockout mice suggest that G6pc2 regulates the glucose sensitivity of insulin secretion. G6PC2 and the related G6PC1 and G6PC3 genes encode glucose-6-phosphatase catalytic subunits. This study describes a functional analysis of 22 non-synonymous G6PC2 SNPs, that alter amino acids that are conserved in human G6PC1, mouse G6pc1 and mouse G6pc2, with the goal of identifying variants that potentially affect G6PC2 activity/expression. Published data suggest strong conservation of catalytically important amino acids between all four proteins and the related G6PC3 isoform. Because human G6PC2 has very low glucose-6-phosphatase activity we used an indirect approach, examining the effect of these SNPs on mouse G6pc1 activity. Using a novel in situ functional assay for glucose-6-phosphatase activity we demonstrate that the amino acid changes associated with the human G6PC2 rs144254880 (Arg79Gln, rs149663725 (Gly114Arg and rs2232326 (Ser324Pro SNPs reduce mouse G6pc1 enzyme activity without affecting protein expression. The Arg79Gln variant alters an amino acid mutation of which, in G6PC1, has previously been shown to cause glycogen storage disease type 1a. We also demonstrate that the rs368382511 (Gly8Glu, rs138726309 (His177Tyr, rs2232323 (Tyr207Ser rs374055555 (Arg293Trp, rs2232326 (Ser324Pro, rs137857125 (Pro313Leu and rs2232327 (Pro340Leu SNPs confer decreased G6PC2 protein expression. In summary, these studies identify multiple G6PC2 variants that have the potential to be associated with altered FBG in humans.
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Renal expression of FGF23 in progressive renal disease of diabetes and the effect of ACE inhibitor.
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Cristina Zanchi
Full Text Available Fibroblast growth factor 23 (FGF23 is a phosphaturic hormone mainly produced by bone that acts in the kidney through FGF receptors and Klotho. Here we investigated whether the kidney was an additional source of FGF23 during renal disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23 and Klotho was assessed in Zucker diabetic fatty (ZDF and control lean rats at 2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of angiotensin converting enzyme (ACE inhibitor in this model was associated with changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric, to 8 months of age. FGF23 mRNA was not detectable in the kidney of lean rats, nor of ZDF rats at 2 months of age. FGF23 became measurable in the kidney of diabetic rats at 4 months and significantly increased thereafter. FGF23 protein localized in proximal and distal tubules. Renal Klotho mRNA and protein decreased during time in ZDF rats. As renal disease progressed, serum phosphate levels increased in parallel with decline of fractional phosphorus excretion. Ramipril limited proteinuria and renal injury, attenuated renal FGF23 upregulation and ameliorated Klotho expression. Ramipril normalized serum phosphate levels and tended to increase fractional phosphorus excretion. These data indicate that during progressive renal disease the kidney is a site of FGF23 production which is limited by ACE inhibition. Interfering pharmacologically with the delicate balance of FGF23 and phosphorus in diabetes may have implications in clinics.
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Directory of Open Access Journals (Sweden)
Elizabeth Benites Estupiñán
2006-01-01
Full Text Available Este artículo describe algunos problemas éticos derivados de los estudios multicéntricos en países en desarrollo, particularmente los referidos al rol de los patrocinadores luego de concluido un ensayo clínico. Luego de pasar revista a algunas normativas internacionales, propone un conjunto de obligaciones éticas para los patrocinadores de estos ensayos. Las evidencias mostradas hacia el final sugieren más bien pesimismo respecto de su cumplimientoEste artigo descreve alguns problemas éticos derivados dos estudos muticêntricos nos países em desenvolvimento, particularmente os relacionados com o papel dos patrocinadores logo após a conclusão de um ensaio clínico. Após análise de algumas normas interaccionáis, propõe um conjunto de obrigações éticas para os patrocinadores destes ensaios. As evidências indicam um certo pessimismo quanto ao seu cumprimentoThis paper describes some ethical problems derived from multi center studies in developing countries, specifically those referred to the role of sponsors after the clinical trial is concluded. After reviewing some international norms, it proposes several ethical obligations fro sponsors of these trials. Finally, the evidence shows pessimism with respect to fulfilling them
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α-Trinositol inhibits FGF-stimulated growth of smooth muscle and breast cancer cells
International Nuclear Information System (INIS)
Siren, Matti J.; Vainiomaeki, Maija; Vaeaenaenen, Kalervo; Haerkoenen, Pirkko
2004-01-01
α-Trinositol (D-myo-inositol-1,2,6-trisphosphate), an isomer of the intracellular messenger IP 3 , has been studied for its anti-inflammatory and other effects in animal experiments and in human. The mechanisms of action remain unknown. Several human pathologies are associated with uncontrolled production of fibroblast growth factors (FGFs). FGF-2 induces vascular smooth muscle cell proliferation, which contributes to restenosis after coronary balloon angioplasty. The expression of several FGFs is also increased in tumors. We studied the effects of the water- and lipid-soluble derivatives of α-trinositol on the FGF-2- and/or FGF-8-induced proliferation of human pulmonary artery smooth muscle cells (HPASMC) and S115 mouse breast cancer cells. α-Trinositol decreased the FGF-mediated proliferation of HPASMC and S115 cells. Membrane permeability did not seem obligatory since the lipid-soluble form of α-trinositol was less effective than the water-soluble derivative. These results suggest a new biological function for certain phosphoinositides in the modulation of FGF-regulated processes
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Subcellular trafficking of FGF controls tracheal invasion of Drosophila flight muscle.
Peterson, Soren J; Krasnow, Mark A
2015-01-15
To meet the extreme oxygen demand of insect flight muscle, tracheal (respiratory) tubes ramify not only on its surface, as in other tissues, but also within T-tubules and ultimately surrounding every mitochondrion. Although this remarkable physiological specialization has long been recognized, its cellular and molecular basis is unknown. Here, we show that Drosophila tracheoles invade flight muscle T-tubules through transient surface openings. Like other tracheal branching events, invasion requires the Branchless FGF pathway. However, localization of the FGF chemoattractant changes from all muscle membranes to T-tubules as invasion begins. Core regulators of epithelial basolateral membrane identity localize to T-tubules, and knockdown of AP-1γ, required for basolateral trafficking, redirects FGF from T-tubules to surface, increasing tracheal surface ramification and preventing invasion. We propose that tracheal invasion is controlled by an AP-1-dependent switch in FGF trafficking. Thus, subcellular targeting of a chemoattractant can direct outgrowth to specific domains, including inside the cell. Copyright © 2015 Elsevier Inc. All rights reserved.
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The USL NASA PC R and D development environment standards
Dominick, Wayne D. (Editor); Moreau, Dennis R.
1984-01-01
The development environment standards which have been established in order to control usage of the IBM PC/XT development systems and to prevent interference between projects being currently developed on the PC's are discussed. The standards address the following areas: scheduling PC resources; login/logout procedures; training; file naming conventions; hard disk organization; diskette care; backup procedures; and copying policies.
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Directory of Open Access Journals (Sweden)
Lei He
2017-01-01
Full Text Available Liver biopsy still remains the gold standard for diagnosing nonalcoholic steatohepatitis (NASH, but with limitations. There is an urgent need to develop noninvasive tests that accurately distinguish NASH from simple steatosis. The purpose of this meta-analysis was to evaluate the diagnostic value of serum biomarkers including cytokeratin 18 (CK-18, fibroblast growth factor 21 (FGF-21, and combined biomarker panel (CBP in the diagnosis of NAFLD, especially NASH. A total of 25 studies met the inclusion criteria. Pooled sensitivity and specificity values for chosen serum markers for diagnosing NASH are as follows: CK-18 (M30, 0.75 and 0.77; CK-18 (M65, 0.71 and 0.77; FGF-21, 0.62 and 0.78; and CBP, 0.92 and 0.85. CBP demonstrated better accuracy with higher sensitivity and specificity than those tested individually. Furthermore, the AUROC of CBP was 0.94 (95% CI, 0.92–0.96, compared to CK-18 or FGF-21 assay, which showed the most significant ability to distinguish NASH from simple steatosis. The results suggest that increased circulating CK-18 and FGF-21 are associated with NASH and may be used for initial assessment, but not enough. Importantly, CBP is potentially used as accurate diagnostic tools for NASH. Further prospective designed studies are warranted to confirm our findings.
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Directory of Open Access Journals (Sweden)
Santos, Vagner Rodrigues
2010-01-01
Full Text Available Objetivo: Investigar a expressão da atividade de fosfatase alcalina (ALP em fibroblastos gengivais de sujeitos com periodontite crônica (PC e hiperplasia gengival medicamentosa (HGM induzida por difenilhidantoína. Metodologia: Os fragmentos gengivais foram obtidos de 13 pacientes (8 mulheres e 5 homens, 22 a 74 anos, sendo 4 fragmentos procedentes de gengiva clinicamente normal (GN, 5 de biópsias de bolsas periodontais com PC e 4 de HGM induzida pela difenilhidantoína. Através de digestão enzimática, suspensões de células gengivais foram preparadas contendo fibroblastos ALP-positivos sem afetar a atividade da enzima ALP. Análises citoquímica e histoquímica foram realizadas. Resultados: Fibroblastos de GN apresentaram fraca positividade para ALP quando comparados com PC e HGM. PC e HGM exibiram níveis elevados e intermediários, respectivamente, de ALP. Observou-se menor proliferação celular na cultura de células em PC e HGM que em GN. Entretanto, a quantidade de células recuperadas das sub-culturas foi similar à quantidade recuperada na cultura inicial para as três linhagens. Conclusões: A expressão de ALP na PC e na HGM encontra-se aumentada e ocorre baixa proliferação de fibroblastos na PC e na HGM. Isto sugere que a inflamação periodontal e a difenilhidantoína podem influenciar a expressão de ALP e a multiplicação de fibroblastos gengivais humanos. Outros estudos são necessários para melhor avaliar a importância de ALP no desenvolvimento e na progressão de PC e HGM
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Ross, Howard (Compiler)
2000-01-01
This document contains the results of a collection of selected cooperative research projects between principal investigators in the microgravity combustion science programs, sponsored by NASA and NEDO. Cooperation involved the use of drop towers in Japan and the United States, and the sharing of subsequent research data and findings. The topical areas include: (1) Interacting droplet arrays, (2) high pressure binary fuel sprays, (3) sooting droplet combustion, (4) flammability limits and dynamics of spherical, premixed gaseous flames and, (5) ignition and transition of flame spread across thin solid fuel samples. All of the investigators view this collaboration as a success. Novel flame behaviors were found and later published in archival journals. In some cases the experiments provided verification of the design and behavior in subsequent experiments performed on the Space Shuttle. In other cases, the experiments provided guidance to experiments that are expected to be performed on the International Space Station.
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FGF23 inhibits extra-renal synthesis of 1,25-dihydroxyvitamin D in human monocytes
Bacchetta, Justine; Sea, Jessica L; Chun, Rene F; Lisse, Thomas S; Wesseling-Perry, Katherine; Gales, Barbara; Adams, John S.; Salusky, Isidro B; Hewison, Martin
2012-01-01
Vitamin D is a potent stimulator of monocyte innate immunity, with this effect being mediated via intracrine conversion of 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25(OH)2D). In the kidney synthesis of 1,25(OH)2D is suppressed by fibroblast growth factor 23 (FGF23), via transcriptional suppression of the vitamin D-activating enzyme 1α-hydroxylase (CYP27B1). We hypothesized that FGF23 also suppresses CYP27B1 in monocytes, with concomitant effects on intracrine responses to 1,25(OH)2D. Monocytes from healthy donor peripheral blood mononuclear cells (PBMCm) and from peritoneal dialysate effluent from kidney disease patients (PDm) were assessed at baseline to confirm the presence of mRNA for FGF23 receptors (FGFRs), with Klotho and FGFR1 being more strongly expressed than FGFR2/3/4 in both cell types. Immunohistochemistry showed co-expression of Klotho and FGFR1 in PBMCm and PDm, with this effect being enhanced following treatment with FGF23 in PBMCm but not PDm. Treatment with FGF23 activated MAP kinase (MAPK) and Akt pathways in PBMCm, demonstrating functional FGFR signaling in these cells. FGF23 treatment of PBMCm and PDm decreased expression of mRNA for CYP27B1. In PBMCm this was associated with downregulation of 25OHD to 1,25(OH)2D metabolism, and concomitant suppression of intracrine induced 24-hydroxylase (CYP24A1) and antibacterial cathelicidin (LL37). FGF23 suppression of CYP27B1 was particularly pronounced in PBMCm treated with interleukin-15 to stimulate synthesis of 1,25(OH)2D. These data indicate that FGF23 can inhibit extra-renal expression of CYP27B1 and subsequent intracrine responses to 1,25(OH)2D in two different human monocyte models. Elevated expression of FGF23 may therefore play a crucial role in defining immune responses to vitamin D and this, in turn, may be a key determinant of infection in patients with CKD. PMID:22886720
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Effect of bFGF on radiation-induced apoptosis of vascular endothelial cells
International Nuclear Information System (INIS)
Gu Qingyang; Wang Dewen; Li Yuejuan; Peng Ruiyun; Dong Bo; Wang Zhaohai; Liu Jie; Deng Hua; Jiang Tao
2003-01-01
Objective: To study the effect of bFGF on radiation-induced apoptosis vascular endothelial cells. Methods: A cell line PAE (porcine aortic endothelial cells) and primary cultured HUVEC (human umbilical vein endothelial cells) were irradiated with 60 Co γ-rays to establish cell apoptosis models. Flow cytometry with annexin-V-FITC + PI labeling was used to evaluate cell apoptosis. Different amounts of bFGF were used to study their effects on radiation-induced endothelial cell apoptosis. Results and Conclusions: It is found that bFGF could inhibit radiation-induced endothelial cell apoptosis in a considerable degree
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Le cancer différencié de la thyroïde chez l’enfant et l’adolescent: à propos de 22 cas
Anajar, Said; Tatari, Mohammed; Lakhbal, Adil; Abada, Reda; Rouadi, Sami; Roubal, Mohammed; Mahtar, Mohammed
2017-01-01
L’obectif était de mettre en relief les particularités du cancer de la thyroïde chez l’enfant et l’adolescent, et d’évaluer nos résultats par rapport à la littérature internationale a travers une série de cas la plus représentatif au Maroc: 22 cas. C'est une étude rétrospective descriptive des patients atteints de cancer différencié de la thyroïde, hospitalisés au service d’ORL et de Chirurgie Cervico-faciale de L’hopital 20 Août de Casablanca-Maroc, sur la période qui s’étend de Janvier 1995 à Mars 2015. Nous avons recueilli les données relatives à 22 cas, qui répondaient à nos critères d’inclusion. L’âge moyen de nos patients était de 14 ans, avec une sex-ratio 3,4, la plupart de nos patients ont consulté pour un nodule thyroïdien, associé dans 22,7% des cas à une adénopathie cervicale, et dans 9,1% à des signes de compression. L’ensemble des patients ont bénéficié d’une thyroïdectomie totale, suivie d’un curage ganglionnaire dans 31,82%. Le diagnostic de cancer thyroïdien a reposé sur l’examen anatomopathologique de la pièce opératoire, qui a objectivé un carcinome papillaire dans 95,4% des cas, et un carcinome vésiculaire dans 4,5%. Le traitement par l’iode radioactif 131 a été réalisé dans 100% des cas. Par la suite tous nos patients ont été mis sous hormonothérapie thyroïdienne. Une surveillance étroite et régulière a permis de détecter des métastases ganglionnaires chez 3 patients, et les métastases à distance chez 4 patients. Le cancer différencié de la thyroïde de l’enfant et l’adolescent est une entité rare mais agressive, son traitement se base sur la chirurgie, associée à l’irathérapie donnant un pronostic excellent. PMID:29255541
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Energy Technology Data Exchange (ETDEWEB)
Juliachs, M
2004-07-01
In this state of the art on parallel scientific visualization applications on PC clusters, we deal with both surface and volume rendering approaches. We first analyze available PC cluster configurations and existing parallel rendering software components for parallel graphics rendering. CEA/DIF has been studying cluster visualization since 2001. This report is part of a study to set up a new visualization research platform. This platform consisting of an eight-node PC cluster under Linux and a tiled display was installed in collaboration with Versailles-Saint-Quentin University in August 2003. (author)
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Myc and Fgf Are Required for Zebrafish Neuromast Hair Cell Regeneration.
Lee, Sang Goo; Huang, Mingqian; Obholzer, Nikolaus D; Sun, Shan; Li, Wenyan; Petrillo, Marco; Dai, Pu; Zhou, Yi; Cotanche, Douglas A; Megason, Sean G; Li, Huawei; Chen, Zheng-Yi
2016-01-01
Unlike mammals, the non-mammalian vertebrate inner ear can regenerate the sensory cells, hair cells, either spontaneously or through induction after hair cell loss, leading to hearing recovery. The mechanisms underlying the regeneration are poorly understood. By microarray analysis on a chick model, we show that chick hair cell regeneration involves the activation of proliferation genes and downregulation of differentiation genes. Both MYC and FGF are activated in chick hair cell regeneration. Using a zebrafish lateral line neuromast hair cell regeneration model, we show that the specific inhibition of Myc or Fgf suppresses hair cell regeneration, demonstrating that both pathways are essential to the process. Rapid upregulation of Myc and delayed Fgf activation during regeneration suggest a role of Myc in proliferation and Fgf in differentiation. The dorsal-ventral pattern of fgfr1a in the neuromasts overlaps with the distribution of hair cell precursors. By laser ablation, we show that the fgfr1a-positive supporting cells are likely the hair cell precursors that directly give rise to new hair cells; whereas the anterior-posterior fgfr1a-negative supporting cells have heightened proliferation capacity, likely to serve as more primitive progenitor cells to replenish lost precursors after hair cell loss. Thus fgfr1a is likely to mark compartmentalized supporting cell subtypes with different capacities in renewal proliferation and hair cell regeneration. Manipulation of c-MYC and FGF pathways could be explored for mammalian hair cell regeneration.
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Circulating FGF21 in humans is potently induced by short term overfeeding of carbohydrates.
Lundsgaard, Anne-Marie; Fritzen, Andreas M; Sjøberg, Kim A; Myrmel, Lene S; Madsen, Lise; Wojtaszewski, Jørgen F P; Richter, Erik A; Kiens, Bente
2017-01-01
Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake. A diet enriched in carbohydrates (80 E% carbohydrate; CHO) and a eucaloric control diet (CON) were provided to nine healthy men for three days. The energy intake during the CHO diet was increased (+75% energy) to ensure similar dietary protein intake in CHO and CON. To control for the effect of caloric surplus, we similarly overfed (+75% energy) the same subjects for three days with a fat-rich diet (78 E% fat; FAT), consisting of primarily unsaturated fatty acids. The three diets were provided in random order. After CHO, plasma FGF21 concentration increased 8-fold compared to CON (329 ± 99 vs. 39 ± 9 pg ml -1 , p FAT only a non-significant tendency (p = 0.073) to an increase in plasma FGF21 concentration was found. The increase in FGF21 concentration after CHO correlated closely (r = 0.88, p carbohydrate, but not fat, led to markedly increased FGF21 secretion in humans, notably without protein restriction, and affected glucose and lipid homeostais.
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Using the AUDIT-PC to predict alcohol withdrawal in hospitalized patients.
Pecoraro, Anna; Ewen, Edward; Horton, Terry; Mooney, Ruth; Kolm, Paul; McGraw, Patty; Woody, George
2014-01-01
Alcohol withdrawal syndrome (AWS) occurs when alcohol-dependent individuals abruptly reduce or stop drinking. Hospitalized alcohol-dependent patients are at risk. Hospitals need a validated screening tool to assess withdrawal risk, but no validated tools are currently available. To examine the admission Alcohol Use Disorders Identification Test-(Piccinelli) Consumption (AUDIT-PC) ability to predict the subsequent development of AWS among hospitalized medical-surgical patients admitted to a non-intensive care setting. Retrospective case–control study of patients discharged from the hospital with a diagnosis of AWS. All patients with AWS were classified as presenting with AWS or developing AWS later during admission. Patients admitted to an intensive care setting and those missing AUDIT-PC scores were excluded from analysis. A hierarchical (by hospital unit) logistic regression was performed and receiver-operating characteristics were examined on those developing AWS after admission and randomly selected controls. Because those diagnosing AWS were not blinded to the AUDIT-PC scores, a sensitivity analysis was performed. The study cohort included all patients age ≥18 years admitted to any medical or surgical units in a single health care system from 6 October 2009 to 7 October 2010. After exclusions, 414 patients were identified with AWS. The 223 (53.9 %) who developed AWS after admission were compared to 466 randomly selected controls without AWS. An AUDIT-PC score ≥4 at admission provides 91.0 % sensitivity and 89.7 % specificity (AUC=0.95; 95 % CI, 0.94–0.97) for AWS, and maximizes the correct classification while resulting in 17 false positives for every true positive identified. Performance remained excellent on sensitivity analysis (AUC=0.92; 95 % CI, 0.90–0.93). Increasing AUDIT-PC scores were associated with an increased risk of AWS (OR=1.68, 95 % CI 1.55–1.82, pAUDIT-PC score is an excellent discriminator of AWS and could be an important component
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An Fgf-Shh signaling hierarchy regulates early specification of the zebrafish skull.
McCarthy, Neil; Sidik, Alfire; Bertrand, Julien Y; Eberhart, Johann K
2016-07-15
The neurocranium generates most of the craniofacial skeleton and consists of prechordal and postchordal regions. Although development of the prechordal is well studied, little is known of the postchordal region. Here we characterize a signaling hierarchy necessary for postchordal neurocranial development involving Fibroblast growth factor (Fgf) signaling for early specification of mesodermally-derived progenitor cells. The expression of hyaluron synthetase 2 (has2) in the cephalic mesoderm requires Fgf signaling and Has2 function, in turn, is required for postchordal neurocranial development. While Hedgehog (Hh)-deficient embryos also lack a postchordal neurocranium, this appears primarily due to a later defect in chondrocyte differentiation. Inhibitor studies demonstrate that postchordal neurocranial development requires early Fgf and later Hh signaling. Collectively, our results provide a mechanistic understanding of early postchordal neurocranial development and demonstrate a hierarchy of signaling between Fgf and Hh in the development of this structure. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Interpretation of the FGF8 morphogen gradient is regulated by endocytic trafficking.
Nowak, Matthias; Machate, Anja; Yu, Shuizi Rachel; Gupta, Mansi; Brand, Michael
2011-02-01
Forty years ago, it was proposed that during embryonic development and organogenesis, morphogen gradients provide positional information to the individual cells within a tissue leading to specific fate decisions. Recently, much insight has been gained into how such morphogen gradients are formed and maintained; however, which cellular mechanisms govern their interpretation within target tissues remains debated. Here we used in vivo fluorescence correlation spectroscopy and automated image analysis to assess the role of endocytic sorting dynamics on fibroblast growth factor 8 (Fgf8) morphogen gradient interpretation. By interfering with the function of the ubiquitin ligase Cbl, we found an expanded range of Fgf target gene expression and a delay of Fgf8 lysosomal transport. However, the extracellular Fgf8 morphogen gradient remained unchanged, indicating that the observed signalling changes are due to altered gradient interpretation. We propose that regulation of morphogen signalling activity through endocytic sorting allows fast feedback-induced changes in gradient interpretation during the establishment of complex patterns.
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DEFF Research Database (Denmark)
Manfè, Valentina; Kochoyan, Artur; Bock, Elisabeth
2010-01-01
J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06718.x Abstract Basic fibroblast growth factor (FGF2, bFGF) is the most extensively studied member of the FGF family and is involved in neurogenesis, differentiation, neuroprotection, and synaptic plasticity in the CNS. FGF2 executes its pleiotropic...... biologic actions by binding, dimerizing, and activating FGF receptors (FGFRs). The present study reports the physiologic impact of various FGF2-FGFR1 contact sites employing three different synthetic peptides, termed canofins, designed based on structural analysis of the interactions between FGF2 and FGFR1...
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Fritsch, Helmut
A project was conducted to increase as well as to professionalize communication between tutors and learners in a West German university's distance education program by the use of personal computers. Two tutors worked on the systematic development of a PC-based correcting system. The goal, apart from developing general language skills in English,…
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Accelerated 3D-OSEM image reconstruction using a Beowulf PC cluster for pinhole SPECT
International Nuclear Information System (INIS)
Zeniya, Tsutomu; Watabe, Hiroshi; Sohlberg, Antti; Iida, Hidehiro
2007-01-01
A conventional pinhole single-photon emission computed tomography (SPECT) with a single circular orbit has limitations associated with non-uniform spatial resolution or axial blurring. Recently, we demonstrated that three-dimensional (3D) images with uniform spatial resolution and no blurring can be obtained by complete data acquired using two-circular orbit, combined with the 3D ordered subsets expectation maximization (OSEM) reconstruction method. However, a long computation time is required to obtain the reconstruction image, because of the fact that 3D-OSEM is an iterative method and two-orbit acquisition doubles the size of the projection data. To reduce the long reconstruction time, we parallelized the two-orbit pinhole 3D-OSEM reconstruction process by using a Beowulf personal computer (PC) cluster. The Beowulf PC cluster consists of seven PCs connected to Gbit Ethernet switches. Message passing interface protocol was utilized for parallelizing the reconstruction process. The projection data in a subset are distributed to each PC. The partial image forward-and back-projected in each PC is transferred to all PCs. The current image estimate on each PC is updated after summing the partial images. The performance of parallelization on the PC cluster was evaluated using two independent projection data sets acquired by a pinhole SPECT system with two different circular orbits. Parallelization using the PC cluster improved the reconstruction time with increasing number of PCs. The reconstruction time of 54 min by the single PC was decreased to 10 min when six or seven PCs were used. The speed-up factor was 5.4. The reconstruction image by the PC cluster was virtually identical with that by the single PC. Parallelization of 3D-OSEM reconstruction for pinhole SPECT using the PC cluster can significantly reduce the computation time, whereas its implementation is simple and inexpensive. (author)
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Directory of Open Access Journals (Sweden)
Clara Martínez
2011-04-01
Full Text Available El 5-fluorouracilo es un antineoplásico usado en la terapia del cáncer y posee acción inmunosupresora al inhibir la proliferación de células del tejido hematopoyético. En este trabajo se evaluó el efecto inmunomodulador de la solución CM-95 tratada magnéticamente en ratones Balb/c inoculados con 5-fluorouracilo a través de su acción protectora rehabilitadora sobre parámetros celulares y tisulares del tejido hematopoyético. A los ratones, entre 20-22 g de peso y 6 semanas de nacidos, se les administró esta solución CM-95 tratada magnéticamente por vía intraperitoneal en un esquema de dos inoculaciones; luego se administró por la misma vía el 5_fluorouracilo a una dosis de 150 mg/m2 de superficie corporal de cada ratón. Se evaluó el conteo total y diferencial de leucocitos antes de inocular el 5-fluorouracilo, y a los tres y siete días de aplicado este. La celularidad de médula ósea y bazo y la observación microscópica del corte histológico de hígado y bazo por la técnica de inclusión en parafina y tinción con eosina hematoxilina al 10% se evaluaron a los siete días de haber aplicado el 5- fluorouracilo. La solución CM-95, tratada magnéticamente, logró modular los efectos del 5-fluorouracilo con una actividad protectora rehabiltadora, para los parámetros evaluados en médula ósea, sangre periférica, bazo e hígado. Estos resultados abren nuevas perspectivas para la aplicación del sistema acuoso tratado magnéticamente como inmunomodulador.
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FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans
DEFF Research Database (Denmark)
Søberg, Susanna; Sandholt, Camilla Helene; Z. Jespersen, Naja
2017-01-01
The liking and selective ingestion of palatable foods—including sweets—is biologically controlled, and dysfunction of this regulation may promote unhealthy eating, obesity, and disease. The hepatokine fibroblast growth factor 21 (FGF21) reduces sweet consumption in rodents and primates, whereas...... knockout of Fgf21 increases sugar consumption in mice. To investigate the relevance of these findings in humans, we genotyped variants in the FGF21 locus in participants from the Danish Inter99 cohort (n = 6,514) and examined their relationship with a detailed range of food and ingestive behaviors....... This revealed statistically significant associations between FGF21 rs838133 and increased consumption of candy, as well as nominal associations with increased alcohol intake and daily smoking. Moreover, in a separate clinical study, plasma FGF21 levels increased acutely after oral sucrose ingestion and were...
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Clasificación de piezas mediante robótica y visión
Moro Muñoz, Santiago
2011-01-01
El propòsit d’aquest projecte és dissenyar i implementar un sistema de classificació de peces mitjançant robòtica i visió artificial. Aquest sistema classificarà peces segons tres característiques bàsiques: el color, la forma i l’àrea o mida. El projecte està constituït per tres elements essencials: una webcam, un PC i un robot. La webcam serà l’encarregada de fotografiar la peça, el PC processarà tota la informació de la fotografia per a determinar quin tipus de peça és ...
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Bao, Hanmei; Lv, Feng; Liu, Tianjun
2017-12-01
Site-specific controlled release of exogenous angiogenic growth factors, such as recombinant human basic fibroblast growth factor (rhbFGF), has become a promising approach to improve peripheral vascular disease. Here, we have developed an implant composed of spiral magnesium (Mg) and a coating made using poly(lactic-co-glycolic acid) (PLGA) with encapsulated rhbFGF (Mg-PLGA-rhbFGF). The encapsulated protein could release continually for 4weeks with well preserved bioactivity. We compared the angiogenic effect produced by Mg-PLGA-rhbFGF with that of a PLGA implant loaded with rhbFGF (PLGA-rhbFGF). The incorporation of Mg in the implant raised the microclimate pH in the polymer, which preserved the stability of rhbFGF. Mg-PLGA-rhbFGF exhibited advantages over PLGA-rhbFGF implant in terms of a cytocompatibility evaluation. An in vivo angiogenesis test further confirmed the efficacy of released rhbFGF. HE, CD31 and α-SMA staining revealed that the controlled release of rhbFGF from the Mg-PLGA-rhbFGF implant was superior in promoting angiogenesis compared with that of the PLGA-rhbFGF implant. Four weeks post-implantation, the capillary density of the Mg-PLGA-rhbFGF group was significantly higher than that of the PLGA-rhbFGF, control and the normal group (pspiral magnesium and a coating made using poly(lactic-co-glycolic acid) (PLGA) with encapsulated rhbFGF (Mg-PLGA-rhbFGF). The preparation method does not involve any complex processes and results in a high encapsulation efficiency (approximately 100%). The degradation of metal Mg raise the microclimate pH in the PLGA polymer, which could well preserve the bioactivity of rhbFGF incorporated in the implant. Mg-PLGA-based, sustained local delivery of rhbFGF promotes post-ischemic angiogenesis and blood flow recovery in rat limb ischemic model. This work marks the first report for controlled release of rhbFGF in combination with metal Mg, and suggests potential therapeutic usefulness of Mg-PLGA-rhbFGF for tissue ischemia
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FGF8 activates proliferation and migration in mouse post-natal oligodendrocyte progenitor cells.
Directory of Open Access Journals (Sweden)
Pablo Cruz-Martinez
Full Text Available Fibroblast growth factor 8 (FGF8 is a key molecular signal that is necessary for early embryonic development of the central nervous system, quickly disappearing past this point. It is known to be one of the primary morphogenetic signals required for cell fate and survival processes in structures such as the cerebellum, telencephalic and isthmic organizers, while its absence causes severe abnormalities in the nervous system and the embryo usually dies in early stages of development. In this work, we have observed a new possible therapeutic role for this factor in demyelinating disorders, such as leukodystrophy or multiple sclerosis. In vitro, oligodendrocyte progenitor cells were cultured with differentiating medium and in the presence of FGF8. Differentiation and proliferation studies were performed by immunocytochemistry and PCR. Also, migration studies were performed in matrigel cultures, where oligodendrocyte progenitor cells were placed at a certain distance of a FGF8-soaked heparin bead. The results showed that both migration and proliferation was induced by FGF8. Furthermore, a similar effect was observed in an in vivo demyelinating mouse model, where oligodendrocyte progenitor cells were observed migrating towards the FGF8-soaked heparin beads where they were grafted. In conclusion, the results shown here demonstrate that FGF8 is a novel factor to induce oligodendrocyte progenitor cell activation, migration and proliferation in vitro, which can be extrapolated in vivo in demyelinated animal models.
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Charrue, P; Ghinet, F; Ribeiro, P
1995-01-01
The CERN SPS and LEP PowerPC project is aimed at introducing a new generation of PowerPC VMEbus processor modules running the LynxOS real-time operating system. This new generation of front end computers using the state-of-the-art microprocessor technology will first replace the obsolete XENIX PC based systems (about 140 installations) successfully used since 1988 to control the LEP accelerator. The major issues addressed in the scope of this large scale project are the technical specification for the new PowerPC technology, the re-engineering aspects, the interfaces with other CERN wide projects, and the set up of a development environment. This project offers also support for other major SPS and LEP projects interested in the PowerPC microprocessor technology.
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Bublik, Débora R.; Bursać, Slađana; Sheffer, Michal; Oršolić, Ines; Shalit, Tali; Tarcic, Ohad; Kotler, Eran; Mouhadeb, Odelia; Hoffman, Yonit; Fuchs, Gilad; Levin, Yishai; Volarević, Siniša; Oren, Moshe
2017-01-01
The microRNA miR-504 targets TP53 mRNA encoding the p53 tumor suppressor. miR-504 resides within the fibroblast growth factor 13 (FGF13) gene, which is overexpressed in various cancers. We report that the FGF13 locus, comprising FGF13 and miR-504, is transcriptionally repressed by p53, defining an additional negative feedback loop in the p53 network. Furthermore, we show that FGF13 1A is a nucleolar protein that represses ribosomal RNA transcription and attenuates protein synthesis. Importantly, in cancer cells expressing high levels of FGF13, the depletion of FGF13 elicits increased proteostasis stress, associated with the accumulation of reactive oxygen species and apoptosis. Notably, stepwise neoplastic transformation is accompanied by a gradual increase in FGF13 expression and increased dependence on FGF13 for survival (“nononcogene addiction”). Moreover, FGF13 overexpression enables cells to cope more effectively with the stress elicited by oncogenic Ras protein. We propose that, in cells in which activated oncogenes drive excessive protein synthesis, FGF13 may favor survival by maintaining translation rates at a level compatible with the protein quality-control capacity of the cell. Thus, FGF13 may serve as an enabler, allowing cancer cells to evade proteostasis stress triggered by oncogene activation. PMID:27994142
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International Nuclear Information System (INIS)
Lemiere, Sylvie; Azar, Rania; Belloc, Francis; Guersel, Demir; Pyronnet, Stephane; Bikfalvi, Andreas; Auguste, Patrick
2008-01-01
In order to clarify the role of HMW FGF-2 in glioma development and angiogenesis, we over-expressed different human FGF-2 isoforms in C6 rat glioma cell line using a tetracycline-regulated expression system. Phenotypic modifications were analyzed in vitro and compared to untransfected cells or to cells over-expressing 18 kDa FGF-2 or all FGF-2 isoforms. In particular, we demonstrate that HMW FGF-2 has unique features in inhibiting glioma cell proliferation. HMW FGF-2 expressing cells showed a cell-cycle arrest at the G2M, demonstrating a role of HMW FGF-2 in controlling the entry in mitosis. Moreover, hydroxyurea was ineffective in blocking cells at the G1S boundary when HMW FGF-2 was expressed. We also show that the HMW FGF-2 isoforms inhibit 4E-BP1 phosphorylation at critical sites restoring the translation inhibitory activity of 4E-BP1. In vivo, inhibition of tumor growth was observed when cells expressed HMW FGF-2. This indicates that HMW FGF-2 inhibits tumor growth in glioma cells by acting on cell-cycle progression and protein translation
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Cellular Responses Modulated by FGF-2 Adsorbed on Albumin/Heparin Layer-by-Layer Assemblies.
Kumorek, Marta; Kubies, Dana; Filová, Elena; Houska, Milan; Kasoju, Naresh; Mázl Chánová, Eliška; Matějka, Roman; Krýslová, Markéta; Bačáková, Lucie; Rypáček, František
2015-01-01
In a typical cell culture system, growth factors immobilized on the cell culture surfaces can serve as a reservoir of bio-signaling molecules, without the need to supplement them additionally into the culture medium. In this paper, we report on the fabrication of albumin/heparin (Alb/Hep) assemblies for controlled binding of basic fibroblast growth factor (FGF-2). The surfaces were constructed by layer-by-layer adsorption of polyelectrolytes albumin and heparin and were subsequently stabilized by covalent crosslinking with glutaraldehyde. An analysis of the surface morphology by atomic force microscopy showed that two Alb/Hep bilayers are required to cover the surface of substrate. The formation of the Alb/Hep assemblies was monitored by the surface plasmon resonance (SPR), the infrared multiinternal reflection spectroscopy (FTIR MIRS) and UV/VIS spectroscopy. The adsorption of FGF-2 on the cross-linked Alb/Hep was followed by SPR. The results revealed that FGF-2 binds to the Alb/Hep assembly in a dose and time-dependent manner up to the surface concentration of 120 ng/cm(2). The bioactivity of the adsorbed FGF-2 was assessed in experiments in vitro, using calf pulmonary arterial endothelial cells (CPAE). CPAE cells could attach and proliferate on Alb/Hep surfaces. The adsorbed FGF-2 was bioactive and stimulated both the proliferation and the differentiation of CPAE cells. The improvement was more pronounced at a lower FGF-2 surface concentration (30 ng/cm(2)) than on surfaces with a higher concentration of FGF-2 (120 ng/cm(2)).
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2012-05-07
... rights and interest in, abbreviated new animal drug application (ANADA) 200-472 for Fomepizole for... [Docket No. FDA-2012-N-0002] New Animal Drugs; Change of Sponsor; Change of Sponsor Address; Change of.... SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect a...
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De Sitter projective relativity
Licata, Ignazio; Benedetto, Elmo
2017-01-01
This book presents the Projective approach to de Sitter Relativity. It traces the development of renewed interest in models of the universe at constant positive curvature such as "vacuum" geometry. The De Sitter Theory of Relativity, formulated in 1917 with Willem De Sitter's solution of the Einstein equations, was used in different fields during the 1950s and 1960s, in the work of H. Bacry, J.M. LevyLeblond and F.Gursey, to name some important contributors. From the 1960s to 1980s, L. Fantappié and G. Arcidiacono provided an elegant group approach to the De Sitter universe putting the basis for special and general projective relativity. Today such suggestions flow into a unitary scenario, and this way the De Sitter Relativity is no more a "missing opportunity" (F. Dyson, 1972), but has a central role in theoretical physics. In this volume a systematic presentation is given of the De Sitter Projective relativity, with the recent developments in projective general relativity and quantum cosmology.
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International Nuclear Information System (INIS)
1990-01-01
There are currently thirteen members of the AGF, government-sponsored research organizations who together employ more than 22.000 people and an annual budget of about DM 2.5 billions, thus representing the largest, compact research potential of the Federal Republic of Germany and building one of the most essential elements of the German scientific research system. The research organizations are financed from Federal Government funds and by contributions from the Federal Land the organization is domiciled, each at a ratio of 90 to 10. Influence and control by the Federal Government is exerted by way of Government representatives having a seat and a vote in the executive bodies of the organization, and by way of budgetary powers. Ever since their establishment, the government-sponsored research organizations have to find a balance between the two poles of scientific and legal independence on the one hand, and governmental influence on the other. Their wish for more effectively safeguarding their common interests have induced the research organizations to establish the AGF on January 30, 1970. (orig./HSCH) [de
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Plasma FGF21 displays a circadian rhythm during a 72-h fast in healthy female volunteers
DEFF Research Database (Denmark)
Andersen, Birgitte; Beck-Nielsen, Henning; Højlund, Kurt
2011-01-01
Fibroblast growth factor (FGF21) is a potent regulator of glucose and lipid metabolism. In rodents, the hepatic expression of FGF21 is controlled by fasting and a circadian regulation, but the physiological role and regulation of FGF21 in humans is not well established. Therefore, the objective...
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Mintzes, Barbara; Swandari, Swestika; Fabbri, Alice; Grundy, Quinn; Moynihan, Ray; Bero, Lisa
2018-02-13
To investigate patterns of industry-sponsored educational events that focus on specific health conditions for which there are concerns about overdiagnosis and overtreatment. This retrospective cohort study examines publicly reported industry-sponsored events in Australia from October 2011 to September 2015 for three conditions potentially subject to overdiagnosis and overtreatment: depression, osteoporosis and overactive bladder. We used a database of transparency reports to identify events with a focus on depression, osteoporosis and overactive bladder and compared these with other sponsored events. We hypothesised that companies marketing treatments for each condition would sponsor related events and that target audiences would mainly work in primary care, reflecting a broad patient population. Event and attendee characteristics, sponsoring companies, related marketed treatments, cost-effectiveness ratings and dispensing rates. Over the study period, we identified 1567 events focusing on depression, 1375 on osteoporosis and 190 on overactive bladder (total n=3132, with 96 660 attendees). These events were attended by primary care doctors more often than sponsored events without a focus on these three conditions: relative risk (RR)=3.06 (95% CI 2.81 to 3.32) for depression, RR=1.48 (95% CI 1.41 to 1.55) for osteoporosis and RR=2.59 (95% CI 2.09 to 3.21) for overactive bladder. Servier, which markets agomelatine and AstraZeneca (quetiapine) sponsored 51.2% and 23.0% of depression events, respectively. Amgen and GlaxoSmithKline, which co-market denosumab, sponsored 49.5% of osteoporosis events and Astellas and Commonwealth Serum Laboratories (CSL) (mirabegron and solifenacin) sponsored 80.5% of overactive bladder events. This 4-year overview of industry-sponsored events on three overdiagnosed and overtreated conditions found that primary care clinicians were often targeted, dinner was often provided and that a few companies sponsored most events. In most cases
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Transforming PC Power Supplies into Smart Car Battery Conditioners
Rodriguez-Ascariz, J. M.; Boquete-Vazquez, L.
2011-01-01
This paper describes a laboratory project consisting of a PC power supply modification into an intelligent car-battery conditioner with both wireless and wired networking capabilities. Adding a microcontroller to an average PC power supply transforms it into a flexible, intelligent device that can be configured and that is suitable to keep car…
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Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J F; Müller, Timo D; Pfluger, Paul T; Seeley, Randy J
2015-10-01
Ketogenic diets (KDs) have increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. The metabolic benefits of KDs are regularly ascribed to enhanced hepatic secretion of fibroblast growth factor 21 (FGF21) and its systemic effects on fatty-acid oxidation, energy expenditure (EE) and body weight. Ambiguous data from Fgf21-knockout animal strains and low FGF21 concentrations reported in humans with ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating the therapeutic benefits of KDs on metabolism and cancer. We established a dietary model of increased vs decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted of protein or enriched with protein. We furthermore used wild-type and Fgf21-knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumour growth after transplantation of Lewis lung carcinoma cells. Hepatic and circulating, but not adipose tissue, FGF21 levels were profoundly increased by protein starvation, independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycaemia upon protein and carbohydrate starvation and is therefore not needed for the effects of KDs on EE. Furthermore, the tumour-suppressing effects of KDs were independent of FGF21 and, rather, driven by concomitant protein and carbohydrate starvation. Our data indicate that the multiple systemic effects of KD exposure in mice, previously ascribed to increased FGF21 secretion, are rather a consequence of protein malnutrition.
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Energy Technology Data Exchange (ETDEWEB)
Kumorek, Marta, E-mail: kumorek@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Janoušková, Olga, E-mail: janouskova@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Höcherl, Anita, E-mail: hocherl@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Houska, Milan, E-mail: houska@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Mázl-Chánová, Eliška, E-mail: chanova@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Kasoju, Naresh, E-mail: naresh.kasoju@eng.ox.ac.uk [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Cuchalová, Lucie, E-mail: cuchaloval@gmail.com [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); and others
2017-07-31
Highlights: • Amine, carboxyl, and induced aldehyde groups of heparin were used for crosslinking of LbL film. • The carbodiimide-mediated cross-linking was the most efficient fixation method. • FGF-2 bound the most effectively to the glutaraldehyde-cross-linked LbL film. • Films cross-linked through carboxyl and aldehyde groups showed a slow FGF-2 release. • FGF-2-loaded LbL films stimulated the HUVECs growth better than the soluble FGF-2. - Abstract: The biomaterials that efficiently deliver growth factors represent an important challenge in cell-based tissue engineering. Layer-by-layer (LbL) thin films are attractive for incorporating controlled amounts of growth factors and releasing them over time. Herein, we investigated the effect of a method of cross-linking of albumin/heparin layer-by-layer (LbL) assembly ((Alb/Hep){sub 3}) on the loading and release of basic fibroblast growth factor (FGF-2), and subsequent proliferation of human endothelial cells (HUVECs). The (Alb/Hep){sub 3} assemblies were cross-linked using glutaraldehyde, reductive amination or carbodiimide chemistries, and then biofunctionalized with FGF-2. The (Alb/Hep){sub 3} assemblies were characterized by the infrared multi-internal reflection spectroscopy, atomic force microscopy, ellipsometry, and surface plasmon resonance (SPR). The FGF-2 loading was quantified by the SPR in situ analysis. Our results showed that the (Alb/Hep){sub 3} cross-linking affected the amount of the bound heparin (from 150 to 315 ng/cm{sup 2}), amount of FGF-2 loaded (from 75 to 125 ng/cm{sup 2}), FGF-2 release (from 15 to 53% over 8 days), and consequently the HUVEC cell proliferation (from 50 to 80 × 10{sup 3} cells/cm{sup 2} at day 5). All FGF-2 loaded assemblies stimulated the cell growth more than a soluble FGF-2 added into the cell media. In particular, the highest HUVECs proliferation was detected on the carbodiimide-cross-linked assembly. Overall, these biocompatible cross-linked assemblies can fine
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IGF-I AND FGF-2 RESPONSES TO WINGATE ANAEROBIC TEST IN OLDER MEN
Directory of Open Access Journals (Sweden)
Ruthie Amir
2007-06-01
Full Text Available Reduced activity of the potent anabolic effectors: insulin-like growth factor-I (IGF-I and fibroblast growth factor-2 (FGF-2, play a role in aging associated muscle loss. The effect of fitness level on IGF-I and FGF-2 responses to all-out anaerobic exercise in older men was studied. Twenty four healthy older males: 12 higher fit (58 ± 1y and 12 lower fit (59 ± 1y underwent the Wingate anaerobic test. Serum levels of IGF-I and FGF-2 were measured before, immediately after exercise, and 50 min into recovery. Immediately post exercise, the average peak power output and serum lactate were higher (p < 0.05 in the higher fit (446.0 ± 14. 9 kgm·min-1 for mean (± SD peak power and 12.6 ± 1.1 mml·l-1 for lactate compared with the lower fit individuals (284.0 ± 6.5 kgm·min-1 and 8.5 ± 0.7 mml·l-1, respectively. Pre-exercise IGF-I was lower and FGF-2 was higher in the higher fit (335.0 ± 54.0 ng·ml-1 and 1.6 ± 0.1 ng·ml-1, respectively compared with lower fit individuals (402.0 ± 50.0 ng·ml-1 and 1.4 ± 0.2 ng·ml-1, respectively. Following the anaerobic exercise, in both groups, FGF-2 decreased dramatically (p < 0.05; in the higher fit individuals FGF-2 level was 0.4 ± 0.1 pg·ml-1 compared to 0.1 ± 0.02 pg·ml-1 in the lower fit individuals. In contrast to FGF-2, IGF-I increased transiently to levels of 405.0 ± 62.0 ng·ml-1 in the higher fit individuals and to levels of 436 ± 57.0 ng·ml-1 in the lower fit individuals. However, the IGF-I elevation was significant (p < 0. 05 only in the higher fit individuals. In conclusion, the present study demonstrates that during aging, fitness level can alter circulating levels of IGF-I and FGF-2. Furthermore, fitness level can affect the response of both mediators to all-out anaerobic exercise.
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DEFF Research Database (Denmark)
Francavilla, Chiara; Rigbolt, Kristoffer T.G.; Emdal, Kristina B
2013-01-01
The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferation...
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International Nuclear Information System (INIS)
1987-05-01
Investigations on the safety of light water reactors (LWR) being performed in the framework of the research program on reactor safety (RS-projects) are sponsored by the Federal Ministry for Research and Technology (BMFT). Objective of this program is to investigate in greater detail the safety margins of nuclear power plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks also projects on the safety of advanced reactors are sponsored by the BMFT. The individual reports are classified according to the research program on the safety of LWRs 1977-1980 of the BMFT. Another table of contents uses the same classification system as applied in the nuclear safety index of the CEC (Commission of the European Communities) and the OECD (Organization for Economic Cooperation and Development). The reports are arranged in the sequence of their project numbers. (orig.) [de
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Shen, Yun; Zhang, Xueli; Pan, Xiaoping; Xu, Yiting; Xiong, Qin; Lu, Zhigang; Ma, Xiaojing; Bao, Yuqian; Jia, Weiping
2017-08-18
The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death. Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan-Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay. A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037-9.500], P = 0.043, OR 9.207 [2.036-41.643], P = 0.004, separately). Further Kaplan-Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years [RR 5.000 (1.326-18.861), P = 0.026; RR 9.643 (2
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PC data station for Hitachi F-2000 spectrofluorimeter
International Nuclear Information System (INIS)
Yakub Ali, Mohd; Dhoble, A.R.; Jadhav, R.T.; Godbole, S.V.
2004-01-01
The paper describes the PC based data station for stand-alone HIT ACHI F-2000 Spectrofluorimeter, for data acquisition, storage and analysis. The hardware link between the instrument and PC is made through RS232 serial port. The state of art software for control and data management is designed, developed and implemented in Visual Basic (Version 6). The software features on-screen editing of all operation parameters of the instrument and the operational control is achieved by Visual Basic command words communicated through serial port. Using this system, in addition to acquiring and storage of spectral data, it was possible to obtain the normalized absorption spectra of the samples. PC adapted Hitachi F-2000 Spectrofluorimeter can be successfully used for various operations such as photometric detection of UO22+ ions, recording of emission and excitation spectra and time evolution of fluorescence intensity on continuous UV irradiation. The data storage achieved through PC adaptation has also enabled recording of absorption spectra. (author)
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FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver
DEFF Research Database (Denmark)
von Holstein-Rathlou, Stephanie; BonDurant, Lucas D; Peltekian, Lila
2016-01-01
The liver is an important integrator of nutrient metabolism, yet no liver-derived factors regulating nutrient preference or carbohydrate appetite have been identified. Here we show that the liver regulates carbohydrate intake through production of the hepatokine fibroblast growth factor 21 (FGF21......), which markedly suppresses consumption of simple sugars, but not complex carbohydrates, proteins, or lipids. Genetic loss of FGF21 in mice increases sucrose consumption, whereas acute administration or overexpression of FGF21 suppresses the intake of both sugar and non-caloric sweeteners. FGF21 does...... not affect chorda tympani nerve responses to sweet tastants, instead reducing sweet-seeking behavior and meal size via neurons in the hypothalamus. This liver-to-brain hormonal axis likely represents a negative feedback loop as hepatic FGF21 production is elevated by sucrose ingestion. We conclude...
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[The effect of bFGF and sucralfate on cell proliferation during continuous tissue expansion].
Hu, Ya-lan; Guo, Shu-zhong; Lu, Kai-hua
2003-05-01
To investigate the effect of local application of bFGF combined with sucralfate on the cell proliferation during continuous tissue expansion (CTE). Nine white pigs were selected to undergo the continuous tissue expansion in this study and treated with bFGF and sucralfate, respectively as the following groups: group 1 with both bFGF and sucralfate, group 2 only with bFGF, group 3 with only sucralfate, and group 4 with saline as control. Fifteen samples were taken in each pig for immunohistochemistry analysis 1-14 days and 6 weeks after the operation. In the group with both bFGF and sucralfate, the epidermic basal cells proliferated significantly after the operation and reached top level in 3 days, which was statistical higher than the control group, but the multiplication of basal cell was the lowest 14 days after the operation, still more than the control group. In dermal layer, proliferation of fibroblasts, vessel endothelial cells, hair follicles epidermic cells and sweat gland epicytes was also significant higher in the group with both bFGF and sucralfate than that the control group and reached top level 7 day after the operation, but the proliferation of cells decreased obviously 14 days after the operation, still higher than the control group. The mitotic activity of cells returned to the basal level in 42 days. There were no significant differences among the group 2, group 3 and group 4. Local application of both bFGF and sucralfate could be more effect to induce cells multiplication during early skin expansion to facilitate the growth of neoformed skin soft tissue.
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Klein, Walter J.
For public relations professionals and would-be sponsors of films, this book provides guidelines for understanding the film medium and its potential as a persuasive force in industry, government, organizations, and religious orders. For filmmakers, it brings together practical information needed to survive in the sponsored-film industry and to…
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International Nuclear Information System (INIS)
Oh, Jae Cheol
1992-03-01
This text book is comprised of five charters, which is about PC communication for beginners who need to learn manners and how to use Ketel and PC serve. So it introduces first, conception of PC and precautions on using PC communication, second, preparation for PC communication with Modem, its program, install, kinds of protocol and how to use protocol, third directions of emulator of PC communication and super session, fourth, instruction of Ketel with join and access, basic command of Ketel, list of Ketel's menu, Ketel editor, service guide, directions of News service, Stock and bond service business and economic figures, exchange rate and interest rate, tax culture and leisure, Ketel BBS service and posting. The last part has a instruction of PC-serve about join, basic command of PC-serve, service guide and practical guideline.
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Energy Technology Data Exchange (ETDEWEB)
Oh, Jae Cheol
1992-03-15
This text book is comprised of five charters, which is about PC communication for beginners who need to learn manners and how to use Ketel and PC serve. So it introduces first, conception of PC and precautions on using PC communication, second, preparation for PC communication with Modem, its program, install, kinds of protocol and how to use protocol, third directions of emulator of PC communication and super session, fourth, instruction of Ketel with join and access, basic command of Ketel, list of Ketel's menu, Ketel editor, service guide, directions of News service, Stock and bond service business and economic figures, exchange rate and interest rate, tax culture and leisure, Ketel BBS service and posting. The last part has a instruction of PC-serve about join, basic command of PC-serve, service guide and practical guideline.
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Takizawa-Shirasawa, Sakiko; Yoshie, Susumu; Yue, Fengming; Mogi, Akimi; Yokoyama, Tadayuki; Tomotsune, Daihachiro; Sasaki, Katsunori
2013-12-01
The major molecular signals of pancreatic exocrine development are largely unknown. We examine the role of fibroblast growth factor 7 (FGF7) in the final induction of pancreatic amylase-containing exocrine cells from induced-pancreatic progenitor cells derived from human embryonic stem (hES) cells. Our protocol consisted in three steps: Step I, differentiation of definitive endoderm (DE) by activin A treatment of hES cell colonies; Step II, differentiation of pancreatic progenitor cells by re-plating of the cells of Step I onto 24-well plates at high density and stimulation with all-trans retinoic acid; Step III, differentiation of pancreatic exocrine cells with a combination of FGF7, glucagon-like peptide 1 and nicotinamide. The expression levels of pancreatic endodermal markers such as Foxa2, Sox17 and gut tube endoderm marker HNF1β were up-regulated in both Step I and II. Moreover, in Step III, the induced cells expressed pancreatic markers such as amylase, carboxypeptidase A and chymotrypsinogen B, which were similar to those in normal human pancreas. From day 8 in Step III, cells immunohistochemically positive for amylase and for carboxypeptidase A, a pancreatic exocrine cell product, were induced by FGF7. Pancreatic progenitor Pdx1-positive cells were localized in proximity to the amylase-positive cells. In the absence of FGF7, few amylase-positive cells were identified. Thus, our three-step culture protocol for human ES cells effectively induces the differentiation of amylase- and carboxypeptidase-A-containing pancreatic exocrine cells.
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FGF: A web tool for Fishing Gene Family in a whole genome database
DEFF Research Database (Denmark)
Zheng, Hongkun; Shi, Junjie; Fang, Xiaodong
2007-01-01
to efficiently search for and identify gene families. The FGF output displays the results as visual phylogenetic trees including information on gene structure, chromosome position, duplication fate and selective pressure. It is particularly useful to identify pseudogenes and detect changes in gene structure. FGF...
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Puranam, Ram S; He, Xiao Ping; Yao, Lijun; Le, Tri; Jang, Wonjo; Rehder, Catherine W; Lewis, Darrell V; McNamara, James O
2015-06-10
We identified a family in which a translocation between chromosomes X and 14 was associated with cognitive impairment and a complex genetic disorder termed "Genetic Epilepsy and Febrile Seizures Plus" (GEFS(+)). We demonstrate that the breakpoint on the X chromosome disrupted a gene that encodes an auxiliary protein of voltage-gated Na(+) channels, fibroblast growth factor 13 (Fgf13). Female mice in which one Fgf13 allele was deleted exhibited hyperthermia-induced seizures and epilepsy. Anatomic studies revealed expression of Fgf13 mRNA in both excitatory and inhibitory neurons of hippocampus. Electrophysiological recordings revealed decreased inhibitory and increased excitatory synaptic inputs in hippocampal neurons of Fgf13 mutants. We speculate that reduced expression of Fgf13 impairs excitability of inhibitory interneurons, resulting in enhanced excitability within local circuits of hippocampus and the clinical phenotype of epilepsy. These findings reveal a novel cause of this syndrome and underscore the powerful role of FGF13 in control of neuronal excitability. Copyright © 2015 the authors 0270-6474/15/358866-16$15.00/0.
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DEFF Research Database (Denmark)
Sørensen, Rikke Kruse; Vienberg, Sara Gry; Vind, Birgitte F
2017-01-01
obesity with and without type 2 diabetes led to reduced expression of KLB, but increased FGFR1c expression. However, the expression of most FGF21 target genes was unaltered except for reduced CIDEA expression in individuals with type 2 diabetes. CONCLUSIONS....../INTERPRETATION: Insulin-induced expression of muscle FGF21 correlates strongly with a rise in serum FGF21, and this response appears intact in overweight/obesity and type 2 diabetes. FGF21 resistance may involve reduced KLB expression in WAT. However, increased FGFR1c expression or other mechanisms seem to ensure...... that insulin and exercise increase FGF21 in plasma. Obesity and type 2 diabetes are potentially FGF21-resistant states, but to what extent FGF21 responses to insulin and exercise training are preserved, and whether FGF21, its receptors and target genes are altered, remains to be established. METHODS...
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Salgado, M Victoria; Mejia, Raul; Kaplan, Celia P; Perez-Stable, Eliseo J
2014-02-06
Internet-based marketing has become an attractive option for promoting tobacco products due to its potential to avoid advertising restrictions. In Argentina, several cigarette brands have designed websites for the local market, which promote user participation. The intent of the study was to report on the use of tobacco company-sponsored websites by medical students and recently graduated physicians. An online self-administered survey was conducted among eligible medical students and recent graduates from the University of Buenos Aires (UBA). Sampling was from lists of email addresses of students enrolled in two required courses. Eligibility criteria were ages 18-30 years and reporting on smoking status. Questions on Internet use included accessing a tobacco brand website at least once during their lifetime and any use of tobacco promotional materials. The response rate was 35.08% (1743/4969). The final sample included 1659 participants: 73.06% (1212/1659) were women and mean age was 26.6 years (SD 1.9). The majority were current medical students (55.70%, 924/1659) and 27.31% (453/1659) were current smokers. Men were more likely to report having seen a tobacco advertisement on the Internet (P=.001), to have received a tobacco promotion personally addressed to them (P=.03), to have used that promotion (P=.02), and to have accessed a tobacco-sponsored website (P=.01). Among respondents, 19.35% (321/1659) reported having accessed a tobacco-sponsored website at least once in their lifetime and almost all of them (93.8%, 301/321) accessed these sites only when it was necessary for participating in a marketing promotion. Most people logging on for promotions reported entering once a month or less (58.9%, 189/321), while 25.5% (82/321) reported accessing the tobacco industry Internet sites once a week or more. In adjusted logistic regression models, participants were more likely to have accessed a tobacco brand website if they were former smokers (OR 2.45, 95% CI 1.42-4.22
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Nrf2 represses FGF21 during long-term high-fat diet-induced obesity in mice.
Chartoumpekis, Dionysios V; Ziros, Panos G; Psyrogiannis, Agathoklis I; Papavassiliou, Athanasios G; Kyriazopoulou, Venetsana E; Sykiotis, Gerasimos P; Habeos, Ioannis G
2011-10-01
Obesity is characterized by chronic oxidative stress. Fibroblast growth factor 21 (FGF21) has recently been identified as a novel hormone that regulates metabolism. NFE2-related factor 2 (Nrf2) is a transcription factor that orchestrates the expression of a battery of antioxidant and detoxification genes under both basal and stress conditions. The current study investigated the role of Nrf2 in a mouse model of long-term high-fat diet (HFD)-induced obesity and characterized its crosstalk to FGF21 in this process. Wild-type (WT) and Nrf2 knockout (Nrf2-KO) mice were fed an HFD for 180 days. During this period, food consumption and body weights were measured. Glucose metabolism was assessed by an intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test. Total RNA was prepared from liver and adipose tissue and was used for quantitative real-time RT-PCR. Fasting plasma was collected and analyzed for blood chemistries. The ST-2 cell line was used for transfection studies. Nrf2-KO mice were partially protected from HFD-induced obesity and developed a less insulin-resistant phenotype. Importantly, Nrf2-KO mice had higher plasma FGF21 levels and higher FGF21 mRNA levels in liver and white adipose tissue than WT mice. Thus, the altered metabolic phenotype of Nrf2-KO mice under HFD was associated with higher expression and abundance of FGF21. Consistently, the overexpression of Nrf2 in ST-2 cells resulted in decreased FGF21 mRNA levels as well as in suppressed activity of a FGF21 promoter luciferase reporter. The identification of Nrf2 as a novel regulator of FGF21 expands our understanding of the crosstalk between metabolism and stress defense.
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Van den Eynden, M
1995-01-01
The CERN SPS and LEP PowerPC project is aimed at introducing a new generation of PowerPC VMEbus processor modules running the LynxOS real-time operating system. This new generation of front end computers using the state-of-the-art microprocessor technology will first replace the obsolete Xenix PC based systems (about 140 installations) successfully used since 1988 to control the LEP accelerator. The major issues addressed in the scope of this large scale project are the technical specification for the new PowerPC technology, the re-engineering aspects, the interfaces with other CERN wide projects, and the set up of a development environment. This project offers also support for other major SPS and LEP projects interested in the PowerPC microprocessor technology.
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Directory of Open Access Journals (Sweden)
Luiz Fernando Teixeira Albino
1999-01-01
Full Text Available Este experimento foi realizado para determinar a exigência nutricional em metionina + cistina (aminoácidos sulfurosos para frangos de corte Hubbard e Ross de ambos os sexos, no período de 1 a 21 e 22 a 42 dias de idade. Ganho de peso, consumo, conversão alimentar e composição de carcaça das aves foram avaliados. Foram usadas 2400 aves na fase de 1 a 21 dias de idade e 1800 na fase de 22 a 42 dias de idade. Rações basais com 21e 19% PB e 3000 e 3100 kcal EM/kg foram suplementadas com seis níveis de metionina + cistina ( 0; 0,06; 0,12; 0,18; 0,24; e 0,30 nas fases de 1 a 21 e 22 a 42 dias de idade, respectivamente. As estimativas das exigências de metionina + cistina para a fase de 1 a 21 dias foram 0,886 e 0,896% e 0,890 e 0,868% e para a fase de 22 a 42 dias, 0,795 e 0,802% e 0,810 e 0,792%, para machos e fêmeas Hubbard e Ross, respectivamente.This experiment was carried out to determine the nutritional requirement of methionine + cystine (sulfur amino acids for Hubbard and Ross broilers from 1 to 21 and from 22 to 42 days of age, of both sexes. Weight gain, intake, feed:gain and carcass composition were evaluated. Two thousand and four hundred broilers were used in the phase from 1 to 21 of age and 1800 broilers in the phase from 22 a 42 days of age. Basal diets with 21 and 19% of the CP and 3000 and 3100 kcal ME/kg were supplemented with six levels of methionine + cystine in the phases from 1 to 21 and from 22 to 42 of age, respectively. The estimated requirements of methionine + cystine ( 0; .06; .12; .18; .24; and .30 for the phase from 1 to 21 days were. 886% and .896%, .890% and .868% and for the phase from 22 to 42 days, .795%, and .802%, .810% and .792% for Hubbard and Ross male and female, respectively.
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`95 computer system operation project
Energy Technology Data Exchange (ETDEWEB)
Kim, Young Taek; Lee, Hae Cho; Park, Soo Jin; Kim, Hee Kyung; Lee, Ho Yeun; Lee, Sung Kyu; Choi, Mi Kyung [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)
1995-12-01
This report describes overall project works related to the operation of mainframe computers, the management of nuclear computer codes and the project of nuclear computer code conversion. The results of the project are as follows ; 1. The operation and maintenance of the three mainframe computers and other utilities. 2. The management of the nuclear computer codes. 3. The finishing of the computer codes conversion project. 26 tabs., 5 figs., 17 refs. (Author) .new.
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'95 computer system operation project
International Nuclear Information System (INIS)
Kim, Young Taek; Lee, Hae Cho; Park, Soo Jin; Kim, Hee Kyung; Lee, Ho Yeun; Lee, Sung Kyu; Choi, Mi Kyung
1995-12-01
This report describes overall project works related to the operation of mainframe computers, the management of nuclear computer codes and the project of nuclear computer code conversion. The results of the project are as follows ; 1. The operation and maintenance of the three mainframe computers and other utilities. 2. The management of the nuclear computer codes. 3. The finishing of the computer codes conversion project. 26 tabs., 5 figs., 17 refs. (Author) .new
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Energy Technology Data Exchange (ETDEWEB)
NONE
1996-01-01
This publication discusses the demonstration of the LIFAC sorbent injection technology at Richmond Power and Light`s Whitewater Valley Unit No. 2, performed under the auspices of the U.S. Department of Energy`s (DOE) Clean Coal Technology Program. LIFAC is a sorbent injection technology capable of removing 75 to 85 percent of a power plant`s SO{sub 2} emissions using limestone at calcium to sulfur molar ratios of between 2 and 2.5 to 1. The site of the demonstration is a coal-fired electric utility power plant located in Richmond, Indiana. The project is being conducted by LIFAC North America (LIFAC NA), a joint venture partnership of Tampella Power Corporation and ICF Kaiser Engineers, in cooperation with DOE, RP&L, and Research Institute (EPRI), the State of Indiana, and Black Beauty Coal Company. The purpose of Public Design Report Volume 2: Project Performance and Economics is to consolidate, for public use, the technical efficiency and economy of the LIFAC Process. The report has been prepared pursuant to the Cooperative Agreement No. DE-FC22-90PC90548 between LIFAC NA and the U.S. Department of Energy.
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Project finance for renewable energy
International Nuclear Information System (INIS)
Mills, S.J.; Taylor, M.
1994-01-01
This paper is intended to provide general advice to sponsors of renewable energy projects who expect to raise project-based financing from commercial banks to fund the development of their projects. It sets out, for the benefit of such sponsors, how bankers typically approach the analysis of these undertakings and in particular the risk areas on which they concentrate. By doing so it should assist sponsors to maximize their prospects of raising bank finance. The watchword for sponsors approaching banks must be ''Be Prepared'' . (author)
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LPS infusion suppresses serum FGF21 levels in healthy adult volunteers
DEFF Research Database (Denmark)
Lauritzen, Esben Stistrup; Rittig, Nikolaj; Bach, Ermina
2017-01-01
circulating levels of FGF21 after lipopolysaccharide (LPS) infusion. DESIGN: Two randomized, single blinded, placebo-controlled crossover trials were used. SETTING: The studies were performed at a university hospital clinical research center. PATIENTS AND INTERVENTIONS: Study 1 (LPS bolus): Eight young......, healthy, lean males were investigated two times: 1) after isotonic saline injection, and 2) after LPS injection (bolus of 1 ng/kg). Each study day lasted 4 hours. Study 2 (continuous LPS infusion): Eight, healthy males were investigated two times: 1) during continuously isotonic saline infusion, and 2......) during continuously LPS infusion (0.06 ng/kg/h). Each study day lasted 4 hours. Circulating FGF21 levels were quantified every second hour by an immunoassay. RESULTS: A LPS bolus resulted in a late suppression (t = 240 minutes) of serum FGF21 (P=0.035). Continuous LPS infusion revealed no significant...
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Experience using EPICS on PC platforms
International Nuclear Information System (INIS)
Hill, J.O.; Kasemire, K.U.
1997-03-01
The Experimental Physics and Industrial Control System (EPICS) has been widely adopted in the accelerator community. Although EPICS is available on many platforms, the majority of implementations have used UNIX workstations as clients, and VME- or VXI-based processors for distributed input output controllers. Recently, a significant portion of EPICS has been ported to personal computer (PC) hardware platforms running Microsoft's operating systems, and also Wind River System's real time vxWorks operating system. This development should significantly reduce the cost of deploying EPICS systems, and the prospect of using EPICS together with the many high quality commercial components available for PC platforms is also encouraging. A hybrid system using both PC and traditional platforms is currently being implemented at LANL for LEDA, the low energy demonstration accelerator under construction as part of the Accelerator Production of Tritium (APT) project. To illustrate these developments the authors compare their recent experience deploying a PC-based EPICS system with experience deploying similar systems based on traditional (UNIX-hosted) EPICS hardware and software platforms
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Directory of Open Access Journals (Sweden)
Tatiana Duobles
2008-12-01
Full Text Available PURPOSE: The neurotrophic factor fibroblast growth factor-2 (FGF-2, bFGF and Ca++ binding protein S100ß are expressed by the Schwann cells of the peripheral nerves and by the satellite cells of the dorsal root ganglia (DRG. Recent studies have pointed out the importance of the molecules in the paracrine mechanisms related to neuronal maintenance and plasticity of lesioned motor and sensory peripheral neurons. Moreover, cultured Schwann cells have been employed experimentally in the treatment of central nervous system lesions, in special the spinal cord injury, a procedure that triggers an enhanced sensorymotor function. Those cells have been proposed to repair long gap nerve injury. METHODS: Here we used double labeling immunohistochemistry and Western blot to better characterize in vitro and in vivo the presence of the proteins in the Schwann cells and in the satellite cells of the DRG as well as their regulation in those cells after a crush of the rat sciatic nerve. RESULTS: FGF-2 and S100ß are present in the Schwann cells of the sciatic nerve and in the satellite cells of the DRG. S100ß positive satellite cells showed increased size of the axotomized DRG and possessed elevated amount of FGF-2 immunoreactivity. Reactive satellite cells with increased FGF-2 labeling formed a ring-like structure surrounding DRG neuronal cell bodies.Reactive S100ß positive Schwann cells of proximal stump of axotomized sciatic nerve also expressed higher amounts of FGF-2. CONCLUSION: Reactive peripheral glial cells synthesizing FGF-2 and S100ß may be important in wound repair and restorative events in the lesioned peripheral nerves.OBJETIVO: O fator neurotrófico fator de crescimento de fibroblastos-2 (FGF-2, bFGF e a proteína ligante de Ca++ S100ß são expressos pelas células de Schwann dos nervos e por células satélites do gânglio da raiz dorsal (GRD. Estudos recentes indicam a importância das moléculas nos mecanismos parácrinos relacionados
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Liang, Qingning; Zhong, Ling; Zhang, Jialiang; Wang, Yu; Bornstein, Stefan R; Triggle, Chris R; Ding, Hong; Lam, Karen S L; Xu, Aimin
2014-12-01
Hepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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PC imaging system for reactor NDE
International Nuclear Information System (INIS)
Anon.
1987-01-01
PC-based systems have been given recent attention by EPRI to organize and manage inspection data (RP-2405-15, TestPro system); integrate with larger, mainframe computers to maintain dialogue for on-site and remote applications; and, in this project, to aid the operator in providing guidance to render decisions on the data. The PC system configuration for this project consisted of a central processing unit (CPU), a hard disk and a floppy disk, 640K bytes of system memory, a high-resolution graphics card and compatible color monitor, and a mouse for operator interaction with software. The software package was written in FORTRAN under the PC Disk Operating System (PC-DOS) and utilized a graphics package for image display. Application of this package to crack-counterbore discrimination in piping welds was investigated. Present automatic techniques utilize signal features from single, A-scan data to render a decision on whether the reflector is benign (i.e., counterbore, weld root) or a crack. However, experienced manual operators in the field make reliable decisions based on the integrated response from the reflector as the transducer is scanned past the suspicious region. Since this software package could display and manipulate ensemble A-scans, spatial features - similar to those used by experts - were developed as discriminants. Ultrasonic responses from intergranular stress corrosion cracks (IGSCCs) were discovered to vary both in time-of-flight and in their amplitude, whereas counterbore responses were more consistent. The software package contains methods for viewing and quantifying these spatial features
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Directory of Open Access Journals (Sweden)
Denis Kole
2017-05-01
Full Text Available Basic fibroblast growth factor (FGF2 is a highly pleiotropic member of a large family of growth factors with a broad range of activities, including mitogenesis and angiogenesis (Ornitz et al., 1996; Zhang et al., 2006, and it is known to be essential for maintenance of balance between survival, proliferation, and self-renewal in human pluripotent stem cells (Eiselleova et al., 2009; Zoumaro-Djayoon et al., 2011. A single FGF2 transcript can be translated into five FGF2 protein isoforms, an 18 kDa low molecular weight (LMW isoform and four larger high molecular weight (HMW isoforms (Arese et al., 1999; Arnaud et al., 1999. As they are not generally secreted, high molecular weight (HMW FGF2 isoforms have predominantly been investigated intracellularly; only a very limited number of studies have investigated their activity as extracellular factors. Here we report over-expression, isolation, and biological activity of all recombinant human FGF2 isoforms. We show that HMW FGF2 isoforms can support self-renewal of human embryonic stem cells (hESCs in vitro. Exogenous supplementation with HMW FGF2 isoforms also activates the canonical FGFR/MAPK pathway and induces mitogenic activity in a manner similar to that of the 18 kDa FGF2 isoform. Though all HMW isoforms, when supplemented exogenously, are able to recapitulate LMW FGF2 activity to some degree, it appears that certain isoforms tend to do so more poorly, demonstrating a lesser functional response by several measures. A better understanding of isoform-specific FGF2 effects will lead to a better understanding of developmental and pathological FGF2 signaling.
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PC-based Multiple Information System Interface (PC/MISI) detailed design and implementation plan
Dominick, Wayne D. (Editor); Hall, Philip P.
1985-01-01
The design plan for the personal computer multiple information system interface (PC/MISI) project is discussed. The document is intended to be used as a blueprint for the implementation of the system. Each component is described in the detail necessary to allow programmers to implement the system. A description of the system data flow and system file structures is given.
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Rottman, G. J.; Cebula, R. P.; Gillotay, D.; Simon, P. A.
1996-01-01
This report summarizes the activities of Working Group 2 and Working Group 3 of the SOLax Electromagnetic Radiation Study for Solar Cycle 22 (SOLERS22) Program. The international (SOLERS22) is Project 1.2 of the Solar-Terrestrial Energy Program (STEP) sponsored by SCOSTEP, a committee of the International Council of Scientific Unions). SOLERS22 is comprised of five Working Groups, each concentrating on a specific wave-length range: WG-1 - visible and infrared, WG-2 - mid-ultraviolet (200 < A < 300 nm), WG-3 - Far-ultraviolet (lambda greater than 100 and lambda less than 200 nanometers), WG-4 - extreme-ultraviolet (lambda greater than 10 and lambda less than 100 nm), and WG-5 - X-ray (lambda greater than 1 and lambda less than 10 nano meters). The overarching goals of SOLERS22 are to: 1) establish daily solar irradiance values in the specified wavelength ranges, 2) consider the evolving solar structures as the cause of temporal variations, and 3) understand the underlying physical processes driving these changes.
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Reuse of the compact nuclear simulator software under PC with Linux
International Nuclear Information System (INIS)
Cha, K. H.; Park, J. C.; Kwon, K. C.; Lee, G. Y.
2000-01-01
This study was approached to reuse source programs for a nuclear simulator under PC with Open Source Software(OSS) and to extend its applicability. Source programs in the Compact Nuclear Simulator(CNS), which has been operated for institutional research and training in KAERI, were reused and implemented for Linux-PC environment with the aim of supporting the study. PC with 500 MHz processor and Linux 2.2.5-22 kernel were utilized for the reuse implementation and it was investigated for some applications, through the functional testing for its main functions as interfaced with compact control panels in the current CNS. Development and upgrade of small-scale simulators, establishment of process simulation for PC, and development of prototype predictive simulation, can effectively be enabled with the experience though the reuse implementation was limited to port only CNS programs for PC with Linux
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Directory of Open Access Journals (Sweden)
Alvaro Ortega León
2010-01-01
Full Text Available Se probó si un incremento en las concentraciones de insulina, provocado por la administración oral de una sustancia glucogénica (glicerol durante los primeros días posinseminación, aumenta el porcentaje de concepción (PC en vacas Holstein. Se utilizaron 190 vacas de uno a tres servicios, con condición corporal de 2.5 a 3. Al momento de la inseminación (día cero, se distribuyeron al azar en dos grupos: el grupo glicerol (n=95 recibió 1 L de solución de glicerol y agua (90:10, v/v, la cual se repitió en los días 2, 4 y 6 posinseminación. El grupo testigo (n=95 recibió 1 L de agua por vía oral en el mismo esquema. El diagnóstico de gestación se realizó por palpación rectal en el día 45 posinseminación. El PC se comparó con una prueba de Ji-cuadrada. En seis animales de cada grupo se determinaron las concentraciones plasmáticas de insulina mediante radioinmunoanálisis antes de la toma de glicerol y en los siguientes 15, 30, 60, 90, 120 y 240 min y se compararon mediante análisis de varianza para mediciones repetidas. El PC fue mayor (P<0.05 en el grupo glicerol (47.4 que en el testigo (31.6. Después de la administración del glicerol se observó un incremento de las concentraciones de insulina (P<0.05. Se concluye que la administración de glicerol durante los primeros seis días posinseminación aumenta el porcentaje de concepción en vacas Holstein; probablemente el incremento de la insulina posterior a la toma del glicerol esté involucrado en dicho efecto.
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Exclusion of pregnant women from industry-sponsored clinical trials.
Shields, Kristine E; Lyerly, Anne Drapkin
2013-11-01
The lack of human data available to inform evidence-based treatment for illness during pregnancy has led to calls for greater inclusion of pregnant women in research, but the extent of their current representation is poorly characterized. Our objective was to measure the current exclusion of pregnant women from industry-sponsored clinical trials as a baseline for future comparison. We compiled data from studies enrolling women of childbearing potential posted on www.ClinicalTrials.gov between 1 October 2011 and 31 January 2012. The review was limited to open United States-based phase IV interventional studies sponsored by the pharmaceutical industry evaluating treatment of conditions that may be experienced by but are not limited to pregnant women and did not involve a medication classified as potentially teratogenic. If there was no mention of pregnancy in the inclusion or exclusion criteria, we contacted a study representative to confirm that pregnant women could be enrolled. Of 558 qualifying industry-sponsored studies, five (1%) were designed specifically for pregnant women. Of 367 phase IV clinical trials with verified inclusion and exclusion criteria, 348 (95%) excluded pregnant women and 19 (5%) did not. We found the exclusion of pregnant women from industry-sponsored clinical trials to be common practice. Moving beyond reflexive exclusion and developing thoughtful criteria for inclusion of pregnant women in clinical research would likely advance the evidence base to inform treatment decisions during pregnancy and lead to better health outcomes for women and children.
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FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice.
Bornstein, Sheila; Brown, Sue A; Le, Phuong T; Wang, Xunde; DeMambro, Victoria; Horowitz, Mark C; MacDougald, Ormond; Baron, Roland; Lotinun, Sutada; Karsenty, Gerard; Wei, Wei; Ferron, Mathieu; Kovacs, Christopher S; Clemmons, David; Wan, Yihong; Rosen, Clifford J
2014-09-01
Lactation is associated with significant alterations in both body composition and bone mass. Systemic and local skeletal factors such as receptor activator of nuclear factor κ-B ligand (RANKL), PTHrP, calcitonin, and estrogen are known to regulate bone remodeling during and after lactation. Fibroblast growth factor 21 (FGF-21) may function as an endocrine factor to regulate body composition changes during lactation by inducing gluconeogenesis and fatty acid oxidation. In this study, we hypothesized that the metabolic changes during lactation were due in part to increased circulating FGF-21, which in turn could accentuate bone loss. We longitudinally characterized body composition in C57BL/6J (B6) mice during (day 7 and day 21 of lactation) and after normal lactation (day 21 postlactation). At day 7 of lactation, areal bone density declined by 10% (P < .001), bone resorption increased (P < .0001), percent fat decreased by 20%, energy expenditure increased (P < .01), and markers of brown-like adipogenesis were suppressed in the inguinal depot and in preformed brown adipose tissue. At day 7 of lactation there was a 2.4-fold increase in serum FGF-21 vs baseline (P < .0001), a 8-fold increase in hepatic FGF-21 mRNA (P < .03), a 2-fold increase in undercarboxylated osteocalcin (Glu13 OCn) (P < .01), and enhanced insulin sensitivity. Recovery of total areal bone density was noted at day 21 of lactation, whereas the femoral trabecular bone volume fraction was still reduced (P < .01). Because FGF-21 levels rose rapidly at day 7 of lactation in B6 lactating mice, we next examined lactating mice with a deletion in the Fgf21 gene. Trabecular and cortical bone masses were maintained throughout lactation in FGF-21(-/-) mice, and pup growth was normal. Compared with lactating control mice, lactating FGF-21(-/-) mice exhibited an increase in bone formation, but no change in bone resorption. In conclusion, in addition to changes in calciotropic hormones, systemic FGF-21 plays a
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Directory of Open Access Journals (Sweden)
Kyung-Suk Moon
2015-01-01
Full Text Available The purpose of this research was to covalently graft fibroblast growth factor 2 (FGF-2 onto biphasic calcium phosphate (BCP via a bifunctional cross-linker technique and to estimate the optimal dose of FGF-2 resulting in the best osteogenic differentiation of human mesenchymal stem cells (hMSCs. SEM observation revealed that the surface of the 100 ng FGF-2 coated BCP was completely covered with the nanoparticles expected to be from the silane coupling agent. XRD, FT-IR, and XPS analysis showed that silane treatment, bifunctional cross-linker coating, and FGF-2 covalent grafts were conducted successfully without deforming the crystalline structure of BCP. An MTT assay demonstrated that FGF-2 coated BCP had good biocompatibility, regardless of the concentration of FGF-2, after 24 or 48 h of incubation. An alkaline phosphatase (ALP activity assay (14 days of incubation and the ALP gene expression level of real-time PCR analysis (7 days of incubation revealed that 50, 100, and 200 ng FGF-2 coated BCP induced the highest activities among all experimental groups and control group (P<0.05. Thus, low concentrations of FGF-2 facilitated excellent osteogenesis and were effective at enhancing osteogenic potential. Also, the bifunctional cross-linker technique is expected to be a more feasible way to induce osteogenic differentiation while minimizing the risk of FGF-2 overdose.
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Directory of Open Access Journals (Sweden)
Zhiqiang Zheng
Full Text Available BACKGROUND: Embryonic stem (ES cells hold considerable promise as a source of cells with therapeutic potential, including cells that can be used for drug screening and in cell replacement therapies. Differentiation of ES cells into the somatic lineages is a regulated process; before the promise of these cells can be realised robust and rational methods for directing differentiation into normal, functional and safe cells need to be developed. Previous in vivo studies have implicated fibroblast growth factor (FGF signalling in lineage specification from pluripotent cells. Although FGF signalling has been suggested as essential for specification of mesoderm and endoderm in vivo and in culture, the exact role of this pathway remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using a culture model based on early primitive ectoderm-like (EPL cells we have investigated the role of FGF signalling in the specification of mesoderm. We were unable to demonstrate any mesoderm inductive capability associated with FGF1, 4 or 8 signalling, even when the factors were present at high concentrations, nor any enhancement in mesoderm formation induced by exogenous BMP4. Furthermore, there was no evidence of alteration of mesoderm sub-type formed with addition of FGF1, 4 or 8. Inhibition of endogenous FGF signalling, however, prevented mesoderm and favoured neural differentiation, suggesting FGF signalling was required but not sufficient for the differentiation of primitive ectoderm into primitive streak-like intermediates. The maintenance of ES cell/early epiblast pluripotent marker expression was also observed in cultures when FGF signalling was inhibited. CONCLUSIONS/SIGNIFICANCE: FGF signalling has been shown to be required for the differentiation of primitive ectoderm to neurectoderm. This, coupled with our observations, suggest FGF signalling is required for differentiation of the primitive ectoderm into the germ lineages at gastrulation.
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Energy Technology Data Exchange (ETDEWEB)
Dai, Xiaoyong; Cai, Cuizan [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Xiao, Fei [Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, Guangdong (China); Xiong, Yaoling [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Huang, Yadong; Zhang, Qihao [Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong (China); Xiang, Qi [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Lou, Guofeng [Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong (China); Lian, Mengyang [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China); Su, Zhijian, E-mail: tjnuszj@jnu.edu.cn [Department of Biopharmaceutical Research and Development Centre, Institute of Biomedicine, Jinan University, Guangzhou 510632, Guangdong (China); Zheng, Qing, E-mail: tzhengq@jnu.edu.cn [College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong (China)
2014-03-21
Highlights: • A specific aFGF-binding peptide AP8 was identified from a phage display library. • AP8 could inhibit aFGF-stimulated cell proliferation in a dose-dependent manner. • AP8 arrested the cell cycle at the G0/G1 phase by suppressing Cyclin D1. • AP8 could block the activation of Erk1/2 and Akt kinase. • AP8 counteracted proliferation and cell cycle via influencing PA2G4 and PCNA. - Abstract: It has been reported that acidic fibroblast growth factor (aFGF) is expressed in breast cancer and via interactions with fibroblast growth factor receptors (FGFRs) to promote the stage and grade of the disease. Thus, aFGF/FGFRs have been considered essential targets in breast cancer therapy. We identified a specific aFGF-binding peptide (AGNWTPI, named AP8) from a phage display heptapeptide library with aFGF after four rounds of biopanning. The peptide AP8 contained two (TP) amino acids identical and showed high homology to the peptides of the 182–188 (GTPNPTL) site of high-affinity aFGF receptor FGFR1. Functional analyses indicated that AP8 specifically competed with the corresponding phage clone A8 for binding to aFGF. In addition, AP8 could inhibit aFGF-stimulated cell proliferation, arrested the cell cycle at the G0/G1 phase by increasing PA2G4 and suppressing Cyclin D1 and PCNA, and blocked the aFGF-induced activation of Erk1/2 and Akt kinase in both breast cancer cells and vascular endothelial cells. Therefore, these results indicate that peptide AP8, acting as an aFGF antagonist, is a promising therapeutic agent for the treatment of breast cancer.
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An overview of the evaluation plan for PC/MISI: PC-based Multiple Information System Interface
Dominick, Wayne D. (Editor); Lim, Bee Lee; Hall, Philip P.
1985-01-01
An initial evaluation plan for the personal computer multiple information system interface (PC/MISI) project is discussed. The document is intend to be used as a blueprint for the evaluation of this system. Each objective of the design project is discussed along with the evaluation parameters and methodology to be used in the evaluation of the implementation's achievement of those objectives. The potential of the system for research activities related to more general aspects of information retrieval is also discussed.
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Two recessive mutations in FGF5 are associated with the long-hair phenotype in donkeys.
Legrand, Romain; Tiret, Laurent; Abitbol, Marie
2014-09-25
Seven donkey breeds are recognized by the French studbook. Individuals from the Pyrenean, Provence, Berry Black, Normand, Cotentin and Bourbonnais breeds are characterized by a short coat, while those from the Poitou breed (Baudet du Poitou) are characterized by a long-hair phenotype. We hypothesized that loss-of-function mutations in the FGF5 (fibroblast growth factor 5) gene, which are associated with a long-hair phenotype in several mammalian species, may account for the special coat feature of Poitou donkeys. To the best of our knowledge, mutations in FGF5 have never been described in Equidae. We sequenced the FGF5 gene from 35 long-haired Poitou donkeys, as well as from a panel of 67 short-haired donkeys from the six other French breeds and 131 short-haired ponies and horses. We identified a recessive c.433_434delAT frameshift deletion in FGF5, present in Poitou and three other donkey breeds and a recessive nonsense c.245G > A substitution, present in Poitou and four other donkey breeds. The frameshift deletion was associated with the long-hair phenotype in Poitou donkeys when present in two copies (n = 31) or combined with the nonsense mutation (n = 4). The frameshift deletion led to a stop codon at position 159 whereas the nonsense mutation led to a stop codon at position 82 in the FGF5 protein. In silico, the two truncated FGF5 proteins were predicted to lack the critical β strands involved in the interaction between FGF5 and its receptor, a mandatory step to inhibit hair growth. Our results highlight the allelic heterogeneity of the long-hair phenotype in donkeys and enlarge the panel of recessive FGF5 loss-of-function alleles described in mammals. Thanks to the DNA test developed in this study, breeders of non-Poitou breeds will have the opportunity to identify long-hair carriers in their breeding stocks.
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Akyol, Murat; Alacacioglu, Ahmet; Demir, Leyla; Kucukzeybek, Yuksel; Yildiz, Yasar; Gumus, Zehra; Kara, Mete; Salman, Tarik; Varol, Umut; Taskaynatan, Halil; Oflazoglu, Utku; Bayoglu, Vedat; Tarhan, Mustafa Oktay
2017-01-01
In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy. Each patient was followed-up over a period of 1 year. Changes in body composition and serum lipid profile, glucose and FGF-21 levels were evaluated. We recorded the type of hormonal therapy, body mass index, waist-to-hip ratio, lipid profile, and FGF-21 levels both at the beginning and after 12 months. There was a statistically significant decrease in serum FGF-21 levels after 12 months of adjuvant endocrine therapy (46 ± 19.21 pg/ml vs. 30.99 ± 13.81 pg/ml, pbody water (pbody composition, glucose, lipid profile and FGF-21 were similar in tamoxifen and aromatase inhibitor groups. A positive correlation was found between basal weight, fat mass, fat-free mass and serum FGF-21 levels; however, the correlation was maintained only for the fat-free mass at the 12th month. As part of the present study, we suggest that both tamoxifen and aromatase inhibitors can reduce FGF-21 levels independently of body compositions, and these drugs can provide antihyperlipidemic, antidiabetic and cardio-protective effects. We also recommend that serum FGF-21 level can be utilized as a tumor biomarker in early-stage breast cancer and for monitoring purposes. FGF-21 levels may help physicians estimate prognosis, too. Further studies with larger populations may shed light on the role of FGF-21 in breast cancer.
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Directory of Open Access Journals (Sweden)
Zhuofeng Lin
Full Text Available BACKGROUND: Fibroblast growth factor 21 (FGF-21 is a metabolic regulator with multiple beneficial effects on glucose homeostasis and lipid metabolism in animal models. The relationship between plasma levels of FGF-21 and coronary heart disease (CHD in unknown. METHODOLOGY/PRINCIPAL FINDINGS: This study aimed to investigate the correlation of serum FGF-21 levels and lipid metabolism in the patients with coronary heart disease. We performed a logistic regression analysis of the relation between serum levels of FGF-21 and CHD patients with and without diabetes and hypertension. This study was conducted in the Departments of Endocrinology and Cardiovascular Diseases at two University Hospitals. Participants consisted of one hundred and thirty-five patients who have been diagnosed to have CHD and sixty-one control subjects. Serum FGF-21 level and levels of fasting blood glucose; triglyceride; apolipoprotein B100; HOMA-IR; insulin; total cholesterol; HDL-cholesterol; LDL-cholesterol; and C-reactive protein were measured. We found that median serum FGF-21 levels were significantly higher in CHD than that of control subjects (P<0.0001. Serum FGF-21 levels in CHD patients with diabetes, hypertension, or both were higher than that of patients without these comorbidities. Serum FGF-21 levels correlated positively with triglycerides, fasting blood glucose, apolipoprotein B100, insulin and HOMA-IR but negatively with HDL-C and apolipoprotein A1 after adjusting for BMI, diabetes and hypertension. Logistic regression analysis demonstrated that FGF-21 showed an independent association with triglyceride and apolipoprotein A1. CONCLUSIONS/SIGNIFICANCE: High levels of FGF-21 are associated with adverse lipid profiles in CHD patients. The paradoxical increase of serum FGF-21 in CHD patients may indicate a compensatory response or resistance to FGF-21.
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Directory of Open Access Journals (Sweden)
Chih-Ping Chung
Full Text Available Endothelial cells (ECs express fibroblast growth factor (FGF receptors and are metabolically active after treatment with FGF-23. It is not known if this effect is α-Klotho independent or mediated by humoral or endogenous endothelial α-Klotho. In the present study, we aimed to characterize EC α-Klotho expression within the human vascular tree and to investigate the potential role of α-Klotho in determining FGF-23 mediated EC regulation. Human tissue and ECs from various organs were used for immunohistochemistry and Western blot. Primary cultures of human aortic endothelial cells (HAECs and human brain microvascular endothelial cells (HBMECs were used to generate in vitro cell models. We found endogenous α-Klotho expression in ECs from various organs except in microvascular ECs from human brain. Furthermore, FGF-23 stimulated endothelial nitric oxide synthase (eNOS expression, nitric oxide (NO production, and cell proliferation in HAECs. Interestingly, these effects were not observed in our HBMEC model in vitro. High phosphate treatment and endothelial α-Klotho knockdown mitigated FGF-23 mediated eNOS induction, NO production, and cell proliferation in HAECs. Rescue treatment with soluble α-Klotho did not reverse endothelial FGF-23 resistance caused by reduced or absent α-Klotho expression in HAECs. These novel observations provide evidence for differential α-Klotho functional expression in the human endothelium and its presence may play a role in determining the response to FGF-23 in the vascular tree. α-Klotho was not detected in cerebral microvascular ECs and its absence may render these cells nonresponsive to FGF-23.
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Emery, Sherry; Wakefield, Melanie A; Terry-McElrath, Yvonne; Saffer, Henry; Szczypka, Glen; O'Malley, Patrick M; Johnston, Lloyd D; Chaloupka, Frank J; Flay, Brian
2005-07-01
Recent state budget crises have dramatically reduced funding for state-sponsored antitobacco media campaigns. If campaigns are associated with reduced smoking, such cuts could result in long-term increases in state health care costs. Commercial ratings data on mean audience exposure to antitobacco advertising that appeared on network and cable television across the largest 75 media markets in the United States for 1999 through 2000 were combined with nationally representative survey data from school-based samples of youth in the contiguous 48 states. Multivariate regression models were used to analyze associations between mean exposure to state antitobacco advertising and youth smoking-related beliefs and behaviors, controlling for individual and environmental factors usually associated with youth smoking and other televised tobacco-related advertising. Mean exposure to at least 1 state-sponsored antitobacco advertisement in the past 4 months was associated with lower perceived rates of friends' smoking (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.58-0.88), greater perceived harm of smoking (OR, 1.25; 95% CI, 1.11-1.42), stronger intentions not to smoke in the future (OR, 1.43; 95% CI, 1.17-1.74), and lower odds of being a smoker (OR, 0.74; 95% CI, 0.63-0.88). To our knowledge, this study is the first to explore the potential impact of state-sponsored antitobacco media campaigns while controlling for other tobacco-related advertising and other tobacco control policies. State-sponsored antitobacco advertising is associated with desired outcomes of greater antitobacco sentiment and reduced smoking among youth. Recent cuts in these campaigns may have future negative health and budgetary consequences.
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Directory of Open Access Journals (Sweden)
Silvânia Suely de Araújo Andrade
Full Text Available OBJETIVO:descrever a prevalência de hipertensão arterial autorreferida na população adulta brasileira, para o conjunto do país, zona urbana/rural, grandes regiões e Unidades da Federação.MÉTODOS:estudo descritivo com dados da Pesquisa Nacional de Saúde 2013; a amostra foi composta por 60.202 adultos (≥18 anos; foram calculadas as prevalências e respectivos intervalos de confiança de 95% (IC95% segundo sexo, faixa etária, escolaridade e cor da pele.RESULTADOS:a prevalência de hipertensão foi de 21,4% (IC95%:20,8-22,0, sendo maior entre mulheres (24,2%; IC95%:23,4-24,9, indivíduos com mais de 75 anos de idade (55,0%; IC95%:51,8-58,3, menos escolarizados (31,1%; IC95%:30,1-32,2, de raça/cor preta (24,2%; IC95%:22,2-26,3, residentes na zona urbana (21,7%; IC95%:21,0-22,3, no Rio Grande do Sul (24,9%; IC95%:22,7-27,1 e na região Sudeste (23,3%; IC95%:23,3-24,3.CONCLUSÃO:a prevalência da hipertensão foi elevada nos adultos brasileiros, principalmente entre pessoas maiores de 60 anos de idade, com baixa escolaridade, residentes em zona urbana e no Sudeste.
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Energy Technology Data Exchange (ETDEWEB)
Martinez, Juan Bonifacio; Urena Nunez, Fernando [Instituto Nacional de Investigaciones Nucleares, Ocoyoacac, Estado de Mexico (Mexico)]. E-mail: juan.bonifacio@inin.gob.mx
2009-09-15
This work presents hydrogen absorption in quaternary alloy Mg1.95Ti0.05Ni0.95Cu0.05 obtained by the mechanical alloying method, followed by thermal treatment in ultra-high pure argon atmosphere. The composition of the phases, microstructure and morphology of ground powders and with thermal treatment were characterized by DRX, SEM/EDS and TEM. After 20 hours of mechanical grinding and recooked at 300 degrees Celsius/1h in argon atmosphere, the quaternary alloy has a Mg{sub 2}Ni crystalline hexagonal structure with a crystallite size under 10 nm. The absorption measurements were performed under a pressure of 0.2 to 1.2 MPa at a temperature of 200 degrees Celsius in a micro-reactor. The quantification of absorption-desorption of hydrogen in the intermetallic was conducted in a TGA-DSC simultaneous calorimeter. Metallic hydride-dehydride powder was characterized with SEM and XRD. [Spanish] En este trabajo se presenta la absorcion de hidrogeno en la aleacion cuaternaria Mg1.95Ti0.05Ni0.95Cu0.05 obtenida por el metodo de aleado mecanico, seguida de tratamiento termico en atmosfera de argon de ultra alta pureza. La composicion de las fases, microestructura y morfologia de los polvos molidos y con tratamiento termico fue caracterizada por DRX, SEM/EDS y TEM. Despues de 20 h de molienda mecanica con recocido a 300 grados Celsios/1h en atmosfera de argon, la aleacion cuaternaria tiene una estructura cristalina hexagonal Mg{sub 2}Ni con tamano de cristalito menor a 10 nm. Las mediciones de absorcion fueron realizadas bajo una presion de 0.2 a 1.2 MPa a una temperatura de 200 grados Celsios en un micro-reactor. La cuantificacion de absorcion-desorcion de hidrogeno en el intermetalico se realizo en un calorimetro simultaneo TGA-DSC. Se determino que la cantidad maxima absorbida de hidrogeno en la aleacion cuaternaria fue de 3.24% en peso cuando la presion fue de 0.8 MPa a dicha temperatura. Polvos metalicos hidrurados-deshidrurados se caracterizaron por SEM y XRD.
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Branching ratio for the isoscalar transition 2+, T = 1, 1.95 MeV→0+, T = 1, 0.66 MeV in 22Na
International Nuclear Information System (INIS)
Vermeer, W.J.; Poletti, A.R.
1982-01-01
The branching ratio for the isoscalar transition 2 + , T = 1, 1.95 MeV→0 + , T = 1, 0.66 MeV in 22 Na was measured as (0.29+-0.05)% of the total decays of the 1.95MeV level. This, together with the measured mean-life of this level, gives an E2 strength of (16+-5) Wu, in good agreement with the estimate of 18 Wu obtained from the analogue transitions in 22 Ne and 22 Mg assuming a linear relationship between M(E2) and Tsub(z). Upper limits for some weak decay branches in 19 F were also obtained. (author)
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Global Precipitation Climatology Project (GPCP) - Pentad, Version 2.2
National Oceanic and Atmospheric Administration, Department of Commerce — The Global Precipitation Climatology Project (GPCP) comprises a total of 27 products. The Version 2.2 Pentad product covers the period January 1979 to the present,...
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FGF: A web tool for Fishing Gene Family in a whole genome database
DEFF Research Database (Denmark)
Zheng, Hongkun; Shi, Junjie; Fang, Xiaodong
2007-01-01
Gene duplication is an important process in evolution. The availability of genome sequences of a number of organisms has made it possible to conduct comprehensive searches for duplicated genes enabling informative studies of their evolution. We have established the FGF (Fishing Gene Family) progr...... is freely available on a web server at http://fgf.genomics.org.cn/...
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45 CFR 2552.24 - What are a sponsor's responsibilities for securing community participation?
2010-10-01
...? (a) A sponsor shall secure community participation in local project operation by establishing an Advisory Council or a similar organizational structure with a membership that includes people: (1...
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45 CFR 2551.24 - What are a sponsor's responsibilities for securing community participation?
2010-10-01
...? (a) A sponsor shall secure community participation in local project operation by establishing an Advisory Council or a similar organizational structure with a membership that includes people: (1...
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fibroblast growth factor, MTDH/Astrocyte elevated gene-1
African Journals Online (AJOL)
2012-12-05
Dec 5, 2012 ... Expression of basic FGF, MTDH/AEG-1, APC, matrix metalloproteinase 9, and COX-2 markers in prostate carcinomas many genetic and epigenetic alterations have been detected in human PC.[1]. Basic fibroblast growth factor (bFGF), also known as. FGF2 is a member of the FGF family, a group of more.
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Angiogenic activity of bFGF and VEGF suppressed by proteolytic cleavage by neutrophil elastase
International Nuclear Information System (INIS)
Ai, Shingo; Cheng Xianwu; Inoue, Aiko; Nakamura, Kae; Okumura, Kenji; Iguchi, Akihisa; Murohara, Toyoaki; Kuzuya, Masafumi
2007-01-01
Neutrophil elastase (NE), a serine protease released from the azurophil granules of activated neutrophil, proteolytically cleaves multiple cytokines, and cell surface proteins. In the present study, we examined whether NE affects the biological abilities of angiogenic growth factors such as basic-fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). NE degraded bFGF and VEGF in a time- and concentration-dependent manner, and these degradations were suppressed by sivelestat, a synthetic inhibitor of NE. The bFGF- or VEGF-mediated proliferative activity of human umbilical vein endothelial cells was inhibited by NE, and the activity was recovered by sivelestat. Furthermore, NE reduced the bFGF- or VEGF-induced tubulogenic response of the mice aortas, ex vivo angiogenesis assay, and these effects were also recovered by sivelestat. Neutrophil-derived NE degraded potent angiogenic factors, resulting in loss of their angiogenic activity. These findings provide additional insight into the role played by neutrophils in the angiogenesis process at sites of inflammation
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FGF9 can induce endochondral ossification in cranial mesenchyme
Directory of Open Access Journals (Sweden)
Overbeek Paul A
2006-02-01
Full Text Available Abstract Background The flat bones of the skull (i.e., the frontal and parietal bones normally form through intramembranous ossification. At these sites cranial mesenchymal cells directly differentiate into osteoblasts without the formation of a cartilage intermediate. This type of ossification is distinct from endochondral ossification, a process that involves initial formation of cartilage and later replacement by bone. Results We have analyzed a line of transgenic mice that expresses FGF9, a member of the fibroblast growth factor family (FGF, in cranial mesenchymal cells. The parietal bones in these mice show a switch from intramembranous to endochondral ossification. Cranial cartilage precursors are induced to proliferate, then hypertrophy and are later replaced by bone. These changes are accompanied by upregulation of Sox9, Ihh, Col2a1, Col10a1 and downregulation of CbfaI and Osteocalcin. Fate mapping studies show that the cranial mesenchymal cells in the parietal region that show a switch in cell fate are likely to be derived from the mesoderm. Conclusion These results demonstrate that FGF9 expression is sufficient to convert the differentiation program of (at least a subset of mesoderm-derived cranial mesenchyme cells from intramembranous to endochondral ossification.
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Abdian, Narges; Ghasemi-Dehkordi, Payam; Hashemzadeh-Chaleshtori, Morteza; Ganji-Arjenaki, Mahbobe; Doosti, Abbas; Amiri, Beheshteh
2015-12-01
Basic fibroblast growth factor (bFGF or FGF-2) is a member of the FGF family secreted by different kinds of cells like HDFs and it is an important nutritional factor for cell growth and differentiation. The HDFs release bFGF in culture media at very low. The present study aims to investigate the HDFs growth rate in culture media supplemented either with or without bFGF. In brief, HDFs were isolated from human foreskin sample and were cultured in vitro in media containing bFGF and lack of this factor. The cells growth rate was calculated by trypan blue. The karyotyping was performed using G-banding to investigate the chromosomal abnormality of HDFs in both groups. Total RNA of each groups were extracted and cDNA samples were synthesized then, real-time Q-PCR was used to measure the expression level of p27kip1 and cyclin D1 genes normalized to internal control gene (GAPDH). The karyotype analysis showed that HDFs cultured in media or without bFGF had normal karyotype (46 chromosomes, XY) and chromosomal abnormalities were not observed. The cell growth rates in both groups were normal with proliferated exponentially but the slope of growth curve in HDFs cultured in media containing bFGF was increased. Karyotyp test showed that bFGF does not affect on cytogenetic stability of cells. The survey of p27kip1 and cyclin D1 genes by real-time Q-PCR showed that the expression level of these genes were up-regulated when adding bFGF in culture media (p culture media with growth factor like bFGF could enhance the proliferation and differentiation capacity of cells and improve cells growth rate. Similarly, fibroblast growth factors did not induce any chromosomal abnormality in cells. Furthermore, in HDFs cultured in bFGF supplemented media, the p27kip1 and cyclin D1 genes were up-regulated and suggesting an important role for bFGF in cell-cycle regulation and progression and fibroblast division stimulation. It also suggests that the effects of bFGF on different cell types with
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45 CFR 2553.24 - What are a sponsor's responsibilities for securing community participation?
2010-10-01
... community participation? (a) A sponsor shall secure community participation in local project operation by establishing an Advisory Council or a similar organizational structure with a membership that includes people...
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Czech Academy of Sciences Publication Activity Database
Feygin, F. Z.; Prikner, Karel; Nekrasov, A. K.
2003-01-01
Roč. 43, č. 6 (2003), s. 701-707 ISSN 0016-7932 R&D Projects: GA AV ČR KSK3012103 Grant - others:INTAS(XE) 99-0335; RFFR(RU) 02-05-64610; RFFR(RU) 02-05-64612 Institutional research plan: CEZ:AV0Z3012916 Keywords : Pc1 bounce effect * inosphere reflection coefficient * EMIC-wave Poynting vector Subject RIV: DE - Earth Magnetism, Geodesy, Geography Impact factor: 0.342, year: 2003
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Choi, Seong Mi; Lee, Kyoung-Mi; Kim, Hyun Jung; Park, Ik Kyu; Kang, Hwi Ju; Shin, Hang-Cheol; Baek, Dawoon; Choi, Yoorim; Park, Kwang Hwan; Lee, Jin Woo
2018-01-15
Diabetes mellitus comprises a multiple metabolic disorder that affects millions of people worldwide and consequentially poses challenges for clinical treatment. Among the various complications, diabetic ulcer constitutes the most prevalent associated disorder and leads to delayed wound healing. To enhance wound healing capacity, we developed structurally stabilized epidermal growth factor (ST-EGF) and basic fibroblast growth factor (ST-bFGF) to overcome limitations of commercially available EGF (CA-EGF) and bFGF (CA-bFGF), such as short half-life and loss of activity after loading onto a matrix. Neither ST-EGF nor ST-bFGF was toxic, and both were more stable at higher temperatures than CA-EGF and CA-bFGF. We loaded ST-EGF and ST-bFGF onto a hyaluronate-collagen dressing (HCD) matrix, a biocompatible carrier, and tested the effectiveness of this system in promoting wound healing in a mouse model of diabetes. Wounds treated with HCD matrix loaded with 0.3 μg/cm 2 ST-EGF or 1 μg/cm 2 ST-bFGF showed a more rapid rate of tissue repair as compared to the control in type I and II diabetes models. Our results indicate that an HDC matrix loaded with 0.3 μg/cm 2 ST-EGF or 1 μg/cm 2 ST-bFGF can promote wound healing in diabetic ulcers and are suitable for use in wound dressings owing to their stability for long periods at room temperature. Various types of dressing materials loaded with growth factors, such as VEGF, EGF, and bFGF, are widely used to effect wound repair. However, such growth factor-loaded materials have several limitations for use as therapeutic agents in healing-impaired diabetic wounds. To overcome these limitations, we have developed new materials containing structurally stabilized EGF (ST-EGF) and bFGF (ST-bFGF). To confirm the wound healing capacity of newly developed materials (ST-EGF and ST-bFGF-loaded hyaluronate-collagen dressing [HCD] matrix), we applied these matrices in type I and type II diabetic wounds. Notably, these matrices were
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FGF signaling regulates the number of posterior taste papillae by controlling progenitor field size.
Directory of Open Access Journals (Sweden)
Camille I Petersen
2011-06-01
Full Text Available The sense of taste is fundamental to our ability to ingest nutritious substances and to detect and avoid potentially toxic ones. Sensory taste buds are housed in papillae that develop from epithelial placodes. Three distinct types of gustatory papillae reside on the rodent tongue: small fungiform papillae are found in the anterior tongue, whereas the posterior tongue contains the larger foliate papillae and a single midline circumvallate papilla (CVP. Despite the great variation in the number of CVPs in mammals, its importance in taste function, and its status as the largest of the taste papillae, very little is known about the development of this structure. Here, we report that a balance between Sprouty (Spry genes and Fgf10, which respectively antagonize and activate receptor tyrosine kinase (RTK signaling, regulates the number of CVPs. Deletion of Spry2 alone resulted in duplication of the CVP as a result of an increase in the size of the placode progenitor field, and Spry1(-/-;Spry2(-/- embryos had multiple CVPs, demonstrating the redundancy of Sprouty genes in regulating the progenitor field size. By contrast, deletion of Fgf10 led to absence of the CVP, identifying FGF10 as the first inductive, mesenchyme-derived factor for taste papillae. Our results provide the first demonstration of the role of epithelial-mesenchymal FGF signaling in taste papilla development, indicate that regulation of the progenitor field size by FGF signaling is a critical determinant of papilla number, and suggest that the great variation in CVP number among mammalian species may be linked to levels of signaling by the FGF pathway.
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Directory of Open Access Journals (Sweden)
Ernesto R. Chavanne
2012-06-01
Full Text Available En este trabajo se presenta el comportamiento productivo y fitosanitario del nuevo cultivar de caña de azúcar (Saccharum spp. TUC 95-37, obtenido y seleccionado por el Programa de Mejoramiento Genético de la Caña de Azúcar de la Estación Experimental Agroindustrial Obispo Colombres (Tucumán, R. Argentina. La información que se presenta proviene de 24 cosechas realizadas en ensayos con 18 genotipos, implantados de acuerdo a un diseño experimental de bloques completamente aleatorizados con tres repeticiones. Los ensayos se replicaron en seis localidades de Tucumán y fueron evaluados en cuatro edades de corte (caña planta, soca 1, soca 2 y soca 3 entre los años 2002 y 2005. Las variables toneladas de caña/ha y de azúcar/ha y rendimiento fabril porciento se evaluaron en mayo. Para cada variable, edad y localidad se realizaron análisis de la varianza y pruebas de comparación de medias. También se aplicó la metodología de GGE biplot como herramienta gráfica, para identificar genotipos superiores y estables frente a distintos ambientes de expresión. Se evaluó además el comportamiento fitosanitario de TUC 95-37. Los resultados indicaron que la nueva variedad evidenció un comportamiento productivo similar al de LCP 85-384 en la mayoría de las edades de corte y localidades evaluadas. En caña planta, el nuevo cultivar fue el genotipo más productivo, presentando además una amplia adaptación a diferentes ambientes. En soca 1 y 2, TUC 95-37 resultó segunda en orden de mérito, siendo estable en las diferentes localidades. En soca 3, la nueva variedad evidenció una menor estabilidad frente al ambiente. Con respecto al comportamiento fitosanitario, TUC 95-37 se comportó como moderadasmente resistente a roya marrón (Puccinia melanocephala, a escaldadura de la hoja (Xanthomonas albilineans y a carbón (Sporisorium scitamineum. Se mostró moderadamente susceptible al mosaico (Sugarcane mosaic virus y a estría roja (Acidovorax
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Energy Technology Data Exchange (ETDEWEB)
Ishino, Ruri; Minami, Kaori; Tanaka, Satowa [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Nagai, Mami [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Matsui, Keiji; Hasegawa, Natsumi [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Roeder, Robert G. [Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Asano, Shigetaka [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Ito, Mitsuhiro, E-mail: itomi@med.kobe-u.ac.jp [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan); Department of Family and Community Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 654-0142 (Japan)
2013-10-11
Highlights: •FGF7 is downregulated in MED1-deficient mesenchymal cells. •FGF7 produced by mesenchymal stromal cells is a novel hematopoietic niche molecule. •FGF7 supports hematopoietic progenitor cells and niche-dependent leukemia cells. •FGF7 activates FGFR2IIIb of bone marrow stromal cells in an autocrine manner. •FGF7 indirectly acts on hematopoietic cells lacking FGFR2IIIb via stromal cells. -- Abstract: FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1{sup +/+} MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1{sup −/−} MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1{sup +/+} and Med1{sup −/−} MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells.
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International Nuclear Information System (INIS)
Ishino, Ruri; Minami, Kaori; Tanaka, Satowa; Nagai, Mami; Matsui, Keiji; Hasegawa, Natsumi; Roeder, Robert G.; Asano, Shigetaka; Ito, Mitsuhiro
2013-01-01
Highlights: •FGF7 is downregulated in MED1-deficient mesenchymal cells. •FGF7 produced by mesenchymal stromal cells is a novel hematopoietic niche molecule. •FGF7 supports hematopoietic progenitor cells and niche-dependent leukemia cells. •FGF7 activates FGFR2IIIb of bone marrow stromal cells in an autocrine manner. •FGF7 indirectly acts on hematopoietic cells lacking FGFR2IIIb via stromal cells. -- Abstract: FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1 +/+ MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1 −/− MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1 +/+ and Med1 −/− MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells
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Directory of Open Access Journals (Sweden)
Li Lan
Full Text Available In this study, porous gelatin microspheres (GMSs were constructed to improve the neuroprotective effect of basic fibroblast growth factor (bFGF on spinal cord injury. GMSs were prepared by a W/O emulsion template, followed by cross-linking, washing and drying. The particle sizes and surface porosity of the blank GMSs were carefully characterized by scan electronic microscopy. The blank GMSs have a mean particle size of 35μm and theirs surface was coarse and porous. bFGF was easily encapsulated inside the bulk GMSs through diffusion along the porous channel. 200μg of bFGF was completely encapsulated in 100mg of GMSs. The bFGF-loaded GMSs displayed a continuous drug release pattern without an obvious burst release over two weeks in vitro. Moreover, the therapeutic effects of bFGF-loaded GMSs were also evaluated in spinal cord injury rat model. After implantation of bFGF-loaded GMSs, the recovery of the motor function of SCI rats were evaluated by behavioral score and foot print experiment. The motor function of SCI rats treated with bFGF-loaded GMSs was more obvious than that treated with free bFGF solution (P<0.05. At the 28th days after treatment, rats were sacrificed and the injured spinal were removed for histopathological and apoptosis examination. Compared with treatment with free bFGF solution, treatment with bFGF-loaded GMSs resulted in a less necrosis, less infiltration of leukocytes, and a reduced the cavity ratio and less apoptotic cells in injured spinal(P<0.01, indicating its better therapeutic effect. Implantable porous GMSs may be a potential carrier to deliver bFGF for therapy of spinal cord injury.
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Project finance for alternative energy
International Nuclear Information System (INIS)
Mills, S.J.
1993-01-01
This paper is intended to provide general advice to sponsors of renewable energy projects who expect to raise project-based financing from commercial banks to fund the development of their projects. It will set out, for the benefit of such sponsors, how bankers typically approach the analysis of these undertakings and in particular the risk areas on which they concentrate. By doing so it should assist sponsors to maximise their prospects of raising bank finance. (author)
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Pabalan, Noel; Jarjanazi, Hamdi; Christofolini, Denise Maria; Bianco, Bianca; Barbosa, Caio Parente
2017-01-01
To evaluate PTPN22 C1858T polymorphism and the risk of endometriosis. A meta-analysis of 10 published case-control studies (from four articles), with a total sample of 971 cases and 1,181 controls, was performed. We estimated risk (odds ratio and 95% confidence intervals) of endometriosis associations with the C1858T polymorphism. A significant increased risk in all genetic models of the variant T allele with endometriosis (odds ratio: 3.14-5.55; pendometriose. Foi realizada uma metanálise de 10 estudos caso-controle publicados (a partir de quatro artigos), com uma amostra total de 971 casos e 1.181 controles. O risco da associação da endometriose com o polimorfismo C1858T foi estimado em razão de chance e intervalo de confiança de 95%. Observou-se um aumento de risco significativo em todos os modelos genéticos com o alelo variante T e a endometriose (razão de chance: 3,14-5,55; pendometriose sugerem que este polimorfismo pode ser um marcador de suscetibilidade para a endometriose.
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International Nuclear Information System (INIS)
Wang, Wenhui; Chen, Xilei; Li, Tao; Li, Yanmei; Wang, Ruixue; He, Dan; Luo, Wu; Li, Xiaokun; Wu, Xiaoping
2013-01-01
Fibroblast growth factor 8b (FGF8b) is the major isoform of FGF8 expressed in prostate cancer and it correlates with the stage and grade of the disease. FGF8b has been considered as a potential target for prostate cancer therapy. Here we isolated 12 specific FGF8b-binding phage clones by screening a phage display heptapeptide library with FGF8b. The peptide (HSQAAVP, named as P12) corresponding to one of these clones showed high homology to the immunoglobulin-like (Ig-like) domain II(D2) of high-affinity FGF8b receptor (FGFR3c), contained 3 identical amino acids (AVP) to the authentic FGFR3 D2 sequence aa 163–169 (LLAVPAA) directly participating in ligand binding, carried the same charges as its corresponding motif (aa163–169) in FGFR3c, suggesting that P12 may have a greater potential to interrupt FGF8b binding to its receptors than other identified heptapeptides do. Functional analysis indicated that synthetic P12 peptides mediate significant inhibition of FGF8b-induced cell proliferation, arrest cell cycle at the G0/G1 phase via suppression of Cyclin D1 and PCNA, and blockade of the activations of Erk1/2 and Akt cascades in both prostate cancer cells and vascular endothelial cells. The results demonstrated that the P12 peptide acting as an FGF8b antagonist may have therapeutic potential in prostate cancer. - Highlights: ► A novel FGF8b-binding peptide P12 was isolated from a phage display library. ► The mechanisms for P12 peptide inhibiting cell proliferation were proposed. ► P12 caused cell cycle arrest at G0/G1 phase via suppression of Cyclin D1 and PCNA. ► P12 suppressed FGF8b-induced activations of Akt and MAP kinases. ► P12 acting as an FGF8b antagonist may have therapeutic potential in prostate cancer
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Energy Technology Data Exchange (ETDEWEB)
Wang, Wenhui; Chen, Xilei; Li, Tao; Li, Yanmei; Wang, Ruixue; He, Dan; Luo, Wu [Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632 (China); Li, Xiaokun [Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632 (China); School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou 325035 (China); Wu, Xiaoping, E-mail: twxp@jnu.edu.cn [Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632 (China); School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou 325035 (China)
2013-05-01
Fibroblast growth factor 8b (FGF8b) is the major isoform of FGF8 expressed in prostate cancer and it correlates with the stage and grade of the disease. FGF8b has been considered as a potential target for prostate cancer therapy. Here we isolated 12 specific FGF8b-binding phage clones by screening a phage display heptapeptide library with FGF8b. The peptide (HSQAAVP, named as P12) corresponding to one of these clones showed high homology to the immunoglobulin-like (Ig-like) domain II(D2) of high-affinity FGF8b receptor (FGFR3c), contained 3 identical amino acids (AVP) to the authentic FGFR3 D2 sequence aa 163–169 (LLAVPAA) directly participating in ligand binding, carried the same charges as its corresponding motif (aa163–169) in FGFR3c, suggesting that P12 may have a greater potential to interrupt FGF8b binding to its receptors than other identified heptapeptides do. Functional analysis indicated that synthetic P12 peptides mediate significant inhibition of FGF8b-induced cell proliferation, arrest cell cycle at the G0/G1 phase via suppression of Cyclin D1 and PCNA, and blockade of the activations of Erk1/2 and Akt cascades in both prostate cancer cells and vascular endothelial cells. The results demonstrated that the P12 peptide acting as an FGF8b antagonist may have therapeutic potential in prostate cancer. - Highlights: ► A novel FGF8b-binding peptide P12 was isolated from a phage display library. ► The mechanisms for P12 peptide inhibiting cell proliferation were proposed. ► P12 caused cell cycle arrest at G0/G1 phase via suppression of Cyclin D1 and PCNA. ► P12 suppressed FGF8b-induced activations of Akt and MAP kinases. ► P12 acting as an FGF8b antagonist may have therapeutic potential in prostate cancer.
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Trastornos menores de salud en una muestra de estudiantes de la Universidad de Barcelona
Directory of Open Access Journals (Sweden)
MT Icart Isern
Full Text Available Introducción: conocer la prevalencia de algunos trastornos menores de salud (TMS en una muestra de estudiantes de la Universidad de Barcelona (2004-05. Material y métodos: El estudio se realizó en las facultades de Ciencias Económicas, Farmacia, Medicina, Psicología y Químicas y Escuela de Enfermería de la Universidad de Barcelona. Se empleó un diseño observacional, descriptivo y transversal mediante un cuestionario mixto administrada a 600 estudiantes durante el mes de diciembre de 2004. Las variables estudiadas corresponden a los siguientes TMS: insomnio, estreñimiento, cefalea, dolor osteomuscular, tics nerviosos, onicofagia y tricotilomania. Resultados: El sexo femenino representa el 64% de la muestra; la media de edad de los encuestados es de 22,7 (DE: 3,27; IC 95%: 22,43-22,96. Las mujeres acumulan el 67,79% de los 1.245 TMS identificados. Por sexo, se observan diferencias estadísticamente significativas en las prevalencias de cefalea, dolor osteomuscular y tricotilomania que afectan en mayor medida al sexo femenino. La onicofagia (264; 21,20%; IC 95%: 18-24,4 es el más extendido de los TMS, seguido de la cefalea (233; 18,72%; IC 95%: 15,6-21,84. los estudiantes de Psicología presentan el mayor número, seguidos de los de Ciencias Económicas; los que presentan un menor número son los de Farmacia y Químicas. Conclusiones: El sexo femenino presenta la mayor prevalencia de TMS. La onicofagia y la cefalea son los principales TMS identificados en la muestra. Los estudiantes de Psicología acumulan el mayor número de TMS, siendo los que presentan más cefalea, dolor osteomuscular y tricotilomania.
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miR-194 Inhibits Innate Antiviral Immunity by Targeting FGF2 in Influenza H1N1 Virus Infection
Directory of Open Access Journals (Sweden)
Keyu Wang
2017-11-01
Full Text Available Fibroblast growth factor 2 (FGF2 or basic FGF regulates a wide range of cell biological functions including proliferation, angiogenesis, migration, differentiation, and injury repair. However, the roles of FGF2 and the underlying mechanisms of action in influenza A virus (IAV-induced lung injury remain largely unexplored. In this study, we report that microRNA-194-5p (miR-194 expression is significantly decreased in A549 alveolar epithelial cells (AECs following infection with IAV/Beijing/501/2009 (BJ501. We found that miR-194 can directly target FGF2, a novel antiviral regulator, to suppress FGF2 expression at the mRNA and protein levels. Overexpression of miR-194 facilitated IAV replication by negatively regulating type I interferon (IFN production, whereas reintroduction of FGF2 abrogated the miR-194-induced effects on IAV replication. Conversely, inhibition of miR-194 alleviated IAV-induced lung injury by promoting type I IFN antiviral activities in vivo. Importantly, FGF2 activated the retinoic acid-inducible gene I signaling pathway, whereas miR-194 suppressed the phosphorylation of tank binding kinase 1 and IFN regulatory factor 3. Our findings suggest that the miR-194-FGF2 axis plays a vital role in IAV-induced lung injury, and miR-194 antagonism might be a potential therapeutic target during IAV infection.
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Directory of Open Access Journals (Sweden)
Shaohui Yuan
2013-01-01
Full Text Available Background & objectives: BMP (bone morphogenetic protein-4/7 and bFGF (basic fibroblast growth factor significantly promote the osteogenic activity and the proliferation of rabbit BMSCs (bone marrow stromal cells, respectively. However, their synergistic effects on the proliferation and the differentiation of BMSCs remain unclear. In the present study, the effects of bFGF and BMP-4/7 were investigated on the proliferation and the differentiation of rat BMSCs in vitro. Methods: BMSCs were isolated from New Zealand white rabbits and cultured to the third passage. The samples were divided into five groups according to the material implanted: (A 80 ng/ml BMP-4/7; (B 80 ng/ml bFGF; (C 30 ng/ml BMP-4/7 and 30 ng/ml bFGF; (D 50 ng/ml BMP-4/7 and 50 ng/ml bFGF; and (E 80 ng/ml BMP-4/7 and 80 ng/ml bFGF. Cell proliferation was analyzed using methyl thiazolyl tetrazolium (MTT assay. Alkaline phosphatase activity and osteocalcin (OC dynamics were also measured. Results: BMP-4/7 alone significantly (P<0.05 promoted the proliferation of BMSCs. At the same time, it also promoted or inhibited the osteogenic differentiation of BMSCs. The synergistic effects of BMP-4/7 and bFGF significantly promoted both the proliferation and the osteogenic differentiation of BMSCs. The treatment of the synergistic effects was dose and time dependent. Interpretation & conclusions: A rational combination of BMP-4/7 and bFGF can promote the proliferation and the osteogenic differentiation of BMSCs. In addition, the synergistic functions are effective.
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NICBR-Sponsored Spring Research Festival Set for May 8 and 9 | Poster
By Ashley DeVine, Staff Writer For the first time, the Spring Research Festival (SRF), scheduled for May 8 and 9, will be sponsored by all of the agencies that are part of the National Interagency Confederation for Biological Research (NICBR).
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Zhao, Ying-Zheng; Tian, Xin-Qiao; Zhang, Ming; Cai, Lu; Ru, Ao; Shen, Xiao-Tong; Jiang, Xi; Jin, Rong-Rong; Zheng, Lei; Hawkins, Kyle; Charkrabarti, Subrata; Li, Xiao-Kun; Lin, Qian; Yu, Wen-Ze; Ge, Shuping; Lu, Cui-Tao; Wong, Ho Lun
2014-07-28
Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality among the diabetic patients and currently there is no effective means to reverse its pathological progress. Basic fibroblast growth factor (bFGF) has shown promise as a molecular therapy for DCM, but its delivery is inefficient and non-specific. In the present study, a therapy combining nanoparticle (NP) carrier and ultrasound-targeted microbubble destruction (UTMD) was reported the first time for bFGF delivery to the heart of diabetic rats. bFGF-loaded NP (bFGF-NP) were prepared with Poloxamer 188-grafted heparin copolymer using water-in-water technique, and the morphology, encapsulation efficiency, and bioactivity of bFGF-NP were studied. The cellular uptake and cytotoxicity of bFGF-NP were evaluated with primary cultures of the left ventricular (LV) cardiomyocytes in vitro. Therapeutic effects of bFGF-NP/UTMD on the heart of DCM rats were studied by measuring LV systolic and diastolic functions, hemodynamic characteristics and indicators of cardiac remodeling including myocardial collagen volume fraction and capillary density. Results demonstrated that bFGF-NP showed good round morphology, efficient bFGF encapsulation and stable bioactivity of bFGF in vitro. bFGF-NP/UTMD combined treatment significantly enhanced the efficiency of bFGF cellular uptake (Pfunctions and tissue morphology in the DCM rats were observed in bFGF-NP/UTMD group. These were not achievable using free bFGF, bFGF-NP or UTMD treatment alone. Our results show that combining a non-viral vector with UTMD technique is an effective strategy to deliver bFGF to the heart, and the resulting growth factor therapy has demonstrated potential to reverse the progress of DCM by restoring the cardiac functions and even the structure of damaged cardiac tissues. Copyright © 2014 Elsevier B.V. All rights reserved.
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WNT7A/β-catenin signaling induces FGF1 and influences sensitivity to niclosamide in ovarian cancer.
King, M L; Lindberg, M E; Stodden, G R; Okuda, H; Ebers, S D; Johnson, A; Montag, A; Lengyel, E; MacLean Ii, J A; Hayashi, K
2015-06-01
We previously characterized the link between WNT7A and the progression of ovarian cancer. Other groups have identified FGF1 as a relevant risk factor in ovarian cancer. Here, we show a linkage between these two signaling pathways that may be exploited to improve treatment and prognosis of patients with ovarian cancer. High expression of WNT7A and FGF1 are correlated in ovarian carcinomas and poor overall patient survival. A chromatin immunoprecipitation assay demonstrated that WNT7A/β-catenin signaling directly regulates FGF1 expression via TCF binding elements in the FGF1-1C promoter locus. In vitro gene manipulation studies revealed that FGF1 is sufficient to drive the tumor-promoting effects of WNT7A. In vivo xenograft studies confirmed that the stable overexpression of WNT7A or FGF1 induced a significant increase in tumor incidence, whereas FGF1 knockdown in WNT7A overexpressing cells caused a significant reduction in tumor size. Niclosamide most efficiently abrogated WNT7A/β-catenin signaling in our model, inhibited β-catenin transcriptional activity and cell viability, and increased cell death. Furthermore, niclosamide decreased cell migration following an increase in E-cadherin subsequent to decreased levels of SLUG. The effects of niclosamide on cell functions were more potent in WNT7A-overexpressing cells. Oral niclosamide inhibited tumor growth and progression in an intraperitoneal xenograft mouse model representative of human ovarian cancer. Collectively, these results indicate that FGF1 is a direct downstream target of WNT7A/β-catenin signaling and this pathway has potential as a therapeutic target in ovarian cancer. Moreover, niclosamide is a promising inhibitor of this pathway and may have clinical relevance.
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Directory of Open Access Journals (Sweden)
Murilo C. A. Britto
2004-01-01
Full Text Available OBJETIVOS: Descrever a prevalência atual (2002 de asma e suas variantes em escolares da cidade do Recife, comparando os dados com o período de 1994-95; analisar a relação entre instrução materna e o surgimento ou o agravamento da asma; e avaliar a acurácia diagnóstica da prevalência anual de sibilância como indicador de asma. MÉTODO: Em um corte transversal, estudou-se, por questionário escrito, uma amostra probabilística de escolares de 13 e 14 anos em Recife, em 1994-95 (n = 3.086 e 2002 (n = 2.774, como parte do projeto ISAAC (International Study of Asthma and Allergies in Childhood. RESULTADOS: Em 1994-95 e 2002, as prevalências foram, respectivamente: cumulativa de asma referida, 21 e 18,2%; cumulativa de sibilância, 39 e 38%; anual de sibilância, 19,7 e 19,4%; anual de tosse equivalente de asma, 31 e 38%; anual de sibilância desencadeada por exercício, 20,6 e 23,8%. A prevalência anual de crises, estratificada em 1 a 3, 4 a 12 e mais de 12 foi: 16,3, 2,7 e 1% em 1994-95 e 15,2, 1,2 e 0,4% em 2002. A prevalência anual de crises que comprometeram o sono foi, respectivamente, de 13 e 10,3%; a prevalência de crises com prejuízo da fala foi de 4,8 e 4,1%. Nível mais elevado de instrução materna associou-se a maior prevalência cumulativa de asma referida, prevalência cumulativa e anual de sibilância. CONCLUSÕES: A prevalência de asma e suas formas graves é elevada em escolares adolescentes do Recife e está associada a maior instrução materna.OBJECTIVES: To describe the prevalence of asthma and asthma variants in schoolchildren from Recife in 2002, and to compare these data with data from 1994-95; to analyze the relationship between maternal schooling and the presence of asthma or worsening asthma; and to evaluate the diagnostic accuracy of the yearly prevalence of wheezing as an asthma indicator. METHODS: Cross-sectional study. A probabilistic sample of 3,086 and 2,774 13- and 14-year-old students answered a
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A Shh-Foxf-Fgf18-Shh Molecular Circuit Regulating Palate Development.
Directory of Open Access Journals (Sweden)
Jingyue Xu
2016-01-01
Full Text Available Cleft palate is among the most common birth defects in humans. Previous studies have shown that Shh signaling plays critical roles in palate development and regulates expression of several members of the forkhead-box (Fox family transcription factors, including Foxf1 and Foxf2, in the facial primordia. Although cleft palate has been reported in mice deficient in Foxf2, whether Foxf2 plays an intrinsic role in and how Foxf2 regulates palate development remain to be elucidated. Using Cre/loxP-mediated tissue-specific gene inactivation in mice, we show that Foxf2 is required in the neural crest-derived palatal mesenchyme for normal palatogenesis. We found that Foxf2 mutant embryos exhibit altered patterns of expression of Shh, Ptch1, and Shox2 in the developing palatal shelves. Through RNA-seq analysis, we identified over 150 genes whose expression was significantly up- or down-regulated in the palatal mesenchyme in Foxf2-/- mutant embryos in comparison with control littermates. Whole mount in situ hybridization analysis revealed that the Foxf2 mutant embryos exhibit strikingly corresponding patterns of ectopic Fgf18 expression in the palatal mesenchyme and concomitant loss of Shh expression in the palatal epithelium in specific subdomains of the palatal shelves that correlate with where Foxf2, but not Foxf1, is expressed during normal palatogenesis. Furthermore, tissue specific inactivation of both Foxf1 and Foxf2 in the early neural crest cells resulted in ectopic activation of Fgf18 expression throughout the palatal mesenchyme and dramatic loss of Shh expression throughout the palatal epithelium. Addition of exogenous Fgf18 protein to cultured palatal explants inhibited Shh expression in the palatal epithelium. Together, these data reveal a novel Shh-Foxf-Fgf18-Shh circuit in the palate development molecular network, in which Foxf1 and Foxf2 regulate palatal shelf growth downstream of Shh signaling, at least in part, by repressing Fgf18
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Czech Academy of Sciences Publication Activity Database
Špolcová, Andrea; Holubová, Martina; Mikulášková, Barbora; Nagelová, Veronika; Štofková, A.; Lacinová, Z.; Jurčovičová, J.; Haluzík, M.; Maletínská, Lenka; Železná, Blanka
2014-01-01
Roč. 63, č. 4 (2014), s. 483-490 ISSN 0862-8408 R&D Projects: GA ČR GAP303/10/1368; GA ČR GAP303/12/0576 Institutional support: RVO:61388963 Keywords : FGF21 * A-ZIP mice * lipodystrophy * insulin resistance * fatty liver * GLUT-1 Subject RIV: CE - Biochemistry Impact factor: 1.293, year: 2014
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Directory of Open Access Journals (Sweden)
Cheng-Liang Kuo
Full Text Available The organizer is one of the earliest structures to be established during vertebrate development and is crucial to subsequent patterning of the embryo. We have previously shown that the SoxB1 transcription factor, Sox3, plays a central role as a transcriptional repressor of zebrafish organizer gene expression. Recent data suggest that Fgf signaling has a positive influence on organizer formation, but its role remains to be fully elucidated. In order to better understand how Fgf signaling fits into the complex regulatory network that determines when and where the organizer forms, the relationship between the positive effects of Fgf signaling and the repressive effects of the SoxB1 factors must be resolved. This study demonstrates that both fgf3 and fgf8 are required for expression of the organizer genes, gsc and chd, and that SoxB1 factors (Sox3, and the zebrafish specific factors, Sox19a and Sox19b can repress the expression of both fgf3 and fgf8. However, we also find that these SoxB1 factors inhibit the expression of gsc and chd independently of their repression of fgf expression. We show that ectopic expression of organizer genes induced solely by the inhibition of SoxB1 function is dependent upon the activation of fgf expression. These data allow us to describe a comprehensive signaling network in which the SoxB1 factors restrict organizer formation by inhibiting Fgf, Nodal and Wnt signaling, as well as independently repressing the targets of that signaling. The organizer therefore forms only where Nodal-induced Fgf signaling overlaps with Wnt signaling and the SoxB1 proteins are absent.
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Directory of Open Access Journals (Sweden)
Verônica Vieira da Costa
2007-08-01
Full Text Available JUSTIFICATIVA E OBJETIVOS: O EEG-BIS foi criado por meio de estudos em pacientes adultos saudáveis e as primeiras publicações em crianças surgiram a partir de 1998. A paralisia cerebral (PC é secundária à lesão estática do encéfalo em desenvolvimento. A necessidade de realização de exames e procedimentos cirúrgicos para correção de deformidades sob anestesia ou sedação é comum nesses pacientes. Torna-se cada vez mais necessária a monitorização do estado de hipnose do paciente anestesiado e pode-se incluir nesse grupo os pacientes com paralisia cerebral. O objetivo desse estudo foi avaliar a eficiência do EEG-BIS nos pacientes com paralisia cerebral (PC em comparação com os pacientes sem doenças neurológicas (sem PC, em estado de vigília. MÉTODO: Foram avaliados dois grupos de pacientes: um com diagnóstico de paralisia cerebral e outro sem doença do sistema nervoso central (SNC. Na véspera da intervenção cirúrgica, na enfermaria, junto aos pacientes despertos era colocado o monitor de EEG-BIS e solicitado que fechassem os olhos. Os valores que apareciam na tela do monitor, em um intervalo de 10 minutos, eram anotados e registrados em ficha padronizada, sendo calculado um valor médio por paciente. RESULTADOS: Foram avaliados 188 pacientes, de ambos os sexos, com idade média de 10, 07 ± 2,9 (PC e 10,21 ± 3,1 (sem PC anos. O grupo PC apresentou EEG-BIS basal de 95,83 ± 5,142 e o grupo sem PC de 96,56 ± 1,941 sem haver diferença estatística significativa entre eles. CONCLUSÕES: Os sinais de EEG são captados normalmente e os valores de EEG-BIS dos pacientes com PC são semelhantes ao dos pacientes sem PC no estado de vigília.JUSTIFICATIVA Y OBJETIVOS: El EEG-BIS fue creado a través de estudios en pacientes adultos saludables y las primeras publicaciones en niños surgieron a partir de 1998. La parálisis cerebral (PC es secundaria a la lesión estática del encéfalo en desarrollo. La necesidad de
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Directory of Open Access Journals (Sweden)
Laura Salanova Villanueva
2016-07-01
Full Text Available Una de las principales causas de morbimortalidad en el paciente con enfermedad renal crónica es la cardiovascular. La inflamación y las alteraciones en el metabolismo óseo mineral son una condición patológica que conlleva aumento del riesgo cardiovascular en la enfermedad renal crónica. Los parámetros bioquímicos clásicos del metabolismo óseo mineral como fósforo, calcio, vitamina D y PTH tienen una implicación muy conocida en el riesgo cardiovascular. Los nuevos marcadores, FGF23 y klotho, también podrían estar implicados en la enfermedad cardiovascular.
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A balance of FGF and BMP signals regulates cell cycle exit and Equarin expression in lens cells
Jarrin, Miguel; Pandit, Tanushree; Gunhaga, Lena
2012-01-01
In embryonic and adult lenses, a balance of cell proliferation, cell cycle exit, and differentiation is necessary to maintain physical function. The molecular mechanisms regulating the transition of proliferating lens epithelial cells to differentiated primary lens fiber cells are poorly characterized. To investigate this question, we used gain- and loss-of-function analyses to modulate fibroblast growth factor (FGF) and/or bone morphogenetic protein (BMP) signals in chick lens/retina explants. Here we show that FGF activity plays a key role for proliferation independent of BMP signals. Moreover, a balance of FGF and BMP signals regulates cell cycle exit and the expression of Ccdc80 (also called Equarin), which is expressed at sites where differentiation of lens fiber cells occurs. BMP activity promotes cell cycle exit and induces Equarin expression in an FGF-dependent manner. In contrast, FGF activity is required but not sufficient to induce cell cycle exit or Equarin expression. Furthermore, our results show that in the absence of BMP activity, lens cells have increased cell cycle length or are arrested in the cell cycle, which leads to decreased cell cycle exit. Taken together, these findings suggest that proliferation, cell cycle exit, and early differentiation of primary lens fiber cells are regulated by counterbalancing BMP and FGF signals. PMID:22718906
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Final Report for DOE Project DE-FC07-99CH11010
Energy Technology Data Exchange (ETDEWEB)
Jed Randall; Robert Kean
2003-10-22
Department of Energy award number DE-FC07-99CH11010, Enhanced Utilization of Corn Based Biomaterials, supported a technology development program sponsored by Cargill Dow LLC from September 30, 1999 through June 30, 2003. The work involved fundamental scientific studies on poly lactic acid (PLA), a new environmentally benign plastic material from renewable resources. DOE funds supported academic research at the Colorado School of Mines and the National Renewable Energy Laboratory (NREL), and industry cost share was directed towards applied research into new product development utilizing the fundamental information generated by the academic partners. Under the arrangement of the grant, the fundamental information is published so that other companies can utilize it in evaluating the applicability of PLA in their own products. The overall project objective is to increase the utilization of PLA, a renewable resource based plastic, currently produced from fermented corn sugar.
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45 CFR 1226.12 - Sponsor employees.
2010-10-01
... 45 Public Welfare 4 2010-10-01 2010-10-01 false Sponsor employees. 1226.12 Section 1226.12 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE PROHIBITIONS ON ELECTORAL AND LOBBYING ACTIVITIES Sponsor Employee Activities § 1226.12 Sponsor employees...
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Coartação de aorta em crianças até um ano: análise de 20 anos de experiência
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Lorier Gabriel
2005-01-01
Full Text Available OBJETIVO: Revisão da experiência com diversas técnicas de correção empregadas, nos últimos 20 anos, em crianças menores de um ano de idade. MÉTODOS: No período de 1978 a 1998, foram operados 148 pacientes (pc consecutivos com coartação de aorta (CoAo com até um ano de idade, com ou sem defeitos intracardíacos associados. A idade apresentou mediana de 50 dias, 92 pc do sexo feminino (62,1%. O peso foi de 4.367?1.897 gramas. O seguimento foi em média de 1.152?1.462 dias. A população foi dividida em 3 grupos: Grupo I, CoAo isolada: 74 pc (50%; Grupo II, CoAo e comunicação interventricular (CIV: 41 pacientes (27,7% e Grupo III, CoAo com malformações complexas: 33 pc (22,3%. RESULTADOS: Mortalidade total foi 43 pc (29%: com menos de 30 dias, foi 53%, p=0,009, OR=4,5, entre 31 e 90 dias, foi 14,7%, p=0,69, e acima de 91 dias, 15%, p=0,004. A probabilidade de sobrevida atuarial de toda a população foi de 67% aos 5 e 10 anos. Trinta e seis pacientes (24,3% recoartaram, dos quais 18 pacientes (50% tinham menos de 30 dias, OR=6,35. A incidência de recoartação foi com a técnica de Waldhausen em 4 pacientes (10% e com a término-terminal clássica em 19 pacientes (26% p=0.03, e a istmoplastia em 6 pacientes (37,5%. A probabilidade de sobrevida atuarial livre de recoartação aos 5 e 10 anos foi de 69% com a técnica de Waldhausen e 63% com a técnica término-terminal clássica. CONCLUSÃO: Pacientes com menos de 30 dias apresentaram risco aumentado de mortalidade e recoartação. A técnica de Waldhausen em pacientes com mais de 30 dias mostrou-se efetiva. A técnica término-terminal clássica mostrou não ser uma boa opção em todas as faixas etárias, sendo imperativo executar variantes técnicas como término-terminal estendida.
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High dose intravenous iron, mineral homeostasis and intact FGF23 in normal and uremic rats
DEFF Research Database (Denmark)
Gravesen, Eva; Hofman-Bang, Jacob; Mace, Maria L.
2013-01-01
High iron load might have a number of toxic effects in the organism. Recently intravenous (iv) iron has been proposed to induce elevation of fibroblast growth factor 23 (FGF23), hypophosphatemia and osteomalacia in iron deficient subjects. High levels of FGF23 are associated with increased...
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Tablet PC interaction with digital micromirror device (DMD)
Refai, Hakki H.; Dahshan, Mostafa H.; Sluss, James J., Jr.
2007-02-01
Digital light processing (DLP) is an innovative display technology that uses an optical switch array, known as a digital micromirror device (DMD), which allows digital control of light. To date, DMDs have been used primarily as high-speed spatial light modulators for projector applications. A tablet PC is a notebook or slate-shaped mobile PC. Its touch screen or digitizing tablet technology allows the user to operate the notebook with a stylus or digital pen instead of using a keyboard or mouse. In this paper, we describe an interface solution that translates any sketch on the tablet PC screen to an identical mirror-copy over the cross-section of the DMD micromirrors such that the image of the sketch can be projected onto a special screen. An algorithm has been created to control each single micromirror of the hundreds of thousands of micromirrors that cover the DMD surface. We demonstrate the successful application of a DMD to a high-speed two-dimensional (2D) scanning environment, acquiring the data from the tablet screen and launching its contents to the projection screen; with very high accuracy up to 13.68 μm x 13.68 μm of mirror pitch.
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International Nuclear Information System (INIS)
2007-01-01
Within its competence for energy research the Federal Ministry of Economics and Technology (BMWi) sponsors research projects on the safety of nuclear power plants currently in operation. The objective of these projects is to provide fundamental knowledge, procedures and methods to contribute to realistic safety assessments of nuclear installations, to the further development of safety technology and to make use of the potential of innovative safety-related approaches. The Gesellschaft fuer Anlagen- und Reaktorsicherheit (GRS) mbH, by order of the BMWi, continuously issues information on the status of such research projects by publishing semi-annual and annual progress reports within the series of GRS-F-Fortschrittsberichte (GRS-F-Progress Reports). Each progress report represents a compilation of individual reports about the objectives, work performed, results achieved, next steps of the work etc. The individual reports are prepared in a standard form by the research organisations themselves as documentation of their progress in work. The progress reports are published by the Research Management Division of GRS. The reports as of the year 2000 are available in the Internet-based information system on results and data of reactor safety research (http://www.grs-fbw.de). The compilation of the reports is classified according to the classification system 'Joint Safety Research Index (JSRI)'. The reports are arranged in sequence of their project numbers. It has to be pointed out that the authors of the reports are responsible for the contents of this compilation. The BMWi does not take any responsibility for the correctness, exactness and completeness of the information nor for the observance of private claims of third parties. (orig.)
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Estilos de vida da população brasileira: resultados da Pesquisa Nacional de Saúde, 2013
Directory of Open Access Journals (Sweden)
Deborah Carvalho Malta
Full Text Available OBJETIVO:descrever os estilos de vida da população brasileira quanto à alimentação, atividade física, consumo de álcool e tabagismo.MÉTODOS:estudo descritivo com dados da Pesquisa Nacional de Saúde 2013, que coletou informações em 64.348 domicílios; foram calculadas prevalências e intervalos de confiança de 95% (IC95% na população ≥18 anos de idade.RESULTADOS:a prevalência do consumo de frutas e hortaliças foi de 37,3% (IC95%: 36,4%- 38,1%, do consumo excessivo de gorduras, 37,2% (IC95%: 36,4%- 38,0%, de refrigerantes, 23,4% (IC95%: 22,7%- 24,1% e de feijão, 71,9% (IC95%: 71,2%- 72,6%; a prática de atividade física no tempo livre foi observada em 22,5% dos adultos (IC95%: 21,8%- 23,1%; a prevalência de tabagismo foi 14,5% (IC95%: 14,0%- 15,0% e o consumo abusivo de álcool, 13,7% (IC95%: 13,1%- 14,2%.CONCLUSÃO:verificou-se elevadas prevalências de fatores de risco para doenças crônicas não transmissíveis em adultos.
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Daverio, M S; Vidal-Rioja, L; Frank, E N; Di Rocco, F
2017-12-01
Llama, the most numerous domestic camelid in Argentina, has good fiber-production ability. Although a few genes related to other productive traits have been characterized, the molecular genetic basis of fiber growth control in camelids is still poorly understood. Fibroblast growth factor 5 (FGF5) is a secreted signaling protein that controls hair growth in humans and other mammals. Mutations in the FGF5 gene have been associated with long-hair phenotypes in several species. Here, we sequenced the llama FGF5 gene, which consists of three exons encoding 813 bp. cDNA analysis from hair follicles revealed the expression of two FGF5 alternative spliced transcripts, in one of which exon 2 is absent. DNA variation analysis showed four polymorphisms in the coding region: a synonymous SNP (c.210A>G), a single base deletion (c.348delA), a 12-bp insertion (c.351_352insCATATAACATAG) and a non-sense mutation (c.499C>T). The deletion was always found together with the insertion forming a haplotype and producing a putative truncated protein of 123 amino acids. The c.499C>T mutation also leads to a premature stop codon at position 168. In both cases, critical functional domains of FGF5, including one heparin binding site, are lost. All animals analyzed were homozygous for one of the deleterious mutations or compound heterozygous for both (i.e. c.348delA, c.351_352insCATATAACATAG/c.499T). Sequencing of guanaco samples showed that the FGF5 gene encodes a full-length 270-amino acid protein. These results suggest that FGF5 is likely functional in short-haired wild species and non-functional in the domestic fiber-producing species, the llama. © 2017 Stichting International Foundation for Animal Genetics.
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Zaritsky, Joshua; Rastogi, Anjay; Fischmann, George; Yan, Jieshi; Kleinman, Kenneth; Chow, Georgina; Gales, Barbara; Salusky, Isidro B; Wesseling-Perry, Katherine
2014-02-01
The utilization of short-term daily hemodialysis has increased over the last few years, but little is known on its effects on the control of serum phosphate and fibroblast growth factor 23 (FGF23) levels. We therefore performed a cross-sectional study to compare FGF23 levels as well as other biochemical variables between 24 patients undergoing short daily hemodialysis using the NxStage System® and 54 patients treated with conventional in-center hemodialysis. FGF23 levels were measured using the second-generation Immutopics® C-terminal assay. Short daily hemodialysis patients were younger than patients on conventional hemodialysis but there were no differences between groups in the duration of end-stage renal disease nor in the number of patients with residual renal function. A greater number of short daily hemodialysis patients received vitamin D sterol therapy than did conventional in-center hemodialysis patients while there were no differences in the use of different phosphate binders and calcimimetic therapy between groups. Overall serum calcium, phosphorus and intact parathyroid hormone levels were similar between groups. While serum phosphorus levels correlated with FGF23 concentrations in each group separately [r=0.522 (P<0.01) and r=0.42 (P<0.01) in short daily and conventional in-center hemodialysis, respectively], FGF23 levels were lower [823 RU/mL (263, 2169)] in the patients receiving short daily hemodialysis than in patients treated with conventional hemodialysis [2521 RU/mL (909, 5556)] (P<0.01 between groups). These findings demonstrate that FGF23 levels are significantly lower in short daily hemodialysis patients and suggest that FGF23 levels may be a more sensitive biomarker of cumulative phosphate burden than single or multiple serum phosphorus determinations in patients treated with hemodialysis.
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Directory of Open Access Journals (Sweden)
João Tomé de Farias Neto
2004-04-01
Full Text Available Conduziu-se este trabalho com o objetivo de estimar os coeficientes de correlação e de repetibilidade envolvendo doze caracteres do fruto de bacurizeiro: comprimento do fruto (CF, diâmetro do fruto (DF, espessura da casca (EC, peso da casca (PC, peso das sementes (PS, número de sementes (NS, volume da cavidade interna (VCI, peso do fruto (PF, peso total de polpa (PTP, porcentagens de casca (%C, sementes (%S e polpa total (%PTP. As estimativas dos coeficientes de repetibilidade das características CF, DF, EC, PC, PS, VCI, PTP, %C e %PTP demonstraram alta regularidade nos indivíduos, e quatro a doze medições são necessárias para obter predições com confiabilidade em torno de 95%. Com exceção do caráter EC, não foram observadas grandes diferenças entre as estimativas dos coeficientes de repetibilidade obtidos pelo método da ANOVA e pelos métodos de análise multivariada. O aumento na precisão em termos de predição do valor real dos indivíduos além de 95% implicará aumentar, sobremaneira, o número de medições, que, por sua vez, pouco acrescentará em termos de precisão, sendo, então, injustificado seu uso. PTP apresentou associações positivas com o DF, VCI e PF.This work had as aim to estimate the repeatability and correlation coefficients involving twelve characters of the bacurizeiro fruit: length of the fruit (CF, diameter of the fruit (DF, thickness of the rind (EC, weight of the rind (PC, weight of the seeds (PS, number of seeds (NS, volume of internal cavity (VCI, weight of the fruit (PF, total weight of pulp (PTP, percentages of rind (%C, seeds (%S and total pulp (%PTP. The estimates of the coefficients of repeatability of characteristics CF, DF, EC, PC, PS, VCI, PTP, %C and %PTP demonstrated high regularity in the individuals and four to twelve measurements are necessary to get predictions with around 95% of reliability. With exception of character EC, had not been observed great differences between the
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International Nuclear Information System (INIS)
1990-08-01
Investigations on the safety of light water reactors (LWR) being performed in the framework of his research program on reactor safety are sponsored by the Bundesminister fuer Forschung und Technologie (BMFT) (Federal Minister for Research and Technology). Objective of this program is to investigate in greater detail the safety margins of nuclear power plants and their systems and the further development of safety technology. Besides the investigations of LWR tasks also projects on the safety of advanced reactors are sponsored by the BMFT. The Gesellschaft fuer Reaktorsicherheit (GRS), (Society for Reactor Safety), by order of the BMFT, informs continuously of the status of such investigations by means of semi-annual and annual publication of progress reports within the series GRS-F-Fortschrittsberichte (GRS-F-Progress Reports). Each progress report represents a compilation of individual reports about objectives, the work performed, the results, the next steps of the work etc. The individual reports are prepared in a standard form by the contractors themselves as a documentation of their progress in work and published by the Forschungsbetreuung at the GRS, (FB) (Research Coordination Department), within the framework of general informations of progress in reactor safety research. The individual reports are classified according to the same classification system as applied in the nuclear index of the CEC (Commission of the European Communities) and the OECD (Organization for Economic Cooperation and Development). The reports are arranged in sequence of their project numbers. (orig./HP)
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Salivary Gland Dysplasia in Fgf10 Heterozygous Mice: A New Mouse Model of Xerostomia
May, A.J.; Chatzeli, L.; Proctor, G.B.; Tucker, A.S.
2017-01-01
Xerostomia, or chronic dry mouth, is a common syndrome caused by a lack of saliva that can lead to severe eating difficulties, dental caries and oral candida infections. The prevalence of xerostomia increases with age and affects approximately 30% of people aged 65 or older. Given the large numbers of sufferers, and the potential increase in incidence given our aging population, it is important to understand the complex mechanisms that drive hyposalivation and the consequences for the dentition and oral mucosa. From this study we propose the Fgf10 +/- mouse as a model to investigate xerostomia. By following embryonic salivary gland development, in vivo and in vitro, we show that a reduction in Fgf10 causes a delay in branching of salivary glands. This leads to hypoplasia of the glands, a phenotype that is not rescued postnatally or by adulthood in both male and female Fgf10 +/- mice. Histological analysis of the glands showed no obvious defect in cellular differentiation or acini/ductal arrangements, however there was a significant reduction in their size and weight. Analysis of saliva secretion showed that hypoplasia of the glands led to a significant reduction in saliva production in Fgf10 +/- adults, giving rise to a reduced saliva pellicle in the oral cavity of these mice. Mature mice were shown to drink more and in many cases had severe tooth wear. The Fgf10 +/- mouse is therefore a useful model to explore the causes and effects of xerostomia. PMID:26321752
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Salivary Gland Dysplasia in Fgf10 Heterozygous Mice: A New Mouse Model of Xerostomia.
May, A J; Chatzeli, L; Proctor, G B; Tucker, A S
2015-01-01
Xerostomia, or chronic dry mouth, is a common syndrome caused by a lack of saliva that can lead to severe eating difficulties, dental caries and oral candida infections. The prevalence of xerostomia increases with age and affects approximately 30% of people aged 65 or older. Given the large numbers of sufferers, and the potential increase in incidence given our aging population, it is important to understand the complex mechanisms that drive hyposalivation and the consequences for the dentition and oral mucosa. From this study we propose the Fgf10 +/- mouse as a model to investigate xerostomia. By following embryonic salivary gland development, in vivo and in vitro, we show that a reduction in Fgf10 causes a delay in branching of salivary glands. This leads to hypoplasia of the glands, a phenotype that is not rescued postnatally or by adulthood in both male and female Fgf10 +/- mice. Histological analysis of the glands showed no obvious defect in cellular differentiation or acini/ductal arrangements, however there was a significant reduction in their size and weight. Analysis of saliva secretion showed that hypoplasia of the glands led to a significant reduction in saliva production in Fgf10 +/- adults, giving rise to a reduced saliva pellicle in the oral cavity of these mice. Mature mice were shown to drink more and in many cases had severe tooth wear. The Fgf10 +/- mouse is therefore a useful model to explore the causes and effects of xerostomia.
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2011-02-01
...;Prices of new books are listed in the first FEDERAL REGISTER issue of each #0;week. #0; #0; #0; #0;#0..., Fairchild Heli Porter PC-6 airplanes, or Fairchild-Hiller Corporation PC-6 airplanes. Discussion Section... [[Page 5469
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Directory of Open Access Journals (Sweden)
Bhavna N. Desai
2017-11-01
Conclusions: Acute or binge ethanol consumption significantly increases circulating FGF21 levels in both humans and mice. However, FGF21 does not play a role in acute ethanol clearance. In contrast, chronic ethanol consumption in the absence of FGF21 is associated with significant liver pathology alone or in combination with excess mortality, depending on the type of diet consumed with ethanol. This suggests that FGF21 protects against long term ethanol induced hepatic damage and may attenuate progression of alcoholic liver disease. Further study is required to assess the therapeutic potential of FGF21 in the treatment of alcoholic liver disease.
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Directory of Open Access Journals (Sweden)
Oliver Puk
Full Text Available Fibroblast growth factor (Fgf signalling plays a crucial role in many developmental processes. Among the Fgf pathway ligands, Fgf9 (UniProt: P54130 has been demonstrated to participate in maturation of various organs and tissues including skeleton, testes, lung, heart, and eye. Here we establish a novel Fgf9 allele, discovered in a dominant N-ethyl-N-nitrosourea (ENU screen for eye-size abnormalities using the optical low coherence interferometry technique. The underlying mouse mutant line Aca12 was originally identified because of its significantly reduced lens thickness. Linkage studies located Aca12 to chromosome 14 within a 3.6 Mb spanning interval containing the positional candidate genes Fgf9 (MGI: 104723, Gja3 (MGI: 95714, and Ift88 (MGI: 98715. While no sequence differences were found in Gja3 and Ift88, we identified an A→G missense mutation at cDNA position 770 of the Fgf9 gene leading to an Y162C amino acid exchange. In contrast to previously described Fgf9 mutants, Fgf9(Y162C carriers were fully viable and did not reveal reduced body-size, male-to-female sexual reversal or skeletal malformations. The histological analysis of the retina as well as its basic functional characterization by electroretinography (ERG did not show any abnormality. However, the analysis of head-tracking response of the Fgf9(Y162C mutants in a virtual drum indicated a gene-dosage dependent vision loss of almost 50%. The smaller lenses in Fgf9(Y162C suggested a role of Fgf9 during lens development. Histological investigations showed that lens growth retardation starts during embryogenesis and continues after birth. Young Fgf9(Y162C lenses remained transparent but developed age-related cataracts. Taken together, Fgf9(Y162C is a novel neomorphic allele that initiates microphakia and reduced vision without effects on organs and tissues outside the eye. Our data point to a role of Fgf9 signalling in primary and secondary lens fiber cell growth. The results
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95 años recorridos hacia el centenario
Directory of Open Access Journals (Sweden)
Renata Virginia González Consuegra
2015-09-01
Full Text Available El éxito de las instituciones está en comprender la importancia del cambio permanente en busca de transformarse y responder a los nuevos y diversos desafíos. Así lo han entendido quienes por espacio de 95 años han integrado el cuerpo directivo y de profesores de la Facultad de Enfermería de la Universidad Nacional de Colombia. Han pasado nueve décadas y un lustro desde cuando el Diario Oficial del Congreso de Colombia promulgara la Ley 39 del 22 de octubre de 1 920, firmada por el Presidente de la República de Colombia Marco Fidel Suárez, estableciendo la enseñanza de Comadronas y Enfermeras, para cuyos gastos se asignó la suma de hasta $3 000 anuales. De esta manera, se hace realidad su ejecución desde el 14 de abril de 1 925 en el Hospital San Juan de Dios. Luego, la enseñanza se traslada al Hospital San José de Bogotá, en virtud de reorganizar la Escuela Superior de Enfermeras decretada en 1937 por el Consejo Directivo de la Universidad Nacional de Colombia mediante Acuerdo 004. Con esto se obtienen mayores espacios para impartir conocimientos teóricos complementados con actividades académicas prácticas, bajo la dependencia directa de la Universidad Nacional de Colombia, cuyo plan de estudio consistía en tres años, una tesis y un examen de grado.
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Characterization of RNA interference in rat PC12 cells
DEFF Research Database (Denmark)
Thonberg, Håkan; Schéele, Camilla C; Dahlgren, Cecilia
2004-01-01
strand of the siRNA guides a multi-protein complex, RNA-induced silencing complex (RISC), to cleave target mRNA. Although the exact function and composition of RISC is still unclear, it has been shown to include several proteins of the Argonaute protein family. Here we report of a robust system...... of the rat Golgi-ER protein 95 kDa (GERp95), an Argonaute family protein, by siRNA methodology. After GERp95-ablation, sequential knockdown of NPY by siRNA was shown to be impaired. Thus, we report that the GERp95 protein is functionally required for RNAi targeting NPY in rat PC12 cells....
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SPONSORING, BRAND VALUE AND SOCIAL MEDIA
Directory of Open Access Journals (Sweden)
Alexander Zauner
2012-10-01
Full Text Available The increasing involvement of individuals in social media over the past decade has enabled firms to pursue new avenues in communication and sponsoring activities. Besides general research on either social media or sponsoring, questions regarding the consequences of a joint activity (sponsoring activities in social media remain unexplored. Hence, the present study analyses whether the perceived image of the brand and the celebrity endorser credibility of a top sports team influence the perceived brand value of the sponsoring firm in a social media setting. Moreover, these effects are compared between existing customers and non-customers of the sponsoring firm. Interestingly, perceived celebrity endorser credibility plays no role in forming brand value perceptions in the case of the existing customers. Implications for marketing theory and practice are derived.
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EFECTO DE LA ENDOGAMIA SOBRE PARÁMETROS PRODUCTIVOS EN VACAS HOLSTEIN Y JERSEY DE COSTA RICA
Directory of Open Access Journals (Sweden)
Judyana Aguirre-Valverde
2013-01-01
Full Text Available Se realizó un estudio longitudinal retrospectivo en 208 148 registros de vacas Holstein y Jersey de 545 hatos lecheros especializados presentes en la Base Nacional de Datos VAMPP Bovino, del Centro Regional de Informática para la Producción Animal Sostenible (CRIPAS, de la Escuela de Medicina Veterinaria, Universidad Nacional (EMV-UNA, período 1995-2010. Se analizó el efecto de la endogamia sobre la producción corregida a 305 días (PC305d y la vida productiva -calculada según la fórmula USDA--, con regresión lineal múltiple, mediante un modelo mixto. Se usó como punto de corte, un valor de coeficiente de endogamia (F de ≥6,25% para valores altos. Además, se estimó la posibilidad de que una vaca con F≥6,25% presente parámetros productivos bajos, mediante regresión logística no condicional. El análisis de supervivencia, mediante la distribución de Weibull, determinó el efecto de endogamia sobre la vida productiva. Se encontró un 17,9% de animales con endogamia, siendo la raza Holstein la de más animales consanguíneos, aunque la Jersey fue la que tuvo, en promedio, los niveles más elevados. Las vacas con baja endogamia produjeron +140,4 kg PC305d en relación con las que tienen niveles elevados (p<0,01. Las vacas con alta endogamia tuvieron más riesgo de PC305d <5000 kg (Jersey y <6500 kg (Holstein que las de baja endogamia (OR=1,3; IC95%: 1,2-1,4. Se observó, para las razas Holstein y Jersey, +10,3 meses y +19,3 meses de vida productiva (USDA para los animales con F bajo. Se concluye que existe un efecto negativo de la consanguinidad elevada sobre la vida productiva (USDA y sobre la PC305d de las vacas Holstein y Jersey en fincas lecheras de Costa Rica.
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IGF-II is up-regulated and myofibres are hypertrophied in regenerating soleus of mice lacking FGF6
International Nuclear Information System (INIS)
Armand, Anne-Sophie; Lecolle, Sylvie; Launay, Thierry; Pariset, Claude; Fiore, Frederic; Della Gaspera, Bruno; Birnbaum, Daniel; Chanoine, Christophe; Charbonnier, Frederic
2004-01-01
Important functions in myogenesis have been proposed for FGF6, a member of the fibroblast growth factor family accumulating almost exclusively in the myogenic lineage. However, the use of FGF6(-/-) mutant mice gave contradictory results and the role of FGF6 during myogenesis remains largely unclear. Using FGF6(-/-) mice, we first analysed the morphology of the regenerated soleus following cardiotoxin injection and showed hypertrophied myofibres in soleus of the mutant mice as compared to wild-type mice. Secondly, to examine the function of the IGF family in the hypertrophy process, we used semiquantitative and real-time RT-PCR assays and Western blots to monitor the expression of the insulin-like growth factors (IGF-I and IGF-II), their receptors [type I IGF receptor (IGF1R) and IGF-II receptor (IGF2R)], and of a binding protein IGFBP-5 in regenerating soleus muscles of FGF6(-/-) knockout mice vs. wild-type mice. In the mutant, both IGF-II and IGF2R, but not IGF-I and IGF1R, were strongly up-regulated, whereas IGFBP5 was down-regulated, strongly suggesting that, in the absence of FGF6, the mechanisms leading to myofibre hypertrophy were mediated specifically by an IGF-II/IGF2R signalling pathway distinct from the classic mechanism involving IGF-I and IGF1R previously described for skeletal muscle hypertrophy. The potential regulating role of IGFBP5 on IGF-II expression is also discussed. This report shows for the first time a specific role for FGF6 in the regulation of myofibre size during a process of in vivo myogenesis
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Directory of Open Access Journals (Sweden)
Jiafei Xi
Full Text Available In guiding hES cell technology toward the clinic, one key issue to be addressed is to culture and maintain hES cells much more safely and economically in large scale. In order to avoid using mouse embryonic fibroblasts (MEFs we isolated human fetal liver stromal cells (hFLSCs from 14 weeks human fetal liver as new human feeder cells. hFLSCs feeders could maintain hES cells for 15 passages (about 100 days. Basic fibroblast growth factor (bFGF is known to play an important role in promoting self-renewal of human embryonic stem (hES cells. So, we established transgenic hFLSCs that stably express bFGF by lentiviral vectors. These transgenic human feeder cells--bFGF-hFLSCs maintained the properties of H9 hES cells without supplementing with any exogenous growth factors. H9 hES cells culturing under these conditions maintained all hES cell features after prolonged culture, including the developmental potential to differentiate into representative tissues of all three embryonic germ layers, unlimited and undifferentiated proliferative ability, and maintenance of normal karyotype. Our results demonstrated that bFGF-hFLSCs feeder cells were central to establishing the signaling network among bFGF, insulin-like growth factor 2 (IGF-2, and transforming growth factor β (TGF-β, thereby providing the framework in which hES cells were instructed to self-renew or to differentiate. We also found that the conditioned medium of bFGF-hFLSCs could maintain the H9 hES cells under feeder-free conditions without supplementing with bFGF. Taken together, bFGF-hFLSCs had great potential as feeders for maintaining pluripotent hES cell lines more safely and economically.
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DEFF Research Database (Denmark)
Søberg, Susanna; Andersen, Emilie S; Dalgaard, Niels B
2018-01-01
. KLB encodes β-klotho, co-receptor for the liver-derived hormone fibroblast growth factor 21 (FGF21). In mice, FGF21 reduces alcohol intake, and human Fgf21 variants are enriched among heavy drinkers. Thus, the liver may limit alcohol consumption by secreting FGF21. However, whether full-length, active...... plasma FGF21 (FGF21 (1-181)) levels in humans increase acutely or sub-chronically in response to alcohol ingestion is uncertain. METHODS: We recruited 10 healthy, fasted male subjects to receive an oral water or alcohol bolus with concurrent blood sampling for FGF21 (1-181) measurement in plasma...... correlated fasting FGF21 (1-181) levels in 49 healthy, non-alcoholic subjects of mixed sex with self-reports of alcohol-related behaviors, emotional responses, and problems. Finally, we characterized the effect of recombinant human FGF21 injection on ad libitum alcohol intake in mice. RESULTS: We show...
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Studsvik`s fuel R and D projects
Energy Technology Data Exchange (ETDEWEB)
Grounes, M [Studsvik Nuclearr AB, Nykoping (Sweden)
1997-08-01
The report reviews some recently performed, ongoing and planned fuel R and D projects, executed by Studsvik Nuclear AB, a subsidiary of Studsvik AB. Data from these projects are used as experimental support for fuel modelling at high burnup. Much of Studsvik Nuclear`s R and D work has been concentrated on fuel testing, which can be made in the R2 test reactor with high precision under realistic water reactor conditions. This type of work started in the early 1960s. The fuel testing projects executed at Studsvik have been organized under three different types of sponsorship: International (multilateral) fuel projects: jointly sponsored internationally on a world-wide basis, with project information remaining restricted to the project participants throughout the project`s duration and for some pre-determined time after project completion; Bilateral fuel projects: sponsored by one single organization, or a few co-operating organizations, with project information remaining restricted to the sponsor, sometimes published later; in-house R and D work: sponsored by Studsvik Nuclear. The fuel testing activities can be divided into a number of well-defined steps as follows: Base irradiation, performed in a power reactor, or in Studsvik`s R2 test reactor; power ramping and/or other in-pile measurements, performed in Studsvik`s R2 test reactor. Non-destructive testing between different phases of an experiment, performed in Studsvik`s R2 reactor pool, or in Studsvik`s Hot Cell Laboratory; destructive post-irradiation examinations, performed in Studsvik`s Hot Cell Laboratory, or in the sponsor`s hot cell laboratory. 47 refs, 2 tabs.
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Alcoholic fatty liver is enhanced in CYP2A5 knockout mice: The role of the PPARα-FGF21 axis
International Nuclear Information System (INIS)
Chen, Xue; Ward, Stephen C.; Cederbaum, Arthur I.; Xiong, Huabao; Lu, Yongke
2017-01-01
Background & aims: Cytochrome P450 2A5 (CYP2A5) is induced by ethanol, and the ethanol induction of CYP2A5 is regulated by nuclear factor-erythroid 2-related factor 2 (NRF2). Cyp2a5 knockout (Cyp2a5 −/− ) mice develop more severe alcoholic fatty liver than Cyp2a5 +/+ mice. Fibroblast growth factor 21 (FGF21), a PPARα-regulated liver hormone, is involved in hepatic lipid metabolism. Alcoholic and non-alcoholic fatty liver are enhanced in Pparα knockout (Pparα −/− ) mice. This study investigates the relationship between the PPARα-FGF21 axis and the enhanced alcoholic fatty liver in Cyp2a5 −/− mice. Methods: Mice were fed the Lieber-Decarli ethanol diet to induce alcoholic fatty liver. Results: More severe alcoholic fatty liver disease was developed in Cyp2a5 −/− mice than in Cyp2a5 +/+ mice. Basal FGF21 levels were higher in Cyp2a5 −/− mice than in Cyp2a5 +/+ mice, but ethanol did not further increase the elevated FGF21 levels in Cyp2a5 −/− mice while FGF21 was induced by ethanol in Cyp2a5 +/+ mice. Basal levels of serum FGF21 were lower in Pparα −/− mice than in Pparα +/+ mice; ethanol induced FGF21 in Pparα +/+ mice but not in Pparα −/− mice, whereas ethanol induced hypertriglyceridemia in Pparα −/− mice but not in Pparα +/+ mice. Administration of recombinant FGF21 normalized serum FGF21 and triglyceride in Pparα −/− mice. Alcoholic fatty liver was enhanced in liver-specific Fgf21 knockout mice. Pparα and Cyp2a5 double knockout (Pparα −/− /Cyp2a5 −/− ) mice developed more severe alcoholic fatty liver than Pparα +/+ /Cyp2a5 −/− mice. Conclusions: These results suggest that CYP2A5 protects against the development of alcoholic fatty liver disease, and the PPARα-FGF21 axis contributes to the protective effects of CYP2A5 on alcoholic fatty liver disease.
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Propuesta de integración de soluciones empresariales VoIP con software libre
Barba Vera, Ruth Genoveva
2012-01-01
Se estudió voip en cisco y elastix para integrarlas y compartir servicios, a través de la troncal sip. Con método experimental, en ambiente de pruebas con tres escenarios, se instaló y configuró Cme 3.3 en router 2811 y elastix 2.2 en pc. Se realizaron llamadas a lo interno de las centrales telefónicas Call Manager Express ó Elastix comprobando la interoperabilidad de las mismas demostrándose que existe una comunicación full dúplex entre tecnologías. Se utilizó equipos cisco: un router 2811,...
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Directory of Open Access Journals (Sweden)
C.A. Rezende
2014-04-01
Full Text Available Em galos de matriz pesada, o peso dos testículos se associa positivamente com a produção diária de espermatozoides e com a fertilidade. Contudo, os testículos de aves se localizam na cavidade abdominal, não sendo acessíveis para exame andrológico como os testículos de mamíferos. A avaliação reprodutiva de galos de matriz pesada é subjetiva e se baseia em características como peso corporal (PC, qualidade de pés e pernas e morfologia de cloaca e crista. Estudos que validem o potencial de associação dessas características fenotípicas com parâmetros da morfometria testicular são raros, principalmente quando se consideram galos de matriz pesada manejados em lotes comerciais. Escores de cloaca e de crista e parâmetros da morfometria testicular foram avaliados em galos Cobb 500 Slow adultos das categorias de PC leve (<4,300kg, médio (entre 4,300 e 5,250kg e pesado (≥5,250kg. O coeficiente de variação para PC foi de 12%. Os galos da categoria de PC pesado apresentaram testículos mais pesados e maiores escores de cloaca e de crista do que os galos da categoria de PC leve. Não houve diferença estatística entre as categorias de PC, considerando-se índice gonadossomático, porcentagens de túbulo seminífero e de tecido intersticial, diâmetro de túbulo seminífero e altura de epitélio seminífero. Correlação positiva, moderada e significativa foi observada entre peso de testículo e características de PC, escores de cloaca e de crista, diâmetro de túbulo seminífero e altura de epitélio seminífero. Um dos seis galos da categoria de PC leve avaliados quanto à histologia de testículo apresentou atrofia testicular. Em galos Cobb 500 Slow, conclui-se que o PC influencia o peso e a qualidade histológica de testículos e que os escores de cloaca e de crista podem ser utilizados com potencial moderado de predição para identificar galos com baixo peso de testículos.
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Directory of Open Access Journals (Sweden)
Sung-Ho Huh
2012-01-01
Full Text Available A large proportion of age-related hearing loss is caused by loss or damage to outer hair cells in the organ of Corti. The organ of Corti is the mechanosensory transducing apparatus in the inner ear and is composed of inner hair cells, outer hair cells, and highly specialized supporting cells. The mechanisms that regulate differentiation of inner and outer hair cells are not known. Here we report that fibroblast growth factor 20 (FGF20 is required for differentiation of cells in the lateral cochlear compartment (outer hair and supporting cells within the organ of Corti during a specific developmental time. In the absence of FGF20, mice are deaf and lateral compartment cells remain undifferentiated, postmitotic, and unresponsive to Notch-dependent lateral inhibition. These studies identify developmentally distinct medial (inner hair and supporting cells and lateral compartments in the developing organ of Corti. The viability and hearing loss in Fgf20 knockout mice suggest that FGF20 may also be a deafness-associated gene in humans.
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Directory of Open Access Journals (Sweden)
Guo-Yin Zheng
2012-01-01
Full Text Available The root of Actinidia valvata dunn has been widely used in the treatment of hepatocellular carcinoma (HCC, proved to be beneficial for a longer and better life in China. In present work, total saponin from root of Actinidia valvata Dunn (TSAVD was extracted, and its effects on hepatoma H22-based mouse in vivo were observed. Primarily transplanted hypodermal hepatoma H22-based mice were used to observe TSAVD effect on tumor growth. The microvessel density (MVD, vascular endothelial growth factor (VEGF, basic fibroblast growth factor (bFGF are characterized factors of angiogenesis, which were compared between TSAVD-treated and control groups. Antimetastasis effect on experimental pulmonary metastasis hepatoma mice was also observed in the study. The results demonstrated that TSAVD can effectively inhibit HCC growth and metastasis in vivo, inhibit the formation of microvessel, downregulate expressions of VEGF and bFGF, and retrain angiogenesis of hepatoma 22 which could be one of the reasons.
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Rapport de frais de 2017-2018 pour Barbara Trenholm | CRDI ...
International Development Research Centre (IDRC) Digital Library (Canada)
Total des frais de déplacement : CAD$13,405.22. Réunion du Conseil des gouverneurs. 19 novembre 2017 au 22 novembre 2017. CAD$1,612.76. Constatation de l'impact de la recherche en Afrique de l'Est. 2 juillet 2017 au 12 juillet 2017. CAD$10,676.95. Réunion du Conseil des gouverneurs. 18 juin 2017 au 21 juin ...
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Energy Technology Data Exchange (ETDEWEB)
Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp
2015-08-07
The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.
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International Nuclear Information System (INIS)
Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki
2015-01-01
The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture
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João M. Pinto
2017-01-01
Project finance is the process of financing a specific economic unit that the sponsors create, in which creditors share much of the venture’s business risk and funding is obtained strictly for the project itself. Project finance creates value by reducing the costs of funding, maintaining the sponsors financial flexibility, increasing the leverage ratios, avoiding contamination risk, reducing corporate taxes, improving risk management, and reducing the costs associated with market ...
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Strategic management of government-sponsored R&D portfolios
Barry Bozeman; Juan Rogers
2001-01-01
Although strategic management of R&D portfolios is common practice in private sector R&D, government R&D management tends to be more discrete and ad hoc, focusing on generating maximum output from individual projects. Often, there is no clear notion of the desired public sector output. Whereas private sector R&D evaluation is generally straightforward, with the function of R&D being measured in terms of a company's internal return on investment, the benefits of public-sponsored R&D tend to be...
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Directory of Open Access Journals (Sweden)
Timothy M. Frayling
2018-04-01
Full Text Available Summary: Fibroblast growth factor 21 (FGF21 is a hormone that has insulin-sensitizing properties. Some trials of FGF21 analogs show weight loss and lipid-lowering effects. Recent studies have shown that a common allele in the FGF21 gene alters the balance of macronutrients consumed, but there was little evidence of an effect on metabolic traits. We studied a common FGF21 allele (A:rs838133 in 451,099 people from the UK Biobank study, aiming to use the human allele to inform potential adverse and beneficial effects of targeting FGF21. We replicated the association between the A allele and higher percentage carbohydrate intake. We then showed that this allele is more strongly associated with higher blood pressure and waist-hip ratio, despite an association with lower total body-fat percentage, than it is with BMI or type 2 diabetes. These human phenotypes of variation in the FGF21 gene will inform research into FGF21’s mechanisms and therapeutic potential. : Drugs targeting the hormone FGF21 may have beneficial health effects. Variations in human DNA in the FGF21 gene provide an indication of what those effects may be. Here, we show that variation in the FGF21 gene is associated with higher blood pressure and altered body shape, despite lower total body-fat percentage. Keywords: FGF21, BMI, waist-hip ratio, blood pressure, body fat, allele, genetic variant, UK Biobank
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Sagomonyants, Karen; Mina, Mina
2014-08-01
Odontoblast differentiation during physiological and reparative dentinogenesis is dependent upon multiple signaling molecules, including fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs) and Wingless/Integrated (Wnt) ligands. Recent studies in our laboratory showed that continuous exposure of primary dental pulp cultures to FGF2 exerted biphasic effects on the expression of markers of dentinogenesis. In the present study, we examined the possible involvement of the BMP and Wnt signaling pathways in mediating the effects of FGF2 on dental pulp cells. Our results showed that stimulatory effects of FGF2 on dentinogenesis during the proliferation phase of growth were associated with increased expression of the components of the BMP (Bmp2, Dlx5, Msx2, Osx) and Wnt (Wnt10a, Wisp2) pathways, and decreased expression of an inhibitor of the Wnt signaling, Nkd2. Further addition of FGF2 during the differentiation/mineralization phase of growth resulted in decreased expression of components of the BMP signaling (Bmp2, Runx2, Osx) and increased expression of inhibitors of the Wnt signaling (Nkd2, Dkk3). This suggests that both BMP and Wnt pathways may be involved in mediating the effects of FGF2 on dental pulp cells.
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Directory of Open Access Journals (Sweden)
Jun Anzai
Full Text Available The long-term stability and qualitative characteristics of periodontium regenerated by FGF-2 treatment were compared with normal physiological healing tissue controls in a Beagle dog 2-wall periodontal defect model 13 months after treatment by assessing tissue histology and three-dimensional microstructure using micro-computed tomography (μCT. After FGF-2 (0.3% or vehicle treatment at the defect sites, serial changes in the bone mineral content (BMC were observed using periodic X-ray imaging. Tissues were harvested at 13 months, evaluated histomorphometrically, and the cortical bone volume and trabecular bone structure of the newly formed bone were analyzed using μCT. FGF-2 significantly increased the BMC of the defect area at 2 months compared with that of the control group, and this difference was unchanged through 13 months. The cortical bone volume was significantly increased by FGF-2, but there was no difference between the groups in trabecular bone structure. Bone maturation was occurring in both groups because of the lower cortical volume and denser trabecular bone than what is found in intact bone. FGF-2 also increased the area of newly formed bone as assessed histomorphometrically, but the ratios of trabecular bone in the defect area were similar between the control and FGF-2 groups. These results suggest that FGF-2 stimulates neogenesis of alveolar bone that is of similar quality to that of the control group. The lengths of the regenerated periodontal ligament and cementum, measured as the distance from the defect bottom to the apical end of the gingival epithelium, and height and area of the newly formed bone in the FGF-2 group were larger than those in the control group. The present study demonstrated that, within the limitation of artificial periodontal defect model, the periodontal tissue regenerated by FGF-2 was maintained for 13 months after treatment and was qualitatively equivalent to that generated through the physiological
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VIDEO-PC, SVGA Routines for FORTRAN on PC
International Nuclear Information System (INIS)
1994-01-01
1 - Description of program or function: These primitives are the lowest level routines needed to perform super VGA graphics on a PC. A sample main program is included that exercises the primitives. Both Lahey and Microsoft FORTRAN's have graphics libraries. However, the libraries do not support 256 color graphics at resolutions greater than 320x200. The primitives bypass these libraries while still conforming to standard usage of BIOS. The supported graphics modes depend upon the PC graphics card and its memory. Super VGA resolutions of 640x480 and 800x600 have been tested on an ATI VGA Wonder card with 512 K memory and on several 80486 PC's (unknown manufacturers) at retail stores. 2 - Method of solution: Both Lahey and Microsoft primitives depend upon sending the correct parameters to the PC BIOS (basic input output system) as discussed in the references. 3 - Restrictions on the complexity of the problem: The primitives were developed for 256 color VGA applications. It is known, for instance, that some CGA and 16 color VGA video modes will not operate correctly using these primitives. Potential users should try the test program on their PC/video card combination to determine applicability
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Energy Technology Data Exchange (ETDEWEB)
Schaller, Bernard
1972-06-26
The mechanical behavior of Ti 6 pc Al 6 pc V Sn alloy during dynamic testing has been investigated versus hydrogen and oxygen content. The hydrogen susceptibility depends only slightly on its microstructure, acicular or equi-axed: it depends much more on conditions of hydrogen contamination and on the thermal history afterward. When the alloy has been stabilized by annealing in {alpha} - {beta} and provided hydrogen absorption does not induce phase transformations, hydrogen sensitivity is relatively low: brittleness occurs suddenly but at a high concentration threshold (2000 ppm H), which coincides with hydrogen saturation of {beta} phase. When the alloy includes unstabilized phases, its response to hydrogen changes whether it has been finally annealed or not, in the 300 - 500 C temperature area, prone to {omega} phase formation. In the absence of such an annealing, a reduction in ductility only occurs at high concentrations (> 1500 ppm H). In the other and, after annealing at 400 C, alloy hardening and a ductility decrease start even at the lowest hydrogen amounts: then hydrogen susceptibility is very high. Low oxygen concentration (up to 2000 ppm) do not sensibly affect the good hydrogen tolerance of this alloy. Beyond 2500 ppm, oxygen, while improving tensile strength, yet severely decreases ductility. [French] Le comportement mecanique de l'alliage TA6-V6-E2 lors d'un essai dynamique a ete etudie en fonction de la teneur en hydrogene et en oxygene. La sensibilite vis-a-vis de l'hydrogene ne depend que tres faiblement de sa structure migrographique, aciculaire ou equiaxe; elle depend bien plus des conditions de contamination par l'hydrogene et de son histoire thermique apres contamination. Lorsque l'alliage a ete stabilise par un recuit dans le domaine biphase, et a condition que l'absorption d'hydrogene n'entraine pas de modification structurale, la sensibilite vis-a-vis de l'hydrogene est relativement faible: la fragilite apparait brutalement mais pour un
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Directory of Open Access Journals (Sweden)
Jaime Vásquez Gómez
2017-11-01
Full Text Available La predicción del consumo máximo de oxígeno (VO2máx se ha realizado en función de la frecuencia cardíaca (FC en el ejercicio submáximo, desarrollándose múltiples ecuaciones para estimarlo a través de pruebas de intensidad submáxima en diferentes ergómetros. El objetivo fue elaborar ecuaciones para estimar el VO2máx a partir de la FC de recuperación (FCr obtenida en la prueba de caminata de seis minutos (PC6M en estudiantes de Educación Física (EEF de una universidad de la ciudad de Concepción, en Chile, y en estudiantes del Grado en Ciencias de la Actividad Física (EGCAF de un instituto de la ciudad de Barcelona, en Cataluña.La investigación consistió en cuatro estudios con un enfoque cuantitativo, con diseño no experimental y de corte transversal, de alcance descriptivo y correlacional, con una muestra no probabilística. En el primer estudio se aplicó el cuestionario PAR-Q, la PC6M y Course Navette (CN en 127 EEF de 21 años; en el segundo se aplicaron las mismas pruebas tipo test-retest en tres días distintos, añadiendo un consentimiento informado en una muestra de 17 EEF de 22 años. En el tercer estudio, además de las pruebas mencionadas, se aplicó el test de Bruce en tapiz en una segunda sesión con medición directa del VO2máx en 20 EEF de 22 años, quienes dieron su consentimiento por escrito. En la cuarta investigación se trabajó con 28 EGCAF de 21 años los que también firmaron un consentimiento informado para realizar la PC6M y CN, en esta última se midió directamente el VO2máx. Las variables de interés fueron la FCr en la PC6M y el VO2máx en CN y en Bruce. En el análisis se emplearon pruebas de normalidad, anova y correlación (p < 0.05 con el programa SPSS versión 19.En la primera investigación se encontró una correlación de rho = –0.44 (p<0.01 entre la FCr (PC6M y el VO2máx (CN. En el segundo estudio no hubo diferencias significativas entre la medición uno, dos y tres en la
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Directory of Open Access Journals (Sweden)
MT Icart Isern
2006-09-01
Full Text Available Introducción: conocer la prevalencia de algunos trastornos menores de salud (TMS en una muestra de estudiantes de la Universidad de Barcelona (2004-05. Material y métodos: El estudio se realizó en las facultades de Ciencias Económicas, Farmacia, Medicina, Psicología y Químicas y Escuela de Enfermería de la Universidad de Barcelona. Se empleó un diseño observacional, descriptivo y transversal mediante un cuestionario mixto administrada a 600 estudiantes durante el mes de diciembre de 2004. Las variables estudiadas corresponden a los siguientes TMS: insomnio, estreñimiento, cefalea, dolor osteomuscular, tics nerviosos, onicofagia y tricotilomania. Resultados: El sexo femenino representa el 64% de la muestra; la media de edad de los encuestados es de 22,7 (DE: 3,27; IC 95%: 22,43-22,96. Las mujeres acumulan el 67,79% de los 1.245 TMS identificados. Por sexo, se observan diferencias estadísticamente significativas en las prevalencias de cefalea, dolor osteomuscular y tricotilomania que afectan en mayor medida al sexo femenino. La onicofagia (264; 21,20%; IC 95%: 18-24,4 es el más extendido de los TMS, seguido de la cefalea (233; 18,72%; IC 95%: 15,6-21,84. los estudiantes de Psicología presentan el mayor número, seguidos de los de Ciencias Económicas; los que presentan un menor número son los de Farmacia y Químicas. Conclusiones: El sexo femenino presenta la mayor prevalencia de TMS. La onicofagia y la cefalea son los principales TMS identificados en la muestra. Los estudiantes de Psicología acumulan el mayor número de TMS, siendo los que presentan más cefalea, dolor osteomuscular y tricotilomania.Background: To determine the prevalence of certain minor health disorders (MHD in a sample of students from the University of Barcelona (2004-05. Methods: The study was carried out in the faculties of Economic Sciences, Pharmacy, Medicine, Psychology and Chemistry, and in the School of Nursing, all of the University of Barcelona. An
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Cumberland, D C; Gunn, J; Malik, N; Holt, C M
1998-01-01
The surface properties of stents can be modified by coating them, for example with a polymer. Phosphorylcoline (PC) is the major component of the outer layer of the cell membrane. The haemo- and biocompatibility of a PC-containing polymer is thus based on biomimicry, and has been confirmed by several experiments showing much reduced thrombogenicity of PC-coated surfaces, and porcine coronary artery implants showing no sign of adverse effect. Clinical experience with the PC-coated BiodivYsio appears favourable. The PC coating can be tailored for take up and controlled elution of various drugs for stent-based local delivery, a property which is being actively explored.
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Polysaccharides purified from wild Cordyceps activate FGF2/FGFR1c signaling
Zeng, Yangyang; Han, Zhangrun; Yu, Guangli; Hao, Jiejie; Zhang, Lijuan
2015-02-01
Land animals as well as all organisms in ocean synthesize sulfated polysaccharides. Fungi split from animals about 1.5 billion years ago. As fungi make the evolutionary journey from ocean to land, the biggest changes in their living environment may be a sharp decrease in salt concentration. It is established that sulfated polysaccharides interact with hundreds of signaling molecules and facilitate many signaling transduction pathways, including fibroblast growth factor (FGF) and FGF receptor signaling pathway. The disappearance of sulfated polysaccharides in fungi and plants on land might indicate that polysaccharides without sulfation might be sufficient in facilitating protein ligand/receptor interactions in low salinity land. Recently, it was reported that plants on land start to synthesize sulfated polysaccharides in high salt environment, suggesting that fungi might be able to do the same when exposed in such environment. Interestingly, Cordyceps, a fungus habituating inside caterpillar body, is the most valued traditional Chinese Medicine. One of the important pharmaceutical active ingredients in Cordyceps is polysaccharides. Therefore, we hypothesize that the salty environment inside caterpillar body might allow the fungi to synthesize sulfated polysaccharides. To test the hypothesis, we isolated polysaccharides from both lava and sporophore of wild Cordyceps and also from Cordyceps militaris cultured without or with added salts. We then measured the polysaccharide activity using a FGF2/FGFR1c signaling-dependent BaF3 cell proliferation assay and found that polysaccharides isolated from wild Cordyceps activated FGF2/FGFR signaling, indicating that the polysaccharides synthesized by wild Cordyceps are indeed different from those by the cultured mycelium.
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Directory of Open Access Journals (Sweden)
Shinsuke Kido
2012-06-01
Full Text Available Muscle atrophy is a significant consequence of chronic kidney disease (CKD that increases a patient’s risk of mortality and decrease their quality of life. In CKD patients, the circulation levels of FGF23 are significantly increased, but the exact pathological significance of the increase and relationship between FGF23 and muscle atrophy are not clear. Because of Klohto, acts as a co-receptor of FGF23 is detectable in limited tissues including in kidney and brain, but not in skeletal muscles. In contrast, recently reports indicated that the extracellular domain of klohto is cleavage for some reason on the cell surface and detected in the blood in animals. In this study, we attempted to identify the causative factors responsible for the shedding of Klotho, and whether both FGF23 and Klohto induced muscle atrophy via reduction of insulin/IGF-I signaling. We first investigated by treating kidney cells with various factors related in pathological factors in CKD. As a result, we found that advanced glycation endproducts (AGEs, an accumulated in patients with CKD and diabetes mellitus, increases shedding of Klohto in kidney cells. It is common knowledge that insulin/IGF-I signaling is necessary for normal skeletal growth. As a result, we showed that both FGF23 and Klohto inhibited differentiation of cultured skeletal muscle cells through down-regulation of insulin/IGF-I signaling. These observations suggested a divergent role of FGF23 and soluble klohto in the regulation of skeletal muscle differentiation and thereby muscle atrophy under pathological conditioned in CKD patients. Our results further imply that FGF23/Klohto may serve a new therapeutic target for CKD-induced muscle atrophy.
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Energy Technology Data Exchange (ETDEWEB)
Levi Lesueur, Ch [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires
1961-03-15
We studied the decay schemes of Tc{sup 93} et Tc{sup 95} to determine the spins of Mo{sup 93} and M{sup 95} levels, and especially the position of the single-particle level 1g 7/2. We found a large spacing between the neutron shells 2d 5/2 and 1g 7/2 like that observed first in Mo{sup 97}. As the subshell 2d 5/2 is so far from its neighbours, we thought that subshell effects could perhaps be discovered in the systematics of separation energies and beta-decay energies. We found such effects. (author) [French] Par l'etude des schemas de desintegration de {sup 93}Tc et {sup 95}Tc, nous avons essaye de determiner les spins des niveaux de {sup 93}Mo et {sup 95}Mo et en particulier la position du niveau de particule 1g 7/2. Nous avons ainsi confirme l'ecart important entre les couches de neutrons 2d 5/2 et 1g 7/2 deja constate a propos de {sup 97}Mo. Nous avons pense que la sous-couche 2d 5/2 ainsi isolee des couches voisines pouvait, peut etre, etre mise en evidence par l'etude des systematiques d'energies de separation et d'energies de desintegration beta. Nous avons verifie qu'il en etait bien ainsi. (auteur)
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Perlecan is required for FGF-2 signaling in the neural stem cell niche
Directory of Open Access Journals (Sweden)
Aurelien Kerever
2014-03-01
Full Text Available In the adult subventricular zone (neurogenic niche, neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.
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Equipment Qualification and Environment Establishment for COTS Dedication of Safety Grade PC
International Nuclear Information System (INIS)
Ahn, Kwang Chul; Bin, Chang Sun; Kwon, Yoon Kwang; Kang, Shin Woo; Koh, Sung Won; Shon, Eui Chan; Jang, Hyun Doo; Song, Il Sup; Lee, Hyun Noh
2010-08-01
Safety grade PCs are required for protection systems of SKN 3 and 4 nuclear power plant and subsequent plants. Commercial grade item (CGI) dedication should be carried out to utilize a commercial PC as a safety grade PC of nuclear power plants. This project is aimed to perform the equipment qualification of the commercial PC, and review and improve the quality system of the PC supplier. As a result of the EQ for the CGI dedication, selected military PCs have passed the environment test, the seismic test, and the EMI test required for the digital controllers of nuclear plants. In addition, a walk-through of the quality system of the PC supplier, ISO 9001, was carried out and the quality system was improved. History data for the PC was gathered. As the analysis of the history data showed that operating experience time of the PC is longer than the plant life time, the history data could be used as an evidence of acceptance. After dedicated according to the CGI dedication process, military rugged PCs could be used for safety grade PCs
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Shao, Meiying; Liu, Chao; Song, Yingnan; Ye, Wenduo; He, Wei; Yuan, Guohua; Gu, Shuping; Lin, Congxin; Ma, Liang; Zhang, Yanding; Tian, Weidong; Hu, Tao; Chen, YiPing
2015-01-01
The cranial neural crest (CNC) cells play a vital role in craniofacial development and regeneration. They are multi-potent progenitors, being able to differentiate into various types of tissues. Both pre-migratory and post-migratory CNC cells are plastic, taking on diverse fates by responding to different inductive signals. However, what sustains the multipotency of CNC cells and derivatives remains largely unknown. In this study, we present evidence that FGF8 signaling is able to sustain progenitor status and multipotency of CNC-derived mesenchymal cells both in vivo and in vitro. We show that augmented FGF8 signaling in pre-migratory CNC cells prevents cell differentiation and organogenesis in the craniofacial region by maintaining their progenitor status. CNC-derived mesenchymal cells with Fgf8 overexpression or control cells in the presence of exogenous FGF8 exhibit prolonged survival, proliferation, and multi-potent differentiation capability in cell cultures. Remarkably, exogenous FGF8 also sustains the capability of CNC-derived mesenchymal cells to participate in organogenesis such as odontogenesis. Furthermore, FGF8-mediated signaling strongly promotes adipogenesis but inhibits osteogenesis of CNC-derived mesenchymal cells in vitro. Our results reveal a specific role for FGF8 in the maintenance of progenitor status and in fate determination of CNC cells, implicating a potential application in expansion and fate manipulation of CNC-derived cells in stem cell-based craniofacial regeneration. PMID:26243590
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Li, Zhi Gang; Mathew, Paul; Yang, Jun; Starbuck, Michael W; Zurita, Amado J; Liu, Jie; Sikes, Charles; Multani, Asha S; Efstathiou, Eleni; Lopez, Adriana; Wang, Jing; Fanning, Tina V; Prieto, Victor G; Kundra, Vikas; Vazquez, Elba S; Troncoso, Patricia; Raymond, Austin K; Logothetis, Christopher J; Lin, Sue-Hwa; Maity, Sankar; Navone, Nora M
2008-08-01
In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor-negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in castrated as well as intact male mice. We identified FGF9 as being overexpressed in the xenografts relative to other bone-derived prostate cancer cells and discovered that FGF9 induced osteoblast proliferation and new bone formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody developed smaller bone tumors and reduced bone formation. Finally, we found positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis cases studied. Collectively, these results suggest that FGF9 contributes to prostate cancer-induced new bone formation and may participate in the osteoblastic progression of prostate cancer in bone. Androgen receptor-null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells.
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Study on the effect of Huo Xue Bo Gu Pill on secretion of endogenous bFGF after fracture
International Nuclear Information System (INIS)
Li Qiang; Wang Xiping; Guo E; Ye Liyan; Liu Yingjie
2006-01-01
Objective: To study the effect of a Chinese traditional preparation Huo Xue Bo Gu Pill on the serum contents of basic fibroblast growth factor (bFGF) after forearm fractures. Method: Serum bFGF contents were measured (with ELISA) in 62 patients with forearm fractures on d1, d8, d14 and d20 after the accident. Thirty-two of the patients were treated with Huo Xue Bo Gu Pills and thirty patients were not. Results: The serum contents of bFGF on d8 and d14 were significantly higher in the patients treated with the pills than those in patients not treated with the pills (P<0.05). Conclusion: This pill could promote the secretion of endogenous bFGF with proliferation of capillaries at the fracture site. (authors)
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Quang, Tara; Marquez, Maribel; Blanco, Giselle; Zhao, Yuanxiang
2014-01-01
Many different culture systems have been developed for expanding human pluripotent stem cells (hESCs and hiPSCs). In general, 4-10 ng/ml of bFGF is supplemented in culture media in feeder-dependent systems regardless of feeder cell types, whereas in feeder-free systems, up to 100 ng/ml of bFGF is required for maintaining long-term culture on various substrates. The amount of bFGF required in native hESCs growth niche is unclear. Here we report using inactivated adipose-derived human mesenchymal stem cells as feeder cells to examine long-term parallel cultures of two hESCs lines (H1 and H9) and one hiPSCs line (DF19-9-7T) in media supplemented with 0, 0.4 or 4 ng/ml of bFGF for up to 23 passages, as well as parallel cultures of H9 and DF19 in media supplemented with 4, 20 or 100 ng/ml bFGF for up to 13 passages for comparison. Across all cell lines tested, bFGF supplement demonstrated inhibitory effect over growth expansion, single cell colonization and recovery from freezing in a dosage dependent manner. In addition, bFGF exerted differential effects on different cell lines, inducing H1 and DF19 differentiation at 4 ng/ml or higher, while permitting long-term culture of H9 at the same concentrations with no apparent dosage effect. Pluripotency was confirmed for all cell lines cultured in 0, 0.4 or 4 ng/ml bFGF excluding H1-4 ng, as well as H9 cultured in 4, 20 and 100 ng/ml bFGF. However, DF19 demonstrated similar karyotypic abnormality in both 0 and 4 ng/ml bFGF media while H1 and H9 were karyotypically normal in 0 ng/ml bFGF after long-term culture. Our results indicate that exogenous bFGF exerts dosage and cell line dependent effect on human pluripotent stem cells cultured on mesenchymal stem cells, and implies optimal use of bFGF in hESCs/hiPSCs culture should be based on specific cell line and its culture system.
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Wojcik, Malgorzata; Janus, Dominika; Dolezal-Oltarzewska, Katarzyna; Kalicka-Kasperczyk, Anna; Poplawska, Karolina; Drozdz, Dorota; Sztefko, Krystyna; Starzyk, Jerzy B
2012-01-01
Fibroblast growth factor 19 (FGF19) is a hormone released from the small intestine; recently, it has emerged as an endocrine regulator of glucose and lipid metabolism. The aim of this study was to investigate the role of FGF19 in the development of nonalcoholic fatty liver disease (NAFLD). This study included 23 (17 boys) obese adolescents (mean age of 14.1 years) with NAFLD. The control group consisted of 34 (13 boys) obese peers with normal ultrasonographic imaging and normal liver function tests. The definition of NAFLD was based on clinical criteria: elevated alanine aminotransferase (>35 U/L) and liver steatosis features on ultrasound imaging. Serum FGF19 levels were measured in a fasting blood sample. The definition of insulin resistance was based on the homeostasis model assessment (HOMA) threshold: >2.5. There was a significant difference between mean FGF19 levels in patients with NAFLD and controls (142.2 vs. 206 pg/mL, p=0.04). Mean fasting FGF19 levels were decreased in insulin-resistant patients in comparison with the non-insulin-resistant group (155.0 vs. 221.0 pg/mL, p=0.05). There was an inverse correlation between FGF19 and alanine aminotransferase levels (R=-0.3, pexogenous delivery of FGF19 might be therapeutically beneficial.
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Energy Technology Data Exchange (ETDEWEB)
Hsu, Yi-Chao [Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan (China); Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan (China); Kao, Chien-Yu [Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan (China); Graduate Program of Biotechnology in Medicine, Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan (China); Chung, Yu-Fen; Lee, Don-Ching [Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan (China); Liu, Jen-Wei [Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan (China); Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chiu, Ing-Ming, E-mail: ingming@nhri.org.tw [Division of Regenerative Medicine, Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan (China); Graduate Program of Biotechnology in Medicine, Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan (China); Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan (China)
2016-06-10
Fibroblast growth factor 1 (FGF1) binds and activates FGF receptors, thereby regulating cell proliferation and neurogenesis. Human FGF1 gene 1B promoter (−540 to +31)-driven SV40 T antigen has been shown to result in tumorigenesis in the brains of transgenic mice. FGF1B promoter (−540 to +31)-driven green fluorescent protein (F1BGFP) has also been used in isolating neural stem cells (NSCs) with self-renewal and multipotency from developing and adult mouse brains. In this study, we provide six lines of evidence to demonstrate that FGF1/FGFR signaling is implicated in the expression of Aurora A (AurA) and the activation of its kinase domain (Thr288 phosphorylation) in the maintenance of glioblastoma (GBM) cells and NSCs. First, treatment of FGF1 increases AurA expression in human GBM cell lines. Second, using fluorescence-activated cell sorting, we observed that F1BGFP reporter facilitates the isolation of F1BGFP(+) GBM cells with higher expression levels of FGFR and AurA. Third, both FGFR inhibitor (SU5402) and AurA inhibitor (VX680) could down-regulate F1BGFP-dependent AurA activity. Fourth, inhibition of AurA activity by two different AurA inhibitors (VX680 and valproic acid) not only reduced neurosphere formation but also induced neuronal differentiation of F1BGFP(+) GBM cells. Fifth, flow cytometric analyses demonstrated that F1BGFP(+) GBM cells possessed different NSC cell surface markers. Finally, inhibition of AurA by VX680 reduced the neurosphere formation of different types of NSCs. Our results show that activation of AurA kinase through FGF1/FGFR signaling axis sustains the stem cell characteristics of GBM cells. Implications: This study identified a novel mechanism for the malignancy of GBM, which could be a potential therapeutic target for GBM. - Highlights: • We report that FGF1 treatment can stimulate AurA kinase expression in human GBM cells. • FGF1/FGFR signaling is involved in the activation of AurA kinase. • FGF1 sustains the self
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International Nuclear Information System (INIS)
Hsu, Yi-Chao; Kao, Chien-Yu; Chung, Yu-Fen; Lee, Don-Ching; Liu, Jen-Wei; Chiu, Ing-Ming
2016-01-01
Fibroblast growth factor 1 (FGF1) binds and activates FGF receptors, thereby regulating cell proliferation and neurogenesis. Human FGF1 gene 1B promoter (−540 to +31)-driven SV40 T antigen has been shown to result in tumorigenesis in the brains of transgenic mice. FGF1B promoter (−540 to +31)-driven green fluorescent protein (F1BGFP) has also been used in isolating neural stem cells (NSCs) with self-renewal and multipotency from developing and adult mouse brains. In this study, we provide six lines of evidence to demonstrate that FGF1/FGFR signaling is implicated in the expression of Aurora A (AurA) and the activation of its kinase domain (Thr288 phosphorylation) in the maintenance of glioblastoma (GBM) cells and NSCs. First, treatment of FGF1 increases AurA expression in human GBM cell lines. Second, using fluorescence-activated cell sorting, we observed that F1BGFP reporter facilitates the isolation of F1BGFP(+) GBM cells with higher expression levels of FGFR and AurA. Third, both FGFR inhibitor (SU5402) and AurA inhibitor (VX680) could down-regulate F1BGFP-dependent AurA activity. Fourth, inhibition of AurA activity by two different AurA inhibitors (VX680 and valproic acid) not only reduced neurosphere formation but also induced neuronal differentiation of F1BGFP(+) GBM cells. Fifth, flow cytometric analyses demonstrated that F1BGFP(+) GBM cells possessed different NSC cell surface markers. Finally, inhibition of AurA by VX680 reduced the neurosphere formation of different types of NSCs. Our results show that activation of AurA kinase through FGF1/FGFR signaling axis sustains the stem cell characteristics of GBM cells. Implications: This study identified a novel mechanism for the malignancy of GBM, which could be a potential therapeutic target for GBM. - Highlights: • We report that FGF1 treatment can stimulate AurA kinase expression in human GBM cells. • FGF1/FGFR signaling is involved in the activation of AurA kinase. • FGF1 sustains the self
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General specifications for the development of a USL/DBMS NASA/PC R and D distributed workstation
Dominick, Wayne D. (Editor); Chum, Frank Y.
1984-01-01
The general specifications for the development of a PC-based distributed workstation (PCDWS) for an information storage and retrieval systems environment are defined. This research proposes the development of a PCDWS prototype as part of the University of Southwestern Louisiana Data Base Management System (USL/DBMS) NASA/PC R and D project in the PC-based workstation environment.
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Charrue, P; Bland, A; Ghinet, F; Ribeiro, P
1995-01-01
The CERN SPS and LEP PowerPC project is aimed at introducing a new generation of PowerPC VMEbus processor modules running the LynxOS real-time operating system. This new generation of front end computers using the state-of-the-art microprocessor technology will first replace the obsolete XENIX PC based systems (about 140 installations) successfully used since 1988 to control the LEP accelerator. The major issues addressed in the scope of this large scale project are the technical specificatio...
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Energy Technology Data Exchange (ETDEWEB)
Fata, Jimmie E; Mori, Hidetoshi; Ewald, Andrew J; Zhang, Hui; Yao, Evelyn; Werb, Zena; Bissell, Mina J
2006-10-03
Transforming growth factor-{alpha} (TGF{alpha}) and fibroblast growth factor-7 (FGF7) exhibit distinct expression patterns in the mammary gland. Both factors signal through mitogen-activated kinase/extracellular regulated kinase-1,2 (MAPK{sup ERK1,2}); however, their unique and/or combined contributions to mammary morphogenesis have not been examined. In ex vivo mammary explants, we show that a sustained activation of MAPK{sup ERK1,2} for 1 h, induced by TGF{alpha}, was necessary and sufficient to initiate branching morphogenesis, whereas a transient activation (15 min) of MAPK{sup ERK1,2}, induced by FGF7, led to growth without branching. Unlike TGF{alpha}, FGF7 promoted sustained proliferation as well as ectopic localization of, and increase in, keratin-6 expressing cells. The response of the explants to FGF10 was similar to that to FGF7. Simultaneous stimulation by FGF7 and TGF{alpha} indicated that the FGF7-induced MAPK{sup ERK1,2} signaling and associated phenotypes were dominant: FGF7 may prevent branching by suppression of two necessary TGF{alpha}-induced morphogenetic effectors, matrix metalloproteinase-3 (MMP-3/stromelysin-1), and fibronectin. Our findings indicate that expression of morphogenetic effectors, proliferation, and cell-type decisions during mammary organoid morphogenesis are intimately dependent on the duration of activation of MAPK{sup ERK1,2} activation.
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Directory of Open Access Journals (Sweden)
Rafael Fabiano Machado Rosa
2011-02-01
Full Text Available OBJETIVO: Verificar a frequência da síndrome de deleção 22q11 (SD22q11 entre pacientes portadores de cardiopatia congênita do tipo complexa. MÉTODOS: A amostra foi constituída por uma coorte prospectiva e consecutiva de pacientes com cardiopatia complexa em sua primeira hospitalização em uma unidade de tratamento intensivo cardiológica de um hospital pediátrico. Para cada paciente foi preenchida uma ficha de avaliação, com coleta de dados clínicos, e realizado o cariótipo de alta resolução e técnica de hibridização in situ fluorescente (FISH com pesquisa de microdeleção 22q11. Os defeitos cardíacos foram classificados por um cardiologista participante do estudo. RESULTADOS: A amostra foi composta de 66 pacientes. Quanto à análise cariotípica, alterações foram observadas em cinco pacientes (7,6%; contudo, nenhum deles apresentava deleção 22q11. A avaliação pela técnica de FISH pôde ser realizada com sucesso em 65 pacientes, sendo que a microdeleção 22q11 foi identificada em dois (3,1%. Dos 66 pacientes com defeitos complexos, 52 eram portadores de malformações do tipo conotruncal, sendo que em 51 a pesquisa para microdeleção 22q11 foi realizada. Os dois pacientes portadores da microdeleção 22q11 fizeram parte deste grupo, representando uma frequência de 3,9%. Eles apresentavam tetralogia de Fallot. CONCLUSÃO: A SD22q11 é uma anormalidade frequente entre pacientes com cardiopatias congênitas complexas e conotruncais. Variações da frequência da SD22q11 entre os estudos parecem estar associadas, principalmente, com a forma adotada para a seleção da amostra e às características da população em análise.OBJECTIVE: Investigate the frequency of 22q11 deletion syndrome among patients with complex congenital heart disease. METHODS: A prospective and consecutive cohort of patients with complex heart defects was evaluated in their first hospitalization at a cardiac intensive care unit of a pediatric
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Satoh, Akira; Makanae, Aki; Nishimoto, Yurie; Mitogawa, Kazumasa
2016-09-01
Urodele amphibians have a remarkable organ regeneration ability that is regulated by neural inputs. The identification of these neural inputs has been a challenge. Recently, Fibroblast growth factor (Fgf) and Bone morphogenic protein (Bmp) were shown to substitute for nerve functions in limb and tail regeneration in urodele amphibians. However, direct evidence of Fgf and Bmp being secreted from nerve endings and regulating regeneration has not yet been shown. Thus, it remained uncertain whether they were the nerve factors responsible for successful limb regeneration. To gather experimental evidence, the technical difficulties involved in the usage of axolotls had to be overcome. We achieved this by modifying the electroporation method. When Fgf8-AcGFP or Bmp7-AcGFP was electroporated into the axolotl dorsal root ganglia (DRG), GFP signals were detectable in the regenerating limb region. This suggested that Fgf8 and Bmp7 synthesized in neural cells in the DRG were delivered to the limbs through the long axons. Further knockdown experiments with double-stranded RNA interference resulted in impaired limb regeneration ability. These results strongly suggest that Fgf and Bmp are the major neural inputs that control the organ regeneration ability. Copyright © 2016 Elsevier Inc. All rights reserved.
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Team sponsors in community-based health leadership programs.
Patterson, Tracy Enright; Dinkin, Donna R; Champion, Heather
2017-05-02
Purpose The purpose of this article is to share the lessons learned about the role of team sponsors in action-learning teams as part of community-based health leadership development programs. Design/methodology/approach This case study uses program survey results from fellow participants, action learning coaches and team sponsors to understand the value of sponsors to the teams, the roles they most often filled and the challenges they faced as team sponsors. Findings The extent to which the sponsors were perceived as having contributed to the work of the action learning teams varied greatly from team to team. Most sponsors agreed that they were well informed about their role. The roles sponsors most frequently played were to provide the teams with input and support, serve as a liaison to the community and serve as a sounding board, motivator and cheerleader. The most common challenges or barriers team sponsors faced in this role were keeping engaged in the process, adjusting to the role and feeling disconnected from the program. Practical implications This work provides insights for program developers and community foundations who are interested in building the capacity for health leadership by linking community sponsors with emerging leaders engaged in an action learning experience. Originality/value This work begins to fill a gap in the literature. The role of team sponsors has been studied for single organization work teams but there is a void of understanding about the role of sponsors with multi-organizational teams working to improve health while also learning about leadership.
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Fries, Ryan; Cross, Brad; Zhou, Jianpeng; Verbais, Chad
2017-01-01
Because many engineering programs use capstone design courses and value strong communication abilities, authors sought to identify how student written communication skills changed because of industry-sponsored capstone design projects. A student exit survey was collected at the end of the capstone design course during faculty-led projects and…
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[Local application of bFGF and sucralfate during continuous tissue expansion].
Hu, Ya-lan; Guo, Shu-zhong; Lu, Kai-hua; Han, Yan; Lei, Yong-hong; Song, Bao-qiang; Pan, Yong
2003-01-01
To investigate the effect of local application of bFGF and sucralfate during continuous tissue expansion (CTE). CTE combined with local administration of bFGF and sucralfate was used in twelve patients with scar and nasal tip defects. Twenty three expanders were placed in the subcutaneous pockets through intralesion short incisions. Continuous expansion began at 1-3 days after expander implantation. The histomorphological changes and epidermal cell proliferation were observed. The clinical results were investigated. The average inflation time was 8.9 days. The average interval of the two operations was 13.5 days. The average hospitalization was 28.4 days. The average immediate stretch-back rate of the expanded skin was 25.7%. The clinical results were satisfactory without any complications. Histological examinations showed that the epidermal, granular and spinous layer became thicker. The basal cells increased significantly. The dermis thinned slightly and the collagen fibers became thicker. The elastic fiber regenerated significantly. Fibroblast and capillary density increased obviously. The immunohistochemistry analysis showed that the proliferation of epidemic basal cells was significant postoperatively. Local application of exogenous bFGF and sucralfate during CTE was feasible in patients. It could accelerate tissue expansion and improve the quality of expanded skin flap.
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Directory of Open Access Journals (Sweden)
Nishal S Patel
Full Text Available Changes in higher order chromatin organisation have been linked to transcriptional regulation; however, little is known about how such organisation alters during embryonic development or how it is regulated by extrinsic signals. Here we analyse changes in chromatin organisation as neural differentiation progresses, exploiting the clear spatial separation of the temporal events of differentiation along the elongating body axis of the mouse embryo. Combining fluorescence in situ hybridisation with super-resolution structured illumination microscopy, we show that chromatin around key differentiation gene loci Pax6 and Irx3 undergoes both decompaction and displacement towards the nuclear centre coincident with transcriptional onset. Conversely, down-regulation of Fgf8 as neural differentiation commences correlates with a more peripheral nuclear position of this locus. During normal neural differentiation, fibroblast growth factor (FGF signalling is repressed by retinoic acid, and this vitamin A derivative is further required for transcription of neural genes. We show here that exposure to retinoic acid or inhibition of FGF signalling promotes precocious decompaction and central nuclear positioning of differentiation gene loci. Using the Raldh2 mutant as a model for retinoid deficiency, we further find that such changes in higher order chromatin organisation are dependent on retinoid signalling. In this retinoid deficient condition, FGF signalling persists ectopically in the elongating body, and importantly, we find that inhibiting FGF receptor (FGFR signalling in Raldh2-/- embryos does not rescue differentiation gene transcription, but does elicit both chromatin decompaction and nuclear position change. These findings demonstrate that regulation of higher order chromatin organisation during differentiation in the embryo can be uncoupled from the machinery that promotes transcription and, for the first time, identify FGF as an extrinsic signal that
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Directory of Open Access Journals (Sweden)
Kemin Yan
2018-03-01
Full Text Available Objective: Ileal transposition (IT surgery has been reported to improve glucose and lipid metabolism, and fibroblast growth factor 21 (FGF21 is a powerful metabolic regulator. In the present study, we aimed to investigate the effects of IT surgery on metabolism and its possible relationship with the FGF21 signaling pathway in diabetic Goto-Kakizaki (GK rats.Methods: Ten-week-old male GK rats were subjected to IT surgery with translocation of a 10 cm ileal segment to the proximal jejunum (IT group or sham surgery without the ileum transposition (Sham-IT group. Rats in the no surgery group did not receive any surgical intervention. Six weeks later, body weight, fat mass, fasting blood glucose (FBG, and serum levels of FGF21 and leptin were measured. The expression of the FGF21 signaling pathway and white adipose tissue (WAT browning-related genes in the WAT and liver were evaluated by real-time reverse transcription polymerase chain reaction (RT-qPCR and western blot.Results: IT surgery significantly decreased the body weights and FBG levels and increased the insulin sensitivity of GK rats. The total WAT mass of the IT rats showed a 41.5% reduction compared with the Sham-IT rats, and serum levels of FGF21 and leptin of the IT rats decreased by 26.3 and 61.7%, respectively (all P < 0.05. The mRNA levels of fibroblast growth factor receptor 1 (FGFR1 and its co-receptor β klotho (KLB in the perirenal WAT (pWAT of the IT rats were 1.4- and 2.4-fold that of the Sham-IT rats, respectively, and the FGFR1 protein levels were 1.7-fold of the Sham-IT rats (all P < 0.05. In accordance with the pWAT, the protein levels of FGFR1 and KLB in the epididymal WAT (eWAT of the IT rats notably increased to 3.0- and 3.9-fold of the Sham-IT rats (P < 0.05. Furthermore, uncoupling protein 1 (UCP1 protein levels in the eWAT and pWAT of the IT rats also increased to 2.2- and 2.3-fold of the Sham-IT rats (P < 0.05. However, the protein levels of FGFR1 and KLB in the
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Neira, J A; Tainturier, D; Peña, M A; Martal, J
2010-03-15
This study examined the influence of the following growth factors and cytokines on early embryonic development: insulin-like growth factors I and II (IGF-I, IGF-II), basic fibroblast growth factor (bFGF), transforming growth factor (TGF-beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), and leukemia inhibitory factor (LIF). Synthetic oviduct fluid (SOF) was used as the culture medium. We studied the development of bovine embryos produced in vitro and cultured until Day 9 after fertilization. TGF-beta1, bFGF, GM-CSF, and LIF used on their own significantly improved the yield of hatched blastocysts. IGF-I, bFGF, TGF-beta1, GM-CSF, and LIF significantly accelerated embryonic development, especially the change from the expanded blastocyst to hatched blastocyst stages. Use of a combination of these growth factors and cytokines (GF-CYK) in SOF medium produced higher percentages of blastocysts and hatched blastocysts than did use of SOF alone (45% and 22% vs. 24% and 12%; PGM-CSF, produces similar results to 10% fetal calf serum for the development of in vitro-produced bovine embryos. This entirely synthetic method of embryo culture has undeniable advantages for the biosecurity of embryo transfer. Copyright 2010 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Klosowiak Julian
2010-10-01
Full Text Available Abstract Background Vertebrate limb development involves a reciprocal feedback loop between limb mesenchyme and the overlying apical ectodermal ridge (AER. Several gene pathways participate in this feedback loop, including Fgf signaling. In the forelimb lateral plate mesenchyme, Tbx5 activates Fgf10 expression, which in turn initiates and maintains the mesenchyme/AER Fgf signaling loop. Recent findings have revealed that Tbx5 transcriptional activity is regulated by dynamic nucleocytoplasmic shuttling and interaction with Pdlim7, a PDZ-LIM protein family member, along actin filaments. This Tbx5 regulation is critical in heart formation, but the coexpression of both proteins in other developing tissues suggests a broader functional role. Results Knock-down of Pdlim7 function leads to decreased pectoral fin cell proliferation resulting in a severely stunted fin phenotype. While early gene induction and patterning in the presumptive fin field appear normal, the pectoral fin precursor cells display compaction and migration defects between 18 and 24 hours post-fertilization (hpf. During fin growth fgf24 is sequentially expressed in the mesenchyme and then in the apical ectodermal ridge (AER. However, in pdlim7 antisense morpholino-treated embryos this switch of expression is prevented and fgf24 remains ectopically active in the mesenchymal cells. Along with the lack of fgf24 in the AER, other critical factors including fgf8 are reduced, suggesting signaling problems to the underlying mesenchyme. As a consequence of perturbed AER function in the absence of Pdlim7, pathway components in the fin mesenchyme are misregulated or absent, indicating a breakdown of the Fgf signaling feedback loop, which is ultimately responsible for the loss of fin outgrowth. Conclusion This work provides the first evidence for the involvement of Pdlim7 in pectoral fin development. Proper fin outgrowth requires fgf24 downregulation in the fin mesenchyme with subsequent
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Warne, Charles D; Zaloumis, Sophie G; Bertalli, Nadine A; Delatycki, Martin B; Nicoll, Amanda J; McLaren, Christine E; Hopper, John L; Giles, Graham G; Anderson, Greg J; Olynyk, John K; Powell, Lawrie W; Allen, Katrina J; Gurrin, Lyle C
2017-04-01
Women who are homozygous for the p.C282Y mutation in the HFE gene are at much lower risk of iron overload-related disease than p.C282Y homozygous men, presumably because of the iron-depleting effects of menstruation and pregnancy. We used data from a population cohort study to model the impact of menstruation cessation at menopause on serum ferritin (SF) levels in female p.C282Y homozygotes, with p.C282Y/p.H63D simple or compound heterozygotes and those with neither p.C282Y nor p.H63D mutations (HFE wild types) as comparison groups. A sample of the Melbourne Collaborative Cohort Study was selected for the "HealthIron" study (n = 1438) including all HFE p.C282Y homozygotes plus a random sample stratified by HFE-genotype (p.C282Y and p.H63D). The relationship between the natural logarithm of SF and time since menopause was examined using linear mixed models incorporating spline smoothing. For p.C282Y homozygotes, SF increased by a factor of 3.6 (95% CI (1.8, 7.0), P HFE genotype groups increase more gradually and did not show a distinction between premenopausal and postmenopausal SF levels. Only p.C282Y homozygotes had predicted SF exceeding 200 μg/L postmenopause, but the projected SF did not increase the risk of iron overload-related disease. These data provide the first documented evidence that physiological blood loss is a major factor in determining the marked gender difference in expression of p.C282Y homozygosity. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
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Morfología de la planta y características de rendimiento y calidad de almidón de sagú
Directory of Open Access Journals (Sweden)
Magda Piedad Valdés Restrepo
2010-07-01
Full Text Available El sagú Maranta arundinacea es una Marantaceae cuyo rizoma es utilizado en algunas zonas de Colombia para la elaboración de productos destinados a la alimentación humana. No obstante, el conocimiento agronómico de este cultivo es limitado. En este trabajo se estudiaron varios métodos de propagación, días a cosecha de rizomas, producción de almidón nativo y el análisis químico de esta planta en las condiciones del Valle del Cauca. El cultivo fue establecido en parcelas de 0.25 m x 1 m entre plantas dentro de surco y entre surcos, respectivamente. Para el análisis de los datos cuantitativos se utilizaron estadísticas descriptivas (medidas de tendencia central, de variación y de desviación. La planta adulta alcanzó una altura entre 50 y 75 cm y un rendimiento de rizoma fresco entre 1.46 y 1.94 kg/planta. El índice de cosecha varió entre 0.06 y 0.60; el rendimiento de almidón por el rizoma fresco varió entre 7.2% y 8.1%; la composición proximal (en % del rizoma fue: 22.3, 7.4, 3.62, 1.02, 6.98 y 80.9 para MS, PC, FC, EE, ceniza y ELN, respectivamente. Las pruebas de antimetabolitos mostraron ausencia de estos compuestos en el forraje fresco, con 41.3; 22.0; 22.5; 15.06; 57.13; 32.3; 9.2; 23.13 y 24.8% de MS, PC, FC, ceniza, FDN, FDA, lignina, celulosa y hemicelulosa, respectivamente. El valor relativo como forraje fue de 103.7. Se realizó el análisis granulométrico: el módulo de fineza, módulo de uniformidad y el tamaño de la partícula. El rendimiento de almidón de rizomas fue de 10.57 ± 1.35%, el gasto de agua de 50.45 l/kg de almidón rendido. El gránulo fue elipsoidal de 8 µm de diámetro y compuesto por 20.54% de amilosa y 79.46% de amilopectina, que genera una pasta opaca y resistente a la retrogradación. La temperatura final de gelificación fue de 73 °C, la viscosidad máxima de la pasta fue de 220 Unidades Brabender (U.B., con un pico de viscosidad definido, y posterior conservación de la trayectoria, con
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Morfología de la planta y características de rendimiento y calidad de almidón de sagú
Directory of Open Access Journals (Sweden)
Sánchez Teresa
2010-09-01
Full Text Available El sagú Maranta arundinacea es una Marantaceae cuyo rizoma es utilizado en algunas zonas de Colombia para la elaboración de productos destinados a la alimentación humana. No obstante, el conocimiento agronómico de este cultivo es limitado. En este trabajo se estudiaron varios métodos de propagación, días a cosecha de rizomas, producción de almidón nativo y el análisis químico de esta planta en las condiciones del Valle del Cauca. El cultivo fue establecido en parcelas de 0.25 m x 1 m entre plantas dentro de surco y entre surcos, respectivamente. Para el análisis de los datos cuantitativos se utilizaron estadísticas descriptivas (medidas de tendencia central, de variación y de desviación. La planta adulta alcanzó una altura entre 50 y 75 cm y un rendimiento de rizoma fresco entre 1.46 y 1.94 kg/planta. El índice de cosecha varió entre 0.06 y 0.60; el rendimiento de almidón por el rizoma fresco varió entre 7.2% y 8.1%; la composición proximal (en % del rizoma fue: 22.3, 7.4, 3.62, 1.02, 6.98 y 80.9 para MS, PC, FC, EE, ceniza y ELN, respectivamente. Las pruebas de antimetabolitos mostraron ausencia de estos compuestos en el forraje fresco, con 41.3; 22.0; 22.5; 15.06; 57.13; 32.3; 9.2; 23.13 y 24.8% de MS, PC, FC, ceniza, FDN, FDA, lignina, celulosa y hemicelulosa, respectivamente. El valor relativo como forraje fue de 103.7. Se realizó el análisis granulométrico: el módulo de fineza, módulo de uniformidad y el tamaño de la partícula. El rendimiento de almidón de rizomas fue de 10.57 ± 1.35%, el gasto de agua de 50.45 l/kg de almidón rendido. El gránulo fue elipsoidal de 8 µm de diámetro y compuesto por 20.54% de amilosa y 79.46% de amilopectina, que genera una pasta opaca y resistente a la retrogradación. La temperatura final de gelificación fue de 73 °C, la viscosidad máxima de la pasta fue de 220 Unidades Brabender (U.B., con un pico de viscosidad definido, y posterior conservación de la
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Tiong, Kai Hung; Tan, Boon Shing; Choo, Heng Lungh; Chung, Felicia Fei-Lei; Hii, Ling-Wei; Tan, Si Hoey; Khor, Nelson Tze Woei; Wong, Shew Fung; See, Sze-Jia; Tan, Yuen-Fen; Rosli, Rozita; Cheong, Soon-Keng; Leong, Chee-Onn
2016-09-06
Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.
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CC-3 CAMAC crate controller for IBM PC
International Nuclear Information System (INIS)
Khare, A.N.; Ghodgaonkar, M.D.; Bairi, B.R.
1991-01-01
The specifications and implementation details of CAMAC Crate Controller CC-3 for IBM-PC compatible as a host computer, having capability to transfer high speed data with direct memory access (DMA) scheme and logic to execute CAMAC cycles directly from the crate controller, to implement the block algorithms specified in ANSI/IEEE Std. 683-1976 (Reaff-1981) are described. The maximum data transfer rate measured with 8 bit interface of PC-AT is 240K byte per second. This work is carried out under Seventh Five Year Plan Project on Modernisation of reactor Control Instrumentation and Development of CAMAC and Fastbus Instrumentation. (author). 9 refs., 5 figs., 4 appendixes
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Employer-sponsored pension plans
Directory of Open Access Journals (Sweden)
Rakonjac-Antić Tatjana N.
2004-01-01
Full Text Available Apart from pension plans within social insurance, in developed pension systems there are also available to individuals schemes which may to a large extent ensure a significant part of their total pension. Among them are the following: employer-sponsored pension plans or individual pension plans. The most widely used employer-sponsored pension plan in the USA is 401(k, in which both the employer and the employee contribute to the financing of the pension. These contributions as well as the return to their investment have a preferential tax treatment, i.e. do not enter a tax base. The funds are taxed only when drawn from the account in the form of a pension. This paper aims to present the functioning of 401(k pension plan as the most widely used employer sponsored pension plan in the USA, which is likely, in a modified form, to have an important place within our future reformed pension insurance system.
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DEFF Research Database (Denmark)
Vienberg, Sara Gry; Brøns, Charlotte; Nilsson, Emma
2012-01-01
of type 2 diabetes and 26 control (normal birth weight (NBW)) young men were subjected to 5 days of high-fat (HF) overfeeding (+50%). Basal and clamp insulin-stimulated serum FGF21 levels were examined before and after the diet, and FGF21 mRNA expression was measured in muscle and fat biopsies......OBJECTIVE: Fibroblast growth factor 21 (FGF21) is a metabolic factor involved in glucose and lipid metabolism. However, little is known about the physiological role of FGF21 during a dietary challenge in humans. RESEARCH DESIGN AND METHODS: Twenty healthy low birth weight (LBW) with known risk...
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Directory of Open Access Journals (Sweden)
Bethany T Nelson
Full Text Available Hibernation is a natural adaptation that allows certain mammals to survive physiological extremes that are lethal to humans. Near freezing body temperatures, heart rates of 3-10 beats per minute, absence of food consumption, and depressed metabolism are characteristic of hibernation torpor bouts that are periodically interrupted by brief interbout arousals (IBAs. The molecular basis of torpor induction is unknown, however starved mice overexpressing the metabolic hormone fibroblast growth factor 21 (FGF21 promote fat utilization, reduce body temperature, and readily enter torpor-all hallmarks of mammalian hibernation. In this study we cloned FGF21 from the naturally hibernating thirteen-lined ground squirrel (Ictidomys tridecemlineatus and found that levels of FGF21 mRNA in liver and FGF21 protein in serum are elevated during hibernation torpor bouts and significantly elevated during IBAs compared to summer active animals. The effects of artificially elevating circulating FGF21 concentrations 50 to 100-fold via adenoviral-mediated overexpression were examined at three different times of the year. This is the first time that a transgenic approach has been used in a natural hibernator to examine mechanistic aspects of hibernation. Surgically implanted transmitters measured various metrics of the hibernation phenotype over a 7-day period including changes in motor activity, heart rate and core body temperature. In April fed-state animals, FGF21 overexpression decreased blood insulin and free fatty acid concentrations, effects similar to those seen in obese mice. However, elevated FGF21 concentrations did not cause torpor in these fed-state animals nor did they cause torpor or affect metabolic parameters in fasted-state animals in March/April, August or October. We conclude that FGF21 is strongly regulated during torpor and IBA but that its overexpression is not sufficient to cause torpor in naturally hibernating ground squirrels.
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Fajol, Abul; Chen, Hong; Umbach, Anja T; Quarles, L Darryl; Lang, Florian; Föller, Michael
2016-02-01
Glycogen synthase kinase (GSK)-3 is a ubiquitously expressed kinase inhibited by insulin-dependent Akt/PKB/SGK. Mice expressing Akt/PKB/SGK-resistant GSK3α/GSK3β (gsk3(KI)) exhibit enhanced sympathetic nervous activity and phosphaturia with decreased bone density. Hormones participating in phosphate homeostasis include fibroblast growth factor (FGF)-23, a bone-derived hormone that inhibits 1,25-dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol) formation and phosphate reabsorption in the kidney and counteracts vascular calcification and aging. FGF23 secretion is stimulated by the sympathetic nervous system. We studied the role of GSK3-controlled sympathetic activity in FGF23 production and phosphate metabolism. Serum FGF23, 1,25(OH)2D3, and urinary vanillylmandelic acid (VMA) were measured by ELISA, and serum and urinary phosphate and calcium were measured by photometry in gsk3(KI) and gsk3(WT) mice, before and after 1 wk of oral treatment with the β-blocker propranolol. Urinary VMA excretion, serum FGF23, and renal phosphate and calcium excretion were significantly higher, and serum 1,25(OH)2D3 and phosphate concentrations were lower in gsk3(KI) mice than in gsk3(WT) mice. Propranolol treatment decreased serum FGF23 and loss of renal calcium and phosphate and increased serum phosphate concentration in gsk3(KI) mice. We conclude that Akt/PKB/SGK-sensitive GSK3 inhibition participates in the regulation of FGF23 release, 1,25(OH)2D3 formation, and thus mineral metabolism, by controlling the activity of the sympathetic nervous system. © FASEB.
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Yucca Mountain Project bibliography, January--June 1989
International Nuclear Information System (INIS)
1990-01-01
Following a reorganization of the Office of Civilian Radioactive Waste Management, the Yucca Mountain Project was renamed Yucca Mountain Site Characterization Project. The title of this bibliography was also changed to Yucca Mountain Site Characterization Project Bibliography. Prior to August 5, 1988, this project was called the Nevada Nuclear Waste Storage Investigations. This bibliography contains information on this ongoing project that was added to the Department of Energy's Energy Science and Technology Database from January 1990 through June 1990. The bibliography is categorized by principal project participating organization. Participant-sponsored subcontractor reports, papers, and articles are included in the sponsoring organization's list. Another section contains information about publications on the Energy Science and Technology Database that were not sponsored by the project but have some relevance to it
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Fucoidan/FGF-2 induces angiogenesis through JNK- and p38-mediated activation of AKT/MMP-2 signalling
Energy Technology Data Exchange (ETDEWEB)
Kim, Beom Su [Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Bonecell Biotech Inc., 77, Dunsan-dong, Seo-gu, Daejeon 302-830 (Korea, Republic of); Park, Ji-Yun [Bonecell Biotech Inc., 77, Dunsan-dong, Seo-gu, Daejeon 302-830 (Korea, Republic of); Kang, Hyo-Jin [Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kim, Hyung-Jin [Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Lee, Jun, E-mail: omslee@wku.ac.kr [Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Bonecell Biotech Inc., 77, Dunsan-dong, Seo-gu, Daejeon 302-830 (Korea, Republic of)
2014-08-08
Graphical abstract: Schematic diagram of the angiogenic activity mechanism by FGF-2/fucoidan treatment in HUVECs. Fucoidan enhances the FGF-2-induced phosphorylation of p38, JNK, and ERK MAPKs. However, p38 and JNK were involved in AKT phosphorylation and MMP-2 activation and resulted in enhanced angiogenic activity, such as tube formation and migration, in HUVECs. - Highlights: • The angiogenic activity of fucoidan in HUVECs was explored. • Fucoidan enhanced HUVEC proliferation, migration, and tube formation. • Fucoidan enhanced angiogenesis through p38 and JNK but not ERK in HUVECs. • Fucoidan targeted angiogenesis-mediated AKT/MMP-2 signalling in HUVECs. - Abstract: Angiogenesis is an important biological process in tissue development and repair. Fucoidan has previously been shown to potentiate in vitro tube formation in the presence of basic fibroblast growth factor (FGF-2). However, the underlying molecular mechanism remains largely unknown. This study was designed to investigate the action of fucoidan in angiogenesis in human umbilical vein endothelial cells (HUVECs) and to explore fucoidan-signalling pathways. First, we evaluated the effect of fucoidan on cell proliferation. Matrigel-based tube formation and wound healing assays were performed to investigate angiogenesis. Matrix metalloproteinase-2 (MMP-2) mRNA expression and activity levels were analysed by reverse transcription polymerase chain reaction (RT-PCR) and zymography, respectively. Additionally, phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) was detected by Western blot. The results indicate that fucoidan treatment significantly increased cell proliferation in the presence of FGF-2. Moreover, compared to the effect of FGF-2 alone, fucoidan and FGF-2 had a greater effect on tube formation and cell migration, and this effect was found to be synergistic. Furthermore, fucoidan enhanced the phosphorylation of extracellular signal-regulated kinase (ERK
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Fucoidan/FGF-2 induces angiogenesis through JNK- and p38-mediated activation of AKT/MMP-2 signalling
International Nuclear Information System (INIS)
Kim, Beom Su; Park, Ji-Yun; Kang, Hyo-Jin; Kim, Hyung-Jin; Lee, Jun
2014-01-01
Graphical abstract: Schematic diagram of the angiogenic activity mechanism by FGF-2/fucoidan treatment in HUVECs. Fucoidan enhances the FGF-2-induced phosphorylation of p38, JNK, and ERK MAPKs. However, p38 and JNK were involved in AKT phosphorylation and MMP-2 activation and resulted in enhanced angiogenic activity, such as tube formation and migration, in HUVECs. - Highlights: • The angiogenic activity of fucoidan in HUVECs was explored. • Fucoidan enhanced HUVEC proliferation, migration, and tube formation. • Fucoidan enhanced angiogenesis through p38 and JNK but not ERK in HUVECs. • Fucoidan targeted angiogenesis-mediated AKT/MMP-2 signalling in HUVECs. - Abstract: Angiogenesis is an important biological process in tissue development and repair. Fucoidan has previously been shown to potentiate in vitro tube formation in the presence of basic fibroblast growth factor (FGF-2). However, the underlying molecular mechanism remains largely unknown. This study was designed to investigate the action of fucoidan in angiogenesis in human umbilical vein endothelial cells (HUVECs) and to explore fucoidan-signalling pathways. First, we evaluated the effect of fucoidan on cell proliferation. Matrigel-based tube formation and wound healing assays were performed to investigate angiogenesis. Matrix metalloproteinase-2 (MMP-2) mRNA expression and activity levels were analysed by reverse transcription polymerase chain reaction (RT-PCR) and zymography, respectively. Additionally, phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) was detected by Western blot. The results indicate that fucoidan treatment significantly increased cell proliferation in the presence of FGF-2. Moreover, compared to the effect of FGF-2 alone, fucoidan and FGF-2 had a greater effect on tube formation and cell migration, and this effect was found to be synergistic. Furthermore, fucoidan enhanced the phosphorylation of extracellular signal-regulated kinase (ERK
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Demonstration of a PC 25 Fuel Cell in Russia
Energy Technology Data Exchange (ETDEWEB)
John C. Trocciola; Thomas N. Pompa; Linda S. Boyd
2004-09-01
This project involved the installation of a 200kW PC25C{trademark} phosphoric-acid fuel cell power plant at Orgenergogaz, a Gazprom industrial site in Russia. In April 1997, a PC25C{trademark} was sold by ONSI Corporation to Orgenergogaz, a subsidiary of the Russian company ''Gazprom''. Due to instabilities in the Russian financial markets, at that time, the unit was never installed and started by Orgenergogaz. In October of 2001 International Fuel Cells (IFC), now known as UTC Fuel Cells (UTCFC), received a financial assistance award from the United States Department of Energy (DOE) entitled ''Demonstration of PC 25 Fuel Cell in Russia''. Three major tasks were part of this award: the inspection of the proposed site and system, start-up assistance, and installation and operation of the powerplant.
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Directory of Open Access Journals (Sweden)
Rafael Fabiano M. Rosa
2010-09-01
Full Text Available OBJETIVO: Relatar dois pacientes com a síndrome de Emanuel (SE ou cromossomo supernumerário der(22t(11;22, secundária a translocações balanceadas familiares, apresentando fenótipos distintos. DESCRIÇÃO DE CASO: O primeiro paciente é uma menina branca de cinco anos de idade, apresentando hipotonia, atraso no desenvolvimento neuropsicomotor, movimentos estereotipados, microcefalia, ptose palpebral, orelhas proeminentes, fossetas e apêndices pré-auriculares, e imperfuração anal. As avaliações adicionais identificaram hipoplasia cerebral e estenose da válvula pulmonar. Possuía história também de laringotraqueomalácia e fenda palatina. O segundo paciente é um menino branco de seis meses de idade com hipotonia, movimentos coreoatetóticos, déficit de crescimento, microcefalia, microssomia hemifacial, fenda palatina, microtia, apêndices pré-auriculares e polegares proximalmente implantados. A ecocardiografia demonstrou estenose da válvula pulmonar, comunicação interatrial e interventricular, persistência do canal arterial e da veia cava superior esquerda. A radiografia de tórax identificou uma costela cervical. O cariótipo por bandas GTG mostrou a presença, em ambos os pacientes, de um cromossomo adicional der(22t(11;22, secundário a uma translocação balanceada materna no primeiro caso e paterna no segundo caso. COMENTÁRIOS: Apesar de a primeira paciente apresentar achados frequentes da SE, o caso adicional representa a segunda descrição da literatura com um fenótipo de espectro óculo-aurículo-vertebral (EOAV. Assim, ambos salientam a variabilidade clínica observada na SE e a importância da avaliação cariotípica em indivíduos com fenótipo de EOAV.OBEJECTIVE: To report two patients with Emanuel syndrome (ES or supernumerary chromosome der(22t(11;22, secondary to familial balanced translocations, presenting distinct phenotypes. CASES DESCRIPTION: The first patient was a five-year-old white girl presenting
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Van den Eynden, M
1995-01-01
The CERN SPS and LEP PowerPC project is aimed at introducing a new generation of PowerPC VMEbus processor modules running the LynxOS real-time operating system. This new generation of front end computers using the state-of-the-art microprocessor technology will first replace the obsolete Xenix PC based systems (about 140 installations) successfully used since 1988 to control the LEP accelerator. The major issues addressed in the scope of this large scale project are the technical specificatio...
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National Research Council Canada - National Science Library
Wiese, Thomas E; Klassen, R. B
2007-01-01
.... One new project has been developed and is involving students. (3) To establish a long-term collaborative relationship between Xavier University and the TCC in PC research. XU faculty in the program are now members of the Tulane Cancer Center and involved in weekly seminars and focus group meetings.
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National Research Council Canada - National Science Library
Wiese, Thomas E; Klassen, R. B
2008-01-01
.... One new project has been developed and is involving students. (3) To establish a long-term collaborative relationship between Xavier University and the TCC in PC research. XU faculty in the program are now members of the Tulane Cancer Center and involved in weekly seminars and focus group meetings.
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Hamidi, Kordiyeh; Darvish, Jamshid; Matin, Maryam M; Javanmard, Athar Sadat; Kilpatrick, C William
2017-12-01
To date, no studies have examined the tooth formation during developmental stages of brush-tailed mice (Calomyscidae) and true hamsters (Cricetidae). Herein, we compared the timing of tooth morphogenesis and FGF4 expression pattern during development of the first lower molar in Goodwin's brush-tailed mouse, Calomyscus elburzensis with two other muroid rodents; the house mouse, Mus musculus (Muridae), model organism for tooth morphogenesis, and the golden hamster, Mesocricetus auratus which shares great similarities in cusp pattern with brush-tailed mice. All three species were bred in captivity and developing embryos were isolated at different embryonic days (E). Histological evaluation of lower molars was performed and spatiotemporal pattern of FGF4 expression was determined by immunohistochemistry. Results indicated that morphogenesis of the tooth cusps starts at the beginning of the cap stage of the first lower molar (E14 in house mouse, about E11.5 in golden hamster and E22 in Goodwin's brush-tailed mouse). During the cap to bell stage (E15 in house mouse, E12 in golden hamster and at about E24 in Goodwin's brush-tailed mouse), a decrease in the expression of FGF4 was observed in the mesenchyme, except for the cusp tips. According to our observations, the developmental process of the first lower molar formation in Goodwin's brush-tailed mouse began much later as compared with the other two species. Despite the differences in the temporal pattern of molar development between these three members of the same superfamily (Muroidea), the correlation in the expression of FGF4 with specific stages of tooth morphogenesis supported its regulatory function. Anat Rec, 300:2138-2149, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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Maurilo Monteiro Terra; Erasmo José Paioli Pires; Sônia Maria Bonilha Marcondes Coelho; Ilene Ribeiro da Silva Passos; Rui Ribeiro dos Santos; Celso Valdevino Pommer; André Camargo Pereira da Silva; Ivan José Antunes Ribeiro
1990-01-01
Em Monte Alegre do Sul, SP, efetuou-se um experimento de longa duração para observar o comportamento do cultivar IAC 138-22 (Máximo) de uvas para vinho, sobre cinco porta-enxertos: RR 101-14, 'Golia', "Ripária do Traviú', IAC 572 e IAC 313. Em oito colheitas sucessivas anuais, de 1974 a 1981, analisaram-se as produções médias de uvas por planta. Os resultados indicaram que o IAC 572' foi o melhor porta-enxerto para o IAC 138-22 'Máximo'. O IAC 313 superou o IAC 572 em um dos anos estudados. T...
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Evidencias de hidrógenos metilénicos gemínales no equivalentes en RMN
Directory of Open Access Journals (Sweden)
Jaime Bernal Castillo
2009-07-01
Full Text Available Se estudian los espectros de RMP para compuestos del tipo PcSi [OCH(CH2Y2]2 en donde Y = NME2, QEt, NH2 y SH. En cuatro de estas ftalocianinas los protrones metilénicos no son equivalentes. Se demuestra que la agrupación YCH2 CH en los primeros dos derivados constituyen nítidamente un sistema de acoplamiento de espines AMX.
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Redactions in protocols for drug trials: what industry sponsors concealed.
Marquardsen, Mikkel; Ogden, Michelle; Gøtzsche, Peter C
2018-04-01
Objective To describe the redactions in contemporary protocols for industry-sponsored randomised drug trials with patient relevant outcomes and to evaluate whether there was a legitimate rationale for the redactions. Design Cohort study. Under the Freedom of Information Act, we requested access to trial protocols approved by a research ethics committee in Denmark from October 2012 to March 2013. We received 17 consecutive protocols, which had been redacted before we got them, and nine protocols without redactions. In five additional cases, the companies refused to let the committees give us access, and in three other cases, documents were missing. Participants Not applicable. Setting Not applicable. Main outcome measure Amount and nature of redactions in 22 predefined key protocol variables. Results The redactions were most widespread in those sections of the protocol where there is empirical evidence of substantial problems with the trustworthiness of published drug trials: data analysis, handling of missing data, detection and analysis of adverse events, definition of the outcomes, interim analyses and premature termination of the study, sponsor's access to incoming data while the study is running, ownership to the data and investigators' publication rights. The parts of the text that were redacted differed widely, both between companies and within the same company. Conclusions We could not identify any legitimate rationale for the redactions. The current mistrust in industry-sponsored drug trials can only change if the industry offers unconditional access to its trial protocols and other relevant documents and data.
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Directory of Open Access Journals (Sweden)
Oderlei Bernardi
2010-03-01
Full Text Available O objetivo foi avaliar a eficiência de inseticidas à base de nim no controle da mariposa-oriental G. molesta em laboratório. A dieta artificial foi cortada em cubos e imersa nas caldas dos respectivos tratamentos; em seguida, lagartas recém-eclodidas foram transferidas para tubos de vidro, contendo os cubos de dieta tratados. Os produtos testados foram: NeemAzal-T/S®, Dalneem emulsionável®, Organic Neem® e Natuneem Agrícola® na concentração de 0,5% do produto comercial (p.c. em comparação com o inseticida químico fenitrotion (Sumithion 500 CE® a 0,15% p.c. e uma testemunha (água. Os inseticidas NeemAzal-T/S® e Dalneem emulsionável® apresentaram a mortalidade de 100% das lagartas, sendo eficientes no controle do inseto em condições de laboratório. Organic Neem® e Natuneem Agrícola® demonstraram menor atividade inseticida, ocasionando mortalidade de 73,5% e 22,5%, respectivamente; no entanto, afetaram significativamente a viabilidade larval.The objective was to evaluate the efficiency of neem insecticides in the control of oriental fruit moth Grapholita molesta at laboratory. The artificial diet was cut in cubes and immersed in the syrups of the respective treatments, soon afterwards, recently-emerged caterpillars were transferred, for glass tubes, containing the diet cubes treated. The tested products were: NeemAzal-T/S®, Dalneem emulsionável®, Organic Neem® and Natuneem Agrícola® in the concentration of 0.5% of the commercial product (p.c. compared with the chemical insecticide fenitrotion (Sumithion 500 CE® to 0.15% p.c. and a witness (water. The insecticides NeemAzal-T/S® and Dalneem emulsionável® presented a mortality of 100% of the caterpillars being efficient in the control of the insect in laboratory conditions. Organic Neem® and Natuneem Agrícola® demonstrated lower insecticidal activity, causing mortality of 73.5% and 22.5% respectively, however, significantly affect the larval viability.
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Directory of Open Access Journals (Sweden)
Shinya Hayashi
2012-01-01
Full Text Available Fibroblast growth factor 23 (FGF23 was recently identified as an important factor involved in the development of hypophosphatemic rickets and osteomalacia. We experienced a rare case of acute prosthesis migration after hemihip arthroplasty due to FGF23-induced tumor. The patient underwent femoral head replacement because of femoral neck fracture, but prosthesis migration was occurred at 1 week after operation. The patient took various examinations, and FGF23-induced tumor was found in his right wrist. The tumor was resected, and he underwent total hip arthroplasty 8 month later. Finally, he was able to obtain free gait without pain.
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Paradigma Baru Sponsor sebagai Mitra Penyelenggaraan Event
Directory of Open Access Journals (Sweden)
Lidia Evelina
2011-10-01
Full Text Available The goals of this article is to know why sponsorship only to be viewed as sources of funding to implement the public relation events or marketing communication events. Method used in this article is qualitative method research to be based on observation, library study and content analysis. The result of this research seems that change happened in role of sponsorship from only fund source to become a partner of cooperation (mutual symbiotism between sponsor and event organizer. This article exploring the change of sponsorship concept from only looking for sponsor as an activity of fund mobilitation to become a partnership cooperation between event organizer and sponsor company. The mean of sponsor itself beside the fund supporter, they are also a side who takes mutual benefit from the cooperation. Conclusion, any close relationship (mutual benefit between two sides who take cooperation in event implementation (sponsor and event organiser.
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Buckley, C T; Kelly, D J
2012-07-01
MSCs from non-cartilaginous knee joint tissues such as the infrapatellar fat pad (IFP) and synovium possess significant chondrogenic potential and provide a readily available and clinically feasible source of chondroprogenitor cells. Fibroblast growth factor-2 (FGF-2) has been shown to be a potent mitotic stimulator during ex vivo expansion of MSCs, as well as regulating their subsequent differentiation potential. The objective of this study was to investigate the longer term effects of FGF-2 expansion on the functional development of cartilaginous tissues engineered using MSCs derived from the IFP. IFP MSCs were isolated and expanded to passage 2 in a standard media formulation with or without FGF-2 (5 ng/ml) supplementation. Expanded cells were encapsulated in agarose hydrogels, maintained in chondrogenic media for 42 days and analysed to determine their mechanical properties and biochemical composition. Culture media, collected at each feed, was also analysed for biochemical constituents. MSCs expanded in the presence of FGF-2 proliferated more rapidly, with higher cell yields and lower population doubling times. FGF-2 expanded MSCs generated the most mechanically functional tissue. Matrix accumulation was dramatically higher after 21 days for FGF-2 expanded MSCs, but decreased between day 21 and 42. By day 42, FGF-2 expanded MSCs had still accumulated ∼1.4 fold higher sGAG and ∼1.7 fold higher collagen compared to control groups. The total amount of sGAG synthesised (retained in hydrogels and released into the media) was ∼2.4 fold higher for FGF-2 expanded MSCs, with only ∼25% of the total amount generated being retained within the constructs. Further studies are required to investigate whether IFP derived MSCs have a diminished capacity to synthesise other matrix components important in the aggregation, assembly and retention of proteoglycans. In conclusion, expanding MSCs in the presence of FGF-2 rapidly accelerates chondrogenesis in 3D agarose
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Repair of spinal cord injury by implantation of bFGF-incorporated HEMA-MOETACL hydrogel in rats
Chen, Bo; He, Jianyu; Yang, Hao; Zhang, Qian; Zhang, Lingling; Zhang, Xian; Xie, En; Liu, Cuicui; Zhang, Rui; Wang, Yi; Huang, Linhong; Hao, Dingjun
2015-03-01
There is no effective strategy for the treatment of spinal cord injury (SCI). An appropriate combination of hydrogel materials and neurotrophic factor therapy is currently thought to be a promising approach. In this study, we performed experiments to evaluate the synergic effect of implanting hydroxyl ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACL) hydrogel incorporated with basic fibroblast growth factor (bFGF) into the site of surgically induced SCI. Prior to implantation, the combined hydrogel was surrounded by an acellular vascular matrix. Sprague-Dawley rats underwent complete spinal cord transection at the T-9 level, followed by implantation of bFGF/HEMA-MOETACL 5 days after transection surgery. Our results showed that the bFGF/HEMA-MOETACL transplant provided a scaffold for the ingrowth of regenerating tissue eight weeks after implantation. Furthermore, this newly designed implant promoted both nerve tissue regeneration and functional recovery following SCI. These results indicate that HEMA-MOETACL hydrogel is a promising scaffold for intrathecal, localized and sustained delivery of bFGF to the injured spinal cord and provide evidence for the possibility that this approach may have clinical applications in the treatment of SCI.
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Energy Technology Data Exchange (ETDEWEB)
NONE
1993-12-31
This paper delineates the results of the demonstration project for electric energy saving, which is one of the twenty four projects in which the Fideicomiso de Apoyo al Programa de Ahorro de Energia (FIDE) sponsors the diagnosis as well as the applied measures and the measures currently in application. Also the potential opportunity areas and the measures applied and in course of application, as well as the required investments and their recuperation periods. [Espanol] En este trabajo se describen los resultados del proyecto de demostracion de ahorro de energia electrica que es uno de los veinticuatro proyectos, en los que el Fideicomiso de Apoyo al Programa de Ahorro de Energia (FIDE) financia tanto el diagnostico como la aplicacion de medidas. Se presentan tanto las areas de oportunidad, potenciales y medidas aplicadas y en aplicacion, asi como las inversiones requeridas y los periodos de recuperacion de las mismas.
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Energy Technology Data Exchange (ETDEWEB)
NONE
1992-12-31
This paper delineates the results of the demonstration project for electric energy saving, which is one of the twenty four projects in which the Fideicomiso de Apoyo al Programa de Ahorro de Energia (FIDE) sponsors the diagnosis as well as the applied measures and the measures currently in application. Also the potential opportunity areas and the measures applied and in course of application, as well as the required investments and their recuperation periods. [Espanol] En este trabajo se describen los resultados del proyecto de demostracion de ahorro de energia electrica que es uno de los veinticuatro proyectos, en los que el Fideicomiso de Apoyo al Programa de Ahorro de Energia (FIDE) financia tanto el diagnostico como la aplicacion de medidas. Se presentan tanto las areas de oportunidad, potenciales y medidas aplicadas y en aplicacion, asi como las inversiones requeridas y los periodos de recuperacion de las mismas.
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A Guide to Community Shared Solar: Utility, Private, and Non-Profit Project Development (Book)
Energy Technology Data Exchange (ETDEWEB)
Coughlin, J.; Grove, J.; Irvine, L.; Jacobs, J. F.; Johnson Phillips, S.; Sawyer, A.; Wiedman, J.
2012-05-01
This guide is organized around three sponsorship models: utility-sponsored projects, projects sponsored by special purpose entities - businesses formed for the purpose of producing community solar power, and non-profit sponsored projects. The guide addresses issues common to all project models, as well as issues unique to each model.
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Energy Technology Data Exchange (ETDEWEB)
Kabiri, Azadeh, E-mail: z_kabiri@resident.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Esfandiari, Ebrahim, E-mail: esfandiari@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Hashemibeni, Batool, E-mail: hashemibeni@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Kazemi, Mohammad, E-mail: m_kazemi@med.mui.ac.i [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Mardani, Mohammad, E-mail: mardani@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Esmaeili, Abolghasem, E-mail: abesmaeili@yahoo.com [Cell, Molecular and Developmental Biology Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan (Iran, Islamic Republic of)
2012-07-27
Highlights: Black-Right-Pointing-Pointer We investigated effects of FGF-2 on hADSCs. Black-Right-Pointing-Pointer We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. Black-Right-Pointing-Pointer FGF-2 induces chondrogenesis in hADSCs, which Bullet Increasing information will decrease quality if hospital costs are very different. Black-Right-Pointing-Pointer The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.
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International Nuclear Information System (INIS)
Kabiri, Azadeh; Esfandiari, Ebrahim; Hashemibeni, Batool; Kazemi, Mohammad; Mardani, Mohammad; Esmaeili, Abolghasem
2012-01-01
Highlights: ► We investigated effects of FGF-2 on hADSCs. ► We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. ► FGF-2 induces chondrogenesis in hADSCs, which •Increasing information will decrease quality if hospital costs are very different. ► The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.
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Cai, Peng; Peng, Yan; Li, Li; Chu, Wei; Wang, Xukai
2018-01-16
In this case-control study, 246 EH patients and 157 healthy controls were selected from Chinese Han population to explore the associations between the fibroblast growth factor 23 (FGF23) gene polymorphisms and essential hypertension (EH).The SequenomMassarray system was used for the genotyping of three FGF23 gene Tag single-nucleotide polymorphisms, namely rs7955866, rs13312756, and rs3812822. The primers were designed by Assay Designer 3.1 software, and then the samples were added to a 384-well plate for the polymerase chain reaction amplification, shrimp alkaline phosphatase reaction, and desalting after extension. The distributions of the alleles, genotypes, and haplotypes were compared between the two groups. Confounding factors (sex, age, BMI, smoking, and drinking) were adjusted in the non-logistic regression, and the results showed that rs7955866 and rs3812822 polymorphisms were independently associated with the risk of developing EH (P control group showed that carrying rs7955866 A allele (P = 0.031) and rs3812822 C allele (P = 0.025) was associated with the increase of systolic blood pressure (SBP). The insulin (INS) level in the peripheral blood was significantly different between the case and control groups (P = 0.014). After confounding factors were excluded, the results showed that the serum INS level was also an independent risk factor of developing EH (P = 0.044; OR = 1.604, 95%CI: 1.014-2.539). In summary, our results suggest that FGF23 gene polymorphisms are associated with the risk of developing EH in Chinese Han population.
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Directory of Open Access Journals (Sweden)
Pablo Pinillos Marambaia
2013-02-01
Full Text Available O SNOT-22 é um questionário para avaliação da qualidade de vida dos pacientes com rinossinusite crônica (RSC. Ele é largamente utilizado para avaliação do tratamento cirúrgico na RSC. No Brasil, não existem estudos utilizando o SNOT-22 em pacientes não cirúrgicos. OBJETIVO: Avaliar por meio do questionário SNOT-22 a qualidade de indivíduos com rinossinusite crônica sem cirurgia prévia e com indicação de tratamento clínico. MÉTODO: Estudo clínico prospectivo e analítico, tipo corte transversal com controle. Foram dois grupos, sendo um constituído de pacientes com RSC e outro por indivíduos sem doença nasossinusal, adultos, atendidos consecutivamente num serviço de otorrinolaringologia em Salvador, Bahia, de agosto de 2011 a junho de 2012. Todos preencheram o termo de consentimento, um cadastro e o SNOT-22. RESULTADOS: Cento e setenta e seis pacientes, sendo 78 com RSC, e 98 sem a doença. Os grupos foram homogêneos quanto ao gênero, alergias medicamentosas e respiratórias. A idade foi de 40,7 + 13,5 anos no grupo caso e 37,8 + 12,9 no controle (p = 0,26. A mediana do SNOT-22 no grupo caso foi 53 contra 8 do controle (p = 0,001. CONCLUSÃO: A rinossinusite crônica reduz a qualidade de vida do paciente de acordo com o questionário SNOT-22.SNOT-22 is a questionnaire used to assess the quality of life of patients with chronic rhinosinusitis (CRS. It is broadly utilized to assess the surgical treatment of patients with CRS. In Brazil there are no studies utilizing the SNOT-22 in non-surgical patients. OBJECTIVE: To use the SNOT-22 questionnaire to assess the quality of life of individuals with chronic rhinosinusitis without previous surgery and with indication for clinical treatment. METHOD: Prospective and analytical cohort and cross-sectional controlled clinical trial. We had 2 groups, one made up of patients with CRS and another one with adult individuals without the sinonasal disease, consecutively seen in an
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Shao, Minglong; Yu, Lechu; Zhang, Fangfang; Lu, Xuemian; Li, Xiaokun; Cheng, Peng; Lin, Xiufei; He, Luqing; Jin, Shunzi; Tan, Yi; Yang, Hong; Zhang, Chi; Cai, Lu
2015-07-01
The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways. Copyright © 2015 the American Physiological Society.
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CARACTERÍSTICAS DE SALUD PÚBLICA DE ESTUDIANTES DE UNA UNIVERSIDAD PRIVADA DE LA CIUDAD DE MANIZALES
Cerezo Correa, María del Pilar; Vergara Quintero, María del Carmen; Nieto Murillo, Eugenia; Cifuentes Aguirre, Olga Lucia; Parra Sánchez, José Hernán
2011-01-01
Objetivo: analizar las características de salud pública de los estudiantes de una universidad privada de la ciudad de Manizales. Materiales y método: estudio descriptivo, muestreo probabilístico, nivel de confiabilidad del 95%, error del 4,5%, selección aleatoria y distribución proporcional. Tamaño de muestra: 465 estudiantes. Análisis univariado y multivariado. Resultados: el 22% de los estudiantes consume cigarrillo sin diferencias por sexo. El análisis de conglomerados mostró dos grupos bi...
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An overview of the USL/DBMS NASA/PC R and D project working paper series
Dominick, Wayne D. (Editor)
1984-01-01
An introduction is given to the University of Southwestern Louisiana Data Base Management System (USL/DBMS) NASA/PC R and D Working Paper Series which has been established to provide a foundation for both a formal and informal information dissemination mechanism concerning PC-based research and development activities being performed pursuant to the NASA contract. This entry also serves as an index to the collection of Working Paper Series reports.
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Modelling Emotional and Attitudinal Evaluations of Major Sponsors
DEFF Research Database (Denmark)
Martensen, Anne; Hansen, Flemming
2004-01-01
The paper reports findings from a larger study of sponsors and their relationship to sponsoredparties. In the present reporting, the focus is on sponsors. Rather than evaluating suchsponsorships in traditional effect hierarchical terms, a conceptual Sponsor Value Model isspecified as a structural...
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Directory of Open Access Journals (Sweden)
M. Macri Troya
2010-06-01
Full Text Available Introducción: El objetivo del trabajo consiste en conocer la prevalencia de la infección por VIH y las conductas de riesgo asociadas en reclusos alojados en el Complejo Penitenciario de Montevideo en el año 2005. Material y Método: Se analiza de prevalencia de la infección VIH y las distintas prácticas de riesgo en una muestra de 291 individuos abordada mediante un estudio serológico y entrevista personal a partir de un cuestionario estructurado. Resultados: Se halló una prevalencia de 6.5% para la infección VIH en prisión. Las variables que demostraron ser factores de riesgo para la infección VIH en la prisión fueron: poseer antecedentes de haber estado en prisión (p=0,009; OR= 9,51; IC95%: 1,31-144,0, el haber tenido una pareja sexual VIH (+ en el pasado (p=0,000025; OR=7,87; IC95%: 2,58-23,9, el tener actualmente una pareja VIH (+ (p=0,0013; OR=14,24; IC95%:2,84-70,65, haberse inyectado drogas I/V (p=0,0001; OR=22,6; IC95%: 6,87-78,9, el haberse inyectado drogas I/V en la prisión (p=0,03; OR=4,93; IC95%: 1,10-22,81 y la práctica de compartir el material de inyección (p=0,004; OR=12,5; IC95%: 1,72-114,7.Introduction: The aim of this study is to establish the prevalence of HIV infection and associated risk behaviours amongst inmates at the Montevideo Prison in 2005. Materials and Methods: The prevalence of HIV infection and different risk practices were analysed in a sample of 191 individuals by means of a serological study and personal interview based on a structured questionnaire. Results: A prevalence of 6.5% was found for HIV infection in prison. The variables that proved to be risk factors were: previous prison sentences (p=0.009; OR= 9.51; IC95%: 1.31-144,0, having had an HIV (+ sexual partner in the past (p=0.000025; OR=7.87; IC95%: 2.58-23.9, current relationship with an HIV (+ partner (p=0.0013; OR=14.24; IC95%: 2.84-70.65, intravenous drug use (p=0.0001; OR=22.6; IC95%: 6.87-78.9, intravenous drug use in prison (p=0
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Prins, Annabel; Bovin, Michelle J; Smolenski, Derek J; Marx, Brian P; Kimerling, Rachel; Jenkins-Guarnieri, Michael A; Kaloupek, Danny G; Schnurr, Paula P; Kaiser, Anica Pless; Leyva, Yani E; Tiet, Quyen Q
2016-10-01
Posttraumatic Stress Disorder (PTSD) is associated with increased health care utilization, medical morbidity, and tobacco and alcohol use. Consequently, screening for PTSD has become increasingly common in primary care clinics, especially in Veteran healthcare settings where trauma exposure among patients is common. The objective of this study was to revise the Primary Care PTSD screen (PC-PTSD) to reflect the new Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for PTSD (PC-PTSD-5) and to examine both the diagnostic accuracy and the patient acceptability of the revised measure. We compared the PC-PTSD-5 results with those from a brief psychiatric interview for PTSD. Participants also rated screening preferences and acceptability of the PC-PTSD-5. A convenience sample of 398 Veterans participated in the study (response rate = 41 %). Most of the participants were male, in their 60s, and the majority identified as non-Hispanic White. The PC-PTSD-5 was used as the screening measure, a modified version of the PTSD module of the MINI-International Neuropsychiatric Interview was used to diagnose DSM-5 PTSD, and five brief survey items were used to assess acceptability and preferences. The PC-PTSD-5 demonstrated excellent diagnostic accuracy (AUC = 0.941; 95 % C.I.: 0.912- 0.969). Whereas a cut score of 3 maximized sensitivity (κ[1]) = 0.93; SE = .041; 95 % C.I.: 0.849-1.00), a cut score of 4 maximized efficiency (κ[0.5] = 0.63; SE = 0.052; 95 % C.I.: 0.527-0.731), and a cut score of 5 maximized specificity (κ[0] = 0.70; SE = 0.077; 95 % C.I.: 0.550-0.853). Patients found the screen acceptable and indicated a preference for administration by their primary care providers as opposed to by other providers or via self-report. The PC-PTSD-5 demonstrated strong preliminary results for diagnostic accuracy, and was broadly acceptable to patients.
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14 CFR 151.121 - Procedures: Offer; sponsor assurances.
2010-01-01
... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Procedures: Offer; sponsor assurances. 151.121 Section 151.121 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... Engineering Proposals § 151.121 Procedures: Offer; sponsor assurances. Each sponsor must adopt the following...
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The effect of burn on serum concentrations of sclerostin and FGF23.
Klein, Gordon L; Herndon, David N; Le, Phuong T; Andersen, Clark R; Benjamin, Debra; Rosen, Clifford J
2015-11-01
Severe burn results in acute bone resorption followed by an adynamic state, most likely due to changes brought about by the inflammatory and glucocorticoid responses to the injury. There is a consequent increase in annual extrapolated fracture incidence in children. While osteoblasts have been reported to disappear from the bone surface and stem cell differentiation into osteoblasts is impaired, the effect of burns on osteocyte function is unknown. We measured serum concentrations of two osteocyte proteins, sclerostin and fibroblast growth factor (FGF)-23 between 6 and 60 days post-burn in pediatric patients, ages 5-18 years who had participated in a randomized controlled double-blind study of acute administration of pamidronate to prevent the resorptive bone loss. While FGF-23 was undetectable in all samples, the plot of sclerostin concentration versus time post-burn yielded a statistically significant difference between slopes, -2.5 in the placebo control group and +3.5 in the group receiving pamidronate, p=0.016 by ANCOVA. The FGF23 data suggest that osteocytes may be apoptotic, although the sclerostin data may indicate partial preservation of osteocyte function in subjects receiving pamidronate or an ectopic source of sclerostin. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.
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LHX2 Mediates the FGF-to-SHH Regulatory Loop during Limb Development
Directory of Open Access Journals (Sweden)
Billy A. Watson
2018-06-01
Full Text Available During limb development, fibroblast growth factors (Fgfs govern proximal–distal outgrowth and patterning. FGFs also synchronize developmental patterning between the proximal–distal and anterior–posterior axes by maintaining Sonic hedgehog (Shh expression in cells of the zone of polarizing activity (ZPA in the distal posterior mesoderm. Shh, in turn, maintains Fgfs in the apical ectodermal ridge (AER that caps the distal tip of the limb bud. Crosstalk between Fgf and Shh signaling is critical for patterned limb development, but the mechanisms underlying this feedback loop are not well-characterized. Implantation of Fgf beads in the proximal posterior limb bud can maintain SHH expression in the former ZPA domain (evident 3 h after application, while prolonged exposure (24 h can induce SHH outside of this domain. Although temporally and spatially disparate, comparative analysis of transcriptome data from these different populations accentuated genes involved in SHH regulation. Comparative analysis identified 25 candidates common to both treatments, with eight linked to SHH expression or function. Furthermore, we demonstrated that LHX2, a LIM Homeodomain transcription factor, is an intermediate in the FGF-mediated regulation of SHH. Our data suggest that LHX2 acts as a competency factor maintaining distal posterior SHH expression subjacent to the AER.
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Energy Technology Data Exchange (ETDEWEB)
David, A.
1995-12-31
In order to reduce the vulnerability of electronic speed variators to load transients and outages, and more especially to short ones (inferior to one second), which represent 95 pc of voltage drop and failures, Electricite de France (EDF) has developed (and patented) several insensitivity techniques: voltage drop compensation, free-wheel machine speed identification, automatic adjustment and synchronization of converter and machine during the drop. These techniques have been validated through experiments
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Directory of Open Access Journals (Sweden)
Isabel de C.N. Sacco
2004-12-01
Full Text Available FUNDAMENTOS E OBJETIVO: O segmento mais freqüentemente lesado no basquetebol é o tornozelo, sendo a entorse por inversão a lesão mais comum. Para evitá-la, é comum o uso de implementos. O objetivo deste estudo foi avaliar a força reação do solo (FRS em jogadores de basquete durante execução do salto em três situações: uso de tênis, bandagem e tênis, e tênis e órtese tipo Aircast. MÉTODOS: Oito atletas foram analisados durante o salto, através de uma plataforma de força, nas três situações citadas, para análise das componentes vertical e horizontal médio-lateral da FRS. RESULTADOS E CONCLUSÃO: Não houve diferença estatística significativa entre as três situações na componente vertical da FRS durante o salto, embora o uso de bandagem tenda a apresentar, na impulsão, maiores valores do pico de força vertical (3,10 ± 0,46PC; 3,01 ± 0,39PC; 3,03 ± 0,41PC e do gradiente de crescimento (GC (12,33 ± 12,21PC; 8,16 ± 3,89PC; 8,46 ± 3,85PC, e durante a aterrissagem, menores valores de pico de força vertical (5,18 ± 1,35PC; 5,56 ± 1,31PC; 5,49 ± 1,44PC e do GC (88,83 ± 33,85PC; 95,63 ± 42,64PC; 94,53 ± 31,69PC. Durante a impulsão, a força medial do salto com Aircast foi significativamente menor que com tênis (p = 0,0249 e apresentou valor semelhante ao do uso da bandagem, enquanto a força lateral foi significativamente maior com a bandagem do que com tênis (p = 0,0485 e tendeu a ser maior do que o Aircast. Na aterrissagem o componente médio-lateral da FRS ficou inalterado nas três situações. Concluiu-se que a bandagem potencializou a força direcionada ao salto vertical durante a impulsão, porém não estabilizou tanto quanto o Aircast os movimentos de inversão e eversão do pé. Durante a aterrissagem, os implementos não foram efetivos para reduzir a força médio-lateral, mas com a bandagem, houve um tempo maior para absorção do impacto.FUNDAMENTOS Y OBJETIVO: EL segmento mas frecuentemente
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Directory of Open Access Journals (Sweden)
Jorge Díaz Bestard
2008-12-01
Full Text Available La Solución CM-95 tratada magnéticamente es un producto en desarrollo que mostró propiedades inmunoestimulantes en ensayos preclínicos, característica que la hacen adecuada como candidata a inmunopotenciador. En este trabajo se evaluaron los posibles efectos tóxicos preclínicos de la Solución CM-95 tratada magnéticamente, por el método de las Clases de Toxicidad Aguda y el de irritación de la mucosa oral, adaptando las normas OECD 423 y la ISO 10993-10, respectivamente. En el método de las Clases de Toxicidad Aguda se utilizó el ensayo límite, en ratas Sprague Dawley hembras, en el cual la dosis estuvo relacionada con el nivel de inducción magnética, en este caso 0,16 T, aplicado a la Solución CM-95; y el volumen a administrar de la misma, calculado sobre la base de 2 ml de la solución por 100 g de peso corporal. La determinación de la irritación de la mucosa oral se llevó a cabo en hámster Sirios Dorados hembras mediante un ensayo a dosis repetidas durante 7 días de tratamiento en la bolsa gular derecha, con pellet de algodón impregnado con 0,5 ml de la solución tratada magnéticamente con la misma inducción. No se encontró mortalidad ni evidencias de signos tóxicos para el ensayo de toxicidad aguda, y se obtuvo un índice de irritación sobre mucosa oral de 0, por lo que la sustancia estudiada se enmarcó como "No clasificada" y "No irritante" según la metodología empleada. Estos resultados complementarán otros estudios toxicológicos para avalar la seguridad de esta Solución para su uso futuro como fármaco por vía oral.CM-95 solution magnetically treated is a product which showed immunologic properties in preliminary tests, characteristic that makes it adequate as inmunopotentiator candidate. In this study the possible preclinical toxic effects of CM-95 Solution magnetically treated were evaluated, by the Acute Toxicity Class method and oral mucosa irritation test, adapting guideline OECD 423 and ISO 10993
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Farrerons Vidal, Óscar; Marti, Miquel
2013-01-01
Auditoria tècnica del projecte, tenint en compte el Plec de Prescripcions per a l’assistència de la revisió de projectes d’infraestructures per a BIMSA. Aquesta revisió té dos parts, un dedicada a l’auditoria general, i una altra dedicada a l’estructuració informàtica del document.
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Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21
Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.
2014-01-01
The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895
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FGF-2 induces behavioral recovery after early adolescent injury to the motor cortex of rats.
Nemati, Farshad; Kolb, Bryan
2011-11-20
Motor cortex injuries in adulthood lead to poor performance in behavioral tasks sensitive to limb movements in the rat. We have shown previously that motor cortex injury on day 10 or day 55 allow significant spontaneous recovery but not injury in early adolescence (postnatal day 35 "P35"). Previous studies have indicated that injection of basic fibroblast growth factor (FGF-2) enhances behavioral recovery after neonatal cortical injury but such effect has not been studied following motor cortex lesions in early adolescence. The present study undertook to investigate the possibility of such behavioral recovery. Rats with unilateral motor cortex lesions were assigned to two groups in which they received FGF-2 or bovine serum albumin (BSA) and were tested in a number of behavioral tests (postural asymmetry, skilled reaching, sunflower seed manipulation, forepaw inhibition in swimming). Golgi-Cox analysis was used to examine the dendritic structure of pyramidal cells in the animals' parietal (layer III) and forelimb (layer V) area of the cortex. The results indicated that rats injected with FGF-2 (but not BSA) showed significant behavioral recovery that was associated with increased dendritic length and spine density. The present study suggests a role for FGF-2 in the recovery of function following injury during early adolescence. Copyright © 2011 Elsevier B.V. All rights reserved.
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Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway.
Rowe, Peter S N
2012-01-01
More than 300 million years ago, vertebrates emerged from the vast oceans to conquer gravity and the dry land. With this transition, new adaptations occurred that included ingenious changes in reproduction, waste secretion, and bone physiology. One new innovation, the egg shell, contained an ancestral protein (ovocleidin-116) that likely first appeared with the dinosaurs and was preserved through the theropod lineage in modern birds and reptiles. Ovocleidin-116 is an avian homolog of matrix extracellular phosphoglycoprotein (MEPE) and belongs to a group of proteins called short integrin-binding ligand-interacting glycoproteins (SIBLINGs). These proteins are all localized to a defined region on chromosome 5q in mice and chromosome 4q in humans. A unifying feature of SIBLING proteins is an acidic serine aspartate-rich MEPE-associated motif (ASARM). Recent research has shown that the ASARM motif and the released ASARM peptide have regulatory roles in mineralization (bone and teeth), phosphate regulation, vascularization, soft-tissue calcification, osteoclastogenesis, mechanotransduction, and fat energy metabolism. The MEPE ASARM motif and peptide are physiological substrates for PHEX, a zinc metalloendopeptidase. Defects in PHEX are responsible for X-linked hypophosphatemic rickets (HYP). There is evidence that PHEX interacts with another ASARM motif containing SIBLING protein, dentin matrix protein-1 (DMP1). DMP1 mutations cause bone and renal defects that are identical with the defects caused by a loss of PHEX function. This results in autosomal recessive hypophosphatemic rickets (ARHR). In both HYP and ARHR, increased FGF23 expression plays a major role in the disease and in autosomal dominant hypophosphatemic rickets (ADHR), FGF23 half-life is increased by activating mutations. ASARM peptide administration in vitro and in vivo also induces increased FGF23 expression. FGF23 is a member of the fibroblast growth factor (FGF) family of cytokines, which surfaced 500
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The Effect of Burn Injury on Serum Concentrations of Sclerostin and FGF23
Klein, Gordon L; Herndon, David N; Le, Phuong T; Andersen, Clark R; Benjamin, Debra; Rosen, Clifford J
2015-01-01
Severe burn injury results in acute bone resorption followed by an adynamic state, most likely due to changes brought about by the inflammatory and glucocorticoid responses to the injury. There is a consequent increase in annual extrapolated fracture incidence in children. While osteoblasts have been reported to disappear from the bone surface and stem cell differentiation into osteoblasts is impaired, the effect of burns on osteocyte function is unknown. We measured serum concentrations of two osteocyte proteins, sclerostin and fibroblast growth factor (FGF)-23 between 6–60 days post-burn in pediatric patients, ages 5–18 years who had participated in a randomized controlled double-blind study of acute administration of pamidronate to prevent the resorptive bone loss. While FGF-23 was undetectable in all samples, the plot of sclerostin concentration versus time post-burn yielded a statistically significant difference between slopes, −2.5 in the placebo control group and +3.5 in the group receiving pamidronate, p=0.016 by ANCOVA. The FGF23 data suggest that osteocytes may be apoptotic, although the sclerostin data may indicate partial preservation of osteocyte function in subjects receiving pamidronate or an ectopic source of sclerostin. PMID:25922302
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Pérez-Martí, Albert; Garcia-Guasch, Maite; Tresserra-Rimbau, Anna; Carrilho-Do-Rosário, Alexandra; Estruch, Ramon; Salas-Salvadó, Jordi; Martínez-González, Miguel Ángel; Lamuela-Raventós, Rosa; Marrero, Pedro F; Haro, Diego; Relat, Joana
2017-08-01
Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic candidate for the treatment of obesity. Since FGF21 production is regulated by various nutritional factors, we analyze the impact of low protein intake on circulating levels of this growth hormone in mice and in a sub cohort of the PREDIMED (Prevención con Dieta Mediterránea) trial. We also describe the role of hepatic FGF21 in metabolic adaptation to a low-protein diet (LPD). We fed control and liver-specific Fgf21 knockout (LFgf21KO) mice a LPD. This diet increased FGF21 production by inducing its overexpression in liver, and this correlated with a body weight decrease without changes in food intake. The LPD also caused FGF21-dependent browning in subcutaneous white adipose tissue (scWAT), as indicated by an increase in the expression of uncoupling protein 1 (UCP1). In a subgroup of 78 individuals from the PREDIMED trial, we observed an inverse correlation between protein intake and circulating FGF21 levels. Our results reinforce the involvement of FGF21 in coordinating energy homeostasis under a range of nutritional conditions. Moreover, here we describe an approach to increase the endogenous production of FGF21, which if demonstrated functional in humans, could generate a treatment for obesity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Níveis séricos de vitamina D e periodontite crônica em pacientes com doença renal crônica
Directory of Open Access Journals (Sweden)
Jessica do Amaral Bastos
2013-03-01
Full Text Available INTRODUÇÃO A concomitância de periodontite crônica (PC em pacientes com doença renal crônica (DRC tem sido associada a desfechos adversos. A deficiência de vitamina D (25(OHD parece desempenhar papel importante na PC e níveis inadequados de vitamina D têm sido descritos em pacientes com DRC. OBJETIVO: Examinar a relação entre níveis séricos de vitamina D e PC em pacientes com DRC pré-dialítica. MÉTODO: Estudo de caso-controle, definidos, respectivamente, como pacientes com DRC e PC e DRC sem PC. Os dados demográficos, de exame físico e laboratoriais foram obtidos no dia da consulta. A DRC foi definida e estagiada segundo a NKF QDOKI TM. Os níveis séricos de 25(OH D foram dosados por quimioluminescência quando da avaliação da PC, a qual foi caracterizada segundo os critérios de Academia Americana de Periodontologia (1999. Os resultados de 25(OHD foram estratificados em deficiência ( 30 ηg/mL. RESULTADOS: Um total de 29 pacientes foram estudados, 15 no grupo caso e 14 no grupo controle. Os pacientes casos apresentaram mediana de 25(OH D inferior a dos pacientes controles (22,6 vs. 28,6 ηg/mL; p < 0,01. A frequência de pacientes casos com insuficiência/deficiência de vitamina D foi maior do que entre os pacientes controles (93,3% vs. 57,1%, p < 0,004. Por outro lado, o percentual de pacientes com suficiência de vitamina D foi maior entre os controles se comparados aos integrantes do grupo casos (42,9% vs. 6,7%, p < 0,004. CONCLUSÃO: Em pacientes com DRC, a deficiência de vitamina D se associa com PC.
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45 CFR 233.51 - Eligibility of sponsored aliens.
2010-10-01
... 45 Public Welfare 2 2010-10-01 2010-10-01 false Eligibility of sponsored aliens. 233.51 Section... CONDITIONS OF ELIGIBILITY IN FINANCIAL ASSISTANCE PROGRAMS § 233.51 Eligibility of sponsored aliens... affidavit(s) of support or similar agreement on behalf of an alien (who is not the child of the sponsor or...
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AVALIAÇÃO DE CUSTOS DE DOIS MODELOS DE HARVESTER NO CORTE DE EUCALIPTO
Directory of Open Access Journals (Sweden)
Elizabeth Neire da Silva
2014-01-01
Full Text Available The present study aimed to carry through the evaluation of costs of two models of harvester in the wood harvesting of Eucalyptus wood. The research evaluated the 6-year old tree fallen and processing, in the cut-to-length system for two models of harvester, in areas located in the cities of Conceição da Barra,Espírito Santo state and Caravelas, Bahia state. It was evaluated the models of harvester PC-228 SHO and PC-200 LC, of the Komatsu Mark. The information was collected during a period of 6 months, from March to August 2010, by the method of census. It was calculated the operational costs of the two models of harvester , for the countable method, which uses values in ‘Reais’, the Brazilian currency. It was conducted further analysis of cost sensitivity for the elements that contribute most to the final cost. We obtained the operating cost models for PC 200 and PC 228 of R$ 156,95 and R$ 168,84 per effective hour, respectively. In relation with the total operational costs, the most significant costs were: fuel, maintenance, and repairs/ depreciation, with 24.41%, 22.39% and 19.08%, respectively. In the sensitivity analysis, simulating a situation where the company gets a real economy of 10% in each one of these items, the same one will be able to get a reduction in the cost of production in 7%, for the two evaluated machines.
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International Nuclear Information System (INIS)
Anzai, Jun; Kitamura, Masahiro; Nozaki, Takenori; Nagayasu, Toshie; Terashima, Akio; Asano, Taiji; Murakami, Shinya
2010-01-01
Research highlights: → Concomitant use of FGF-2 and β-TCP (an osteo-conductive scaffold) significantly promotes periodontal regeneration in the severe periodontitis model (1-wall defect model) of beagle dog. → FGF-2 enhanced new bone formation via β-TCP at the defects. → In particular, FGF-2 dramatically regenerated new periodontal ligament and cementum formations at the defects, that is one of the most important healing outcomes during the process of periodontal regeneration. → Epithelial downgrowth (undesirable wound healing) was decreased by administration of FGF-2. → This manuscript indicates for the first time that concomitant use of FGF-2 and β-TCP is efficacious in regenerating periodontal tissue following severe destruction of the tissue by progression of periodontitis. -- Abstract: The effects of concomitant use of fibroblast growth factor-2 (FGF-2) and beta-tricalcium phosphate (β-TCP) on periodontal regeneration were investigated in the beagle dog 1-wall periodontal defect model. One-wall periodontal defects were created in the mesial portion of both sides of the mandibular first molars, and 0.3% FGF-2 plus β-TCP or β-TCP alone was administered. Radiographic evaluation was performed at 0, 3, and 6 weeks. At 6 weeks, the periodontium with the defect site was removed and histologically analyzed. Radiographic findings showed that co-administration of FGF-2 significantly increased bone mineral contents of the defect sites compared with β-TCP alone. Histologic analysis revealed that the length of the regenerated periodontal ligament, the cementum, distance to the junctional epithelium, new bone height, and area of newly formed bone were significantly increased in the FGF-2 group. No abnormal inflammatory response or ankylosis was observed in either group. These findings indicate the efficacy of concomitant use of FGF-2 and β-TCP as an osteoconductive material for periodontal regeneration following severe destruction by progressive
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Energy Technology Data Exchange (ETDEWEB)
Anzai, Jun, E-mail: anzai_jun@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Kitamura, Masahiro, E-mail: kitamura@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nozaki, Takenori, E-mail: tnozaki@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nagayasu, Toshie, E-mail: nagayasu_toshie@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Terashima, Akio, E-mail: terashima_akio@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Asano, Taiji, E-mail: asano_taiji@kaken.co.jp [Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042 (Japan); Murakami, Shinya, E-mail: ipshinya@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871 (Japan)
2010-12-17
Research highlights: {yields} Concomitant use of FGF-2 and {beta}-TCP (an osteo-conductive scaffold) significantly promotes periodontal regeneration in the severe periodontitis model (1-wall defect model) of beagle dog. {yields} FGF-2 enhanced new bone formation via {beta}-TCP at the defects. {yields} In particular, FGF-2 dramatically regenerated new periodontal ligament and cementum formations at the defects, that is one of the most important healing outcomes during the process of periodontal regeneration. {yields} Epithelial downgrowth (undesirable wound healing) was decreased by administration of FGF-2. {yields} This manuscript indicates for the first time that concomitant use of FGF-2 and {beta}-TCP is efficacious in regenerating periodontal tissue following severe destruction of the tissue by progression of periodontitis. -- Abstract: The effects of concomitant use of fibroblast growth factor-2 (FGF-2) and beta-tricalcium phosphate ({beta}-TCP) on periodontal regeneration were investigated in the beagle dog 1-wall periodontal defect model. One-wall periodontal defects were created in the mesial portion of both sides of the mandibular first molars, and 0.3% FGF-2 plus {beta}-TCP or {beta}-TCP alone was administered. Radiographic evaluation was performed at 0, 3, and 6 weeks. At 6 weeks, the periodontium with the defect site was removed and histologically analyzed. Radiographic findings showed that co-administration of FGF-2 significantly increased bone mineral contents of the defect sites compared with {beta}-TCP alone. Histologic analysis revealed that the length of the regenerated periodontal ligament, the cementum, distance to the junctional epithelium, new bone height, and area of newly formed bone were significantly increased in the FGF-2 group. No abnormal inflammatory response or ankylosis was observed in either group. These findings indicate the efficacy of concomitant use of FGF-2 and {beta}-TCP as an osteoconductive material for periodontal
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48 CFR 35.017-1 - Sponsoring agreements.
2010-10-01
... of the FFRDC's relationship with its sponsor(s). (3) A provision for the identification of retained earnings (reserves) and the development of a plan for their use and disposition. (4) A prohibition against...
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Marcelin, Geneviève; Jo, Young-Hwan; Li, Xiaosong; Schwartz, Gary J.; Zhang, Ying; Dun, Nae J.; Lyu, Rong-Ming; Blouet, Clémence; Chang, Jaw K.; Chua, Streamson
2013-01-01
Tight control of glucose excursions has been a long-standing goal of treatment for patients with type 2 diabetes mellitus in order to ameliorate the morbidity and mortality associated with hyperglycemia. Fibroblast growth factor (FGF) 19 is a hormone-like enterokine released postprandially that emerged as a potential therapeutic agent for metabolic disorders, including diabetes and obesity. Remarkably, FGF19 treatment has hypoglycemic actions that remain potent in models of genetic and acquir...
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Directory of Open Access Journals (Sweden)
Mohamed Asrih
Full Text Available Beside its beneficial effects on weight loss, ketogenic diet (KD causes dyslipidemia, a pro-inflammatory state involved in the development of hepatic steatosis, glucose intolerance and insulin resistance, although the latter is still being debated. Additionally, KD is known to increase fibroblast growth factor 21 (FGF21 plasma levels. However, FGF21 cannot initiate its beneficial actions on metabolism in these conditions. We therefore hypothesized and tested in the present study that KD may impair FGF21 signaling.Using indirect calorimetry, we found that KD-fed mice exhibited higher energy expenditure than regular chow (RC-fed mice associated with increased Ucp1 levels in white adipose tissue (WAT, along with increased plasma FGF21 levels. We then assessed the effect of KD on FGF21 signaling in both the liver and WAT. We found that Fgfr4 and Klb (β-klotho were downregulated in the liver, while Fgfr1 was downregulated in WAT of KD-fed mice. Because inflammation could be one of the mechanisms linking KD to impaired FGF21 signaling, we measured the expression levels of inflammatory markers and macrophage accumulation in WAT and liver and found an increased inflammation and macrophage accumulation in the liver, but surprisingly, a reduction of inflammation in WAT.We also showed that KD enhances lipid accumulation in the liver, which may explain hepatic inflammation and impaired Fgfr4 and Klb expression. In contrast, import of lipids from the circulation was significantly reduced in WAT of KD-fed mice, as suggested by a downregulation of Lpl and Cd36. This was further associated with reduced inflammation in WAT.Altogether, these results indicate that KD could be beneficial for a given tissue but deleterious for another.
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Ma, Qianli; Mei, Shenglin; Ji, Kun; Zhang, Yumei; Chu, Paul K
2011-08-01
The objective of this study was to form a rapid and firm soft tissue sealing around dental implants that resists bacterial invasion. We present a novel approach to modify Ti surface by immobilizing Ag nanoparticles/FGF-2 compound bioactive factors onto a titania nanotubular surface. The titanium samples were anodized to form vertically organized TiO(2) nanotube arrays and Ag nanoparticles were electrodeposited onto the nanotubular surface, on which FGF-2 was immobilized with repeated lyophilization. A uniform distribution of Ag nanoparticles/FGF-2 was observed on the TiO(2) nanotubular surface. The L929 cell line was used for cytotoxicity assessment. Human gingival fibroblasts (HGFs) were cultured on the modified surface for cytocompatibility determination. The Ag/FGF-2 immobilized samples displayed excellent cytocompatibility, negligible cytotoxicity, and enhanced HGF functions such as cell attachment, proliferation, and ECM-related gene expression. The Ag nanoparticles also exhibit some bioactivity. In conclusion, this modified TiO(2) nanotubular surface has a large potential for use in dental implant abutment. Copyright © 2011 Wiley Periodicals, Inc.
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The Energy Economics of Financial Structuring for Renewable Energy Projects
Rana, Vishwajeet
2011-12-01
This dissertation focuses on the various financial structuring options for the renewable energy sector. The projects in this sector are capital-intensive to build but have relatively low operating costs in the long run when compared to traditional energy resources. The large initial capital requirements tend to discourage investors. To encourage renewable investments the government needs to provide financial incentives. Since these projects ultimately generate returns, the government's monetary incentives go to the sponsors and tax equity investors who build and operate such projects and invest capital in them. These incentives are usually in the form of ITCs, PTCs and accelerated depreciation benefits. Also, in some parts of the world, carbon credits are another form of incentive for the sponsors and equity investors to invest in such turnkey projects. The relative importance of these various considerations, however, differs from sponsor to sponsor, investor to investor and from project to project. This study focuses mainly on the US market, the federal tax benefits and incentives provided by the government. This study focuses on the energy economics that are used for project decision-making and parties involved in the transaction as: Project Developer/Sponsor, Tax equity investor, Debt investor, Energy buyer and Tax regulator. The study fulfils the knowledge gap in the decision making process that takes advantage of tax monetization in traditional after-tax analysis for renewable energy projects if the sponsors do not have the tax capacity to realize the total benefits of the project. A case-study for a wind farm, using newly emerging financial structures, validates the hypothesis that these renewable energy sources can meet energy industry economic criteria. The case study also helps to validate the following hypotheses: a) The greater a sponsor's tax appetite, the tower the sponsor's equity dilution. b) The use of leverage increases the cost of equity financing
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Kamiya, Nobuhiro; Yamaguchi, Ryosuke; Aruwajoye, Olumide; Kim, Audrey J; Kuroyanagi, Gen; Phipps, Matthew; Adapala, Naga Suresh; Feng, Jian Q; Kim, Harry Kw
2017-08-01
Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi-system abnormalities, including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown. This study investigated the role of neurofibromin in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout (Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an osteomalacia-like bone phenotype. Serum FGF23 levels were 4 times increased in cKO mice compared with age-matched controls. In addition, calcium-phosphorus metabolism was significantly altered (calcium reduced; phosphorus reduced; parathyroid hormone [PTH] increased; 1,25(OH) 2 D decreased). Bone histomorphometry showed dramatically increased osteoid parameters, including osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP staining showed a reduced osteoclast number. Micro-CT demonstrated thinner and porous cortical bones in the cKO mice, in which osteocyte dendrites were disorganized as assessed by electron microscopy. Interestingly, the cKO mice exhibited spontaneous fractures in long bones, as found in NF1 patients. Mechanical testing of femora revealed significantly reduced maximum force and stiffness. Immunohistochemistry showed significantly increased FGF23 protein in the cKO bones. Moreover, primary osteocytes from cKO femora showed about eightfold increase in FGF23 mRNA levels compared with control cells. The upregulation of FGF23 was specifically and significantly inhibited by PI3K inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1-deficient osteocytes. Taken together, these results indicate that Nf1 deficiency in osteocytes dramatically increases FGF23 production and causes a mineralization
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DEFF Research Database (Denmark)
Schmal, H; Mehlhorn, A T; Zwingmann, J
2005-01-01
Human epidermal growth factor (hEGF) and basic fibroblast growth factor (bFGF) influence critical characteristics of chondrocytes. The effects on metabolism and differentiation were evaluated following transfection using specific plasmids coding for both cytokines. Chondrocytes were isolated from...... of recombinant hEGF and bFGF resulted in a significant increase in cell proliferation and glucosaminoglycan production. Chondrocytes were transfected with vectors coding for either hEGF or bFGF and the production of these proteins was measured in supernatants by ELISA. Expression kinetics showed different...... patterns: hEGF was detectable 2.5 days following transfection and peaked at day 5.5, whereas bFGF-production reached its maximum 1.5 days after transfection, declining thereafter. Chondrocytes endogenously produced significant amounts of bFGF within 5 days following isolation. Proliferation of h...
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Sivashanmugam, A; Charoenlarp, Pornkawee; Deepthi, S; Rajendran, Arunkumar; Nair, Shantikumar V; Iseki, Sachiko; Jayakumar, R
2017-12-13
For craniofacial bone regeneration, shear-thinning injectable hydrogels are favored over conventional scaffolds because of their improved defect margin adaptability, easier handling, and ability to be injected manually into deeper tissues. The most accepted method, after autografting, is the use of recombinant human bone morphogenetic protein-2 (BMP-2); however, complications such as interindividual variations, edema, and poor cost-efficiency in supraphysiological doses have been reported. The endogenous synthesis of BMP-2 is desirable, and a molecule which induces this is fibroblast growth factor-18 (FGF-18) because it can upregulate the BMP-2 expression by supressing noggin. We developed a chitin-poly(lactide-co-glycolide) (PLGA) composite hydrogel by regeneration chemistry and then incorporated CaSO 4 and FGF-18 for this purpose. Rheologically, a 7-fold increase in the elastic modulus was observed in the CaSO 4 -incorporated chitin-PLGA hydrogels as compared to the chitin-PLGA hydrogel. Shear-thinning Herschel-Bulkley fluid nature was observed for both hydrogels. Chitin-PLGA/CaSO 4 gel showed sustained release of FGF-18. In vitro osteogenic differentiation showed an enhanced alkaline phosphatase (ALP) expression in the FGF-18-containing chitin-PLGA/CaSO 4 gel when compared to cells alone. Further, it was confirmed by studying the expression of osteogenic genes [RUNX2, ALP, BMP-2, osteocalcin (OCN), and osteopontin (OPN)], immunofluorescence staining of BMP-2, OCN, and OPN, and alizarin red S staining. Incorporation of FGF-18 in the hydrogel increased the endothelial cell migration. Further, the regeneration potential of the prepared hydrogels was tested in vivo, and longitudinal live animal μ-CT was performed. FGF-18-loaded chitin-PLGA/CaSO 4 showed early and almost complete bone healing in comparison with chitin-PLGA/CaSO 4 , chitin-PLGA/FGF-18, chitin-PLGA, and sham control systems, as confirmed by hematoxylin and eosin and osteoid tetrachrome stainings
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Pierozan, Paula; Biasibetti, Helena; Schmitz, Felipe; Ávila, Helena; Parisi, Mariana M; Barbe-Tuana, Florencia; Wyse, Angela T S; Pessoa-Pureur, Regina
2016-12-01
QUIN is a glutamate agonist playing a role in the misregulation of the cytoskeleton, which is associated with neurodegeneration in rats. In this study, we focused on microglial activation, FGF2/Erk signaling, gap junctions (GJs), inflammatory parameters and redox imbalance acting on cytoskeletal dynamics of the in QUIN-treated neural cells of rat striatum. FGF-2/Erk signaling was not altered in QUIN-treated primary astrocytes or neurons, however cytoskeleton was disrupted. In co-cultured astrocytes and neurons, QUIN-activated FGF2/Erk signaling prevented the cytoskeleton from remodeling. In mixed cultures (astrocyte, neuron, microglia), QUIN-induced FGF-2 increased level failed to activate Erk and promoted cytoskeletal destabilization. The effects of QUIN in mixed cultures involved redox imbalance upstream of Erk activation. Decreased connexin 43 (Cx43) immunocontent and functional GJs, was also coincident with disruption of the cytoskeleton in primary astrocytes and mixed cultures. We postulate that in interacting astrocytes and neurons the cytoskeleton is preserved against the insult of QUIN by activation of FGF-2/Erk signaling and proper cell-cell interaction through GJs. In mixed cultures, the FGF-2/Erk signaling is blocked by the redox imbalance associated with microglial activation and disturbed cell communication, disrupting the cytoskeleton. Thus, QUIN signal activates differential mechanisms that could stabilize or destabilize the cytoskeleton of striatal astrocytes and neurons in culture, and glial cells play a pivotal role in these responses preserving or disrupting a combination of signaling pathways and cell-cell interactions. Taken together, our findings shed light into the complex role of the active interaction of astrocytes, neurons and microglia in the neurotoxicity of QUIN. Copyright © 2016 Elsevier B.V. All rights reserved.
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Yucca Mountain Site characterization project bibliography, January--June 1991
International Nuclear Information System (INIS)
Lorenz, J.J.; Stephan, P.M.
1991-09-01
Following a reorganization of the Office of Civilian Radioactive Waste Management in 1990, the Yucca Mountain Project was renamed Yucca Mountain Site Characterization Project. The title of this bibliography was also changed to Yucca Mountain Site Characterization Project Bibliography. Prior to August 5, 1988, this project was called the Nevada Nuclear Waste Storage Investigations. This bibliography contains information on this ongoing project that was added to the Department of Energy's Energy Science and Technology Database from January 1991 through June 1991. The bibliography is categorized by principal project participating organization. Participant-sponsored subcontractor reports, papers, and articles are included in the sponsoring organization's list. Another section contains information about publications on the Energy Science and Technology Database that were not sponsored by the project but have some relevance to it
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Yucca Mountain Site Characterization Project bibliography, January--June 1992
International Nuclear Information System (INIS)
1992-01-01
Following a reorganization of the Office of Civilian Radioactive Waste Management in 1990, the Yucca Mountain Project was renamed Yucca Mountain Site Characterization Project. The title of this bibliography was also changed to Yucca Mountain Site Characterization Project Bibliography. Prior to August 5, 1988, this project was called the Nevada Nuclear Waste Storage Investigations. This bibliography contains information on this ongoing project that was added to the Department of Energy's Energy Science and Technology Database from January 1, 1993, through June 30, 1993. The bibliography is categorized by principal project participating organization. Participant-sponsored subcontractor reports, papers, and articles are included in the sponsoring organization's list. Another section contains information about publications on the Energy Science and Technology Database that were not sponsored by the project but have some relevance to it
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Yucca Mountain Site Characterization Project Bibliography, July--December 1990
International Nuclear Information System (INIS)
1991-05-01
Following a reorganization of the Office of Civilian Radioactive Waste Management, the Yucca Mountain Project was renamed Yucca Mountain Site Characterization Project. The title of this bibliography was also changed to Yucca Mountains Site Characterization Project Bibliography. Prior to August 5, 1988, this project was called the Nevada Nuclear Waste Storage Investigations. This bibliography contains information on this ongoing project that was added to the Department of Energy's Energy Science and Technology Database from July 1990 through December 1990. The bibliography is categorized by principal project participating organization. Participant-sponsored subcontractor reports, papers and articles are included in the sponsoring organizations list. Another section contains information about publications on the Energy Science and Technology Database that were not sponsored by the project but have some relevance to it
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Yucca Mountain Site characterization project bibliography, January--June 1992
International Nuclear Information System (INIS)
1992-09-01
Following a reorganization of the Office of Civilian Radioactive Waste Management in 1990, the Yucca Mountain Project was renamed Yucca Mountain Site Characterization Project. The title of this bibliography was also changed to Yucca Mountain Site Characterization Project Bibliography. Prior to August 5, 1988, this project was called the Nevada Nuclear Waste Storage Investigations. This bibliography contains information on this ongoing project that was added to the Department of Energy's Energy Science and Technology Database from January 1, 1992, through June 30, 1992. The bibliography is categorized by principal project participating organization. Participant-sponsored subcontractor resorts, papers, and articles are included in the sponsoring organization's list. Another section contains information about publications on the Energy Science and Technology Database that were not sponsored by the project but have some relevance to it
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Chris B. LeDoux; John E. Baumgras; R. Bryan Selbe
1989-01-01
PROFIT-PC is a menu driven, interactive PC (personal computer) program that estimates optimum product mix and maximum net harvesting revenue based on projected product yields and stump-to-mill timber harvesting costs. Required inputs include the number of trees/acre by species and 2 inches diameter at breast-height class, delivered product prices by species and product...
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International Nuclear Information System (INIS)
Bressan, Raul Bardini; Melo, Fernanda Rosene; Almeida, Patricia Alves; Bittencourt, Denise Avani; Visoni, Silvia; Jeremias, Talita Silva; Costa, Ana Paula; Leal, Rodrigo Bainy; Trentin, Andrea Gonçalves
2014-01-01
Epidermal neural crest stem cells (EPI-NCSCs), which reside in the bulge of hair follicles, are attractive candidates for several applications in cell therapy, drug screening and tissue engineering. As suggested remnants of the embryonic neural crest (NC) in an adult location, EPI-NCSCs are able to generate a wide variety of cell types and are readily accessible by a minimally invasive procedure. Since the combination of epidermal growth factor (EGF) and fibroblast growth factor type 2 (FGF 2 ) is mitogenic and promotes the neuronal commitment of various stem cell populations, we examined its effects in the proliferation and neuronal potential of mouse EPI-NCSCs. By using a recognized culture protocol of bulge whiskers follicles, we were able to isolate a population of EPI-NCSCs, characterized by the migratory potential, cell morphology and expression of phenotypic markers of NC cells. EPI-NCSCs expressed neuronal, glial and smooth muscle markers and exhibited the NC-like fibroblastic morphology. The treatment with the combination EGF and FGF 2 , however, increased their proliferation rate and promoted the acquisition of a neuronal-like morphology accompanied by reorganization of neural cytoskeletal proteins βIII-tubulin and nestin, as well as upregulation of the pan neuronal marker βIII-tubulin and down regulation of the undifferentiated NC, glial and smooth muscle cell markers. Moreover, the treatment enhanced the response of EPI-NCSCs to neurogenic stimulation, as evidenced by induction of GAP43, and increased expression of Mash-1 in neuron-like cell, both neuronal-specific proteins. Together, the results suggest that the combination of EGF–FGF2 stimulates the proliferation and improves the neuronal potential of EPI-NCSCs similarly to embryonic NC cells, ES cells and neural progenitor/stem cells of the central nervous system and highlights the advantage of using EGF–FGF 2 in neuronal differentiation protocols. - Highlights: • EPI-NCSCs express
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International Nuclear Information System (INIS)
Rades, D.; Seibold, N.D.; Gebhard, M.P.; Noack, F.; Schild, S.E.
2014-01-01
Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy. The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95 %-confidence interval (CI): 2.88-19.05; p < 0.001], lower T-category (RR: 2.42; 95 %-CI: 1.47-4.33; p < 0.001), lower N-category (RR: 12.36; 95 %-CI: 3.48-78.91; p < 0.001), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 4.18; 95 %-CI: 1.73-10.53; p = 0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95 %-CI: 0.97-2.82; p = 0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80; p < 0.001), lower T-category (RR: 2.17; 95 %-CI: 1.38-3.68; p < 0.001), lower N-category (RR: 3.86; 95 %-CI: 1.60-10.85; p = 0.002), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 3.20; 95 %-CI: 1.46-7.30; p = 0.004). HPV-positivity showed a trend (RR: 2.36; 95 %-CI: n.a.; p = 0.054). Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials. (orig.)
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Energy Technology Data Exchange (ETDEWEB)
Rades, D.; Seibold, N.D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); Gebhard, M.P.; Noack, F. [University of Luebeck, Institute of Pathology, Luebeck (Germany); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale (United States)
2014-01-15
Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy. The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95 %-confidence interval (CI): 2.88-19.05; p < 0.001], lower T-category (RR: 2.42; 95 %-CI: 1.47-4.33; p < 0.001), lower N-category (RR: 12.36; 95 %-CI: 3.48-78.91; p < 0.001), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 4.18; 95 %-CI: 1.73-10.53; p = 0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95 %-CI: 0.97-2.82; p = 0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80; p < 0.001), lower T-category (RR: 2.17; 95 %-CI: 1.38-3.68; p < 0.001), lower N-category (RR: 3.86; 95 %-CI: 1.60-10.85; p = 0.002), and pre-radiotherapy hemoglobin levels ≥12 g/dl (RR: 3.20; 95 %-CI: 1.46-7.30; p = 0.004). HPV-positivity showed a trend (RR: 2.36; 95 %-CI: n.a.; p = 0.054). Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials. (orig.)
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Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver.
Chukijrungroat, Natsasi; Khamphaya, Tanaporn; Weerachayaphorn, Jittima; Songserm, Thaweesak; Saengsirisuwan, Vitoon
2017-08-01
The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potential mechanisms. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were fed either a control diet or HFFD for 12 wk. Indexes of liver damage and hepatic steatosis were analyzed biochemically and histologically together with monitoring changes in hepatic gene and protein expression. HFFD induced a higher degree of hepatic steatosis in females, with significant increases in proteins involved in hepatic lipogenesis, whereas HFFD significantly induced liver injury, inflammation, and oxidative stress only in males. Interestingly, a significant increase in hepatic fibroblast growth factor 21 (FGF21) protein expression was observed in HFFD-fed males but not in HFFD-fed females. Ovarian hormone deprivation by itself led to a significant reduction in FGF21 with hepatic steatosis, and HFFD further aggravated hepatic fat accumulation in OVX rats. Importantly, estrogen replacement restored hepatic FGF21 levels and reduced hepatic steatosis in HFFD-fed OVX rats. Collectively, our results indicate that male rats are more susceptible to HFFD-induced hepatic inflammation and that the mechanism underlying this sex dimorphism is mediated through hepatic FGF21 expression. Our findings reveal sex differences in the development of HFFD-induced fatty liver and indicate the protective role of estrogen against HFFD-induced hepatic steatosis. Copyright © 2017 the American Physiological Society.
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Fgf signaling controls pharyngeal taste bud formation through miR-200 and Delta-Notch activity.
Kapsimali, Marika; Kaushik, Anna-Lila; Gibon, Guillaume; Dirian, Lara; Ernest, Sylvain; Rosa, Frederic M
2011-08-01
Taste buds, the taste sensory organs, are conserved in vertebrates and composed of distinct cell types, including taste receptor, basal/presynaptic and support cells. Here, we characterize zebrafish taste bud development and show that compromised Fgf signaling in the larva results in taste bud reduction and disorganization. We determine that Fgf activity is required within pharyngeal endoderm for formation of Calb2b(+) cells and reveal miR-200 and Delta-Notch signaling as key factors in this process. miR-200 knock down shows that miR-200 activity is required for taste bud formation and in particular for Calb2b(+) cell formation. Compromised delta activity in mib(-/-) dramatically reduces the number of Calb2b(+) cells and increases the number of 5HT(+) cells. Conversely, larvae with increased Notch activity and ascl1a(-/-) mutants are devoid of 5HT(+) cells, but have maintained and increased Calb2b(+) cells, respectively. These results show that Delta-Notch signaling is required for intact taste bud organ formation. Consistent with this, Notch activity restores Calb2b(+) cell formation in pharyngeal endoderm with compromised Fgf signaling, but fails to restore the formation of these cells after miR-200 knock down. Altogether, this study provides genetic evidence that supports a novel model where Fgf regulates Delta-Notch signaling, and subsequently miR-200 activity, in order to promote taste bud cell type differentiation.
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Directory of Open Access Journals (Sweden)
José Carneiro Leão Filho
2003-12-01
Full Text Available Trata-se de estudo do tipo observacional, de corte transversal, para descrever as características antropométricas e proporcionalidade corporal de 549 recém-nascidos a termo (RNT. As medidas antropométricas usadas foram: peso (P, comprimento (C, perímetro cefálico (PC, índice ponderal de Rohrer (IP, razão peso/perímetro cefálico (P/PC e razão comprimento/ perímetro cefálico (C/PC. Também foi estudada a severidade do retardo de crescimento intra-uterino (RCIU, através da distribuição do escore z quanto ao desvio do peso ao nascer. Os recém-nascidos pequenos para idade gestacional (PIG foram definidos como aqueles com escore z < -2, e o ponto de corte do IP, P/PC e C/PC foi definido como a média menos 1 desvio-padrão na população local de referência. De acordo com o IP, 72,8% dos PIG e 12,8% dos adequados para idade gestacional (AIG foram classificados como desproporcionais. Segundo o C/PC, 25,6% dos PIG e 11,6% dos AIG foram classificados como desproporcionais, o que ocorreu com todos os PIG e 16,3% dos AIG quando se usou a P/PC. Em todos os critérios, observou-se tendência linear significativa para aumento da desproporcionalidade à medida que aumenta o grau de severidade do RCIU.
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Directory of Open Access Journals (Sweden)
Leão Filho José Carneiro
2003-01-01
Full Text Available Trata-se de estudo do tipo observacional, de corte transversal, para descrever as características antropométricas e proporcionalidade corporal de 549 recém-nascidos a termo (RNT. As medidas antropométricas usadas foram: peso (P, comprimento (C, perímetro cefálico (PC, índice ponderal de Rohrer (IP, razão peso/perímetro cefálico (P/PC e razão comprimento/ perímetro cefálico (C/PC. Também foi estudada a severidade do retardo de crescimento intra-uterino (RCIU, através da distribuição do escore z quanto ao desvio do peso ao nascer. Os recém-nascidos pequenos para idade gestacional (PIG foram definidos como aqueles com escore z < -2, e o ponto de corte do IP, P/PC e C/PC foi definido como a média menos 1 desvio-padrão na população local de referência. De acordo com o IP, 72,8% dos PIG e 12,8% dos adequados para idade gestacional (AIG foram classificados como desproporcionais. Segundo o C/PC, 25,6% dos PIG e 11,6% dos AIG foram classificados como desproporcionais, o que ocorreu com todos os PIG e 16,3% dos AIG quando se usou a P/PC. Em todos os critérios, observou-se tendência linear significativa para aumento da desproporcionalidade à medida que aumenta o grau de severidade do RCIU.
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STREAK CAMERA MEASUREMENTS OF THE APS PC GUN DRIVE LASER
Energy Technology Data Exchange (ETDEWEB)
Dooling, J. C.; Lumpkin, A. H.
2017-06-25
We report recent pulse-duration measurements of the APS PC Gun drive laser at both second harmonic and fourth harmonic wavelengths. The drive laser is a Nd:Glass-based chirped pulsed amplifier (CPA) operating at an IR wavelength of 1053 nm, twice frequency-doubled to obtain UV output for the gun. A Hamamatsu C5680 streak camera and an M5675 synchroscan unit are used for these measurements; the synchroscan unit is tuned to 119 MHz, the 24th subharmonic of the linac s-band operating frequency. Calibration is accomplished both electronically and optically. Electronic calibration utilizes a programmable delay line in the 119 MHz rf path. The optical delay uses an etalon with known spacing between reflecting surfaces and is coated for the visible, SH wavelength. IR pulse duration is monitored with an autocorrelator. Fitting the streak camera image projected profiles with Gaussians, UV rms pulse durations are found to vary from 2.1 ps to 3.5 ps as the IR varies from 2.2 ps to 5.2 ps.
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Pallesen, Lars-Peder; Gerber, Johannes; Dzialowski, Imanuel; van der Hoeven, Erik J R J; Michel, Patrik; Pfefferkorn, Thomas; Ozdoba, Christoph; Kappelle, L Jaap; Wiedemann, Baerbel; Khomenko, Andrei; Algra, Ale; Hill, Michael D; von Kummer, Ruediger; Demchuk, Andrew M; Schonewille, Wouter J; Puetz, Volker
2015-01-01
The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality. Copyright © 2014 by the American Society of Neuroimaging.
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Directory of Open Access Journals (Sweden)
Shusaku Uchida
2017-01-01
Full Text Available Summary: Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription cofactor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner. After both weak and strong training, the HDAC3-N-CoR corepressor complex leaves the Fgf1b promoter and a complex involving the translocated CRTC1, phosphorylated CREB, and histone acetyltransferase CBP induces transient transcription. Strong training later substitutes KAT5 for CBP, a process that is dependent on CRTC1, but not on CREB phosphorylation. This in turn leads to long-lasting Fgf1b transcription and memory enhancement. Thus, memory strength relies on activity-dependent changes in chromatin and temporal regulation of gene transcription on specific CREB/CRTC1 gene targets. : Uchida et al. link CRTC1 synapse-to-nucleus shuttling in memory. Weak and strong training induce CRTC1 nuclear transport and transient Fgf1b transcription by a complex including CRTC1, CREB, and histone acetyltransferase CBP, whereas strong training alone maintains Fgf1b transcription through CRTC1-dependent substitution of KAT5 for CBP, leading to memory enhancement. Keywords: memory enhancement, long-term potentiation, hippocampus, nuclear transport, epigenetics, FGF1, CRTC1, KAT5/Tip60, HDAC3, CREB
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DEFF Research Database (Denmark)
Ghoussaini, Maya; French, Juliet D; Michailidou, Kyriaki
2016-01-01
expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers......, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis....
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Directory of Open Access Journals (Sweden)
Claudia Ramírez Cano
2014-06-01
Full Text Available En el municipio de Puerto Wilches el monocultivo de palma africana actualmente es un eje trasversal de la economía, modificando la diversidad de los ecosistemas y cultivos tradicionales de la zona. Por lo cual, el objetivo de esta investigación es medir y evaluar los impactos de los cultivos de palma africana en el lapso de 1987 a 2010 adaptando la metodología desarrollada por Mathis Wackernagel y William Rees y algunos aportes de los desarrollos realizados por Juan Luis Doménech, aunando a estos tecnología satelital e indicadores de biocapacidad y déficit ecológico para conocer los requerimientos de espacios y recursos naturales necesarios para la producción de los derivados de la palma. El análisis de la época arrojó para el año 1987 un indicador de huella ecológica con un valor de 1.255 ha/pc, biocapacidad del cultivo 0.470 ha/pc, déficit ecológico correspondiente a -0.785 ha/pc; se estima un valor del 16 % en cuanto a la producción y uso de recursos. Con relación a los indicadores de sostenibilidad, en 2010 se obtuvieron valores de huella ecológica de 5.492 ha/pc, biocapacidad 1.454 ha/pc y déficit ecológico de -4.038 ha/pc, cifras que evidencian los efectos originados por la implementación del monocultivo en la zona, que para la fecha aumento en un 63 % la producción y uso de recursos naturales. Por lo anterior, es necesario y urgente elaborar e implementar políticas de planificación territorial así como alternativas de producción económica para mejorar la calidad ambiental y social del municipio, deteniendo la acelerada antropización de la región.
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Directory of Open Access Journals (Sweden)
César Henríquez Camacho
2002-04-01
Full Text Available Objetivo: Determinar la incidencia y factores de riesgo para adquirir diarrea aguda en una comunidad rural localizada en la selva del departamento de San Martín, Perú. Material y métodos: Una cohorte de 119 personas fue seleccionada al azar entre la población de 446 habitantes y seguida diariamente por un mes entre enero y febrero de 1999, buscando casos de diarrea aguda, definida como tres ó más cámaras de deposiciones al día por no más de 3 días. Un estudio caso control pareado fue diseñado para determinar los factores de riesgo para adquirir diarrea. Resultados: Fueron observados 18 casos de diarrea aguda; la incidencia fue 15.1 casos por 100 personas-mes (IC 95%: 9.45-23.12. La edad media de los casos fue de 10.7 años (rango: 1-34 años y 66% de los casos fueron niños menores de 10 años de edad. Los factores de riesgo para adquirir diarrea fueron: consumo de alimentos crudos, RR: 2.2 (IC 95%: 1.12-4.33, consumo de alimentos no lavados, RR: 4.47 (IC 95%: 1.56-12.82, falta de lavado de manos antes de alimentarse, RR: 9.61 (95% IC: 1.44-64.16, consumo de agua no hervida, RR: 4.52 (IC 95%: 1.23-16.65 y alimentación fuera de casa, RR: 2.2 (IC 95%: 1.51-3.20. La diferencia en el número promedio (DE de personas que vivían por casa entre casos y controles fue de 4.38 (1.03 vs. 3.22 (0.54, p=0.0003, respectivamente. No hubo diferencia en el tiempo de residencia en la comunidad entre casos y controles, media de 5.61 ( 5.04 años vs. 8.83 (9.79, p=0.5747. Conclusiones: Diarrea aguda es un problema de salud pública en la selva de San Martín. Hacinamiento, carencia de saneamiento y pobres prácticas higiénicas son los responsables para adquirir diarrea aguda en esta comunidad de bajo nivel socioeconómico. Campañas educativas y mejora en las condiciones sanitarias son claramente necesarias para superar este problema.
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22 CFR 62.27 - Alien physicians.
2010-04-01
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Alien physicians. 62.27 Section 62.27 Foreign... Provisions § 62.27 Alien physicians. (a) Purpose. Pursuant to the Mutual Educational and Cultural Exchange... Foreign Medical Graduates must sponsor alien physicians who wish to pursue programs of graduate medical...
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AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle.
Kim, Young-Chae; Seok, Sunmi; Byun, Sangwon; Kong, Bo; Zhang, Yang; Guo, Grace; Xie, Wen; Ma, Jian; Kemper, Byron; Kemper, Jongsook Kim
2018-02-07
Phosphatidylcholines (PC) and S-adenosylmethionine (SAM) are critical determinants of hepatic lipid levels, but how their levels are regulated is unclear. Here, we show that Pemt and Gnmt, key one-carbon cycle genes regulating PC/SAM levels, are downregulated after feeding, leading to decreased PC and increased SAM levels, but these effects are blunted in small heterodimer partner (SHP)-null or FGF15-null mice. Further, aryl hydrocarbon receptor (AhR) is translocated into the nucleus by insulin/PKB signaling in the early fed state and induces Pemt and Gnmt expression. This induction is blocked by FGF15 signaling-activated SHP in the late fed state. Adenoviral-mediated expression of AhR in obese mice increases PC levels and exacerbates steatosis, effects that are blunted by SHP co-expression or Pemt downregulation. PEMT, AHR, and PC levels are elevated in simple steatosis patients, but PC levels are robustly reduced in steatohepatitis-fibrosis patients. This study identifies AhR and SHP as new physiological regulators of PC/SAM levels.
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Directory of Open Access Journals (Sweden)
Jorge R. Moll
2007-12-01
Full Text Available JUSTIFICATIVA E OBJETIVOS: A Resolução 1.355/92 do Conselho Federal de Medicina aprovou os padrões mínimos para instalação e funcionamento das usinas concentradoras de oxigênio (P.S.A. e recomendou que os hospitais universitários fizessem análise prospectiva, permitindo o aperfeiçoamento do sistema, o que motivou a realização deste estudo piloto, cujo objetivo foi estudar a viabilidade clínica do uso do oxigênio proveniente das P.S.A., por meio da análise da variação da concentração de oxigênio no fluxo de gás fresco e da fração inspirada de oxigênio. MÉTODO: Estudo observacional, 30 pacientes ASA I, submetidos a cirurgias do abdome superior, utilizando-se sistema com absorvedor de CO2 e fluxo de gases frescos (FGF de O(293 500 mL.min-1. Foram avaliadas as variáveis peso, idade, tipo e tempo dos procedimentos cirúrgicos; fração inspirada e expirada do CO2 (FiCO2, P ET CO2; fração inspirada O2 (FiO2 e concentração O2 (O2ent do FGF. As variáveis P ET CO2, FiO2 e O2ent foram medidas após a intubação e a cada 10 minutos até o final da anestesia. Os resultados foram submetidos a tratamento estatístico, considerando-se significativo p JUSTIFICATIVA Y OBJETIVOS: La Resolución 1355/92, del Conselho Federal de Medicina aprobó los estándares mínimos para la instalación y el funcionamiento de las fábricas concentradoras de oxígeno (P.S.A. y recomendó que los Hospitales Universitarios hiciesen un análisis prospectivo, permitiendo el perfeccionamiento del sistema, lo que motivó la realización de este estudio piloto, cuyo objetivo fue el de estudiar la viabilidad clínica del uso del oxígeno proveniente de las P.S.A., por medio del análisis de la variación de la concentración de oxígeno en el flujo de gas fresco y de la fracción inspirada de oxígeno. MÉTODO: Estudio de observación, 30 pacientes ASA I, sometidos a cirugías del abdomen superior, utilizando sistema con absorvedor de CO2 y flujo de gases
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Comparative Evaluation of TRAIL, FGF-2 and VEGF-A-Induced Angiogenesis In Vitro and In Vivo.
Cartland, Siân P; Genner, Scott W; Zahoor, Amna; Kavurma, Mary M
2016-12-02
Tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL) has been implicated in angiogenesis; the growth of new blood vessels from an existing vessel bed. Our aim was to compare pro-angiogenic responses of TRAIL, vascular endothelial growth-factor-A (VEGF-A) and fibroblast growth-factor-2 (FGF-2) either separately (10 ng/mL) or in combination, followed by the assessment of proliferation, migration and tubule formation using human microvascular endothelial-1 (HMEC-1) cells in vitro. Angiogenesis was also measured in vivo using the Matrigel plug assay. TRAIL and FGF-2 significantly augmented HMEC-1 cell proliferation and migration, with combination treatment having an enhanced effect on cell migration only. In contrast, VEGF-A did not stimulate HMEC-1 migration at 10 ng/mL. Tubule formation was induced by all three factors, with TRAIL more effective compared to VEGF-A, but not FGF-2. TRAIL at 400 ng/mL, but not VEGF-A, promoted CD31-positive staining into the Matrigel plug. However, FGF-2 was superior, stimulating cell infiltration and angiogenesis better than TRAIL and VEGF-A in vivo. These findings demonstrate that each growth factor is more effective at different processes of angiogenesis in vitro and in vivo. Understanding how these molecules stimulate different processes relating to angiogenesis may help identify new strategies and treatments aimed at inhibiting or promoting dysregulated angiogenesis in people.
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International Nuclear Information System (INIS)
Roettger, R.; Bueger, J. de; Schoots, T.
1977-01-01
A large variety of HTR fuel specimens, loose coated particles, coupons and compacts provided by Belgonucleaire, the Dragon Project and the KFA Juelich have been irradiated in the HFR at Petten at about 900 0 C up to a maximum fast neutron fluence of about 7x10 21 cm -2 (EDN) as a Euratom sponsored experiment. The maximum burn-ups were between 11 and 18.5% FIMA. The results of the post-irradiation examinations, comprising visual inspection, dimensional measurements, microradiography, metallography, and burn-up determinations are presented in this part 2 of the final report. The examinations have shown that the endurance limit of most of the tested fuel varieties is beyond the reached irradiation values
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Escoté, Xavier; Félix-Soriano, Elisa; Gayoso, Lucía; Huerta, Ana Elsa; Alvarado, María Antonella; Ansorena, Diana; Astiasarán, Iciar; Martínez, J Alfredo; Moreno-Aliaga, María Jesús
2018-05-23
FGF21 has emerged as a key metabolism and energy homeostasis regulator. Dietary supplementation with eicosapentaenoic acid (EPA) and/or α-lipoic acid (LIP) has shown beneficial effects on obesity. In this study, we evaluated EPA and/or LIP effects on plasma FGF21 and the fatty acid (FA) profile in overweight/obese women following hypocaloric diets. At the baseline, FGF21 levels were negatively related to the AST/ALT ratio and HMW adiponectin. The weight loss did not cause any significant changes in FGF21 levels, but after the intervention FGF21 increased in EPA-supplemented groups compared to non-EPA-supplemented groups. EPA supplementation decreased the plasma n-6-PUFA content and increased n-3-PUFAs, mainly EPA and DPA, but not DHA. In the LIP-alone supplemented group a decrease in the total SFA and n-6-PUFA content was observed after the supplementation. Furthermore, EPA affected the desaturase activity, lowering Δ4D and raising Δ5/6D. These effects were not observed in the LIP-supplemented groups. Besides, the changes in FGF21 levels were associated with the changes in EPA, n-3-PUFAs, Δ5/6D, and n-6/n-3 PUFA ratio. Altogether, our study suggests that n-3-PUFAs influence FGF21 levels in obesity, although the specific mechanisms implicated remain to be elucidated.
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Directory of Open Access Journals (Sweden)
Oscar Olivares Paulette
2016-03-01
Full Text Available El crecimiento de juveniles de pargo mancha (Lutjanus guttatus, peso inicial 42g, coeficiente de variación 13,8%, alimentados con alimento granulado, se evaluó en dependencia de la ración por un período de 14 días: Se aplicaron 5 tasas de alimentación entre 0 y 5% del peso corporal/día. La tasa de crecimiento específica aumentó desde valores negativos en ayunas (-0,32% PC/día hasta un máximo de 2,05% PC/día. La tasa óptima de crecimiento se estimó en 1,09% PC/día. El factor de conversión en condiciones de crecimiento óptimo y máximo fue de 0,94 y 1,86, respectivamente.
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Nocardial infections: report of 22 cases Infecções por Nocardia species: relato de 22 casos
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Maria Bernadete F. Chedid
2007-08-01
Full Text Available Twenty-two cases of nocardial infections were diagnosed in our city between 1977- 1998. All patients whose clinical specimens showed Nocardia spp. at Gram stain, which were further confirmed by culture, were selected to be included in the study. Data from patients who were cured were compared with those from patients who died by statistical tests using EPIINFO version 6.04 software. Six isolates were identified as Nocardia asteroides complex, one as Nocardia asteroides sensu stricto and other as Nocardia brasiliensis. We had 17 cases of lung nocardiosis, being one out of them also a systemic disease. Other four cases of systemic nocardiosis were diagnosed: nocardial brain abscesses (one; nocardiosis of the jejunum (one; multiple cutaneous abscesses (one; and a case of infective nocardial endocarditis of prosthetic aortic valve. One patient had a mycetoma by N. brasiliensis. Fifteen (68.2% out of 22 patients were immunosuppressed, being most (93.3% by high-doses corticotherapy. Mortality by nocardial infection was 41%; mortality of systemic nocardiosis was 60%. Nocardiosis has a bad prognosis in immunosuppressed patients and also in non-immunosuppressed patients if the diagnosis is delayed. We propose that the delay in diagnosis should be examined in larger series to document its influence in the prognosis of the disease.São apresentados 22 casos de infecção por Nocardia species entre 1977 e 1998, apresentando-se seu quadro clínico e evolução. Todos os pacientes cujos espécimes clínicos mostraram microorganismos sugestivos de Nocardia spp. à coloração de Gram, confirmados posteriormente por cultura, foram incluídos no estudo. Os dados dos pacientes que obtiveram cura foram comparados com aqueles dos pacientes que foram a óbito pelo programa EPIINFO versão 6.04; nível de significância menor que 5% foi considerado estatisticamente significativo. Foram obtidos 22 casos de infecção por Nocardia spp.: seis isolamentos identificados