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Sample records for gdf experience le

  1. GDF v2.0, an enhanced version of GDF

    NASA Astrophysics Data System (ADS)

    Tsoulos, Ioannis G.; Gavrilis, Dimitris; Dermatas, Evangelos

    2007-12-01

    -output functions and it can be used for classification problems. Summary of revisions: The following features have been added to the package GDF: Multi-output function approximation. The package can now approximate any function f:R→R. This feature gives also to the package the capability of performing classification and not only regression. User defined function can be added to the repertoire of the grammar, extending the regression capabilities of the package. This feature is limited to 3 functions, but easily this number can be increased. Capability of selecting the error function. The package offers now to the user apart from the mean square error other error functions such as: mean absolute square error, maximum square error. Also, user defined error functions can be added to the set of error functions. More verbose output. The main program displays more information to the user as well as the default values for the parameters. Also, the package gives to the user the capability to define an output file, where the output of the gdf program for the testing set will be stored after the termination of the process. Additional comments: A technical report describing the revisions, experiments and test runs is packaged with the source code. Running time: Depending on the train data.

  2. Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity.

    PubMed

    Sándor, Nikolett; Schilling-Tóth, Boglárka; Kis, Enikő; Benedek, Anett; Lumniczky, Katalin; Sáfrány, Géza; Hegyesi, Hargita

    2015-11-01

    We have investigated the importance of GDF-15 (secreted cytokine belonging to the TGF-β superfamily) in low and high dose radiation-induced cellular responses. A telomerase immortalized human fibroblast cell line (F11hT) was used in the experiments. A lentiviral system encoding small hairpin RNAs (shRNA) was used to establish GDF-15 silenced cells. Secreted GDF-15 levels were measured in culture medium by ELISA. Cell cycle analysis was performed by flow cytometry. The experiments demonstrated that in irradiated human fibroblasts GDF-15 expression increased with dose starting from 100mGy. Elevated GDF-15 expression was not detected in bystander cells. The potential role of GDF-15 in radiation response was investigated by silencing GDF-15 in immortalized human fibroblasts with five different shRNA encoded in lentiviral vectors. Cell lines with considerably reduced GDF-15 levels presented increased radiation sensitivity, while a cell line with elevated GDF-15 was more radiation resistant than wild type cells. We have investigated how the reduced GDF-15 levels alter the response of several known radiation inducible genes. In F11hT-shGDF-15 cells the basal expression level of CDKN1A was unaltered relative to F11hT cells, while GADD45A and TGF-β1 mRNA levels were slightly higher, and TP53INP1 was considerably reduced. The radiation-induced expression of TP53INP1 was lower in the silenced than in wild type fibroblast cells. Cell cycle analysis indicated that radiation-induced early G2/M arrest was abrogated in GDF-15 silenced cells. Moreover, radiation-induced bystander effect was less pronounced in GDF-15 silenced fibroblasts. In conclusion, the results suggest that GDF-15 works as a radiation inducible radiation resistance increasing factor in normal human fibroblast cells, acts by regulating the radiation-induced transcription of several genes and might serve as a radiation-induced early biomarker in exposed cells. PMID:26520384

  3. Association of plasma GDF-9 or GDF-15 levels with bone parameters in polycystic ovary syndrome.

    PubMed

    Berberoglu, Zehra; Aktas, Aynur; Fidan, Yasemin; Yazici, Ayse Canan; Aral, Yalcin

    2015-01-01

    We aimed to determine plasma levels of growth and differentiation factor (GDF)-9 and GDF-15, and their possible association with bone turnover parameters and bone mineral density (BMD), in patients with polycystic ovary syndrome (PCOS). Forty-two obese PCOS women aged 25-35 years, 23 women with idiopathic hirsutism (IH) and 20 healthy controls matched for age and body mass index were enrolled. Anthropometric, metabolic and hormonal patterns, plasma GDF-9 and GDF-15 concentrations, bone turnover markers and BMD were measured. No significant differences were observed in bone turnover markers, BMD measurements, plasma GDF-9 and GDF-15 levels in subjects with PCOS compared with the other two groups. In the combined population of all three groups, GDF-15 concentrations were negatively correlated with osteocalcin (r = -0.317, p < 0.01). Analysis of PCOS patients showed a significant correlation of GDF-15 concentrations with age and homeostasis model assessment index (r = 0.319, p < 0.05, and r = 0.312, p < 0.05, respectively). In addition, GDF-15 concentrations were negatively correlated with osteocalcin (r = -0.395, p < 0.01) and positively correlated with urine deoxypyridinoline (r = 0.353, p < 0.05). GDF-9 did not correlate with bone markers and BMD measurements. In conclusion, plasma GDF-9 and GDF-15 levels as well as bone turnover markers and BMD measurements in subjects with PCOS (25-35 years of age) were comparable with those either in subjects with IH or in healthy controls with similar anthropometric and metabolic profiles. GDF-15 might be a marker of a crossregulation between bone and energy metabolism. PMID:24430093

  4. Crystal structure of human GDF11.

    PubMed

    Padyana, Anil K; Vaidialingam, Bhamini; Hayes, David B; Gupta, Priyanka; Franti, Michael; Farrow, Neil A

    2016-03-01

    Members of the TGF-β family of proteins are believed to play critical roles in cellular signaling processes such as those involved in muscle differentiation. The extent to which individual family members have been characterized and linked to biological function varies greatly. The role of myostatin, also known as growth differentiation factor 8 (GDF8), as an inhibitor of muscle differentiation is well understood through genetic linkages. In contrast, the role of growth differentiation factor 11 (GDF11) is much less well understood. In humans, the mature forms of GDF11 and myostatin are over 94% identical. In order to understand the role that the small differences in sequence may play in the differential signaling of these molecules, the crystal structure of GDF11 was determined to a resolution of 1.50 Å. A comparison of the GDF11 structure with those of other family members reveals that the canonical TGF-β domain fold is conserved. A detailed structural comparison of GDF11 and myostatin shows that several of the differences between these proteins are likely to be localized at interfaces that are critical for the interaction with downstream receptors and inhibitors. PMID:26919518

  5. Control of glioma cell migration and invasiveness by GDF-15

    PubMed Central

    Codó, Paula; Weller, Michael; Kaulich, Kerstin; Schraivogel, Daniel; Silginer, Manuela; Reifenberger, Guido; Meister, Gunter; Roth, Patrick

    2016-01-01

    Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-β family of proteins. GDF-15 levels are increased in the blood and cerebrospinal fluid of glioblastoma patients. Using a TCGA database interrogation, we demonstrate that high GDF-15 expression levels are associated with poor survival of glioblastoma patients. To elucidate the role of GDF-15 in glioblastoma in detail, we confirmed that glioma cells express GDF-15 mRNA and protein in vitro. To allow for a detailed functional characterization, GDF-15 expression was silenced using RNA interference in LNT-229 and LN-308 glioma cells. Depletion of GDF-15 had no effect on cell viability. In contrast, GDF-15-deficient cells displayed reduced migration and invasion, in the absence of changes in Smad2 or Smad1/5/8 phosphorylation. Conversely, exogenous GDF-15 stimulated migration and invasiveness. Large-scale expression profiling revealed that GDF-15 gene silencing resulted in minor changes in the miRNA profile whereas several genes, including members of the plasminogen activator/inhibitor complex, were deregulated at the mRNA level. One of the newly identified genes induced by GDF-15 gene silencing was the serpin peptidase inhibitor, clade E nexin group 1 (serpine1) which is induced by TGF-β and known to inhibit migration and invasiveness. However, serpine1 down-regulation alone did not mediate GDF-15-induced promotion of migration and invasiveness. Our findings highlight the complex contributions of GDF-15 to the invasive phenotype of glioma cells and suggest anti-GDF-15 approaches as a promising therapeutic strategy. PMID:26741507

  6. MAP3K11/GDF15 axis is a critical driver of cancer cachexia

    PubMed Central

    Tao, Julie; Liu, Qing; Nicoletti, Richard; Feng, Bin; Krieger, Brian; Mazsa, Elizabeth; Siddiquee, Zakir; Wang, Ruoji; Huang, Lucia; Shen, Luhua; Lin, Jie; Vigano, Antonio; Chiu, M. Isabel; Weng, Zhigang; Winston, William; Weiler, Solly

    2015-01-01

    Abstract Background Cancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro‐inflammatory state may be associated with this syndrome although the molecular mechanisms responsible for the development of cachexia are poorly understood. The purpose of this work was the identification of key drivers of cancer cachexia that could provide a potential point of intervention for the treatment and/or prevention of this syndrome. Methods Genetically engineered and xenograft tumour models were used to dissect the molecular mechanisms driving cancer cachexia. Cytokine profiling from the plasma of cachectic and non‐cachectic cancer patients and mouse models was utilized to correlate circulating cytokine levels with the cachexia phenotype. Results Utilizing engineered tumour models we identified MAP3K11/GDF15 pathway activation as a potent inducer of cancer cachexia. Increased expression and high circulating levels of GDF15 acted as a key mediator of this process. In animal models, tumour‐produced GDF15 was sufficient to trigger the cachexia phenotype. Elevated GDF15 circulating levels correlated with the onset and progression of cachexia in animal models and in patients with cancer. Inhibition of GDF15 biological activity with a specific antibody reversed body weight loss and restored muscle and fat tissue mass in several cachectic animal models regardless of their complex secreted cytokine profile. Conclusions The combination of correlative observations, gain of function, and loss of function experiments validated GDF15 as a key driver of cancer cachexia and as a potential therapeutic target for the treatment and/or prevention of this syndrome. PMID:27239403

  7. Effects of GDF5 overexpression on embryonic rat dopaminergic neurones in vitro and in vivo.

    PubMed

    O'Sullivan, David B; Harrison, Patrick T; Sullivan, Aideen M

    2010-05-01

    Transplantation of embryonic dopaminergic neurones has shown promise for the treatment of Parkinson's disease (PD), but this approach is limited by the poor survival of the transplanted cells. Exogenous dopaminergic neurotrophic factors such as growth/differentiation factor 5 (GDF5) have been found to enhance the survival of transplanted dopaminergic neurones. However, this approach is limited by the rapid degradation of such factors in vivo; thus, methods for long-term delivery of these factors are under investigation. The present study shows, using optimised lipid-mediated transfection procedures, that overexpression of GDF5 significantly improves the survival of dopaminergic neurones in cultures of embryonic day (E) 13 rat ventral mesencephalon (VM) and protects them against 6-hydroxydopamine (6-OHDA)-induced toxicity. In another experiment, E13 VM cells were transfected with GDF5 after 1 day in vitro (DIV), then transplanted into 6-OHDA-lesioned adult rat striata after 2 DIV. The survival of these E13 VM dopaminergic neurones after transfection and transplantation was as least as high as that of freshly dissected E14 VM dopaminergic neurones, demonstrating that transfection was not detrimental to these cells. Furthermore, GDF5-overexpressing E13 VM transplants significantly reduced amphetamine-induced rotational asymmetry in the lesioned rats. This study shows that lipid-mediated transfection in vitro prior to transplantation is a valid approach for the introduction of neurotrophic proteins such as GDF5, as well as lending further support to the potential use of GDF5 in neuroprotective therapy for PD. PMID:20349094

  8. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2.

    PubMed

    Seemann, Petra; Schwappacher, Raphaela; Kjaer, Klaus W; Krakow, Deborah; Lehmann, Katarina; Dawson, Katherine; Stricker, Sigmar; Pohl, Jens; Plöger, Frank; Staub, Eike; Nickel, Joachim; Sebald, Walter; Knaus, Petra; Mundlos, Stefan

    2005-09-01

    Here we describe 2 mutations in growth and differentiation factor 5 (GDF5) that alter receptor-binding affinities. They cause brachydactyly type A2 (L441P) and symphalangism (R438L), conditions previously associated with mutations in the GDF5 receptor bone morphogenetic protein receptor type 1b (BMPR1B) and the BMP antagonist NOGGIN, respectively. We expressed the mutant proteins in limb bud micromass culture and treated ATDC5 and C2C12 cells with recombinant GDF5. Our results indicated that the L441P mutant is almost inactive. The R438L mutant, in contrast, showed increased biological activity when compared with WT GDF5. Biosensor interaction analyses revealed loss of binding to BMPR1A and BMPR1B ectodomains for the L441P mutant, whereas the R438L mutant showed normal binding to BMPR1B but increased binding to BMPR1A, the receptor normally activated by BMP2. The binding to NOGGIN was normal for both mutants. Thus, the brachydactyly type A2 phenotype (L441P) is caused by inhibition of the ligand-receptor interaction, whereas the symphalangism phenotype (R438L) is caused by a loss of receptor-binding specificity, resulting in a gain of function by the acquisition of BMP2-like properties. The presented experiments have identified some of the main determinants of GDF5 receptor-binding specificity in vivo and open new prospects for generating antagonists and superagonists of GDF5. PMID:16127465

  9. GDF15 Is a Novel Biomarker for Impaired Fasting Glucose

    PubMed Central

    Hong, Jun Hwa; Chung, Hyo Kyun; Park, Hye Yoon; Joung, Kyong-Hye; Lee, Ju Hee; Jung, Jin Gyu; Kim, Koon Soon; Kim, Hyun Jin

    2014-01-01

    Background Growth differentiation factor-15 (GDF15) is a protein that belongs to the transforming growth factor β superfamily. An elevated serum level of GDF15 was found to be associated with type 2 diabetes mellitus (T2DM). T2DM is an inflammatory disease that progresses from normal glucose tolerance (NGT) to impaired fasting glucose (IFG). Hence, we aimed to validate the relationship between GDF15 and IFG. Methods The participants were divided into the following three groups: NGT (n=137), IFG (n=29), and T2DM (n=75). The controls and T2DM outpatients visited the hospital for routine health check-ups. We used fasting blood glucose to detect IFG in nondiabetic patients. We checked the body mass index (BMI), C-reactive protein level, metabolic parameters, and fasting serum GDF15 level. Results Age, BMI, triglyceride, insulin, glucose, homeostatic model assessment-insulin resistance (HOMA-IR), and GDF15 levels were elevated in the IFG and T2DM groups compared to the NGT group. In the correlation analysis between metabolic parameters and GDF15, age and HOMA-IR had a significant positive correlation with GDF15 levels. GDF15 significantly discriminated between IFG and NGT, independent of age, BMI, and HOMA-IR. The serum levels of GDF15 were more elevated in men than in women. As a biomarker for IFG based on the receiver operating characteristic curve analysis, the cutoff value of GDF15 was 510 pg/mL in males and 400 pg/mL in females. Conclusion GDF15 had a positive correlation with IR independent of age and BMI, and the serum level of GDF15 was increased in the IFG and T2DM groups. GDF15 may be a novel biomarker for detecting IFG in nondiabetic patients. PMID:25541611

  10. IDENTIFICATION OF A TENDON PHENOTYPE IN GDF6 DEFICIENT MICE

    PubMed Central

    Mikic, Borjana; Rossmeier, Kerri; Bierwert, LouAnn

    2009-01-01

    Increasing evidence suggests that the growth/differentiation factors, GDFs 5, 6, and 7 in particular, may play a role in tendon and ligament biology. Mice with genetic mutations in Gdf5 have altered tendon composition and mechanical behavior, while animals with functional null mutations in Gdf7 have a more subtle tendon phenotype. The present study demonstrates for the first time that a null mutation in Gdf6 is associated with substantially lower levels of tail tendon collagen content (−33%) in four-week-old male mice, which has direct functional consequences for the mechanical integrity of the tissue (45-50% reduction in material properties). These data support a role for GDF6 in tendon matrix modeling. PMID:19248159

  11. Foxg1 promotes olfactory neurogenesis by antagonizing Gdf11.

    PubMed

    Kawauchi, Shimako; Kim, Joon; Santos, Rosaysela; Wu, Hsiao-Huei; Lander, Arthur D; Calof, Anne L

    2009-05-01

    Foxg1, a winged-helix transcription factor, promotes the development of anterior neural structures; in mice lacking Foxg1, development of the cerebral hemispheres and olfactory epithelium (OE) is severely reduced. It has been suggested that Foxg1 acts by positively regulating the expression of growth factors, such as Fgf8, which support neurogenesis. However, Foxg1 also binds Smad transcriptional complexes, allowing it to negatively regulate the effects of TGFbeta family ligands. Here, we provide evidence that this latter effect explains much of the ability of Foxg1 to drive neurogenesis in the OE. We show that Foxg1 is expressed in developing OE at the same time as the gene encoding growth differentiation factor 11 (Gdf11), a TGFbeta family member that mediates negative-feedback control of OE neurogenesis. Mutations in Gdf11 rescue, to a considerable degree, the major defects in Foxg1(-/-) OE, including the early, severe loss of neural precursors and olfactory receptor neurons, and the subsequent collapse of both neurogenesis and nasal cavity formation. Rescue is gene-dosage dependent, with loss of even one allele of Gdf11 restoring substantial neurogenesis. Notably, we find no evidence for a disruption of Fgf8 expression in Foxg1(-/-) OE. However, we do observe both a failure of expression of follistatin (Fst), which encodes a secreted Gdf11 antagonist normally expressed in and around OE, and an increase in the expression of Gdf11 itself within the remaining OE in these mutants. Fst expression is rescued in Foxg1(-/-);Gdf11(-/-) and Foxg1(-/-);Gdf11(+/-) mice. These data suggest that the influence of Foxg1 on Gdf11-mediated negative feedback of neurogenesis may be both direct and indirect. In addition, defects in development of the cerebral hemispheres in Foxg1(-/-) mice are not rescued by mutations in Gdf11, nor is Gdf11 expressed at high levels within these structures. Thus, the pro-neurogenic effects of Foxg1 are likely to be mediated through different

  12. Foxg1 promotes olfactory neurogenesis by antagonizing Gdf11

    PubMed Central

    Kawauchi, Shimako; Kim, Joon; Santos, Rosaysela; Wu, Hsiao-Huei; Lander, Arthur D.; Calof, Anne L.

    2009-01-01

    Summary Foxg1, a winged-helix transcription factor, promotes the development of anterior neural structures; in mice lacking Foxg1, development of the cerebral hemispheres and olfactory epithelium (OE) is severely reduced. It has been suggested that Foxg1 acts by positively regulating the expression of growth factors, such as Fgf8, which support neurogenesis. However, Foxg1 also binds Smad transcriptional complexes, allowing it to negatively regulate the effects of TGFβ family ligands. Here, we provide evidence that this latter effect explains much of the ability of Foxg1 to drive neurogenesis in the OE. We show that Foxg1 is expressed in developing OE at the same time as the gene encoding growth differentiation factor 11 (Gdf11), a TGFβ family member that mediates negative-feedback control of OE neurogenesis. Mutations in Gdf11 rescue, to a considerable degree, the major defects in Foxg1-/- OE, including the early, severe loss of neural precursors and olfactory receptor neurons, and the subsequent collapse of both neurogenesis and nasal cavity formation. Rescue is gene-dosage dependent, with loss of even one allele of Gdf11 restoring substantial neurogenesis. Notably, we find no evidence for a disruption of Fgf8 expression in Foxg1-/- OE. However, we do observe both a failure of expression of follistatin (Fst), which encodes a secreted Gdf11 antagonist normally expressed in and around OE, and an increase in the expression of Gdf11 itself within the remaining OE in these mutants. Fst expression is rescued in Foxg1-/-;Gdf11-/- and Foxg1-/-;Gdf11+/- mice. These data suggest that the influence of Foxg1 on Gdf11-mediated negative feedback of neurogenesis may be both direct and indirect. In addition, defects in development of the cerebral hemispheres in Foxg1-/- mice are not rescued by mutations in Gdf11, nor is Gdf11 expressed at high levels within these structures. Thus, the pro-neurogenic effects of Foxg1 are likely to be mediated through different signaling

  13. Can Serum Gdf-15 be Associated with Functional Iron Deficiency in Hemodialysis Patients?

    PubMed

    Yilmaz, Hakki; Cakmak, Muzaffer; Darcin, Tahir; Inan, Osman; Bilgic, Mukadder Ayse; Bavbek, Nuket; Akcay, Ali

    2016-06-01

    Functional iron deficiency (FID) incidence is gradually increasing in hemodialysis (HD) patients. Recently, high levels of GDF-15 supressed the iron regulatory protein hepcidin and GDF-15 expression increased in iron-deficient patients. The relationship between FID, GDF-15, and hepcidin is currently unknown. The present study aimed to evaluate the association between GDF-15, hepcidin, and FID in chronic HD patients. Serum GDF-15 and hepcidin concentrations were measured in 105 HD patients and 40 controls. FID is defined as serum ferritin >800 ng/mL, TSAT <25 %, Hb levels <11 g/dL, and reticulocyte haemoglobin content (CHr) <29 pg. Serum GDF-15 and hepcidin levels were increased significantly in HD patients with FID, compared to HD patients without anemia and controls. GDF-15 correlated with ferritin, hepcidin, and CRP in the entire cohort. GDF-15 was related to ferritin and CRP in HD patients with FID. GDF-15 is better diagnostic marker than hepcidin for detection of FID [AUC = 0.982 (0.013) versus AUC = 0.921 (0.027); P = 0.0324]. GDF-15 appears to be a promising tool for detection of FID. High levels of ferritin and CRP correlated with GDF-15. Our results support GDF-15 as a new mediator of FID via hepcidin, chronic inflammation, or unknown pathways. PMID:27065587

  14. Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice.

    PubMed

    Machado, Venissa; Gilsbach, Ralf; Das, Richa; Schober, Andreas; Bogatyreva, Lioudmila; Hauschke, Dieter; Krieglstein, Kerstin; Unsicker, Klaus; Spittau, Björn

    2016-08-01

    Growth/differentiation factor-15 (Gdf-15) is a member of the transforming growth factor-β (Tgf-β) superfamily and has been shown to be a potent neurotrophic factor for midbrain dopaminergic (DAergic) neurons both in vitro and in vivo. Gdf-15 has also been shown to be involved in inflammatory processes. The aim of this study was to identify the role of endogenous Gdf-15 in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease (PD) by comparing Gdf-15 (+/+) and Gdf-15 (-/-) mice. At 4 days and 14 days post-MPTP administration, both Gdf-15 (+/+) and Gdf-15 (-/-) mice showed a similar decline in DAergic neuron numbers and in striatal dopamine (DA) levels. This was followed by a comparable restorative phase at 90 days and 120 days, indicating that the absence of Gdf-15 does not affect the susceptibility or the recovery capacity of the nigrostriatal system after MPTP administration. The MPTP-induced microglial and astrocytic response was not significantly altered between the two genotypes. However, pro-inflammatory and anti-inflammatory cytokine profiling revealed the differential expression of markers in Gdf-15 (+/+) and Gdf-15 (-/-) mice after MPTP administration. Thus, the MPTP mouse model fails to uncover a major role of endogenous Gdf-15 in the protection of MPTP-lesioned nigrostriatal DAergic neurons, in contrast to its capacity to protect the 6-hydroxydopamine-intoxicated nigrostriatal system. PMID:27115420

  15. Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease.

    PubMed

    Schafer, Marissa J; Atkinson, Elizabeth J; Vanderboom, Patrick M; Kotajarvi, Brian; White, Thomas A; Moore, Matthew M; Bruce, Charles J; Greason, Kevin L; Suri, Rakesh M; Khosla, Sundeep; Miller, Jordan D; Bergen, H Robert; LeBrasseur, Nathan K

    2016-06-14

    Growth and differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in aging processes. We have developed a highly specific LC-MS/MS assay to quantify GDF11, resolved from its homolog, myostatin (MSTN), based on unique amino acid sequence features. Here, we demonstrate that MSTN, but not GDF11, declines in healthy men throughout aging. Neither GDF11 nor MSTN levels differ as a function of age in healthy women. In an independent cohort of older adults with severe aortic stenosis, we show that individuals with higher GDF11 were more likely to be frail and have diabetes or prior cardiac conditions. Following valve replacement surgery, higher GDF11 at surgical baseline was associated with rehospitalization and multiple adverse events. Cumulatively, our results show that GDF11 levels do not decline throughout aging but are associated with comorbidity, frailty, and greater operative risk in older adults with cardiovascular disease. PMID:27304512

  16. The Potassium-Argon Laser Experiment (KarLE): In Situ Geochronology for Mars and Beyond

    NASA Technical Reports Server (NTRS)

    Cohen, Barbara A.

    2014-01-01

    The search for life in the solar system depends upon discovering the right moments in planetary evolution: when habitable environments existed, when they declined, and when geologic processes operated to preserve traces of life after death. However, an incomplete knowledge of absolute Martian geochronology limits our ability to understand the timing of Martian evolutionary milestones, major climate changes, and stratigraphic epochs [1, 2]. Absolute dating relates these habitability markers to planetarywide geologic, atmospheric, and climate history places, and ties their occurrence to the history of the solar system, especially the Earth-Moon system and the timescale of evolution of life on Earth. KArLE is being developed to anchor the relative timeline of geological events to an absolute chronology that puts Mars into a wider solar system context. KArLE makes its measurements on rock samples that can be obtained by landers or rovers and inserted into a small, mechanically simple chamber. KArLE interrogates the samples using laser-induced breakdown spectrocopy (LIBS), mass spectrometry, and optical imaging. The KArLE experiment is flexible enough to accommodate any partner providing these instrument components, a creative approach that extends the ability of mission payloads to accomplish an additional highly-desirable science measurement for low cost and risk and minimal extra hardware.

  17. Developement of the Potassium-Argon Laser Experiment (KArLE) for In Situ Geochronology

    NASA Technical Reports Server (NTRS)

    Cohen, Barbara A.

    2012-01-01

    Absolute dating of planetary samples is an essential tool to establish the chronology of geological events, including crystallization history, magmatic evolution, and alteration. Thus far, radiometric geochronology of planetary samples has only been accomplishable in terrestrial laboratories on samples from dedicated sample return missions and meteorites. In situ instruments to measure rock ages have been proposed, but none have yet reached TRL 6, because isotopic measurements with sufficient resolution are challenging. We have begun work under the NASA Planetary Instrument Definition and Development Program (PIDDP) to develop the Potassium (K) - Argon Laser Experiment (KArLE), a novel combination of several flight-proven components that will enable accurate KAr isochron dating of planetary rocks. KArLE will ablate a rock sample, measure the K in the plasma state using laser-induced breakdown spectroscopy (LIBS), measure the liberated Ar using quadrupole mass spectrometry (QMS), and relate the two by measuring the volume of the abated pit using a optical methods such as a vertical scanning interferometer (VSI). Our preliminary work indicates that the KArLE instrument will be capable of determining the age of several kinds of planetary samples to 100 Myr, sufficient to address a wide range of geochronology problems in planetary science. Additional benefits derive from the fact that each KArLE component achieves analyses common to most planetary surface missions.

  18. The Potassium-Argon Laser Experiment (KArLE): In Situ Geochronology for Planetary Robotic Missions

    NASA Technical Reports Server (NTRS)

    Cohen, Barbara

    2016-01-01

    The Potassium (K) - Argon (Ar) Laser Experiment (KArLE) will make in situ noble-gas geochronology measurements aboard planetary robotic landers and roverss. Laser-Induced Breakdown Spectroscopy (LIBS) is used to measure the K abun-dance in a sample and to release its noble gases; the evolved Ar is measured by mass spectrometry (MS); and rela-tive K content is related to absolute Ar abundance by sample mass, determined by optical measurement of the ablated volume. KArLE measures a whole-rock K-Ar age to 10% or better for rocks 2 Ga or older, sufficient to resolve the absolute age of many planetary samples. The LIBS-MS approach is attractive because the analytical components have been flight proven, do not require further technical development, and provide complementary measurements as well as in situ geochronology.

  19. GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective.

    PubMed

    Adela, Ramu; Banerjee, Sanjay K

    2015-01-01

    Growth differentiation factor-15 (GDF-15) is a stress responsive cytokine. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. GDF-15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk. Increased GDF-15 levels are associated with cardiovascular diseases such as hypertrophy, heart failure, atherosclerosis, endothelial dysfunction, obesity, insulin resistance, diabetes, and chronic kidney diseases in diabetes. Increased GDF-15 level is linked with the progression and prognosis of the disease condition. Age, smoking, and environmental factors are other risk factors that may increase GDF-15 level. Most of the scientific studies reported that GDF-15 plays a protective role in different tissues. However, few reports show that the deficiency of GDF-15 is beneficial against vascular injury and inflammation. GDF-15 protects heart, adipose tissue, and endothelial cells by inhibiting JNK (c-Jun N-terminal kinase), Bad (Bcl-2-associated death promoter), and EGFR (epidermal growth factor receptor) and activating Smad, eNOS, PI3K, and AKT signaling pathways. The present review describes the different animal and clinical studies and patent updates of GDF-15 in diabetes and cardiovascular diseases. It is a challenge for the scientific community to use GDF-15 information for patient monitoring, clinical decision-making, and replacement of current treatment strategies for diabetic and cardiovascular diseases. PMID:26273671

  20. Role of GDF15 (growth and differentiation factor 15) in pulmonary oxygen toxicity.

    PubMed

    Tiwari, Kirti Kumar; Moorthy, Bhagavatula; Lingappan, Krithika

    2015-10-01

    GDF15 (growth and differentiation factor 15) is a secreted cytokine, a direct target of p53 and plays a role in cell proliferation and apoptosis. It is induced by oxidative stress and has anti-apoptotic effects. The role of GDF15 in hyperoxic lung injury is unknown. We tested the hypothesis that GDF15 will be induced in vitro, in a model of pulmonary oxygen toxicity, and will play a critical role in decreasing cell death and oxidative stress. BEAS-2B (human bronchial epithelial cells) and human pulmonary vascular endothelial cells (HPMEC) were exposed to hyperoxia, and expression of GDF15 and effect of GDF15 disruption on cell viability and oxidative stress was determined. Furthermore, we studied the effect of p53 knockdown on GDF15 expression. In vitro, both BEAS-2B and HPMEC cells showed a significant increase in GDF15 expression upon exposure to hyperoxia. After GDF15 knockdown, there was a significant decrease in cell viability and increase in oxidative stress compared to control cells transfected with siRNA with a scrambled sequence. Knockdown of p53 significantly decreased the induction of GDF15 by hyperoxia. In conclusion, we show that GDF15 has a pro-survival and anti-oxidant role in hyperoxia and that p53 plays a key role in its induction. PMID:26004619

  1. Development of the Potassium-Argon Laser Experiment (KArLE) Instrument for In Situ Geochronology

    NASA Technical Reports Server (NTRS)

    Cohen, Barbara A.; Li, Z.-H.; Miller, J. S.; Brinckerhoff, W. B.; Clegg, S. M.; Mahaffy, P. R.; Swindle, T. D.; Wiens, R. C.

    2012-01-01

    Absolute dating of planetary samples is an essential tool to establish the chronology of geological events, including crystallization history, magmatic evolution, and alteration. Traditionally, geochronology has only been accomplishable on samples from dedicated sample return missions or meteorites. The capability for in situ geochronology is highly desired, because it will allow one-way planetary missions to perform dating of large numbers of samples. The success of an in situ geochronology package will not only yield data on absolute ages, but can also complement sample return missions by identifying the most interesting rocks to cache and/or return to Earth. In situ dating instruments have been proposed, but none have yet reached TRL 6 because the required high-resolution isotopic measurements are very challenging. Our team is now addressing this challenge by developing the Potassium (K) - Argon Laser Experiment (KArLE) under the NASA Planetary Instrument Definition and Development Program (PIDDP), building on previous work to develop a K-Ar in situ instrument [1]. KArLE uses a combination of several flight-proven components that enable accurate K-Ar isochron dating of planetary rocks. KArLE will ablate a rock sample, determine the K in the plasma state using laser-induced breakdown spectroscopy (LIBS), measure the liberated Ar using quadrupole mass spectrometry (QMS), and relate the two by the volume of the ablated pit using an optical method such as a vertical scanning interferometer (VSI). Our preliminary work indicates that the KArLE instrument will be capable of determining the age of several kinds of planetary samples to +/-100 Myr, sufficient to address a wide range of geochronology problems in planetary science.

  2. Evaluation of growth differentiation factor 11 (GDF11) levels in dogs with chronic mitral valve insufficiency

    PubMed Central

    Ahn, Sung-Taek; Suh, Sang-Il; Moon, Hyeongsun; Hyun, Changbaig

    2016-01-01

    Growth differentiation factor 11 (GDF11) regulates cell growth and differentiation in both embryonic and adult tissues. Circulating GDF11 levels have recently been reported to be significantly lower in aging mice and restoration of GDF11 reversed age-related cardiac hypertrophy in old mice. Here, we evaluated the potential of serum levels of GDF11 as a circulating biomarker in dogs at different stages of heart failure, due to chronic mitral valve insufficiency (CMVI). We found no significant differences in serum GDF11 levels between dogs at different stages of CMVI-associated heart failure. Furthermore, the circulating levels of GDF11 did not correlate with age, body weight, echocardiographic variables, and the severity of CMVI-induced heart failure in dogs. PMID:26733738

  3. Lack of evidence for GDF11 as a rejuvenator of aged skeletal muscle satellite cells.

    PubMed

    Hinken, Aaron C; Powers, Janine M; Luo, Guizhen; Holt, Jason A; Billin, Andrew N; Russell, Alan J

    2016-06-01

    Recent high-profile studies report GDF11 to be a key circulating 'anti-aging' factor. However, a screen of extracellular proteins attempting to identify factors with 'anti-aging' phenotypes in aged murine skeletal muscle satellite cells did not identify GDF11 activity. We have been unable to confirm the reported activity of GDF11, similar to other laboratories offering conflicting data and describe our attempts to do so in this short take. PMID:27139744

  4. Brachydactyly type A2 associated with a defect in proGDF5 processing.

    PubMed

    Plöger, Frank; Seemann, Petra; Schmidt-von Kegler, Mareen; Lehmann, Katarina; Seidel, Jörg; Kjaer, Klaus W; Pohl, Jens; Mundlos, Stefan

    2008-05-01

    We investigated a family with a brachydactyly type A2 and identified a heterozygous arginine to glutamine (R380Q) substitution in the growth/differentiation factor 5 (GDF5) in all affected individuals. The observed mutation is located at the processing site of the protein, at which the GDF5 precursor is thought to be cleaved releasing the mature molecule from the prodomain. In order to test the effect of the mutation, we generated the GDF5-R380Q mutant and a cleavage-resistant proGDF5 mutant (R380A/R381A) in vitro. Both mutants were secreted from chicken micromass cultures, but showed diminished biological activity. Western blot analyses showed that wt GDF5 was processed by the chicken micromass cells, whereas the mutants were not, indicating that the mutations interfere with processing and that this leads to a strong reduction of biological activity. To test the requirements for GDF5 processing in vitro we produced recombinant human (rh) proGDF5 wild-type protein in Escherichia coli. The results show that unprocessed (rh) proGDF5 is virtually inactive but can be proteolytically activated by different enzymes such as trypsin, furin, and MMP3. (rh) proGDF5 could thus be used as a locally administered depot form with retarded release of activity. In contrast to mature rhGDF5, (rh) proGDF5 shows a high solubility at physiological pH, a characteristic that might be useful for therapeutic applications. PMID:18203755

  5. 75 FR 57911 - Application To Export Electric Energy; GDF SUEZ Energy Marketing NA, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-23

    ... Application To Export Electric Energy; GDF SUEZ Energy Marketing NA, Inc. AGENCY: Office of Electricity Delivery and Energy Reliability, DOE. ACTION: Notice of application. SUMMARY: GDF SUEZ Energy Marketing NA... utilities, Federal power marketing agencies and other entities within the United States. The...

  6. Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury

    SciTech Connect

    Saiga, Kenta; Furumatsu, Takayuki; Yoshida, Aki; Masuda, Shin; Takihira, Shota; Abe, Nobuhiro; Ozaki, Toshifumi

    2010-11-12

    Research highlights: {yields} bFGF/GDF-5 treatment increases cellular proliferation and migration of MCL fibroblasts. {yields} bFGF/GDF-5 hydrogels stimulate the healing of MCL injury in vivo. {yields} bFGF/GDF-5 hydrogels stimulate Col1a1 expression and type I collagen synthesis. {yields} Combined use of bFGF/GDF-5 enhances MCL healing. -- Abstract: Basic fibroblast growth factor (bFGF) and growth and differentiation factor (GDF)-5 stimulate the healing of medial collateral ligament (MCL) injury. However, the effect of isolated and combined use of bFGF/GDF-5 remains still unclear. We investigated cellular proliferation and migration responding to bFGF/GDF-5 using rabbit MCL fibroblasts. Rabbit MCL injury was treated by bFGF and/or GDF-5 with peptide hydrogels. Gene expression and deposition of collagens in healing tissues were evaluated. bFGF/GDF-5 treatment additively enhanced cell proliferation and migration. bFGF/GDF-5 hydrogels stimulated Col1a1 expression without increasing Col3a1 expression. Combined use of bFGF/GDF-5 stimulated type I collagen deposition and the reorganization of fiber alignment, and induced better morphology of fibroblasts in healing MCLs. Our study indicates that combined use of bFGF/GDF-5 might enhance MCL healing by increasing proliferation and migration of MCL fibroblasts, and by regulating collagen synthesis and connective fiber alignment.

  7. Cost estimate for a proposed GDF Suez LNG testing program

    SciTech Connect

    Blanchat, Thomas K.; Brady, Patrick Dennis; Jernigan, Dann A.; Luketa, Anay Josephine; Nissen, Mark R.; Lopez, Carlos; Vermillion, Nancy; Hightower, Marion Michael

    2014-02-01

    At the request of GDF Suez, a Rough Order of Magnitude (ROM) cost estimate was prepared for the design, construction, testing, and data analysis for an experimental series of large-scale (Liquefied Natural Gas) LNG spills on land and water that would result in the largest pool fires and vapor dispersion events ever conducted. Due to the expected cost of this large, multi-year program, the authors utilized Sandia's structured cost estimating methodology. This methodology insures that the efforts identified can be performed for the cost proposed at a plus or minus 30 percent confidence. The scale of the LNG spill, fire, and vapor dispersion tests proposed by GDF could produce hazard distances and testing safety issues that need to be fully explored. Based on our evaluations, Sandia can utilize much of our existing fire testing infrastructure for the large fire tests and some small dispersion tests (with some modifications) in Albuquerque, but we propose to develop a new dispersion testing site at our remote test area in Nevada because of the large hazard distances. While this might impact some testing logistics, the safety aspects warrant this approach. In addition, we have included a proposal to study cryogenic liquid spills on water and subsequent vaporization in the presence of waves. Sandia is working with DOE on applications that provide infrastructure pertinent to wave production. We present an approach to conduct repeatable wave/spill interaction testing that could utilize such infrastructure.

  8. GDF-15 Is Elevated in Children with Mitochondrial Diseases and Is Induced by Mitochondrial Dysfunction

    PubMed Central

    Montero, Raquel; Yubero, Delia; Villarroya, Joan; Henares, Desiree; Jou, Cristina; Rodríguez, Maria Angeles; Ramos, Federico; Nascimento, Andrés; Ortez, Carlos Ignacio; Campistol, Jaume; Perez-Dueñas, Belen; O'Callaghan, Mar; Pineda, Mercedes; Garcia-Cazorla, Angeles; Oferil, Jaume Colomer; Montoya, Julio; Ruiz-Pesini, Eduardo; Emperador, Sonia; Meznaric, Marija; Campderros, Laura; Kalko, Susana G.; Villarroya, Francesc; Artuch, Rafael; Jimenez-Mallebrera, Cecilia

    2016-01-01

    Background We previously described increased levels of growth and differentiation factor 15 (GDF-15) in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21). To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction. Methods We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA. Results Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM) relative to healthy (350, 21) and myopathic (350, 32) controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4%) and 92.3% (81.5%-97.9%), respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated levels of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated. Conclusions Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochondrial dysfunction and that its levels

  9. Relationship of serum GDF11 levels with bone mineral density and bone turnover markers in postmenopausal Chinese women.

    PubMed

    Chen, Yusi; Guo, Qi; Zhang, Min; Song, Shumin; Quan, Tonggui; Zhao, Tiepeng; Li, Hongliang; Guo, Lijuan; Jiang, Tiejian; Wang, Guangwei

    2016-01-01

    Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47-78 years old). GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index (BMI), the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase (BAP) was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen (NTX) and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation. PMID:27408764

  10. Relationship of serum GDF11 levels with bone mineral density and bone turnover markers in postmenopausal Chinese women

    PubMed Central

    Chen, Yusi; Guo, Qi; Zhang, Min; Song, Shumin; Quan, Tonggui; Zhao, Tiepeng; Li, Hongliang; Guo, Lijuan; Jiang, Tiejian; Wang, Guangwei

    2016-01-01

    Growth differentiation factor 11 (GDF11) is an important circulating factor that regulates aging. However, the role of GDF11 in bone metabolism remains unclear. The present study was undertaken to investigate the relationship between serum GDF11 level, bone mass, and bone turnover markers in postmenopausal Chinese women. Serum GDF11 level, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 169 postmenopausal Chinese women (47–78 years old). GDF11 serum levels increased with aging. There were negative correlations between GDF11 and BMD at the various skeletal sites. After adjusting for age and body mass index (BMI), the correlations remained statistically significant. In the multiple linear stepwise regression analysis, age or years since menopause, BMI, GDF11, and estradiol were independent predictors of BMD. A significant negative correlation between GDF11 and bone alkaline phosphatase (BAP) was identified and remained significant after adjusting for age and BMI. No significant correlation was noted between cross-linked N-telopeptides of type I collagen (NTX) and GDF11. In conclusion, GDF11 is an independent negative predictor of BMD and correlates with a biomarker of bone formation, BAP, in postmenopausal Chinese women. GDF11 potentially exerts a negative effect on bone mass by regulating bone formation. PMID:27408764

  11. Volume Measurements of Laser-generated Pits for in Situ Geochronology Using KArLE (Potassium-Argon Laser Experiment)

    NASA Technical Reports Server (NTRS)

    French, R. A.; Cohen, B. A.; Miller, J. S.

    2014-01-01

    KArLE (Potassium-­-Argon Laser Experiment) has been developed for in situ planetary geochronology using the K - Ar (potassium-­-argon) isotope system, where material ablated by LIBS (Laser-­-Induced Breakdown Spectroscopy) is used to calculate isotope abundances. We are determining the accuracy and precision of volume measurements of these pits using stereo and laser microscope data to better understand the ablation process for isotope abundance calculations. If a characteristic volume can be determined with sufficient accuracy and precision for specific rock types, KArLE will prove to be a useful instrument for future planetary rover missions.

  12. GDF10 Is a Signal for Axonal Sprouting and Functional Recovery after Stroke

    PubMed Central

    Li, S; Nie, EH; Yin, Y; Benowitz, LI; Tung, S; Vinters, HV; Bahjat, FR; Stenzel-Poore, MP; Kawaguchi, R; Coppola, G; Carmichael, ST

    2016-01-01

    Stroke produces a limited process of neural repair. Axonal sprouting in cortex adjacent to the infarct is part of this recovery process, but the signal that initiates axonal sprouting is not known. Growth and Differentiation Factor 10 (GDF10) is induced in peri-infarct neurons in mouse, non-human primate and human. GDF10 promotes axonal outgrowth in vitro in mouse, rat and human neurons through TGFβRI/II signaling. Using pharmacogenetic gain and loss of function studies, GDF10 produces axonal sprouting and enhanced functional recovery after stroke; knocking down GDF10 blocks axonal sprouting and reduces recovery. RNA-seq from peri-infarct cortical neurons indicates that GDF10 downregulates PTEN and upregulates PI3 kinase signaling and induces specific axonal guidance molecules. Unsupervised genome-wide association analysis of the GDF10 transcriptome shows that it is not related to neurodevelopment but may partially overlap with other CNS injury patterns. GDF10 is a stroke-induced signal for axonal sprouting and functional recovery. PMID:26502261

  13. Regulation of GDF-11 and myostatin activity by GASP-1 and GASP-2.

    PubMed

    Lee, Yun-Sil; Lee, Se-Jin

    2013-09-24

    Myostatin (MSTN) and growth and differentiation factor-11 (GDF-11) are highly related TGF-β family members that have distinct biological functions. MSTN is expressed primarily in skeletal muscle and acts to limit muscle growth. GDF-11 is expressed more widely and plays multiple roles, including regulating axial skeletal patterning during development. Several MSTN and GDF-11 binding proteins have been identified, including GDF-associated serum protein-1 (GASP-1) and GASP-2, which are capable of inhibiting the activities of these ligands. Here, we show that GASP-1 and GASP-2 act by blocking the initial signaling event (namely, the binding of the ligand to the type II receptor). Moreover, we show that mice lacking Gasp1 and Gasp2 have phenotypes consistent with overactivity of MSTN and GDF-11. Specifically, we show that Gasp2(-/-) mice have posteriorly directed transformations of the axial skeleton, which contrast with the anteriorly directed transformations seen in Gdf11(-/-) mice. We also show that both Gasp1(-/-) and Gasp2(-/-) mice have reductions in muscle weights, a shift in fiber type from fast glycolytic type IIb fibers to fast oxidative type IIa fibers, and impaired muscle regeneration ability, which are the reverse of what are seen in Mstn(-/-) mice. All of these findings suggest that both GASP-1 and GASP-2 are important modulators of GDF-11 and MSTN activity in vivo. PMID:24019467

  14. Epigenetic Regulation of GDF2 Suppresses Anoikis in Ovarian and Breast Epithelia1

    PubMed Central

    Varadaraj, Archana; Patel, Pratik; Serrao, Anne; Bandyopadhay, Tirthankar; Lee, Nam Y.; Jazaeri, Amir A.; Huang, Zhiqing; Murphy, Susan K.; Mythreye, Karthikeyan

    2015-01-01

    Anoikis, a cell death mechanism triggered upon cell-matrix detachment, is regarded as a physiological suppressor of metastasis that can be regulated by a diverse array of signals. The protein encoded by GDF2 is BMP9 and is a member of the bone morphogenetic protein family and the transforming growth factor (TGF) β superfamily with emerging yet controversial roles in carcinogenesis. In an attempt to identify the function of growth and differentiation factor 2 (GDF2) in epithelial systems, we examined the signaling machinery that is involved and cell fate decisions in response to GDF2 in ovarian and breast epithelia. We find that GDF2 can robustly activate the SMAD1/5 signaling axis by increasing complex formation between the type I receptor serine threonine kinases activin receptor-like kinase (ALK) 3 and ALK6 and the type II receptor serine threonine kinase BMPRII. This activation is independent of cross talk with the SMAD2-transforming growth factor β pathway. By activating SMAD1/5, epithelial cells regulate anchorage-independent growth by increasing anoikis sensitivity that is dependent on GDF2’s ability to sustain the activation of SMAD1/5 via ALK3 and ALK6. Consistent with a role for GDF2 in promoting anoikis susceptibility, the analysis of cell lines and patient data suggests epigenetic silencing of GDF2 in cancer cell lines and increased promoter methylation in patients. These findings collectively indicate an antimetastatic role for GDF2 in ovarian and breast cancer. The work also implicates loss of GDF2 via promoter methylation-mediated downregulation in promotion of carcinogenesis with significant relevance for the use of epigenetic drugs currently in clinical trials. PMID:26678910

  15. Update on Development of the Potassium-Argon Laser Experiment (KArLE) Instrument for In Situ Geochronology

    NASA Technical Reports Server (NTRS)

    Cohen, Barbara A.; Li, Z.-H.; Miller, J. S.; Brinckerhoff, W. B.; Clegg, S. M.; Mahaffy, P. R.; Swindle, T. D.; Wiens, R. C.

    2013-01-01

    Absolute dating of planetary samples is an essential tool to establish the chronology of geological events, including crystallization history, magmatic evolution, and alteration. We are addressing this challenge by developing the Potassium (K) -- Argon Laser Experiment (KArLE), building on previous work to develop a K-Ar in situ instrument. KArLE ablates a rock sample, determines the K in the plasma state using laser-induced breakdown spectroscopy (LIBS), measures the liberated Ar using quadrupole mass spectrometry (QMS), and relates the two by the volume of the ablated pit using laser confocal microscopy (LCM). Our goal is for the KArLE instrument to be capable of determining the age of several kinds of planetary samples to address a wide range of geochronolgy problems in planetary science.

  16. Effect of growth differentiation factor-9 (GDF-9) on the progression of buffalo follicles in vitrified-warmed ovarian tissues.

    PubMed

    Abdel-Ghani, M A; El-Sherry, T M; Abdelhafeez, H H

    2016-10-01

    To improve the reproductive performance of water buffalo to level can satisfy our needs, the mechanisms controlling ovarian follicular growth and development should be thoroughly investigated. Therefore, in this study, the expressions of growth differentiation factor-9 (GDF-9) in buffalo ovaries were examined by immunohistochemistry, and the effects of GDF-9 treatment on follicle progression were investigated using a buffalo ovary organ culture system. Frozen-thawed buffalo ovarian follicles within slices of ovarian cortical tissue were cultured for 14 days in the presence or absence of GDF-9. After culture, ovarian slices were fixed, sectioned and stained. The follicles were morphologically analysed and counted. Expression pattern of GDF-9 was detected in oocytes from primordial follicles onwards, besides, also presented in granulosa cells. Moreover, GDF-9 was detected in mural granulosa cells and theca cells of pre-antral follicles. In antral follicles, cumulus cells and theca cells displayed positive expression of GDF-9. In corpora lutea, GDF-9 was expressed in both granulosa and theca lutein cells. After in vitro culture, there was no difference in the number of primordial follicles between cultured plus GDF-9 and cultured control that indicated the GDF-9 treatment has no effect on the primordial to primary follicle transition. GDF-9 treatment caused a significant decrease in the number of primary and secondary follicles compared with controls accompanied with a significant increase in pre-antral and antral follicles. These results suggest that a larger number of primary and secondary follicles were stimulated to progress to later developmental stages when treated with GDF-9. Vitrification/warming of buffalo ovarian tissue had a little remarkable effect, in contrast to culturing for 14 days, on the expression of GDF-9. In conclusion, treatment with GDF-9 was found to promote progression of primary follicle that could provide an alternative approach to

  17. Differential effects of GDF5 on the medial and lateral rat ventral mesencephalon.

    PubMed

    Clayton, Kevin B; Sullivan, Aideen M

    2007-11-12

    Growth/differentiation factor 5 (GDF5) is a member of the transforming growth factor-beta (TGF-beta) superfamily that has potent neurotrophic and protective effects on dopaminergic neurones and is expressed in the developing rat substantia nigra (the ventral mesencephalon; VM). GDF5 has the potential to be used in the treatment of Parkinson's disease (PD), a neurodegenerative disorder characterised by the selective degeneration of nigrostriatal dopaminergic neurones. One therapy being explored for PD involves transplantation of fetal VM tissue into the striatum in order to replace lost dopaminergic neurones. The majority of transplantation studies have used transplants incorporating the whole VM. The principal location of dopaminergic neurones in the E14 rat VM is in the medial VM. In the present study, the effects of GDF5 on cultures prepared from medial, lateral and whole E14 rat VM tissue were compared. GDF5 treatment increased the number of dopaminergic neurones in whole and lateral, but not in medial, VM cultures, whereas it increased total cell number in medial, but not in whole or lateral, VM cultures. RT-PCR studies showed that the receptors for GDF5 were differentially expressed in E14 VM; the expression of BMPR-IB and Ror2 was low in medial but high in lateral VM tissue. This study suggests that GDF5 increases the number of dopaminergic neurones in whole VM cultures by acting on BMPR-IB and Ror2-expressing cells in the lateral VM. PMID:17935884

  18. In Situ Geochronology on the Mars 2020 Rover with KArLE (Potassium-Argon Laser Experiment)

    NASA Technical Reports Server (NTRS)

    Cohen, B. A.; Swindle, T. D.; Roark, S. E.

    2014-01-01

    If extinct and/or extant life is discovered on Mars, knowledge of the chronology of the biosphere will be of paramount importance. KArLE will provide absolute ages of Mars 2020 rocks, which will allow us to understand them in the context of Mars' geologic history, connect them to other landing sites, and compare Martian epochs of habitability with the Earth's history and evolution of life. KArLE significantly enhances the ability of Mars 2020 to meet its science objectives by performing in situ age dating on key lithologies, enabling targeted searches for ancient biosignatures and increasing the chances of identifying evidence for Martian microbial life. The KArLE investigation makes its measurements on a core sample obtained with the rover drill, inserted into a small, mechanically simple chamber, followed by interrogation by laser-induced breakdown spectroscopy (LIBS), mass spectrometry, and optical imaging. The KArLE experiment is flexible enough to accommodate any partner providing these instrument components, a creative approach that extends the ability of the Mars 2020 payload to accomplish an additional highly-desirable science measurement for low cost and risk and minimal extra hardware.

  19. Nodal·Gdf1 Heterodimers with Bound Prodomains Enable Serum-independent Nodal Signaling and Endoderm Differentiation

    PubMed Central

    Fuerer, Christophe; Nostro, M. Cristina; Constam, Daniel B.

    2014-01-01

    The TGFβ family member Nodal is central to control pluripotent stem cell fate, but its use as a stem cell differentiation factor is limited by low specific activity. During development, Nodal depends on growth and differentiation factor (Gdf)-1 and on the shared co-receptor Cryptic to specify visceral left-right axis asymmetry. We therefore asked whether the functionality of Nodal can be augmented by Gdf1. Because Nodal and Gdf1 coimmunoprecipitate each other, they were predicted to form heterodimers, possibly to facilitate diffusion or to increase the affinity for signaling receptors. Here, we report that Gdf1 suppresses an unexpected dependence of Nodal on serum proteins and that it is critically required for non-autonomous signaling in cells expressing Cryptic. Nodal, Gdf1, and their cleaved propeptides copurified as a heterodimeric low molecular weight complex that stimulated Activin receptor (Acvr) signaling far more potently than Nodal alone. Although heterodimerization with Gdf1 did not increase binding of Nodal to Fc fusions of co-receptors or Acvr extracellular domains, it was essential for soluble Acvr2 to inhibit Nodal signaling. This implies that Gdf1 potentiates Nodal activity by stabilizing a low molecular weight fraction that is susceptible to neutralization by soluble Acvr2. Finally, in differentiating human ES cells, endodermal markers were more efficiently induced by Nodal·Gdf1 than by Nodal, suggesting that Nodal·Gdf1 is an attractive new reagent to direct stem cell differentiation. PMID:24798330

  20. Serum GDF-8 levels change dynamically during controlled ovarian hyperstimulation in patients undergoing IVF/ICSI-ET.

    PubMed

    Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

    2016-01-01

    Growth differentiation factor-8 (GDF-8) is found in the human serum, follicular fluid and granulosa cells. Our previous studies have shown that the human cumulus expansion and steroidogenesis can be regulated by GDF-8. However, thus far, the expression profile of GDF-8 in serum and whether the level of serum GDF-8 influences pregnancy results for patients treated with in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) is totally unknown. In this study, we showed that GDF-8 had a dynamic trend during controlled ovarian hyperstimulation (COH) procedure. On human chorionic gonadotropin (hCG) administration day, patients with a GDF-8 level higher than 4.7 ng/ml had lower progesterone levels and a higher pregnancy rate. From hCG day to oocyte pick-up day, patients with a GDF-8 decrease greater than 1.3 ng/ml had a higher progesterone increase and a higher pregnancy rate. Importantly, the levels of GDF-8 were negatively correlated with progesterone levels. Our findings provide evidences that GDF-8 plays an important role in ensuring successful pregnancy by regulating progesterone levels. PMID:27329327

  1. Serum GDF-8 levels change dynamically during controlled ovarian hyperstimulation in patients undergoing IVF/ICSI-ET

    PubMed Central

    Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

    2016-01-01

    Growth differentiation factor-8 (GDF-8) is found in the human serum, follicular fluid and granulosa cells. Our previous studies have shown that the human cumulus expansion and steroidogenesis can be regulated by GDF-8. However, thus far, the expression profile of GDF-8 in serum and whether the level of serum GDF-8 influences pregnancy results for patients treated with in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) is totally unknown. In this study, we showed that GDF-8 had a dynamic trend during controlled ovarian hyperstimulation (COH) procedure. On human chorionic gonadotropin (hCG) administration day, patients with a GDF-8 level higher than 4.7 ng/ml had lower progesterone levels and a higher pregnancy rate. From hCG day to oocyte pick-up day, patients with a GDF-8 decrease greater than 1.3 ng/ml had a higher progesterone increase and a higher pregnancy rate. Importantly, the levels of GDF-8 were negatively correlated with progesterone levels. Our findings provide evidences that GDF-8 plays an important role in ensuring successful pregnancy by regulating progesterone levels. PMID:27329327

  2. Volume Measurements of Laser-generated Pits for In Situ Geochronology using KArLE (Potassium-Argon Laser Experiment)

    NASA Technical Reports Server (NTRS)

    French, R. A.; Cohen, B. A.; Miller, J. S.

    2014-01-01

    The Potassium-Argon Laser Experiment( KArLE), is composed of two main instruments: a spectrometer as part of the Laser-Induced Breakdown Spectroscopy (LIBS) method and a Mass Spectrometer (MS). The LIBS laser ablates a sample and creates a plasma cloud, generating a pit in the sample. The LIBS plasma is measured for K abundance in weight percent and the released gas is measured using the MS, which calculates Ar abundance in mols. To relate the K and Ar measurements, total mass of the ablated sample is needed but can be difficult to directly measure. Instead, density and volume are used to calculate mass, where density is calculated based on the elemental composition of the rock (from the emission spectrum) and volume is determined by pit morphology. This study aims to reduce the uncertainty for KArLE by analyzing pit volume relationships in several analog materials and comparing methods of pit volume measurements and their associated uncertainties.

  3. GDF: A tool for function estimation through grammatical evolution

    NASA Astrophysics Data System (ADS)

    Tsoulos, Ioannis G.; Gavrilis, Dimitris; Dermatas, Evangelos

    2006-04-01

    This article introduces a tool for data fitting that is based on genetic programming and especially on the grammatical evolution technique. The user needs to input a series of points and the accompanied dimensionality n and the tool will produce via the genetic programming paradigm a function f:R→R which is an approximate solution to the symbolic regression problem. The tool is entirely written in ANSI C++ and it can be installed in any UNIX system. Program summaryTitle of program: GDF Catalogue identifier:ADXC Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADXC Computer for which the program is designed and others on which is has been tested:The tool is designed to be portable in all systems running the GNU C++ compiler Installation: University of Ioannina and University of Patras, Greece Programming language used:GNU-C++ Memory required to execute with typical data:200 KB No. of bits in a word: 32 No. of processors used: 1 Has the code been vectorized or parallelized?: No No. of bytes in distributed program, including test data, etc.: 33 469 No. of lines in distributed program, including test data, etc.: 5704 Distribution format: tar.gz Solution method: Functional forms are being created by genetic programming which are approximations for the symbolic regression problem.

  4. POLYMORPHISM IN THE CODING REGION SEQUENCE OF GDF8 GENE IN INDIAN SHEEP.

    PubMed

    Pothuraju, M; Mishra, S K; Kumar, S N; Mohamed, N F; Kataria, R S; Yadav, D K; Arora, R

    2015-11-01

    The present study was undertaken to identify polymorphism in the coding sequence of GDF8gene across indigenous meat type sheep breeds. A 1647 bp sequence was generated, encompassing 208 bp of the 5'UTR, 1128 bp of coding region (exon1, 2 and 3) as well as 311 bp of 3'UTR. The sheep and goat GDF8 gene sequences were observed to be highly conserved as compared to cattle, buffalo, horse and pig. Several nucleotide variations were observed across coding sequence of GDF8 gene in Indian sheep. Three polymorphic sites were identified in the 5'UTR, one in exon 1 and one in the exon 2 regions. Both SNPs in the exonic region were found to be non-synonymous. The mutations c.539T > G and c.821T > A discovered in this study in the exon 1 and exon 2, respectively, have not been previously reported. The information generated provides preliminary indication of the functional diversity present in Indian sheep at the coding region of GDF8gene. The novel as well as the previously reported SNPs discovered in the Indian sheep warrant further analysis to see whether they affect the phenotype. Future studies will need to establish the affect of reported SNPs in the expression of the GDF8 gene in Indian sheep population. PMID:26845859

  5. In-situ Geochronology on the Mars 2020 Rover with KArLE (The Potassium-Argon Laser Experiment)

    NASA Technical Reports Server (NTRS)

    Cohen, Barbara A.; Li, Z. -H.; Miller, J. S.; Devismes, D.; Swindle, T. D.; Schwenzer, S. P.; Kelley, S. P.; Zacny, K. A.; Roark, S. E.; Hardaway, L. R.; Weinberg, J. D.

    2014-01-01

    A successful Mars exploration program has revealed chapters of Mars history, but in this book, the pages are ripped out of the binding and scattered across the surface. An examination of each page reveals interesting information, but there is no way to read the book in a logical order. Geochronology is the tool that puts page number onto the individual pages, and allows the book of Martian history to be read in its proper order. The KArLE experiment performs the first dedicated in situ geochronology investigation on Mars, bringing clarity to Mars 2020 samples and context to its landing site.

  6. GDF15 contributes to radiation-induced senescence through the ROS-mediated p16 pathway in human endothelial cells.

    PubMed

    Park, Hyejin; Kim, Chun-Ho; Jeong, Jae-Hoon; Park, Myungjin; Kim, Kwang Seok

    2016-03-01

    Growth differentiation factor 15 (GDF15) is an emerging biomarker of cardiovascular risk and disease. Microarray analyses revealed that GDF15 levels were increased during cellular senescence induced by ionizing radiation (IR) in human aortic endothelial cells (HAECs). However, the role of GDF15 in HAEC cellular senescence remains unclear. This study demonstrated that downregulation of GDF15 in HAECs partially prevented cellular senescence triggered by IR, which was confirmed by recovery of cell proliferation and reverse senescence-associated β-galactosidase (SA-β-gal) staining. Conversely, upregulation of GDF15-induced cellular senescence in HAECs, confirmed by G0/G1 cell cycle arrest, decreased during cell proliferation and increased SA-β-gal staining. GDF15-induced cellular senescence was observed in p16-knockdown cells but not in p53-knockdown cells. GDF15 expression in endothelial cells also generated reactive oxygen species (ROS), which led to activation of extracellular signal-regulated kinases (ERKs) and induction of senescence by oxidative stress. These results suggested that GDF15 might play an important role in cellular senescence through a ROS-mediated p16 pathway and contribute to the pathogenesis of atherosclerosis via pro-senescent activity. PMID:26909594

  7. GDF15 contributes to radiation-induced senescence through the ROS-mediated p16 pathway in human endothelial cells

    PubMed Central

    Park, Hyejin; Kim, Chun-Ho; Jeong, Jae-Hoon

    2016-01-01

    Growth differentiation factor 15 (GDF15) is an emerging biomarker of cardiovascular risk and disease. Microarray analyses revealed that GDF15 levels were increased during cellular senescence induced by ionizing radiation (IR) in human aortic endothelial cells (HAECs). However, the role of GDF15 in HAEC cellular senescence remains unclear. This study demonstrated that downregulation of GDF15 in HAECs partially prevented cellular senescence triggered by IR, which was confirmed by recovery of cell proliferation and reverse senescence-associated β-galactosidase (SA-β-gal) staining. Conversely, upregulation of GDF15-induced cellular senescence in HAECs, confirmed by G0/G1 cell cycle arrest, decreased during cell proliferation and increased SA-β-gal staining. GDF15-induced cellular senescence was observed in p16-knockdown cells but not in p53-knockdown cells. GDF15 expression in endothelial cells also generated reactive oxygen species (ROS), which led to activation of extracellular signal-regulated kinases (ERKs) and induction of senescence by oxidative stress. These results suggested that GDF15 might play an important role in cellular senescence through a ROS-mediated p16 pathway and contribute to the pathogenesis of atherosclerosis via pro-senescent activity. PMID:26909594

  8. Association between Growth Differentiation Factor 15 (GDF15) and Cardiovascular Risk in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

    PubMed Central

    2016-01-01

    We investigated an association between serum Growth Differentiation Factor 15 (GDF15) level and cardiovascular risk in patients with newly diagnosed type 2 diabetes mellitus (T2D). A total of 107 participants were screened for T2D and divided into a T2D group and a control group (without diabetes). We used the Framingham risk score (FRS) and the New Pooled Cohort Equation score to estimate the 10-year risk of atherosclerotic cardiovascular disease. Serum GDF15 levels were measured using an enzyme-linked immunosorbent assay. Correlation analyses were performed to evaluate the associations between GDF15 level and cardiovascular risk scores. The mean serum GDF15 level was elevated in the T2D group compared to the control group (P < 0.001). A positive correlation was evident between serum GDF15 level and age (r = 0.418, P = 0.001), the FRS (r = 0.457, P < 0.001), and the Pooled Cohort Equation score (r = 0.539, P < 0.001). After adjusting for age, LDL-C level, and body mass index (BMI), the serum GDF15 level was positively correlated with the FRS and the New Pooled Cohort Equation score. The serum GDF15 level is independently associated with cardiovascular risk scores of newly diagnosed T2D patients. This suggests that the level of GDF15 may be a useful predictive biomarker of cardiovascular risk in newly diagnosed T2D patients. PMID:27510384

  9. Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation.

    PubMed

    Liu, Jia; Saito, Kan; Maruya, Yuriko; Nakamura, Takashi; Yamada, Aya; Fukumoto, Emiko; Ishikawa, Momoko; Iwamoto, Tsutomu; Miyazaki, Kanako; Yoshizaki, Keigo; Ge, Lihong; Fukumoto, Satoshi

    2016-01-01

    Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to cause osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue; however, its role during tooth development is unclear. Here, we used cell culture and in vivo analyses to determine the role of GDF5 during tooth development. GDF5 and its associated BMP receptors are expressed at the protein and mRNA levels during postnatal tooth development, particularly at a stage associated with enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed enhanced enamel formation in both the incisors and molars, but not in the tooth roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2-mediated mRNA expression of enamel matrix proteins and downstream phosphorylation of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-signalling. PMID:27030100

  10. Association between Growth Differentiation Factor 15 (GDF15) and Cardiovascular Risk in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

    PubMed

    Shin, Min Young; Kim, Ji Min; Kang, Yea Eun; Kim, Min Kyeong; Joung, Kyong Hye; Lee, Ju Hee; Kim, Koon Soon; Kim, Hyun Jin; Ku, Bon Jeong; Shong, Minho

    2016-09-01

    We investigated an association between serum Growth Differentiation Factor 15 (GDF15) level and cardiovascular risk in patients with newly diagnosed type 2 diabetes mellitus (T2D). A total of 107 participants were screened for T2D and divided into a T2D group and a control group (without diabetes). We used the Framingham risk score (FRS) and the New Pooled Cohort Equation score to estimate the 10-year risk of atherosclerotic cardiovascular disease. Serum GDF15 levels were measured using an enzyme-linked immunosorbent assay. Correlation analyses were performed to evaluate the associations between GDF15 level and cardiovascular risk scores. The mean serum GDF15 level was elevated in the T2D group compared to the control group (P < 0.001). A positive correlation was evident between serum GDF15 level and age (r = 0.418, P = 0.001), the FRS (r = 0.457, P < 0.001), and the Pooled Cohort Equation score (r = 0.539, P < 0.001). After adjusting for age, LDL-C level, and body mass index (BMI), the serum GDF15 level was positively correlated with the FRS and the New Pooled Cohort Equation score. The serum GDF15 level is independently associated with cardiovascular risk scores of newly diagnosed T2D patients. This suggests that the level of GDF15 may be a useful predictive biomarker of cardiovascular risk in newly diagnosed T2D patients. PMID:27510384

  11. Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation

    PubMed Central

    Liu, Jia; Saito, Kan; Maruya, Yuriko; Nakamura, Takashi; Yamada, Aya; Fukumoto, Emiko; Ishikawa, Momoko; Iwamoto, Tsutomu; Miyazaki, Kanako; Yoshizaki, Keigo; Ge, Lihong; Fukumoto, Satoshi

    2016-01-01

    Bone morphogenetic proteins (BMPs) regulate hard tissue formation, including bone and tooth. Growth differentiation factor 5 (GDF5), a known BMP, is expressed in cartilage and regulates chondrogenesis, and mutations have been shown to cause osteoarthritis. Notably, GDF5 is also expressed in periodontal ligament tissue; however, its role during tooth development is unclear. Here, we used cell culture and in vivo analyses to determine the role of GDF5 during tooth development. GDF5 and its associated BMP receptors are expressed at the protein and mRNA levels during postnatal tooth development, particularly at a stage associated with enamel formation. Furthermore, whereas BMP2 was observed to induce evidently the differentiation of enamel-forming ameloblasts, excess GDF5 induce mildly this differentiation. A mouse model harbouring a mutation in GDF5 (W408R) showed enhanced enamel formation in both the incisors and molars, but not in the tooth roots. Overexpression of the W408R GDF5 mutant protein was shown to induce BMP2-mediated mRNA expression of enamel matrix proteins and downstream phosphorylation of Smad1/5/8. These results suggest that mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-signalling. PMID:27030100

  12. Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) Gene Deletion Promotes Cancer Growth in TRAMP Prostate Cancer Prone Mice

    PubMed Central

    Husaini, Yasmin; Lockwood, Glen P.; Nguyen, Trung V.; Tsai, Vicky Wang-Wei; Mohammad, Mohammad G.; Russell, Pamela J.; Brown, David A.; Breit, Samuel N.

    2015-01-01

    The divergent TGF-β superfamily member, macrophage inhibitory cytokine-1 (MIC-1/GDF15), is overexpressed by most cancers, including prostate cancer (PCa). Whilst its circulating levels are linked to cancer outcome, the role MIC-1/GDF15 plays in cancer development and progression is incompletely understood. To investigate its effect on PCa development and spread, we have used TRAMP prostate cancer prone mice bearing a germline deletion of MIC-1/GDF15 (TRAMPMIC-/-). On average TRAMPMIC-/- mice died about 5 weeks earlier and had larger prostatic tumors compared with TRAMP mice that were wild type for MIC-1/GDF15 (TRAMPMIC+/+). Additionally, at the time of death or ethical end point, even when adjusted for lifespan, there were no significant differences in the number of mice with metastases between the TRAMPMIC+/+ and TRAMPMIC-/- groups. However, consistent with our previous data, more than twice as many TRAMP mice overexpressing MIC-1/GDF15 (TRAMPfmsmic-1) had metastases than TRAMPMIC+/+ mice (p<0.0001). We conclude that germ line gene deletion of MIC-1/GDF15 leads to increased local tumor growth resulting in decreased survival consistent with an overall protective role for MIC-1/GDF15 in early primary tumor development. However, in advancing disease, as we have previously noted, MIC-1/GDF15 overexpression may promote local invasion and metastatic spread. PMID:25695521

  13. Macrophage inhibitory cytokine-1 (MIC-1/GDF15) gene deletion promotes cancer growth in TRAMP prostate cancer prone mice.

    PubMed

    Husaini, Yasmin; Lockwood, Glen P; Nguyen, Trung V; Tsai, Vicky Wang-Wei; Mohammad, Mohammad G; Russell, Pamela J; Brown, David A; Breit, Samuel N

    2015-01-01

    The divergent TGF-β superfamily member, macrophage inhibitory cytokine-1 (MIC-1/GDF15), is overexpressed by most cancers, including prostate cancer (PCa). Whilst its circulating levels are linked to cancer outcome, the role MIC-1/GDF15 plays in cancer development and progression is incompletely understood. To investigate its effect on PCa development and spread, we have used TRAMP prostate cancer prone mice bearing a germline deletion of MIC-1/GDF15 (TRAMPMIC-/-). On average TRAMPMIC-/- mice died about 5 weeks earlier and had larger prostatic tumors compared with TRAMP mice that were wild type for MIC-1/GDF15 (TRAMPMIC+/+). Additionally, at the time of death or ethical end point, even when adjusted for lifespan, there were no significant differences in the number of mice with metastases between the TRAMPMIC+/+ and TRAMPMIC-/- groups. However, consistent with our previous data, more than twice as many TRAMP mice overexpressing MIC-1/GDF15 (TRAMPfmsmic-1) had metastases than TRAMPMIC+/+ mice (p<0.0001). We conclude that germ line gene deletion of MIC-1/GDF15 leads to increased local tumor growth resulting in decreased survival consistent with an overall protective role for MIC-1/GDF15 in early primary tumor development. However, in advancing disease, as we have previously noted, MIC-1/GDF15 overexpression may promote local invasion and metastatic spread. PMID:25695521

  14. LeFort I segmented osteotomy experience with piezosurgery in orthognathic surgery

    PubMed Central

    Olate, Sergio; Pozzer, Leandro; Unibazo, Alejandro; Huentequeo-Molina, Claudio; Martinez, Felipe; de Moraes, Márcio

    2014-01-01

    The aim of this work was to present the LeFort I segmented osteotomy in consecutive patients using the piezoelectric system. A descriptive study was designed for patients operated on between November 2012 and January 2014. All the patients presented some type of skeletal anomaly and underwent orthognatic surgery via piezoelectric osteotomies. Each maxillary surgery was developed with that system and those patients who also received osteotomies with a reciprocating saw were excluded. Surgical time and complications were analyzed. 19 patients underwent surgery consecutively with an osteotomy average time of 45 minutes. The patients operated on at the beginning were longer surgeries, whereas the final cases were 40 minutes. No type of laceration of vascular elements or laceration of palatal tissue was observed. The protocol was fully implemented, incorporating all the advantages of piezoelectric systems. It is concluded that the LeFort I segmented osteotomy can be performed with low risk of injuring soft tissues and in a time probably less than 50 minutes for the maxillary osteotomy. PMID:25232392

  15. Le Pseudomonas: Experience du Centre des Brules D’Annaba et Revue de la Litterature

    PubMed Central

    Chaibdraa, A.; Medjellekh, M.S.; Saouli, A.; Bentakouk, M.C.

    2008-01-01

    Summary Le Pseudomonasest un agent pathogène à l'origine d'infections nosocomiales graves dans les centres des brûlés. Son opportunisme et sa virulence en font une préoccupation majeure. Ce travail se propose d'évaluer la place de cette bactérie dans l'écologie bactérienne locale et d'en apprécier la sensibilité aux antibiotiques. Cette étude rétrospective préliminaire porte sur la période de juin 2003 à décembre 2005. Elle intéresse l'ensemble des prélèvements bactériologiques ayant pu être réalisés au centre des brûlés d'Annaba. L'effectif est de 633 micro-organismes isolés dont 128 Pseudomonas (20,2%): 127 aeruginosa (99,2%), 1 fluorescens (0,8%); distribution selon le site de prélèvement: écouvillon (87,5%), prélèvement trachéobronchique (4,6%), hémoculture (3,1%), cathéters (1,6%), urine (1,6%) et sonde urinaire (1,6%). Le pyocyanique se situe après le staphylocoque pour les prélèvements précoces et repasse en tête après un séjour supérieur à une semaine, où 89% des pyocyaniques sont identifiés. Il est en première position dans les pneumopathies sous ventilation assistée invasive. Il se classe troisième dans les hémocultures et les cultures de cathéters. Dans les infections urinaires il est devancé par Candida et la flore périnéale. Les 128 antibiogrammes regroupent 314 réponses sensibles. La sensibilité à plus de deux antibiotiques est de 68%, à deux antibiotiques 24% et à un antibiotique 8%. Seules quatre molécules restent actives: ciprofloxacine > péfloxacine > pipéracilline > ceftazidime. Une résistance absolue est retrouvée pour trois Pseudomonas (2,4%). Le pronostic sévère des infections nosocomiales à pyocyanique et les risques d'options thérapeutiques très limitées font toute leur gravité, d'où l'intérêt de respecter des règles strictes de prescription des antibiotiques et des mesures de prévention. PMID:21991140

  16. Integral Role of GDF-9 and BMP-15 in Ovarian Function

    PubMed Central

    Otsuka, Fumio; McTavish, Kirsten; Shimasaki, Shunichi

    2011-01-01

    The oocyte plays an important role in regulating and promoting follicle growth, and thereby its own development, by the production of oocyte growth factors that predominantly act on supporting granulosa cells via paracrine signaling. Genetic studies in mice demonstrated critical roles of two key oocyte-derived growth factors belonging to the transforming growth factor-β (TGF-β) superfamily, growth and differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) in ovarian function. The identification of Bmp15 and Gdf9 gene mutations as the causal mechanism underlying the highly prolific or infertile nature of several sheep strains in a dosage-sensitive manner also highlighted the crucial role these two genes play in ovarian function. Similarly, large numbers of mutations in the GDF9 and BMP15 genes have been identified in women with premature ovarian failure and in mothers of dizygotic twins. The purpose of this article is to review the genetic studies of GDF-9 and BMP-15 mutations identified in women and sheep as well as describing the various knockout and over-expressing mouse models, and to summarize the molecular and biological functions that underlie the crucial role of these two oocyte factors in female fertility. PMID:21226076

  17. Genetic effects of GDF8 and CAPN1 for carcass and meat traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to improve genetic marker effect estimates of SNP previously associated with muscle traits in beef cattle (F94L marker in GDF8 and 316 marker of CAPN1). Multiyear selection in a composite population segregating both SNP increased minor allele frequency (MAF) to intermediate levels...

  18. Regeneration of periodontal tissues in non-human primates with rhGDF-5 and beta-tricalcium phosphate.

    PubMed

    Emerton, K B; Drapeau, S J; Prasad, H; Rohrer, M; Roffe, P; Hopper, K; Schoolfield, J; Jones, A; Cochran, D L

    2011-12-01

    The application of growth factors has been advocated in support of periodontal regeneration. Recombinant human growth and differentiation factor-5 (rhGDF-5), a member of the bone morphogenetic protein family, has been used to encourage periodontal tissue regeneration. This study evaluated the dose response of rhGDF-5 lyophilized onto beta-tricalcium phosphate (bTCP) granules for periodontal tissue regeneration in a baboon model. Periodontal defects were created bilaterally in 12 baboons by a split-mouth design. Plaque was allowed to accumulate around wire ligatures to create chronic disease. After 2 mos, the ligatures were removed, and a notch was placed at the base of the defect. Two teeth on each side of the mouth were randomly treated with bTCP only, 0.5, 1.0, or 2.0 mg rhGDF-5/g bTCP. Animals were sacrificed 5 mos post-treatment, with micro-CT and histomorphometric analysis performed. After 5 mos, analysis showed alveolar bone, cementum, and periodontal ligament formation in all treatment groups, with a dose-dependent increase in rhGDF-5-treated groups. Height of periodontal tissues also increased with the addition of rhGDF-5, and the amount of residual graft material decreased with rhGDF-5 treatment. Therefore, rhGDF-5 delivered on bTCP demonstrated effective regeneration of all 3 tissues critical for periodontal repair. PMID:21940517

  19. Enhanced reconstruction of long bone architecture by a growth factor mutant combining positive features of GDF-5 and BMP-2.

    PubMed

    Kleinschmidt, Kerstin; Ploeger, Frank; Nickel, Joachim; Glockenmeier, Julia; Kunz, Pierre; Richter, Wiltrud

    2013-08-01

    Non healing bone defects remain a worldwide health problem and still only few osteoinductive growth factors are available for clinical use in bone regeneration. By introducing BMP-2 residues into growth and differentiation factor (GDF)-5 we recently produced a mutant GDF-5 protein BB-1 which enhanced heterotopic bone formation in mice. Designed to combine positive features of GDF-5 and BMP-2, we suspected that this new growth factor variant may improve long bone healing compared to the parent molecules and intended to unravel functional mechanisms behind its action. BB-1 acquired an increased binding affinity to the BMP-IA receptor, mediated enhanced osteogenic induction of human mesenchymal stem cells versus GDF-5 and higher VEGF secretion than BMP-2 in vitro. Rabbit radius defects treated with a BB-1-coated collagen carrier healed earlier and with increased bone volume compared to BMP-2 and GDF-5 according to in vivo micro-CT follow-up. While BMP-2 callus often remained spongy, BB-1 supported earlier corticalis and marrow cavity formation, showing no pseudojoint persistence like with GDF-5. Thus, by combining positive angiogenic and osteogenic features of GDF-5 and BMP-2, only BB-1 restored a natural bone architecture within 12 weeks, rendering this promising growth factor variant especially promising for long bone regeneration. PMID:23680368

  20. Epigenetic silencing of GDF1 disrupts SMAD signaling to reinforce gastric cancer development.

    PubMed

    Yang, W; Mok, M T S; Li, M S M; Kang, W; Wang, H; Chan, A W; Chou, J-L; Chen, J; Ng, E K W; To, K-F; Yu, J; Chan, M W Y; Chan, F K L; Sung, J J Y; Cheng, A S L

    2016-04-21

    Accumulating evidence reveals the effectiveness of epigenetic therapy in gastric cancer. However, the molecular mechanisms and targets underlying such therapeutic responses remain elusive. Herein, we report an aberrant yet therapeutically rectifiable epigenetic signaling in gastric carcinogenesis. Administration of DNA-demethylating drug 5-aza-2'-deoxycytidine (5-aza-dC) reduced gastric cancer incidence by ~74% (P<0.05) in N-nitroso-N-methylurea-treated mice. Through genome-wide methylation scanning, novel promoter hypermethylation-silenced and drug-targeted genes were identified in the resected murine stomach tumors and tissues. We uncovered that growth/differentiation factor 1 (Gdf1), a member of the transforming growth factor-β superfamily, was silenced by promoter hypermethylation in control tumor-bearing mice, but became reactivated in 5-aza-dC-treated mice (P<0.05). In parallel, the downregulated SMAD2/3 phosphorylation in gastric cancer was revived by 5-aza-dC in vivo. Such hypermethylation-dependent silencing and 5-aza-dC-mediated reactivation of GDF1-SMAD2/3 activity was conserved in human gastric cancer cells (P<0.05). Subsequent functional characterization further revealed the antiproliferative activity of GDF1, which was exerted through activation of SMAD2/3/4-mediated signaling, transcriptional controls on p15, p21 and c-Myc cell-cycle regulators and phosphorylation of retinoblastoma protein. Clinically, hypermethylation and loss of GDF1 was significantly associated with reduced phosphorylated-SMAD2/3 and poor survival in stomach cancer patients (P<0.05). Taken together, we demonstrated a causal relationship between DNA methylation and a tumor-suppressive pathway in gastric cancer. Epigenetic silencing of GDF1 abrogates the growth-inhibitory SMAD signaling and renders proliferation advantage to gastric epithelial cells during carcinogenesis. This study lends support to epigenetic therapy for gastric cancer chemoprevention and identifies a potential

  1. Temporal expression of GDF-9 and BMP-15 mRNAs in canine ovarian follicles.

    PubMed

    Palomino, Jaime; De Los Reyes, Monica

    2016-10-01

    This study aimed to investigate the expression profiles of growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15) mRNA in canine oocytes and follicular cells throughout development at the different phases of the estrus cycle. Ovarian structures (follicles and CL) and plasma progesterone concentration were used to confirm the physiological status of each donor. Denuded oocytes and their follicular cells were recovered from follicles (n = 675) distributed into 4 types (preantral, small antral ∼0.2-0.39 mm, medium antral ∼0.4-5.9 mm, and large antral ∼6-8 mm). Total RNA was extracted and reverse transcribed, and the levels of expression for these 2 genes were determined using a quantitative real-time polymerase chain reaction technique; the data were evaluated by ANOVA. Relative expressions levels of GDF-9 and BMP-15 transcripts were detected in the oocyte and follicular cells in all follicular stages evaluated, showing differential changes (P < 0.05) during development over the estrus cycle. The expression patterns of both transcripts were highly correlated between follicles cells and oocytes (r > 0.8; P < 0.05 for GDF-9 and BMP-15), although GDF-9 was expressed at higher levels (P < 0.05) in the oocyte compared with the follicle cells. All cell types showed more GDF-9 mRNA abundance at early developing stages, mainly in the anestrus phase, and declining levels in the later stages (P < 0.05), whereas BMP-15 mRNA levels increased (P < 0.05) in follicular cells and oocytes from the preantral to the later stages, and remained constant during the final preovulatory stage. In conclusion, these two genes were detected in follicular cells and oocytes and were differentially expressed during the follicular development across the estrus cycle. PMID:27341772

  2. "Dans le sillon des voyageurs": Thunder Bay's Experiment in French Community Television

    ERIC Educational Resources Information Center

    Lewis, David W. P.

    1976-01-01

    Thunder Bay French Television was begun as an experiment in amateur community television designed to appeal to francophones, elementary school pupils, students, and the public at large. Organization and programming are described. (RM)

  3. GDF-15 enhances intracellular Ca2+ by increasing Cav1.3 expression in rat cerebellar granule neurons

    PubMed Central

    Lu, Jun-Mei; Wang, Chang-Ying; Hu, Changlong; Fang, Yan-Jia; Mei, Yan-Ai

    2016-01-01

    GDF-15 (growth/differentiation factor 15) is a novel member of the TGF (transforming growth factor)-β superfamily that has critical roles in the central and peripheral nervous systems. We reported previously that GDF-15 increased delayed rectifier outward K+ currents and Kv2.1 α subunit expression through TβRII (TGF-β receptor II) to activate Src kinase and Akt/mTOR (mammalian target of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present study, we found that treatment of CGNs with GDF-15 for 24 h increased the intracellular Ca2+ concentration ([Ca2+]i) in response to membrane depolarization, as determined by Ca2+ imaging. Whole-cell current recordings indicated that GDF-15 increased the inward Ca2+ current (ICa) without altering steady-state activation of Ca2+ channels. Treatment with nifedipine, an inhibitor of L-type Ca2+ channels, abrogated GDF-15-induced increases in [Ca2+]i and ICa. The GDF-15-induced increase in ICa was mediated via up-regulation of the Cav1.3 α subunit, which was attenuated by inhibiting Akt/mTOR and ERK (extracellular-signal-regulated kinase) pathways and by pharmacological inhibition of Src-mediated TβRII phosphorylation. Given that Cav1.3 is not only a channel for Ca2+ influx, but also a transcriptional regulator, our data confirm that GDF-15 induces protein expression via TβRII and activation of a non-Smad pathway, and provide novel insight into the mechanism of GDF-15 function in neurons. PMID:27114559

  4. Age Related Changes in Craniofacial Morphology in GDF-8 (Myostatin) Deficient Mice

    PubMed Central

    Vecchione, Lisa; Miller, Jeffrey; Byron, Craig; Cooper, Gregory M.; Barbano, Timothy; Cray, James; Losee, Joseph E.; Hamrick, Mark W.; Sciote, James J.; Mooney, Mark P.

    2011-01-01

    It is well recognized that masticatory muscle function helps determine morphology, although the extent of function on final form is still debated. GDF-8 (myostatin), a transcription factor is a negative regulator of skeletal muscle growth. A recent study has shown that mice homozygous for the myostatin mutation had increased muscle mass and craniofacial dysmorphology in adulthood. However, it is unclear whether such dysmorphology is present at birth. This study examines the onset and relationship between hypermuscularity and craniofacial morphology in neonatal and adult mice with GDF-8 deficiency. Fifteen (8 wild-type and 7 GDF-8 −/−), 1 day old and 16 (9 wt and 7 GDF-8 −/−), 180 day old male CD-1 mice were used. Standardized radiographs were taken of each head, scanned, traced, and cephalometric landmarks identified. Significant mean differences were assessed using a group × age, two-way ANOVA. Myostatin-deficient mice had significantly (p<0.01) smaller body and masseter muscle weights and craniofacial skeletons at 1 day of age and significantly greater body and masseter muscle weights at 180 days of age compared to controls. Myostatin-deficient mice showed significantly (p<0.001) longer and “rocker-shaped” mandibles and shorter and wider crania compared to controls at 180 days. Significant correlations were noted between masseter muscle weight and all cephalometric measurements in 180 day old Myostatin-deficient mice. Results suggest in this mouse model, there may be both early systemic skeletal growth deficiencies and later compensatory changes from hypermuscularity. These findings reiterate the role that masticatory muscle function plays on the ontogeny of the cranial vault, base, and most notably the mandible. PMID:19899116

  5. Freeze-Dried Tendon Allografts as Tissue Engineering Scaffolds for Gdf5 Gene Delivery

    PubMed Central

    Basile, Patrick; Dadali, Tulin; Jacobson, Justin; Hasslund, Sys; Ulrich-Vinther, Michael; Søballe, Kjeld; Nishio, Yasuhiko; Drissi, M Hicham; Langstein, Howard N; Mitten, David J; O’Keefe, Regis J; Schwarz, Edward M; Awad, Hani A

    2009-01-01

    Tendon reconstruction using grafts often results in adhesions that limit joint flexion. These adhesions are precipitated by inflammation, fibrosis, and paucity of tendon differentiation signals during healing. To study this problem, we developed a mouse model in which the FDL tendon is reconstructed using a live autograft or a freeze-dried allograft and identified Gdf5 as a therapeutic target. Here we investigate the potential of rAAV-Gdf5 coated freeze-dried tendon allografts as “therapeutically-endowed” tissue engineering scaffolds to reduce adhesions. In reporter gene studies we demonstrate that rAAV-coated tendon allografts mediate efficient transduction of adjacent soft tissues, with expression peaking at 7-days. We also demonstrate that rAAV-Gdf5 vector significantly accelerates wound healing in an in vitro fibroblast scratch model, and when loaded onto freeze-dried FDL tendon allografts significantly improves the metatarsophalangeal joint flexion compared to rAAV-lacZ controls. Collectively, our data demonstrate the feasibility and efficacy of therapeutic tendon allograft processing as a novel paradigm in tissue engineering to address difficult clinical problems such as tendon adhesions. PMID:18180771

  6. GDF6, a Novel Locus for a Spectrum of Ocular Developmental Anomalies

    PubMed Central

    Asai-Coakwell, Mika ; French, Curtis R. ; Berry, Karyn M. ; Ye, Ming ; Koss, Ron ; Somerville, Martin ; Mueller, Rosemary ; van Heyningen, Veronica ; Waskiewicz, Andrew J. ; Lehmann, Ordan J. 

    2007-01-01

    Colobomata represent visually impairing ocular closure defects that are associated with a diverse range of developmental anomalies. Characterization of a chromosome 8q21.2-q22.1 segmental deletion in a patient with chorioretinal coloboma revealed elements of nonallelic homologous recombination and nonhomologous end joining. This genomic architecture extends the range of chromosomal rearrangements associated with human disease and indicates that a broader spectrum of human chromosomal rearrangements may use coupled homologous and nonhomologous mechanisms. We also demonstrate that the segmental deletion encompasses GDF6, encoding a member of the bone-morphogenetic protein family, and that inhibition of gdf6a in a model organism accurately recapitulates the proband’s phenotype. The spectrum of disorders generated by morpholino inhibition and the more severe defects (microphthalmia and anophthalmia) observed at higher doses illustrate the key role of GDF6 in ocular development. These results underscore the value of integrated clinical and molecular investigation of patients with chromosomal anomalies. PMID:17236135

  7. Description and status of NASA-LeRC/DOE photovoltaic applications systems experiments

    NASA Technical Reports Server (NTRS)

    Ratajczak, A. F.

    1978-01-01

    In its role of supporting the DOE Photovoltaic Program, the NASA-Lewis Research Center has designed, fabricated and installed 16 geographically dispersed photovoltaic systems. These systems are powering a refrigerator, highway warning sign, forest lookout towers, remote weather stations, a water chiller at a visitor center, and insect survey traps. Each of these systems is described in terms of load requirements, solar array and battery size, and instrumentation and controls. Operational experience is described and present status is given for each system. The P/V power systems have proven to be highly reliable with almost no problems with modules and very few problems overall

  8. Continued Development of in Situ Geochronology for Planetary Using KArLE (Potassium-Argon Laser Experiment)

    NASA Technical Reports Server (NTRS)

    Devismes, D.; Cohen, B. A.

    2016-01-01

    Geochronology is a fundamental measurement for planetary samples, providing the ability to establish an absolute chronology for geological events, including crystallization history, magmatic evolution, and alteration events, and providing global and solar system context for such events. The capability for in situ geochronology will open up the ability for geochronology to be accomplished as part of lander or rover complement, on multiple samples rather than just those returned. An in situ geochronology package can also complement sample return missions by identifying the most interesting rocks to cache or return to Earth. The K-Ar radiometric dating approach to in situ dating has been validated by the Curiosity rover on Mars as well as several laboratories on Earth. Several independent projects developing in situ rock dating for planetary samples, based on the K-Ar method, are giving promising results. Among them, the Potassium (K)-Argon Laser Experiment (KArLE) at MSFC is based on techniques already in use for in planetary exploration, specifically, Laser-induced Breakdown Spectroscopy (LIBS, used on the Curiosity Chemcam), mass spectroscopy (used on multiple planetary missions, including Curiosity, ExoMars, and Rosetta), and optical imaging (used on most missions).

  9. GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-βRII heterodimer.

    PubMed

    Artz, Annette; Butz, Stefan; Vestweber, Dietmar

    2016-07-28

    Growth differentiation factor 15 (GDF-15) is the first cytokine known to counteract chemokine-induced activation of leukocyte integrins. We showed recently that this activity dampens neutrophil recruitment into inflamed tissue and is required for survival of myocardial infarction in mice. The receptor responsible for this GDF-15-triggered anti-inflammatory mechanism on myeloid cells is not known. Here, we identify this receptor as transforming growth factor β receptor I (TGF-βRI) (activin receptor-like kinase 5 [ALK-5]) and TGF-β receptor II (TGF-βRII). We show that interference with these receptors by small-molecule inhibitors, antibodies, or small interfering RNA, blocked the GDF-15 effect on leukocyte integrin activation. Likewise, gene inactivation of each of the 2 receptors in neutrophils isolated from conditional gene-deficient mice abolished the inhibitory effect of GDF-15 on CXCL1-induced β2-integrin activation and neutrophil diapedesis. Rapid neutrophil arrest induced by CXCL1 in vivo was inhibited by GDF-15 in an ALK-5 and TGF-βRII dependent way. As for GDF-15 gene-deficient mice, we found that extravasation of neutrophils deficient for ALK-5 or TGF-βRII was strongly increased in the interleukin-1β inflamed cremaster. The inhibitory effects of GDF-15 on neutrophil integrin activation and in vivo neutrophil arrest were also found for TGF-β1. Mechanistically, GDF-15 and TGF-β1 interfered with integrin activation by inhibiting the activation of Ras-related protein 1 (Rap-1), an effect that depended on CalDAG- guanine nucleotide exchange factor 1 (GEF1) and cell division control protein 42 homolog. We conclude that both GDF-15 and TGF-β1 counteract chemokine-induced integrin activation on neutrophils via the ALK-5/TGF-βRII heterodimer. This represents a novel, rapid anti-inflammatory activity of the 2 TGF-β receptors and of TGF-β1. PMID:27235139

  10. Small Molecules Dorsomorphin and LDN-193189 Inhibit Myostatin/GDF8 Signaling and Promote Functional Myoblast Differentiation*

    PubMed Central

    Horbelt, Daniel; Boergermann, Jan H.; Chaikuad, Apirat; Alfano, Ivan; Williams, Eleanor; Lukonin, Ilya; Timmel, Tobias; Bullock, Alex N.; Knaus, Petra

    2015-01-01

    GDF8, or myostatin, is a member of the TGF-β superfamily of secreted polypeptide growth factors. GDF8 is a potent negative regulator of myogenesis both in vivo and in vitro. We found that GDF8 signaling was inhibited by the small molecule ATP competitive inhibitors dorsomorphin and LDN-193189. These compounds were previously shown to be potent inhibitors of BMP signaling by binding to the BMP type I receptors ALK1/2/3/6. We present the crystal structure of the type II receptor ActRIIA with dorsomorphin and demonstrate that dorsomorphin or LDN-193189 target GDF8 induced Smad2/3 signaling and repression of myogenic transcription factors. As a result, both inhibitors rescued myogenesis in myoblasts treated with GDF8. As revealed by quantitative live cell microscopy, treatment with dorsomorphin or LDN-193189 promoted the contractile activity of myotubular networks in vitro. We therefore suggest these inhibitors as suitable tools to promote functional myogenesis. PMID:25368322

  11. Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation.

    PubMed

    Horbelt, Daniel; Boergermann, Jan H; Chaikuad, Apirat; Alfano, Ivan; Williams, Eleanor; Lukonin, Ilya; Timmel, Tobias; Bullock, Alex N; Knaus, Petra

    2015-02-01

    GDF8, or myostatin, is a member of the TGF-β superfamily of secreted polypeptide growth factors. GDF8 is a potent negative regulator of myogenesis both in vivo and in vitro. We found that GDF8 signaling was inhibited by the small molecule ATP competitive inhibitors dorsomorphin and LDN-193189. These compounds were previously shown to be potent inhibitors of BMP signaling by binding to the BMP type I receptors ALK1/2/3/6. We present the crystal structure of the type II receptor ActRIIA with dorsomorphin and demonstrate that dorsomorphin or LDN-193189 target GDF8 induced Smad2/3 signaling and repression of myogenic transcription factors. As a result, both inhibitors rescued myogenesis in myoblasts treated with GDF8. As revealed by quantitative live cell microscopy, treatment with dorsomorphin or LDN-193189 promoted the contractile activity of myotubular networks in vitro. We therefore suggest these inhibitors as suitable tools to promote functional myogenesis. PMID:25368322

  12. Natural or controlled experiment? Disentangling anthropogenic and geologic contributions to the sediment load of the Le Sueur River, MN, USA

    NASA Astrophysics Data System (ADS)

    Finnegan, N. J.; Gran, K. B.

    2012-12-01

    Catastrophic draining of glacial Lake Agassiz at the end of the Pleistocene triggered a pulse of incision along the Minnesota River, MN, USA, that is currently propagating into tributary channels and elevating channel incision rates far above regional background levels. At the same time, installation of artificial drainage to remove excess soil water (tiling) in tributaries of the Minnesota has resulted in shorter and higher amplitude hydrographs during spring snow melt and storm events. Thus both natural and anthropogenic explanations exist for high sediment loads from tributaries to the Minnesota River, among them the Le Sueur River, which is currently impaired for turbidity under EPA Clean Water Act standards. Here we investigate the transient incision history of the Le Sueur River to aid in the development of Total Maximum Daily Loads (TMDLs) for sediment in the Le Sueur. Establishing TMDLs for the Le Sueur requires separation of anthropogenic and geologic contributions to current sediment loads. Towards this end, we ran a series of numerical simulations of the excavation of the Le Sueur River valley over the Holocene in order to constrain pre-settlement rates of sediment export. Our approach relies on coupling (with varying strength) a 2D numerical model for river meandering to various 1D numerical models for river incision. Fortuitously, both the initial profile of the Le Sueur (prior to the flood from Lake Agassiz) as well as the timing of the flood itself can be reasonably constrained from LiDAR data and previous Quaternary studies, respectively. Additionally, LiDAR-mapping of discontinuous, unpaired strath terraces combined with OSL and/or 14C dates on 18 strath terrace deposits pin pieces of the long profile of the Le Sueur River in time and space. By minimizing the model misfit for strath terrace ages, the current river elevation long profile, and the width between bluffs along the Le Sueur River valley, we identify a preferred valley excavation history

  13. The role of growth/differentiation factor 5 (GDF5) in the induction and survival of midbrain dopaminergic neurones: relevance to Parkinson's disease treatment.

    PubMed

    Sullivan, Aideen M; O'Keeffe, Gerard W

    2005-09-01

    Growth/differentiation factor-5 (GDF5) is a member of the transforming growth factor-beta superfamily which has potent effects on dopaminergic neurones in vitro and in vivo. GDF5 is under investigation as a potential therapeutic agent for Parkinson's disease (PD), which is caused by the progressive degeneration of dopaminergic neurones projecting from the substantia nigra (SN) to the striatum. In the rat ventral mesencephalon (VM; the developing SN), GDF5 expression peaks at embryonic day 14, the time at which dopaminergic neurones undergo terminal differentiation. Addition of GDF5 protein to cultures of embryonic rat VM increases the survival and improves the morphology of dopaminergic neurones in these cultures. GDF5 treatment also increases the number of cells which adopt a dopaminergic phenotype in cultures of VM progenitor cells. Intracerebral administration of GDF5 has potent neuroprotective and restorative effects on the nigrostriatal pathway in animal models of PD. Furthermore, addition of GDF5 protein to embryonic rat dopaminergic neuronal transplants improves their survival and function in a rat model of PD. Thus, GDF5 has potential applications to PD therapy as a dopaminergic neuroprotective agent and as a factor that may induce a dopaminergic neuronal fate in unrestricted progenitor cells. PMID:16185246

  14. Stokes emission in GdF3:Nd3+ nanoparticles for bioimaging probes

    NASA Astrophysics Data System (ADS)

    Pokhrel, M.; Mimun, L. C.; Yust, B.; Kumar, G. A.; Dhanale, A.; Tang, L.; Sardar, D. K.

    2014-01-01

    There is increasing interest in rare earth (RE) doped nanoparticles (NPs) due to their sharp absorption and photoluminescence (PL) in the near infrared (NIR) spectral region. These NIR based nanoparticles (NPs) could allow biological imaging at substantial depths with enhanced contrast and high spatial resolution due to the absence of auto fluorescence in biological samples under infrared excitation. Here, we present the highly efficient infrared photoluminescence in GdF3:Nd3+ nanoparticles under 800 nm excitation within the hydrodynamic size limitations for bio-applications. The downconversion (Stokes emission) absolute quantum yields (QY) in powder, polymaleic anhydride-alt-1-octadicene (PMAO) coated powder and colloidal solutions have been investigated. QY measurements have revealed that downconversion (Stokes emission) QYs of approximately 5 +/- 2 nm sized GdF3:1% Nd3+ colloidal NPs are 2000 times higher than those of efficient upconversion (UC) particles NaYF4:20% Er/2% Yb of the same size. Furthermore, the utility of these NIR emitting nanoparticles for bioimaging probes has been demonstrated by confocal imaging and spectroscopic study.There is increasing interest in rare earth (RE) doped nanoparticles (NPs) due to their sharp absorption and photoluminescence (PL) in the near infrared (NIR) spectral region. These NIR based nanoparticles (NPs) could allow biological imaging at substantial depths with enhanced contrast and high spatial resolution due to the absence of auto fluorescence in biological samples under infrared excitation. Here, we present the highly efficient infrared photoluminescence in GdF3:Nd3+ nanoparticles under 800 nm excitation within the hydrodynamic size limitations for bio-applications. The downconversion (Stokes emission) absolute quantum yields (QY) in powder, polymaleic anhydride-alt-1-octadicene (PMAO) coated powder and colloidal solutions have been investigated. QY measurements have revealed that downconversion (Stokes emission) QYs

  15. Tendon tissue engineering: Adipose 1 derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems

    PubMed Central

    James, R; Kumbar, S G; Laurencin, C T; Balian, G; Chhabra, A B

    2011-01-01

    Tendon tissue engineering with a biomaterial scaffold that mimics the tendon extracellular matrix (ECM) and is biomechanically suitable when combined with readily available autologous cells may provide successful regeneration of defects in tendon. Current repair strategies using suitable autografts and freeze-dried allografts lead to a slow repair process that is sub-optimal and fails to restore function, particularly in difficult clinical situations such as zone II flexor tendon injuries of the hand. We have investigated the effect of GDF-5 on cell proliferation and gene expression by primary rat adipose-derived stromal cells (ADSCs) that were cultured on poly(DL-lactide-co-glycolide) PLAGA fiber scaffold and compared to PLAGA 2D film scaffold. The electrospun scaffold mimics the collagen fiber bundles present in native tendon tissue, and supports the adhesion and proliferation of multipotent ADSCs. Gene expression of scleraxis, the neotendon marker was upregulated 7 – 8 fold at 1 week with GDF-5 treatment when cultured on 3D electrospun scaffold, and was significantly higher at 2 weeks compared to 2D films with or without GDF-5 treatment. Expression of the genes that encode the major tendon ECM protein, collagen type I, was increased by 4 fold starting at 1 week on treatment with 100ng/mL GDF-5, and at all time points the expression was significantly higher compared to 2D films irrespective of GDF-5 treatment. Thus stimulation with GDF-5 can modulate primary ADSCs on PLAGA fiber scaffold to produce a soft, collagenous musculoskeletal tissue that fulfills the need for tendon regeneration. PMID:21436509

  16. Characterization of oocyte-expressed GDF9 gene in buffalo and mapping of its TSS and putative regulatory elements.

    PubMed

    Roy, B; Rajput, S; Raghav, S; Kumar, P; Verma, A; Jain, A; Jain, T; Singh, D; De, S; Goswami, S L; Datta, T K

    2013-05-01

    Summary In spite of emerging evidence about the vital role of GDF9 in determination of oocyte competence, there is insufficient information about its regulation of oocyte-specific expression, particularly in livestock animals. Because of the distinct prominence of buffalo as a dairy animal, the present study was undertaken to isolate and characterize GDF9 cDNA using orthologous primers based on the bovine GDF9 sequence. GDF9 transcripts were found to be expressed in oocytes irrespective of their follicular origin, and shared a single transcription start site (TSS) at -57 base pairs (bp) upstream of ATG. Assignment of the TSS is consistent with the presence of a TATA element at -23 of the TSS mapped in this study. Localization of a buffalo-specific minimal promoter within 320 bp upstream of ATG was consolidated by identification of an E-box element at -113bp. Presence of putative transcription factor binding sites and other cis regulatory elements were analyzed at ~5 kb upstream of TSS. Various germ cell-specific cis-acting regulatory elements (BNCF, BRNF, NR2F, SORY, Foxh1, OCT1, LHXF etc.) have been identified in the 5' flanking region of the buffalo GDF9 gene, including NOBOX DNA binding elements and consensuses E-boxes (CANNTG). Presence of two conserved E-boxes found on buffalo sequence at -520 and -718 positions deserves attention in view of its sequence deviation from other species. Two NOBOX binding elements (NBE) were detected at the -3471 and -203 positions. The fall of the NBE within the putative minimal promoter territory of buffalo GDF9 and its unique non-core binding sequence could have a possible role in the control of the core promoter activity. PMID:22230197

  17. Energy transfer and tunable multicolor emission and paramagnetic properties of GdF3:Dy(3+),Tb(3+),Eu(3+) phosphors.

    PubMed

    Guan, Hongxia; Sheng, Ye; Xu, Chengyi; Dai, Yunzhi; Xie, Xiaoming; Zou, Haifeng

    2016-07-20

    A series of Dy(3+), Tb(3+), Eu(3+) singly or doubly or triply doped GdF3 phosphors were synthesized by a glutamic acid assisted one-step hydrothermal method. The samples were characterized by X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM) and photoluminescence (PL) spectroscopy. The results show that the synthesized samples are all pure GdF3. The obtained samples have a peanut-like morphology with a diameter of about 270 nm and a length of about 600 nm. Under UV excitation, GdF3:Dy(3+), GdF3:Tb(3+) and GdF3:Eu(3+) samples exhibit strong blue, green and red emissions, respectively. By adjusting their relative doping concentrations in the GdF3 host, the different color hues of green and red light are obtained by co-doped Dy(3+), Tb(3+) and Tb(3+), Eu(3+) ions in the GdF3 host, respectively. Besides, there exist two energy transfer pairs in the GdF3 host: (1) Dy(3+) → Tb(3+) and (2) Tb(3+) → Eu(3+). More significantly, in the Dy(3+), Tb(3+), and Eu(3+) tri-doped GdF3 phosphors, white light can also be achieved upon excitation of UV light by adjusting the doping concentration of Eu(3+). In addition, the obtained samples also exhibit paramagnetic properties at room temperature (300 K) and low temperature (2 K). It is obvious that multifunctional Dy(3+), Tb(3+), Eu(3+) tri-doped GdF3 materials including tunable multicolors and intrinsic paramagnetic properties may have potential applications in the field of full-color displays. PMID:27388285

  18. Serum Levels of Human MIC-1/GDF15 Vary in a Diurnal Pattern, Do Not Display a Profile Suggestive of a Satiety Factor and Are Related to BMI.

    PubMed

    Tsai, Vicky Wang-Wei; Macia, Laurence; Feinle-Bisset, Christine; Manandhar, Rakesh; Astrup, Arne; Raben, Anne; Lorenzen, Janne Kunchel; Schmidt, Peter T; Wiklund, Fredrik; Pedersen, Nancy L; Campbell, Lesley; Kriketos, Adamandia; Xu, Aimin; Pengcheng, Zhou; Jia, Weiping; Curmi, Paul M G; Angstmann, Christopher N; Lee-Ng, Ka Ki Michelle; Zhang, Hong Ping; Marquis, Christopher P; Husaini, Yasmin; Beglinger, Christoph; Lin, Shu; Herzog, Herbert; Brown, David A; Sainsbury, Amanda; Breit, Samuel N

    2015-01-01

    The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC-1/GDF15 on feeding centres in the hypothalamus and brainstem. More recent studies in germline gene deleted mice also suggest that this cytokine may play a role in physiological regulation of energy homeostasis. To further characterize the role of MIC-1/GDF15 in physiological regulation of energy homeostasis in man, we have examined diurnal and food associated variation in serum levels and whether variation in circulating levels relate to BMI in human monozygotic twin pairs. We found that the within twin pair differences in serum MIC-1/GDF15 levels were significantly correlated with within twin pair differences in BMI, suggesting a role for MIC-1/GDF15 in the regulation of energy balance in man. MIC-1/GDF15 serum levels altered slightly in response to a meal, but comparison with variation its serum levels over a 24 hour period suggested that these changes are likely to be due to bimodal diurnal variation which can alter serum MIC-1/GDF15 levels by about plus or minus 10% from the mesor. The lack of a rapid and substantial postprandial increase in MIC-1/GDF15 serum levels suggests that MIC1/GDF15 is unlikely to act as a satiety factor. Taken together, our findings suggest that MIC-1/GDF15 may be a physiological regulator of energy homeostasis in man, most probably due to actions on long-term regulation of energy homeostasis. PMID:26207898

  19. The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk.

    PubMed

    Becker, Jessica; May, Andrea; Gerges, Christian; Anders, Mario; Schmidt, Claudia; Veits, Lothar; Noder, Tania; Mayershofer, Rupert; Kreuser, Nicole; Manner, Hendrik; Venerito, Marino; Hofer, Jan-Hinnerk; Lyros, Orestis; Ahlbrand, Constantin J; Arras, Michael; Hofer, Sebastian; Heinrichs, Sophie K M; Weise, Katharina; Hess, Timo; Böhmer, Anne C; Kosiol, Nils; Kiesslich, Ralf; Izbicki, Jakob R; Hölscher, Arnulf H; Bollschweiler, Elfriede; Malfertheiner, Peter; Lang, Hauke; Moehler, Markus; Lorenz, Dietmar; Ott, Katja; Schmidt, Thomas; Nöthen, Markus M; Hackelsberger, Andreas; Schumacher, Brigitte; Pech, Oliver; Vashist, Yogesh; Vieth, Michael; Weismüller, Josef; Knapp, Michael; Neuhaus, Horst; Rösch, Thomas; Ell, Christian; Gockel, Ines; Schumacher, Johannes

    2016-05-01

    Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) represent two stages within the esophagitis-metaplasia-dysplasia-adenocarcinoma sequence. Previously genetic risk factors have been identified that confer risk to BE and EAC development. However, to which extent the genetic variants confer risk to different stages of the BE/EAC sequence remains mainly unknown. In this study we analyzed three most recently identified BE variants at the genes GDF7 (rs3072), TBX5 (rs2701108), and ALDH1A2 (rs3784262) separately in BE and EAC samples in order to determine their risk effects during BE/EAC sequence. Our data show that rs3072 at GDF7 and rs2701108 at TBX5 are also associated with EAC and conclude that both loci confer disease risk also at later stages of the BE/EAC sequence. In contrast, rs3784262 at ALDH1A2 was highly significantly associated with BE, but showed no association with EAC. Our data do not provide evidence that the ALDH1A2 locus confers equal risk in early and late stages of BE/EAC sequence. PMID:26783083

  20. 77 FR 39689 - Application To Export Electric Energy; IPR-GDF SUEZ Energy Marketing North America, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-05

    ... Application To Export Electric Energy; IPR-GDF SUEZ Energy Marketing North America, Inc. AGENCY: Office of... Marketing North America, Inc. (GSEMNA) has applied for authority to transmit electric energy from the United..., Federal power marketing agencies, and other entities within the United States. The existing...

  1. Controllable synthesis and upconversion emission of ultrasmall lanthanide-doped Sr2GdF7 nanocrystals

    NASA Astrophysics Data System (ADS)

    Xiang, Lijun; Ren, Guozhong; Mao, Yifu; He, Jin; Su, Rui

    2015-11-01

    The effect of rare-earth ions content on the phase structure, crystal size and morphology of SrF2-GdF3 system were studied under solvothermal conditions. By tuning the molar ratio of reactants, tetragonal phase Sr2GdF7 nanocrystals (NCs) were synthesized via solvothermal method using oleic acid as capping ligands. The effects of reaction conditions on the phase structure, crystal size, morphology, and upconversion (UC) emission properties of the products were investigated. The results reveal that apropos Gd3+ ions content (0.30-0.45 mmol) is favorable to the formation of pure phase Sr2GdF7 NCs with more uniform size distribution. The average crystalline size of the products can be controlled less than 10 nm. The energy transfer UC mechanisms for the fluorescent intensity were also investigated. Following Yb3+, Er3+, Tm3+ and Ho3+ ions doping, the Sr2GdF7 NCs show intense green, yellow, and white-color UC emission under the excitation of a 980 nm laser, and the doping concentration of lanthanide ions was optimized, which makes the NCs show maximum intensities under the excitation of a 980 nm laser.

  2. A phase IIa randomized controlled pilot study evaluating the safety and clinical outcomes following the use of rhGDF-5/β-TCP in regenerative periodontal therapy.

    PubMed

    Windisch, Péter; Stavropoulos, Andreas; Molnár, Bálint; Szendröi-Kiss, Dóra; Szilágyi, Emese; Rosta, Péter; Horváth, Attila; Capsius, Björn; Wikesjö, Ulf M E; Sculean, Anton

    2012-08-01

    To present the safety profile, the early healing phase and the clinical outcomes at 24 weeks following treatment of human intrabony defects with open flap debridement (OFD) alone or with OFD and rhGDF-5 adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier. Twenty chronic periodontitis patients, each with at least one tooth exhibiting a probing depth ≥6 mm and an associated intrabony defect ≥4 mm entered the study. Ten subjects (one defect/patient) were randomized to receive OFD alone (control) and ten subjects OFD combined with rhGDF-5/β-TCP. Blood samples were collected at screening, and at weeks 2 and 24 to evaluate routine hematology and clinical chemistry, rhGDF-5 plasma levels, and antirhGDF-5 antibody formation. Plaque and gingival indices, bleeding on probing, probing depth, clinical attachment level, and radiographs were recorded pre- and 24 weeks postsurgery. Comparable safety profiles were found in the two treatment groups. Neither antirhGDF-5 antibody formation nor relevant rhGDF-5 plasma levels were detected in any patient. At 6 months, treatment with OFD + rhGDF-5/β-TCP resulted in higher but statistically not significant PD reduction (3.7 ± 1.2 vs. 3.1 ± 1.8 mm; p = 0.26) and CAL gain (3.2 ± 1.7 vs. 1.7 ± 2.2 mm; p = 0.14) compared to OFD alone. In the tested concentration, the use of rhGDF-5/β-TCP appeared to be safe and the material possesses a sound biological rationale. Thus, further adequately powered, randomized controlled clinical trials are warranted to confirm the clinical relevance of this new approach in regenerative periodontal therapy. rhGDF-5/β-TCP may represent a promising new techology in regenerative periodontal therapy. PMID:21887500

  3. GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells

    PubMed Central

    Wang, Chang-Ying; Huang, An-Qi; Zhou, Meng-Hua; Mei, Yan-Ai

    2014-01-01

    GDF15 (growth/differentiation factor 15), a novel member of the TGFβ (transforming growth factor β) superfamily, plays critical roles in the central and peripheral nervous systems, but the signal transduction pathways and receptor subtypes involved are not well understood. In the present paper, we report that GDF15 specifically increases the IK (delayed-rectifier outward K+ current) in rat CGNs (cerebellar granule neurons) in time- and concentration-dependent manners. The GDF15-induced amplification of the IK is mediated by the increased expression and reduced lysosome-dependent degradation of the Kv2.1 protein, the main α-subunit of the IK channel. Exposure of CGNs to GDF15 markedly induced the phosphorylation of ERK (extracellular-signal-regulated kinase), Akt and mTOR (mammalian target of rapamycin), but the GDF15-induced IK densities and increased expression of Kv2.1 were attenuated only by Akt and mTOR, and not ERK, inhibitors. Pharmacological inhibition of the Src-mediated phosphorylation of TGFβR2 (TGFβ receptor 2), not TGFβR1, abrogated the effect of GDF15 on IK amplification and Kv2.1 induction. Immunoprecipitation assays showed that GDF15 increased the tyrosine phosphorylation of TGFβRII in the CGN lysate. The results of the present study reveal a novel regulation of Kv2.1 by GDF15 mediated through the TGFβRII-activated Akt/mTOR pathway, which is a previously uncharacterized Smad-independent mechanism of GDF15 signalling. PMID:24597762

  4. Digital outcrop characterisation and fracture modelling for a GDF in a crystalline basement.

    NASA Astrophysics Data System (ADS)

    Head, William S.; Hodgetts, David; Smith, Nicholas T.

    2013-04-01

    Plans to dispose of the UK's legacy nuclear waste in a Geological Disposal Facility (GDF) depend heavily on the geological suitability of the host bedrock. Characterising the geology at the proposed depth of the GDF (500 m to 1 km) is a major challenge facing the industry. Clastic surface outcrop analogues are used in the hydrocarbon industry to characterise potential reservoirs that do not outcrop at the surface. The same approach has, to our knowledge, never been applied to crystalline rocks: one of the proposed settings for a GDF. This project utilises terrestrial lidar scanning to create 3D Digital Outcrop Models (DOM's) of geological exposures which form part of the Borrowdale Volcanic Group (BVG) exposed in several localities around the Lake District of the UK. The BVG is a laterally extensive, highly heterogeneous 6 km thick unit, comprising mainly igneous rocks with associated sedimentary and metamorphic rocks. The rocks, which have a complex tectonic history, were formed by explosive caldera-type eruptions in the Late Ordovician (Caradoc) period, and include lavas, ignimbrites, sills and dykes. Using the lidar data collected with a Riegl LMS-Z420i terrestrial laser scanner, a DOM has been constructed and the fracture distributions mapped using a combination of manual and automated approaches. The resulting fracture data are analysed to give statistical information on fracture dimension, distribution and spacing. Stochastically generated Discrete Fracture Networks (DFN's) have then been modelled from these fractures statistical data. Uncertainties in the data include biases due to exposure orientation and extent, resolution of lidar data and whether fractures are open or closed at depth (which may be estimated from the current stress regime). Multiple realisations of the DFN are generated to help take into account uncertainty in the fracture-derived statistics. The DFN is then used to calculate porosity and permeability values for the fracture network

  5. Synthesis and Luminescence Properties of Transparent Nanocrystalline GdF3:Tb Glass-Ceramic Scintillator.

    PubMed

    Lee, Gyuhyon; Savage, Nicholas; Wagner, Brent; Zhang, Yuelan; Jacobs, Benjamin; Menkara, Hisham; Summers, Christopher; Kang, Zhitao

    2014-03-01

    Transparent glass-ceramic containing rare-earth doped halide nanocrystals exhibits enhanced luminescence performance. In this study, a glass-ceramic with Tb doped gadolinium fluoride nanocrystals embedded in an aluminosilicate glass matrix is investigated for X-ray imaging applications. The nanocrystalline glass-ceramic scintillator was prepared by a melt-quench method followed by an anneal. The GdF3:Tb nanocrystals precipitated within the oxide glass matrix during the processing and their luminescence and scintillation properties were investigated. In this nanocomposite scintillator system, the incorporation of high atomic number Gd compound into the glass matrix increases the X-ray stopping power of the glass scintillator, and effective energy transfer between Gd(3+) and Tb(3+) ions in the nanocrystals enhances the scintillation efficiency. PMID:24610960

  6. Synthesis and Luminescence Properties of Transparent Nanocrystalline GdF3:Tb Glass-Ceramic Scintillator

    PubMed Central

    Lee, Gyuhyon; Savage, Nicholas; Wagner, Brent; Zhang, Yuelan; Jacobs, Benjamin; Menkara, Hisham; Summers, Christopher; Kang, Zhitao

    2014-01-01

    Transparent glass-ceramic containing rare-earth doped halide nanocrystals exhibits enhanced luminescence performance. In this study, a glass-ceramic with Tb doped gadolinium fluoride nanocrystals embedded in an aluminosilicate glass matrix is investigated for X-ray imaging applications. The nanocrystalline glass-ceramic scintillator was prepared by a melt-quench method followed by an anneal. The GdF3:Tb nanocrystals precipitated within the oxide glass matrix during the processing and their luminescence and scintillation properties were investigated. In this nanocomposite scintillator system, the incorporation of high atomic number Gd compound into the glass matrix increases the X-ray stopping power of the glass scintillator, and effective energy transfer between Gd3+ and Tb3+ ions in the nanocrystals enhances the scintillation efficiency. PMID:24610960

  7. S100A4 influences cancer stem cell-like properties of MGC803 gastric cancer cells by regulating GDF15 expression.

    PubMed

    Guo, Junfu; Bian, Yue; Wang, Yu; Chen, Lisha; Yu, Aiwen; Sun, Xiuju

    2016-08-01

    Many studies have revealed that S100A4 is involved in cancer progression by affecting a variety of biological functions. Our previous study showed that S100A4 influences many biological properties of gastric cancer cells; however, the underlying mechanisms are far from clear. In this study, we used cDNA microarray analysis to investigate the global alterations in gene expression in MGC803 gastric cancer cells after siRNA-mediated S100A4 inhibition. Among the total genes investigated, 179 differentially expressed genes (38 upregulated and 141 downregulated) were detected in S100A4-siRNA transfected MGC803 cells compared with NC-siRNA transfected cells. We focused on the GDF15 gene, which was significantly downregulated after S100A4 inhibition. ChIP studies showed that the S100A4 protein binds to the GDF15 promoter, implicating S100A4 in GDF15 regulation at the transcriptional level. GDF15 overexpression promoted CSC-like properties of MGC803 cells, such as spheroid and soft-agar colony forming abilities. S100A4 inhibition suppressed the CSC-like properties of the cells, whereas, GV141-GDF15 vector transfection reversed these effects. Our results suggest that S100A4 influences the CSC-like properties of MGC803 gastric cancer cells by regulating GDF15 expression. PMID:27278086

  8. Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation

    PubMed Central

    Ishige, Takayuki; Nishimura, Motoi; Satoh, Mamoru; Fujimoto, Mai; Fukuyo, Masaki; Semba, Toshihisa; Kado, Sayaka; Tsuchida, Sachio; Sawai, Setsu; Matsushita, Kazuyuki; Togawa, Akira; Matsubara, Hisahiro; Kaneda, Atsushi; Nomura, Fumio

    2016-01-01

    Gastric cancer is classified into two subtypes, diffuse and intestinal. The diffuse-type gastric cancer (DGC) has poorer prognosis, and the molecular pathology is not yet fully understood. The purpose of this study was to identify functional secreted molecules involved in DGC progression. We integrated the secretomics of six gastric cancer cell lines and gene expression analysis of gastric cancer tissues with publicly available microarray data. Hierarchical clustering revealed characteristic gene expression differences between diffuse- and intestinal-types. GDF15 was selected as a functional secreted molecule owing to high expression only in fetal tissues. Protein expression of GDF15 was higher in DGC cell lines and tissues. Serum levels of GDF15 were significant higher in DGC patients as compared with healthy individuals and chronic gastritis patients, and positively correlated with wall invasion and lymph node metastasis. In addition, the stimulation of GDF15 on NIH3T3 fibroblast enhanced proliferation and up-regulated expression of extracellular matrix genes, which were similar to TGF-β stimulation. These results indicate that GDF15 contributes to fibroblast activation. In conclusion, this study revealed that GDF15 may be a novel functional secreted molecule for DGC progression, possibly having important roles for cancer progression via the affecting fibroblast function, as well as TGF-β. PMID:26892343

  9. Novel indel Mutation in the GDF5 Gene Is Associated with Brachydactyly Type C in a Four-Generation Turkish Family

    PubMed Central

    Uyguner, Z.O.; Kocaoğlu, M.; Toksoy, G.; Basaran, S.; Kayserili, H.

    2014-01-01

    Heterozygous loss-of-function mutations of GDF5 are reported to cause hypoplasia/aplasia of certain skeletal elements (brachydactyly), and heterozygous gain-of-function mutations, occurring either on the gene itself or through the loss of its inhibitor noggin, result in joint fusion (symphalangism). We present here the clinical and molecular investigation of a family with disproportionate shortness of the second and third fingers which comprises 9 variably affected members spanning 4 generations. In this study, we performed clinical and radiographical examinations of 2 patients of this family, sequencing of GDF5 and 3D protein modeling of the wildtype and mutated polypeptide to predict the structural alteration. Diagnoses were compatible with familial brachydactyly type C. GDF5 analysis revealed a novel heterozygous in-frame indel mutation (c.803_ 827del25ins25), involving the propeptide domain of GDF5 that alters the number of random coil and beta-strand structures, creating a 1-turn-helix at the mutated site. The mutation described here is the second indel reported in GDF5. The previously published homozygous indel mutation affected the TGF-beta like domain and was associated with Du Pan syndrome. The novel mutation reported here presents further allelic heterogeneity and a probable intrafamilial variable clinical expressivity of GDF5. PMID:24715855

  10. Reconstitution of TGFBR2-Mediated Signaling Causes Upregulation of GDF-15 in HCT116 Colorectal Cancer Cells

    PubMed Central

    Lee, Jennifer; Fricke, Fabia; Warnken, Uwe; Schnölzer, Martina; Kopitz, Jürgen; Gebert, Johannes

    2015-01-01

    Although inactivating frameshift mutations in the Transforming growth factor beta receptor type 2 (TGFBR2) gene are considered as drivers of microsatellite unstable (MSI) colorectal tumorigenesis, consequential alterations of the downstream target proteome are not resolved completely. Applying a click-it chemistry protein labeling approach combined with mass spectrometry in a MSI colorectal cancer model cell line, we identified 21 de novo synthesized proteins differentially expressed upon reconstituted TGFBR2 expression. One candidate gene, the TGF-ß family member Growth differentiation factor-15 (GDF-15), exhibited TGFBR2-dependent transcriptional upregulation causing increased intracellular and extracellular protein levels. As a new TGFBR2 target gene it may provide a link between the TGF-ß branch and the BMP/GDF branch of SMAD-mediated signaling. PMID:26114631

  11. Absolute quantification of DcR3 and GDF15 from human serum by LC-ESI MS

    PubMed Central

    Lancrajan, Ioana; Schneider-Stock, Regine; Naschberger, Elisabeth; Schellerer, Vera S; Stürzl, Michael; Enz, Ralf

    2015-01-01

    Biomarkers are widely used in clinical diagnosis, prognosis and therapy monitoring. Here, we developed a protocol for the efficient and selective enrichment of small and low concentrated biomarkers from human serum, involving a 95% effective depletion of high-abundant serum proteins by partial denaturation and enrichment of low-abundant biomarkers by size exclusion chromatography. The recovery of low-abundance biomarkers was above 97%. Using this protocol, we quantified the tumour markers DcR3 and growth/differentiation factor (GDF)15 from 100 μl human serum by isotope dilution mass spectrometry, using 15N metabolically labelled and concatamerized fingerprint peptides for the both proteins. Analysis of three different fingerprint peptides for each protein by liquid chromatography electrospray ionization mass spectrometry resulted in comparable concentrations in three healthy human serum samples (DcR3: 27.23 ± 2.49 fmol/ml; GDF15: 98.11 ± 0.49 fmol/ml). In contrast, serum levels were significantly elevated in tumour patients for DcR3 (116.94 ± 57.37 fmol/ml) and GDF15 (164.44 ± 79.31 fmol/ml). Obtained data were in good agreement with ELISA and qPCR measurements, as well as with literature data. In summary, our protocol allows the reliable quantification of biomarkers, shows a higher resolution at low biomarker concentrations than antibody-based strategies, and offers the possibility of multiplexing. Our proof-of-principle studies in patient sera encourage the future analysis of the prognostic value of DcR3 and GDF15 for colon cancer patients in larger patient cohorts. PMID:25823874

  12. Estrogen Promotes the Development of Mouse Cumulus Cells in Coordination with Oocyte-Derived GDF9 and BMP15

    PubMed Central

    Sugiura, Koji; Su, You-Qiang; Li, Qinglei; Wigglesworth, Karen; Matzuk, Martin M.; Eppig, John J.

    2010-01-01

    The differentiation and function of cumulus cells depend upon oocyte-derived paracrine factors, but studies on the estrogen receptor knockout mice suggested that estrogen also participates in these processes. This study investigates the possible coordination of estrogen and oocytes in the development and function of cumulus cells using cumulus expansion and the expression of transcripts required for expansion as functional endpoints. Preantral granulosa cell-oocyte complexes developed in vitro with 17β-estradiol (E2) exhibited increased levels of cumulus expansion and Has2 transcripts, encoding hyaluronan synthase 2, compared with those developed without E2. Moreover, cumulus cell-oocyte complexes (COCs) isolated from antral follicles and maintained in culture without E2 exhibited reduced cumulus expansion and Has2 mRNA levels compared with freshly isolated COCs. Exogenous E2, provided during the maintenance culture, alleviated these deficiencies. However, when oocytes were removed from COCs, E2 supplementation did not maintain competence to undergo expansion; the presence in culture of either fully grown oocytes or recombinant growth differentiation factor 9 (GDF9) was required. Recombinant bone morphogenetic protein 15, but not fibroblast growth factor 8, augmented the GDF9 effect. Oocytes or GDF9 suppressed cumulus cell levels of Nrip1 transcripts encoding nuclear receptor-interacting protein 1, a potential inhibitor of estrogen receptor signals. Therefore, E2 and oocyte-derived paracrine factors GDF9 and bone morphogenetic protein 15 coordinate to promote the development of cumulus cells and maintain their competence to undergo expansion. Furthermore, suppression of Nrip1 expression in cumulus cells by oocyte may be one mechanism mediating cross talk between oocyte and E2 signals that promotes follicular development. PMID:21047911

  13. Association of GDF5, SMAD3 and RUNX2 polymorphisms with temporomandibular joint osteoarthritis in female Han Chinese.

    PubMed

    Xiao, J-L; Meng, J-H; Gan, Y-H; Zhou, C-Y; Ma, X-C

    2015-07-01

    Temporomandibular joint osteoarthritis (TMJOA) is a complex disease and has a strong genetic component in its pathogenesis. Experimental evidence suggests the involvement of biological pathway in the disease. This case-control study was designed to investigate whether five common single nucleotide polymorphisms (SNPs) in GDF5, SMAD3, RUNX2, TGFβ1 and CHST11, respectively, are associated with TMJOA in female Han Chinese patients. A total of 240 participants were evaluated comprising 114 female patients diagnosed with TMJOA based on Research Diagnostic Criteria for Temporomandibular Disorders and 126 healthy female controls. The SNPs of the five genes in the genomic DNA were examined by sequencing, and their allelic, genotypic and carriage rate frequency distributions, as well as the triple combination of the risk genotypes, were analysed using the logistic regression model. The SNP in GDF5 or SMAD3 showed significant association with TMJOA, a relatively weak association was observed in RUNX2. In the triple combinational analysis, the risk of TMJOA grew 5·09 times in the patients with five or six risk alleles (P < 0·01). This is the first study to evaluate the association of GDF5, SMAD3, RUNX2, TGFβ1 and CHST11 with TMJOA in female Han Chinese. Our study suggests that the SNPs of genes related to TGFβ family might contribute to the risk of TMJOA. PMID:25757091

  14. Synthesis, modified optical properties, and energy transfer of Tb3+ doped GdF3

    NASA Astrophysics Data System (ADS)

    Cao, Chunyan; Guo, Siling; Kee Moon, Byung; Chun Choi, Byung; Hyun Jeong, Jung

    2013-08-01

    By controlling the volume of HF and the alkaline earth ion introducing, a series of GdF3 samples have been synthesized by a hydrothermal method without any surfactant. The samples are characterized by X-ray diffraction (XRD) patterns, field emission scanning electron microscopy (FE-SEM) images, energy-dispersive spectroscopy (EDS) spectra, photoluminescence (PL) excitation and emission spectra as well as the luminescence dynamic decay curves. The optical properties of Tb3+ and the energy transfer from host Gd3+ to Tb3+ have been investigated and discussed in detail based on the volume of HF used in the synthesis procedure and the alkaline earth ion introducing. The experimental results suggest that the optical properties of Tb3+ can be controlled by the deliberately ion introducing as well as the volume of HF used in the synthesis procedure. Though the optical properties of Tb3+ can be adjusted by different ways, a green, easy, and cost saving way, such as deliberately ion introducing, is a good choice in modifying the optical properties of Tb3+.

  15. GDF11/BMP11 activates both smad1/5/8 and smad2/3 signals but shows no significant effect on proliferation and migration of human umbilical vein endothelial cells

    PubMed Central

    Zhang, Yong-Hui; Cheng, Feng; Du, Xue-Ting; Gao, Jin-Lai; Xiao, Xiao-Lin; Li, Na; Li, Shan-Liang; Dong, De-Li

    2016-01-01

    GDF11/BMP11, a member of TGF-β superfamily, was reported to rejuvenate heart, skeletal muscle and blood vessel architecture in aged mice. However, the rejuvenative effects of GDF11 were questioned recently. Here, we investigated the effects of GDF11 on smad and non-smad signals in human umbilical vein endothelial cells (HUVECs) and the effects of GDF11 on proliferation and migration of HUVECs and primary rat aortic endothelial cells (RAECs). GDF11 factor purchased from two different companies (PeproTech and R&D Systems) was comparatively studied. Western blot was used to detect the protein expressions. The cell viability and migration were examined by using MTT and wound healing assays. Results showed that GDF11 activated both smad1/5/8 and smad2/3 signals in HUVECs. GDF11 increased protein expression of NADPH oxidase 4(NOX4) in HUVECs. GDF11 showed no significant effect on the protein level of p38, p-p38, ERK, p-ERK, Akt, p-Akt (Ser473) and p-Akt(Thr308), but increased the protein level of p-JNK and p-AMPK in HUVECs, and these increases were inhibited by antioxidant mitoTEMPO treatment. GDF11 slightly increased cell viability after short-term treatment and slightly decreased cell viability after long-term treatment. GDF11 showed no significant effect on cell proliferation and migration. These data indicated that the notion of GDF11 as a rejuvenation-related factor for endothelial cells needs to be cautious. PMID:26919250

  16. Antagonism between Gdf6a and retinoic acid pathways controls timing of retinal neurogenesis and growth of the eye in zebrafish

    PubMed Central

    Valdivia, Leonardo E.; Lamb, Dayna B.; Horner, Wilson; Wierzbicki, Claudia; Tafessu, Amanuel; Williams, Audrey M.; Gestri, Gaia; Krasnow, Anna M.; Vleeshouwer-Neumann, Terra S.; Givens, McKenzie; Young, Rodrigo M.; Lawrence, Lisa M.; Stickney, Heather L.; Hawkins, Thomas A.; Schwarz, Quenten P.; Cavodeassi, Florencia; Wilson, Stephen W.; Cerveny, Kara L.

    2016-01-01

    Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors, similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model in which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation to differentiation in the growing eye. PMID:26893342

  17. Updates of the KArLE Experiment: New Libs Calibration Under High Vacuum for the Quantification of Potassium in Basalt for In Situ Geochronology

    NASA Technical Reports Server (NTRS)

    Devismes, D.; Cohen, B. A.; Li, Z.-H.; Miller, J. S.

    2014-01-01

    In planetary exploration, in situ absolute geochronology is one of the main important measurements that needs to be accomplished. Until now, on Mars, the age of the surface is only determined by crater density counting, which gives relative ages. These ages can have a lot of uncertainty as they depend on many parameters. More than that, the curves must be ties to absolute ages. Thus far, only the lost lander Beagle 2 was designed to conduct absolute geochronology measurements, though some recent attempts using MSL Curiosity show that this investigation is feasible and should be strongly encouraged for future flight. Experimental: The Potassium (K)-Argon Laser Experiment (KArLE) is being developed at MSFC through the NASA Planetary Instrument Definition and Development Program (PIDDP). The goal of this experiment is to provide in situ geochronology based on the K-Ar method. A laser ablates a rock under high vacuum, creating a plasma which is sensed by an optical spectrometer to do Laser Induced Breakdown Spectroscopy (LIBS). The ablated material frees gases, including radiogenic 40Ar,which is measured by a mass spectrometer (MS). As the potassium is a content and the 40Ar is a quantity, the ablated mass needed in order to relate them. The mass is given by the product of the ablated volume by the density of this material. So we determine the mineralogy of the ablated material with the LIBS spectra and images and calculate its density. The volume of the pit is measured by using microscopy. LIBS measurement of K under high vacuum: Three independant projects [1, 2, 3] including KArLE, are developing geochronological instruments based on this LA-LIBS-MS method. Despite several differences in their setup, all of them have validated the methods with analyses and ages. However, they all described difficulties with the LIBS measurements of K [3,4]. At ambient pressure, the quantification of K by LIBS on geological materials can be accurate [5]. However the protocol of the LA

  18. WHITE UPCONVERSION LUMINESCENCE FROM (Yb3+/Tm3+/Ho3+) TRIDOPED GdF3 NANORODS AFTER HEAT TREATMENT

    NASA Astrophysics Data System (ADS)

    Guo, Linna; Wang, Yuhua; Zhang, Jia; Wang, Yanzhao; Dong, Pengyu

    2012-09-01

    A series of Ho3+/Yb3+/Tm3+ tridoped GdF3 nanorods with different dopant concentrations were synthesized by a hydrothermal method. Transmission electron microscope (TEM) images indicate that the length and diameter of the nanorods is about 90 nm and 31 nm, respectively on average. No bright white upconversion light was observed from the samples with different Yb3+, Ho3+ or Tm3+ concentrations. Unexpectedly, the emission color coordinates of the samples after heat treatment move toward the central white region of the chromaticity diagram, and among these samples, the color coordinate (0.349, 0.329) of GdF3:15% Yb3+, 0.1% Ho3+, 0.8% Tm3+ is the most close to the standard white light (0.333, 0.333). This is unlike previous reports in which white light was achieved via tuning dopant concentration or excitation power. The reasons for the above phenomenon are presented by means of FT-IR spectra and the energy level diagram of dopants.

  19. A New Subtype of Multiple Synostoses Syndrome Is Caused by a Mutation in GDF6 That Decreases Its Sensitivity to Noggin and Enhances Its Potency as a BMP Signal.

    PubMed

    Wang, Jian; Yu, Tingting; Wang, Zhigang; Ohte, Satoshi; Yao, Ru-En; Zheng, Zhaojing; Geng, Juan; Cai, Haiqing; Ge, Yihua; Li, Yuchan; Xu, Yunlan; Zhang, Qinghua; Gusella, James F; Fu, Qihua; Pregizer, Steven; Rosen, Vicki; Shen, Yiping

    2016-04-01

    Growth and differentiation factors (GDFs) are secreted signaling molecules within the BMP family that have critical roles in joint morphogenesis during skeletal development in mice and humans. Using genetic data obtained from a six-generation Chinese family, we identified a missense variant in GDF6 (NP_001001557.1; p.Y444N) that fully segregates with a novel autosomal dominant synostoses (SYNS) phenotype, which we designate as SYNS4. Affected individuals display bilateral wrist and ankle deformities at birth and progressive conductive deafness after age 40 years. We find that the Y444N variant affects a highly conserved residue of GDF6 in a region critical for binding of GDF6 to its receptor(s) and to the BMP antagonist NOG, and show that this mutant GDF6 is a more potent stimulator of the canonical BMP signaling pathway compared with wild-type GDF6. Further, we determine that the enhanced BMP activity exhibited by mutant GDF6 is attributable to resistance to NOG-mediated antagonism. Collectively, our findings indicate that increased BMP signaling owing to a GDF6 gain-of-function mutation is responsible for loss of joint formation and profound functional impairment in patients with SYNS4. More broadly, our study highlights the delicate balance of BMP signaling required for proper joint morphogenesis and reinforces the critical role of BMP signaling in skeletal development. PMID:26643732

  20. Regulation of α5 and αV Integrin Expression by GDF-5 and BMP-7 in Chondrocyte Differentiation and Osteoarthritis

    PubMed Central

    Garciadiego-Cázares, David; Aguirre-Sánchez, Hilda I.; Abarca-Buis, René F.; Kouri, Juan B.; Velasquillo, Cristina; Ibarra, Clemente

    2015-01-01

    The Integrin β1 family is the major receptors of the Extracellular matrix (ECM), and the synthesis and degradation balance of ECM is seriously disrupted during Osteoarthritis (OA). In this scenario, integrins modify their pattern expression and regulate chondrocyte differen-tiation in the articular cartilage. Members of the Transforming growth factor beta (Tgf-β) Su-perfamily, such as Growth differentiation factor 5 (Gdf-5) and Bone morphogenetic protein 7 (Bmp-7), play a key role in joint formation and could regulate the integrin expression during chondrocyte differentiation and osteoarthritis progression in an experimental OA rat model. Decrease of α5 integrin expression in articular cartilage was related with chondrocyte dedif-ferentiation during OA progression, while increase of α1, α2, and α3 integrin expression was related with fibrous areas in articular cartilage during OA. Hypertrophic chondrocytes expressedαV integrin and was increased in the articular cartilage of rats with OA. Integrin expression during chondrocyte differentiation was also analyzed in a micromass culture system of mouse embryo mesenchymal cells, micromass cultures was treated with Gdf-5 or Bmp-7 for 4 and 6 days, respectively. Gdf-5 induced the expression of theα5 sub-unit, while Bmp-7 induced the expression of the αV sub-unit. This suggests a switch in signaling for prehypertrophic chondrocyte differentiation towards hypertrophy, where Gdf-5 could maintain the articular chondrocyte phenotype and Bmp-7 would induce hypertrophy. Decrease of Ihh expression during late stages of OA in rat model suggest that the ossification in OA rat knees and endochondral ossification could be activated by Bmp-7 and αV integrin in absence of Ihh. Thus, chondrocyte phenotype in articular cartilage is similar to prehypetrophic chondrocyte in growth plate, and is preserved due to the presence of Indian hedgehog (Ihh), Gdf-5 and α5 integrin to maintain articular cartilage and prevent hy

  1. GDF9 is Transiently Expressed in Oocytes before Follicle Formation in the Human Fetal Ovary and is Regulated by a Novel NOBOX Transcript

    PubMed Central

    Bayne, Rosemary A. L.; Kinnell, Hazel L.; Coutts, Shiona M.; He, Jing; Childs, Andrew J.; Anderson, Richard A.

    2015-01-01

    During human fetal ovary development, the process of primordial follicle formation is immediately preceded by a highly dynamic period of germ cell and somatic cell reorganisation. This is regulated by germ-cell specific transcription regulators, by the conserved RNA binding proteins DAZL and BOLL and by secreted growth factors of the TGFβ family, including activin βA: these all show changing patterns of expression preceding follicle formation. In mice, the transcription factor Nobox is essential for follicle formation and oocyte survival, and NOBOX regulates the expression of GDF9 in humans. We have therefore characterised the expression of GDF9 in relation to these known key factors during follicle formation in the human fetal ovary. mRNA levels of GDF9, BMP15 and NOBOX were quantified by qRT-PCR and showed dramatic increases across gestation. GDF9 protein expression was localised by immunohistochemistry to the same population of germ cells as those expressing activin βA prior to follicle formation but did not co-localise with either BOLL or DAZL. A novel NOBOX isoform was identified in fetal ovary that was shown to be capable of up-regulating the GDF9 promoter in reporter assays. Thus, during oogenesis in humans, oocytes go through a dynamic and very sharply demarcated sequence of changes in expression of these various proteins, even within individual germ cell nests, likely to be of major functional significance in determining selective germ cell survival at this key stage in ovarian development. Transcriptional variation may contribute to the range of age of onset of POI in women with NOBOX mutations. PMID:25790371

  2. Differential expression of GDF9, TGFB1, TGFB2 and TGFB3 in porcine oocytes isolated from follicles of different size before and after culture in vitro.

    PubMed

    Jackowska, Marta; Kempisty, Bartosz; Woźna, Magdalena; Piotrowska, Hanna; Antosik, Paweł; Zawierucha, Piotr; Bukowska, Dorota; Nowicki, Michał; Jaśkowski, Jędrzej M; Brüssow, Klaus-Peter

    2013-03-01

    The TGFB superfamily genes are involved in several important cell functions, including proliferation and differentiation, and the role of the expression of these genes in growth and development of theca and granulosa cells is well recognised. However, the dependence between the stage of oocyte maturation or follicular size and the expression of these genes in pigs is still not entirely known. This study was aimed at investigating the expression pattern of GDF9, TGFB1, TGFB2 and TGFB3 in porcine oocytes before and after in vitro maturation (IVM) as well as in oocytes collected from follicles of different sizes. RQ-PCR was performed to analyse the expression of GDF9, TGFB1, TGFB2 and TGFB3 in oocytes before and after IVM (oocytes cultured for 44 h in TCM-199), isolated from large (> 5 mm), medium (3-5 mm) and small (< 3 mm) follicles collected from ovaries of 28 puberal crossbred Landrace gilts after slaughter. We found an increased expression of both TGFB1 and TGFB2 in oocytes before IVM collected from large as compared to medium and small follicles (P < 0.05, P < 0.001, P < 0.01, P < 0.05, respectively). In these groups of oocytes we did not observe differences in GDF9 and TGFB3 mRNA levels. However, after IVM, GDF9 protein distribution in oocytes was significantly higher in large and medium follicles as compared to small ones (P < 0.01, P < 0.001, respectively). Moreover, an increased TGFB1, TGFB2 and TGFB3 proteins pattern was observed in oocytes of large compared to small follicles. The highest GDF9 and TGFB1 mRNA levels were found in oocytes after IVM compared to those before IVM. Based on our study we can suppose that the distribution pattern of TGFB superfamily genes is associated with the stage of maturation of porcine oocytes and the follicle size. Furthermore, GDF9 and TGFB1 may serve as molecular markers of the develop-mental potential of porcine oocytes. The confocal microscopic observation revealed that TGFB1 and TGFB3 were translocated between the zona

  3. Anorexia-cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15.

    PubMed

    Tsai, V W W; Lin, S; Brown, D A; Salis, A; Breit, S N

    2016-02-01

    Anorexia-cachexia associated with cancer and other diseases is a common and often fatal condition representing a large area of unmet medical need. It occurs most commonly in advanced cancer and is probably a consequence of molecules released by tumour cells, or tumour-associated interstitial or immune cells. These may then act directly on muscle to cause atrophy and/or may cause anorexia, which then leads to loss of both fat and lean mass. Although the aetiological triggers for this syndrome are not well characterized, recent data suggest that MIC-1/GDF15, a transforming growth factor-beta superfamily cytokine produced in large amounts by cancer cells and as a part of other disease processes, may be an important trigger. This cytokine acts on feeding centres in the hypothalamus and brainstem to cause anorexia leading to loss of lean and fat mass and eventually cachexia. In animal studies, the circulating concentrations of MIC-1/GDF15 required to cause this syndrome are similar to those seen in patients with advanced cancer, and at least some epidemiological studies support an association between MIC-1/GDF15 serum levels and measures of nutrition. This article will discuss its mechanisms of central appetite regulation, and the available data linking this action to anorexia-cachexia syndromes that suggest it is a potential target for therapy of cancer anorexia-cachexia and conversely may also be useful for the treatment of severe obesity. PMID:26620888

  4. Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice

    PubMed Central

    Zhao, Lihua; Du, Xinhua; Huang, Kun; Zhang, Tuo; Teng, Zhen; Niu, Wanbao; Wang, Chao; Xia, Guoliang

    2016-01-01

    The size of the primordial follicle pool determines the reproductive potential of mammalian females, and establishment of the pool is highly dependent on specific genes expression. However, the molecular mechanisms by which the essential genes are regulated coordinately to ensure primordial follicle assembly remain a mystery. Here, we show that the small GTPase Rac1 plays an indispensable role in controlling the formation of primordial follicles in mouse ovary. Employing fetal mouse ovary organ culture system, we demonstrate that disruption of Rac1 retarded the breakdown of germline cell cysts while Rac1 overexpression accelerated the formation of primordial follicles. In addition, in vivo inhibitor injection resulted in the formation of multi-oocyte follicles. Subsequent investigation showed that Rac1 induced nuclear import of STAT3 by physical binding. In turn, nuclear STAT3 directly activated the transcription of essential oocyte-specific genes, including Jagged1, GDF9, BMP15 and Nobox. Further, GDF9 and BMP15 regulated the translation of Notch2 via mTORC1 activation in pregranulosa cells. Overexression or addition of Jagged1, GDF9 and BMP15 not only reversed the effect of Rac1 disruption, but also accelerated primordial follicle formation via Notch2 signaling activation. Collectively, these results indicate that Rac1 plays important roles as a key regulator in follicular assembly. PMID:27050391

  5. Genotyping of Novel SNPs in BMPR1B, BMP15, and GDF9 Genes for Association with Prolificacy in Seven Indian Goat Breeds.

    PubMed

    Ahlawat, Sonika; Sharma, Rekha; Roy, Manoranjan; Mandakmale, Sanjay; Prakash, Ved; Tantia, M S

    2016-07-01

    Goats form the backbone of rural livelihood and financial security systems in India but their population is showing decreasing trend. Improvement of reproductive traits such as prolificacy offers a solution to stabilize the decreasing goat population and to meet the nutritional needs of growing human population. In the present study, six novel SNPs in three candidate genes for prolificacy (BMPR1B, BMP15, and GDF9) were genotyped in seven breeds of Indian goats to evaluate their association with litter size. Tetra primer ARMS-PCR and PCR-RFLP based protocols were developed for genotyping six novel SNPs, namely, T(-242)C in BMPR1B; G735A and C808G in BMP15; and C818T, A959C, and G1189A in GDF9 gene. The effect of breed was highly significant (p ≤ 0.01) on litter size but the effect of genotype was nonsignificant. The effect of parity on litter size was also significant in the prolific Black Bengal breed. The litter size differences observed between breeds are attributed to breed differences. Novel mutations observed at different loci in GDF9, BMP15, and BMPR1B genes do not contribute to the reproductive capability of the investigated breeds. Further studies with more number of breeds and animals exploring association of these novel SNPs with reproductive traits may be fruitful. PMID:27135147

  6. GDF15(MIC1) H6D Polymorphism Does Not Influence Cardiovascular Disease in a Latin American Population with Rheumatoid Arthritis

    PubMed Central

    Amaya-Amaya, Jenny; Rojas-Villarraga, Adriana; Molano-Gonzalez, Nicolas; Montoya-Sánchez, Laura; Nath, Swapan K.; Anaya, Juan-Manuel

    2015-01-01

    Objective. Rheumatoid arthritis (RA) is the most common autoimmune arthropathy worldwide. The increased prevalence of cardiovascular disease (CVD) in RA is not fully explained by classic risk factors. The aim of this study was to determine the influence of rs1058587 SNP within GDF15(MIC1) gene on the risk of CVD in a Colombian RA population. Methods. This was a cross-sectional analytical study in which 310 consecutive Colombian patients with RA and 228 age- and sex-matched controls were included and assessed for variables associated with CVD. The mixed cluster methodology based on multivariate descriptive methods such as principal components analysis and multiple correspondence analyses and regression tree (CART) predictive model were performed. Results. Of the 310 patients, 87.4% were women and CVD was reported in 69.5%. Significant differences concerning GDF15 polymorphism were not observed between patients and controls. Mean arterial pressure, current smoking, and some clusters were significantly associated with CVD. Conclusion. GDF15 (rs1058587) does not influence the development of CVD in the population studied. PMID:26090487

  7. Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis.

    PubMed

    Dyment, Nathaniel A; Breidenbach, Andrew P; Schwartz, Andrea G; Russell, Ryan P; Aschbacher-Smith, Lindsey; Liu, Han; Hagiwara, Yusuke; Jiang, Rulang; Thomopoulos, Stavros; Butler, David L; Rowe, David W

    2015-09-01

    The sequence of events that leads to the formation of a functionally graded enthesis is not clearly defined. The current study demonstrates that clonal expansion of Gdf5 progenitors contributes to linear growth of the enthesis. Prior to mineralization, Col1+ cells in the enthesis appose Col2+ cells of the underlying primary cartilage. At the onset of enthesis mineralization, cells at the base of the enthesis express alkaline phosphatase, Indian hedgehog, and ColX as they mineralize. The mineralization front then extends towards the tendon midsubstance as cells above the front become encapsulated in mineralized fibrocartilage over time. The hedgehog (Hh) pathway regulates this process, as Hh-responsive Gli1+ cells within the developing enthesis mature from unmineralized to mineralized fibrochondrocytes in response to activated signaling. Hh signaling is required for mineralization, as tissue-specific deletion of its obligate transducer Smoothened in the developing tendon and enthesis cells leads to significant reductions in the apposition of mineralized fibrocartilage. Together, these findings provide a spatiotemporal map of events - from expansion of the embryonic progenitor pool to synthesis of the collagen template and finally mineralization of this template - that leads to the formation of the mature zonal enthesis. These results can inform future tendon-to-bone repair strategies to create a mechanically functional enthesis in which tendon collagen fibers are anchored to bone through mineralized fibrocartilage. PMID:26141957

  8. Portevin-Le chatelier effect

    PubMed

    Franklin; Mertens; Marder

    2000-12-01

    Aluminum subjected to smooth mechanical loading does not often deform in a correspondingly smooth manner. Typically it deforms inhomogeneously through the propagation of deformation fronts that slowly traverse the sample. These are called Portevin-Le Chatelier fronts; what determines their velocity has been somewhat mysterious. We present a phenomenological theory for deformation fronts that centers on a nonlocal rate dependence of the flow stress. In a one-dimensional idealization the equations can be solved exactly, and compared directly with experiment. Many significant features of deformation fronts are captured, including a well-known transition from hopping to continuous front motion. The phenomenology's predictions are confirmed by our experiments. PMID:11138118

  9. Feed restriction as a biostimulant of the production of oocyte, their quality and GDF-9 gene expression in rabbit oocytes.

    PubMed

    Daoud, Niveen M; Mahrous, Karima F; Ezzo, Omaima H

    2012-12-01

    The use of short-term feed restriction (R) without or with subsequent refeeding (F) as biostimulant of rabbit fertility was examined in this study. A total of 40 mature, non-pregnant, non-lactating New Zealand white female rabbits were allocated to five treatments. The rabbits were individually caged and fed a complete pelleted diet (16.7% CP; 13.1 CF; 2490kcalDE/kg). Rabbits on the control (C) treatment received 150g/d of the diet. Two groups of 8 rabbits received 70% of the control daily feed intake (105g/d; moderate restriction; M) and the other two groups received 50% of the control feed intake (75g/d; severe restriction; S) for 21d. At the end of this period, one group each of M and S fed rabbits were slaughtered for oocyte recovery. Rabbits in the remaining three groups (C, MF and SF) were retained for a further 8d before slaughter and fed the control level of the diet during this period. The effects on body weight, oocyte number and quality, GDF-9 gene expression in oocytes, and changes in serum levels of leptin and IGF-1 were recorded. Initial mean body weights were not significantly different ranging from 2.50±0.33kg (S) to 2.58±0.24kg (C). After 3wk on treatment the C rabbits were significantly heavier (2.65±0.32kg; P<0.05) than rabbits on the M (2.26±0.33kg) or S (2.10±0.33kg) treatments. Following 8d of refeeding, the remaining group of S treated rabbits (SF) were still significantly lighter (2.40±0.21kg; P<0.05) than C (2.71±0.31kg) with MF rabbits having an intermediate weight (2.50±0.20kg). The number of mature grade A oocytes recovered per ovary was significantly lower for control (3.3±0.35) than the refed treatments (MF 4.0±0.30; SF 4.5±0.39; P<0.05). Semi-quantitative PCR analysis of GDF-9 expression showed that control mature grade A oocytes had significantly lower levels of expression (1.27±0.20; P<0.05) than those of refed rabbits (MF 1.60±0.10; SF 1.39±0.01). Leptin and IGF-1 values for refed rabbits were significantly higher (P

  10. Purification, crystallization and preliminary data analysis of the ligand–receptor complex of the growth and differentiation factor 5 variant R57A (GDF5R57A) and BMP receptor IA (BRIA)

    PubMed Central

    Nickel, Joachim; Kotzsch, Alexander; Sebald, Walter; Mueller, Thomas D.

    2011-01-01

    The binary ligand–receptor complex of human growth and differentiation factor 5 (GDF5) bound to its type I receptor BMP receptor IA (BRIA) was prepared and crystallized. By utilizing the GDF5 variant R57A, which exhibits a high affinity in the subnanomolar range for BRIA, the binary complex of GDF5R57A bound to the extracellular domain of BRIA could be produced and purified. Crystals of this complex belonged to a monoclinic space group: either I2, with unit-cell parameters a = 63.81, b = 62.85, c = 124.99 Å, β = 95.9°, or C2, with unit-cell parameters a = 132.17, b = 62.78, c = 63.53 Å, β = 112.8°. PMID:21543859

  11. Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett’s Esophagus

    PubMed Central

    Palles, Claire; Chegwidden, Laura; Li, Xinzhong; Findlay, John M.; Farnham, Garry; Castro Giner, Francesc; Peppelenbosch, Maikel P.; Kovac, Michal; Adams, Claire L.; Prenen, Hans; Briggs, Sarah; Harrison, Rebecca; Sanders, Scott; MacDonald, David; Haigh, Chris; Tucker, Art; Love, Sharon; Nanji, Manoj; deCaestecker, John; Ferry, David; Rathbone, Barrie; Hapeshi, Julie; Barr, Hugh; Moayyedi, Paul; Watson, Peter; Zietek, Barbara; Maroo, Neera; Gay, Laura; Underwood, Tim; Boulter, Lisa; McMurtry, Hugh; Monk, David; Patel, Praful; Ragunath, Krish; Al Dulaimi, David; Murray, Iain; Koss, Konrad; Veitch, Andrew; Trudgill, Nigel; Nwokolo, Chuka; Rembacken, Bjorn; Atherfold, Paul; Green, Elaine; Ang, Yeng; Kuipers, Ernst J.; Chow, Wu; Paterson, Stuart; Kadri, Sudarshan; Beales, Ian; Grimley, Charles; Mullins, Paul; Beckett, Conrad; Farrant, Mark; Dixon, Andrew; Kelly, Sean; Johnson, Matthew; Wajed, Shahjehan; Dhar, Anjan; Sawyer, Elinor; Roylance, Rebecca; Onstad, Lynn; Gammon, Marilie D.; Corley, Douglas A.; Shaheen, Nicholas J.; Bird, Nigel C.; Hardie, Laura J.; Reid, Brian J.; Ye, Weimin; Liu, Geoffrey; Romero, Yvonne; Bernstein, Leslie; Wu, Anna H.; Casson, Alan G.; Fitzgerald, Rebecca; Whiteman, David C.; Risch, Harvey A.; Levine, David M.; Vaughan, Tom L.; Verhaar, Auke P.; van den Brande, Jan; Toxopeus, Eelke L.; Spaander, Manon C.; Wijnhoven, Bas P.L.; van der Laan, Luc J.W.; Krishnadath, Kausilia; Wijmenga, Cisca; Trynka, Gosia; McManus, Ross; Reynolds, John V.; O’Sullivan, Jacintha; MacMathuna, Padraic; McGarrigle, Sarah A.; Kelleher, Dermot; Vermeire, Severine; Cleynen, Isabelle; Bisschops, Raf; Tomlinson, Ian; Jankowski, Janusz

    2015-01-01

    Background & Aims Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. Methods We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. Results We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09–1.18; P = 1.8 × 10−11) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86–0.93; P = 7.5 × 10−9). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87–0.93; P = 3.72 × 10−9). Conclusions We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response. PMID:25447851

  12. Synthesis of a BSA-Le(x) glycoconjugate and recognition of Le(x) analogues by the anti-Le(x) monoclonal antibody SH1: the identification of a non-cross reactive analogue.

    PubMed

    Wang, Jo-Wen; Asnani, Ari; Auzanneau, France-Isabelle

    2010-10-15

    A Le(x) trisaccharide functionalized with a cysteamine arm was prepared and this synthesis provided additional information on the reactivity of N-acetylglucosamine O-4 acceptors when they are glycosylated with trichloroacetimidate donors activated with excess BF(3)·OEt(2). In turn, this trisaccharide was conjugated to BSA lysine side chains through a squarate-mediated coupling. This BSA-Le(x) glycoconjugate displayed 35 Le(x) haptens per BSA molecule. The relative affinity of the anti-Le(x) monoclonal antibody SH1 for the Le(x) antigen and analogues of Le(x) in which the D-glucosamine, L-fucose or D-galactose residues were replaced with D-glucose, L-rhamnose and D-glucose, respectively, was measured by competitive ELISA experiments. While all analogues were weaker inhibitors than the Le(x) antigen, only the analogue of Le(x) in which the galactose residue was replaced by a glucose unit showed no binding to the SH1 mAb. To confirm that the reduced or loss of recognition of the Le(x) analogues by the anti-Le(x) mAb SH1 did not result from different conformations adopted by the analogues when compared to the native Le(x) antigen, we assessed the conformational behavior of all trisaccharides by a combination of stochastic searches and NMR experiments. Our results showed that, indeed, the analogues adopted the same stacked conformation as that identified for the Le(x) antigen. The identification of a trisaccharide analogue that does not cross-react with Le(x) but still retains the same conformation as Le(x) constitutes the first step to the design of a safe anti-cancer vaccine based on the dimeric Le(x) tumor associated carbohydrate antigen. PMID:20843695

  13. Le Indeterminacy in Spanish.

    ERIC Educational Resources Information Center

    Foster, David William

    The standard treatment of object pronouns in Latin American Spanish assigns a direct-object function to "lo" and "la" and an indirect-object function to "le." This study challenges this descriptive attribution in light of the contradictory and refractory evidence in Spanish morphosyntax. It is suggested that more detailed research, especially…

  14. Le Figaro. Revised.

    ERIC Educational Resources Information Center

    Crawford, Linda

    These instructional materials are designed for students with some French reading skills and vocabulary in late beginning or early intermediate senior high school French. The objectives are to introduce students to a French newspaper, "Le Figaro," and develop reading skills for skimming, gathering specific information, and relying on cognates. The…

  15. Le mouvement du pôle

    NASA Astrophysics Data System (ADS)

    Bizouard, Christian

    2012-03-01

    Les variations de la rotation terrestre. En conditionnant à la fois notre vie quotidienne, notre perception du ciel, et bon nombre de phénomènes géophysiques comme la formation des cyclones, la rotation de la Terre se trouve au croisement de plusieurs disciplines. Si le phenomena se faisait uniformément, le sujet serait vite discuté, mais c'est parce que la rotation terrestre varie, même imperceptiblement pour nos sens, dans sa vitesse angulaire comme dans la direction de son axe, qu'elle suscite un grand intérêt. D'abord pour des raisons pratiques : non seulement les aléas de la rotation terrestre modi_ent à la longue les pointés astrométriques à un instant donné de la journée mais in_uencent aussi les mesures opérées par les techniques spatiales ; en consequence l'exploitation de ces mesures, par exemple pour déterminer les orbites des satellites impliqués ou pratiquer le positionnement au sol, nécessite une connaissance précise de ces variations. Plus fondamentalement, elles traduisent les propriétés globales de la Terre comme les processus physiques qui s'y déroulent, si bien qu'en analysant les causes des fluctuations observées, on dispose d'un moyen de mieux connaître notre globe. La découverte progressive des fluctuations de la rotation de la Terre a une longue histoire. Sous l'angle des techniques d'observation, trois époques se pro-celle du pointé astrométrique à l'oeil nu, à l'aide d'instruments en bois ou métalliques (quart de cercle muraux par exemple). À partir du XVIIe siècle débute l'astrométrie télescopique dont les pointés sont complétés par des datations de plus en plus précises grâce à l'invention d'horloges régulées par balancier. Cette deuxième époque se termine vers 1960, avec l'avènement des techniques spatiales : les pointés astrométriques sont délaissés au profit de la mesure ultra-précise de durées ou de fréquences de signaux électromagnétiques, grâce à l'invention des horloges

  16. Potential migration of buoyant LNAPL from intermediate level waste (ILW) emplaced in a geological disposal facility (GDF) for U.K. radioactive waste.

    PubMed

    Benbow, Steven J; Rivett, Michael O; Chittenden, Neil; Herbert, Alan W; Watson, Sarah; Williams, Steve J; Norris, Simon

    2014-10-15

    A safety case for the disposal of Intermediate Level (radioactive) Waste (ILW) in a deep geological disposal facility (GDF) requires consideration of the potential for waste-derived light non-aqueous phase liquid (LNAPL) to migrate under positive buoyancy from disposed waste packages. Were entrainment of waste-derived radionuclides in LNAPL to occur, such migration could result in a shorter overall travel time to environmental or human receptors than radionuclide migration solely associated with the movement of groundwater. This paper provides a contribution to the assessment of this issue through multiphase-flow numerical modelling underpinned by a review of the UK's ILW inventory and literature to define the nature of the associated ILW LNAPL source term. Examination has been at the waste package-local GDF environment scale to determine whether proposed disposal of ILW would lead to significant likelihood of LNAPL migration, both from waste packages and from a GDF vault into the local host rock. Our review and numerical modelling support the proposition that the release of a discrete free phase LNAPL from ILW would not present a significant challenge to the safety case even with conservative approximations. 'As-disposed' LNAPL emplaced with the waste is not expected to pose a significant issue. 'Secondary LNAPL' generated in situ within the disposed ILW, arising from the decomposition of plastics, in particular PVC (polyvinyl chloride), could form the predominant LNAPL source term. Released high molecular weight phthalate plasticizers are judged to be the primary LNAPL potentially generated. These are expected to have low buoyancy-based mobility due to their very low density contrast with water and high viscosity. Due to the inherent uncertainties, significant conservatisms were adopted within the numerical modelling approach, including: the simulation of a deliberately high organic material--PVC content wastestream (2D03) within an annular grouted waste package

  17. Oocytes lacking O-glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9:BMP15 expression.

    PubMed

    Grasa, Patricia; Ploutarchou, Panayiota; Williams, Suzannah A

    2015-02-01

    The number of eggs ovulated varies within and between species and is influenced by many variables. However, the regulatory mechanisms remain poorly understood. We previously demonstrated a key role for the oocyte because mice generating oocytes deficient in core 1-derived O-glycans ovulate ∼40-50% more eggs than Controls. Here we analyze the basis of this phenotype using Mutant [core 1 β1,3-galactosyltransferase 1 (C1galt1)(FF):zona pellucida glycoprotein 3 Cre (ZP3Cre)] and Control (C1galt1(FF)) female mice. In culture, Mutant follicles exhibited delayed antrum formation [indicative of follicle stimulant hormone (FSH) dependence] and increased sensitivity to FSH. Although the Mutant estrous cycle was extended, comprehensive endocrine changes were not observed; rather FSH, LH, inhibin B, and anti-Mullerian hormone were temporally altered, revealing estrous cycle stage-specific modifications to the hypothalamic-pituitary-gonadal axis. At proestrus, when FSH levels were decreased in Mutants, ovaries contained more, smaller, preantral follicles. Mutant follicles exhibited reduced levels of apoptosis, and both B-cell lymphoma 2 (Bcl-2) and BCL-2-associated X protein (Bax) were altered compared with Controls. Mutant ovaries also had an increase in the expression ratio of growth differentiation factor 9 (GDF9):bone morphogenetic protein 15 (BMP15) at diestrus. On the basis of these data, we propose that modified oocyte glycoproteins alter GDF9:BMP15 expression modifying follicle development resulting in the generation of more follicles. Thus, the oocyte is a key regulator of follicle development and has a crucial role in determining ovulation rate. PMID:25416550

  18. Infrared study of lattice dynamics and spin-phonon and electron-phonon interactions in multiferroic TbF e3(BO3) 4 and GdF e3(BO3) 4

    NASA Astrophysics Data System (ADS)

    Klimin, S. A.; Kuzmenko, A. B.; Kashchenko, M. A.; Popova, M. N.

    2016-02-01

    We present a comparative far-infrared reflection spectroscopy study of phonons, phase transitions, spin-phonon, and electron-phonon interactions in isostructural multiferroic iron borates of gadolinium and terbium. The behavior of phonon modes registered in a wide temperature range is consistent with a weak first-order structural phase transition [Ts=143 for GdF e3(BO3) 4 and 200 K for TbF e3(BO3) 4 ] from a high-symmetry high-temperature R 32 structure into a low-symmetry low-temperature P 3121 one. The temperature dependences of frequencies, oscillator strengths, and damping constants of some low-frequency modes reveal an appreciable lattice anharmonicity. Peculiarities in the phonon mode behavior in both compounds at the temperature of an antiferromagnetic ordering [TN=32 K for GdF e3(BO3) 4 and 40 K for TbF e3(BO3) 4 ] evidence the spin-phonon interaction. In the energy range of phonons, GdF e3(BO3) 4 has no electronic levels, but TbF e3(BO3) 4 possesses several. We observe an onset of new bands in the excitation spectrum of TbF e3(BO3) 4 due to a resonance interaction between a lattice phonon and 4 f electronic crystal-field (CF) excitations of T b3 + . This interaction causes delocalization of the CF excitations, their Davydov splitting, and formation of coupled electron-phonon modes.

  19. NEP facilities (LeRC)

    NASA Astrophysics Data System (ADS)

    Vetrone, Robert H.

    The topics are presented in viewgraph form and include the following: the Electric Propulsion Research Building (no. 16) the Electric Power Laboratory (BLDG. 301); the Tank 6 Vacuum Facility; and test facilities for electric propulsion and LeRC.

  20. Le bégaiement

    PubMed Central

    Perez, Hector R.; Stoeckle, James H.

    2016-01-01

    Résumé Objectif Fournir une mise à jour sur l’épidémiologie, l’hérédité, la physiopathologie, le diagnostic et le traitement du bégaiement développemental. Qualité des données Une recherche d’études récentes ou non portant sur l’épidémiologie, l’hérédité, la physiopathologie, le diagnostic et le traitement du bégaiement développemental a été effectuée dans les bases de données MEDLINE et Cochrane. La plupart des recommandations s’appuient sur des études de petite envergure, des données probantes de qualité limitée ou des consensus. Message principal Le bégaiement est un trouble d’élocution fréquent chez les personnes de tous âges, il altère la fluidité verbale normale et l’enchaînement du discours. Le bégaiement a été lié à des différences de l’anatomie, du fonctionnement et de la régulation dopaminergique du cerveau qui seraient de source génétique. Il importe de poser le diagnostic avec attention et de faire les recommandations qui conviennent chez les enfants, car de plus en plus, le consensus veut que l’intervention précoce par un traitement d’orthophonie soit cruciale chez les enfants bègues. Chez les adultes, le bégaiement est lié à une morbidité psychosociale substantielle, dont l’anxiété sociale et une piètre qualité de vie. Les traitements pharmacologiques ont soulevé l’intérêt depuis quelques années, mais les données cliniques sont limitées. Le traitement des enfants et des adultes repose sur l’orthophonie. Conclusion De plus en plus de recherches ont tenté de lever le voile sur la physiopathologie du bégaiement. La meilleure solution pour les enfants et les adultes bègues demeure la recommandation à un traitement d’orthophonie.

  1. Le pompage optique naturel dans le milieu astrophysique

    NASA Astrophysics Data System (ADS)

    Pecker, J.-C.

    The title of this lecture abstracts only a part of it : the importance in astrophysics of the study of non-LTE situations has become considerable, as well in the stellar atmospheres as, still more, in the study of fortuitous coincidences as a mechanism of formation of emission line nebular spectra, or of molecular interstellar « masers ». Another part of this talk underlines the role of Kastler in his time, and describes his warm personality through his public reactions in front of the nuclear armement, of the Viet-Nam and Algerian wars, of the problems of political refugees... Kastler was a great scientist ; he was also a courageous humanist. 1976 : Les accords nucléaires du Brésil : allocution d'ouverture (19 mars). Colloque sur le sujet ci-dessus. 1976 : La promotion de la culture dans le nouvel ordre économique international, allocution à l'occasion d'une table ronde sur ce thème par l'UNESCO (23-27 juin 1976) ; « Sciences et Techniques », octobre 1976. 1979 : La bête immonde (avec J.-C. Pecker), « Le Matin », 20 mars. 1979 : Appel à nos ministres (avec J.-C. Pecker), « Le Monde », 13 décembre. 1979 : Le flou, le ténébreux, l'irrationnel (avec J.-C. Pecker), « Le Monde », 14 septembre. 1980 : Education à la paix, Préface, in : Publ. UNESCO. 1981 : Le vrai danger, « Le Monde », 6 août 1981. 1982 : Nucléaire civil et militaire, « Le Monde », 1er juin 1982. 1982 : Les scientifiques face à la perspective d'holocauste nucléaire (texte inédit). Le titre de cette communication en résume seulement une partie : l'importance prise en astrophysique par l'analyse des situations hors ETL est devenue considérable, qu'il s'agisse des atmosphères stellaires, ou plus encore, des coïncidences fortuites de la formation des spectres d'émission nébulaires, ou des « masers » moléculaires interstellaires. Une autre partie de cet exposé souligne lele de Kastler dans son époque, et décrit sa personnalité généreuse à travers ses r

  2. LeRC in-house experimental research

    NASA Technical Reports Server (NTRS)

    Lyons, Valerie J.

    1992-01-01

    The topics covered include the following: LeRC in-house experimental research; combustion concepts; schedule for in-house experiments; lean premixed prevaporized combustion; comparisons of low NO(x) lean premixed/prevaporized data; rich burn/quick quench/lean burn (RQL); RQL combustion; fuel rich catalytic combustion; advanced diagnostics; and ceramic matrix liner test rig.

  3. La Greffe de Peau dans le Traitement des Sequelles de la Main Brulee. A Propos de 152 Cas - Experience du Service de Chirurgie Plastique du Centre Hospitalier Universitaire Ibn-Sina, Rabat, Maroc

    PubMed Central

    El Mazouz, S.; Fejjal, N.; Hafidi, J.; Cherkab, L.; Mejjati, H.; Belfqih, R.; Gharib, N.; Abbassi, A.

    2010-01-01

    Summary La main est fréquemment exposée aux brûlures, entraînant des séquelles esthétiques et fonctionnelles. Le traitement de ces séquelles est surtout chirurgical et consiste en la greffe de peau, dont le type dépend de la localisation de la brûlure et du type des séquelles. Dans ce travail rétrospectif, nous rapportons une série de 152 cas de brûlures des mains colligés au service de chirurgie plastique du Centre Hospitalier Universitaire Ibn-Sina de Rabat sur une période de dix ans, allant de 1998 à 2007. Les indications thérapeutiques dépendent du type de séquelles et de la localisation de la brûlure. En tout, 97 patients ont bénéficié d'une greffe cutanée, dont 76% par greffe de peau totale, 21% par greffe de peau demi-épaisse et 3% par peau fine. Les séquelles des brûlures des mains posent un problème thérapeutique majeur, malgré la diversité des procédés chirurgicaux, d'où l'intérêt de la prévention. PMID:21991196

  4. Le LHC, un tunnel cosmique

    ScienceCinema

    None

    2011-10-06

    Et si la lumière au bout du tunnel du LHC était cosmique ? En d?autres termes, qu?est-ce que le LHC peut nous apporter dans la connaissance de l?Univers ? Car la montée en énergie des accélérateurs de particules nous permet de mieux appréhender l?univers primordial, chaud et dense. Mais dans quel sens dit-on que le LHC reproduit des conditions proches du Big bang ? Quelles informations nous apporte-t-il sur le contenu de l?Univers ? La matière noire est-elle détectable au LHC ? L?énergie noire ? Pourquoi l?antimatière accumulée au CERN est-elle si rare dans l?Univers ? Et si le CERN a bâti sa réputation sur l?exploration des forces faibles et fortes qui opèrent au sein des atomes et de leurs noyaux, est-ce que le LHC peut nous apporter des informations sur la force gravitationnelle qui gouverne l?évolution cosmique ? Depuis une trentaine d?années, notre compréhension de l?univers dans ses plus grandes dimensions et l?appréhension de son comportement aux plus petites distances sont intimement liées : en quoi le LHC va-t-il tester expérimentalement cette vision unifiée ? Tout public, entrée libre / Réservations au +41 (0)22 767 76 76

  5. Le Planetaire (Around the World)

    ERIC Educational Resources Information Center

    Rebouillet, Andre; And Others

    1977-01-01

    This section, "Le Planetaire," contains an interview with Anne Slack on the American Association of Teachers of French and contemporary French culture, a review of a dictionary of familiar French for students, dates to remember, events of interest to French teachers and a general bibliography. (Text is in French.) (AMH)

  6. Understanding the recognition of Lewis X by anti-Le(x) monoclonal antibodies.

    PubMed

    Moore, Christopher J; Auzanneau, France-Isabelle

    2013-10-24

    The recognition of the Le(x) antigen by the anti-Le(x) monoclonal antibody (mAb) SH1 was studied by ELISA using a panel of 4″-modified Le(x) analogues. We confirmed that these analogues maintained the stacked conformation adopted by natural Le(x) antigen using 1D ROESY experiments and measuring intramolecular distances. Our binding studies show that the 4-OH″ of galactose behaves as an H-bond donor to an electronegative amino acid side chain in the SH1 binding site. While removal of this H-bond leads to reduced inhibition, disturbing the hydrophobic α face of the β-galactosyl residue leads to complete loss of binding to SH1. We compared our results to the crystal structure of the Fab fragment of anti-Le(x) mAb 291-2G3-A complexed with Le(x) (PDB entry 1UZ8 ). While no H-bond involving the 4-OH″ was described, hydrophobic interactions between a tryptophan residue and the β-galactoside α face are observed. We conclude that the hydrophobic α face that is uniquely displayed by β-galactosyl residues is essential to the recognition of the Le(x) antigen by anti-Le(x) antibodies. PMID:24059473

  7. In re LePage.

    PubMed

    2001-01-01

    Court Decision: 18 Pacific Reporter, 3d Series 1177; 2001 Mar 8 (date of decision). The Supreme Court of Wyoming held that the state Department of Health was not authorized to inquire about the sincerity of a mother's religious beliefs when determining whether her daughter was exempt from a public school immunization requirement. Susan LePage submitted a request to the Department of Health seeking to exempt her daughter from receiving the hepatitis B vaccination. The Department of Health inquired into the sincerity of LePage's religious beliefs against vaccination and determined that her objections were of a personal or philosophical nature and not on religious grounds. The Department of Health denied LePage's request. The Supreme Court of Wyoming held that state law requires the Department of Health to grant an exemption upon the submission of a written objection and does not allow the Department of Health to make an inquiry into the sincerity of the requestor's religious beliefs. The court balanced a valid state interest in protecting schoolchildren from disease with the relatively low number of requests for exemption and its confidence in parents to make decisions in the best interest of their children's physical and spiritual health. Since there was no justification within the statute to allow a religious inquiry, the court held that the Department of Health had exceeded its authority with LePage. Furthermore, state law did not require a religious waiver to exempt a child from this particular vaccine. The lower court's holding was reversed. PMID:16479706

  8. Le Fevre [Le Fèvre; LeFebvre], Jean (1652-1706)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Born in Lisieux, France, became an associate of JEAN PICARD and PHILIPPE DE LA HIRE, became a member of the Académie des Sciences and worked on rather routine work calculating ephemeredes, and surveying. Le Fevre accused La Hire of stealing his tables after Philippe de La Hire published Tabulae Astronomicae in 1687. In 1701, resentful at not having been named official publisher of ephemerides to ...

  9. Search for the Higgs Boson and for Anomalous Quartic Gauge Boson Couplings in the WW Channel with Dielectron Events with the D0 Experiment at the Tevatron; Recherche du boson de Higgs et de couplages de jauge quartiques anormaux dans le canal WW en électrons dans l'expérience D0 au Tevatron

    SciTech Connect

    Chapon, Emilien

    2013-01-01

    Le paysage de la physique des particules a subi des changements majeurs entre le début de cette thèse, en septembre 2010, et sa n en juin 2013. On peut notamment qualier l'année 2012 de date-clé dans l'histoire de la physique des particules. En 2012, une nouvelle particule a été découverte au LHC [1, 2], dont la majeure partie de la communauté s'accorde aujourd'hui à dire qu'il s'agit très probablement du boson de Higgs. Cet événement est intervenu peu après une sorte de passage de relais entre le Tevatron, arrêté le 30 septembre 2011, et le LHC, dont les toutes premières collisions sont intervenues le 23 novembre 2009.

  10. L'astronomie dans le monde

    NASA Astrophysics Data System (ADS)

    Manfroid, J.

    2008-09-01

    Fragmentation et astéroïdes binaires; Astéroïde géocroiseur triple; Rosetta sort de son hibernation; Messenger; Transit lunaire vu par Deep Impact; Titan; Phobos; Phoenix; Einstein avait raison; Le ballet des taches rouges; Le poids des lentilles;

  11. Le syndrome d'apert

    PubMed Central

    Benmiloud, Sarra; Chaouki, Sana; Atmani, Samir; Hida, Moustapha

    2013-01-01

    Le syndrome d'Apert est une affection congénitale rare, caractérisée par une sténose cranio-faciale associée à une syndactylie des mains et des pieds. Sa prise en charge doit être précoce et multidisciplinaire. Sa gravité réside dans la coexistence de plusieurs malformations avec un risque d'hypertension intracrânienne chronique responsable d'une cécité et d'une débilité mentale. Les auteurs rapportent une nouvelle observation à travers laquelle ils illustrent les aspects cliniques et évolutifs ainsi que les difficultés thérapeutiques de cette affection. PMID:23565313

  12. Intraday LeBaron effects

    PubMed Central

    Bianco, Simone; Corsi, Fulvio; Renò, Roberto

    2009-01-01

    We study the relation at intraday level between serial correlation and volatility of the Standard and Poor (S&P) 500 stock index futures returns. At daily and weekly levels, serial correlation and volatility forecasts have been found to be negatively correlated (LeBaron effect). After finding a significant attenuation of the original effect over time, we show that a similar but more pronounced effect holds by using intraday measures, by such as realized volatility and variance ratio. We also test the impact of unexpected volatility, defined as the part of volatility which cannot be forecasted, on the presence of intraday serial correlation in the time series by employing a model for realized volatility based on the heterogeneous market hypothesis. We find that intraday serial correlation is negatively correlated to volatility forecasts, whereas it is positively correlated to unexpected volatility.

  13. LeSTIG1, an extracellular binding partner for the pollen receptor kinases LePRK1 and LePRK2, promotes pollen tube growth in vitro.

    PubMed

    Tang, Weihua; Kelley, Dior; Ezcurra, Inés; Cotter, Robyn; McCormick, Sheila

    2004-08-01

    As pollen tubes grow through the pistil they are thought to perceive and respond to diverse signals. The tomato pollen-specific receptor kinases LePRK1 and LePRK2 might participate in signaling during pollen tube growth. We previously showed that the extracellular domain of LePRK2 interacts with a pollen protein, LAT52, before but not after pollen germination. To determine whether LePRK2 might have different binding partner(s) after pollen germination, we characterized two more proteins that, like LAT52, were identified in yeast two-hybrid screens using the extracellular domains of LePRK1 and LePRK2 as baits. We show that LeSHY, a leucine-rich repeat protein from pollen, and LeSTIG1, a small cysteine-rich protein from pistil, can bind the extracellular domains of both LePRK1 and LePRK2 in vitro. In vitro binding assays with the extracellular domain of LePRK2 suggested that LeSTIG1 could displace binding of LAT52, consistent with the idea that LePRK1 and LePRK2 might interact with different ligands at different stages of pollen tube growth. Exogenous LeSTIG1 promotes pollen tube growth in vitro. The interaction of these pollen kinases with LeSTIG1 supports the notion that LePRK1 and LePRK2 are involved in mediating pollen-pistil interactions. PMID:15255864

  14. Jan Potocki et le "Gothic Novel"

    ERIC Educational Resources Information Center

    Finne, Jacques

    1970-01-01

    Establishes a parallel between the supernatural and fantastic qualities of Le Comte Jan Potocki's literary works, and the English gothic novels by comparing the elements of terror, mysterious atmosphere, and the supernatural beings involved. (DS)

  15. Entrevue avec le Dr Charley Zeanah

    PubMed Central

    2013-01-01

    Le Dr Charles Zeanah est titulaire de la chaire de psychiatrie Mary K. Sellars-Polchow, professeur de pédiatrie clinique et vice-président de la pédopsychiatrie au département de psychiatrie et des sciences du comportement de la faculté de médecine de l’Université Tulane, à la Nouvelle-Orléans. Il est également directeur général de l’institut de la santé mentale des nourrissons et des jeunes enfants de Tulane. Il est récipiendaire de nombreux prix, notamment le prix de prévention Irving Phillips (AACAP), la mention élogieuse présidentielle pour sa recherche et son leadership exceptionnels en santé mentale des nourrissons (American Orthopsychiatric Association), le prix d’excellence clinique Sarah Haley Memorial (International Society for Traumatic Stress Studies), le prix de recherche en pédopsychiatrie Blanche F. Ittelson (APA), et le prix Serge Lebovici Award soulignant les contributions internationales à la santé mentale des nourrissons (World Association for Infant Mental Health). Le Dr Zeanah est fellow distingué de l’AACAP, fellow distingué de l’APA et membre du conseil d’administration de Zero to Three. Il est l’éditeur scientifique de Handbook of Infant Mental Health (3e édition) qui est considéré comme étant le manuel de pointe et la référence de base du domaine de la santé mentale des nourrissons.

  16. List processing software for the LeCroy 1821 Segment Manager Interface

    SciTech Connect

    Dorries, T.; Moore, C.; Pordes, R.

    1987-05-01

    Many experiments at Fermilab now include some FASTBUS electronics in their data readout. The software reported in this paper provides general support for the LeCroy 1821 interface. The list processing device drivers allow FASTBUS data to be read out efficiently into the Fermilab Computing Department supported data acquisition systems.

  17. Synthesis, characterization, phase diagrams and superconducting and normal state magnetic properties of La{sub 2{minus}x}Sr{sub x}CuO{sub 4} (0 {le} x {le} 0.08) and electrochemically oxidized La{sub 2{minus}x}Sr{sub x}CuO{sub 4+{delta}} (0 {le} x {le} 0.33, 0 {le} {delta} {le} 0.12)

    SciTech Connect

    Chou, F.

    1993-08-01

    La{sub 2{minus}x}Sr{sub x}CuO{sub 4} (0 {le} x {le} 0.15) can all be intercalated with oxygen by a novel electrochemical oxidation method. Bulk superconductivity is found with an onset {Tc} {approx} 40 K for the whole range 0.01 {le} x {le} 0.15; for x = 0.25 and 0.33, the electrochemical oxidation did not improve the superconducting properties. The magnetic susceptibility {chi}(T = 50--320 K) data for La{sub 2}CuO{sub 4.11} and La{sub 1.92}Sr{sub 0.08}CuO{sub 4.07} are nearly identical with those of conventionally prepared La{sub 1.85}Sr{sub 0.15}CuO{sub 4}, indicating that the hole doping level (p) in the CuO{sub 2} planes of the three compounds is nearly the same. Combined thermogravimetric analysis and iodometric titration experiments indicate that part of the intercalated oxygen has a formal valence close to {minus}1. The maximum doped-hole concentration in the CuO{sub 2} planes that can be achieved from combined Sr-doping and electrochemical oxygen doping for 0 {le} x {le} 0.15 is p {approx} 0.16 holes/formula unit. Oxygen can also intercalate into single crystal La{sub 2}CuO{sub 4} through a slow electrochemical oxidation process. The required low current and long time for the charging process reflects that the oxygen intercalation for a single crystal is limited by its small specific surface area and long diffusion distance. The anisotropic superconducting, magnetic and transport properties are summarized and compared with those of polycrystalline La{sub 2}CuO{sub 4+{delta}} as well as of YBa{sub 2}Cu{sub 3}O{sub 7{minus}{delta}} and La{sub 2{minus}x}Sr{sub x}CuO{sub 4} single crystals. The single crystal La{sub 2}CuO{sub 4+{delta}} has a maximum {Tc} {approx} 40 K, which is lower than that ({Tc} {approx} 42--45) of the corresponding polycrystalline samples. The magnetic phase diagram of La{sub 2{minus}x}Sr{sub x}CuO{sub 4} in the antiferromagnetic (AF) regime (0 {le} x {le} 0.02) has been derived from {sup 139}La NQR studies from 4 to 250 K.

  18. L'astronomie dans le monde

    NASA Astrophysics Data System (ADS)

    Manfroid, J.

    2014-06-01

    Future lune ? - L'âge de la Lune - Des volcans actifs sur Vénus - Un lac dans le cratère Gusev ? - Météorites et atmosphère martiennes - L’hexagone de Saturne - Pluton - Exo-Terre - Bêta Pictoris b - Cérès et Vesta depuis Mars - Naine froide - Parallaxes par Hubble - L2 Puppis et le sort du Soleil - Supernova et lentille gravitationnelle - Champ magnétique galactique - L’objet de Sakurai - Fermi et la matière noire - Lentille naine

  19. 23. VIEW OF LE CLAIRE LOCK (19211925), SHOWING OPERATING MACHINERY, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    23. VIEW OF LE CLAIRE LOCK (1921-1925), SHOWING OPERATING MACHINERY, DOWSTREAM GATES, UPSTREAM SIDE - Mississippi River 9-Foot Channel, Lock & Dam No. 14, Upper Mississippi River, Le Claire, Scott County, IA

  20. 20. VIEW OF LE CLAIRE LOCK (19211925), SHOWING UPSTREAM GATES, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. VIEW OF LE CLAIRE LOCK (1921-1925), SHOWING UPSTREAM GATES, DOWNSTREAM SIDE AND SOUTH LOCKWALL - Mississippi River 9-Foot Channel, Lock & Dam No. 14, Upper Mississippi River, Le Claire, Scott County, IA

  1. 30. INTERIOR VIEW OF MISSISSIPPI RIVER RECREATION OFFICE, LE CLAIRE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    30. INTERIOR VIEW OF MISSISSIPPI RIVER RECREATION OFFICE, LE CLAIRE BASE COMPOUND, LOOKING EAST - Mississippi River 9-Foot Channel, Lock & Dam No. 14, Upper Mississippi River, Le Claire, Scott County, IA

  2. 29. INTERIOR VIEW OF MISSISSIPPI RIVER RECREATION OFFICE BUILDING, LE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    29. INTERIOR VIEW OF MISSISSIPPI RIVER RECREATION OFFICE BUILDING, LE CLAIRE BASE COMPOUND, LOOKING WEST - Mississippi River 9-Foot Channel, Lock & Dam No. 14, Upper Mississippi River, Le Claire, Scott County, IA

  3. Restart function of the LE-5 engine

    NASA Astrophysics Data System (ADS)

    Hirata, Kunio; Koyari, Yukio; Yanagawa, Koji; Katsuta, Hideaki; Taniguchi, Hirofumi; Torii, Yoshihiro

    1993-10-01

    This report presents the restart function of the LE-5 (Liquid Engine-5). The development of a de/anti-ice system and a sufficient pump precooling system was key in establishing this function. To ensure high reliability, a contingency device was also adopted. The functions were proved through actual flights.

  4. Le Francais Courant: Part V, French.

    ERIC Educational Resources Information Center

    Dade County Public Schools, Miami, FL.

    Instructional objectives of the Dade County Public Schools Quinmester Program in French for use with "Le Francais Courant: Part 5" focus on the development of mastery of the basic numbering system and other grammatical structures. Structures include the formation of the present tense of the irregular verbs "vouloir,""pouvoir," and "venir,"…

  5. Le Francais Moderne: Part I, French.

    ERIC Educational Resources Information Center

    Dade County Public Schools, Miami, FL.

    Instructional objectives of the Dade County Public Schools Quinmester Program in French for use with "Le Francais Moderne: Part 1" focus on the development of vocabulary and mastery of grammatical structures. The formation of the passe compose with "avoir," object pronouns, the present tense of regular "-ir" verbs, and the irregular verbs…

  6. Le Chatelier's principle in replicator dynamics

    NASA Astrophysics Data System (ADS)

    Allahverdyan, Armen E.; Galstyan, Aram

    2011-10-01

    The Le Chatelier principle states that physical equilibria are not only stable, but they also resist external perturbations via short-time negative-feedback mechanisms: a perturbation induces processes tending to diminish its results. The principle has deep roots, e.g., in thermodynamics it is closely related to the second law and the positivity of the entropy production. Here we study the applicability of the Le Chatelier principle to evolutionary game theory, i.e., to perturbations of a Nash equilibrium within the replicator dynamics. We show that the principle can be reformulated as a majorization relation. This defines a stability notion that generalizes the concept of evolutionary stability. We determine criteria for a Nash equilibrium to satisfy the Le Chatelier principle and relate them to mutualistic interactions (game-theoretical anticoordination) showing in which sense mutualistic replicators can be more stable than (say) competing ones. There are globally stable Nash equilibria, where the Le Chatelier principle is violated even locally: in contrast to the thermodynamic equilibrium a Nash equilibrium can amplify small perturbations, though both types of equilibria satisfy the detailed balance condition.

  7. A Colorful Demonstration of Le Chbtelier's Principle.

    ERIC Educational Resources Information Center

    Last, Arthur M.; Slade, Peter W.

    1997-01-01

    Le Chbtelier's Principle states that, when a system at equilibrium is subjected to stress, the system will respond in such a way as to minimize the effect of the stress. Describes a lecture demonstration that illustrates shifts in the position of equilibrium caused by a variety of factors. The equilibrium mixture contains iron (III) and…

  8. Type-1 chain histo-blood group antigens (Le(a), monosialosyl-Le(a), disialosyl-Le(a), Le(b), and H) in normal and malignant human endometrium.

    PubMed

    Ravn, V; Mandel, U; Svenstrup, B; Dabelsteen, E

    1994-01-01

    Type-1 chain histo-blood group antigens such as the Lewis (Le)a, monosialosyl-Le(a), Le(b) and H antigens show an increased expression in endometrial carcinomas. However, the possibility that these antigens are expressed under genetic or hormonal influence in endometrial carcinomas has not been considered. In the present study, the expression of type-1 chain carbohydrate antigens in normal and malignant endometrium was evaluated by immunohistochemistry and related to both genetic and hormonal factors. The glands of normal, non-secretory endometria expressed, in contrast with surface epithelial cells, Le(a), Le(b), disialosyl-Le(a), and H determinants infrequently. Adenomatous hyperplasias and endometrial carcinomas showed an increased expression of type-1 chain carbohydrates that was qualitatively influenced by the erythrocyte Lewis phenotype and the secretor status. Whereas Le(a+b-) non-secretors mainly accumulated Le(a) antigen, and only limited amounts of Le(b) antigen, Le(a-b+) secretors expressed H, Le(b) and Le(a) antigens. The expression of type-1 chain antigens showed no association with the serum-oestrogen level or to the hormone-receptor status. Thus the Lewis secretor status has a qualitative influence on the increased expression of type-1 chain antigens, which, however, seem to be unrelated to hormonal factors. Our findings suggest an increased activity of the Se-gene-defined or a closely related fucosyl-transferase in neoplastic endometrial epithelial cells. PMID:8032530

  9. Le syndrome d’alcoolisme foetal

    PubMed Central

    2002-01-01

    L’alcool est un tératogène physique et comportemental. Le syndrome d’alcoolisme foetal (SAF) est un trouble courant mais encore sous-diagnostiqué découlant de la consommation d’alcool par la mère pendant la grossesse. Bien qu’il puisse être prévenu, le SAF est également invalidant. Même si le SAF est présent dans tous les groupes socioéconomiques du Canada, sa prévalence est élevée dans certaines communautés inuites et des Premières nations du Canada. Le présent énoncé porte sur la prévention, le diagnostic, le dépistage précoce et la prise en charge du SAF par les professionnels de la santé. La prévention du SAF doit s’effectuer à deux échelons. La prévention primaire consiste à éliminer le SAF par une formation en classe ou dans la collectivité et à inciter les femmes à éviter de consommer de l’alcool avant la conception et pendant la grossesse. La prévention secondaire consiste à repérer les femmes qui boivent pendant leur grossesse et à réduire leur consommation. Le présent énoncé décrit plusieurs stratégies de dépistage, dont la stratégie T-ACE (tolérance-agacement, réduction, éveil). Les dispensateurs de soins devraient recommander l’abstinence dès la première visite prénatale. Un envoi rapide en consultation en vue de traiter l’alcoolisme est recommandé pour les femmes enceintes incapables d’arrêter de boire. Le présent énoncé décrit le diagnostic de SAF, de SAF partiel ou atypique, d’anomalies congénitales et de troubles neurodéveloppementaux reliés à l’alcool. En cas d’exposition à l’alcool in utero, un diagnostic de SAF devrait être envisagé en présence d’un retard de croissance courant ou antérieur, de certaines anomalies faciales touchant la lèvre supérieure et les yeux et d’anomalies neurodéveloppementales. Ces caractéristiques sont mieux quantifiées au moyen d’une méthode diagnostique à quatre chiffres. Des stratégies de dépistage précoce des

  10. Design of Multidimensional Shinnar-Le Roux RF Pulses

    PubMed Central

    Ma, Chao; Liang, Zhi-Pei

    2014-01-01

    Purpose To generalize the conventional Shinnar-Le Roux (SLR) method for the design of multidimensional RF pulses. Methods Using echo-planar gradients, the multidimensional RF pulse design problem was converted into a series of 1D polynomial design problems. Each of the 1D polynomial design problems was solved efficiently. B0 inhomogeneity compensation and design of spatial-spectral pulses were also considered. Results The proposed method was used to design 2D excitation and refocusing pulses. The results were validated through Bloch equation simulation and experiments on a 3.0 T scanner. Large-tip-angle, equiripple-error, multidimensional excitation was achieved with ripple levels closely matching the design specifications. Conclusion The conventional SLR method can be extended to design multidimensional RF pulses. The proposed method achieves almost equiripple excitation errors, allows easy control of the tradeoff among design parameters, and is computationally efficient. PMID:24578212

  11. L'astronomie dans le monde

    NASA Astrophysics Data System (ADS)

    Manfroid, J.

    2013-06-01

    Une binaire remarquable; Collision de galaxies; La nébuleuse planétaire C1295; ALMA (suite); Couple massif; Astéroïdes lointains; L’eau de Jupiter; Occultation par Pluton; Super-Terres; Première image d’une planète massive autour d’une étoile double; Tempête au pôle de Saturne

  12. Les Troubles Respiratoires Chez Le Brule

    PubMed Central

    Fassi Fihri, J.; Ezzoubi, M.; Boukind, E.H.

    2010-01-01

    Summary A travers une revue de la littérature, cet article se propose d'exposer les particularités des troubles respiratoires chez le brûlé. Ces troubles sont liés à un mécanisme direct, lorsque l'arbre respiratoire est lésé par le transfert d'énergie thermique du à la brûlure et/ou par un mécanisme indirect, lorsque la fonction respiratoire et ventilatoire du poumon est perturbée par les phénomènes loco-régionaux ou généraux du brûlé. Ces troubles respiratoires sont aggravés par l'inhalation des gaz contenus dans la fumée d'incendie. Le diagnostic de ces troubles est clinique et paraclinique. Il doit être précoce et continu. Les patients nécessitent de différents moyens thérapeutiques tels que l'oxygénothérapie, la libération des voies respiratoires, l'amélioration de la mécanique ventilatoire et de la fonction respiratoire, l'antibiothérapie ou la chirurgie des séquelles. Cette prise en charge doit nécessairement être multidisciplinaire. PMID:21991224

  13. Le déficit immunitaire humoral: mieux le connaître pour mieux le prendre en charge

    PubMed Central

    El Bakkouri, Jalila; Aadam, Zahra; Ailal, Fatima; Alj, Hanane Salih; Bousfiha, Ahmed Aziz

    2014-01-01

    Les déficits immunitaires humoraux (DIH) sont des maladies hétérogènes allant des formes asymptomatiques rencontrés lors des déficits sélectifs en immunoglobulines A (IgA) et en sous-classes d'IgG aux formes graves des agammaglobulinémies congénitales. Les patients atteints de DIH présentent souvent des infections ORL ou des voies respiratoires récidivantes ou sévères. Ces patients peuvent présenter un certain nombre de complications non infectieuses, telles que des manifestations auto-immunes et des entéropathies, qui pourraient être le seul symptôme clinique révélateur. Les formes sévères des DIH sont facilement diagnostiquées grâce au dosage des IgG totaux, des IgA et des IgM. La thérapie substitutive par les immunoglobulines reste le traitement de choix chez ces patients. PMID:25489366

  14. Lele de l’omalizumab dans le traitement de l’asthme allergique grave

    PubMed Central

    Chapman, Kenneth R; Cartier, André; Hébert, Jacques; McIvor, R Andrew; Schellenberg, R Robert

    2006-01-01

    CONTEXTE : Un nouveau traitement anti-immunoglobuline E (anti-IgE) contre l’asthme, l’omalizumab, a été approuvé au Canada. OBJECTIF : Passer en revue les données fondamentales et cliniques sur l’omalizumab et examiner lele possible de ce médicament dans la prise en charge de l’asthme au Canada. MÉTHODOLOGIE : Une recherche documentaire a été effectuée dans MEDLINE afin de repérer les études menées de 1960 à 2006 sur l’omalizumab. La recherche a également porté sur les résumés de réunions scientifiques récentes dans le domaine des maladies respiratoires et des allergies; par ailleurs, toute donnée non publiée a été demandée au fabricant. Après avoir revu et résumé les données, un comité mixte constitué de spécialistes des maladies respiratoires et des allergies a rédigé un ensemble de recommandations relatives à l’utilisation de l’omalizumab. RÉSULTATS : L’omalizumab est un anticorps monoclonal humanisé qui se lie au domaine C epsilon 3 de la molécule d’IgE pour former des complexes immuns solubles qui sont éliminés par le système réticulo-endothélial. L’administration d’injections sous-cutanées espacées de deux ou de quatre semaines à la dose recommandée entraîne une diminution rapide des taux d’IgE circulantes libres. Lors de deux essais cliniques de phase III menés auprès de 1 405 adultes et adolescents atteints d’asthme modéré à grave qui recevaient des doses moyennes stables de corticostéroïdes en inhalation (CSI), l’omalizumab a diminué les taux d’exacerbation par rapport au placebo et a été associé à une amélioration des symptômes ainsi qu’à une épargne plus importante des corticostéroïdes. Dans un essai mené auprès de 419 patients atteints d’asthme grave non maîtrisé malgré l’utilisation de doses élevées de CSI et de la prise concomitante d’agonistes bêta-2 à action prolongée, les exacerbations graves étaient de 50 % moins fréquentes chez

  15. Intracranial subdural hygroma after Le Fort I osteotomy.

    PubMed

    Thompson, William L; Lee, Michael; MacIntosh, Robert Bruce

    2015-04-01

    Various intra- and postoperative complications have been well-documented after Le Fort I osteotomies; however, an intracranial subdural hygroma has not yet been reported in oral and maxillofacial studies. We report a unique case of an intracranial subdural hygroma requiring neurosurgical intervention after Le Fort I advancement. PMID:25631863

  16. Deep inelastic structure functions from electron scattering on hydrogen, deuterium, and iron at 0. 6 GeV sup 2 le Q sup 2 le 30. 0 GeV sup 2

    SciTech Connect

    Whitlow, L.W.

    1990-03-01

    We report the final results from experiment E140, a recent deep inelastic electron-deuterium and electron-iron scattering experiment at SLAC. In addition, we present the results of a combined global analysis of all SLAC deep inelastic electron-hydrogen and electron-deuterium cross section measurements between 1970 and 1983. Data from seven earlier experiments are re-radiatively corrected and normalized to experiment E140. We report extractions of R(x,Q{sup 2}) and F{sub 2}(x,Q{sup 2}) for hydrogen and deuterium over the entire SLAC kinematic range: .06{le} x {le}.90 and 0.6{le} Q{sup 2} {le}30.0 (GeV{sup 2}). We fine that R{sup p} = R{sup d}, as expected by QCD. Extracted values of R(x,Q{sup 2}) are significantly larger than predictions based on QCD and on QCD with the inclusion of kinematic target mass terms. This difference indicates that dynamical higher twist effects may be important in the SLAC kinematic range. A best fit empirical model of R(x,Q{sup 2}) is used to extract F{sub 2} from each cross section measurement. These F{sub 2} extractions are compared with F{sub 2} data from EMC and BCDMS. Agreement is observed with EMC when the EMC data are multiplied by 1.07. Agreement is observed with BCDMS over a limited range in x. The ratios of F{sub 2}{sup d}/F{sub 2}{sup p} are examined for Q{sup 2} dependence. We observe a significant negative slope for x {le} .6, and a significant positive slope above x > .7, in excellent agreement with predictions based on QCD with the inclusion of kinematic target mass terms. 111 refs., 40 figs., 34 tabs.

  17. The Use of Le by L1 Chinese Speakers and the Acquisition of Le by L2 Chinese Learners

    ERIC Educational Resources Information Center

    Bredeche, Chi Chen

    2011-01-01

    The perfective marker V-"le" is claimed to be one of the most problematic items in the acquisition of L2 Chinese, perhaps because no unified and comprehensive treatment of it exists in the literature. Although much has been written on this topic, the semantic and pragmatic functions of V-"le" have remained elusive. While linguists and grammarians…

  18. Energy levels, wavelengths, and radiative transition probabilities for the Na-like ions with 38 [le] Z [le] 45

    SciTech Connect

    Ying Zhang; Qiren Zhu; Shoufu Pan )

    1992-11-01

    The investigation by Z.-Q Zhang et al. (Acta Optica Sinica 11, 193, 1991) shows that it is possible to realize soft X-ray lasing in the water window 23.3-43.8 [Angstrom] with the Na-like recombination scheme, which requires a lower pumping power at a high-power laser facility than that with other schemes. The fine-structure levels with n [le] 15 and l [le] 6 in Na-like ions with 38 [le] Z [le] 45 and the probabilities for radiative transitions between these levels are calculated using the multiconfiguration Dirac-Fock approach. The calculations show that the wavelengths of the anticipated laser transitions 6 f-4d and 6g-4f in the Na-like ions with 38 [le] Z [le] 43 and 5f-4d and 5g-4f in the Na-like ions with 40 [le] Z [le] 45 lie in the region of the water window.

  19. Le contrôle des infections au cabinet du pédiatre

    PubMed Central

    2008-01-01

    RÉSUMÉ La transmission des infections au cabinet du pédiatre est de plus en plus préoccupante. Le présent document expose les voies de transmission des infections et les principes sous-jacents aux mesures actuelles pour contrôler les infections. Pour prévenir les infections, il faut bien concevoir le cabinet et adopter des politiques administratives et de triage convenables, de même que des pratiques de base pour les soins de tous les patients (p. ex., hygiène des mains, port de gants, de masques, de lunettes de protection et d’une blouse d’hôpital pour des interventions précises; nettoyage, désinfection et stérilisation convenables des surfaces et du matériel, y compris les jouets, et techniques d’asepsie en cas d’interventions effractives) et des précautions additionnelles en cas d’infections précises. Le personnel doit avoir reçu les vaccins pertinents, et les personnes infectées doivent respecter les politiques de restriction au travail.

  20. [Mr. Wang Le-ting: a master of acupuncture].

    PubMed

    Niu, Xue-Song; Wang, Fan

    2012-11-01

    Mr. WANG Le-ting attaches great importance to accurate differentiation of syndromes, strict selection of acupoints, technique and direction of needle insertion, clear reinforcing and reducing methods after the appearance of needling sensations, proper opportunities of manipulations as well as needle withdrawal techniques, and reasonable application of acupuncture and moxibustion respectively. The above mentioned principles are known as his "5 agreements". He emphasizes that the selection of acupoints should be "in accordance with both the meridians and the accurate location of the points", and "needling sensation is necessary for each point". He holds that the back-shu points of the five-zang organs and Geshu (BL 17) can be adopted for patient with deficiency of qi, blood, yin and yang. In the aspect of acupoint theory, he insists the accurate location of Xuanzhong (GB 39). He also adjusts the locations of Huatuo Jiaji (EX-B 2) points, and finds the location of the new Dubi (ST 35). For easier applications, he divides the functions of acupoints into different schools of qi, blood, cold, heat, deficiency, excess, wind and dampness. And 41 combinations of acupoints are also invented as innovation. He is always strict to his students, instructing and influencing them by his own words and deeds. He is always conscientious and meticulous, which benefit immensely his followers, and remains a lot of precious experiences for the later generations. PMID:23214000

  1. Les Hemorragies Gastroduodenales de Stress Chez le Brule Grave

    PubMed Central

    Siah, S.; Fouadi, F.E.; Ababou, K.; Nassim Sabah, T.; Ihrai, I.

    2008-01-01

    Summary Les Auteurs rapportent trois observations d'hémorragies gastroduodénales de stress chez le brûlé grave. Ils rappellent l'importance des mesures thérapeutiques qui doivent être prises chez le brûlé grave, comme le traitement du choc, du sepsis, des plaies et de la douleur, la nutrition entérale précoce et l'oxygénothérapie. Tout cela permet de réduire les facteurs de risque de survenue d'une hémorragie gastroduodénale de stress. PMID:21991137

  2. Automated Verification of Design Patterns with LePUS3

    NASA Technical Reports Server (NTRS)

    Nicholson, Jonathan; Gasparis, Epameinondas; Eden, Ammon H.; Kazman, Rick

    2009-01-01

    Specification and [visual] modelling languages are expected to combine strong abstraction mechanisms with rigour, scalability, and parsimony. LePUS3 is a visual, object-oriented design description language axiomatized in a decidable subset of the first-order predicate logic. We demonstrate how LePUS3 is used to formally specify a structural design pattern and prove ( verify ) whether any JavaTM 1.4 program satisfies that specification. We also show how LePUS3 specifications (charts) are composed and how they are verified fully automatically in the Two-Tier Programming Toolkit.

  3. Impact de la varicocèle sur le volume testiculaire et les paramètres spermatiques

    PubMed Central

    Benazzouz, Mohamed Hicham; Essatara, Younes; El Sayegh, Hachem; Iken, Ali; Benslimane, Lounis; Nouini, Yassine

    2014-01-01

    Introduction La varicocèle est une pathologie masculine fréquente dont l'incidence est encore plus importante dans dans la population des hommes infertiles. Si ses mécanismes sont à ce jour incomplètement expliqués il semble acquis que la varicocèle peut être associée a une dysfonction testiculaire avec diminution du volume testiculaire et de la concentration en spermatozoïde de l’éjaculat. Méthodes Dans un premier temps nous exposons les résultats d'une étude rétrospective sur 5 ans (de Mars 2009 à Mars 2014), réalisée au service d'urologie A de l'hôpital Ibn Sina de Rabat et ayant comme objectif d’évaluer l'impact de la varicocèle palpable sur le volume testiculaire et les paramètres spermatiques. Tous les patients inclus dans notre étude avaient une varicocèle palpable. Dans un deuxième temps, et à travers une revue de la littérature nous discutons l'impact du traitement de la varicocèle sur la fertilité. Résultats 39 patients ont été inclus dans notre étude. L’âge moyen était de 29,71 ans et la varicocèle siégeait dans 89,74% des cas du coté gauche. Une atrophie testiculaire homolatérale à la varicocèle était retrouvée dans 7% des cas alors que des anomalies du spermogramme se voyaient dans 69,23% des cas. Conclusion L'impact de la varicocèle sur l'altération des paramètres spermatiques a été clairement établi bien que sa physio pathogénie ne soit pas bien élucidée. Le traitement chirurgical de la varicocèle semble indiqué chez les hommes infertiles présentant une varicocèle clinique et une altération significative du sperme. PMID:25918574

  4. Development status of LE-7 fuel turbopump

    NASA Astrophysics Data System (ADS)

    Nakano, T.; Nagao, R.; Ohta, T.; Warashina, S.; Watanabe, H.; Oguchi, H.

    The liquid hydrogen turbopump (LH2 T/P) for the LE-7 engine has been developed since 1984. The component PDR was held in June 1988 and the basic troubles occurred at the development test were solved. Next, the component CDR-1 was held in December 1989 in order to feed back the test results of prototype LH2 T/P model to the design of qualification phase T/P. So, the production of these turbopumps was admitted. Recently, the component CDR-2 was held in February 1992 to reflect the counterparts adopted for some troubles (impeller and turbine blade cracks and so on) in long-time engine tests to the design of qualification phase T/P. In the qualification phase, the hydraulic characteristics and strength in the engine operating range were examined at the LH2 T/P component test, and its endurance confirmed at the engine tests. The LH2 turbopump component test was held at NASDA Kakuda and the engine test at Tashiro and Tanegashima. This paper describes the development status of LH2 T/P, containing the design description and the content of some troubles and its counterplans.

  5. L'astronomie dans le monde

    NASA Astrophysics Data System (ADS)

    Manfroid, J.

    2007-09-01

    Anions interstellaires; S Orionis; Altaîr; Courants stellaires; Etoiles jeunes; 2MASSW J1207334-393254; Alpha Andromède; Etoiles à neutrons (1); LH54-425; AGNs invisibles; Deux supernovae; Les GRBs seon Swift; Peser les trous noirs; Formation de trous noirs; Trou noir; ondes gravitationnelles : Virgo entre dans sa phase d'exploitation scientifique; Amas de galaxies actifs; Amas de galaxies; Galaxies actives d'amas; L'univers statique: le retour; Macho; Exoplanètes; Exoplanètes habitables?; Exoplanètes habitables? (suite); Une année d'un an; Une année de 31 heures; Valse des Jupiters; Disque de HD 15115; Impact majeur; Planètes isolées; Super-Jupiter; Impact et mini-extinction; L'effet Pioneer; Toungouska; Spéléo martienne; Autres lunes dactives; Encelade; Hypérion; Pluton dépassé; Satellites d'Uranus; Titan

  6. Transmaxillary Sinus Approach for Le Fort II Osteotomy

    PubMed Central

    Fukawa, Toshihiko; Hirakawa, Takashi; Satake, Toshihiko; Maegawa, Jiro

    2016-01-01

    Summary: The Le Fort II osteotomy is a relatively rare operation. The posterior wall osteotomy of the maxillary sinus (MS) is often difficult for Le Fort III. We developed the transmaxillary sinus approach (TSA) for the Le Fort II osteotomy that cuts the posterior wall of the MS directly. This report illustrates this easy-to-use procedure for the Le Fort II osteotomy in syndromic craniosynostosis. This procedure was performed in an 18-year-old patient with Apert syndrome and a 15-year-old patient with Pfeiffer syndrome. The thin anterior walls of the MS were removed through an intraoral approach to look inside the MS. Then, the posterior walls were cut by chisel under direct vision using light. The other osteotomy was performed as usual. Distraction osteogenesis with internal and external devices was used in combination. The advantages of TSA are the direct posterior wall osteotomy of the MS with no down fracture and minimal invasiveness to the mucosa of the MS under direct vision. However, the disadvantage is that TSA becomes a blind procedure in a case with no MS or hypoplasia. We developed the TSA for the Le Fort II osteotomy, which could provide direct observation and perform the posterior wall osteotomy of the MS without down fracture. We believe that TSA is an effective surgical procedure for the Le Fort II osteotomy. PMID:27014548

  7. Transmaxillary Sinus Approach for Le Fort II Osteotomy.

    PubMed

    Kobayashi, Shinji; Fukawa, Toshihiko; Hirakawa, Takashi; Satake, Toshihiko; Maegawa, Jiro

    2016-02-01

    The Le Fort II osteotomy is a relatively rare operation. The posterior wall osteotomy of the maxillary sinus (MS) is often difficult for Le Fort III. We developed the transmaxillary sinus approach (TSA) for the Le Fort II osteotomy that cuts the posterior wall of the MS directly. This report illustrates this easy-to-use procedure for the Le Fort II osteotomy in syndromic craniosynostosis. This procedure was performed in an 18-year-old patient with Apert syndrome and a 15-year-old patient with Pfeiffer syndrome. The thin anterior walls of the MS were removed through an intraoral approach to look inside the MS. Then, the posterior walls were cut by chisel under direct vision using light. The other osteotomy was performed as usual. Distraction osteogenesis with internal and external devices was used in combination. The advantages of TSA are the direct posterior wall osteotomy of the MS with no down fracture and minimal invasiveness to the mucosa of the MS under direct vision. However, the disadvantage is that TSA becomes a blind procedure in a case with no MS or hypoplasia. We developed the TSA for the Le Fort II osteotomy, which could provide direct observation and perform the posterior wall osteotomy of the MS without down fracture. We believe that TSA is an effective surgical procedure for the Le Fort II osteotomy. PMID:27014548

  8. Three-dimensional Nasolabial Morphologic Alterations Following Le Fort I

    PubMed Central

    DeSesa, Christopher R.; Metzler, Philip; Sawh-Martinez, Rajendra

    2016-01-01

    Background: Le Fort I osteotomy imparts significant changes to the nasolabial region. Past studies have relied on 2-dimensional data and have not delineated differences among various Le Fort I subtypes. The purpose of this study is to 3-dimensionally analyze Le Fort I–induced nasal and lip changes comparing advancement alone versus widening alone [surgically assisted maxillary expansion (SAME)] versus advancement and widening. We hypothesize that the combination of maxillary advancement with widening will result in the most profound changes. Methods: A retrospective cohort study was performed. Included Le Fort I patients were grouped as: (1) nonsegmental straight advancement, (2) widening without advancement, and (3) segmental advancement and widening. Pre- and postoperative 3-dimensional photogrammetry (Canfield) were analyzed. Anthropometric landmarks were placed and measured by 2 independent observers. Statistics involved both paired and unpaired t tests (significance = P < 0.05). Results: One hundred eight photogrammetric data sets were analyzed, including 46 single-piece, 26 SAME, and 36 segmental. Significant postoperative nasal changes were observed within each intragroup analysis. The most dramatic changes were seen after segmental Le Fort I with advancement and widening, which included alar base width, alar width, nostril width, and soft triangle angle, all P < 0.05. Conclusions: Le Fort I osteotomy results in significant alteration of the nasolabial morphology. This is the first study to 3-dimensionally analyze nasal changes that occur comparing maxillary advancement alone versus widening alone (SAME) versus advancement with widening. These objective data permit improved patient counseling and surgical planning. PMID:27622116

  9. Lactobacillus equigenerosi Strain Le1 Invades Equine Epithelial Cells

    PubMed Central

    Botha, Marlie; Botes, Marelize; Loos, Ben; Smith, Carine

    2012-01-01

    Lactobacillus equigenerosi strain Le1, a natural inhabitant of the equine gastrointestinal tract, survived pH 3.0 and incubation in the presence of 1.5% (wt/vol) bile salts for at least 2 h. Strain Le1 showed 8% cell surface hydrophobicity, 60% auto-aggregation, and 47% coaggregation with Clostridium difficile C6. Only 1% of the cells adhered to viable buccal epithelial cells and invaded the cells within 20 min after contact. Preincubation of strain Le1 in a buffer containing pronase prevented adhesion to viable epithelial cells. Preincubation in a pepsin buffer delayed invasion from 20 min to 1 h. Strain Le1 did not adhere to nonviable epithelial cells. Administration of L. equigenerosi Le1 (1 × 109 CFU per 50 kg body weight) to healthy horses did not increase white blood cell numbers. Differential white blood cell counts and aspartate aminotransferase levels remained constant. Glucose, lactate, cholesterol, and urea levels remained constant during administration with L. equigenerosi Le1 but decreased during the week after administration. PMID:22504808

  10. Searching the animal psyche with Charles Le Brun.

    PubMed

    Cohen, Sarah R

    2010-07-01

    Around 1670 the French court painter and Academician Charles Le Brun produced a series of drawings featuring naturalistic animal heads, as well as imaginary heads in which he refashioned various nonhuman animal species to make humanoid physiognomies. What were the purpose and significance of these unusual works? I argue that they show Le Brun's interest in what we today would call animal psychology: focusing upon the sensory organs and their connections with the animal's brain, Le Brun studied his animals as conscious protagonists of the natural realm. One source that may have served him in this project was Marin Cureau de La Chambre's De la Connoissance des bestes of 1645, in which the physician argued that animals possess a conscious soul grounded in the senses. However, Le Brun's animal-humans have no clear place in the artist's taxonomy--nor, indeed, in any seventeenth-century understandings of species. It is rather John Locke, at his most skeptical, who offers the best parallel in the realm of natural philosophy to Le Brun's unsettling animal-humans. Probably without meaning to, Le Brun demonstrated through his eerie, boundary-crossing creatures the limits of visual classification. PMID:20853815

  11. Le Point sur la Pharmacologie des Agents Anesthesiques Chez le Brule Grave

    PubMed Central

    Siah, S.; Ababou, K.; Benziane, H.; El Jaoudi; Bensghir, M.; Bakali, H.; El Wali, A.; Ihrai, I.; Drissi, N.K.

    2008-01-01

    Summary La pharmacologie des agents anesthésiques chez le brûlé est variable et imprévisible. Dans les premières 48 h, il y a une hypovolémie avec chute du débit cardiaque et des fuites plasmatiques. Après 48 h, il y a une hypervolémie avec augmentation du débit cardiaque, hypermétabolisme et la clearance des médicaments est augmentée. Parmi les facteurs de déséquilibre, on retrouve les variations des protéines plasmatiques. Deux protéines sont importantes chez le brûlé grave : l'albumine et l'alpha 1- glycoprotéine. Leur taux varie beaucoup au cours de l'évolution de la brûlure. Les agents anesthésiques dont la liaison avec ces deux protéines est prédominante verront leur pharmacocinétique modifiée. L'anesthésiste-réanimateur du service des brûlés va maîtriser ces notions pharmacologiques pour utiliser à bon escient les agents anesthésiques. PMID:21991108

  12. Un exemple de transfert de technologie dans le domaine des polymères conducteurs : le projet ``HYRA"

    NASA Astrophysics Data System (ADS)

    Parneix, J. P.; Miane, J. L.; Colin, T.; Ruffie, G.; Mege, J.

    1998-06-01

    The HYRA project is a response to the restructuration of local companies : these are purveyors of high technology military and spatial especially in the radars business. Furthermore, the development of mobile communications needs devices and materials in the millimeter range (from 20 to 100Ghz). The aim of the HYRA project is the development of materials with specific properties - particularly conducting materials - in the millimeter wave range. The results obtained on thermoplastic/conducting polymer composites are presented. Le projet HYRA répond à des préoccupations régionales liées à des restructurations industrielles : les industries régionales fournissant les marchés militaires et spatiaux disposent de techniques très performantes mais coûteuses, en particulier dans le domaine des radars. Par ailleurs le développement des communications mobiles a besoin de dispositifs et de matériaux dans tout le domaine millimétrique (de 20 à 100 Ghz). Le projet HYRA a pour but le développement de matériaux à propriétés spécifiques - en particulier conducteurs - dans ce domaine de fréquence. Les résultats obtenus sur des composites thermoplastiques/polymères conducteurs sont présentés.

  13. Transitions de phase dans le oxyde de yttrium vanadium

    NASA Astrophysics Data System (ADS)

    Roberge, Benoit

    Dans le mémoire qui suit, les ordres structural, magnétiques et orbital dans le YVO3 sont étudiés avec l'aide de la diffraction des rayons X,de la spectroscopie Raman et de la technique de la cavité résonnante hyperfréquence. L'objectif premier consiste à observer l'évolution de ces ordres en fonction de la température. Le mémoire met ensuite en évidence le couplage entre les différents ordres cohabitants dans le YVO3 . Les mesures effectuées par la diffraction des rayons X permettent de mesurer le caractère polycrystallin des échantillons du YVO 3. Une comparaison de nos mesures avec des mesures de diffraction des rayons X faites sur la poudre de YVO3 indique la faible présence de maclage. Les mesures effectuées avec la technique de résonnance hyperfréquence permettent de suivre l'évolution de la constante diélectrique en fonction de la température. Les changements impliquant l'ordre orbital se manifestent de manière évidente dans la constante diélectrique à 200 K et à 77 K. La transition diélectrique détectée à 77 K est une transition de premier ordre. Un couplage entre les propriétés diélectriques et magnétiques est observable à la température de Néel à 114 K. L'effet d'un champ magnétique fixe sur la température de transition de l'ordre orbital survenant à 77 K est également remarquable. Cela indique un couplage magnétodiélectrique démontrant ainsi le caractère multiferroïque du YVO 3. Finalement, l'observation d'un mécanisme de relaxation pouvant être modélisé par le modèle d'Havriliak-Negami est observé en dessous de 77 K. En utilisant le modèle d'Arrhénius et le modèle d'Havriliak-Negami, on peut caractériser le mécanisme avec son énergie d'activation et son temps de relaxation. Les mesures effectuées en spectroscopie Raman permettent de suivre l'évolution de la structure du YVO3 en fonction de la température. Les deux changements structuraux survenant à 200 K et 77 K sont observés. Le

  14. Programmable lithography engine (ProLE) grid-type supercomputer and its applications

    NASA Astrophysics Data System (ADS)

    Petersen, John S.; Maslow, Mark J.; Gerold, David J.; Greenway, Robert T.

    2003-06-01

    There are many variables that can affect lithographic dependent device yield. Because of this, it is not enough to make optical proximity corrections (OPC) based on the mask type, wavelength, lens, illumination-type and coherence. Resist chemistry and physics along with substrate, exposure, and all post-exposure processing must be considered too. Only a holistic approach to finding imaging solutions will accelerate yield and maximize performance. Since experiments are too costly in both time and money, accomplishing this takes massive amounts of accurate simulation capability. Our solution is to create a workbench that has a set of advanced user applications that utilize best-in-class simulator engines for solving litho-related DFM problems using distributive computing. Our product, ProLE (Programmable Lithography Engine), is an integrated system that combines Petersen Advanced Lithography Inc."s (PAL"s) proprietary applications and cluster management software wrapped around commercial software engines, along with optional commercial hardware and software. It uses the most rigorous lithography simulation engines to solve deep sub-wavelength imaging problems accurately and at speeds that are several orders of magnitude faster than current methods. Specifically, ProLE uses full vector thin-mask aerial image models or when needed, full across source 3D electromagnetic field simulation to make accurate aerial image predictions along with calibrated resist models;. The ProLE workstation from Petersen Advanced Lithography, Inc., is the first commercial product that makes it possible to do these intensive calculations at a fraction of a time previously available thus significantly reducing time to market for advance technology devices. In this work, ProLE is introduced, through model comparison to show why vector imaging and rigorous resist models work better than other less rigorous models, then some applications of that use our distributive computing solution are shown

  15. Lele de métrologie de SOLEIL

    NASA Astrophysics Data System (ADS)

    Idir, M.; Brochet, S.; Delmotte, A.; Lagarde, B.; Mercere, P.; Moreno, T.; Polack, F.; Thomasset, M.

    2006-12-01

    Lele de METROLOGIE de SOLEIL a pour objet de créer sur le synchrotron SOLEIL, une plateforme constituée : - une ligne de lumière utilisant le rayonnement synchrotron (métrologie dite à la longueur d'onde) - d'un laboratoire de métrologie associé (métrologie dite ll classique gg ) Ces deux types de Métrologie sont l'une et l'autre indispensables pour soutenir l'activité de recherche instrumentale en optique X et X-UV. Ce projet de pôle de METROLOGIE ne répondra pas seulement aux besoins des groupes chargés de l'équipement du synchrotron SOLEIL en optiques et détecteurs mais aussi pour préparer, tester et mettre au point les postes expérimentaux, ce qui concerne déjà une large communauté d'utilisateurs. Il sera aussi largement ouvert, dès sa mise en service, à l'ensemble de la communauté scientifique concernée par l'instrumentation X et XUV en Ile de France, en France, voire même en Europe si la demande continue de croître plus vite que l'offre dans ce domaine. Ligne de lumière Métrologie à la longueur d'onde La ligne de lumière sera équipée de plusieurs stations permettant de mesurer, dans la plus grande partie du spectre couvert par le synchrotron, les paramètres photométriques qui caractérisent les éléments optiques, tels que : la réflectivité de surfaces, l'efficacité de diffraction des réseaux, la diffusion des surfaces ou l'efficacité des détecteurs X et X-UV et la calibration absolue. Cette installation pourra servir également à développer des instruments et des diagnostics nécessaires à la caractérisation des faisceaux de rayons X (intensité, taille, degré de cohérence, polarisation etc.) Métrologie Classique La métrologie des surfaces optiques est devenue une nécessité critique pour les laboratoires et les industries qui utilisent les photons X et X-UV (synchrotrons, centres laser, etc. .). En effet, les progrès de calcul et de conception des systèmes optiques pour ces longueurs d'onde (optiques

  16. Expression of blood group antigens H-2, Le(y), and sialylated-Le(a) in human colorectal carcinoma. An immunohistochemical study using double-labeling techniques.

    PubMed Central

    Cooper, H. S.; Malecha, M. J.; Bass, C.; Fagel, P. L.; Steplewski, Z.

    1991-01-01

    In this study, double-labeling immunohistochemistry was used to gain insight into the coexpression or interrelationship between blood group antigens (BGA) that are differentiation antigens in the normal colon, and BGA that are sequential moieties in the same synthetic pathway. Paired-wise Sialylated-Le(a)/Le(y) and H-2/Le(y) was studied. The Sialylated-Le(a) and Le(y) are synthesized from type 1 and type 2 backbones, respectively. In the normal colon, the Le(y) and Sialylated-Le(a) are expressed by cells at the base and surface of the crypt, respectively, representing undifferentiated and differentiated enterocytes. The H-2 is considered oncofetal in nature, and is considered to be the immediate precursor in the synthesis of Le(y). In individual cancers. Sialylated-Lea and Le(y) were detected in different cancer cells within the same malignant glands, separately in different glands, and in different subcellular compartments of the same cell. Both H-2 and Le(y) were coexpressed in the same individual cells in 92% of cancers expressing both these BGA. In 50% of the cancers, the H-2 and Le(y) also were expressed separately in different malignant glands within individual tumors. These findings indicate that, in colorectal cancers, differentiation antigens (Sialylated Le(a) and Le(y)) are expressed by different individual cells within the same malignant gland somewhat, recapitulating the normal colon crypt. Antigens of different backbones occasionally may be expressed in the same cells but within different subcellular compartments. Precursor accumulation is common in cancers, and antigens in the same synthetic pathway are coexpressed in the same cell. The expression of H-2 and Le(y) in different glands (lack of coexpression) may be explained possibly by aberrant synthesis of Le(y) by an alternate pathway. Images Figure 1 PMID:1987759

  17. Trigeminocardiac reflex and haemodynamic changes during Le Fort I osteotomy.

    PubMed

    Kiani, M T; Tajik, G; Ajami, M; Fazli, H; Kharazifard, M J; Mesgarzadeh, A

    2016-05-01

    The Le Fort I osteotomy is performed under general anaesthesia and specific haemodynamic conditions, i.e. hypotensive general anaesthesia. This study assessed the incidence of the trigeminocardiac reflex (TCR) during the different stages of the Le Fort I osteotomy. Forty-seven patients requiring a Le Fort I osteotomy were included. General anaesthesia was induced. In terms of haemodynamic changes, each patient's oxygen saturation (SpO2), mean arterial pressure (MAP), heart rate (HR), and electrocardiogram (ECG) were monitored by SADAAT Monitoring System and recorded during the different stages of osteotomy: before the induction of anaesthesia, before osteotomy cuts, after finishing the right pterygoid plate osteotomy, after finishing the left pterygoid plate osteotomy, and after performing down-fracture of the maxilla. No significant alteration in haemodynamic values was seen at the different stages of Le Fort I osteotomy. One patient showed arrhythmia with non-sinus junction rhythm after sinus bradycardia and two premature atrial contractions in the down-fracture stage, which led to the abrupt cessation of the procedure by the surgeon. This study showed no significant alterations in haemodynamic values during the different stages of Le Fort I osteotomy. Halting the procedure momentarily was sufficient to allow spontaneous normalization of the HR, blood pressure, and dysrhythmia. PMID:26794400

  18. Exploratory depth-of-burst experiments

    SciTech Connect

    Reichenbach, H.; Behrens, K.; Kuhl, A.

    1991-12-12

    This report describes the first small-scale explosion experiments with aerated grout (i.e., YTONG). Apart from data referring to crater depth and volume versus depth of burst (DOB), isobaric DOB curves in the range of 1.5 psi {le} p {le} 15 psi were established. The comparison with previous HOB values shows that the ground range to a given overpressure is considerably reduced with increasing depth of burst. The authors plan to continue the airblast investigations with different types of soil materials.

  19. Leishmania infantum LeIF protein is an ATP-dependent RNA helicase and an eIF4A-like factor that inhibits translation in yeast.

    PubMed

    Barhoumi, Mourad; Tanner, N K; Banroques, Josette; Linder, Patrick; Guizani, Ikram

    2006-11-01

    LeIF, a Leishmania protein similar to the eukaryotic initiation factor eIF4A, which is a prototype of the DEAD box protein family, was originally described as a Th1-type natural adjuvant and as an antigen that induces an IL12-mediated Th1 response in the peripheral blood mononuclear cells of leishmaniasis patients. This study aims to characterize this protein by comparative biochemical and genetic analysis with eIF4A in order to assess its potential as a target for drug development. We show that a His-tagged, recombinant, LeIF protein of Leishmania infantum, which was purified from Escherichia coli, is both an RNA-dependent ATPase and an ATP-dependent RNA helicase in vitro, as described previously for other members of the DEAD box helicase protein family. In vivo experiments show that the LeIF gene cannot complement the deletion of the essential TIF1 and TIF2 genes in the yeast Saccharomyces cerevisiae that encode eIF4A. In contrast, expression of LeIF inhibits yeast growth when endogenous eIF4A is expressed off only one of its two encoding genes. Furthermore, in vitro binding assays show that LeIF interacts with yeast eIF4G. These results show an unproductive interaction of LeIF with translation initiation factors in yeast. Furthermore, the 25 amino terminal residues were shown to enhance the ability of LeIF to interfere with the translation machinery in yeast. PMID:17087726

  20. Le lipome para testiculaire: à propos d'un cas rare

    PubMed Central

    Lasri, Abdelouahed; Lamchahab, Hamza; Lahyani, Mounir; Karmouni, Tarik; Elkhader, Khalid; Koutani, Abdellatif; Andaloussi, Ahmed Ibn Attya

    2015-01-01

    Les tumeurs para testiculaires sont des tumeurs rares et complexes qui ont une symptomatologie insidieuse et pauvre. Les formes bénignes représentent 70%. Le lipome para testiculaire étant le type le plus fréquent. L'examen clinique est peu spécifique. L'examen échographique est la pierre angulaire pour assoir le diagnostic. Le traitement chirurgical s'impose en cas de tumeur symptomatique, l'histologie étant habituellement typique permet la confirmation diagnostique. Le pronostic est bon malgré d’éventuelles récidives. PMID:26175802

  1. Pterygoid Plate Fractures: Not Limited to Le Fort Fractures.

    PubMed

    Garg, Ravi K; Alsheik, Nila H; Afifi, Ahmed M; Gentry, Lindell R

    2015-09-01

    Pterygoid plate fractures are often described in the setting of Le Fort fractures. The goal of this study was to define other craniofacial fracture patterns causing injury to the pterygoid plates. A retrospective review of computed tomography (CT) scans obtained on craniofacial trauma patients over a 5-year period revealed 209 patients with pterygoid plate fractures. Pterygoid plate fractures in 78 patients (37.3%) were unrelated to Le Fort fractures. Common causes included sphenotemporal buttress fractures in 26 patients (33.3%), temporal bone fractures in 18 patients (23.1%), zygomaticomaxillary complex fractures in 17 patients (21.8%), and displaced mandible fractures in 14 patients (17.9%). These findings indicate that approximately one third of pterygoid plate fractures do not result from Le Fort pattern injuries and that the craniofacial surgeon should have a broad differential for causes of pterygoid plate fractures when reviewing trauma imaging. PMID:26147022

  2. Le zona ophtalmique: une dermatose rare chez l'enfant

    PubMed Central

    Zakia, Douhi; Meziane, Marieme; Salim, Gallouj; Zahra, Mernissi Fatima

    2015-01-01

    Le zona est dû a une réactivation du virus varicelle-zona (VZV) qui reste quiescent dans les ganglions sensitifs dorsaux après la varicelle. Le zona de l'enfant est rare et particulièrement la forme ophtalmique, qui peut être responsable de complications oculaires graves nécessitant une prise en charge adéquate et précoce. Il est parfois associé à des douleurs post-zostériennes dont le traitement est difficile. L'aciclovir per os administré dans les 72 heures après l’éruption a prouvé son efficacité dans la prévention des complications oculaires. Nous en rapportant un nouveaux cas chez un garçon immunocompétent de 9 ans, sans notion de varicelle antérieure. PMID:26955408

  3. Le Francais Courant, I (Contemporary French, I).

    ERIC Educational Resources Information Center

    Dade County Public Schools, Miami, FL.

    Performance objectives focusing on the development of introductory skills in comprehension, speaking, reading, and writing are presented in this text of instructional materials. Lessons center about the use of short dialogues based on everyday, teenage experiences. Special emphasis is placed on vocabulary expansion, present tense of selected…

  4. Le Francais Courant (Contemporary French), Part II.

    ERIC Educational Resources Information Center

    Dade County Public Schools, Miami, FL.

    This course has been developed basically within the limits of Units 4-6 of "A-LM French: Level 1", second edition. The primary objectives are to develop French vocabulary relative to the family, home, transportation, and foods by continuing to work with short dialogues based on everyday, teenage experiences. While reviewing previously studied…

  5. Constraining PCP Violating Varying Alpha Theory through Laboratory Experiments

    SciTech Connect

    Maity, Debaprasad; Chen, Pisin; /NCTS, Taipei /Taiwan, Natl. Taiwan U. /KIPAC, Menlo Park /SLAC

    2012-06-06

    In this report we have studied the implication of a parity and charge-parity (PCP) violating interaction in varying alpha theory. Due to this interaction, the state of photon polarization can change when it passes through a strong background magnetic field. We have calculated the optical rotation and ellipticity of the plane of polarization of an electromagnetic wave and tested our results against different laboratory experiments. Our model contains a PCP violating parameter {beta} and a scale of alpha variation {omega}. By analyzing the laboratory experimental data, we found the most stringent constraints on our model parameters to be 1 {le} {omega} {le} 10{sup 13} GeV{sup 2} and -0.5 {le} {beta} {le} 0.5. We also found that with the existing experimental input parameters it is very difficult to detect the ellipticity in the near future.

  6. Ursula LeGuin's Magical World of Earthsea.

    ERIC Educational Resources Information Center

    Griffin, Jan M.

    1996-01-01

    Discusses how Ursula LeGuin's Earthsea Trilogy reflects her belief in Taoist philosophy as well as her skill in telling stories of magic and adventure. Notes that the three books can be described as coming-of-age novels in which three separate individuals struggle to become mature, responsible, whole adults. (RS)

  7. Le Dernier Cartoucherie: Refuge and the Performance of Care

    ERIC Educational Resources Information Center

    Fisek, Emine

    2008-01-01

    In 2003, the Paris-based theatre company Theatre du Soleil launched "Le Dernier Caravanserail: Odyssees", a collaborative creation based on stories that company members had collected from refugees at the Sangatte refugee camp outside Calais, among other locations. Scenes of moral reasoning dotted the six-hour spectacle, calling to mind the…

  8. Restorative Justice Scripts in Ursula K. Le Guin's "Voices"

    ERIC Educational Resources Information Center

    Oziewicz, Marek C.

    2011-01-01

    This essay examines restorative justice scripting in "Voices", the second volume of Ursula K. Le Guin's "Annals of the Western Shore." Narrated by a rape-child, "Voices" is the story of an occupied city-state and of how the conquered and the conquerors negotiate a formula for peaceful coexistence. They are able to do so by enacting a restorative…

  9. Decolonizing the Choctaws: Teaching LeAnne Howe's "Shell Shaker"

    ERIC Educational Resources Information Center

    Hollrah, Patrice

    2004-01-01

    "Shell Shaker" (2001) by LeAnne Howe (Choctaw) is a novel that gives students an opportunity to learn that the history and culture of the Choctaw Nation of Oklahoma are alive today. Winner of the Before Columbus Foundation American Book Award in 2002, the novel deals with two parallel stories that converge in the present, one about the eighteenth…

  10. LHC, le Big Bang en éprouvette

    ScienceCinema

    None

    2011-10-06

    Notre compréhension de l?Univers est en train de changer? Bar des Sciences - Tout public Débat modéré par Marie-Odile Montchicourt, journaliste de France Info. Evenement en vidéoconférence entre le Globe de la science et de l?innovation, le bar le Baloard de Montpellier et la Maison des Métallos à Paris. Intervenants au CERN : Philippe Charpentier et Daniel Froideveaux, physiciens au CERN. Intervenants à Paris : Vincent Bontemps, philosophe et chercheur au CEA ; Jacques Arnould, philosophe, historien des sciences et théologien, Jean-Jacques Beineix, réalisateur, producteur, scénariste de cinéma. Intervenants à Montpellier (LPTA) : André Neveu, physicien théoricien et directeur de recherche au CNRS ; Gilbert Moultaka, physicien théoricien et chargé de recherche au CNRS. Partenariat : CERN, CEA, IN2P3, Université MPL2 (LPTA) Dans le cadre de la Fête de la science 2008

  11. MoLeNET Mobile Learning Conference 2009: Research Papers

    ERIC Educational Resources Information Center

    Guy Parker, Ed.

    2010-01-01

    The Mobile Learning Network (MoLeNET) is a unique collaborative approach to encouraging, supporting, expanding and promoting mobile learning, primarily in English post-14 education and training, via supported shared cost mobile learning projects. Collaboration at national level involves participating institutions and the Learning and Skills…

  12. Le syndrome d'embolie graisseuse post traumatique

    PubMed Central

    Berdai, Adnane Mohamed; Shimi, Abdelkarim; Khatouf, Mohammed

    2014-01-01

    Le syndrome d'embolie graisseuse est une complication grave des fractures des os longs, il est la conséquence de la dissémination des particules graisseuses dans la microcirculation. L'objectif de ce travail est de déterminer le profil épidémiologique, la présentation clinique et paraclinique de ce syndrome et sa prise en charge thérapeutique. Notre étude porte sur 11 cas de syndrome d'embolie graisseuse colligés au service de réanimation A1 au centre hospitalier universitaire Hassan II de Fès, de Janvier 2009 à Juin 2012. Le diagnostic positif est basé sur les critères de Gurd. Les cas collectés se caractérisent par la prédominance du sexe masculin, d'un âge inférieur à 40 ans, présentant une fracture fémorale. Ce syndrome survient souvent dans les 72 heures après le traumatisme. La présentation clinique est dominée par l'hypoxémie et les troubles de conscience. Sur le plan biologique: l'anémie et la thrombopénie sont les manifestations les plus fréquentes. La prise en charge est symptomatique, 63% des patients ont nécessité l'intubation et la ventilation. L’évolution n'est pas toujours bénigne. Nos résultats confirme le polymorphisme de la présentation clinique et paraclinique du syndrome d'embolie graisseuse. Le diagnostic de ce syndrome se base sur des critères cliniques, mais reste essentiellement un diagnostic d’élimination. La prise en charge est symptomatique. La prévention de ce syndrome est essentielle et se base sur une fixation précoce des fractures des os longs. PMID:25452829

  13. Connecting Instructional and Cognitive Aspects of an LE: A Study of the Global Seminar Project

    ERIC Educational Resources Information Center

    Savelyeva, Tamara

    2012-01-01

    My research problem is based on the lack of unifying conceptual cohesion between the discourses concerning cognitive and instructional aspects of learning environments (LE). I contrast that lack with practical developments of LE studies connected at the level of practical implementation and evaluation. Next, I briefly review the LE boundaries,…

  14. Le traitement familial des enfants et des adolescents anorexiques : Des lignes directrices pour le médecin communautaire

    PubMed Central

    Findlay, S; Pinzon, J; Taddeo, D; Katzman, DK

    2010-01-01

    L’anorexie mentale (AM) est une maladie grave qui met la vie en danger et qui fait généralement son apparition pendant l’adolescence. Les données probantes au sujet du traitement optimal de l’AM chez les enfants et les adolescents sont en croissance, mais il reste beaucoup à apprendre. Même si les démarches thérapeutiques actuelles varient au Canada et ailleurs, les données jusqu’à présent indiquent que le traitement familial (TF) est le plus efficace pour les enfants et les adolescents anorexiques. Un élément essentiel du modèle de TF, c’est que les parents sont investis de la responsabilité de rétablir la santé physique de leur enfant et de s’assurer de la reprise complète de son poids. Le médecin qui comprend les principes fondamentaux et la philosophie du TF peut mettre en place les éléments de cette intervention fondée sur des faits probants auprès des jeunes patients anorexiques et de leur famille.

  15. LeProT1, a transporter for proline, glycine betaine, and gamma-amino butyric acid in tomato pollen.

    PubMed Central

    Schwacke, R; Grallath, S; Breitkreuz, K E; Stransky, E; Stransky, H; Frommer, W B; Rentsch, D

    1999-01-01

    During maturation, pollen undergoes a period of dehydration accompanied by the accumulation of compatible solutes. Solute import across the pollen plasma membrane, which occurs via proteinaceous transporters, is required to support pollen development and also for subsequent germination and pollen tube growth. Analysis of the free amino acid composition of various tissues in tomato revealed that the proline content in flowers was 60 times higher than in any other organ analyzed. Within the floral organs, proline was confined predominantly to pollen, where it represented >70% of total free amino acids. Uptake experiments demonstrated that mature as well as germinated pollen rapidly take up proline. To identify proline transporters in tomato pollen, we isolated genes homologous to Arabidopsis proline transporters. LeProT1 was specifically expressed both in mature and germinating pollen, as demonstrated by RNA in situ hybridization. Expression in a yeast mutant demonstrated that LeProT1 transports proline and gamma-amino butyric acid with low affinity and glycine betaine with high affinity. Direct uptake and competition studies demonstrate that LeProT1 constitutes a general transporter for compatible solutes. PMID:10072398

  16. On violations of Le Chatelier's principle for a temperature change in small systems observed for short times

    NASA Astrophysics Data System (ADS)

    Dasmeh, Pouria; Searles, Debra J.; Ajloo, Davood; Evans, Denis J.; Williams, Stephen R.

    2009-12-01

    Le Chatelier's principle states that when a system is disturbed, it will shift its equilibrium to counteract the disturbance. However for a chemical reaction in a small, confined system, the probability of observing it proceed in the opposite direction to that predicted by Le Chatelier's principle, can be significant. This work gives a molecular level proof of Le Chatelier's principle for the case of a temperature change. Moreover, a new, exact mathematical expression is derived that is valid for arbitrary system sizes and gives the relative probability that a single experiment will proceed in the endothermic or exothermic direction, in terms of a microscopic phase function. We show that the average of the time integral of this function is the maximum possible value of the purely irreversible entropy production for the thermal relaxation process. Our result is tested against computer simulations of the unfolding of a polypeptide. We prove that any equilibrium reaction mixture on average responds to a temperature increase by shifting its point of equilibrium in the endothermic direction.

  17. The scope of the LeChatelier Principle

    NASA Astrophysics Data System (ADS)

    George M., Lady; Quirk, James P.

    2007-07-01

    LeChatelier [Comptes Rendus 99 (1884) 786; Ann. Mines 13 (2) (1888) 157] showed that a physical system's “adjustment” to a disturbance to its equilibrium tended to be smaller as constraints were added to the adjustment process. Samuelson [Foundations of Economic Analysis, Harvard University Press, Cambridge, 1947] applied this result to economics in the context of the comparative statics of the actions of individual agents characterized as the solutions to optimization problems; and later (1960), extended the application of the Principle to a stable, multi-market equilibrium and the case of all commodities gross substitutes [e.g., L. Metzler, Stability of multiple markets: the hicks conditions. Econometrica 13 (1945) 277-292]. Refinements and alternative routes of derivation have appeared in the literature since then, e.g., Silberberg [The LeChatelier Principle as a corollary to a generalized envelope theorem, J. Econ. Theory 3 (1971) 146-155; A revision of comparative statics methodology in economics, or, how to do comparative statics on the back of an envelope, J. Econ. Theory 7 (1974) 159-172], Milgrom and Roberts [The LeChatelier Principle, Am. Econ. Rev. 86 (1996) 173-179], W. Suen, E. Silberberg, P. Tseng [The LeChatelier Principle: the long and the short of it, Econ. Theory 16 (2000) 471-476], and Chavas [A global analysis of constrained behavior: the LeChatelier Principle ‘in the large’, South. Econ. J. 72 (3) (2006) 627-644]. In this paper, we expand the scope of the Principle in various ways keyed to Samuelson's proposed means of testing comparative statics results (optimization, stability, and qualitative analysis). In the optimization framework, we show that the converse LeChatelier Principle also can be found in constrained optimization problems and for not initially “conjugate” sensitivities. We then show how the Principle and its converse can be found through the qualitative analysis of any linear system. In these terms, the Principle and

  18. Convergent syntheses of LeX analogues

    PubMed Central

    Wang, An; Hendel, Jenifer

    2010-01-01

    Summary The synthesis of three Lex derivatives from one common protected trisaccharide is reported. These analogues will be used respectively for competitive binding experiments, conjugation to carrier proteins and immobilization on gold. An N-acetylglucosamine monosaccharide acceptor was first glycosylated at O-4 with a galactosyl imidate. This coupling was performed at 40 °C under excess of BF3·OEt2 activation and proceeded best if the acceptor carried a 6-chlorohexyl rather than a 6-azidohexyl aglycon. The 6-chlorohexyl disaccharide was then converted to an acceptor and submitted to fucosylation yielding the corresponding protected 6-chlorohexyl Lex trisaccharide. This protected trisaccharide was used as a precursor to the 6-azidohexyl, 6-acetylthiohexyl and 6-benzylthiohexyl trisaccharide analogues which were obtained in excellent yields (70–95%). In turn, we describe the deprotection of these intermediates in one single step using dissolving metal conditions. Under these conditions, the 6-chlorohexyl and 6-azidohexyl intermediates led respectively to the n-hexyl and 6-aminohexyl trisaccharide targets. Unexpectedly, the 6-acetylthiohexyl analogue underwent desulfurization and gave the n-hexyl glycoside product, whereas the 6-benzylthiohexyl analogue gave the desired disulfide trisaccharide dimer. This study constitutes a particularly efficient and convergent preparation of these three Lex analogues. PMID:20485599

  19. Ultrafast intramolecular charge transfer with N-(4-cyanophenyl)carbazole. Evidence for a LE precursor and dual LE + ICT fluorescence.

    PubMed

    Galievsky, Victor A; Druzhinin, Sergey I; Demeter, Attila; Mayer, Peter; Kovalenko, Sergey A; Senyushkina, Tamara A; Zachariasse, Klaas A

    2010-12-01

    The photophysics of N-(4-cyanophenyl)carbazole (NP4CN) was investigated by using absorption and fluorescence spectra, picosecond fluorescence decays, and femtosecond transient absorption. In the nonpolar n-hexane as well as in the polar solvent acetonitrile (MeCN), a locally excited (LE) state is detected, as a precursor for the intramolecular charge transfer (ICT) state. A LE → ICT reaction time τ(2) at 22 °C of 0.95 ps in ethyl cyanide (EtCN) and 0.32 ps in MeCN is determined from the decay of the LE excited state absorption (ESA) maximum around 620 nm. In the ESA spectrum of NP4CN in n-hexane at a pump-probe delay time of 100 ps, an important contribution of the LE band remains alongside the ICT band, in contrast to what is observed in EtCN and MeCN. This shows that a LE ⇄ ICT equilibrium is established in this solvent and the ICT reaction time of 0.5 ps is equal to the reciprocal of the sum of the forward and backward ICT rate constants 1/(k(a) + k(d)). In the photostationary S(0) → S(n) absorption spectrum of NP4CN in n-hexane and MeCN, an additional CT absorption band appears, absent in the sum of the spectra of its electron donor (D) and acceptor (A) subgroups carbazole and benzonitrile. This CT band is located at an energy of ∼4000 cm(-1) lower than for N-phenylcarbazole (NPC), due to the larger electron affinity of the benzonitrile moiety of NP4CN than the phenyl subunit of NPC. The fluorescence spectrum of NP4CN in n-hexane at 25 °C mainly consists of a structured LE emission, with a small ICT admixture, indicating that a LE → ICT reaction just starts to occur under these conditions. In di-n-pentyl ether (DPeE) and di-n-butyl ether (DBE), a LE emission is found upon cooling at the high-energy edge of the ICT fluorescence band, caused by the onset of dielectric solvent relaxation. This is not the case in more polar solvents, such as diethyl ether (DEE) and MeCN, in which a structureless ICT emission band fully overlaps the strongly quenched LE

  20. LeCroy MQT300A - charge to time converter

    SciTech Connect

    Yamrone, B.; Roberts, K.; Kelly, J.

    1997-12-31

    The MQT300A was developed to offer high resolution (12 bit) and wide dynamic range (18 bit) with reasonable cost, high density and fast conversion time (< 10 {mu}s). The reduced conversion time has allowed its first users the option to choose whether or not to develop a fast clear strategy as part of their trigger system. It can also be used for chamber-mounted applications allowing compact digital data cabling to the remote TDC. The MQT300A is a custom development produced in collaboration with the BELLE collaboration at KEK and the CLEO group at Cornell. In this collaboration Cornell and KEK were partners with LeCroy in both the specification and evaluation of the first prototypes. LeCroy has been responsible for the remainder of the project. The MQT300A is available in LeCroy modules and also as a separate monolithic. The MQT300A was designed to take advantage of the latest generation of multi-hit TDCs, for example the LeCroy 1877S FASTBUS ADC. The 1877S was specifically optimized to improve conversion time and to intelligently minimize the data record size for the MQT300A application. A prototype part was designed and fabricated using a custom bipolar process. Though fully functional it did not meet several important performance specifications. A reiteration with significant redesign of two sections resulted in a part that meets all specifications. The unique encoding algorithm used to provide auto-ranging has had a U.S. patent allowed. The part is now commercially available in production volumes.

  1. Airborne pollen and spores of León (Spain)

    NASA Astrophysics Data System (ADS)

    Fernández-González, Delia; Suarez-Cervera, María; Díaz-González, Tomás; Valencia-Barrera, Rosa María

    1993-06-01

    A qualitative and quantitative analysis of airborne pollen and spores was carried out over 2 years (from September 1987 to August 1989) in the city of León. Slides were prepared daily using a volumetric pollen trap, which was placed on the Faculty of Veterinary Science building (University of León) 12m above ground-level. Fifty-one pollen types were observed; the most important of these were: Cupressaceae during the winter, Pinus and Quercus in spring, and Poaceae, Leguminosae and Chenopodiaceae in the summer. The results also showed the existence of a rich mould spore assemblage in the atmosphere. The group of Amerospores ( Penicillium, Aspergillus and Cladosporium) as well as Dictyospores ( Alternaria) were the most abundant; Puccinia was common in the air in August. Fluctuations in the total pollen and spores m3 of air were compared with meteorological parameters (temperature, relative humidity and rainfall). From the daily sampling of the atmosphere of León, considering the maximum and minimum temperature and duration of rainfall, the start of the pollen grain season was observed generally to coincide with a rise in temperature in the absence of rain.

  2. Le sumatriptan intranasal pour la migraine chez les enfants

    PubMed Central

    Goldman, Ran D.; Meckler, Garth D.

    2015-01-01

    Résumé Question Je vois de plus en plus d’enfants et d’adolescents qui souffrent de céphalées pouvant se classer dans la catégorie des migraines. J’ai fait des lectures sur le sumatriptan par voie intranasale comme thérapie abortive. Est-ce un traitement efficace? Réponse La migraine aiguë chez les enfants et les adolescents est fréquente et difficile à traiter. Le sumatriptan intranasal est une option sûre et généralement efficace pour les enfants et les adolescents. La dose actuellement recommandée est de 20 mg pour les enfants qui pèsent plus de 40 kg et de 10 mg pour ceux dont le poids se situe entre 20 et 39 kg. Il faudrait faire des études de plus grande envergure pour contrecarrer les limitations des échantillons de petite taille et mieux comprendre la faible concentration plasmique et les effets placebo observés dans les études jusqu’à présent.

  3. Le kyste hydatique du cordon spermatique: une localisation exceptionnelle

    PubMed Central

    Hamdane, Mohamed Moncef; Bougrine, Fethi; Msakni, Issam; Dhaoui-Ghozzi, Amen; Bouziani, Ammar

    2011-01-01

    L’ hydatidose est une anthropo-zoonose due au développement chez l'homme de la forme larvaire du taenia Echinococcus granulosis. La plupart des kystes hydatiques se localisent dans le foie et les poumons. Le kyste hydatique du cordon spermatique est extrêmement rare avec seulement 4 cas rapportés dans la littérature. Les auteurs rapportent dans cet article un nouveau cas d'hydatidose du cordon spermatique. Il s'agissait d'un homme de 40 ans qui consultait pour des douleurs scrotales évoluant depuis huit mois. L'examen clinique a mis en évidence une tuméfaction mobile, inguino-scrotale, droite. L’échographie testiculaire a objectivé une hernie inguinale droite associée à deux kystes épididymaires bilatéraux. Le patient a été opéré pour cure de son hernie avec découverte en per-opératoire d'un kyste du cordon spermatique qui a été réséqué. L'examen anatomopathologique a conclu à une hydatidose du cordon spermatique. PMID:22384304

  4. Le tetanos chez le grand enfant dans un hôpital pédiatrique à Yaoundé, Cameroun

    PubMed Central

    Ntoto Njiki Kinkela, Mina; Nguefack, Félicitée; Mbassi Awa, Hubert; Chelo, David; Enyama, Dominique; Mbollo Kobela, Marie; Koki Ndombo, Paul Olivier

    2012-01-01

    Le tétanos est évitable par la vaccination, mais peut survenir en cas d'une immunisation incomplète. Nous avons mené une étude sur les dossiers médicaux des enfants admis pour tétanos entre 2008-2009 au Centre Mère et Enfant de la Fondation Chantal BIYA à Yaoundé. Le but était d'analyser les circonstances de survenue et les manifestations cliniques du tétanos chez le grand enfant, afin de proposer des stratégies de prévention adaptées au contexte camerounais. Le statut vaccinal était inconnu chez un patient, les autres (80%) n'avaient pas reçu de rappel vaccinal. Les portes d'entrée étaient les plaies aux membres, l'une était secondaire à une injection médicamenteuse. Tous ont présenté le tétanos généralisé. Le décès était survenu chez un patient. Le tétanos n'est pas rare chez le grand enfant au Cameroun. Il se dégage ainsi la problématique des rappels vaccinaux. PMID:22514771

  5. Le médicament générique au Maroc: le point de vue du consommateur

    PubMed Central

    Zaoui, Sanaa; Hakkou, Farid; Filali, Houda; Khabal, Youssef; Tazi, Illias; Mahmal, Lahoucine

    2013-01-01

    Introduction Le médicament générique est souvent une origine de préjugés négatifs et de méfiance chez les professionnels de santé et les patients. Ceci pourrait être dû à plusieurs facteurs entre autre le manque des connaissances du patient sur ces médicaments. Le but de notre étude était d’évaluer l'information du consommateur sur les médicaments génériques et apprécier leur utilisation de ces médicaments. Méthodes Il s'agit d'une étude transversale réalisée de Janvier à Mars 2010 auprès de 251 sujets. Un questionnaire comprenant dix questions fermées a été utilisé. Les questions concernaient l’évaluation des connaissances sur les médicaments génériques, les sources d'information, le degré de confiance et d'information des patients sur ces médicaments. Une analyse descriptive simple des différentes variables a été réalisée. Résultats Dans notre étude, 126 sujets (50,2%) ont répondu connaître les médicaments génériques. Parmi eux, 52,3% les utilisaient et 67,4% estimaient qu'ils étaient insuffisamment informés sur ces médicaments. Les cadres supérieurs et les étudiants ont représenté la catégorie qui utilisait le plus les médicaments génériques (respectivement dans 40,9% et 25,7%) et qui était la mieux informée (respectivement dans 61,9% et 23,81%). Le faible coût a été la principale motivation d'utilisation du médicament générique (93,9%). Les médias ont représenté la première source d'information (59,5%). Après sensibilisation, 88,8% des sujets qui ne connaissaient pas le médicament générique ont été favorable à son utilisation. Conclusion Une promotion efficace par une politique d'information soutenue auprès des consommateurs et par des mesures incitatrices à la prescription et à la délivrance du générique par les médecins et les pharmaciens, pourront améliorer l'utilisation de ces médicaments dans notre pays. PMID:24009794

  6. Free-living Acanthamoeba and Naegleria spp. amebae in water sources of León, Nicaragua.

    PubMed

    Leiva, Byron; Clasdotter, Emma; Linder, Ewert; Winiecka-Krusnell, Jadwiga

    2008-06-01

    Free-living amebae (FLA) are known to occur worldwide in water-related biotopes, but only limited information is available on these organisms in developing countries and so far no information on their presence is available from Nicaragua. The aims of this study were to evaluate the prevalence of potentially pathogenic Acanthamoeba spp. and Naegleria spp. in different water sources to which the population of Le6n municipality is exposed. Since pathogenic amebae are thermotolerant, we were especially interested in the occurrence of FLA in geothermal areas. Water samples were collected from Le6n area in Nicaragua: 88 samples were from rivers and springs, 111 from wells, 74 from water taps and 21 from water tanks in urban and suburban Le6n and from three nearby geothermal areas of San Jacinto, Posoltega and Tipitapa. Amebae were identified using morphological and physiological criteria, immunohistochemical staining procedures and molecular methods. Indirect immunofluorescent test was performed on cysts and trophozoites fixed on microscopical slides and incubated for 30 min at room temperature in separate experiments with the following antibodies: rabbit-anti N fowleri/N lovanensis (Nf-Pab), mouse monoclonal antibody anti N. fowleri (Nf-5D12u), rabbit antibodies against Acanthamoeba spp. And fluorescent in situ hybridization (FISH) was performed using 18S rRNA-targeted fluorescent oligonucleotide probes. Probes: GSP for the detection of Acanthamoeba and NAEG1088 for the detection of Naegleria. Free-living amebae were recovered from approximately 43 % of the samples. Acanthamoeba spp was found in 21% of samples from León municipality and in 2% of samples from geothermal areas. Amoeboflagellates were found in 10 % of samples from Le6n and in 19% in geothermal areas. Fifty three percent of tested wells in the geothermal area contained thermotolerant amoeboflagellates. Naegleria spp. was identified in 24 out of 39 (61.5 %) of isolated amoeboflagellates. Twelve of them were

  7. La prévention des infections par le virus respiratoire syncytial

    PubMed Central

    Robinson, JL

    2011-01-01

    RÉSUMÉ L’infection par le virus respiratoire syncytial (VRS) est la principale cause d’infections des voies respiratoires inférieures chez les jeunes enfants. Le palivizumab, un anticorps monoclonal anti-VRS, réduit le taux d’hospitalisation des enfants à haut risque mais est très coûteux. Le présent document de principes remplace les trois précédents documents de principes de la Société canadienne de pédiatrie sur le sujet et est mis à jour principalement pour traiter des récentes modifications aux lignes directrices de l’American Academy of Pediatrics dans le contexte canadien. Il contient une analyse des publications ainsi que des recommandations au sujet de l’utilisation du palivizumab chez les enfants à haut risque

  8. Le consentement libre et éclairé aux soins en psychiatrie

    PubMed Central

    Neilson, Grainne; Chaimowitz, Gary

    2015-01-01

    Résumé Le patient a le droit d’être informé sur les soins de santé qui lui sont proposés et de participer activement à la prise de décisions relativement à ces soins. Le respect de la dignité et de l’autonomie de la personne passe par le respect de son droit de prendre des décisions à propos de ses soins psychiatriques, notamment de refuser un traitement, pour autant qu’elle soit apte à prendre des décisions. Il importe que le psychiatre connaisse les fondements éthiques du consentement libre et éclairé et les exigences prévues par le droit en cette matière, y compris la jurisprudence. Le consentement n’est pas immuable, pouvant changer avec le temps, au fil de l’évolution des conditions et des circonstances. Par conséquent, le consentement doit être un processus continu.

  9. Le gingembre contre la nausée et les vomissements de la grossesse

    PubMed Central

    Lindblad, Adrienne J.; Koppula, Sudha

    2016-01-01

    Question clinique Le gingembre peut-il traiter la nausée et les vomissements de la grossesse? Résultats Durant le premier trimestre, le gingembre soulagerait la nausée et les vomissements de quelque 4 points sur une échelle de 40 points, ou éliminerait les vomissements chez 1 femme sur 3 au jour 6. L’étude la plus vaste ne laisse croire à aucune hausse des malformations congénitales ou de la mortinatalité, mais les études de moins grande envergure laissent croire le contraire.

  10. 4. Historic American Buildings Survey, Arthur W. LeBoeuf, Photographer, 1937 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Historic American Buildings Survey, Arthur W. LeBoeuf, Photographer, 1937 DETAIL OF WINDOW BREAKING INTO PEDIMENT. - First Congregational Church, 301 Benefit Street, Providence, Providence County, RI

  11. The JPL 'long ephemeris', DE102/LE51

    NASA Technical Reports Server (NTRS)

    Standish, E. M., Jr.

    1983-01-01

    A number of applications exist in astronomical research for planetary and lunar ephemerides covering an extended length of time. This paper discusses such a set of ephemerides, DE102/LE51, produced at JPL, covering the time 1411 B.C. to 3001 A.D. The ephemerides are dynamically self-consistent, in that the equations of motion were integrated simultaneously. They also represent the most accurately known positions covering such a time span. They have already been used by a number of different users in a variety of different applications.

  12. Snow in Castile-León: trends and variability

    NASA Astrophysics Data System (ADS)

    Merino, A.; Campos, L.; López, L.; García-Ortega, E.; Sánchez, J. L.; Marcos, J. L.; Guerrero-Higueras, A. M.

    2012-04-01

    The location of Castile and León, inside the Iberian Peninsula, in the Northwestern quadrant, determines, in large measure, the climatic conditions of its territory, granting it very characteristic traits, mostly in the mountainous areas. It is important to note that during a large part of the year, the region is under the influence of Jet Stream, and thus, gives way to very diverse dynamic situations, which turn into different and heterogeneous types of weather. So, in many areas of the region, especially in the most elevated areas, these synoptic and mesoscale situations generate snow precipitation. We should point out that snowfall is one of the principal meteorological risks of Castile and León. Thus, on average, in some mountainous areas there are more than 40 events of snowfall registered annually, with the month of January being the month in which the highest frequency of snowfall appears. The social repercussions of this snowfall are represented in the isolation of places, essentially mountainous, highways being blocked, increase in traffic accidents, etc. As proof of this, it is this type of episode that receives ample coverage by the media, which has a linear relationship with the social perception of risk. As such, the objective of the current work is to analyze the annual trend of days with snow in the different meteorological stations pertaining to AEMET placed in the Community. The period of study is from 1960-2010. Additionally, we have also evaluated trends in annual days of freezing temperature and annual absolute minimum temperature, with the objective of facilitating a meteorological interpretation of the trends obtained on days with snowfall. Finally, the results show that in the majority of stations, a significant negative trend in days with snowfall and annual days with freezing temperatures, and a positive trend in annual absolute minimum temperatures. However, we observed variability in the different regions in the area of study

  13. Le genre Tunga Jarocki, 1838 (Siphonaptera : Tungidae). I – Taxonomie, phylogénie, écologie, rôle pathogène

    PubMed Central

    Beaucournu, J.-C.; Degeilh, B.; Mergey, T.; Muñoz-Leal, S.; González-Acuña, D.

    2012-01-01

    Pour la première fois, les 12 espèces actuellement décrites dans le genre Tunga sont étudiées sur le plan de la taxonomie et de la répartition. Divers aspects de leur biologie et leur rôle pathogène sont également envisagés, et en particulier leur phylogénie, leur chorologie, leur phénologie, leur sexe-ratio et leurs dermecos. PMID:23193514

  14. Characterization of a new bacteriocin from Lactobacillus plantarum LE5 and LE27 isolated from ensiled corn.

    PubMed

    Amortegui, Jairo; Rodríguez-López, Alexander; Rodríguez, Deicy; Carrascal, Ana K; Alméciga-Díaz, Carlos J; Melendez, Adelina del P; Sánchez, Oscar F

    2014-04-01

    Bacteriocins are low molecular peptides with antimicrobial activity, which are of great interest as food bio-preservatives and for treating diseases caused by pathogenic bacteria. In this study, we present the characterization of bacteriocins produced by Lactobacillus plantarum LE5 and LE27 isolated from ensiled corn. Bacteriocins were purified through ammonium sulfate precipitation and double dialysis by using 12- and 1-kDa membranes. Bacteriocins showed activity against Listeria innocua, Listeria monocytogenes, and Enteroccocus faecalis. Molecular weight was estimated through Tricine-SDS-PAGE and overloading the gel onto Mueller-Hinton agar seeded with L. monocytogenes, showing an inhibition zone between 5 and 10 kDa. NanoLC-MS/MS analysis allowed the identification of UPF0291 protein (UniProtKB/Swiss-Prot Q88VI7), which is also presented in other lactic acid bacteria without assigned function. Ab initio modeling showed it has an α-helix-rich structure and a large positive-charged region. Bacteriocins were stable between 4 and 121 °C and pH 2 and 12, and the activity was inhibited by SDS and proteases. Mode of action assay suggests that the bacteriocin causes of target microorganism. Taken together, these results describe a possible new class IIa bacteriocin produced by L. plantarum, which has a wide stability to physicochemical conditions, and that could be used as an alternative for the control of foodborne diseases. PMID:24532444

  15. MODeLeR: A Virtual Constructivist Learning Environment and Methodology for Object-Oriented Design

    ERIC Educational Resources Information Center

    Coffey, John W.; Koonce, Robert

    2008-01-01

    This article contains a description of the organization and method of use of an active learning environment named MODeLeR, (Multimedia Object Design Learning Resource), a tool designed to facilitate the learning of concepts pertaining to object modeling with the Unified Modeling Language (UML). MODeLeR was created to provide an authentic,…

  16. Use of Mobile Testing System PeLe for Developing Language Skills

    ERIC Educational Resources Information Center

    Titova, Svetlana

    2015-01-01

    One of the objectives of this paper is to investigate the pedagogical impact of both the mobile testing system PeLe (Norway, HiST) and the enquiry-based learning approach on language skills development in the context of mobile-assisted learning. The research aims to work out a methodological framework of PeLe implementation into the language…

  17. CoLeMo: A Collaborative Learning Environment for UML Modelling

    ERIC Educational Resources Information Center

    Chen, Weiqin; Pedersen, Roger Heggernes; Pettersen, Oystein

    2006-01-01

    This paper presents the design, implementation, and evaluation of a distributed collaborative UML modelling environment, CoLeMo. CoLeMo is designed for students studying UML modelling. It can also be used as a platform for collaborative design of software. We conducted formative evaluations and a summative evaluation to improve the environment and…

  18. Mercury methylation and demethylation in highly contaminated sediments from the Deûle River in Northern France using species-specific enriched stable isotopes.

    PubMed

    Ouddane, Baghdad; Monperrus, Mathilde; Kadlecova, Milada; Daye, Mirna; Amouroux, David

    2015-01-01

    The methylation-demethylation processes in sediments of the Deûle River were determined using well-established isotope experiments. For this purpose, species-specific isotopically enriched tracers in the form of inorganic mercury IHg ((199)Hg) and methylmercury MeHg (Me(201)Hg) were used to determine Hg dynamics in the Deûle River. Sediment cores were collected at two sampling locations chosen in the most polluted zone of the Deûle River (Northern France) in proximity of a Zn, Pb, Cu, and Ni smelter called "Metaleurop" that had closed in 2003. Site I was chosen in the vicinity of the historic smelter site and site II upstream of the Deûle River. The incubation was realized directly in the sediment cores during the 24 hour experiment under environmental conditions close to the real natural systems (the same temperature, pH, humidity, light/dark conditions, oxygen levels…). The enriched isotopes were injected by needle into different sections of the core. After incubation, the core was sliced and the concentration of Hg species was determined in each section. The highest methylation potentials were found at sediment depths away from the sediment-water-interface. At site I, the methylation potential varied between 0.02-0.9% and at site II between 0.001-0.2%. The demethylation potentials fluctuated between 0.001-60% at site I and between 4-53% at site II. In both sites, negative net methylation potentials were obtained in several sediment depths, representing a net sink for MeHg. The average net methylation potential in site I demonstrated a negative value of 1919 ng g(-1) day(-1). It seems that in site I the demethylation process predominates methylation. Whereas, in site II, the average net methylation potential was a positive value of 138 ng g(-1) day(-1), demonstrating the dominance of methylation over demethylation. PMID:25421488

  19. An Overview-NASA LeRC Structures Program

    NASA Technical Reports Server (NTRS)

    Zaretsky, Erwin V.

    1997-01-01

    The Structures and Acoustics Division of the NASA Lewis Research Center has its genesis dating back to 1943. It has been an independent Division at Lewis since 1979. Its two primary capabilities are performance and life analysis of static and dynamic systems such as those found in aircraft and spacecraft propulsion systems and experimental verification of these analyses. Research is conducted in-house, through university grants and contracts, and through cooperative programs with industry. Our work directly supports NASA's Advanced Subsonic Technology (AST), Smart Green Engine, Fast Quiet Engine, High-Temperature Materials and Processing (HiTEMP), Hybrid Hyperspeed Propulsion, Rotorcraft, High-Speed Research (HSR), and Aviation Safety Program (AvSP). A general overview is given discussing these programs and other technologies that are being developed at NASA LeRC.

  20. The NASA-LeRC wind turbine sound prediction code

    NASA Technical Reports Server (NTRS)

    Viterna, L. A.

    1981-01-01

    Since regular operation of the DOE/NASA MOD-1 wind turbine began in October 1979 about 10 nearby households have complained of noise from the machine. Development of the NASA-LeRC with turbine sound prediction code began in May 1980 as part of an effort to understand and reduce the noise generated by MOD-1. Tone sound levels predicted with this code are in generally good agreement with measured data taken in the vicinity MOD-1 wind turbine (less than 2 rotor diameters). Comparison in the far field indicates that propagation effects due to terrain and atmospheric conditions may be amplifying the actual sound levels by about 6 dB. Parametric analysis using the code has shown that the predominant contributions to MOD-1 rotor noise are: (1) the velocity deficit in the wake of the support tower; (2) the high rotor speed; and (3) off column operation.

  1. The ERDA/LeRC Photovoltaic Systems Test Facility

    NASA Technical Reports Server (NTRS)

    Forestieri, A. F.

    1978-01-01

    The ERDA/LeRC Photovoltaic Systems Test Facility (STF) provides a vital support function to the overall ERDA National Solar Photovoltaic Program. It allows preliminary investigation and checkout of components, subsystems, and complete photovoltaic systems before installation in actual service. The STF can also be used to determine optimum system configurations and operating modes. A facility description is presented, taking into account the solar cell array, the energy storage equipment, the power conditioning equipment, electric utility distribution network and loads, and instrumentation and data acquisition systems. Safety procedures which have been set up for maintenance and inspection of the solar array are discussed. Attention is also given to a number of investigations regarding the effect of environmental factors on solar cell array operation.

  2. Neptune's Discovery: Le Verrier, Adams, and the Assignment of Credit

    NASA Astrophysics Data System (ADS)

    Sheehan, William

    2011-01-01

    As one of the most significant achievements of 19th century astronomy, the discovery of Neptune has been the subject of a vast literature. A large part of this literature--beginning with the period immediately after the optical discovery in Berlin--has been the obsession with assigning credit to the two men who attempted to calculate the planet's position (and initially this played out against the international rivalry between France and England). Le Verrier and Adams occupied much different positions in the Scientific Establishments of their respective countries; had markedly different personalities; and approached the investigation using different methods. A psychiatrist and historian of astronomy tries to provide some new contexts to the familiar story of the discovery of Neptune, and argues that the personalities of these two men played crucial roles in their approaches to the problem they set themselves and the way others reacted to their stimuli. Adams had features of high-functioning autism, while Le Verrier's domineering, obsessive, orderly personality--though it allowed him to be immensely productive--eventually led to serious difficulties with his peers (and an outright revolt). Though it took extraordinary smarts to calculate the position of Neptune, the discovery required social skills that these men lacked--and thus the process to discovery was more bumbling and adventitious than it might have been. The discovery of Neptune occurred at a moment when astronomy was changing from that of heroic individuals to team collaborations involving multiple experts, and remains an object lesson in the sociological aspects of scientific endeavor.

  3. Dysfonctionnements radio-induits du transport colique chez le rat

    NASA Astrophysics Data System (ADS)

    François, A.; Lebrun, F.; Ksas, B.; Aigueperse, J.; Gourmelon, P.; MacNaughton, W. K.; Griffiths, N. M.

    1998-04-01

    The symptom commonly associated with whole body irradiation is diarrhoea, a still quite obscure phenomenon, which leads to decreased chance of cure of irradiated people. The aim of this study was to provide evidence for dysfunction of intestinal water and electrolyte transport regulation by the enteric nervous system after exposure to ionising radiation. This study shows decreased capacity of enteric nervous system to influence colonic transport 3days after irradiation, correlated to a diminished response to a neurotransmitter: serotonin. Radio-induced diarrhea may result from epithelial structural injury but also from impaired regulatory processes of intestinal transport. L'un des symptômes majeurs d'une irradiation corporelle totale ou abdominale est l'apparition de diarrhées, dont les causes sont encore mal connues, et qui mettent en jeu le pronostique vital de l'individu irradié. Cette étude vise à mettre en évidence l'atteinte de la régulation du transport intestinal d'eau et d'électrolytes par les rayonnements ionisants. On observe une diminution de la capacité du système nerveux entérique à influencer le transport colique 3jours après irradiation, corrélée à une diminution de la réponse épithéliale à un neurotransmetteur : la sérotonine. Les diarrhées radio-induites résulteraient d'une atteinte structurelle de l'épithélium mais également des processus de régulation du transport intestinal.

  4. Overexpression of the tomato pollen receptor kinase LePRK1 rewires pollen tube growth to a blebbling mode

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The tubular growth of a pollen tube cell is crucial for the sexual reproduction of flowering plants. LePRK1 is a pollen-specific and plasma membrane–localized receptor-like kinase from tomato (Solanum lycopersicum). LePRK1 interacts with another receptor, LePRK2, and with KINASE PARTNER PROTEIN (KPP...

  5. Les fluctuations supraconductrices dans le compose praseodyme-cerium-oxyde de cuivre

    NASA Astrophysics Data System (ADS)

    Renaud, Jacques

    Ce travail etudie les fluctuations supraconductrices dans le compose supraconducteur a haute temperature critique dope aux electrons Pr2-xCe xCuO4+delta. La technique utilisee pour sonder ces fluctuations est le transport electrique DC dans le plan ab. Il s'agit, a notre connaissance, de la premiere etude de ce type dans la classe generale des supraconducteurs a haute temperature critique dopes aux electrons et, plus particulierement, dans Pr2-xCe xCuO4+delta. De plus, l'etude est effectuee pour trois regimes de dopage, soit sous-dope x = 0.135, dopage optimal x = 0.15 et surdope x = 0.17. Les echantillons etudies sont des couches minces d'epaisseur plus grande que 100 nm crues par ablation laser. Les mesures electriques DC effectuees dans ce travail sont la resistance en reponse lineaire et les courbes IV en reponse non lineaire en fonction de la temperature. La mise en oeuvre experimentale de ces mesures a necessite une grande attention au filtrage et aux effets de chauffage a haut courant. Nous montrons que, sans cette attention, les donnees experimentales sont toujours erronees dans le regime pertinent pour nos echantillons. Les resultats pour le dopage optimal x = 0.15 sont expliques de facon tres convaincante dans le cadre de fluctuations purement 2D. D'abord, le regime des fluctuations gaussiennes est tres bien decrit par le modele d'Aslamazov-Larkin en deux dimensions. Ensuite, le regime de fluctuations critiques, se trouvant a plus basse temperature que le regime gaussien, est tres bien decrit par la physique 2D de Kosterlitz-Thouless. Dans cette analyse, les deux regimes ont des temperatures critiques coherentes entre elles, ce qui semble confirmer ce scenario 2D. Une analyse des donnees dans le cadre de fluctuations 3D est exploree mais donne des conclusions incoherentes. Les resultats pour les autres dopages sont qualitativement equivalents avec le dopage optimal et permettent donc une explication purement 2D. Par contre, contrairement au dopage optimal

  6. Preparer une firme-reseau dans le transport routier des hydrocarbures le cas de TOTAL Madagascar

    NASA Astrophysics Data System (ADS)

    Razakamanifidiny, Patrick Dany

    2009-12-01

    allowed: 44 managers of 27 participating firms to be trained, certified and sensitized with the network firm practice, 78% of the participating firms to be enthusiastic to pass to the creation of a network firm, and the enterprise pivot TOTAL Madagascar to record a significant diminution of the number of tankers accidents which is passed from 10 (77% of the total number of the tankers accidents) at the beginning of the process in 2003 to 5 (36%) at the end of this process in 2005 and to 3 (27%) in 2007. These tangible and positive results seem to prove the commitment of firms participating in the preparation step of the network firm. In this way, it is appropriate to put the hypothesis according to the experience done within the framework of this study that could be considered as a learning trajectory type of the preparation step which efficiently stimulates the intention of the participating firms to be organized in network. This present case, through these results, strengthens the consideration according to the success of the network firm which depends in the efficiency of the change process related to its preparation. Thus, a main scientific contribution of this present step rely on its originality which is the integration of two change models (implementation and understanding) inside the same research conceptual framework. In a managerial side, the essential of this step may be transferable to the other contexts which look upon the determinant role of the researcher acting as a change co-leader. That shows the utility of this step within the framework of a doctorate applied in administration. Keywords: Subcontracting -- Change -- Network firm -- Hydrocarbon Road Transport -- Small and Medium Enterprises

  7. Approximation auto-coherente a deux particules, pseudogap et supraconductivite dans le modele de Hubbard attractif

    NASA Astrophysics Data System (ADS)

    Allen, Steve

    2000-10-01

    Dans cette these nous presentons une nouvelle methode non perturbative pour le calcul des proprietes d'un systeme de fermions. Notre methode generalise l'approximation auto-coherente a deux particules proposee par Vilk et Tremblay pour le modele de Hubbard repulsif. Notre methode peut s'appliquer a l'etude du comportement pre-critique lorsque la symetrie du parametre d'ordre est suffisamment elevee. Nous appliquons la methode au probleme du pseudogap dans le modele de Hubbard attractif. Nos resultats montrent un excellent accord avec les donnees Monte Carlo pour de petits systemes. Nous observons que le regime ou apparait le pseudogap dans le poids spectral a une particule est un regime classique renormalise caracterise par une frequence caracteristique des fluctuations supraconductrices inferieure a la temperature. Une autre caracteristique est la faible densite de superfluide de cette phase demontrant que nous ne sommes pas en presence de paires preformees. Les resultats obtenus semblent montrer que la haute symetrie du parametre d'ordre et la bidimensionalite du systeme etudie elargissent le domaine de temperature pour lequel le regime pseudogap est observe. Nous argumentons que ce resultat est transposable aux supraconducteurs a haute temperature critique ou le pseudogap apparait a des' temperatures beaucoup plus grandes que la temperature critique. La forte symetrie dans ces systemes pourraient etre reliee a la theorie SO(5) de Zhang. En annexe, nous demontrons un resultat tout recent qui permettrait d'assurer l'auto-coherence entre les proprietes a une et a deux particules par l'ajout d'une dynamique au vertex irreductible. Cet ajout laisse entrevoir la possibilite d'etendre la methode au cas d'une forte interaction.

  8. LE135, a retinoid acid receptor antagonist, produces pain through direct activation of TRP channels

    PubMed Central

    Yin, Shijin; Luo, Jialie; Qian, Aihua; Yu, Weihua; Hu, Hongzhen

    2014-01-01

    Background and PurposeRetinoids, through their activation of retinoic acid receptors (RARs) and retinoid X receptors, regulate diverse cellular processes, and pharmacological intervention in their actions has been successful in the treatment of skin disorders and cancers. Despite the many beneficial effects, administration of retinoids causes irritating side effects with unknown mechanisms. Here, we demonstrate that LE135 [4-(7,8,9,10-tetrahydro-5,7,7,10,10-pentamethyl-5H-benzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid], a selective antagonist of RARβ, is a potent activator of the capsaicin (TRPV1) and wasabi (TRPA1) receptors, two critical pain-initiating cation channels. Experimental ApproachWe performed to investigate the excitatory effects of LE135 on TRPV1 and TRPA1 channels expressed in HEK293T cells and in dorsal root ganglia neurons with calcium imaging and patch-clamp recordings. We also used site-directed mutagenesis of the channels to determine the structural basis of LE135-induced activation of TRPV1 and TRPA1 channels and behavioural testing to examine if pharmacological inhibition and genetic deletion of the channels affected LE135-evoked pain-related behaviours. Key ResultsLE135 activated both the capsaicin receptor (TRPV1) and the allyl isothiocyanate receptor (TRPA1) heterologously expressed in HEK293T cells and endogenously expressed by sensory nociceptors. Mutations disrupting the capsaicin-binding site attenuated LE135 activation of TRPV1 channels and a single mutation (K170R) eliminated TRPA1 activity evoked by LE135. Intraplantar injection of LE135 evoked pain-related behaviours. Both TRPV1 and TRPA1 channels were involved in LE135-elicited pain-related responses, as shown by pharmacological and genetic ablation studies. Conclusions and ImplicationsThis blocker of retinoid acid signalling also exerted non-genomic effects through activating the pain-initiating TRPV1 and TRPA1 channels. PMID:24308840

  9. LeRoy Meisinger, Part I: Biographical Tribute with an Assessment of His Contributions to Meteorology.

    NASA Astrophysics Data System (ADS)

    Lewis, John M.

    1995-01-01

    LeRoy Meisinger was a U.S. Weather Bureau meteorologist and aeronaut who worked vigorously to bring meteorology to the aid of aviation in the post-World War 1 period. He was killed at the age of 29 in a scientific ballooning accident that has been detailed in a companion paper by Lewis and Moore. Meisinger's personality and scientific profile are reconstructed by examination of his oeuvre, which contains research contributions augmented by popular articles in the magazines of the period.Meisinger's personal characteristics were those of a quiet, scholarly man with strong interests in science, music, and art. His experiences as a Signal Corps weather officer during World War 1 inclined him toward a career in meteorology. While stationed at the Fort Omaha Balloon School, he became intrigued with the possibilities of using the tree balloon as a platform for tracking air currents.As a research meteorologist with the U.S. Weather Bureau after the war, Meisinger melded adventurous scientific ballooning with the more painstaking and arduous task of scrutinizing data from the limited upper-air network of kite stations. His principal research contribution was a form of differential analysis that extrapolated surface data to the 1- and 2-km levels by using climatological statistics from the upper-air network. The impressive line of research he pioneered at the bureau came to an immediate and abrupt end with his accidental death in 1924.

  10. Psychology Experiments.

    ERIC Educational Resources Information Center

    McGraw, Ken; Tew, Mark D.; Williams, John E.

    2001-01-01

    A goal of the PsychExperiments project was to reduce the financial burden on psychology departments for hardware/software used in their laboratories. In its third year, the PsychExperiments site now hosts 39 experiments. Over 200 classrooms worldwide have signed up as official site users and there have been nearly 10,000 data sessions conducted.…

  11. Hitting is contagious: experience and action induction.

    PubMed

    Gray, Rob; Beilock, Sian L

    2011-03-01

    In baseball, it is believed that "hitting is contagious," that is, probability of success increases if the previous few batters get a hit. Could this effect be partially explained by action induction--that is, the tendency to perform an action related to one that has just been observed? A simulation was used to investigate the effect of inducing stimuli on batting performance for more-experienced (ME) and less-experienced (LE) baseball players. Three types of inducing stimuli were compared with a no-induction condition: action (a simulated ball traveling from home plate into left, right, or center field), outcome (a ball resting in either left, right, or center field), and verbal (the word "left", "center", or "right"). For both ME and LE players, fewer pitchers were required for a successful hit in the action condition. For ME players, there was a significant relationship between the inducing stimulus direction and hit direction for both the action and outcome prompts. For LE players, the prompt only had a significant effect on batting performance in the action condition, and the magnitude of the effect was significantly smaller than for ME. The effect of the inducing stimulus decreased as the delay (i.e., no. of pitches between prompt and hit) increased, with the effect being eliminated after roughly 4 pitches for ME and 2 pitches for LE. It is proposed that the differences in the magnitude and time course of action induction as a function of experience occurred because ME have more well-developed perceptual-motor representations for directional hitting. PMID:21443380

  12. STIL, a peculiar molecule from styles, specifically dephosphorylates the pollen receptor kinase LePRK2 and stimulates pollen tube growth in vitro

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: LePRK1 and LePRK2 are two pollen receptor kinases localized to the plasma membrane, where they are present in a high molecular weight complex (LePRK complex). LePRK2 is phosphorylated in mature and germinated pollen, but is dephosphorylated when pollen membranes are incubated with tomato...

  13. An Overhead Demonstration of Some Descriptive Chemistry of the Halogens and LeChatelier's Principle.

    ERIC Educational Resources Information Center

    Hansen, Robert C.

    1988-01-01

    Describes a demonstration procedure using controlled reduction potentials to predict observed color changes which are then experimentally verified. Demonstrates the usefulness of this procedure in helping students understand LeChatelier's principle and the solubilit rule "like dissolves like." (CW)

  14. General parameter relations for the Shinnar-Le Roux pulse design algorithm.

    PubMed

    Lee, Kuan J

    2007-06-01

    The magnetization ripple amplitudes from a pulse designed by the Shinnar-Le Roux algorithm are a non-linear function of the Shinnar-Le Roux A and B polynomial ripples. In this paper, the method of Pauly et al. [J. Pauly, P. Le Roux, D. Nishimura, A. Macovski, Parameter relations for the Shinnar-Le Roux selective excitation pulse design algorithm, IEEE Transactions on Medical Imaging 10 (1991) 56-65.] has been extended to derive more general parameter relations. These relations can be used for cases outside the five classes considered by Pauly et al., in particular excitation pulses for flip angles that are not small or 90 degrees. Use of the new relations, together with an iterative procedure to obtain polynomials with the specified ripples from the Parks-McClellan algorithm, are shown to give simulated slice profiles that have the desired ripple amplitudes. PMID:17408999

  15. 1. Historic American Buildings Survey, Arthur W. LeBoeuf, Photographer, 1937 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Historic American Buildings Survey, Arthur W. LeBoeuf, Photographer, 1937 DETAIL OF MANTEL. - John Mason House (Mantel), Weybosset Street (moved to Rhode Island School of Design), Providence, Providence County, RI

  16. 5. Former P&LE tracks (now CSXT) adjacent to trestle towards ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Former P&LE tracks (now CSXT) adjacent to trestle towards west. - Monongahela Connecting Railroad Company, Y Trestle, South side of Monongahela River between Thirty-fourth & Twenty-ninth Streets, Pittsburgh, Allegheny County, PA

  17. A Multistep Equilibria-Redox-Complexation Demonstration to Illustrate Le Chatelier's Principle.

    ERIC Educational Resources Information Center

    Berger, Tomas G.; Mellon, Edward K.

    1996-01-01

    Describes a process that can be used to illustrate a number of chemical principles including Le Chatelier's principle, redox chemistry, equilibria versus steady state situations, and solubility of species. (JRH)

  18. Le volvulus gastrique idiopathique aigu: à propos d'une nouvelle observation

    PubMed Central

    Abdelilah, Mouhsine; Jihad, Anzaoui; Rachid, Bouchentouf

    2013-01-01

    Le volvulus gastrique est une rotation anormale de l'estomac autour de son axe. La forme aiguë constitue une urgence chirurgicale. Le diagnostic est souvent retardé en raison d'une symptomatologie fréquemment non spécifique. Des signes respiratoires tels la dyspnée et le hoquet peuvent révéler cette pathologie. Les auteurs rapportent une nouvelle observation de volvulus gastrique aigu chez un adolescent de 17 ans, diagnostiqué par la tomodensitométrie, et confirmé par une intervention chirurgicale. Le traitement est chirurgical et consiste à détordre et fixer l'estomac pour prévenir la récidive. PMID:23503200

  19. Portevin-Le Chatelier effect and Tsallis nonextensive statistics

    NASA Astrophysics Data System (ADS)

    Iliopoulos, A. C.; Nikolaidis, N. S.; Aifantis, E. C.

    2015-11-01

    In this paper, we estimate Tsallis' entropic index q ≡qstat (stat denotes stationary states) for various stress serration time series of Cu-15%Al alloys corresponding to different deformation temperatures and types (A, B, C) of Portevin-Le Chatelier (PLC) bands. Tsallis statistical analysis is also conducted on experimental data derived from correlation diagrams focusing on PLC type C bands' spatial organization at the surface of various specimens. The results concerning the stress serrations analysis reveal the non-Gaussian (Tsallis q-Gaussian), nonextensive, sub-additive, character of the underlying dynamics of the PLC type-A bands (q > 1) indicating dynamics at the edge of chaos, with global long range correlations and power law scaling. Similarly, for PLC type B bands, a Tsallis q-Gaussian, non-extensive, super-additive, statistical profile was found with q < 1, while for the PLC type C bands, a near Boltzmann-Gibbs (BG) statistical character was verified indicating Gaussian dynamics with short (weak) range correlations. Finally, Tsallis q-index for the spatial data of PLC type C bands was found above unity (q > 1) indicating that type C bands are not randomly nucleated in the specimen (e.g. yielding a Gaussian distribution) but there exist spatial coupling and long range deformation correlations in the PLC type C bands spatial localization.

  20. Le Fort's procedure--an option for the aged.

    PubMed

    Chaudhury, Nilanjana; Sen, Mainak

    2011-03-01

    The changing demographics of the world's population will result in an increasing prevalence of pelvic organ prolapse and consequently a greater demand for healthcare services related to it. The objective of the study is to evaluate the efficacy of partial colpocleisis (Le Fort's operation) in a selected group of patients who are: (a) Not desirous of sexual function, (b) very elderly medically fragile, hence not fit for anaesthesia, (c) not fit for prolonged lithotomy position. After careful selection of cases 10 patients were included in the study from August 2005 to March 2006. USG(TVS) and cervical cytology were done to exclude any pathology. Partial colpocleisis was done under local anaesthesia with delayed absorbable sutures which closed the vagina from inside leaving drainage tracts on either side for egress of blood and cervicovaginal secretions postoperatively. A levator plication and high perineorrhaphy was also done. All patients(100%) had symptomatic relief. Only one patient (10%) had postoperative bleeding. Rest all had uneventful recovery. No recurrence of prolapse or SUI has developed till date. Operative time on average was 15 minutes. Hospital stay was 24 hours. Peroperative bleeding was negligible. Partial colpocleisis is an excellent operation for the treatment of pelvic organ prolapse (POP) for very selective group of patients. The advantage of the procedure lies in its simple technique, permanent cure, symptomatic relief and minimal surgical risk. Hence it can be done as a day care procedure at a very low cost. PMID:22010590

  1. Facteurs de risque de l'infection par le VIH dans le district de santé de Meyomessala au Cameroun

    PubMed Central

    Mbopi-Keou, Francois-Xavier; Nguefack-Tsague, Georges; Kalla, Ginette Claude Mireille; Abessolo, Stéphanie Abo'o; Angwafo, Fru; Muna, Walinjom

    2014-01-01

    Introduction L'objectif de ce travail était de déterminer les facteurs de risque de l'infection par le VIH dans le district de santé de Meyomessala (Région du Sud) au Cameroun. Méthodes Il s'agissait d'une étude transversale, descriptive et analytique qui s'est déroulée de Février à Mai 2011. Pour cette étude, nous avons obtenu une clairance éthique. Résultats L’échantillon était constitué de 315 participants dont 181 (57,46%) hommes et 134 (42,54%) femmes. L’âge moyen était de 24,5±8ans (extrême: 15-45ans). Quarante personnes (40) étaient séropositifs, soit une prévalence de l'infection par le VIH de 12,7%. Cette prévalence augmentait significativement (p = 0) avec le nombre de partenaires occasionnels au cours des douze derniers mois, allant de 2,7% chez ceux n'ayant eu aucun partenaire occasionnel à 21,25% chez ceux ayant plus de trois partenaires occasionnels (RC = 9,72; IC = 1,27-74,14; P = 0,03). le fait d’être âgé entre 20 et 24 ans (RC = 4,88; IC = 1,74-13,67; p = 0), avoir plus de trois partenaires sexuels au cours des douze derniers mois (RC = 9,72; IC = 1,27-74,14; p = 0,03), avoir les rapports sexuels avec les prostitués (RC = 2,86; IC = 1,42-5,76; p = 0), avoir eu le chlamydia (RC = 3,00; IC = 1,07-8,39; p = 0,04), avoir eu la syphilis (RC = 3,35; IC = 1,57-7,14; p = 0), avoir des avantages sociaux lors du premier rapport sexuel (RC = 2,57; IC = 1,03-6,43; p = 0,04) constituaient des potentiels facteurs de risque du VIH. Conclusion Il apparait urgent d'intensifier les campagnes de sensibilisation au risque d'infection par le VIH et les maladies sexuellement transmissibles dans le district de santé de Meyomessala PMID:25419299

  2. 'Le roi le veult'.

    PubMed

    Sholl, W T

    1997-06-14

    Following the fiftieth anniversary of the National Health Service Act 1946, I make the case in this article that professional provision of health care must remain the property of the citizen under common law and must not become a commodity that is bought and sold by third parties, including the state. PMID:9217334

  3. Facteurs déterminants le regret après ligature tubaire

    PubMed Central

    Boufettal, Houssine; Mahdaoui, Sakher; Samouh, Naïma

    2014-01-01

    Introduction La ligature tubaire peut générer regret. Le but de cette étude est d’étudier le vécu après la stérilisation ainsi que le regret et ses facteurs de risque. Méthodes Il s'agit d'une étude rétrospective chez 52 femmes stérilisées entre 2004 et 2010. Résultats Vingt cinq (48%) femmes avaient regretté la réalisation de la ligature tubaire. La moyenne d’âge était de 40,5 ans. Le temps consacré aux explications était très court dans tous les cas. Trois quart des femmes n’était pas au courant des complications de la ligature tubaire. Le regret était dû au facteur religieux (23%), aux algies pelviennes (11,5%), au désir d'autres enfants (9,6%) ou à la prise de connaissance d'autres moyens contraceptifs (3,9%). Conclusion Un certains nombre de facteurs de risque de regret de la ligature tubaire sont retrouvés dans la littérature, comme dans notre série, dont l’âge, le désir de procréer, l'information incomplète, le délai de réflexion et le facteur religieux. PMID:25309644

  4. La tuberculose pulmonaire et le tabac: à propos de 100 cas

    PubMed Central

    Janah, Hicham; Souhi, Hicham; Kouissmi, Hatim; Marc, Karima; Zahraoui, Rachida; Benamor, Jouda; Soualhi, Mona; Bourkadi, Jamal Eddine

    2014-01-01

    Le tabagisme et la tuberculose sont deux enjeux majeurs de santé publique au niveau mondial, en particulier dans les pays émergents. Pour déterminer les particularités cliniques, radiologiques, bactériologiques et thérapeutiques de la tuberculose pulmonaire chez les sujets tabagiques nous avons mené une étude prospective au service de phtisiologie de l'hôpital Moulay Youssef sur une période de 10 mois, portant sur 100 nouveaux cas de tuberculose pulmonaire, répartis en 2 groupes, 50 patients tabagiques: Groupe A et 50 patients non tabagiques: Groupe B. Tous nos patients étaient de sexe masculin, l’âge moyen était de 41 ans ± 12 chez le groupe A et de 36 ans ± 16 chez le groupe B. Le délai de consultation était plus long chez les tabagiques, la médiane était de 60j (30; 98) contre 40j (30; 60), la symptomatologie clinique était variable chez les deux groupes, dominée par les expectorations chez les tabagiques 96% contre 60%. Les lésions radiologiques étaient similaires chez les deux groupes ainsi que la charge bacillaire. Tous les patients ont été mis sous traitement antituberculeux. Après un mois du traitement, la Bacilloscopie était négative chez 50% du groupe A contre 66% chez le groupe B. la régression des lésions radiologiques était similaire chez les deux groupes. Le retard diagnostique et le retard de négativation des frottis sont les principales particularités de la tuberculose pulmonaire du sujet tabagique. Le sevrage tabagique doit faire partie intégrante de la prise en charge des patients atteints de tuberculose. PMID:25821545

  5. [LE cells in synovial fluid: prevalence and diagnostic usefulness in rheumatic diseases].

    PubMed

    Puszczewicz, Mariusz; Białkowska-Puszczewicz, Grazyna

    2010-01-01

    This study was undertaken to determine the prevalence of LE cells in synovial fluid and their importance for the diagnosis of rheumatic disease. Synovial fluid was obtained from 631 patients: 31 with systemic lupus erythematosus (SLE), 337 with rheumatoid arthritis (RA), 4 with Still's disease, 9 with systemic scleroderma (SS), 27 with the overlap syndrome (RA/SLE), 132 with ankylosing spondylitis (AS), 57 with Reiter's syndrome, and 34 with psoriatic arthritis (PA). The fluid was centrifuged, precipitate smears were done and were May-Grünwald-Giemsa stained for cytologic assessment. The supernatant was collected for antinuclear antibody (ANA) testing. Physicochemical and serologic properties of the synovial fluid were routinely determined. All synovial fluids demonstrated signs of inflammation. The presence of LE cells was ascertained in five patients with SLE and nine patients with the overlap syndrome. In these cases, LE cells were accompanied by ANA. In addition, hematoxylin bodies were revealed in SLE patients. LE cells were observed in 2.6% of patients with RA but were not accompanied by ANA. Patients with SS, Still's disease, AS, Reiter's syndrome, and PA tested negative for LE cells. It appears from these results that LE cells are rarely present in the synovial fluid of patients with rheumatic diseases. In contrast, they occur in more than 40% of patients with the overlap syndrome and may thus be regarded as important for the diagnosis of this condition. PMID:21365954

  6. SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes.

    PubMed

    Shen, Yue; Stracquadanio, Giovanni; Wang, Yun; Yang, Kun; Mitchell, Leslie A; Xue, Yaxin; Cai, Yizhi; Chen, Tai; Dymond, Jessica S; Kang, Kang; Gong, Jianhui; Zeng, Xiaofan; Zhang, Yongfen; Li, Yingrui; Feng, Qiang; Xu, Xun; Wang, Jun; Wang, Jian; Yang, Huanming; Boeke, Jef D; Bader, Joel S

    2016-01-01

    Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome arm synIXR (43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64 synIXR SCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designed loxPsym sites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3' UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes. PMID:26566658

  7. SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes

    PubMed Central

    Shen, Yue; Stracquadanio, Giovanni; Wang, Yun; Yang, Kun; Mitchell, Leslie A.; Xue, Yaxin; Cai, Yizhi; Chen, Tai; Dymond, Jessica S.; Kang, Kang; Gong, Jianhui; Zeng, Xiaofan; Zhang, Yongfen; Li, Yingrui; Feng, Qiang; Xu, Xun; Wang, Jun; Wang, Jian; Yang, Huanming; Boeke, Jef D.; Bader, Joel S.

    2016-01-01

    Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome arm synIXR (43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64 synIXR SCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designed loxPsym sites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3′ UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes. PMID:26566658

  8. Architectural Kansei of ‘Wall’ in The Façade Design by Le Corbusier

    NASA Astrophysics Data System (ADS)

    Sendai, Shoichiro

    The purpose of this paper is to discuss the modern architect Le Corbusier's architectural Kansei (sensibility) on wall in site environment through the analysis of his façade design, using Œuvres complètes (1910-1965, 8 vols., Les éditions d'architecture, Artemis, Zurich) and Le Corbusier Archives (1982-1984, 32 vols., Garland Publishing, Inc. and Fondation Le Corbusier, New York, London, Paris). At first, I arrange five façade types, according to the explanation by Le Corbusier ; ‘fenêtre en longueur (strip window)’, ‘pan de verre (glass wall)’, ‘brise-soleil (sun-breaker)’, ‘loggia’ and ‘claustra’. Through the analysis of the relationship between these types and the design process of each building, we find that Le Corbusier's façade design includes the affirmation and the negation of the ‘wall’ at the same time. In fact, the nature of façade modification during design process is divers: increase in transparency, decrease in transparency and spatialization of façade. That means, Le Corbusier studied the environmental condition by these façade types, and tried to realize the phenomenal openness. This trial bases on the function of architectural Kansei as correspondence between body and environment beyond the physical design.

  9. Lymphome et grossesse: le point de vue de l'obstétricien, à propos de 2 cas

    PubMed Central

    Amourak, Sarah; Alaoui, Fatimazahra Fdili; Jayi, Sofia; Bouguern, Hakima; Chaara, Hikmat; Melhouf, Moulay Abdelilah

    2014-01-01

    L'association lymphome et grossesse est une situation rare, mais non exceptionnelle, relevant de la coïncidence. Le lymphome vient en 4ème position des cancers rencontrés chez la femme enceinte, La clinique est trompeuse et inconstante, le diagnostic reste histologique et on distingue 2 types: lymphome malin hodgkinien (LMH) et le lymphome malin non hodgkinien (LMNH). Malgré le contexte de véritable urgence hématologique, la décision d'initier ou de différer le traitement est délicate, influencée par le type de lymphome, son extension et sa localisation, la répercussion organique, le degré de maturation f'tale, les risques obstétricaux et les valeurs éthiques, culturelles et religieuses de la patiente. Le traitement consiste essentiellement à une chimiothérapie. Le LH durant la grossesse est relativement moins agressif et d’évolution plus favorable que le LMNH. PMID:25883744

  10. Simulated Experiments

    ERIC Educational Resources Information Center

    Snadden, R. B.; Runquist, O.

    1975-01-01

    Presents an experiment in which a programmable calculator is employed as a data generating system for simulated laboratory experiments. The example used as an illustration is a simulated conductimetric titration of an aqueous solution of HC1 with an aqueous solution of NaOH. (Author/EB)