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Sample records for evangelos gr avdikos

  1. GR uniqueness and deformations

    NASA Astrophysics Data System (ADS)

    Krasnov, Kirill

    2015-10-01

    In the metric formulation gravitons are described with the parity symmetric S + 2 ⊗ S - 2 representation of Lorentz group. General Relativity is then the unique theory of interacting gravitons with second order field equations. We show that if a chiral S + 3 ⊗ S - representation is used instead, the uniqueness is lost, and there is an infinite-parametric family of theories of interacting gravitons with second order field equations. We use the language of graviton scattering amplitudes, and show how the uniqueness of GR is avoided using simple dimensional analysis. The resulting distinct from GR gravity theories are all parity asymmetric, but share the GR MHV amplitudes. They have new all same helicity graviton scattering amplitudes at every graviton order. The amplitudes with at least one graviton of opposite helicity continue to be determinable by the BCFW recursion.

  2. Glucocorticoid receptor (GR) {beta} has intrinsic, GR{alpha}-independent transcriptional activity

    SciTech Connect

    Kino, Tomoshige; Manoli, Irini; Kelkar, Sujata; Wang, Yonghong; Su, Yan A.; Chrousos, George P.

    2009-04-17

    The human glucocorticoid receptor (GR) gene produces C-terminal GR{beta} and GR{alpha} isoforms through alternative use of specific exons 9{beta} and {alpha}, respectively. We explored the transcriptional activity of GR{beta} on endogenous genes by developing HeLa cells stably expressing EGFP-GR{beta} or EGFP. Microarray analyses revealed that GR{beta} had intrinsic gene-specific transcriptional activity, regulating mRNA expression of a large number of genes negatively or positively. Majority of GR{beta}-responsive genes was distinct from those modulated by GR{alpha}, while GR{beta} and GR{alpha} mutually modulated each other's transcriptional activity in a subpopulation of genes. We did not observe in HCT116 cells nuclear translocation of GR{beta} and activation of this receptor by RU 486, a synthetic steroid previously reported to bind GR{beta} and to induce nuclear translocation. Our results indicate that GR{beta} has intrinsic, GR{alpha}-independent, gene-specific transcriptional activity, in addition to its previously reported dominant negative effect on GR{alpha}-induced transactivation of GRE-driven promoters.

  3. Impaired spermatogenesis and gr/gr deletions related to Y chromosome haplogroups in Korean men.

    PubMed

    Choi, Jin; Song, Seung-Hun; Bak, Chong Won; Sung, Se Ra; Yoon, Tae Ki; Lee, Dong Ryul; Shim, Sung Han

    2012-01-01

    Microdeletion of the Azoospermia Factor (AZF) regions in Y chromosome is a well-known genetic cause of male infertility resulting from spermatogenetic impairment. However, the partial deletions of AZFc region related to spermatogenetic impairment are controversial. In this study, we characterized partial deletion of AZFc region in Korean patients with spermatogenetic impairment and assessed whether the DAZ and CDY1 contributes to the phenotype in patients with gr/gr deletions. Total of 377 patients with azoo-/oligozoospermia and 217 controls were analyzed using multiplex polymerase chain reaction (PCR), analysis of DAZ-CDY1 sequence family variants (SFVs), and quantitative fluorescent (QF)-PCR. Of the 377 men with impaired spermatogenesis, 59 cases (15.6%) had partial AZFc deletions, including 32 gr/gr (8.5%), 22 b2/b3 (5.8%), four b1/b3 (1.1%) and one b3/b4 (0.3%) deletion. In comparison, 14 of 217 normozoospermic controls (6.5%) had partial AZFc deletions, including five gr/gr (2.3%) and nine b2/b3 (4.1%) deletions. The frequency of gr/gr deletions was significantly higher in the azoo-/oligozoospermic group than in the normozoospermic control group (p = 0.003; OR = 3.933; 95% CI = 1.509-10.250). Concerning Y haplogroup, we observed no significant differences in the frequency of gr/gr deletions between the case and the control groups in the YAP+ lineages, while gr/gr deletion were significantly higher in azoo-/oligozoospermia than normozoospermia in the YAP- lineage (p = 0.004; OR = 6.341; 95% CI = 1.472-27.312). Our data suggested that gr/gr deletion is associated with impaired spermatogenesis in Koreans with YAP- lineage, regardless of the gr/gr subtypes.

  4. Differential effect of specific gr/gr deletion subtypes on spermatogenesis in the Chinese Han population.

    PubMed

    Yang, Y; Ma, M; Li, L; Su, D; Chen, P; Ma, Y; Liu, Y; Tao, D; Lin, L; Zhang, S

    2010-10-01

    As a common variation in the azoospermia factor c (AZFc) region of Y chromosome, the gr/gr deletion is regarded as a significant risk factor for spermatogenic impairment, whereas the association of the deletion's phenotypic expression with Y-chromosomal background is still a subject of debate. To further investigate the contribution of the deletion to spermatogenic impairment in different Y-chromosomal haplogroups, the partial AZFc deletion was detected with AZFc-specific sequence tagged sites, gene dosage and gene copy analyses of deleted in azoospermia (DAZ), chromodomain Y1 (CDY1) and basic protein Y2 (BPY2) in 1426 azoo/oligozoospermic and 672 normozoospermic men from a Chinese population. The haplogrouping was performed in 231 deletion carriers with 12 polymorphic loci of Y chromosome. As a result, five gr/gr rearrangement types in eight Y haplogroups were observed, in which the simple gr/gr deletion was the most common type, and its frequency was significantly higher in men with azoo/oligozoospermia relative to normozoospermia. Also the distribution of gr/gr-rearranged Y haplogroups was significantly different between the two groups, in which gr/gr-deleted haplogroups C and DE were more common in men with azoo/oligozoospermia. In the 6 gr/gr copy deletion haplotypes, the frequencies of DAZ1/DAZ2+CDY1a or CDY1b deletion were significantly higher in men with azoo/oligozoospermia, while all DAZ3/DAZ4+CDY1b+BPY2.2 or 2.3 deletions were found only in haplogroup Q1 without any distribution difference between the azoo/oligozoospermic and normozoospermic groups. This study provided further evidence for the existence of multiple subtypes of gr/gr deletion and indicates that gr/gr-DAZ1/DAZ2 deletion is a significant risk factor. However, the association of the phenotypic variation of gr/gr deletion with Y-chromosomal haplogroups is not definite yet, because of the limited amounts of the deletions observed in each of the haplogroups and the lack of the quantitative

  5. An evaluation of the stability of synthetic groundwater formulations GR-3 and GR-4

    SciTech Connect

    Dill, J.A.; Jones, T.E.; Marcy, A.D.; Baechler, M.O.; Payne, J.R.

    1984-10-08

    Simple solubility calculations indicate that synthetic groundwater formulations GR-3 and GR-4 may be unstable with respect to the precipitation of certain components. However, the validity of calculations of this type is limited by the complexity of these solutions. In order to properly address the chemical stability of these formulations, an experimental evaluation has been accomplished. The findings were that GR-3 and GR-4 were similar in their chemical stability. Both were found to be quite stable with respect to all constituents except silicate and inorganic carbon over a 30-day period. Some instability of monomeric silicate was observed. However, this did not result in a concentration change of greater than 5%, and no evidence of particulate formation was observed. 6 refs., 30 tabs.

  6. A GR/Impedance probe proves unsuitable for measuring GR depth in Australian lamb carcases.

    PubMed

    Fowler, Stephanie M; Hoban, Jordan M; van de Ven, Remy; Boyce, Mal; Williams, Andrew; Pethick, David W; Hopkins, David L

    2017-02-27

    Multiple studies were conducted at 3 abattoirs to determine the potential of a dual function GR/Impedance probe to measure GR soft- tissue depth (depth at the 12th rib, 110mm from the mid line of the carcase) of typical lamb carcases processed in Australia. Lamb carcases (1016) were measured approximately 25min post slaughter with the probe and a GR knife as the most commonly used measurement. Modelling indicated that variation in the measurement using the probe compared to the measurement using the knife occurred with increasing carcase weight and fatness as well as between different abattoirs. Consequently, the probe in its current design cannot provide the repeatable measurement required by industry.

  7. AB056. Establishing the procedure for detection of gr/gr deletions on the Y chromosome in Vietnamese infertile men

    PubMed Central

    Nguyễn, Trâm Bảo; Nguyễn, Ngọc-Anh Thị; Phạm, Thảo-Trang Nguyễn; Nguyễn, Trung Tấn

    2015-01-01

    Background and objective About 2-10% cases of both azoospermia or cryptospermia have a micro Y deletion. These deletions mainly locate at AZFa, b, or c which containing several crucial genes for normal spermatogenesis. Among various category of deletions is gr/gr deletions on AZFc. The influence on spermatogenesis mostly depend on characteristics of the Y chromosome which may vary among different ethnicity and geographical locations. In Vietnam, there is no study about gr/gr deletions. (I) To establish an approachable procedure to detect gr/gr deletions on the Y chromosome, which is applicable for hospitals and clinics in Vietnam; (II) to determine the percentage of gr/gr deletions carriers among infertile men (azoospermia and severe oligozoospermia). Methods Blood samples were collected for DNA extraction. Based on inclusive and exclusive criteria, 3 fertile and 32 infertile men (azoospermia and cryptozoospermia) were recruited to our study with informed consent. Sequence tagged sites (STSs) và primers were designed by using design software (Ape, PrimerPlex2, Oligoanalyzer IDT) based on the information of NCBI. DNA was extracted in silico from blood sample and applied to Multiplex PCR to detect gr/gr deletions. To ensure the true positive result of gr/gr deletions, MLPA was subjected to perform. Results and discussion With our designed primers, an approachable procedure was successfully established to detect gr/gr deletions that resulted at a high level of sensitivity (at 0.5ng DNA sample/reaction) and high level of stability. The percentage of gr/gr-deletion carriers among infertile men was 12.5% (4 positive samples), higher than 10.6% in an Asian population from a current study. All positive samples are confirmed significantly by MLPA technique. Conclusions An approachable procedure was successfully established to detect gr/gr deletions that resulted at a high level of sensitivity (at 0.5 ng DNA sample/reaction) and high level of stability. The percentage of gr/gr

  8. Associations of Y-chromosome subdeletion gr/gr with the prevalence of Y-chromosome haplogroups in infertile patients.

    PubMed

    Shahid, Mohammad; Dhillon, Varinderpal S; Khalil, Hesham Saleh; Sexana, Anubha; Husain, Syed Akhtar

    2011-01-01

    Microdeletions in azoospermia factor (AZF) region on distal Yq are associated with male infertility and spermatogenic failure due to intra-chromosomal homologous recombination between large nearly identical repeat amplicons and are found in ∼10% of azoospermic and severe oligozoospermic cases. Although AZFc is deleted in azoospermia or oligozoospermia, no definitive conclusion has been drawn for the role of partial AZFc deletions to spermatogenic failure. Therefore, this study is planned to investigate the role of gr/gr subdeletions in individuals with spermatogenic failure and to find its relationship with Y chromosome haplogroups (HGs) in infertile men from Indian population. It is a case-control study involving 236 azoospermic, 182 oligospermic and 240 healthy normozoospermic men. We found 18 gr/gr, 11 b1/b3 and 2 b2/b3 subdeletions in azoospermic patients and 12 gr/gr, 5 b1/b3 and 4 b2/b3 subdeletions in oligospermic patients. However, we also found seven gr/gr deletions in normozoospermic men. Seven patients each with spermatogenic arrest and oligospermia who carry gr/gr subdeletions have deleted DAZ3/DAZ4 genes. A total of 11 patients with sertoli cell-only syndrome (SCOS) and 5 oligospermic patients with gr/gr subdeletions also have DAZ1/DAZ2 genes deleted indicating that deletions of DAZ genes contributed differently to damage to spermatogenic process. L1 HG is found in patients showing b1/b3 subdeletions, whereas HG H1a2 and H1b were found in normozoospermic individuals with gr/gr subdeletions. Our results provide evidence of association between the occurrence of subdeletions and male infertility as well as the severity of the spermatogenic failure.

  9. An evaluation of the stability of synthetic Grande Ronde groundwater formulations GR-3 and GR-4

    SciTech Connect

    Dill, J.A.; Jones, T.E.; Marcy, A.D.; Baechler, M.O.; Payne, J.R.

    1987-03-01

    Simple solubility calculations indicate that synthetic Grande Ronde groundwater formulations GR-3 and GR-4 may be unstable with respect to the precipitation of certain components. The validity of calculations of this type is, however, limited by the complexity of the solutions. To address the chemical stability of these formulations properly, an experimental evaluation was performed. The evaluation revealed that GR-3 and GR-4 were similar in their chemical stability. Both were found to be quite stable with respect to all constituents, except silicate and inorganic carbon, over a 30-d period. Some instability of monomeric silicate was observed. However, this did not result in a concentration change of greater than 5%, and no evidence of particulate formation was observed. Both formulations were found to be relatively unstable with respect to inorganic carbon concentration. A general trend toward increasing carbon concentration was observed. This was attributed to absorption of CO/sub 2/ from the atmosphere. Storing the synthetic groundwater in sealed containers eliminated this problem. 5 refs., 24 tabs.

  10. Genetics Home Reference: Imerslund-Gräsbeck syndrome

    MedlinePlus

    ... Page Gräsbeck R. Imerslund-Gräsbeck syndrome (selective vitamin B(12) malabsorption with proteinuria). Orphanet J Rare Dis. 2006 ... 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin. Blood. 2000 Jul 15;96(2): ...

  11. The role of glucocorticoid receptor (GR) polymorphisms in human erythropoiesis.

    PubMed

    Varricchio, Lilian; Migliaccio, Anna Rita

    2014-01-01

    Glucocorticoids are endogenous steroid hormones that regulate several biological functions including proliferation, differentiation and apoptosis in numerous cell types in response to stress. Synthetic glucocorticoids, such as dexamethasone (Dex) are used to treat a variety of diseases ranging from allergy to depression. Glucocorticoids exert their effects by passively entering into cells and binding to a specific Glucocorticoid Receptor (GR) present in the cytoplasm. Once activated by its ligand, GR may elicit cytoplasmic (mainly suppression of p53), and nuclear (regulation of transcription of GR responsive genes), responses. Human GR is highly polymorphic and may encode > 260 different isoforms. This polymorphism is emerging as the leading cause for the variability of phenotype and response to glucocorticoid therapy observed in human populations. Studies in mice and clinical observations indicate that GR controls also the response to erythroid stress. This knowledge has been exploited in-vivo by using synthetic GR agonists for treatment of the erythropoietin-refractory congenic Diamond Blackfan Anemia and in-vitro to develop culture conditions that may theoretically generate red cells in numbers sufficient for transfusion. However, the effect exerted by GR polymorphism on the variability of the phenotype of genetic and acquired erythroid disorders observed in the human population is still poorly appreciated. This review will summarize current knowledge on the biological activity of GR and of its polymorphism in non-hematopoietic diseases and discuss the implications of these observations for erythropoiesis.

  12. Hippocampal GR expression is increased in elderly depressed females.

    PubMed

    Wang, Q; Joels, M; Swaab, D F; Lucassen, P J

    2012-01-01

    Hyperactivity of the Hypthalamus-Pituitary-Adrenal (HPA)-axis is common in major depression and evident from e.g., a frequently exaggerated response to combined application of dexamethasone and CRH in this disorder. HPA-axis activity and hence the secretion of glucocorticoids (GC), the endpoint of the HPA-axis, depends to some extent on GC binding to glucocorticoid receptors (GR) that are abundantly expressed in the hippocampus. To assess whether differences in hippocampal GR expression occur in association with depression, we investigated GR-alpha protein immunoreactivity (ir) in postmortem hippocampal tissue of an elderly cohort of 9 well-characterized depressed patients and 9 control subjects that were pair-wise matched for age, sex, CSF-pH and postmortem delay. Abundant nuclear GR-ir was observed in neurons of the hippocampal Ammon's horn (CA) and dentate gyrus (DG) subregions. GR-ir in the DG correlated positively with age in the depressed but not the control group. Although no significant differences were found in GR-ir between the depressed and control groups, a significant increase in GR-ir was present in depressed females compared to depressed males. Whether this sex difference in hippocampal GR-ir in depression relates to the increased incidence of depression in females awaits further study. This article is part of a Special Issue entitled 'Anxiety and Depression'.

  13. The role of glucocorticoid receptor (GR) polymorphisms in human erythropoiesis

    PubMed Central

    Varricchio, Lilian; Migliaccio, Anna Rita

    2014-01-01

    Glucocorticoids are endogenous steroid hormones that regulate several biological functions including proliferation, differentiation and apoptosis in numerous cell types in response to stress. Synthetic glucocorticoids, such as dexamethasone (Dex) are used to treat a variety of diseases ranging from allergy to depression. Glucocorticoids exert their effects by passively entering into cells and binding to a specific Glucocorticoid Receptor (GR) present in the cytoplasm. Once activated by its ligand, GR may elicit cytoplasmic (mainly suppression of p53), and nuclear (regulation of transcription of GR responsive genes), responses. Human GR is highly polymorphic and may encode > 260 different isoforms. This polymorphism is emerging as the leading cause for the variability of phenotype and response to glucocorticoid therapy observed in human populations. Studies in mice and clinical observations indicate that GR controls also the response to erythroid stress. This knowledge has been exploited in-vivo by using synthetic GR agonists for treatment of the erythropoietin-refractory congenic Diamond Blackfan Anemia and in-vitro to develop culture conditions that may theoretically generate red cells in numbers sufficient for transfusion. However, the effect exerted by GR polymorphism on the variability of the phenotype of genetic and acquired erythroid disorders observed in the human population is still poorly appreciated. This review will summarize current knowledge on the biological activity of GR and of its polymorphism in non-hematopoietic diseases and discuss the implications of these observations for erythropoiesis. PMID:25755906

  14. The power of weak-field GR gravity

    NASA Astrophysics Data System (ADS)

    Cooperstock, F. I.

    2016-10-01

    While general relativity (GR) is our premier theory of gravity, galactic dynamics from the outset has been studied with Newtonian gravity (NG), guided by the long-held belief in the idea of the “Newtonian-limit” of GR. This maintains that when the gravitational field is weak and the velocities are nonrelativistic, NG is the appropriate theory, apart from small corrections at best (such as in GPS tracking). However, there are simple examples of phenomena where there is no NG counterpart. We present a particularly simple new example of the stark difference that NG and weak-field GR exhibit for a modified van Stockum source, which speaks to the flat galactic rotation curve problem. We note that the linear GR compatibility equation in the literature is incomplete. Its completion is vital for our case, leading to a stark contrast between GR and NG for totally flat van Stockum rotation curves.

  15. Cardiac GR and MR: From Development to Pathology.

    PubMed

    Richardson, Rachel V; Batchen, Emma J; Denvir, Martin A; Gray, Gillian A; Chapman, Karen E

    2016-01-01

    The efficacy of mineralocorticoid receptor (MR) antagonism in the treatment of certain patients with heart failure has highlighted the pivotal role of aldosterone and MR in heart disease. The glucocorticoid (GC) receptor (GR) is also expressed in heart, but the role of cardiac GR had received much less attention until recently. GR and MR are highly homologous in both structure and function, although not in cellular readout. Recent evidence in animal models has uncovered a tonic role for GC action via GR in cardiomyocytes in prevention of heart disease. Here, we review this evidence and the implications for a balance between GR and MR activation in the early life maturation of the heart and its subsequent health and disease.

  16. Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy

    PubMed Central

    Hapgood, Janet P.; Avenant, Chanel; Moliki, Johnson M.

    2016-01-01

    Pharmacological doses of glucocorticoids (GCs), acting via the glucocorticoid receptor (GR) to repress inflammation and immune function, remain the most effective therapy in the treatment of inflammatory and immune diseases. Since many patients on GC therapy exhibit GC-resistance and severe side-effects, much research is focussed on developing more selective GCs and combination therapies, with greater anti-inflammatory potency. GCs mediate their classical genomic transcriptional effects by binding to the cytoplasmic GR, followed by nuclear translocation and modulation of transcription of target genes by direct DNA-binding of the GR or its tethering to other transcription factors. Recent evidence suggests, however, that the responses mediated by the GR are much more complex and involve multiple parallel mechanisms integrating simultaneous signals from other receptors, both in the absence and presence of GCs, to shift the sensitivity of a target cell to GCs. The level of cellular stress, immune activation status, or the cell cycle phase may be crucial for determining GC sensitivity and GC responsiveness as well as subcellular localization of the GR and GR levels. Central to the development of new drugs that target GR signalling alone or as add-on therapies, is an in-depth understanding of the molecular mechanisms of GC-independent GR desensitization, priming and activation of the unliganded GR, as well as synergy and cross-talk with other signalling pathways. This review will discuss the information currently available on these topics and their relevance to immunotherapy, as well as identify unanswered questions and future areas of research. PMID:27288728

  17. Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy.

    PubMed

    Hapgood, Janet P; Avenant, Chanel; Moliki, Johnson M

    2016-09-01

    Pharmacological doses of glucocorticoids (GCs), acting via the glucocorticoid receptor (GR) to repress inflammation and immune function, remain the most effective therapy in the treatment of inflammatory and immune diseases. Since many patients on GC therapy exhibit GC resistance and severe side-effects, much research is focused on developing more selective GCs and combination therapies, with greater anti-inflammatory potency. GCs mediate their classical genomic transcriptional effects by binding to the cytoplasmic GR, followed by nuclear translocation and modulation of transcription of target genes by direct DNA binding of the GR or its tethering to other transcription factors. Recent evidence suggests, however, that the responses mediated by the GR are much more complex and involve multiple parallel mechanisms integrating simultaneous signals from other receptors, both in the absence and presence of GCs, to shift the sensitivity of a target cell to GCs. The level of cellular stress, immune activation status, or the cell cycle phase may be crucial for determining GC sensitivity and GC responsiveness as well as subcellular localization of the GR and GR levels. Central to the development of new drugs that target GR signaling alone or as add-on therapies, is an in-depth understanding of the molecular mechanisms of GC-independent GR desensitization, priming and activation of the unliganded GR, as well as synergy and cross-talk with other signaling pathways. This review will discuss the information currently available on these topics and their relevance to immunotherapy, as well as identify unanswered questions and future areas of research.

  18. Regioselective and stereospecific hydroxylation of GR24 by Sorghum bicolor and evaluation of germination inducing activities of hydroxylated GR24 stereoisomers toward seeds of Striga species.

    PubMed

    Ueno, Kotomi; Ishiwa, Shunsuke; Nakashima, Hitomi; Mizutani, Masaharu; Takikawa, Hirosato; Sugimoto, Yukihiro

    2015-09-15

    Bioconversion of GR24, the most widely used synthetic strigolactone (SL), by hydroponically grown sorghum (Sorghum bicolor) and biological activities of hydroxylated GR24 stereoisomers were studied. Analysis of extracts and exudates of sorghum roots previously fed with a racemic and diastereomeric mixture of GR24, using liquid chromatography-tandem mass spectrometry with multiple reaction monitoring (MRM), confirmed uptake of GR24 and suggested its conversion to mono-hydroxylated products. Two major GR24 metabolites, 7-hydroxy-GR24 and 8-hydroxy-GR24, were identified in the root extracts and exudates by direct comparison of chromatographic behavior with a series of synthetic mono-hydroxylated GR24 analogues. Separate feeding experiments with each of the GR24 stereoisomers revealed that the hydroxylated products were derived from 2'-epi-GR24, an evidence of sterical recognition of the GR24 molecule by sorghum. Trans-4-hydroxy-GR24 isomers derived from all GR24 stereoisomers were detected in the exudates as minor metabolites. The synthetic hydroxy-GR24 isomers induced germination of Striga hermonthica in decreasing order of C-8>C-7>C-6>C-5>C-4. In contrast the stereoisomers having the same configuration of orobanchol, irrespective of position of hydroxylation, induced germination of Striga gesnerioides. The results confirm previous reports on structural requirements of SLs and ascribe a critical role to hydroxylation, but not to the position of the hydroxyl group in the AB part of the molecule, in induction of S. gesnerioides seed germination.

  19. Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses

    NASA Astrophysics Data System (ADS)

    Bansal, Sandeep Kumar; Jaiswal, Deepika; Gupta, Nishi; Singh, Kiran; Dada, Rima; Sankhwar, Satya Narayan; Gupta, Gopal; Rajender, Singh

    2016-02-01

    We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39–2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.

  20. Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses.

    PubMed

    Bansal, Sandeep Kumar; Jaiswal, Deepika; Gupta, Nishi; Singh, Kiran; Dada, Rima; Sankhwar, Satya Narayan; Gupta, Gopal; Rajender, Singh

    2016-02-15

    We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39-2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.

  1. Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses

    PubMed Central

    Bansal, Sandeep Kumar; Jaiswal, Deepika; Gupta, Nishi; Singh, Kiran; Dada, Rima; Sankhwar, Satya Narayan; Gupta, Gopal; Rajender, Singh

    2016-01-01

    We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39–2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations. PMID:26876364

  2. Modeling Gravitational Waves to Test GR Dispersion and Polarization

    NASA Astrophysics Data System (ADS)

    Tso, Rhondale; Chen, Yanbei; Isi, Maximilliano

    2017-01-01

    Given continued observation runs from the Laser Interferometer Gravitational-Wave Observatory Scientific Collaboration, further gravitational wave (GW) events will provide added constraints on beyond-general relativity (b-GR) theories. One approach, independent of the GW generation mechanism at the source, is to look at modification to the GW dispersion and propagation, which can accumulate over vast distances. Generic modification of GW propagation can also, in certain b-GR theories, impact the polarization content of GWs. To this end, a comprehensive approach to testing the dispersion and polarization content is developed by modeling anisotropic deformations to the waveforms' phase, along with birefringence effects and corollary consequences for b-GR polarizations, i.e., breathing, vector, and longitudinal modes. Such an approach can be mapped to specific theories like Lorentz violation, amplitude birefringence in Chern-Simons, and provide hints at additional theories to be included. An overview of data analysis routines to be implemented will also be discussed.

  3. Variable stars in the dwarf galaxy GR 8 (DDO 155)

    NASA Technical Reports Server (NTRS)

    Tolstoy, Eline; Saha, A.; Hoessel, John G.; Danielson, G. Edward

    1995-01-01

    Observations of the resolved stars in dwarf galaxy GR 8, obtained over the period 1980 February to 1994 March, are presented. Thirty-four separate epochs were searched for variable stars, and a total of six were found, of which one has Cepheid characteristics. After correction for Galactic extinction this single Cepheid yields a distance modulus of m - M = 26.75 +/- 0.35. This corresponds to a distance of 2.24 Mpc, placing GR 8 near the Local Group (LG) zero-velocity surface. The other five variable stars are very red, and possibly have long periods of order 100 days or more.

  4. Saikosaponin D acts against corticosterone-induced apoptosis via regulation of mitochondrial GR translocation and a GR-dependent pathway.

    PubMed

    Li, Zong-Yang; Jiang, Yu-Mao; Liu, Ya-Min; Guo, Zhi; Shen, Sheng-Nan; Liu, Xin-Min; Pan, Rui-Le

    2014-08-04

    Saikosaponin D is an agonist of the glucocorticoid receptor (GR), and our preliminary study showed that it possesses neuroprotective effects in corticosterone-treated PC12 cells. However, further proof is required, and the molecular mechanisms of this neuroprotection remain unclear. This study sought to further examine the cytoprotective efficiency and potential mechanisms of action of Saikosaponin D in corticosterone-treated PC12 cells. The cells were treated with 250 μM corticosterone in the absence or presence of Saikosaponin D for 24 h; cell viability was then determined, and Hoechst 33342/propidium iodide (PI) and annexin/PI double staining, and TUNEL staining were performed. Next, mPTP, MMP, [Ca(2+)]i, translocation of the GR to the nucleus and Western blot analyses for caspase-3, caspase-9, cytochrome C, GR, GILZ, SGK-1, NF-Κb (P65), IκB-α, Bad, Akt, Hsp90 and HDAC-6 were investigated. The neuroprotective effects of Saikosaponin D were further confirmed by Hoechst 33342/PI, annexin/PI and TUNEL staining assays. These additional data suggested that Saikosaponin D partially reversed the physiological changes induced by corticosterone by inhibiting the translocation of the GR to the mitochondria, restoring mitochondrial function, down-regulating the expression of pro-apoptotic-related signalling events and up-regulating anti-apoptotic-related signalling events. These findings suggest that SSD exhibited its anti-apoptotic effects via differential regulation of mitochondrial and nuclear GR translocation, partial reversal of mitochondrial dysfunction, inhibition of the mitochondrial apoptotic pathway, and selective activation of the GR-dependent survival pathway.

  5. CRTC2 Is a Coactivator of GR and Couples GR and CREB in the Regulation of Hepatic Gluconeogenesis.

    PubMed

    Hill, Micah J; Suzuki, Shigeru; Segars, James H; Kino, Tomoshige

    2016-01-01

    Glucocorticoid hormones play essential roles in the regulation of gluconeogenesis in the liver, an adaptive response that is required for the maintenance of circulating glucose levels during fasting. Glucocorticoids do this by cooperating with glucagon, which is secreted from pancreatic islets to activate the cAMP-signaling pathway in hepatocytes. The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting. We show here that CRTC2 also functions as a coactivator for the glucocorticoid receptor (GR). CRTC2 strongly enhances GR-induced transcriptional activity of glucocorticoid-responsive genes. CRTC2 physically interacts with the ligand-binding domain of the GR through a region spanning amino acids 561-693. Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB. CRTC2 is required for the maintenance of blood glucose levels during fasting in mice by enhancing the GR transcriptional activity on both the G6p and phosphoenolpyruvate carboxykinase (Pepck) genes. Finally, CRTC2 modulates the transcriptional activity of the progesterone receptor, indicating that it may influence the transcriptional activity of other steroid/nuclear receptors. Taken together, these results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR- and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK.

  6. Preparation of Polyclonal Antibody and Expression Analysis of GR in Tomato

    NASA Astrophysics Data System (ADS)

    Xie, Yuanhong; Zhu, Benzhong; Luo, Yunbo; Chen, Xiangning; Zhang, Hongxing

    The fruit ripening of Green-ripe (Gr) mutant tomato was inhibited dramatically. To determine the expression patterns of Gr in tomato, we first produced the polyclonal antibody of Gr protein. RT-PCR was used to amplify the Gr gene from green ripe tomato fruit. And the PCR product was subcloned into prokaryotic protein expression vectors pET-30a to generate recombinant plasmid. The Gr protein was induced by IPTG in BL21 (DE3) and purified by Ni-NTA agarose column. The anti-Gr serum was produced by immunizing rabbits, and the titer of the anti-Gr serum was above 5000 by ELISA analysis. Purified by the DEAE-52 ion-column, the high purification level of anti-Gr polyclonal antibody was obtained. Furthermore, RT-CPR was used in the RNA level to demonstrate that the expression of Gr gene was specialized in some cultures of tomato. For example, the expressions of Gr were higher in seed, flower and green ripe fruit than others, and the expression level were reduced by exogenous ethylene treatment in the flower and green ripe fruit. Moreover, Polyclonal antibody of Gr was used to investigate the expression pattern of Gr in protein level by the Western blotting. Our results show that the expression level of Gr in protein level was complied with the expressions in RNA. So, we suggested that the regulation of Gr was transcriptional.

  7. Alpha-plutonium's Grüneisen parameter.

    PubMed

    Ledbetter, Hassel; Lawson, Andrew; Migliori, Albert

    2010-04-28

    Reported Grüneisen parameters γ of alpha-plutonium range from 3.0 to 9.6, which is remarkable because typical Grüneisen parameter uncertainty seldom exceeds ± 0.5. Our six new estimates obtained by different methods range from 3.2 to 9.6. The new estimates arise from Grüneisen's rule, from Einstein model and Debye model fits to low-temperature ΔV/V, from the bulk modulus temperature dependence, from the zero-point-energy contribution to the bulk modulus, and from another Grüneisen relationship whereby γ is estimated from only the bulk modulus and volume changes with temperature (or pressure). We disregard several high estimates because of the itinerant-localized 5f-electron changes during temperature changes and pressure changes. Considering all these estimates, for alpha-plutonium, we recommend γ = 3.7 ± 0.4, slightly high compared with values for all elemental metals.

  8. Iceland: Grímsvötn Volcano

    Atmospheric Science Data Center

    2013-04-17

    article title:  Grímsvötn Volcano Injects Ash into the Stratosphere     ... p.m. local time (1730 UTC) on Saturday, May 21, 2011. The volcano, located approximately 140 miles (220 kilometers) east of the capital ...

  9. Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background

    PubMed Central

    Krausz, Csilla; Giachini, Claudia; Xue, Yali; O’Brya, Moira K.; Gromoll, Joerg; Rajpert-de Meyts, Ewa; Oliva, Rafael; Aknin-Seifer, Isabelle; Erdei, Edit; Jorgensen, Niels; Simoni, Manuela; Ballescà, José Luis; Levy, Rachel; Balercia, Giancarlo; Piomboni, Paola; Nieschlag, Eberhard; Forti, Gianni; McLachlan, Rob; Tyler-Smith, Chris

    2009-01-01

    Background Previous studies have compared sperm phenotypes between men with partial [1] deletions within the AZFc region of the Y chromosome with non-carriers, with variable results. Here, we have investigated a separate question, the basis of the variation in sperm phenotype within gr/gr deletion carriers, which ranges from normozoospermia to azoospermia. Differences in the genes removed by independent gr/gr deletions, the occurrence of subsequent duplications or the presence of linked modifying variants elsewhere on the chromosome have been suggested as possible causal factors. We set out to test these possibilities in a large sample of gr/gr deletion carriers with known phenotypes spanning the complete range. Results We assembled a collection of 169 men diagnosed with gr/gr deletions from six centres in Europe and one in Australia, and characterized the DAZ and CDY1 copies retained, the presence or absence of duplications and the Y-chromosomal haplogroup. Although our study had good power to detect factors that accounted for ≥5.5% of the variation in sperm concentration, no such factor was detected. A negative effect of gr/gr deletions followed by b2/b4 duplication was observed within the normospermic group, which remains to be further explored in a larger study population. Finally, we observed significant geographical differences in the frequency of different subtypes of gr/gr deletions which may have relevance for the interpretation of case control studies dealing with admixed populations. Conclusions We conclude that the phenotypic variation of gr/gr carriers in men of European origin is largely independent of the Y-chromosomal background. PMID:18782837

  10. Pin1 promotes GR transactivation by enhancing recruitment to target genes.

    PubMed

    Poolman, Toryn M; Farrow, Stuart N; Matthews, Laura; Loudon, Andrew S; Ray, David W

    2013-10-01

    The glucocorticoid receptor (GR) is a ligand activated transcription factor, serving to regulate both energy metabolism and immune functions. Factors that influence cellular sensitivity to glucocorticoids (GC) are therefore of great interest. The N-terminal of the GR contains numerous potential proline-directed phosphorylation sites, some of which can regulate GR transactivation. Unrestricted proline isomerisation can be inhibited by adjacent serine phosphorylation and requires a prolyl isomerise, Pin1. Pin1 therefore determines the functional outcome of proline-directed kinases acting on the GR, as cis/trans isomers are distinct pools with different interacting proteins. We show that Pin1 mediates GR transactivation, but not GR trans-repression. Two N-terminal GR serines, S203 and S211, are targets for Pin1 potentiation of GR transactivation, establishing a direct link between Pin1 and the GR. We also demonstrate GC-activated co-recruitment of GR and Pin1 to the GILZ gene promoter. The Pin1 effect required both its WW and catalytic domains, and GR recruitment to its GRE was Pin1-dependent. Therefore, Pin1 is a selective regulator of GR transactivation, acting through N-terminal phospho-serine residues to regulate GR recruitment to its target sites in the genome. As Pin1 is dysregulated in disease states, this interaction may contribute to altered GC action in inflammatory conditions.

  11. Breed-specific expression of GR exon 1 mRNA variants and profile of GR promoter CpG methylation in the hippocampus of newborn piglets.

    PubMed

    Sun, Q; Jia, Y; Li, R; Li, X; Yang, X; Zhao, R

    2014-11-01

    Glucocorticoid receptor (GR) transcription is driven by alternative promoters to produce different exon 1 mRNA variants. CpG methylation on GR promoters profoundly affects GR transcription. GR in hippocampus is critical for energy homeostasis and stress responses, yet it remains unclear whether hippocampal expression of GR exon 1 mRNA variants and the methylation status of GR promoters differ between Large White (LW) and Erhualian (EHL) pigs showing distinct metabolic and stress-coping characteristics. EHL pigs had higher hippocampus weight relative to BW (P<0.01), which was associated with higher serum cortisol level compared with LW pigs. Hippocampal expression of brain-derived neurotrophic factor (P<0.05) was significantly higher, while Bax, a pro-apoptotic gene, was significantly lower in EHL pigs (P<0.05). Hippocampal expression of total GR did not differ between breeds, yet GR exon 1 to 11 mRNA was significantly higher (P<0.01) in EHL pigs, which was associated with a trend of increase (P=0.057) in GR protein content. No significant breed difference was detected for the methylation status across the whole region of the proximal GR promoter, while CpG334 and CpG266.267 were differentially methylated, in a reversed manner, between breeds. The methylation status of CpGs 248, 259, 260, 268 and 271 was negatively correlated (P<0.05) with GR exon 1 to 11 mRNA abundance. Our results provide fundamental information on the breed-specific characteristics of GR and its mRNA variants expression and the status of DNA methylation on the proximal GR promoter in the pig hippocampus.

  12. The Grid Analysis and Display System (GrADS)

    NASA Technical Reports Server (NTRS)

    Kinter, James L., III

    1994-01-01

    During the period 1 September 1993 - 31 August 1994, further development of the Grid Analysis and Display System (GrADS) was conducted at the Center for Ocean-Land-Atmosphere Studies (COLA) of the Institute of Global Environment and Society, Inc. (IGES) under subcontract 5555-31 from the University Space Research Association (USRA) administered by The Center of Excellence in Space Data and Information Sciences (CESDIS). This final report documents progress made under this subcontract and provides directions on how to access the software and documentation developed therein. A short description of GrADS is provided followed by summary of progress completed and a summary of the distribution of the software to date and the establishment of research collaborations.

  13. An alternative approach to Mie-Grüneisen

    NASA Astrophysics Data System (ADS)

    Anderson, William W.

    2017-01-01

    The Mie-Grüneisen model, because of its simplicity and analyticity, is probably the most-used thermal equation of state in high-pressure physics. However, the usual method of implementing this model places unnecessary constraints on temperature calculations and fails to take advantage of information that can be obtained from the compression behavior of a material. As multiphase models that require explicit accounting for temperature become more common, these issues suggest that a return to the internal energy as the starting point for an EOS model is useful. Such a model, based on the Einstein thermal energy, is analytic and consistent with the Mie-Grüneisen model and can be coupled directly to the behavior of the 0 K isotherm when an appropriate model for Poisson's ratio is used. Additional terms can be incorporated to account for anharmonic and other effects.

  14. GR712RC- Dual-Core Processor- Product Status

    NASA Astrophysics Data System (ADS)

    Sturesson, Fredrik; Habinc, Sandi; Gaisler, Jiri

    2012-08-01

    The GR712RC System-on-Chip (SoC) is a dual core LEON3FT system suitable for advanced high reliability space avionics. Fault tolerance features from Aeroflex Gaisler’s GRLIB IP library and an implementation using Ramon Chips RadSafe cell library enables superior radiation hardness.The GR712RC device has been designed to provide high processing power by including two LEON3FT 32- bit SPARC V8 processors, each with its own high- performance IEEE754 compliant floating-point-unit and SPARC reference memory management unit.This high processing power is combined with a large number of serial interfaces, ranging from high-speed links for data transfers to low-speed control buses for commanding and status acquisition.

  15. Iceland's Grímsvötn volcano erupts

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2011-05-01

    About 13 months after Iceland's Eyjafjallajökull volcano began erupting on 14 April 2010, which led to extensive air traffic closures over Europe, Grímsvötn volcano in southeastern took its turn. Iceland's most active volcano, which last erupted in 2004 and lies largely beneath the Vatnajökull ice cap, began its eruption activity on 21 May, with the ash plume initially reaching about 20 kilometers in altitude, according to the Icelandic Meteorological Office. Volcanic ash from Grímsvötn has cancelled hundreds of airplane flights and prompted U.S. president Barack Obama to cut short his visit to Ireland. As Eos went to press, activity at the volcano was beginning to subside.

  16. e-VLBI detection of SN2007gr

    NASA Astrophysics Data System (ADS)

    Paragi, Z.; Kouveliotou, C.; Garrett, M. A.; Ramirez-Ruiz, E.; van Langevelde, H. J.; Szomoru, A.; Argo, M.

    2007-09-01

    We observed the Type Ibc SN2007gr on 6-7 September for 12 hours (21:00-09:00 UTC) at 4.97 GHz with the the European VLBI Network (EVN) using the e- VLBI technique. Participating telescopes were Darnhall, Jodrell Bank (MkII), Medicina, Onsala, Torun and Westerbork (phased array of 14 telescopes). The aggregate bitrate was 256 Mbps, except for Darnhall which contributed with an effective data rate of 128 Mbps due to analog bandwidth restrictions.

  17. Multidimensional multichannel FIR deconvolution using Gröbner bases.

    PubMed

    Zhou, Jianping; Do, Minh N

    2006-10-01

    We present a new method for general multidimensional multichannel deconvolution with finite impulse response (FIR) convolution and deconvolution filters using Gröbner bases. Previous work formulates the problem of multichannel FIR deconvolution as the construction of a left inverse of the convolution matrix, which is solved by numerical linear algebra. However, this approach requires the prior information of the support of deconvolution filters. Using algebraic geometry and Gröbner bases, we find necessary and sufficient conditions for the existence of exact deconvolution FIR filters and propose simple algorithms to find these deconvolution filters. The main contribution of our work is to extend the previous Gröbner basis results on multidimensional multichannel deconvolution for polynomial or causal filters to general FIR filters. The proposed algorithms obtain a set of FIR deconvolution filters with a small number of nonzero coefficients (a desirable feature in the impulsive noise environment) and do not require the prior information of the support. Moreover, we provide a complete characterization of all exact deconvolution FIR filters, from which good FIR deconvolution filters under the additive white noise environment are found. Simulation results show that our approaches achieve good results under different noise settings.

  18. Application of Gr/PMR-15 to commercial aircraft

    NASA Technical Reports Server (NTRS)

    Postlewaite, J.; Porter, K.; Mclaren, D.

    1985-01-01

    Following from early experience with polyimides on the SST program and Shuttle aft flap studies the Boeing Company is now working on collaborative programs with its principal nacelle suppliers to pursue the development of Gr/PMR-15 nacelle components. Two programs are currently in effect. The first program is directed specifically towards the flight test and service evaluation at the earliest possible date of a 747 nacelle core cowl structure. The second program seeks to firmly establish the producibility and cost of a 757 thrust reverser C duct in a production environment. The near term objectives of these programs include: (1) the comparison of estimated cost and weight of Gr/PMR-15 versus metal structure, (2) the engine test of representative composite structure, (3) the preliminary design and analysis of the C duct structure, and (4) the preparation of cost data and time schedules for the development and producibility program. In addition to powerplant structure, the propulsion ducting system has shown to be a strong candidate for Gr/PMR-15 application. Currently, the Boeing 747 Organization is evaluating the use of PMR-15 matrix composites to replace nearly 800 lbs of titanium ducting per airplane.

  19. Riboflavin supplementation does not attenuate hyperoxic lung injury in transgenic (spc-mt)hGR mice.

    PubMed

    Heyob, Kathryn M; Rogers, Lynette K; Tipple, Trent E; Welty, Stephen E

    2011-04-01

    The aims of this study were to test the hypothesis that mice expressing mitochondrially targeted human glutathione reductase (GR) driven by a surfactant protein C promoter ((spc-mt)hGR) are functionally riboflavin deficient and that this deficiency exacerbates hyperoxic lung injury. The authors further hypothesized that dietary supplementation with riboflavin (FADH) will improve the bioactivity of GR, thus enhancing resistance to hyperoxic lung injury. Transgenic (mt-spc)hGR mice and their nontransgenic littermates were fed control or riboflavin-supplemented diets upon weaning. At 6 weeks of age the mice were exposed to either room air (RA) or >95% O(2) for up to 84 hours. GR activities (with and without exogenous FADH) and GR protein levels were measured in lung tissue homogenates. Glutathione (GSH) and glutathione disulfide (GSSG) concentrations were assayed to identify changes in GR activity in vivo. Lung injury was assessed by right lung to body weight ratios and bronchoalveolar lavage protein concentrations. The data showed that enhanced GR activity in the mitochondria of lung type II cells does not protect adult mice from hyperoxic lung injury. Furthermore, the addition of riboflavin to the diets of (spc-mt)hGR mice neither enhances GR activities nor offers protection from hyperoxic lung injury. The results indicated that modulation of mitochondrial GR activity in lung type II cells is not an effective therapy to minimize hyperoxic lung injury.

  20. A significant effect of the TSPY1 copy number on spermatogenesis efficiency and the phenotypic expression of the gr/gr deletion.

    PubMed

    Shen, Ying; Yan, Yuanlong; Liu, Yunqiang; Zhang, Sizhong; Yang, Dong; Zhang, Peng; Li, Lei; Wang, Yan; Ma, Yongxin; Tao, Dachang; Yang, Yuan

    2013-04-15

    AZFc deletions cause a significant phenotypic heterogeneity with respect to spermatogenesis; however, the reason for this is poorly understood. Recently, testis-specific protein Y-encoded 1 (TSPY1) copy number variation (CNV) was determined to be a potential genetic modifier of spermatogenesis. We performed a large-scale cohort study to investigate the effect of TSPY1 CNV on spermatogenesis and to elucidate the possible contribution of TSPY1 genetic variation to the phenotypic expression of AZFc deletions. Haplogrouping of the Y-chromosome and quantification of the TSPY1 copy number were performed in 2272 Han Chinese males with different spermatogenic statuses (704 males with the b2/b4 or gr/gr deletion and 1568 non-AZFc-deleted males). Our data revealed that the TSPY1 copy number distributions were significantly different among non-AZFc-deleted males with different spermatogenic phenotypes. Lower sperm production and an elevated risk of spermatogenic failure were observed in males with fewer than 21 TSPY1 copies and in those with more than 55 copies relative to men with 21-35 copies. Similar results were observed in males with the gr/gr deletion. These findings indicate that TSPY1 CNV affects an individual's susceptibility to spermatogenic failure by modulating the efficiency of spermatogenesis and strongly suggest that there is a significant quantity effect of the TSPY1 copy number on the phenotypic expression of the gr/gr deletion. To our knowledge, this CNV is the first independent genetic factor that has been clearly observed to influence the spermatogenic status of gr/gr deletion carriers. A combined genetic analysis of the TSPY1 copy number and the gr/gr deletion could inform the clinical counselling of infertile couples.

  1. Long-term intermittent feeding restores impaired GR signaling in the hippocampus of aged rat.

    PubMed

    Tesic, Vesna; Perovic, Milka; Lazic, Divna; Kojic, Snezana; Smiljanic, Kosara; Ruzdijic, Sabera; Rakic, Ljubisav; Kanazir, Selma

    2015-05-01

    Diminished glucocorticoid signaling is associated with an age-related decline in hippocampal functioning. In this study we demonstrate the effect of intermittent, every other day (EOD) feeding on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the hippocampus of middle-aged (18-month-old) and aged (24-month-old) Wistar rats. In aged ad libitum-fed rats, a decrease in the level of total GR and GR phosphorylated at Ser(232) (pGR) was detected. Conversely, aged rats subjected to EOD feeding, starting from 6 months of age, showed an increase in GR and pGR levels and a higher content of hippocampal corticosterone. Furthermore, prominent nuclear staining of pGR was observed in CA1 pyramidal and DG granule neurons of aged EOD-fed rats. These changes were accompanied by increased Sgk-1 and decreased GFAP transcription, pointing to upregulated transcriptional activity of GR. EOD feeding also induced an increase in the expression of the mineralocorticoid receptor. Our results reveal that intermittent feeding restores impaired GR signaling in the hippocampus of aged animals by inducing rather than by stabilizing GR signaling during aging.

  2. Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer.

    PubMed

    Abduljabbar, Rezvan; Negm, Ola H; Lai, Chun-Fui; Jerjees, Dena A; Al-Kaabi, Methaq; Hamed, Mohamed R; Tighe, Patrick J; Buluwela, Lakjaya; Mukherjee, Abhik; Green, Andrew R; Ali, Simak; Rakha, Emad A; Ellis, Ian O

    2015-04-01

    The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily of transcription factors, which exerts anti-proliferative and anti-apoptotic activities. The GR is expressed in a large proportion of breast cancer (BC) although levels generally decrease during cancer progression. This study aimed to determine the clinical and biological significance of GR expression using a large series of early-stage BC with long-term follow-up and BC cell lines. Immunohistochemistry was used to assess the expression of GR in 999 cases of primary invasive BC prepared as tissue microarrays. Reverse phase protein microarray was used to assess the expression of GR in MCF7 and MDA-MB-231 cell lines. Nuclear expression of GR was observed in 61.6 % of breast tumours and was associated with features of good prognosis including smaller tumour size and lower grade with less pleomorphism and low mitotic count. GR expression was positively correlated with expression of oestrogen (ER) and progesterone receptors. In ER-positive tumours, GR was associated with other features of favourable outcome including FOXA1, GATA3 and BEX1 expression, while low GR expression was associated with high Ki67, p53 and CD71 expression. GR expression is associated with features of good outcome but does not provide prognostic information independent of size, stage and grade. Understanding the receptor and its effects on BC behaviour is essential for avoiding any unwanted effects from the use of glucocorticoids in routine oncology practice.

  3. Microstrain in pyrope-grossular garnet solid solution at high pressure: a case study of Py90Gr10 and Py10Gr90 up to 15 GPa

    NASA Astrophysics Data System (ADS)

    Du, Wei; Li, Xuefei; Li, Baosheng

    2016-12-01

    Single-phase, well-sintered, translucent polycrystalline garnets with compositions of Py90Gr10 and Py10Gr90 were synthesized at 6 GPa and 1400 °C using a multi-anvil apparatus. X-ray diffraction (XRD) data for these garnet solid solutions were collected with both high-resolution synchrotron X-ray and standard laboratory X-ray sources. Analysis of the FWHM of the XRD peaks using Williamson-Hall plot yields microstrains around 0.12% for Py90Gr10 and 0.09% for Py10Gr90. The FWHM of Py10Gr90 garnet as well as the derived microstrain remains constant up to 11 GPa, followed by a continuous increase to the experimental peak pressure 15 GPa caused by elastic strain in response to deviatoric/anisotropic stresses. The FWHM and microstrain for Py90Gr10 remain constant to the measurement limit at 7 GPa. The microstrain of pyrope-grossular garnets exhibits a nonlinear dependence on composition, showing two peaks near Py20Gr80 and Py80Gr20, which may be associated with local structural heterogeneities arising from Mg and Ca substitution. Using a third-order Birch-Murnaghan equation of state, the bulk modulus is constrained to be Κ 0 = 171.8 ± 2.1 GPa (with Κ {0/'} fixed to 5.92) for Py10Gr90 and Κ 0 = 174.3 ± 2.5 GPa (with Κ {0/'} fixed to 4.4) for Py90Gr10, both of which are much larger than that for intermediate composition close to Py50Gr50 but comparable to that for their corresponding end members. The relatively larger microstrain and higher bulk moduli for Py10Gr90 and Py90Gr10 garnets could be related to short-range ordering of Mg and Ca cations in garnet structure due to substitution, which results in different local environments for Mg and Ca cations along the pyrope-grossular solid solution.

  4. A topological extension of GR: Black holes induce dark energy

    NASA Astrophysics Data System (ADS)

    Spaans, M.

    2013-02-01

    A topological extension of general relativity is presented. The superposition principle of quantum mechanics, as formulated by the Feynman path integral, is taken as a starting point. It is argued that the trajectories that enter this path integral are distinct and thus that space-time topology is multiply connected. Specifically, space-time at the Planck scale consists of a lattice of three-tori that facilitates many distinct paths for particles to travel along. To add gravity, mini black holes are attached to this lattice. These mini black holes represent Wheeler's quantum foam and result from the fact that GR is not conformally invariant. The number of such mini black holes in any time-slice through four-space is found to be equal to the number of macroscopic (so long-lived) black holes in the entire universe. This connection, by which macroscopic black holes induce mini black holes, is a topological expression of Mach's principle. The proposed topological extension of GR can be tested because, if correct, the dark energy density of the universe should be proportional the total number of macroscopic black holes in the universe at any time. This prediction, although strange, agrees with current astrophysical observations.

  5. TLR7/9-mediated monocytosis and maturation of Gr-1(hi) inflammatory monocytes towards Gr-1(lo) resting monocytes implicated in murine lupus.

    PubMed

    Santiago-Raber, Marie-Laure; Baudino, Lucie; Alvarez, Montserrat; van Rooijen, Nico; Nimmerjahn, Falk; Izui, Shozo

    2011-11-01

    Circulating monocytes are divided into two major, phenotypically and functionally distinct subsets: Gr-1(hi) "inflammatory" and Gr-1(lo) "resting" monocytes. One of the unique cellular abnormalities in lupus-prone mice is monocytosis, which is characterized by a selective expansion of Gr-1(lo) monocytes and dependent on the expression of stimulatory IgG Fc receptors (FcγR). We speculated that IgG immune complexes containing nuclear antigens could stimulate Gr-1(hi) monocytes through interaction with FcγRs and then TLR7 and TLR9, thereby promoting the maturation towards Gr-1(lo) monocytes. In the present study, we assessed this hypothesis by analyzing effects of TLR9 or TLR7 agonist on monocytes in vivo. The analysis of various surface markers differentially expressed on both subsets of monocytes in combination with selective depletion of either subset revealed that within 48 h after injection of the TLR9 agonist CpG, approximately one third of Gr-1(hi) monocytes became phenotypically identical to Gr-1(lo) monocytes. In addition, we observed approximately two-fold increases in the total monocyte population 8-24 h after injection of CpG. Moreover, the activation of TLR9 resulted in an increased expression of stimulatory FcγRIV relative to inhibitory FcγRIIB on monocytes, thereby enhancing their responsiveness to IgG immune complexes. Essentially identical results were obtained after stimulation of TLR7 with a synthetic agonist (1V136). Our results indicate that the activation of TLR7 and TLR9 not only induced the maturation of a fraction of Gr-1(hi) monocytes towards Gr-1(lo) monocytes but also promoted the overall generation of monocytes, thereby supporting the critical role of TLR7 and TLR9 for the development of monocytosis in lupus-prone mice.

  6. Cisplatin-Induced Conditioned Taste Aversion: Attenuation by Dexamethasone but not Zacopride or GR38032F

    DTIC Science & Technology

    1992-01-01

    1988, The potential anxiolytic activity of GR38032F, a 5 - HT3 - receptor antagonist . Br. J. Pharmacol. 93, 985. References Kilpatrick. G.J.. B.J. Jones...April IM92 accepted 5 May 1992 3 7 The 54HT, receptor antagonists zacotiride and GR38032F are highly effective inhibitors of emcsii induced by...to 5 -H1’, receptor blockade. 5 -HT., receptor antagonists ; Zacopridc: GR38032F; Desamethasone: Cisplatin: Taste aversion (conditioned) I. Introductlon

  7. Reduced hippocampal neurogenesis in the GR(+/-) genetic mouse model of depression.

    PubMed

    Kronenberg, Golo; Kirste, Imke; Inta, Dragos; Chourbaji, Sabine; Heuser, Isabella; Endres, Matthias; Gass, Peter

    2009-12-01

    Glucocorticoid receptor (GR) heterozygous mice (GR(+/- )) represent a valuable animal model for major depression. GR(+/- ) mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR(+/- ) animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied here the effects of the GR(+/- ) genotype on neurogenesis in vivo. In a 2 x 2 design, GR(+/- ) mice and GR(+/+) littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks later. BrdU cell counts were significantly reduced as an effect of GR(+/- ) genotype and as an effect of stress. Majority of the BrdU+ cells showed co-labeling with mature neuronal marker NeuN or astrocytic marker S100beta with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced neurogenesis in GR(+/- ) mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis, stress, neurotrophins, and behavioral symptoms of and susceptibility to depression.

  8. 77 FR 40511 - Safety Zone; GR Symphony Fireworks Display, Kalamazoo Lake, Saugatuck, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-10

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; GR Symphony Fireworks Display, Kalamazoo... restrict vessels from a portion of Kalamazoo Lake during the GR Symphony Fireworks display. This temporary safety zone is necessary to protect spectators and vessels from the hazards associated with a...

  9. Genome-wide analysis of glutathione reductase (GR) genes from rice and Arabidopsis.

    PubMed

    Trivedi, Dipesh Kumar; Gill, Sarvajeet Singh; Yadav, Sandep; Tuteja, Narendra

    2013-02-01

    Plant cells and tissues remain always on risk under abiotic and biotic stresses due to increased production of reactive oxygen species (ROS). Plants protect themselves against ROS induced oxidative damage by the upregulation of antioxidant machinery. Out of many components of antioxidant machinery, glutathione reductase (GR, EC 1.6.4.2) and glutathione (GSH, γ-Glu-Cys-Gly) play important role in the protection of cell against oxidative damage. In stress condition, the GR helps in maintaining the reduced glutathione pool for strengthening the antioxidative processes in plants. Present study investigates genome wide analysis of GR from rice and Arabidopsis. We were able to identify 3 rice GR genes (LOC_Os02 g56850, LOC_Os03 g06740, LOC_Os10 g28000) and 2 Arabidopsis GR genes (AT3G54660, AT3G24170) from their respective genomes on the basis of their annotation as well as the presence of pyridine nucleotide-disulphide oxidoreductases class-I active site. The evolutionary relationship of the GR genes from rice and Arabidopsis genomes was analyzed using the multiple sequence alignment and phylogenetic tree. This revealed evolutionary conserved pyridine nucleotide-disulphide oxidoreductases class-I active site among the GR protein in rice and Arabidopsis. This study should make an important contribution to our better understanding of the GR under normal and stress condition in plants.

  10. Evolutionary differences in food preference rely on Gr64e, a receptor for glycerol.

    PubMed

    Wisotsky, Zev; Medina, Adriana; Freeman, Erica; Dahanukar, Anupama

    2011-11-06

    Very little is known about how stimuli that are typically not rich in sugars, such as beer, trigger attractive gustatory responses in Drosophila. We identified a member of the gustatory receptor family, Gr64e, as a receptor that is required for feeding preference for beer and other sources that have fermenting yeast. We found that Gr64e is required for neuronal and behavioral responses to glycerol, an abundant component of growing yeast and fermentation products. Ectopic expression of Gr64e in an olfactory neuron conferred responsiveness to glycerol. We also found that Drosophila species that are predicted to carry pseudogenes of Gr64e had reduced glycerol sensitivity. Our results provide insight into the molecular mechanisms of feeding acceptance of yeast products and raise the possibility that Gr64e contributes to specific evolutionary variations in appetitive selectivity across Drosophila species.

  11. The selective carotid arterial vasoconstrictor action of GR43175 in anaesthetized dogs.

    PubMed Central

    Feniuk, W.; Humphrey, P. P.; Perren, M. J.

    1989-01-01

    1. GR43175 is a highly selective agonist at 5-HT1-like receptors in the dog saphenous vein. This study describes the haemodynamic effects of GR43175 in barbitone-anaesthetized dogs. 2. GR43175 (1-1000 micrograms kg-1, i.v.) produced dose-dependent decreases in carotid arterial blood flow with little or no change in arterial blood pressure. The decrease in blood flow was associated with an increase in carotid arterial vascular resistance. In preliminary studies, the dose of GR43175 producing 50% of the maximum carotid vasoconstrictor response was 39 +/- 8 micrograms kg-1, i.v. 3. In comparative regional haemodynamic studies, GR43175 (1-1000 micrograms kg-1, i.v.) had little effect on total peripheral resistance or resistance in the mesenteric, vertebral and coronary arterial vascular beds. Low doses of GR43175 decreased, whilst high doses (100 micrograms kg-1, i.v. and above) increased femoral arterial vascular resistance. GR43175 (1-1000 micrograms kg-1, i.v.) had no effect on respiratory inflation pressure. In doses of 100 micrograms kg-1 i.v. and above, GR43175 caused small decreases in heart rate. 4. The carotid arterial vasoconstrictor action of GR43175 was resistant to antagonism by the 5-HT2 receptor, 5-HT3 receptor and alpha-adrenoceptor blocking drugs, ketanserin, MDL72222 and phentolamine respectively, but could be antagonized by the non-selective 5-HT1-like receptor blocking drug methiothepin. Methiothepin had no effect on the carotid vasoconstrictor action of the thromboxane A2 mimetic, U46619. 5. The results demonstrate that GR43175 produces a selective vasoconstriction in the carotid arterial circulation of anaesthetized dogs via activation of 5-HT1-like receptors, which appear similar to those mediating contraction of the dog isolated saphenous vein. PMID:2538184

  12. Hepatic Glucocorticoid Receptor Plays a Greater Role Than Adipose GR in Metabolic Syndrome Despite Renal Compensation.

    PubMed

    Bose, Sandip K; Hutson, Irina; Harris, Charles A

    2016-12-01

    Exogenous glucocorticoid administration results in hyperglycemia, insulin resistance, hepatic dyslipidemia, and hypertension, a constellation of findings known as Cushing's syndrome. These effects are mediated by the glucocorticoid receptor (GR). Because GR activation in liver and adipose has been implicated in metabolic syndrome (MS), we wanted to determine the role of GR in these tissues in the development of MS. Because GR knockout (KO) mice (whole-body KO) exhibit perinatal lethality due to respiratory failure, we generated tissue-specific (liver or adipose) GRKO mice using cre-lox technology. Real-time PCR analysis of liver mRNA from dexamethasone-treated wildtype (WT) and liver GRKO mice indicated that hepatic GR regulates the expression of key genes involved in gluconeogenesis and glycogen metabolism. Interestingly, we have observed that liver-specific deletion of GR resulted in a significant increase in mRNA expression of key genes involved in gluconeogenesis and glycogen metabolism in kidney tissue, indicating a compensatory mechanism to maintain glucose homeostasis. We have also observed that GR plays an important role in regulating the mRNA expression of key genes involved in lipid metabolism. Liver GRKO mice demonstrated decreased fat mass and liver glycogen content compared with WT mice administered dexamethasone for 2 weeks. Adipose-specific deletion of GR did not alter glucose tolerance or insulin sensitivity of adipose GRKO mice compared with WT mice administrated dexamethasone. This indicates that liver GR might be more important in development of MS in dexamethasone-treated mice, whereas adipose GR plays a little role in these paradigms.

  13. Role of ligand-dependent GR phosphorylation and half-life in determination of ligand-specific transcriptional activity.

    PubMed

    Avenant, Chanel; Ronacher, Katharina; Stubsrud, Elisabeth; Louw, Ann; Hapgood, Janet P

    2010-10-07

    A central question in glucocorticoid mechanism of action via the glucocorticoid receptor (GR) is what determines ligand-selective transcriptional responses. Using a panel of 12 GR ligands, we show that the extent of GR phosphorylation at S226 and S211, GR half-life and transcriptional response, occur in a ligand-selective manner. While GR phosphorylation at S226 was shown to inhibit maximal transcription efficacy, phosphorylation at S211 is required for maximal transactivation, but not for transrepression efficacy. Both ligand-selective GR phosphorylation and half-life correlated with efficacy for transactivation and transrepression. For both expressed and endogenous GR, in two different cell lines, agonists resulted in the greatest extent of phosphorylation and the greatest extent of GR downregulation, suggesting a link between these functions. However, using phosphorylation-deficient GR mutants we established that phosphorylation of the GR at S226 or S211 does not determine the rank order of ligand-selective GR transactivation. These results are consistent with a model whereby ligand-selective GR phosphorylation and half-life are a consequence of upstream events, such as ligand-specific GR conformations, which are maintained in the phosphorylation mutants.

  14. Evaluating the cytotoxicity of innate immune effector cells using the GrB ELISPOT assay

    PubMed Central

    Shafer-Weaver, Kimberly A; Sayers, Thomas; Kuhns, Douglas B; Strobl, Susan L; Burkett, Mark W; Baseler, Michael; Malyguine, Anatoli

    2004-01-01

    Background This study assessed the Granzyme B (GrB) ELISPOT as a viable alternative to the 51Cr-release assay for measuring cytotoxic activity of innate immune effector cells. We strategically selected the GrB ELISPOT assay because GrB is a hallmark effector molecule of cell-mediated destruction of target cells. Methods We optimized the GrB ELISPOT assay using the human-derived TALL-104 cytotoxic cell line as effectors against K562 target cells. Titration studies were performed to assess whether the ELISPOT assay could accurately enumerate the number of GrB-secreting effector cells. TALL-104 were treated with various secretion inhibitors and utilized in the GrB ELISPOT to determine if GrB measured in the ELISPOT was due to degranulation of effector cells. Additionally, CD107a expression on effector cells after effector-target interaction was utilized to further confirm the mechanism of GrB release by TALL-104 and lymphokine-activated killer (LAK) cells. Direct comparisons between the GrB ELISPOT, the IFN-γ ELISPOT and the standard 51Cr-release assays were made using human LAK cells. Results Titration studies demonstrated a strong correlation between the number of TALL-104 and LAK effector cells and the number of GrB spots per well. GrB secretion was detectable within 10 min of effector-target contact with optimal secretion observed at 3–4 h; in contrast, optimal IFN-γ secretion was not observed until 24 h. The protein secretion inhibitor, brefeldin A, did not inhibit the release of GrB but did abrogate IFN-γ production by TALL-104 cells. GrB secretion was abrogated by BAPTA-AM (1,2-bis-(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid tetra(acetoxymethyl) ester), which sequesters intracellular Ca2+, thereby preventing degranulation. The number of effector cells expressing the degranulation associated glycoprotein CD107a increased after interaction with target cells and correlated with the stimulated release of GrB measured in the ELISPOT assay. Conclusions

  15. Genomic redistribution of GR monomers and dimers mediates transcriptional response to exogenous glucocorticoid in vivo.

    PubMed

    Lim, Hee-Woong; Uhlenhaut, N Henriette; Rauch, Alexander; Weiner, Juliane; Hübner, Sabine; Hübner, Norbert; Won, Kyoung-Jae; Lazar, Mitchell A; Tuckermann, Jan; Steger, David J

    2015-06-01

    Glucocorticoids (GCs) are commonly prescribed drugs, but their anti-inflammatory benefits are mitigated by metabolic side effects. Their transcriptional effects, including tissue-specific gene activation and repression, are mediated by the glucocorticoid receptor (GR), which is known to bind as a homodimer to a palindromic DNA sequence. Using ChIP-exo in mouse liver under endogenous corticosterone exposure, we report here that monomeric GR interaction with a half-site motif is more prevalent than homodimer binding. Monomers colocalize with lineage-determining transcription factors in both liver and primary macrophages, and the GR half-site motif drives transcription, suggesting that monomeric binding is fundamental to GR's tissue-specific functions. In response to exogenous GC in vivo, GR dimers assemble on chromatin near ligand-activated genes, concomitant with monomer evacuation of sites near repressed genes. Thus, pharmacological GCs mediate gene expression by favoring GR homodimer occupancy at classic palindromic sites at the expense of monomeric binding. The findings have important implications for improving therapies that target GR.

  16. Y chromosome gr/gr subdeletion is associated with lower semen quality in young men from the general Japanese population but not in fertile Japanese Men.

    PubMed

    Sato, Youichi; Iwamoto, Teruaki; Shinka, Toshikatsu; Nozawa, Shiari; Yoshiike, Miki; Koh, Eitetsue; Kanaya, Jiro; Namiki, Mikio; Matsumiya, Kiyomi; Tsujimura, Akira; Komatsu, Kiyoshi; Itoh, Naoki; Eguchi, Jiro; Yamauchi, Aiko; Nakahori, Yutaka

    2014-06-01

    Several case-control studies have investigated whether Y chromosome haplogroups or deletions are associated with spermatogenic failure. However, the relationships between Y chromosome haplogroups or deletions and semen quality in general population have not been elucidated. In this study, we assessed relationships between Y chromosome haplogroups or deletions and semen parameters in 791 fertile Japanese men and 1221 young men from the general Japanese population. We found that the haplogroup D2 (M55 lineage) was significantly associated with lower semen parameters, especially total motile sperm count (P = 0.00051, beta = -0.097), in men from the general population but not in fertile men. In addition, we found that the gr/gr subdeletion was associated with semen quality and in particular, strongly associated with decreased sperm motility (P = 0.00041, beta = -3.14) and total motile sperm count (P = 0.00031, beta = -0.099) in men from the general population but not in fertile men. The combined analysis of fertile Japanese men and men from the general Japanese population showed that the haplogroup D2 (M55 lineage) and the gr/gr subdeletion were strongly associated with reduced sperm motility (P = 0.00056, beta = -2.71, and P = 7.7 × 10(-5), beta = -3.05, respectively) and that haplogroup O2b1 was strongly associated with elevated sperm motility (P = 0.00089, beta = 2.94). These observations add further support for the view that the gr/gr subdeletion diminishes sperm motility that consequently may result in male infertility.

  17. Extending Clause Learning of SAT Solvers with Boolean Gröbner Bases

    NASA Astrophysics Data System (ADS)

    Zengler, Christoph; Küchlin, Wolfgang

    We extend clause learning as performed by most modern SAT Solvers by integrating the computation of Boolean Gröbner bases into the conflict learning process. Instead of learning only one clause per conflict, we compute and learn additional binary clauses from a Gröbner basis of the current conflict. We used the Gröbner basis engine of the logic package Redlog contained in the computer algebra system Reduce to extend the SAT solver MiniSAT with Gröbner basis learning. Our approach shows a significant reduction of conflicts and a reduction of restarts and computation time on many hard problems from the SAT 2009 competition.

  18. Proposed Consent Agreement and Final Order: Gene R. Cheeseman and GR Cheeseman Construction LLC

    EPA Pesticide Factsheets

    EPA's proposed Consent Agreement and Final Order in the matter of Gene R. Cheeseman and GR Cheeseman Construction LLC for violations of the Clean Water Act at their 5230 Shaune Drive property located in Juneau, Alaska.

  19. Proposed Settlement with Gene R. Cheeseman and GR Cheeseman Construction LLC

    EPA Pesticide Factsheets

    Public notice of EPA's proposed penalty against Gene R. Cheeseman and GR Cheeseman Construction LLC for violations of the Clean Water Act at their 5230 Shaune Drive property located in Juneau, Alaska.

  20. HDAC6 regulates GR signaling in serotonin pathways with critical impact on stress resilience

    PubMed Central

    Espallergues, Julie; Teegarden, Sarah L.; Veerakumar, Avin; Boulden, Janette; Challis, Collin; Jochems, Jeanine; Chan, Michael; Petersen, Tess; Deneris, Evan; Matthias, Patrick; Hahn, Chang-Gyu; Lucki, Irwin; Beck, Sheryl G.; Berton, Olivier

    2012-01-01

    Genetic variations in certain components of the glucocorticoid receptor (GR) chaperone complex have been associated with the development of stress-related affective disorders and individual variability in therapeutic responses to antidepressants. Mechanisms that link GR chaperoning and stress susceptibility are not well understood. Here, we show that the effects of glucocorticoid hormones on socioaffective behaviors are critically regulated via reversible acetylation of Hsp90, a key component of the GR chaperone complex. We provide pharmacological and genetic evidence indicating that the cytoplasmic lysine deacetylase HDAC6 controls Hsp90 acetylation in the brain, and thereby modulates Hsp90-GR protein-protein interactions, as well as hormone- and stress-induced GR translocation, with a critical impact on GR downstream signaling and behavior. Pet1-Cre driven deletion of HDAC6 in serotonin neurons, the densest HDAC6-expressing cell group in the mouse brain, dramatically reduced acute anxiogenic effects of the glucocorticoid hormone corticosterone in the open field, elevated plus maze, and social interaction tests. Serotonin-selective depletion of HDAC6 also blocked the expression of social avoidance in mice exposed to chronic social defeat and concurrently prevented the electrophysiological and morphological changes induced, in serotonin neurons, by this murine model of traumatic stress. Together, these results identify HDAC6 inhibition as a potential new strategy for pro-resilience and antidepressant interventions through regulation of the Hsp90-GR heterocomplex and focal prevention of GR signaling in serotonin pathways. Our data thus uncover an alternate mechanism by which pan-HDAC inhibitors may regulate stress-related behaviors independently of their action on histones. PMID:22457490

  1. The Stat3/GR interaction code: predictive value of direct/indirect DNA recruitment for transcription outcome.

    PubMed

    Langlais, David; Couture, Catherine; Balsalobre, Aurélio; Drouin, Jacques

    2012-07-13

    Transcription factor recruitment to genomic sites of action is primarily due to direct protein:DNA interactions. The subsequent recruitment of coregulatory complexes leads to either transcriptional activation or repression. In contrast to this canonical scheme, some transcription factors, such as the glucocorticoid receptor (GR), behave as transcriptional repressors when recruited to target genes through protein tethering. We have investigated the genome-wide prevalence of tethering between GR and Stat3 and found nonreciprocal interactions, namely that GR tethering to DNA-bound Stat3 results in transcriptional repression, whereas Stat3 tethering to GR results in synergism. Further, other schemes of GR and Stat3 corecruitment to regulatory modules result in transcriptional synergism, including neighboring and composite binding sites. The results indicate extensive transcriptional interactions between Stat3 and GR; further, they provide a genome-wide assessment of transcriptional regulation by tethering and a molecular basis for integration of signals mediated by GR and Stats in health and disease.

  2. Octopamine neuromodulation regulates Gr32a-linked aggression and courtship pathways in Drosophila males.

    PubMed

    Andrews, Jonathan C; Fernández, María Paz; Yu, Qin; Leary, Greg P; Leung, Adelaine K W; Kavanaugh, Michael P; Kravitz, Edward A; Certel, Sarah J

    2014-05-01

    Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-Fru(M) neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway.

  3. Activation of GR but not PXR by dexamethasone attenuated acetaminophen hepatotoxicities via Fgf21 induction.

    PubMed

    Vispute, Saurabh G; Bu, Pengli; Le, Yuan; Cheng, Xingguo

    2017-03-01

    Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity. Our results showed that DEX dose/concentration- and time-dependently increased Fgf21 mRNA and protein expression in mouse liver as well as cultured mouse and human hepatoma cells. By using PXR-null mouse model, we demonstrated that DEX induced Fgf21 expression by a PXR-independent mechanism. In cultured mouse and human hepatoma cells, inhibition of GR signaling, by RU486 (Mifepristone) or GR silencing using GR-specific siRNA, attenuated DEX-induced Fgf21 expression. In addition, DEX increased luciferase reporter activity driven by the 3.0-kb mouse and human Fgf21/FGF21 gene promoter. Further, ChIP-qPCR assays demonstrated that DEX increased the binding of GR to the specific cis-regulatory elements located in the 3.0-kb mouse and human Fgf21/FGF21 gene promoter. Pretreatment of 2mg/kg DEX ameliorated APAP-induced liver injury in wild-type but not Fgf21-null mice. In conclusion, via GR activation, DEX induced Fgf21 expression in mouse liver and human hepatoma cells.

  4. Chronic Psychosocial Stress and Negative Feedback Inhibition: Enhanced Hippocampal Glucocorticoid Signaling despite Lower Cytoplasmic GR Expression

    PubMed Central

    Füchsl, Andrea M.; Reber, Stefan O.

    2016-01-01

    Chronic subordinate colony housing (CSC), a pre-clinically validated mouse model for chronic psychosocial stress, results in increased basal and acute stress-induced plasma adrenocorticotropic hormone (ACTH) levels. We assessed CSC effects on hippocampal glucocorticoid (GC) receptor (GR), mineralocorticoid receptor (MR), and FK506 binding protein (FKBP51) expression, acute heterotypic stressor-induced GR translocation, as well as GC effects on gene expression and cell viability in isolated hippocampal cells. CSC mice showed decreased GR mRNA and cytoplasmic protein levels compared with single-housed control (SHC) mice. Basal and acute stress-induced nuclear GR protein expression were comparable between CSC and SHC mice, as were MR and FKBP51 mRNA and/or cytoplasmic protein levels. In vitro the effect of corticosterone (CORT) on hippocampal cell viability and gene transcription was more pronounced in CSC versus SHC mice. In summary, CSC mice show an, if at all, increased hippocampal GC signaling capacity despite lower cytoplasmic GR protein expression, making negative feedback deficits in the hippocampus unlikely to contribute to the increased ACTH drive following CSC. PMID:27057751

  5. Chronic Psychosocial Stress and Negative Feedback Inhibition: Enhanced Hippocampal Glucocorticoid Signaling despite Lower Cytoplasmic GR Expression.

    PubMed

    Füchsl, Andrea M; Reber, Stefan O

    2016-01-01

    Chronic subordinate colony housing (CSC), a pre-clinically validated mouse model for chronic psychosocial stress, results in increased basal and acute stress-induced plasma adrenocorticotropic hormone (ACTH) levels. We assessed CSC effects on hippocampal glucocorticoid (GC) receptor (GR), mineralocorticoid receptor (MR), and FK506 binding protein (FKBP51) expression, acute heterotypic stressor-induced GR translocation, as well as GC effects on gene expression and cell viability in isolated hippocampal cells. CSC mice showed decreased GR mRNA and cytoplasmic protein levels compared with single-housed control (SHC) mice. Basal and acute stress-induced nuclear GR protein expression were comparable between CSC and SHC mice, as were MR and FKBP51 mRNA and/or cytoplasmic protein levels. In vitro the effect of corticosterone (CORT) on hippocampal cell viability and gene transcription was more pronounced in CSC versus SHC mice. In summary, CSC mice show an, if at all, increased hippocampal GC signaling capacity despite lower cytoplasmic GR protein expression, making negative feedback deficits in the hippocampus unlikely to contribute to the increased ACTH drive following CSC.

  6. Aberrant corticosteroid metabolism in tumor cells enables GR takeover in enzalutamide resistant prostate cancer.

    PubMed

    Li, Jianneng; Alyamani, Mohammad; Zhang, Ao; Chang, Kai-Hsiung; Berk, Michael; Li, Zhenfei; Zhu, Ziqi; Petro, Marianne; Magi-Galluzzi, Cristina; Taplin, Mary-Ellen; Garcia, Jorge A; Courtney, Kevin; Klein, Eric A; Sharifi, Nima

    2017-02-13

    Prostate cancer is driven by androgen stimulation of the androgen receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs survival, but resistance and lethal disease eventually prevail. Emerging data suggest that the glucocorticoid receptor (GR) is upregulated in this context, stimulating expression of AR-target genes that permit continued growth despite AR blockade. However, countering this mechanism by administration of GR antagonists is problematic because GR is essential for life. We show that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, AMFR, mediating loss of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate GR and enzalutamide resistance. Remarkably, reinstatement of 11β-HSD2 expression, or AMFR loss, reverses enzalutamide resistance in mouse xenograft tumors. Together, these findings reveal a surprising metabolic mechanism of enzalutamide resistance that may be targeted with a strategy that circumvents a requirement for systemic GR ablation.

  7. Aberrant corticosteroid metabolism in tumor cells enables GR takeover in enzalutamide resistant prostate cancer

    PubMed Central

    Li, Jianneng; Alyamani, Mohammad; Zhang, Ao; Chang, Kai-Hsiung; Berk, Michael; Li, Zhenfei; Zhu, Ziqi; Petro, Marianne; Magi-Galluzzi, Cristina; Taplin, Mary-Ellen; Garcia, Jorge A; Courtney, Kevin; Klein, Eric A; Sharifi, Nima

    2017-01-01

    Prostate cancer is driven by androgen stimulation of the androgen receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs survival, but resistance and lethal disease eventually prevail. Emerging data suggest that the glucocorticoid receptor (GR) is upregulated in this context, stimulating expression of AR-target genes that permit continued growth despite AR blockade. However, countering this mechanism by administration of GR antagonists is problematic because GR is essential for life. We show that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, AMFR, mediating loss of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate GR and enzalutamide resistance. Remarkably, reinstatement of 11β-HSD2 expression, or AMFR loss, reverses enzalutamide resistance in mouse xenograft tumors. Together, these findings reveal a surprising metabolic mechanism of enzalutamide resistance that may be targeted with a strategy that circumvents a requirement for systemic GR ablation. DOI: http://dx.doi.org/10.7554/eLife.20183.001 PMID:28191869

  8. Evaluation of the Comparative Corrosion Resistance Between AKOT Ti Alloy and Ti Gr 7 Alloy

    SciTech Connect

    Lian, T

    2005-08-01

    In its current design, the drip shields for the high-level nuclear waste containers for the Yucca Mountain repository will be mainly made using Ti Gr 7 (R52400). Ti Gr 7 is a highly corrosion resistant alloy, especially because it contains 0.15% palladium (Pd). The goal of this study was to determine whether an AKOT low-Pd (0.01%) titanium alloy would have a similar corrosion resistance than the more expensive Ti Gr 7 in environments that could be related to the performance of the drip shield. The focus of this testing program was on the susceptibility of the alloys to localized corrosion. Therefore, only artificially creviced specimens were used.

  9. Grüneisen parameter studies on heavy fermion quantum criticality

    NASA Astrophysics Data System (ADS)

    Gegenwart, Philipp

    2016-11-01

    The Grüneisen parameter, experimentally determined from the ratio of thermal expansion to specific heat, quantifies the pressure dependence of characteristic energy scales of matter. It is highly enhanced for Kondo lattice systems, whose properties are strongly dependent on the pressure sensitive antiferromagnetic exchange interaction between f- and conduction electrons. In this review, we focus on the divergence of the Grüneisen parameter and its magnetic analogue, the adiabatic magnetocaloric effect, for heavy-fermion metals near quantum critical points. We compare experimental results with current theoretical models, including the effect of strong geometrical frustration. We also discuss the possibility of using materials with the divergent magnetic Grüneisen parameter for adiabatic demagnetization cooling to very low temperatures.

  10. Grüneisen parameter studies on heavy fermion quantum criticality.

    PubMed

    Gegenwart, Philipp

    2016-11-01

    The Grüneisen parameter, experimentally determined from the ratio of thermal expansion to specific heat, quantifies the pressure dependence of characteristic energy scales of matter. It is highly enhanced for Kondo lattice systems, whose properties are strongly dependent on the pressure sensitive antiferromagnetic exchange interaction between f- and conduction electrons. In this review, we focus on the divergence of the Grüneisen parameter and its magnetic analogue, the adiabatic magnetocaloric effect, for heavy-fermion metals near quantum critical points. We compare experimental results with current theoretical models, including the effect of strong geometrical frustration. We also discuss the possibility of using materials with the divergent magnetic Grüneisen parameter for adiabatic demagnetization cooling to very low temperatures.

  11. Effect of Grīvā Vasti in management of Grīvā Asthi Sandhi Gata Vāta (Cervical Spondylosis)

    PubMed Central

    Pandey, Yogesh Kumar; Shalini; Sharma, Ajay Kumar

    2013-01-01

    Introduction: Cervical spondylosis is a general term for age-related wear and tear affecting the spinal disks in the neck. Keeping in view the increasing incidence of this problem in modern society a study was conducted with following. Aims and Objectives: The aim of the following study is to assess the efficacy of Grīvā Vasti in the management of cervical spondylosis. Materials and Methods: The study was conducted on 10 clinically, pathologically, and radiologically diagnosed patients of cervical spondylosis, selected from outpatient department/In -patient department wing of P.G. Department of Kāya Chikitsā, N.I.A., Jaipur, satisfying the inclusion criteria. Patients were treated with Grīvā Vasti with Daśamūla Tailam for 35-45 min duration, for 14 days. Assessments were performed with regard to neck disability index before and after treatment. Statistical Analysis: Statistical analysis was done with the help of Instat GraphPad 3 using Wilcoxon matched-pairs signed ranks test. Result: Relief in neck disability index was 65.70%, which was statistically significant (P < 0.01). Conclusion: Result indicates that Grīvā Vasti is an effective treatment in cervical spondylosis. PMID:25161334

  12. Grüneisen analysis of thermodynamic properties of δ-phase Pu-Ga alloys

    NASA Astrophysics Data System (ADS)

    Lawson, A. C.

    2014-07-01

    We present a Grüneisen analysis of the intriguing temperature dependence of the thermal expansion and bulk modulus of delta phase plutonium alloys. This analysis exploits the thermodynamic relationship between these quantities and the heat capacity and reduces the description of complicated behaviour to the determination of a manageable number of numerical constants. We conclude from the analysis (1) that there is a small Schottky-like heat capacity anomaly at high temperatures and (2) that the size of this anomaly depends strongly on alloy concentration. Grüneisen analysis provides an economical description of the thermal expansion and bulk modulus of δ-Pu.

  13. Investigation of static and cyclic bearing failure mechanisms for GR/EP laminates

    NASA Technical Reports Server (NTRS)

    Walter, R. W.; Tuttle, M. M.

    1992-01-01

    Static, cyclic load (fatigue), and residual strength testing of graphite-epoxy (GR/EP) and aluminum pin bearing joints was completed to study bearing failure mechanisms. Parameters investigated included static strength, failure mode, fatigue life, hole growth, joint stiffness, and residual strength. Comparative evaluation of these results show that the MIL-HDBK-5 convention for the definition of bearing strength can be used for GR/EP materials while maintaining the same, or improved, level of structural integrity shown for metal joints.

  14. The C.A.M.S. 54 G.R. transatlantic seaplane (French)

    NASA Technical Reports Server (NTRS)

    Ide, John Jay

    1928-01-01

    Tested at the end of March, 1928, the C.A.M.S. 54 G.R. was built for the purpose of crossing the Atlantic from Europe by way of the azores. It has a biplane construction with wings mounted above the hull. It is powered by two new series 500 HP. geared Hispano Suiza V type engines.

  15. NRIP enhances HPV gene expression via interaction with either GR or E2

    SciTech Connect

    Chang, Szu-Wei; Lu, Pei-Yu; Guo, Jih-Huong; Tsai, Tzung-Chieh; Tsao, Yeou-Ping; Chen, Show-Li

    2012-02-05

    We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, in a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.

  16. User Manual for the Data-Series Interface of the Gr Application Software

    USGS Publications Warehouse

    Donovan, John M.

    2009-01-01

    This manual describes the data-series interface for the Gr Application software. Basic tasks such as plotting, editing, manipulating, and printing data series are presented. The properties of the various types of data objects and graphical objects used within the application, and the relationships between them also are presented. Descriptions of compatible data-series file formats are provided.

  17. NRIP enhances HPV gene expression via interaction with either GR or E2.

    PubMed

    Chang, Szu-Wei; Lu, Pei-Yu; Guo, Jih-Huong; Tsai, Tzung-Chieh; Tsao, Yeou-Ping; Chen, Show-Li

    2012-02-05

    We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, in a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.

  18. Semi-Automatic Contacting System ’GR-1’ in Marine Radios,

    DTIC Science & Technology

    1982-10-26

    TECIHOOY Do. 100411 TECNOLOGY IVISION VISION. WP.APG. OHIO. FMD -ID(RS)T-1043-92 Date 26 Oct 19 62 * 6~~ * -’ *(.* b ~ ~ ~ -C *; PVN’ 7 ’.\\ Th’% q...duction of GR-2 without the prior Installation of OR-1. - a significant Improvement of the conditions of radio oomunioations In the mobile marine service in

  19. Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia.

    PubMed

    Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs) are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  20. Helix 8 of the ligand binding domain of the glucocorticoid receptor (GR) is essential for ligand binding.

    PubMed

    Deng, Qiong; Waxse, Bennett; Riquelme, Denise; Zhang, Jiabao; Aguilera, Greti

    2015-06-15

    Membrane association of estrogen receptors (ER) depends on cysteine palmitoylation and two leucines in the ligand binding domain (LBD), conserved in most steroid receptors. The role of this region, corresponding to helix 8 of the glucocorticoid receptor (GR) LBD, on membrane association of GR was studied in 4B cells, expressing endogenous GR, and Cos-7 cells transfected EGFP-GR constructs. 4B cells preloaded with radiolabeled palmitic acid showed no radioactivity incorporation into immunoprecipitated GR. Moreover, mutation C683A (corresponding to ER palmitoylation site) did not affect corticosterone-induced membrane association of GR. Mutations L687-690A, L682A, E680G and K685G prevented membrane and also nuclear localization through reduced ligand binding. L687-690A mutation decreased association of GR with heat shock protein 90 and transcriptional activity, without overt effects on receptor protein stability. The data demonstrate that palmitoylation does not mediate membrane association of GR, but that the region 680-690 (helix 8) is critical for ligand binding and receptor function.

  1. Using optoacoustic imaging for measuring the temperature dependence of Grüneisen parameter in optically absorbing solutions

    PubMed Central

    Petrova, Elena; Ermilov, Sergey; Su, Richard; Nadvoretskiy, Vyacheslav; Conjusteau, André; Oraevsky, Alexander

    2013-01-01

    Grüneisen parameter is a key temperature-dependent physical characteristic responsible for thermoelastic efficiency of materials. We propose a new methodology for accurate measurements of temperature dependence of Grüneisen parameter in optically absorbing solutions. We use two-dimensional optoacoustic (OA) imaging to improve accuracy of measurements. Our approach eliminates contribution of local optical fluence and absorbance. To validate the proposed methodology, we studied temperature dependence of aqueous cupric sulfate solutions in the range from 22 to 4°C. Our results for the most diluted salt perfectly matched known temperature dependence for the Grüneisen parameter of water. We also found that Grüneisen-temperature relationship for cupric sulfate exhibits linear trend with respect to the concentration. In addition to accurate measurements of Grüneisen changes with temperature, the developed technique provides a basis for future high precision OA temperature monitoring in live tissues. PMID:24150350

  2. The role of Gr-1(+) cells and tumour necrosis factor-α signalling during Clostridium difficile colitis in mice.

    PubMed

    McDermott, Andrew J; Higdon, Kathryn E; Muraglia, Ryan; Erb-Downward, John R; Falkowski, Nicole R; McDonald, Roderick A; Young, Vincent B; Huffnagle, Gary B

    2015-04-01

    The host response to Clostridium difficile infection in antibiotic-treated mice is characterized by robust recruitment of Gr-1(+) cells, increased expression of inflammatory cytokines including tumour necrosis factor-α (TNF-α), and the development of severe epithelial damage. To investigate the role of Gr-1(+) cells and TNF-α during C. difficile colitis, we treated infected mice with monoclonal antibodies against Gr-1 or TNF-α. Mice were challenged with vegetative cells of C. difficile strain VPI 10463 following treatment with the third-generation cephalosporin ceftriaxone. Ceftriaxone treatment alone was associated with significant changes in cytokine expression within the colonic mucosa but not overt inflammatory histopathological changes. In comparison, C. difficile infection following ceftriaxone treatment was associated with increased expression of inflammatory cytokines and chemokines including Cxcl1, Cxcl2, Il1b, Il17f and Tnfa, as well as robust recruitment of Ly6C(Mid)  Gr-1(High) neutrophils and Ly6C(High) Gr-1(Mid) monocytes and the development of severe colonic histopathology. Anti-Gr-1 antibody treatment resulted in effective depletion of both Ly6C(Mid) Gr-1(High) neutrophils and Ly6C(High) Gr-1(Mid) monocytes: however, we observed no protection from the development of severe pathology or reduction in expression of the pro-inflammatory cytokines Il1b, Il6, Il33 and Tnfa following anti-Gr-1 treatment. By contrast, anti-TNF-α treatment did not affect Gr-1(+) cell recruitment, but was associated with increased expression of Il6 and Il1b. Additionally, Ffar2, Ffar3, Tslp, Tff and Ang4 expression was significantly reduced in anti-TNF-α-treated animals, in association with marked intestinal histopathology. These studies raise the possibility that TNF-α may play a role in restraining inflammation and protecting the epithelium during C. difficile infection.

  3. Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets.

    PubMed

    Sun, Qinwei; Li, Xi; Jia, Yimin; Pan, Shifeng; Li, Runsheng; Yang, Xiaojing; Zhao, Ruqian

    2016-07-01

    Methyl donor nutrients are critical for embryonic development of brain. Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress sensitivity. Hippocampal GR expression is highly susceptible to epigenetic regulation, yet the effect of maternal methyl donor supplementation on epigenetic regulation of GR transcription in offspring hippocampus remains unclear. In this study, we fed sows with betaine (3 g/kg) throughout the gestation and analyzed the hippocampal expression of GR mRNA and its variants, as well as the CpG methylation status of the promoter and the microRNAs predicted to target 3' UTR of porcine GR gene in neonatal piglets. Total GR mRNA (P<0.01) and its variants GR 1-4 (P<0.05) and 1-9,10 (P<0.01), were significantly higher in the hippocampus of betaine-treated piglets, while the content of GR protein was not significantly changed. The CpGs located in the -1650 ~ -1515 segment of GR gene were hypermethylated (P<0.05). The hippocampal expression of miR-130b (P<0.05), miR-181a (P<0.05) and miR-181d (P<0.01) was significantly up-regulated. The targeting efficacy of miR-130b and miR-181d was validated in vitro using dual-luciferase reporter assay system. Our results demonstrate that maternal betaine supplementation during gestation enhances GR mRNA expression in offspring hippocampus, which involves alterations in miRNAs expression.

  4. Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets

    PubMed Central

    SUN, Qinwei; LI, Xi; JIA, Yimin; PAN, Shifeng; LI, Runsheng; YANG, Xiaojing; ZHAO, Ruqian

    2016-01-01

    Methyl donor nutrients are critical for embryonic development of brain. Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress sensitivity. Hippocampal GR expression is highly susceptible to epigenetic regulation, yet the effect of maternal methyl donor supplementation on epigenetic regulation of GR transcription in offspring hippocampus remains unclear. In this study, we fed sows with betaine (3 g/kg) throughout the gestation and analyzed the hippocampal expression of GR mRNA and its variants, as well as the CpG methylation status of the promoter and the microRNAs predicted to target 3’ UTR of porcine GR gene in neonatal piglets. Total GR mRNA (P<0.01) and its variants GR 1-4 (P<0.05) and 1-9,10 (P<0.01), were significantly higher in the hippocampus of betaine-treated piglets, while the content of GR protein was not significantly changed. The CpGs located in the –1650 ~ –1515 segment of GR gene were hypermethylated (P<0.05). The hippocampal expression of miR-130b (P<0.05), miR-181a (P<0.05) and miR-181d (P<0.01) was significantly up-regulated. The targeting efficacy of miR-130b and miR-181d was validated in vitro using dual-luciferase reporter assay system. Our results demonstrate that maternal betaine supplementation during gestation enhances GR mRNA expression in offspring hippocampus, which involves alterations in miRNAs expression. PMID:26875838

  5. gr/gr-DAZ2-DAZ4-CDY1b deletion is a high-risk factor for male infertility in Tunisian population.

    PubMed

    Ghorbel, Myriam; Baklouti-Gargouri, Siwar; Keskes, Rim; Chakroun, Nozha; Sellami, Afifa; Fakhfakh, Faiza; Ammar-Keskes, Leila

    2016-10-30

    The azoospermia factor c (AZFc) region harbors multi-copy genes that are expressed in the testis. Deletions of this region lead to reduced copy numbers of these genes. In this present study we aimed to determine the frequency of AZFc subdeletion in infertile and fertile men from Tunisia and to identify whether deletions of DAZ and CDY1 gene copies are deleterious on spermatogenesis and on semen quality. We studied a group of 241 infertile men and 115 fertile healthy males using a sequence tagged site (STS)±method. To gain insight into the molecular basis of the heterogeneous phenotype observed in men with the deletion we defined the type of DAZ and CDY1 genes deleted. We reported in the present study and for the first time a new type of AZFc deletion (gr/gr-DAZ2-DAZ4-CDY1b) and hypothesis that this new deletion is the result of two successive events. We also demonstrated that this deletion constitutes a relative high-risk factor for male infertility in Tunisian population.

  6. Dexamethasone-mediated changes in adipose triacylglycerol metabolism are exaggerated, not diminished, in the absence of a functional GR dimerization domain.

    PubMed

    Roohk, Donald J; Mascharak, Smita; Khambatta, Cyrus; Leung, Ho; Hellerstein, Marc; Harris, Charles

    2013-04-01

    The glucocorticoid (GC) receptor (GR) has multiple effector mechanisms, including dimerization-mediated transactivation of target genes via DNA binding and transcriptional repression mediated by protein-protein interactions. Much attention has been focused on developing selective GR modulators that would dissociate adverse effects from therapeutic anti-inflammatory effects. The GR(dim/dim) mouse has a mutation in the dimerization domain of GR and has been shown to have attenuated transactivation with intact repression. To understand the role of GR dimerization-dependent targets in multiple tissues, we measured metabolic fluxes through several disease-relevant GC target pathways using heavy water labeling and mass spectrometry in wild-type and GR(dim/dim) mice administered the potent GC dexamethasone (DEX). Absolute triglyceride synthesis was increased in both wild-type and GR(dim/dim) mice by DEX in the inguinal and epididymal fat depots. GR(dim/dim) mice showed an exaggerated response to DEX in both depots. De novo lipogenesis was also greatly increased in both depots in response to DEX in GR(dim/dim), but not wild-type mice. In contrast, the inhibitory effect of DEX on bone and skin collagen synthesis rates was greater in wild-type compared with GR(dim/dim) mice. Wild-type mice were more sensitive to DEX-dependent decreases in insulin sensitivity than GR(dim/dim) mice. Wild-type and GR(dim/dim) mice were equally sensitive to DEX-dependent decreases in muscle protein synthesis. Chronic elevation of GCs in GR(dim/dim) mice results in severe runting and lethality. In conclusion, some metabolic effects of GC treatment are exaggerated in adipose tissue of GR(dim/dim) mice, suggesting that selective GR modulators based on dissociating GR transactivation from repression should be evaluated carefully.

  7. Modulation of GR activity does not affect the in vitro metabolism of cortisol by rainbow trout ovarian follicles.

    PubMed

    Li, Mao; Christie, Heather; Leatherland, John

    2014-12-01

    The goal of the study was to determine whether the metabolic clearance of cortisol from rainbow trout (Oncorhynchus mykiss) ovarian follicles is affected by the level of ovarian steroidogenesis, and whether it involves the activation of glucocorticoid receptors (GRs). Ovarian follicles were incubated in vitro; the adenylate cyclase activator, forskolin, was used to stimulate ovarian steroidogenesis, and the modulation of GR activity was brought about using GR agonists (cortisol and dexamethasone) or the GR antagonist, mifepristone (RU486). The follicles were co-incubated with [2, 4, 6, 7 (3)H] cortisol, and the tritium-labelled steroid products were separated by HPLC. In addition, the rates of expression of genes encoding for the two forms of GR (gr1 and gr2) were measured. Cortisone, cortisol sulphate, and cortisone sulphate were the major glucocorticoid products of cortisol metabolism, indicative of the action of 11β-hydroxysteroid dehydrogenase and glucocorticoid sulphotransferase in the follicular cells. There were no effects of RU486 or forskolin on the rates of [(3)H]cortisol metabolism suggesting that cortisol metabolism by ovarian follicles was independent of GR activation, and not influenced by increased activation of gonadal reproductive steroidogenesis.

  8. GR712RC- The Dual-Core LEON3FT System-on-Chip Avionics Solution

    NASA Astrophysics Data System (ADS)

    Habinc, Sandi; Glembo, Kristoffer; Gaisler, Jiri

    2010-08-01

    The GR712RC System-on-Chip (SoC) is a dual core LEON3FT system suitable for advanced high reliability space avionics. Fault tolerance features from Aeroflex Gaisler's GRLIB IP library [1][2] and an implementation using Ramon Chips RadSafe cell library enables superior radiation hardness. The GR712RC device has been designed to provide high processing power by including two LEON3FT 32-bit SPARC V8 processors, each with its own high-performance IEEE754 compliant floating-point-unit and SPARC reference memory management unit. This high processing power is combined with a large number of serial interfaces, ranging from high-speed links for data transfers to low-speed control buses for commanding and status acquisition.

  9. Propagation of Flexural Mode AE Signals in GR/EP Composite Plates

    NASA Technical Reports Server (NTRS)

    Prosser, W. H.; Gorman, M. R.

    1992-01-01

    It has been documented that AE signals propagate in thin plates as extensional and flexural plate modes. This was demonstrated using simulated AE sources (pencil lead breaks) by Gorman on thin aluminum and gr/ep composite plates and by Gorman and Prosser on thin aluminum plates. A typical signal from a pencil lead break source which identifies these two modes is shown. AE signals from transverse matrix cracking sources in gr/ep composite plates were also shown to propagate as plate modes by Gorman and Ziola. Smith showed that crack growth events in thin aluminum plates under spectrum fatigue loading produced signals that propagated as plate modes. Additionally, Prosser et al. showed that AE signals propagated as plate modes in a thin walled composite tube.

  10. Term Cancellations in Computing Floating-Point Gröbner Bases

    NASA Astrophysics Data System (ADS)

    Sasaki, Tateaki; Kako, Fujio

    We discuss the term cancellation which makes the floating-point Gröbner basis computation unstable, and show that error accumulation is never negligible in our previous method. Then, we present a new method, which removes accumulated errors as far as possible by reducing matrices constructed from coefficient vectors by the Gaussian elimination. The method manifests amounts of term cancellations caused by the existence of approximate linearly dependent relations among input polynomials.

  11. Effect of the chemical composition and austenitizing conditions on the hardenability of 35GR steel

    NASA Astrophysics Data System (ADS)

    Potapov, A. I.; Malikov, I. T.; Urazov, V. I.; Semin, A. E.

    2010-12-01

    The effect of the content of impurity elements (in particular, chromium), the heating temperature before rolling, and the austenitizing schedule on the hardenability of boron-containing 35 GR steel is studied. It is shown that a change in the heating temperature of the steel for rolling by 50-100°C does not influence the hardenability depth, which is mainly dependent on the austenitizing temperature and time and the chromium content.

  12. Optical Observations of the Type Ic Supernova 2007gr in NGC 1058

    NASA Astrophysics Data System (ADS)

    Chen, Juncheng; Wang, Xiaofeng; Ganeshalingam, Mohan; Silverman, Jeffrey M.; Filippenko, Alexei V.; Li, Weidong; Chornock, Ryan; Li, Junzheng; Steele, Thea

    2014-08-01

    We present extensive optical observations of the normal Type Ic supernova (SN) 2007gr, spanning from about one week before maximum light to more than one year thereafter. The optical light and color curves of SN 2007gr are very similar to those of the broad-lined Type Ic SN 2002ap, but the spectra show remarkable differences. The optical spectra of SN 2007gr are characterized by unusually narrow lines, prominent carbon lines, and slow evolution of the line velocity after maximum light. The earliest spectrum (taken at t = -8 days) shows a possible signature of helium (He I λ5876 at a velocity of ~19,000 km s-1). Moreover, the larger intensity ratio of the [O I] λ6300 and λ6364 lines inferred from the early nebular spectra implies a lower opacity of the ejecta shortly after the explosion. These results indicate that SN 2007gr perhaps underwent a less energetic explosion of a smaller-mass Wolf-Rayet star (~8-9 M ⊙) in a binary system, as favored by an analysis of the progenitor environment through pre-explosion and post-explosion Hubble Space Telescope images. In the nebular spectra, asymmetric double-peaked profiles can be seen in the [O I] λ6300 and Mg I] λ4571 lines. We suggest that the two peaks are contributed by the blueshifted and rest-frame components. The similarity in velocity structure and the different evolution of the strength of the two components favor an aspherical explosion with the ejecta distributed in a torus or disk-like geometry, but inside the ejecta the O and Mg have different distributions.

  13. Nonlinear Elastic Effects on the Energy Flux Deviation of Ultrasonic Waves in GR/EP Composites

    NASA Technical Reports Server (NTRS)

    Prosser, William H.; Kriz, R. D.; Fitting, Dale W.

    1992-01-01

    In isotropic materials, the direction of the energy flux (energy per unit time per unit area) of an ultrasonic plane wave is always along the same direction as the normal to the wave front. In anisotropic materials, however, this is true only along symmetry directions. Along other directions, the energy flux of the wave deviates from the intended direction of propagation. This phenomenon is known as energy flux deviation and is illustrated. The direction of the energy flux is dependent on the elastic coefficients of the material. This effect has been demonstrated in many anisotropic crystalline materials. In transparent quartz crystals, Schlieren photographs have been obtained which allow visualization of the ultrasonic waves and the energy flux deviation. The energy flux deviation in graphite/epoxy (gr/ep) composite materials can be quite large because of their high anisotropy. The flux deviation angle has been calculated for unidirectional gr/ep composites as a function of both fiber orientation and fiber volume content. Experimental measurements have also been made in unidirectional composites. It has been further demonstrated that changes in composite materials which alter the elastic properties such as moisture absorption by the matrix or fiber degradation, can be detected nondestructively by measurements of the energy flux shift. In this research, the effects of nonlinear elasticity on energy flux deviation in unidirectional gr/ep composites were studied. Because of elastic nonlinearity, the angle of the energy flux deviation was shown to be a function of applied stress. This shift in flux deviation was modeled using acoustoelastic theory and the previously measured second and third order elastic stiffness coefficients for T300/5208 gr/ep. Two conditions of applied uniaxial stress were considered. In the first case, the direction of applied uniaxial stress was along the fiber axis (x3) while in the second case it was perpendicular to the fiber axis along the

  14. Transcriptional regulation of human paraoxonase 1 by PXR and GR in human hepatoma cells.

    PubMed

    Ponce-Ruiz, N; Rojas-García, A E; Barrón-Vivanco, B S; Elizondo, G; Bernal-Hernández, Y Y; Mejía-García, A; Medina-Díaz, I M

    2015-12-25

    Human paraoxonase 1 (PON1) is A-esterase synthesized in the liver and secreted into the plasma, where it associates with HDL. PON1 acts as an antioxidant preventing lipid oxidation and detoxifies a wide range of substrates, including organophosphate compounds. The variability of PON1 (enzyme activity/serum levels) has been attributed to internal and external factors. However, the molecular mechanisms involved in the transcriptional regulation of PON1 have not been well-studied. The aim of this study was to evaluate and characterize the transcriptional activation of PON1 by nuclear receptors (NR) in human hepatoma cells. In silico analysis was performed on the promoter region of PON1 to determine the response elements of NR. Real-time PCR was used to evaluate the effect of specific NR ligands on the mRNA levels of genes regulated by NR and PON1. The results indicated that NR response elements had 95% homology to pregnenolone (PXR), glucocorticoids (GR), retinoic acid (RXR) and peroxisomes proliferator-activated receptor alpha (PPARα). Treatments with Dexamethasone (GR ligand), Rifampicin (PXR ligand) and TCDD (AhR ligand) increased the mRNA levels of PON1 at 24 and 48 h. We showed that the activation of GR by Dexamethasone results in PON1 gene induction accompanied by an increase in activity levels. In conclusion, these results demonstrate that GR regulates PON1 gene transcription through directly binding to NR response elements at -95 to -628 bp of the PON1 promoter. This study suggests new molecular mechanisms for the transcriptional regulation of PON1 through a process involving the activation of PXR.

  15. Optical observations of the type Ic supernova 2007gr in NGC 1058

    SciTech Connect

    Chen, Juncheng; Wang, Xiaofeng; Li, Junzheng; Ganeshalingam, Mohan; Silverman, Jeffrey M.; Filippenko, Alexei V.; Li, Weidong; Chornock, Ryan; Steele, Thea E-mail: wang_xf@mail.tsinghua.edu.cn

    2014-08-01

    We present extensive optical observations of the normal Type Ic supernova (SN) 2007gr, spanning from about one week before maximum light to more than one year thereafter. The optical light and color curves of SN 2007gr are very similar to those of the broad-lined Type Ic SN 2002ap, but the spectra show remarkable differences. The optical spectra of SN 2007gr are characterized by unusually narrow lines, prominent carbon lines, and slow evolution of the line velocity after maximum light. The earliest spectrum (taken at t = –8 days) shows a possible signature of helium (He I λ5876 at a velocity of ∼19,000 km s{sup –1}). Moreover, the larger intensity ratio of the [O I] λ6300 and λ6364 lines inferred from the early nebular spectra implies a lower opacity of the ejecta shortly after the explosion. These results indicate that SN 2007gr perhaps underwent a less energetic explosion of a smaller-mass Wolf-Rayet star (∼8-9 M{sub ☉}) in a binary system, as favored by an analysis of the progenitor environment through pre-explosion and post-explosion Hubble Space Telescope images. In the nebular spectra, asymmetric double-peaked profiles can be seen in the [O I] λ6300 and Mg I] λ4571 lines. We suggest that the two peaks are contributed by the blueshifted and rest-frame components. The similarity in velocity structure and the different evolution of the strength of the two components favor an aspherical explosion with the ejecta distributed in a torus or disk-like geometry, but inside the ejecta the O and Mg have different distributions.

  16. Mobility and Economic Feasibility of the Greenland Inland Traverse (GrIT)

    DTIC Science & Technology

    2011-03-01

    towing four GrIT08 bladder sleds at NEEM . ........................................... 29 Figure 15. John Deere 8530 tractor equipped with Soucy tracks...19 Table 2. LC130 parameters for flights from Kanger to NEEM and Summit. ...................................... 36 Table 3. Summary...initiated a 705-mile (1410-mile round trip) over-snow traverse, de- parting from Thule Air Base, to re-supply the international drilling camp at NEEM and

  17. Structural Modeling of GR Interactions with the SWI/SNF Chromatin Remodeling Complex and C/EBP.

    PubMed

    Muratcioglu, Serena; Presman, Diego M; Pooley, John R; Grøntved, Lars; Hager, Gordon L; Nussinov, Ruth; Keskin, Ozlem; Gursoy, Attila

    2015-09-15

    The glucocorticoid receptor (GR) is a steroid-hormone-activated transcription factor that modulates gene expression. Transcriptional regulation by the GR requires dynamic receptor binding to specific target sites located across the genome. This binding remodels the chromatin structure to allow interaction with other transcription factors. Thus, chromatin remodeling is an essential component of GR-mediated transcriptional regulation, and understanding the interactions between these molecules at the structural level provides insights into the mechanisms of how GR and chromatin remodeling cooperate to regulate gene expression. This study suggests models for the assembly of the SWI/SNF-A (SWItch/Sucrose-NonFermentable) complex and its interaction with the GR. We used the PRISM algorithm (PRotein Interactions by Structural Matching) to predict the three-dimensional complex structures of the target proteins. The structural models indicate that BAF57 and/or BAF250 mediate the interaction between the GR and the SWI/SNF-A complex, corroborating experimental data. They further suggest that a BAF60a/BAF155 and/or BAF60a/BAF170 interaction is critical for association between the core and variant subunits. Further, we model the interaction between GR and CCAAT-enhancer-binding proteins (C/EBPs), since the GR can regulate gene expression indirectly by interacting with other transcription factors like C/EBPs. We observe that GR can bind to bZip domains of the C/EBPα homodimer as both a monomer and dimer of the DNA-binding domain. In silico mutagenesis of the predicted interface residues confirm the importance of these residues in binding. In vivo analysis of the computationally suggested mutations reveals that double mutations of the leucine residues (L317D+L335D) may disrupt the interaction between GR and C/EBPα. Determination of the complex structures of the GR is of fundamental relevance to understanding its interactions and functions, since the function of a protein or a

  18. A mildly relativistic radio jet from the otherwise normal type Ic supernova 2007gr.

    PubMed

    Paragi, Z; Taylor, G B; Kouveliotou, C; Granot, J; Ramirez-Ruiz, E; Bietenholz, M; van der Horst, A J; Pidopryhora, Y; van Langevelde, H J; Garrett, M A; Szomoru, A; Argo, M K; Bourke, S; Paczyński, B

    2010-01-28

    The class of type Ic supernovae have drawn increasing attention since 1998 owing to their sparse association (only four so far) with long duration gamma-ray bursts (GRBs). Although both phenomena originate from the core collapse of a massive star, supernovae emit mostly at optical wavelengths, whereas GRBs emit mostly in soft gamma-rays or hard X-rays. Though the GRB central engine generates ultra-relativistic jets, which beam the early emission into a narrow cone, no relativistic outflows have hitherto been found in type Ib/c supernovae explosions, despite theoretical expectations and searches. Here we report radio (interferometric) observations that reveal a mildly relativistic expansion in a nearby type Ic supernova, SN 2007gr. Using two observational epochs 60 days apart, we detect expansion of the source and establish a conservative lower limit for the average apparent expansion velocity of 0.6c. Independently, a second mildly relativistic supernova has been reported. Contrary to the radio data, optical observations of SN 2007gr indicate a typical type Ic supernova with ejecta velocities approximately 6,000 km s(-1), much lower than in GRB-associated supernovae. We conclude that in SN 2007gr a small fraction of the ejecta produced a low-energy mildly relativistic bipolar radio jet, while the bulk of the ejecta were slower and, as shown by optical spectropolarimetry, mildly aspherical.

  19. Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα

    PubMed Central

    Ratman, Dariusz; Mylka, Viacheslav; Bougarne, Nadia; Pawlak, Michal; Caron, Sandrine; Hennuyer, Nathalie; Paumelle, Réjane; De Cauwer, Lode; Thommis, Jonathan; Rider, Mark H.; Libert, Claude; Lievens, Sam; Tavernier, Jan; Staels, Bart; De Bosscher, Karolien

    2016-01-01

    Adaptation to fasting involves both Glucocorticoid Receptor (GRα) and Peroxisome Proliferator-Activated Receptor α (PPARα) activation. Given both receptors can physically interact we investigated the possibility of a genome-wide cross-talk between activated GR and PPARα, using ChIP- and RNA-seq in primary hepatocytes. Our data reveal extensive chromatin co-localization of both factors with cooperative induction of genes controlling lipid/glucose metabolism. Key GR/PPAR co-controlled genes switched from transcriptional antagonism to cooperativity when moving from short to prolonged hepatocyte fasting, a phenomenon coinciding with gene promoter recruitment of phosphorylated AMP-activated protein kinase (AMPK) and blocked by its pharmacological inhibition. In vitro interaction studies support trimeric complex formation between GR, PPARα and phospho-AMPK. Long-term fasting in mice showed enhanced phosphorylation of liver AMPK and GRα Ser211. Phospho-AMPK chromatin recruitment at liver target genes, observed upon prolonged fasting in mice, is dampened by refeeding. Taken together, our results identify phospho-AMPK as a molecular switch able to cooperate with nuclear receptors at the chromatin level and reveal a novel adaptation mechanism to prolonged fasting. PMID:27576532

  20. Direct GR Binding Sites Potentiate Clusters of TF Binding across the Human Genome.

    PubMed

    Vockley, Christopher M; D'Ippolito, Anthony M; McDowell, Ian C; Majoros, William H; Safi, Alexias; Song, Lingyun; Crawford, Gregory E; Reddy, Timothy E

    2016-08-25

    The glucocorticoid receptor (GR) binds the human genome at >10,000 sites but only regulates the expression of hundreds of genes. To determine the functional effect of each site, we measured the glucocorticoid (GC) responsive activity of nearly all GR binding sites (GBSs) captured using chromatin immunoprecipitation (ChIP) in A549 cells. 13% of GBSs assayed had GC-induced activity. The responsive sites were defined by direct GR binding via a GC response element (GRE) and exclusively increased reporter-gene expression. Meanwhile, most GBSs lacked GC-induced reporter activity. The non-responsive sites had epigenetic features of steady-state enhancers and clustered around direct GBSs. Together, our data support a model in which clusters of GBSs observed with ChIP-seq reflect interactions between direct and tethered GBSs over tens of kilobases. We further show that those interactions can synergistically modulate the activity of direct GBSs and may therefore play a major role in driving gene activation in response to GCs.

  1. The Oxygen and Nitrogen Abundance of Leo A and GR 8

    NASA Astrophysics Data System (ADS)

    van Zee, L.; Skillman, E. D.; Haynes, M. P.

    1999-05-01

    Gas phase abundances are one of the best measures of the intrinsic metallicity of low mass galaxies. We recently obtained low resolution long slit optical spectra of several HII regions in Leo A and GR 8 with the Palomar 5m telescope. Previous studies of the resolved stellar population of Leo A indicated that the stars have metallicities approximately 2% of solar (Tolstoy et al. 1998). Preliminary analysis of the HII region spectra, and that of a planetary nebula, indicates that the gas phase oxygen abundance of Leo A is approximately 3% of solar. This confirms the result of Skillman et al. (1989), who also derived an oxygen abundance for Leo A from a planetary nebula. Similarly, for GR 8 we find a mean oxygen abundance of 5% of solar. For all the HII regions, the derived log(N/O) is -1.5 +/- 0.1, as has been found for other low metallicity systems. These new observations of multiple HII regions in Leo A and GR 8 confirm that metals in low mass galaxies are well mixed.

  2. Volvulus du grêle sur paquet d’ascaris: à propos d’un cas

    PubMed Central

    Diouf, Cheikh; Kane, Ahmed; Ndoye, Ndeye Aby; Ndour, Oumar; Faye-Fall, Aimé Lakh; Fall, Mbaye; Alumeti, Désiré Munyali; Ngom, Gabriel

    2016-01-01

    Nous rapportons un cas exceptionnel de volvulus nécrosé de l'intestin grêle dû à des ascaris adultes chez un enfant de 7 ans. A l'admission, l'enfant présentait le tableau d'occlusion intestinale qui évoluait depuis deux jours avec altération de l'état général. La radiographie de l'abdomen sans préparation retrouvait des niveaux hydroaériques de type grêlique et un aspect tigré évoquant le diagnostic d'une occlusion intestinale haute sur masse abdominale. Après la réanimation, le traitement chirurgical consistait en une laparotomie qui avait retrouvé un volvulus nécrosé de l'iléon terminale contenant des ascaris adultes. Une résection du grêle sur environ un mètre emportant le segment nécrosé suivie d'une iléostomie était réalisée. L'évolution a été favorable, l'anastomose iléo-colique fut réalisée quatre semaines plus tard. Au recul de deux ans l'enfant est indemne de tout symptôme. PMID:27795803

  3. The 2011 Grímsvötn Eruption From High Rate Geodesy

    NASA Astrophysics Data System (ADS)

    Hreinsdottir, S.; Grapenthin, R.; Sigmundsson, F.; Roberts, M. J.; Holmjarn, J.; Geirsson, H.; Arnadottir, T.; Bennett, R. A.; Villemin, T.; Ofeigsson, B. G.; Sturkell, E. C.

    2011-12-01

    High rate geodetic measurements at volcanoes can give displacements at sub second intervals, revealing surface deformation associated with magma movements. The Grímsvötn volcano lies beneath the Vatnajökull icecap, Iceland, limiting the near field monitoring efforts to a single nunatak, Mt. Grímsfjall, on the southern caldera rim. A 5 Hz GPS station and an electronic tilt meter are located at Grímsfjall. The colocation of these instruments (GPS and tilt station) allows us to relate the observed surface deformation to pressure change in a magma chamber assuming a simple Mogi source within an elastic half space. During the 21-28 May 2011 Grímsvötn eruption a continuous stream of data, despite the eruption plume and lightning, was transmitted to Reykjavík. The tiltmeter measures N-S and E-W components of tilt, the N-S component was recorded at 100 samples per second (sps) but the E-W component at 4 sps. The high rate data from the GPS station at Grímsfjall (GFUM) were analyzed using the Track part of GAMIT/GLOBK. We produced kinematic solutions at 5 Hz and 1 Hz intervals using reference stations in 40-120 km distance of the volcano. To minimize multipath effects we applied sidereal filtering and stacked the individual solutions to further improve the signal to noise ratio. The resulting deformation time series suggests a rapid pressure drop starting about 50 minutes prior to the onset of the eruption when over 20 km high plume formed. The characteristics of the GPS and tilt data time series suggests that the main signal was induced by a single source of fixed location and geometry throughout the eruption; a shallow magma chamber. Small deviations in displacement direction prior to the onset of the eruption can be explained by the opening of the feeder dike. We see a total displacement of 57 cm in direction ˜N38.5°W and down at the GPS station, suggesting a source depth of ~1.7 km. About 20% of the displacement preceded the eruption and more than 95% took

  4. GR-127935-sensitive mechanism mediating hypotension in anesthetized rats: are 5-HT5B receptors involved?

    PubMed

    Sánchez-Maldonado, Carolina; López-Sánchez, Pedro; Anguiano-Robledo, Liliana; Leopoldo, Marcello; Lacivita, Enza; Terrón, José A

    2015-04-01

    The 5-HT1B/1D receptor antagonist, GR-127935, inhibits hypotensive responses produced by the 5-HT1A, 5-HT1B/1D and 5-HT7 receptor agonist, and 5-HT5A/5B receptor ligand, 5-carboxamidotryptamine (5-CT), in rats. This work further characterized the above mechanism using more selective 5-HT1B and 5-HT1D receptor antagonists. Also, expression of 5-HT5A and 5-HT5B receptor mRNAs in blood vessels was searched by reverse transcription polymerase chain reaction. Decreases in diastolic blood pressure induced by 5-CT (0.001-10 μg/kg, intravenously) were analyzed in anesthetized rats that had received intravenous vehicle (1 mL/kg), SB-224289 (5-HT1B antagonist; 0.3 and 1.0 mg/kg), BRL15572 (5-HT1D antagonist; 0.3 and 1.0 mg/kg), SB-224289 + BRL15572 (0.3 mg/kg, each), or SB-224289 + BRL15572 (0.3 mg/kg, each) + GR-127935 (1 mg/kg). Because only the latter treatment inhibited 5-CT-induced hypotension, suggestive of a mechanism unrelated to 5-HT1B/1D receptors, the effects of antagonists/ligands at 5-HT5A (SB-699551, 1 mg/kg), 5-HT6 (SB-399885, 1 mg/kg), and 5-HT1B/1D/5A/5B/7 receptors (ergotamine, 0.1 mg/kg) on 5-CT-induced hypotension were tested. Interestingly, only ergotamine blocked 5-CT-induced responses; this effect closely paralleled that of SB-224289 + BRL-15572 + GR-127935. Neither did ergotamine nor GR-127935 inhibit hypotensive responses induced by the 5-HT7 receptor agonist, LP-44. Faint but clear bands corresponding to 5-HT5A and 5-HT5B receptor mRNAs in aorta and mesenteric arteries were detected. Results suggest that the GR-127935-sensitive mechanism mediating hypotension in rats is unrelated to 5-HT1B, 5-HT1D, 5-HT5A, 5-HT6, and 5-HT7 receptors. This mechanism, however, resembles putative 5-HT5B receptors.

  5. FXR mediates a chromatin looping in the GR promoter thus promoting the resolution of colitis in rodents.

    PubMed

    Renga, Barbara; D'Amore, Claudio; Cipriani, Sabrina; Mencarelli, Andrea; Carino, Adriana; Sepe, Valentina; Zampella, Angela; Distrutti, Eleonora; Fiorucci, Stefano

    2013-11-01

    Glucocorticoids (GCs) are important endocrine regulators of a wide range of physiological processes ranging from immune function to glucose and lipid metabolism. For decades, synthetic glucocorticoids such as dexamethasone have been the cornerstone for the clinical treatment of inflammatory bowel diseases (IBD). A previous study has shown that farnesoid X receptor (FXR) enhances the transcription of NR3C1 gene, which encodes for human GR, by binding to a conserved FXR response element (FXRE) in the distal promoter of this gene. In the present study we demonstrate that FXR promotes the resolution of colitis in rodents by enhancing Gr gene transcription. We used the chromatin conformation capture (3C) assay to demonstrate that this FXRE is functional in mediating a head-to-tail chromatin looping, thus increasing Gr transcription efficiency. These findings underscore the importance of FXR/GR axis in the control of intestinal inflammation.

  6. A comparative study of Burakovsky's and Jacobs's volume dependence Grüneisen parameter for fcc aluminum

    NASA Astrophysics Data System (ADS)

    Nie, Chuanhui; Zong, Baochun; Wang, Junping

    2015-07-01

    We compare two expressions for the volume dependence of the Grüneisen parameter γ for fcc Al presented by Burakovsky and Preston (2004) [3] and Jacobs and Schmid-Fetzer (2010) [4], respectively. It's found that both calculated results of the melting temperature Tm are in good agreement with experimental data. But the higher order Grüneisen parameters are different. We obtain the values of the third order Grüneisen parameter λ∞ and the pressure derivative of bulk modulus K‧∞ at extreme pressure, and the parameter f in the generalized free volume formula for the two models. The results show that the Jacobs's expression of Grüneisen parameter is more suitable for fcc Al.

  7. A Report on the Hysteroscopic Removal of a Gräfenberg Ring After Almost Fifty Years in Utero

    PubMed Central

    Baldauf, P.; Tönnes, R.; Simon, S.; David, M.

    2014-01-01

    A report on the hysteroscopic removal of a Gräfenberg ring after almost fifty years in utero. In addition to the differential diagnostic considerations, the medical history aspects of this case are particularly interesting. PMID:25484377

  8. Injury-induced GR-1+ macrophage expansion and activation occurs independently of CD4 T-cell influence.

    PubMed

    O'Leary, Fionnuala M; Tajima, Goro; Delisle, Adam J; Ikeda, Kimiko; Dolan, Sinead M; Hanschen, Marc; Mannick, John A; Lederer, James A

    2011-08-01

    Burn injury initiates an enhanced inflammatory condition referred to as the systemic inflammatory response syndrome or the two-hit response phenotype. Prior reports indicated that macrophages respond to injury and demonstrate a heightened reactivity to Toll-like receptor stimulation. Since we and others observed a significant increase in splenic GR-1 F4/80 CD11b macrophages in burn-injured mice, we wished to test if these macrophages might be the primary macrophage subset that shows heightened LPS reactivity. We report here that burn injury promoted higher level TNF-α expression in GR-1, but not GR-1 macrophages, after LPS activation both in vivo and ex vivo. We next tested whether CD4 T cells, which are known to suppress injury-induced inflammatory responses, might control the activation and expansion of GR-1 macrophages. Interestingly, we found that GR-1 macrophage expansion and LPS-induced TNF-α expression were not significantly different between wild-type and CD4 T cell-deficient CD4(-/-) mice. However, further investigations showed that LPS-induced TNF-α production was significantly influenced by CD4 T cells. Taken together, these data indicate that GR-1 F4/80 CD11b macrophages represent the primary macrophage subset that expands in response to burn injury and that CD4 T cells do not influence the GR-1 macrophage expansion process, but do suppress LPS-induced TNF-α production. These data suggest that modulating GR-1 macrophage activation as well as CD4 T cell responses after severe injury may help control the development of systemic inflammatory response syndrome and the two-hit response phenotype.

  9. The alc-GR system: a modified alc gene switch designed for use in plant tissue culture.

    PubMed

    Roberts, Gethin R; Garoosi, G Ali; Koroleva, Olga; Ito, Masaki; Laufs, Patrick; Leader, David J; Caddick, Mark X; Doonan, John H; Tomsett, A Brian

    2005-07-01

    The ALCR/alcA (alc) two-component, ethanol-inducible gene expression system provides stringent control of transgene expression in genetically modified plants. ALCR is an ethanol-activated transcription factor that can drive expression from the ALCR-responsive promoter (alcA). However, the alc system has been shown to have constitutive expression when used in plant callus or cell suspension cultures, possibly resulting from endogenous inducer produced in response to lowered oxygen availability. To widen the use of the alc system in plant cell culture conditions, the receptor domain of the rat glucocorticoid receptor (GR) was translationally fused to the C terminus of ALCR to produce ALCR-GR, which forms the basis of a glucocorticoid-inducible system (alc-GR). The alc-GR switch system was tested in tobacco (Nicotiana tabacum) Bright Yellow-2 suspension cells using a constitutively expressed ALCR-GR with four alternative alcA promoter-driven reporter genes: beta-glucuronidase, endoplasmic reticulum-targeted green fluorescent protein, haemagglutinin, and green fluorescent protein-tagged Arabidopsis (Arabidopsis thaliana) Arath;CDKA;1 cyclin-dependent kinase. Gene expression was shown to be stringently dependent on the synthetic glucocorticoid dexamethasone and, in cell suspensions, no longer required ethanol for induction. Thus, the alc-GR system allows tight control of alcA-driven genes in cell culture and complements the conventional ethanol switch used in whole plants.

  10. Gr-1+CD11b+ cells are responsible for tumor promoting effect of TGF-β in breast cancer progression.

    PubMed

    Li, Zhaoyang; Pang, Yanli; Gara, Sudheer Kumar; Achyut, B R; Heger, Christopher; Goldsmith, Paul K; Lonning, Scott; Yang, Li

    2012-12-01

    One great challenge in our understanding of TGF-β cancer biology and the successful application of TGF-β-targeted therapy is that TGF-β works as both a tumor suppressor and a tumor promoter. The underlying mechanisms for its functional change remain to be elucidated. Using 4T1 mammary tumor model that shares many characteristics with human breast cancer, particularly its ability to spontaneously metastasize to the lungs, we demonstrate that Gr-1+CD11b+ cells or myeloid derived suppressor cells are important mediators in TGF-β regulation of mammary tumor progression. Depletion of Gr-1+CD11b+ cells diminished the antitumor effect of TGF-β neutralization. Two mechanisms were involved: first, treatment with TGF-β neutralization antibody (1D11) significantly decreased the number of Gr-1+CD11b+ cells in tumor tissues and premetastatic lung. This is mediated through increased Gr-1+CD11b+ cell apoptosis. In addition, 1D11 treatment significantly decreased the expression of Th2 cytokines and Arginase 1. Interestingly, the number and property of Gr-1+CD11b+ cells in peripheral blood/draining lymph nodes correlated with tumor size and metastases in response to 1D11 treatment. Our data suggest that the efficacy of TGF-β neutralization depends on the presence of Gr-1+CD11b+ cells, and these cells could be good biomarkers for TGF-β-targeted therapy.

  11. GR 290 (Romano’s Star). II. Light History and Evolutionary State

    NASA Astrophysics Data System (ADS)

    Polcaro, V. F.; Maryeva, O.; Nesci, R.; Calabresi, M.; Chieffi, A.; Galleti, S.; Gualandi, R.; Haver, R.; Mills, O. F.; Osborn, W. H.; Pasquali, A.; Rossi, C.; Vasilyeva, T.; Viotti, R. F.

    2016-06-01

    We have investigated the past light history of the luminous variable star GR 290 (M33/V532, Romano’s Star) in the M33 galaxy, and collected new spectrophotometric observations in order to analyze links between this object, the LBV category, and the Wolf-Rayet stars of the nitrogen sequence. We have built the historical light curve of GR 290 back to 1901, from old observations of the star found in several archival plates of M33. These old recordings together with published and new data on the star allowed us to infer that for at least half a century the star was in a low luminosity state, with B ≃ 18-19, most likely without brighter luminosity phases. After 1960, five large variability cycles of visual luminosity were recorded. The amplitude of the oscillations was seen increasing toward the 1992-1994 maximum, then decreasing during the last maxima. The recent light curve indicates that the photometric variations have been quite similar in all the bands and that the B - V color index has been constant within ±0.1m despite the 1.5m change of the visual luminosity. The spectrum of GR 290 at the large maximum of 1992-94 was equivalent to late-B-type, while, during 2002-2014, it varied between WN10h-11h near the visual maxima to WN8h-9h at the luminosity minima. We have detected, during this same period, a clear anti-correlation between the visual luminosity, the strength of the He ii 4686 Å emission line, the strength of the 4600-4700 Å lines’ blend, and the spectral type. From a model analysis of the spectra collected during the whole 2002-2014 period, we find that the Rosseland radius R2/3, changed between the minimum and maximum luminosity phases by a factor of three while Teff varied between about 33,000 and 23,000 K. We confirm that the bolometric luminosity of the star has not been constant, but has increased by a factor of ˜1.5 between minimum and maximum luminosity, in phase with the apparent luminosity variations. Presently, GR 290 falls in the H

  12. A high mass progenitor for the Type Ic Supernova 2007gr inferred from its environment

    NASA Astrophysics Data System (ADS)

    Maund, Justyn R.; Ramirez-Ruiz, Enrico

    2016-03-01

    We present an analysis of late-time Hubble Space Telescope Wide Field Camera 3 (WFC3) and Wide Field Planetary Camera 2 (WFPC2) observations of the site of the Type Ic supernova (SN) 2007gr in NGC 1058. The SN is barely recovered in the late-time WFPC2 observations, while a possible detection in the later WFC3 data is debatable. These observations were used to conduct a multiwavelength study of the surrounding stellar population. We fit spatial profiles to a nearby bright source that was previously proposed to be a host cluster. We find that, rather than being an extended cluster, it is consistent with a single point-like object. Fitting stellar models to the observed spectral energy distribution of this source, we conclude it is A1-A3 Yellow Supergiant, possibly corresponding to a star with MZAMS = 40 M⊙. SN 2007gr is situated in a massive star association, with diameter of ≈300 pc. We present a Bayesian scheme to determine the properties of the surrounding massive star population, in conjunction with the Padova isochrones. We find that the stellar population, as observed in either the WFC3 and WFPC2 observations, can be well fit by two age distributions with mean ages: ˜6.3 Myr and ˜50 Myr. The stellar population is clearly dominated by the younger age solution (by factors of 3.5 and 5.7 from the WFPC2 and WFC3 observations, respectively), which corresponds to the lifetime of a star with MZAMS ˜ 30 M⊙. This is strong evidence in favour of the hypothesis that SN 2007gr arose from a massive progenitor star, possibly capable of becoming a Wolf-Rayet star.

  13. gr-MRI: A software package for magnetic resonance imaging using software defined radios

    NASA Astrophysics Data System (ADS)

    Hasselwander, Christopher J.; Cao, Zhipeng; Grissom, William A.

    2016-09-01

    The goal of this work is to develop software that enables the rapid implementation of custom MRI spectrometers using commercially-available software defined radios (SDRs). The developed gr-MRI software package comprises a set of Python scripts, flowgraphs, and signal generation and recording blocks for GNU Radio, an open-source SDR software package that is widely used in communications research. gr-MRI implements basic event sequencing functionality, and tools for system calibrations, multi-radio synchronization, and MR signal processing and image reconstruction. It includes four pulse sequences: a single-pulse sequence to record free induction signals, a gradient-recalled echo imaging sequence, a spin echo imaging sequence, and an inversion recovery spin echo imaging sequence. The sequences were used to perform phantom imaging scans with a 0.5 Tesla tabletop MRI scanner and two commercially-available SDRs. One SDR was used for RF excitation and reception, and the other for gradient pulse generation. The total SDR hardware cost was approximately 2000. The frequency of radio desynchronization events and the frequency with which the software recovered from those events was also measured, and the SDR's ability to generate frequency-swept RF waveforms was validated and compared to the scanner's commercial spectrometer. The spin echo images geometrically matched those acquired using the commercial spectrometer, with no unexpected distortions. Desynchronization events were more likely to occur at the very beginning of an imaging scan, but were nearly eliminated if the user invoked the sequence for a short period before beginning data recording. The SDR produced a 500 kHz bandwidth frequency-swept pulse with high fidelity, while the commercial spectrometer produced a waveform with large frequency spike errors. In conclusion, the developed gr-MRI software can be used to develop high-fidelity, low-cost custom MRI spectrometers using commercially-available SDRs.

  14. gr-MRI: A software package for magnetic resonance imaging using software defined radios.

    PubMed

    Hasselwander, Christopher J; Cao, Zhipeng; Grissom, William A

    2016-09-01

    The goal of this work is to develop software that enables the rapid implementation of custom MRI spectrometers using commercially-available software defined radios (SDRs). The developed gr-MRI software package comprises a set of Python scripts, flowgraphs, and signal generation and recording blocks for GNU Radio, an open-source SDR software package that is widely used in communications research. gr-MRI implements basic event sequencing functionality, and tools for system calibrations, multi-radio synchronization, and MR signal processing and image reconstruction. It includes four pulse sequences: a single-pulse sequence to record free induction signals, a gradient-recalled echo imaging sequence, a spin echo imaging sequence, and an inversion recovery spin echo imaging sequence. The sequences were used to perform phantom imaging scans with a 0.5Tesla tabletop MRI scanner and two commercially-available SDRs. One SDR was used for RF excitation and reception, and the other for gradient pulse generation. The total SDR hardware cost was approximately $2000. The frequency of radio desynchronization events and the frequency with which the software recovered from those events was also measured, and the SDR's ability to generate frequency-swept RF waveforms was validated and compared to the scanner's commercial spectrometer. The spin echo images geometrically matched those acquired using the commercial spectrometer, with no unexpected distortions. Desynchronization events were more likely to occur at the very beginning of an imaging scan, but were nearly eliminated if the user invoked the sequence for a short period before beginning data recording. The SDR produced a 500kHz bandwidth frequency-swept pulse with high fidelity, while the commercial spectrometer produced a waveform with large frequency spike errors. In conclusion, the developed gr-MRI software can be used to develop high-fidelity, low-cost custom MRI spectrometers using commercially-available SDRs.

  15. The Modified Debye-Grüneisen Model for Highly Compressed Diamond

    NASA Astrophysics Data System (ADS)

    Yakub, Eugene

    2017-04-01

    A new modification of the Debye-Grüneisen model is proposed. It takes explicitly into account the anharmonicity of phonon modes, which leads to the nonlinear dependence of energy levels on quantum numbers. The low-temperature version of this model considering anharmonic displacement of only the lowest energy levels of both longitudinal and transverse phonons is developed. This model, calibrated on results of DFT ab initio calculations, reproduces all predicted low-temperature thermodynamic properties of diamond at pressures up to 1 TPa, including the region of its negative thermal expansion.

  16. A Biased and Personal Description of GR at Syracuse University, 1951-1961

    NASA Astrophysics Data System (ADS)

    Newman, E. T.

    In mid-century, General Relativity was largely in the doldrums. Though at the time I was completely unaware of it, there were perhaps only four or five active groups around the world working in GR; Hamburg (Jordan), London (Bondi), Princeton (Wheeler), Warsaw (Infeld) and Syracuse (Bergmann). I had the privilege and pleasure of being a member of the Syracuse group working under Peter G. Bergmann. I would like to describe some of the things that took place there, who were the active participants, who we interacted with, what was accomplished and finally conjecture what role we played in the revitalization of relativity in the late 1950s and early 1960s.

  17. Understanding and correcting the Up erroneous signal in GR2 IGS series

    NASA Astrophysics Data System (ADS)

    Loyer, Sylvain; Mercier, Flavien; Capdeville, Hugues; Mezerette, Adrien; Perosanz, Felix

    2015-04-01

    The CNES-CLS IGS Analysis Center has participated for its first time to the REPRO2 IGS reprocessing campaign in order to participate in the IGS combined product for a new ITRF realization. Preliminary comparisons between the different ACs contributions highlighted an anomalous behavior of GR2 CNES-CLS solution. The daily global RMS of the station coordinates difference exhibited a spurious annual signal on the Up and North component of respectively 6 and 2 mm. We first investigated if any specific option in terms of parameter or model in our processing could explain such difference. For example we quantified the impact of using time-variable-gravity field models (instead of static), of using FES2012 instead of FES2004 oceanic model, of changing the cut-off elevation angle. Even if these tests remain instructive, none of them could explain the anomalous signal. We finally discovered an error of parameterization of the GPT2/GMF2 tropospheric model affecting the full reprocessing effort: the constant atmospheric pressure option (without taking into account seasonal terms) has been considered. As a consequence, the hydrostatic tropospheric a priori correction to the GNSS measurements couldn't be totally compensated by the wet tropospheric parameter estimated a posteriori. After confirming that this error was the major reason of our problem, we investigated if an a posteriori correction could be applied to the station coordinate series. One full year of data has been reprocessed again using an identical configuration except the consideration of a variable atmospheric pressure from GTP2 model. For each station, the coordinate comparison between the new solution called GR2P and the initial GR2 one clearly shown a smooth "annual" function. As the difference between a constant and a variable atmospheric pressure in GPT2 model is stationary from one year to the next, we concluded that this station specific function is also stationary and that it could be applied to full

  18. Pharmacological profile of GR117289 in vitro: a novel, potent and specific non-peptide angiotensin AT1 receptor antagonist.

    PubMed Central

    Robertson, M. J.; Barnes, J. C.; Drew, G. M.; Clark, K. L.; Marshall, F. H.; Michel, A.; Middlemiss, D.; Ross, B. C.; Scopes, D.; Dowle, M. D.

    1992-01-01

    1. This paper describes the effects of GR117289 (1-[[3-bromo-2-[2-(1H-tetrazol-5-yl)phenyl]-5-benzo-furanyl]methyl ]-2-butyl-4-chloro-1H-imidazole-5-carboxylic acid) at angiotensin receptors and binding sites in rabbit aorta, rat liver and bovine cerebellum preparations in vitro. 2. In rabbit isolated aortic strips, GR117289 (0.3, 1 and 3 nM) caused a concentration-related, insurmountable suppression of the concentration-response curve to angiotensin II (AII). When the contact time was increased, a greater degree of antagonism of AII was observed, suggesting that GR117289 is slow to reach equilibrium. A pKB of 9.8 +/- 0.1 was calculated for GR117289 after 3 h incubation. GR117289 (1 microM) did not affect contractile responses to phenylephrine or 5-hydroxytryptamine (5-HT) in the rabbit aorta. 3. GR117289 (1 nM) alone caused a marked suppression and a slight rightward displacement of the AII concentration-response curve. Co-incubation with the competitive, surmountable AT1 receptor antagonist, losartan (10 nM, 100 nM and 1 microM), resulted in a concentration-related upward and rightward displacement of the concentration-response curve to subsequently administered AII. In separate experiments in which preparations were pre-incubated with GR117289 (1 nM), subsequent addition of losartan (1 microM) for 2, 15 or 45 min caused a further, but similar, rightward displacement of the concentration-response curve to subsequently administered AII with a time-dependent increase in the maximum response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1467838

  19. Novel insights into the neuroendocrine control of inflammation: the role of GR and PARP1

    PubMed Central

    Aprile-Garcia, Fernando; Antunica-Noguerol, María; Budziñski, Maia Ludmila; Liberman, Ana C; Arzt, Eduardo

    2013-01-01

    Inflammatory responses are elicited after injury, involving release of inflammatory mediators that ultimately lead, at the molecular level, to the activation of specific transcription factors (TFs; mainly activator protein 1 and nuclear factor-κB). These TFs propagate inflammation by inducing the expression of cytokines and chemokines. The neuroendocrine system has a determinant role in the maintenance of homeostasis, to avoid exacerbated inflammatory responses. Glucocorticoids (GCs) are the key neuroendocrine regulators of the inflammatory response. In this study, we describe the molecular mechanisms involved in the interplay between inflammatory cytokines, the neuroendocrine axis and GCs necessary for the control of inflammation. Targeting and modulation of the glucocorticoid receptor (GR) and its activity is a common therapeutic strategy to reduce pathological signaling. Poly (ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes the addition of PAR on target proteins, a post-translational modification termed PARylation. PARP1 has a central role in transcriptional regulation of inflammatory mediators, both in neuroendocrine tumors and in CNS cells. It is also involved in modulation of several nuclear receptors. Therefore, PARP1 and GR share common inflammatory pathways with antagonic roles in the control of inflammatory processes, which are crucial for the effective maintenance of homeostasis. PMID:24243533

  20. GR718- Radiation-Tolerant 18x SpaceWire Router

    NASA Astrophysics Data System (ADS)

    Ekergaren, Jonas; Habinc, Sandi; Johansson, Fredrik; Sturesson, Fredrik; Simlastik, Martin; Hernandez, Francisco; Redant, Steven; Stinkens, Kurt; Thys, Geert; Das Arul Mahesh, Jagadeesa; Suess, Martin

    2015-09-01

    GR718 is a radiation tolerant 18 port standalone SpaceWire router component that has been developed by Cobham Gaisler together with IMEC (BE), in an activity initiated by the European Space Agency under ESTEC contract 4000105402/12/NL/Cbi. Out of the 18 SpaceWire ports, 16 use on-chip LVDS transceivers, and two use LVTTL signaling. Included also is the mandatory configuration port, as well as an internal port for system level testing. All ports are capable of operating in 200 Mbit/s. UART and JTAG interfaces, that gives access to the on-chip AMBA AHB bus, are provided for configuration and debugging. SPI and GPIO interfaces are accessible through the configuration port, which allows SPI devices to be accessed and general purpose signaling to be performed through RMAP commands. In addition to the mandatory features in the current ECSS SpaceWire standard, GR718 supports group adaptive routing for path addresses, and packet distribution. It also includes support for the incoming SpaceWire standard revision 1 (ECSS-E-ST-50-12C Rev.1), the SpaceWire-D protocol, and the SpaceWire Plug-and-Play protocol currently being developed for ECSS. The technology used is UMC 180 nm, using the DARE library from IMEC, and the package is a 256 pin CQFP. A development board for evaluation and software development has been manufactured as well.

  1. Friction Stir Welding of GR-Cop 84 for Combustion Chamber Liners

    NASA Technical Reports Server (NTRS)

    Russell, Carolyn K.; Carter, Robert; Ellis, David L.; Goudy, Richard

    2004-01-01

    GRCop-84 is a copper-chromium-niobium alloy developed by the Glenn Research Center for liquid rocket engine combustion chamber liners. GRCop-84 exhibits superior properties over conventional copper-base alloys in a liquid hydrogen-oxygen operating environment. The Next Generation Launch Technology program has funded a program to demonstrate scale-up production capabilities of GR-Cop 84 to levels suitable for main combustion chamber production for the prototype rocket engine. This paper describes a novel method of manufacturing the main combustion chamber liner. The process consists of several steps: extrude the GR-Cop 84 powder into billets, roll the billets into plates, bump form the plates into cylinder halves and friction stir weld the halves into a cylinder. The cylinder is then metal spun formed to near net liner dimensions followed by finish machining to the final configuration. This paper describes the friction stir weld process development including tooling and non-destructive inspection techniques, culminating in the successful production of a liner preform completed through spin forming.

  2. airGR: a suite of lumped hydrological models in an R-package

    NASA Astrophysics Data System (ADS)

    Coron, Laurent; Perrin, Charles; Delaigue, Olivier; Andréassian, Vazken; Thirel, Guillaume

    2016-04-01

    Lumped hydrological models are useful and convenient tools for research, engineering and educational purposes. They propose catchment-scale representations of the precipitation-discharge relationship. Thanks to their limited data requirements, they can be easily implemented and run. With such models, it is possible to simulate a number of hydrological key processes over the catchment with limited structural and parametric complexity, typically evapotranspiration, runoff, underground losses, etc. The Hydrology Group at Irstea (Antony) has been developing a suite of rainfall-runoff models over the past 30 years with the main objectives of designing models as efficient as possible in terms of streamflow simulation, applicable to a wide range of catchments and having low data requirements. This resulted in a suite of models running at different time steps (from hourly to annual) applicable for various issues including water balance estimation, forecasting, simulation of impacts and scenario testing. Recently, Irstea has developed an easy-to-use R-package (R Core Team, 2015), called airGR, to make these models widely available. It includes: - the water balance annual GR1A (Mouehli et al., 2006), - the monthly GR2M (Mouehli, 2003) models, - three versions of the daily model, namely GR4J (Perrin et al., 2003), GR5J (Le Moine, 2008) and GR6J (Pushpalatha et al., 2011), - the hourly GR4H model (Mathevet, 2005), - a degree-day snow module CemaNeige (Valéry et al., 2014). The airGR package has been designed to facilitate the use by non-expert users and allow the addition of evaluation criteria, models or calibration algorithms selected by the end-user. Each model core is coded in FORTRAN to ensure low computational time. The other package functions (i.e. mainly the calibration algorithm and the efficiency criteria) are coded in R. The package is already used for educational purposes. The presentation will detail the main functionalities of the package and present a case

  3. [Mexican medicinal plants and Grüninger's diet. Documentation No.25].

    PubMed

    Deplazes, G; Hauser, S P

    1990-05-29

    A decoction is prepared from 14 Mexican medicinal plants. This phytotherapy is supplemented by a special diet ('food with a high nutritional value') and nutritional supplements such as lactoferment, enzyme preparations (e.g. Wobenzym), co-enzymes (e.g. Becozym forte) Ossopulvit, vitamin C, iron preparations and raw melasses. The following indications are mentioned: all stages of cancer, following surgery, during radiotherapy or chemotherapy in order to alleviate side effects and stimulate the immune system and hematopoiesis, detoxification in all other diseases. The initial fasting period is followed by a diet, phytotherapy and the ingestion of nutritional supplements. The only side effects are caused by tumour degradation products as a result of excessively rapid tumour degradation. The documentation brochure costs Fr. 30.-. The patient pays what he likes for the tea bag of a cure. F.A. Grüninger is a chemist living in the Bernese Oberland (Switzerland). He spends most of his time in Mexico, where he himself collects the individual plants. According to Grüninger, cancer is an intoxication of the entire body as a result of an inappropriate diet (demineralized, poor in cellulose, high in hormone levels). The intoxication in counteracted by fasting, phytotherapy and dietary measures. Only subjective statements are available about the Mexican medicinal plants. Toxicity studies in rats revealed no signs of toxicity. There are no preclinical or clinical data in man.

  4. Nonlinear elastic effects on the energy flux deviation of ultrasonic waves in gr/ep composites

    NASA Technical Reports Server (NTRS)

    Prosser, William H.; Kriz, R. D.; Fitting, Dale W.

    1992-01-01

    The effects of nonlinear elasticity on energy flux deviation in undirectional gr/ep composites are examined. The shift in the flux deviation is modeled using acoustoelasticity theory and the second- and third-order elastic stiffness coefficients for T300/5208 gr/ep. Two conditions of applied uniaxial stress are considered. In the first case, the direction of applied uniaxial stress was along the fiber axis (x3), while in the second case it was perpendicular to the fiber axis along the laminate stacking direction (x1). For both conditions, the change in the energy flux deviation angle from the condition of zero applied stress is computed over the range of propagation directions of 0 to 60 deg from the fiber axis at two-degree intervals. A positive flux deviation angle implies the energy deviates away from the fiber direction toward the x1 axis, while a negative deviation means that the energy deviates toward the fibers. Over this range of fiber orientation angles, the energy of the quasi-longitudinal and pure mode transverse waves deviates toward the fibers, while that of the quasi-transverse mode deviates away from the fibers.

  5. Quantitative Analysis of Seismicity Before Large Taiwanese Earthquakes Using the G-R Law

    NASA Astrophysics Data System (ADS)

    Li, H.-C.; Chang, C.-H.; Chen, C.-C.

    2016-01-01

    Seismicity has been identified as an example of a natural, nonlinear system for which the distribution of frequency and event size follow a power law called the "Gutenberg-Richter (G-R) law." The parameters of the G-R law, namely b- and a-values, have been widely used in many studies about seismic hazards, earthquake forecasting models, and other related topics. However, the plausibility of the power law model and applicability of parameters were mainly verified by statistical error σ of the b-value, the effectiveness of which is still doubtful. In this research, we used a newly defined p value developed by Clauset et al. ( Power- Law Distributions in Empirical Data, SIAM Rev. 51, 661-703, 2009) instead of the statistical error σ of the b-value and verified its effectiveness as a plausibility index of the power-law model. Furthermore, we also verified the effectiveness of K-S statistics as a goodness-of-fit test in estimating the crucial parameter M_{c} of the power-law model.

  6. Developing an Optimum Protocol for Thermoluminescence Dosimetry with GR-200 Chips using Taguchi Method.

    PubMed

    Sadeghi, Maryam; Faghihi, Reza; Sina, Sedigheh

    2016-11-24

    Thermoluminescence dosimetry (TLD) is a powerful technique with wide applications in personal, environmental and clinical dosimetry. The optimum annealing, storage and reading protocols are very effective in accuracy of TLD response. The purpose of this study is to obtain an optimum protocol for GR-200; LiF: Mg, Cu, P, by optimizing the effective parameters, to increase the reliability of the TLD response using Taguchi method. Taguchi method has been used in this study for optimization of annealing, storage and reading protocols of the TLDs. A number of 108 GR-200 chips were divided into 27 groups, each containing four chips. The TLDs were exposed to three different doses, and stored, annealed and read out by different procedures as suggested by Taguchi Method. By comparing the signal-to-noise ratios the optimum dosimetry procedure was obtained. According to the results, the optimum values for annealing temperature (°C), Annealing Time (s), Annealing to Exposure time (d), Exposure to Readout time (d), Pre-heat Temperature (°C), Pre-heat Time (s), Heating Rate (°C/s), Maximum Temperature of Readout (°C), readout time (s) and Storage Temperature (°C) are 240, 90, 1, 2, 50, 0, 15, 240, 13 and -20, respectively. Using the optimum protocol, an efficient glow curve with low residual signals can be achieved. Using optimum protocol obtained by Taguchi method, the dosimetry can be effectively performed with great accuracy.

  7. Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes

    PubMed Central

    Fujisawa, Takeshi; Wang, Keqing; Niu, Xi-Lin; Egginton, Stuart; Ahmad, Shakil; Hewett, Peter; Kontos, Christopher D.; Ahmed, Asif

    2017-01-01

    Aims Atherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse. Methods and results Apo-E knockout (Apo-E-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1+ monocytes in the circulation, while the cell-surface expression of CD11b, which mediates monocyte emigration, was significantly reduced. Conclusions Ang-1 specifically increases circulating Gr1+ inflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis. PMID:28069704

  8. Mapping soil erosion risk in Serra de Grândola (Portugal)

    NASA Astrophysics Data System (ADS)

    Neto Paixão, H. M.; Granja Martins, F. M.; Zavala, L. M.; Jordán, A.; Bellinfante, N.

    2012-04-01

    Geomorphological processes can pose environmental risks to people and economical activities. Information and a better knowledge of the genesis of these processes is important for environmental planning, since it allows to model, quantify and classify risks, what can mitigate the threats. The objective of this research is to assess the soil erosion risk in Serra de Grândola, which is a north-south oriented mountain ridge with an altitude of 383 m, located in southwest of Alentejo (southern Portugal). The study area is 675 km2, including the councils of Grândola, Santiago do Cacém and Sines. The process for mapping of erosive status was based on the guidelines for measuring and mapping the processes of erosion of coastal areas of the Mediterranean proposed by PAP/RAC (1997), developed and later modified by other authors in different areas. This method is based on the application of a geographic information system that integrates different types of spatial information inserted into a digital terrain model and in their derivative models. Erosive status are classified using information from soil erodibility, slope, land use and vegetation cover. The rainfall erosivity map was obtained using the modified Fournier index, calculated from the mean monthly rainfall, as recorded in 30 meteorological stations with influence in the study area. Finally, the soil erosion risk map was designed by ovelaying the erosive status map and the rainfall erosivity map.

  9. Ultraviolet Light B-Mediated Inhibition of Skin Catalase Activity Promotes Gr-1+CD11b+ Myeloid Cell Expansion

    PubMed Central

    Sullivan, Nicholas J.; Tober, Kathleen L.; Burns, Erin M.; Schick, Jonathan S.; Riggenbach, Judith A.; Mace, Thomas A.; Bill, Matthew A.; Young, Gregory S.; Oberyszyn, Tatiana M.; Lesinski, Gregory B.

    2011-01-01

    Skin cancer incidence and mortality are higher in men compared to women, but the causes of this sex discrepancy remain largely unknown. Ultraviolet light exposure induces cutaneous inflammation and neutralizes cutaneous antioxidants. Gr-1+CD11b+ myeloid cells are heterogeneous bone marrow-derived cells that promote inflammation-associated carcinogenesis. Reduced activity of catalase, an antioxidant present within skin, has been associated with skin carcinogenesis. We utilized the outbred, immune competent Skh-1 hairless mouse model of ultraviolet light B (UVB)-induced inflammation and non-melanoma skin cancer to further define sex discrepancies in UVB-induced inflammation. Our results demonstrated that male skin had relatively lower baseline catalase activity, which was inhibited following acute UVB exposure in both sexes. Further analysis revealed that skin catalase activity inversely correlated with splenic Gr-1+CD11b+ myeloid cell percentage. Acute UVB exposure induced Gr-1+CD11b+ myeloid cell skin infiltration, which was inhibited to a greater extent in males by topical catalase treatment. In chronic UVB studies, we demonstrated that the percentage of splenic Gr-1+CD11b+ myeloid cells was 55% higher in male tumor-bearing mice compared to their female counterparts. Together, our findings indicate that lower skin catalase activity in male mice may at least in part contribute to increased UVB-induced Gr-1+CD11b+ myeloid cells and subsequent skin carcinogenesis. PMID:22030957

  10. Enhanced decolorization and biodegradation of textile azo dye Scarlet R by using developed microbial consortium-GR.

    PubMed

    Saratale, R G; Saratale, G D; Kalyani, D C; Chang, J S; Govindwar, S P

    2009-05-01

    A developed consortium-GR, consisting of Proteus vulgaris NCIM-2027 (PV) and Micrococcus glutamicus NCIM-2168 (MG), completely decolorized an azo dye Scarlet R under static anoxic condition with an average decolorization rate of 16,666 microg h(-1); which is much faster than that of the pure cultures (PV, 3571 microg h(-1); MG, 2500 microg h(-1)). Consortium-GR gave best decolorization performance with nearly complete mineralization of Scarlet R (over 90% TOC and COD reduction) within 3h, much shorter relative to the individual strains. Induction in the riboflavin reductase and NADH-DCIP reductase was observed in the consortium, suggesting the involvement of these enzymes during the fast decolorization process. The FTIR and GC-MS analysis showed that 1,4-benzenediamine was formed during decolorization/degradation of Scarlet R by consortium-GR. Phytotoxicity studies revealed no toxicity of the biodegraded products of Scarlet R by consortium-GR. In addition, consortium-GR applied for mixture of industrial dyes showed 88% decolorization under static condition with significant reduction in TOC (62%) and COD (68%) within 72 h, suggesting potential application of this microbial consortium in bioremediation of dye-containing wastewater.

  11. IUGR increases chromatin-remodeling factor Brg1 expression and binding to GR exon 1.7 promoter in newborn male rat hippocampus.

    PubMed

    Ke, Xingrao; McKnight, Robert A; Gracey Maniar, Lia E; Sun, Ying; Callaway, Christopher W; Majnik, Amber; Lane, Robert H; Cohen, Susan S

    2015-07-15

    Intrauterine growth restriction (IUGR) increases the risk for neurodevelopment delay and neuroendocrine reprogramming in both humans and rats. Neuroendocrine reprogramming involves the glucocorticoid receptor (GR) gene that is epigenetically regulated in the hippocampus. Using a well-characterized rodent model, we have previously shown that IUGR increases GR exon 1.7 mRNA variant and total GR expressions in male rat pup hippocampus. Epigenetic regulation of GR transcription may involve chromatin remodeling of the GR gene. A key chromatin remodeler is Brahma-related gene-1(Brg1), a member of the ATP-dependent SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. Brg1 regulates gene expression by affecting nucleosome repositioning and recruiting transcriptional components to target promoters. We hypothesized that IUGR would increase hippocampal Brg1 expression and binding to GR exon 1.7 promoter, as well as alter nucleosome positioning over GR promoters in newborn male pups. Further, we hypothesized that IUGR would lead to accumulation of specificity protein 1 (Sp1) and RNA pol II at GR exon 1.7 promoter. Indeed, we found that IUGR increased Brg1 expression and binding to GR exon 1.7 promoter. We also found that increased Brg1 binding to GR exon 1.7 promoter was associated with accumulation of Sp1 and RNA pol II carboxy terminal domain pSer-5 (a marker of active transcription). Furthermore, the transcription start site of GR exon 1.7 was located within a nucleosome-depleted region. We speculate that changes in hippocampal Brg1 expression mediate GR expression and subsequently trigger neuroendocrine reprogramming in male IUGR rats.

  12. Characterisation of the specific binding of the histamine H3 receptor antagonist radioligand [3H]GR168320.

    PubMed

    Brown, J D; O'Shaughnessy, C T; Kilpatrick, G J; Scopes, D I; Beswick, P; Clitherow, J W; Barnes, J C

    1996-09-12

    We have examined the specific binding of the tritiated derivative of the potent histamine H3 receptor antagonist, [3,4-3H2]-cyclohex-yl-¿[4-(3H-imidazol-4-yl)-piperidin-l-yl] iminomethyl¿- amine ([3H]GR168320), to homogenates of rat cerebral cortex. Specific binding of [3H]GR168320 at 37 degrees C associated and dissociated rapidly. Binding was saturable (Bmax 412 +/- 89 fmol/mg protein) and of high affinity (Kd 0.12 +/- 0.11 nM). Saturation studies suggested the involvement of a single site. Histamine H3 receptor agonists and antagonists inhibited [3H]GR168320 binding with high affinity. Agonist and antagonist affinities correlated when compared with affinities obtained using the tritiated histamine H3 agonist radioligand N alpha-methylhistamine.

  13. Long-term orbital period behaviour of low mass ratio contact binaries GR Vir and FP Boo

    NASA Astrophysics Data System (ADS)

    Ćetinkaya, Halil; Soydugan, Faruk

    2017-02-01

    In this study, we investigated orbital period variations of two low mass ratio contact binaries GR Vir and FP Boo based on published minima times. From the O-C analysis, it was found that FP Boo indicates orbital period decrease while the period of GR Vir is increasing. Mass transfer process was used to explain increase and decrease in the orbital periods. In the O-C diagrams of both systems periodic variations also exist. Cyclic changes can be explained as being the result of a light-travel time effect via a third component around the eclipsing binaries. In order to interpret of cyclic orbital period changes for GR Vir, which has late-type components, possible magnetic activity cycles of the components have been also considered.

  14. Expression of a sugar clade gustatory receptor, BmGr6, in the oral sensory organs, midgut, and central nervous system of larvae of the silkworm Bombyx mori.

    PubMed

    Mang, Dingze; Shu, Min; Endo, Haruka; Yoshizawa, Yasutaka; Nagata, Shinji; Kikuta, Shingo; Sato, Ryoichi

    2016-03-01

    Insects taste nonvolatile chemicals through gustatory receptors (Grs) and make choices for feeding, mating, and oviposition. To date, genome projects have identified 69 Gr genes in the silkworm, Bombyx mori; however, the expression sites of these Grs remain to be explored. In this study, we used reverse transcription (RT)-PCR to investigate expression of the B. mori Gr-6 (BmGr6) gene, a member of the putative sugar clade gene family in various tissues. BmGr6 is expressed in the midgut, central nervous system (CNS), and oral sensory organs. Moreover, immunohistochemistry using an anti-BmGr6 antiserum demonstrated that BmGr6 is expressed in cells by oral sensory organs, midgut and nervous system. Furthermore, double-immunohistochemistry indicated that BmGr6 is expressed in midgut enteroendocrine cells, also in CNS neurosecretory cells. In particular, a portion of BmGr6-expressing cells, in both midgut and CNS, secretes FMRFamide-related peptides (FaRPs). These results suggest that BmGr6 functions not only as a taste receptor, but also as a chemical sensor such as for the regulation of gut movement, physiological conditions, and feeding behavior of larvae.

  15. Reduced expression of 15-hydroxy prostaglandin dehydrogenase in chorion during labor is associated with decreased PRB and increased PRA and GR expression.

    PubMed

    Li, Yuan; He, Ping; Sun, Qianqian; Liu, Jie; Gao, Lu; You, Xingji; Gu, Hang; Ni, Xin

    2013-05-01

    The chorion laeve controls the levels of active prostaglandins within the uterus by NAD-dependent 15-hydroxy prostaglandin dehydrogenase (PGDH). The expression of PGDH in chorion is modulated by glucocorticoids and progesterone. In this study, we investigated glucocorticoid receptor (GR) and progesterone receptor A and B (PRA and PRB) in the regulation of PGDH expression in chorion, and we determined whether reduced PGDH expression in chorion during labor is associated with the changes in GR and PR expression by real-time RT-PCR and Western blot analysis. Dexamethasone (DEX) inhibited PGDH expression whereas progesterone stimulated PGDH expression in chorionic trophoblasts. DEX suppressed PGDH expression in GR overexpression and PR knockdown cells. The inhibitory effect of DEX did not occur in GR knockdown cells. Progesterone inhibited PGDH in GR overexpression and PR knockdown cells and it stimulated PGDH in PRB overexpression cells whereas it suppressed PGDH in PRA overexpression cells. Knockdown of c-Jun resulted in a loss of progesterone- and DEX-induced effects. PGDH was down-regulated in chorion tissues during labor. PRB was decreased whereas PRA and GR were increased in chorion during labor. Glucocorticoids inhibit PGDH expression via GR in chorionic trophoblasts. Progesterone enhances PGDH expression through PRB, whereas it inhibits PGDH expression via GR and PRA. Decreased PGDH expression is associated with increased GR and PRA, although decreased PRB, in chorion during labor.

  16. Acupuncture Relieves the Excessive Excitation of Hypothalamic-Pituitary-Adrenal Cortex Axis Function and Correlates with the Regulatory Mechanism of GR, CRH, and ACTHR.

    PubMed

    Wang, Shao-Jun; Zhang, Jiao-Jiao; Qie, Li-Li

    2014-01-01

    It had been indicated in the previous studies that acupuncture relieved the excessive excitation of hypothalamic-pituitary-adrenal cortex axis (HPAA) function induced by stress stimulation. But the changes in glucocorticoid receptor (GR) induced by acupuncture have not been detected clearly. The objective of the study was to observe the impacts of acupuncture on the protein expressions of corticotrophin releasing hormone (CRH), adrenocorticotropic hormone receptor (ACTHR), and GR under the physiological and stress states. The results showed that under the stress state, acupuncture upregulated the protein expression of GR in the hippocampus, hypothalamic paraventricular nucleus (PVN), and pituitary gland, downregulated the protein expression of GR in the adrenal cortex, and obviously reduced the protein expressions of CRH and ACTHR. Under the physiological state, acupuncture promoted GR protein expression in the hippocampus and CRH protein expression in the hippocampus and PVN. The results explained that acupuncture regulated the stress reaction via promoting the combination of glucocorticoids (GC) with GR, and GR protein expression. The increase of GR protein expression induced feedback inhibition on the overexpression of CRH and ACTHR, likely decreased GC level, and caused the reduction of GR protein expression in the adrenal cortex.

  17. Effects of chronic cortisol administration on global expression of GR and the liver transcriptome in Sparus aurata.

    PubMed

    Teles, Mariana; Boltaña, Sebastian; Reyes-López, Felipe; Santos, Maria Ana; Mackenzie, Simon; Tort, Lluis

    2013-02-01

    The present work was designed to assess the effects of artificially increased high plasma cortisol levels induced by slow-release cortisol implants on the mRNA abundance of the glucocorticoid receptor (GR) in different organs of Sparus aurata (Gilthead sea bream), as well as to evaluate global transcriptional changes in the liver, using the Aquagenomics S. aurata oligo-nucleotide microarray technology. For that purpose, groups of fish were intraperitoneally injected with implants containing two different concentrations of cortisol (50 or 200 μg/g body weight). Blood and organs were sampled after 7 and 14 days of cortisol implantation. Only fish with 200 μg/g implants exhibited a significant rise in plasma cortisol. Thus, we evaluated the expression of the GR in different organs in these fish 7 and 14 days post-implantation. GR mRNA abundance was upregulated in head kidney and heart of fish at both sampling times. In liver and muscle, GR mRNA abundance was upregulated after 14 days, whereas in gills, the GR mRNA transcript was upregulated earlier, at day 7. These results suggest that increased plasma cortisol induced by a slow-release implant of cortisol mimics the overall effects of stress and affects the expression of GR mRNA in a time- and organ-specific manner. Data obtained with the Aquagenomics S. aurata oligo-nucleotide microarray allowed the identification of a total of 491 cortisol-responsive transcripts and highlight the strong intensity of transcriptional modulation in liver of fish implanted with cortisol after 7 days, in contrast to that observed at day 14. Transcriptional remodeling highlighted a significant activity in carbohydrate metabolism mainly in the gluconeogenic pathway linked to downregulation of inflammatory and immune response processes in implanted fish.

  18. Goneis.gr: Training Greek Parents on ICT and Safer Internet

    NASA Astrophysics Data System (ADS)

    Manouselis, Nikos; Riviou, Katerina; Palavitsinis, Nikos; Giannikopoulou, Vasiliki; Tsanakas, Panayotis

    Children's use of the Internet has significantly risen in the last decade. Nevertheless, children spend a lot of time online which makes them susceptible to various threats (such as inappropriate material, offensive language, etc). Parents are the last frontier to this menace but they also need to be educated and trained in order to protect their children. Goneis.gr is an initiative launched by the Greek government that aims to educate parents on safer Internet and the use of parental control software. Parents are also entitled to distance learning courses covering basic computer skills. This paper presents the results of two separate surveys that took place in the last few months (December 2008-January 2009). The first survey targeted the parents that have completed the programme and the second one the educational providers that participate in the programme and offer the training to the beneficiaries.

  19. Geodetic constraints on volcanic plume height at Grímsvötn volcano, Iceland

    NASA Astrophysics Data System (ADS)

    Hreinsdóttir, Sigrún; Sigmundsson, Freysteinn; Roberts, Matthew; Björnsson, Halldór; Grapenthin, Ronni; Arason, Pórdur; Árnadóttir, Thóra; Hólmjárn, Jósef; Geirsson, Halldór; Bennett, Richard; Gudmundsson, Magnús; Oddsson, Björn; Ófeigsson, Benedikt; Villemin, Thierry; Jónsson, Torsteinn; Sturkell, Erik; Höskuldsson, Ármann; Larsen, Gudrún; Thordarson, Thor; Óladóttir, Bergrún

    2014-05-01

    In 2011 a VEI 4 explosive eruption took place at Grímsvötn volcano, Iceland. Grímsvötn is a subglacial basaltic volcano beneath the Vatnajökull ice cap. It is Iceland's most frequently erupting volcano, with recent eruptions in 1983, 1998, 2004, and 2011. The volcano has a low seismic velocity anomaly down to about 3 km depth, interpreted as a magma chamber. A continuous GPS station and a tiltmeter are located on a nunatak, Mount Grímsfjall, which protrudes from the ice at the southern rim of the caldera. The 21-28 May 2011 eruption was Grímsvötn's largest since 1873, resulting in airspace closure in northern Europe and the cancellation of about 900 passenger flights. The eruption was preceded by gradual inflation following the 2004 eruption and progressive increase in seismicity. Kinematic 1 Hz solutions were derived for the position of the GPS station in the hours immediately before and during the 2011 eruption. The onset of deformation preceded the eruption by one hour and reached maximum of 0.57 m within 48 hours. Throughout the eruption the GPS station moved consistently in direction N38.4+/-0.5W, opposite to the direction of movements during the 2004-2011 inter eruptive phase. The deformation characteristics suggest that the signal was mostly due to pressure change in a source at 1.7 +/- 0.2 km depth. We use the geodetic measurements to infer co-eruptive pressure change in the magma chamber using the Mogi model. The rate of pressure drop is then used to estimate the magma flow rate from the chamber. Numerous studies have shown that plume height in explosive eruptions can be related to magma discharge. Using an empirical relationship between the volcanic plume height and magma flow rate (Mastin et al., 2009) we estimate the evolution of the plume height from the geodetic data. Two weather radars monitored the height of the volcanic plume during the eruption. A strong initial plume with peaks at 20-25 km was followed by a declining, pulsating activity

  20. Characterization of a new bioactive peptide from Potamotrygon gr. orbignyi freshwater stingray venom.

    PubMed

    Conceição, Katia; Santos, Juliane M; Bruni, Fernanda M; Klitzke, Clécio F; Marques, Elineide E; Borges, Márcia H; Melo, Robson L; Fernandez, Jorge H; Lopes-Ferreira, Mônica

    2009-12-01

    Brazilian freshwater stingrays, Potamotrygon gr. orbigyni, are relatively common in the middle-western regions of Brazil, where they are considered an important public health threat. In order to identify some of their naturally occurring toxin peptides available in very low amounts, we combine analytical protocols such as reversed-phase high-performance liquid chromatography (RP-HPLC), followed by a biological microcirculatory screening and mass spectrometry analysis. Using this approach, one bioactive peptide was identified and characterized, and two analogues were synthesized. The natural peptide named Porflan has the primary structure ESIVRPPPVEAKVEETPE (MW 2006.09 Da) and has no similarity with any bioactive peptide or protein found in public data banks. Bioassay protocols characterized peptides as presenting potent activity in a microcirculatory environment. The primary sequences and bioassay results, including interactions with the membrane phospholipids, suggest that these toxins are a new class of fish toxins, directly involved in the inflammatory processes of a stingray sting.

  1. Thermal equation of state and thermodynamic Grüneisen parameter of beryllium metal

    SciTech Connect

    Zhang, Jianzhong Zhu, Jinlong; Velisavljevic, Nenad; Wang, Liping; Zhao, Yusheng

    2013-11-07

    We conducted in-situ high-pressure synchrotron x-ray experiments on beryllium metal at pressures up to 7.9 GPa and temperatures up to 1373 K. A complete pressure (P)–volume (V)–temperature (T) equation of state (EOS) is determined based on the experiment, which includes temperature derivatives of elastic bulk modulus (at both constant pressure and constant volume) and pressure dependence of thermal expansivity. From this EOS, we calculate thermal pressure, heat capacity at constant volume, and thermodynamic Grüneisen parameter as a function of temperature. Above ∼600 K, our results show notable deviation from theoretical predictions using the quasiharmonic and local-density approximations, indicating that the free energy calculations need to be further improved within the current scheme of approximations.

  2. Modelling of activation processes for GR-280 graphite at Ignalina NPP.

    PubMed

    Smaizys, Arturas; Narkunas, Ernestas; Poskas, Povilas

    2005-01-01

    Ignalina Nuclear Power Plant (INPP) operates two RBMK-1500 water-cooled graphite-moderated channel-type power reactors. The total mass of graphite in the cores of both units at INPP is about 3600 tons. Modelling of activation processes in the reactor's structural materials is necessary for decommissioning planning, because large amounts of activated structural materials (graphite, stainless steel, concrete, etc.) should be managed as radioactive waste. Knowledge of radiological characteristics and a radioactive inventory of irradiated materials are essential in planning of the decommissioning processes. The purpose of this work was to perform conservative neutron activation analysis for decommissioning purposes of INPP. ORIGEN computer code was used for the calculations. Activity levels were calculated for different nuclides present in the graphite and estimates were made how these activity levels depend on irradiation time, neutron flux value and other parameters. Obtained results were compared with the data available from other investigations for GR-280 graphite.

  3. Ancient founder mutation is responsible for Imerslund-Gräsbeck Syndrome among diverse ethnicities

    PubMed Central

    2011-01-01

    Background Imerslund-Gräsbeck syndrome (IGS) was described just over 50 years ago by Olga Imerslund and Ralph Gräsbeck and colleagues. IGS is caused by specific malabsorption of cobalamin (Cbl) due to bi-allelic mutations in either the cubilin gene (CUBN) or the human amnionless homolog (AMN). Mutations in the two genes are commonly seen in founder populations or in societies with a high degree of consanguineous marriages. One particular mutation in AMN, c.208-2A>G, causing an out-of-frame loss of exon 4 in the mRNA, is responsible for some 15% of IGS cases globally. We present evidence that this founder mutation causes a substantial percentage of cases among diverse ethnicities and that the mutation is as old as human civilization. Methods Partial genotyping indicated a founder event but its presence in diverse peoples of Arabic, Turkish, Jewish, and Hispanic ancestry suggested that the mutation might be recurrent. We therefore studied the flanking sequence spanning 3.5 Mb to elucidate the origin of the haplotype and estimate the age of the mutation using a Bayesian inference method based on observed linkage disequilibrium. Results The mutation's distribution, the size of the shared haplotype, and estimates of growth rate and carrier frequency indicated that the mutation was a single prehistoric event. Dating back to the ancient Middle East around 11,600 BC, the mutation predates the advent of writing, farming, and the monotheistic religions of the region. Conclusions This mutation causes over 50% of the IGS cases among Arabic, Turkish, and Sephardic Jewish families, making it a primary target for genetic screening among diverse IGS cases originating from the Middle East. Thus, rare founder mutations may cause a substantial number of cases, even among diverse ethnicities not usually thought to be related. PMID:22078000

  4. Tumor-conditioned Gr-1(+)CD11b(+) myeloid cells induce angiogenesis through the synergistic action of CCL2 and CXCL16 in vitro.

    PubMed

    Han, Eun Chun; Lee, Jungwhoi; Ryu, Seung-Wook; Choi, Chulhee

    2014-01-24

    Gr-1(+)CD11b(+) cells can suppress innate and adaptive immunity, and the functional immunosuppressive characteristics of these cells can be modulated by the tumor microenvironment. Since Gr-1(+)CD11(+) cells are also involved in tumor-associated angiogenesis, we hypothesized that the angiogenic nature of Gr-1(+)CD11b(+) cells could be regulated by the tumor milieu. To address this hypothesis, we imitated a tumor microenvironment by exposing Gr-1(+)CD11b(+) cells isolated from spleen of 4T1 mammary carcinoma-bearing mice to tumor-conditioned medium. Supernatants from tumor-conditioned Gr-1(+)CD11b(+) cells significantly induced capillary-like tube formation and migration of human umbilical vein endothelial cells (HUVECs) compared to naive Gr-1(+)CD11b(+) cells. Incubation of Gr-1(+)CD11b(+) cells with tumor-conditioned medium induced production of pro-angiogenic chemokines CCL2 and CXCL16. Pretreatment with an anti-CCL2 antibody, but not an anti-CXCL16 antibody, suppressed the angiogenic effects of tumor-conditioned Gr-1(+)CD11b(+) cells on HUVECs. Simultaneous neutralization of CCL2 and CXCL16 significantly inhibited tube formation and migration of HUVECs compared to the sole neutralization against CCL2. Supernatants from tumor-conditioned Gr-1(+)CD11b(+) cells induced phosphorylation of ERK1/2 in HUVECs, and inhibition of the ERK pathway blocked angiogenic effects. ERK pathway activity was partially abrogated by neutralization of CCL2 and more suppressed by simultaneous neutralization of CCL2 and CXCL16. These results collectively indicate that CCL2 and CXCL16 chemokines produced by tumor-conditioned Gr-1(+)CD11b(+) myeloid cells synergistically induce angiogenesis in vitro by stimulating the ERK1/2 signaling pathway. Thus, regulation of Gr-1(+)CD11b(+) cells in the tumor microenvironment may contribute to angiogenesis through the secretion of pro-angiogenic chemokines.

  5. Functional validation of Phragmites communis glutathione reductase (PhaGR) as an essential enzyme in salt tolerance.

    PubMed

    Zhang, Xia; Quan, Geng; Wang, Jing; Han, Huiling; Chen, ShiHua; Guo, ShanLi; Yin, HaiBo

    2015-04-01

    Reed plants (Phragmites communis (Linn.) Trin) are hydrophilic perennial grasses growing in fresh and brackish waters. These plants readily adapt to arid and high salinity conditions; however, their resistance mechanism against abiotic stresses, especially high salinity, is largely unknown. In the present study, we cloned a glutathione reductase gene from P. communis and investigated its role in conferring salt tolerance in reed plants. The expression of PhaGR at the transcriptional level was affected by multiple abiotic stresses including NaCl, Cd(2+), heat, cold, PEG 6000, and abscisic acid (ABA). Furthermore, NaCl and Cd(2+) could increase its expressions at the translational level. NaCl and Cd(2+) also increased the biosynthesis of soluble protein and reduced glutathione (GSH). Reed seedlings that were challenged with NaCl showed higher levels of GR activities, which corroborated our gene expression data. The increase in GR possibly increased the salt tolerance of reed plants through GSH production. Thus, PhaGR is a potential target gene in improving the salt tolerance of crops through genetic manipulation.

  6. Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes.

    PubMed

    Saja, Maha F; Baudino, Lucie; Jackson, William D; Cook, H Terence; Malik, Talat H; Fossati-Jimack, Liliane; Ruseva, Marieta; Pickering, Matthew C; Woollard, Kevin J; Botto, Marina

    2015-09-22

    Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. However, their response to hyperlipidemia remains poorly understood. Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1(low) monocytes drop, while the number of bone marrow progenitors remains similar. We observed an increased crawling and retention of the Gr1(low) monocytes at the endothelial interface and a marked accumulation of CD68(+) macrophages in several organs. Hypertriglyceridemia was accompanied by an increased expression of tissue, and plasma CCL4 and blood Gr1(low) monocyte depletion involved a pertussis-toxin-sensitive receptor axis. Collectively, these findings demonstrate that a triglyceride-rich environment can alter blood monocyte distribution, promoting the extravasation of Gr1(low) cells. The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells.

  7. Gr-1+CD11b+ myeloid cells efficiently home to site of injury after intravenous administration and enhance diabetic wound healing by neoangiogenesis.

    PubMed

    Tong, Xiaozhe; Lv, Gang; Huang, Jianhua; Min, Yongfen; Yang, Li; Lin, Pengnian Charles

    2014-06-01

    Vascularization is an important factor that affects diabetic wound healing. There is increasing evidence that myeloid cell lineages play a role in neovascularization. In this study, the efficiency of Gr-1+CD11b+ myeloid cells to home to the site of injury and enhance diabetic wound healing by neoangiogenesis after intravenous administration was investigated. Gr-1+CD11b+ myeloid cells were injected into tail vein after establishment of dorsal window chamber, hindlimb ischaemia and ear-punch injury in diabetic or non-diabetic mice. The Gr-1+CD11b+ myeloid cells efficiently homed to the site of injury after intravenous administration and increased neoangiogenesis. The chemokine receptor type 4 (CXCR4) is robustly expressed by Gr-1+CD11b+ myeloid cells. Inhibition of CXCR4 decreases the homing ability of Gr-1+CD11b+ myeloid cells to the site of injury, which indicates that the CXCR4/SDF-1 axis plays an important role in the homing of Gr-1+CD11b+ myeloid cells to the site of injury. In addition, Gr-1+CD11b+ myeloid cells were found to improve blood flow recovery of ischaemic limb and enhance wound healing in diabetic mice by neoangiogenesis after intravenous administration. Taken together, the results of this study suggest that Gr-1+CD11b+ myeloid cells may serve as a potential cell therapy for diabetic wound healing.

  8. Gr-1intCD11b+ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival.

    PubMed

    Choi, Wungrak; Ji, Yong Woo; Ham, Hwa-Yong; Yeo, Areum; Noh, Hyemi; Jin, Su-Eon; Song, Jong Suk; Kim, Hyeon Chang; Kim, Eung Kwon; Lee, Hyung Keun

    2016-12-01

    We identified the characteristics of myeloid-derived suppressor cells (MDSCs) and investigated their mechanism of induction and their functional role in allograft rejection using a murine corneal allograft model. In mice, MDSCs coexpress CD11b and myeloid differentiation antigen Gr-1. Gr-1(+)CD11b(+) cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1(+)CD11b(+) cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1(int)CD11b(+) cells, but not Gr-1(hi)CD11b(+) cells, infiltrated the accepted graft early after surgery and expressed high levels of immunosuppressive cytokines, including IL-10, TGF-β, and TNF-related apoptosis-inducing ligand. This population remained until 4 wk after surgery. In vitro, only high dose (>100 ng/ml) of IFN-γ plus GM-CSF could induce immunosuppressive cytokine expression in Gr-1(int)CD11b(+) cells. Furthermore, adoptive transfer of Gr-1(int)CD11b(+) cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-γ in allograft areas is essential for development of Gr-1(int)CD11b(+) MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival.

  9. Common data model for natural language processing based on two existing standard information models: CDA+GrAF.

    PubMed

    Meystre, Stéphane M; Lee, Sanghoon; Jung, Chai Young; Chevrier, Raphaël D

    2012-08-01

    An increasing need for collaboration and resources sharing in the Natural Language Processing (NLP) research and development community motivates efforts to create and share a common data model and a common terminology for all information annotated and extracted from clinical text. We have combined two existing standards: the HL7 Clinical Document Architecture (CDA), and the ISO Graph Annotation Format (GrAF; in development), to develop such a data model entitled "CDA+GrAF". We experimented with several methods to combine these existing standards, and eventually selected a method wrapping separate CDA and GrAF parts in a common standoff annotation (i.e., separate from the annotated text) XML document. Two use cases, clinical document sections, and the 2010 i2b2/VA NLP Challenge (i.e., problems, tests, and treatments, with their assertions and relations), were used to create examples of such standoff annotation documents, and were successfully validated with the XML schemata provided with both standards. We developed a tool to automatically translate annotation documents from the 2010 i2b2/VA NLP Challenge format to GrAF, and automatically generated 50 annotation documents using this tool, all successfully validated. Finally, we adapted the XSL stylesheet provided with HL7 CDA to allow viewing annotation XML documents in a web browser, and plan to adapt existing tools for translating annotation documents between CDA+GrAF and the UIMA and GATE frameworks. This common data model may ease directly comparing NLP tools and applications, combining their output, transforming and "translating" annotations between different NLP applications, and eventually "plug-and-play" of different modules in NLP applications.

  10. Natural killer cells require monocytic Gr-1(+)/CD11b(+) myeloid cells to eradicate orthotopically engrafted glioma cells.

    PubMed

    Baker, Gregory J; Chockley, Peter; Zamler, Daniel; Castro, Maria G; Lowenstein, Pedro R

    2016-06-01

    Malignant gliomas are resistant to natural killer (NK) cell immune surveillance. However, the mechanisms used by these cancers to suppress antitumor NK cell activity remain poorly understood. We have recently reported on a novel mechanism of innate immune evasion characterized by the overexpression of the carbohydrate-binding protein galectin-1 by both mouse and rat malignant glioma. Here, we investigate the cytokine profile of galectin-1-deficient GL26 cells and describe the process by which these tumors are targeted by the early innate immune system in RAG1(-/-) and C57BL/6J mice. Our data reveal that galectin-1 knockdown in GL26 cells heightens their inflammatory status leading to the rapid recruitment of Gr-1(+)/CD11b(+) myeloid cells and NK1.1(+) NK cells into the brain tumor microenvironment, culminating in tumor clearance. We show that immunodepletion of Gr-1(+) myeloid cells in RAG1(-/-) mice permits the growth of galectin-1-deficient glioma despite the presence of NK cells, thus demonstrating an essential role for myeloid cells in the clearance of galectin-1-deficient glioma. Further characterization of tumor-infiltrating Gr-1(+)/CD11b(+) cells reveals that these cells also express CCR2 and Ly-6C, markers consistent with inflammatory monocytes. Our results demonstrate that Gr-1(+)/CD11b(+) myeloid cells, often referred to as myeloid-derived suppressor cells (MDSCs), are required for antitumor NK cell activity against galectin-1-deficient GL26 glioma. We conclude that glioma-derived galectin-1 represents an important factor in dictating the phenotypic behavior of monocytic Gr-1(+)/CD11b(+) myeloid cells. Galectin-1 suppression may be a valuable treatment approach for clinical glioma by promoting their innate immune-mediated recognition and clearance through the concerted effort of innate myeloid and lymphoid cell lineages.

  11. Plinian vs. phreatomagmatic eruptions at Grímsvötn volcano, Iceland

    NASA Astrophysics Data System (ADS)

    Haddadi, Baptiste; Sigmarsson, Olgeir; Larsen, Guðrún

    2016-04-01

    Grímsvötn is a subglacial central volcano located under the Vatnajökull ice cap, above the assumed centre of the Iceland mantle plume. Historical explosive eruptions are mostly of phreatomagmatic character whereas pure magmatic behaviour may characterize the largest eruptions. What causes this different eruption behaviour is uncertain. Here, we report petrological estimates of crystallization depth and volatile degassing as recorded by sulfur concentrations in melt inclusions (MI) hosted by ferromagnesian minerals and the groundmass glass. Tephra from four eruptions, AD 1823, 1873, 2004 and 2011, were selected. The 2011 and 1873 are the largest known historical eruptions, whereas the 2004 eruption is probably amongst the smallest. The repose time preceding those eruptions is surprisingly similar, or 6 to 7 years, and the major-element compositions are uniform. Plagioclase, clinopyroxene (cpx) and olivine are the three coexisting phases at the liquidus in the quartz-tholeiites of Grímsvötn. The cpx-melt geothermobarometer (Putirka 2008) applied to the 2011 tephra reveals that cpx crystallized over a large range of P from 60 to 640 MPa (depth range: 1.7-18km) and T between 1060 and 1175°C before the Plinian eruption, therefore mobilizing the entire crustal magma system. In contrast, the phreatomagmatic tephra do not record the shallowest crystallization but interestingly all four tephra have identical median entrapment pressure of approximately 400 MPa. Therefore, the depth from which the magma bodies are derived, does not explain the difference in explosivity between those eruptions nor the variable magma volume (V) produced. Sulfur concentrations in MI are only slightly higher in the Plinian products, the difference (10%) being insufficient to explain the different eruption regimes. The ΔS, the difference between the maximum S concentrations in MI and the mean of the groundmass glass for a given eruption, is higher in the Plinian tephra. Based on literature

  12. Electrical Properties Of Volcanic Ash Samples From Grímsvötn

    NASA Astrophysics Data System (ADS)

    Houghton, I. M.; Aplin, K. L.; Nicoll, K. A.; Green, O.; Mather, T. A.

    2012-12-01

    Recent Icelandic eruptions in 2012 and 2011 were associated with sustained charging of the ash plume (Harrison et al., 2010) and significant volcanic lightning (Bennett et al., 2010; Arason et al., 2012). The sustained charging suggests that some charging of the plume is independent of the eruption process, in addition to other electrification mechanisms such as triboelectric or fractoemission processes at the vent, the 'dirty thunderstorm' mechanism if ice forms in the plume, and the internal radioactivity of the plume (Mather and Harrison, 2006; James et al., 2008). We investigate the triboelectric charging of volcanic material using a charged particle apparatus, which allows the charged particles to fall under gravity in a screened metallic cylinder. This apparatus comprises two induction rings connected to sensitive electrometers, which detect charge induced by the falling ash, and a Faraday cup to measure the total ash charge. The release mechanism has been designed to facilitate only self charging of the ash, as is expected in the atmospheric plume. Previous work on triboelectric charging of single-material particle systems has shown that the charging is likely to be determined by the number size distribution (Lacks and Levandovsky, 2007). We present a mass distribution measurement for a sample of volcanic ash provided by the Icelandic Meteorological Office collected 70 km from the crater of the 2011 Grímsvötn eruption. This shows a high proportion of fine particles compared with the volumetric size distribution reported in Piper et al. (2012). Optical microscopy of the different size fractions of the Grímsvötn sample indicates that the composition varies with size. In addition to charge transfer as a function of size, the different substances will triboelectrically interact with each other, which complicates the nature of the charge interactions. To separate the dependence of particle charging on size from composition, particle charging experiments were

  13. Volume dependence of the Grüneisen parameter and maximum compression limit for iron

    NASA Astrophysics Data System (ADS)

    Shanker, J.; Singh, B. P.; Baghel, H. K.

    2007-01-01

    Relationships for the volume dependence of the Grüneisen parameter γ have been used to discuss the behaviour of solids in the limit of infinite pressure ( P→∞). The model recently developed by Burakovsky and Preston (J. Phys. Chem. Solids 65 (2004) 1581) yields γ∞, q∞ and λ∞, the values of Grüneisen parameter γ and its logarithmic volume derivatives q and λ at P→∞, which are found to have fixed values, same for all the solids studied. On the other hand, the thermodynamics of solids at P→∞ formulated by Stacey (Geophys. J. Int. 143 (2000) 621) reveals that γ∞ and pressure derivative of bulk modulus are different for different materials. The empirical formulation for the volume dependence of γ used by Stacey and Davis (Phys. Earth Planet. Intr. 142 (2004) 137) has been shown to be approximately equivalent to the relationship proposed earlier by Al’tshuler et al. (J. Appl. Mech. Tech. Phys. 28 (1987) 129). The shock-pressure data for iron have been used to discuss the maximum compression limit for iron and to emphasize the invalidity of our recent criterion based on the lattice potential energy (Physica B 364 (2005) 186). The Burakovsky-Preston model based on the Thomas-Fermi approximation ( γ∞=1/2 and =5/3) has been found to be more consistent with the shock-compression data. The constraints γ∞>2/3 and >5/3 developed by Stacey are not in agreement with the strong shock compression limit reported for several materials. It is shown here that the Slater formula for γ which was found by Stacey to assume the status of an identity at P→∞ and used by him to derive the constraints for γ∞ and , is invalid when =5/3 It is also pointed out that γ∞=1/2 is to be preferred over γ∞=2/3 because of the thermodynamic constraint >1+ γ∞ developed by Stacey.

  14. Glucocorticoid receptor 1B and 1C mRNA transcript alterations in schizophrenia and bipolar disorder, and their possible regulation by GR gene variants.

    PubMed

    Sinclair, Duncan; Fullerton, Janice M; Webster, Maree J; Shannon Weickert, Cynthia

    2012-01-01

    Abnormal patterns of HPA axis activation, under basal conditions and in response to stress, are found in individuals with schizophrenia and bipolar disorder. Altered glucocorticoid receptor (GR) mRNA and protein expression in the dorsolateral prefrontal cortex (DLPFC) in psychiatric illness have also been reported, but the cause of these abnormalities is not known. We quantified expression of GR mRNA transcript variants which employ different 5' promoters, in 35 schizophrenia cases, 31 bipolar disorder cases and 34 controls. We also explored whether sequence variation within the NR3C1 (GR) gene is related to GR mRNA variant expression. Total GR mRNA was decreased in the DLPFC in schizophrenia cases relative to controls (15.1%, p<0.0005) and also relative to bipolar disorder cases (8.9%, p<0.05). GR-1B mRNA was decreased in schizophrenia cases relative to controls (20.2%, p<0.05), while GR-1C mRNA was decreased in both schizophrenia and bipolar disorder cases relative to controls (16.1% and 17.2% respectively, both p<0.005). A dose-dependent effect of rs10052957 genotype on GR-1B mRNA expression was observed, where CC homozygotes displayed 18.4% lower expression than TC heterozygotes (p<0.05), and 31.8% lower expression than TT homozygotes (p<0.005). Similarly, a relationship between rs6190 (R23K) genotype and GR-1C expression was seen, with 24.8% lower expression in GG homozygotes than GA heterozygotes (p<0.01). We also observed an effect of rs41423247 (Bcl1) SNP on expression of 67 kDa GRα isoform, the most abundant GRα isoform in the DLPFC. These findings suggest possible roles for the GR-1B and GR-1C promoter regions in mediating GR gene expression changes in psychotic illness, and highlight the potential importance of sequence variation within the NR3C1 gene in modulating GR mRNA expression in the DLPFC.

  15. Triboelectric charging of volcanic ash from the 2011 Grímsvötn eruption.

    PubMed

    Houghton, Isobel M P; Aplin, Karen L; Nicoll, Keri A

    2013-09-13

    The plume from the 2011 eruption of Grímsvötn was highly electrically charged, as shown by the considerable lightning activity measured by the United Kingdom Met Office's low-frequency lightning detection network. Previous measurements of volcanic plumes have shown that ash particles are electrically charged up to hundreds of kilometers away from the vent, which indicates that the ash continues to charge in the plume [R. G. Harrison, K. A. Nicoll, Z. Ulanowski, and T. A. Mather, Environ. Res. Lett. 5, 024004 (2010); H. Hatakeyama J. Meteorol. Soc. Jpn. 27, 372 (1949)]. In this Letter, we study triboelectric charging of different size fractions of a sample of volcanic ash experimentally. Consistently with previous work, we find that the particle size distribution is a determining factor in the charging. Specifically, our laboratory experiments demonstrate that the normalized span of the particle size distribution plays an important role in the magnitude of charging generated. The influence of the normalized span on plume charging suggests that all ash plumes are likely to be charged, with implications for remote sensing and plume lifetime through scavenging effects.

  16. Triboelectric Charging of Volcanic Ash from the 2011 Grímsvötn Eruption

    NASA Astrophysics Data System (ADS)

    Houghton, Isobel M. P.; Aplin, Karen L.; Nicoll, Keri A.

    2013-09-01

    The plume from the 2011 eruption of Grímsvötn was highly electrically charged, as shown by the considerable lightning activity measured by the United Kingdom Met Office’s low-frequency lightning detection network. Previous measurements of volcanic plumes have shown that ash particles are electrically charged up to hundreds of kilometers away from the vent, which indicates that the ash continues to charge in the plume [R. G. Harrison, K. A. Nicoll, Z. Ulanowski, and T. A. Mather, Environ. Res. Lett. 5, 024004 (2010)1748-932610.1088/1748-9326/5/2/024004; H. Hatakeyama J. Meteorol. Soc. Jpn. 27, 372 (1949)JMSJAU0026-1165]. In this Letter, we study triboelectric charging of different size fractions of a sample of volcanic ash experimentally. Consistently with previous work, we find that the particle size distribution is a determining factor in the charging. Specifically, our laboratory experiments demonstrate that the normalized span of the particle size distribution plays an important role in the magnitude of charging generated. The influence of the normalized span on plume charging suggests that all ash plumes are likely to be charged, with implications for remote sensing and plume lifetime through scavenging effects.

  17. Grünwald-Letnikov operators for fractional relaxation in Havriliak-Negami models

    NASA Astrophysics Data System (ADS)

    Garrappa, Roberto

    2016-09-01

    Several classes of differential and integral operators of non integer order have been proposed in the past to model systems exhibiting anomalous and hereditary properties. A wide range of complex and heterogeneous systems are described in terms of laws of Havriliak-Negami type involving a special fractional relaxation whose behavior in the time-domain can not be represented by any of the existing operators. In this work we introduce new integral and differential operators for the description of Havriliak-Negami models in the time-domain. In particular we propose a formulation of Grünwald-Letnikov type which turns out to be effective not only to provide a theoretical characterization of the operators associated to Havriliak-Negami systems but also for computational purposes. We study some properties of the new operators and, by means of some numerical experiments, we present their use in practical computation and we show the superiority with respect to the few other approaches previously proposed in literature.

  18. Leak before break evaluation for main steam piping system made of SA106 Gr.C

    SciTech Connect

    Yang, Kyoung Mo; Jee, Kye Kwang; Pyo, Chang Ryul; Ra, In Sik

    1997-04-01

    The basis of the leak before break (LBB) concept is to demonstrate that piping will leak significantly before a double ended guillotine break (DEGB) occurs. This is demonstrated by quantifying and evaluating the leak process and prescribing safe shutdown of the plant on the basis of the monitored leak rate. The application of LBB for power plant design has reduced plant cost while improving plant integrity. Several evaluations employing LBB analysis on system piping based on DEGB design have been completed. However, the application of LBB on main steam (MS) piping, which is LBB applicable piping, has not been performed due to several uncertainties associated with occurrence of steam hammer and dynamic strain aging (DSA). The objective of this paper is to demonstrate the applicability of the LBB design concept to main steam lines manufactured with SA106 Gr.C carbon steel. Based on the material properties, including fracture toughness and tensile properties obtained from the comprehensive material tests for base and weld metals, a parametric study was performed as described in this paper. The PICEP code was used to determine leak size crack (LSC) and the FLET code was used to perform the stability assessment of MS piping. The effects of material properties obtained from tests were evaluated to determine the LBB applicability for the MS piping. It can be shown from this parametric study that the MS piping has a high possibility of design using LBB analysis.

  19. Heat treatment temperature influence on ASTM A890 GR 6A super duplex stainless steel microstructure

    SciTech Connect

    Martins, Marcelo; E-mail: marcelo.martins@sulzer.com; Casteletti, Luiz Carlos

    2005-09-15

    Duplex and super duplex stainless steels are ferrous alloys with up to 26% chromium, 8% nickel, 5% molybdenum and 0.3% nitrogen, which are largely used in applications in media containing ions from the halogen family, mainly the chloride ion (Cl{sup -}). The emergence of this material aimed at substituting Copper-Nickel alloys (Cupro-Nickel) that despite presenting good corrosion resistance, has mechanical properties quite inferior to steel properties. The metallurgy of duplex and super duplex stainless steel is complex due to high sensitiveness to sigma phase precipitation that becomes apparent, due to the temperatures they are exposed on cooling from solidification as well as from heat treatment processes. The objective of this study was to verify the influence of heat treating temperatures on the microstructure and hardness of ASTM A890/A890M Gr 6A super duplex stainless steel type. Microstructure control is of extreme importance for castings, as the chemical composition and cooling during solidification inevitably provide conditions for precipitation of sigma phase. Higher hardness in these materials is directly associated to high sigma phase concentration in the microstructure, precipitated in the ferrite/austenite interface. While heat treatment temperature during solution treatment increases, the sigma phase content in the microstructure decreases and consequently, the material hardness diminishes. When the sigma phase was completely dissolved by the heat treatment, the material hardness was influenced only due to ferrite and austenite contents in the microstructure.

  20. Mach's principle as action-at-a-distance in GR: The causality question

    NASA Astrophysics Data System (ADS)

    Hoefer, Carl

    2014-11-01

    A part of the revival of interest in Mach's principle since the early 1960s has involved work by physicists aimed at calculating various sorts of frame-dragging effects by matter shells surrounding an interior region, and arguing that under certain conditions or in certain limits (ideally, ones that can be viewed as plausibly similar to conditions in our cosmos) the frame dragging becomes "complete" (e.g. Lynden-Bell, Katz, & Bičák, 1995) . Such results can bolster the argument for the satisfaction of Mach's principle by certain classes of models of GR. Interestingly, the frame-dragging "effect" of (say) a rotational movement of cosmic matter around a central point is argued by these physicists to be instantaneous-not an effect propagating at the speed of light. Not all physicists regard this as unproblematic. But rather than exploring whether there is something unphysical about such instantaneous "action at a distance", or a violation of the precepts of Special Relativity, I am interested in exploring whether these physicists' calculations should be thought of as showing local inertia (resistance to acceleration) to be an effect, with distant matter distributions being the cause. I will try to apply some leading philosophical accounts of causation to the physical models of frame dragging, to see whether they imply that the frame dragging is superluminal causation. I will then offer reflections on the difficulties of applying causal talk in physical theories.

  1. Application of the shock reverberation technique to determine Grüneisen gamma for float glass

    NASA Astrophysics Data System (ADS)

    Gibson, Michael; Appleby-Thomas, Gareth; Roberts, Andrew; Hazell, Paul

    2013-06-01

    Determination of high strain-rate material properties following loading from a non-principle Hugoniot ground state requires detailed knowledge of the shape of a materials equation-of-state. The material-specific variable Grüneisen gamma, γ(v), defines the shape of ``off-Hugoniot'' points in energy-volume-pressure space. Comparison between experimental and simulated results of ``ring-up'' experiments, where shock reflection allows a material to be loaded successively into a series of off-Hugoniot states, has the potential to allow ready access to values of gamma. However, previous attempts to determine γ1 via comparison to ANSYS Autodyn ® simulations for the temperature-resistant polymer polyether ether ketone (PEEK) only produced a partial success, due to the highly non-linear nature and poorly defined residual deviatoric (strength) effects inherent in the material response. Consequently, in this study an attempt is made using a similar approach to calculate γ1 for the well-defined material float glass (whose high elastic limit should also minimise deviatoric effects).

  2. Balloon Angioplasty – The Legacy of Andreas Grüntzig, M.D. (1939–1985)

    PubMed Central

    Barton, Matthias; Grüntzig, Johannes; Husmann, Marc; Rösch, Josef

    2014-01-01

    In 1974, at the Medical Policlinic of the University of Zürich, German-born physician-scientist Andreas Grüntzig (1939–1985) for the first time applied a balloon-tipped catheter to re-open a severely stenosed femoral artery, a procedure, which he initially called “percutaneous transluminal dilatation”. Balloon angioplasty as a therapy of atherosclerotic vascular disease, for which Grüntzig and Charles T. Dotter (1920–1985) received a nomination for the Nobel Prize in Physiology or Medicine in 1978, became one of the most successful examples of translational medicine in the twentieth century. Known today as percutaneous transluminal angioplasty (PTA) in peripheral arteries or percutaneous transluminal coronary angioplasty (PTCA) or percutaneous coronary intervention (PCI) in coronary arteries, balloon angioplasty has become the method of choice to treat patients with acute myocardial infarction or occluded leg arteries. On the occasion of the 40th anniversary of balloon angioplasty, we summarize Grüntzig’s life and career in Germany, Switzerland, and the United States and also review the developments in vascular medicine from the 1890s to the 1980s, including Dotter’s first accidental angioplasty in 1963. The work of pioneers of catheterization, including Pedro L. Fariñas in Cuba, André F. Cournand in France, Werner Forssmann, Werner Porstmann and Eberhard Zeitler in Germany, António Egas Moniz and Reynaldo dos Santos in Portugal, Sven-Ivar Seldinger in Sweden, and Barney Brooks, Thomas J. Fogarty, Melvin P. Judkins, Richard K. Myler, Dickinson W. Richards, and F. Mason Sones in the United States, is discussed. We also present quotes by Grüntzig and excerpts from his unfinished autobiography, statements of Grüntzig’s former colleagues and contemporary witnesses, and have included hitherto unpublished historic photographs and links to archive recordings and historic materials. This year, on June 25, 2014, Andreas Grüntzig would have celebrated

  3. Interaction of glucocorticoid receptor (GR) with estrogen receptor (ER) α and activator protein 1 (AP1) in dexamethasone-mediated interference of ERα activity.

    PubMed

    Karmakar, Sudipan; Jin, Yetao; Nagaich, Akhilesh K

    2013-08-16

    The role of glucocorticoids in the inhibition of estrogen (17-β-estradiol (E2))-regulated estrogen receptor (ER)-positive breast cancer cell proliferation is well established. We and others have seen that synthetic glucocorticoid dexamethasone (Dex) antagonizes E2-stimulated endogenous ERα target gene expression. However, how glucocorticoids negatively regulate the ERα signaling pathway is still poorly understood. ChIP studies using ERα- and glucocorticoid receptor (GR)-positive MCF-7 cells revealed that GR occupies several ERα-binding regions (EBRs) in cells treated with E2 and Dex simultaneously. Interestingly, there was little or no GR loading to these regions when cells were treated with E2 or Dex alone. The E2+Dex-dependent GR recruitment is associated with the displacement of ERα and steroid receptor coactivator-3 from the target EBRs leading to the repression of ERα-mediated transcriptional activation. The recruitment of GR to EBRs requires assistance from ERα and FOXA1 and is facilitated by AP1 binding within the EBRs. The GR binding to EBRs is mediated via direct protein-protein interaction between the GR DNA-binding domain and ERα. Limited mutational analyses indicate that arginine 488 located within the C-terminal zinc finger domain of the GR DNA-binding domain plays a critical role in stabilizing this interaction. Together, the results of this study unravel a novel mechanism involved in glucocorticoid inhibition of ERα transcriptional activity and E2-mediated cell proliferation and thus establish a foundation for future exploitation of the GR signaling pathway in the treatment of ER-positive breast cancer.

  4. The anti-inflammatory role of granulocyte colony-stimulating factor in macrophage-dendritic cell crosstalk after Lactobacillus rhamnosus GR-1 exposure.

    PubMed

    Martins, Andrew J; Spanton, Sarah; Sheikh, Haroon I; Kim, Sung Ouk

    2011-06-01

    MΦs are important sensory cells of the innate immune system and regulate immune responses through releasing different combinations of cytokines. In this study, we examined whether cytokines released by MΦs in response to the probiotic bacterial strain GR-1 modulate the responses of DCs. The cytokine profile released by GR-1-treated MΦs was characterized by low levels of TNF-α, GM-CSF, IL-6, and IL-12 but very high levels of G-CSF. GR-1 CM did not induce expression of the shared p40 subunit of IL-12 and IL-23 and costimulatory molecules CD80 or CD86 or increase T cell stimulatory capacity in DCs. However, in G-CSFR-deficient DCs or after antibody-mediated neutralization of G-CSF, GR-1 CM induced IL-12/23 p40 production significantly, indicating that G-CSF within the GR-1 CM inhibits IL-12/23 p40 production induced by other CM components. GR-1 CM and rG-CSF also inhibited LPS-induced IL-12 production at the mRNA and protein levels. The inhibition of IL-12 production by G-CSF was at least in part mediated through inhibition of JNK activation. Finally, splenic DCs of GR-1-injected mice produced less IL-12/23 p40 than those of PBS-injected mice in response to LPS ex vivo, and this was at least partially dependent on exposure to GR-1-induced G-CSF in vivo. Altogether, these results suggest that G-CSF modulates the IL-12/23 p40 response of DCs in the context of the probiotic GR-1 through MΦ-DC crosstalk.

  5. Measurements of Sound Velocity and Grüneisen Parameter in CH and MgO Shocked to Mbar Pressures

    NASA Astrophysics Data System (ADS)

    McCoy, C. A.; Gregor, M. C.; Polsin, D. N.; Boehly, T. R.; Meyerhofer, D. D.; Fratanduono, D. E.; Celliers, P. M.

    2015-11-01

    We present sound velocity measurements using an unsteady wave analysis to relate acoustic perturbations in a sample to those in a standard with known sound velocity and Grüneisen parameter. The contraction and dilation of perturbations in the shock velocities in each material provide information on the sound velocity. Experiments measured the sound velocity and Grüneisen parameter in shocked CH and MgO (periclase) relative to a quartz standard. Hugoniot measurements were also made for MgO shocked to the fluid state; a modified Us -up relation is presented. The results are compared to SESAME and LEOS tables for CH and MgO. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

  6. Physiological effects of the synthetic strigolactone analog GR24 on root system architecture in Arabidopsis: another belowground role for strigolactones?

    PubMed

    Ruyter-Spira, Carolien; Kohlen, Wouter; Charnikhova, Tatsiana; van Zeijl, Arjan; van Bezouwen, Laura; de Ruijter, Norbert; Cardoso, Catarina; Lopez-Raez, Juan Antonio; Matusova, Radoslava; Bours, Ralph; Verstappen, Francel; Bouwmeester, Harro

    2011-02-01

    In this study, the role of the recently identified class of phytohormones, strigolactones, in shaping root architecture was addressed. Primary root lengths of strigolactone-deficient and -insensitive Arabidopsis (Arabidopsis thaliana) plants were shorter than those of wild-type plants. This was accompanied by a reduction in meristem cell number, which could be rescued by application of the synthetic strigolactone analog GR24 in all genotypes except in the strigolactone-insensitive mutant. Upon GR24 treatment, cells in the transition zone showed a gradual increase in cell length, resulting in a vague transition point and an increase in transition zone size. PIN1/3/7-green fluorescent protein intensities in provascular tissue of the primary root tip were decreased, whereas PIN3-green fluorescent protein intensity in the columella was not affected. During phosphate-sufficient conditions, GR24 application to the roots suppressed lateral root primordial development and lateral root forming potential, leading to a reduction in lateral root density. Moreover, auxin levels in leaf tissue were reduced. When auxin levels were increased by exogenous application of naphthylacetic acid, GR24 application had a stimulatory effect on lateral root development instead. Similarly, under phosphate-limiting conditions, endogenous strigolactones present in wild-type plants stimulated a more rapid outgrowth of lateral root primordia when compared with strigolactone-deficient mutants. These results suggest that strigolactones are able to modulate local auxin levels and that the net result of strigolactone action is dependent on the auxin status of the plant. We postulate that the tightly balanced auxin-strigolactone interaction is the basis for the mechanism of the regulation of the plants' root-to-shoot ratio.

  7. IFN-γ differentially regulates subsets of Gr-1(+)CD11b(+) myeloid cells in chronic inflammation.

    PubMed

    Zhan, Xiaoxia; Fang, Yimin; Hu, Shengfeng; Wu, Yongjian; Yang, Kun; Liao, Chunxin; Zhang, Yuanqing; Huang, Xi; Wu, Minhao

    2015-08-01

    During chronic inflammation, prolonged over-reactive immune response may lead to tissue destruction, while immune suppression hinders tissue repair and pathogen elimination. Therefore, precise regulation of the immune response is needed to avoid immuno-pathology. Interferon-gamma (IFN-γ) is widely used in clinical treatment of inflammatory diseases. However, the underlying mechanism remains unclear. Here, we evaluated the role of IFN-γ on CD11b(+)Gr-1(+) myeloid cell differentiation and function, using a heat-killed Mycobacterium bovis BCG-induced chronic inflammation model. After challenge with heat-killed BCG, two subpopulations of CD11b(+)Gr-1(+) myeloid cells were generated in the mouse spleen. Phenotypical, morphological and functional analysis indicated that the CD11b(+)Gr-1(high) Ly6G(high) Ly6C(low) subset was neutrophil-like myeloid-derived inducer cells (N-MDICs), which promoted T cell activation, while the other subset was CD11b(+)Gr-1(low) Ly6G(neg) Ly6C(high) monocyte-like myeloid-derived suppressor cells (M-MDSCs) that displayed extensive suppressor function. IFN-γ treatment dampened N-MDICs-mediated T cell activation through up-regulating T cell suppressive mediators, reactive oxygen species (ROS) and arginase I. While for M-MDSCs, IFN-γ reduced their suppressing activity by decreasing the arginase activity. Our study provides evidence that IFN-γ balances the over-reactive vs compromised immune response through different regulation of distinct myeloid subsets, and therefore displays significant therapeutic potential for effective immuno-therapy of chronic inflammatory diseases.

  8. Computational investigation on thermal expansivity behavior of Al 6061-SiC-Gr hybrid metal matrix composites

    NASA Astrophysics Data System (ADS)

    Mohan Krishna, S. A.; Shridhar, T. N.; Krishnamurthy, L.

    2015-08-01

    Metal matrix composites (MMCs) have been regarded as one of the most principal classifications in composite materials. The thermal characterization of hybrid MMCs has been increasingly important in a wide range of applications. The coefficient of thermal expansion is one of the most important properties of MMCs. Since nearly all MMCs are used in various temperature ranges, measurement of coefficient of thermal expansion (CTE) as a function of temperature is necessary in order to know the behavior of the material. In this research paper, the evaluation of thermal expansivity has been accomplished for Al 6061, silicon carbide (SiC) and Graphite (Gr) hybrid MMCs from room temperature to 300°C. Aluminum (Al)-based composites reinforced with SiC and Gr particles have been prepared by stir casting technique. The thermal expansivity behavior of hybrid composites with different percentage compositions of reinforcements has been investigated. The results have indicated that the thermal expansivity of the different compositions of hybrid MMCs decreases by the addition of Gr with SiC and Al 6061. Few empirical models have been validated for the evaluation of thermal expansivity of composites. Using the experimental values namely modulus of elasticity, Poisson's ratio and thermal expansivity, computational investigation has been carried out to evaluate the thermal parameters namely thermal displacement, thermal strain and thermal stress.

  9. Computational investigation on thermal conductivity behavior of Al 6061-SiC-Gr hybrid metal matrix composites

    NASA Astrophysics Data System (ADS)

    Krishna, S. A. Mohan; Shridhar, T. N.; Krishnamurthy, L.

    2015-10-01

    Metal matrix composites (MMCs) are regarded to be one of the most principal classifications in composite materials. The thermal characterization of hybrid MMCs has become increasingly important in a wide range of applications. Thermal conductivity is one of the most important properties of MMCs. Since nearly all MMCs are used in various temperature ranges, measurement of thermal conductivity as a function of temperature is necessary in order to know the behavior of the material. In the present research, evaluation of thermal conductivity has been accomplished for aluminum alloy (Al) 6061, silicon carbide (SiC) and graphite (Gr) hybrid MMCs from room temperature to 300∘C. Al-based composites reinforced with SiC and Gr particles have been prepared by stir casting technique. The thermal conductivity behavior of hybrid composites with different percentage compositions of reinforcements has been investigated using laser flash technique. The results have indicated that the thermal conductivity of the different compositions of hybrid MMCs decreases by the addition of Gr with SiC and Al 6061. Few empirical models have been validated concerning with the evaluation of thermal conductivity of composites. Using the experimental values namely density, thermal conductivity, specific heat capacity and enthalpy at varying temperature ranges, computational investigation has been carried out to evaluate the thermal gradient and thermal flux.

  10. Purification of a dimeric arginine deiminase from Enterococcus faecium GR7 and study of its anti-cancerous activity.

    PubMed

    Kaur, Baljinder; Kaur, Rajinder

    2016-09-01

    The arginine deiminase (ADI, E.C 3.5.3.6) - a key enzyme of ADI pathway of Enterococcus faecium GR7 was purified to homogeneity. A sequential purification strategy involving ammonium sulfate fractionation, molecular sieve followed by Sephadex G-100 gel filtration was applied to the crude culture filtrate to obtain a pure enzyme preparation. The enzyme was purified with a fold of 16.92 and showed a final specific activity of 76.65IU/mg with a 49.17% yield. The dimeric ADI has a molecular mass of about 94,364.929Da, and comprises of hetrodimers of 49.1kDa and 46.5kDa as determined by MALDI-TOF and PAGE analysis. To assess anti-cancerous activity of ADI by MTT assay was carried out against cancer cell lines (MCF-7, Sp2/0-Ag14 and Hep-G2). Purified ADI exhibited the most profound antiproliferative activity against Hep-G2 cells; with half-maximal inhibitory concentration (IC50) of 1.95μg/ml. Purified ADI from E. faecium GR7 was observed to induce apoptosis in the Hep-G2 cells by DNA fragmentation assay. Our findings suggest the possibility of a future use of ADI from E. faecium GR7 as a potential anticancer drug.

  11. Soils developed from alluvial and proluvial deposits in the Gröndalselva River valley in West Spitsbergen

    NASA Astrophysics Data System (ADS)

    Pereverzev, V. N.; Litvinova, T. I.

    2012-05-01

    The genetic characterization of soils developed from alluvial and proluvial deposits in the Gröndalselva River valley (West Spitsbergen) is presented. These soils are compared with analogous soils formed on marine terraces along the coasts of Isfjord and Grönfjord. Gray-humus (soddy) soils with an O-AY-C profile have been described on parent materials of different origins, including alluvial and proluvial sediments. The texture of the soils in the Gröndalselva River valley varies from medium to heavy loam and differs from the texture of the soils on other geomorphic positions in the higher content of fine particles. The soils developed from the alluvial deposits are characterized by their richer mineralogical and chemical composition in comparison with the soils developed from proluvial deposits, marine deposits, and bedrocks. All the deposits are impoverished in CaO. No differentiation of the chemical composition of the soils along the soil profiles has been found in the soils of the coastal areas and the river valley. Some accumulation of oxalate-soluble Al and Fe compounds takes place in the uppermost mineral horizon. The soils of all the geomorphic positions have a high humus content and a high exchange capacity.

  12. OPTICAL SPECTROPHOTOMETRIC MONITORING OF THE EXTREME LUMINOUS BLUE VARIABLE STAR GR 290 (ROMANO's STAR) IN M 33

    SciTech Connect

    Polcaro, V. F.; Viotti, R. F.; Rossi, C.; Galleti, S.; Gualandi, R.; Norci, L.

    2011-01-15

    We study the long-term, S Dor-type variability and the present hot phase of the luminous blue variable (LBV) star GR 290 (Romano's Star) in M 33 in order to investigate possible links between the LBV and the late, nitrogen sequence Wolf-Rayet Stars (WNL) stages of very massive stars. We use intermediate-resolution spectra, obtained with the William Herschel Telescope (WHT) in 2008 December, when GR 290 was at minimum (V = {approx}18.6), as well as new low-resolution spectra and BVRI photometry obtained with the Loiano and Cima Ekar telescopes during 2007-2010. We identify more than 80 emission lines in the 3100-10000 A range covered by the WHT spectra, belonging to different species: the hydrogen Balmer and Paschen series, neutral and ionized helium, C III, N II-III, S IV, Si III-IV, and many forbidden lines of [N II], [O III], [S III], [A III], [Ne III], and [Fe III]. Many lines, especially the He I triplets, show a P Cygni profile with an a-e radial velocity difference of -300 to -500 km s{sup -1}. The shape of the 4630-4713 A emission blend and of other emission lines resembles that of WN9 stars; the blend deconvolution shows that the He II 4686 A has a strong broad component with FWHM {approx_equal} 1700 km s{sup -1}. During 2003-2010 the star underwent large spectral variations, best seen in the 4630-4686 A emission feature. Using the late-WN spectral types of Crowther and Smith, GR 290 apparently varied between the WN11 and WN8-9 spectral types; the hotter the star was the fainter its visual magnitude was. This spectrum-visual luminosity anticorrelation of GR 290 is reminiscent of the behavior of the best-studied LBVs, such as S Dor and AG Car. During the 2008 minimum, we found a significant decrease in bolometric luminosity, which could be attributed to absorption by newly formed circumstellar matter. We suggest that the broad 4686 A line and the optical continuum formed in a central Wolf-Rayet region, while the narrow emission line spectrum originated in an

  13. Compositional time-series from tephra and the temporal evolution of Grímsvötn's magma chamber

    NASA Astrophysics Data System (ADS)

    Sigmarsson, Olgeir; Arna Óladóttir, Bergrun; Larsen, Guőrún

    2010-05-01

    Improved understanding of magma chambers and the related plumbing system is needed for active volcanoes. Their architecture, size and location determine the magma dynamics from source to surface, and the rate of magma transfer is in part controlled by variable sizes and forms of magma chambers. Since these are not constant features but evolve with time, only detailed studies of fine-tuned time-series allow quantitative assessment of their physical evolution, such as their volume. The subglacial volcano Grímsvötn is the most active of all Icelandic volcanoes. Interaction between the hot basaltic magma and glacier melt-water results in tephra formation during each eruption. Careful soil inspection around the Vatnajökull ice-cap has revealed an eruption frequency, higher than 7 eruptions per century. A compositional record of major- and trace element concentrations has been obtained by electron microprobe and laser ablation ICP-MS measurements of tephra glasses for the last 7600 years. We combine these results with more precise data from isotope-dilution mass-spectrometry on historical tephra from the Vatnajökull glacier. The Holcene basalts from Grímsvötn clearly form two distinct compositional groups, G-1 and G2. The group G-1 is characterized by Mg#> 47, K2O< 0.4 wt% and Th< 0.9 ppm, whereas the G-2 magma has more evolved composition. Simple fractional crystallization readily explains the compositional variations within group G-1, while the G-2 magmas have suffered from additional crustal contamination (through AFC). The Holocene tephra record reveals that both magma types are erupted contemporaneously, and even during the same eruption such as produced during the last eruption in 2004. This clearly indicates a polybaric origin of the emitted basalts, and eliminates the possibility of a single well-mixed, steady-state magma chamber beneath Grímsvötn. After the large fissure eruption of Laki (1783-84), which is on the same volcanic system, the composition of

  14. Comparative pharmacokinetics of bismuth from ranitidine bismuth citrate (GR122311X), a novel anti-ulcerant and tripotassium dicitrato bismuthate (TDB).

    PubMed

    Lacey, L F; Frazer, N M; Keene, O N; Smith, J T

    1994-01-01

    GR122311X (ranitidine bismuth citrate, Glaxo Group Research Ltd.) is a salt of ranitidine with a complex of bismuth and citric acid which is being developed for the treatment of peptic ulceration. In this study, 4 groups of 12 healthy male subjects were dosed for 10 days with either GR122311X 500 mg bid (301 mg bismuth per day), GR122311X 1.0 g bid (602 mg bismuth per day), tripotassium dicitrato bismuthate (TDB, DeNoltab, Gist Brocades Ltd., Weybridge, England) 240 mg bid (431 mg bismuth per day) or placebo. After the last dose the geometric mean for Cmax for 500 mg bid of GR122311X was 5 ng.g-1, for 1.0 g bid GR122311X it was 12 ng.g-1 and it was 21 ng.g-1 for 240 mg TDB bid. The corresponding trough plasma levels were 2 ng.g-1, 4 ng.g-1 and 4 ng.g-1, respectively. The AUC over a dosing interval after the last dose (AUC tau) were 34 ng.h.g-1, 71 ng.h.g-1 and 79 ng.h.g-1, respectively. The bismuth urinary recoveries over the last dosing interval (Ae tau) were 97 micrograms, 227 micrograms and 309 micrograms, respectively, which is less than 1% of the administered doses. The renal clearance of bismuth was less than the glomerular filtration rate. After adjustment for bismuth dose, the Cmax for GR122311X 500 mg was 35% that of TDB, while for GR122311X 1.0 g the Cmax was 42% that of TDB. Similar differences were observed for Ae tau. In conclusion bismuth pharmacokinetics after oral administration of GR1223311X exhibited lower Ae tau and Cmax, with a much narrower Cmax range than those observed for TDB.

  15. Glucocorticoid-induced tethered transrepression requires SUMOylation of GR and formation of a SUMO-SMRT/NCoR1-HDAC3 repressing complex.

    PubMed

    Hua, Guoqiang; Ganti, Krishna Priya; Chambon, Pierre

    2016-02-02

    Upon binding of a glucocorticoid (GC), the GC receptor (GR) can exert one of three transcriptional regulatory functions. We recently reported that SUMOylation of the GR at position K293 in humans (K310 in mice) within the N-terminal domain is indispensable for GC-induced evolutionary conserved inverted repeated negative GC response element (IR nGRE)-mediated direct transrepression. We now demonstrate that the integrity of this GR SUMOylation site is mandatory for the formation of a GR-small ubiquitin-related modifiers (SUMOs)-SMRT/NCoR1-HDAC3 repressing complex, which is indispensable for NF-κB/AP1-mediated GC-induced tethered indirect transrepression in vitro. Using GR K310R mutant mice or mice containing the N-terminal truncated GR isoform GRα-D3 lacking the K310 SUMOylation site, revealed a more severe skin inflammation than in WT mice. Importantly, cotreatment with dexamethasone (Dex) could not efficiently suppress a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in these mutant mice, whereas it was clearly decreased in WT mice. In addition, in mice selectively ablated in skin keratinocytes for either nuclear receptor corepressor 1 (NCoR1)/silencing mediator for retinoid or thyroid-hormone receptors (SMRT) corepressors or histone deacetylase 3 (HDAC3), Dex-induced tethered transrepression and the formation of a repressing complex on DNA-bound NF-κB/AP1 were impaired. We previously suggested that GR ligands that would lack both (+)GRE-mediated transactivation and IR nGRE-mediated direct transrepression activities of GCs may preferentially exert the therapeutically beneficial GC antiinflammatory properties. Interestingly, we now identified a nonsteroidal antiinflammatory selective GR agonist (SEGRA) that selectively lacks both Dex-induced (+)GRE-mediated transactivation and IR nGRE-mediated direct transrepression functions, while still exerting a tethered indirect transrepression activity and could therefore be clinically lesser

  16. Bisphenol A suppresses glucocorticoid target gene (ENaCγ) expression via a novel ERβ/NF-κB/GR signalling pathway in lung epithelial cells.

    PubMed

    Hijazi, Ayten; Guan, Haiyan; Yang, Kaiping

    2016-08-13

    We previously demonstrated that prenatal exposure to Bisphenol A (BPA) disrupts fetal lung maturation likely through the glucocorticoid signalling pathway, but the precise molecular mechanisms remain obscure. Given that BPA diminished the expression of epithelial sodium channel-γ (ENaCγ), a well-known glucocorticoid receptor (GR) target gene, in fetal lungs, we used this GR target gene to delineate the molecular pathway through which BPA exerts its effects on lung cells. The A549 lung epithelial cell line was used as an in vitro model system. As a first step, we validated our in vitro cell model by demonstrating a robust concentration-dependent suppression of ENaCγ expression following BPA exposure. We also showed that both dexamethasone and siRNA-mediated knockdown of GR expression blocked/abrogated the inhibitory effects of BPA on ENaCγ expression, suggesting that BPA repressed ENaCγ expression via inhibition of GR activity. Given the well-known antagonistic interactions between the pro-inflammatory transcriptional factor NF-κB and GR, we then showed that BPA inhibited GR activity through the activation of NF-κB. Lastly, since BPA is known to function as a pro-inflammatory factor via the estrogen receptor β (ERβ), we provided evidence that BPA signals through ERβ to activate the NF-κB signalling pathway. Taken together, these findings demonstrate that BPA acts on ERβ to activate the NF-κB signalling pathway, which in turn leads to diminished GR activity and consequent repression of ENaCγ expression in lung epithelial cells. Thus, our present study reveals a novel BPA signalling pathway that involves ERβ, NF-κB and GR.

  17. Breed-dependent transcriptional regulation of 5'-untranslated GR (NR3C1) exon 1 mRNA variants in the liver of newborn piglets.

    PubMed

    Zou, Huafeng; Li, Runsheng; Jia, Yimin; Yang, Xiaojing; Ni, Yingdong; Cong, Rihua; Soloway, Paul D; Zhao, Ruqian

    2012-01-01

    Glucocorticoids are vital for life and regulate an array of physiological functions by binding to the ubiquitously expressed glucocorticoid receptor (GR, also known as NR3C1). Previous studies demonstrate striking breed differences in plasma cortisol levels in pigs. However, investigation into the breed-dependent GR transcriptional regulation is hampered by lacking porcine GR promoter information. In this study, we sequenced 5.3 kb upstream of the translation start codon of the porcine GR gene, and identified seven alternative 5'-untranslated exons 1-4, 1-5, 1-6, 1-7, 1-8, 1-9,10 and 1-11. Among all these mRNA variants, exons 1-4 and 1-5, as well as the total GR were expressed significantly (P<0.05) higher in the liver of newborn piglets of Large White (LW) compared with Erhualian, a Chinese indigenous breed. Overall level of CpG methylation in the region flanking exons 1-4 and 1-5 did not show breed difference. However, nuclear content of Sp1, p-CREB and GR in the liver was significantly (P<0.05) higher in LW piglets, associated with enhanced binding of p-CREB, and higher level of histone H3 acetylation in 1-4 and 1-5 promoters. In contrast, GR binding to promoters of exons 1-4 and 1-5 was significantly diminished in LW piglets, implicating the presence of negative GREs. These results indicate that the difference in the hepatic expression of GR transcript variants between two breeds of pigs is determined, at least partly, by the disparity in the binding of transcription factors and the enrichment of histone H3 acetylation to the promoters.

  18. Involvement of Gr-1 dull+ cells in the production of TNF-α and IL-17 and exacerbated systemic inflammatory response caused by lipopolysaccharide.

    PubMed

    Tanno, Daiki; Akahori, Yukiko; Toyama, Masahiko; Sato, Ko; Kudo, Daisuke; Abe, Yuzuru; Miyasaka, Tomomitsu; Yamamoto, Hideki; Ishii, Keiko; Kanno, Emi; Maruyama, Ryoko; Kushimoto, Shigeki; Iwakura, Yoichiro; Kawakami, Kazuyoshi

    2014-02-01

    Systemic inflammatory response syndrome (SIRS) is a life-threatening disease. Recent reports have demonstrated that the immunoregulatory cells that express Gr-1, a granulocyte surface antigen, play a critical role in various pathological conditions. In the present study, we have established a mouse model of SIRS and addressed the possible contribution of Gr-1+ cells in this model. C57BL/6 mice were injected intraperitoneally with anti-Gr-1 mAb or control IgG 1 day before administration of lipopolysaccharide (LPS). All of the mice that received anti-Gr-1 mAb and LPS died early as a result of hypothermia and severe emaciation, whereas mice treated with control IgG and LPS survived the observation period. In mice treated with anti-Gr-1 mAb and LPS, acute inflammatory changes with alveolar hemorrhage were observed in the lung and proximal convoluted tubule necrosis was observed in the kidney. Serum TNF-α and IL-17A levels were markedly increased in anti-Gr-1 mAb-pretreated mice compared with those in control IgG-treated mice at 1 and 3 h after LPS administration, respectively. Flow cytometric analysis revealed an increase in TNF-α and IL-17A expression in Gr-1 dull+ cells in the peripheral blood mononuclear cells. Neutralization of TNF-α by a specific mAb almost completely reversed the clinical course and inhibited the increased production of IL-17A. In addition, IL-17A KO mice were less susceptible to the lethality in this model. Thus, we established a mouse model of severe SIRS and suggested that Gr-1 dull+ cells may play a critical role in the development of this pathological condition.

  19. GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy.

    PubMed

    Johansson, Maja; Agusti, Ana; Llansola, Marta; Montoliu, Carmina; Strömberg, Jessica; Malinina, Evgenya; Ragagnin, Gianna; Doverskog, Magnus; Bäckström, Torbjörn; Felipo, Vicente

    2015-09-01

    Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABAA receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABAA receptors by neurosteroids such as allopregnanolone and 3α,21-dihydroxy-5α-pregnan-20-one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE.

  20. FTD/ALS-associated poly(GR) protein impairs the Notch pathway and is recruited by poly(GA) into cytoplasmic inclusions.

    PubMed

    Yang, Dejun; Abdallah, Abbas; Li, Zhaodong; Lu, Yubing; Almeida, Sandra; Gao, Fen-Biao

    2015-10-01

    C9ORF72 repeat expansion is the most common genetic mutation in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Abnormal dipeptide repeat proteins (DPRs) generated from repeat-associated non-AUG (RAN) translation of repeat-containing RNAs are thought to be pathogenic; however, the mechanisms are unknown. Here we report that (GR)80 and (PR)80 are toxic in neuronal and non-neuronal cells in Drosophila. In contrast to reported shorter poly(GR) forms, (GR)80 is mostly localized throughout the cytosol without detectable accumulation in the nucleolus, accompanied by suppression of Notch signaling and cell loss in the wing. Some Notch target genes are also downregulated in brains and iPSC-derived cortical neurons of C9ORF72 patients. Increased Notch expression largely suppressed (GR)80-induced cell loss in the wing. When co-expressed in Drosophila, HeLa cells, or human neurons, (GA)80 recruited (GR)80 into cytoplasmic inclusions, partially decreasing the toxicity of (GR)80 and restoring Notch signaling in Drosophila. Thus, different DPRs have opposing roles in cell loss and we identify the Notch pathway as one of the receptor signaling pathways that might be compromised in C9ORF72 FTD/ALS.

  1. GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy

    PubMed Central

    Johansson, Maja; Agusti, Ana; Llansola, Marta; Montoliu, Carmina; Strömberg, Jessica; Malinina, Evgenya; Ragagnin, Gianna; Doverskog, Magnus; Bäckström, Torbjörn

    2015-01-01

    Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABAA receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABAA receptors by neurosteroids such as allopregnanolone and 3α,21-dihydroxy-5α-pregnan-20-one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE. PMID:26138462

  2. Teleseismic P-wave polarization analysis at the Gräfenberg array

    NASA Astrophysics Data System (ADS)

    Cristiano, L.; Meier, T.; Krüger, F.; Keers, H.; Weidle, C.

    2016-12-01

    P-wave polarization at the Gräfenberg array (GRF) in southern Germany is analysed in terms of azimuthal deviations and deviations in the vertical polarization using 20 yr of broad-band recordings. An automated procedure for estimating P-wave polarization parameters is suggested, based on the definition of a characteristic function, which evaluates the polarization angles and their time variability as well as the amplitude, linearity and the signal-to-noise ratio of the P wave. P-wave polarization at the GRF array is shown to depend mainly on frequency and backazimuth and only slightly on epicentral distance indicating depth-dependent local anisotropy and lateral heterogeneity. A harmonic analysis is applied to the azimuthal anomalies to analyse their periodicity as a function of backazimuth. The dominant periods are 180° and 360°. At low frequencies, between 0.03 and 0.1 Hz, the observed fast directions of azimuthal anisotropy inferred from the 180° periodicity are similar across the array. The average fast direction of azimuthal anisotropy at these frequencies is N20°E with an uncertainty of about 8° and is consistent with fast directions of Pn-wave propagation. Lateral velocity gradients determined for the low-frequency band are compatible with the Moho topography of the area. A more complex pattern in the horizontal fast axis orientation beneath the GRF array is observed in the high-frequency band between 0.1 and 0.5 Hz, and is attributed to anisotropy in the upper crust. A remarkable rotation of the horizontal fast axis orientation across the suture between the geological units Moldanubicum and Saxothuringicum is observed. In contrast, the 360° periodicity at high frequencies is rather consistent across the array and may either point to lower velocities in the upper crust towards the Bohemian Massif and/or to anisotropy dipping predominantly in the NE-SW direction. Altogether, P-wave polarization analysis indicates the presence of layered lithospheric

  3. Energy Partitioning in the Phreatomagmatic Basaltic Eruption of Grímsvötn in 2004

    NASA Astrophysics Data System (ADS)

    Gudmundsson, M. T.; Zimanowski, B.; Jude-Eton, T. C.; Oddsson, B.; Buettner, R.; Dellino, P.; Thordarson, T.; Larsen, G.

    2009-12-01

    The energy of an explosive eruption is transferred to the surroundings in a variety of ways, but for plinian magmatic eruptions it is commonly assumed that most of the energy is lost to the atmosphere through the eruption plume. For a phreatomagmatic eruption some energy is also lost to a surrounding water body, by heating and boiling, and in the case of a partly subglacial eruption, a substantial part may be lost to ice melting. However, detailed studies of energy partitioning have been lacking. The eruption of Grímsvötn in November 2004 lasted for six days and produced only basaltic tephra. About half of the erupted material was deposited at the eruption site, within a 500-700 m wide and 150-200 m deep ice cauldron. The remaining half formed a well defined tephra fan towards north and northeast. Through repeated pre- and post-eruption surveying of glacier geometry the volume of ice melted in the eruption could be measured. Detailed measurements of key parameters such as volume and mass of erupted material were carried out and a total deposit grain size distribution could be determined on the basis of extensive sieving of both proximal and distal parts of the deposit. The heat capacity of the tephra and energy used for generation of new surface (fragmentation energy) was determined through laboratory measurements. On the basis of these data, the total mass of erupted material was determined as about 6 x 1010 kg, and the total thermal energy of the eruption was found to be 7 x 1016 J. Moreover, the partitioning of the total energy into energy lost to: a) ice melting, b) meltwater heating, c) residual heat in volcanic pile, d) kinetic energy and e) total fragmentation energy could be determined. The results indicate that about a third of the energy was used for ice melting, that about a tenth was expended for meltwater heating and remained as heat in the crater, and that energy expended for fragmenting the magma amounted to a few percent. The remaining energy

  4. Detailed investigations of proximal tubular function in Imerslund-Gräsbeck syndrome

    PubMed Central

    2013-01-01

    Background Imerslund-Gräsbeck Syndrome (IGS) is a rare genetic disorder characterised by juvenile megaloblastic anaemia. IGS is caused by mutations in either of the genes encoding the intestinal intrinsic factor-vitamin B12 receptor complex, cubam. The cubam receptor proteins cubilin and amnionless are both expressed in the small intestine as well as the proximal tubules of the kidney and exhibit an interdependent relationship for post-translational processing and trafficking. In the proximal tubules cubilin is involved in the reabsorption of several filtered plasma proteins including vitamin carriers and lipoproteins. Consistent with this, low-molecular-weight proteinuria has been observed in most patients with IGS. The aim of this study was to characterise novel disease-causing mutations and correlate novel and previously reported mutations with the presence of low-molecular-weight proteinuria. Methods Genetic screening was performed by direct sequencing of the CUBN and AMN genes and novel identified mutations were characterised by in silico and/or in vitro investigations. Urinary protein excretion was analysed by immunoblotting and high-resolution gel electrophoresis of collected urines from patients and healthy controls to determine renal phenotype. Results Genetic characterisation of nine IGS patients identified two novel AMN frameshift mutations alongside a frequently reported AMN splice site mutation and two CUBN missense mutations; one novel and one previously reported in Finnish patients. The novel AMN mutations were predicted to result in functionally null AMN alleles with no cell-surface expression of cubilin. Also, the novel CUBN missense mutation was predicted to affect structural integrity of the IF-B12 binding site of cubilin and hereby most likely cubilin cell-surface expression. Analysis of urinary protein excretion in the patients and 20 healthy controls revealed increased urinary excretion of cubilin ligands including apolipoprotein A

  5. Low glucocorticoid receptor (GR), high Dig2 and low Bcl-2 expression in double positive thymocytes of BALB/c mice indicates their endogenous glucocorticoid hormone exposure.

    PubMed

    Boldizsár, Ferenc; Pálinkás, László; Czömpöly, Tamás; Bartis, Domokos; Németh, Péter; Berki, Timea

    2006-01-01

    Several studies have shown that of the four major thymocyte subsets, the CD4/CD8 double positive (DP) thymocytes are the most sensitive to in vivo glucocorticoid hormone (GC)-induced apoptosis. Our aim was to analyse fine molecular differences among thymocyte subgroups that could underlie this phenomenon. Therefore, we characterised the glucocorticoid hormone receptor (GR) expression of thymocyte subgroups both at the mRNA and protein levels by real-time PCR and flow cytometry, and correlated these features to their apoptotic sensitivity. We also investigated the time-dependent effects of the GC agonist dexamethasone (DX) with or without GC antagonist (RU486) treatments on GR mRNA/protein expression. We also analysed the expression of two apoptosis-related gene products: dexamethasone-induced gene 2 (Dig2) mRNA and Bcl-2 protein. We found that DN thymocytes had the highest GR expression, followed by CD8 single positive (SP), CD4 SP and DP thymocytes in 4-week-old BALB/c mice, both at the mRNA and protein levels, respectively. In DP cells, the Dig2 expression was significantly higher, while the Bcl-2 expression was significantly lower than in DN, CD4 SP and CD8 SP thymocytes. Single high dose DX treatment caused time-dependent depletion of DP thymocytes due to their higher apoptosis rate, which could not be abolished with RU486 pretreatment. After a single high dose DX treatment, there was a transient, significant increase of the GR mRNA and protein level of unsorted thymocytes after 8 and 16 h, followed by a significant decrease at 24 h, respectively. The time-dependent GR expression changes after DX administration could not be inhibited by the GC antagonist RU486. Twenty-four hours after exposure to high dose DX the DN, CD4 SP and CD8 SP cells showed a significant decrease of GR mRNA and protein expression, whereas the DP thymocytes, showed no significant alteration of GR mRNA or protein expression. The kinetical analysis of GR expression and apoptotic marker

  6. Cannabinoids and traumatic stress modulation of contextual fear extinction and GR expression in the amygdala-hippocampal-prefrontal circuit.

    PubMed

    Ganon-Elazar, Eti; Akirav, Irit

    2013-09-01

    Considerable evidence suggests that cannabinoids modulate the behavioral and physiological response to stressful events. We have recently shown that activating the cannabinoid system using the CB1/CB2 receptor agonist WIN55,212-2 (WIN) in proximity to exposure to single-prolonged stress (SPS), a rat model of emotional trauma, prevented the stress-induced enhancement of acoustic startle response, the impairment in avoidance extinction and the enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis (Ganon-Elazar and Akirav, 2012). Some of the effects were found to be mediated by CB1 receptors in the basolateral amygdala (BLA). Here we examined whether cannabinoid receptor activation in a putative brain circuit that includes the BLA, hippocampus and prefrontal cortex (PFC), could prevent the effects of traumatic stress on contextual fear extinction and alterations in glucocorticoid receptor (GR) protein levels. We found that: (i) SPS impaired contextual fear extinction tested one week after trauma exposure and that WIN prevented the stress-induced impairment of extinction when microinjected immediately after trauma exposure into the BLA or hippocampus (5 μg), but not when microinjected into the PFC, (ii) the ameliorating effects of WIN on contextual extinction were prevented by blocking GRs in the BLA and hippocampus, and (iii) SPS up regulated GRs in the BLA, PFC and hippocampus and systemic WIN administration (0.5 mg/kg) after trauma exposure normalized GR levels in the BLA and hippocampus, but not in the PFC. Cannabinoid receptor activation in the aftermath of trauma exposure may regulate the emotional response to the trauma and prevent stress-induced impairment of extinction and GR up regulation through the mediation of CB1 receptors in the BLA and hippocampus. Taken together, the findings suggest that the interaction between the cannabinoid and glucocorticoid systems is crucial in the modulation of emotional trauma.

  7. Recruitment of bone marrow CD11b+Gr-1+ cells by polymeric nanoparticles for antigen cross-presentation

    PubMed Central

    Yang, Ya-Wun; Luo, Wen-Hui

    2017-01-01

    The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8+ T cell responses via the CD11b+Gr−1+ myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b+Gr-1lowLy-6Chigh and CD11b+Gr-1highLy-6Clow subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8+ cells. Co-culture of OT-I CD8+ T cells with PLGA/OVA NPs-primed CD11b+Gr-1+ subsets upregulated the expression of IL-2, TNF-α, INF-γ, granzyme B, and perforin, resulting in proliferation of CD8+ T cells and differentiation into effector cytotoxic T lymphocytes (CTLs). In vivo proliferation of CFSE-labelled OT-I CD8+ cells in response to OVA was also obtained in the animals immunized with PLGA/OVA NPs. The results presented in this study demonstrate the ability of polymeric NPs to recruit two CD11b+Gr−1+ myeloid subsets for effective presentation of exogenous antigen to OT-I CD8+ T cells in the context of major histocompatibility complex (MHC) class I, leading to an induction of antigen-specific cell proliferation and differentiation into effector cells. PMID:28317931

  8. Recruitment of bone marrow CD11b+Gr-1+ cells by polymeric nanoparticles for antigen cross-presentation

    NASA Astrophysics Data System (ADS)

    Yang, Ya-Wun; Luo, Wen-Hui

    2017-03-01

    The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8+ T cell responses via the CD11b+Gr‑1+ myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b+Gr-1lowLy-6Chigh and CD11b+Gr-1highLy-6Clow subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8+ cells. Co-culture of OT-I CD8+ T cells with PLGA/OVA NPs-primed CD11b+Gr-1+ subsets upregulated the expression of IL-2, TNF-α, INF-γ, granzyme B, and perforin, resulting in proliferation of CD8+ T cells and differentiation into effector cytotoxic T lymphocytes (CTLs). In vivo proliferation of CFSE-labelled OT-I CD8+ cells in response to OVA was also obtained in the animals immunized with PLGA/OVA NPs. The results presented in this study demonstrate the ability of polymeric NPs to recruit two CD11b+Gr‑1+ myeloid subsets for effective presentation of exogenous antigen to OT-I CD8+ T cells in the context of major histocompatibility complex (MHC) class I, leading to an induction of antigen-specific cell proliferation and differentiation into effector cells.

  9. Application of response surface methodology for optimizing arginine deiminase production medium for Enterococcus faecium sp. GR7.

    PubMed

    Kaur, Baljinder; Kaur, Rajinder

    2013-01-01

    Arginine metabolism in Enterococcus faecium sp. GR7 was enhanced via arginine deiminase pathway. Process parameters including fermentation media and environmental conditions were optimized using independent experiments and response surface methodology (central composite design). Fermentation media (EAPM) were optimized using independent experiments which resulted in 4-fold increase in arginine deiminase specific activity as compared to basal medium. To further enhance arginine deiminase activity in E. faecium sp. GR7 and biomass production including a five-level central composite design (CCD) was employed to study the interactive effect of three-process variables. Response surface methodology suggested a quadratic model which was further validated experimentally where it showed approximately 15-fold increase in arginine metabolism (in terms of arginine deiminase specific activity) over basal medium. By solving the regression equation and analyzing the response surface cartons, optimal concentrations of the media components (g/L) were determined as arginine 20.0; tryptone 15.0; lactose 10.0; K2HPO4 3.0; NaCl 1.0, MnSO4 0.6 mM; Tween 80 1%; pH 6.0 for achieving specific arginine deiminase activity of 4.6 IU/mG with concomitant biomass production of 12.1 mg/L. The model is significant as the coefficient of determination (R (2)) was 0.87 to 0.90 for all responses. Enhanced arginine deiminase yield from E. faecium, a GRAS lactic acid bacterial strain, is desirable to explore in vitro therapeutic potential of the arginine metabolizing E. faecium sp. GR7.

  10. Blockade of porcine carotid vascular response to sumatriptan by GR 127935, a selective 5-HT1D receptor antagonist.

    PubMed Central

    De Vries, P.; Heiligers, J. P.; Villalón, C. M.; Saxena, P. R.

    1996-01-01

    1. It has previously been shown that the antimigraine drug, sumatriptan, a putative 5-HT1D receptor agonist, decreases porcine common carotid and arteriovenous anastomotic blood flows, but slightly increases the arteriolar (capillary) blood flow to the skin and ears. Interestingly, such responses, being mediated by 5-HT1-like receptors, are resistant to blockade by metergoline, which, in addition to displaying a very high affinity for (and occasionally intrinsic efficacy at) the 5-HT1D receptor subtypes, blocks (with lower potency than methiothepin) some 5-HT1D receptor-mediated vascular responses. These findings raise doubts whether sumatriptan-sensitive 5-HT1-like receptors mediating changes in the distribution of porcine carotid blood flow are identical to cloned 5-HT1D receptors. With the recent advent of the potent and selective 5-HT1D receptor antagonist, GR127935, we have examined in the present study whether the carotid vascular effects of sumatriptan in the pig are amenable to blockade by GR127935. 2. In animals pretreated with saline, sumatriptan (30, 100 and 300 micrograms kg-1, i.v.) reduced the total carotid and arteriovenous anastomotic blood flows in a dose dependent manner. In contrast, sumatriptan increased blood flow to the skin, ears and fat, although the total capillary fraction was not significantly affected. 3. While GR127935 pretreatment (0.25 and 0.5 mg kg-1) itself slightly reduced the total carotid and arteriovenous anastomotic blood flows, carotid vasoconstrictor responses to sumatriptan were either partly (0.25 mg kg-1) or completely (0.5 mg kg-1) blocked by the compound. In GR127935 pretreated animals, the sumatriptan-induced increases in blood flow to the skin, ears and fat were also attenuated. 4. Taken together, the results suggest that arteriovenous anastomotic constriction and, possibly, arteriolar dilatation in the skin, ears and fat by sumatriptan are mediated by 5-HT1D receptors. Therefore, vascular 5-HT1-like receptors in the

  11. Study of the Phototransference in GR-200 Dosimetric Material and its Convenience for Dose Re-estimation

    SciTech Connect

    Baly, L.; Otazo, M. R.; Molina, D.; Pernas, R.

    2006-09-08

    A study of the phototransference of charges from deep to dosimetric traps in GR-200 material is presented and its convenience for dose re-estimation in the dose range between 2 and 100mSv is also analyzed. The recovering coefficient (RC) defined as the ratio between the phototransferred thermoluminescence (PTTL) and the original thermoluminescence (TL) of the dosimetric trap was used to evaluate the ratio of phototransferred charges from deep traps and the original charges in the dosimetric traps. The results show the convenience of this method for dose re-estimation for this material in the selected range of doses.

  12. Complement regulates conventional DC-mediated NK-cell activation by inducing TGF-β1 in Gr-1+ myeloid cells.

    PubMed

    Qing, Xiaoping; Koo, Gloria C; Salmon, Jane E

    2012-07-01

    Complement activation modulates DC-mediated T-cell activation, but whether complement affects DC-mediated priming of NK cells is unknown. Here, we demonstrated that conventional DCs (cDCs) from C3(-/-) and C5aR(-/-) mice are hyperresponsive to polyI:C, a TLR3 ligand, leading to enhanced NK-cell activation. We found that cDCs lack C5a receptor (C5aR) and do not respond to C5a directly. Depletion of Gr-1(+) myeloid cells augments polyI:C-induced cDC activation in WT but not in C3(-/-) or C5aR(-/-) mice, indicating that the effect of complement activation on cDCs is indirectly mediated through C5aR-expressing Gr-1(+) myeloid cells. We further demonstrated that the mechanism by which Gr-1(+) myeloid cells regulate the activity of cDCs involves C5a-dependent TGF-β1 production in Gr-1(+) myeloid cells. C5a enhances and blocking C5aR decreases TGF-β1 production in cultured bone marrow Gr-1(+) CD11b(+) cells. C5aR deficiency is associated with reduced circulating TGF-β1 levels, while depleting Gr-1(+) myeloid cells abrogates this difference between WT and C5aR(-/-) mice. Lastly, we showed that enhanced cDC-NK-cell activity in C3(-/-) mice led to delayed melanoma tumor growth. Thus, complement activation indirectly regulates cDC-NK-cell activation in response to inflammatory stimuli such as TLR3 by promoting TGF-β1 production in Gr-1(+) myeloid cells at steady state.

  13. Effects of the 5-HT receptor antagonists GR127935 (5-HT1B/1D) and MDL100907 (5-HT2A) in the consolidation of learning.

    PubMed

    Meneses, A; Terrón, J A; Hong, E

    1997-12-01

    We have previously reported that 5-HT1B/1D and 5-HT2A/2B/2C receptors play a role in learning and memory. The present investigation was devoted to analyze further in the autoshaping learning task: (1) the effects of the 5-HT1A/1B/1D receptor agonist, GR46611, the 5-HT1B/1D receptor antagonist, GR127935, and the selective 5-HT2A receptor antagonist, MDL100907. Consistent with a role of 5-HT1B/1D receptors in learning, the post-training injection of GR46611 (1-10 mg/kg) decreased the consolidation of learning whereas GR127935 (10 mg/kg) increased it; the effects of both drugs were reversed by PCA pretreatment. GR127935 abolished the decrease induced by GR46611, TFMPP and mCPP, whereas MDL100907 (0.1-3.0 mg/kg) had no effect by itself but abolished the effects of DOI, ketanserin and TFMPP and moderately inhibited the effects elicited by mCPP, 1-NP and mesulergine. Neither did GR127935 nor MDL100907 significantly modify the increase in the consolidation of learning induced by 8-OH-DPAT. Thus, the present findings suggest that stimulation of presynaptic 5-HT1B/1D receptors impairs the consolidation of learning whilst stimulation of 5-HT2A/2C receptors enhances it; the blockade of 5-HT2A receptors has no effects. In addition, 5-HT2 receptors seem to modulate this cognitive stage.

  14. Lactobacillus rhamnosus GR-1 Attenuates Induction of Hypertrophy in Cardiomyocytes but Not through Secreted Protein MSP-1 (p75)

    PubMed Central

    Ettinger, Grace; Burton, Jeremy P.; Gloor, Gregory B.; Reid, Gregor

    2017-01-01

    Previous animal studies have shown that the administration of probiotic Lactobacillus rhamnosus can provide a protective effect against ischemia/reperfusion and necrotic injury to the intestine, liver, and heart, as well as a therapeutic effect to the outcome of ischemic injury to the heart, including cardiac hypertrophy and heart failure. We hypothesized that L. rhamnosus GR-1 major secreted protein 1 (MSP-1), also known as p75, plays a major role in this phenomenon. Experiments using neonatal rat ventricular cardiomyocytes showed that live and dead GR-1 bacteria, probiotic-conditioned media, and other probiotic species and strains inhibited the α1-adrenergic receptor agonist phenylephrine-induced hypertrophy as assessed by markers atrial natriuretic peptide and α-skeletal actin. However, using a mutant strain, we showed that this MSP-1 was not required for the inhibition. The ability of factors produced by lactobacilli to improve cardiac function warrants further study for the management of cardiac hypertrophy and heart failure. PMID:28085895

  15. Theoretical prediction of Grüneisen parameter for SiO2.TiO2 bulk metallic glasses

    NASA Astrophysics Data System (ADS)

    Singh, Chandra K.; Pandey, Anjani K.; Pandey, Brijesh K.

    2016-05-01

    The Grüneisen parameter (γ) is very important to decide the limitations for the prediction of thermoelastic properties of bulk metallic glasses. It can be defined in terms of microscopic and macroscopic parameters of the material in which former is based on vibrational frequencies of atoms in the material while later is closely related to its thermodynamic properties. Different formulation and equation of states are used by the pioneer researchers of this field to predict the true sense of Gruneisen parameter for BMG but for SiO2.TiO2 very few and insufficient information is available till now. In the present work we have tested the validity of two different isothermal EOS viz. Poirrior-Tarantola EOS and Usual-Tait EOS to predict the true value of Gruneisen parameter for SiO2.TiO2 as a function of compression. Using different thermodynamic limitations related to the material constraints and analyzing obtained result it is concluded that the Poirrior-Tarantola EOS gives better numeric values of Grüneisen parameter (γ) for SiO2.TiO2 BMG.

  16. An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs.

    PubMed

    Fyfe, John C; Hemker, Shelby L; Venta, Patrick J; Fitzgerald, Caitlin A; Outerbridge, Catherine A; Myers, Sherry L; Giger, Urs

    2013-08-01

    Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome.

  17. An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs

    PubMed Central

    Fyfe, John C.; Hemker, Shelby L.; Venta, Patrick J.; Fitzgerald, Caitlin A.; Outerbridge, Catherine A.; Myers, Sherry L.; Giger, Urs

    2013-01-01

    Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9 Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome. PMID:23746554

  18. Gr-1 Ab administered after bone marrow transplantation plus thymus transplantation suppresses tumor growth by depleting granulocytic myeloid-derived suppressor cells.

    PubMed

    Shi, Ming; Li, Ming; Cui, Yunze; Adachi, Yasushi; Ikehara, Susumu

    2014-01-01

    It has been shown that allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) plus thymus transplantation (TT) is effective in treating recipients with malignant tumors. Although TT increases the percentage of T cells in the early term after BMT, the myeloid-derived suppressor cells (MDSCs) are still the dominant population. We used the Gr-1 Ab to deplete the granulocytic MDSCs (G-MDSCs) in tumor-bearing mice that had received BMT+TT. Two weeks after the BMT, the mice injected with Gr-1 Ab showed smaller tumors than those in the control group. In addition, Gr-1 Ab significantly increased the percentages and numbers of CD4+ and CD8+ T cells, and decreased the percentages and numbers of MDSCs and G-MDSCs. No side effects of the Gr-1 Ab on recipient or donor thymus were observed. These findings indicate that Gr-1 Ab administered after BMT+TT may enhance the effectiveness of tumor suppression.

  19. Genetic map of the region around grizzled (gr) and mocha (mh) on mouse chromosome 10, homologous to human 19p13.3.

    PubMed

    Kapfhamer, D; Burmeister, M

    1994-10-01

    Grizzled (gr) is a recessive mouse mutation resulting in a gray coat color and reduced perinatal viability. Mocha (mh) is one of several recessive mouse mutants characterized by platelet storage pool disorder, pigment abnormalities, reduced fertility, kidney function deficiencies, and, in some mutants, inner ear and natural killer cell deficiencies. Murine platelet storage pool deficient mutants may be models for Chediak-Higashi and Hermansky-Pudlak syndromes in humans. The genes for gr and mh are very closely linked to each other (0 +/- 1.2 cM). However, their relative position with respect to molecular markers was previously unknown. Thus, genetic mapping of the gr locus will also yield information about the mh location. To map these two genes genetically, we have performed an intersubspecific backcross of grizzled mice with Mus musculus castaneus. In 539 progeny tested, we found no recombination between the gr gene, the gene for anti-Muellerian hormone (Amh), and the microsatellite markers D10Mit7, D10Mit21, and D10Mit23. One recombination event for each of the flanking markers Basigin (Bsg) and D10Mit22 was identified. These closely linked markers should provide entry points for positional cloning of the gr and mh genes. The region linked to grizzled is homologous to a gene-rich region on human Chromosome 19p13.3.

  20. The HPV16 E7 Oncoprotein Disrupts Dendritic Cell Function and Induces the Systemic Expansion of CD11b+Gr1+ Cells in a Transgenic Mouse Model

    PubMed Central

    Damian-Morales, Gabriela; Serafín-Higuera, Nicolás; Moreno-Eutimio, Mario Adán; Cortés-Malagón, Enoc M.; Bonilla-Delgado, José; Rodríguez-Uribe, Genaro; Ocadiz-Delgado, Rodolfo; Lambert, Paul F.

    2016-01-01

    Objective. The aim of this study was to analyze the effects of the HPV16 E7 oncoprotein on dendritic cells (DCs) and CD11b+Gr1+ cells using the K14E7 transgenic mouse model. Materials and Methods. The morphology of DCs was analyzed in male mouse skin on epidermal sheets using immunofluorescence and confocal microscopy. Flow cytometry was used to determine the percentages of DCs and CD11b+Gr1+ cells in different tissues and to evaluate the migration of DCs. Results. In the K14E7 mouse model, the morphology of Langerhans cells and the migratory activity of dendritic cells were abnormal. An increase in CD11b+Gr1+ cells was observed in the blood and skin of K14E7 mice, and molecules related to CD11b+Gr1+ chemoattraction (MCP1 and S100A9) were upregulated. Conclusions. These data suggest that the HPV16 E7 oncoprotein impairs the function and morphology of DCs and induces the systemic accumulation of CD11b+Gr1+ cells. PMID:27478837

  1. Rac1 regulates skin tumors by regulation of keratin 17 through recruitment and interaction with CD11b+Gr1+ cells

    PubMed Central

    Zhou, Ying; Zhu, Shaojun; Liu, Juanjuan; Wang, Dong; Deng, Anmei; Wang, Zhipeng

    2014-01-01

    Rac1 is a member of the Rho family of small GTPases that control cells proliferation, differentiation, migration, and inflammation. Rac1 is crucial in tumorigenesis and development. Keratin17 and CD11b+Gr1+ cells are considered to regulate skin inflmmation. Here we discuss the regulation of Rac1 on skin tumor formation and its relationship. In samples from human skin squamous cell carcinoma (SCC), Rac1 activity was higher in cancer tissues than in normal skin and activity correlated with keratin 17 overexpression. In a DMBA/TPA-induced mouse skin tumor model, inhibition of Rac1 activity and depletion of CD11b+Gr1+ cells resulted in significant tumor formation. TPA induced recruitment of CD11b+Gr1+ cells into dermis; however, Rac1 inhibitor abolished this recruitment. In vitro, Rac1 induced interferon (IFN) and interlukin (IL6) production in keratinocytes, repression of keratin 17 inhibited IFN and IL6 production induced by Rac1. Moreover, both inhibition of Rac1 activity and repression of keratin 17 restricted proliferation and induction of differentiation in keratinocytes. Coculture of CD11b+Gr1+ cells with keratinocytes activated Wnt pathway in keratinocytes, resulting in enhanced Rac1 activity, overexpression of keratin 17, and hyperproliferation of keratinocytes. Our results suggested that hyperactive Rac1 recruited and interacted with CD11b+Gr1+ cells, inducing keratin 17-regulated inflammation and promoting skin tumor formation. PMID:24962779

  2. Expression of hepatic miRNAs targeting porcine glucocorticoid receptor (GR) 3'UTR in the neonatal piglets under a maternal gestational betaine supplementation.

    PubMed

    Cai, Demin; Liu, Haoyu; Yuan, Mengjie; Pan, Shifeng; Jia, Yimin; Zhao, Ruqian

    2016-03-01

    Glucocorticoid receptor (GR) has been previously demonstrated an important transcriptional factor of hepatic metabolic genes in the neonates under a maternal gestational betaine supplementation ("Gestational dietary betaine supplementation suppresses hepatic expression of lipogenic genes in neonatal piglets through epigenetic and glucocorticoid receptor-dependent mechanisms" Cai et al., 2015 [1]). Here we provide accompanying data about the expression of hepatic miRNAs targeting porcine GR 3'UTR in the neonatal piglets. Liver samples were obtained and RNA was isolated. RNA was polyadenylated by poly (A) polymerase and then dissolved and reverse transcribed using poly (T) adapter. The diluted cDNA were used in each real-time PCR assay. The sequences of all the porcine miRNAs were acquired from miRBase (http://www.mirbase.org/). miRNAs targeting GR were predicted using the PITA algorithm. Among all the predicted miRNAs, 4 miRNAs targeting GR were quantitated by real-time PCR and miRNA-124a, which has been identified to target GR 3'UTR [2], [3], was more highly expressed in betaine-exposed neonatal livers.

  3. G-CSF preferentially supports the generation of gut-homing Gr-1high macrophages in M-CSF-treated bone marrow cells.

    PubMed

    Meshkibaf, Shahab; Gower, Mark William; Dekaban, Gregory A; Kim, Sung Ouk

    2014-10-01

    The G-CSF is best known for its activity in the generation and activation of neutrophils. In addition, studies on G-CSF(-/-) or G-CSFR(-/-) mice and BMC cultures suggested a role of G-CSF in macrophage generation. However, our understanding on the role of G-CSF in macrophage development is limited. Here, using in vitro BMC models, we demonstrated that G-CSF promoted the generation of Gr-1(high)/F4/80(+) macrophage-like cells in M-BMCs, likely through suppressing cell death and enhancing generation of Gr-1(high)/F4/80(+) macrophage-like cells. These Gr-1(high) macrophage-like cells produced "M2-like" cytokines and surface markers in response to LPS and IL-4/IL-13, respectively. Adoptive transfer of EGFP-expressing (EGFP(+)) M-BMCs showed a dominant, gut-homing phenotype. The small intestinal lamina propria of G-CSFR(-/-) mice also harbored significantly reduced numbers of Gr-1(high)/F4/80(+) macrophages compared with those of WT mice, but levels of Gr-1(+)/F4/80(-) neutrophil-like cells were similar between these mice. Collectively, these results suggest a novel function of G-CSF in the generation of gut-homing, M2-like macrophages.

  4. Gr-1dimCD11b+ immature myeloid-derived suppressor cells but not neutrophils are markers of lethal tuberculosis infection in mice.

    PubMed

    Tsiganov, Evgeny N; Verbina, Elena M; Radaeva, Tatiana V; Sosunov, Vasily V; Kosmiadi, George A; Nikitina, Irina Yu; Lyadova, Irina V

    2014-05-15

    Tuberculosis (TB) disease may progress at different rates and have different outcomes. Neutrophils have been implicated in TB progression; however, data on their role during TB are controversial. In this study, we show that in mice, TB progression is associated with the accumulation of cells that express neutrophilic markers Gr-1 and Ly-6G but do not belong to conventional neutrophils. The cells exhibit unsegmented nuclei, have Gr-1(dim)Ly-6G(dim)CD11b(+) phenotype, and express F4/80, CD49d, Ly-6C, CD117, and CD135 markers characteristic not of neutrophils but of immature myeloid cells. The cells accumulate in the lungs, bone marrow, spleen, and blood at the advanced (prelethal) stage of Mycobacterium tuberculosis infection and represent a heterogeneous population of myeloid cells at different stages of their differentiation. The accumulation of Gr-1(dim)CD11b(+) cells is accompanied by the disappearance of conventional neutrophils (Gr-1(hi)Ly-6G(hi)-expressing cells). The Gr-1(dim)CD11b(+) cells suppress T cell proliferation and IFN-γ production in vitro via NO-dependent mechanisms, that is, they exhibit characteristics of myeloid-derived suppressor cells. These results document the generation of myeloid-derived suppressor cells during TB, suggesting their role in TB pathogenesis, and arguing that neutrophils do not contribute to TB pathology at the advanced disease stage.

  5. RADIO AND X-RAY OBSERVATIONS OF THE TYPE Ic SN 2007gr REVEAL AN ORDINARY, NON-RELATIVISTIC EXPLOSION

    SciTech Connect

    Soderberg, A. M.; Brunthaler, A.; Nakar, E.; Chevalier, R. A.; Bietenholz, M. F.

    2010-12-10

    We present extensive radio and X-ray observations of the nearby Type Ic SN 2007gr in NGC 1058 obtained with the Very Large Array (VLA) and the Chandra X-ray Observatory and spanning 5 to 150 days after explosion. Through our detailed modeling of these data, we estimate the properties of the blast wave and the circumstellar environment. We find evidence for a freely expanding and non-relativistic explosion with an average blast wave velocity, v-bar {approx}0.2c, and a total internal energy for the radio emitting material of E {approx} 2 x 10{sup 46} erg assuming equipartition of energy between electrons and magnetic fields ({epsilon}{sub e} = {epsilon}{sub B} = 0.1). The temporal and spectral evolution of the radio emission points to a stellar wind-blown environment shaped by a steady progenitor mass loss rate of M-dot {approx}6x10{sup -7} M{sub sun} yr{sup -1} (wind velocity, v{sub w} = 10{sup 3} km s{sup -1}). These parameters are fully consistent with those inferred for other SNe Ibc and are in line with the expectations for an ordinary, homologous SN explosion. Our results are at odds with those of Paragi et al. who recently reported evidence for a relativistic blast wave in SN 2007gr based on their claim that the radio emission was resolved away in a low signal-to-noise Very Long Baseline Interferometry (VLBI) observation. Here we show that the exotic physical scenarios required to explain the claimed relativistic velocity-extreme departures from equipartition and/or a highly collimated outflow-are excluded by our detailed VLA radio observations. Moreover, we present an independent analysis of the VLBI data and propose that a modest loss of phase coherence provides a more natural explanation for the apparent flux density loss which is evident on both short and long baselines. We conclude that SN 2007gr is an ordinary Type Ibc supernova.

  6. Vaccination inhibits TLR2 transcription via suppression of GR nuclear translocation and binding to TLR2 promoter in porcine lung infected with Mycoplasma hyopneumoniae.

    PubMed

    Sun, Zhiyuan; Liu, Maojun; Zou, Huafeng; Li, Xian; Shao, Guoqing; Zhao, Ruqian

    2013-12-27

    Toll-like receptors (TLRs) and glucocorticoid receptor (GR) act respectively as effectors of innate immune and stress responses. The crosstalk between them is critical for the maintenance of homeostasis during the immune response. Vaccination is known to boost adaptive immunity, yet it remains elusive whether vaccination may affect GR/TLR interactions following infection. Duroc×Meishan crossbred piglets were allocated to three groups. The control group (CC) received neither vaccination nor infection; the non-vaccinated infection group (NI) was artificially infected intratracheally with Mycoplasma hyopneumoniae (M. hyopneumoniae); while the vaccinated, infected group (VI) was vaccinated intramuscularly with inactivated M. hyopneumoniae one month before infection. The clinical signs and macroscopic lung lesions were significantly reduced by vaccination. However, vaccination did not affect the concentration of M. hyopneumoniae DNA in the lung. Serum cortisol was significantly decreased in both NI and VI pigs (P<0.01), but only VI pigs demonstrated significantly diminished nuclear GR content. TLRs 1-10 were all expressed in lung, among which TLR2 was the most abundant and was significantly up-regulated (P<0.05) in NI pigs, but not in VI pigs. Accordingly, GR binding to the GR response element on TLR2 promoter was significantly increased (P<0.05) in NI pigs, but not in VI pigs. These results suggest that the inhibition of GR nuclear translocation and binding to the TLR2 promoter, which results in diminished TLR2 expression, is associated with the protective effect of vaccination on M. hyopneumoniae-induced lung lesions in the pig.

  7. Gr-1+ myeloid cells derived from tumor-bearing mice inhibit primary T cell activation induced through CD3/CD28 costimulation.

    PubMed

    Kusmartsev, S A; Li, Y; Chen, S H

    2000-07-15

    Activation of T cells is a necessary step in the development of a specific antitumor immune response. In the present study, we evaluated the ability of Gr-1+ myeloid cells, derived from the bone marrow or spleen of tumor-bearing mice, to inhibit CD3/CD28-mediated T cell activation. Using flow cytometry, we found that growth of a murine colon carcinoma (MCA-26) induces a significant increase in the number of Gr-1+ and Gr-1+/Mac-1+ myeloid cells in both bone marrow and spleen of the tumor host. The proliferative response of T cells was dramatically decreased when naive T cells were activated by anti-CD3 and anti-CD28 Abs in the presence of a myeloid-enriched cell fraction derived from spleen or bone marrow of tumor-bearing mice vs the bone marrow of naive mice. Reversal of the inhibitory effect could be achieved by adding a combination of MnTBAP (manganese [III] tetrakis [4-benzoic acid]) porphyrin and l -NMMA (NG-monomethyl-l -arginine), a superoxide dismutase mimetic and inducible NO synthase inhibitor, respectively, or by depletion of the Gr-1-positive cells. IFN-gamma, which is endogenously produced by CD3/CD28-stimulated naive T cells, is involved in induction of the inhibitory activity of myeloid cells. Importantly, when T cells pre-activated with anti-CD3 Abs were used as responder cells, the bone marrow- or spleen-derived Gr-1+ myeloid cells were unable to suppress CD3/CD28-induced T cell proliferation. Our findings suggest that one mechanism by which an increased number of immune suppressive Gr-1+ cells can induce T cell unresponsiveness or immune tolerance in tumor hosts could be through peroxynitrite production upon primary T cell activation.

  8. Local mechanical properties of Alloy 82/182 dissimilar weld joint between SA508 Gr.1a and F316 SS at RT and 320C

    SciTech Connect

    Byun, Thak Sang; Kim, Jin Weon

    2009-01-01

    This paper presents the variations of local mechanical and microstructural properties in dissimilar metal weld joints consisting of the SA508 Gr.1a ferritic steel, Alloy 82/182 filler metal, and F316 austenitic stainless steel. Flat or round tensile specimens and transmission electron microscopy disks were taken from the base metals, welds, and heat-affected zones (HAZ) of the joints and tested at room temperature (RT) and/or at 320 C. The tensile test results indicated that the mechanical property was relatively uniform within each material zone, but varied considerably between different zones. Further, significant variations were observed both in the austenitic HAZ of F316 SS and in the ferritic HAZ of SA508 Gr.1a. The yield stress (YS) of the weld metal was under-matched with respect to the HAZs of SA508 Gr.1a and F316 SS by 0.78 to 0.92, although the YS was over-matched with respect to both base metals. The minimum ductility occurred in the HAZ of SA508 Gr.1 at both test temperatures. The plastic instability stress also varied considerably in the weld joints, with minimum values occurring in the SA508 Gr.1a base metal at RT and in the HAZ of F316 SS at 320 C, suggesting that the probability of ductile failure caused by a unstable deformation at the Alloy 82/182 buttering layer is low. Within the HAZ of SA508 Gr.1a, the gradient of the YS and ultimate tensile strength (UTS) was significant, primarily because of the different microstructures produced by the phase transformation during the welding process. The increment of YS was unexpectedly high in the HAZ of F316 SS, which was explained by the strain hardening induced by a strain mismatch between the weldment and the base metal. This was confirmed by the transmission electron micrographs showing high dislocation density in the HAZ.

  9. Lactobacillus rhamnosus GR-1 Ameliorates Escherichia coli-Induced Inflammation and Cell Damage via Attenuation of ASC-Independent NLRP3 Inflammasome Activation.

    PubMed

    Wu, Qiong; Liu, Ming-Chao; Yang, Jun; Wang, Jiu-Feng; Zhu, Yao-Hong

    2015-12-11

    Escherichia coli is a major environmental pathogen causing bovine mastitis, which leads to mammary tissue damage and cell death. We explored the effects of the probiotic Lactobacillus rhamnosus GR-1 on ameliorating E. coli-induced inflammation and cell damage in primary bovine mammary epithelial cells (BMECs). Increased Toll-like receptor 4 (TLR4), NOD1, and NOD2 mRNA expression was observed following E. coli challenge, but this increase was attenuated by L. rhamnosus GR-1 pretreatment. Immunofluorescence and Western blot analyses revealed that L. rhamnosus GR-1 pretreatment decreased the E. coli-induced increases in the expression of the NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3) and the serine protease caspase 1. However, expression of the adaptor protein apoptosis-associated speck-like protein (ASC, encoded by the Pycard gene) was decreased during E. coli infection, even with L. rhamnosus GR-1 pretreatment. Pretreatment with L. rhamnosus GR-1 counteracted the E. coli-induced increases in interleukin-1β (IL-1β), -6, -8, and -18 and tumor necrosis factor alpha mRNA expression but upregulated IL-10 mRNA expression. Our data indicate that L. rhamnosus GR-1 reduces the adhesion of E. coli to BMECs, subsequently ameliorating E. coli-induced disruption of cellular morphology and ultrastructure and limiting detrimental inflammatory responses, partly via promoting TLR2 and NOD1 synergism and attenuating ASC-independent NLRP3 inflammasome activation. Although the residual pathogenic activity of L. rhamnosus, the dosage regimen, and the means of probiotic supplementation in cattle remain undefined, our data enhance our understanding of the mechanism of action of this candidate probiotic, allowing for development of specific probiotic-based therapies and strategies for preventing pathogenic infection of the bovine mammary gland.

  10. Enhanced expression of PD-L1 in oral squamous cell carcinoma-derived CD11b(+)Gr-1(+) cells and its contribution to immunosuppressive activity.

    PubMed

    Fuse, Hiroki; Tomihara, Kei; Heshiki, Wataru; Yamazaki, Manabu; Akyu-Takei, Rie; Tachinami, Hidetake; Furukawa, Ken-Ichiro; Sakurai, Kotaro; Rouwan, Moniruzzaman; Noguchi, Makoto

    2016-08-01

    Cancer is often associated with dysregulation of both the humoral and cellular immune response, which in some instances is believed to result from changes in immune cell populations. For example, immunosuppressive CD11b(+)Gr-1(+) myeloid-derived suppressor cells have been shown to proliferate in the tumor microenvironment and surrounding tissues, highlighting the relationship between tumor growth and impairment of the immune response. However, the role of myeloid-derived suppressor cells in cancer progression has not been fully characterized because these cells are heterogeneous with properties influenced by the type and location of the tumor. Here, we show that CD11b(+)Gr-1(+) cells are elevated in the peripheral blood, spleen, and tumor of mice with oral squamous cell carcinoma. The phenotype and function of these cells varied depending on the tissue of origin. In particular, CD11b(+)Gr-1(+) cells in tumors expressed PD-L1 more abundantly than those in other tissues. Accordingly, CD11b(+)Gr-1(+) cells from tumors, but not from the spleen, suppressed T cell proliferation in vitro. The results suggest that tumor-derived or immune factors result in the accumulation of phenotypically and functionally diverse populations of CD11b(+)Gr-1(+) cells in mice with oral squamous cell carcinoma. The data also indicate that PD-L1 expression in CD11b(+)Gr-1(+) cells contributes to immune suppression, implying that targeting both myeloid-derived suppressor cells and PD-L1 would be an effective immunotherapeutic strategy against oral cancer.

  11. Field Efficacy of Vectobac GR as a Mosquito Larvicide for the Control of Anopheline and Culicine Mosquitoes in Natural Habitats in Benin, West Africa

    PubMed Central

    Djènontin, Armel; Pennetier, Cédric; Zogo, Barnabas; Soukou, Koffi Bhonna; Ole-Sangba, Marina; Akogbéto, Martin; Chandre, Fabrice; Yadav, Rajpal; Corbel, Vincent

    2014-01-01

    Introduction The efficacy of Vectobac GR (potency 200 ITU/mg), a new formulation of bacterial larvicide Bacillus thuringiensis var. israelensis Strain AM65-52, was evaluated against Anopheles gambiae and Culex quinquefasciatus in simulated field and natural habitats in Benin. Methods In simulated field conditions, Vectobac GR formulation was tested at 3 dosages (0.6, 0.9, 1.2 g granules/m2 against An. gambiae and 1, 1.5, 2 g granules/m2 against Cx. quinquefasciatus) according to manufacturer’s product label recommendations. The dosage giving optimum efficacy under simulated field conditions were evaluated in the field. The efficacy of Vectobac GR in terms of emergence inhibition in simulated field conditions and of reduction of larval and pupal densities in rice fields and urban cesspits was measured following WHO guidelines for testing and evaluation of mosquito larvicides. Results Vectobac GR caused emergence inhibition of ≥80% until 21 [20]–[22] days for An. gambiae at 1.2 g/m2 dose and 28 [27–29] days for Cx. quinquefasciatus at 2 g/m2 in simulated field habitats. The efficacy of Vectobac GR in natural habitats was for 2 to 3 days against larvae and up to 10 days against pupae. Conclusions Treatment with Vectobac GR caused complete control of immature mosquito within 2–3 days but did not show prolonged residual action. Larviciding can be an option for malaria and filariasis vector control particularly in managing pyrethroid-resistance in African malaria vectors. Since use of larvicides among several African countries is being emphasized through Economic Community of West Africa States, their epidemiological impact should be carefully investigated. PMID:24505334

  12. Elastic properties of amorphous Si and derived Debye temperatures and Grüneisen parameters: Model calculation

    NASA Astrophysics Data System (ADS)

    Feldman, J. L.; Broughton, J. Q.; Wooten, F.

    1991-01-01

    Calculations, based on the Stillinger-Weber (SW) interatomic-potential model and the method of long waves, are presented for the elastic properties of amorphous Si (a-Si) and for pressure derivatives of the elastic constants of crystalline Si. Several models of a-Si, relaxed on the basis of the SW potential, are considered, and the external stresses that are associated with these models are evaluated using the Born-Huang relations. The elastic constants appear to obey the isotropy conditions to within a reasonable accuracy and are also consistent with other predictions based on the SW potential at finite temperature obtained by Kluge and Ray. Estimates of the pressure dependence of the elastic constants, Debye temperature, and Grüeisen parameter for a-Si are also provided on the basis of these calculations.

  13. On the volume-dependence of the Grüneisen parameter and the Lindemann law of melting

    NASA Astrophysics Data System (ADS)

    Kushwah, S. S.; Tomar, Y. S.; Upadhyay, A. K.

    2013-08-01

    It has been shown by Errandonea (Physica B 357 (2005) 356) that the Lindemann law cannot reproduce the high pressure melting curves of transition metals. Using an expression for the volume dependence of the Grüneisen parameter γ originally due to Burakovsky and Preston (J. Phys. Chem. Solids 65 (2004) 1581), Errandonea determined the constants appearing in the expression of gamma by making the Lindemann law to match the experimental melting data. The results for the volume dependence of gamma thus obtained by Errandonea are shown here to be much different from those determined using the Burakovsky-Preston approach. A direct comparison of the results based on the two approaches has been presented for the transition metal Mo. It is reinforced that the Lindemann law does not work satisfactorily for the transition metals with low slopes of melting curves.

  14. Rapid release of metal salts and nutrients from the 2011 Grímsvötn, Iceland volcanic ash

    NASA Astrophysics Data System (ADS)

    Olsson, J.; Stipp, S. L. S.; Dalby, K. N.; Gislason, S. R.

    2013-12-01

    On May 21st, 2011, one of Iceland’s most active volcano, Grímsvötn, started its strongest eruption in a century. Grímsvötn produced hundreds of megatonnes of fine basaltic ash, which spread over Iceland, the North Atlantic and Europe. Such fine grained ash can impact human activity and health both with fertilization and with toxicity potential for aquatic environments. The purpose of this study was: (1) to investigate the basic physical and chemical properties of the ash from the 2011 Grímsvötn eruption, (2) to identify surface salts deposited on the ash during the eruption, (3) to identify which elements are released during ash-water interactions and their release rates, (4) to characterize the secondary phases formed during water exposure, and (5) to assess impact of the ash on humans and the environment. During the eruption, we collected a unique set of pristine ash samples over a range of 50-115 km from the source and examined them with X-ray powder diffraction (XRPD), X-ray fluorescence (XRF), surface area analysis (BET), laser absorption, electron microprobe (EMPA), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The ash could be classified as glassy tholeiitic basalt with <10 mass% crystalline plagioclase (Al1.6Ca0.6Na0.4Si2.4O8) and pyroxene. The particles were small (<125 μm) and elongated with sharp edges. About 50% of the particle mass was fine ash (<63 μm), which could travel long distances, and ∼8% was very fine ash (<10 μm), which is harmful if inhaled. The specific surface area of the pristine ash ranged from 0.4 to 0.7 m2/g. Material taken up on particle surfaces contributed the equivalent of <0.5 nm thick layer, consisting of salts such as CaSO4, Na2SO4, NaCl, CaF2, CaCl2, MgSO4 and MgCl2. We exposed the pristine ash to ultrapure deionised (MilliQ) water in a single pass, plug, flow through reactor and the effluent was analyzed for 73 elements using inductively coupled plasma sector field mass

  15. Experimental determination of Grüneisen gamma for polyether ether ketone (PEEK) using the shock-reverberation technique

    NASA Astrophysics Data System (ADS)

    Roberts, Andrew; Appleby-Thomas, Gareth James; Hazell, Paul

    2012-03-01

    Following multiple loading events the resultant shock state of a material will lie away from the principle Hugoniot. Prediction of such states requires knowledge of a materials equation-of-state. The material-specific variable Grüneisen gamma, γ(v), defines the shape of "off-Hugoniot" points in energy-volume-pressure space. Here, the shock response of the important temperature-resistant polymer polyether ether ketone (PEEK) was compared to ANSYS Autodyn® simulations in an attempt to estimate a value of γ1. However, inconsistencies between experimental and computational results were found, highlighting the importance of full knowledge of material properties for such analyses. In particular, this approach led to revision of the established equation-of-state for PEEK, with a new nonlinear form identified.

  16. The Laki (Skaftár Fires) and Grímsvötn eruptions in 1783 1785

    NASA Astrophysics Data System (ADS)

    Thordarson, Th; Self, S.

    1993-05-01

    The Laki (Skaftár Fires) fissure eruption in southern Iceland lasted for eight months during 1783 to 1784, and produced one of the largest basaltic lava flows in historic times (14.7±1.0 km3). In addition, neighboring Grímsvötn central volcano was frequently active during the period from May 1783 to May 1785. The combined activity is interpreted as having been the result of a two-year-long volcano-tectonic episode on the Grímsvötn volcanic system. Contemporary descriptions of the explosive activity make it possible to relate the tephra stratigraphy to the progress of the eruption on a weekly basis and show that activity on the fissures propagated to the NE with time, towards Grímsvötn. The eruption at Laki began on 8 June with a brief explosive event on a short fissure, and lava rapidly began to flow into the Skaftá river gorge. It reached the lowlands, 35 km away, four days later and continued to flow, with variable discharge, until 7 February 1784. Approximately 90% of the lava was emplaced in the first five months of activity. The 27-km-long vent complex is composed of ten en echelon fissures distributed on both sides of the much older Laki hyaloclastite mountain. The surface expression of each fissure is a continuous row of vents consisting of scoria cones, spatter cones, and tuff cones. Six tephra fall units are positively identified; two units are completely compsed of phreatomagmatic tephra derived from two tuff cones and the others are Strombolian deposits. The volume of tephra, including ash fall that extended to mainland Europe, is 0.4 km3 dense rock equivalent volume, or 2.6% of the total erupted volume. Interpretation of contemporary descriptions of tephra falls, combined with the preserved stratigraphy, allow the identification of ten eruptive episodes during the eight months of activity on the Laki fissures. These eruptive episodes are inferred to have resulted from the unsteady flow of magma in the feeder system. In addition, at least eight

  17. Andreas Grüntzig's balloon catheter for angioplasty of peripheral arteries (PTA) is 25 years old.

    PubMed

    Bollinger, A; Schlumpf, M

    1999-02-01

    History of Andreas Grüntzig's time spent in Angiology and Radiology of the Zürich University Hospital (1969-1975). First, the pioneer of catheter therapy discovered that the Achilles tendon reflex is significantly prolonged during claudication pain. Furthermore, he participated actively in the clinical evaluation of Doppler ultrasound. After a stay in the Aggertalklinik (Engelskirchen near Köln, Germany), where he learnt Charles Dotter's original procedure with Eberhard Zeitler, he introduced catheter therapy of peripheral arteries in Zürich. In the same period he developed a new, rigid, sausage-shaped balloon catheter (polyvinylchloride), manufactured the device on his kitchen table together with his wife Michaela, Maria and Walter Schlumpf, and used it first on February 12, 1974 in a patient with intermittent claudication due to subtotal stenosis of the superficial femoral artery. The first successful dilatation of an iliac artery stenosis by his double-lumen catheter, which was modified later on into the famous coronary catheter, followed on January 23, 1975. Soon, the innovative catheter became commercially available (Cook and Schneider Companies). Andreas Grüntzig not only excelled in pioneering novel techniques, but also in patient care, in a prospective follow-up study of his own 242 patients lasting 15 years (results summarized in this article), in the teaching of Swiss scholars like Felix Mahler, Ernst Schneider and Bernhard Meier and many more in the world, and in organizing life demonstrations for large numbers of participants. His career in Cardiology, his work in Atlanta Georgia, USA, and his early tragic death in an airplane accident are briefly mentioned.

  18. Activation of mucosal mast cells promotes inflammation-related colon cancer development through recruiting and modulating inflammatory CD11b(+)Gr1(+) cells.

    PubMed

    Xu, Lingzhi; Yi, Hong-Gan; Wu, Zhiyuan; Han, Wenxiao; Chen, Kun; Zang, Mengya; Wang, Dongmei; Zhao, Xinhua; Wang, Hongying; Qu, Chunfeng

    2015-08-10

    Mast cells (MCs) have been reported to be one of the important immunoregulatory cells in promoting the development of colitis-related colon cancer (CRC). It is not clear which MC subtypes play critical roles in CRC progression from colitis to cancer because mucosal mast cells (MMCs) are distinct from connective tissue mast cells (CTMCs) in maintaining intestinal barrier function under homeostatic and inflammatory conditions. In the current study, we found that MMC numbers and the gene expressions of MMC-specific proteases increased significantly in an induced CRC murine model. The production of mast cell protease-1 (mMCP-1) after MMC activation not only resulted in the accumulation of CD11b(+)Gr1(+) inflammatory cells in the colon tissues but also modulated the activities of CD11b(+)Gr1(+) cells to support tumor cell growth and to inhibit T cell activation. Blocking the MMC activity in mice that had developed colitis-related epithelium dysplasia, CD11b(+)Gr1(+) infiltration was reduced and CRC development was inhibited. Our results suggest that MMC activation recruited and modulated the CD11b(+)Gr1(+) cells to promote CRC and that MMCs can be potential therapeutic targets for the prevention of CRC development.

  19. CD8 T cells are involved in skeletal muscle regeneration through facilitating MCP-1 secretion and Gr1(high) macrophage infiltration.

    PubMed

    Zhang, Jing; Xiao, Zhicheng; Qu, Chao; Cui, Wei; Wang, Xiaonan; Du, Jie

    2014-11-15

    Inflammatory microenvironments play a key role in skeletal muscle regeneration. The infiltration of CD8 T cells into injured muscle has been reported. However, the role of CD8 T cells during skeletal muscle regeneration remains unclear. In this study, we used cardiotoxin-induced mouse skeletal muscle injury/regeneration model to investigate the role of CD8 T cells. Muscle regeneration was impaired and matrix deposit was increased in CD8α-deficient mice compared with wild-type (WT) mice whose CD8 T cells were infiltrated into damaged muscle after cardiotoxin injection. Adoptive transfer of CD8 T cells to CD8α-deficient mice improved muscle regeneration and inhibited matrix remodeling. Compared with WT mice, CD8α deficiency limited the recruitment of Gr1(high) macrophages (MPs) into muscle, resulting in the reduction of satellite cell number. The expression of MCP-1 (MCP-1/CCL2), which regulates the migration of Gr1(high) MPs, was reduced in CD8α-deficient mice compared with WT mice. Coculture CD8 T cells with MPs promoted MCP-1 secretion. The i.m. injection of MCP-1 markedly promoted the recruitment of Gr1(high) MPs and improved muscle regeneration in CD8α-deficient mice. We conclude that CD8 T cells are involved in skeletal muscle regeneration by regulating the secretion of MCP-1 to recruit Gr1(high) MPs, which facilitate myoblast proliferation.

  20. Effects of artificial sweeteners on the AhR- and GR-dependent CYP1A1 expression in primary human hepatocytes and human cancer cells.

    PubMed

    Kamenickova, Alzbeta; Pecova, Michaela; Bachleda, Petr; Dvorak, Zdenek

    2013-12-01

    Food constituents may cause a phenomenon of food-drug interactions. In the current study, we examined the effects of artificial sweeteners (aspartame, acesulfame, cyclamate, saccharin) on the aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR)-dependent expression of CYP1A1 in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cell lines. Sweeteners were tested in concentrations up to those occurring in non-alcoholic beverages. Basal and ligand-inducible AhR- and GR-dependent reporter gene activation in stably transfected HepG2 and HeLa cells, respectively, were not affected by either of the sweeteners tested after 24h of incubation. The expression of CYP1A1 mRNA and protein in primary cultures of human hepatocytes and in LS174T and HepG2 cells was not induced by any of the tested sweeteners. Overall, aspartame, acesulfame, saccharin and cyclamate had no effects on CYP1A1 expression and transcriptional activities of AhR and GR. These data imply the safety of artificial sweeteners in terms of interference with AhR, GR and CYP1A1.

  1. Tumor-induced CD11b(+) Gr-1(+) myeloid-derived suppressor cells exacerbate immune-mediated hepatitis in mice in a CD40-dependent manner.

    PubMed

    Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba; Weiss, Jonathan M; Wiltrout, Robert H; Kapoor, Veena; Hawk, Nga; Terabe, Masaki; Berzofsky, Jay A; Manns, Michael P; Wang, Ena; Marincola, Francesco M; Korangy, Firouzeh; Greten, Tim F

    2015-04-01

    Immunosuppressive CD11b(+) Gr-1(+) myeloid-derived suppressor cells (MDSCs) accumulate in the livers of tumor-bearing (TB) mice. We studied hepatic MDSCs in two murine models of immune-mediated hepatitis. Unexpectedly, treatment of TB mice with Concanavalin A (Con A) or α-galactosylceramide resulted in increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels in comparison to tumor-free mice. Adoptive transfer of hepatic MDSCs into naïve mice exacerbated Con A induced liver damage. Hepatic CD11b(+) Gr-1(+) cells revealed a polarized proinflammatory gene signature after Con A treatment. An IFN-γ-dependent upregulation of CD40 on hepatic CD11b(+) Gr-1(+) cells along with an upregulation of CD80, CD86, and CD1d after Con A treatment was observed. Con A treatment resulted in a loss of suppressor function by tumor-induced CD11b(+) Gr-1(+) MDSCs as well as enhanced reactive oxygen species (ROS)-mediated hepatotoxicity. CD40 knockdown in hepatic MDSCs led to increased arginase activity upon Con A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40(-/-) tumor-induced myeloid cells resulted in exacerbation of hepatitis and increased ROS production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSCs act as proinflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner.

  2. The lectin-like protein 1 in Lactobacillus rhamnosus GR-1 mediates tissue-specific adherence to vaginal epithelium and inhibits urogenital pathogens.

    PubMed

    Petrova, Mariya I; Lievens, Elke; Verhoeven, Tine L A; Macklaim, Jean M; Gloor, Gregory; Schols, Dominique; Vanderleyden, Jos; Reid, Gregor; Lebeer, Sarah

    2016-11-21

    The probiotic Lactobacillus rhamnosus GR-1 has been documented to survive implantation onto the vaginal epithelium and interfere with urogenital pathogens. However, the molecular mechanisms involved are largely unknown. Here, we report for the first time the construction of dedicated knock-out mutants in L. rhamnosus GR-1 to enable the study of gene functions. In a search for genes responsible for the adherence capacity of L. rhamnosus GR-1, a genomic region encoding a protein with homology to lectin-like proteins was identified. Phenotypic analyses of the knock-out mutant of L. rhamnosus GR-1 revealed a two-fold decreased adhesion to the vaginal and ectocervical epithelial cell lines compared to wild-type. In contrast, the adhesion to gastro-intestinal epithelial (Caco2) and endocervical cell lines (Hela and End1/E6E7) was not drastically affected by the mutation, suggesting that the LGR-1_Llp1 lectins mediates tissue tropism. The purified LGR-1_Llp1 protein also inhibited biofilm formation and adhesion of uropathogenic Escherichia coli. For the first time, an important role for a novel lectin-like protein in the adhesion capacity and host cell-specific interaction of a vaginal probiotic Lactobacillus strain has been discovered, with an additional role in pathogen inhibition.

  3. The lectin-like protein 1 in Lactobacillus rhamnosus GR-1 mediates tissue-specific adherence to vaginal epithelium and inhibits urogenital pathogens

    PubMed Central

    Petrova, Mariya I.; Lievens, Elke; Verhoeven, Tine L. A.; Macklaim, Jean M.; Gloor, Gregory; Schols, Dominique; Vanderleyden, Jos; Reid, Gregor; Lebeer, Sarah

    2016-01-01

    The probiotic Lactobacillus rhamnosus GR-1 has been documented to survive implantation onto the vaginal epithelium and interfere with urogenital pathogens. However, the molecular mechanisms involved are largely unknown. Here, we report for the first time the construction of dedicated knock-out mutants in L. rhamnosus GR-1 to enable the study of gene functions. In a search for genes responsible for the adherence capacity of L. rhamnosus GR-1, a genomic region encoding a protein with homology to lectin-like proteins was identified. Phenotypic analyses of the knock-out mutant of L. rhamnosus GR-1 revealed a two-fold decreased adhesion to the vaginal and ectocervical epithelial cell lines compared to wild-type. In contrast, the adhesion to gastro-intestinal epithelial (Caco2) and endocervical cell lines (Hela and End1/E6E7) was not drastically affected by the mutation, suggesting that the LGR-1_Llp1 lectins mediates tissue tropism. The purified LGR-1_Llp1 protein also inhibited biofilm formation and adhesion of uropathogenic Escherichia coli. For the first time, an important role for a novel lectin-like protein in the adhesion capacity and host cell-specific interaction of a vaginal probiotic Lactobacillus strain has been discovered, with an additional role in pathogen inhibition. PMID:27869151

  4. Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog.

    PubMed

    Gram, Aykut; Trachsel, Alexandra; Boos, Alois; Kowalewski, Mariusz P

    2016-10-01

    The endocrine mechanisms that lead to initiation of parturition in dogs are still not fully understood. The prepartum luteolysis is associated with increased prostaglandin (PG) F2α secretion; however, there is no pregnancy- or parturition-related increase in estrogens. Moreover, unlike in other mammalian species, in the dog, increased peripartum levels of cortisol measured sporadically in maternal peripheral blood are not mandatory for normal parturition. Nevertheless, auto/paracrine effects of cortisol at the placental feto-maternal level cannot be excluded. Therefore, the aim of this study was to investigate the expression and localization of glucocorticoid receptor (GR/NR3C1) in canine utero/placental (Ut/Pl) units and uterine interplacental sites at selected time points during pregnancy (pre-implantation, post-implantation and mid-gestation), and at normal and antigestagen-induced parturition. The Ut/Pl expression of GR/NR3C1 did not change significantly from pre-implantation until mid-gestation; however, it was strongly induced during the prepartum luteolysis. Within the interplacental samples, expression of GR/NR3C1-mRNA was greater post-implantation than pre-implantation and did not change afterward, i.e. toward mid-gestation. Compartmentalization studies within the Ut/Pl units, involving placenta, endometrium and myometrium separately, performed at the prepartum luteolysis revealed the highest GR/NR3C1-mRNA levels in placenta compared with endometrium and myometrium. Interestingly, in antigestagen-treated mid-pregnancy dogs, Ut/Pl and interplacental GR/NR3C1-mRNA expression remained unaffected. At the cellular level, placental GR/NR3C1 was clearly detectable in placenta fetalis, i.e. in trophoblast cells. In conclusion, increased expression of GR/NR3C1 during normal parturition, but not following antigestagen-treatment, suggest that it is not required for initiating the signaling cascade of PG synthesis leading to the induction of parturition in the dog.

  5. LPS converts Gr-1(+)CD115(+) myeloid-derived suppressor cells from M2 to M1 via P38 MAPK.

    PubMed

    Yang, Yi; Zhang, Ruihua; Xia, Fei; Zou, Ting; Huang, Anfei; Xiong, Sidong; Zhang, Jinping

    2013-07-15

    Myeloid-derived suppressor cells (MDSCs) are heterogeneous populations of immature myeloid cells with strong immunosuppressive function, and play a critical role in the immune evasion of cancer. A subset of MDSCs share many similar characteristics with tumor-associated macrophages (TAMs), but it is largely unclear whether MDSCs also have M1/M2 type polarization in tumor microenvironments. In the present study, we found that Gr-1(+)CD115(+) monocytes in tumor-bearing mice exhibited M2 characteristics with significantly lower expression of iNOS and higher expression of Arginase I. Immunofluorescence staining showed that Gr-1(+)CD115(+) monocytes in tumor sites from LPS-injected mice had a higher expression of iNOS. Similarly, in vitro experiments displayed that LPS-treated Gr-1(+)CD115(+) cells expressed higher levels of iNOS, IL-6, TNF, IL-12, and IL-10 compared with those in non-treated Gr-1(+)CD115(+) monocytes. Extensive study showed that LPS-treated Gr-1(+)CD115(+) monocytes had less ability to convert the CD4(+)CD25(-)cells into CD4(+)CD25(+) Tregs, and also had less suppressive function on CD4(+)CD25(-) conventional T cells. LLC tumors in LPS-injected mice grew significantly slower than those in non-LPS-injected mice. Further experiments suggested that LPS may function through the P38 MAPK signaling pathway to increase the expression of iNOS, and of MyD88 independently. Thus, we can get conclusion that Gr-1(+)CD115(+) monocytes in tumor-bearing mice show M2 type characteristics and LPS can skew this M2 type cells into M1 type through the P38 MAPK pathway and lead to inhibition of the suppressive function of Gr-1(+)CD115(+) monocytes. It suggests that LPS or its analogs may be potential drugs for tumor treatment, inflammation induced by LPS or other components of bacterium or virus may be benefit to the inhibition of tumor cell growth in vivo.

  6. Lipopolysaccharide-Induced Profiles of Cytokine, Chemokine, and Growth Factors Produced by Human Decidual Cells Are Altered by Lactobacillus rhamnosus GR-1 Supernatant

    PubMed Central

    Li, Wei; Yang, Siwen; Kim, Sung O.; Reid, Gregor; Challis, John R. G.

    2014-01-01

    The aim of this study was to assess the effects of bacterial lipopolysaccharide (LPS) and Lactobacillus rhamnosus GR-1 supernatant (GR-1SN) on secretion profiles of cytokines, chemokines, and growth factors from primary cultures of human decidual cells. Lipopolysaccharide significantly increased the output of proinflammatory cytokines (interleukin [IL]-1B, IL-2, IL-6, IL-12p70, IL-15, IL-17A, interferon gamma [IFN-γ], and tumor necrosis factor [TNF]); anti-inflammatory cytokines (IL-1RN, IL-4, IL-9, and IL-10); chemokines (IL-8, eotaxin, IFN-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein-1α [MIP-1α], macrophage inflammatory protein-1β [MIP-1β], and regulated on activation normal T cell expressed and secreted [RANTES]); and growth factors (granulocyte colony-stimulating factor [CSF] 3, CSF-2, and vascular endothelial growth factor A [VEGFA]). Lactobacillus rhamnosus GR-1SN alone significantly increased CSF-3, MIP-1α MIP-1β, and RANTES but decreased IL-15 and IP-10 output. The GR-1SN also significantly or partially reduced LPS-induced proinflammatory cytokines TNF, IFN-γ, IL-1β, IL-2 IL-6, IL-12p70, IL-15, IL-17, and IP-10; partially reduced LPS-induced anti-inflammatory cytokines IL-1RN, IL-4 and IL-10, and LPS-induced VEGFA output but did not affect CSF-3, MIP-1α, MIP-1β, MCP-1, IL-8, and IL-9. Our results demonstrate that GR-1SN attenuates the inflammatory responses to LPS by human decidual cells, suggesting its potential role in ameliorating intrauterine infection. PMID:24429676

  7. Folate deprivation modulates the expression of autophagy- and circadian-related genes in HT-22 hippocampal neuron cells through GR-mediated pathway.

    PubMed

    Sun, Qinwei; Yang, Yang; Li, Xi; He, Bin; Jia, Yimin; Zhang, Nana; Zhao, Ruqian

    2016-08-01

    Folic acid (FA) is an extremely important nutrient for brain formation and development. FA deficiency is highly linked to brain degeneration and age-related diseases, which are also associated with autophagic activities and circadian rhythm in hippocampal neurons. However, little is known how autophagy- and circadian-related genes in hippocampal neurons are regulated under FA deficiency. Here, hippocampal neuroncells (HT-22) were employed to determine the effect of FA deprivation (FD) on the expression of relevant genes and to reveal the potential role of glucocorticoid receptor (GR). FD increased autophagic activities in HT-22 cells, associated with significantly (P<0.05) enhanced GR activation indicated by higher ratio of GR phosphorylation. Out of 17 autophagy-related genes determined, 8 was significantly (P<0.05) up-regulated in FD group, which includes ATG2b, ATG3, ATG4c, ATG5, ATG10, ATG12, ATG13 and ATG14. Meanwhile, 4 out of 7 circadian-related genes detected, Clock, Cry1, Cry2 and Per2, were significantly (P<0.05) up-regulated. The protein content of autophagy markers, LC3A and LC3B, was also increased significantly (P<0.05). ChIP assay showed that FD promoted (P<0.05) GR binding to the promoter sequence of ATG3 and Per2. Moreover, MeDIP analysis demonstrated significant (P<0.05) hypomethylation in the promoter sequence of ATG12, ATG13 and Per2 genes. Together, we speculate that FD increases the transcription of autophagy- and circadian-related genes through, at least partly, GR-mediated pathway. Our results provide a basis for future investigations into the intracellular regulatory network in response to folate deficiency.

  8. Lipopolysaccharide-Induced Profiles of Cytokine, Chemokine, and Growth Factors Produced by Human Decidual Cells Are Altered by Lactobacillus rhamnosus GR-1 Supernatant.

    PubMed

    Li, Wei; Yang, Siwen; Kim, Sung O; Reid, Gregor; Challis, John R G; Bocking, Alan D

    2014-07-01

    The aim of this study was to assess the effects of bacterial lipopolysaccharide (LPS) and Lactobacillus rhamnosus GR-1 supernatant (GR-1SN) on secretion profiles of cytokines, chemokines, and growth factors from primary cultures of human decidual cells. Lipopolysaccharide significantly increased the output of proinflammatory cytokines (interleukin [IL]-1B, IL-2, IL-6, IL-12p70, IL-15, IL-17A, interferon gamma [IFN-γ], and tumor necrosis factor [TNF]); anti-inflammatory cytokines (IL-1RN, IL-4, IL-9, and IL-10); chemokines (IL-8, eotaxin, IFN-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein-1α [MIP-1α], macrophage inflammatory protein-1β [MIP-1β], and regulated on activation normal T cell expressed and secreted [RANTES]); and growth factors (granulocyte colony-stimulating factor [CSF] 3, CSF-2, and vascular endothelial growth factor A [VEGFA]). Lactobacillus rhamnosus GR-1SN alone significantly increased CSF-3, MIP-1α MIP-1β, and RANTES but decreased IL-15 and IP-10 output. The GR-1SN also significantly or partially reduced LPS-induced proinflammatory cytokines TNF, IFN-γ, IL-1β, IL-2 IL-6, IL-12p70, IL-15, IL-17, and IP-10; partially reduced LPS-induced anti-inflammatory cytokines IL-1RN, IL-4 and IL-10, and LPS-induced VEGFA output but did not affect CSF-3, MIP-1α, MIP-1β, MCP-1, IL-8, and IL-9. Our results demonstrate that GR-1SN attenuates the inflammatory responses to LPS by human decidual cells, suggesting its potential role in ameliorating intrauterine infection.

  9. Reflection seismic characterization of the Grängesberg iron deposit and its mining-induced structures, central Sweden

    NASA Astrophysics Data System (ADS)

    Place, Joachim; Malehmir, Alireza; Högdahl, Karin; Juhlin, Christopher; Persson Nilsson, Katarina

    2014-05-01

    Reflection seismic investigation has been conducted on the Grängesberg apatite iron deposit where over 150 Mt of iron ore were produced until the mine closed in 1989. The mine infrastructure with shafts and tunnels extend down to ca. 650 m below the surface. Both natural and mine induced fracture and fault systems are today water-filled (some of them extending to the surface). The disputed ore genesis of the apatite-iron ores and its exploration potential due to large remaining quantities once again attracts both scientific and commercial interests. A good understanding of the geometry of mineral deposits and their hostrock structures at depth is essential for optimizing their exploration and exploitation. In addition, deep understanding of the fracture system is vital if mining activity is resumed as these may impact the terrain stability and seismicity, which may put at risk new populated and industrial areas. To address some of these challenging issues related to the past mining and also to obtain information about the depth continuation of the existing deposit, two E-W oriented reflection lines with a total length of 3.5 km were acquired in May 2013 by Uppsala University. A weight drop mounted on an hydraulic bobcat truck (traditionally used for concrete breaking in demolition sector) was used to generate seismic signal. In order to increase the signal-to-noise ratio, several impacts were generated at each shot point and stacked together. The seismic lines intersect at high angle the Grängesberg ore body and open pit, as well as several mining-induced faults. A combination of cabled and wireless receivers placed at every 10 m was used for the data recording. Use of wireless receivers was necessary as deploying cabled sensors was not possible due to city infrastructures, roads and houses. A careful analysis of the data suggested that several field-related issues such as (1) the crooked geometry of the lines (due to the available path and road network), (2

  10. Characteristic of retained austenite decomposition during tempering and its effect on impact toughness in SA508 Gr.3 steel

    NASA Astrophysics Data System (ADS)

    Yan, Guanghua; Han, Lizhan; Li, Chuanwei; Luo, Xiaomeng; Gu, Jianfeng

    2017-01-01

    Retained austenite(RA) usually presents in the quenched Nuclear Pressure-Vessel SA508 Gr.3 steel. In the present work, the characteristic of RA decomposition and its effect on the impact toughness were investigated by microstructure observation, dilatometric experiments and Charpy impact tests. The results show that the RA transformed into martensite and bainite during tempering at 230 °C and 400 °C respectively, while mixture of long rod carbides and ferrite formed at 650 °C. The long rod carbides formed from RA decomposition decrease the critical cleavage stress for initiation of micro-cracks, and deteriorate the impact toughness of the steel. Pre-tempering at a low temperature such as 230 °C or 400 °C leading to the decomposition of RA into martensite or baintie can eliminate the deterioration of the toughness caused by direct decomposition into long rod carbides. The absorbed energy indicate that pre-tempering at 400 °C can drive dramatically improvement in the toughness of the steel.

  11. Efficacy of ferterra 0.4% GR (chlorantraniliprole) against stem borers and leaffolder insect-pests of basmati rice.

    PubMed

    Sarao, P S; Kaur, H

    2014-09-01

    Field experiments were conducted during three kharif seasons from 2009 to 2011 at Sudhar village, Ludhiana and Rice Research Area of Department of Plant Breeding and Genetics, Punjab Agricultural University, Ludhiana. Four doses of Ferterra 0.4% GR (chlorantraniliprole) a new chemistry @ 20, 30, 40 and 50 g a.i. ha(-1) and standard check Cartap hydrochloride 4 G @ 1000 g a.i. ha(-1) was tested against stem borers and leaffolder infesting basmati rice. Over the years, dead heart in all the Ferterra doses and standard check (1.01-1.80%) were at par70 DAT, whereas, at 80 DAT doses @ 40, 50 and standard check were at par (1.04-1.13%) but significantly better than lower doses and untreated control. Similarly, over the years, Ferterra doses @ 40 and 50 g a.i. ha(-1) was significantly better than control in reducing white ear incidence, whereas, at 30 g a.i. ha(-1) and standard check intermediately reduced the white ears incidence. Leaffolder infestation at all the Ferterra doses were at par with standard check 70 DAT (2.69-3.87%), whereas, 80 DAT, Ferterra doses @ 30, 40, 50 and standard check were at par (2.95-3.49%) but significantly better than lower dose and untreated control. Over the years the cost : benefit ratio was maximum (1 : 23.67) in the Ferterra @40 g a.i. ha(-1) dose followed by 50 g a.i. ha(-1) dose.

  12. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis.

    PubMed

    Anukam, Kingsley C; Osazuwa, Emmanuel; Osemene, Gibson I; Ehigiagbe, Felix; Bruce, Andrew W; Reid, Gregor

    2006-10-01

    Bacterial vaginosis (BV) is particularly common in black women, and in Nigeria it is often caused by Mycoplasma, as well as Atopobium, Prevotella and Gardnerella sp. Antimicrobial metronidazole oral therapy is poorly effective in eradicating the condition and restoring the Lactobacillus microbiota in the vagina. In this study, 40 women diagnosed with BV by discharge, fishy odor, sialidase positive test and Nugent Gram stain scoring, were randomized to receive either two dried capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each night for 5 days, or 0.75% metronidazole gel, applied vaginally twice a day (in the morning and evening). Follow-up at day 6, 15 and 30 showed cure of BV in significantly more probiotic treated subjects (16, 17 and 18/20, respectively) compared to metronidazole treatment (9, 9 and 11/20: P=0.016 at day 6, P=0.002 at day 15 and P=0.056 at day 30). This is the first report of an effective (90%) cure of BV using probiotic lactobacilli. Given the correlation between BV and HIV, and the high risk of the latter in Nigeria, intravaginal use of lactobacilli could provide women with a self-use therapy, similar to over-the-counter anti-yeast medication, for treatment of urogenital infections.

  13. A frameshift mutation in the cubilin gene (CUBN) in Beagles with Imerslund-Gräsbeck syndrome (selective cobalamin malabsorption).

    PubMed

    Drögemüller, Michaela; Jagannathan, Vidhya; Howard, Judith; Bruggmann, Rémy; Drögemüller, Cord; Ruetten, Maja; Leeb, Tosso; Kook, Peter H

    2014-02-01

    Mammals are unable to synthesize cobalamin or vitamin B12 and rely on the uptake of dietary cobalamin. The cubam receptor expressed on the intestinal endothelium is required for the uptake of cobalamin from the gut. Cubam is composed of two protein subunits, amnionless and cubilin, which are encoded by the AMN and CUBN genes respectively. Loss-of-function mutations in either the AMN or the CUBN gene lead to hereditary selective cobalamin malabsorption or Imerslund-Gräsbeck syndrome (IGS). We investigated Beagles with IGS and resequenced the whole genome of one affected Beagle at 15× coverage. The analysis of the AMN and CUBN candidate genes revealed a homozygous deletion of a single cytosine in exon 8 of the CUBN gene (c.786delC). This deletion leads to a frameshift and early premature stop codon (p.Asp262Glufs*47) and is, thus, predicted to represent a complete loss-of-function allele. We tested three IGS-affected and 89 control Beagles and found perfect association between the IGS phenotype and the CUBN:c.786delC variant. Given the known role of cubilin in cobalamin transport, which has been firmly established in humans and dogs, our data strongly suggest that the CUBN:c.786delC variant is causing IGS in the investigated Beagles.

  14. Corrosion rate of API 5L Gr. X60 multipurpose steel pipeline under combined effect of water and crude oil

    NASA Astrophysics Data System (ADS)

    Miao, Jian; Wang, Qiang

    2016-09-01

    Multipurpose pipeline is often seriously corroded during its service life, and the phenomenon is more prominent once the transportation medium is changed. Electrochemical polarization curves and impedance spectroscopy of the API 5L Gr. X60 steel pipeline's corrosion process in sedimentary water with different ion types and their concentrations have been studied in this work. The results showed that the corrosion rates were found to be 0.00418 and 0.00232 mm/a for pure water and crude oil, respectively. However, for the mixtures of water and crude oil (with water content increased from 0.2 vol% to 10 vol%), the corrosion rate increased consistently and reached a maximum value of 0.15557 mm/a for 10 vol% water in crude oil. The effect of the concentration of various ions, namely, chloride, bicarbonate and sulfate in (oil/water) mixtures on the corrosion rate was characterized by weight-loss method. The results showed that with increasing the ions' concentrations, the corresponding exchange current density increased significantly. The results were further supported by the observations of corrosion morphology using scanning electron microscopy and are helpful in devising guidelines which would help in reducing corrosion in multipurpose transport pipelines involving a change of transported medium during their service life.

  15. Epidemiological characteristics of Malassezia folliculitis and use of the May-Grünwald-Giemsa stain to diagnose the infection.

    PubMed

    Durdu, Murat; Güran, Mümtaz; Ilkit, Macit

    2013-08-01

    Various bacterial, fungal, parasitic, and viral pathogens can cause folliculitis, which is often mistakenly treated with antibiotics for months or even years. A laboratory diagnosis is required before therapy can be planned. Here, we describe the prevalence and risk factors, as well as the clinical, cytological, and mycological characteristics, of patients with Malassezia folliculitis (MF) in Adana, Turkey. We also report the treatment responses of the MF patients and describe the Malassezia spp. using culture-based molecular methods. Cytological examinations were performed in 264 folliculitis patients, 49 of whom (18.5%) were diagnosed with MF. The positivity of the May-Grünwald-Giemsa (MGG) smear was higher (100%) than that of the potassium hydroxide test (81.6%). Using Wood's light, yellow-green fluorescence was observed in 66.7% of the MF patients. Identification using the rDNA internal transcribed spacer region revealed that Malassezia globosa was the most common species, followed by Malassezia sympodialis, Malassezia restricta, and Malassezia furfur. The MF patients were treated with itraconazole capsules (200 mg/d) for 2 weeks. Complete recovery was observed in 79.6% of the patients. These novel findings help improve our current understanding of the epidemiological characteristics of MF and establish MGG as a practical tool for the diagnosis of MF.

  16. Simulating atmospheric transport of the 2011 Grímsvötn ash cloud using a data insertion update scheme

    NASA Astrophysics Data System (ADS)

    Wilkins, K. L.; Western, L. M.; Watson, I. M.

    2016-09-01

    Effective modelling of atmospheric volcanic ash dispersion is important to ensure aircraft safety, and has been the subject of much study since the Eyjafjallajökull ash crisis in Europe in 2010. In this paper, a novel modelling method is presented, where the atmospheric transport of the 2011 Grímsvötn ash cloud is simulated using a data insertion update scheme. Output from the volcanic ash transport and dispersion model, NAME, is updated using satellite retrievals and the results of a probabilistic ash, cloud and clear sky classification algorithm. A range of configurations of the scheme are compared with each other, in addition to a simple data insertion method presented in a previous study. Results show that simulations in which ash layer heights and depths are updated using the model output generally perform worse in relation to satellite derived ash coverage and ash column loading than simulations that use satellite-retrieved heights and an assumed layer depth of 1.0 km. Simulated ash column loading and concentration tends to be under-predicted using this update scheme, but the timing of the arrival of the ash cloud at Stockholm is well captured, as shown by comparison with lidar-derived mass concentration profiles. Most of the updated simulations in this comparison make small gains in skill on the simple data insertion scheme.

  17. According to the strict solution of GR there is no the un-modeled anomalous acceleration of Pioneer

    NASA Astrophysics Data System (ADS)

    Chen, Shao-Guang

    According to the definition of force f = d (m v) /d t = m (d v / d t) + v (d m / d t ) and the change in masses ( the exchange of momentum-energy tensors bwtween two bodies Tµυ via the field tµν ) deduced by Bondi from Einstein equation ( H.Bondi, Proc. R. Soc. London A 427, 249, 1990 ), we get a new gravitational equation: f GR = f P + f C , f P = -G (m M /r 2 ) (r /r), f C = -G (m M / r 2 ) (v /c) (1). The deductive process is: First if mass is invariable, which implies that the mass may produce the gravitational field but the gravitational field should not lead to the change in mass, i.e., the mass should be an invariable parameter and the fourth dimension momentum i E/c should be entirely independent of three-dimension momentum P. In other words, the energy and the momentum should not compose the four-dimension momentum-energy vector and tensor. Thus, the gravitational equation is no longer a nonlinear but a linear one and Einstein equation should be reduced to Newtonian law: f GR = f P = -G (m M /r 2 ) (r /r). Second according to the mass-energy relation we get: dm /dt = dE /c2 dt, where E = EK + m0 c2 , then from the conservation of four dimension momentum-energy vector P 2 -(E/c) 2 = 0, we obtain: dE/dt = c dP/dt, dm/dt = dP/c dt = f P /c, f C = v (dm/dt) = v (f P /c) = -G (m M /r 2 ) (v /c). Then, we educe Eq.(1) from the special relativity when the mass is variable. In Eq.(1) the gravitational mass is just the inertial mass and the equivalent principle come absolutely into existence. Einstein equation can also be deduced from Eq.(1) and is equivalent to Eq.(1). Now the nonlinear gravitation problems can be solved with the one by one substitute method of masses solved by alone f P and alone f C in Eq.(1), e.g., from one loop Σf P • d s = 0, the energy loss of celestial body running one loop by f C is a typical dipole radiation and a gravitational wave of dipole radiation is predicted.When mass-point B nearing mass-point A, the masses MA and MB will

  18. GR SUMOylation and formation of an SUMO-SMRT/NCoR1-HDAC3 repressing complex is mandatory for GC-induced IR nGRE-mediated transrepression.

    PubMed

    Hua, Guoqiang; Paulen, Laetitia; Chambon, Pierre

    2016-02-02

    Unique among the nuclear receptor superfamily, the glucocorticoid (GC) receptor (GR) can exert three distinct transcriptional regulatory functions on binding of a single natural (cortisol in human and corticosterone in mice) and synthetic [e.g., dexamethasone (Dex)] hormone. The molecular mechanisms underlying GC-induced positive GC response element [(+)GRE]-mediated activation of transcription are partially understood. In contrast, these mechanisms remain elusive for GC-induced evolutionary conserved inverted repeated negative GC response element (IR nGRE)-mediated direct transrepression and for tethered indirect transrepression that is mediated by DNA-bound NF-κB/activator protein 1 (AP1)/STAT3 activators and instrumental in GC-induced anti-inflammatory activity. We demonstrate here that SUMOylation of lysine K293 (mouse K310) located within an evolutionary conserved sequence in the human GR N-terminal domain allows the formation of a GR-small ubiquitin-related modifiers (SUMOs)-NCoR1/SMRT-HDAC3 repressing complex mandatory for GC-induced IR nGRE-mediated direct repression in vitro, but does not affect transactivation. Importantly, these results were validated in vivo: in K310R mutant mice and in mice ablated selectively for nuclear receptor corepressor 1 (NCoR1)/silencing mediator for retinoid or thyroid-hormone receptors (SMRT) corepressors in skin keratinocytes, Dex-induced direct repression and the formation of repressing complexes on IR nGREs were impaired, whereas transactivation was unaffected. In mice selectively ablated for histone deacetylase 3 (HDAC3) in skin keratinocytes, GC-induced direct repression, but not bindings of GR and of corepressors NCoR1/SMRT, was abolished, indicating that HDAC3 is instrumental in IR nGRE-mediated repression. Moreover, we demonstrate that the binding of HDAC3 to IR nGREs in vivo is mediated through interaction with SMRT/NCoR1. We also show that the GR ligand binding domain (LBD) is not required for SMRT

  19. Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in neurofibromatosis type I (NF1) disease model cells.

    PubMed

    Hirayama, Mio; Kobayashi, Daiki; Mizuguchi, Souhei; Morikawa, Takashi; Nagayama, Megumi; Midorikawa, Uichi; Wilson, Masayo M; Nambu, Akiko N; Yoshizawa, Akiyasu C; Kawano, Shin; Araki, Norie

    2013-05-01

    Neurofibromatosis type 1 (NF1) tumor suppressor gene product, neurofibromin, functions in part as a Ras-GAP, and though its loss is implicated in the neuronal abnormality of NF1 patients, its precise cellular function remains unclear. To study the molecular mechanism of NF1 pathogenesis, we prepared NF1 gene knockdown (KD) PC12 cells, as a NF1 disease model, and analyzed their molecular (gene and protein) expression profiles with a unique integrated proteomics approach, comprising iTRAQ, 2D-DIGE, and DNA microarrays, using an integrated protein and gene expression analysis chart (iPEACH). In NF1-KD PC12 cells showing abnormal neuronal differentiation after NGF treatment, of 3198 molecules quantitatively identified and listed in iPEACH, 97 molecules continuously up- or down-regulated over time were extracted. Pathway and network analysis further revealed overrepresentation of calcium signaling and transcriptional regulation by glucocorticoid receptor (GR) in the up-regulated protein set, whereas nerve system development was overrepresented in the down-regulated protein set. The novel up-regulated network we discovered, "dynein IC2-GR-COX-1 signaling," was then examined in NF1-KD cells. Validation studies confirmed that NF1 knockdown induces altered splicing and phosphorylation patterns of dynein IC2 isomers, up-regulation and accumulation of nuclear GR, and increased COX-1 expression in NGF-treated cells. Moreover, the neurite retraction phenotype observed in NF1-KD cells was significantly recovered by knockdown of the dynein IC2-C isoform and COX-1. In addition, dynein IC2 siRNA significantly inhibited nuclear translocation and accumulation of GR and up-regulation of COX-1 expression. These results suggest that dynein IC2 up-regulates GR nuclear translocation and accumulation, and subsequently causes increased COX-1 expression, in this NF1 disease model. Our integrated proteomics strategy, which combines multiple approaches, demonstrates that NF1-related neural

  20. Integrated Proteomics Identified Novel Activation of Dynein IC2-GR-COX-1 Signaling in Neurofibromatosis Type I (NF1) Disease Model Cells*

    PubMed Central

    Hirayama, Mio; Kobayashi, Daiki; Mizuguchi, Souhei; Morikawa, Takashi; Nagayama, Megumi; Midorikawa, Uichi; Wilson, Masayo M.; Nambu, Akiko N.; Yoshizawa, Akiyasu C.; Kawano, Shin; Araki, Norie

    2013-01-01

    Neurofibromatosis type 1 (NF1) tumor suppressor gene product, neurofibromin, functions in part as a Ras-GAP, and though its loss is implicated in the neuronal abnormality of NF1 patients, its precise cellular function remains unclear. To study the molecular mechanism of NF1 pathogenesis, we prepared NF1 gene knockdown (KD) PC12 cells, as a NF1 disease model, and analyzed their molecular (gene and protein) expression profiles with a unique integrated proteomics approach, comprising iTRAQ, 2D-DIGE, and DNA microarrays, using an integrated protein and gene expression analysis chart (iPEACH). In NF1-KD PC12 cells showing abnormal neuronal differentiation after NGF treatment, of 3198 molecules quantitatively identified and listed in iPEACH, 97 molecules continuously up- or down-regulated over time were extracted. Pathway and network analysis further revealed overrepresentation of calcium signaling and transcriptional regulation by glucocorticoid receptor (GR) in the up-regulated protein set, whereas nerve system development was overrepresented in the down-regulated protein set. The novel up-regulated network we discovered, “dynein IC2-GR-COX-1 signaling,” was then examined in NF1-KD cells. Validation studies confirmed that NF1 knockdown induces altered splicing and phosphorylation patterns of dynein IC2 isomers, up-regulation and accumulation of nuclear GR, and increased COX-1 expression in NGF-treated cells. Moreover, the neurite retraction phenotype observed in NF1-KD cells was significantly recovered by knockdown of the dynein IC2-C isoform and COX-1. In addition, dynein IC2 siRNA significantly inhibited nuclear translocation and accumulation of GR and up-regulation of COX-1 expression. These results suggest that dynein IC2 up-regulates GR nuclear translocation and accumulation, and subsequently causes increased COX-1 expression, in this NF1 disease model. Our integrated proteomics strategy, which combines multiple approaches, demonstrates that NF1-related neural

  1. High quality draft genome sequence of Meganema perideroedes str. Gr1(T) and a proposal for its reclassification to the family Meganemaceae fam. nov.

    PubMed

    McIlroy, Simon J; Lapidus, Alla; Thomsen, Trine R; Han, James; Haynes, Matthew; Lobos, Elizabeth; Huntemann, Marcel; Pati, Amrita; Ivanova, Natalia N; Markowitz, Victor; Verbarg, Susanne; Woyke, Tanja; Klenk, Hans-Peter; Kyrpides, Nikos; Nielsen, Per H

    2015-01-01

    Meganema perideroedes Gr1(T) is a filamentous bacterium isolated from an activated sludge wastewater treatment plant where it is implicated in poor sludge settleability (bulking). M. perideroedes is the sole described species of the genus Meganema and of the proposed novel family "Meganemaceae". Here we describe the features of the type strain Gr1(T) along with its annotated genome sequence. The 3,409,949 bp long draft genome consists of 22 scaffolds with 3,033 protein-coding and 59 RNA genes and is a part of Genomic Encyclopedia of Type Strains, Phase I: the one thousand microbial genomes KMG project. Notably, genome annotation indicated the potential for facultative methylotrophy. However, the ability to utilize methanol as a carbon source could not be empirically demonstrated for the type strain or for in situ Meganema spp. strains.

  2. Thermal expansion, heat capacity and Grüneisen parameter of iridium phosphide Ir2P from quasi-harmonic Debye model

    NASA Astrophysics Data System (ADS)

    Liu, Z. J.; Song, T.; Sun, X. W.; Ma, Q.; Wang, T.; Guo, Y.

    2017-03-01

    Thermal expansion coefficient, heat capacity, and Grüneisen parameter of iridium phosphide Ir2P are reported by means of quasi-harmonic Debye model for the first time in the current study. This model combines with first-principles calculations within generalized gradient approximation using pseudopotentials and a plane-wave basis in the framework of density functional theory, and it takes into account the phononic effects within the quasi-harmonic approximation. The Debye temperature as a function of volume, the Grüneisen parameter, thermal expansion coefficient, constant-volume and constant-pressure heat capacities, and entropy on the temperature T are also successfully obtained. All the thermodynamic properties of Ir2P in the whole pressure range from 0 to 100 GPa and temperature range from 0 to 3000 K are summarized and discussed in detail.

  3. The disruption of two salt bridges of the cold-active xylanase XynGR40 results in an increase in activity, but a decrease in thermostability.

    PubMed

    Wang, Guozeng; Wu, Jingjing; Lin, Juan; Ye, Xiuyun; Yao, Bin

    2016-12-02

    Cold-active xylanases are of great interest due to their large potential for application in the food industry. In this study, salt bridges of the eight glycoside hydrolase (GH) family 10 cold-active xylanases reported to date were predicted and the salt bridges specific to the cold-active xylanase XynGR40 were identified. Seven mutants were constructed to disrupt salt bridges specific to XynGR40. The results suggested that five mutants lost their xylanase activity, while the other two mutants, D30N and D83N, displayed different properties when compared with the wild-type XynGR40. First, both mutations showed an obvious decrease in thermostability, with the T1/2 of D30N and D83N at 50 °C being about one half and one sixth of the wild-type, respectively. Second, both D30N and D83N had a higher specific activity than the wild-type, with activities about 13 and 163% higher, respectively. Third, both D30N and D83N had high kcat and Km values, which resulted in a higher catalytic efficiency of the mutant D83N, but a lower catalytic efficiency of the mutant D30N compared to the wild-type. Our results suggested that salt bridges play important roles in both the activity and thermostability of the cold-active xylanase XynGR40. The mutant D83N had a higher kcat and higher relative activity at low temperatures than the wild-type, and is a good candidate for application in the food industry.

  4. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats

    PubMed Central

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-01-01

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways. PMID:27271793

  5. Exact period-four solutions of a family of n-dimensional quadratic maps via harmonic balance and Gröbner bases.

    PubMed

    D'Amico, María Belén; Calandrini, Guillermo L

    2015-11-01

    Analytical solutions of the period-four orbits exhibited by a classical family of n-dimensional quadratic maps are presented. Exact expressions are obtained by applying harmonic balance and Gröbner bases to a single-input single-output representation of the system. A detailed study of a generalized scalar quadratic map and a well-known delayed logistic model is included for illustration. In the former example, conditions for the existence of bistability phenomenon are also introduced.

  6. Lack of Muc1-regulated beta-catenin stability results in aberrant expansion of CD11b+Gr1+ myeloid derived suppressor cells from the bone marrow

    PubMed Central

    Poh, Tze Wei; Bradley, Judy M.; Mukherjee, Pinku; Gendler, Sandra J.

    2009-01-01

    Myeloid Derived Suppressor Cells (MDSCs) are a heterogeneous population of myeloid cells that inhibit T cell activity and contribute to the immune suppression characteristic of most tumors. We discovered that bone marrow (BM) progenitor cells from the Muc1 knockout (KO) mice differentiated into CD11b+Gr1+ MDSCs in vitro under GM-CSF and IL-4 signaling. MUC1 is a tumor-associated mucin and its cytoplasmic tail (MUC1-CT) can regulate beta-catenin to promote oncogenesis. Given the importance of beta-catenin in hematopoiesis, we hypothesized that the MUC1 regulation of beta-catenin is important for MDSC development. Our current study shows that the aberrant development of BM progenitors into CD11b+Gr1+ MDSCs is dependent on the down regulation of beta-catenin levels that occurs in the absence of Muc1. In light of this, KO mice showed enhanced EL4 tumor growth and were able to better tolerate allogeneic BM185 tumor growth, with an accumulation of CD11b+Gr1+ cells in the blood and tumor draining lymph nodes. WT mice were able to similarly tolerate allogeneic tumor growth when they were injected with CD11b+Gr1+ cells from tumor-bearing KO mice, suggesting that tolerance of allogeneic tumors is dependent on MDSC-mediated immune suppression. This further delineates the ability of Muc1 to control MDSC development which could directly impact tumorigenesis. Knowledge of the biology by which Muc1 regulates the development of myeloid progenitors into MDSCs would also be very useful in enhancing the efficacy of cancer vaccines in the face of tumor immune suppression. PMID:19351842

  7. Intrathecal dihydroergotamine inhibits capsaicin-induced vasodilatation in the canine external carotid circulation via GR127935- and rauwolscine-sensitive receptors.

    PubMed

    Marichal-Cancino, Bruno A; González-Hernández, Abimael; Manrique-Maldonado, Guadalupe; Ruiz-Salinas, Inna I; Altamirano-Espinoza, Alain H; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

    2012-10-05

    It has been suggested that during a migraine attack trigeminal nerves release calcitonin gene-related peptide (CGRP), producing central nociception and vasodilatation of cranial arteries, including the extracranial branches of the external carotid artery. Since trigeminal inhibition may prevent this vasodilatation, the present study has investigated the effects of intrathecal dihydroergotamine on the external carotid vasodilatation to capsaicin, α-CGRP and acetylcholine. Anaesthetized vagosympathectomized dogs were prepared to measure blood pressure, heart rate and external carotid conductance. A catheter was inserted into the right common carotid artery for the continuous infusion of phenylephrine (to restore the carotid vascular tone), whereas the corresponding thyroid artery was cannulated for one-min intracarotid infusions of capsaicin, α-CGRP and acetylcholine (which dose-dependently increased the external carotid conductance). Another cannula was inserted intrathecally (C(1)-C(3)) for the administration of dihydroergotamine, the α(2)-adrenoceptor antagonist rauwolscine or the serotonin 5-HT(1B/1D) receptor antagonist GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide hydrochloride monohydrate). Intrathecal dihydroergotamine (10, 31 and 100μg) inhibited the vasodilatation to capsaicin, but not that to α-CGRP or acetylcholine. This inhibition was: (i) unaffected by 10μg GR127935 or 100μg rauwolscine, but abolished by 31μg GR127935 or 310μg rauwolscine at 10μg dihydroergotamine; and (ii) abolished by the combination 10μg GR127935+100μg rauwolscine at 100μg dihydroergotamine. Thus, intrathecal (C(1)-C(3)) dihydroergotamine seems to inhibit the external carotid vasodilatation to capsaicin by spinal activation of serotonin 5-HT(1B/1D) (probably 5-HT(1B)) receptors and α(2) (probably α(2A/2C))-adrenoceptors.

  8. Physiological Effects of the Synthetic Strigolactone Analog GR24 on Root System Architecture in Arabidopsis: Another Belowground Role for Strigolactones?1[C][W][OA

    PubMed Central

    Ruyter-Spira, Carolien; Kohlen, Wouter; Charnikhova, Tatsiana; van Zeijl, Arjan; van Bezouwen, Laura; de Ruijter, Norbert; Cardoso, Catarina; Lopez-Raez, Juan Antonio; Matusova, Radoslava; Bours, Ralph; Verstappen, Francel; Bouwmeester, Harro

    2011-01-01

    In this study, the role of the recently identified class of phytohormones, strigolactones, in shaping root architecture was addressed. Primary root lengths of strigolactone-deficient and -insensitive Arabidopsis (Arabidopsis thaliana) plants were shorter than those of wild-type plants. This was accompanied by a reduction in meristem cell number, which could be rescued by application of the synthetic strigolactone analog GR24 in all genotypes except in the strigolactone-insensitive mutant. Upon GR24 treatment, cells in the transition zone showed a gradual increase in cell length, resulting in a vague transition point and an increase in transition zone size. PIN1/3/7-green fluorescent protein intensities in provascular tissue of the primary root tip were decreased, whereas PIN3-green fluorescent protein intensity in the columella was not affected. During phosphate-sufficient conditions, GR24 application to the roots suppressed lateral root primordial development and lateral root forming potential, leading to a reduction in lateral root density. Moreover, auxin levels in leaf tissue were reduced. When auxin levels were increased by exogenous application of naphthylacetic acid, GR24 application had a stimulatory effect on lateral root development instead. Similarly, under phosphate-limiting conditions, endogenous strigolactones present in wild-type plants stimulated a more rapid outgrowth of lateral root primordia when compared with strigolactone-deficient mutants. These results suggest that strigolactones are able to modulate local auxin levels and that the net result of strigolactone action is dependent on the auxin status of the plant. We postulate that the tightly balanced auxin-strigolactone interaction is the basis for the mechanism of the regulation of the plants’ root-to-shoot ratio. PMID:21119044

  9. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats.

    PubMed

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-06-07

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways.

  10. Activation of GRs-Akt-nNOs-NR2B signaling pathway by second dose GR agonist contributes to exacerbated hyperalgesia in a rat model of radicular pain.

    PubMed

    Zhang, Jing; Zhang, Wei; Sun, Yu'e; Liu, Yue; Song, Lihua; Ma, Zhengliang; Gu, Xiaoping

    2014-06-01

    Central Akt, neuronal nitric oxide synthase (nNOS) and N-methyl-D-aspartate receptor subunit 2B (NR2B) play key roles in the development of neuropathic pain. Here we investigate the effects of glucocorticoid receptors (GRs) on the expression and activation of spinal Akt, nNOS and NR2B after chronic compression of dorsal root ganglia (CCD). Thermal hyperalgesia test and mechanical allodynia test were used to measure rats after intrathecal injection of GR antagonist mifepristone or GR agonist dexamethasone for 21 days postoperatively. Expression of spinal Akt, nNOS, NR2B and their phosphorylation state after CCD was examined by western blot. The effects of intrathecal treatment with dexamethasone or mifepristone on nociceptive behaviors and the corresponding expression of Akt, nNOS and NR2B in spinal cord were also investigated. Intrathecal injection of mifepristone or dexamethasone inhibited PWMT and PWTL in CCD rats. However, hyperalgesia was induced by intrathecal injection of dexamethasone on days 12 to 14 after surgery. Treatment of dexamethasone increased the expression and phosphorylation levels of spinal Akt, nNOS, GR and NR2B time dependently, whereas administration of mifepristone downregulated the expression of these proteins significantly. GRs activated spinal Akt-nNOS/NR2B pathway play important roles in the development of neuropathic pain in a time-dependent manner.

  11. Hydrogen Sulfide Attenuates the Recruitment of CD11b+Gr-1+ Myeloid Cells and Regulates Bax/Bcl-2 Signaling in Myocardial Ischemia Injury

    PubMed Central

    Zhang, Youen; Li, Hua; Zhao, Gang; Sun, Aijun; Zong, Nobel C.; Li, Zhaofeng; Zhu, Hongming; Zou, Yunzeng; Yang, Xiangdong; Ge, Junbo

    2014-01-01

    Hydrogen sulfide, an endogenous signaling molecule, plays an important role in the physiology and pathophysiology of the cardiovascular system. Using a mouse model of myocardial infarction, we investigated the anti-inflammatory and anti-apoptotic effects of the H2S donor sodium hydrosulfide (NaHS). The results demonstrated that the administration of NaHS improved survival, preserved left ventricular function, limited infarct size, and improved H2S levels in cardiac tissue to attenuate the recruitment of CD11b+Gr-1+ myeloid cells and to regulate the Bax/Bcl-2 pathway. Furthermore, the cardioprotective effects of NaHS were enhanced by inhibiting the migration of CD11b+Gr-1+ myeloid cells from the spleen into the blood and by attenuating post-infarction inflammation. These observations suggest that the novel mechanism underlying the cardioprotective function of H2S is secondary to a combination of attenuation the recruitment of CD11b+Gr-1+ myeloid cells and regulation of the Bax/Bcl-2 apoptotic signaling. PMID:24758901

  12. Source parameters for the 2013-2015 earthquake sequence in Nógrád county, Hungary

    NASA Astrophysics Data System (ADS)

    Wéber, Zoltán

    2016-07-01

    Between 2013 June and 2015 January, 35 earthquakes with local magnitude M L ranging from 1.1 to 4.2 occurred in Nógrád county, Hungary. This earthquake sequence represents above average seismic activity in the region and is the first one that was recorded by a significant number of three-component digital seismographs in the county. Using a Bayesian multiple-event location algorithm, we have estimated the hypocenters of 30 earthquakes with M L ≥1.5. The events occurred in two small regions of a few squared kilometers: one to the east of Érsekvadkert and the other at Iliny. The uncertainty of the epicenters is about 1.5-1.7 km in the E-W direction and 1.8-2.1 km in the N-S direction at the 95 % confidence level. The estimated event depths are confined to the upper 3 km of the crust. We have successfully estimated the full moment tensors of 4 M w ≥3.6 earthquakes using a probabilistic waveform inversion procedure. The non-double-couple components of the retrieved moment tensor solutions are statistically insignificant. The negligible amount of the isotropic component implies the tectonic nature of the investigated events. All of the analyzed earthquakes have strike-slip mechanism with either right-lateral slip on an approximately N-S striking or left-lateral movement on a roughly E-W striking nodal plane. The orientations of the obtained focal mechanisms are in good agreement with the main stress pattern published for the epicentral region. Both the P and T principal axes are horizontal, and the P axis is oriented along a NE-SW direction.

  13. EPSAH, an exopolysaccharide from Aphanothece halophytica GR02, improves both cellular and humoral immunity as a novel polysaccharide adjuvant.

    PubMed

    Zhu, Lei; Zhang, Fan; Yang, Li-Jun; Ge, Yang; Wei, Qing-Fang; Ou, Yu

    2016-07-01

    EPSAH is an exopolysaccharide from Aphanothece halophytica GR02. The present study was designed to evaluate its toxicity and adjuvant potential in the specific cellular and humoral immune responses in ovalbumin (OVA) in mice. EPSAH did not cause any mortality and side effects when the mice were administered subcutaneously twice at the dose of 50 mg·kg(-1). Hemolytic activity in vitro indicated that EPSAH was non-hemolytic. Splenocyte proliferation in vitro was assayed with different concentrations of EPSAH. The mice were immunized subcutaneously with OVA 0.1 mg alone or with OVA 0.1 mg dissolved in saline containing Alum (0.2 mg) or EPSAH (0.2, 0.4, or 0.8 mg) on Day 1 and 15. Two weeks later, splenocyte proliferation, natural killer (NK) cell activity, production of cytokines IL-2 from splenocytes, and serum OVA-specific antibody titers were measured. Phagocytic activity, production of pro-inflammatory cytokines IL-1 and IL-12 in mice peritoneal macrophages were also determined. EPSAH showed a dose-dependent stimulating effect on mitogen-induced proliferation. The Con A-, LPS-, and OVA-induced splenocyte proliferation and the serum OVA-specific IgG, IgG1, and IgG2a antibody titers in the immunized mice were significantly enhanced. EPSAH also significantly promoted the production of Th1 cytokine IL-2. Besides, EPSAH remarkably increased the killing activities of NK cells from splenocytes in the immunized mice. In addition, EPSAH enhanced phagocytic activity and the generation of pro-inflammatory cytokines IL-1 and IL-12 in macrophages. These results indicated that EPSAH had a strong potential to increase both cellular and humoral immune responses, particularly promoting the development of Th1 polarization.

  14. On the jet collision: General model and reduction to the Mie-Grüneisen state equation

    NASA Astrophysics Data System (ADS)

    Osipenko, K. Yu.; Simonov, I. V.

    2009-08-01

    We study the stationary direct supersonic collision of jets of condensed materials. We determine the basic flow characteristics: the maximum values of pressure, temperature, and densities on outgoing shock wave fronts and at the wave stagnation and penetration points. To this end, just as in the Lavrentiev problem about the jet collision in the framework of an incompressible fluid model, it suffices to consider the flow only along the central streamline, i.e., the symmetry axis. We consider the general caloric (incomplete) equation of state and, to close the thermodynamic construction and determine the temperature dependence on the state parameters, supplement them with thermodynamic identities. We also consider the conditions on discontinuities, the Bernoulli integrals, i.e., the conservation laws, to relate the states behind the wave front and the stagnation point, and the continuity conditions at this point. Just as in the collision problem for jets of incompressible fluid, we neglect the strength, viscosity, and heat conduction. As a result, we construct a mathematical model, i.e., a system of 12 integro-algebraic equations, and propose a semi-inverse solution method, in which the system splits into separate equations. In the special case of the Mie-Grüneisen state equation, the system becomes much simpler. We perform computations and construct the dependence of maximal pressures and temperatures on the impact velocity in the range 1-20 km/s for many pairs of materials of the colliding jets. We also compare the results with the solution obtained according to the incompressible fluid model.

  15. Field evaluation of an insect growth regulator, pyriproxyfen 0.5% GR against Culex quinquefasciatus, the vector of Bancroftian filariasis in Pondicherry, India.

    PubMed

    Jambulingam, P; Sadanandane, C; Boopathi Doss, P S; Subramanian, S; Zaim, M

    2008-07-01

    Pyriproxyfen, 0.5% granular formulation (GR), an insect growth regulator (IGR) was tested against Culex quinquefasciatus larvae and pupae in disused wells, cesspits and drains at the dosages of 0.1, 0.25, and 0.5kg(ai)/ha to determine the most appropriate field dosage. The IGR was found to be effective against C. quinquefasciatus larvae and pupae in all the larval habitats tested. In drains with slow moving water, application of pyriproxyfen 0.5% GR at 0.5kg(ai)/ha resulted in >80% emergence inhibition (EI) of adults for 4 weeks. At 0.1 and 0.25kg(ai)/ha, the EI was always less than 80%. In stagnant drains, the IGR yielded >80% EI for 1-week period at 0.1kg(ai)/ha. At 0.25 and 0.5kg(ai)/ha, the efficacy was 5-10 times higher. In cesspits, the EI was >80% for 6 weeks when pyriproxyfen 0.5% GR was applied at 0.1kg(ai)/ha, for 11 weeks at 0.25kg(ai)/ha and 9 weeks at 0.5kg(ai)/ha. In disused wells treated at the dosage 0.1kg(ai)/ha, there was >80% EI for 15 weeks and at 0.25 and 0.5kg(ai)/ha, the effective duration was about 1.6-1.8 times longer (24-28 weeks). Considering the quantum of IGR required and the cost and also for safety reasons, the low dosage 0.1kg(ai)/ha is recommended as the field dosage to be applied at weekly interval in stagnant drains, 6 weeks interval in cesspits and 15 weeks interval in disused wells. Since pyriproxyfen 0.5% GR has a relatively longer residual effect than the other IGRs the operational cost could be minimized. Pyriproxyfen 0.5% GR could be one of the choices in the chemical control strategy in Integrated Vector Control Programmes.

  16. Structural and biochemical analysis of the Hordeum vulgare L. HvGR-RBP1 protein, a glycine-rich RNA-binding protein involved in the regulation of barley plant development and stress response.

    PubMed

    Tripet, Brian P; Mason, Katelyn E; Eilers, Brian J; Burns, Jennifer; Powell, Paul; Fischer, Andreas M; Copié, Valérie

    2014-12-23

    The timing of whole-plant senescence influences important agricultural traits such as yield and grain protein content. Post-transcriptional regulation by plant RNA-binding proteins is essential for proper control of gene expression, development, and stress responses. Here, we report the three-dimensional solution NMR structure and nucleic acid-binding properties of the barley glycine-rich RNA-binding protein HvGR-RBP1, whose transcript has been identified as being >45-fold up-regulated in early-as compared to late-senescing near-isogenic barley germplasm. NMR analysis reveals that HvGR-RBP1 is a multidomain protein comprising a well-folded N-terminal RNA Recognition Motif (RRM) and a structurally disordered C-terminal glycine-rich domain. Chemical shift differences observed in 2D (1)H-(15)N correlation (HSQC) NMR spectra of full-length HvGR-RBP1 and N-HvGR-RBP1 (RRM domain only) suggest that the two domains can interact both in-trans and intramolecularly, similar to what is observed in the tobacco NtGR-RBP1 protein. Further, we show that the RRM domain of HvGR-RBP1 binds single-stranded DNA nucleotide fragments containing the consensus nucleotide sequence 5'-TTCTGX-3' with low micromolar affinity in vitro. We also demonstrate that the C-terminal glycine-rich (HvGR) domain of Hv-GR-RBP1 can interact nonspecifically with ssRNA in vitro. Structural similarities with other plant glycine-rich RNA-binding proteins suggest that HvGR-RBP1 may be multifunctional. Based on gene expression analysis following cold stress in barley and E. coli growth studies following cold shock treatment, we conclude that HvGR-RBP1 functions in a manner similar to cold-shock proteins and harbors RNA chaperone activity. HvGR-RBP1 is therefore not only involved in the regulation of barley development including senescence, but also functions in plant responses to environmental stress.

  17. Structural and Biochemical Analysis of the Hordeum vulgare L. HvGR-RBP1 Protein, a Glycine-Rich RNA-Binding Protein Involved in the Regulation of Barley Plant Development and Stress Response

    PubMed Central

    2015-01-01

    The timing of whole-plant senescence influences important agricultural traits such as yield and grain protein content. Post-transcriptional regulation by plant RNA-binding proteins is essential for proper control of gene expression, development, and stress responses. Here, we report the three-dimensional solution NMR structure and nucleic acid-binding properties of the barley glycine-rich RNA-binding protein HvGR-RBP1, whose transcript has been identified as being >45-fold up-regulated in early—as compared to late—senescing near-isogenic barley germplasm. NMR analysis reveals that HvGR-RBP1 is a multidomain protein comprising a well-folded N-terminal RNA Recognition Motif (RRM) and a structurally disordered C-terminal glycine-rich domain. Chemical shift differences observed in 2D 1H–15N correlation (HSQC) NMR spectra of full-length HvGR-RBP1 and N-HvGR-RBP1 (RRM domain only) suggest that the two domains can interact both in-trans and intramolecularly, similar to what is observed in the tobacco NtGR-RBP1 protein. Further, we show that the RRM domain of HvGR-RBP1 binds single-stranded DNA nucleotide fragments containing the consensus nucleotide sequence 5′-TTCTGX-3′ with low micromolar affinity in vitro. We also demonstrate that the C-terminal glycine-rich (HvGR) domain of Hv-GR-RBP1 can interact nonspecifically with ssRNA in vitro. Structural similarities with other plant glycine-rich RNA-binding proteins suggest that HvGR-RBP1 may be multifunctional. Based on gene expression analysis following cold stress in barley and E. coli growth studies following cold shock treatment, we conclude that HvGR-RBP1 functions in a manner similar to cold-shock proteins and harbors RNA chaperone activity. HvGR-RBP1 is therefore not only involved in the regulation of barley development including senescence, but also functions in plant responses to environmental stress. PMID:25495582

  18. Poly(GR) in C9ORF72-Related ALS/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons.

    PubMed

    Lopez-Gonzalez, Rodrigo; Lu, Yubing; Gendron, Tania F; Karydas, Anna; Tran, Helene; Yang, Dejun; Petrucelli, Leonard; Miller, Bruce L; Almeida, Sandra; Gao, Fen-Biao

    2016-10-19

    GGGGCC repeat expansions in C9ORF72 are the most common genetic cause of both ALS and FTD. To uncover underlying pathogenic mechanisms, we found that DNA damage was greater, in an age-dependent manner, in motor neurons differentiated from iPSCs of multiple C9ORF72 patients than control neurons. Ectopic expression of the dipeptide repeat (DPR) protein (GR)80 in iPSC-derived control neurons increased DNA damage, suggesting poly(GR) contributes to DNA damage in aged C9ORF72 neurons. Oxidative stress was also increased in C9ORF72 neurons in an age-dependent manner. Pharmacological or genetic reduction of oxidative stress partially rescued DNA damage in C9ORF72 neurons and control neurons expressing (GR)80 or (GR)80-induced cellular toxicity in flies. Moreover, interactome analysis revealed that (GR)80 preferentially bound to mitochondrial ribosomal proteins and caused mitochondrial dysfunction. Thus, poly(GR) in C9ORF72 neurons compromises mitochondrial function and causes DNA damage in part by increasing oxidative stress, revealing another pathogenic mechanism in C9ORF72-related ALS and FTD.

  19. Equation of state and thermodynamic Grüneisen parameter of monoclinic 1,1-diamino-2,2-dinitroethylene

    NASA Astrophysics Data System (ADS)

    Zhang, Jianzhong; Velisavljevic, Nenad; Zhu, Jinlong; Wang, Liping

    2016-10-01

    In situ synchrotron x-ray diffraction experiments were conducted on 1,1-diamino-2,2-dinitroethylene (FOX-7) at pressures up to 6.8 GPa and temperatures up to 485 K. Within the resolution of the present diffraction data, our results do not reveal evidence for a pressure-induced structural phase transition near 2 GPa, previously observed in several vibrational spectroscopy experiments. Based on unit-cell volume measurements, the least-squares fit using the third-order Birch-Murnaghan equation of state (EOS) yields K 0  =  12.6  ±  1.4 GPa and K0\\prime   =  11.3  ±  2.1 for the α-phase of FOX-7, which are in good agreement with recently reported values for the deuterated sample, indicating that the effect of hydrogen-deuterium substitution on the compressibility of FOX-7 is negligibly small. A thermal EOS is also obtained for the α-phase of FOX-7, including pressure dependence of thermal expansivity, (∂α/∂P)T  =  -7.0  ±  2.0  ×  10-5 K-1 GPa-1, and temperature derivative of the bulk modulus, (∂K T/∂T)P  =  -1.1  ×  10-2 GPa K-1. From these EOS parameters, we calculate heat capacity at constant volume (C V) and thermodynamic Grüneisen parameter (γ TH) as a function of temperature. At ambient conditions, the calculated γ TH is 1.055, which is in good agreement with the value (1.09) previously obtained from density functional theory (DFT). The obtained C V, however, is 13% larger than that calculated from the first-principles calculations, indicating that the dispersion correction in the DFT calculations may need to be further improved for describing intermolecular interactions of molecular crystals.

  20. Structural health monitoring of the Gröndals Bridge in Sweden: the behaviour of CFRP strengthening in cold temperature

    NASA Astrophysics Data System (ADS)

    Hejll, Arvid; Täljsten, Björn; Carolin, Anders

    2006-03-01

    To obtain a better knowledge of existing structures behaviour monitoring can be used. The use of monitoring in bridge structures by the use of instruments to assess the integrity of structures is not new and there are reports from structures tested as early as in the 19th century according to ISIS Canada1 However, the term SHM (Structural Health Monitoring) is relatively new to civil engineering and the driving force to implement SHM comes from recognising the limitations of conventional visual inspections and evaluations using conservative codes of practice. The possibilities to monitor existing structures with help of the rapidly evolving Information Technology are to day carried out. The objective of SHM is to monitor the in-situ behaviour of a structure accurately and efficiently, to assess its performance under various service conditions, to detect damage or deterioration, and to determine the health or condition of the structure1. In Sweden strengthening and periodic monitoring of a large freivorbau bridge (pre-stresed concrete box girder bridge) has been carried out, the Gröndals Bridge. The bridge is located in Stockholm and is approximately 400 m in length with a free span of 120 m. It was opened to tram traffic in year 2000. Just after opening cracks were noticed in the webs, these cracks have then increased, the size of the largest cracks exceeded 0.5 mm, and at the end of year 2001 the bridge was temporarily strengthened. This was carried out with externally placed prestressed steel stays. The reason for cracking is quite clear but the responsibility is still debated. Nevertheless, it was evidently that the bridge needed to be strengthened. The strengthening methods used were CFRP plates in the Service Limit State (SLS) and prestressed dywidag stays in the Ultimate Limit State (ULS). The strengthening was carried out during year 2002. At the same time monitoring of the bridge commenced, using LVDT crack gauges as well as optical fibre sensors. This

  1. Equation of state and thermodynamic Grüneisen parameter of monoclinic 1,1-diamino-2,2-dinitroethylene.

    PubMed

    Zhang, Jianzhong; Velisavljevic, Nenad; Zhu, Jinlong; Wang, Liping

    2016-10-05

    In situ synchrotron x-ray diffraction experiments were conducted on 1,1-diamino-2,2-dinitroethylene (FOX-7) at pressures up to 6.8 GPa and temperatures up to 485 K. Within the resolution of the present diffraction data, our results do not reveal evidence for a pressure-induced structural phase transition near 2 GPa, previously observed in several vibrational spectroscopy experiments. Based on unit-cell volume measurements, the least-squares fit using the third-order Birch-Murnaghan equation of state (EOS) yields K 0  =  12.6  ±  1.4 GPa and [Formula: see text]  =  11.3  ±  2.1 for the α-phase of FOX-7, which are in good agreement with recently reported values for the deuterated sample, indicating that the effect of hydrogen-deuterium substitution on the compressibility of FOX-7 is negligibly small. A thermal EOS is also obtained for the α-phase of FOX-7, including pressure dependence of thermal expansivity, (∂α/∂P)T  =  -7.0  ±  2.0  ×  10(-5) K(-1) GPa(-1), and temperature derivative of the bulk modulus, (∂K T/∂T)P  =  -1.1  ×  10(-2) GPa K(-1). From these EOS parameters, we calculate heat capacity at constant volume (C V) and thermodynamic Grüneisen parameter (γ TH) as a function of temperature. At ambient conditions, the calculated γ TH is 1.055, which is in good agreement with the value (1.09) previously obtained from density functional theory (DFT). The obtained C V, however, is 13% larger than that calculated from the first-principles calculations, indicating that the dispersion correction in the DFT calculations may need to be further improved for describing intermolecular interactions of molecular crystals.

  2. Determining intensive parameters through clinopyroxene-liquid equilibrium in Grímsvötn 2011 and Bárðarbunga 2014 basalts.

    NASA Astrophysics Data System (ADS)

    Haddadi, Baptiste; Sigmarsson, Olgeir; Devidal, Jean-Luc

    2015-04-01

    Pressure (P) and temperature (T) at which magma is stored before eruption are parameters needed for better understanding of pre-eruptive signals. Putirka (2008) reviewed various igneous geothermobarometers based on crystal-liquid equilibrium. These allow evaluating early melt inclusion (MI) entrapment conditions and final crystal-matrix glass P-T equilibrium conditions. In this study, the former is based on clinopyroxene (cpx)-hosted MI and cpx-host measurements, whereas the latter is estimated from analyses of crystal rims and adjacent matrix glass. Olivine (ol)-liquid equilibrium is rapidly attained and records the last thermal equilibrium before basalt eruptions. In contrast, more sluggish reaction between cpx and liquid makes MI in cpx cores the choice for estimating the deepest (and hottest) crystal-liquid equilibrium. Equilibrium criteria were evaluated from the apparent Fe-Mg exchange and textural relationships. Tephra erupted at Grímsvötn central volcano 2011 is of quartz tholeiite composition whereas the 2014 tephra from Bárðarbunga volcanic system is a more primitive olivine tholeiite. These two basalt types are the most common in Iceland and form a crust with estimated density of 2800 kg/m3. Both basalts contain approximately 1-5% phenocrysts of plagioclases, cpx and ol with sparse sulphides and, in the Grímsvötn case, ubiquitous FeTi-oxides. The geothermobarometers suggest that cpx crystallized at P from 60 to 620 MPa (depth range: 1.7-17 km) and T between 1030 and 1135 °C before the Grímsvötn 2011 eruption. In marked contrast, the Bárðarbunga ol-tholeiite crystallized at higher P from 410 to 660 MPa (depth range: 11-18 km) at restricted T of 1176 to 1182 °C. The shallowest recorded crystallization depth at Grímsvötn coincides with geophysical depth estimates of its high-level magma chamber (1.8 km; Hreinsdóttir et al., 2014), whereas the deepest crystallization is within error of the estimated mantle-crust boundary, as also observed for

  3. Volcanic ash leaching as a means of tracing the environmental impact of the 2011 Grímsvötn eruption, Iceland.

    PubMed

    Cabré, J; Aulinas, M; Rejas, M; Fernandez-Turiel, J L

    2016-07-01

    The Grímsvötn volcanic eruption, from 21 to 28 May, 2011, was the largest eruption of the Grímsvötn Volcanic System since 1873, with a Volcanic Explosivity Index (VEI) of magnitude 4. The main geochemical features of the potential environmental impact of the volcanic ash-water interaction were determined using two different leaching methods as proxies (batch and vertical flow-through column experiments). Ash consists of glass with minor amounts of plagioclase, clinopyroxene, diopside, olivine and iron sulphide; this latter mineral phase is very rare in juvenile ash. Ash grain morphology and size reflect the intense interaction of magma and water during eruption. Batch and column leaching tests in deionised water indicate that Na, K, Ca, Mg, Si, Cl, S and F had the highest potential geochemical fluxes to the environment. Release of various elements from volcanic ash took place immediately through dissolution of soluble salts from the ash surface. Element solubilities of Grímsvötn ash regarding bulk ash composition were <1 %. Combining the element solubilities and the total estimated mass of tephra (7.29 × 10(14) g), the total inputs of environmentally important elements were estimated to be 8.91 × 10(9) g Ca, 7.02 × 10(9) g S, 1.10 × 10(9) g Cl, 9.91 × 10(8) g Mg, 9.91 × 10(8) g Fe and 1.45 × 10(8) g P The potential environmental problems were mainly associated with the release of F (5.19 × 10(9) g).

  4. GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A

    PubMed Central

    Barcala Tabarrozzi, Andres E.; Andreone, Luz; Deckers, Julie; Castro, Carla N.; Gimeno, María L.; Ariolfo, Laura; Berguer, Paula M.; Antunica-Noguerol, María; Liberman, Ana C.; Vettorazzi, Sabine; Tuckermann, Jan P.; De Bosscher, Karolien; Perone, Marcelo J.

    2016-01-01

    Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties. We investigated the effects of CpdA on in vitro generated GM-CSF-conditioned bone marrow-derived DC (BMDC). CpdA-exposed BMDC exhibited low expression of cell-surface molecules and diminution of the release of proinflammatory cytokines upon LPS stimulation; processes associated with BMDC maturation and activation. CpdA-treated BMDC were inefficient at Ag capture via mannose receptor-mediated endocytosis and displayed reduced T-cell priming. CpdA prevented the LPS-induced rise in pErk1/2 and pP38, kinases involved in TLR4 signaling. CpdA fully inhibited LPS-induced pAktSer473, a marker associated with the generation of tolerogenic DC. We used pharmacological blockade and selective genetic loss-of-function tools and demonstrated GR-independent inhibitory effects of CpdA in BMDC. Mechanistically, CpdA-mediated inactivation of the NF-κB intracellular signaling pathway was associated with a short-circuiting of pErk1/2 and pP38 upstream signaling. Assessment of the in vivo function of CpdA-treated BMDC pulsed with the hapten trinitrobenzenesulfonic acid showed impaired cell-mediated contact hypersensitivity. Collectively, we provide evidence that CpdA is an effective BMDC modulator that might have a benefit for immune disorders, even when GR is not directly targeted. PMID:27857212

  5. [Technical recommendations and best practice guidelines for May-Grünwald-Giemsa staining: literature review and insights from the quality assurance].

    PubMed

    Piaton, Eric; Fabre, Monique; Goubin-Versini, Isabelle; Bretz-Grenier, Marie-Françoise; Courtade-Saïdi, Monique; Vincent, Serge; Belleannée, Geneviève; Thivolet, Françoise; Boutonnat, Jean; Debaque, Hervé; Fleury-Feith, Jocelyne; Vielh, Philippe; Cochand-Priollet, Béatrix; Egelé, Caroline; Bellocq, Jean-Pierre; Michiels, Jean-François

    2015-08-01

    May-Grünwald-Giemsa (MGG) stain is a Romanowsky-type, polychromatic stain as those of Giemsa, Leishman and Wright. Apart being the reference method of haematology, it has become a routine stain of diagnostic cytopathology for the study of air-dried preparations (lymph node imprints, centrifuged body fluids and fine needle aspirations). In the context of their actions of promoting the principles of quality assurance in cytopathology, the French Association for Quality Assurance in Anatomic and Cytologic Pathology (AFAQAP) and the French Society of Clinical Cytology (SFCC) conducted a proficiency test on MGG stain in 2013. Results from the test, together with the review of literature data allow pre-analytical and analytical steps of MGG stain to be updated. Recommendations include rapid air-drying of cell preparations/imprints, fixation using either methanol or May-Grünwald alone for 3-10minutes, two-step staining: 50% May-Grünwald in buffer pH 6.8 v/v for 3-5minutes, followed by 10% buffered Giemsa solution for 10-30minutes, and running water for 1-3minutes. Quality evaluation must be performed on red blood cells (RBCs) and leukocytes, not on tumour cells. Under correct pH conditions, RBCs must appear pink-orange (acidophilic) or buff-coloured, neither green nor blue. Leukocyte cytoplasm must be almost transparent, with clearly delineated granules. However, staining may vary somewhat and testing is recommended for automated methods (slide stainers) which remain the standard for reproducibility. Though MGG stain remains the reference stain, Diff-Quik(®) stain can be used for the rapid evaluation of cell samples.

  6. Deformation of Grímsvötn volcano, Iceland, 1992-2014: Constraints on magma flow in relation to eruptions in 1998, 2004 and 2011

    NASA Astrophysics Data System (ADS)

    Sigmundsson, Freysteinn; Hreinsdottir, Sigrun; Sturkell, Erik; Ofeigsson, Benedikt; Einarsson, Pall; Roberts, Matthew; Grapenthin, Ronni; Villemin, Thierry; Arnadottir, Thora; Geirsson, Halldor

    2014-05-01

    A time series of ground deformation at Grímsvötn volcano, Iceland from 1992 to 2014 reveals deformation due to plate movements, glacial-isostatic uplift in response to the melting of the Vatnajökull ice cap, annual changes due to snow loading and magma movements. GPS measurements have been made at one nunatak, conducted intermittently since 1992 and continuously since 2004. During this period eruptions have occurred at Grímsvötn in 1998, 2004 and 2011. The component of displacement related to magma movements is obtained after the time series are corrected for signals due to other processes. Uplift and displacement away from the caldera occurs between eruptions at a rate of few cm/yr, interrupted by sudden co-eruptive subsidence and displacement towards the caldera (up to half a meter). This inflation/deflation pattern suggests deformation driven by pressure change in an upper crustal magma chamber, similar to other highly active calderas in Iceland such as Askja and Krafla. A simple model of pressure change variation in a magma chamber at shallow depth, with variable inflow between eruptions and outflow during eruptions can explain the observed deformation pattern. The erupted volume of magma in the 2011 eruption is about 10 times larger than the inferred co-eruptive volume change, attributed to compressibility of magma in the chamber. The magma compressibility is inferred to have remained constant during the 2011 eruption, as about constant scale factor is found during that eruption between eruption rate and displacement rate. This scale factor is, however, about five times lower for the 2004 eruption. This difference implies higher compressibility of magma in the shallow Grímsvötn magma chamber during the 2011 eruption compared to 2004, assuming the active part of the Grimsvötn magma plumbing system remained the same in both eruptions.

  7. Detection and Location of Transverse Matrix Cracks in Cross-Ply Gr/Ep Composites Using Acoustic Emission

    NASA Technical Reports Server (NTRS)

    Prosser, W. H.; Jackson, K. E.; Kellas, S.; Smith, B. T.; McKeon, J.; Friedman, A.

    1995-01-01

    Transverse matrix cracking in cross-ply gr/ep laminates was studied with advanced acoustic emission (AE) techniques. The primary goal of this research was to measure the load required to initiate the first transverse matrix crack in cross-ply laminates of different thicknesses. Other methods had been previously used for these measurements including penetrant enhanced radiography, optical microscopy, and audible acoustic microphone measurements. The former methods required that the mechanical test be paused for measurements at load intervals. This slowed the test procedure and did not provide the required resolution in load. With acoustic microphones, acoustic signals from cracks could not be clearly differentiated from other noise sources such as grip damage, specimen slippage, or test machine noise. A second goal for this work was to use the high resolution source location accuracy of the advanced acoustic emission techniques to determine whether the crack initiation site was at the specimen edge or in the interior of the specimen.In this research, advanced AE techniques using broad band sensors, high capture rate digital waveform acquisition, and plate wave propagation based analysis were applied to cross-ply composite coupons with different numbers of 0 and 90 degree plies. Noise signals, believed to be caused by grip damage or specimen slipping, were eliminated based on their plate wave characteristics. Such signals were always located outside the sensor gage length in the gripped region of the specimen. Cracks were confirmed post-test by microscopic analysis of a polished specimen edge, backscatter ultrasonic scans, and in limited cases, by penetrant enhanced radiography. For specimens with three or more 90 degree plies together, there was an exact 1-1 correlation between AE crack signals and observed cracks. The ultrasonic scans and some destructive sectioning analysis showed that the cracks extended across the full width of the specimen. Furthermore, the

  8. GR@PPA 2.8: Initial-state jet matching for weak-boson production processes at hadron collisions

    NASA Astrophysics Data System (ADS)

    Odaka, Shigeru; Kurihara, Yoshimasa

    2012-04-01

    The initial-state jet matching method introduced in our previous studies has been applied to the event generation of single W and Z production processes and diboson (WW, WZ and ZZ) production processes at hadron collisions in the framework of the GR@PPA event generator. The generated events reproduce the transverse momentum spectra of weak bosons continuously in the entire kinematical region. The matrix elements (ME) for hard interactions are still at the tree level. As in previous versions, the decays of weak bosons are included in the matrix elements. Therefore, spin correlations and phase-space effects in the decay of weak bosons are exact at the tree level. The program package includes custom-made parton shower programs as well as ME-based hard interaction generators in order to achieve self-consistent jet matching. The generated events can be passed to general-purpose event generators to make the simulation proceed down to the hadron level. Catalogue identifier: ADRH_v3_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADRH_v3_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 112 146 No. of bytes in distributed program, including test data, etc.: 596 667 Distribution format: tar.gz Programming language: Fortran; with some included libraries coded in C and C++ Computer: All Operating system: Any UNIX-like system RAM: 1.6 Mega bytes at minimum Classification: 11.2 Catalogue identifier of previous version: ADRH_v2_0 Journal reference of previous version: Comput. Phys. Comm. 175 (2006) 665 External routines: Bash and Perl for the setup, and CERNLIB, ROOT, LHAPDF, PYTHIA according to the user's choice. Does the new version supersede the previous version?: No, this version supports only a part of the processes included in the previous versions. Nature of problem: We

  9. The Recent Star Formation History of GR 8 from Hubble Space Telescope Photometry of the Resolved Stars

    NASA Astrophysics Data System (ADS)

    Dohm-Palmer, Robbie C.; Skillman, E. D.; Gallagher, J.; Tolstoy, E.; Mateo, Mario; Dufour, R. J.; Saha, A.; Hoessel, J.; Chiosi, C.

    1998-09-01

    We have used the Hubble Space Telescope to observe the resolved stars in the dwarf irregular galaxy GR 8 (DDO 155, UGC 8091). The data consisted of dithered Wide Field Planetary Camera 2 images in three bands: F439W (1 hr), F555W (30 minutes), and F814W (30 minutes). The stellar photometry was extracted with a modified version of DoPHOT. Artificial star tests showed the data to be 50% complete to V = 26.3, B = 25.4, and I = 25.2. The color-magnitude diagrams contain well-defined populations, including a very young main sequence (MS) (<10 Myr), and a red giant branch as old as several Gyr. These features align well with stellar evolution models of the appropriate metallicity. The distance based on the tip of the red giant branch is in excellent agreement with the Cepheid determination of mu = 26.75 +/- 0.35 (2.2 Mpc), which we adopted. An extended stellar ``halo'' was discovered well beyond the H i. Based on the MS and blue HeB luminosity function, we calculated the star formation rate (SFR) over the past 500 Myr. The SFR has been fairly constant, at 400 M_⊙ Myr^-1 kpc^-2 with up to 60% variations. The blue HeB stars were used as a tracer for the location of star formation over this time period. The star formation occurred in superassociation size regions (100-200 pc), which lasted ~100 Myr. These regions come and go with no obvious pattern, except that they seem to concentrate in the current locations of H i clumps. This suggested that the H i clumps are long-lived features that support several star-forming events over time. The most likely explanation is that the star-forming regions are gravitationally bound. We estimated the gas-to-star conversion efficiency to be 6%. We compared our results with those of three other dI galaxies: Sextans A, Pegasus DIG, and Leo A. There is a trend of higher SFR per area with larger M_HI/L_B. Also, the star formation pattern is similar in all four galaxies. Finally, none of the four dI galaxies contained a large starburst

  10. HIF-α/MIF and NF-κB/IL-6 axes contribute to the recruitment of CD11b+Gr-1+ myeloid cells in hypoxic microenvironment of HNSCC.

    PubMed

    Zhu, Guiquan; Tang, Yaling; Geng, Ning; Zheng, Min; Jiang, Jian; Li, Ling; Li, Kaide; Lei, Zhengge; Chen, Wei; Fan, Yunlong; Ma, Xiangrui; Li, Longjiang; Wang, Xiaoyi; Liang, Xinhua

    2014-02-01

    CD11b+Gr-1+ myeloid cells have gained much attention due to their roles in tumor immunity suppression as well as promotion of angiogenesis, invasion, and metastases. However, the mechanisms by which CD11b+Gr-1+ myeloid cells recruit to the tumor site have not been well clarified. In the present study, we showed that hypoxia could stimulate the migration of CD11b+Gr-1+ myeloid cells through increased production of macrophage migration inhibitory factor (MIF) and interleukin-6 (IL-6) by head and neck squamous cell carcinoma (HNSCC) cells. Hypoxia-inducible factor-1α (HIF-1α)- and HIF-2α-dependent MIF regulated chemotaxis, differentiation, and pro-angiogenic function of CD11b+Gr-1+ myeloid cells through binding to CD74/CXCR2, and CD74/CXCR4 complexes, and then activating p38/mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinases (PI3K)/AKT signaling pathways. Knockdown (KD) of HIF-1α and HIF-2α in HNSCC cells decreased MIF level but failed to inhibit the CD11b+Gr-1+ myeloid cell migration, because HIF-1α/2α KD enhanced nuclear factor κB (NF-κB) activity that increased IL-6 secretion. Simultaneously blocking NF-κB and HIF-1α/HIF-2α had better inhibitory effect on CD11b+Gr-1+ myeloid cell recruitment in the hypoxic zone than individually silencing HIF-1α/2α or NF-κB. In conclusion, the interaction between HIF-α/MIF and NF-κB/IL-6 axes plays an important role in the hypoxia-induced accumulation of CD11b+Gr-1+ myeloid cells and tumor growth in HNSCC.

  11. Disruption of glucocorticoid receptors in the noradrenergic system leads to BDNF up-regulation and altered serotonergic transmission associated with a depressive-like phenotype in female GR(DBHCre) mice.

    PubMed

    Chmielarz, Piotr; Kreiner, Grzegorz; Kot, Marta; Zelek-Molik, Agnieszka; Kowalska, Marta; Bagińska, Monika; Daniel, Władysława Anna; Nalepa, Irena

    2015-10-01

    Recently, we have demonstrated that conditional inactivation of glucocorticoid receptors (GRs) in the noradrenergic system, may evoke depressive-like behavior in female but not male mutant mice (GR(DBHCre) mice). The aim of the current study was to dissect how selective ablation of glucocorticoid signaling in the noradrenergic system influences the previously reported depressive-like phenotype and whether it might be linked to neurotrophic alterations or secondary changes in the serotonergic system. We demonstrated that selective depletion of GRs enhances brain derived neurotrophic factor (BDNF) expression in female but not male GR(DBHCre) mice on both the mRNA and protein levels. The possible impact of the mutation on brain noradrenergic and serotonergic systems was addressed by investigating the tissue neurotransmitter levels under basal conditions and after acute restraint stress. The findings indicated a stress-provoked differential response in tissue noradrenaline content in the GR(DBHCre) female but not male mutant mice. An analogous gender-specific effect was identified in the diminished content of 5-hydroxyindoleacetic acid, the main metabolite of serotonin, in the prefrontal cortex, which suggests down-regulation of this monoamine system in female GR(DBHCre) mice. The lack of GR also resulted in an up-regulation of alpha2-adrenergic receptor (α2-AR) density in the female but not male mutants in the locus coeruleus. We have also confirmed the utility of the investigated model in pharmacological studies, which demonstrates that the depressive-like phenotype of GR(DBHCre) female mice can be reversed by antidepressant treatment with desipramine or fluoxetine, with the latter drug evoking more pronounced effects. Overall, our study validates the use of female GR(DBHCre) mice as an interesting and novel genetic tool for the investigation of the cross-connected mechanisms of depression that is not only based on behavioral phenotypes.

  12. An analysis of the origin of an early medieval group of individuals from Gródek based on the analysis of stable oxygen isotopes.

    PubMed

    Lisowska-Gaczorek, A; Kozieł, S; Cienkosz-Stepańczak, B; Mądrzyk, K; Pawlyta, J; Gronkiewicz, S; Wołoszyn, M; Szostek, K

    2016-08-01

    In the early Middle Ages, the region of the Cherven Towns, which is now located on both sides of the Polish-Ukrainian border, was fiercely contested by Slavs in the process of forming their early states. The main objective of the present study was to investigate the homogeneity of an early medieval population uncovered in that region, in the town of Gródek on the Bug River, by screening for non-local individuals. The origin of the studied skeletons was ascertained using analysis of oxygen isotopes in the phosphates isolated from bone tissue. In this paper, the isotope ratios obtained for samples collected from 62 human skeletons were compared to the background δ(18)O (in precipitation water) from the regions of Kraków (south-eastern Poland), Lviv (western Ukraine), Brest (western Belarus), and Gródek, as well as to the ratios determined for the animals coexisting with the studied population. Proportions of oxygen isotopes obtained for all the studied individuals were found to be similar to those for the precipitation water and animals, which indicates the absence of bone fragments of individuals originating in other regions.

  13. Characterization of volcanic ash from the 2011 Grímsvötn eruption by means of single-particle analysis

    NASA Astrophysics Data System (ADS)

    Lieke, K. I.; Kristensen, T. B.; Korsholm, U. S.; Sørensen, J. H.; Kandler, K.; Weinbruch, S.; Ceburnis, D.; Ovadnevaite, J.; O'Dowd, C. D.; Bilde, M.

    2013-11-01

    This work focuses on transport and properties of ash from the Icelandic volcano Grímsvötn that erupted in spring 2011. Atmospheric transport of volcanic ash from the eruption was simulated using the Danish Emergency Response Model of the Atmosphere (DERMA). The arrivals of volcanic particles were detected on-line at Mace Head at the West coast of Ireland during volcanic plume advection identified by high resolution time of flight aerosol mass spectrometry (HR-ToF AMS). Based on DERMA information aerosol particles were collected in Copenhagen, Denmark, before predicted arrival of the ash plume and during a period where ash was present in the air. Analysis of the meteorological conditions shows that the particles collected before arrival of the volcanic ash may serve as a good reference sample allowing identification of significant changes in ambient aerosol properties during the volcanic ash event over Copenhagen. Using single particle analysis in scanning electron microscopy (SEM), data on structure, chemical composition, size and morphology of individual volcanic ash particles from the Grímsvötn eruption after atmospheric transport to Scandinavia are provided. Particles were sliced with Focused Ion Beam (FIB). Element mappings from cross-sections through collected volcanic ash particles reveal inhomogeneous distributions of the elements K, Mg, Fe and Ti.

  14. A novel sandwich-type electrochemical aptasensor based on GR-3D Au and aptamer-AuNPs-HRP for sensitive detection of oxytetracycline.

    PubMed

    Liu, Su; Wang, Yu; Xu, Wei; Leng, Xueqi; Wang, Hongzhi; Guo, Yuna; Huang, Jiadong

    2017-02-15

    In this paper, a novel sandwich-type electrochemical aptasensor has been fabricated and applied for sensitive and selective detection of antibiotic oxytetracycline (OTC). This sensor was based on graphene-three dimensional nanostructure gold nanocomposite (GR-3D Au) and aptamer-AuNPs-horseradish peroxidase (aptamer-AuNPs-HRP) nanoprobes as signal amplification. Firstly, GR-3D Au film was modified on glassy carbon electrode only by one-step electrochemical coreduction with graphite oxide (GO) and HAuCl4 at cathodic potentials, which enhanced the electron transfer and loading capacity of biomolecules. Then the aptamer and HRP modified Au nanoparticles provide high affinity and ultrasensitive electrochemical probe with excellent specificity for OTC. Under the optimized conditions, the peak current was linearly proportional to the concentration of OTC in the range of 5×10(-10)-2×10(-3)gL(-1), with a detection limit of 4.98×10(-10)gL(-1). Additionally, this aptasensor had the advantages in high sensitivity, superb specificity and showed good recovery in synthetic samples. Hence, the developed sandwich-type electrochemical aptasensor might provide a useful and practical tool for OTC determination and related food safety analysis and clinical diagnosis.

  15. Energy response of GR-200A thermoluminescence dosemeters to 60Co and to monoenergetic synchrotron radiation in the energy range 28-40 keV.

    PubMed

    Emiro, F; Di Lillo, F; Mettivier, G; Fedon, C; Longo, R; Tromba, G; Russo, P

    2016-01-01

    The response of LiF:Mg,Cu,P thermoluminescence dosemeters (type GR-200A) to monoenergetic radiation of energy 28, 35, 38 and 40 keV was evaluated with respect to irradiation with a calibrated (60)Co gamma-ray source. High-precision measurements of the relative air kerma response performed at the SYRMEP beamline of the ELETTRA synchrotron radiation facility (Trieste, Italy) showed a significant deviation of the average response to low-energy X-rays from that to (60)Co, with an over-response from 6 % (at 28 keV) to 22 % (at 40 keV). These data are not consistent with literature data for these dosemeters, where model predictions gave deviation from unity of the relative air kerma response of about 10 %. The authors conclude for the need of additional determinations of the low-energy relative response of GR-200A dosemeters, covering a wider range of monoenergetic energies sampled at a fine energy step, as planned in future experiments by their group at the ELETTRA facility.

  16. In Mice, Tuberculosis Progression Is Associated with Intensive Inflammatory Response and the Accumulation of Gr-1dim Cells in the Lungs

    PubMed Central

    Lyadova, Irina V.; Tsiganov, Evgeny N.; Kapina, Marina A.; Shepelkova, Galena S.; Sosunov, Vasily V.; Radaeva, Tatiana V.; Majorov, Konstantin B.; Shmitova, Natalya S.; van den Ham, Henk-Jan; Ganusov, Vitaly V.; De Boer, Rob J.; Racine, Rachael; Winslow, Gary M.

    2010-01-01

    Background Infection with Mycobacterium tuberculosis (Mtb) results in different clinical outcomes ranging from asymptomatic containment to rapidly progressing tuberculosis (TB). The mechanisms controlling TB progression in immunologically-competent hosts remain unclear. Methodology/Principal Findings To address these mechanisms, we analyzed TB progression in a panel of genetically heterogeneous (A/SnxI/St) F2 mice, originating from TB-highly-susceptible I/St and more resistant A/Sn mice. In F2 mice the rates of TB progression differed. In mice that did not reach terminal stage of infection, TB progression did not correlate with lung Mtb loads. Nor was TB progression correlated with lung expression of factors involved in antibacterial immunity, such as iNOS, IFN-γ, or IL-12p40. The major characteristics of progressing TB was high lung expression of the inflammation-related factors IL-1β, IL-6, IL-11 (p<0.0003); CCL3, CCL4, CXCL2 (p<0.002); MMP-8 (p<0.0001). The major predictors of TB progression were high expressions of IL-1β and IL-11. TNF-α had both protective and harmful effects. Factors associated with TB progression were expressed mainly by macrophages (F4-80+ cells) and granulocytes (Gr-1hi/Ly-6Ghi cells). Macrophages and granulocytes from I/St and A/Sn parental strains exhibited intrinsic differences in the expression of inflammatory factors, suggesting that genetically determined peculiarities of phagocytes transcriptional response could account for the peculiarities of gene expression in the infected lungs. Another characteristic feature of progressing TB was the accumulation in the infected lungs of Gr-1dim cells that could contribute to TB progression. Conclusions/Significance In a population of immunocompetent hosts, the outcome of TB depends on quantitatively- and genetically-controlled differences in the intensity of inflammatory responses, rather than being a direct consequence of mycobacterial colonization. Local accumulation of Gr-1dim cells is

  17. Connections of the macaque Granular Frontal Opercular (GrFO) area: a possible neural substrate for the contribution of limbic inputs for controlling hand and face/mouth actions.

    PubMed

    Gerbella, Marzio; Borra, Elena; Rozzi, Stefano; Luppino, Giuseppe

    2016-01-01

    We traced the connections of the macaque Granular Frontal Opercular (GrFO) area, located in the rostralmost part of the frontal opercular margin, and compared them with those of the caudally adjacent dorsal opercular (DO) and precentral opercular (PrCO) areas. Area GrFO displays strong connections with areas DO, PrCO, and ventrolateral prefrontal (VLPF) area 12l, and even more with the mostly hand-related ventral premotor (PMv) area F5a. Other connections involve the mostly face/mouth-related PMv area F5c, the arm-related area F6/pre-SMA, the hand-related fields of VLPF areas 46v and 12r, and area SII, mostly the hand representation. Furthermore, area GrFO shows rich connectivity with several components of the limbic system including orbitofrontal areas 12o, 12m, and 11, the agranular and dysgranular insula, the agranular cingulate area 24, and the amygdala. Thalamic afferents originate primarily from the parvocellular and the magnocellular subdivisions of the mediodorsal nucleus and from midline and intralaminar nuclei. This connectivity pattern clearly distinguishes area GrFO from areas DO and PrCO, characterized by a connectivity mostly involving oral sensorimotor and gustatory areas/subcortical structures. The present data suggest, based on connectivity patterns, an involvement of area GrFO in the cortical circuits for controlling goal-directed hand and face/mouth actions. In this context, area GrFO could represent a gateway for the access of limbic inputs, for example about subjective values, emotional significance of stimuli or internal states, to the PMv areas involved in selecting appropriate goal-directed hand and mouth/face actions.

  18. Scaling Theory of the Mott Transition and Breakdown of the Gr"uneisen Scaling Near a Finite-Temperature Critical End Point

    NASA Astrophysics Data System (ADS)

    Bartosch, Lorenz

    2012-02-01

    We discuss a scaling theory of the lattice response in the vicinity of a finite-temperature critical end point. The thermal expansivity is shown to be more singular than the specific heat such that the Gr"uneisen ratio diverges as the critical point is approached, except for its immediate vicinity. More generally, we express the thermal expansivity in terms of a scaling function which we explicitly evaluate for the two-dimensional Ising universality class. Recent thermal expansivity measurements on the layered organic conductor κ-(BEDT-TTF)2X close to the Mott transition are well described by our theory.[2mm] [1] Lorenz Bartosch, Mariano de Souza, and Michael Lang, Physical Review Letters 104, 245701 (2010).

  19. Imerslund-Gräsbeck syndrome in a 25-month-old Italian girl caused by a homozygous mutation in AMN

    PubMed Central

    2013-01-01

    Imerslund-Gräsbeck syndrome is a rare autosomal recessive disorder, characterized by vitamin B12 deficiency due to selective malabsorption of the vitamin and usually results in megaloblastic anemia appearing in childhood. It is responsive to parenteral vitamin B12 therapy. The estimated prevalence (calculated based on Scandinavian data) is less than 6:1,000,000. However, many cases may be misdiagnosed. When there is reasonable evidence to suspect that a patient suffers from IGS, a new and straightforward approach to diagnosis is mutational analysis of the appropriate genes. We report for the first time the case of a girl of Italian ancestry with IGS genetically confirmed by the detection of a homozygous missense mutation in the AMN gene (c.208-2 A > G). PMID:24044590

  20. Systemic Scedosporium prolificans infection in an 11-month-old Border collie with cobalamin deficiency secondary to selective cobalamin malabsorption (canine Imerslund-Gräsbeck syndrome).

    PubMed

    Erles, K; Mugford, A; Barfield, D; Leeb, T; Kook, P H

    2017-04-08

    An 11-month-old Border collie presented collapsed and continued to deteriorate rapidly despite supportive treatment. The dog had a history of failure to thrive and recurring respiratory infection. Laboratory abnormalities included neutrophilic leucocytosis, Heinz body anaemia, hyperammonaemia, hyperbilirubinaemia, proteinuria and hypocobalaminaemia. Post-mortem examination revealed multi-focal necrosis within the heart, kidneys, pancreas, liver, meninges and cerebral cortex. Fungal hyphae in lesions were identified as Scedosporium prolificans following culture. Subsequent genotyping confirmed that the dog carried the CUBN:c.8392delC mutation in a homozygous state, verifying hereditary cobalamin deficiency (a.k.a. Imerslund-Gräsbeck syndrome). Cobalamin deficiency may have been a predisposing factor for the development of systemic fungal infection in this dog.

  1. Performance analysis of the GR712RC dual-core LEON3FT SPARC V8 processor in an asymmetric multi-processing environment

    NASA Astrophysics Data System (ADS)

    Giusi, Giovanni; Liu, Scige J.; Galli, Emanuele; Di Giorgio, Anna M.; Farina, Maria; Vertolli, Nello; Di Lellis, Andrea M.

    2016-07-01

    In this paper we present the results of a series of performance tests carried out on a prototype board mounting the Cobham Gaisler GR712RC Dual Core LEON3FT processor. The aim was the characterization of the performances of the dual core processor when used for executing a highly demanding lossless compression task, acting on data segments continuously copied from the static memory to the processor RAM. The selection of the compression activity to evaluate the performances was driven by the possibility of a comparison with previously executed tests on the Cobham/Aeroflex Gaisler UT699 LEON3FT SPARC™ V8. The results of the test activity have shown a factor 1.6 of improvement with respect to the previous tests, which can easily be improved by adopting a faster onboard board clock, and provided indications on the best size of the data chunks to be used in the compression activity.

  2. MODIS-derived albedo changes of Vatnajökull (Iceland) due to tephra deposition from the 2004 Grímsvötn eruption

    NASA Astrophysics Data System (ADS)

    Möller, Rebecca; Möller, Marco; Björnsson, Helgi; Guðmundsson, Sverrir; Pálsson, Finnur; Oddsson, Björn; Kukla, Peter A.; Schneider, Christoph

    2014-02-01

    Occasionally, the surface albedo of glaciers may be abruptly altered by deposition of light-absorbing aerosols, which consequently has a sustained impact on their energy- and mass balance. Volcanic eruptions may spread tephra deposits over regional-scale glacierized areas. In November 2004, an explosive, phreatomagmatic eruption of the subglacial Grímsvötn volcano, located in the centre of the Icelandic ice cap Vatnajökull, produced ash fall covering an area of ∼1280 km2 in the northwestern part of the ice cap. This event affected the surface albedo of the glacier over several years after the eruption. We use MODIS surface-albedo data and an ash-dispersal dataset obtained from in situ measurements on the ice cap to develop a novel, empirically based modelling approach to describe the albedo decrease across the glacier surface caused by the deposited tephra. We present analyses of the temporal and spatial variability of the albedo pattern over the post-eruption period from November 2004 to December 2008. The tephra-induced albedo changes were largest and most widely distributed over the glacier surface during the summer season 2005. The observed albedo decrease reached 0.35 when compared to modelled, undisturbed conditions. In the low-lying ablation area, where strong surface melting takes place, the tephra influence on albedo diminished with time and completely faded out within four years after the eruption. In contrast, at the rim of the Grímsvötn caldera surrounding the eruption site the tephra influences on albedo considerably increased with time. Throughout the rest of the high-lying accumulation area, the influences were scattered in both space and time.

  3. Volvulus du grêle sur mésentère commun incomplet - une redoutable complication rare chez l'adulte: à propos de 1 cas

    PubMed Central

    Coulibaly, Mahamadoun; Boukatta, Brahim; Derkaoui, Ali; Sbai, Hicham; Ousadden, Abdelmalek; Kanjaa, Nabil

    2015-01-01

    Le mésentère commun résulte d'une anomalie de rotation du tube digestif. Il est caractérisé par la persistance d'une disposition anatomique embryonnaire secondaire à une anomalie de rotation de l'anse ombilicale primitive, constituant ainsi un méso commun à toute l'anse intestinale et une racine du mésentère extrêmement courte. Cette insuffisance de rotation est le plus souvent associée à un défaut d'accolement. Ces anomalies de rotation intestinale peuvent aboutir à des complications redoutables parfois mortelles, qui surviennent généralement au cours de la période néonatale où à l’âge pédiatrique. On estime que la prévalence de ces malformations congénitales à l’âge adulte est de l'ordre de 0,2% à 0,5% âge auquel elles demeurent très souvent asymptomatiques et donc non diagnostiquées. Le diagnostic de volvulus total du grêle peut se faire dans des circonstances très variées: en urgence devant un tableau d'occlusion intestinale aiguë, voire un état de choc pouvant conduire au décès, devant un tableau de douleurs abdominales répétées plus ou moins associées à des troubles du transit. Nous rapportons l'observation d'un patient de 18 ans admis pour volvulus total du grêle sur mésentère commun incomplet chez qui l’évolution était favorable. PMID:26113900

  4. Immature myeloid Gr-1+ CD11b+ cells from lipopolysaccharide-immunosuppressed mice acquire inhibitory activity in the bone marrow and migrate to lymph nodes to exert their suppressive function.

    PubMed

    Landoni, Veronica I; Martire-Greco, Daiana; Rodriguez-Rodrigues, Nahuel; Chiarella, Paula; Schierloh, Pablo; Isturiz, Martin A; Fernández, Gabriela C

    2016-02-01

    Secondary infections due to post-sepsis immunosuppression are a major cause of death in patients with sepsis. Repetitive inoculation of increasing doses of lipopolysaccharide (LPS) into mice mimics the immunosuppression associated with sepsis. Myeloid-derived suppressor cells (MDSCs, Gr-1(+) CD11b(+)) are considered a major component of the immunosuppressive network, interfering with T-cell responses in many pathological conditions. We used LPS-immunosuppressed (IS) mice to address whether MDSCs acquired their suppressive ability in the bone marrow (BM) and whether they could migrate to lymph nodes (LNs) to exert their suppressive function. Our results showed that Gr-1(+) CD11b(+) cells of IS mice already had the potential to inhibit T-cell proliferation in the BM. Moreover, soluble factors present in the BM from IS mice were responsible for inducing this inhibitory ability in control BM cells. In addition, migration of Gr-1(+) CD11b(+) to LNs in vivo was maximal when cells obtained from the BM of IS mice were inoculated into an IS context. In this regard, we found chemoattractant activity in cell-free LN extracts (LNEs) from IS mice and an increased expression of the LN-homing chemokine receptor C-C chemokine receptor type 7 (CCR7) in IS BM Gr-1(+) CD11b(+) cells. These results indicate that Gr-1(+) CD11b(+) cells found in BM from IS mice acquire their suppressive activity in the same niche where they are generated, and migrate to LNs to exert their inhibitory role. A better understanding of MDSC generation and/or regulation of factors able to induce their inhibitory function may provide new and more effective tools for the treatment of sepsis-associated immunosuppression.

  5. Mediation of 5-HT-induced external carotid vasodilatation in GR 127935-pretreated vagosympathectomized dogs by the putative 5-HT7 receptor

    PubMed Central

    Villalón, Carlos M; Centurión, David; Luján-Estrada, Miguel; Terrón, José A; Sánchez-López, Araceli

    1997-01-01

    The vasodilator effects of 5-hydroxytryptamine (5-HT) in the external carotid bed of anaesthetized dogs with intact sympathetic tone are mediated by prejunctional sympatho-inhibitory 5-HT1B/1D receptors and postjunctional 5-HT receptors. The prejunctional vasodilator mechanism is abolished after vagosympathectomy which results in the reversal of the vasodilator effect to vasoconstriction. The blockade of this vasoconstrictor effect of 5-HT with the 5-HT1B/1D receptor antagonist, GR 127935, unmasks a dose-dependent vasodilator effect of 5-HT, but not of sumatriptan. Therefore, the present study set out to analyse the pharmacological profile of this postjunctional vasodilator 5-HT receptor in the external carotid bed of vagosympathectomized dogs pretreated with GR 127935 (20 μg kg−1, i.v.).One-minute intracarotid (i.c.) infusions of 5-HT (0.330 μg min−1), 5-carboxamidotryptamine (5-CT; 0.010.3 μg min−1), 5-methoxytryptamine (1100 μg min−1) and lisuride (31000 μg min−1) resulted in dose-dependent increases in external carotid blood flow (without changes in blood pressure or heart rate) with a rank order of agonist potency of 5-CT>>5-HT⩾5-methoxytryptamine>lisuride, whereas cisapride (1001000 μg min−1, i.c.) was practically inactive. Interestingly, lisuride (mean dose of 85±7 μg kg−1, i.c.), but not cisapride (mean dose of 67±7 μg kg−1, i.c.), specifically abolished the responses induced by 5-HT, 5-CT and 5-methoxytryptamine, suggesting that a common site of action may be involved. In contrast, 1 min i.c. infusions of 8-OH-DPAT (33000 μg min−1) produced dose-dependent decreases, not increases, in external carotid blood flow and failed to antagonize (mean dose of 200±33 μg kg−1, i.c.) the agonist-induced vasodilator responses.The external carotid vasodilator responses to 5-HT, 5-CT and 5-methoxytryptamine were not modified by intravenous (i.v.) pretreatment with either saline, (±)-pindolol (4

  6. Crime detection of R. F. Navarro building using terrestrial/close-range photogrammetry as used in a Supreme Court case GR-102313

    NASA Astrophysics Data System (ADS)

    Navarro, Angel A.; Navarro, Marcela Z.

    1993-10-01

    Our space organization expertise has already been in full-blown space high-technological operations for pedagogical uses. Our space sciences are integrated into a cycle on terrestrial/close-range photogrammetry and remote sensing laboratory set-up. We have used terrestrial/close-range photogrammetry for crime detection on the R. F. Navarro Building as used for support in Supreme Court Case No. 102313 because of the principal need for accurate scale references. But if the photogrammetric work must be tied to an object coordinate system, this can usually be done later by rigid transformations to a few (even partially) known points on the object and as our organization is now specializing with the crime detection of a certain prewar R. F. Navarro Building with Cadastral Record Survey No. 189 (MNL-Manila, Philippines) using terrestrial/close-range photogrammetry to detect the criminal culprits in using preponderance-of-evidence for legal and scientific uses in Supreme Court Case G.R. No. 102313. So far, the results of our legal and scientific uses in Supreme Court case research are outlined and the outcome of this position paper.

  7. A search for Wolf-Rayet stars in active star forming regions of low mass galaxies - GR8, NGC 2366, IC 2574, and NGC 1569

    NASA Astrophysics Data System (ADS)

    Drissen, Laurent; Roy, Jean-Rene; Moffat, Anthony F. J.

    1993-10-01

    We report the detection, via narrow-band 4686 A filter imagery, of possible new Wolf-Rayet stars in the most massive giant H II regions of the irregular galaxies NGC 2366 and IC 2574. One stellar knot in the post-starburst galaxy NGC 1569 also appears to contain a weak excess of light at 4686 A. A similar search yielded negative results in the very low mass galaxy GR8. The strongest 4686 A excess is located close to the secondary eastern knot in the core of NGC 2366-I (NGC 2363). If this excess is of stellar origin, about five Wolf-Rayet stars of the luminous late-type can account for the excess emission. Nebular emission wraps around this cluster in the form of a shell. The putative Wolf-Rayet stars appear to be close to the center of the large expanding H II bubble discovered by Roy et al. (1991). A possible nebular origin of the 4686 A excess is also discussed.

  8. The first cytogenetic characterization of the poisonous black widow spider Latrodectus gr. curacaviensis from Brazil, with chromosomal review of the family Theridiidae (Arachnida, Araneae).

    PubMed

    Araujo, Douglas; Maia, Ulysses Madureira; Brescovit, Antonio Domingos

    2010-02-01

    In this paper we present, for the first time, cytogenetical data on Latrodectus gr. curacaviensis (Theridiidae) from Brazil, as well as the first data on meiosis and sex chromosome system of this genus. Testes were submitted to colchicine, hypotonic, and fixation treatment, and chromosomal preparations were stained with Giemsa solution. The analysis showed 2n=26 telo/acrocentric chromosomes in spermatogonial metaphases. Metaphase I exhibited 12 autosomal bivalents and two sex chromosome univalents (12II + X(1)X(2)). All bivalents revealed one terminal chiasma. Metaphases II confirmed the sex chromosome system, showing 12 autosomes or 12 autosomes plus two X chromosomes, respectively. Male karyotype prevailing in theridiids is formed by 2n=22 chromosomes, including sex chromosome system X(1)X(2) in all species. The Latrodectus species of the geometricus clade analyzed until now showed smaller diploid number (2nfemale symbol=16 and 2nfemale symbol=18) than the species of the mactans clade (2nfemale symbol=24 and 2nfemale symbol=26). Thus, according to the chromosome number, the examined Latrodectus species seems to be related to the mactans clade.

  9. Molecular and Functional Characterization of GR2-R1 Event Based Backcross Derived Lines of Golden Rice in the Genetic Background of a Mega Rice Variety Swarna.

    PubMed

    Bollinedi, Haritha; S, Gopala Krishnan; Prabhu, Kumble Vinod; Singh, Nagendra Kumar; Mishra, Sushma; Khurana, Jitendra P; Singh, Ashok Kumar

    2017-01-01

    Homozygous Golden Rice lines developed in the background of Swarna through marker assisted backcross breeding (MABB) using transgenic GR2-R1 event as a donor for the provitamin A trait have high levels of provitamin A (up to 20 ppm) but are dwarf with pale green leaves and drastically reduced panicle size, grain number and yield as compared to the recurrent parent, Swarna. In this study, we carried out detailed morphological, biochemical and molecular characterization of these lines in a quest to identify the probable reasons for their abnormal phenotype. Nucleotide blast analysis with the primer sequences used to amplify the transgene revealed that the integration of transgene disrupted the native OsAux1 gene, which codes for an auxin transmembrane transporter protein. Real time expression analysis of the transgenes (ZmPsy and CrtI) driven by endosperm-specific promoter revealed the leaky expression of the transgene in the vegetative tissues. We propose that the disruption of OsAux1 disturbed the fine balance of plant growth regulators viz., auxins, gibberellic acid and abscisic acid, leading to the abnormalities in the growth and development of the lines homozygous for the transgene. The study demonstrates the conserved roles of OsAux1 gene in rice and Arabidopsis.

  10. Effect of Cutting Parameters on Thrust Force and Surface Roughness in Drilling of Al-2219/B4C/Gr Metal Matrix Composites

    NASA Astrophysics Data System (ADS)

    Ravindranath, V. M.; Basavarajappa, G. S. Shiva Shankar S.; Suresh, R.

    2016-09-01

    In aluminium matrix composites, reinforcement of hard ceramic particle present inside the matrix which causes tool wear, high cutting forces and poor surface finish during machining. This paper focuses on effect of cutting parameters on thrust force, surface roughness and burr height during drilling of MMCs. In the present work, discuss the influence of spindle speed and feed rate on drilling the pure base alloy (Al-2219), mono composite (Al- 2219+8% B4C) and hybrid composite (Al-2219+8%B4C+3%Gr). The composites were fabricated using liquid metallurgy route. The drilling experiments were conducted by CNC machine with TiN coated HSS tool, M42 (Cobalt grade) and carbide tools at various spindle speeds and feed rates. The thrust force, surface roughness and burr height of the drilled hole were investigated in mono composite and hybrid composite containing graphite particles, the experimental results show that the feed rate has more influence on thrust force and surface roughness. Lesser thrust force and discontinuous chips were produced during machining of hybrid composites when compared with mono and base alloy during drilling process. It is due to solid lubricant property of graphite which reduces the lesser thrust force, burr height and lower surface roughness. When machining with Carbide tool at low feed and high speeds good surface finish was obtained compared to other two types of cutting tool materials.

  11. Molecular and Functional Characterization of GR2-R1 Event Based Backcross Derived Lines of Golden Rice in the Genetic Background of a Mega Rice Variety Swarna

    PubMed Central

    Bollinedi, Haritha; S., Gopala Krishnan; Prabhu, Kumble Vinod; Singh, Nagendra Kumar; Mishra, Sushma; Khurana, Jitendra P.; Singh, Ashok Kumar

    2017-01-01

    Homozygous Golden Rice lines developed in the background of Swarna through marker assisted backcross breeding (MABB) using transgenic GR2-R1 event as a donor for the provitamin A trait have high levels of provitamin A (up to 20 ppm) but are dwarf with pale green leaves and drastically reduced panicle size, grain number and yield as compared to the recurrent parent, Swarna. In this study, we carried out detailed morphological, biochemical and molecular characterization of these lines in a quest to identify the probable reasons for their abnormal phenotype. Nucleotide blast analysis with the primer sequences used to amplify the transgene revealed that the integration of transgene disrupted the native OsAux1 gene, which codes for an auxin transmembrane transporter protein. Real time expression analysis of the transgenes (ZmPsy and CrtI) driven by endosperm-specific promoter revealed the leaky expression of the transgene in the vegetative tissues. We propose that the disruption of OsAux1 disturbed the fine balance of plant growth regulators viz., auxins, gibberellic acid and abscisic acid, leading to the abnormalities in the growth and development of the lines homozygous for the transgene. The study demonstrates the conserved roles of OsAux1 gene in rice and Arabidopsis. PMID:28068433

  12. Insertion mutation of the int-1 and int-2 loci by mouse mammary tumor virus in premalignant and malignant neoplasms from the GR mouse strain.

    PubMed Central

    Morris, D W; Barry, P A; Bradshaw, H D; Cardiff, R D

    1990-01-01

    Mouse mammary tumor virus (MMTV)-induced mammary adenocarcinomas can develop from several different premalignant precursors common in GR mice. Insertion mutagenesis of the mammary protooncogenes int-1 and int-2 was studied in this multistep system by analyzing samples from various stages of neoplastic development for novel int-1 and int-2 restriction fragments generated by MMTV provirus integration. int-1 and int-2 insertion mutations were observed in both premalignant lesions and malignant tumors. Some of the tumors with insertion mutations were experimentally derived from insertion mutation-free premalignant precursors. Each class of neoplasm examined had a characteristic frequency of int-1 and int-2 insertion mutations; however, no correspondence was observed between neoplasm morphology and mutation of either gene. These results indicate that insertion mutation of the int-1 and int-2 loci by MMTV provirus can be involved in the earliest identifiable stages of neoplastic development as well as during progression of premalignant lesions to tumors. Insertion mutation of int-1 and int-2 is therefore not stage specific in this system. Images PMID:2157060

  13. Influence of xc functional on thermal-elastic properties of Ceria: A DFT-based Debye-Grüneisen model approach

    NASA Astrophysics Data System (ADS)

    Lee, Ji-Hwan; Tak, Youngjoo; Lee, Taehun; Soon, Aloysius

    Ceria (CeO2-x) is widely studied as a choice electrolyte material for intermediate-temperature (~ 800 K) solid oxide fuel cells. At this temperature, maintaining its chemical stability and thermal-mechanical integrity of this oxide are of utmost importance. To understand their thermal-elastic properties, we firstly test the influence of various approximations to the density-functional theory (DFT) xc functionals on specific thermal-elastic properties of both CeO2 and Ce2O3. Namely, we consider the local-density approximation (LDA), the generalized gradient approximation (GGA-PBE) with and without additional Hubbard U as applied to the 4 f electron of Ce, as well as the recently popularized hybrid functional due to Heyd-Scuseria-Ernzehof (HSE06). Next, we then couple this to a volume-dependent Debye-Grüneisen model to determine the thermodynamic quantities of ceria at arbitrary temperatures. We find an explicit description of the strong correlation (e.g. via the DFT + U and hybrid functional approach) is necessary to have a good agreement with experimental values, in contrast to the mean-field treatment in standard xc approximations (such as LDA or GGA-PBE). We acknowledge support from Samsung Research Funding Center of Samsung Electronics (SRFC-MA1501-03).

  14. EDITORIAL: 19th International Conference on General Relativity and Gravitation (GR19), México, 4-9 July 2010 19th International Conference on General Relativity and Gravitation (GR19), México City, México, 4-9 July 2010

    NASA Astrophysics Data System (ADS)

    Marolf, Don; Sudarsky, Daniel

    2011-06-01

    The GR19 meeting was held in México City from 6-9 July 2010. The decision to have the meeting in México was taken during the GR18 meeting in Sydney, Australia in 2007, and represented a great milestone for the scientific community working in the fields related to gravitation in México. This fact was evidenced by the commitment of the most important institutions in México where the field is developed, by the support the meeting received at various governmental levels, and also by a promotional campaign dedicated to educate the public about our subject, which was undertaken by important segments of the gravitational physics community in Mexico. This campaign was named 'El Mes de Einstein' or 'The Einsteinian Month', and consisted of a series of presentations, talks and movies about topics related to General Relativity which culminated with the public talk of the GR19 meeting (now a traditional aspect of the GR events). This talk was given by George Smoot, Nobel laureate in physics 2006, on the amazing developments around the detailed studies of the Cosmic Microwave Background, and was held at the Nezahualc'oyotl Hall in the main campus of the National Autonomous University of México, which was filled to capacity by enthusiastic crowds of lay people fascinated with the subject. The meeting itself was a very successful one with participants from dozens of countries spanning the five continents, with a rich, varied and informative plenary program. Highlights, featured in this issue, were perhaps the talk by Veronika Hubeny on the fluid/gravity correspondence, a subject that has grown dramatically during the last few years, the lecture by Tarun Souradeep on the enormous potential for discovery offered by the ever increasing accuracy of cosmological observations, the presentation by Jeffrey McClintock, about accreting black holes and the exciting possibility of measuring their spins, the informative review about Loop Quantum Gravity from one of the pioneers of the

  15. A brain-specific Ca sup 2+ /calmodulin-dependent protein kinase (CaM kinase-Gr) is regulated by autophosphorylation. Relevance to neuronal Ca sup 2+ signaling

    SciTech Connect

    Frangakis, M.V.; Ohmstede, C.A.; Sahyoun, N. )

    1991-06-15

    A neuronal Ca2+/calmodulin-dependent protein kinase (CaM kinase-Gr) undergoes autophosphorylation on a serine residue(s) in response to Ca2+ and calmodulin. Phosphate incorporation leads to the formation of a Ca(2+)-independent (autonomous) activity state, as well as potentiation of the Ca2+/calmodulin-dependent response. The autonomous enzyme activity of the phosphorylated enzyme {approximately} equals the Ca2+/calmodulin-stimulated activity of the unphosphorylated enzyme, but displays diminished affinity toward ATP and the synthetic substrate, syntide-2. The Km(app) for ATP and syntide-2 increased 4.3- and 1.7-fold, respectively. Further activation of the autonomous enzyme by Ca2+/calmodulin yields a marked increase in the affinity for ATP and peptide substrate such that the Km(app) for ATP and syntide-2 decreased by 14- and 8-fold, respectively. Both autophosphorylation and the addition of Ca2+/calmodulin are required to produce the maximum level of enzyme activation and to increase substrate affinity. Unlike Ca2+/calmodulin-dependent protein kinase type II that is dephosphorylated by the Mg(2+)-independent phosphoprotein phosphatases 1 and 2A, CaM kinase-Gr is dephosphorylated by a Mg(2+)-dependent phosphoprotein phosphatase that may be related to the type 2C enzyme. Dephosphorylation of CaM kinase-Gr reverses the effects of autophosphorylation on enzyme activity. A comparison between the autophosphorylation and dephosphorylation reactions of CaM kinase-Gr and Ca2+/calmodulin-dependent protein kinase type II provides useful insights into the operation of Ca(2+)-sensitive molecular switches.

  16. Lactobacillus rhamnosus GR-1 Limits Escherichia coli-Induced Inflammatory Responses via Attenuating MyD88-Dependent and MyD88-Independent Pathway Activation in Bovine Endometrial Epithelial Cells.

    PubMed

    Liu, Mingchao; Wu, Qiong; Wang, Mengling; Fu, Yunhe; Wang, Jiufeng

    2016-08-01

    Intrauterine Escherichia coli infection after calving reduces fertility and causes major economic losses in the dairy industry. We investigated the protective effect of the probiotic Lactobacillus rhamnosus GR-1 on E. coli-induced cell damage and inflammation in primary bovine endometrial epithelial cells (BEECs). L. rhamnosus GR-1 reduced ultrastructure alterations and the percentage of BEECs apoptosis after E. coli challenge. Increased messenger RNA (mRNA) expression of immune response indicators, including pattern recognition receptors (toll-like receptor [TLR]2, TLR4, nucleotide-binding oligomerization domain [NOD]1, and NOD2), inflammasome proteins (NOD-like receptor family member pyrin domain-containing protein 3, apoptosis-associated speck-like protein, and caspase-1), TLR4 downstream adaptor molecules (myeloid differentiation antigen 88 [MyD88], toll-like receptor adaptor molecule 2 [TICAM2]), nuclear transcription factor kB (NF-kB), and the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-18, and interferon (IFN)-β, was observed following E. coli challenge. However, these increases were attenuated by L. rhamnosus GR-1 pretreatment. Our data indicate that L. rhamnosus GR-1 ameliorates the E. coli-induced disruption of cellular ultrastructure, subsequently reducing the percentage of BEECs apoptosis and limiting inflammatory responses, partly via attenuation of MyD88-dependent and MyD88-independent pathway activation. Certain probiotics could potentially prevent postpartum uterine diseases in dairy cows, ultimately reducing the use of antibiotics.

  17. Kinematics of long lived faults in intraplate settings: case study of the Río Grío Fault (Iberian Range).

    NASA Astrophysics Data System (ADS)

    Marcén, Marcos; Román-Berdiel, Teresa; Casas, Antonio; Calvín-Ballester, Pablo; Oliva-Urcia, Belen; García-Lasanta, Cristina

    2015-04-01

    This study is based on the comparison of structural analysis and AMS data of Río Grío Fault, associated with the Datos Fault System, in the Iberian Chain (Northeastern Iberian Plate, Spain). The Río Grío Fault, with NW-SE strike, has a tectonic evolution of probably Mesozoic extension and Tertiary transpressive dextral movement, and it is characterized by the presence of a well-developed cataclastic zone 200m width. The structure of the core is characterized by elongated along strike and narrow lenses separated by subvertical fault planes with well-developed fault breccias and gouges. The lenses usually conserve intact stratification, and it may be recognized several lithologies, including Ordovician quartzites, slates and clay, and red-colored Permo-triassic clay and sandstones. The internal structure of these lenses shows folds, brechified zones, and localized foliation in clay lenses. Cinematic indicators (striations, S/C structures…) show strong reverse dip-slip and dextral strike-slip components, indicating strain partitioning between the different lenses, and it is interpreted as the result of the reactivation of previous normal faults, like a strike-slip shear, during the NNE-SSW to NE-SW Cenozoic compression of the NE Iberian Plate. Samples of AMS study were collected from two areas (SG and RG) of the fault zone, separated by 4.5km along strike. Samples provide a magnetic susceptibility highly dependent on lithology, between ±5*10-5 [SI] in the white fault gouge and ±20*10-5 [SI] in red-colored clay. The low susceptibility in several sites results in high imprecise AMS measurements. AMS results for the first area (SG), obtained in red and black colored clays, show the same magnetic fabric in all sites. K-min axis of the magnetic ellipsoid corresponds to the pole of the fault planes measured in the outcrop, and the magnetic lineation is nearly horizontal, probably related to strike-slip movements. In the second area (RG), the AMS shows a grater

  18. Correlation between ground weather radar and satellite observations at microwaves for the Grímsvötn volcanic eruption on May 2011

    NASA Astrophysics Data System (ADS)

    Montopoli, Mario; Cimini, Domenico; Vulpiani, Gianfranco; Marzano, Frank S.

    2013-04-01

    The potential use of passive and active microwaves sensors to provide quantitative information about near-source volcanic ash cloud parameters during an eruptive event is analyzed in this work from an experimental point of view. To this aim ground-based microwave (MW) weather radar and satellite MW radiometer observations are used together. The target area where the collected measurements are compared is the Icelandic subglacial volcanic region and the analyzed case study is that of the Grímsvötn eruption on May 2011. The analyzed weather radar data include those of the Keflavík (Iceland) site (260 km far from the volcano vent) operating at single polarization and working at the frequency of 5.6 GHz with a range resolution of 2 km and that of a portable radar system positioned 70 km far from the volcano vent with polarimetry capabilities (i.e. able to measure signals from both the orthogonal polarizations of the backscattered power as well as the phase shift returns) and working at the frequency of 10 GHz with a range spatial resolution of 0.25 km. On the other hand, the measurements from the satellite passive radiometer are derived from the Special Sensor Microwave Imager/Sounder (SSMIS) in terms of brightness temperature. SSMIS is a conically scanning passive microwave radiometer aboard of a low-earth- orbit platform with several channels (from about 19 GHz to 189 GHz) and with a ground resolution variable from 12.5 and 25 km depending from the frequency channel used. The diversity in terms of spatial scale, frequency, polarization and observation point of view of the collected data gives an original contribution to the characterization of the near source parameters of the Grímsvötn eruption in May 2011 highlighting the advantages and drawbacks of microwave sensors used for volcanic purposes. Traditionally, the monitoring of ash plumes is performed exploiting thermal infrared (TIR) and optical channels of spaceborne radiometers. These measurements can be

  19. Seismic tremor signals from Bárðarbunga, Grímsvötn and other glacier covered volcanoes in Iceland's Vatnajökull ice cap

    NASA Astrophysics Data System (ADS)

    Vogfjörd, Kristin S.; Eibl, Eva; Bean, Chris; Roberts, Matthew; Ófeigsson, Benedikt; Jóhannesson, Tómas

    2016-04-01

    Many of Iceland's most active volcanoes, like Grímsvötn and Bárðarbunga are located under glaciers giving rise to a range of volcanic hazards having both local and cross-border effects on humans, infrastructures and aviation. Volcanic eruptions under ice can lead to explosive hydromagmatic volcanism and generate small to catastrophic subglacial floods that may take hours to days to emerge from the glacier edge. Unrest in subglacial hydrothermal systems and the draining of subglacial meltwater can also lead to flood hazards. These processes and magma-ice interactions in general, generate seismic tremor signals that are commonly observed on seismic systems during volcanic unrest and/or eruptions. The tremor signals exhibit certain characteristics in frequency content, amplitude and behavior with time, but their characteristics overlap. Ability to discriminate between the different processes in real-time or near-real time can support early eruption and flood warnings and help mitigate their detrimental effects. One of the goals set forth in the FUTUREVOLC volcano supersite project was in fact to understand and discriminate between the different types of seismic tremor recorded at subglacial volcanoes. In that pursuit, the seismic network was expanded into the Vatnajökull glacier with four permanent stations on rock and in the ice, in addition to three seismic arrays installed at the ice margin, to enable location and possible tracking of the tremor sources. To track subglacial floods with better resolution three GPS receivers were also installed on the ice, one in an ice cauldron above the Skaftárkatlar geothermal melting area and two down glacier, above the track of the expected subglacial flood. During FUTUREVOLC this infrastructure has recorded all the types of process expected: Magmatic dyke intrusion and propagation from Bárðarbunga, subaerial fissure eruption of that magma at Holuhraun, two subglacial floods, one small and one large, draining from the

  20. Additional insights. Commentary on “the musical stroop effect: opening a new avenue to research on automatisms” by l. Grégoire, P. Perruchet, and B. Poulin-Charronnat (Experimental Psychology, 2013, vol. 60, pp. 269–278).

    PubMed

    Akiva-Kabiri, Lilach; Henik, Avishai

    2014-01-01

    In their paper "The Musical Stroop Effect: Opening a New Avenue to Research on Automatisms," Grégoire, Perruchet, and Poulin-Charronnat (2013) use a musical Stroop-like task to demonstrate the automaticity of musical note naming in musicians. In addition, the authors suggest that music training can serve as a tool in order to study the acquisition of automaticity. In the following commentary, we aim to address three main issues concerning the paper by Grégoire et al. (2013). First, we will suggest some additional interpretations of the results; specifically, we will relate to the association between music and space. Second, we will discuss a methodological issue dealing with interference, facilitation, and the role of the neutral condition. We suggest that the study by Grégoire et al. (2013) lacks a proper neutral condition and thus it is impossible to assert that the congruency effect is interference based. Third, we will discuss the authors' suggestion of using the musical Stroop effect as a tool for studying automatism. We consider the practical relevance of music training as a tool for studying the acquisition of automaticity by pointing out that music training is highly heterogeneous.

  1. TLR4/MyD88-Induced CD11b+Gr-1intF4/80+ Non-Migratory Myeloid Cells Suppress Th2 Effector Function in the Lung

    PubMed Central

    Arora, Meenakshi; Poe, Stephanie L.; Oriss, Timothy B.; Krishnamoorthy, Nandini; Yarlagadda, Manohar; Wenzel, Sally E.; Billiar, Timothy R.; Ray, Anuradha; Ray, Prabir

    2010-01-01

    In humans, environmental exposure to a high dose of lipopolysaccharide (LPS) protects from allergic asthma the immunological underpinnings of which are not well understood. In mice, exposure to a high LPS dose blunted house dust mite-induced airway eosinophilia and Th2 cytokine production. While adoptively transferred Th2 cells induced allergic airway inflammation in control mice, they were unable to do so in LPS-exposed mice. LPS promoted the development of a CD11b+Gr1intF4/80+ lung-resident cell resembling myeloid-derived suppressor cells in a TLR4- and MyD88-dependent fashion that suppressed lung dendritic cell (DC)-mediated reactivation of primed Th2 cells. LPS effects switched from suppressive to stimulatory in MyD88-/- mice. Suppression of Th2 effector function was reversed by anti-IL-10 or inhibition of Arginase 1. Lineageneg bone marrow progenitor cells could be induced by LPS to develop into CD11b+Gr1intF4/80+ cells both in vivo and in vitro which when adoptively transferred suppressed allergen-induced airway inflammation in recipient mice. These data suggest that CD11b+Gr1intF4/80+ cells contribute to the protective effects of LPS in allergic asthma by tempering Th2 effector function in the tissue. PMID:20664577

  2. Influence of the thermodynamic parameters on the temper embrittlement of SA508 Gr.4N Ni-Cr-Mo low alloy steel with variation of Ni, Cr and Mn contents

    NASA Astrophysics Data System (ADS)

    Park, Sang-Gyu; Lee, Ki-Hyoung; Min, Ki-Deuk; Kim, Min-Chul; Lee, Bong-Sang

    2012-07-01

    It is well known that SA508 Gr.4N low alloy steel offers improved fracture toughness and strength compared to commercial low alloy steels such as SA508 Gr.3 Mn-Mo-Ni low alloy steel. In this study, the effects of Cr, Mn, and Ni on temper embrittlement in SA508 Gr.4N low alloy steel were evaluated from the viewpoint of thermodynamic parameters such as P diffusivity and C activity. The changes of the ductile-brittle transition temperatures before and after aging were correlated with varying alloying element content, and the diffusivity of P and the activity of C were calculated and correlated with the transition behaviors. The addition of Ni, Cr, and Mn reduce the resistance to temper embrittlement, showing increased Transition-Temperature Shift (TTS) and an increased fraction of intergranular fracture. Although the diffusivity of P is changed by the addition of alloying elements, it does not considerably affect the temper embrittlement. The Mn and Cr content in the matrix significantly reduce the C activity, with showing an inversely proportional relationship to TTS. The change of susceptibility to temper embrittlement caused by Cr and Mn addition could be explained by the variation of C activity. Unlike Cr and Mn, Ni has little effect on the temper embrittlement and C activity.

  3. Effects of HDM2 antagonism on sunitinib resistance, p53 activation, SDF-1 induction, and tumor infiltration by CD11b+/Gr-1+ myeloid derived suppressor cells

    PubMed Central

    2013-01-01

    Background The studies reported herein were undertaken to determine if the angiostatic function of p53 could be exploited as an adjunct to VEGF-targeted therapy in the treatment of renal cell carcinoma (RCC). Methods Nude/beige mice bearing human RCC xenografts were treated with various combinations of sunitinib and the HDM2 antagonist MI-319. Tumors were excised at various time points before and during treatment and analyzed by western blot and IHC for evidence of p53 activation and function. Results Sunitinib treatment increased p53 levels in RCC xenografts and transiently induced the expression of p21waf1, Noxa, and HDM2, the levels of which subsequently declined to baseline (or undetectable) with the emergence of sunitinib resistance. The development of resistance and the suppression of p53-dependent gene expression temporally correlated with the induction of the p53 antagonist HDMX. The concurrent administration of MI-319 markedly increased the antitumor and anti-angiogenic activities of sunitinib and led to sustained p53-dependent gene expression. It also suppressed the expression of the chemokine SDF-1 (CXCL12) and the influx of CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSC) otherwise induced by sunitinib. Although p53 knockdown markedly reduced the production of the angiostatic peptide endostatin, the production of endostatin was not augmented by MI-319 treatment. Conclusions The evasion of p53 function (possibly through the expression of HDMX) is an essential element in the development of resistance to VEGF-targeted therapy in RCC. The maintenance of p53 function through the concurrent administration of an HDM2 antagonist is an effective means of delaying or preventing the development of resistance. PMID:23497256

  4. Increased biomass, seed yield and stress tolerance is conferred in Arabidopsis by a novel enzyme from the resurrection grass Sporobolus stapfianus that glycosylates the strigolactone analogue GR24.

    PubMed

    Islam, Sharmin; Griffiths, Cara A; Blomstedt, Cecilia K; Le, Tuan-Ngoc; Gaff, Donald F; Hamill, John D; Neale, Alan D

    2013-01-01

    Isolation of gene transcripts from desiccated leaf tissues of the resurrection grass, Sporobolus stapfianus, resulted in the identification of a gene, SDG8i, encoding a Group 1 glycosyltransferase (UGT). Here, we examine the effects of introducing this gene, under control of the CaMV35S promoter, into the model plant Arabidopsis thaliana. Results show that Arabidopsis plants constitutively over-expressing SDG8i exhibit enhanced growth, reduced senescence, cold tolerance and a substantial improvement in protoplasmic drought tolerance. We hypothesise that expression of SDG8i in Arabidopsis negatively affects the bioactivity of metabolite/s that mediate/s environmentally-induced repression of cell division and expansion, both during normal development and in response to stress. The phenotype of transgenic plants over-expressing SDG8i suggests modulation in activities of both growth- and stress-related hormones. Plants overexpressing the UGT show evidence of elevated auxin levels, with the enzyme acting downstream of ABA to reduce drought-induced senescence. Analysis of the in vitro activity of the UGT recombinant protein product demonstrates that SDG8i can glycosylate the synthetic strigolactone analogue GR24, evoking a link with strigolactone-related processes in vivo. The large improvements observed in survival of transgenic Arabidopsis plants under cold-, salt- and drought-stress, as well as the substantial increases in growth rate and seed yield under non-stress conditions, indicates that overexpression of SDG8i in crop plants may provide a novel means of increasing plant productivity.

  5. Determination of the Lithosphere-Asthenosphere Boundary (LAB) beneath the Nógrád-Gömör Volcanic Field by combined geophysical (magnetotellurics) and geochemical methods

    NASA Astrophysics Data System (ADS)

    Novák, Attila; Klébesz, Rita; Szabó, Csaba; Patkó, Levente; Liptai, Nóra; Kovács, Zoltán; Wesztergom, Viktor; Ádám, Antal; Lemperger, István; Kis, Árpád; Molnár, Csaba; Szendrői, Judit

    2014-05-01

    Understanding the fundamental role of LAB is substantial for the investigation of the geodynamic evolution of the Earth. The LAB depths can be estimated by different geophysical methods (seismology, magnetotellurics), however these depths are controversial. It has been emphasized in the literature that combined geophysical and geochemical approach may lead to better understanding of these depths. The magnetotellurics (MT) is very powerful method because it indicates the sudden increase in conductivity at the LAB. The mantle xenoliths (small fragments of the lithospheric mantle) provide the information to reconstruct their P-T paths. In the Carpathian-Pannon region (CPR) five, well-studied occurrences of mantle xenoliths-bearing Plio-Pleistocene alkali basalts are known, which makes the CPR a very promising area for investigating the inconsistency in the LAB estimates. As a test area Nógrád-Gömör Volcanic Field (NGVF) has been chosen. The host basalt erupted at the NGVF collected mantle xenoliths from a small volume of the upper mantle in a depth of about 40-50 km. The major element geochemistry of the studied xenoliths indicates that most of them represent common lherzolitic mantle, whereas others show strong wehrlitisation process. This metasomatism is supposed to be caused by a migrating mafic melt agent, resulting in the transformation of a large portion of lherzolite to wehrlite beneath the NGVF, possibly just below the crust mantle boundary. In aim to detect the LAB at the research area and find the correlation with petrologic and geochemical results we carried out MT deep soundings. The campaign contained 12 long period MT stations with 3-5 km average spacing along 60 km long profile SSE to NNW direction. This presentation summarizes the preliminary results of the combined geophysical and geochemical approaches to determine the LAB depths.

  6. A Frameshift Mutation in the Cubilin Gene (CUBN) in Border Collies with Imerslund-Gräsbeck Syndrome (Selective Cobalamin Malabsorption)

    PubMed Central

    Owczarek-Lipska, Marta; Jagannathan, Vidhya; Drögemüller, Cord; Lutz, Sabina; Glanemann, Barbara

    2013-01-01

    Imerslund-Gräsbeck syndrome (IGS) or selective cobalamin malabsorption has been described in humans and dogs. IGS occurs in Border Collies and is inherited as a monogenic autosomal recessive trait in this breed. Using 7 IGS cases and 7 non-affected controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 3.53 Mb interval on chromosome 2. We re-sequenced the genome of one affected dog at ∼10× coverage and detected 17 non-synonymous variants in the critical interval. Two of these non-synonymous variants were in the cubilin gene (CUBN), which is known to play an essential role in cobalamin uptake from the ileum. We tested these two CUBN variants for association with IGS in larger cohorts of dogs and found that only one of them was perfectly associated with the phenotype. This variant, a single base pair deletion (c.8392delC), is predicted to cause a frameshift and premature stop codon in the CUBN gene. The resulting mutant open reading frame is 821 codons shorter than the wildtype open reading frame (p.Q2798Rfs*3). Interestingly, we observed an additional nonsense mutation in the MRC1 gene encoding the mannose receptor, C type 1, which was in perfect linkage disequilibrium with the CUBN frameshift mutation. Based on our genetic data and the known role of CUBN for cobalamin uptake we conclude that the identified CUBN frameshift mutation is most likely causative for IGS in Border Collies. PMID:23613799

  7. Amnionless (AMN) mutations in Imerslund-Gräsbeck syndrome may be associated with disturbed vitamin B12 transport into the CNS.

    PubMed

    Luder, A S; Tanner, S M; de la Chapelle, A; Walter, J H

    2008-12-01

    Familial selective vitamin B12 (cobalamin, Cbl) malabsorption (Imerslund-Gräsbeck syndrome, IGS, OMIM 261100) is a group of autosomal recessive disorders characterized by selective malabsorption of Cbl from the terminal ileum in the presence of normal histology. Mutations in the amnionless (AMN) and cubilin (CUBN) genes are known to be causes of IGS. Their gene products combine to form a receptor complex (cubam), which is instrumental in the binding and transport of Cbl in the gut. As opposed to Cbl transport in the terminal ileum, normal transport of Cbl into the CNS is poorly understood and little is known regarding its molecular basis. Studies in adults with neuropsychiatric disease have suggested the presence of an active transport mechanism into the central nervous system constituting a blood-brain barrier (BBB) for Cbl. A child with IGS, compound heterozygous for a missense and a nonsense mutation in the amnionless (AMN) protein gene, was noted to have a high daily cobalamin (Cbl) requirement for neuropsychiatric, but not for systemic metabolic and haematological, remission. Measurements of CSF Cbl revealed evidence that the transport of Cbl into the central nervous system was impaired, and a standard Schilling test was consistent with a dose response of cobalamin transport across the terminal ileum. Amnionless protein is known to be expressed in the fetal and postnatal central nervous system, and is known to be involved in Cbl transport in other tissues such as kidney as well as the gut. It is possible that an active Cbl transport mechanism at the BBB exists, and that the amnionless (AMN) protein may be part of this mechanism, as it is in cobalamin transport in the terminal ileum.

  8. A frameshift mutation in the cubilin gene (CUBN) in Border Collies with Imerslund-Gräsbeck syndrome (selective cobalamin malabsorption).

    PubMed

    Owczarek-Lipska, Marta; Jagannathan, Vidhya; Drögemüller, Cord; Lutz, Sabina; Glanemann, Barbara; Leeb, Tosso; Kook, Peter H

    2013-01-01

    Imerslund-Gräsbeck syndrome (IGS) or selective cobalamin malabsorption has been described in humans and dogs. IGS occurs in Border Collies and is inherited as a monogenic autosomal recessive trait in this breed. Using 7 IGS cases and 7 non-affected controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 3.53 Mb interval on chromosome 2. We re-sequenced the genome of one affected dog at ∼10× coverage and detected 17 non-synonymous variants in the critical interval. Two of these non-synonymous variants were in the cubilin gene (CUBN), which is known to play an essential role in cobalamin uptake from the ileum. We tested these two CUBN variants for association with IGS in larger cohorts of dogs and found that only one of them was perfectly associated with the phenotype. This variant, a single base pair deletion (c.8392delC), is predicted to cause a frameshift and premature stop codon in the CUBN gene. The resulting mutant open reading frame is 821 codons shorter than the wildtype open reading frame (p.Q2798Rfs*3). Interestingly, we observed an additional nonsense mutation in the MRC1 gene encoding the mannose receptor, C type 1, which was in perfect linkage disequilibrium with the CUBN frameshift mutation. Based on our genetic data and the known role of CUBN for cobalamin uptake we conclude that the identified CUBN frameshift mutation is most likely causative for IGS in Border Collies.

  9. Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol.

    PubMed

    Horwell, C J; Baxter, P J; Hillman, S E; Calkins, J A; Damby, D E; Delmelle, P; Donaldson, K; Dunster, C; Fubini, B; Kelly, F J; Le Blond, J S; Livi, K J T; Murphy, F; Nattrass, C; Sweeney, S; Tetley, T D; Thordarson, T; Tomatis, M

    2013-11-01

    The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995. For Eyjafjallajökull, the grain size distributions were variable: 2-13 vol% of the bulk samples were <4 µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5 vol%<4 µm material). Surface area ranged from 0.3 to 7.7 m2 g(-1) for Eyjafjallajökull but was very low for Grímsvötn (<0.6 m2 g(-1)). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples

  10. Interpretation of observed microwave signatures from ground dual polarization radar and space multi frequency radiometer for the 2011 Grímsvötn volcanic eruption

    NASA Astrophysics Data System (ADS)

    Montopoli, M.; Vulpiani, G.; Cimini, D.; Picciotti, E.; Marzano, F. S.

    2013-07-01

    The important role played by ground-based microwave weather radars for the monitoring of volcanic ash clouds has been recently demonstrated. The potential of microwaves from satellite passive and ground-based active sensors to estimate near-source volcanic ash cloud parameters has been also proposed, though with little investigation of their synergy and the role of the radar polarimetry. The goal of this work is to show the potentiality and drawbacks of the X-band Dual Polarization radar measurements (DPX) through the data acquired during the latest Grímsvötn volcanic eruptions that took place on May 2011 in Iceland. The analysis is enriched by the comparison between DPX data and the observations from the satellite Special Sensor Microwave Imager/Sounder (SSMIS) and a C-band Single Polarization (SPC) radar. SPC, DPX, and SSMIS instruments cover a large range of the microwaves spectrum, operating respectively at 5.4, 3.2, and 0.16-1.6 cm wavelengths. The multi-source comparison is made in terms of Total Columnar Concentration (TCC). The latter is estimated from radar observables using the "Volcanic Ash Radar Retrieval for dual-Polarization X band systems" (VARR-PX) algorithm and from SSMIS brightness temperature (BT) using a linear BT-TCC relationship. The BT-TCC relationship has been compared with the analogous relation derived from SSMIS and SPC radar data for the same case study. Differences between these two linear regression curves are mainly attributed to an incomplete observation of the vertical extension of the ash cloud, a coarser spatial resolution and a more pronounced non-uniform beam filling effect of SPC measurements (260 km far from the volcanic vent) with respect to the DPX (70 km from the volcanic vent). Results show that high-spatial-resolution DPX radar data identify an evident volcanic plume signature, even though the interpretation of the polarimetric variables and the related retrievals is not always straightforward, likely due to the

  11. Constraints on the seismic properties of the mantle beneath the Nógrád-Gömör Volcanic Field (Northern Pannonian Basin)

    NASA Astrophysics Data System (ADS)

    Klebesz, Rita; Liptai, Nora; Kovacs, Istvan; Patko, Levente; Pinter, Zsanett; Falus, Gyorgy; Graczer, Zoltan; Szanyi, Gyongyver; Wesztergom, Viktor; Szabo, Csaba

    2014-05-01

    In the Carpathian Pannonian Region (CPR) Plio-Pleistocene alkali basalts have sampled the upper mantle at five known occurrences, bringing upper mantle xenoliths to the surface. One of these is the Nógrád-Gömör Volcanic Field (NGVF), which is located in the northern part of the Pannonian Basin. For this study, 25 representative lherzolite and wehrlite xenoliths were selected from the central and southern parts of the NGVF. These xenoliths sample a small volume (~4000 km3) of the upper mantle from a depth of about 35-50 km. Xenoliths collected from the southern part of NGVF originate from shallower depth (35-40 km) than those from the central part (40-50 km) [1]. Crystal preferred orientations (CPO) of the minerals were measured by electron backscatter diffraction (EBSD). Two distinct orientation types (A-Type, D-Type) based on the distribution and alignment of crystallographic axes were recognized, which show some correlation not only with the macroscopic texture, but also with olivine J-factors that indicate the strength of the xenolith fabric [2]. The seismic properties, i.e. seismic anisotropy and velocities, of these 25 mantle xenoliths were calculated based on the CPO and volume fractions of olivine, ortho- and clinopyroxene. It was found that P wave and fast split shear wave polarization direction is always close to the density maximum of the a-axis of olivine. Seismic anisotropy is higher for stronger CPO. Maximum P wave azimuthal anisotropy ranges are 4.5%-6.9% and 5.3%-11.9%, for the southern and the central area respectively. Maximum S wave polarization anisotropy ranges are 2.92%-5.31% and 3.97%-7.46%for the southern area and the central area respectively. The anisotropy that would be measured by SKS, Rayleigh and Love waves for end-member orientations of the lineation and foliation could be predicted based on the already calculated seismic properties of the xenoliths [3]. The calculated anisotropy is compared to the results of S receiver function

  12. A Nd -and O isotopic study of the carbonatite-syenite association in the Grønnedal-Ika complex, Gardar Province, South Greenland

    NASA Astrophysics Data System (ADS)

    Halama, R.; Markl, G.

    2003-04-01

    The Grønnedal-Ika alkaline complex in the Gardar Province, South Greenland, comprises layered nepheline syenites which were intruded by a xenolithic syenite and a plug of carbonatite. The complex, dated at 1299 ± 17 Ma by a Rb-Sr whole-rock isochron (Blaxland et al. 1978), was emplaced into early Proterozoic gneisses and metasediments. Pearce et al. (1997) concluded on the basis of C and O whole-rock isotope data that the carbonatites and syenites were not genetically related. New O and Nd isotope data of mineral separates from the syenites and of whole-rock carbonatites are presented below. These are consistent with a common mantle source and may indicate that the carbonatites could have been generated by liquid immiscibility from a CO_2-rich nepheline syenite magma. Aegirine-augitic clinopyroxene is the most common mafic mineral in the syenites. Oxygen isotope measurements of clinopyroxene separates show homogeneous δ18O values from 4.2 to 4.8 per mil. δ18O values for the coexisting melts were calculated using fractionation factors by Kalamarides (1986) and a temperature estimate for the syenites of 700 degree C derived from phase equilibria between clinopyroxene, alkali feldspar and nepheline. The resulting δ18Omelt values range between 5.1 and 5.7 per mil. These values are within the lower range of typical mantle-derived magmas. Published oxygen isotope analyses of the carbonatites are also compatible with a mantle origin for the carbonatites (Pearce et al. 1997). Initial ɛNd values at T = 1.30 Ga of selected clinopyroxene separates yield values between +1.8 and +2.8 for the syenites and -1.7 for a gabbroic xenolith. Whole-rock Nd analyses of carbonatites gave initial ɛNd values of +2.4 to +2.8. Hence, there appears to be no significant difference in Nd isotope composition between syenites and carbonatites and both indicate an isotopically slightly depleted mantle source region. The initial ɛNd of the gabbroic xenolith is compatible with minor amounts

  13. The mode of emplacement of Neogene flood basalts in Eastern Iceland: The plagioclase ultraphyric basalts in the Grænavatn group

    NASA Astrophysics Data System (ADS)

    V. Óskarsson, Birgir; B. Andersen, Christina; S. Riishuus, Morten; Sørensen, Erik Vest; Tegner, Christian

    2017-02-01

    Plagioclase ultraphyric basalt lava with high fraction of solids have a mode of emplacement that is poorly understood. In this study we conduct detailed mapping of a PUB group in eastern Iceland, namely the Grænavatn group, and assess the group architecture, flow morphology and internal structure with additional constraints from petrography, petrology and crystal size distribution, to derive information on emplacement dynamics of plagioclase ultraphyric basalts. We also derive information on the plumbing system of the group with reference to the source of the macrocysts. The group is exposed in steep glacially carved fjords and can be traced for more than 70 km along strike. The flows have mixed architecture of simple and compound flows. Individual flow lobes have thicknesses in the range of 1-24 m and many reach widths and lengths exceeding 1000 m. The flows vary from rubbly to slabby pahoehoe, but are predominantly of pahoehoe type. The aspect ratio of the group and the nature of the flows indicate fissure-fed eruptions. The plagioclase macrocrysts (5-30 mm) are An-rich, exhibit bimodal size distribution and the modal proportions within the group varies from 15-40%. Clinopyroxene macrocrysts are also present ranging from 1-6%. The lowermost flow is thickest and carries the greatest crystal cargo load. The morphology of the lava flows suggests low viscous behavior, at odds with the high crystal content. The very calcic plagioclase macrocrysts (An80-85) are in disequilibrium with the groundmass and plagioclase microlaths therein (An50-70), meaning that the crystal-laden magmas quickly ascended from deeper crustal levels to the surface. The flows with highest crystal content may have maintained high temperatures by heat exchange with the primitive macrocrysts in the flows and developed non-Newtonian behavior such as shear thinning. Such conditions would have enabled the flows to advance rapidly during episodes with high effusion rates forming the simple flows, and

  14. Maternal exposure to low levels of corticosterone during lactation protects adult rat progeny against TNBS-induced colitis: A study on GR-mediated anti-inflammatory effect and prokineticin system

    PubMed Central

    Marconi, Veronica; Petrella, Carla; Fusco, Ilaria; Giuli, Chiara; Canu, Nadia; Severini, Cinzia; Broccardo, Maria; Theodorou, Vassilia; Lattanzi, Roberta; Casolini, Paola

    2017-01-01

    The early phase of life represents a critical period for the development of an organism. Interestingly, early life experiences are able to influence the development of the gastrointestinal tract and the reactivity to colonic inflammatory stress. We recently demonstrated that adult male rats exposed to low doses of corticosterone during lactation (CORT-nursed rats) are protected against experimental colitis induced by the intracolonic infusion of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Based on these interesting results, we wanted to better investigate which cellular actors could be involved in the protection of CORT-nursed rats from TNBS-induced experimental colitis. Therefore, in the present work, we focused our attention on different factors implicated in GR-mediated anti-inflammatory effect. To address this issue, colonic tissues, collected from control and CORT-nursed healthy animals and from control and CORT-nursed colitic rats, were processed and the following inflammatory factors were evaluated: the expression of (i) glucocorticoid receptors (GR), (ii) glucocorticoid-induced leucine zipper (GILZ), (iii) phospho-p65NF-κB, (iv) the pro-inflammatory cytokines IL-1β and TNF-α, (v) the prokineticins PK2 and PK2L and (vi) their receptors PKR1 and PKR2. We found that adult CORT-nursed rats, in comparison to controls, showed increased expression of colonic GR and reduced expression of pro-inflammatory molecules (IL-1β, TNF-α, PK2 and PK2L) in response to inflammatory colitis. The observed changes were associated with an increase in GILZ colonic expression and with a reduction in phospo-p65NF-κB colonic expression. PMID:28267767

  15. Maternal exposure to low levels of corticosterone during lactation protects adult rat progeny against TNBS-induced colitis: A study on GR-mediated anti-inflammatory effect and prokineticin system.

    PubMed

    Zinni, Manuela; Zuena, Anna Rita; Marconi, Veronica; Petrella, Carla; Fusco, Ilaria; Giuli, Chiara; Canu, Nadia; Severini, Cinzia; Broccardo, Maria; Theodorou, Vassilia; Lattanzi, Roberta; Casolini, Paola

    2017-01-01

    The early phase of life represents a critical period for the development of an organism. Interestingly, early life experiences are able to influence the development of the gastrointestinal tract and the reactivity to colonic inflammatory stress. We recently demonstrated that adult male rats exposed to low doses of corticosterone during lactation (CORT-nursed rats) are protected against experimental colitis induced by the intracolonic infusion of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Based on these interesting results, we wanted to better investigate which cellular actors could be involved in the protection of CORT-nursed rats from TNBS-induced experimental colitis. Therefore, in the present work, we focused our attention on different factors implicated in GR-mediated anti-inflammatory effect. To address this issue, colonic tissues, collected from control and CORT-nursed healthy animals and from control and CORT-nursed colitic rats, were processed and the following inflammatory factors were evaluated: the expression of (i) glucocorticoid receptors (GR), (ii) glucocorticoid-induced leucine zipper (GILZ), (iii) phospho-p65NF-κB, (iv) the pro-inflammatory cytokines IL-1β and TNF-α, (v) the prokineticins PK2 and PK2L and (vi) their receptors PKR1 and PKR2. We found that adult CORT-nursed rats, in comparison to controls, showed increased expression of colonic GR and reduced expression of pro-inflammatory molecules (IL-1β, TNF-α, PK2 and PK2L) in response to inflammatory colitis. The observed changes were associated with an increase in GILZ colonic expression and with a reduction in phospo-p65NF-κB colonic expression.

  16. Une maladie immunoproliférative de l'intestin grêle révélée par une invagination intestinale aigue: à propos d'un cas

    PubMed Central

    Bennani, Amal; Znati, Kaoutar; Rezzouk, Salima; Bouhadouti, Hicham; Maazaz, Khalid; Amarti, Affaf

    2014-01-01

    La maladie immunoproliférative de l'intestin grêle IPSID est un lymphome rare qui se développé à partir du système lymphoïde associé aux muqueuses au niveau de l'intestin grêle. Sa révélation par une invagination intestinale aigue est exceptionnelle et n'a jamais été rapporté dans la littérature auparavant. Nous rapportons le cas d'un patient de 65ans, admis aux urgences dans un tableau d'invagination intestinale aigue. Le scanner abdominal a mis en évidence masse grêlique à paroi concentrique avec incarcération du segment mésentérique au sein de la lésion fortement évocatrice d'une invagination intestinale. Le patient a été opéré et a bénéficié d'une résection iléale emportant le boudin d'invagination. L'examen histologique de la masse a été en faveur d'une maladie des chaines alpha transformée en un lymphome B diffus à grandes cellules. Les auteurs rapportent un cas rare d'une IPSID révélée par une invagination intestinale aigue et à travers cette observation, mettent en relief les principaux aspects cliniques, histologiques, thérapeutiques de cette entité avec une revue de la littérature. PMID:24932323

  17. Uptake of algal carbon and the synthesis of an "essential" fatty acid by Uvigerina ex. gr. semiornata (Foraminifera) within the Pakistan margin oxygen minimum zone: evidence from fatty acid biomarker and 13C tracer experiments

    NASA Astrophysics Data System (ADS)

    Larkin, K. E.; Gooday, A. J.; Woulds, C.; Jeffreys, R.; Schwartz, M.; Cowie, G.; Whitcraft, C.; Levin, L.; Dick, J. R.; Pond, D. W.

    2014-01-01

    Foraminifera are an important component of benthic communities in oxygen depleted settings, where they potentially play a~significant role in the processing of organic matter. We tracked the uptake of a 13C-labeled algal food source into individual fatty acids in the benthic foraminiferal species, Uvigerina ex. gr. semiornata, from the Arabian Sea oxygen minimum zone (OMZ). The tracer experiments were conducted on the Pakistan Margin during the late/post monsoon period (August-October 2003). A monoculture of the diatom Thalassiosira weisflogii was 13C-labeled and used to simulate a pulse of phytoplankton in two complementary experiments. A lander system was used for in situ incubations at 140 m and for 2.5 days duration, whilst a laboratory incubation used an oxystat system to maintain ambient dissolved oxygen concentrations. These shipboard experiments were terminated after 5 days. Uptake of diatoms was rapid, with high incorporation of diatom fatty acids into foraminifera after ~2 days in both experiments. Ingestion of the diatom food source was indicated by the increase over time in the quantity of diatom biomarker fatty acids in the foraminifera and by the high percentage of 13C in many of the fatty acids present at the endpoint of both in~situ and laboratory-based experiments. These results indicate that U. ex. gr. semiornata rapidly ingested the diatom food source and that this foraminifera will play an important role in the short-term cycling of organic matter within this OMZ environment. The experiments also suggested that U. ex. gr. semiornata consumed non-labeled bacterial food items, particularly bacteria, and synthesised the polyunsaturated fatty acid 20:4(n-6) de novo. 20:4(n-6) is often abundant in benthic fauna yet its origins and function have remained unclear. This study demonstrates that U. ex. gr. semiornata is capable of de novo synthesis of this "essential fatty acid" and is potentially a major source of this dietary nutrient in benthic food

  18. Uptake of algal carbon and the likely synthesis of an "essential" fatty acid by Uvigerina ex. gr. semiornata (Foraminifera) within the Pakistan margin oxygen minimum zone: evidence from fatty acid biomarker and 13C tracer experiments

    NASA Astrophysics Data System (ADS)

    Larkin, K. E.; Gooday, A. J.; Woulds, C.; Jeffreys, R. M.; Schwartz, M.; Cowie, G.; Whitcraft, C.; Levin, L.; Dick, J. R.; Pond, D. W.

    2014-07-01

    Foraminifera are an important component of benthic communities in oxygen-depleted settings, where they potentially play a significant role in the processing of organic matter. We tracked the uptake of a 13C-labelled algal food source into individual fatty acids in the benthic foraminiferal species Uvigerina ex. gr. semiornata from the Arabian Sea oxygen minimum zone (OMZ). The tracer experiments were conducted on the Pakistan margin during the late/post monsoon period (August-October 2003). A monoculture of the diatom Thalassiosira weisflogii was 13C-labelled and used to simulate a pulse of phytoplankton in two complementary experiments. A lander system was used for in situ incubations at 140 m water depth and for 2.5 days in duration. Shipboard laboratory incubations of cores collected at 140 m incorporated an oxystat system to maintain ambient dissolved oxygen concentrations and were terminated after 5 days. Uptake of diatoms was rapid, with a high incorporation of diatom fatty acids into foraminifera after ~ 2 days in both experiments. Ingestion of the diatom food source was indicated by the increase over time in the quantity of diatom biomarker fatty acids in the foraminifera and by the high percentage of 13C in many of the fatty acids present at the endpoint of both in situ and laboratory-based experiments. These results indicate that gr. semiornata rapidly ingested the diatom food source and that these foraminifera will play an important role in the short-term cycling of organic matter within this OMZ environment. The presence of 18:1(n-7) in the experimental foraminifera suggested that U. ex. gr. semiornata also consumed non-labelled bacterial food items. In addition, levels of 20:4(n-6), a PUFA only present in low amounts in the diatom food, increased dramatically in the foraminifera during both the in situ and shipboard experiments, possibly because it was synthesised de novo. This "essential fatty acid" is often abundant in benthic fauna, yet

  19. Evaluation of the Agonist PET Radioligand [11C]GR103545 to Image Kappa Opioid Receptor in Humans: Kinetic Model Selection, Test-Retest Reproducibility and Receptor Occupancy by the Antagonist PF-04455242

    PubMed Central

    Naganawa, Mika; Jacobsen, Leslie K.; Zheng, Ming-Qiang; Lin, Shu-Fei; Banerjee, Anindita; Byon, Wonkyung; Weinzimmer, David; Tomasi, Giampaolo; Nabulsi, Nabeel; Grimwood, Sarah; Badura, Lori L.; Carson, Richard E.; McCarthy, Timothy J.; Huang, Yiyun

    2014-01-01

    Introduction Kappa opioid receptors (KOR) are implicated in several brain disorders. In this report, a first-in-human Positron Emission Tomography (PET) study was conducted with the potent and selective KOR agonist tracer, [11C]GR103545, to determine an appropriate kinetic model for analysis of PET imaging data and assess the test-retest reproducibility of model-derived binding parameters. The non-displaceable distribution volume (VND) was estimated from a blocking study with naltrexone. In addition, KOR occupancy of PF-04455242, a selective KOR antagonist that is active in preclinical models of depression, was also investigated. Methods For determination of a kinetic model and evaluation of test-retest reproducibility, 11 subjects were scanned twice with [11C]GR103545. Seven subjects were scanned before and 75 min after oral administration of naltrexone (150 mg). For the KOR occupancy study, six subjects were scanned at baseline and 1.5 h and 8 h after an oral dose of PF-04455242 (15 mg, n = 1 and 30 mg, n = 5). Metabolite-corrected arterial input functions were measured and all scans were 150 min in duration. Regional time-activity curves (TACs) were analyzed with 1- and 2-tissue compartment models (1TC and 2TC) and the multilinear analysis (MA1) method to derive regional volume of distribution (VT). Relative test-retest variability (TRV), absolute test-retest variability (aTRV) and intra-class coefficient (ICC) were calculated to assess test-retest reproducibility of regional VT. Occupancy plots were computed for blocking studies to estimate occupancy and VND. The half maximal inhibitory concentration (IC50) of PF-04455242 was determined from occupancies and drug concentrations in plasma. [11C]GR103545 in vivo KD was also estimated. Results Regional TACs were well described by the 2TC model and MA1. However, 2TC VT was sometimes estimated with high standard error. Thus MA1 was the model of choice. Test-retest variability was ~15%, depending on the outcome

  20. Magma flow, eruption column and magma pressure change during 2010 Eyjafjallajökull and 2011 Grímsvötn eruptions, Iceland: Constraints from volcano geodesy on physical models of eruptive processes

    NASA Astrophysics Data System (ADS)

    Sigmundsson, F.; Hreinsdottir, S.; Hooper, A. J.; Grapenthin, R.; Heimisson, E. R.; Ofeigsson, B.; Sturkell, E. C.; Roberts, M. J.; Gudmundsson, M. T.; Hoskuldsson, A.; Bjornsson, H.; Arason, P.; Parks, M.; Dumont, S.; Drouin, V.

    2014-12-01

    Ground deformation in relation to 2010 Eyjafjallajökull and 1998, 2004 and 2011 Grímsvötn eruptions in Iceland provide constraints on subsurface magma flow and pressure change. When compared with eruptive activity, eruption column and estimates of mass flow rate they can be used to constrain physical models of eruptive processes. The 1998 and 2004 Grímsvötn eruptions were captured by intermittent GPS observations but in 2011 the detailed temporal evolution of co-eruptive deformation was revealed by a kinematic 1 Hz solutions for the position of a single continuous GPS site on the volcano, supplemented with ground tilt observations. The observations can be explained by inflow of magma and pressure buildup between eruptions in a shallow chamber at about 1.7 km depth beneath the center of the Grímsvötn caldera complex, and pressure drop and magma outflow during eruptions. The rate of pressure change in the magma chamber correlates with the height of the volcanic plume over the course of the 2011 eruption. Peaks in activity relate to periods of rapid pressure drop in the chamber. GPS observations and interferometric analysis of satellite radar images from the TerraSAR-X satellite show that the explosive 2010 eruption at Eyjafjallajökull was on the other hand associated with gradual contraction of a source, distinct from pre-eruptive inflation sources at the volcano. For the initial 10-days of the summit eruption, a deflating sill source under the summit at about 5 km depth can explain the observed deformation, but then the source geometry appears to evolve. The rate of deflation was interrupted by inflow of new magma into the deflating source during the eruption in relation to peaks in explosive activity. The contrasting behavior of the two volcanoes is interpreted in terms of different magma plumbing systems of the volcanoes. In both cases, the erupted volume of magma is much larger than the inferred co-eruptive volume change, attributed to compressibility of

  1. On the fractional Eulerian numbers and equivalence of maps with long term power-law memory (integral Volterra equations of the second kind) to Grünvald-Letnikov fractional difference (differential) equations.

    PubMed

    Edelman, Mark

    2015-07-01

    In this paper, we consider a simple general form of a deterministic system with power-law memory whose state can be described by one variable and evolution by a generating function. A new value of the system's variable is a total (a convolution) of the generating functions of all previous values of the variable with weights, which are powers of the time passed. In discrete cases, these systems can be described by difference equations in which a fractional difference on the left hand side is equal to a total (also a convolution) of the generating functions of all previous values of the system's variable with the fractional Eulerian number weights on the right hand side. In the continuous limit, the considered systems can be described by the Grünvald-Letnikov fractional differential equations, which are equivalent to the Volterra integral equations of the second kind. New properties of the fractional Eulerian numbers and possible applications of the results are discussed.

  2. Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a) immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET) biosensor.

    PubMed

    Lau, Hui-Chong; Lee, In-Kyu; Ko, Pan-Woo; Lee, Ho-Won; Huh, Jeung-Soo; Cho, Won-Ju; Lim, Jeong-Ok

    2015-01-01

    Body fluids are often used as specimens for medical diagnosis. With the advent of advanced analytical techniques in biotechnology, the diagnostic potential of saliva has been the focus of many studies. We recently reported the presence of excess salivary sugars, in patients with Alzheimer's disease (AD). In the present study, we developed a highly sensitive, cell-based biosensor to detect trehalose levels in patient saliva. The developed biosensor relies on the overexpression of sugar sensitive gustatory receptors (Gr5a) in Drosophila cells to detect the salivary trehalose. The cell-based biosensor was built on the foundation of an improved extended gate ion-sensitive field-effect transistor (EG-ISFET). Using an EG-ISFET, instead of a traditional ion-sensitive field-effect transistor (ISFET), resulted in an increase in the sensitivity and reliability of detection. The biosensor was designed with the gate terminals segregated from the conventional ISFET device. This design allows the construction of an independent reference and sensing region for simultaneous and accurate measurements of samples from controls and patients respectively. To investigate the efficacy of the cell-based biosensor for AD screening, we collected 20 saliva samples from each of the following groups: participants diagnosed with AD, participants diagnosed with Parkinson's disease (PD), and a control group composed of healthy individuals. We then studied the response generated from the interaction of the salivary trehalose of the saliva samples and the Gr5a in the immobilized cells on an EG-ISFET sensor. The cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups. Based on these findings, we propose that salivary trehalose, might be a potential biomarker for AD and could be detected using our cell-based EG-ISFET biosensor. The cell-based EG-ISFET biosensor provides a sensitive and direct approach for salivary sugar detection and

  3. The GR127935-sensitive 5-HT1 receptors mediating canine internal carotid vasoconstriction: resemblance to the 5-HT1B, but not to the 5-HT1D or 5-ht1F, receptor subtype

    PubMed Central

    Centurión, David; Sánchez-López, Araceli; De Vries, Peter; Saxena, Pramod R; Villalón, Carlos M

    2001-01-01

    This study has further investigated the pharmacological profile of the GR127935-sensitive 5-HT1 receptors mediating vasoconstriction in the internal carotid bed of anaesthetized vagosympathectomized dogs. One-minute intracarotid infusions of the agonists 5-hydroxytryptamine (5-HT; 0.1–10 μg min−1; endogenous ligand) and sumatriptan (0.3–10 μg min−1; 5-HT1B/1D), but not PNU-142633 (1–1000 μg min−1; 5-HT1D) or LY344864 (1–1000 μg min−1; 5-ht1F), produced dose-dependent decreases in internal carotid blood flow without changing blood pressure or heart rate. The responses to 5-HT were apparently resistant to blockade by i.v. administration of the antagonists SB224289 (300 μg kg−1; 5-HT1B), BRL15572 (300 μg kg−1; 5-HT1D) or ritanserin (100 μg kg−1; 5-HT2). In contrast, the responses to sumatriptan were antagonized by SB224289, but not by BRL15572. In the animals receiving SB224289, but not those receiving BRL15572, the subsequent administration of ritanserin abolished the 5-HT-induced vasoconstriction and unmasked a vasodilator component. Similarly, in ritanserin-treated animals, the subsequent administration of SB224289, but not BRL15572, completely blocked the 5-HT-induced vasoconstriction, revealing vasodilatation. In animals receiving initially BRL15572, the subsequent administration of SB224289 did not affect (except at 10 μg min−1) the vasoconstrictor responses to 5-HT. Notably, in animals pretreated with 1000 μg kg−1 of mesulergine, a 5-HT2/7 receptor antagonist, 5-HT produced a dose-dependent vasoconstriction, which was practically abolished by SB224289. After BRL15572, no further blockade was produced and the subsequent administration of ritanserin was similarly inactive. These results suggest that the GR127935-sensitive 5-HT1 receptors mediating canine internal carotid vasoconstriction resemble the 5-HT1B but not the 5-HT1D or 5-ht1F, receptor subtype. PMID:11226129

  4. Bacterial consortia at different wine fermentation phases of two typical Central European grape varieties: Blaufränkisch (Frankovka modrá) and Grüner Veltliner (Veltlínske zelené).

    PubMed

    Godálová, Zuzana; Kraková, Lucia; Puškárová, Andrea; Bučková, Mária; Kuchta, Tomáš; Piknová, Ľubica; Pangallo, Domenico

    2016-01-18

    This is the first study focused to bacterial diversity and dynamic during the vinification of two important Central Europe grape vines: Blaufränkisch and Grüner Veltliner. The investigation strategy included culture-dependent and culture-independent approaches. Four different agar media were utilized for the isolation of various bacteria occurring in several fermentation stages. The isolates were clustered by fluorescent-ITS PCR and, one or more representatives of each cluster, were identified by 16 rRNA gene sequencing. The culture-independent approach, based on 16S rRNA gene amplification, combined the denaturing gradient gel electrophoresis (DGGE) method and the construction of bacterial clone library for each wine fermentation step. A complex bacterial community was identified, comprising different lactic acid bacteria and acetic acid bacteria, such as Leuconostoc spp., Lactobacillus spp. and Gluconobacter spp. Other OTUs and bacterial isolates embraced the Actinobacteria, Bacilli, Alpha-, Beta- and Gamma-proteobacteria classes. Different taxa already detected by recent studies, such as Sphingomonas, Variovorax, Pantoea, Enterobacter and Tatumella, were detected confirming the continuous occurrence of these kinds of bacteria in wine environment. Moreover, novel genera (Amycolatopsis, Hydrogenophilus, Snodgrassella, Telluria, Gilliamella, Lelliottia, and Lonsdale quercina) never detected before were recognized, too. The role of these, until now anonymous, bacteria during vinification deserves investigation, which could open a new research field in wine technology.

  5. Comparison of the spatiotemporal variability of rainfall from four different interpolation methods and impact on the result of GR2M hydrological modeling—case of Bani River in Mali, West Africa

    NASA Astrophysics Data System (ADS)

    Louvet, S.; Paturel, J. E.; Mahé, G.; Rouché, N.; Koité, M.

    2016-01-01

    The climatic evolution of the Bani river watershed, the main tributary to the upper Niger River, is approached through the spatiotemporal variability of rainfall grids over the 1950-2006 period. The analyses are conducted, and their results compared, using four different methods of spatial interpolation of rainfall fields: the spline, kriging, weighted inverse distance, and nearest neighbor methods. The largest changes are observed for all of these grids, but differences—and in some cases divergent results—appear in the details. The analysis shows a substantial decline in rainfall, particularly marked in the center of the basin, during the 1970-2000 period with respect to the 1950-1969 period, and a slight upturn in the northern part, mainly since the beginning of the 1990s. The rainfall deficit can be attributed to a combination of factors: an earlier and drier end of the rainy season, less precipitation in the middle of the rainy season, more dry days and lower amounts of precipitation on rainy days. Two drought indices—the Effective Drought Index and Standardized Precipitation Index—revealed that the maximum duration of drought events increased most in the central part of the basin. Lastly, to supplement this comparison of methods of spatial interpolation of rainfall fields, the sensitivity of a hydrological model (GR2M) to rainfall data was tested. Given the distribution and density of rain gauge stations available in the Bani watershed, the kriging method is found to yield the best hydrological modeling performance.

  6. What is learned, and when? Commentary on “the musical stroop effect: opening a new avenue to research on automatisms” by l. Grégoire, P. Perruchet, and B. Poulin-Charronnat (Experimental Psychology, 2013, vol. 60, pp. 269–278).

    PubMed

    Gast, Anne

    2014-01-01

    In the musical Stroop task, which has recently been introduced by Grégoire, Perruchet, and Poulin-Charronat (2013), participants respond to note names that are placed inside musical notes. Musicians respond more slowly to note names that are incongruent with the note than to note names that are congruent with the note. Grégoire et al. propose to use this task to study the acquisition of automaticity by relating musical Stroop effects to the amount of musical experience. I discuss some caveats that have to be considered for these types of analyses. Specifically, I focus on how different contingencies in the learning situation relate to the Stroop effect and on the question whether a long-term perspective is suitable for studying the acquisition of automaticity.

  7. The evolution and storage of primitive melts in the Eastern Volcanic Zone of Iceland: the 10 ka Grímsvötn tephra series (i.e. the Saksunarvatn ash)

    NASA Astrophysics Data System (ADS)

    Neave, David A.; Maclennan, John; Thordarson, Thorvaldur; Hartley, Margaret E.

    2015-08-01

    Major, trace and volatile elements were measured in a suite of primitive macrocrysts and melt inclusions from the thickest layer of the 10 ka Grímsvötn tephra series (i.e. Saksunarvatn ash) at Lake Hvítárvatn in central Iceland. In the absence of primitive tholeiitic eruptions (MgO > 7 wt%) within the Eastern Volcanic Zone (EVZ) of Iceland, these crystal and inclusion compositions provide an important insight into magmatic processes in this volcanically productive region. Matrix glass compositions show strong similarities with glass compositions from the AD 1783-1784 Laki eruption, confirming the affinity of the tephra series with the Grímsvötn volcanic system. Macrocrysts can be divided into a primitive assemblage of zoned macrocryst cores (An78-An92, Mg#cpx = 82-87, Fo79.5-Fo87) and an evolved assemblage consisting of unzoned macrocrysts and the rims of zoned macrocrysts (An60-An68, Mg#cpx = 71-78, Fo70-Fo76). Although the evolved assemblage is close to being in equilibrium with the matrix glass, trace element disequilibrium between primitive and evolved assemblages indicates that they were derived from different distributions of mantle melt compositions. Juxtaposition of disequilibrium assemblages probably occurred during disaggregation of incompatible trace element-depleted mushes (mean La/Ybmelt = 2.1) into aphyric and incompatible trace element-enriched liquids (La/Ybmelt = 3.6) shortly before the growth of the evolved macrocryst assemblage. Post-entrapment modification of plagioclase-hosted melt inclusions has been minimal and high-Mg# inclusions record differentiation and mixing of compositionally variable mantle melts that are amongst the most primitive liquids known from the EVZ. Coupled high-field strength element (HFSE) depletion and incompatible trace element enrichment in a subset of primitive plagioclase-hosted melt inclusions can be accounted for by inclusion formation following plagioclase dissolution driven by interaction with plagioclase

  8. (Quasi)-convexification of Barta's (multi-extrema) bounding theorem: Inf_x\\big(\\ssty\\frac{H\\Phi(x)}{\\Phi(x)} \\big) \\le E_gr \\le Sup_x \\big(\\ssty\\frac{H\\Phi(x)}{\\Phi(x)} \\big)

    NASA Astrophysics Data System (ADS)

    Handy, C. R.

    2006-03-01

    There has been renewed interest in the exploitation of Barta's configuration space theorem (BCST) (Barta 1937 C. R. Acad. Sci. Paris 204 472) which bounds the ground-state energy, Inf_x\\big({{H\\Phi(x)}\\over {\\Phi(x)}} \\big ) \\leq E_gr \\leq Sup_x \\big({{H\\Phi(x)}\\over {\\Phi(x)}}\\big) , by using any Φ lying within the space of positive, bounded, and sufficiently smooth functions, {\\cal C} . Mouchet's (Mouchet 2005 J. Phys. A: Math. Gen. 38 1039) BCST analysis is based on gradient optimization (GO). However, it overlooks significant difficulties: (i) appearance of multi-extrema; (ii) inefficiency of GO for stiff (singular perturbation/strong coupling) problems; (iii) the nonexistence of a systematic procedure for arbitrarily improving the bounds within {\\cal C} . These deficiencies can be corrected by transforming BCST into a moments' representation equivalent, and exploiting a generalization of the eigenvalue moment method (EMM), within the context of the well-known generalized eigenvalue problem (GEP), as developed here. EMM is an alternative eigenenergy bounding, variational procedure, overlooked by Mouchet, which also exploits the positivity of the desired physical solution. Furthermore, it is applicable to Hermitian and non-Hermitian systems with complex-number quantization parameters (Handy and Bessis 1985 Phys. Rev. Lett. 55 931, Handy et al 1988 Phys. Rev. Lett. 60 253, Handy 2001 J. Phys. A: Math. Gen. 34 5065, Handy et al 2002 J. Phys. A: Math. Gen. 35 6359). Our analysis exploits various quasi-convexity/concavity theorems common to the GEP representation. We outline the general theory, and present some illustrative examples.

  9. Metasomatism and current state of the lithospheric mantle beneath the Nógrád-Gömör Volcanic Field constrained by trace element modelling and magnetotelluric survey

    NASA Astrophysics Data System (ADS)

    Klébesz, Rita; Patkó, Levente; Novák, Attila; Wesztergom, Viktor; Szabó, Csaba

    2016-04-01

    The Nógrád-Gömör Volcanic Field (NGVF) is one of the five mantle xenolith bearing alkali basalt locations in the Carpathian-Pannonian Region, where Plio-Pleistocene alkali basalt brought to the surface lherzolite and wehrlite xenoliths. Petrographic and geochemical signature (i.e. newly formed clinopyroxene and olivine grains, Ti, Al, Fe, Mn and LRRE enrichment in rock-forming minerals) of the wehrlite xenoliths suggest that a portion of the upper mantle was transformed to wehrlite beneath the NGVF by upward migrating mafic melt agents. Based on trace element modelling, we argue that the metasomatic agent had an OIB-like trace element composition, similar to the host alkali basalts. In order to study the current state of the lithospheric mantle and to test whether the spatial distribution of the metasomatism can be imaged, magnetotelluric (MT) survey was carried out. Long period MT data were collected at 14 locations along a ~50 km long NNW-SSE profile in the NGVF. The lithosphere-asthenosphere boundary was detected at 70-90 km of depth. A low resistivity anomaly (~5-10 Ωm) was observed at 30-45 km in depth below the central part of the NNW-SSE profile, indicating the presence of a conductive body barely below the Moho. We suggest that the low resistivity body is related to the presence of residual, connected melt and/or the conductivity differences between the lherzolitic and wehrlitic mantle domain due to different chemical composition and ratio of the rock-forming minerals.

  10. Thermomechanical response of Gr/Pi composites

    NASA Technical Reports Server (NTRS)

    Rosen, B. W.; Nagarkar, A. P.; Hashin, Z.

    1981-01-01

    The effects of temperature changes upon the stresses and strains in composite laminates having carbon fibers in a polyimide matrix were evaluated. Composites having laminae in which there were nonlinear stress-strain relations for stresses transverse to the fibers and for axial shear stresses were treated. Material properties were considered to be temperature dependent. Separately, the effects of laminae viscoelastic response were also treated. The results suggest that, for this material, nonlinearities due either to stress or time dependent effects do not appear to be of major practical importance for conventional high temperature composite structures.

  11. GaAs/InAs Multi Quantum Well Solar Cell

    DTIC Science & Technology

    2012-12-01

    4. TITLE AND SUBTITLE GaAs /InAs MULTI QUANTUM WELL SOLAR CELL 5. FUNDING NUMBERS 6. AUTHOR(S) Evangelos Koletsios 7. PERFORMING ORGANIZATION NAME... GaAs /InAs MULTI QUANTUM WELL SOLAR CELL Evangelos Koletsios Lieutenant, Hellenic Navy B.S., Hellenic Naval Academy, 2001 Submitted in...similar, such as a GaAs crystal, which is mainly used in solar cells and it is described as a direct bandgap semiconductor. On the other hand, for

  12. ¹H, ¹³C, ¹⁵N backbone and side chain NMR resonance assignments for the N-terminal RNA recognition motif of the HvGR-RBP1 protein involved in the regulation of barley (Hordeum vulgare L.) senescence.

    PubMed

    Mason, Katelyn E; Tripet, Brian P; Parrott, David; Fischer, Andreas M; Copié, Valérie

    2014-04-01

    Leaf senescence is an important process in the developmental life of all plant species. Senescence efficiency influences important agricultural traits such as grain protein content and plant growth, which are often limited by nitrogen use. Little is known about the molecular mechanisms regulating this highly orchestrated process. To enhance our understanding of leaf senescence and its regulation, we have undertaken the structural and functional characterization of previously unknown proteins that are involved in the control of senescence in barley (Hordeum vulgare L.). Previous microarray analysis highlighted several barley genes whose transcripts are differentially expressed during senescence, including a specific gene which is greater than 40-fold up-regulated in the flag leaves of early- as compared to late-senescing near-isogenic barley lines at 14 and 21 days past flowering (anthesis). From inspection of its amino acid sequence, this gene is predicted to encode a glycine-rich RNA-binding protein herein referred to as HvGR-RBP1. HvGR-RBP1 has been expressed as a recombinant protein in Escherichia coli, and preliminary NMR data analysis has revealed that its glycine-rich C-terminal region [residues: 93-162] is structurally disordered whereas its N-terminal region [residues: 1-92] forms a well-folded domain. Herein, we report the complete (1)H, (13)C, and (15)N resonance assignments of backbone and sidechain atoms, and the secondary structural topology of the N-terminal RNA recognition motif (RRM) domain of HvGR-RBP1, as a first step to unraveling its structural and functional role in the regulation of barley leaf senescence.

  13. How automatic is the musical stroop effect? Commentary on “the musical stroop effect: opening a new avenue to research on automatisms” by l. Grégoire, P. Perruchet, and B. Poulin-Charronnat (Experimental Psychology, 2013, vol. 60, pp. 269–278).

    PubMed

    Moeller, Birte; Frings, Christian

    2014-01-01

    Grégoire, Perruchet, and Poulin-Charronnat (2013) investigated a musical variant of the reversed Stroop effect. According to the authors, one big advantage of this variant is that the automaticity of note naming can be better controlled than in other Stroop variants as musicians are very practiced in note reading whereas non-musicians are not. In this comment we argue that at present the exact impact of automaticity in this Stroop variant remains somewhat unclear for at least three reasons, namely due to the type of information that is automatically retrieved when notes are encountered, due to the possible influence of object-based attention, and finally due to the fact that the exact influence of expertise on interference cannot be pinpointed with an extreme group design.

  14. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 may help downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70) in the neurogenic bladder of spinal cord injured patient with urinary tract infections: a two-case study.

    PubMed

    Anukam, Kingsley C; Hayes, Keith; Summers, Kelly; Reid, Gregor

    2009-01-01

    The management of urinary tract infection (UTI) in individuals with spinal cord injury (SCI) continues to be of concern, due to complications that can occur. An emerging concept that is a common underlying pathophysiological process is involved, wherein pathogens causing UTI have a role in inflammatory progression. We hypothesized that members of the commensal flora, such as lactobacilli, may counter this reaction through anti-inflammatory mediation. This was assessed in a pilot two-patient study in which probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri were administered to one patient and placebo to another, both along with antibiotics to treat acute UTI. Urinary TNF-alpha was significantly downregulated (P = .015) in the patient who received the probiotic and who used intermittent catheterization compared with patient on placebo and using an indwelling catheter. The extent to which this alteration resulted in improved well-being in spinal cord injured patients remains to be determined in a larger study.

  15. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 May Help Downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70) in the Neurogenic Bladder of Spinal Cord Injured Patient with Urinary Tract Infections: A Two-Case Study

    PubMed Central

    Anukam, Kingsley C.; Hayes, Keith; Summers, Kelly; Reid, Gregor

    2009-01-01

    The management of urinary tract infection (UTI) in individuals with spinal cord injury (SCI) continues to be of concern, due to complications that can occur. An emerging concept that is a common underlying pathophysiological process is involved, wherein pathogens causing UTI have a role in inflammatory progression. We hypothesized that members of the commensal flora, such as lactobacilli, may counter this reaction through anti-inflammatory mediation. This was assessed in a pilot two-patient study in which probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri were administered to one patient and placebo to another, both along with antibiotics to treat acute UTI. Urinary TNF-alpha was significantly downregulated (P = .015) in the patient who received the probiotic and who used intermittent catheterization compared with patient on placebo and using an indwelling catheter. The extent to which this alteration resulted in improved well-being in spinal cord injured patients remains to be determined in a larger study. PMID:19753131

  16. Current and future engine applications of Gr/PI composites

    NASA Technical Reports Server (NTRS)

    Cavano, P. J.; Schmid, T. E.

    1985-01-01

    The application of organic matrix composites to gas turbine engine components has been the subject of numerous government and company funded programs since the 1960's. The possibility of significant weight reductions, performance improvements and lower component costs have made the organic matrix composites extremely attractive to aircraft engine designers. Very little of this potential was incorporated into production engines over the years even though a significant number of components were designed, fabricated and tested. Some of the reasons behind the slow rate of incorporation include the following: (1) criticality; (2) engine operating temperature; (3) small component size; (4) small production volume; (5) high production cost; and (6) interfacing with metal parts.

  17. Summary of session B3 at GR20/Amaldi10

    NASA Astrophysics Data System (ADS)

    Garfinkle, David

    2014-05-01

    A wide variety of results was presented in session B3, the "non-astrophysical" numerical relativity parallel session. some results included improved numerical methods for such things as asymptotically flat spacetimes, generation of initial data, and characterization of binary black hole systems. Others included the propagation of various types of matter fields in the presence of black holes, naked singularities, and wormholes. There were also several simulations of spacetimes asymptotic to anti-de Sitter space. These simulations are of interest both for general relativity and (through the AdS/CFT correspondence) for the behavior of quantum field theories.

  18. Status of Gr/glass composites technology at UTOS

    NASA Technical Reports Server (NTRS)

    Mayor, Ramon A.

    1988-01-01

    The TSC (Thermally Stable Composite) refers to a family of graphite reinforced glass matrix composite materials developed by UTOS. This fiber matrix combination exhibits low coefficients of thermal expansion (CTE), exceptional dimensional stability, high specific strength and stiffness, adequate fracture toughness, and space environment compatibility. The dimensional stability of a TSC mirror structure was experimentally characterized at the Steward Observatory. Preliminary results indicate that TSC is significantly more thermally stable than most current structural composite materials. In addition, the use of lower CTE glass matrix materials, such as 96 percent silica glass, have the potential for producing graphite/glass panels with expansion rates and stability comparable to that of fused silica.

  19. Regulation of Heat Stress by HSF1 and GR

    DTIC Science & Technology

    2015-09-01

    integrity is central to resistance of muscle cells against heat-induced injury. 15. SUBJECT TERMS heat adaptation , heat tolerance, skeletal muscle...Keywords hyperthermia, heat shock, heat injury, heat adaptation , rodent, skeletal muscle, C2C12, myotube, hsp, inflammation, cytokines, oxidative stress

  20. Vacuum Energy and Inflation: 3. Newtonian Cosmology & GR

    ERIC Educational Resources Information Center

    Huggins, Elisha

    2013-01-01

    This is paper #3 in a series of four papers on "vacuum energy" and inflation. In paper #1 [see EJ1024183] we discussed an example of what we have been calling vacuum energy. It is an energy with negative pressure whose energy density remains constant in an expanding space. We showed that an energy density with these properties exists…

  1. GR angular momentum in the quadratic spinor Lagrangian formulation

    NASA Astrophysics Data System (ADS)

    Li, Siao-Jing

    2016-08-01

    We inquire into the question of whether the quadratic spinor Lagrangian (QSL) formulation can describe the angular momentum for a general-relativistic system. The QSL Hamiltonian has previously been shown to be able to yield an energy-momentum quasilocalization which brings a proof of the positive gravitational energy when the spinor satisfies the conformal Witten equation. After inspection, we find that, under the constraint that the spinor on the asymptotic boundary is a constant, the QSL Hamiltonian is successful in giving an angular momentum quasilocalization. We also make certain the spinor in the Hamiltonian plays the role of a gauge field, a warrant of our permission to impose constraints on the spinor. Then, by some adjustment of the QSL Hamiltonian, we gain a covariant center-of-mass moment quasilocalization only under the condition that the displacement on the asymptotic boundary is a Killing boost vector. We expect the spinor expression will bring a proof of some connection between the gravitational energy and angular momentum.

  2. Grüt: A Gardening Sensor Kit for Children.

    PubMed

    Valpreda, Fabrizio; Zonda, Ilaria

    2016-02-16

    Food waste is one of the main problems in our society. This is mainly caused by people's behaviors and attitudes, which influence the whole food chain, from production to final consumption. In fact, food is generally perceived as a commodity by adults, who transmit this behavior to children, who in turn do not develop any consciousness about food's source. One way to reduce the problem seems to be by changing consumers' attitudes, which develop during the early years of childhood. Research has shown that after attending school garden classes, children's food-related behavior changes. Growing crops is not always easy--it can't be done in the domestic space, and this lead to a loss of the long term positive effects. This paper presents a project that tries to teach children how to grow their own food indoors and outdoors, mixing real and virtual reality, connecting something natural like a plant to the Internet of Things (or IOT, a network of physical objects virtually connected to each other and to the web). The use of sensors related to an app makes this process more fun and useful for educational purposes. The aim of the project is to change children's attitude towards food, increasing their knowledge about production and consumption, in order to reduce waste on a long term basis. The research has been developed in collaboration with Cisco NL and MediaLAB Amsterdam. The user testing has been executed with Dutch children in Amsterdam.

  3. Economic Analysis of the Greenland Inland Traverse (GrIT)

    DTIC Science & Technology

    2016-06-01

    17 5.3 Skiway maintenance costs... maintenance costs ............................................................. 18 7 Airlift payload handling costs for Kanger–Summit and Kanger–NEEM resupply... maintenance costs, and cargo-handling costs. The average LC-130 payload delivered to Summit is 21,100 lb, and round-trip flying time is 4.0 hr

  4. Resource Letter GrW-1: Gravitational Waves

    NASA Technical Reports Server (NTRS)

    White, Nicholas E. (Technical Monitor); Centrella, Joan M.

    2003-01-01

    The phenomenon of gravitational radiation was one of the first predictions of Einstein's general theory of relativity. Progress in understanding this radiation theoretically was slow at first, owing to the difficulty of the nonlinear field equations and the subtleties of their physical effects. The experimental side of this subject also has taken a long time to develop, with efforts at detection severely challenged by the extreme weakness of the waves impinging on the Earth. However, as the 21st century begins, observations of the gravitational waves from astrophysical sources such as black holes, neutron stars, and stellar collapse are expected to open a new window on the universe. Vigorous experimental programs centered on ground-based detectors are being carried out worldwide, and a space-based detector is in the planning stages. On the theoretical side, much effort is being expended to produce robust models of the astrophysical sources and accurate calculations of the waveforms they produce. In this Resource Letter, a set of basic references will be presented first, to provide a general introduction to and overview of the literature in this field. The focus then will shift to highlighting key resources in more specialized areas at the forefront of current research.

  5. Grüt: A Gardening Sensor Kit for Children

    PubMed Central

    Valpreda, Fabrizio; Zonda, Ilaria

    2016-01-01

    Food waste is one of the main problems in our society. This is mainly caused by people’s behaviors and attitudes, which influence the whole food chain, from production to final consumption. In fact, food is generally perceived as a commodity by adults, who transmit this behavior to children, who in turn do not develop any consciousness about food’s source. One way to reduce the problem seems to be by changing consumers’ attitudes, which develop during the early years of childhood. Research has shown that after attending school garden classes, children’s food-related behavior changes. Growing crops is not always easy—it can’t be done in the domestic space, and this lead to a loss of the long term positive effects. This paper presents a project that tries to teach children how to grow their own food indoors and outdoors, mixing real and virtual reality, connecting something natural like a plant to the Internet of Things (or IOT, a network of physical objects virtually connected to each other and to the web). The use of sensors related to an app makes this process more fun and useful for educational purposes. The aim of the project is to change children’s attitude towards food, increasing their knowledge about production and consumption, in order to reduce waste on a long term basis. The research has been developed in collaboration with Cisco NL and MediaLAB Amsterdam. The user testing has been executed with Dutch children in Amsterdam. PMID:26891301

  6. Inhibiting Corrosion in Gr/Al and Gr/Mg Metal Matrix Composites Using Nonequilibrium Alloying Techniques

    DTIC Science & Technology

    1992-06-01

    the alloy was immediately visually inspected and the appearance recorded. Distinguishing features such as reflectivity, cloudiness, color and surface...solid solution in the Al, and lack of properly oriented planes in the highly textured film. After heat treating, several new peaks were present in the AI...done to determine If the alloy composition or film texture were dependent on the type of substrate. The rationale behind using glass was that it would

  7. Comparison of Notch Strength between Gr/PEEK (APC-1 and APC-2) and Gr/Epoxy Composite Materials at Elevated Temperature.

    DTIC Science & Technology

    1985-12-01

    Compression Failure Specimen, In-hole View. 0" Crippled Fibers, Inter- i minar Failure, 2750 F...... 1󈧽 59. C8 mpression Failure Specimen, In-hole Vie a...sulphur and selenium, or a molecule, as in asbestos , sili- cones and organic polymers. Single linear polymers have the form X-A-A-... etc.... -A-A-Y

  8. 2-D Signal Generation Using State-Space Formulation.

    DTIC Science & Technology

    1985-12-01

    published that have established nonoptical .~ -~ Iimage processing as a viable area of research. A large portion of this research emphasizes the linear...research and the study of time-discrete linear systems. This thesis develops the discrete model of Roesser [Ref. 5] for linear image processing which... THESIS 2-D SIGNAL GENERATION USING STATE-SPACE FORMULATION - • by (.) Evangelos Theofilou December 1985 • Thesis Advisor: Sydney R. Parker Approved

  9. Type IV Creep Damage Behavior in Gr.91 Steel Welded Joints

    NASA Astrophysics Data System (ADS)

    Hongo, Hiromichi; Tabuchi, Masaaki; Watanabe, Takashi

    2012-04-01

    Modified 9Cr-1Mo steel (ASME Grade 91 steel) is used as a key structural material for boiler components in ultra-supercritical (USC) thermal power plants at approximately 873 K (600 °C). The creep strength of welded joints of this steel decreases as a result of Type IV creep cracking that forms in the heat-affected zone (HAZ) under long-term use at high temperatures. The current article aims to elucidate the damage processes and microstructural degradations that take place in the HAZ of these welded joints. Long-term creep tests for base metal, simulated HAZ, and welded joints were conducted at 823 K, 873 K, and 923 K (550 °C, 600 °C, and 650 °C). Furthermore, creep tests of thick welded joint specimens were interrupted at several time steps at 873 K (600 °C) and 90 MPa, after which the distribution and evolution of creep damage inside the plates were measured quantitatively. It was found that creep voids are initiated in the early stages (0.2 of life) of creep rupture life, which coalesce to form a crack at a later stage (0.8 of life). In a fine-grained HAZ, creep damage is concentrated chiefly in an area approximately 20 pct below the surface of the plate. The experimental creep damage distributions coincide closely with the computed results obtained by damage mechanics analysis using the creep properties of a simulated fine-grained HAZ. Both the concentration of creep strain and the high multiaxial stress conditions in the fine-grained HAZ influence the distribution of Type IV creep damage.

  10. Simulation on friction taper plug welding of AA6063-20Gr metal matrix composite

    NASA Astrophysics Data System (ADS)

    Hynes, N. Rajesh Jesudoss; Nithin, Abeyram M.

    2016-05-01

    Friction taper plug welding a variant of friction welding is useful in welding of similar and dissimilar materials. It could be used for joining of composites to metals in sophisticated aerospace applications. In the present work numerical simulation of friction taper plug welding process is carried out using finite element based software. Graphite reinforced AA6063 is modelled using the software ANSYS 15.0 and temperature distribution is predicted. Effect of friction time on temperature distribution is numerically investigated. When the friction time is increased to 30 seconds, the tapered part of plug gets detached and fills the hole in the AA6063 plate perfectly.

  11. GR simulations of binary black hole-neutron stars: Precursor electromagnetic signals

    NASA Astrophysics Data System (ADS)

    Paschalidis, Vasileios; Etienne, Zachariah B.; Shapiro, Stuart L.

    2014-03-01

    We present a new computational method for smoothly matching general relativistic ideal magnetohydrodynamics (MHD) to its force-free limit. The method is based on a flux-conservative formalism for MHD and its force-free limit, and a vector potential formulation for the induction equation to maintain the zero divergence constraint for the magnetic field. The force-free formulation evolves the magnetic field and the Poynting vector. Our force-free code passes a robust suite of tests, performed both in 1D flat spacetime and in 3D curved (black hole) spacetimes. Our matching technique successfully reproduces the aligned rotator force-free solution. As an application, we performed the first general relativistic, force-free simulations of neutron star (NS) magnetospheres in orbit about spinning and non-spinning black holes with BH:NS mass ratio 3:1. We find promising precursor EM emission: typical Poynting luminosities at, e.g., an orbital separation of 6.6 times the NS radius, are L ~ 6 ×1042 erg/s for a 1 . 4M⊙ NS endowed with a dipolar magnetic field with polar strength 1013G. The Poynting flux peaks within a broad beam of 40 degrees in the azimuthal direction, establishing a possible lighthouse effect.

  12. Scientific Potential of Decigo Pathfinder and Testing GR with Space-Borne Gravitational Wave Interferometers

    NASA Astrophysics Data System (ADS)

    Yagi, Kent

    2013-01-01

    Deci-Hertz Interferometer Gravitational Wave Observatory (DECIGO) Pathfinder (DPF) has an ability to detect gravitational waves (GWs) from galactic intermediate mass black hole binaries. If the signal is detected, it would be possible to determine parameters of the binary components. Furthermore, by using future space-borne GW interferometers, it would be possible to test alternative theories of gravity in the strong field regime. In this review paper, we first explain how the detectors like DPF and DECIGO/BBO work and discuss the expected event rates. Then, we review how the observed gravitational waveforms from precessing compact binaries with slightly eccentric orbits can be calculated both in general relativity and in alternative theories of gravity. For the latter, we focus on Brans-Dicke (BD) and massive gravity (MG) theories. After reviewing these theories, we show the results of the parameter estimation with DPF using the Fisher analysis. We also discuss a possible joint search of DPF and ground-based interferometers. Then, we show the results of testing alternative theories of gravity using future space-borne interferometers. DECIGO/BBO would be able to place 4-5 orders of magnitude stronger constraint on BD theory than the solar system experiment. This is still 1-2 orders of magnitude stronger than the future solar system mission such as ASTROD I. On the other hand, LISA should be able to put four orders of magnitude more stringent constraint on the mass of the graviton than the current solar system bound. DPF may be able to place comparable constraint on the MG theories as the solar system bound. We also discuss the prospects of using eLISA and ASTROD-GW in testing alternative theories of gravity. The bounds using eLISA are similar to the LISA ones, but ASTROD-GW performs the best in constraining MG theories among all the GW detectors considered in this paper.

  13. Adhesives for bonding RSI tile to GrPI structure for advanced space transportation systems

    NASA Technical Reports Server (NTRS)

    Smith, K. E.; Hamermesh, C. L.; Hogenson, P. A.

    1979-01-01

    A system was developed for bonding RSI tiles to a graphite/polymide composite substrate which would withstand the full range of environmental conditions. The bonding system, designated RA59, consists of a mixture of glass (sesquisiloxane) resin in RTV 560 silicone. A significant number of data points for the RA59 are in the 65-psi failure range both when tested, and after exposure to 700 F. This is over two times the best shear and tensile values obtained with RV60 at this temperature. It is concluded that with a thorough understanding of the critical parameters involved, the higher values should be obtained consistently with the RA59. This is of particular significance if higher strength tiles were to be used in a hard-bonded configuration.

  14. Making Breakfast with 5 oz of Cinnamon Porridge and 150 gr of Sweet Oatmeal

    NASA Astrophysics Data System (ADS)

    Rieke, Matthes; Bermudez, Luis; Pross, Benjamin; Chen, Aijun; Yu, Genong Eugene

    2013-04-01

    Have you ever had two or more data sources for the same region and the data don't seem to fit? One data source has incomplete attributes, features are missing in one source or there seems to be overlapping features representing the same feature? Can we run a process where the differences appear to become lost? Such process is called conflation. Conflation is important to help users see different sources in a clean way, all at once, via one known model. Conflation is a sophisticated process of unifying two or more separate datasets, which share certain characteristics, into one integrated all-encompassing dataset. In the process, different representations of a feature get folded into one feature. That target feature follows a particular model that is used to capture complementary information. Conflation was one of the topics advanced in a recent activity within the Open Geospatial Consortium (OGC). OGC is a consortium with about 500 members and serves as a global forum for the collaboration of developers and users of spatial data products and services, and to advance the development of international standards for geospatial interoperability. The OGC Interoperability Program conducts international interoperability testbeds, such as the OGC Web Services Phase 9 (OWS-9), that encourages rapid development, testing, validation, demonstration and adoption of open, consensus based standards and best practices. The OWS-9 advanced conflation of OGC Web Feature Services (WFS) that use heterogeneous GML application schemas. The conflation was performed in two phases. One performed geometry conflation, while the other performed attribute conflation. The attribute conflation makes use of mappings captured via ontologies in a knowledge base and available via a SPARQL server. To provide the conflation functionality in an interoperable way, a profile for the OGC Web Processing Service (WPS) was developed. In this service, various conflation rules setups have been integrated to define the behavior of attribute resolving. A simple "add-only" scenario copies those attributes, which are not present in the target dataset. A more advanced "add and update" scenario adjusts the values of present target attributes with values from one of the input datasets. "Qualitative update" methods require the interaction with an expert user who decides on the resulting value of attributes that are present in both the target and input sources. The work also included capturing of the provenance in a way that will allow a client application to display the information of the resulting conflated dataset at both feature and dataset level using ISO 19115 part I/II Metadata. The captured provenance at dataset level can be registered into an OGC standard compatible catalog service and further retrieved by client applications following interoperable and standard procedures.

  15. rHARM: Accretion and Ejection in Resistive GR-MHD

    NASA Astrophysics Data System (ADS)

    Qian, Qian; Fendt, Christian; Noble, Scott; Bugli, Matteo

    2017-01-01

    Turbulent magnetic diffusivity plays an important role for accretion disks and the launching of disk winds. We have implemented magnetic diffusivity and respective resistivity in the general relativistic MHD code HARM. This paper describes the theoretical background of our implementation, its numerical realization, our numerical tests, and preliminary applications. The test simulations of the new code rHARM are compared to an analytic solution of the diffusion equation and a classical shock tube problem. We have further investigated the evolution of the magnetorotational instability (MRI) in tori around black holes (BHs) for a range of magnetic diffusivities. We find an indication for a critical magnetic diffusivity (for our setup) beyond which no MRI develops in the linear regime and for which accretion of torus material to the BH is delayed. Preliminary simulations of magnetically diffusive thin accretion disks around Schwarzschild BHs that are threaded by a large-scale poloidal magnetic field show the launching of disk winds with mass fluxes of about 50% of the accretion rate. The disk magnetic diffusivity allows for efficient disk accretion that replenishes the mass reservoir of the inner disk area and thus allows for long-term simulations of wind launching for more than 5000 time units.

  16. GenASiS: A full GR-RMHD simulation framework: overview, goals, and preliminary tests

    NASA Astrophysics Data System (ADS)

    Tsatsin, Petr; Budiardja, Reuben; Cardall, Christian; Endeve, Eirik; Marronetti, Pedro; Mezzacappa, Anthony

    2011-04-01

    I present an overview of the General Astrophysics Simulation System (GenASiS). GenASiS is currently under development by a collaboration between researchers at the Oak Ridge National Laboratory (ORNL) and Florida Atlantic University (FAU) and features a high-resolution magnetohydrodynamics solver, a full general relativistic description of gravity based on the BSSN formalism, and will feature a two-moment multi-frequency neutrino radiation field evolution. We intend to use GenASiS to study core collapse supernovae, neutron star mergers, and their associated gamma-ray bursts.

  17. Quantitative structure-property relationship modeling of Grätzel solar cell dyes.

    PubMed

    Venkatraman, Vishwesh; Åstrand, Per-Olof; Alsberg, Bjørn Kåre

    2014-01-30

    With fossil fuel reserves on the decline, there is increasing focus on the design and development of low-cost organic photovoltaic devices, in particular, dye-sensitized solar cells (DSSCs). The power conversion efficiency (PCE) of a DSSC is heavily influenced by the chemical structure of the dye. However, as far as we know, no predictive quantitative structure-property relationship models for DSSCs with PCE as one of the response variables have been reported. Thus, we report for the first time the successful application of comparative molecular field analysis (CoMFA) and vibrational frequency-based eigenvalue (EVA) descriptors to model molecular structure-photovoltaic performance relationships for a set of 40 coumarin derivatives. The results show that the models obtained provide statistically robust predictions of important photovoltaic parameters such as PCE, the open-circuit voltage (V(OC)), short-circuit current (J(SC)) and the peak absorption wavelength λ(max). Some of our findings based on the analysis of the models are in accordance with those reported in the literature. These structure-property relationships can be applied to the rational structural design and evaluation of new photovoltaic materials.

  18. Adhesives for bonding RSI tile to Gr/Pi structure for advanced space transportation systems

    NASA Technical Reports Server (NTRS)

    Smith, K. E.; Hamermesh, C. L.; Hogenson, P. A.

    1979-01-01

    An adhesive was developed having improved high-temperature capability while retaining the ideal processing characteristics of RTV silicones. After evaluating several possibilities, mixtures of RTV with glass resins were selected as most promising. While results are not conclusive, tests of the final mixture evaluated, designated RA59, indicated capability of performing as a tile bonding agent to temperatures approaching 370C (700F) during repeated cycling.

  19. Maria Goeppert-Mayer Award Lecture: Kinetic Control in Heteroepitaxial Gr

    NASA Astrophysics Data System (ADS)

    Olmstead, Marjorie A.

    1996-03-01

    During the heteroepitaxy of strongly dissimilar materials, the complex growth kinetics and interface reactions of the first few atomic or molecular layers can control the structure and morphology of the next several hundred layers. Within these first few layers, the atomic and electronic structure continuously evolves as the bare substrate reacts to form a new interface compound, which in turn serves as the substrate for the nucleation and coalescence of subsequent layers. The substrate, reacted interface layer and subsequent layers each have distinct activation barriers for diffusion, and may have different step and island distributions. This results in variation of the time scales for diffusion to a step edge and interlayer transport (crossing atomic steps) relative to that for deposition of a monolayer, both during deposition and in different places on the growing surface. Using the powerful in-situ combination of X-ray photoelectron spectroscopy and diffraction, we have monitored this evolution of the atomic and electronic structure when the insulator calcium fluoride is deposited on silicon. We observe and explain different photoemission and auger emission energies for the first eight atomic layers (Ca-F-F-Ca-F-F-Ca-F), and exploit energy- resolved diffraction to separately determine their local structure. Using transmission electron microscopy, we relate the patterns of strain relaxation in thicker films to the initial nucleation behavior deduced from photoemission measurements. We find that terrace or step nucleation leads to laminar films, although with different relaxation patterns; combined step and terrace nucleation leads to rough films due to different upper- layer nucleation rates on the differently sized step- and terrace- nucleated islands. The results are explained within a general phenomenological model we have developed for the heteroepitaxy of dissimilar materials. This work was performed in collaboration with U. Hessinger, M. Leskovar, E. Rotenberg and J. D. Denlinger, and supported by the U. S. Department of Energy

  20. Theory-Agnostic Tests of GR with Multi-Band Gravitational Waves

    NASA Astrophysics Data System (ADS)

    Yunes, Nicolas; Barausse, Enrico; Chamberlain, Katherine

    2017-01-01

    The aLIGO detection of the black-hole binary GW150914 opened a new era for testing General Relativity in extreme gravity. One generic feature that can be constrained is the emission of dipole gravitational radiation by compact binaries. This is excluded to high accuracy in binary pulsars, but entire classes of gravitational theories predict this effect in binaries predominantly (or only) involving black holes. In this talk, I will describe how future, joint observations of GW150914-like systems by aLIGO and eLISA will dramatically improve bounds on dipole emission from black-hole binaries, probing extreme gravity with unprecedented accuracy. We acknowledge support from the NSF CAREER Grant PHY-1250636.

  1. Effect of stress on energy flux deviation of ultrasonic waves in GR/EP composites

    NASA Technical Reports Server (NTRS)

    Prosser, William H.; Kriz, R. D.; Fitting, Dale W.

    1990-01-01

    Ultrasonic waves suffer energy flux deviation in graphite/epoxy because of the large anisotropy. The angle of deviation is a function of the elastic coefficients. For nonlinear solids, these coefficients and thus the angle of deviation is a function of stress. Acoustoelastic theory was used to model the effect of stress on flux deviation for unidirectional T300/5208 using previously measured elastic coefficients. Computations were made for uniaxial stress along the x3 axis (fiber axis) and the x1 for waves propagating in the x1x3 plane. These results predict a shift as large as three degrees for the quasi-transverse wave. The shift in energy flux offers a new nondestructive technique of evaluating stress in composites.

  2. It's All Connected: The Power of Proportional Reasoning to Understand Mathematics Concepts, Gr. 6-8

    ERIC Educational Resources Information Center

    Whitman, Carmen

    2011-01-01

    "It's All Connected" provides teachers of mathematics the support they need to improve their instruction. This in-demand collection of lessons for grades 6-8 explores proportionality, proportional relationships, and proportional reasoning, acknowledging that the ability to reason proportionally is crucial in the middle school mathematics…

  3. Construction of moment-matching multinomial lattices using Vandermonde matrices and Gröbner bases

    NASA Astrophysics Data System (ADS)

    Lundengârd, Karl; Ogutu, Carolyne; Silvestrov, Sergei; Ni, Ying; Weke, Patrick

    2017-01-01

    In order to describe and analyze the quantitative behavior of stochastic processes, such as the process followed by a financial asset, various discretization methods are used. One such set of methods are lattice models where a time interval is divided into equal time steps and the rate of change for the process is restricted to a particular set of values in each time step. The well-known binomial- and trinomial models are the most commonly used in applications, although several kinds of higher order models have also been examined. Here we will examine various ways of designing higher order lattice schemes with different node placements in order to guarantee moment-matching with the process.

  4. Quasi-Local Energy-Momentum and Angular Momentum in GR: A Review Article

    NASA Astrophysics Data System (ADS)

    Szabados, László B.

    2004-12-01

    The present status of the quasi-local mass-energy-momentum and angular momentum constructions in general relativity is reviewed. First the general ideas, concepts, and strategies, as well as the necessary tools to construct and analyze the quasi-local quantities are recalled. Then the various specific constructions and their properties (both successes and defects) are discussed. Finally, some of the (actual and potential) applications of the quasi-local concepts and specific constructions are briefly mentioned. This review is based on the talks given at the Erwin Schrödinger Institute, Vienna, in July 1997, at the Universität Tübingen, in May 1998, and at the National Center for Theoretical Sciences in Hsinchu and at the National Central University, Chungli, Taiwan, in July 2000.

  5. Propagation of flexural mode AE signals in GR/EP composite plates

    NASA Technical Reports Server (NTRS)

    Prosser, W. H.; Gorman, Michael R.

    1992-01-01

    A Fourier phase technique has been used to measure the dispersion of the flexural plate mode in graphite-epoxy composite laminates. Classical plate theory is shown to be of limited value in predicting the dispersion of this mode because it assumes that the effects of shear deformation and rotatory inertia are negligible. Higher-order plate theory, which includes these effects, gives much better agreement with measured values.

  6. Characterization of Longitudinal Splitting and Fiber Breakage in Gr/Ep using Acoustic Emission Data

    NASA Technical Reports Server (NTRS)

    Ely, Thomas M.; Hill, Eric K.

    1993-01-01

    A composite tensile test specimen was designed such that fiber breakage and longitudinal splitting occurred at a known position in the specimen. By studying the acoustic signature of each failure mechanism distinct characteristics in the data were identified that uniquely related the acoustic emission parameters with either fiber breakage or longitudinal splitting.

  7. VizieR Online Data Catalog: Lowell GR* red stars (Giclas+ 1972-1978)

    NASA Astrophysics Data System (ADS)

    Giclas, H. L.; Burnham, R.; Thomas, N. G.

    2009-10-01

    This file shows accurate coordinates for the ~500 red stars found by Giclas et al. near the south galactic pole. This was part of a general survey of large proper motion stars. In 2002 August I sent Gerard Jasniewicz corrections for the first batch of 47 stars, mainly just to see for myself what sorts of stars are involved. These 47 stars were observed photoelectrically by Warren (1976MNRAS.176..667W), who obtained UBV photometry. Although every star was a dwarf, they were not extraordinarily red, but merely garden-variety late-K and early-M dwarfs. Gerard corrected all those entries in SIMBAD, and the UBV data are linked. I have now gone through the entire list and show improved positions below. For most stars UCAC3 positions were adopted. In this part of the sky UCAC3 draws from both the Schmidt plate-scans and the Yale SPM series as well as the UCAC astrograph series. The multiple epochs mean the positions and proper motions for the fainter stars are usually the best ones. There are still a few where the motion is forced to zero or is blank, and UCAC2, 2MASS, or other source is used, as specified in the column 's' following the position. I show V magnitudes for all the stars. For stars brighter than between V = 14.5 and 15.0, the ASAS-3 is preferred. For the fainter stars this is merely average of the GSC-2.3 blue and red magnitudes. Where there is overlap, the naive b+r/2 from the Schmidt plates matches ASAS-3 to within 0.1 mag usually, and only sometimes differs by as much as 0.3 mag. Stars with motion >0".15/year are flagged 'lg pm' (large proper motion). In identifying the stars, I also found a substantial number of common-motion pairs, which have all been sent to Brian Mason (USNO) for possible inclusion in the WDS. I noticed a few stars whose 2MASS J-K colors are >0.9mag; these must be late-K/early-M giants --- interesting in themselves, since at Vmag 15 they are ~10 kpc out in the halo. Those I noticed are flagged in the remarks, but there could be more early/mid-K giants whose colors are similar to the ~M0 dwarfs. A bunch of SIMBAD aliases have sent to the CDS, mostly now fixed in the database by Arnaud Siebert. Though there are no spectral types here, the list will help deal with the Pesch & Sanduleak objective-prism survey for M dwarfs at the south galactic pole (1978AJ.....83.1090P, 1982PASP...94..345P), which needs a similar going-over. (1 data file).

  8. The importance of GR for the radius of massive white dwarfs

    SciTech Connect

    Carvalho, Geanderson; Marinho, Rubens; Malheiro, Manuel

    2015-12-17

    In this work we investigate the structure of WD stars using the Tolman-Oppenheimer-Volkoff equations and compare with the Newtonian equations of gravitation in order to put in evidence the importance of the General Relativity in the study of these stars. Instead of using politropic equations of state we have solved the equations using the exact relativistic energy equation for the model of completely degenerate electron gas. We find a good fit of the TOV solution with the general EoS for the WD mass-radius diagram. We propose that our fit has to be used as relation between mass and radius for general relativistic WD instead of that Newtonian M ∼ 1/R{sup 3}, this fit is given by M = R/(a + bR + cR{sup 2} + dR{sup 3} + kR{sup 4}), where a, b, c and d are parameters and 1/k is the constant of the Newtonian mass-radius relation and it can be used in simulation study of binary systems that occurs accretion.

  9. Greenland Inland Traverse (GrIT): 2010 Mobility Performance and Implications

    DTIC Science & Technology

    2011-10-01

    to resupply science stations at NEEM and Summit via over-snow transport. The inaugural traverse in 2008, while successful, encountered mobility...route varied from the 2008 route through the transition to avoid new crevasses and from NEEM to Summit to travel over snow predicted to have lower...The National Science Foundation Office of Polar Programs has imple- mented an over-snow traverse to resupply science stations at NEEM and Summit on the

  10. Evaluation of a thermoplastic polyimide (422) for bonding GR/PI composite

    NASA Technical Reports Server (NTRS)

    Progar, Donald J.

    1988-01-01

    A hot-melt processable copolyimide previously studied and characterized as an adhesive for bonding Ti-6Al-4V was used to bond Celion 6000/LARC-160 composite. Comparisons are made for the two adherend systems. A bonding cycle was determined for the composite bonding and lap shear specimens were prepared which were thermally exposed in a forced-air oven for up to 5000 h at 204 C. The lap shear strengths (LSSs) were determined at RT, 177, and 204 C. After thermal exposure at RT, 177, and 204 C the LSS decreased significantly; however, a slight increase was noted for the 204 C tests. Initially the LSS values are higher for the bonded Ti-6Al-4V than for the bonded composite, however, the LSS decreases dramatically between 5000 and 10,000 h of 204 C thermal exposure. Longer periods of thermal exposure up to 20,000 h results in further decreases in the LSSs. Although the bonded composite retained useful strengths for exposures up to 5000 h, based on the poor results of the bonded Ti-6Al-4V beyond 5000 h, the 422 adhesive bonded composites would most likely also produce poor strengths beyond 5000 h exposure. Adhesive bonded composite lap shear specimens exposed to boiling water for 72 h exhibited greatly reduced strengths at all test temperatures. The percent retained after water boil for each test temperature was essentially the same for both systems.

  11. Evaluation of a thermoplastic polyimide (422) for bonding GR/PI composite

    NASA Technical Reports Server (NTRS)

    Progar, Donald J.

    1988-01-01

    A hot-melt processable copolyimide previously studied and characterized as an adhesive for bonding Ti-6Al-4V was used to bond Celion 6000/LARC-160 composite. Comparisons are made for the two adherend systems. A bonding cycle was determined for the composite bonding and lap shear specimens were prepared which were thermally exposed in a forced-air oven for up to 5000 h at 204 C. The lap shear strengths (LSSs) were determined at RT, 177, and 204 C. After thermal exposure at RT, 177, and 204 C the LSS decreased significantly; however, a slight increase was noted for the 204 C tests. Initially the LSS values are higher for the bonded Ti-6Al-4V than for the bonded composite, however, the LSS decreases dramatically between 5000 and 10,000 h of 204 C thermal exposure. Longer periods of thermal exposure up to 20,000 h results in further decreases in the LSSs. Although the bonded composite retained useful strengths for exposures up to 5000 h, based on the por results of the bonded Ti-6Al-4V beyond 5000 h, the 422 adhesive bonded composites would most likely also produce poor strengths beyond 5000 h exposure. Adhesive bonded composite lap shear specimens exposed to boiling water for 72 h exhibited greatly reduced strengths at all test temperatures. The percent retained after water boil for each test temperature was essentially the same for both systems.

  12. GrB-TWEAK: A Potential Novel Biologic for NSCLC Therapy

    DTIC Science & Technology

    2015-09-01

    Che- motherapeutic agents include doxorubicin, GemZAR, cisplatin (CDDP), 5-fluorouracil (5-FU), TAXOL, and vinblastine. Apoptosis assays Western blot...in combination with doxorubicin, 5-FU, cisplatin , GemZAR, taxol, or vinblastine revealed the mean CI to be less than 1.0 at multiple doses on HT-29...also observed with cisplatin , GemZAR, and 5-FU on theTNBC cell lineMDA-MB-231 (Supplementary Fig. S4). Interestingly, doxorubicin in combination with

  13. Gr and hp-1 tomato mutants unveil unprecedented interactions between arbuscular mycorrhizal symbiosis and fruit ripening

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The roots of plants interact with soil mycorrhizal fungi to facilitate soil nutrient acquisition by the plant and carbon transfer to the fungus. Here we use tomato fruit ripening mutations to demonstrate that this root interaction communicates with and supports genetic mechanisms associated with th...

  14. Dry Sliding Tribological Studies of AA6061-B4C-Gr Hybrid Composites

    NASA Astrophysics Data System (ADS)

    Monikandan, V. V.; Joseph, M. A.; Rajendrakumar, P. K.

    2016-10-01

    The dry sliding behavior of stir-cast AA6061-10 wt.% B4C composites containing 2.5, 5 and 7.5 wt.% graphite particles was studied as a function of applied load, sliding speed and sliding distance on a pin-on-disk tribotester. The wear rate and friction coefficient increased with increase in applied load and sliding distance. The increase in graphite addition reduced the increase in wear rate and friction coefficient in the sliding speed range 2-2.5 m/s. Scanning electron microscopy of the worn pin revealed a graphite tribolayer, and transmission electron microscopy revealed overlapping deformation bands under 30 N applied load. Upon increasing the applied load to 40 N, welded region with fine crystalline structure was formed due to dynamic recrystallization of AA6061 alloy matrix.

  15. GR-AMRVAC code applications: accretion onto compact objects, boson stars versus black holes

    NASA Astrophysics Data System (ADS)

    Meliani, Z.; Grandclément, P.; Casse, F.; Vincent, F. H.; Straub, O.; Dauvergne, F.

    2016-08-01

    In the close vicinity of a compact object strong gravity imprints its signature onto matter. Systems that contain at least one compact object are observed to exhibit extreme physical properties and typically emit highly energetic radiation. The nature of the compact objects that produce the strongest gravitational fields is to date not settled. General relativistic numerical simulations of fluid dynamics around black holes, neutron stars, and other compact objects such as boson stars (BSs) may give invaluable insights into this fundamental question. In order to study the behavior of fluid in the strong gravity regime of an arbitrary compact object we develop a new general relativistic hydrodynamics code. To this end we extend the existing versatile adaptive mesh refinement code MPI-AMRVAC into a general relativistic hydrodynamics framework and adapt it for the use of numerically given spacetime metrics. In the present article we study accretion flows in the vicinity of various types of BSs whose numerical metrics are calculated by the KADATH spectral solver library. We design specific tests to check the reliability of any code intending to study BSs and compare the solutions with those obtained in the context of Schwarzschild black holes. We perform the first ever general relativistic hydrodynamical simulations of gas accretion by a BS. The behavior of matter at small distances from the center of a BS differs notably from the black hole case. In particular we demonstrate that in the context of Bondi spherical accretion the mass accretion rate onto non-rotating BSs remains constant whereas it increases for Schwarzschild black holes. We also address the scenario of non-spherical accretion onto BSs and show that this may trigger mass ejection from the interior of the BS. This striking feature opens the door to forthcoming investigations regarding accretion-ejection flows around such types of compact objects.

  16. VizieR Online Data Catalog: GALEX-GR6/7 data release (Bianchi+ 2014)

    NASA Astrophysics Data System (ADS)

    Bianchi, L.; Conti, A.; Shiao, B

    2014-10-01

    The Galaxy Evolution Explorer (GALEX) was a NASA Small Explorer mission which imaged the sky in 2 ultraviolet bands, FUV (far-UV) and NUV (near-UV) and provided the first UV sky surveys. Its characteristics are: -------------------------------------------------------------------- FUV NUV -------------------------------------------------------------------- Bandwidth 1344-1786 1771-2831 (Å) Effective wavelength 1538.6 2315.7 (Å) Astrometry (R<0.6deg) 0.59 0.49 (arcsec) Photometry (1 sigma) 0.05 0.03 (ABmag) Zero point 18.82 20.08 (ABmag) Image resolution 4.2 5.3 (arcsec/pix) Spectral resolution 200 118 (δλ/λ) -------------------------------------------------------------------- GALEX data products include a series of sky imaging surveys with different depth and coverage, UV photometry of over 200 million sources, and about 100,000 slitless grism spectra. The Bianchi et al.2014 catalog includes all the FUV, NUV data at the end of the mission, for the surveys with the widest sky-coverage (AIS and MIS); it gives a unique source list (duplicate measurements are removed) and excludes the artifact-plagued data along the field rim. Details, subcatalogs, and science tools for using this catalog can be found at http://dolomiti.pha.jhu.edu/uvsky (1 data file).

  17. Report on the Results of Site Testing to Determine National Register Eligibility for Sites 39GR32, 39GR53, 39LM33 and 39LM39, in the Lake Francis Case Area, South Dakota. Volume 2. Appendices

    DTIC Science & Technology

    1987-06-01

    Engineers, Omaha District, Contract No. DACW45-78-C-0131. Weakly, Ward F. 1971 Tree -Ring Dating and Archaeology in South Dakota. Plains...considered an intergral part of the total analysis of the sites. Other forms of special analysis may be necessary, such as radiocarbon dating, pollen ...carefully labeled and provided with the final report. If features are found, samples should be collected for flotation, pollen , and radiocarbon analysis

  18. Tactile stimulation during different developmental periods modifies hippocampal BDNF and GR, affecting memory and behavior in adult rats.

    PubMed

    Antoniazzi, Caren T D; Metz, Vinícia G; Roversi, Karine; Freitas, Daniele L; Vey, Luciana T; Dias, Verônica T; Segat, Hecson J; Duarte, Marta M M F; Burger, Marilise E

    2017-02-01

    Recent studies have shown that tactile stimulation (TS) in pups is able to prevent and/or minimize fear, anxiety behaviors, and addiction to psychostimulant drugs in adult rats. In these studies, animals have been exposed to handling from postnatal day (PND) 1-21. This study was designed to precisely establish which period of preweaning development has a greater influence of TS on neuronal development. After birth, male pups were exposed to TS from PND1-7, PND8-14, and PND15-21. In adulthood, the different periods of postnatal TS were assessed through behavioral, biochemical, and molecular assessments. Animals that received TS from PND8-14 showed lower anxiety-like symptoms, as observed by decreased anxiety index in elevated plus maze. This same TS period was able to improve rats' working memory by increasing the percentage of alternation rate in Y-maze, and induce better ability to cope with stressful situations, as showed in the defensive burying test by a reduced time of burying behavior. On the other hand, animals receiving TS in the first week of life showed longest cumulative burying time, which is directly related to increased anxiety-like behavior. Moreover, TS from PND8-14 showed lower corticosterone levels and better oxidative status, as observed by decreased lipid peroxidation and increased catalase activity in the hippocampus. Brain-derived neurotrophic factor (BDNF) immunocontent was increased in the hippocampus of animals receiving TS from PND8-14, while glucocorticoid receptors immunocontent was decreased in both TS1-7 and TS15-21 , but not TS8-14 . To the best of our knowledge, this study is the first to show TS can be more efficient if applied over a focused period of neonatal development (PND8-14) and this beneficial influence can be reflected on reduced emotionality and increased ability to address stressful situations in adulthood. © 2016 Wiley Periodicals, Inc.

  19. The Grüneisen parameter and its higher order derivatives for the Earth lower mantle and core

    NASA Astrophysics Data System (ADS)

    Shanker, J.; Sunil, K.; Sharma, B. S.

    2017-01-01

    In the present study we propose a simple formula for the reciprocal γ versus pressure-bulk modulus ratio. This formula satisfies the boundary conditions at zero pressure and also at infinite pressure which is a basic requirement for any thermodynamic relationship or equation of state to be physically acceptable. It should be mentioned that the infinite pressure values of thermoelastic properties (Kumar et al., 2015; Stacey, 2005) are the extrapolated values in the limit of infinite pressure by considering the material to remain in the same structure or same phase. In fact, no material can exist at infinite pressure. This point has been elaborated very convincingly by Stacey and Davis (2004).

  20. Society News: RAS Awards 2011; Prof. Richard Ellis; Prof. Eberhard Grün; Prof. Gilles Chabrier; Prof. Roger Searle;

    NASA Astrophysics Data System (ADS)

    2011-02-01

    Each year the RAS recognizes outstanding achievement in astronomy and geophysics by the award of medals and prizes. Candidates are nominated by Fellows and the awards made by a committee of Fellows, ensuring that these scientists have earned the respect and admiration of their peers in the research community.

  1. Effect of Stress on Energy Flux Deviation of Ultrasonic Waves in Ultrasonic Waves in GR/EP Composites

    NASA Technical Reports Server (NTRS)

    Prosser, William H.; Kriz, R. D.; Fitting, Dale W.

    1990-01-01

    Ultrasonic waves suffer energy flux deviation in graphite/epoxy because of the large anisotropy. The angle of deviation is a function of the elastic coefficients. For nonlinear solids, these coefficients and thus the angle of deviation is a function of stress. Acoustoelastic theory was used to model the effect of stress on flux deviation for unidirectional T300/5208 using previously measured elastic coefficients. Computations were made for uniaxial stress along the x3 axis fiber axis) and the x1 axis for waves propagating in the x1x3 plane. These results predict a shift as large as three degrees for the quasi-transverse wave. The shift in energy flux offers new nondestructive technique of evaluating stress in composites.

  2. Develop and demonstrate manufacturing processes for fabricating graphite filament reinforced polymide (Gr/PI) composite structural elements

    NASA Technical Reports Server (NTRS)

    Chase, V. A.; Harrison, E. S.

    1985-01-01

    A study was conducted to assess the merits of using graphite/polyimide, NR-150B2 resin, for structural applications on advanced space launch vehicles. The program was divided into two phases: (1) Fabrication Process Development; and (2) Demonstration Components. The first phase of the program involved the selection of a graphite fiber, quality assurance of the NR-150B2 polyimide resin, and the quality assurance of the graphite/polyimide prepreg. In the second phase of the program, a limited number of components were fabricated before the NR-150B2 resin system was removed from the market by the supplier, Du Pont. The advancement of the NR-150B2 polyimide resin binder was found to vary significantly based on previous time and temperature history during the prepregging operation. Strength retention at 316C (600F) was found to be 50% that of room temperature strength. However, the composite would retain its initial strength after 200 hours exposure at 316C (600F). Basic chemistry studies are required for determining NR-150B2 resin binder quality assurance parameters. Graphite fibers are available that can withstand high temperature cure and postcure cycles.

  3. Detailed Observations and Sampling of the Sea Cliff Hydrothermal Field (GR-14) on the Northern Gorda Ridge

    NASA Astrophysics Data System (ADS)

    McClain, J. S.; Zierenberg, R.; Clague, D. A.; Von Damm, K. L.; Davis, A.; Goffredi, S.; Mayer, N.; Orphan, V.; Olsen, E.; Ross, S. L.

    2001-12-01

    During the summer of 2000, on a research cruise of the MBARI research ship, Western Flyer, we deployed the ROV Tiburon for a series of dives at the Sea Cliff Hydrothermal site on the northern Gorda Ridge. The Sea Cliff site is near the top of a terrace on the west facing rift valley wall (fault), about 300 meters above, and 3 km east of the ridge axis. The 1996 Gorda Ridge eruption occurred on axis in the region west and south of the vent site. The vents were first predicted on the basis of water column anomalies and seafloor structure, and the field was discovered in 1988 during dives of the Sea Cliff submersible. In 2000, we made 4 dives at the site and collected a suite of rock and vent fluid samples. The high temperature water vents from as many as 10 individual chimneys. Measured vent temperatures at several of the chimneys fall in a narrow range of around 304\\deg C. The chimneys are arrayed along two low ridges that are oriented roughly perpendicular to the strike of the rift valley. Venting fluids have low salinity indicating subsurface phase separation. The waters are isotopically enriched (\\delta 18O = 1.9%), suggesting extensive water-rock interaction. The chimneys themselves are primarily anhydrite and a pale green Mg-rich clay with minor amounts of amorphous silica, pyrrhotite, wurtzite, and isocubanite. The chimneys are delicate and are surrounded by aprons (5 -10 m) of collapsed chimney material. As a result, no macro fauna were observed colonizing the high temperature vents. Silica-rich hydrothermal crust and talus cover the fault slope. A broad region of diffuse venting surrounds the active chimneys and locally supports a rich biological community that includes blue ciliate mats near the vents, that give way to tube worm fields and low tube worm mounds formed on massive barite. The Sea Cliff Hydrothermal site is unusual in that it lies off axis and above the rift valley floor. Faulting must play a role in its location and perhaps geometry, and the orientation of the chimney ridges is consistent with east-west lineaments noted in previous work. It is unclear if the faults link the site to the axis, where recent volcanism has been observed. Temporal variations in the Sea Cliff site are difficult to assess based on the limited information from previous dives in the area. In general, the geometry of the field appears unchanged since first visited in 1988, and we observed many of the same types of hydrothermal features. We found slightly higher vent temperatures and many more chimneys than observed previously, but that may reflect the improved navigation and the increased bottom time permitted by the use of the ROV. Future studies will better constrain the answers to the questions about the stability of the field.

  4. Anti-Gr-1 antibody depletion fails to eliminate hepatic myeloid-derived suppressor cells in tumor-bearing mice.

    PubMed

    Ma, Chi; Kapanadze, Tamar; Gamrekelashvili, Jaba; Manns, Michael P; Korangy, Firouzeh; Greten, Tim F

    2012-12-01

    Recent studies show that the liver is a preferred organ for the accumulation of MDSC. In this study, we examined the effect of systemic RB6-8C5 treatment on hepatic MDSC in tumor-bearing mice. EL4 tumor-bearing mice were injected i.p. with RB6-8C5, and hepatic, splenic, and blood MDSCs were analyzed by flow cytometry. Unexpectedly, hepatic MDSC remained in the liver, although RB6-8C5 completely eliminated them from the spleen and peripheral blood 24 h after treatment. Secondary antibody staining confirmed the presence of RB6-8C5-bound MDSC in the liver of mice with s.c. tumors. Similar observations were made in two other (colon and melanoma) tumor models. Whereas RB6-8C5 injection induced cell death of hepatic MDSC, as shown by Annexin V/7-AAD staining, these cells were replaced immediately, leading to a constant, increased frequency of hepatic MDSC. Adoptively transferred MDSC migrated preferentially to the liver after RB6-8C5 treatment, suggesting that hepatic MDSCs are reconstituted rapidly after depletion. Finally, hepatic MDSC remained immunosuppressive despite RB6-8C5 injection. Our study demonstrates that RB6-8C5 is not suitable for depletion of hepatic MDSCs and analysis of their function.

  5. Durabilité chimique de l'uraninite précipitée sur le grès du Navajo

    NASA Astrophysics Data System (ADS)

    Abdelouas, Abdesselam; Lutze, Werner; Nuttall, Eric

    1998-07-01

    Batch and sand column experiments were conducted with sandstone and ground water to investigate the oxidation of uraninite. Uraninite and mackinawite precipitated by indigenous bacteria in contaminated ground water from a former uranium mill tailings site near Tuba City, Arizona, USA. Leaching of a sand column containing uraninite and mackinawite by oxygen-saturated uncontaminated ground water from the same site showed that uraninite was slowly dissolved. U(VI) concentration in the effluent of column did not exceed 4 μg·L -1. Batch experiments showed that most of the oxygen was consumed by mackinawite oxidation. Hence it is concluded that the oxidation of uraninite is insignificant in the presence of mackinawite.

  6. Grüne Infrastruktur in den Städten Nordrhein-Westfalens. Bedeutung als Standortfaktor und Einfluss auf das Standortmarketing

    NASA Astrophysics Data System (ADS)

    Schäffer, Ina

    2016-06-01

    Hardly any other city in North Rhine-Westphalia has such a green image as the city of Münster. It embodies the image of a livable city in Germany. Other North Rhine-Westphalian cities also work on their external perception and are approaching the task of getting a greener image for themselves in many ways. A central question is how it is done precisely and whether urban green infrastructure can be a locational factor to affect location-based marketing. This article deals with the strategies of various cities in North Rhine-Westphalia.

  7. Enhancer-like activity of A1gR1-binding site in alginate gene activation: positional, orientational, and sequence specificity.

    PubMed Central

    Fujiwara, S; Zielinski, N A; Chakrabarty, A M

    1993-01-01

    Significant activation of promoters of alginate genes such as algD or algC occurs in mucoid Pseudomonas aeruginosa during its proliferation in the lungs of cystic fibrosis patients. These promoters have been shown to be responsive to environmental signals such as high osmolarity. The signaling is mediated by a so-called two-component signal transduction system, in which a soluble protein, AlgR2, undergoes autophosphorylation and transfers the phosphate to a DNA-binding response regulator protein, AlgR1. The phosphorylated form of AlgR1 has a high affinity for binding at upstream sequences of both the algC and algD promoters. Two AlgR1-binding sites (ABS) have been reported upstream of the algC gene. One of the two ABSs (algC-ABS1, located at -94 to -81) is critical for the algC activation process, while the second ABS (algC-ABS2, located at +161 to +174) is only weakly active. We now report the presence of a third ABS within the structural gene of algC, and this ABS (algC-ABS3) is also important for algC promoter activation. algC-ABS1 can be replaced functionally by algC-ABS2, algD-ABS1, or algD-ABS2 and somewhat weakly by algD-ABS3. Introduction of a half-integral turn in the DNA helix between the algC site of transcription initiation and algC-ABS1 allowed only slight reduction of promoter activity, suggesting that the binding site could be appreciably functional even when present in the opposite face of the helix. Activation of the algC promoter is independent of the relative location (upstream or downstream of the mRNA start site), the number of copies, or the orientation of algC-ABS1, suggesting that it behaves like a eukaryotic enhancer element in promoting transcription from the algC promoter. Images PMID:8366031

  8. ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.

    PubMed

    Gallego-Ortega, David; Ledger, Anita; Roden, Daniel L; Law, Andrew M K; Magenau, Astrid; Kikhtyak, Zoya; Cho, Christina; Allerdice, Stephanie L; Lee, Heather J; Valdes-Mora, Fatima; Herrmann, David; Salomon, Robert; Young, Adelaide I J; Lee, Brian Y; Sergio, C Marcelo; Kaplan, Warren; Piggin, Catherine; Conway, James R W; Rabinovich, Brian; Millar, Ewan K A; Oakes, Samantha R; Chtanova, Tatyana; Swarbrick, Alexander; Naylor, Matthew J; O'Toole, Sandra; Green, Andrew R; Timpson, Paul; Gee, Julia M W; Ellis, Ian O; Clark, Susan J; Ormandy, Christopher J

    2015-12-01

    During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angiogenesis, and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis. Myeloid-derived suppressor cells, a group of immature neutrophils recently identified as mediators of vasculogenesis and metastasis, were recruited to the tumor in response to ELF5. Depletion of these cells using specific Ly6G antibodies prevented ELF5 from driving vasculogenesis and metastasis. Expression signatures in luminal A breast cancers indicated that increased myeloid cell invasion and inflammation were correlated with ELF5 expression, and increased ELF5 immunohistochemical staining predicted much shorter metastasis-free and overall survival of luminal A patients, defining a group who experienced unexpectedly early disease progression. Thus, in the MMTV-PyMT mouse mammary model, increased ELF5 levels drive metastasis by co-opting the innate immune system. As ELF5 has been previously implicated in the development of antiestrogen resistance, this finding implicates ELF5 as a defining factor in the acquisition of the key aspects of the lethal phenotype in luminal A breast cancer.

  9. High-throughput computational screening of thermal conductivity, Debye temperature, and Grüneisen parameter using a quasiharmonic Debye model

    NASA Astrophysics Data System (ADS)

    Toher, Cormac; Plata, Jose J.; Levy, Ohad; de Jong, Maarten; Asta, Mark; Nardelli, Marco Buongiorno; Curtarolo, Stefano

    2014-11-01

    The quasiharmonic Debye approximation has been implemented within the aflow and Materials Project frameworks for high-throughput computational materials science (Automatic Gibbs Library, agl), in order to calculate thermal properties such as the Debye temperature and the thermal conductivity of materials. We demonstrate that the agl method, which is significantly cheaper computationally compared to the fully ab initio approach, can reliably predict the ordinal ranking of the thermal conductivity for several different classes of semiconductor materials. In particular, a high Pearson (i.e., linear) correlation is obtained between the experimental and agl computed values of the lattice thermal conductivity for a set of 75 compounds including materials with cubic, hexagonal, rhombohedral, and tetragonal symmetry.

  10. Längengrad. Die wahre Geschichte eines einsamen Genies, welches das größte wissenschaftliche Problem seiner Zeit löste.

    NASA Astrophysics Data System (ADS)

    Sobel, D.

    This book is a German translation, by M. Fienbork, from the American original "Longitude", published in 1995. It tells the story of John Harrison (1693 - 1776), the inventor of a chronometer for precise time determination onboard of ships.

  11. Wie grün wünscht sich die Bevölkerung Deutschlands ihre Städte?. Ergebnisse der Naturbewusstseinsstudie 2015

    NASA Astrophysics Data System (ADS)

    Ströher, Helena; Mues, Andreas Wilhelm

    2016-06-01

    Green areas are of high importance for the population in Germany. This is demonstrated by the representative outcomes of the latest Awareness-of-Nature survey for 2015. Most interviewees do not only value urban greens as personally important but also state that they perceive them as crucial for society and environment. The article focuses especially on the perception by people from different age groups and levels of education. It highlights that the strong awareness of the population provides a good fundament for the objectives and strategies of social, environmental and nature conservation policies.

  12. Detection of High Levels of Endocrine Activity in Selected Environmental Surface Water Samples Using ER, AR, and GR-mediated In Vitro Bioassays

    EPA Science Inventory

    Determining the associated health risks of exposure to complex mixtures in the environment is a recognized challenge. The Chemical Mixtures project, a collaborative effort between USEPA and USGS, is making a step in that direction by examining the co-occurrence of chemicals and b...

  13. Un nouveau genre de dinosaure sauropode de la formation des Grès supérieurs (Aptien-Albien) du Laos

    NASA Astrophysics Data System (ADS)

    Allain, Ronan; Taquet, Philippe; Battail, Bernard; Dejax, Jean; Richir, Philippe; Véran, Monette; Limon-Duparcmeur, Franck; Vacant, Renaud; Mateus, Octavio; Sayarath, Phouvong; Khenthavong, Bounxou; Phouyavong, Sitha

    1999-10-01

    The partly-articulated postcranial remains of two sauropod skeletons recently found in Tang Vay (Savannakhet Province, Laos) are assigned to the species Tangvayosaurus hoffeti (nov. gen., nov. sp.). The derived characters present in the new material confirm the presence of titanosaurs in South East Asia at the end of the Early Cretaceous, but are not consistent with its placement within Titanosaurus genus as first done by Hoffet in 1942. All of the material relative to this species is therefore referred to a new genus: Tangvayosaurus. Tangvayosaurus and the Thai genus Phuwiangosaurus have strong affinities and are considered as primitive titanosaurs.

  14. MHD simulations of NSNS mergers in full GR: the role of the initial B field on the emergence of sGRB jets I

    NASA Astrophysics Data System (ADS)

    Ruiz, Milton; Lang, Ryan; Paschalidis, Vasileios; Shapiro, Stuart L.

    2016-03-01

    Mergers of neutron star-neutron star (NSNS) binaries are among the most promising candidates for the engines that power short gamma-ray bursts (sGRBs). The most likely sGRB model requires the presence of a highly relativistic jet. However, recent relativistic simulations of NSNS mergers have shown that it is difficult for such jets to emerge following the delayed collapse of the hypermassive neutron star (HMNS) remnant. Varying the initial NS magnetic field in an NSNS binary, we have performed magnetohydrodynamic simulations in full general relativity that explore the formation of jets from the black hole-disk system following the HMNS collapse. In this talk we focus on initial dipole magnetic fields confined to the neutron star interior. This work was supported by NSF Grant PHY-1300903 and NASA Grant NNX13AH44G at the University of Illinois at Urbana- Champaign, as well as by the Simons Foundation and NSF Grant PHY-1305682 at Princeton University.

  15. Eichfunktion und analysenfehler in der spektrochemischen Analytik—I. Regression bei konstanter standardabweichung für die meßgröße

    NASA Astrophysics Data System (ADS)

    Klockenkämper, R.; Bubert, H.

    For spectrochemical analyses, calibration is a basic operation generally necessary for quantitative determinations. It yields the calibration function and by inversion the analytical function which is not directly accessible.—In the following, a scheme is developed in order to find-according to different methods of analysis-the respective suitable calibration function: it should give an expectable standard deviation as small as possible for the estimated content, it should, if possible, be linear and it should be applicable in a range of content as large as possible. The condition of Part I of this paper is the constant standard deviation for the measuring quantity in this range.-The scheme is examined by five analytical examples: for trace analyses (OES-ICP and AAS) the simple relationship between the intensity I and the concentration c is linear anyhow and yields a constant absolute standard deviation not dependent on the trace content. For analyses over a large range of concentration, a double-logarithmic transformation leads to linearity and constant relative standard deviation (OES with Laser). If physical matrix effects are existing, for example in surface analysis (ISS) the 'binary-ratio method' is recommended; in this case, the relative standard deviation is proportional to (1 - c). For XRF of main and additional components, the non-linear regression of the equation of Beattie and Brissey is to be realized with √ I-values.

  16. Stent thrombosis and restenosis: what have we learned and where are we going? The Andreas Grüntzig Lecture ESC 2014

    PubMed Central

    Byrne, Robert A.; Joner, Michael; Kastrati, Adnan

    2015-01-01

    Modern-day stenting procedures leverage advances in pharmacotherapy and device innovation. Patients treated with contemporary antiplatelet agents, peri-procedural antithrombin therapy and new-generation drug-eluting stents (DES) have excellent outcomes over the short to medium term. Indeed, coupled with the reducing costs of these devices in most countries there remain very few indications where patients should be denied treatment with standard-of-care DES therapy. The two major causes of stent failure are stent thrombosis (ST) and in-stent restenosis (ISR). The incidence of both has reduced considerably in recent years. Current clinical registries and randomized trials with broad inclusion criteria show rates of ST at or <1% after 1 year and ∼0.2–0.4% per year thereafter; rates of clinical ISR are 5% respectively. Angiographic surveillance studies in large cohorts show rates of angiographic ISR of ∼10% with new-generation DES. The advent of high-resolution intracoronary imaging has shown that in many cases of late stent failure neoatherosclerotic change within the stented segment represents a final common pathway for both thrombotic and restenotic events. In future, a better understanding of the pathogenesis of this process may translate into improved late outcomes. Moreover, the predominance of non-stent-related disease as a cause of subsequent myocardial infarction during follow-up highlights the importance of lifestyle and pharmacological interventions targeted at modification of the underlying disease process. Finally, although recent developments focus on strategies which circumvent the need for chronically indwelling stents—such as drug-coated balloons or fully bioresorbable stents—more data are needed before the wider use of these therapies can be advocated. PMID:26417060

  17. The Air Force Global Reach Laydown (GR1): An Allowance Standard Review Using the Estimating Supplies Program to Develop a Requirements-Based Materiel Solution

    DTIC Science & Technology

    2008-07-02

    Trichinosis Ascariasis Giardiasis Tapeworm Hookworm Pinworm 255 Migraine All Cases 256 Hemorrhoidal Disease All Cases 258 Severe Hypertension 259...Diarrheal Disease Severe 1 253 Helminthic Disease Including Trichinosis Ascariasis Giardiasis Tapeworm Hookworm Pinworm 1 258 Severe Hypertension 1 275

  18. Luminal expression of cubilin is impaired in Imerslund-Gräsbeck syndrome with compound AMN mutations in intron 3 and exon 7

    PubMed Central

    Namour, Fares; Dobrovoljski, Gabriele; Chery, Celine; Audonnet, Sandra; Feillet, François; Sperl, Wolfgang; Gueant, Jean-Louis

    2011-01-01

    Juvenile megaloblastic anaemia 1 (OMIM # 261100) is a rare autosomic disorder characterized by selective cobalamin mal-absorption and inconstant proteinuria produced by mutations in either CUBN or AMN genes. Amnionless, the gene product of AMN, is a transmembrane protein that binds tightly to the N-terminal end of cubilin, the gene product of CUBN. Cubilin binds to intrinsic factor-cobalamin complex and is expressed in the distal intestine and the proximal renal tubule. We report a compound AMN heterozygosity with c.742C>T, p.Gln248X and c.208-2A>G mutations in 2 siblings that led to premature termination codon in exon 7 and exon 6, respectively. It produced a dramatic decrease in receptor activity in urine, despite absence of CUBN mutation and normal affinity of the receptor for intrinsic factor binding. Heterozygous carriers for c.742T and c.208-2G had no pathological signs. These results indicate that amnionless is essential for the correct luminal expression of cubilin in humans. PMID:21750092

  19. Elektroninės cigaretės: naujas būdas mesti rūkyti ar nauja grėsmė?

    PubMed Central

    Aistė, Aleknaitė; Monika, Andrijauskaitė; Justė, Latauskienė; Viktorija, Andrejevaitė

    2016-01-01

    Nuo 2010 m. tarp suaugusiųjų ir paauglių išaugo elektroninių cigarečių vartojimas. Dauguma el. cigarečių vartotojų anksčiau yra rūkę tradicinius tabako gaminius. Didžioji dalis žmonių el. cigaretes suvokia kaip priemonę, padėsiančią mesti rūkyti ar sumažinti surūkomų įprastinių cigarečių kiekį. Elektroninės cigaretės yra prietaisas, susidedantis iš skysčiu užpildytos kasetės, kaitiklio bei baterijos. Nuspaudus mygtuką įjungiamas kaitiklis, kuris šildo skystį, o, šiam tapus garais, jie įkvepiami. Visų rūšių el. skysčių pagrindinės sudedamosios dalys yra glicerolis arba propileno glikolis, papildomai gali būti pridedama nikotino ir / ar aromatų. Skysčiuose taip pat nustatyta įvairių kitų cheminių medžiagų. Ilgalaikio el. cigarečių vartojimo pasekmės sveikatai nėra išaiškintos, manoma, kad jos turėtų būti saugesnės nei rūkyti įprastines cigaretes. Nėra pakankamai ištirtas el. cigarečių skysčiuose esančių medžiagų toksiškumas. Trūksta duomenų apie el. cigarečių, kaip pagalbinės priemonės norint mesti rūkyti, veiksmingumą ir saugumą. Gydytojas norinčiam mesti rūkyti pacientui pirmiausia turėtų pasiūlyti patvirtintas pakaitinės nikotino terapijos ar kitas pagalbines priemones ir užtikrinti, kad pacientas gautų informaciją apie naujausius medikamentus, galinčius jam padėti. Jei pacientas atsisako šių priemonių ir renkasi el. cigaretes, gydytojas turėtų informuoti apie abejotiną jų saugumą ir veiksmingumą. Visuomenėje kyla susirūpinimas, kad el. cigarečių rūkymas gali paskatinti priklausomybę nikotinui ir padidinti norą išbandyti įprastines cigaretes. Nerimą kelia ir neapribotas el. cigarečių vartojimas viešosiose vietose. Nėra žinoma, kokią įtaką aplinkinių sveikatai gali turėti pasyvus garinimas. El. cigarečių reglamentavimas visame pasaulyje skiriasi ir laikui bėgant kinta. PMID:28356791

  20. Grüne Infrastruktur -. Konzepte und Strategien zur Förderung eines Bewusstseins für den Wert von Stadtgrün

    NASA Astrophysics Data System (ADS)

    Menke, Peter

    2016-06-01

    Due to climate change, but also because of the demographic change and financial constraints in many municipalities, the future of cities is a currently much-discussed topic. Conflicts over land-use are inevitable: As densification is an essential principle in growing cities, the pressure on open (green) spaces rises. Climate Change and water-management as well as mobility-issues and air-quality confront municipalities with new challenges, in terms of open space planning and greenery in the city. It is necessary to save the existing green in these days of budget-shortage and other priorities in communities. Municipalities have to raise new strategies to strengthen the awareness of the value of green in public and in the local business.

  1. Synthesis of new C-25 and C-26 steroidal acids as potential ligands of the nuclear receptors DAF-12, LXR and GR.

    PubMed

    Dansey, María V; Del Fueyo, María C; Veleiro, Adriana S; Di Chenna, Pablo H

    2017-05-01

    A new methodology to obtain C-25 and C-26 steroidal acids starting from pregnenolone is described. Construction of the side chain was achieved by applying the Mukaiyama aldol reaction with a non-hydrolytic work-up to isolate the trapped silyl enol ether with higher yields. Using this methodology we synthesized three new steroidal acids as potential ligands of DAF-12, Liver X and Glucocorticoid nuclear receptors and studied their activity in reporter gene assays. Our results show that replacement of the 21-CH3 by a 20-keto group in the side chains of the cholestane scaffold of DAF-12 or Liver X receptors ligands causes the loss of the activity.

  2. Assessment of Negligible Creep, Off-Normal Welding and Heat Treatment of Gr91 Steel for Nuclear Reactor Pressure Vessel Application

    SciTech Connect

    Ren, Weiju; Terry, Totemeier

    2006-10-01

    Two different topics of Grade 91 steel are investigated for Gen IV nuclear reactor pressure vessel application. On the first topic, negligible creep of Grade 91 is investigated with the motivation to design the reactor pressure vessel in negligible creep regime and eliminate costly surveillance programs during the reactor operation. Available negligible creep criteria and creep strain laws are reviewed, and new data needs are evaluated. It is concluded that modifications of the existing criteria and laws, together with their associated parameters, are needed before they can be reliably applied to Grade 91 for negligible creep prediction and reactor pressure vessel design. On the second topic, effects of off-normal welding and heat treatment on creep behavior of Grade 91 are studied with the motivation to better define the control over the parameters in welding and heat treatment procedures. The study is focused on off-normal austenitizing temperatures and improper cooling after welding but prior to post-weld heat treatment.

  3. "Was für Grün in der Stadt?". Politische Aushandlungsprozesse um städtische Grün- und Freiräume am Beispiel des urbanen Gärtnerns in Schweizer Städten

    NASA Astrophysics Data System (ADS)

    Klöti, Tanja; Tappert, Simone; Drilling, Matthias

    2016-06-01

    Urban green space is a key subject of actual urban negotiation processes on how the city shall develop. Visions of the ideal city are reflected in the meanings currently ascribed to urban gardening. Thereby the relation between human and nature as well as between build and natural environment in the city plays a central role. Results from different Swiss cities show that allotment gardens as well as newer forms of urban gardening are oscillating between a compensatory and a complementary understanding of nature, and they equally combine the desire for pristine nature with the demand for functional green space in the city.

  4. Erratum: Hayward IP, Bridle KR, Campbell GR, Underwood PA, Campbell JH (1995) Effect of Extracellular Matrix Proteins on Vascular Smooth Muscle Cell Phenotype. Cell Biology International 19: 839-846. doi: 10.1006/cbir.1995.1019.

    PubMed

    2016-02-01

    The above article, published in print in Cell Biology International in September 1995 and online on 2 January 2013 in Wiley Online Library (http://onlinelibrary.wiley.com/doi/10.1006/cbir.1995.1019/abstract), is an exact duplicate of the article 'Effect of Extracellular Matrix Proteins on Vascular Smooth Muscle Cell Phenotype' (Hayward et al., ), which was published in the previous issue of Cell Biology International (Hayward et al., ). The duplicate publication is the result of an administrative error. The publisher apologises for any inconvenience.

  5. Bipolar transurethral enucleation and resection of the prostate versus bipolar resection of the prostate for prostates larger than 60gr: A retrospective study at a single academic tertiary care center

    PubMed Central

    Wei, Yong; Xu, Ning; Chen, Shao-Hao; Li, Xiao-Dong; Zheng, Qing-Shui; Lin, Yun-Zhi; Xue, Xue-Yi

    2016-01-01

    ABSTRACT Objective: To evaluate the efficacy and safety of bipolar transurethral enucleation and resection of the prostate (B-TUERP) versus bipolar transurethral resection of the prostate (B-TURP) in the treatment of prostates larger than 60g. Material and Methods: Clinical data for 270 BPH patients who underwent B-TUERP and 204 patients who underwent B-TURP for BPH from May 2007 to May 2013 at our center were retrospectively analyzed. Outcome measures included operative time, decreased hemoglobin level, total prostate specific antigen (TPSA), International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), quality of life (QoL) score, post void residual urine volume (RUV), bladder irrigation duration, hospital stay, and the weight of resected prostatic tissue. Other measures included perioperative complications including transurethral resection syndrome (TURS), hyponatremia, blood transfusion, bleeding requiring surgery, postoperative acute urinary retention, urine incontinence and urinary sepsis. Patients in both groups were followed for two years. Results: Compared with the B-TURP group, the B-TUERP group had shorter operative time, postoperative bladder irrigation duration and hospital stay, a greater amount of resected prostatic tissue, less postoperative hemoglobin decrease, better postoperative IPSS and Qmax, as well as lower incidences of hyponatremia, urinary sepsis, blood transfusion requirement, urine incontinence and reoperation (P<0.05 for all). Conclusions: B-TUERP is superior to B-TURP in the management of large volume BPH in terms of efficacy and safety, but this finding needs to be validated in further prospective, randomized, controlled studies. PMID:27564286

  6. Initiation d'un bassin transporté: l'exemple du ≪ sillon méso-hellénique ≫ au Tertiaire (Grèce)

    NASA Astrophysics Data System (ADS)

    Ferrière, Jacky; Reynaud, Jean-Yves; Migiros, Georges; Proust, Jean-Noël; Bonneau, Michel; Pavlopoulos, Andreas; Houze, Alexandre

    1998-04-01

    The Mesohellenic trough (MHT), northern Greece, is a Tertiary molassic piggy-back basin that formed in several stages. This evolution is related to the underthrusting of the external Hellenides below the internal Hellenides. Sedimentologic and tectonic studies of its western border allow us to reconstruct the first stages of the basin differentiation and to propose a new interpretation of the mechanisms at the origin of the MHT. The MHT is made of several overlapping individual basins that evolved successively through time, from west to east, starting in the Upper Eocene. These basins develop along the border of dissymetrical faulted flexures, which are controlled by the characteristics of the major tectonic units.

  7. Response to Comment by H. Lough, Department of Civil Engineering, University of Canterbury, Christchurch, New Zealand, on the Paper " Stream Depletion Predictions using Pumping Test Data from A Heterogeneous Stream-Aquifer System (A Case Study from the Gr

    SciTech Connect

    Kollet, S J; Zlotnik, V A

    2004-12-20

    We thank H. Lough for her interest in our data set and the attempt to re-analyze our results (Kollet and Zlotnik, 2003) using the recent model by Hunt (2003). We welcome others to share our unique data set of the pumping test from the Prairie Creek site, Nebraska, USA. Nevertheless we believe that this particular attempt failed, because H. Lough selected a wrong model of semi-confined aquifer conditions for the interpretation of the pumping test data, which was collected in an unconfined aquifer. H. Lough based her selection on the three distinct drawdown segments observed during the test. It is well known that geologically distinct aquifers can yield a three-segment drawdown response under pumping conditions (e.g., Streltsova, 1988). Examples include unconfined aquifers (e.g., Neuman, 1972; Moench, 1997), aquifers with double porosity or fractures (e.g., Barenblatt et al., 1960; Boulton and Streltsova-Adams, 1978), and (semi-) confined aquifers in contact with aquitards (e.g. Cooley and Case, 1973; Moench, 1985). At the Prairie Creek site the aquifer is unconfined. The interpretation of the pumping test data collected at the site using type curves that are valid for an aquifer-aquitard system is a mistake. In fact, this approach illustrates a typical problem associated with inverse modeling: drastically different models can closely reproduce a system response and yield some parameter estimates, although the models do not represent the real system adequately. Here, the improper model yields some parameter estimates for an aquitard, although the aquitard does not exist at the Prairie Creek test site. We must also unequivocally state that the model by Hunt (2003) is clearly formulated and correct for stream-aquifer-aquitard systems within the stated limitations (pumping wells screened only in the lowest stratigraphic layer, etc.). However, the Hunt (1999) or BZT (Butler et al., 2001) models should be used for interpreting pumping tests near streams in non-leaky aquifers as outlined in our study (Kollet and Zlotnik, 2003). The purpose of the comment by H. Lough is to examine three drawdown segments and results from Kollet and Zlotnik (2003) using a newer analytical model of stream-aquifer interactions by Hunt (2003). We will address the key issues of this comment in this paper.

  8. Marine Structural Steel Toughness Data Bank. Volume 4

    DTIC Science & Technology

    1990-08-31

    A588 GR A K11430 1-12A588 Gr B A588 Gr B K12043 1-12 A588 Gr C A588 Gr C K11538 1-12A537-A A537 Gr A K02400 1-13 API 5L Gr X60 1-14 A656-70 A656 Gr 70...and HSLA 80 containing primarily Cu, Ni, Cr and Mo; • Medium to high strength low alloy steels A537, CG-537, A656, A737, ABS-EH36, and API 5L...ASTM UNS PRIORITY NAME SPEC NUMBER HYS0 A543 Gr C(1) K31820 1-1 A710-A A710 Gr A K20747 1-2 CG A537M A537 Cl 1 K12437 1-3ABS-B A131 Gr B K02102 1-4 API

  9. Graduation Rates for Selected Cohorts, 2006-11; Student Financial Aid, Academic Year 2013-14; and Admissions in Postsecondary Institutions, Fall 2014. First Look (Provisional Data). NCES 2015-181

    ERIC Educational Resources Information Center

    Ginder, Scott A.; Kelly-Reid, Janice E.; Mann, Farrah B.

    2015-01-01

    This "First Look" presents findings from the provisional data of the IPEDS winter 2014-15 data collection, which included four survey components: (1) Graduation Rates (GR); (2) 200 Percent Graduation Rates (GR200); (3) Student Financial Aid (SFA); and (4) Admissions (ADM). GR and GR200 present graduation rates for selected cohorts within…

  10. 40 CFR Table 1 to Subpart Rrrrr of... - Emission Limits

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... indurating furnace processing magnetite ExistingNew 0.01 gr/dscf.0.006 gr/dscf. 3. Grate kiln indurating furnace processing magnetite ExistingNew 0.01 gr/dscf.0.006 gr/dscf. 4. Grate kiln indurating...

  11. 40 CFR Table 1 to Subpart Rrrrr of... - Emission Limits

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... indurating furnace processing magnetite ExistingNew 0.01 gr/dscf.0.006 gr/dscf. 3. Grate kiln indurating furnace processing magnetite ExistingNew 0.01 gr/dscf.0.006 gr/dscf. 4. Grate kiln indurating...

  12. The first X-ray crystal structure of the glucocorticoid receptor bound to a non-steroidal agonist

    SciTech Connect

    Madauss, Kevin P.; Bledsoe, Randy K.; Mclay, Iain; Stewart, Eugene L.; Uings, Iain J.; Weingarten, Gordon; Williams, Shawn P.

    2009-07-23

    The amino-pyrazole 2,6-dichloro-N-ethyl benzamide 1 is a selective GR agonist with dexamethasone-like in vitro potency. Its X-ray crystal structure in the GR LBD (Glucocorticoid ligand-binding domain) is described and compared to other reported structures of steroidal GR agonists in the GR LBD (3E7C).

  13. First increment of second specimen results to performance assessment-long term corrosion

    SciTech Connect

    Wang, F.

    1998-01-01

    In this correspondence, we report the 6 month corrosion data of corrosion resistant alloys (alloys 825, C22 & C4, and Ti Gr 12 & Ti Gr 16, and Inconel 625) and one year data of corrosion-allowance materials (A387 Gr22, A516 Gr55 and A27 Gr70-40), intermediate resistance alloys (Monel 400 and CDA 715) and corrosion resistant materials (alloys C22 and 625 only).

  14. Interaction of nucleobases with silicon doped and defective silicon doped graphene and optical properties.

    PubMed

    Mudedla, Sathish Kumar; Balamurugan, Kanagasabai; Kamaraj, Manoharan; Subramanian, Venkatesan

    2016-01-07

    The interaction of nucleobases (NBs) with the surface of silicon doped graphene (SiGr) and defective silicon doped graphene (dSiGr) has been studied using electronic structure methods. A systematic comparison of the calculated interaction energies (adsorption strength) of NBs with the surface of SiGr and dSiGr with those of pristine graphene (Gr) has also been made. The doping of graphene with silicon increases the adsorption strength of NBs. The introduction of defects in SiGr further enhances the strength of interaction with NBs. The appreciable stability of complexes (SiGr-NBs and dSiGr-NBs) arises due to the partial electrostatic and covalent (Si···O(N)) interaction in addition to π-π stacking. The interaction energy increases with the size of graphene models. The strong interaction between dSiGr-NBs and concomitant charge transfer causes significant changes in the electronic structure of dSiGr in contrast to Gr and SiGr. Further, the calculated optical properties of all the model systems using time dependent density functional theory (TD-DFT) reveal that absorption spectra of SiGr and dSiGr undergo appreciable changes after adsorption of NBs. Thus, the significant variations in the HOMO-LUMO gap and absorption spectra of dSiGr after interaction with the NBs can be exploited for possible applications in the sensing of DNA nucleobases.

  15. Granzyme H induces cell death primarily via a Bcl-2-sensitive mitochondrial cell death pathway that does not require direct Bid activation.

    PubMed

    Ewen, Catherine L; Kane, Kevin P; Bleackley, R Chris

    2013-07-01

    Natural killer and T cell-mediated cytotoxicity is important for the elimination of viruses and transformed cells. The granule lytic pathway utilizes perforin and granzymes to induce cell death, while receptor-mediated lytic pathways rely on molecules such as FasL. Pro-apoptotic activities of Granzyme B (GrB) and Fas are well-established, and many of their cellular targets have been identified. However, humans express additional related granzymes - GrA, GrM, GrK, and GrH. Neither the cytotoxic potential of GrH, nor the mechanism by which GrH may induce target cell death is currently understood. We proposed that GrH would have pro-apoptotic activity that would be distinct from that of GrB and FasL, which could be relevant when Fas/FasL or GrB activity or death pathways were impaired. Our results, using a purified recombinant form of GrH, revealed that GrH induced cell death via a Bcl-2-sensitive mitochondrial pathway without direct processing of Bid. Additionally, neither the apoptosome nor caspase-3 was essential to the induction of GrH-mediated cell death. However, GrH did directly process DFF45, potentially leading to DNA damage. Our findings support the idea that multiple, non-redundant death pathways may be initiated by cytotoxic cells to counteract various immune evasion strategies.

  16. Effect of carbamate pesticides on perforin, granzymes A-B-3/K, and granulysin in human natural killer cells.

    PubMed

    Li, Qing; Kobayashi, Maiko; Kawada, Tomoyuki

    2015-09-01

    We previously found that ziram, a carbamate pesticide, significantly reduced perforin, granzyme A (GrA), granzyme B (GrB), granzyme 3/K (Gr3/K), and granulysin (GRN) levels in NK-92MI cells, a human natural killer (NK) cell line. To investigate whether other carbamate pesticides also show similar toxicity on human NK cells, we conducted further experiments with NK-92CI cells, a human NK cell line, using a more sensitive assay. We previously confirmed that NK-92CI cells express CD56, perforin, GrA, GrB, Gr3/K, and GRN and are highly cytotoxic to K562 cells in a chromium release assay, which are more sensitive to organophosphorus pesticides and ziram than the NK-92MI cell line. NK-92CI cells were treated with ziram, thiram, maneb, or carbaryl at various concentrations for 4-24 h at 37°C in vitro. Thereafter, intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN were determined by flow cytometry. It was found that all carbamate pesticides significantly reduced the intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN in NK-92CI cells in a dose-dependent manner. However, the strength of the effect differed among the pesticides, and the order was thiram > ziram > maneb > carbaryl. In addition, it was also found that the degree of the reductions differed among the five proteins, with perforin more sensitive to pesticides than GRN, GrA, GrB, and Gr3/K, and the order was perforin > GRN > Gr3/K ≒ GrA ≒ GrB.

  17. Slip Activity in Single Grains Extracted from Polycrystalline Specimen by X-Ray Line Broadening (Preprint)

    DTIC Science & Technology

    2010-01-01

    4 6 8 0.005 0.010 -101-3 -110-2 1-10-2F W H M [ 1 /n m ] K [ 1/nm ] Gr #44 Gr #50 Gr #72 -101-1 1-101 (a...0 2 4 6 0.000 0.005 0.010 (b) K2Ccalc [ 1/nm ] FW H M [ 1 /n m ] Gr #44 Gr #50 Gr #72 17 Figure 5. The FWHM (in 1/nm scales) in...Preprint 01 January 2010 – 01 January 2010 4 . TITLE AND SUBTITLE SLIP ACTIVITY IN SINGLE GRAINS EXTRACTED FROM POLYCRYSTALLINE SPECIMEN BY X-RAY

  18. Identification and characterization of a novel chloroplast/mitochondria co-localized glutathione reductase 3 involved in salt stress response in rice.

    PubMed

    Wu, Tsung-Meng; Lin, Wan-Rong; Kao, Yun-Ting; Hsu, Yi-Ting; Yeh, Ching-Hui; Hong, Chwan-Yang; Kao, Ching Huei

    2013-11-01

    Glutathione reductases (GRs) are important components of the antioxidant machinery that plants use to respond against abiotic stresses. In rice, one cytosolic and two chloroplastic GR isoforms have been identified. In this work, we describe the cloning and characterization of the full-length cDNA encoding OsGR3, a chloroplast-localized GR that up to now was considered as a non-functional enzyme because of assumed lack of N-terminal conserved domains. The expression of OsGR3 in E. coli validated that it can be translated as a protein with GR activity. OsGR3 shows 76 and 53 % identity with OsGR1 (chloroplastic) and OsGR2 (cytosolic), respectively. Phylogenetic analysis revealed 2 chloroplastic GRs in Poaceae species, including rice, sorghum and brachypodium, but only one chloroplastic GR in dicots. A plastid transit peptide is located at the N terminus of OsGR3, and genetic transformation of rice with a GR3-GFP fusion construct further confirmed its localization in chloroplasts. Furthermore, OsGR1 and OsGR3 are also targeted to mitochondria, which suggest a combined antioxidant mechanism in both chloroplasts and mitochondria. However, both isoforms showed a distinct response to salinity: the expression of OsGR3 but not OsGR1 was induced by salt stress. In addition, the transcript level of OsGR3 was greatly increased with salicylic acid treatment but was not significantly affected by methyl jasmonate, dehydration or heat shock stress. Our results provide new clues about the possible roles of functional OsGR3 in salt stress and biotic stress tolerance.

  19. Electrochemical sensors and biosensors based on less aggregated graphene.

    PubMed

    Bo, Xiangjie; Zhou, Ming; Guo, Liping

    2017-03-15

    As a novel single-atom-thick sheet of sp(2) hybridized carbon atoms, graphene (GR) has attracted extensive attention in recent years because of its unique and remarkable properties, such as excellent electrical conductivity, large theoretical specific surface area, and strong mechanical strength. However, due to the π-π interaction, GR sheets are inclined to stack together, which may seriously degrade the performance of GR with the unique single-atom layer. In recent years, an increasing number of GR-based electrochemical sensors and biosensors are reported, which may reflect that GR has been considered as a kind of hot and promising electrode material for electrochemical sensor and biosensor construction. However, the active sites on GR surface induced by the irreversible GR aggregations would be deeply secluded inside the stacked GR sheets and therefore are not available for the electrocatalysis. So the alleviation or the minimization of the aggregation level for GR sheets would facilitate the exposure of active sites on GR and effectively upgrade the performance of GR-based electrochemical sensors and biosensors. Less aggregated GR with low aggregation and high dispersed structure can be used in improving the electrochemical activity of GR-based electrochemical sensors or biosensors. In this review, we summarize recent advances and new progress for the development of electrochemical sensors based on less aggregated GR. To achieve such goal, many strategies (such as the intercalation of carbon materials, surface modification, and structural engineering) have been applied to alleviate the aggregation level of GR in order to enhance the performance of GR-based electrochemical sensors and biosensors. Finally, the challenges associated with less aggregated GR-based electrochemical sensors and biosensors as well as related future research directions are discussed.

  20. Biogenic hydroxysulfate green rust, a potential electron acceptor for SRB activity

    NASA Astrophysics Data System (ADS)

    Zegeye, Asfaw; Huguet, Lucie; Abdelmoula, Mustapha; Carteret, Cédric; Mullet, Martine; Jorand, Frédéric

    2007-11-01

    Microbiological reduction of a biogenic sulfated green rust (GR2(SO42-)), was examined using a sulfate reducing bacterium ( Desulfovibrio alaskensis). Experiments investigated whether GR2(SO42-) could serve as a sulfate source for D. alaskensis anaerobic respiration by analyzing mineral transformation. Batch experiments were conducted using lactate as the electron donor and biogenic GR2(SO42-) as the electron acceptor, at circumneutral pH in unbuffered medium. GR2(SO42-) transformation was monitored with time by X-ray diffraction (XRD), Transmission Mössbauer Spectroscopy (TMS), Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS), Transmission Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy (XPS). The reduction of sulfate anions and the formation of iron sulfur mineral were clearly identified by XPS analyses. TMS showed the formation of additional mineral as green rust (GR) and vivianite. XRD analyses discriminated the type of the newly formed GR as GR1. The formed GR1 was GR1(CO32-) as indicated by DRIFTS analysis. Thus, the results presented in this study indicate that D. alaskensis cells were able to use GR2(SO42-) as an electron acceptor. GR1(CO32-), vivianite and an iron sulfur compound were formed as a result of GR2(SO42-) reduction by D. alaskensis. Hence, in environments where geochemical conditions promote biogenic GR2(SO42-) formation, this mineral could stimulate the anaerobic respiration of sulfate reducing bacteria.

  1. Brain-derived neurotrophic factor signaling rewrites the glucocorticoid transcriptome via glucocorticoid receptor phosphorylation.

    PubMed

    Lambert, W Marcus; Xu, Chong-Feng; Neubert, Thomas A; Chao, Moses V; Garabedian, Michael J; Jeanneteau, Freddy D

    2013-09-01

    Abnormal glucocorticoid and neurotrophin signaling has been implicated in numerous psychiatric disorders. However, the impact of neurotrophic signaling on glucocorticoid receptor (GR)-dependent gene expression is not understood. We therefore examined the impact of brain-derived neurotrophic factor (BDNF) signaling on GR transcriptional regulatory function by gene expression profiling in primary rat cortical neurons stimulated with the selective GR agonist dexamethasone (Dex) and BDNF, alone or in combination. Simultaneous treatment with BDNF and Dex elicited a unique set of GR-responsive genes associated with neuronal growth and differentiation and also enhanced the induction of a large number of Dex-sensitive genes. BDNF via its receptor TrkB enhanced the transcriptional activity of a synthetic GR reporter, suggesting a direct effect of BDNF signaling on GR function. Indeed, BDNF treatment induces the phosphorylation of GR at serine 155 (S155) and serine 287 (S287). Expression of a nonphosphorylatable mutant (GR S155A/S287A) impaired the induction of a subset of BDNF- and Dex-regulated genes. Mechanistically, BDNF-induced GR phosphorylation increased GR occupancy and cofactor recruitment at the promoter of a BDNF-enhanced gene. GR phosphorylation in vivo is sensitive to changes in the levels of BDNF and TrkB as well as stress. Therefore, BDNF signaling specifies and amplifies the GR transcriptome through a coordinated GR phosphorylation-dependent detection mechanism.

  2. Glyphosate Effects on Plant Mineral Nutrition, Crop Rhizosphere Microbiota, and Plant Disease in Glyphosate-Resistant Crops

    PubMed Central

    2012-01-01

    Claims have been made recently that glyphosate-resistant (GR) crops sometimes have mineral deficiencies and increased plant disease. This review evaluates the literature that is germane to these claims. Our conclusions are: (1) although there is conflicting literature on the effects of glyphosate on mineral nutrition on GR crops, most of the literature indicates that mineral nutrition in GR crops is not affected by either the GR trait or by application of glyphosate; (2) most of the available data support the view that neither the GR transgenes nor glyphosate use in GR crops increases crop disease; and (3) yield data on GR crops do not support the hypotheses that there are substantive mineral nutrition or disease problems that are specific to GR crops. PMID:23013354

  3. Molecular mechanisms of glucocorticoid receptor signaling.

    PubMed

    Labeur, Marta; Holsboer, Florian

    2010-01-01

    This review highlights the most recent findings on the molecular mechanisms of the glucocorticoid receptor (GR). Most effects of glucocorticoids are mediated by the intracellular GR which is present in almost every tissue and controls transcriptional activation via direct and indirect mechanisms. Nevertheless the glu-cocorticoid responses are tissue -and gene- specific. GR associates selectively with corticosteroid ligands produced in the adrenal gland in response to changes of humoral homeostasis. Ligand interaction with GR promotes either GR binding to genomic glucocorticoid response elements, in turn modulating gene transcription, or interaction of GR monomers with other transcription factors activated by other signalling pathways leading to transrepression. The GR regulates a broad spectrum of physiological functions, including cell differentiation, metabolism and inflammatory responses. Thus, disruption or dysregulation of GR function will result in severe impairments in the maintenance of homeostasis and the control of adaptation to stress.

  4. 37 CFR 201.3 - Fees for registration, recordation, and related services, special services, and services...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Registration of a claim in a group of contributions to periodicals (Form GR/CP), published photographs, or... updates thereto or group registration of published photographs 35 Forms GR/CP, PA, SR, VA and SE...

  5. 37 CFR 201.3 - Fees for registration, recordation, and related services, special services, and services...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) Registration of a claim in a group of contributions to periodicals (Form GR/CP), published photographs, or... updates thereto or group registration of published photographs 35 Forms GR/CP, PA, SR, VA and SE...

  6. Grass immunotherapy induces inhibition of allergen-specific human peripheral blood mononuclear cell proliferation.

    PubMed

    Baskar, S; Hamilton, R G; Norman, P S; Ansari, A A

    1997-02-01

    The peripheral blood mononuclear cells (PBMC) from humans allergic to grass pollens (GR+ subjects) show strong in vitro proliferative responses to purified allergens from Lolium perenne pollen Lol p 1, and to a lesser extent to Lol p 2 and Lol p 3. By contrast, PBMC from grass allergic patients undergoing immunotherapy (GR + IT subjects) exhibit a very poor Lol p-specific proliferative response, similar to that observed in nongrass allergic subjects (GR-subjects). Unlike GR-subjects, both GR+ and GR + IT subjects have high levels of antigen-specific serum IgG and IgE antibodies to Lol p 1, Lol p 2 and Lol p 3. While GR+ subjects exhibit a significant correlation between antigen-specific serum antibody and PBMC responses, GR + IT subjects do not show a correlation between the two responses. The possible mechanisms by which immunotherapy may modulate allergen-specific T cell proliferative response are discussed.

  7. 40 CFR 63.11162 - What are the standards and compliance requirements for existing sources?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-gases from each roaster to a particulate matter (PM) control device and to a sulfuric acid plant... cubic foot (gr/dscf) from the exhaust vent of an anode casting furnace. (5) 0.015 gr/dscf from...

  8. Glyphosate-resistant Palmer Amaranth in the U.S.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since glyphosate-resistant (GR) crops were commercialized, glyphosate has been extensively used to effectively and economically manage weeds. The adoption of GR technology also provided growers with the capabilities needed to rapidly adopt conservation tillage production systems. Selection pressure ...

  9. PREFACE: The 5th International Conference on Radiotherapy Gel Dosimetry (DOSGEL 2008)

    NASA Astrophysics Data System (ADS)

    Maris, Thomas G.; Pappas, Evangelos

    2009-07-01

    The International Conference on Radiotherapy Gel Dosimetry (DOSGEL) is held every two years. Its purpose is to bring together basic science and clinical researchers, medical physicists and clinicians from around the world to discuss the state-of-the-art of the gel dosimetry technique and to set the directions and trends for its future improvements. Gel dosimetry can be broadly defined as using a gel that can react to the absorption of ionizing radiation, and that can retain this information which can subsequently be retrieved by an external imaging modality. Examples of radiation-sensitive gels include, but are not limited to, polymer gel dosimeters, Fricke gel dosimeters and others. Imaging modalities that are of general use in this field are (in alphabetical order) magnetic resonance imaging (MRI), optical light computed tomography and x-ray computed tomography. This volume comprises the proceedings of the 5th International Conference on Radiotherapy Gel Dosimetry (DOSGEL 2008). The conference, organised by the University of Crete, Medical Physics Department, took place in Hersonissos, Crete, Greece from 29 September to 3 October 2008. The meeting aimed to continue the series of biannual DOSGEL conferences and focused on the promotion of gel dosimetry techniques by setting the trends for their future improvements. The main scientific session topics of DOSGEL 2008 were the following: Chemistry and fundamental properties of polymer gel dosimeters Gel dosimetry with Optical Computed Tomography Gel dosimetry with Magnetic Resonance Imaging Gel dosimetry with other than Optical CT and MR scan Techniques Other 3D dosimeters Gel dosimetry applications Local Organizing Committee Thomas G Maris (University of Crete, Greece, Chairman DOSGEL 2008) John Damilakis (University of Crete, Greece) Evangelos Pappas (University of Crete, Greece) Antonios Papadakis (University of Crete, Greece) Fotini Zacharopoulou (University of Crete, Greece) John Stratakis (University of Crete

  10. Constitutive Activation of NF-kappaB in Prostate Carcinoma Cells Through a Positive Feedback Loop: Implication of Inducible IKK-Related Kinase (IKKi)

    DTIC Science & Technology

    2006-08-01

    strongly suggests that GR is constitutively active in both normal and hyperplastic prostate glands. In contrast, GR levels were low or below detection... BPH ; (b) PC (Gleason score 7); (c) HGPIN and (d) prostate stroma. Note: Low GR expression in PC (B1) and high GR expression in apparently normal...was increased in human prostate carcinomas in comparison to BPH samples (see progress report for FY02), these recent results suggest an important

  11. 40 CFR Table 2a to Subpart Ce of... - Emissions Limits for Small HMIWI Which Meet the Criteria Under § 60.33e(b)(1)

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... time 1 Method for demonstrating compliance 2 Particulate matter mg/dscm (gr/dscf) 197 (0.086) 3-run... total dioxins/furans (gr/109 dscf) or ng/dscm TEQ (gr/109 dscf) 800 (350) or 15 (6.6) 3-run average (4... sample time per run) EPA Reference Method 7 or 7E of appendix A-4 of part 60. Lead mg/dscm (gr/103...

  12. 40 CFR Table 2b to Subpart Ce of... - Emissions Limits for Small HMIWI Which Meet the Criteria Under § 60.33e(b)(2)

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... time 1 Method for demonstrating compliance 2 Particulate matter mg/dscm (gr/dscf) 87 (0.038) 3-run... total dioxins/furans (gr/109 dscf) or ng/dscm TEQ (gr/109 dscf) 240 (100) or 5.1 (2.2) 3-run average (4... sample time per run) EPA Reference Method 7 or 7E of appendix A-4 of part 60. Lead mg/dscm (gr/103...

  13. 40 CFR Table 1b to Subpart Ce of... - Emissions Limits for Small, Medium, and Large HMIWI at Designated Facilities as Defined in § 60...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... standard cubic meter (mg/dscm) (grains per dry standard cubic foot (gr/dscf)) 66 (0.029) 46 (0.020) 25 (0... dioxins/furans (ng/dscm) (grains per billion dry standard cubic feet (gr/109 dscf)) or ng/dscm TEQ (gr/109... 60. Lead mg/dscm (grains per thousand dry standard cubic feet (gr/103 dscf)) 0.31 (0.14) 0.018...

  14. 40 CFR Table 1b to Subpart Ce of... - Emissions Limits for Small, Medium, and Large HMIWI at Designated Facilities as Defined in § 60...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... standard cubic meter (mg/dscm) (grains per dry standard cubic foot (gr/dscf)) 66 (0.029) 46 (0.020) 25 (0... dioxins/furans (ng/dscm) (grains per billion dry standard cubic feet (gr/109 dscf)) or ng/dscm TEQ (gr/109... 60. Lead mg/dscm (grains per thousand dry standard cubic feet (gr/103 dscf)) 0.31 (0.14) 0.018...

  15. 40 CFR Table 1b to Subpart Ce of... - Emissions Limits for Small, Medium, and Large HMIWI at Designated Facilities as Defined in § 60...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... standard cubic meter (mg/dscm) (grains per dry standard cubic foot (gr/dscf)) 66 (0.029) 46 (0.020) 25 (0... dioxins/furans (ng/dscm) (grains per billion dry standard cubic feet (gr/109 dscf)) or ng/dscm TEQ (gr/109... 60. Lead mg/dscm (grains per thousand dry standard cubic feet (gr/103 dscf)) 0.31 (0.14) 0.018...

  16. Trehalose induces functionally active conformation in the intrinsically disordered N-terminal domain of glucocorticoid receptor.

    PubMed

    Khan, Shagufta H; Jasuja, Ravi; Kumar, Raj

    2016-08-05

    Glucocorticoid receptor (GR) is a classic member of the nuclear receptor superfamily and plays pivotal roles in human physiology at the level of gene regulation. Various constellations of cellular cofactors are required to associate with GR to activate/repress genes. The effects of specific ligands on the AF2 structure and consequent preferential binding of co-activators or co-repressors have helped our understanding of the mechanisms involved. But the data so far fall short of fully explaining GR actions. We believe that this is because work so far has largely avoided detailed examination of the contributions of AF1 to overall GR actions. It has been shown that the GR containing only the N-terminal domain (NTD) and the DNA-binding domain (GR500) is constitutively quite active in stimulating transcription from simple promoters. However, we are only beginning to understand structure and functions of GR500 in spite of the fact that AF1 located within the NTD serves as major transactivation domain for GR. Lack of this information has hampered our complete understanding of how GR regulates its target gene(s). The major obstacle in determining GR500 structure has been due to its intrinsically disordered NTD conformation, frequently found in transcription factors. In this study, we tested whether a naturally occurring osmolyte, trehalose, can promote functionally ordered conformation in GR500. Our data show that in the presence of trehalose, GR500 is capable of formation of a native-like functionally folded conformation.

  17. Marine Structural Steel Toughness Data Bank. Volume 3

    DTIC Science & Technology

    1991-08-28

    A A588 GR A K11430 1-12 A588 Gr B A588 Gr B K12043 1-12 A588 Gr C A588 Gr C K11538 1-12 A537-A A537 Gr A K02400 1-13 API 5L Gr X60 1-14 A656-70 A656...steel A710 and HSLA 80 containing primarily Cu, Ni, Cr and Mo; " Medium to high strength low alloy steels A537, CG-537, A656, A737, ABS-EH36, and API ... API 5L Gr X70 1-5 HSLA 80 1-6 ABS-EH36 A131 Gr EH36 K11852 1-7 A514E A514 Gr E K21604 1-8 A36 A36 1-9 BS 4360 Gr 50D 1-10 HY100 -K32045 1-11 A588-81 Gr

  18. New insights into the anti-inflammatory mechanisms of glucocorticoids: an emerging role for glucocorticoid-receptor-mediated transactivation.

    PubMed

    Vandevyver, Sofie; Dejager, Lien; Tuckermann, Jan; Libert, Claude

    2013-03-01

    Glucocorticoids are anti-inflammatory drugs that are widely used for the treatment of numerous (autoimmune) inflammatory diseases. They exert their actions by binding to the glucocorticoid receptor (GR), a member of the nuclear receptor family of transcription factors. Upon ligand binding, the GR translocates to the nucleus, where it acts either as a homodimeric transcription factor that binds glucocorticoid response elements (GREs) in promoter regions of glucocorticoid (GC)-inducible genes, or as a monomeric protein that cooperates with other transcription factors to affect transcription. For decades, it has generally been believed that the undesirable side effects of GC therapy are induced by dimer-mediated transactivation, whereas its beneficial anti-inflammatory effects are mainly due to the monomer-mediated transrepressive actions of GR. Therefore, current research is focused on the development of dissociated compounds that exert only the GR monomer-dependent actions. However, many recent reports undermine this dogma by clearly showing that GR dimer-dependent transactivation is essential in the anti-inflammatory activities of GR. Many of these studies used GR(dim/dim) mutant mice, which show reduced GR dimerization and hence cannot control inflammation in several disease models. Here, we review the importance of GR dimers in the anti-inflammatory actions of GCs/GR, and hence we question the central dogma. We summarize the contribution of various GR dimer-inducible anti-inflammatory genes and question the use of selective GR agonists as therapeutic agents.

  19. Recruitment of cAMP-response element-binding protein and histone deacetylase has opposite effects on glucocorticoid receptor gene transcription.

    PubMed

    Govindan, Manjapra Variath

    2010-02-12

    Glucocorticoids control the synthesis of the glucocorticoid receptor (GR) in various tissues through a negative feedback regulation of the mRNA. In this study, we have identified feedback regulatory domains in the human GR gene promoter and examined the roles of GR, the cAMP-response element-binding protein (CREB), and HDAC-6 in association with promoter elements of the human GR gene. Using breast cancer T47D and HeLa-GR cells, we identify specific negative glucocorticoid-response elements in the GR gene. The feedback regulatory domains were also involved in interactions with CREB. GR-bound negative glucocorticoid-response elements recruited HDAC-6, and this was dependent on treatment with dexamethasone. Both CREB and HDAC-6 formed complexes with GR-dexamethasone. The HDAC-6 LXXLL motif between amino acids 313 and 418 made direct contact with the GR AF-1 domain. Interestingly enough, although the level of GR decreased in CREB knockdown cells, it was elevated in HDAC-6 knockdown cells. Our results suggest that CREB-P is dephosphorylated and that HDAC-6 is recruited by the GR, and they play opposite roles in the negative feedback regulation of the GR gene.

  20. Golden Rice Can Provide Vitamin A Effectively as Assessed Using Isotope Reference Method

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Golden Rice (GR) is enriched with beta-carotene (beta-C) genetically. To determine its vitamin A value, intrinsically labeled GR was obtained by growing plants in a nutrient solution containing 23% D2O. The GR beta-C was enriched with deuterium with the highest abundance isotopomer peak at M+9. Hea...

  1. 40 CFR 63.7734 - How do I demonstrate initial compliance with the emissions limitations that apply to me?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...), did not exceed 0.005 gr/dscf; or (ii) The average total metal HAP concentration in the exhaust stream, determined according to the performance test procedures in § 63.7732(c), did not exceed 0.0004 gr/dscf. (2...), did not exceed 0.006 gr/dscf; or (ii) The average total metal HAP concentration in the exhaust...

  2. Can the "musical stroop" task replace the classical stroop task? Commentary on “The musical Stroop effect: Opening a new avenue to research on automatisms” by l. Grégoire, P. Perruchet, and B. Poulin-Charronnat (Experimental Psychology, 2013, vol. 60, pp. 269–278).

    PubMed

    Zakay, Dan

    2014-01-01

    The musical Stroop task is analyzed and compared to the classical Stroop task. The analysis indicates that the two tasks differ in the following significant characteristics: ecological validity, the interrelations between the two perceptual dimensions involved, the nature of the automatic process and the existence of a potential Garner interference. It is concluded that the musical task has no advantage over the classical task.

  3. Première datation des lydiennes paléozoïques dans les Hellénides internes (mont Parnis, Grèce); implications géologiquesFirst age dating of the Lydian stones in the Inner Hellenides (Mount Parnis, Greece); geological significances.

    NASA Astrophysics Data System (ADS)

    Caridroit, Martial; Ferrière, Jacky; Dégardin, Jean-Marie; Vachard, Daniel; Clément, Bernard

    2000-09-01

    Using radiolarian and conodont remains, a Tournaisian age has been obtained from the Lydian rocks (or lydites) of the Parnis Mount (Greece); this result is the first direct age dating of the Lydian rocks of continental Greece. In the same area, some limestone strata, interbedded in sandstones, yield Carboniferous and Permian foraminifers; the established stratigraphy is not consistent and so, the Lydian rocks have to be considered as blocks in an olistostrome unconformably overlain or thrusted by Triassic limestones. Otherwise, the Lydian rocks are interpreted as biogenic siliceous deposits due to the absence of carbonate sedimentation (not as a high siliceous production).

  4. On the size of the ptolemaic system of the world - a study based on two figures by Johannes Kepler. (German Title: Über die Gröszlig;e des ptolemäischen Weltsystems - Eine Studie, veranlasst durch zwei Bilder bei Johannes Kepler)

    NASA Astrophysics Data System (ADS)

    Oberschelp, Arnold

    It is well known that the geocentric system according to Ptolemy is almost twice as large as the heliocentric planetary system of Copernicus. There are, however, two pictures, given by Kepler in his «Mysterium Cosmographicum» of 1596 which - at first glance - seem to contradict this. The first picture of the heliocentric system is drawn to scale. The second picture shows a geocentric system, which seems to be too small. The puzzle about the size is solved rather trivially by the fact - which is not mentioned by Kepler and which may be overlooked - that the geocentric picture is not drawn to scale and that the angles do not correspond to the degrees noted at them. In order to get a geocentric picture drawn to scale - taking Kepler's degrees for granted - it is necessary to discuss some details of the ptolemaic system. The result is, however, a geocentric system which is too big. The solution of this new puzzle is not obvious. It turns out that one of Keplers degrees (for Mars) does not correspond to the parameters of Ptolemy. Actually, in his book of 1596, Kepler's topic is not the ptolemaic system nor the copernican distances, but his heliocentric model with the five regular polyhedra. While it is interesting to note all these facts, Kepler's pictures and degrees, for the size of the ptolemaic system, lead to a dead end. Using the parameters from the «Almagest» and the principle of nested spheres from the «Planetary Hypotheses» a distance scale (Tab. 10) for the geocentric system is derived. This distance scale, however, is somewhat different from the well known ptolemaic distance scale (Tab. 1). This puzzle is not resolved, but due to the fact that different sources («Almagest» and «Planetary Hypotheses») of Ptolemy are involved. The distances of Tab. 10 correspond better to the ptolemaic system, since the relative thickness of the spheres is computed from the rather precise parameters (eccentricities and epicycle radii) of the «Almagest». The distances of Tab. I, given in the «Planetary Hypotheses», use values for the relative thicknesses of the spheres which are rounded off. Since the pictures of Kepler, when viewed together, are misleading, two new pictures of the copernican and ptolemaic planetary systems are given drawn to the same scale. A final remark is about the radius of the «tychonic system».

  5. Méthode quantitative d'étude des formations détritiques azoïques: grès anté-panafricains du Centrafrique et du Nord de la République Démocratique du Congo (ex-Zaïre)

    NASA Astrophysics Data System (ADS)

    Alvarez, P.

    2000-08-01

    The stratigraphical correlation of discontinuous outcrops without biostratigraphical markers requires specific methods: a statistical distribution analysis of noteworthy components that allows characterisation of sediment source areas and reconstitution of particle supply variations; and a frequency histogram study that allows comparison and grouping, and subsequent correlation. These methods, applied to Pal˦oproterozoic and Neoproterozoic sandstone formations of the Central African Republic, suggest a Neoproterozoic-Cambrian fluvio-deltaic system with a paludal-lacustrine outlet. The sediment source area corresponded to a weathered and laterised grano-gneissic basement associated with a quartzite cover with acid volcanism. The fluvio-deltaic system settled during an interglacial period between a lower fluvio-giacial episode and an upper glacial episode of global character. It was marked by a substantial detntal flow, contemporaneous with basic volcanism, which filled up extensional basins. The sedimentary dynamics of this detrital system has been determined in the Central African Republic. It forms an integral part of a global model not only peculiar to the northern periphery of the Central African Craton (Congo, Cameroon, the northern part of the Democratic Republic of Congo), but also to its southeastern (Congo, Lower-Zaire, Angola) and southwestern (Democratic Republic of Congo) borders. In the Central African Republic and Congo, the channalised and conglomeratic base of this fluvio-deltaic system are favoured for diamond prospecting.

  6. Originalité des mécanismes d'altération sur les vestiges archéologiques de Délos (Cyclades, Grèce)Originality of weathering mechanisms on the archaeological remains of Delos (Cyclades, Greece).

    NASA Astrophysics Data System (ADS)

    Jeannette, Daniel

    2000-05-01

    The pore structure analysis of the granites and calcarenites of Delos archaeological site (Cyclades) has allowed us to verify a usual weathering mechanism by capillary transfer and evaporation of solutions from the ground loaded with marine salts. Not applicable to marble, another weathering mechanism is proposed, involving the water fixation of marine salts deposited on the monuments by wind, their migration, then their crystallization in the subsurface of the marble. The small-scale analysis of the condition of exposure, taking into account the ancient degradations, allows us to understand the development of decay which was inexplicable using the previous methods.

  7. Alteration of the glucocorticoid receptor subcellular localization by non steroidal compounds.

    PubMed

    Prima, V; Depoix, C; Masselot, B; Formstecher, P; Lefebvre, P

    2000-01-01

    The glucocorticoid receptor (GR) engages transient or stable interactions with chaperones (hsp90, hsp70), co-chaperones (p60/hop, hsp40) and several other polypeptides such as immunophilins (Cyp40, FKBP59) and p23 to achieve a high affinity ligand binding state. This complex dissociates in response to hormonal stimuli and holo-GR translocates into the nucleus, where it regulates the activity of glucocorticoid-sensitive genes. GR activity is controlled through its ligand binding domain by steroids displaying either agonistic or antagonistic activity. An alternative approach to modulate GR activity is to target receptor-associated proteins (RAPs), and several non steroidal compounds binding to RAPs affect GR transcriptional activity. We have studied the effect of such drugs on the intracellular localization of a EGFP-GR fusion protein, which has wild type GR pharmacological properties. Agonist and antagonist binding induced nuclear translocation of GR, whereas rifampicin was found to be inactive in our system. Immunosuppressants FK506 and cyclosporin A were able to induce partial nuclear translocation of GR, suggesting that potentiation of glucocorticoid action by these compounds may also proceed through enhanced GR nuclear transfer. Short treatment of cells with the hsp90 inhibitor geldanamycin (GA) did not prevent nuclear translocation of GR. However, longer treatments, in parrallel to the inhibition of GR transcriptional activity, strongly perturbed GR subcellular localization concomitantly to the disruption of the actin network, and caused GR aggregation and down-regulation. The GA-induced transcriptional shutdown was also observed for other nuclear receptors which do not interact stably with hsp90. Thus RAP-binding compounds may exert their effects at least in part through perturbation of the GR cytosol to nucleus partitioning, and identify these proteins as valuable therapeutic targets to control nuclear receptor activity.

  8. Abiotic Reductive Dechlorination of Tetrachloroethylene and Trichloroethylene in Anaerobic Environments

    DTIC Science & Technology

    2009-01-15

    the Presence of Chloride Green Rust (GR- Cl), pyrite , Sulfate Green Rust (GR-SO4), and Magnetite at pH 8. Lines Represent a Pseudo first-order Model...Rust (GR- Cl), Pyrite , Sulfate Green Rust (GR-SO4), and Magnetite at pH 8. Lines Represent a Pseudo first-order Model fit. The Insets Show Reaction...Rust (GR-Cl) and Pyrite at pH 8. Lines Represent a Rayleigh Model Fit. Uncertainties are 95% Confidence Intervals Calculated by Nonlinear Regression

  9. Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities

    SciTech Connect

    Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Kitai, Yuichi; Kon, Shigeyuki; Oritani, Kenji; Matsuda, Tadashi

    2015-07-31

    Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.

  10. Improving the visible light photoactivity of In2S3-graphene nanocomposite via a simple surface charge modification approach.

    PubMed

    Yang, Min-Quan; Weng, Bo; Xu, Yi-Jun

    2013-08-20

    We report an efficient and easily accessible self-assembly route to synthesize In2S3-GR nanocomposites via electrostatic interaction of positively charged In2S3 nanoparticles with negatively charged graphene oxide (GO) followed by a hydrothermal process for reduction of GO to graphene (GR). The as-synthesized In2S3-GR nanocomposites exhibit much higher visible light photocatalytic activity toward selective reduction of nitroaromatic compounds in water than bare In2S3 nanoparticles and In2S3-GR-H that is obtained from the simple "hard" integration of GR nanosheets with solid In2S3 nanoparticles without modification of surface charge. On the basis of the joint characterizations and structure-photoactivity correlation it is disclosed that the enhanced photocatalytic performance of In2S3-GR is mainly ascribed to the more efficient interfacial contact between In2S3 and the GR nanosheets than In2S3-GR-H, which would amplify the use of electron conductivity and mobility of GR to improve the lifetime and transfer of photogenerated charge carriers more efficiently and thus boost the photoactivity more effectively. This work highlights the significant effect of preparation methods on the photoactivity of GR-semiconductor nanocomposites. It is expected that such a simple electrostatic self-assembly strategy could aid to rationally fabricate more efficient GR-semiconductor nanocomposites with improved interfacial contact and photocatalytic performance toward various photocatalytic selective transformations.

  11. RSUME Enhances Glucocorticoid Receptor SUMOylation and Transcriptional Activity

    PubMed Central

    Druker, Jimena; Liberman, Ana C.; Antunica-Noguerol, María; Gerez, Juan; Paez-Pereda, Marcelo; Rein, Theo; Iñiguez-Lluhí, Jorge A.; Holsboer, Florian

    2013-01-01

    Glucocorticoid receptor (GR) activity is modulated by posttranslational modifications, including phosphorylation, ubiquitination, and SUMOylation. The GR has three SUMOylation sites: lysine 297 (K297) and K313 in the N-terminal domain (NTD) and K721 within the ligand-binding domain. SUMOylation of the NTD sites mediates the negative effect of the synergy control motifs of GR on promoters with closely spaced GR binding sites. There is scarce evidence on the role of SUMO conjugation to K721 and its impact on GR transcriptional activity. We have previously shown that RSUME (RWD-containing SUMOylation enhancer) increases protein SUMOylation. We now demonstrate that RSUME interacts with the GR and increases its SUMOylation. RSUME regulates GR transcriptional activity and the expression of its endogenous target genes, FKBP51 and S100P. RSUME uncovers a positive role for the third SUMOylation site, K721, on GR-mediated transcription, demonstrating that GR SUMOylation acts positively in the presence of a SUMOylation enhancer. Both mutation of K721 and small interfering RNA-mediated RSUME knockdown diminish GRIP1 coactivator activity. RSUME, whose expression is induced under stress conditions, is a key factor in heat shock-induced GR SUMOylation. These results show that inhibitory and stimulatory SUMO sites are present in the GR and at higher SUMOylation levels the stimulatory one becomes dominant. PMID:23508108

  12. An active nuclear retention signal in the glucocorticoid receptor functions as a strong inducer of transcriptional activation.

    PubMed

    Carrigan, Amanda; Walther, Rhian F; Salem, Houssein Abdou; Wu, Dongmei; Atlas, Ella; Lefebvre, Yvonne A; Haché, Robert J G

    2007-04-13

    The glucocorticoid receptor (GR) cycles between a naive chaperone-complexed form in the cytoplasm and a transcriptionally active steroid-bound nuclear form. Nuclear import of GR occurs rapidly and is mediated through the importin alpha/beta karyopherin import pathway. By contrast, nuclear export of GR occurs only slowly under most conditions, despite a dependence on active signaling. In this study we have defined a nuclear retention signal (NRS) in the hinge region of GR that actively opposes the nuclear export of GR as well as the nuclear export mediated through an ectopic CRM1-dependent nuclear export signal (NES). The GR NRS overlaps closely with the basic NL1 nuclear localization signal (NLS) but can be distinguished from NL1 by targeted mutagenesis. Substitution of the classical NLS from SV40 T antigen for the GR NL1 results in a receptor in which nuclear export is accelerated. Remarkably, although the SV40-modified GR remains predominantly nuclear in the presence of steroid and is recruited to transcriptional regulatory regions indistinguishably from wild-type GR, the substitution dramatically weakens the ability of GR to activate transcription of a mouse mammary tumor virus reporter gene. These results suggest that active nuclear retention of GR plays an integral role in glucocorticoid signaling.

  13. Mechanical properties of nickel-graphene composites synthesized by electrochemical deposition.

    PubMed

    Ren, Zhaodi; Meng, Nan; Shehzad, Khurram; Xu, Yang; Qu, Shaoxing; Yu, Bin; Luo, J K

    2015-02-13

    Graphene (Gr) nanosheets with multilayer structures were dispersed in a nickel (Ni) plating solution by using a surfactant with a magnetic stirring method. Gr nanosheets were incorporated into a Ni matrix through a plating process to form Ni-Gr composites on a target substrate. Gr nanosheets were uniformly dispersed in the Ni matrix, and the oxygen radicals present in the Gr were reduced during the electro-deposition process. The incorporation of Gr in the Ni matrix increases both the inter-planar spacing and the degree of preferred orientation of crystalline Ni. With the addition of Gr content as low as 0.05 g L(-1), the elastic modulus and hardness of the Ni-Gr composites reach 240 GPa and 4.6 GPa, respectively, which are about 1.7 and 1.2 times that of the pure Ni deposited under the same condition. The enhancement in mechanical properties of the composites is attributed to the preferred formation of the Ni crystalline phases in its (111) plane, the high interaction between Ni and Gr and the prevention of the dislocation sliding in the Ni matrix by the Gr. The results suggest that the method of using Gr directly instead of graphene oxide (GO) is efficient and scalable.

  14. Selected physico-mechanical characteristics of cryogenic and ambient ground turmeric

    NASA Astrophysics Data System (ADS)

    Barnwal, Pradyuman; Mohite, Ashish M.; Singh, Krishna K.; Kumar, Pankaj

    2014-03-01

    In this communication, selected physicomechanical characteristics of ground turmeric (cv. Prabha) were investigated for cryogenic and ambient grinding conditions of turmeric at different moisture contents (4, 6, 8 and 10% w.b.). A cryogenic grinder (Model: 100 UPZ, Hosokawa Alpine, Germany) and a micro pulverizer (hammer mill) were used for cryogenic and ambient grinding, respectively. The ground turmeric was graded in three grades viz. Gr-I, Gr-II and Gr-III with a sieve shaker using BSS Nos. 40, 85 and pan, respectively. Tap densities for cryogenic and ambient ground turmeric decreased from 678.7 (Gr-I) to 546.7 kgm-3 (Gr-III) and from 642.3 (Gr-I) to 468.6 kgm-3 (Gr-III), respectively, with the moisture increase. The angle of repose for cryogenic and ambient ground turmeric increased linearly from 26.85 (Gr-I) to 34.0° (Gr-III) and from 23.10 (Gr-I) to 28.06° (Gr-III), respectively with the increase in moisture content. The static coefficient of friction was the highest on plywood surface followed by mild steel sheet and galvanized iron sheet. The cryoground samples were found better in colour. Thermal conductivity of cryo-ground samples was higher than that of ambient ground samples. These physico-mechanical characteristics of cryogenic and ambient ground turmeric will be helpful for packaging, handling, and storage.

  15. Cobalt nanoparticles/nitrogen-doped graphene with high nitrogen doping efficiency as noble metal-free electrocatalysts for oxygen reduction reaction.

    PubMed

    Liang, Jingwen; Hassan, Mehboob; Zhu, Dongsheng; Guo, Liping; Bo, Xiangjie

    2017-03-15

    Nitrogen-doped graphene (N/GR) has been considered as active metal-free electrocatalysts for oxygen reduction reaction (ORR). However, the nitrogen (N) doping efficiency is very low and only few N atoms are doped into the framework of GR. To boost the N doping efficiency, in this work, a confined pyrolysis method with high N doping efficiency is used for the preparation of cobalt nanoparticles/nitrogen-doped GR (Co/N/GR). Under the protection of SiO2, the inorganic ligand NH3 in cobalt amine complex ([Co(NH3)6](3+)) is trapped in the confined space and then can be effectively doped into the framework of GR without the introduction of any carbon residues. Meanwhile, due to the redox reaction between the cobalt ions and carbon atoms of GR, Co nanoparticles are supported into the framework of N/GR. Due to prevention of GR layer aggregation with SiO2, the Co/N/GR with high dispersion provides sufficient surface area and maximum opportunity for the exposure of Co nanoparticles and active sites of N dopant. By combination of enhanced N doping efficiency, Co nanoparticles and high dispersion of GR sheets, the Co/N/GR is remarkably active, cheap and selective noble-metal free catalysts for ORR.

  16. Exploring manifold structure of face images via multiple graphs

    NASA Astrophysics Data System (ADS)

    Alghamdi, Masheal

    2013-12-01

    Geometric structure in the data provides important information for face image recognition and classification tasks. Graph regularized non-negative matrix factorization (GrNMF) performs well in this task. However, it is sensitive to the parameters selection. Wang et al. proposed multiple graph regularized non-negative matrix factorization (MultiGrNMF) to solve the parameter selection problem by testing it on medical images. In this paper, we introduce the MultiGrNMF algorithm in the context of still face Image classification, and conduct a comparative study of NMF, GrNMF, and MultiGrNMF using two well-known face databases. Experimental results show that MultiGrNMF outperforms NMF and GrNMF for most cases.

  17. Two monoclonal antibodies raised against different epitopes of chloroplast fructose-1. 6-bisphosphatase (FBPase)

    SciTech Connect

    Hermoso, R.; Fonolla, J.; Lopez-Gorge, J. ); Ruiz-Cabello, F.; Garrido, F. )

    1990-05-01

    Two monoclonal antibodies (GR-BP5 and GR-BP8) were obtained by fusion of spleen cells of mice immunized against pea photosynthetic FBPase with cells of myeloma NSI. Both mAbs showed by double immunodiffusion a {chi} light chain, and the GR-BP8 secreted an IgM. By Western-blotting and immunoprecipitation of the in vivo labelled pea FBPase, GR-BP5 and GR-BP8 showed specificity for the chloroplast enzyme. Competition binding of the {sup 125}I-labelled mAbs against pea FBPase showed specific binding sites to different epitopes of the enzyme molecule. Cross reaction assays between both monoclonal antibodies and pea and spinach chloroplast FBPases showed a 90-100% homology in the corresponding epitopes of both enzymes. Preliminary assays showed a moderate inhibition of FBPase by GR-BP5 monoclonal antibody, but a weak enhancement by the GR-BP8 monoclonal one.

  18. The structural basis of direct glucocorticoid-mediated transrepression.

    PubMed

    Hudson, William H; Youn, Christine; Ortlund, Eric A

    2013-01-01

    A newly discovered negative glucocorticoid response element (nGRE) mediates DNA-dependent transrepression by the glucocorticoid receptor (GR) across the genome and has a major role in immunosuppressive therapy. The nGRE differs dramatically from activating response elements, and the mechanism driving GR binding and transrepression is unknown. To unravel the mechanism of nGRE-mediated transrepression by the GR, we characterized the interaction between GR and an nGRE in the thymic stromal lymphopoietin (TSLP) promoter. We show using structural and mechanistic approaches that nGRE binding is a new mode of sequence recognition by human GR and that nGREs prevent receptor dimerization through a unique GR-binding orientation and strong negative cooperativity, ensuring the presence of monomeric GR at repressive elements.

  19. Black hole mergers: beyond general relativity

    NASA Astrophysics Data System (ADS)

    Stein, Leo; Okounkova, Maria

    2017-01-01

    One hundred years after the birth of general relativity, advanced LIGO has finally directly detected gravitational waves. The source: two black holes merging into one. Advanced LIGO will soon provide the opportunity to test GR, using gravitational waves, in the dynamical strong-field regime-a setting where GR has not yet been tested. GR has passed all weak-field tests with flying colors. Yet it should eventually break down, so we must look to the strong-field. To perform strong-field tests of GR, we need waveform models from theories beyond GR. To date there are no numerical simulations of black hole mergers in theories which differ from GR. The main obstacle is the mathematical one of well-posedness. I will explain how to overcome this obstacle, and demonstrate the success of this approach by presenting the first numerical simulations of black hole mergers in a theory beyond GR.

  20. Insight into the mechanisms of chemical doping of graphene on silicon carbide.

    PubMed

    Giannazzo, Filippo

    2016-02-19

    Graphene (Gr) is currently the object of intense research investigations, owing to its rich physics and wide potential for applications. In particular, epitaxial Gr on silicon carbide (SiC) holds great promise for the development of new device concepts based on the vertical current transport at Gr/SiC heterointerface. Precise tailoring of Gr workfunction (WF) represents a key requirement for these device structures. In this context, Günes et al (2015 Nanotechnology 26 445702) recently reported a straightforward approach for WF modulation in epitaxial Gr on silicon carbide by using nitric acid solutions at different dilutions. This paper provides a deep insight on the peculiar mechanisms of chemical doping of epitaxial Gr on 4H-SiC(0001), using several characterization techniques (Raman, UPS, AFM) and density functional theory calculations. The relevance of these findings and their perspective applications in emerging device concepts based on monolithic integration of Gr and SiC will be discussed.

  1. Unveiling the Mechanisms Leading to H2 Production Promoted by Water Decomposition on Epitaxial Graphene at Room Temperature.

    PubMed

    Politano, Antonio; Cattelan, Mattia; Boukhvalov, Danil W; Campi, Davide; Cupolillo, Anna; Agnoli, Stefano; Apostol, Nicoleta G; Lacovig, Paolo; Lizzit, Silvano; Farías, Daniel; Chiarello, Gennaro; Granozzi, Gaetano; Larciprete, Rosanna

    2016-04-26

    By means of a combination of surface-science spectroscopies and theory, we investigate the mechanisms ruling the catalytic role of epitaxial graphene (Gr) grown on transition-metal substrates for the production of hydrogen from water. Water decomposition at the Gr/metal interface at room temperature provides a hydrogenated Gr sheet, which is buckled and decoupled from the metal substrate. We evaluate the performance of Gr/metal interface as a hydrogen storage medium, with a storage density in the Gr sheet comparable with state-of-the-art materials (1.42 wt %). Moreover, thermal programmed reaction experiments show that molecular hydrogen can be released upon heating the water-exposed Gr/metal interface above 400 K. The Gr hydro/dehydrogenation process might be exploited for an effective and eco-friendly device to produce (and store) hydrogen from water, i.e., starting from an almost unlimited source.

  2. Identification of SET Domain-Containing Proteins in Gossypium raimondii and Their Response to High Temperature Stress

    PubMed Central

    Huang, Yong; Mo, Yijia; Chen, Pengyun; Yuan, Xiaoling; Meng, Funing; Zhu, Shengwei; Liu, Zhi

    2016-01-01

    SET (Su(var), E(z), and Trithorax) domain-containing proteins play an important role in plant development and stress responses through modifying lysine methylation status of histone. Gossypium raimondii may be the putative contributor of the D-subgenome of economical crops allotetraploid G. hirsutum and G. barbadense and therefore can potentially provide resistance genes. In this study, we identified 52 SET domain-containing genes from G. raimondii genome. Based on conserved sequences, these genes are grouped into seven classes and are predicted to catalyze the methylation of different substrates: GrKMT1 for H3K9me, GrKMT2 and GrKMT7 for H3K4me, GrKMT3 for H3K36me, GrKMT6 for H3K27me, but GrRBCMT and GrS-ET for nonhistones substrate-specific methylation. Seven pairs of GrKMT and GrRBCMT homologous genes are found to be duplicated, possibly one originating from tandem duplication and five from a large scale or whole genome duplication event. The gene structure, domain organization and expression patterns analyses suggest that these genes’ functions are diversified. A few of GrKMTs and GrRBCMTs, especially for GrKMT1A;1a, GrKMT3;3 and GrKMT6B;1 were affected by high temperature (HT) stress, demonstrating dramatically changed expression patterns. The characterization of SET domain-containing genes in G. raimondii provides useful clues for further revealing epigenetic regulation under HT and function diversification during evolution. PMID:27601353

  3. Alternative splicing: a novel mechanism of regulation identified in the chorismate mutase gene of the potato cyst nematode Globodera rostochiensis.

    PubMed

    Lu, Shun-Wen; Tian, Duanhua; Borchardt-Wier, Harmony B; Wang, Xiaohong

    2008-11-01

    Chorismate mutase (CM) secreted from the stylet of plant-parasitic nematodes plays an important role in plant parasitism. We isolated and characterized a new nematode CM gene (Gr-cm-1) from the potato cyst nematode, Globodera rostochiensis. The Gr-cm-1 gene was found to exist in the nematode genome as a single-copy gene that has two different alleles, Gr-cm-1A and Gr-cm-1B, both of which could give rise to two different mRNA transcripts of Gr-cm-1 and Gr-cm-1-IRII. In situ mRNA hybridization showed that the Gr-cm-1 gene was exclusively expressed within the subventral oesophageal gland cells of the nematode. Gr-cm-1 was demonstrated to encode a functional CM (GR-CM-1) potentially having a dimeric structure as the secreted bacterial *AroQ CMs. Gr-cm-1-IRII, generated by retention of intron 2 of the Gr-cm-1 pre-mRNA through alternative splicing (AS), would encode a truncated protein (GR-CM-1t) lacking the CM domain with no CM activity. The quantitative real-time reverse transcription-PCR assay revealed that splicing of the Gr-cm-1 gene was developmentally regulated; Gr-cm-1 was up-regulated whereas Gr-cm-1-IRII was down-regulated in early nematode parasitic stages compared to the preparasitic juvenile stage. Low-temperature SDS-PAGE analysis revealed that GR-CM-1 could form homodimers when expressed in Escherichia coli and the dimerization domain was retained in the truncated GR-CM-1t protein. The specific interaction between the two proteins was demonstrated in yeast. Our data suggested that the novel splice variant might function as a dominant negative isoform through heterodimerization with the full-length GR-CM-1 protein and that AS may represent an important mechanism for regulating CM activity during nematode parasitism.

  4. Ultrasound assisted simultaneous reduction and direct functionalization of graphene oxide with thermal and cytotoxicity profile.

    PubMed

    Maktedar, Shrikant S; Avashthi, Gopal; Singh, Man

    2017-01-01

    The new sonochemical approach for simultaneous reduction and direct functionalization of graphene oxide (GrO) has been developed. The GrO was functionalized with 2-Aminobenzoxazole (2-ABOZ) in twenty min with complete deletion of hazardous steps. The significance of ultrasound was exemplified with the comparative conventional methods. The newly prepared f-(2-ABOZ)GrO was extensively characterized with near edge X-ray absorption fine structure (NEXAFS) spectroscopy, (13)C solid state NMR, XPS, XRD, HRTEM, SAED, AFM, Raman, UV-vis, FTIR and TGA. The thermal stability of f-(2-ABOZ)GrO was confirmed with total percentage weight loss in TGA. The biological activity of f-(2-ABOZ)GrO was explored with MCF-7 and Vero cell lines. The inherent cytotoxicity was evaluated with SRB assay at 10, 20, 40 and 80μgmL(-1). The estimated cell viabilities were >78% with f-(2-ABOZ) GrO. A high cytocompatibility of f-(2-ABOZ)GrO was ensured with in vitro evaluation on living cell lines, and low toxicity of f-(2-ABOZ)GrO was confirmed its excellent biocompatibility. The morphological effect on Vero cell line evidently supports the formation of biocompatible f-(2-ABOZ)GrO. Therefore, f-(2-ABOZ)GrO was emerged as an advanced functional material for thermally stable biocompatible coatings.

  5. The enhanced efficiency of graphene-silicon solar cells by electric field doping.

    PubMed

    Yu, Xuegong; Yang, Lifei; Lv, Qingmin; Xu, Mingsheng; Chen, Hongzheng; Yang, Deren

    2015-04-28

    The graphene-silicon (Gr-Si) Schottky junction solar cell has been recognized as one of the most low-cost candidates in photovoltaics due to its simple fabrication process. However, the low Gr-Si Schottky barrier height largely limits the power conversion efficiency of Gr-Si solar cells. Here, we demonstrate that electric field doping can be used to tune the work function of a Gr film and therefore improve the photovoltaic performance of the Gr-Si solar cell effectively. The electric field doping effects can be achieved either by connecting the Gr-Si solar cell to an external power supply or by polarizing a ferroelectric polymer layer integrated in the Gr-Si solar cell. Exploration of both of the device architecture designs showed that the power conversion efficiency of Gr-Si solar cells is more than twice of the control Gr-Si solar cells. Our study opens a new avenue for improving the performance of Gr-Si solar cells.

  6. Structure of Greyhound hemoglobin: origin of high oxygen affinity.

    PubMed

    Bhatt, Veer S; Zaldívar-López, Sara; Harris, David R; Couto, C Guillermo; Wang, Peng G; Palmer, Andre F

    2011-05-01

    This study presents the crystal structure of Greyhound hemoglobin (GrHb) determined to 1.9 Å resolution. GrHb was found to crystallize with an α₁β₁ dimer in the asymmetric unit and belongs to the R2 state. Oxygen-affinity measurements combined with the fact that GrHb crystallizes in the R2 state despite the high-salt conditions used for crystallization strongly indicate that GrHb can serve as a model high-oxygen-affinity hemoglobin (Hb) for higher mammals, especially humans. Structural analysis of GrHb and its comparison with the R2-state of human Hb revealed several regions that can potentially contribute to the high oxygen affinity of GrHb and serve to rationalize the additional stability of the R2-state of GrHb. A previously well studied hydrophobic cluster of bar-headed goose Hb near α119 was also incorporated in the comparison between GrHb and human Hb. Finally, a structural comparison with generic dog Hb and maned wolf Hb was conducted, revealing that in contrast to GrHb these structures belong to the R state of Hb and raising the intriguing possibility of an additional allosteric factor co-purifying with GrHb that can modulate its quaternary structure.

  7. Insights into negative regulation by the glucocorticoid receptor from genome-wide profiling of inflammatory cistromes.

    PubMed

    Uhlenhaut, N Henriette; Barish, Grant D; Yu, Ruth T; Downes, Michael; Karunasiri, Malith; Liddle, Christopher; Schwalie, Petra; Hübner, Norbert; Evans, Ronald M

    2013-01-10

    How the glucocorticoid receptor (GR) activates some genes while potently repressing others remains an open question. There are three current models for suppression: transrepression via GR tethering to AP-1/NF-κB sites, direct GR association with inhibitory elements (nGREs), and GR recruitment of the corepressor GRIP1. To gain insights into GR suppression, we used genomic analyses and genome-wide profiling of GR, p65, and c-Jun in LPS-stimulated macrophages. We show that GR mediates both activation and repression at tethered sites, GREs, and GRIP1-bound elements, indicating that motif classification is insufficient to predict regulatory polarity of GR binding. Interestingly, sites of GR repression utilize GRIP1's corepressor function and display reduced histone acetylation. Together, these findings suggest that while GR occupancy confers hormone responsiveness, the receptor itself may not participate in the regulatory effects. Furthermore, transcriptional outcome is not established by sequence but is influenced by epigenetic regulators, context, and other unrecognized regulatory determinants.

  8. Expansion of a bitter taste receptor family in a polyphagous insect herbivore

    PubMed Central

    Xu, Wei; Papanicolaou, Alexie; Zhang, Hui-Jie; Anderson, Alisha

    2016-01-01

    The Insect taste system plays a central role in feeding behaviours and co-evolution of insect-host interactions. Gustatory receptors form the interface between the insect taste system and the environment. From genome and transcriptome sequencing we identified 197 novel gustatory receptor (GR) genes from the polyphagous pest Helicoverpa armigera. These GRs include a significantly expanded bitter receptor family (180 GRs) that could be further divided into three categories based on polypeptide lengths, gene structure and amino acid sequence. Type 1 includes 29 bitter Gr genes that possess introns. Type 2 includes 13 long intronless bitter Gr genes, while Type 3 comprises 131 short intronless bitter Gr genes. Calcium imaging analysis demonstrated that three Type 3 GRs (HarmGR35, HarmGR50 and HarmGR195) can be activated by a crude extract of cotton leaves. HarmGR195, a GR specifically and selectively expressed in adult tarsi, showed a specific response to proline, an amino acid widely present in plant tissues. We hypothesise that the expansion in the H. armigera GR family may be functionally tied to its polyphagous behavior. Understanding the molecular basis of polyphagy may provide opportunities for the development of new environmentally friendly pest control strategies. PMID:27032373

  9. Neonatal Growth Restriction-Related Leptin Deficiency Enhances Leptin-Triggered Sympathetic Activation and Central Angiotensin II Receptor-Dependent Stress-Evoked Hypertension

    PubMed Central

    Peotta, Veronica; Rahmouni, Kamal; Segar, Jeffrey L.; Morgan, Donald A.; Pitz, Kate M.; Rice, Olivia M.; Roghair, Robert D.

    2016-01-01

    Background Neonatal growth restriction (nGR) leads to leptin deficiency and increases the risk of hypertension. Previous studies have shown nGR-related hypertension is normalized by neonatal leptin (nLep) and exacerbated by psychological stress. With recent studies linking leptin and angiotensin signaling, we hypothesized that nGR-induced nLep deficiency increases adult leptin sensitivity; leading to leptin- or stress-induced hypertension, through a pathway involving central angiotensin II type 1 receptors. Methods We randomized mice with incipient nGR, by virtue of their presence in large litters, to vehicle or physiologic nLep supplementation (80 ng/g/d). Adult caloric intake and arterial pressure were monitored at baseline, during intracerebroventricular losartan infusion and during systemic leptin administration. Results nGR increased leptin-triggered renal sympathetic activation and hypertension with increased leptin receptor expression in the arcuate nucleus of the hypothalamus; all of those nGR-associated phenotypes were normalized by nLep. nGR mice also had stress-related hyperphagia and hypertension, but only the stress hypertension was blocked by central losartan infusion. Conclusion nGR leads to stress hypertension through a pathway that involves central angiotensin II receptors, and nGR-associated leptin deficiency increases leptin-triggered hypertension in adulthood. These data suggest potential roles for preservation of neonatal growth and nLep supplementation in the prevention of nGR-related hypertension. PMID:27049292

  10. New Insights in Glucocorticoid Receptor Signaling—More Than Just a Ligand-Binding Receptor

    PubMed Central

    Scheschowitsch, Karin; Leite, Jacqueline Alves; Assreuy, Jamil

    2017-01-01

    The clinical use of classical glucocorticoids (GC) is narrowed by the many side effects it causes and the resistance to GC observed in some diseases. Since the great majority of GC effects depend on the activation of a glucocorticoid receptor (GR), many research groups had focused to better understand the signaling pathways involving those receptors. Transgenic animal models and genetic modifications of the receptor brought a huge insight into GR mechanisms of action. This in turn opened a new window for the search of selective GR modulators that ideally may have agonistic and antagonistic combined effects and activate one specific signaling pathway, inducing mostly transrepression or transactivation mechanisms. Another important research field concerns to posttranslational modifications that affect the GR and consequently also affect its signaling and function. In this mini review, we discuss many of those aspects of GR signaling, as well as findings like the ligand-independent activation of GR, which add another layer of complexity in GR signaling pathways. Although several recent data have been added to the GR field, much work has yet to be done, especially to find out the biological relevance of those alternative GR signaling pathways. Improving the knowledge about alternative GR signaling pathways and understanding how these pathways intercommunicate and in which situations they are relevant might help to develop new strategies to take benefit of it and to improve GC or other compounds efficacy causing minimal side effects. PMID:28220107

  11. Observation of Localized Vibrational Modes of Graphene Nanodomes by Inelastic Atom Scattering.

    PubMed

    Maccariello, D; Al Taleb, A; Calleja, F; Vázquez de Parga, A L; Perna, P; Camarero, J; Gnecco, E; Farías, D; Miranda, R

    2016-01-13

    Inelastic helium atom scattering (HAS) is suitable to determine low-energy (few meV) vibrations spatially localized on structures in the nanometer range. This is illustrated for the nanodomes that appear often on graphene (Gr) epitaxially grown on single crystal metal surfaces. The nature of the inelastic losses observed in Gr/Ru(0001) and Gr/Cu/Ru(0001) has been clarified by intercalation of Cu below the Gr monolayer, which decouples the Gr layer from the Ru substrate and changes substantially the out-of-plane, flexural phonon dispersion of epitaxial Gr, while maintaining the nanodomes and their localized vibrations. He diffraction proves that the Cu-intercalated Gr layer is well ordered structurally, while scanning tunneling microscopy reveals the persistence of the (slightly modified) periodic array of Gr nanodomes. A simple model explains the order of magnitude of the energy losses associated with the Gr nanodomes and their size dependence. The dispersionless, low-energy phonon branches may radically alter the transport of heat in intercalated Gr.

  12. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    SciTech Connect

    Li, Qun-Yi; Zhang, Meng; Hallis, Tina M.; DeRosier, Therese A.; Yue, Jian-Min; Ye, Yang; Mais, Dale E.; Wang, Ming-Wei

    2010-01-15

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  13. Drosophila Sugar Receptors in Sweet Taste Perception, Olfaction and Internal Nutrient Sensing

    PubMed Central

    Slone, Jesse; Jagge, Christopher; Song, Xiangyu; Amrein, Hubert

    2015-01-01

    SUMMARY Identification of nutritious compounds is dependent on expression of specific taste receptors in appropriate taste cell types [1]. In contrast to mammals, which rely on a single, broadly tuned heterodimeric sugar receptor [2], the Drosophila genome harbors a small subfamily of eight, closely related gustatory receptor (Gr) genes, Gr5a, Gr61a and Gr64a-f, of which three have been proposed to mediate sweet taste [3-6]. However, expression and function of several of these putative sugar Gr genes are not known. Here we present a comprehensive expression and functional analysis using GrLEXA/GAL4 alleles that were generated through homologous recombination. We show that sugar Gr genes are expressed in a combinatorial manner to yield at least eight sets of sweet sensing neurons. Behavioral investigations show that most sugar Gr mutations affect taste responses to only a small number of sugars and that effective detection of most sugars is dependent on more than one Gr gene. Surprisingly, Gr64a, one of three Gr genes previously proposed to play a major role in sweet taste [3, 4], is not expressed in labellar taste neurons, and Gr64a mutant flies exhibit normal sugar responses elicited from the labellum. Our analysis provides a molecular rationale for distinct tuning profiles of sweet taste neurons, and it favors a model whereby all sugar Grs contribute to sweet taste. Furthermore, expression in olfactory organs and the brain implies novel roles for sugar Gr genes in olfaction and internal nutrient sensing, respectively. Thus, sugar receptors may contribute to feeding behavior via multiple sensory systems. PMID:25702577

  14. Modulation of HIV-1 virulence via the host glucocorticoid receptor: towards further understanding the molecular mechanisms of HIV-1 pathogenesis.

    PubMed

    Hapgood, Janet Patricia; Tomasicchio, Michele

    2010-07-01

    The glucocorticoid receptor (GR) is a steroid receptor that regulates diverse functions, which include the immune response. In humans, the GR acts via binding to cortisol, resulting in the transcriptional modulation of key host genes. Several lines of evidence suggest that the host GR could be a key protein exploited by HIV at multiple levels to ensure its pathogenic success. Endogenous and therapeutic glucocorticoids play important roles in patients with HIV due to their well-established effects on immune function. AIDS patients develop glucocorticoid hypersensitivity, consistent with a mechanism involving an HIV-1-induced increase in expression or activity of the GR. Both the HIV-1 accessory protein Vpr and the host GR affect transcription of viral proteins from the long terminal repeat (LTR) region of the HIV-1 promoter. In addition, Vpr modulates host GR function to affect transcription of host genes, most likely via direct interaction with the GR. Vpr appears to regulate GR function by acting as a co-activator for the GR. Since both the GR and Vpr are involved in apoptosis in T cells and dendritic cells, crosstalk between these proteins may also regulate apoptosis in these and other cells. Given that cortisol is not the only ligand that activates the GR, other endogenous as well as synthetic GR ligands such as progestins may also modulate HIV pathogenesis, in particular in the cervicovaginal environment. Investigating the molecular determinants, ligand-selectivity and role in HIV pathogenesis of the GR-Vpr interaction may lead to new strategies for development of anti-HIV drugs.

  15. Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF.

    PubMed

    Dolcetti, Luigi; Peranzoni, Elisa; Ugel, Stefano; Marigo, Ilaria; Fernandez Gomez, Audry; Mesa, Circe; Geilich, Markus; Winkels, Gregor; Traggiai, Elisabetta; Casati, Anna; Grassi, Fabio; Bronte, Vincenzo

    2010-01-01

    CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSC) contribute to tumor immune evasion by restraining the activity of CD8+ T-cells. Two major MDSC subsets were recently shown to play an equal role in MDSC-induced immune dysfunctions: monocytic- and granulocytic-like. We isolated three fractions of MDSC, i.e. CD11b+/Gr-1high, CD11b+/Gr-1int, and CD11b+/Gr-1low populations that were characterized morphologically, phenotypically and functionally in different tumor models. In vitro assays showed that CD11b+/Gr-1int cell subset, mainly comprising monocytes and myeloid precursors, was always capable to suppress CD8+ T-cell activation, while CD11b+/Gr-1high cells, mostly granulocytes, exerted appreciable suppression only in some tumor models and when present in high numbers. The CD11b+/Gr-1int but not CD11b+/Gr-1high cells were also immunosuppressive in vivo following adoptive transfer. CD11b+/Gr-1low cells retained the immunosuppressive potential in most tumor models. Gene silencing experiments indicated that GM-CSF was necessary to induce preferential expansion of both CD11b+/Gr-1int and CD11b+/Gr-1low subsets in the spleen of tumor-bearing mice and mediate tumor-induced tolerance whereas G-CSF, which preferentially expanded CD11b+/Gr-1high cells, did not create such immunosuppressive environment. GM-CSF also acted on granulocyte-macrophage progenitors in the bone marrow inducing local expansion of CD11b+/Gr-1low cells. These data unveil a hierarchy of immunoregulatory activity among MDSC subsets that is controlled by tumor-released GM-CSF.

  16. Glyphosate effect on shikimate, nitrate reductase activity, yield, and seed composition in corn.

    PubMed

    Reddy, Krishna N; Bellaloui, Nacer; Zablotowicz, Robert M

    2010-03-24

    When glyphosate is applied to glyphosate-resistant (GR) crops, drift to nonglyphosate-resistant (non-GR) crops may cause significant injury and reduce yields. Tools are needed to quantify injury and predict crop losses. In this study, glyphosate drift was simulated by direct application at 12.5% of the recommended label rate to non-GR corn (Zea mays L.) at 3 or 6 weeks after planting (WAP) during two field seasons in the Mississippi delta region of the southeastern USA. Visual plant injury, shikimate accumulation, nitrate reductase activity, leaf nitrogen, yield, and seed composition were evaluated. Effects were also evaluated in GR corn and GR corn with stacked glufosinate-resistant gene at the recommended label rate at 3 and 6 WAP. Glyphosate at 105 g ae/ha was applied once at 3 or 6 weeks after planting to non-GR corn. Glyphosate at 840 (lower label limit) or 1260 (upper label limit) g ae/ha was applied twice at 3 and 6 WAP to transgenic corn. Glyphosate caused injury (45-55%) and increased shikimate levels (24-86%) in non-GR compared to nontreated corn. In non-GR corn, glyphosate drift did not affect starch content but increased seed protein 8-21% while reducing leaf nitrogen reductase activity 46-64%, leaf nitrogen 7-16%, grain yield 49-54%, and seed oil 18-23%. In GR and GR stacked with glufosinate-resistant corn, glyphosate applied at label rates did not affect corn yield, leaf and seed nitrogen, or seed composition (protein, oil, and starch content). Yet, nitrate reductase activity was reduced 5-19% with glyphosate at 840 + 840 g/ha rate and 8-42% with glyphosate at 1260 + 1260 g/ha rate in both GR and GR stacked corn. These results demonstrate the potential for severe yield loss in non-GR corn exposed to glyphosate drift.

  17. General Relativity and Cosmology: Unsolved Questions and Future Directions

    NASA Astrophysics Data System (ADS)

    Debono, Ivan; Smoot, George F.

    2016-09-01

    For the last 100 years, General Relativity (GR) has taken over the gravitational theory mantle held by Newtonian Gravity for the previous 200 years. This article reviews the status of GR in terms of its self-consistency, completeness, and the evidence provided by observations, which have allowed GR to remain the champion of gravitational theories against several other classes of competing theories. We pay particular attention to the role of GR and gravity in cosmology, one of the areas in which one gravity dominates and new phenomena and effects challenge the orthodoxy. We also review other areas where there are likely conflicts pointing to the need to replace or revise GR to represent correctly observations and consistent theoretical framework. Observations have long been key both to the theoretical liveliness and viability of GR.We conclude with a discussion of the likely developments over the next 100 years.

  18. Crystal Structure of a Human Single Domain Antibody Dimer Formed through VH-VH Non-Covalent Interactions

    PubMed Central

    Li, Shenghua; Tanha, Jamshid; Arbabi-Ghahroudi, Mehdi; Zhang, Jianbing; Wang, Shuying

    2012-01-01

    Single-domain antibodies (sdAbs) derived from human VH are considered to be less soluble and prone to aggregate which makes it difficult to determine the crystal structures. In this study, we isolated and characterized two anti-human epidermal growth factor receptor-2 (HER2) sdAbs, Gr3 and Gr6, from a synthetic human VH phage display library. Size exclusion chromatography and surface plasmon resonance analyses demonstrated that Gr3 is a monomer, but that Gr6 is a strict dimer. To understand this different molecular behavior, we solved the crystal structure of Gr6 to 1.6 Å resolution. The crystal structure revealed that the homodimer assembly of Gr6 closely mimics the VH-VL heterodimer of immunoglobulin variable domains and the dimerization interface is dominated by hydrophobic interactions. PMID:22253912

  19. Outcome of gastrocnemius recession and tendo-achilles lengthening in ambulatory children with cerebral palsy.

    PubMed

    Kay, Robert M; Rethlefsen, Susan A; Ryan, James A; Wren, Tishya A L

    2004-03-01

    Preoperative and postoperative gait analysis data were retrospectively studied for 54 children with cerebral palsy who had undergone either gastrocnemius recession (GR) or tendo-achilles lengthening (TAL) as part of multi-level surgery. Decision-making between GR and TAL was based on the Silfverskiöld test. The TAL group had greater equinus preoperatively than the GR group. Both groups showed significant improvement in static and dynamic dorsiflexion and in outcome measured by a modified Physician Rating Scale (PRS) postoperatively. Calf spasticity decreased and push-off power increased after GR. Both GR and TAL are effective in appropriately selected patients. However, a potential for over- and under-correction with both GR and TAL was demonstrated.

  20. Gustatory Receptors Required for Avoiding the Toxic Compound Coumarin in Drosophila melanogaster.

    PubMed

    Poudel, Seeta; Lee, Youngseok

    2016-04-30

    Coumarin is a phenolic compound that mainly affects the liver due to its metabolization into a toxic compound. The deterrent and ovicidal activities of coumarin in insect models such as Drosophila melanogaster have been reported. Here we explore the molecular mechanisms by which these insects protect themselves and their eggs from this toxic plant metabolite. Coumarin was fatal to the flies in a dosage-dependent manner. However, coumarin feeding could be inhibited through activation of the aversive gustatory receptor neurons (GRNs), but not the olfactory receptor neurons. Furthermore, three gustatory receptors, GR33a, GR66a, and GR93a, functioned together in coumarin detection by the proboscis. However, GR33a, but not GR66a and GR93a, was required to avoid coumarin during oviposition, with a choice of the same substrates provided as in binary food choice assay. Taken together, these findings suggest that anti-feeding activity and oviposition to avoid coumarin occur via separate mechanisms.

  1. In situ sonochemical reduction and direct functionalization of graphene oxide: A robust approach with thermal and biomedical applications.

    PubMed

    Maktedar, Shrikant S; Mehetre, Shantilal S; Avashthi, Gopal; Singh, Man

    2017-01-01

    The rapid, robust, scalable and non-hazardous sonochemical approach for in situ reduction and direct functionalization of graphene oxide has been developed for non-toxic biomedical applications. The graphene oxide (GrO) was directly functionalized with tryptamine (TA) without using any hazardous acylating and coupling reagents. The reaction was completed within 20min. An impact of ultrasound was inferred for a direct functionalization with other conventional methods. The evolved electronic states were confirmed with near edge X-ray absorption fine structure (NEXAFS). The direct covalent functionalization and formation of f-(TA) GrO was proven with FTIR, (13)C solid state NMR, XPS, XRD, Raman' HRTEM, AFM and TGA. The total percentage weight loss in TGA confirms an enhanced thermal stability of f-(TA) GrO. The f-(TA) GrO was further explored for an investigation of in vitro antimicrobial activity to ensure the health and environmental safety. An outstanding antibacterial activity of f-(TA) GrO was found against gram positive Staphylococcus aureus at MIC 128mgmL(-1). It confirms a suitability of f-(TA) GrO for thermally stable antibacterial coating. The f-(TA) GrO showed 39.14-48.9% antioxidant activities, evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assay. The inherent cytotoxicity of f-(TA) GrO was evaluated with SRB assay to living cells, MCF-7 and Vero. The estimated cell viabilities were >80% upon addition of f-(TA) GrO over a wide concentration range of 10-80μgmL(-1). The high cytocompatibility of f-(TA) GrO confirms the low toxicity and an excellent biocompatibility. The morphological effect on Vero cell line, evidently confirmed the biocompatibility of f-(TA) GrO. Therefore, f-(TA) GrO was emerged as an advanced functional biomaterial for thermal and biomedical applications.

  2. Glucocorticoid Receptor Activation Inhibits Chemotherapy-induced Cell Death in High-grade Serous Ovarian Carcinoma

    PubMed Central

    Stringer-Reasor, Erica M.; Baker, Gabrielle M.; Skor, Maxwell N.; Kocherginsky, Masha; Lengyel, Ernst; Fleming, Gini F.; Conzen, Suzanne D.

    2015-01-01

    Objectives To test the hypothesis that glucocorticoid receptor (GR) activation increases resistance to chemotherapy in high-grade serous ovarian cancer (HGS-OvCa) and that treatment with a GR antagonist will improve sensitivity to chemotherapy. Methods GR expression was assessed in OvCa cell lines by qRT-PCR and Western blot analysis and in xenografts and primary human tumors using immunohistochemistry (IHC). We also examined the effect of GR activation versus inhibition on chemotherapy-induced cytotoxicity in OvCa cell lines and in a xenograft model. Results With the exception of IGROV-1 cells, all OvCa cell lines tested had detectable GR expression by Western blot and qRT-PCR analysis. Twenty-five out of the 27 human primary HGS-OvCas examined expressed GR by IHC. No cell line expressed detectable progesterone receptor (PR) or androgen receptor (AR) by Western blot analysis. In vitro assays showed that in GR-positive HeyA8 and SKOV3 cells, dexamethasone (100 nM) treatment upregulated the pro-survival genes SGK1 and MKP1/DUSP1 and inhibited carboplatin/gemcitabine-induced cell death. Concurrent treatment with two GR antagonists, either mifepristone (100 nM) or CORT125134 (100 nM), partially reversed these effects. There was no anti-apoptotic effect of dexamethasone on chemotherapy-induced cell death in IGROV-1 cells, which did not have detectable GR protein. Mifepristone treatment alone was not cytotoxic in any cell line. HeyA8 OvCa xenograft studies demonstrated that adding mifepristone to carboplatin/gemcitabine increased tumor shrinkage by 48% compared to carboplatin/gemcitabine treatment alone (P=0.0004). Conclusions These results suggest that GR antagonism sensitizes GR+ OvCa to chemotherapy-induced cell death through inhibition of GR-mediated cell survival pathways. PMID:26115975

  3. Potent and multiple regulatory actions of microglial glucocorticoid receptors during CNS inflammation

    PubMed Central

    Carrillo-de Sauvage, M Á; Maatouk, L; Arnoux, I; Pasco, M; Sanz Diez, A; Delahaye, M; Herrero, M T; Newman, T A; Calvo, C F; Audinat, E; Tronche, F; Vyas, S

    2013-01-01

    In CNS, glucocorticoids (GCs) activate both GC receptor (GR) and mineralocorticoid receptor (MR), whereas GR is widely expressed, the expression of MR is restricted. However, both are present in the microglia, the resident macrophages of the brain and their activation can lead to pro- or anti-inflammatory effects. We have therefore addressed the specific functions of GR in microglia. In mice lacking GR in macrophages/microglia and in the absence of modifications in MR expression, intraparenchymal injection of lipopolysaccharide (LPS) activating Toll-like receptor 4 signaling pathway resulted in exacerbated cellular lesion, neuronal and axonal damage. Global inhibition of GR by RU486 pre-treatment revealed that microglial GR is the principal mediator preventing neuronal degeneration triggered by lipopolysaccharide (LPS) and contributes with GRs of other cell types to the protection of non-neuronal cells. In vivo and in vitro data show GR functions in microglial differentiation, proliferation and motility. Interestingly, microglial GR also abolishes the LPS-induced delayed outward rectifier currents by downregulating Kv1.3 expression known to control microglia proliferation and oxygen radical production. Analysis of GR transcriptional function revealed its powerful negative control of pro-inflammatory effectors as well as upstream inflammatory activators. Finally, we analyzed the role of GR in chronic unpredictable mild stress and aging, both known to prime or sensitize microglia in vivo. We found that microglial GR suppresses rather than mediates the deleterious effects of stress or aging on neuronal survival. Overall, the results show that microglial GR acts on several key processes limiting pro-inflammatory actions of activated microglia. PMID:24013726

  4. Glyphosate-Resistant and Conventional Canola (Brassica napus L.) Responses to Glyphosate and Aminomethylphosphonic Acid (AMPA) Treatment.

    PubMed

    Corrêa, Elza Alves; Dayan, Franck E; Owens, Daniel K; Rimando, Agnes M; Duke, Stephen O

    2016-05-11

    Glyphosate-resistant (GR) canola contains two transgenes that impart resistance to the herbicide glyphosate: (1) the microbial glyphosate oxidase gene (gox) encoding the glyphosate oxidase enzyme (GOX) that metabolizes glyphosate to aminomethylphosphonic acid (AMPA) and (2) cp4 that encodes a GR form of the glyphosate target enzyme 5-enolpyruvylshikimic acid-3-phosphate synthase. The objectives of this research were to determine the phytotoxicity of AMPA to canola, the relative metabolism of glyphosate to AMPA in GR and conventional non-GR (NGR) canola, and AMPA pool sizes in glyphosate-treated GR canola. AMPA applied at 1.0 kg ha(-1) was not phytotoxic to GR or NGR. At this AMPA application rate, NGR canola accumulated a higher concentration of AMPA in its tissues than GR canola. At rates of 1 and 3.33 kg ae ha(-1) of glyphosate, GR canola growth was stimulated. This stimulatory effect is similar to that of much lower doses of glyphosate on NGR canola. Both shikimate and AMPA accumulated in tissues of these glyphosate-treated plants. In a separate experiment in which young GR and NGR canola plants were treated with non-phytotoxic levels of [(14)C]-glyphosate, very little glyphosate was metabolized in NGR plants, whereas most of the glyphosate was metabolized to AMPA in GR plants at 7 days after application. Untreated leaves of GR plants accumulated only metabolites (mostly AMPA) of glyphosate, indicating that GOX activity is very high in the youngest leaves. These data indicate that more glyphosate is transformed to AMPA rapidly in GR canola and that the accumulated AMPA is not toxic to the canola plant.

  5. Polyclonal Anti-Peptide Antibodies Against Both Activated and Unactivated Forms of the Human Glucocorticoid Receptor

    DTIC Science & Technology

    1993-04-30

    1982, 198 7 ), using a variety of p r oteolytic enzymes , and insert i on and dele tion mutagenesis (Gigue:::-e et al . , 198~i Kumar et al ., 1986...synthetic peptide. To confirm the specificity of the antibody-GR interaction, antisera were preadsorbed with free peptide before reaction with the GR...immunization is a reproduc ible phenomenon. However, none of the three rabbits yielded high-titer serum for reaction with tne native forms of the hGR

  6. An Investigation of Graphite Peek Composite under Compression with a Centrally Located Circular Discontinuity

    DTIC Science & Technology

    1993-03-01

    body of research conducted on Gr/PEEK exists and includes the investigation of Gr/PEEK under both tension and compression with a centrally located cutout...Some of this research has discussed a need to include the nonlinear stress-strain behavior of the materials in the evaluation of the composite. This... research will investigate the nonlinear properties of Gr/PEEK using the nonlinear finite element program, PLNRS, and validate the results both with a

  7. A genetic tool kit for cellular and behavioral analyses of insect sugar receptors.

    PubMed

    Yavuz, Ahmet; Jagge, Christopher; Slone, Jesse; Amrein, Hubert

    2014-01-01

    Arthropods employ a large family of up to 100 putative taste or gustatory receptors (Grs) for the recognition of a wide range of non-volatile chemicals. In Drosophila melanogaster, a small subfamily of 8 Gr genes is thought to mediate the detection of sugars, the fly's major nutritional source. However, the specific roles for most sugar Gr genes are not known. Here, we report the generation of a series of mutant sugar Gr knock-in alleles and several composite sugar Gr mutant strains, including a sugar blind strain, which will facilitate the characterization of this gene family. Using Ca(2+) imaging experiments, we show that most gustatory receptor neurons (GRNs) of sugar blind flies (lacking all 8 sugar Gr genes) fail to respond to any sugar tested. Moreover, expression of single sugar Gr genes in most sweet GRNs of sugar-blind flies does not restore sugar responses. However, when pair-wise combinations of sugar Gr genes are introduced to sweet GRNs, responses to select sugars are restored. We also examined the cellular phenotype of flies homozygous mutant for Gr64a, a Gr gene previously reported to be a major contributor for the detection of many sugars. In contrast to these claims, we find that sweet GRNs of Gr64a homozygous mutant flies show normal responses to most sugars, and only modestly reduced responses to maltose and maltotriose. Thus, the precisely engineered genetic mutations of single Gr genes and construction of a sugar-blind strain provide powerful analytical tools for examining the roles of Drosophila and other insect sugar Gr genes in sweet taste.

  8. Pseudo and true visible light photocatalytic activity of nanotube titanic acid/graphene composites

    NASA Astrophysics Data System (ADS)

    Wang, Xiaodong; Liu, Xiaogang; Xue, Xiaoxiao; Pan, Hui; Zhang, Min; Li, Qiuye; Yu, Laigui; Yang, Jianjun; Zhang, Zhijun

    2013-09-01

    Nanotube titanic acid/graphene (NTA/Gr) composites were prepared by an easy hydrothermal treatment of graphene oxide (GO) and NTA in a mixed solvent of ethanol-water. As-prepared NTA/Gr composites and GO were characterized by means of Fourier transform infrared spectrometry, X-ray diffraction, diffuse-reflection spectrometry, thermal analysis, and transmission electron microscopy. Besides, the photocatalytic activities of as-prepared NTA/Gr composites were evaluated by monitoring the degradation of methyl orange (MO) under visible light irradiation. It has been found that extending hydrothermal reaction time (24 h instead of 3 h) leads to great changes in the morphology and crystal structure of as-prepared composites. Namely, the orthorhombic NTA (ca. 10 nm in diameter) in the composite transformed to anatase TiO2 particle (ca. 20-30 nm in diameter) while the Gr sheets (with micrometers-long wrinkles) in it transformed to a few Gr fragments (ca. 50 nm in diameter). Correspondingly, the NTA/Gr composite transformed to titanium dioxide/graphene (TiO2/Gr) composite. In the meantime, pure GO only has adsorption effect but it has no photocatalytic activity in the visible light region. Nevertheless, increasing Gr ratio results in enhanced visible light absorption capability and photocatalytic activity of NTA/Gr composites as well as the TiO2/Gr composites. This demonstrates that the true visible light photocatalytic activity of NTA/Gr composites as well as the TiO2/Gr composites for the degradation of MO is not as excellent as expected, and their high apparent activity is attributed to the strong adsorption of MO on the composites.

  9. 40 CFR 60.244 - Test methods and procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... “i,” mg/dscm (gr/dscf). Qsdi=volumetric flow rate of effluent gas from emission point “i,” dscm/hr... (tons). K=conversion factor, 1000 mg/g (7,000 gr/lb). (2) Method 13A or 13B shall be used to determine... the definition of the term “K” to read “(7,000 gr/lb).” . . . ” could not be incorporated because...

  10. Carbon dioxide receptor genes in cotton bollworm Helicoverpa armigera

    NASA Astrophysics Data System (ADS)

    Xu, Wei; Anderson, Alisha

    2015-04-01

    Carbon dioxide (CO2) is important in insect ecology, eliciting a range of behaviours across different species. Interestingly, the numbers of CO2 gustatory receptors (GRs) vary among insect species. In the model organism Drosophila melanogaster, two GRs (DmelGR21a and DmelGR63a) have been shown to detect CO2. In the butterfly, moth, beetle and mosquito species studied so far, three CO2 GR genes have been identified, while in tsetse flies, four CO2 GR genes have been identified. In other species including honeybees, pea aphids, ants, locusts and wasps, no CO2 GR genes have been identified from the genome. These genomic differences may suggest different mechanisms for CO2 detection exist in different insects but, with the exception of Drosophila and mosquitoes, limited attention has been paid to the CO2 GRs in insects. Here, we cloned three putative CO2 GR genes from the cotton bollworm Helicoverpa armigera and performed phylogenetic and expression analysis. All three H. armigera CO2 GRs (HarmGR1, HarmGR2 and HarmGR3) are specifically expressed in labial palps, the CO2-sensing tissue of this moth. HarmGR3 is significantly activated by NaHCO3 when expressed in insect Sf9 cells but HarmGR1 and HarmGR2 are not. This is the first report characterizing the function of lepidopteran CO2 receptors, which contributes to our general understanding of the molecular mechanisms of insect CO2 gustatory receptors.

  11. Nuclear translocation of UDCA by the glucocorticoid receptor is required to reduce TGF-beta1-induced apoptosis in rat hepatocytes.

    PubMed

    Solá, Susana; Amaral, Joana D; Castro, Rui E; Ramalho, Rita M; Borralho, Pedro M; Kren, Betsy T; Tanaka, Hirotoshi; Steer, Cifford J; Rodrigues, Cecília M P

    2005-10-01

    Ursodeoxycholic acid (UDCA) inhibits classical mitochondrial pathways of apoptosis by either directly stabilizing mitochondrial membranes or modulating specific upstream targets. Furthermore, UDCA regulates apoptosis-related genes from transforming growth factor beta1 (TGF-beta1)-induced hepatocyte apoptosis by a nuclear steroid receptor (NSR)-dependent mechanism. In this study, we further investigated the potential role of the glucocorticoid receptor (GR) in the anti-apoptotic function of UDCA. Our results with short interference RNA (siRNA) technology confirmed that UDCA significantly reduces TGF-beta1-induced apoptosis of primary rat hepatocytes through a GR-dependent effect. Immunoprecipitation assays and confocal microscopy showed that UDCA enhanced free GR levels with subsequent GR nuclear translocation. Interestingly, when a carboxy-terminus deleted form of GR was used, UDCA no longer increased free GR and/or GR translocation, nor did it protect against TGF-beta1-induced apoptosis. In co-transfection experiments with GR response element reporter and overexpression constructs, UDCA did not enhance the transactivation of GR with TGF-beta1. Finally, using a fluorescently labeled UDCA molecule, the bile acid appeared diffuse in the cytosol but was aggregated in the nucleus of hepatocytes. Both siRNA assays and transfection experiments with either wild-type or mutant forms of GR showed that nuclear trafficking occurs through a GR-dependent mechanism. In conclusion, these results further clarify the anti-apoptotic mechanism(s) of UDCA and suggest that GR is crucial for the nuclear translocation of this bile acid for reducing apoptosis.

  12. Carbon dioxide receptor genes in cotton bollworm Helicoverpa armigera.

    PubMed

    Xu, Wei; Anderson, Alisha

    2015-04-01

    Carbon dioxide (CO2) is important in insect ecology, eliciting a range of behaviours across different species. Interestingly, the numbers of CO2 gustatory receptors (GRs) vary among insect species. In the model organism Drosophila melanogaster, two GRs (DmelGR21a and DmelGR63a) have been shown to detect CO2. In the butterfly, moth, beetle and mosquito species studied so far, three CO2 GR genes have been identified, while in tsetse flies, four CO2 GR genes have been identified. In other species including honeybees, pea aphids, ants, locusts and wasps, no CO2 GR genes have been identified from the genome. These genomic differences may suggest different mechanisms for CO2 detection exist in different insects but, with the exception of Drosophila and mosquitoes, limited attention has been paid to the CO2 GRs in insects. Here, we cloned three putative CO2 GR genes from the cotton bollworm Helicoverpa armigera and performed phylogenetic and expression analysis. All three H. armigera CO2 GRs (HarmGR1, HarmGR2 and HarmGR3) are specifically expressed in labial palps, the CO2-sensing tissue of this moth. HarmGR3 is significantly activated by NaHCO3 when expressed in insect Sf9 cells but HarmGR1 and HarmGR2 are not. This is the first report characterizing the function of lepidopteran CO2 receptors, which contributes to our general understanding of the molecular mechanisms of insect CO2 gustatory receptors.

  13. Balancing the Budget: Accounting for Glucocorticoid Bioactivity and Fate during Water Treatment.

    PubMed

    Jia, Ai; Wu, Shimin; Daniels, Kevin D; Snyder, Shane A

    2016-03-15

    Numerous studies have identified the presence and bioactivity of glucocorticoid receptor (GR) active substances in water; however, the identification and activity-balance of GR compounds remained elusive. This study determined the occurrence and attenuation of GR bioactivity and closed the balance by determining those substances responsible. The observed in vitro GR activity ranged from 39 to 155 ng dexamethasone-equivalent/L (ng Dex-EQ/L) in the secondary effluents of four wastewater treatment plants. Monochromatic ultraviolet light of 80 mJ/cm(2) disinfection dose was efficient for GR activity photolysis, whereas chlorination could not appreciably attenuate the observed GR activity. Ozonation was effective only at relatively high dose (ozone/TOC 1:1). Microfiltration membranes were not efficient for GR activity attenuation; however, reverse osmosis removed GR activity to levels below the limits of detection. A high-sensitivity liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was then developed to screen 27 GR agonists. Twelve were identified and quantified in effluents at summed concentrations of 9.6-21.2 ng/L. The summed Dex-EQ of individual compounds based on their measured concentrations was in excellent agreement with the Dex-EQ obtained from bioassay, which demonstrated that the detected glucocorticoids can entirely explain the observed GR bioactivity. Four synthetic glucocorticoids (triamcinolone acetonide, fluocinolone acetonide, clobetasol propionate, and fluticasone propionate) predominantly accounted for GR activity. These data represent the first known publication where a complete activity balance has been determined for GR agonists in an aquatic environment.

  14. In vitro inhibition of human erythrocyte glutathione reductase by some new organic nitrates.

    PubMed

    Sentürk, Murat; Talaz, Oktay; Ekinci, Deniz; Cavdar, Hüseyin; Küfrevioğlu, Omer Irfan

    2009-07-01

    Glutathione reductase (GR), is responsible for the existence of GSH molecule, a crucial antioxidant against oxidative stress reagents. The antimalarial activities of some redox active compounds are attributed to their inhibition of antioxidant flavoenzyme glutathione reductase, and inhibitors are therefore expected to be useful for the treatment of malaria. Twelve organic nitrate derivatives were synthesized and treated with human erythrocyte GR. The molecules were identified as strong GR inhibitors and novel antimalaria candidates.

  15. [In Process Citation

    PubMed

    Manner; Koeth; Geelhaar; Stickel

    1999-01-01

    Cryophlebectomy, a more recent technique in varicose veins surgery, was evaluated in comparision with conventional techniques. Group IA: Microphlebectomy, invaginative stripping of the long saphenous vein, tourniquet, n = 90; group IB: only microphlebektomie and tourniquet, n = 72. Group IIA: Cryostripping of the long saphenous vein in combination with cryosurgical distal avulsion of varicosities and microphlebectomy, n = 112; gr. IIB: only cryosurgical distal avulsion of varicosities and microphlebe