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Sample records for fulvestrant faslodex ici

  1. Impact on estrogen receptor binding and target tissue uptake of [18F]fluorine substitution at the 16α-position of fulvestrant (faslodex; ICI 182,780)

    International Nuclear Information System (INIS)

    Seimbille, Yann; Benard, Francois; Rousseau, Jacques; Pepin, Emilie; Aliaga, Antonio; Tessier, Guillaume; Lier, Johan E. van

    2004-01-01

    Fulvestrant (Faslodex; ICI 182,780) is a pure estrogen receptor (ER) antagonist recently approved for the treatment of hormone-sensitive breast cancer in post-menopausal women with disease progression following antiestrogen therapy. Fulvestrant strongly binds to the ER and its mode of action consists of inhibition of ER dimerization leading to a down regulation of ER protein cellular levels. With the aim to develop a probe for positron emission tomography (PET) imaging capable of predicting the potential therapeutic efficacy of selective ER modulators (SERM), we prepared three new 16α-[ 18 F]fluoro-fulvestrant derivatives. These new radiopharmaceuticals were evaluated for their binding affinity to the human ERα and for their target tissue uptake in immature female rats. Substitution of one of the side-chain F-atoms of fulvestrant for 18 F would have led to a product of low specific activity; instead we selected the 16α-position for 18 F-labeling, which at least in the case of estradiol (ES) is well tolerated by the ER. Radiochemical synthesis proceeds by stereoselective introduction of the [ 18 F]fluoride at the 16- 18 F-position of fulvestrant via opening of an intermediate O-cyclic sulfate followed by hydrolysis of the protecting methoxymethyl (MOM) ether and sulfate groups. Three analogs with different oxidation states of the side chain sulfur, i.e. sulfide, sulfone or sulfoxide (fulvestrant) were prepared. Introduction of the 16 18 F-fluorine led to a dramatic decrease of the apparent binding affinity for ER, as reported by Wakeling et al. (Cancer Res. 1991;51:3867-73). Likewise, in vivo ER-mediated uterus uptake values in immature female rats were disappointing. Overall, our findings suggest that these new PET radiopharmaceuticals are not suitable as tracers to predict ER(+) breast cancer response to hormonal therapy with selective ER modulators

  2. Impact on estrogen receptor binding and target tissue uptake of [{sup 18}F]fluorine substitution at the 16{alpha}-position of fulvestrant (faslodex; ICI 182,780)

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    Seimbille, Yann; Benard, Francois E-mail: francois.benard@USherbrooke.ca; Rousseau, Jacques; Pepin, Emilie; Aliaga, Antonio; Tessier, Guillaume; Lier, Johan E. van

    2004-08-01

    Fulvestrant (Faslodex; ICI 182,780) is a pure estrogen receptor (ER) antagonist recently approved for the treatment of hormone-sensitive breast cancer in post-menopausal women with disease progression following antiestrogen therapy. Fulvestrant strongly binds to the ER and its mode of action consists of inhibition of ER dimerization leading to a down regulation of ER protein cellular levels. With the aim to develop a probe for positron emission tomography (PET) imaging capable of predicting the potential therapeutic efficacy of selective ER modulators (SERM), we prepared three new 16{alpha}-[{sup 18}F]fluoro-fulvestrant derivatives. These new radiopharmaceuticals were evaluated for their binding affinity to the human ER{alpha} and for their target tissue uptake in immature female rats. Substitution of one of the side-chain F-atoms of fulvestrant for {sup 18}F would have led to a product of low specific activity; instead we selected the 16{alpha}-position for {sup 18}F-labeling, which at least in the case of estradiol (ES) is well tolerated by the ER. Radiochemical synthesis proceeds by stereoselective introduction of the [{sup 18}F]fluoride at the 16-{sup 18}F-position of fulvestrant via opening of an intermediate O-cyclic sulfate followed by hydrolysis of the protecting methoxymethyl (MOM) ether and sulfate groups. Three analogs with different oxidation states of the side chain sulfur, i.e. sulfide, sulfone or sulfoxide (fulvestrant) were prepared. Introduction of the 16{sup 18}F-fluorine led to a dramatic decrease of the apparent binding affinity for ER, as reported by Wakeling et al. (Cancer Res. 1991;51:3867-73). Likewise, in vivo ER-mediated uterus uptake values in immature female rats were disappointing. Overall, our findings suggest that these new PET radiopharmaceuticals are not suitable as tracers to predict ER(+) breast cancer response to hormonal therapy with selective ER modulators.

  3. TIMP1 overexpression mediates resistance of MCF-7 human breast cancer cells to fulvestrant and down-regulates progesterone receptor expression

    DEFF Research Database (Denmark)

    Bjerre, Christina; Vinther, Lena; Belling, Kirstine C.

    2013-01-01

    is associated with endocrine sensitivity. We established a panel of 11 MCF-7 subclones with a wide range of TIMP1 mRNA and protein expression levels. Cells with high expression of TIMP1 versus low TIMP1 displayed significantly reduced sensitivity to the antiestrogen fulvestrant (ICI 182,780, Faslodex®), while......, the effects of fulvestrant, 4-hydroxytamoxifen, or estrogen on estrogen receptor expression were not associated with TIMP1 levels. Gene expression analyses revealed associations between expression of TIMP1 and genes involved in metabolic pathways, epidermal growth factor receptor 1/cancer signaling pathways......, and cell cycle. Gene and protein expression analyses showed no general defects in estrogen receptor signaling except from lack of progesterone receptor expression and estrogen inducibility in clones with high TIMP1. The present study suggests a relation between high expression level of TIMP1 and loss...

  4. Prognostic value of monitoring tumour markers CA 15-3 and CEA during fulvestrant treatment

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    Locker Gottfried J

    2006-03-01

    Full Text Available Abstract Background At many centres tumour markers are used to detect disease recurrence and to monitor response to therapy in patients with advanced disease, although the real value of serial observation of marker levels remains disputed. In this study, we evaluated the prognostic value of tumour markers for predicting response (partial response [PR], stable disease [SD] ≥ 6 months, de novo disease progression (PD and secondary PD in patients receiving fulvestrant ('Faslodex' 250 mg/month for the treatment of metastatic breast cancer (MBC. Methods Changes in cancer antigen 15–3 (CA 15-3 and carcinoembryonic antigen (CEA were prospectively monitored (monthly and were also evaluated for the 3 months preceding secondary PD. Data from 67 patients with previously treated MBC participating in a Compassionate Use Programme were analysed. Results In patients with a PR (n = 7 [10.4%], a non-significant increase in CA 15-3 occurred during the first 6 months of treatment; CEA was significantly reduced (P = 0.0165. In patients with SD ≥ 6 months (n = 28 [41.8%], both CA 15-3 (P P = 0.0399 levels increased significantly after 6 months treatment. In those experiencing de novo PD (n = 32 [47.8%], CA 15-3 increased significantly (P P = 0.0002 during the same time period. Both CA 15-3 (P P Conclusion CA 15-3 increases in patients progressing on fulvestrant but may also increase in those experiencing clinical benefit; this should not be taken as a sign of PD without verification. Overall, both CA 15-3 and CEA appear to be poor prognostic markers for determining progression in patients receiving fulvestrant.

  5. Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis.

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    Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D; Parkhitko, Andrey; Morrison, Tasha A; Silverman, Edwin K; Henske, Elizabeth P; Yu, Jane J

    2013-07-01

    Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)-2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)-2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM.

  6. Faslodex Inhibits Estradiol-Induced Extracellular Matrix Dynamics and Lung Metastasis in a Model of Lymphangioleiomyomatosis

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    Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D.; Parkhitko, Andrey; Morrison, Tasha A.; Silverman, Edwin K.; Henske, Elizabeth P.

    2013-01-01

    Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)–2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)–2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM. PMID:23526212

  7. Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell–matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis

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    Chen, Yan; Li, Zheng; He, Yan; Shang, Dandan; Pan, Jigang; Wang, Hongmei; Chen, Huamei; Zhu, Zhuxia [Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, 9 Beijing Road, Guiyang 550004, Guizhou (China); Wan, Lei [Department of Pharmacology, Guiyang Medical University School of Basic Medicine, 9 Beijing Road, Guiyang 550004, Guizhou (China); Wang, Xudong, E-mail: xdwang@gmc.edu.cn [Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, 9 Beijing Road, Guiyang 550004, Guizhou (China)

    2014-03-01

    Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but not calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded calpain activation triggered by estrogenic and antiestrogenic stimulations indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or ICI-induced cell adhesion was dramatically impaired by calpain-specific inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30-associated action. These data show that enhanced cell adhesion by E2 and ICI occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that targeting the GPR30 signaling may be a potential strategy to reduce metastasis and improve the efficacy of antiestrogens in treatment of advanced breast cancer. - Highlights: • Estrogen and ICI augment adhesion to matrigel with calpain activation in MCF-7 cells. • GPR30 mediates cell–matrigel adhesion and calpain activation via ERK1/2. • Calpain is required in the cell–matrigel adhesion induced by E2 and ICI.

  8. Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell–matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis

    International Nuclear Information System (INIS)

    Chen, Yan; Li, Zheng; He, Yan; Shang, Dandan; Pan, Jigang; Wang, Hongmei; Chen, Huamei; Zhu, Zhuxia; Wan, Lei; Wang, Xudong

    2014-01-01

    Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but not calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded calpain activation triggered by estrogenic and antiestrogenic stimulations indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or ICI-induced cell adhesion was dramatically impaired by calpain-specific inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30-associated action. These data show that enhanced cell adhesion by E2 and ICI occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that targeting the GPR30 signaling may be a potential strategy to reduce metastasis and improve the efficacy of antiestrogens in treatment of advanced breast cancer. - Highlights: • Estrogen and ICI augment adhesion to matrigel with calpain activation in MCF-7 cells. • GPR30 mediates cell–matrigel adhesion and calpain activation via ERK1/2. • Calpain is required in the cell–matrigel adhesion induced by E2 and ICI

  9. High CDK6 protects cells from fulvestrant-mediated apoptosis and is a predictor of resistance to fulvestrant in estrogen receptor-positive metastatic breast cancer

    DEFF Research Database (Denmark)

    Alves, Carla Maria Lourenco; Elias, Daniel; Lyng, Maria B

    2016-01-01

    expression impaired fulvestrant-resistant cell growth and induced apoptosis. Treatment with palbociclib re-sensitized fulvestrant-resistant cells to fulvestrant through alteration of retinoblastoma protein phosphorylation. High CDK6 levels in metastatic samples from two independent cohorts of breast cancer...

  10. Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

    International Nuclear Information System (INIS)

    Wang, Jing; Yang, Qifeng; Haffty, Bruce G.; Li, Xiaoyan; Moran, Meena S.

    2013-01-01

    Highlights: ► Fulvestrant radiosensitizes MCF-7 cells. ► Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ► Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy ± fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 ± 0.013 vs. 0.622 ± 0.029 @2 Gy, 0.599 ± 0.045 vs. 0.475 ± 0.054 @4 Gy, and 0.472 ± 0.021 vs. 0.380 ± 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT

  11. Silencing MED1 sensitizes breast cancer cells to pure anti-estrogen fulvestrant in vitro and in vivo.

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    Lijiang Zhang

    Full Text Available Pure anti-estrogen fulvestrant has been shown to be a promising ER antagonist for locally advanced and metastatic breast cancer. Unfortunately, a significant proportion of patients developed resistance to this type of endocrine therapy but the molecular mechanisms governing cellular responsiveness to this agent remain poorly understood. Here, we've reported that knockdown of estrogen receptor coactivator MED1 sensitized fulvestrant resistance breast cancer cells to fulvestrant treatment. We found that MED1 knockdown further promoted cell cycle arrest induced by fulvestrant. Using an orthotopic xenograft mouse model, we found that knockdown of MED1 significantly reduced tumor growth in mice. Importantly, knockdown of MED1 further potentiated tumor growth inhibition by fulvestrant. Mechanistic studies indicated that combination of fulvestrant treatment and MED1 knockdown is able to cooperatively inhibit the expression of ER target genes. Chromatin immunoprecipitation experiments further supported a role for MED1 in regulating the recruitment of RNA polymerase II and transcriptional corepressor HDAC1 on endogenous ER target gene promoter in the presence of fulvestrant. These results demonstrate a role for MED1 in mediating resistance to the pure anti-estrogen fulvestrant both in vitro and in vivo.

  12. Efficacy of palbociclib plus fulvestrant after everolimus in hormone receptor-positive metastatic breast cancer.

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    du Rusquec, Pauline; Palpacuer, Clément; Campion, Loic; Patsouris, Anne; Augereau, Paule; Gourmelon, Carole; Robert, Marie; Dumas, Laurence; Caroline, Folliard; Campone, Mario; Frenel, Jean-Sébastien

    2018-04-01

    Palbociclib, a CDK4-6 inhibitor, combined with endocrine therapy (ET) is a new standard of treatment for Hormone Receptor-positive Metastatic Breast Cancer. We present the first real-life efficacy and tolerance data of palbociclib plus fulvestrant in this population. From November 2015 to November 2016, patients receiving in our institution palbociclib + fulvestrant according to the Temporary Authorization for Use were prospectively analyzed. 60 patients were treated accordingly; median age was 61 years; 50 patients (83.3%) had visceral metastasis, and 10 (16.7%) had bone-only disease. Patients had previously received a median of 5 (1-14) lines of treatment, including ET (median 3) and chemotherapy (median 2); 28 (46.7%) received previously fulvestrant and all everolimus. With a median follow-up of 10.3 months, median progression-free survival (mPFS) was 5.8 months (95% CI 3.9-7.3). Patients pretreated with fulvestrant had a similar PFS of 6.4 months (HR 1.00; 95% CI 0.55-1.83; P = 1.00). The most common AEs (adverse events) were neutropenia (93%), anemia (65%), and thrombocytopenia (55%). In this heavily pretreated population including everolimus, fulvestrant plus palbociclib provides an mPFS of 5.8 months with the same magnitude of benefit for fulvestrant-pretreated patients.

  13. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.

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    Cristofanilli, Massimo; Turner, Nicholas C; Bondarenko, Igor; Ro, Jungsil; Im, Seock-Ah; Masuda, Norikazu; Colleoni, Marco; DeMichele, Angela; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Zhang, Ke; Theall, Kathy Puyana; Jiang, Yuqiu; Bartlett, Cynthia Huang; Koehler, Maria; Slamon, Dennis

    2016-04-01

    In the PALOMA-3 study, the combination of the CDK4 and CDK6 inhibitor palbociclib and fulvestrant was associated with significant improvements in progression-free survival compared with fulvestrant plus placebo in patients with metastatic breast cancer. Identification of patients most suitable for the addition of palbociclib to endocrine therapy after tumour recurrence is crucial for treatment optimisation in metastatic breast cancer. We aimed to confirm our earlier findings with this extended follow-up and show our results for subgroup and biomarker analyses. In this multicentre, double-blind, randomised phase 3 study, women aged 18 years or older with hormone-receptor-positive, HER2-negative metastatic breast cancer that had progressed on previous endocrine therapy were stratified by sensitivity to previous hormonal therapy, menopausal status, and presence of visceral metastasis at 144 centres in 17 countries. Eligible patients-ie, any menopausal status, Eastern Cooperative Oncology Group performance status 0-1, measurable disease or bone disease only, and disease relapse or progression after previous endocrine therapy for advanced disease during treatment or within 12 months of completion of adjuvant therapy-were randomly assigned (2:1) via a centralised interactive web-based and voice-based randomisation system to receive oral palbociclib (125 mg daily for 3 weeks followed by a week off over 28-day cycles) plus 500 mg fulvestrant (intramuscular injection on days 1 and 15 of cycle 1; then on day 1 of subsequent 28-day cycles) or placebo plus fulvestrant. The primary endpoint was investigator-assessed progression-free survival. Analysis was by intention to treat. We also assessed endocrine therapy resistance by clinical parameters, quantitative hormone-receptor expression, and tumour PIK3CA mutational status in circulating DNA at baseline. This study is registered with ClinicalTrials.gov, NCT01942135. Between Oct 7, 2013, and Aug 26, 2014, 521 patients were

  14. The use of fulvestrant, a parenteral endocrine agent, in intestinal obstruction due to metastatic lobular breast carcinoma

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    Rampaul Rajendra Singh

    2008-12-01

    Full Text Available Abstract Background The role of fulvestrant in the management of intestinal obstruction associated with lobular carcinoma has not been specifically described. Case presentation Herein we present two cases where fulvestrant, as the only available parenteral endocrine agent for postmenopausal advanced breast cancer has the opportunity to provide a means to initiate treatment in those patients who present with varying degrees of intestinal obstruction. Conclusion Fulvestrant may obviate the use of chemotherapy while achieving sustained clinical benefit with less toxicity, in appropriately selected patients.

  15. Sulfation of fulvestrant by human liver cytosols and recombinant SULT1A1 and SULT1E1

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    Edavana VK

    2011-11-01

    Full Text Available Vineetha Koroth Edavana1, Xinfeng Yu1, Ishwori B Dhakal1, Suzanne Williams1, Baitang Ning2, Ian T Cook3, David Caldwell1, Charles N Falany3, Susan Kadlubar11Division of Medical Genetics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, USA; 3Department of Pharmacology, University of Alabama, Birmingham, AL, USAAbstract: Fulvestrant (Faslodex™ is a pure antiestrogen that is approved to treat hormone receptor-positive metastatic breast cancer in postmenopausal women. Previous studies have demonstrated that fulvestrant metabolism in humans involves cytochromes P450 and UDP-glucuronosyltransferases (UGTs. To date, fulvestrant sulfation has not been characterized. This study examined fulvestrant sulfation with nine recombinant sulfotransferases and found that only SULT1A1 and SULT1E1 displayed catalytic activity toward this substrate, with Km of 4.2 ± 0.99 and 0.2 ± 0.16 µM, respectively. In vitro assays of 104 human liver cytosols revealed marked individual variability that was highly correlated with β-naphthol sulfation (SULT1A1 diagnostic substrate; r = 0.98, P < 0.0001, but not with 17ß-estradiol sulfation (SULT1E1 diagnostic substrate; r = 0.16, P = 0.10. Fulvestrant sulfation was correlated with both SULT1A1*1/2 genotype (P value = 0.023 and copy number (P < 0.0001. These studies suggest that factors influencing SULT1A1/1E1 tissue expression and/or enzymatic activity could influence the efficacy of fulvestrant therapy.Keywords: fulvestrant, sulfotransferase, genotype, copy number

  16. Clinical activity of fulvestrant in metastatic breast cancer previously treated with endocrine therapy and/or chemotherapy.

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    Heo, Mi Hwa; Kim, Hee Kyung; Lee, Hansang; Kim, Ji-Yeon; Ahn, Jin-Seok; Im, Young-Hyuck; Park, Yeon Hee

    2018-03-16

    We conducted a retrospective analysis of the clinical activity of fulvestrant in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with endocrine therapy and/or chemotherapy. We reviewed the medical records of all patients with MBC treated at Samsung Medical Center between January 2009 and August 2016. Patients received fulvestrant 250 mg intramuscularly every 28 days (from January 2009 to November 2010) or 500 mg intramuscularly every 28 days (from December 2010 to August 2016). Tumor responses were assessed every 8 weeks and at the end of treatment, as well as when disease progression was suspected. A total of 84 patients were included in this study. A median of two previous endocrine treatments had been performed; 79% of the patients had received two or more endocrine treatments. Forty-five patients (54%) had been treated with chemotherapy for MBC before the fulvestrant treatment course. Visceral metastasis was found in 49 patients (58%). The estimated median progression-free survival and overall survival were 4.4 months (95% confidence interval [CI], 3.4 to 5.5) and 32.5 months (95% CI, 17.6 to 47.4), respectively. The disease control rate was 40.5% (95% CI, 30.5 to 51.5); partial response was observed in 16% of the patients and stable disease was observed in 25% of the patients. The most frequently reported adverse reactions were mild-to-moderate grade myalgia (10.5% of the patients), injection site pain (7%), and fatigue (7%). Fulvestrant was generally well tolerated. Fulvestrant showed encouraging clinical activity and favorable feasibility in postmenopausal women with MBC who had been treated with multiple endocrine therapies and/or cytotoxic chemotherapies.

  17. Paradoxical action of fulvestrant in estradiol-induced regression of tamoxifen-stimulated breast cancer.

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    Osipo, Clodia; Gajdos, Csaba; Liu, Hong; Chen, Bin; Jordan, V Craig

    2003-11-05

    Long-term tamoxifen treatment of breast cancer can result in tamoxifen-stimulated breast cancer, in which estrogen inhibits tumor growth after tamoxifen withdrawal. We investigated the molecular mechanism(s) of estradiol-induced tumor regression by using an in vivo model of tamoxifen-stimulated human breast cancer. Growth of parental estradiol-stimulated MCF-7E2 and long-term tamoxifen-stimulated MCF-7TAMLT xenografts in athymic mice was measured during treatment with vehicle, estradiol, estradiol plus tamoxifen, tamoxifen alone, estradiol plus fulvestrant, or fulvestrant alone. Apoptosis was detected by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Protein expression was assessed by western blot analysis. mRNA expression was assessed by real-time reverse transcription-polymerase chain reaction. All statistical tests were two-sided. MCF-7E2 tumor growth was stimulated by estradiol (cross-sectional area at week 13 = 1.06 cm2, 95% confidence interval [CI] = 0.82 to 1.30 cm2; Pestradiol-induced regression to 0.18 cm2 (95% CI = 0.15 to 0.21 cm2; P<.001), and tamoxifen or estradiol plus fulvestrant enhanced tumor growth to 1.00 cm2 (95% CI = 0.88 to 1.22 cm2). Estradiol increased the number of apoptotic cells in tumors by 23% (95% CI = 20% to 26%; P<.001) compared with all other treatments, decreased estrogen receptor alpha(ERalpha) protein expression, increased the expression of Fas mRNA and protein, decreased the expression of HER2/neu mRNA and protein and nuclear factor kappaB (NF-kappaB) protein but did not affect Fas ligand protein expression compared with control. Paradoxically, fulvestrant reversed this effect and stimulated MCF-7TAMLT tumor growth apparently through ERalpha-mediated regulation of Fas, HER2/neu, and NF-kappaB. Physiologic levels of estradiol induced regression of tamoxifen-stimulated breast cancer tumors, apparently by inducing the death receptor Fas and suppressing the antiapoptotic

  18. Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial.

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    Harbeck, N; Iyer, S; Turner, N; Cristofanilli, M; Ro, J; André, F; Loi, S; Verma, S; Iwata, H; Bhattacharyya, H; Puyana Theall, K; Bartlett, C H; Loibl, S

    2016-06-01

    In the PALOMA-3 study, palbociclib plus fulvestrant demonstrated improved progression-free survival compared with fulvestrant plus placebo in hormone receptor-positive, HER2- endocrine-resistant metastatic breast cancer (MBC). This analysis compared patient-reported outcomes (PROs) between the two treatment groups. Patients were randomized 2 : 1 to receive palbociclib 125 mg/day orally for 3 weeks followed by 1 week off (n = 347) plus fulvestrant (500 mg i.m. per standard of care) or placebo plus fulvestrant (n = 174). PROs were assessed on day 1 of cycles 1-4 and of every other subsequent cycle starting with cycle 6 using the EORTC QLQ-C30 and its breast cancer module, QLQ-BR23. High scores (range 0-100) could indicate better functioning/quality of life (QoL) or worse symptom severity. Repeated-measures mixed-effect analyses were carried out to compare on-treatment overall scores and changes from baseline between treatment groups while controlling for baseline. Between-group comparisons of time to deterioration in global QoL and pain were made using an unstratified log-rank test and Cox proportional hazards model. Questionnaire completion rates were high at baseline and during treatment (from baseline to cycle 14, ≥95.8% in each group completed ≥1 question on the EORTC QLQ-C30). On treatment, estimated overall global QoL scores significantly favored the palbociclib plus fulvestrant group [66.1, 95% confidence interval (CI) 64.5-67.7 versus 63.0, 95% CI 60.6-65.3; P = 0.0313]. Significantly greater improvement from baseline in pain was also observed in this group (-3.3, 95% CI -5.1 to -1.5 versus 2.0, 95% CI -0.6 to 4.6; P = 0.0011). No significant differences were observed for other QLQ-BR23 functioning domains, breast or arm symptoms. Treatment with palbociclib plus fulvestrant significantly delayed deterioration in global QoL (P < 0.025) and pain (P < 0.001) compared with fulvestrant alone. Palbociclib plus fulvestrant allowed patients to maintain good Qo

  19. Effects of fulvestrant alone or combined with different steroids in human breast cancer cells

    NARCIS (Netherlands)

    Jansen, G.H.; Franke, H.R.; Wolbers, F.; Brinkhuis, M.; Brinkhuis, M.; Vermes, I.

    2008-01-01

    Objectives Fulvestrant is an estrogen receptor (ER) antagonist that binds, blocks and degrades the estrogen receptor and is currently used in adjuvant treatment in postmenopausal women with ER-positive breast cancer as an alternative for tamoxifen. As an antagonist, it may induce or aggravate

  20. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial.

    Science.gov (United States)

    Johnston, Stephen Rd; Kilburn, Lucy S; Ellis, Paul; Dodwell, David; Cameron, David; Hayward, Larry; Im, Young-Hyuck; Braybrooke, Jeremy P; Brunt, A Murray; Cheung, Kwok-Leung; Jyothirmayi, Rema; Robinson, Anne; Wardley, Andrew M; Wheatley, Duncan; Howell, Anthony; Coombes, Gill; Sergenson, Nicole; Sin, Hui-Jung; Folkerd, Elizabeth; Dowsett, Mitch; Bliss, Judith M

    2013-09-01

    The optimum endocrine treatment for postmenopausal women with advanced hormone-receptor-positive breast cancer that has progressed on non-steroidal aromatase inhibitors (NSAIs) is unclear. The aim of the SoFEA trial was to assess a maximum double endocrine targeting approach with the steroidal anti-oestrogen fulvestrant in combination with continued oestrogen deprivation. In a composite, multicentre, phase 3 randomised controlled trial done in the UK and South Korea, postmenopausal women with hormone-receptor-positive breast cancer (oestrogen receptor [ER] positive, progesterone receptor [PR] positive, or both) were eligible if they had relapsed or progressed with locally advanced or metastatic disease on an NSAI (given as adjuvant for at least 12 months or as first-line treatment for at least 6 months). Additionally, patients had to have adequate organ function and a WHO performance status of 0-2. Participants were randomly assigned (1:1:1) to receive fulvestrant (500 mg intramuscular injection on day 1, followed by 250 mg doses on days 15 and 29, and then every 28 days) plus daily oral anastrozole (1 mg); fulvestrant plus anastrozole-matched placebo; or daily oral exemestane (25 mg). Randomisation was done with computer-generated permuted blocks, and stratification was by centre and previous use of an NSAI as adjuvant treatment or for locally advanced or metastatic disease. Participants and investigators were aware of assignment to fulvestrant or exemestane, but not of assignment to anastrozole or placebo. The primary endpoint was progression-free survival (PFS). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, numbers NCT00253422 (UK) and NCT00944918 (South Korea). Between March 26, 2004, and Aug 6, 2010, 723 patients underwent randomisation: 243 were assigned to receive fulvestrant plus anastrozole, 231 to fulvestrant plus placebo, and 249 to exemestane. Median PFS was 4·4 months (95% CI 3·4-5·4) in patients assigned to

  1. Health-related quality of life from the FALCON phase III randomised trial of fulvestrant 500 mg versus anastrozole for hormone receptor-positive advanced breast cancer.

    Science.gov (United States)

    Robertson, John F R; Cheung, Kwok-Leung; Noguchi, Shinzaburo; Shao, Zhimin; Degboe, Arnold; Lichfield, Jasmine; Thirlwell, Jackie; Fazal, Mehdi; Ellis, Matthew J

    2018-05-01

    The phase III randomised FALCON trial (NCT01602380) demonstrated improved progression-free survival with fulvestrant 500 mg versus anastrozole 1 mg in endocrine therapy-naïve postmenopausal women with hormone receptor-positive (HR+) locally advanced or metastatic breast cancer (LA/MBC). Furthermore, overall health-related quality of life (HRQoL) was maintained and comparable for fulvestrant and anastrozole. Here, we present additional analyses of patient-reported HRQoL outcomes from FALCON. Women with endocrine therapy-naïve HR+ LA/MBC were randomised 1:1 to fulvestrant (days 0, 14, 28, then every 28 d) or anastrozole (daily) until disease progression or discontinuation. HRQoL was assessed by FACT-B questionnaire (TOI and FACT-B total score) at randomisation and every 12 weeks during treatment. HRQoL data post-treatment (with or without progression) were also collected. In total, 462 patients were randomised (fulvestrant, n = 230; anastrozole, n = 232). Compliance to FACT-B overall ranged from 60.0 to 97.4%. Mean change from baseline in TOI and FACT-B total score remained broadly stable (approximately ± 3 points to week 132) and was similar between arms during treatment. HRQoL was also maintained in FACT-B subscales. Approximately one-third of patients had improved TOI (≥+6 points) and FACT-B (≥+8 points) total scores from baseline up to week 120 and 132, respectively, of treatment with fulvestrant (ranges 26.4-45.0% and 22.4-35.8%, respectively) and anastrozole (ranges 18.6-32.9%, and 22.7-37.9%, respectively). Mean change from baseline in TOI and FACT-B total score was maintained for fulvestrant and anastrozole; similar proportions of patients in both arms had improved TOI and FACT-B total scores. CLINICALTRIALS. NCT01602380. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy-Safety and Efficacy in Asian Patients.

    Science.gov (United States)

    Iwata, Hiroji; Im, Seock-Ah; Masuda, Norikazu; Im, Young-Hyuck; Inoue, Kenichi; Rai, Yoshiaki; Nakamura, Rikiya; Kim, Jee Hyun; Hoffman, Justin T; Zhang, Ke; Giorgetti, Carla; Iyer, Shrividya; Schnell, Patrick T; Bartlett, Cynthia Huang; Ro, Jungsil

    2017-08-01

    To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy-resistant metastatic breast cancer. The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

  3. Comparison of palbociclib in combination with letrozole or fulvestrant with endocrine therapies for advanced/metastatic breast cancer: network meta-analysis.

    Science.gov (United States)

    Chirila, Costel; Mitra, Debanjali; Colosia, Ann; Ling, Caroline; Odom, Dawn; Iyer, Shrividya; Kaye, James A

    2017-08-01

    Palbociclib is the first cyclin-dependent kinase 4/6 inhibitor approved in the United States for HR+/HER2- advanced/metastatic breast cancer, in combination with letrozole as initial endocrine-based therapy in postmenopausal women or with fulvestrant in women with disease progression following endocrine therapy. We compared progression-free survival (PFS) and discontinuations due to adverse events for palbociclib combinations against other endocrine therapies using a mixed-treatment comparison meta-analysis of randomized, controlled trials. A systematic literature review identified relevant trials. Separate analyses were conducted for each palbociclib combination using a Bayesian approach. Treatment rankings were established using the surface under the cumulative ranking curve (SUCRA). Sixty-five unique studies met inclusion criteria. Palbociclib plus letrozole had the highest SUCRA value (99.9%) and was associated with significantly longer PFS than all comparators in treatment-naïve patients (hazard ratios [HRs] ranged from 0.41 to 0.58). Palbociclib plus fulvestrant had the second highest SUCRA value (93.9%) and, in previously treated patients, yielded significantly longer PFS than most comparators (HRs ranged from 0.26 to 0.46); the exception was everolimus plus exemestane, with similar PFS (HR, 1.04; 95% credible interval [CrI], 0.58-1.76). Palbociclib plus fulvestrant was associated with significantly lower odds of discontinuation due to adverse events than everolimus plus exemestane (odds ratio, 0.14; 95% CrI, 0.05-0.39). The results suggest that the two palbociclib combinations yielded significantly greater PFS than endocrine therapy in treatment-naïve and previously treated patients with advanced/metastatic breast cancer. Palbociclib plus fulvestrant was associated with significantly less toxicity than everolimus plus exemestane.

  4. PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

    Science.gov (United States)

    Im, Seock-Ah; Masuda, Norikazu; Im, Young-Hyuck; Inoue, Kenichi; Rai, Yoshiaki; Nakamura, Rikiya; Kim, Jee Hyun; Hoffman, Justin T.; Zhang, Ke; Giorgetti, Carla; Iyer, Shrividya; Schnell, Patrick T.; Bartlett, Cynthia Huang; Ro, Jungsil

    2017-01-01

    Purpose To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer. Patients and Methods The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. Results This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. Conclusion This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study. PMID:28831437

  5. PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

    Directory of Open Access Journals (Sweden)

    Hiroji Iwata

    2017-08-01

    Full Text Available Purpose: To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer. Patients and Methods: The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3 trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs were assessed on study treatment and at the end of treatment. Results: This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71 or placebo plus fulvestrant (n = 31. Palbociclib plus fulvestrant improved progression-free survival (PFS compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065. The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92% and leukopenia (29%; febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. Conclusion: This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

  6. Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.

    Science.gov (United States)

    O'Leary, Ben; Hrebien, Sarah; Morden, James P; Beaney, Matthew; Fribbens, Charlotte; Huang, Xin; Liu, Yuan; Bartlett, Cynthia Huang; Koehler, Maria; Cristofanilli, Massimo; Garcia-Murillas, Isaac; Bliss, Judith M; Turner, Nicholas C

    2018-03-01

    CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.

  7. Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

    DEFF Research Database (Denmark)

    Kümler, Iben; Knoop, Ann S; Jessing, Christina A R

    2016-01-01

    . However, overall survival was not significantly increased. CONCLUSION: Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin...

  8. Thermal evolution of trans-Neptunian objects, icy satellites, and minor icy planets in the early solar system

    Science.gov (United States)

    Bhatia, Gurpreet Kaur; Sahijpal, Sandeep

    2017-12-01

    Numerical simulations are performed to understand the early thermal evolution and planetary scale differentiation of icy bodies with the radii in the range of 100-2500 km. These icy bodies include trans-Neptunian objects, minor icy planets (e.g., Ceres, Pluto); the icy satellites of Jupiter, Saturn, Uranus, and Neptune; and probably the icy-rocky cores of these planets. The decay energy of the radionuclides, 26Al, 60Fe, 40K, 235U, 238U, and 232Th, along with the impact-induced heating during the accretion of icy bodies were taken into account to thermally evolve these planetary bodies. The simulations were performed for a wide range of initial ice and rock (dust) mass fractions of the icy bodies. Three distinct accretion scenarios were used. The sinking of the rock mass fraction in primitive water oceans produced by the substantial melting of ice could lead to planetary scale differentiation with the formation of a rocky core that is surrounded by a water ocean and an icy crust within the initial tens of millions of years of the solar system in case the planetary bodies accreted prior to the substantial decay of 26Al. However, over the course of billions of years, the heat produced due to 40K, 235U, 238U, and 232Th could have raised the temperature of the interiors of the icy bodies to the melting point of iron and silicates, thereby leading to the formation of an iron core. Our simulations indicate the presence of an iron core even at the center of icy bodies with radii ≥500 km for different ice mass fractions.

  9. PAINT SUPPLIES AND LOCATION: EXAMINING ICI

    Directory of Open Access Journals (Sweden)

    M. Herron

    2016-01-01

    Full Text Available How important is location to an international retailer? Not just any retailer but the second largest paint retailer in the world. Imperial Chemical Industries (ICI was a British chemical company and was at one stage the largest manufacturer in Britain. Formed from the merger of several leading British chemical companies in 1926, ICI makes paints and speciality products, including food ingredients, speciality polymers, electronic materials, fragrances and flavourings. ICI paints purchased the Cleveland Ohiobased Glidden Coatings & Resins (Glidden Paint Company in 1986 for USD$580 million. The addition of Glidden to ICI's North American operations more than doubled that subsidiary's annual sales to $3 billion and increased ICI's corporate presence in the United States dramatically. A decline in paint and solvent consumption during the 2000 decade slowed the average growth of the paint industry to about 2% annually. Rauch Associates, the leading US paint analyst firm, predicted near-term growth to slow even further to 1.2% per annum. Through the 1990’s and early 2000’s Glidden paint was sold only through Glidden-badged paint stores and smaller retailers under licence, developing a strong identifiable brand and reputation. How were potential Glidden retail paint store locations chosen across America to enable and support this market growth? This paper investigates the real process that was developed and applied to construct a national network of retail outlets across the United States. It also highlights the change in direction that occurred at ICI paints culminating in its eventual acquisition by AkzoNobel in 2008 who immediately sold parts of ICI to Henkel, and integrated ICI's remaining operations within its existing organisation. This sale and the associated corporate restructure caused considerable change in marketing directions allowing for the first time the selling of Glidden paint products to mass market centres

  10. Raman Life Detection Instrument Development for Icy Worlds

    Science.gov (United States)

    Thomson, Seamus; Allen, A'Lester; Gutierrez, Daniel; Quinn, Richard C.; Chen, Bin; Koehne, Jessica E.

    2017-01-01

    The objective of this project is to develop a compact, high sensitivity Raman sensor for detection of life signatures in a flow cell configuration to enable bio-exploration and life detection during future mission to our Solar Systems Icy Worlds. The specific project objectives are the following: 1) Develop a Raman spectroscopy liquid analysis sensor for biosignatures; 2) Demonstrate applicability towards a future Enceladus or other Icy Worlds missions; 3) Establish key parameters for integration with the ARC Sample Processor for Life on Icy Worlds (SPLIce); 4) Position ARC for a successful response to upcoming Enceladus or other Icy World mission instrument opportunities.

  11. Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results.

    Science.gov (United States)

    Loibl, Sibylle; Turner, Nicholas C; Ro, Jungsil; Cristofanilli, Massimo; Iwata, Hiroji; Im, Seock-Ah; Masuda, Norikazu; Loi, Sherene; André, Fabrice; Harbeck, Nadia; Verma, Sunil; Folkerd, Elizabeth; Puyana Theall, Kathy; Hoffman, Justin; Zhang, Ke; Bartlett, Cynthia Huang; Dowsett, Mitchell

    2017-09-01

    The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET). One hundred eight premenopausal endocrine-refractory women ≥18 years with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) ABC were among 521 women randomized 2:1 (347:174) to fulvestrant (500 mg) ± goserelin with either palbociclib (125 mg/day orally, 3 weeks on, 1 week off) or placebo. This analysis assessed whether the overall tolerable safety profile and significant progression-free survival (PFS) improvement extended to premenopausal women. Potential drug-drug interactions (DDIs) and ovarian suppression with goserelin were assessed via plasma pharmacokinetics and biochemical analyses, respectively. (ClinicalTrials.gov identifier: NCT01942135) RESULTS: Median PFS for premenopausal women in the palbociclib ( n  = 72) versus placebo arm ( n  = 36) was 9.5 versus 5.6 months, respectively (hazard ratio, 0.50, 95% confidence interval: 0.29-0.87), and consistent with the significant PFS improvement in the same arms for postmenopausal women. Any-grade and grade ≤3 neutropenia, leukopenia, and infections were among the most frequent adverse events reported in the palbociclib arm with concurrent goserelin administration. Hormone concentrations were similar between treatment arms and confirmed sustained ovarian suppression. Clinically relevant DDIs were not observed. Palbociclib combined with fulvestrant and goserelin was an effective and well-tolerated treatment for premenopausal women with prior endocrine-resistant HR+/HER2- ABC. Inclusion of both premenopausal and postmenopausal women in pivotal combination ET trials facilitates access to novel drugs for young women and should be considered as a new standard for clinical trial design. PALOMA-3, the first registrational

  12. Radiation Induced Chemistry of Icy Surfaces: Laboratory Simulations

    Science.gov (United States)

    Gudipati, Murthy S.; Lignell, Antti; Li, Irene; Yang, Rui; Jacovi, Ronen

    2011-01-01

    We will discuss laboratory experiments designed to enhance our understanding the chemical processes on icy solar system bodies, enable interpretation of in-situ and remote-sensing data, and help future missions to icy solar system bodies, such as comets, Europa, Ganymede, Enceladus etc.

  13. IcyTree: rapid browser-based visualization for phylogenetic trees and networks.

    Science.gov (United States)

    Vaughan, Timothy G

    2017-08-01

    IcyTree is an easy-to-use application which can be used to visualize a wide variety of phylogenetic trees and networks. While numerous phylogenetic tree viewers exist already, IcyTree distinguishes itself by being a purely online tool, having a responsive user interface, supporting phylogenetic networks (ancestral recombination graphs in particular), and efficiently drawing trees that include information such as ancestral locations or trait values. IcyTree also provides intuitive panning and zooming utilities that make exploring large phylogenetic trees of many thousands of taxa feasible. IcyTree is a web application and can be accessed directly at http://tgvaughan.github.com/icytree . Currently supported web browsers include Mozilla Firefox and Google Chrome. IcyTree is written entirely in client-side JavaScript (no plugin required) and, once loaded, does not require network access to run. IcyTree is free software, and the source code is made available at http://github.com/tgvaughan/icytree under version 3 of the GNU General Public License. tgvaughan@gmail.com. © The Author(s) 2017. Published by Oxford University Press.

  14. Modeling of light scattering by icy bodies

    Science.gov (United States)

    Kolokolova, L.; Mackowski, D.; Pitman, K.; Verbiscer, A.; Buratti, B.; Momary, T.

    2014-07-01

    As a result of ground-based, space-based, and in-situ spacecraft mission observations, a great amount of photometric, polarimetric, and spectroscopic data of icy bodies (satellites of giant planets, Kuiper Belt objects, comet nuclei, and icy particles in cometary comae and rings) has been accumulated. These data have revealed fascinating light-scattering phenomena, such as the opposition surge resulting from coherent backscattering and shadow hiding and the negative polarization associated with them. Near-infrared (NIR) spectra of these bodies are especially informative as the depth, width, and shape of the absorption bands of ice are sensitive not only to the ice abundance but also to the size of icy grains. Numerous NIR spectra obtained by Cassini's Visual and Infrared Mapping Spectrometer (VIMS) have been used to map the microcharacteristics of the icy satellites [1] and rings of Saturn [2]. VIMS data have also permitted a study of the opposition surge for icy satellites of Saturn [3], showing that coherent backscattering affects not only brightness and polarization of icy bodies but also their spectra [4]. To study all of the light-scattering phenomena that affect the photopolarimetric and spectroscopic characteristics of icy bodies, including coherent backscattering, requires computer modeling that rigorously considers light scattering by a large number of densely packed small particles that form either layers (in the case of regolith) or big clusters (ring and comet particles) . Such opportunity has appeared recently with a development of a new version MSTM4 of the Multi-Sphere T-Matrix code [5]. Simulations of reflectance and absorbance spectra of a ''target'' (particle layer or cluster) require that the dimensions of the target be significantly larger than the wavelength, sphere radius, and layer thickness. For wavelength-sized spheres and packing fractions typical of regolith, targets can contain dozens of thousands of spheres that, with the original MSTM

  15. ICIS Contacts Subject Area Model

    Science.gov (United States)

    The Integrated Compliance Information System (ICIS) is a web-based system that provides information for the federal enforcement and compliance (FE&C) and the National Pollutant Discharge Elimination System (NPDES) programs.

  16. Integrated Compliance Information System (ICIS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The purpose of ICIS is to meet evolving Enforcement and Compliance business needs for EPA and State users by integrating information into a single integrated data...

  17. ICI optical data storage tape: An archival mass storage media

    Science.gov (United States)

    Ruddick, Andrew J.

    1993-01-01

    At the 1991 Conference on Mass Storage Systems and Technologies, ICI Imagedata presented a paper which introduced ICI Optical Data Storage Tape. This paper placed specific emphasis on the media characteristics and initial data was presented which illustrated the archival stability of the media. More exhaustive analysis that was carried out on the chemical stability of the media is covered. Equally important, it also addresses archive management issues associated with, for example, the benefits of reduced rewind requirements to accommodate tape relaxation effects that result from careful tribology control in ICI Optical Tape media. ICI Optical Tape media was designed to meet the most demanding requirements of archival mass storage. It is envisaged that the volumetric data capacity, long term stability and low maintenance characteristics demonstrated will have major benefits in increasing reliability and reducing the costs associated with archival storage of large data volumes.

  18. Polymerization of Building Blocks of Life on Europa and Other Icy Moons.

    Science.gov (United States)

    Kimura, Jun; Kitadai, Norio

    2015-06-01

    The outer Solar System may provide a potential habitat for extraterrestrial life. Remote sensing data from the Galileo spacecraft suggest that the jovian icy moons--Europa, Ganymede, and possibly Callisto--may harbor liquid water oceans underneath their icy crusts. Although compositional information required for the discussion of habitability is limited because of significantly restricted observation data, organic molecules are ubiquitous in the Universe. Recently, in situ spacecraft measurements and experiments suggest that amino acids can be formed abiotically on interstellar ices and comets. These amino acids could be continuously delivered by meteorite or comet impacts to icy moons. Here, we show that polymerization of organic monomers, in particular amino acids and nucleotides, could proceed spontaneously in the cold environment of icy moons, in particular the jovian icy moon Europa as a typical example, based on thermodynamic calculations, though kinetics of formation are not addressed. Observed surface temperature on Europa is 120 and 80 K in the equatorial region and polar region, respectively. At such low temperatures, Gibbs energies of polymerization become negative, and the estimated thermal structure of the icy crust should contain a shallow region (i.e., at a depth of only a few kilometers) favorable for polymerization. Investigation of the possibility of organic monomer polymerization on icy moons could provide good constraints on the origin and early evolution of extraterrestrial life.

  19. L'espion d'ici

    CERN Document Server

    Omnes, Roland

    2000-01-01

    On les appelle " ceux-qui-savent-le-savoir-inutile ". De leur planète puissante qui répond au nom orgueilleux d'" Ici ", ils dépêchent sur Terre un agent : à charge pour lui d'évaluer l'état d'avancement des connaissances chez les humains et de mesurer les risques que ceux-ci représentent. L'espion sera introduit auprès des sages grecs, il s'initiera aux mystères de Pythagore, il tiendra tête à Aristote, il se réincarnera en Merlin, il fréquentera le salon de Mme du Châtelet, il s'entretiendra avec Darwin, il côtoiera Einstein, il assistera à la naissance de la mécanique quantique, il fera un détour par les cafés de philosophie... Au terme de ses pérégrinations, il devra finalement choisir. Prendra-t-il le parti d'" Ici ", dont les connaissances plongent dans des temps insondables, ou celui de la Terre, au savoir étonnamment neuf ?

  20. A Novel OFDM Channel Estimation Algorithm with ICI Mitigation over Fast Fading Channels

    Directory of Open Access Journals (Sweden)

    C. Tao

    2010-06-01

    Full Text Available Orthogonal frequency-division multiplexing (OFDM is well-known as a high-bit-rate transmission technique, but the Doppler frequency offset due to the high speed movement destroys the orthogonality of the subcarriers resulting in the intercarrier interference (ICI, and degrades the performance of the system at the same time. In this paper a novel OFDM channel estimation algorithm with ICI mitigation based on the ICI self-cancellation scheme is proposed. With this method, a more accurate channel estimation is obtained by comb-type double pilots and then ICI coefficients can be obtained to mitigate the ICI on each subcarrier under the assumption that the channel impulse response (CIR varies in a linear fashion. The theoretical analysis and simulation results show that the bit error rate (BER and spectral efficiency performances are improved significantly under high-speed mobility conditions (350 km/h – 500 km/h in comparison to ZHAO’s ICI self-cancellation scheme.

  1. Heating of Porous Icy Dust Aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Sirono, Sin-iti [Earth and Environmental Sciences, Nagoya University, Tikusa-ku, Furo-cho, Nagoya 464-8601 (Japan)

    2017-06-10

    At the beginning of planetary formation, highly porous dust aggregates are formed through coagulation of dust grains. Outside the snowline, the main component of an aggregate is H{sub 2}O ice. Because H{sub 2}O ice is formed in amorphous form, its thermal conductivity is extremely small. Therefore, the thermal conductivity of an icy dust aggregate is low. There is a possibility of heating inside an aggregate owing to the decay of radionuclides. It is shown that the temperature increases substantially inside an aggregate, leading to crystallization of amorphous ice. During the crystallization, the temperature further increases sufficiently to continue sintering. The mechanical properties of icy dust aggregates change, and the collisional evolution of dust aggregates is affected by the sintering.

  2. An icy-glue model of cometary nuclei

    International Nuclear Information System (INIS)

    Gombosi, T.I.; Houpis, H.L.F.

    1986-05-01

    Since 1950 a number of models have been proposed to explain the observations of comets. For the most part the icy conglomerate model of Whipple was the standard. Based on the recent images made by VEGA and GIOTTO spacecrafts of comet Halley, a model of the nucleus is suggested that retains the advantages of the icy conglomerate formalism on a local level, while a new global framework is introduced. The model is disscussed in terms of the mounting knowledge of comets, the creation of the nucleus in the cosmogenic sence, and expectations of future analysis of data and observations are presented. A new methodology for calculating the evolution and thermal profiles of the nucleus is also presented. (author)

  3. Thermal Conductivity Measurements on Icy Satellite Analogs

    Science.gov (United States)

    Javeed, Aurya; Barmatz, Martin; Zhong, Fang; Choukroun, Mathieu

    2012-01-01

    With regard to planetary science, NASA aspires to: "Advance scientific knowledge of the origin and history of the solar system, the potential for life elsewhere, and the hazards and resources present as humans explore space". In pursuit of such an end, the Galileo and Cassini missions garnered spectral data of icy satellite surfaces implicative of the satellites' structure and material composition. The potential for geophysical modeling afforded by this information, coupled with the plausibility of life on icy satellites, has pushed Jupiter's Europa along with Saturn's Enceladus and Titan toward the fore of NASA's planetary focus. Understanding the evolution of, and the present processes at work on, the aforementioned satellites falls squarely in-line with NASA's cited goal.

  4. Morphology and Scaling of Ejecta Deposits on Icy Satellites

    Science.gov (United States)

    Schenk, Paul M.; Ridolfi, Francis J.; Bredekamp, Joe (Technical Monitor)

    2002-01-01

    Continuous ejecta deposits on Ganymede consist of two major units, or facies: a thick inner hummocky pedestal facies, and a relatively thin outer radially scoured facies defined also by the inner limit of the secondary crater field. Both ejecta facies have a well-defined power-law relationship to crater diameter for craters ranging from 15 to approx. 600 km across. This relationship can be used to estimate the nominal crater diameter for impact features on icy satellites (such as palimpsests and multiring basins) for which the crater rim is no longer recognizable. Ejecta deposits have also been mapped on 4 other icy satellites. Although morphologically similar to eject deposits on the Moon, ejecta deposits for smaller craters are generally significantly broader in extent on the icy satellites, in apparent defiance of predictions of self-similarity. A greater degree of rim collapse and enlargement on the Moon may explain the observed difference.

  5. Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer.

    Science.gov (United States)

    Hao, Yanni; Lin, Peggy L; Xie, Jipan; Li, Nanxin; Koo, Valerie; Ohashi, Erika; Wu, Eric Q; Rogerio, Jaqueline

    2015-08-01

    Assessing real-world effectiveness of everolimus-based therapy (EVE) versus fulvestrant monotherapy (FUL) among postmenopausal women with hormone receptor-positive (HR(+))/HER2(-) metastatic breast cancer (mBC) after progression on nonsteroidal aromatase inhibitor (NSAI). Medical charts of community-based patients who received EVE or FUL for mBC after NSAI were examined. Progression-free survival (PFS), time on treatment and time to chemotherapy were compared using Kaplan-Meier curves and Cox proportional hazards models adjusting for line of therapy and patient characteristics. 192 patients received EVE and 156 FUL. After adjusting for patient characteristics, EVE was associated with significantly longer PFS than FUL (hazard ratio: 0.71; p = 0.045). EVE was associated with better PFS than FUL among NSAI-refractory postmenopausal HR(+)/HER2(-) mBC patients.

  6. The Scattering Properties of Natural Terrestrial Snows versus Icy Satellite Surfaces

    Science.gov (United States)

    Domingue, Deborah; Hartman, Beth; Verbiscer, Anne

    1997-01-01

    Our comparisons of the single particle scattering behavior of terrestrial snows and icy satellite regoliths to the laboratory particle scattering measurements of McGuire and Hapke demonstrate that the differences between icy satellite regoliths and their terrestrial counterparts are due to particle structures and textures. Terrestrial snow particle structures define a region in the single particle scattering function parameter space separate from the regions defined by the McGuire and Hapke artificial laboratory particles. The particle structures and textures of the grains composing icy satellites regoliths are not simple or uniform but consist of a variety of particle structure and texture types, some of which may be a combination of the particle types investigated by McGuire and Hapke.

  7. Thermo-chemical Ice Penetrator for Icy Moons

    Science.gov (United States)

    Arenberg, J. W.; Lee, G.; Harpole, G.; Zamel, J.; Sen, B.; Ross, F.; Retherford, K. D.

    2016-12-01

    The ability to place sensors or to take samples below the ice surface enables a wide variety of potential scientific investigations. Penetrating an ice cap can be accomplished via a mechanical drill, laser drill, kinetic impactor, or heated penetrator. This poster reports on the development of technology for the latter most option, namely a self-heated probe driven by an exothermic chemical reaction: a Thermo-chemical ice penetrator (TChIP). Our penetrator design employs a eutectic mix of alkali metals that produce an exothermic reaction upon contact with an icy surface. This reaction increases once the ice starts melting, so no external power is required. This technology is inspired by a classified Cold-War era program developed at Northrop Grumman for the US Navy. Terrestrial demonstration of this technology took place in the Arctic; however, this device cannot be considered high TRL for application at the icy moons of the solar system due to the environmental differences between Earth's Arctic and the icy moons. These differences demand a TChIP design specific to these cold, low mass, airless worlds. It is expected that this model of TChIP performance will be complex, incorporating all of the forces on the penetrator, gravity, the thermo-chemistry at the interface between penetrator and ice, and multi-phase heat and mass transport, and hydrodynamics. Our initial efforts are aimed at the development of a validated set of tools and simulations to predict the performance of the penetrator for both the environment found on these icy moons and for a terrestrial environment. The purpose of the inclusion of the terrestrial environment is to aid in model validation. Once developed and validated, our models will allow us to design penetrators for a specific scientific application on a specific body. This poster discusses the range of scientific investigations that are enabled by TChIP. We also introduce the development plan to advance TChIP to the point where it can be

  8. Preclinical evaluation of an 18F-labelled beta1-adrenoceptor selective radioligand based on ICI 89,406.

    Science.gov (United States)

    Law, Marilyn P; Wagner, Stefan; Kopka, Klaus; Renner, Christiane; Pike, Victor W; Schober, Otmar; Schäfers, Michael

    2010-05-01

    Radioligand binding studies indicate a down-regulation of myocardial beta(1)-adrenoceptors (beta(1)-AR) in cardiac disease which may or may not be associated with a decrease in beta(2)-ARs. We have chosen ICI 89,406, a beta(1)-selective AR antagonist, as the lead structure to develop new beta(1)-AR radioligands for PET and have synthesised a fluoro-ethoxy derivative (F-ICI). (S)-N-[2-[3-(2-Cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]-N'-[4-(2-[(18)F]fluoro-ethoxy)-phenyl]-urea ((S)-[(18)F]F-ICI) was synthesised. Myocardial uptake of radioactivity after intravenous injection of (S)-[(18)F]F-ICI into adult CD(1) mice or Wistar rats was assessed with positron emission tomography (PET) and postmortem dissection. Metabolism was assessed by high-performance liquid chromatography analysis of plasma and urine. The heart was visualised with PET after injection of (S)-[(18)F]F-ICI but neither unlabelled F-ICI nor propranolol (non-selective beta-AR antagonist) injected 15 min after (S)-[(18)F]F-ICI affected myocardial radioactivity. Ex vivo dissection demonstrated that predosing with propranolol or CGP 20712 (beta(1)-selective AR-antagonist) did not affect myocardial radioactivity. Radiometabolites rapidly appeared in plasma and both (S)-[(18)F]F-ICI and radiometabolites accumulated in urine. Myocardial uptake of (S)-[(18)F]F-ICI after intravenous injection was mainly at sites unrelated to beta(1)-ARs. (S)-[(18)F]F-ICI is not a suitable beta(1)-selective-AR radioligand for PET. (c) 2010 Elsevier Inc. All rights reserved.

  9. Photometric Properties of Icy Bodies: A Comparison

    Science.gov (United States)

    Arakalian, B. J.; Buratti, T.

    1997-01-01

    Photometry is the quantitative measurement of reflected or emitted radiation. In the past 15 years, the classical study on planetary surfaces of arbitrary albedo, including bright icy satellites (e.g., Hapke, 1981 JGR, 1984 and 1986, Icarus).

  10. Decommissioning of the ICI TRIGA Mark I reactor

    International Nuclear Information System (INIS)

    Parry, D.R.; England, M.R.; Ward, A.; Green, D.

    2000-01-01

    This paper considers the fuel removal, transportation and subsequent decommissioning of the ICI TRIGA Mark I Reactor at Billingham, UK. BNFL Waste Management and Decommissioning carried out this work on behalf of ICI. The decommissioning methodology was considered in the four stages to be described, namely Preparatory Works, Reactor Defueling, Intermediate Level Waste Removal and Low Level Waste Removal. This paper describes the principal methodologies involved in the defueling of the reactor and subsequent decommissioning operations, highlighting in particular the design and safety case methodologies used in order to achieve a solution which was completed without incident or accident and resulted in a cumulative radiation dose to personnel of only 1.57 mSv. (author)

  11. ICI bites demerger bullet, Zeneca guns for Brit-pounds 1.3-billion rights issue

    International Nuclear Information System (INIS)

    Jackson, D.; Alperowicz, N.

    1993-01-01

    Any lingering doubts as to ICI's (London) intentions to follow through its demerger proposals were dispelled last week. The company will hive off its bioscience business into Zeneca Group plc, which will make a Brit-pounds 1.3-billion ($1.9 billion) rights issue in June 1993. Shareholders, whose approval for the historic move will be sought in late May, will receive one fully paid Zeneca share for each ICI share. Proceeds from the rights issue will be used to reduce Zeneca's indebtedness to ICI by about 70%. Acknowledging that ICI had 'spread the jam too thinly' during its expansion in the 1980s, chief executive Ronnie Hampel says the new ICI will be a cost-conscious, no-frills' organization and that businesses that failed to perform would be restructured or closed. He is 'not expecting any help from the economy' in 1993. Of ICI's remaining petrochemicals and plastics businesses, Hampel says that despite 'stringent measures to reduce the cost base hor-ellipsis it is clear they will not reach a return on capital that will justify reinvestment by ICI.' He does not see them as closure candidates but as 'businesses that will require further restructuring.' Hampel notes 'a dozen clearly identified areas for expansion,' including paints, catalysts, titanium dioxide, and chlorofluorocarbon replacements. Losses in materials, where substantial rationalization has failed to halt the slide, will be reduced on completion of the DuPont deal - expected by midyear. 'Further measures' would be necessary for the 'residual bit of advanced materials in the US,' he says

  12. Synthesis of novel ICIE16/BSG and ICIE16/BSG-NITRI bioglasses and description of ionic release kinetics upon immersion in SBF fluid: Effect of nitridation

    Directory of Open Access Journals (Sweden)

    Felipe Orgaz

    2016-03-01

    Full Text Available A novel bioactive glass scaffold ICIE16/BSG has been prepared from a mixture of two different melt-derived glasses: a silicate bioglass (ICIE16 and a borosilicate bioglass (BSG. Combined processing techniques (gel casting and foam replication were used to form three-dimensional, interconnected porous monolith scaffolds (Orgaz et al., 2016 [1]. They were then nitrided with a hot ammonia flow as described in (Aleixandre et al., 1973 [3] and (Nieto, 1984 [4] to synthesize the ICIE16/BSG-NITRI bioglass (Orgaz et al., 2016 [1]. Herein we present a flow chart summarizing the forming process, plus images of the resulting scaffold after sintering and drying. Bioactivity was characterized in vitro by immersion in simulated body fluid (SBF for up to seven days. Data of ionic release kinetics upon SBF immersion are presented. Keywords: Biomaterials, Bioglass, Simulated body fluid, Degradability, Biomaterial resorption, Bone repair

  13. Analyzing surface features on icy satellites using a new two-layer analogue model

    Science.gov (United States)

    Morales, K. M.; Leonard, E. J.; Pappalardo, R. T.; Yin, A.

    2017-12-01

    The appearance of similar surface morphologies across many icy satellites suggests potentially unified formation mechanisms. Constraining the processes that shape the surfaces of these icy worlds is fundamental to understanding their rheology and thermal evolution—factors that have implications for potential habitability. Analogue models have proven useful for investigating and quantifying surface structure formation on Earth, but have only been sparsely applied to icy bodies. In this study, we employ an innovative two-layer analogue model that simulates a warm, ductile ice layer overlain by brittle surface ice on satellites such as Europa and Enceladus. The top, brittle layer is composed of fine-grained sand while the ductile, lower viscosity layer is made of putty. These materials were chosen because they scale up reasonably to the conditions on Europa and Enceladus. Using this analogue model, we investigate the role of the ductile layer in forming contractional structures (e.g. folds) that would compensate for the over-abundance of extensional features observed on icy satellites. We do this by simulating different compressional scenarios in the analogue model and analyzing whether the resulting features resemble those on icy bodies. If the resulting structures are similar, then the model can be used to quantify the deformation by calculating strain. These values can then be scaled up to Europa or Enceladus and used to quantity the observed surface morphologies and the amount of extensional strain accommodated by certain features. This presentation will focus on the resulting surface morphologies and the calculated strain values from several analogue experiments. The methods and findings from this work can then be expanded and used to study other icy bodies, such as Triton, Miranda, Ariel, and Pluto.

  14. ICI 182,780 has agonistic effects and synergizes with estradiol-17 beta in fish liver, but not in testis

    Directory of Open Access Journals (Sweden)

    Power Deborah M

    2006-12-01

    Full Text Available Abstract Background ICI 182,780 (ICI belongs to a new class of antiestrogens developed to be pure estrogen antagonists and, in addition to its therapeutic use, it has been used to knock-out estrogen and estrogen receptor (ER actions in several mammalian species. In the present study, the effects and mechanism of action of ICI were investigated in the teleost fish, sea bream (Sparus auratus. Methods Three independent in vivo experiments were performed in which mature male tilapia (Oreochromis mossambicus or sea bream received intra-peritoneal implants containing estradiol-17 beta (E2, ICI or a combination of both compounds. The effects of E2 and ICI on plasma calcium levels were measured and hepatic and testicular gene expression of the three ER subtypes, ER alpha, ER beta a and ER beta b, and the estrogen-responsive genes, vitellogenin II and choriogenin L, were analyzed by semi-quantitative RT-PCR in sea bream. Results E2 treatment caused an increase in calcium levels in tilapia, while ICI alone had no noticeable effect, as expected. However, pretreatment with ICI synergistically potentiated the effect of E2 on plasma calcium in both species. ICI mimicked some E2 actions in gene expression in sea bream liver upregulating ER alpha, vitellogenin II and choriogenin L, although, unlike E2, it did not downregulate ER beta a and ER beta b. In contrast, no effects of E2 or ICI alone were detected in the expression of ERs in testis, while vitellogenin II and choriogenin L were upregulated by E2 but not ICI. Finally, pretreatment with ICI had a synergistic effect on the hepatic E2 down-regulation of ER beta b, but apparently blocked the ER alpha up-regulation by E2. Conclusion These results demonstrate that ICI has agonistic effects on several typical estrogenic responses in fish, but its actions are tissue-specific. The mechanisms for the ICI agonistic activity are still unknown; although the ICI induced up-regulation of ER alpha mRNA could be one of

  15. Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

    Science.gov (United States)

    Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

    2018-05-01

    The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

  16. EPA Enforcement and Compliance History Online: ICIS-NPDES Limit

    Data.gov (United States)

    U.S. Environmental Protection Agency — Integrated Compliance Information System (ICIS) National Pollutant Discharge Elimination System (NPDES) Permit Limits data set for Clean Water Act permitted...

  17. IS Research and Policy: Notes From the 2015 ICIS Senior Scholar’s Forum

    DEFF Research Database (Denmark)

    Niederman, Fred; Applegate, Lynda; Beck, Roman

    2017-01-01

    Based on the International Conference on Information Systems’ (ICIS) 2015 senior scholars’ forum, we provide insights on the role and opportunities of IS researchers in shaping policy.......Based on the International Conference on Information Systems’ (ICIS) 2015 senior scholars’ forum, we provide insights on the role and opportunities of IS researchers in shaping policy....

  18. Icy Dwarf Planets: Colored popsicles in the Solar System

    Science.gov (United States)

    Pinilla-Alonso, Noemi

    2015-08-01

    In 1992 the discovery of 1992 QB1 was the starting signal of a race to characterize the trans-Neptunian belt. The detection of icy “asteroids”, similar to Pluto, in the outer Solar System had been largely hypothesized but it had also being an elusive goal. This belt was considered by the planetary scientists as the icy promised land, the largest reservoir of primordial ices in the Solar System.From 1992 to 2005 about 1000 trans-Neptunian objects and Centaurs had been discovered and a lot of “first ever” science had been published: 1996 TO66, first ever detection of the water ice bands in a TNO's spectrum; 1998 WW31, first detection of a binary; first estimation of size and albedo from thermal and visible observations, Varuna; discovery of Sedna, at that moment “the coldest most distant place known in the Solar System”2005 was the year of the discovery of three large TNOs: (136108) Haumea, (136472) Makemake and (136199) Eris (a.k.a 2003 EL61, 2005 FY9 and 2003 UB313). These three big guys entered the schoolyard showing off as colored popsicles and making a clear statement: “We are special”, and sure they are!The discovery of these large TNOs resulted in 2006 in the adoption by the IAU of a new definition of planet and in the introduction of a new category of minor bodies: the “dwarf planets”. With only three members at this moment (although this can change anytime) the exclusive club of the icy dwarf planets is formed by the TNOs at the higher end of the size distribution. By virtue of their size and low surface temperatures, these bodies can retain most of their original inventory of ices. As a consequence, their visible and near-infrared spectra show evidences of water ice, nitrogen, methane and longer chains of hydrocarbons. Moreover, they have high geometric albedo in the visible. Also the accretional and radiogenic heating for these bodies was likely more than sufficient to have caused their internal differentiation.In this talk we will

  19. High non-specific binding of the {beta}{sub 1}-selective radioligand 2-{sup 125}I-ICI-H

    Energy Technology Data Exchange (ETDEWEB)

    Riemann, B. [Muenster Univ. (Germany). Department of Nuclear Medicine; Law, M.P. [Muenster Univ. (Germany). Department of Nuclear Medicine; Hammersmith Hospital, London (United Kingdom). MRC Clinical Sciences Centre; Kopka, K. [Muenster Univ. (DE). Department of Nuclear Medicine] [and others

    2003-08-01

    Aim: As results of cardiac biopsies suggest, myocardial {beta}{sub 1}-adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac {beta}{sub 2}-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess {beta}-adrenoceptors non-invasively. Among the novel racemic analogues of the established {beta}{sub 1}-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to {beta}{sub 1}-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative subtype selective {beta}{sub 1}-adrenergic radioligand in cardiac imaging. Methods: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac {beta}-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-{sup 125}I-ICI-H from the silylated precursor 2-SiMe{sub 3}-ICI-H was established. The specific activity was 80 GBq/{mu}mol, the radiochemical yield ranged from 70 to 80%. Results: The unlabelled compound 2-I-ICI-H showed high {beta}{sub 1}-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac {beta}-adrenoceptors. The radiolabelled counterpart 2-{sup 125}I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac {beta}{sub 1}-adrenoceptors in vivo. Conclusion: Because of its high non-specific binding 2-{sup 125}I-ICI-H is no suitable radiotracer for imaging in vivo. (orig.)

  20. Glaciers and Ice Sheets As Analog Environments of Potentially Habitable Icy Worlds

    Directory of Open Access Journals (Sweden)

    Eva Garcia-Lopez

    2017-07-01

    Full Text Available Icy worlds in the solar system and beyond have attracted a remarkable attention as possible habitats for life. The current consideration about whether life exists beyond Earth is based on our knowledge of life in terrestrial cold environments. On Earth, glaciers and ice sheets have been considered uninhabited for a long time as they seemed too hostile to harbor life. However, these environments are unique biomes dominated by microbial communities which maintain active biochemical routes. Thanks to techniques such as microscopy and more recently DNA sequencing methods, a great biodiversity of prokaryote and eukaryote microorganisms have been discovered. These microorganisms are adapted to a harsh environment, in which the most extreme features are the lack of liquid water, extremely cold temperatures, high solar radiation and nutrient shortage. Here we compare the environmental characteristics of icy worlds, and the environmental characteristics of terrestrial glaciers and ice sheets in order to address some interesting questions: (i which are the characteristics of habitability known for the frozen worlds, and which could be compatible with life, (ii what are the environmental characteristics of terrestrial glaciers and ice sheets that can be life-limiting, (iii What are the microbial communities of prokaryotic and eukaryotic microorganisms that can live in them, and (iv taking into account these observations, could any of these planets or satellites meet the conditions of habitability? In this review, the icy worlds are considered from the point of view of astrobiological exploration. With the aim of determining whether icy worlds could be potentially habitable, they have been compared with the environmental features of glaciers and ice sheets on Earth. We also reviewed some field and laboratory investigations about microorganisms that live in analog environments of icy worlds, where they are not only viable but also metabolically active.

  1. Genome Sequence of Enterococcus faecium Strain ICIS 96 Demonstrating Intermicrobial Antagonism Associated with Bacteriocin Production.

    Science.gov (United States)

    Pashkova, Tatiana M; Vasilchenko, Alexey S; Khlopko, Yuriy A; Kochkina, Elena E; Kartashova, Olga L; Sycheva, Maria V

    2018-03-08

    We report here the complete genome sequence of Enterococcus faecium strain ICIS 96, which was isolated from the feces of a horse. Bacteriological characterization of strain ICIS 96 revealed the absence of pathogenicity factors, while its spectrum of antagonistic activity was found to be broad, having activities associated with both Gram-positive and Gram-negative bacteria. Analysis of the E. faecium ICIS 96 genome revealed five genes associated with antimicrobial activity (enterocin [ent] A, ent B, lactobin A/cerein 7b, and ent L50 A/B). No genes that correlate with human pathogenicity were identified. Copyright © 2018 Pashkova et al.

  2. Mineralogy of Sediments on a Cold and Icy Early Mars

    Science.gov (United States)

    Rampe, E. B.; Horgan, B. H. N.; Smith, R.; Scudder, N.; Rutledge, A. M.; Bamber, E.; Morris, R. V.

    2017-12-01

    The water-related minerals discovered in ancient martian terrains suggest liquid water was abundant on the surface and/or near subsurface during Mars' early history. The debate remains, however, whether these minerals are indicative of a warm and wet or cold and icy climate. To characterize mineral assemblages of cold and icy mafic terrains, we analyzed pro- and supraglacial rocks and sediments from the Collier and Diller glacial valleys in Three Sisters, Oregon. We identified primary and secondary phases using X-ray diffraction (XRD), scanning and transmission electron microscopies with energy dispersive spectroscopy (SEM, TEM, EDS), and visible/short-wave-infrared (VSWIR) and thermal-infrared (TIR) spectroscopies. Samples from both glacial valleys are dominated by primary igneous minerals (i.e., plagioclase and pyroxene). Sediments in the Collier glacial valley contain minor to trace amounts of phyllosilicates and zeolites, but these phases are likely detrital and sourced from hydrothermally altered units on North Sister. We find that the authigenic phases in cold and icy mafic terrains are poorly crystalline and/or amorphous. TEM-EDS analyses of the materials, including iron oxides, devitrified volcanic glass, and Fe-Si-Al (e.g., proto-clay) phases. A variety of primary and secondary amorphous materials (e.g., volcanic glass, leached glass, allophane) have been suggested from orbital IR data from Mars, and the CheMin XRD on the Curiosity rover has identified X-ray amorphous materials in all rocks and soils measured to date. The compositions of the Gale Crater amorphous components cannot be explained by primary volcanic glass alone and likely include secondary silicates, iron oxides, and sulfates. We suggest that the prevalence of amorphous materials on the martian surface and the variety of amorphous components may be a signature of a cold and icy climate on Early Mars.

  3. Emergence of Habitable Environments in Icy World Interiors

    Science.gov (United States)

    Neveu, Marc

    2016-07-01

    Finding habitable worlds is a key driver of solar system exploration. Many solar system missions seek environments providing liquid water, energy, and nutrients, the three ingredients necessary to sustain life [1]. Such environments include hydrothermal systems, spatially confined systems where hot aqueous fluid circulates through rock by convection. Hydrothermal activity may be widespread in the solar system. Most solar system worlds larger than 200 km in radius are icy moons and dwarf planets, likely composed of an icy, cometary mantle surrounding a rocky, chondritic core [2]. By improving an icy world evolution code [3] to include the effects of core fracturing and hydrothermal circulation, I show that several icy moons and dwarf planets likely have undergone extensive water-rock interaction [4,5]. This supports observations of aqueous products on their surfaces [6,7]. I simulated the alteration of chondritic rock [8] by pure water or fluid of cometary composition [9] to show that aqueous alteration feeds back on geophysical evolution: it modifies the fluid antifreeze content, affecting its persistence over geological timescales; and the distribution of radionuclides, whose decay is a chief heat source on dwarf planets [10]. Hydrothermal circulation also efficiently transports heat from the core into the ocean, thereby increasing ocean persistence [4]. Thus, these coupled geophysical-geochemical models provide a comprehensive picture of icy world evolution and the emergence of liquid environments in chemical disequilibrium with underlying rock in their interiors. Habitable settings also require a suitable supply of bioessential elements; but what constitutes "suitable"? I sought to quantify the bulk elemental composition of hydrothermal microbial communities, collected in hot spring sediments and mats at Yellowstone National Park, USA. To do so, one must minimize the contribution of non-biological material to the samples analyzed. This was achieved using a

  4. Performance Comparison between CDTD and STTD for DS-CDMA/MMSE-FDE with Frequency-Domain ICI Cancellation

    Science.gov (United States)

    Takeda, Kazuaki; Kojima, Yohei; Adachi, Fumiyuki

    Frequency-domain equalization (FDE) based on the minimum mean square error (MMSE) criterion can provide a better bit error rate (BER) performance than rake combining. However, the residual inter-chip interference (ICI) is produced after MMSE-FDE and this degrades the BER performance. Recently, we showed that frequency-domain ICI cancellation can bring the BER performance close to the theoretical lower bound. To further improve the BER performance, transmit antenna diversity technique is effective. Cyclic delay transmit diversity (CDTD) can increase the number of equivalent paths and hence achieve a large frequency diversity gain. Space-time transmit diversity (STTD) can obtain antenna diversity gain due to the space-time coding and achieve a better BER performance than CDTD. Objective of this paper is to show that the BER performance degradation of CDTD is mainly due to the residual ICI and that the introduction of ICI cancellation gives almost the same BER performance as STTD. This study provides a very important result that CDTD has a great advantage of providing a higher throughput than STTD. This is confirmed by computer simulation. The computer simulation results show that CDTD can achieve higher throughput than STTD when ICI cancellation is introduced.

  5. Seismic Wave Propagation in Icy Ocean Worlds

    Science.gov (United States)

    Stähler, Simon C.; Panning, Mark P.; Vance, Steven D.; Lorenz, Ralph D.; van Driel, Martin; Nissen-Meyer, Tarje; Kedar, Sharon

    2018-01-01

    Seismology was developed on Earth and shaped our model of the Earth's interior over the twentieth century. With the exception of the Philae lander, all in situ extraterrestrial seismological effort to date was limited to other terrestrial planets. All have in common a rigid crust above a solid mantle. The coming years may see the installation of seismometers on Europa, Titan, and Enceladus, so it is necessary to adapt seismological concepts to the setting of worlds with global oceans covered in ice. Here we use waveform analyses to identify and classify wave types, developing a lexicon for icy ocean world seismology intended to be useful to both seismologists and planetary scientists. We use results from spectral-element simulations of broadband seismic wavefields to adapt seismological concepts to icy ocean worlds. We present a concise naming scheme for seismic waves and an overview of the features of the seismic wavefield on Europa, Titan, Ganymede, and Enceladus. In close connection with geophysical interior models, we analyze simulated seismic measurements of Europa and Titan that might be used to constrain geochemical parameters governing the habitability of a sub-ice ocean.

  6. The Status that the program to relieve set-point for the number of operable ICIs is applied to OPR1000

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Kyung-ho; Moon, Sang-rae [KHNP, Daejeon (Korea, Republic of)

    2016-10-15

    The Core Operating Limit Supervisory System (COLSS) of OPR1000 monitors in-core neutron power distribution, Linear Heat Rate (LHR) and Departure from Nucleate Boiling Ratio (DNBR) using In-Core Instrumentation (ICI). It is required that above 75% of ICI be operable to perform this functions. 45 EA strings of ICI have been installed and operated in Hanbit no.3, 4, 5, 6 and Hanul no. 3, 4, 5, 6. Their signals are transferred to Plant Monitoring System (PMS) via four Plant Data Acquisition System (PDAS) channels. PMS includes a few application programs like COLSS. In a case that one of 4 PDAS channels fails, COLSS is inoperable. It means that reactor power should be reduced and monitored by CPCS because FSAR of OPR1000 requires that 75% ICIs should be operable. This action can induce transient of reactor core. In order to complement such a trouble, KHNP, KEPCO NF and KEPCO ENC have proposed the way that COLSS can be operable though operable ICIs exist between 60% - 75%. KHNP, KEPCONF and KEPCO ENC have proposed the way that COLSS can be operable though operable ICIs exist between 60% - 75%. Conservatively, the analysis was performed assuming 50% ICIs are inoperable. Though 50% ICIs are inoperable, the power distribution of COLSS is more accurate than that of CPC. The technology was applied to OPR1000s based on above technical background. Shin-Kori no.1, 2 and Shin-Wolsong no.1, 2 are waiting for an application.

  7. Technology for a Thermo-chemical Ice Penetrator for Icy Moons

    Science.gov (United States)

    Arenberg, Jonathan; Harpole, George; Zamel, James; Sen, Bashwar; Lee, Greg; Ross, Floyd; Retherford, Kurt D.

    2016-10-01

    The ability to place sensors or to take samples below the ice surface enables a wide variety of potential scientific investigations. Penetrating an ice cap can be accomplished via a mechanical drill, laser drill, kinetic impactor, or heated penetrator. This poster reports on the development of technology for the latter most option, namely a self-heated probe driven by an exothermic chemical reaction: a Thermo-chemical ice penetrator (TChIP). Our penetrator design employs a eutectic mix of alkali metals that produce an exothermic reaction upon contact with an icy surface. This reaction increases once the ice starts melting, so no external power is required. This technology is inspired by a classified Cold-War era program developed at Northrop Grumman for the US Navy. Terrestrial demonstration of this technology took place in the Arctic; however, this device cannot be considered high TRL for application at the icy moons of the solar system due to the environmental differences between Earth's Arctic and the icy moons. These differences demand a TChIP design specific to these cold, low mass, airless worlds. It is expected that this model of TChIP performance will be complex, incorporating all of the forces on the penetrator, gravity, the thermo-chemistry at the interface between penetrator and ice, and multi-phase heat and mass transport, and hydrodynamics. Our initial efforts are aimed at the development of a validated set of tools and simulations to predict the performance of the penetrator for both the environment found on these icy moons and for a terrestrial environment. The purpose of the inclusion of the terrestrial environment is to aid in model validation. Once developed and validated, our models will allow us to design penetrators for a specific scientific application on a specific body. This poster discusses the range of scientific investigations that are enabled by TChIP. We also introduce the development plan to advance TChIP to the point where it can be

  8. A putative Type IIS restriction endonuclease GeoICI

    Indian Academy of Sciences (India)

    As opposed to the unstable prototype, which cleaves DNA at 30°C, GeoICI is highly active at elevated temperatures, up to 73°C and over a very wide salt concentration range. Recognition/cleavage sites were determined by: (i) digestion of plasmid and bacteriophage lambda DNA (λ); (ii) cleavage of custom PCR substrates, ...

  9. Tamoxifen and ICI 182,780 activate hypothalamic G protein-coupled estrogen receptor 1 to rapidly facilitate lordosis in female rats.

    Science.gov (United States)

    Long, Nathan; Long, Bertha; Mana, Asma; Le, Dream; Nguyen, Lam; Chokr, Sima; Sinchak, Kevin

    2017-03-01

    In the female rat, sexual receptivity (lordosis) can be facilitated by sequential activation of estrogen receptor (ER) α and G protein-coupled estrogen receptor 1 (GPER) by estradiol. In the estradiol benzoate (EB) primed ovariectomized (OVX) rat, EB initially binds to ERα in the plasma membrane that complexes with and transactivates metabotropic glutamate receptor 1a to activate β-endorphin neurons in the arcuate nucleus of the hypothalamus (ARH) that project to the medial preoptic nucleus (MPN). This activates MPN μ-opioid receptors (MOP), inhibiting lordosis. Infusion of non-esterified 17β-estradiol into the ARH rapidly reduces MPN MOP activation and facilitates lordosis via GPER. Tamoxifen (TAM) and ICI 182,780 (ICI) are selective estrogen receptor modulators that activate GPER. Therefore, we tested the hypothesis that TAM and ICI rapidly facilitate lordosis via activation of GPER in the ARH. Our first experiment demonstrated that injection of TAM intraperitoneal, or ICI into the lateral ventricle, deactivated MPN MOP and facilitated lordosis in EB-primed rats. We then tested whether TAM and ICI were acting rapidly through a GPER dependent pathway in the ARH. In EB-primed rats, ARH infusion of either TAM or ICI facilitated lordosis and reduced MPN MOP activation within 30min compared to controls. These effects were blocked by pretreatment with the GPER antagonist, G15. Our findings demonstrate that TAM and ICI deactivate MPN MOP and facilitate lordosis in a GPER dependent manner. Thus, TAM and ICI may activate GPER in the CNS to produce estrogenic actions in neural circuits that modulate physiology and behavior. Published by Elsevier Inc.

  10. ICI 182,780 has agonistic effects and synergizes with estradiol-17 beta in fish liver, but not in testis

    OpenAIRE

    Pinto, Patricia; Singh, Pratap B.; Condeça, João B.; Teodósio, H. R.; Power, Deborah; Canario, Adelino V. M.

    2006-01-01

    Abstract Background ICI 182,780 (ICI) belongs to a new class of antiestrogens developed to be pure estrogen antagonists and, in addition to its therapeutic use, it has been used to knock-out estrogen and estrogen receptor (ER) actions in several mammalian species. In the present study, the effects and mechanism of action of ICI were investigated in the teleost fish, sea bream (Sparus auratus). Methods Three independent in vivo experiments were performed in which mature male tilapia (Oreochrom...

  11. Le CERN va supprimer 600 postes d'ici a 2007

    CERN Multimedia

    2002-01-01

    "Le Laboratoire europeen pour la physique des particules (CERN), qui doit economiser quelque 340 millions d'euros jusqu'en 2008, va reduire ses effectifs de 600 postes d'ici a 2007, a annonce jeudi son porte-parole, James Gillies" (1/2/ page).

  12. Sustainability Development Research at ICIS : Taking Stock and Looking Ahead

    NARCIS (Netherlands)

    Cörvers, Ron; de Kraker, J.; Kemp, René; Martens, P.; van Lente, Harro

    2016-01-01

    This book presents an overview of the diversity and richness of ongoing and recent sustainable development research at ICIS (international Centre for Integrated assessment and Sustainable development, Maastricht University) in 35 short chapters, and it introduces the research agenda for the coming

  13. Low Force Penetration of Icy Regolith

    Science.gov (United States)

    Mantovani, J. G.; Galloway, G. M.; Zacny, K.

    2016-01-01

    A percussive cone penetrometer measures the strength of granular material by using percussion to deliver mechanical energy into the material. A percussive cone penetrometer was used in this study to penetrate a regolith ice mixture by breaking up ice and decompacting the regolith. As compared to a static cone penetrometer, percussion allows low reaction forces to push a penetrometer probe tip more easily into dry regolith in a low gravity environment from a planetary surface rover or a landed spacecraft. A percussive cone penetrates icy regolith at ice concentrations that a static cone cannot penetrate. In this study, the percussive penetrator was able to penetrate material under 65 N of down-force which could not be penetrated using a static cone under full body weight. This paper discusses using a percussive cone penetrometer to discern changes in the concentration of water-ice in a mixture of lunar regolith simulant and ice to a depth of one meter. The rate of penetration was found to be a function of the ice content and was not significantly affected by the down-force. The test results demonstrate that this method may be ideal for a small platform in a reduced gravity environment. However, there are some cases where the system may not be able to penetrate the icy regolith, and there is some risk of the probe tip becoming stuck so that it cannot be retracted. It is also shown that a percussive cone penetrometer could be used to prospect for water ice in regolith at concentrations as high as 8 by weight.

  14. Heliosheath Space Environment Interactions with Icy Bodies in the Outermost Solar System

    Science.gov (United States)

    Cooper, John F.; Hill, Matthew E.; Richardson, John D.; Sturner, Steven J.

    2006-01-01

    The Voyager 1 and 2 spacecraft are exploring the space environment of the outermost solar system at the same time that earth-based astronomy continues to discover new icy bodies, one larger than Pluto, in the transitional region outward from the Classical Kuiper Belt to the Inner Oort Cloud. Some of the Scattered Disk Objects in this region periodically pass through the heliosheath, entered by Voyager 1 in Dec. 2004 and later expected to be reached by Voyager 2, and out even beyond the heliopause into the Very Local Interstellar Medium. The less energetic heliosheath ions, important for implantation and sputtering processes, are abundant near and beyond the termination shock inner boundary, but the source region of the more penetrating anomalous cosmic ray component has not yet been found. Advantageous for modeling of icy body interactions, the measured heliosheath flux spectra are relatively more stable within this new regime of isotropic compressional magnetic turbulence than in the upstream heliospheric environment. The deepest interactions and resultant radiation-induced chemistry arise from the inwardly diffusing component of the galactic cosmic ray ions with significant intensity modulation also arising in the heliosheath beyond Voyager 1. Surface gardening by high-velocity impacts of smaller bodies (e.g., fragments of previous KBO collisions) and dust is a further space weathering process setting the time scales for long term exposure of different regolith layers to the ion irradiation. Sputtering and ionization of impact ejecta grains may provide a substantial feedback of pickup ions for multiple cycles of heliosheath acceleration and icy body interaction. Thus the space weathering interactions are potentially of interest not only for effects on sensible surface composition of the icy bodies but also for evolution of the heliosheath plasma energetic ion, and neutral emission environment.

  15. Rotational Dynamics of Icy Satellites : Tidal response and forced longitudinal librations at the surface of a viscoelastic Europa

    NARCIS (Netherlands)

    Jara Orue, H.M.

    2016-01-01

    The icy satellites of the giant planets Jupiter and Saturn are among the most interesting celestial bodies in our Solar System. The interpretation of various remote sensing observations performed by the Voyager, Galileo and Cassini-Huygens missions strongly suggests that many icy satellites harbor a

  16. A putative Type IIS restriction endonuclease GeoICI from ...

    Indian Academy of Sciences (India)

    2016-02-15

    Feb 15, 2016 ... 41(1), 27–38 * Indian Academy of Sciences. 27. Keywords. ... tis (Subang Jaya, Malaysia), DEAE-cellulose and Phosphocel- lulose P11 were from ... conditions at 67.5°C, subsequently the culture was chilled down and centrifuged. ..... influence of ionic strength on GeoICI REase activity. 0.3 μg PCR.

  17. BENZENE FORMATION ON INTERSTELLAR ICY MANTLES CONTAINING PROPARGYL ALCOHOL

    Energy Technology Data Exchange (ETDEWEB)

    Sivaraman, B.; Mukherjee, R.; Subramanian, K. P.; Banerjee, S. B., E-mail: bhala@prl.res.in [Space and Atmospheric Sciences Division, Physical Research Laboratory, Ahmedabad (India)

    2015-01-10

    Propargyl alcohol (CHCCH{sub 2}OH) is a known stable isomer of the propenal (CH{sub 2}CHCHO) molecule that was reported to be present in the interstellar medium (ISM). At astrochemical conditions in the laboratory, icy layers of propargyl alcohol grown at 85 K were irradiated by 2 keV electrons and probed by a Fourier Transform InfraRed spectrometer in the mid-infrared (IR) region, 4000-500 cm{sup –1}. Propargyl alcohol ice under astrochemical conditions was studied for the first time; therefore, IR spectra of reported amorphous (85 K) and crystalline (180 K) propargyl alcohol ices can be used to detect its presence in the ISM. Moreover, our experiments clearly show benzene (C{sub 6}H{sub 6}) formation to be the major product from propargyl alcohol irradiation, confirming the role of propargyl radicals (C{sub 3}H{sub 3}) formed from propargyl alcohol dissociation that was long expected based on theoretical modeling to effectively synthesize C{sub 6}H{sub 6} in the interstellar icy mantles.

  18. Brine Pockets in the Icy Shell on Europa: Distribution, Chemistry, and Habitability

    Science.gov (United States)

    Zolotov, M. Yu; Shock, E. L.; Barr, A. C.; Pappalardo, R. T.

    2004-01-01

    On Earth, sea ice is rich in brine, salt, and gas inclusions that form through capturing of seawater during ice formation. Cooling of the ice over time leads to sequential freezing of captured sea-water, precipitation of salts, exsolution of gases, and formation of brine channels and pockets. Distribution and composition of brines in sea ice depend on the rate of ice formation, vertical temperature gradient, and the age of the ice. With aging, the abundance of brine pockets decreases through downward migration. De- spite low temperatures and elevated salinities, brines in sea ice provide a habitat for photosynthetic and chemosynthetic organisms. On Europa, brine pockets and channels could exist in the icy shell that may be from a few km to a few tens of km thick and is probably underlain by a water ocean. If the icy shell is relatively thick, convection could develop, affecting the temperature pattern in the ice. To predict the distribution and chemistry of brine pockets in the icy shell we have combined numerical models of the temperature distribution within a convecting shell, a model for oceanic chemistry, and a model for freezing of Europan oceanic water. Possible effects of brine and gas inclusions on ice rheology and tectonics are discussed.

  19. Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3).

    Science.gov (United States)

    Verma, Sunil; Bartlett, Cynthia Huang; Schnell, Patrick; DeMichele, Angela M; Loi, Sherene; Ro, Jungsil; Colleoni, Marco; Iwata, Hiroji; Harbeck, Nadia; Cristofanilli, Massimo; Zhang, Ke; Thiele, Alexandra; Turner, Nicholas C; Rugo, Hope S

    2016-10-01

    Palbociclib enhances endocrine therapy and improves clinical outcomes in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Because this is a new target, it is clinically important to understand palbociclib's safety profile to effectively manage toxicity and optimize clinical benefit. Patients with endocrine-resistant, HR-positive/HER2-negative MBC (n = 521) were randomly assigned 2:1 to receive fulvestrant (500 mg intramuscular injection) with or without goserelin with oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments at baseline and day 1 of each cycle included blood counts on day 15 for the first 2 cycles. Hematologic toxicity was assessed by using laboratory data. A total of 517 patients were treated (palbociclib, n = 345; placebo, n = 172); median follow-up was 8.9 months. With palbociclib, neutropenia was the most common grade 3 (55%) and 4 (10%) adverse event; median times to onset and duration of grade ≥3 episodes were 16 and 7 days, respectively. Asian ethnicity and below-median neutrophil counts at baseline were significantly associated with an increased chance of developing grade 3-4 neutropenia with palbociclib. Dose modifications for grade 3-4 neutropenia had no adverse effect on progression-free survival. In the palbociclib arm, febrile neutropenia occurred in 3 (<1%) patients. The percentage of grade 1-2 infections was higher than in the placebo arm. Grade 1 stomatitis occurred in 8% of patients. Palbociclib plus fulvestrant treatment was well-tolerated, and the primary toxicity of asymptomatic neutropenia was effectively managed by dose modification without apparent loss of efficacy. This study appears at ClinicalTrials.gov, NCT01942135. Treatment with palbociclib in combination with fulvestrant was generally safe and well-tolerated in patients with hormone receptor (HR)-positive metastatic breast cancer. Consistent with the drug's proposed

  20. An Overview of the Jupiter Icy Moons Orbiter (JIMO) Mission, Environments, and Materials Challenges

    Science.gov (United States)

    Edwards, Dave

    2012-01-01

    Congress authorized NASA's Prometheus Project in February 2003, with the first Prometheus mission slated to explore the icy moons of Jupiter with the following main objectives: (1) Develop a nuclear reactor that would provide unprecedented levels of power and show that it could be processed safely and operated reliably in space for long-duration. (2) Explore the three icy moons of Jupiter -- Callisto, Ganymede, and Europa -- and return science data that would meet the scientific goals as set forth in the Decadal Survey Report of the National Academy of Sciences.

  1. Does a selective 5-hydroxytryptamine antagonist (ICI 169, 369) lower blood pressure in hypertensive patients?

    OpenAIRE

    Scott, A K; Roy-Chaudhury, P; Webster, J; Petrie, J C

    1989-01-01

    1. The effect of single doses (10, 30 and 50 mg) of a selective 5-HT2 receptor antagonist, ICI 169, 369, on blood pressure, heart rate and the electrocardiogram was studied using a double-blind, placebo-controlled, within subject design in hypertensive patients. 2. ICI 169, 369 did not reduce blood pressure or increase QT interval as has been reported with ketanserin. This suggests that it is the other properties of ketanserin which are responsible for its antihypertensive effect. 3. Plasma c...

  2. Kidnapping small icy asteroids in Earth near encounter to harbour life and to deflect trajectory

    Science.gov (United States)

    Fargion, Daniele

    2016-07-01

    The inter-planetary flight for human being is under danger because of unscreened and lethal solar flare radioactive showers. The screening of the astronauts by huge superconducting magnetic fields is unrealistic by many reasons. On the contrary the ability to reach nearby icy asteroids, to harbour there a complete undergound room where ecological life systems are first set, this goal may offer a later natural and safe currier for future human stations and enterprise. The need to deflect such a small size (a few thousands tons objects) maybe achieved by micro nuclear engines able to dig the asteroid icy skin, to heat and propel the soil by a synchronous jet engine array, bending and driving it to any desired trajectories. The need for such a wide collection of icy asteroid stations, often in a robotic ibernated state, it will offer the safe help station, raft in the wide space sea, where to collect material or energy in long human planetary travels.

  3. Unraveling the Reaction Chemistry of Icy Ocean World Surfaces

    Science.gov (United States)

    Hudson, R.; Loeffler, M. J.; Gerakines, P.

    2017-12-01

    The diverse endogenic chemistry of ocean worlds can be divided among interior, surface, and above-surface process, with contributions from exogenic agents such as solar, cosmic, and magnetospheric radiation. Bombardment from micrometeorites to comets also can influence chemistry by both delivering new materials and altering pre-existing ones, and providing energy to drive reactions. Geological processes further complicate the chemistry by transporting materials from one environment to another. In this presentation the focus will be on some of the thermally driven and radiation-induced changes expected from icy materials, primarily covalent and ionic compounds. Low-temperature conversions of a few relatively simple molecules into ions possessing distinct infrared (IR) features will be covered, with an emphasis on such features as might be identified through either orbiting spacecraft or landers. The low-temperature degradation of a few bioorganic molecules, such as DNA nucleobases and some common amino acids, will be used as examples of the more complex, and potentially misleading, chemistry expected for icy moons of the outer solar system. This work was supported by NASA's Emerging Worlds and Outer Planets Research programs, as well as the NASA Astrobiology Institute's Goddard Center for Astrobiology.

  4. Heating and melting of small icy satellites by the decay of Al-26

    International Nuclear Information System (INIS)

    Prialnik, D.; Bar-Nun, A.

    1990-01-01

    The effect of radiogenic heating due to Al-26 on the thermal evolution of small icy satellites is studied. The object is to find the extent of internal melting as a function of the satellite radius and of the initial Al-26 abundance. The implicit assumption, based on observations of young stars, is that planet and satellite accretion occurred on a time scale of about 10 to the 6th yr (comparable with the lifetime of Al-26). The icy satellites are modeled as spheres of initially amorphous ice, with chondritic abundances of K-40, Th-232, U-235, and U-238, corresponding to an ice/dust mass ratio of 1. Evolutionary calculations are carried out, spanning 4.5 x 10 to the 9th yr, for different combinations of the two free parameters. Heat transfer by subsolidus convection is neglected for these small satellites. The main conclusion is that the initial Al-26 abundance capable of melting icy bodies of satellite size to a significant extent is more than 10 times lower than that prevailing in the interstellar medium (or that inferred from the Ca-Al rich inclusions of the Allende meteorite, about 7 x 10 to the -7th by mass). 34 refs

  5. Heating and melting of small icy satellites by the decay of Al-26

    Science.gov (United States)

    Prialnik, Dina; Bar-Nun, Akiva

    1990-05-01

    The effect of radiogenic heating due to Al-26 on the thermal evolution of small icy satellites is studied. The object is to find the extent of internal melting as a function of the satellite radius and of the initial Al-26 abundance. The implicit assumption, based on observations of young stars, is that planet and satellite accretion occurred on a time scale of about 10 to the 6th yr (comparable with the lifetime of Al-26. The icy satellites are modeled as spheres of initially amorphous ice, with chondritic abundances of K-40, Th-232, U-235, and U-238, corresponding to an ice/dust mass ratio of 1. Evolutionary calculations are carried out, spanning 4.5 x 10 to the 9th yr, for different combinations of the two free parameters. Heat transfer by subsolidus convection is neglected for these small satellites. The main conclusion is that the initial Al-26 abundance capable of melting icy bodies of satellite size to a significant extent is more than 10 times lower than that prevailing in the interstellar medium (or that inferred from the Ca-Al rich inclusions of the Allende meteorite, about 7 x 10 to the -7th by mass).

  6. Stabilization of ammonia-rich hydrate inside icy planets.

    Science.gov (United States)

    Naden Robinson, Victor; Wang, Yanchao; Ma, Yanming; Hermann, Andreas

    2017-08-22

    The interior structure of the giant ice planets Uranus and Neptune, but also of newly discovered exoplanets, is loosely constrained, because limited observational data can be satisfied with various interior models. Although it is known that their mantles comprise large amounts of water, ammonia, and methane ices, it is unclear how these organize themselves within the planets-as homogeneous mixtures, with continuous concentration gradients, or as well-separated layers of specific composition. While individual ices have been studied in great detail under pressure, the properties of their mixtures are much less explored. We show here, using first-principles calculations, that the 2:1 ammonia hydrate, (H 2 O)(NH 3 ) 2 , is stabilized at icy planet mantle conditions due to a remarkable structural evolution. Above 65 GPa, we predict it will transform from a hydrogen-bonded molecular solid into a fully ionic phase O 2- ([Formula: see text]) 2 , where all water molecules are completely deprotonated, an unexpected bonding phenomenon not seen before. Ammonia hemihydrate is stable in a sequence of ionic phases up to 500 GPa, pressures found deep within Neptune-like planets, and thus at higher pressures than any other ammonia-water mixture. This suggests it precipitates out of any ammonia-water mixture at sufficiently high pressures and thus forms an important component of icy planets.

  7. Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant

    DEFF Research Database (Denmark)

    Frogne, Thomas; Benjaminsen, Rikke; Sonne-Hansen, Katrine

    2008-01-01

    cell lines concomitant with inhibition of Erk and unaltered Akt activation. In concert, inhibition of Erk with U0126 preferentially reduced growth of resistant cell lines. Treatment with ErbB3 neutralizing antibodies inhibited ErbB3 activation and resulted in a modest but statistically significant...... activation was observed only in the parental MCF-7 cells. The downstream kinases pAkt and pErk were increased in five of seven and in all seven resistant cell lines, respectively. Treatment with the EGFR inhibitor gefitinib preferentially inhibited growth and reduced the S phase fraction in the resistant...... growth inhibition of two resistant cell lines. These data indicate that ligand activated ErbB3 and EGFR, and Erk signaling play important roles in fulvestrant resistant cell growth. Furthermore, the decreased level of ErbB4 in resistant cells may facilitate heterodimerization of ErbB3 with EGFR and ErbB2...

  8. Jupiter Icy Moons Explorer (JUICE) : Science Objectives, Mission and Instruments (abstract)

    NARCIS (Netherlands)

    Gurvits, L.; Plaut, J.J.; Barabash, S.; Bruzzone, L.; Dougherty, M.; Erd, C.; Fletcher, L.; Gladstone, R.; Grasset, O.; Hartogh, P.; Hussmann, H.; Iess, L.; Jaumann, R.; Langevin, Y.; Palumbo, P.; Piccioni, G.; Titov, D.; Wahlund, J.E.

    2014-01-01

    The JUpiter ICy Moons Explorer (JUICE) is a European Space Agency mission that will fly by and observe the Galilean satellites Europa, Ganymede and Callisto, characterize the Jovian system in a lengthy Jupiter-orbit phase, and ultimately orbit Ganymede for in-depth studies of habitability, evolution

  9. Theoretical calculation on ICI reduction using digital coherent superposition of optical OFDM subcarrier pairs in the presence of laser phase noise.

    Science.gov (United States)

    Yi, Xingwen; Xu, Bo; Zhang, Jing; Lin, Yun; Qiu, Kun

    2014-12-15

    Digital coherent superposition (DCS) of optical OFDM subcarrier pairs with Hermitian symmetry can reduce the inter-carrier-interference (ICI) noise resulted from phase noise. In this paper, we show two different implementations of DCS-OFDM that have the same performance in the presence of laser phase noise. We complete the theoretical calculation on ICI reduction by using the model of pure Wiener phase noise. By Taylor expansion of the ICI, we show that the ICI power is cancelled to the second order by DCS. The fourth order term is further derived out and only decided by the ratio of laser linewidth to OFDM subcarrier symbol rate, which can greatly simplify the system design. Finally, we verify our theoretical calculations in simulations and use the analytical results to predict the system performance. DCS-OFDM is expected to be beneficial to certain optical fiber transmissions.

  10. Fatal outcome after reactivation of inherited chromosomally integrated HHV-6A (iciHHV-6A) transmitted through liver transplantation.

    Science.gov (United States)

    Bonnafous, P; Marlet, J; Bouvet, D; Salamé, E; Tellier, A-C; Guyetant, S; Goudeau, A; Agut, H; Gautheret-Dejean, A; Gaudy-Graffin, C

    2018-06-01

    HHV-6A and HHV-6B are found as inherited and chromosomally integrated forms (iciHHV-6A and -6B) into all germinal and somatic cells and vertically transmitted in a Mendelian manner in about 1% of the population. They were occasionally shown to be horizontally transmitted through hematopoietic stem cell transplantation. Here, we present a clinical case of horizontal transmission of iciHHV-6A from donor to recipient through liver transplantation. Molecular analysis performed on three viral genes (7.2 kb) in the recipient and donor samples supports transmission of iciHHV-6A from the graft. Transmission was followed by reactivation, with high viral loads in several compartments. The infection was uncontrollable, leading to severe disease and death, despite antiviral treatments and the absence of resistance mutations. This case highlights the fact that physicians should be aware of the possible horizontal transmission of iciHHV-6 and its consequences in case of reactivation in immunocompromised patients. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

  11. Laboratory study of hyper-elocity impact-driven chemical reactions and surface evolution in icy targets.

    Science.gov (United States)

    Ulibarri, Z.; Munsat, T.; Dee, R.; Horanyi, M.; James, D.; Kempf, S.; Nagle, M.; Sternovsky, Z.

    2017-12-01

    Although ice is prevalent in the solar system and the long-term evolution of many airless icy bodies is affected by hypervelocity micrometeoroid bombardment, there has been little experimental investigation into these impact phenomena, especially at the impact speeds encountered in space. For example, there is little direct information about how dust impacts alter the local chemistry, and dust impacts may be an important mechanism for creating complex organic molecules necessary for life. Laser ablation and light-gas gun experiments simulating dust impacts have successfully created amino acid precursors from base components in ice surfaces. Additionally, the Cassini mission revealed CO2 deposits in icy satellites of Saturn, which may have been created by dust impacts. With the creation of a cryogenically cooled ice target for the dust accelerator facility at the NASA SSERVI-funded Institute for Modeling Plasma, Atmospheres, and Cosmic Dust (IMPACT), it is now possible to study the effects of micrometeoroid impacts in a controlled environment under conditions and at energies typically encountered in nature. Complex ice-target mixtures are created with a flash-freezing target which allows for homogeneous mixtures to be frozen in place even with salt mixtures that otherwise would form inhomogeneous ice surfaces. Coupled with the distinctive capabilities of the IMPACT dust facility, highly valuable data concerning the evolution of icy bodies under hypervelocity bombardment and the genesis of complex organic chemistry on these icy bodies can be gathered in unique and tightly controlled experiments. Results from recent and ongoing investigations will be presented.

  12. ICI Holland hanteert ISO 9001 ook voor arbozorg: audit is ons toverwoord

    NARCIS (Netherlands)

    Torenvliet, S.; Pennekamp, E.

    1994-01-01

    In verschillende fabrieken van ICI Holland worden grondstoffen voor polyrethaan, acrylaat, polyesterfilm en grondstoffen voor PET-flessen gemaakt. Werknemers in deze fabrieken krijgen training over de specifieke gevaren. Ook moeten examens afgelegd worden over die gevaren. Dit artikel beschrijft hoe

  13. An excess of pedestrian injuries in icy conditions

    DEFF Research Database (Denmark)

    Merrild, Ulrik; Bak, Soeren

    1983-01-01

    An "icy condition epidemic" has been analyzed in an investigation of patients treated in the casualty department of Odense University Hospital: it was found that the victims were mainly comprised of pedestrians and that the pedestrians had 14 times more injuries than during a normal winter period...... clearing of the snow, and (3) spreading of sand, and possibly salt, on footpaths and bicycle paths. Specific measures should be launched to help the elderly during such periods, in order that outdoor activities may be cut to a minimum....

  14. Habitability potential of icy moons: a comparative study

    Science.gov (United States)

    Solomonidou, Anezina; Coustenis, Athena; Encrenaz, Thérèse; Sohl, Frank; Hussmann, Hauke; Bampasidis, Georgios; Wagner, Frank; Raulin, François; Schulze-Makuch, Dirk; Lopes, Rosaly

    2014-05-01

    Looking for habitable conditions in the outer solar system our research focuses on the natural satellites rather than the planets themselves. Indeed, the habitable zone as traditionally defined may be larger than originally con-ceived. The strong gravitational pull caused by the giant planets may produce enough energy to sufficiently heat the interiors of orbiting icy moons. The outer solar system satellites then provide a conceptual basis within which new theories for understanding habitability can be constructed. Measurements from the ground but also by the Voyager, Galileo and the Cassini spacecrafts revealed the potential of these satellites in this context, and our understanding of habitability in the solar system and beyond can be greatly enhanced by investigating several of these bodies together [1]. Their environments seem to satisfy many of the "classical" criteria for habitability (liquid water, energy sources to sustain metabolism and chemical compounds that can be used as nutrients over a period of time long enough to allow the development of life). Indeed, several of the moons show promising conditions for habitability and the de-velopment and/or maintenance of life. Europa, Callisto and Ganymede may be hiding, under their icy crust, putative undersurface liquid water oceans [3] which, in the case of Europa [2], may be in direct contact with a silicate mantle floor and kept warm by tidally generated heat [4]. Titan and Enceladus, Saturn's satellites, were found by the Cassini-Huygens mission to possess active organic chemistries with seasonal variations, unique geological features and possibly internal liquid water oceans. Titan's rigid crust and the probable existence of a subsurface ocean create an analogy with terrestrial-type plate tectonics, at least surficial [5], while Enceladus' plumes find an analogue in gey-sers. As revealed by Cassini the liquid hydrocarbon lakes [6] distributed mainly at polar latitudes on Titan are ideal isolated

  15. Water and the Interior Structure of Terrestrial Planets and Icy Bodies

    Science.gov (United States)

    Monteux, J.; Golabek, G. J.; Rubie, D. C.; Tobie, G.; Young, E. D.

    2018-02-01

    Water content and the internal evolution of terrestrial planets and icy bodies are closely linked. The distribution of water in planetary systems is controlled by the temperature structure in the protoplanetary disk and dynamics and migration of planetesimals and planetary embryos. This results in the formation of planetesimals and planetary embryos with a great variety of compositions, water contents and degrees of oxidation. The internal evolution and especially the formation time of planetesimals relative to the timescale of radiogenic heating by short-lived 26Al decay may govern the amount of hydrous silicates and leftover rock-ice mixtures available in the late stages of their evolution. In turn, water content may affect the early internal evolution of the planetesimals and in particular metal-silicate separation processes. Moreover, water content may contribute to an increase of oxygen fugacity and thus affect the concentrations of siderophile elements within the silicate reservoirs of Solar System objects. Finally, the water content strongly influences the differentiation rate of the icy moons, controls their internal evolution and governs the alteration processes occurring in their deep interiors.

  16. Laboratory Reference Spectroscopy of Icy Satellite Candidate Surface Materials (Invited)

    Science.gov (United States)

    Dalton, J. B.; Jamieson, C. S.; Shirley, J. H.; Pitman, K. M.; Kariya, M.; Crandall, P.

    2013-12-01

    The bulk of our knowledge of icy satellite composition continues to be derived from ultraviolet, visible and infrared remote sensing observations. Interpretation of remote sensing observations relies on availability of laboratory reference spectra of candidate surface materials. These are compared directly to observations, or incorporated into models to generate synthetic spectra representing mixtures of the candidate materials. Spectral measurements for the study of icy satellites must be taken under appropriate conditions (cf. Dalton, 2010; also http://mos.seti.org/icyworldspectra.html for a database of compounds) of temperature (typically 50 to 150 K), pressure (from 10-9 to 10-3 Torr), viewing geometry, (i.e., reflectance), and optical depth (must manifest near infrared bands but avoid saturation in the mid-infrared fundamentals). The Planetary Ice Characterization Laboratory (PICL) is being developed at JPL to provide robust reference spectra for icy satellite surface materials. These include sulfate hydrates, hydrated and hydroxylated minerals, and both organic and inorganic volatile ices. Spectral measurements are performed using an Analytical Spectral Devices FR3 portable grating spectrometer from .35 to 2.5 microns, and a Thermo-Nicolet 6500 Fourier-Transform InfraRed (FTIR) spectrometer from 1.25 to 20 microns. These are interfaced with the Basic Extraterrestrial Environment Simulation Testbed (BEEST), a vacuum chamber capable of pressures below 10-9 Torr with a closed loop liquid helium cryostat with custom heating element capable of temperatures from 30-800 Kelvins. To generate optical constants (real and imaginary index of refraction) for use in nonlinear mixing models (i.e., Hapke, 1981 and Shkuratov, 1999), samples are ground and sieved to six different size fractions or deposited at varying rates to provide a range of grain sizes for optical constants calculations based on subtractive Kramers-Kronig combined with Hapke forward modeling (Dalton and

  17. Le CERN va devoir supprimer quelques 600 postes d'ici a 2007

    CERN Multimedia

    2002-01-01

    "Le Laboratoire europeen pour la physique des particules (CERN) qui procede actuellement a la construction du LHC (Large Hadron Collider) , le plus grand accelerateur de particules du monde, va devoir supprimer, comme cela avait ete evoque en juin, quelques 600 postes d'ici a 2007" (1 paragraph).

  18. Multi-Modal Active Perception for Autonomously Selecting Landing Sites on Icy Moons

    Science.gov (United States)

    Arora, A.; Furlong, P. M.; Wong, U.; Fong, T.; Sukkarieh, S.

    2017-01-01

    Selecting suitable landing sites is fundamental to achieving many mission objectives in planetary robotic lander missions. However, due to sensing limitations, landing sites which are both safe and scientifically valuable often cannot be determined reliably from orbit, particularly, in icy moon missions where orbital sensing data is noisy and incomplete. This paper presents an active perception approach to Entry Descent and Landing (EDL) which enables the lander to autonomously plan informative descent trajectories, acquire high quality sensing data during descent and exploit this additional information to select higher utility landing sites. Our approach consists of two components: probabilistic modeling of landing site features and approximate trajectory planning using a sampling based planner. The proposed framework allows the lander to plan long horizons paths and remain robust to noisy data. Results in simulated environments show large performance improvements over alternative approaches and show promise that our approach has strong potential to improve science return of not only icy moon missions but EDL systems in general.

  19. High pressure ices are not the end of the story for large icy moons habitability: experimental studies of salts effects on high pressure ices and the implications for icy worlds large hydrosphere structure and chemical evolution

    Science.gov (United States)

    Journaux, Baptiste; Abramson, Evan; Brown, J. Michael; Bollengier, Olivier

    2017-10-01

    The presence of several phases of deep high-pressure ices in large icy moons hydrosphere has often been pointed as a major limitation for the habitability of an uppermost ocean. As they are gravitationally stable bellow liquid H2O, they are thought to act as a chemical barrier between the rocky bed and the ocean. Solutes, including salt species such as NaCl and MgSO4, have been suggested inside icy world oceans from remote sensing, magnetic field measurements and chondritic material alteration models. Unfortunately, the pressures and temperatures inside these hydrospheres are very different from the one found in Earth aqueous environments, so most of our current thermodynamic databases do not cover the range of conditions relevant for modeling realistically large icy worlds interiors.Recent experimental results have shown that the presence of solutes, and more particularly salts, in equilibrium with high pressure ices have large effects on the stability, buoyancy and chemistry of all the phases present at these extreme conditions.In particular brines have been measured to be sometimes more dense than the high pressure ices at melting conditions, possibly creating several oceanic layer "sandwiched" in between two ices shells or in contact with the rocky bed.Other effects currently being investigated by our research group also covers ice melting curve depressions that depend on the salt species and incorporation of solutes inside the crystallographic lattice of high pressure ices. Both of these could have very important implication at the planetary scale, enabling thicker/deeper liquid oceans, and allowing chemical transportation through the high pressure ice layer in large icy worlds.We will present the latest results obtained in-situ using diamond anvil cell high pressure allowing to probe the density, chemistry and thermodynamic properties of high pressure ice and aqueous solutions in equilibrium with Na-Mg-SO4-Cl ionic species.We will also discuss the new

  20. Selective adrenergic beta-2-receptor blocking drug, ICI-118.551, is effective in essential tremor.

    Science.gov (United States)

    Teräväinen, H; Huttunen, J; Larsen, T A

    1986-07-01

    Eighteen patients with essential tremor were treated for 2 days with a non-selective adrenergic beta-blocking drug (dl-propranolol, 80 mg X 3), a beta-2-selective blocker (ICI-118.551, 50 mg X 3) and placebo (X 3) in a randomized double blind cross-over study. Postural hand tremor was recorded with an accelerometer before administration of the drugs and at the end of each treatment period. Compared with placebo, both the beta-blocking drugs caused a statistically significant decrease in tremor intensity and they possessed approximately similar antitremor potency. Subjective benefit was reported by 12 of the 18 patients receiving ICI-118.551, 13 when on propranolol and 3 when on placebo.

  1. Cost-Effective Icy Bodies Exploration using Small Satellite Missions

    Science.gov (United States)

    Jonsson, Jonas; Mauro, David; Stupl, Jan; Nayak, Michael; Aziz, Jonathan; Cohen, Aaron; Colaprete, Anthony; Dono-Perez, Andres; Frost, Chad; Klamm, Benjamin; hide

    2015-01-01

    It has long been known that Saturn's moon Enceladus is expelling water-rich plumes into space, providing passing spacecraft with a window into what is hidden underneath its frozen crust. Recent discoveries indicate that similar events could also occur on other bodies in the solar system, such as Jupiter's moon Europa and the dwarf planet Ceres in the asteroid belt. These plumes provide a possible giant leap forward in the search for organics and assessing habitability beyond Earth, stepping stones toward the long-term goal of finding extraterrestrial life. The United States Congress recently requested mission designs to Europa, to fit within a cost cap of $1B, much less than previous mission designs' estimates. Here, innovative cost-effective small spacecraft designs for the deep-space exploration of these icy worlds, using new and emerging enabling technologies, and how to explore the outer solar system on a budget below the cost horizon of a flagship mission, are investigated. Science requirements, instruments selection, rendezvous trajectories, and spacecraft designs are some topics detailed. The mission concepts revolve around a comparably small-sized and low-cost Plume Chaser spacecraft, instrumented to characterize the vapor constituents encountered on its trajectory. In the event that a plume is not encountered, an ejecta plume can be artificially created by a companion spacecraft, the Plume Maker, on the target body at a location timed with the passage of the Plume Chaser spacecraft. Especially in the case of Ceres, such a mission could be a great complimentary mission to Dawn, as well as a possible future Europa Clipper mission. The comparably small volume of the spacecraft enables a launch to GTO as a secondary payload, providing multiple launch opportunities per year. Plume Maker's design is nearly identical to the Plume Chaser, and fits within the constraints for a secondary payload launch. The cost-effectiveness of small spacecraft missions enables the

  2. Characterization of the permittivity of controlled porous water ice-dust mixtures to support the radar exploration of icy bodies

    OpenAIRE

    Brouet, Y.; Neves, L.; Sabouroux, P.; Levasseur-Regourd, A. C.; Poch, O.; Encrenaz, P.; Pommerol, Antoine; Thomas, N.; Kofman, W.

    2016-01-01

    The internal properties of porous and icy bodies in the solar system can be investigated by ground-penetrating radars (GPRs), like the COmet Nucleus Sounding Experiment by Radiowave Transmission instrument on board the Rosetta spacecraft which has sounded the interior of the nucleus of comet 67P/Churyumov-Gerasimenko. Accurate constraints on the permittivity of icy media are needed for the interpretation of the data. We report novel permittivity measurements performed on water ice samples and...

  3. JUICE: A European Mission to Jupiter and its Icy Moons

    Science.gov (United States)

    Grasset, Olivier; Witasse, Olivier; Barabash, Stas; Brandt, Pontus; Bruzzone, Lorenzo; Bunce, Emma; Cecconi, Baptiste; Cavalié, Thibault; Cimo, Giuseppe; Coustenis, Athena; Cremonese, Gabriele; Dougherty, Michele; Fletcher, Leigh N.; Gladstone, Randy; Gurvits, Leonid; Hartogh, Paul; Hoffmann, Holger; Hussmann, Hauke; Iess, Luciano; Jaumann, Ralf; Kasaba, Yasumasa; Kaspi, Yohai; Krupp, Norbert; Langevin, Yves; Mueller-Wodarg, Ingo; Palumbo, Pasquale; Piccioni, Giuseppe; Plaut, Jeffrey; Poulet, Francois; Roatsch, Thomas; Retherford, Kurt D.; Rothkaehl, Hanna; Stevenson, David J.; Tosi, Federico; Van Hoolst, Tim; Wahlund, Jan-Erik; Wurz, Peter; Altobelli, Nicolas; Accomazzo, A.; Boutonnet, Arnaud; Erd, Christian; Vallat, Claire

    2016-10-01

    JUICE - JUpiter ICy moons Explorer - is the first large mission in the ESA Cosmic Vision programme [1]. The implementation phase started in July 2015. JUICE will arrive at Jupiter in October 2029, and will spend 3 years characterizing the Jovian system, the planet itself, its giant magnetosphere, and the giant icy moons: Ganymede, Callisto and Europa. JUICE will then orbit Ganymede.The first goal of JUICE is to explore the habitable zone around Jupiter [2]. Ganymede is a high-priority target because it provides a unique laboratory for analyzing the nature, evolution and habitability of icy worlds, including the characteristics of subsurface oceans, and because it possesses unique magnetic fields and plasma interactions with the environment. On Europa, the focus will be on recently active zones, where the composition, surface and subsurface features (including putative water reservoirs) will be characterized. Callisto will be explored as a witness of the early Solar System.JUICE will also explore the Jupiter system as an archetype of gas giants. The circulation, meteorology, chemistry and structure of the Jovian atmosphere will be studied from the cloud tops to the thermosphere and ionosphere. JUICE will investigate the 3D properties of the magnetodisc, and study the coupling processes within the magnetosphere, ionosphere and thermosphere. The mission also focuses on characterizing the processes that influence surface and space environments of the moons.The payload consists of 10 instruments plus a ground-based experiment (PRIDE) to better constrain the S/C position. A remote sensing package includes imaging (JANUS) and spectral-imaging capabilities from UV to sub-mm wavelengths (UVS, MAJIS, SWI). A geophysical package consists of a laser altimeter (GALA) and a radar sounder (RIME) for exploring the moons, and a radio science experiment (3GM) to probe the atmospheres and to determine the gravity fields. The in situ package comprises a suite to study plasma and

  4. The Global Contribution of Secondary Craters on the Icy Satellites

    Science.gov (United States)

    Hoogenboom, T.; Johnson, K. E.; Schenk, P.

    2014-12-01

    At present, surface ages of bodies in the Outer Solar System are determined only from crater size-frequency distributions (a method dependent on an understanding of the projectile populations responsible for impact craters in these planetary systems). To derive accurate ages using impact craters, the impactor population must be understood. Impact craters in the Outer Solar System can be primary, secondary or sesquinary. The contribution of secondary craters to the overall population has recently become a "topic of interest." Our objective is to better understand the contribution of dispersed secondary craters to the small crater populations, and ultimately that of small comets to the projectile flux on icy satellites in general. We measure the diameters of obvious secondary craters (determined by e.g. irregular crater shape, small size, clustering) formed by all primary craters on Ganymede for which we have sufficiently high resolution data to map secondary craters. Primary craters mapped range from approximately 40 km to 210 km. Image resolution ranges from 45 to 440 m/pixel. Bright terrain on Ganymede is our primary focus. These resurfaced terrains have relatively low crater densities and serve as a basis for characterizing secondary populations as a function of primary size on an icy body for the first time. Although focusing on Ganymede, we also investigate secondary crater size, frequency, distribution, and formation, as well as secondary crater chain formation on icy satellites throughout the Saturnian and Jovian systems principally Rhea. We compare our results to similar studies of secondary cratering on the Moon and Mercury. Using Galileo and Voyager data, we have identified approximately 3,400 secondary craters on Ganymede. In some cases, we measured crater density as a function of distance from a primary crater. Because of the limitations of the Galileo data, it is necessary to extrapolate from small data sets to the global population of secondary craters

  5. The ICY1 gene from Saccharomyces cerevisiae affects nitrogen consumption during alcoholic fermentation

    Directory of Open Access Journals (Sweden)

    Claudio Martínez

    2014-07-01

    Conclusions: Our results suggest that the expression of ICY1 is regulated by the amount of nitrogen available in the must and it is involved in the consumption of ammonium, given the increase in the consumption of this nitrogen source observed in the null mutant strain.

  6. Efficacy of a rubber outsole with a hybrid surface pattern for preventing slips on icy surfaces.

    Science.gov (United States)

    Yamaguchi, Takeshi; Hsu, Jennifer; Li, Yue; Maki, Brian E

    2015-11-01

    Conventional winter-safety footwear devices, such as crampons, can be effective in preventing slips on icy surfaces but the protruding studs can lead to other problems such as trips. A new hybrid (rough and smooth) rubber outsole was designed to provide high slip resistance without use of protruding studs or asperities. In the present study, we examined the slip resistance of the hybrid rubber outsole on both dry (-10 °C) and wet (0 °C) icy surfaces, in comparison to three conventional strap-on winter anti-slip devices: 1) metal coils ("Yaktrax Walker"), 2) gritted (sandpaper-like) straps ("Rough Grip"), and 3) crampons ("Altagrips-Lite"). Drag tests were performed to measure static (SCOF) and dynamic (DCOF) coefficients of friction, and gait trials were conducted on both level and sloped ice surfaces (16 participants). The drag-test results showed relatively high SCOF (≧0.37) and DCOF (≧0.31) values for the hybrid rubber sole, at both temperatures. The other three footwear types exhibited lower DCOF values (0.06-0.20) when compared with the hybrid rubber sole at 0 °C (p footwear types, when descending a slope at -10 °C (6% of trials vs 0%; p footwear-related differences in slip frequency, distance or velocity. These results indicate that the slip-resistance of the hybrid rubber sole on icy surfaces was comparable to conventional anti-slip footwear devices. Given the likely advantages of the hybrid rubber sole (less susceptibility to tripping, better slip resistance on non-icy surfaces), this type of sole should contribute to a decrease in fall accidents; however, further research is needed to confirm its effectiveness under a wider range of test conditions. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  7. Sublimation of icy planetesimals and the delivery of water to the habitable zone around solar type stars

    Science.gov (United States)

    Brunini, Adrián; López, María Cristina

    2018-06-01

    We present a semi analytic model to evaluate the delivery of water to the habitable zone around a solar type star carried by icy planetesimals born beyond the snow line. The model includes sublimation of ice, gas drag and scattering by an outer giant planet located near the snow line. The sublimation model is general and could be applicable to planetary synthesis models or N-Body simulations of the formation of planetary systems. We perform a short series of simulations to asses the potential relevance of sublimation of volatiles in the process of delivery of water to the inner regions of a planetary system during early stages of its formation. We could anticipate that erosion by sublimation would prevent the arrival of much water to the habitable zone of protoplanetary disks in the form of icy planetesimals. Close encounters with a massive planet orbiting near the outer edge of the snow line could make possible for planetesimals to reach the habitable zone somewhat less eroded. However, only large planetesimals could provide appreciable amounts of water. Massive disks and sharp gas surface density profiles favor icy planetesimals to reach inner regions of a protoplanetary disk.

  8. Potential Biospheres of the icy world in our solar systems

    OpenAIRE

    de Vera, Jean Pierre Paul; Baque, Mickael

    2016-01-01

    The challenge in astrobiology and planetary research in the near future is to realize space missions to study the habitability of Mars and the icy moons of the Jovian and Saturnian systems. Mars is an interesting object to search for habitable environments and for fossilized (and potentially present) life because of its past water driven wet history. On the other hand the Jovian moon Europa and the Saturnian moon Enceladus are promising candidates, where liquid water oceans beneath the surfac...

  9. Thermal Conductive Heat Transfer and Partial Melting of Volatiles in Icy Moons, Asteroids, and Kuiper Belt Objects (Invited)

    Science.gov (United States)

    Kargel, J. S.; Furfaro, R.

    2013-12-01

    Thermal gradients within conductive layers of icy satellite and asteroids depend partly on heat flow, which is related to the secular decay of radioactive isotopes, to heat released by chemical phase changes, by conversion of gravitational potential energy to heat during differentiation, tidal energy dissipation, and to release of heat stored from prior periods. Thermal gradients are also dependent on the thermal conductivity of materials, which in turn depends on their composition, crystallinity, porosity, crystal fabric anisotropy, and details of their mixture with other materials. Small impurities can produce lattice defects and changes in polymerization, and thereby have a huge influence on thermal conductivity, as can cage-inclusion (clathrate) compounds. Heat flow and thermal gradients can be affected by fluid phase advection of mass and heat (in oceans or sublimating upper crusts), by refraction related to heterogeneities of thermal conductivity due to lateral variations and composition or porosity. Thermal profiles depend also on the surface temperature controlled by albedo and climate, surface relief, and latitude, orbital obliquity and surface insolation, solid state greenhouses, and endogenic heating of the surface. The thermal state of icy moon interiors and thermal gradients can be limited at depth by fluid phase advection of heat (e.g., percolating meteoric methane or gas emission), by the latent heat of phase transitions (melting, solid-state transitions, and sublimation), by solid-state convective or diapiric heat transfer, and by foundering. Rapid burial of thick volatile deposits can also affect thermal gradients. For geologically inactive or simple icy objects, most of these controls on heat flow and thermal gradients are irrelevant, but for many other icy objects they can be important, in some cases causing large lateral and depth variations in thermal gradients, large variations in heat flow, and dynamically evolving thermal states. Many of

  10. Deep ice and salty oceans of icy worlds, how high pressures influence their thermodynamics and provide constrains on extraterrestrial habitability

    Science.gov (United States)

    Journaux, B.; Brown, J. M.; Bollengier, O.; Abramson, E.

    2017-12-01

    As in Earth arctic and Antarctic regions, suspected extraterrestrial deep oceans in icy worlds (i.e. icy moons and water-rich exoplanets) chemistry and thermodynamic state will strongly depend on their equilibrium with H2O ice and present solutes. Na-Mg-Cl-SO4 salt species are currently the main suspected ionic solutes to be present in deep oceans based on remote sensing, magnetic field measurements, cryovolcanism ice grains chemical analysis and chondritic material aqueous alteration chemical models. Unlike on our planet, deep extraterrestrial ocean might also be interacting at depth with high pressure ices (e.g. III, V, VI, VI, X) which have different behavior compared to ice Ih. Unfortunately, the pressures and temperatures inside these hydrospheres differ significantly from the one found in Earth aqueous environments, so most of our current thermodynamic databases do not cover the range of conditions relevant for modeling realistically large icy worlds interiors. Recent experimental results have shown that the presence of solutes, and more particularly salts, in equilibrium with high pressure ices have large effects on the stability, buoyancy and chemistry of all the phases present at these extreme conditions. High pressure in-situ measurements using diamond anvil cell apparatus were operated both at the University of washington and at the European Synchrotron Radiation Facility on aqueous systems phase diagrams with Na-Mg-Cl-SO4 species, salt incorporation in high pressure ices and density inversions between the solid and the fluids. These results suggest a more complex picture of the interior structure, dynamic and chemical evolution of large icy worlds hydrospheres when solutes are taken into account, compared to current models mainly using pure water. Based on our in-situ experimental measurements, we propose the existence of new liquid environments at greater depths and the possibility of solid state transport of solute through the high pressure ices

  11. ICI system for protecting underwater structures

    Energy Technology Data Exchange (ETDEWEB)

    1977-10-14

    The new ICI Offshore product consists of polypropylene fibers about 4.4 m long, and with a density lower than that of sea water and thus a good buoyancy coefficient. Bundles of the fibers are passed through a braided mat of polyester, ''Paraweb'', which is weighted in accordance with the density of the entire system. The system is installed at the foot of platform legs and axially along pipelines to prevent scouring by ocean currents. The system has been installed in 144.8 m of water along the pipeline linking the Piper field to the Flotta terminal in the Orkney Islands. By reducing the velocity of the marine currents, the system causes sand and other material to be deposited along the fibers, forming a protective ''talus'' cone at first, then completely covering the structure. A sizable sand deposit had accumulated along the test segment of the pipeline less than one month after installation of the system. Use of the system on the Ekofisk-Emden gas pipeline where it is uncovered in the Danish North Sea sector is proposed.

  12. Characterization of the permittivity of controlled porous water ice-dust mixtures to support the radar exploration of icy bodies

    Science.gov (United States)

    Brouet, Y.; Neves, L.; Sabouroux, P.; Levasseur-Regourd, A. C.; Poch, O.; Encrenaz, P.; Pommerol, A.; Thomas, N.; Kofman, W.

    2016-12-01

    The internal properties of porous and icy bodies in the solar system can be investigated by ground-penetrating radars (GPRs), like the COmet Nucleus Sounding Experiment by Radiowave Transmission instrument on board the Rosetta spacecraft which has sounded the interior of the nucleus of comet 67P/Churyumov-Gerasimenko. Accurate constraints on the permittivity of icy media are needed for the interpretation of the data. We report novel permittivity measurements performed on water ice samples and icy mixtures with porosities in the 31-91% range. The measurements have been performed between 50 MHz and 2 GHz with a coaxial cell on a total of 38 samples with a good reproducibility. We used controlled procedures to produce fine-grained and coarse-grained ice samples with a mean diameter of 4.5 μm and 67 μm, respectively, and to prepare icy mixtures. The JSC-1A lunar regolith simulant was used as the dust component in the mixtures. The results are focused on the real-part ɛ' of the permittivity, which constrains the phase velocity of the radio waves in low-loss media. The values of ɛ' show a nondispersive behavior and are within the range of 1.1 to 2.7. They decrease with the increasing porosity Φ according to E(1 - Φ), with E equal to about 3.13 for pure water ice, and in the 3.8-7.5 range for ice-dust mixtures with a dust-to-ice volumetric ratio in the 0.1-2.8 range, respectively. These measurements are also relevant for radiometers operating in the millimeter-submillimeter domains, as suggested by the nondispersive behavior of the mixtures and of the pure components.

  13. Do we manage incontinence in children and adults with special needs adequately? ICI-RS 2014

    NARCIS (Netherlands)

    von Gontard, Alexander; de Jong, Tom P. V. M.; Rantell, Angie; Nieuwhof-Leppink, Anka; Badawi, Jasmin Katrin; Cardozo, Linda

    2016-01-01

    To review studies on the associations of incontinence and special needs in children and adults and to outline future directions in research and clinical care. A review of literature was conducted. Open questions and future directions were discussed during the ICI-RS meeting in 2014. Special needs

  14. Estimation of a melting probe's penetration velocity range to reach icy moons' subsurface ocean

    Science.gov (United States)

    Erokhina, Olga; Chumachenko, Eugene

    2014-05-01

    In modern space science one of the actual branches is icy satellites explorations. The main interest is concentrated around Jovian's moons Europa and Ganymede, Saturn's moons Titan and Enceladus that are covered by thick icy layer according to "Voyager1", "Voyager2", "Galileo" and "Cassini" missions. There is a big possibility that under icy shell could be a deep ocean. Also conditions on these satellites allow speculating about possible habitability, and considering these moons from an astrobiological point of view. One of the possible tasks of planned missions is a subsurface study. For this goal it is necessary to design special equipment that could be suitable for planetary application. One of the possible means is to use a melting probe which operates by melting and moves by gravitational force. Such a probe should be relatively small, should not weight too much and should require not too much energy. In terrestrial case such kind of probe has been successfully used for glaciers study. And it is possible to extrapolate the usage of such probe to extraterrestrial application. One of the tasks is to estimate melting probe's penetration velocity. Although there are other unsolved problems such as analyzing how the probe will move in low gravity and low atmospheric pressure; knowing whether hole will be closed or not when probe penetrate thick enough; and considering what order could be a penetration velocity. This study explores two techniques of melting probe's movement. One of them based on elasto-plastic theory and so-called "solid water" theory, and other one takes phase changing into account. These two techniques allow estimating melting probe's velocity range and study whole process. Based on these technique several cases of melting probe movement were considered, melting probe's velocity range estimated, influence of different factors studied and discussed and an easy way to optimize parameters of the melting probe proposed.

  15. Experimentally Testing Hydrothermal Vent Origin of Life on Enceladus and Other Icy/Ocean Worlds.

    Science.gov (United States)

    Barge, Laura M; White, Lauren M

    2017-09-01

    We review various laboratory strategies and methods that can be utilized to simulate prebiotic processes and origin of life in hydrothermal vent systems on icy/ocean worlds. Crucial steps that could be simulated in the laboratory include simulations of water-rock chemistry (e.g., serpentinization) to produce hydrothermal fluids, the types of mineral catalysts and energy gradients produced in vent interfaces where hydrothermal fluids interface with the surrounding seawater, and simulations of biologically relevant chemistry in flow-through gradient systems (i.e., far-from-equilibrium experiments). We describe some examples of experimental designs in detail, which are adaptable and could be used to test particular hypotheses about ocean world energetics or mineral/organic chemistry. Enceladus among the ocean worlds provides an ideal test case, since the pressure at the ocean floor is more easily simulated in the lab. Results for Enceladus could be extrapolated with further experiments and modeling to understand other ocean worlds. Key Words: Enceladus-Ocean worlds-Icy worlds-Hydrothermal vent-Iron sulfide-Gradient. Astrobiology 17, 820-833.

  16. Thermally-Induced Chemistry and the Jovian Icy Satellites: A Laboratory Study of the Formation of Sulfur Oxyanions

    Science.gov (United States)

    Loeffler, Mark J.; Hudson, Reggie L.

    2011-01-01

    Laboratory experiments have demonstrated that magnetospheric radiation in the Jovian system drives reaction chemistry in ices at temperatures relevant to Europa and other icy satellites. Here we present new results on thermally-induced reactions at 50-100 K in solid H2O-SO2 mixtures, reactions that take place without the need for a high-radiation environment. We find that H2O and SO2 react to produce sulfur Oxyanions, such as bisulfite, that as much as 30% of the SO2 can be consumed through this reaction, and that the products remain in the ice when the temperature is lowered, indicating that these reactions are irreversible. Our results suggest that thermally-induced reactions can alter the chemistry at temperatures relevant to the icy satellites in the Jovian system.

  17. Flow and fracture of ices, with application to icy satellites (Invited)

    Science.gov (United States)

    Durham, W. B.; Stern, L. A.; Pathare, A.; Golding, N.

    2013-12-01

    Exploration of the outer planets and their satellites by spacecraft over the past 4 decades has revealed that the prevailing low temperatures in the outer solar system have not produced "dead" cryoworlds of generic appearance. Rather, there is an extraordinary diversity in average densities, presence/absence and compositions of atmospheres and planetary rings, average albedos and their seasonal changes, near-surface compositions, and surface records of impact cratering and endogenic tectonic and igneous processes. One reason for this diversity is that the icy minerals present in abundance on many of these worlds are now or once were at significant fractions of their melting temperatures. Hence, a host of thermally activated processes related to endogenic activity (such as crystal defect migration, mass diffusion, surface transport, solid-solid changes of state, and partial melting) may occur that can enable inelastic flow on the surfaces and in the interiors of these bodies. Planetary manifestations include viscous crater relaxation in ice-rich terrain, cryovolcanism, the presence of a stable subsurface ocean, and the effects of solid-ice convection in deep interiors. We make the connection between theoretical mechanisms of deformation and planetary geology through laboratory experiment. Specifically, we develop quantitative constitutive flow laws (strain rate vs. stress) that describe the effects of relevant environmental variables (hydrostatic pressure, temperature, phase composition, chemical impurities). Our findings speak to topics including (1) the behavior of an outer ice I layer, its thickness, the depth to which a stagnant lid might extend, and possibility of wholesale overturn; (2) softening effects of dissolved species such as ammonia and perchlorate; (3) hardening effects of enclathration and of rock dust; and (4) effects of grain size on strength and factors affecting grain size. Other applications of lab data include dynamics of the deep interiors of

  18. A Holographic Microscope for Detection of Microorganisms on Icy Worlds

    Science.gov (United States)

    Lindensmith, C. A.; Nadeau, J. L.; Deming, J. W.; Showalter, G. M.; Rider, S.; Bedrossian, M.

    2015-12-01

    Holography is a well-established imaging technique that uses the interference of light to record and reproduce three-dimensional images of objects. Its use began in the 1960s with the invention of the laser. Digital holographic microscopy (DHM) has several advantages over ordinary imaging microscopy which make it ideal for field and astrobiology use, including no need for focus or scanning so that instruments are readily made autonomous. DHM can produce simultaneous bright-field and quantitative phase-contrast images of the same field, providing additional information about transparent objects, e.g., refractive index and/or thickness; thus it inherently supports effective label-free imaging. We have built a fieldable DHM for detection of microorganisms in bodies of water and in brines collected from sea ice. Ice that appears solid to the eye contains interconnected brine-filled microscopic pores and veins which are occupied by populations of prokaryotes and eukaryotes. The presence of life in "solid" ice has important implications for exploration of icy worlds, where it is unlikely that the first missions will be able to access the subsurface oceans. Using this new instrument, we examined several dozen samples from three different sites around Nuuk, Greenland. In all samples, mixed populations of both prokaryotic and eukaryotic microorganisms were observed. Many of the organisms were motile immediately upon extraction from sea ice, and others became motile after warming or addition of sugars and/or amino acids. Meaningful motility was readily distinguished from turbulence or fluid flow. The spatial resolution of the instrument was better than 1 μm, leading to unambiguous recognition of subcellular structures in eukaryotes, including nuclei and chloroplasts. We present mission scenrios for both orbiters and landers in which DHM may be used as a valuable complement to chemical-based life detection techniques for discovery of cellular life on icy worlds.

  19. Impact strength of small icy bodies that experienced multiple collisions

    Science.gov (United States)

    Yasui, Minami; Hayama, Ryo; Arakawa, Masahiko

    2014-05-01

    Frequent collisions are common for small bodies in the Solar System, and the cumulative damage to these bodies is thought to significantly affect their evolution. It is important to study the effects of multiple impacts such as the number of impacts on the impact strength and the ejection velocity of impact fragments. Here we conducted multiple-impact experiments using a polycrystalline water ice target, varying the number of impacts from 1 to 10 times. An ice cylindrical projectile was impacted at 84-502 m s-1 by using a single-stage gas gun in a cold room between -10 and -15 °C. The impact strength of the ice target that experienced a single impact and multiple impacts is expressed by the total energy density applied to the same target, ΣQ, and this value was observed to be 77.6 J kg-1. The number of fine impact fragments at a fragment mass normalized by an initial target mass, m/Mt0 ∼ 10-6, nm, had a good correlation with the single energy density at each shot, Qj, and the relationship was shown to be nm=10·Qj1.31±0.12. We also estimated the cumulative damage of icy bodies as a total energy density accumulated by past impacts, according to the crater scaling laws proposed by Housen et al. (Housen, K.R., Schmidt, R.M., Holsapple, K.A. [1983]. J. Geophys. Res. 88, 2485-2499) of ice and the crater size distributions observed on Phoebe, a saturnian icy satellite. We found that the cumulative damage of Phoebe depended significantly on the impact speed of the impactor that formed the craters on Phoebe; and the cumulative damage was about one-third of the impact strength ΣQ* at 500 m s-1 whereas it was almost zero at 3.2 km s-1.

  20. Experimental simulation of impact cratering on icy satellites

    Science.gov (United States)

    Greeley, R.; Fink, J. H.; Gault, D. E.; Guest, J. E.

    1982-01-01

    Cratering processes on icy satellites were simulated in a series of 102 laboratory impact experiments involving a wide range of target materials. For impacts into homogeneous clay slurries with impact energies ranging from five million to ten billion ergs, target yield strengths ranged from 100 to 38 Pa, and apparent viscosities ranged from 8 to 200 Pa s. Bowl-shaped craters, flat-floored craters, central peak craters with high or little relief, and craters with no relief were observed. Crater diameters increased steadily as energies were raised. A similar sequence was seen for experiment in which impact energy was held constant but target viscosity and strength progressively decreases. The experiments suggest that the physical properties of the target media relative to the gravitationally induced stresses determined the final crater morphology. Crater palimpsests could form by prompt collapse of large central peak craters formed in low target strength materials. Ages estimated from crater size-frequency distributions that include these large craters may give values that are too high.

  1. Update of monotherapy trials with the new anti-androgen, Casodex (ICI 176,334). International Casodex Investigators

    DEFF Research Database (Denmark)

    Iversen, P

    1994-01-01

    Casodex (ICI 176,334) is a non-steroidal anti-androgen, which has a half-life compatible with once-daily oral dosing. In an open, phase II study on 267 patients given Casodex, 50 mg/day, an overall objective response (i.e. partial regression) was seen in 55.5% of patients (146 of 263) with a furt...

  2. Kilometer-Scale Transient Atmospheres for Kinetic Payload Deposition on Icy Bodies

    Science.gov (United States)

    Koch, James

    Entry, descent, and landing technologies for space exploration missions to atmospheric bodies traditionally exploit the body's ambient atmosphere as a medium through which a spacecraft or probe can interact to transfer momentum and energy for a soft landing. For bodies with no appreciable atmosphere, a significant engineering challenge exists to overcome the lack of passive methods to decelerate a spacecraft or probe. Proposed is a novel means for the creation of a transient atmosphere for airless icy bodies through the use of a two stage payload-penetrator probe. The first stage is a hyper-velocity penetrator that impacts the icy body. The second stage is an aero-braking-capable probe directed to pass through the ejecta plume from the hyper-velocity impact. Both experimental and computational studies show that a controlled high-energy impact can direct and transfer energy and momentum to a probe via a collimated ejecta plume. In an effort to provide clarity to this unexplored class of missions, a modeling-based engineering approach is taken to provide a first-order estimation of some of the involved physical phenomena. Three sub-studies are presented: an examination and characterization of ice plumes, modeling plume-probe interaction, and the extension of plume modeling as the basis for conceptual mission design. The modeling efforts are centered about two modeling formulations: smoothed particle hydrodynamics (SPH) and the arbitrary Largrangian-Eulerian (ALE) set of techniques. A database of fully-developed hypervelocity impacts and their associated plumes is created and used as inputs to a 1-D mathematical model for the interaction of a continuum-based plume and probe. A parametric study based on the hyper-velocity impact and staging of the probe-penetrator system is presented and discussed. Shown is that a tuned penetrator-probe mission has the potential to increase spacecraft payload mass fraction over conventional soft landing schemes.

  3. Basalt Weathering in a Cold and Icy Climate: Three Sisters, Oregon as an Analog for Early Mars

    Science.gov (United States)

    Rampe, E. B.; Horgan, B.; Smith, R. J.; Scudder, N. A.; Rutledge, A. M.; Bamber, E.; Morris, R. V.

    2017-01-01

    There is abundant evidence for liquid water on early Mars, but the debate remains whether early Mars was warm and wet or cold and icy with punctuated periods of melting. To further investigate the hypothesis of a cold and icy early Mars, we collected rocks and sediments from the Collier and Diller glacial valleys in the Three Sisters volcanic complex in Oregon. We analyzed rocks and sediments with X-ray diffraction (XRD), scanning and transmission electron microscopies with energy dispersive spectroscopy (SEM, TEM, EDS), and visible, short-wave infrared (VSWIR) and thermal-IR (TIR) spectroscopies to characterize chemical weathering and sediment transport through the valleys. Here, we focus on the composition and mineralogy of the weathering products and how they compare to those identified on the martian surface. Phyllosilicates (smectite), zeolites, and poorly crystalline phases were discovered in pro- and supra-glacial sediments, whereas Si-rich regelation films were found on hand samples and boulders in the proglacial valleys. Most phyllosilicates and zeolites are likely detrital, originating from hydrothermally altered units on North Sister. TEM-EDS analyses of the flour samples demonstrate a variety of poorly crystalline (i.e., no long-range crystallographic order) phases: iron oxides, devitrified volcanic glass, and Fe-Si-Al phases. The CheMin XRD on the Curiosity rover in Gale crater has identified significant amounts of X-ray amorphous materials in all samples measured to date. The amorphous component is likely a combination of silicates, iron oxides, and sulfates. Although we have not yet observed amorphous sulfate in the samples from Three Sisters, the variety of poorly crystalline weathering products found at this site is consistent with the variable composition of the X-ray amorphous component identified by CheMin. We suggest that these amorphous phases on Mars could have formed in a similarly cold and icy environment.

  4. Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis.

    Science.gov (United States)

    Zhang, Jingwen; Huang, Yanhong; Wang, Changyi; He, Yuanfang; Zheng, Shukai; Wu, Kusheng

    2017-08-01

    Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients. The main outcomes were objective response rate (ORR), time to progression (TTP), and progression-free survival (PFS). Secondary outcomes were adverse events. We identified 27 articles of 8 randomized controlled trials including 3492 patients in the network meta-analysis. For ORR, the treatments ranked in descending order of effectiveness were letrozole > exemestane > anastrozole > fulvestrant 500 mg > tamoxifen > fulvestrant 250 mg. For TTP/PFS, the order was fulvestrant 500 mg > letrozole > anastrozole > exemestane > tamoxifen > fulvestrant 250 mg. We directly compared adverse events and found that tamoxifen produced more hot flash events than fulvestrant 250 mg. Fulvestrant 500 mg and letrozole might be optimal first-line endocrine monotherapy choices for HR+ HER2- ABC because of efficacious ORR and TTP/PFS, with a favorable tolerability profile. However, direct comparisons among endocrine monotherapies in the first-line therapy setting are still required to robustly demonstrate any differences among these endocrine agents. Clinical choices should also depend on the specific disease situation and duration of endocrine therapy.

  5. Overexpression of HvIcy6 in Barley Enhances Resistance against Tetranychus urticae and Entails Partial Transcriptomic Reprogramming

    Directory of Open Access Journals (Sweden)

    M. Estrella Santamaria

    2018-03-01

    Full Text Available Cystatins have been largely used for pest control against phytophagous species. However, cystatins have not been commonly overexpressed in its cognate plant species to test their pesticide capacity. Since the inhibitory role of barley HvCPI-6 cystatin against the phytophagous mite Tetranychus urticae has been previously demonstrated, the purpose of our study was to determine if barley transgenic lines overexpressing its own HvIcy6 gene were more resistant against this phytophagous infestation. Besides, a transcriptomic analysis was done to find differential expressed genes among wild-type and transformed barley plants. Barley plants overexpressing HvIcy6 cystatin gene remained less susceptible to T. urticae attack when compared to wild-type plants, with a significant lesser foliar damaged area and a lower presence of the mite. Transcriptomic analysis revealed a certain reprogramming of cellular metabolism and a lower expression of several genes related to photosynthetic activity. Therefore, although caution should be taken to discard potential deleterious pleiotropic effects, cystatins may be used as transgenes with impact on agricultural crops by conferring enhanced levels of resistance to phytophagous pests.

  6. Distributed Multi-Cell Resource Allocation with Price Based ICI Coordination in Downlink OFDMA Networks

    Science.gov (United States)

    Lv, Gangming; Zhu, Shihua; Hui, Hui

    Multi-cell resource allocation under minimum rate request for each user in OFDMA networks is addressed in this paper. Based on Lagrange dual decomposition theory, the joint multi-cell resource allocation problem is decomposed and modeled as a limited-cooperative game, and a distributed multi-cell resource allocation algorithm is thus proposed. Analysis and simulation results show that, compared with non-cooperative iterative water-filling algorithm, the proposed algorithm can remarkably reduce the ICI level and improve overall system performances.

  7. The sulfur dilemma: Are there biosignatures on Europa's icy and patchy surface?

    International Nuclear Information System (INIS)

    Chela-Flores, J.

    2006-12-01

    We discuss whether sulphur traces on Jupiter's moon Europa could be of biogenic origin. The compounds detected by the Galileo mission have been conjectured to be endogenic, most likely of cryovolcanic origin, due to their non-uniform distribution in patches. The Galileo space probe first detected the sulphur compounds, as well as revealing that this moon almost certainly has a volcanically heated and potentially habitable ocean hiding beneath a surface layer of ice. In planning future exploration of Europa there are options for sorting out the source of the surficial sulphur. For instance, one possibility is searching for the sulphur source in the context of the study of the Europa Microprobe In Situ Explorer (EMPIE), which has been framed within the Jovian Minisat Explorer Technology Reference Study (ESA). It is conceivable that sulphur may have come from the nearby moon Io, where sulphur and other volcanic elements are abundant. Secondly, volcanic eruptions in Europa's seafloor may have brought sulphur to the surface. Can waste products rising from bacterial colonies beneath the icy surface be a third alternative significant factor in the sulphur patches on the Europan surface? Provided that microorganisms on Europa have the same biochemical pathways as those on Earth, over geologic time it is possible that autochthonous microbes can add substantially to the sulphur deposits on the surface of Europa. We discuss possible interpretations of the non-water-ice elements (especially the sulphur compound mercaptan) in the context of the studies for future missions. To achieve reliable biosignatures it seems essential to go back to Europa. Our work highlights the type of biogenic signatures that can be searched for when probing Europa's icy and patchy surface. (author)

  8. Palbociclib for Advanced Breast Cancer

    Science.gov (United States)

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  9. Thermodynamic Equations of State for Aqueous Solutions Applied to Deep Icy Satellite and Exoplanet Oceans

    Science.gov (United States)

    Vance, S.; Brown, J. M.; Bollengier, O.; Journaux, B.; Sotin, C.; Choukroun, M.; Barnes, R.

    2014-12-01

    Supporting life in icy world or exoplanet oceans may require global seafloor chemical reactions between water and rock. Such interactions have been regarded as limited in larger icy worlds such as Ganymede and Titan, where ocean depths approach 800 km and GPa pressures (>10katm). If the oceans are composed of pure water, such conditions are consistent with the presence of dense ice phases V and VI that cover the rocky seafloor. Exoplanets with oceans can obtain pressures sufficient to generate ices VII and VIII. We have previously demonstrated temperature gradients in such oceans on the order of 20 K or more, resulting from fluid compressibility in a deep adiabatic ocean based on our experimental work. Accounting for increases in density for highly saline oceans leads to the possibility of oceans perched under and between high pressure ices. Ammonia has the opposite effect, instead decreasing ocean density, as reported by others and confirmed by our laboratory measurements in the ammonia water system. Here we report on the completed equation of state for aqueous ammonia derived from our prior measurements and optimized global b-spline fitting methods We use recent diamond anvil cell measurements for water and ammonia to extend the equation of state to 400°C and beyond 2 GPa, temperatures and pressures applicable to icy worlds and exoplanets. Densities show much less temperature dependence but comparabe high-pressure derivatives to previously published ammonia-water properties derived for application to Titan (Croft et al. 1988). Thermal expansion is in better agreement with the more self-consistent equation of state of Tillner-Roth and Friend (1998). We also describe development of a planetary NaCl equation of state using recent measurements of phase boundaries and sound speeds. We examine implications of realistic ocean-ice thermodynamics for Titan and exoplanet interiors using the methodology recently applied to Ganymede for oceans dominated by MgSO4. High

  10. Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease

    DEFF Research Database (Denmark)

    Bonde, J; Svendsen, T L; Lyngborg, K

    1987-01-01

    administration of four sequential doses (0.5, 0.5, 1.0 and 2.0 mg) of ICI 141,292 was examined. HR decreased 7% (P less than 0.05) following ICI 141,292 1 mg with no further decrease following the succeeding doses. Cardiac output decreased 5.2% (P less than 0.05) following a cumulative dose of 4 mg...... as atenolol) beta 1-adrenoceptor blocking agent possessing moderate intrinsic sympathomimetic activity....

  11. When should video be added to conventional urodynamics in adults and is it justified by the evidence? ICI-RS 2014

    NARCIS (Netherlands)

    Anding, Ralf; Rosier, Peter; Smith, Phillip; Gammie, Andrew; Giarenis, Ilias; Rantell, Angela; Thiruchelvam, Nikesh; Arlandis, Salvador; Cardozo, Linda

    AIMS: To debate and evaluate the evidence base regarding the added value of video to urodynamics in adults and to define research questions. METHODS: In the ICI-RS Meeting 2014 a Think Tank analyzed the current guidelines recommending video urodynamics (VUD) and performed a literature search to

  12. Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.

    Science.gov (United States)

    Ribas, Ricardo; Pancholi, Sunil; Rani, Aradhana; Schuster, Eugene; Guest, Stephanie K; Nikitorowicz-Buniak, Joanna; Simigdala, Nikiana; Thornhill, Allan; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dowsett, Mitch; Johnston, Stephen R; Martin, Lesley-Ann

    2018-06-08

    Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER + ) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. A panel of ER + BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1 wt or ESR1 Y537S , modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER

  13. Local delivery of hormonal therapy with silastic tubing for prevention and treatment of breast cancer.

    Science.gov (United States)

    Park, Jeenah; Thomas, Scott; Zhong, Allison Y; Wolfe, Alan R; Krings, Gregor; Terranova-Barberio, Manuela; Pawlowska, Nela; Benet, Leslie Z; Munster, Pamela N

    2018-01-08

    Broad use of germline testing has identified an increasing number of women at risk for breast cancer with a need for effective chemoprevention. We report a novel method to selectively deliver various anti-estrogens at high drug levels to the breast tissue by implanting a device comprised of silastic tubing. Optimized tubing properties allow elution of otherwise poorly bioavailable anti-estrogens, such as fulvestrant, into mammary tissue in vitro and in vivo with levels sufficient to inhibit estrogen receptor activation and tumor cell proliferation. Implantable silastic tubing delivers fulvestrant selectively to mouse mammary fat tissue for one year with anti-tumor effects similar to those achieved with systemic fulvestrant exposure. Furthermore, local delivery of fulvestrant significantly decreases cell proliferation, as assessed by Ki67 expression, most effectively in tumor sections adjacent to tubing. This approach may thereby introduce a potential paradigm shift and offer a promising alternative to systemic therapy for prevention and early interception of breast cancer.

  14. Coagulation calculations of icy planet formation around 0.1-0.5 M {sub ☉} stars: Super-Earths from large planetesimals

    Energy Technology Data Exchange (ETDEWEB)

    Kenyon, Scott J. [Smithsonian Astrophysical Observatory, 60 Garden Street, Cambridge, MA 02138 (United States); Bromley, Benjamin C., E-mail: skenyon@cfa.harvard.edu, E-mail: bromley@physics.utah.edu [Department of Physics, University of Utah, 201 JFB, Salt Lake City, UT 84112 (United States)

    2014-01-01

    We investigate formation mechanisms for icy super-Earth-mass planets orbiting at 2-20 AU around 0.1-0.5 M {sub ☉} stars. A large ensemble of coagulation calculations demonstrates a new formation channel: disks composed of large planetesimals with radii of 30-300 km form super-Earths on timescales of ∼1 Gyr. In other gas-poor disks, a collisional cascade grinds planetesimals to dust before the largest planets reach super-Earth masses. Once icy Earth-mass planets form, they migrate through the leftover swarm of planetesimals at rates of 0.01-1 AU Myr{sup –1}. On timescales of 10 Myr to 1 Gyr, many of these planets migrate through the disk of leftover planetesimals from semimajor axes of 5-10 AU to 1-2 AU. A few percent of super-Earths might migrate to semimajor axes of 0.1-0.2 AU. When the disk has an initial mass comparable with the minimum-mass solar nebula, scaled to the mass of the central star, the predicted frequency of super-Earths matches the observed frequency.

  15. Sample Processor for Life on Icy Worlds (SPLIce): Design and Test Results

    Science.gov (United States)

    Chinn, Tori N.; Lee, Anthony K.; Boone, Travis D.; Tan, Ming X.; Chin, Matthew M.; McCutcheon, Griffin C.; Horne, Mera F.; Padgen, Michael R.; Blaich, Justin T.; Forgione, Joshua B.; hide

    2017-01-01

    We report the design, development, and testing of the Sample Processor for Life on Icy Worlds (SPLIce) system, a microfluidic sample processor to enable autonomous detection of signatures of life and measurements of habitability parameters in Ocean Worlds. This monolithic fluid processing-and-handling system (Figure 1; mass 0.5 kg) retrieves a 50-L-volume sample and prepares it to supply a suite of detection instruments, each with unique preparation needs. SPLIce has potential applications in orbiter missions that sample ocean plumes, such as found in Saturns icy moon Enceladus, or landed missions on the surface of icy satellites, such as Jupiters moon Europa. Answering the question Are we alone in the universe? is captivating and exceptionally challenging. Even general criteria that define life very broadly include a significant role for water [1,2]. Searches for extinct or extant life therefore prioritize locations of abundant water whether in ancient (Mars), or present (Europa and Enceladus) times. Only two previous planetary missions had onboard fluid processing: the Viking Biology Experiments [3] and Phoenixs Wet Chemistry Laboratory (WCL) [4]. SPLIce differs crucially from those systems, including its capability to process and distribute L-volume samples and the integration autonomous control of a wide range of fluidic functions, including: 1) retrieval of fluid samples from an evacuated sample chamber; 2) onboard multi-year storage of dehydrated reagents; 3) integrated pressure, pH, and conductivity measurement; 4) filtration and retention of insoluble particles for microscopy; 5) dilution or vacuum-driven concentration of samples to accommodate instrument working ranges; 6) removal of gas bubbles from sample aliquots; 7) unidirectional flow (check valves); 8) active flow-path selection (solenoid-actuated valves); 9) metered pumping in 100 nL volume increments. The SPLIce manifold, made of three thermally fused layers of precision-machined cyclo

  16. Troughs in Ice Sheets and Other Icy Deposits on Mars: Analysis of Their Radiative Balance

    Science.gov (United States)

    Fountain, A.; Kargel, J.; Lewis, K.; MacAyeal, D.; Pfeffer, T.; Zwally, H. J.

    2000-01-01

    It has long been known that groove-like structures in glaciers and ice sheets can trap more incoming solar radiation than is the case for a 'normal' flat, smooth surface. In this presentation, we shall describe the radiative regimes of typical scarps and troughs on icy surfaces of Mars, and suggest how these features originate and evolve through time. The basis of our analysis is the radiation balance model presented by Pfeffer and Bretherton. Their model considers the visible band radiation regime of a V-shaped groove on a terrestrial ice surface, and shows that absorbed energy can be enhanced by up to 50 percent for grooves with small opening angles and with typical polar values of the solar zenith angle. Our work extends this model by considering: (a) departures from V-shaped geometry, (b) both englacial and surficial dust and debris, and (c) the infrared spectrum. We apply the extended model to various features on the Martian surface, including the spiral-like scarps on the Northern and Southern ice sheets, the large-scale chasms (e.g., Chasm Borealis), and groove-like lineations on valley floors thought to be filled with mixtures of dust and icy substances. In conjunction with study of valley-closure experiments, we suggest that spiral-like scarps and chasms are stable features of the Martian climate regime. We also suggest that further study of scarps and chasms may shed light on the composition (i.e., relative proportions of water ice, carbon-dioxide ice and dust) of the Martian ice sheets and valley fills.

  17. The compression behavior of blödite at low and high temperature up to ~10GPa: Implications for the stability of hydrous sulfates on icy planetary bodies

    Energy Technology Data Exchange (ETDEWEB)

    Comodi, Paola; Stagno, Vincenzo; Zucchini, Azzurra; Fei, Yingwei; Prakapenka, Vitali

    2017-03-01

    Recent satellite inferences of hydrous sulfates as recurrent minerals on the surface of icy planetary bodies link with the potential mineral composition of their interior. Blödite, a mixed Mg-Na sulfate, is here taken as representative mineral of icy satellites surface to investigate its crystal structure and stability at conditions of the interior of icy bodies. To this aim we performed in situ synchrotron angle-dispersive X-ray powder diffraction experiments on natural blödite at pressures up to ~10.4 GPa and temperatures from ~118.8 K to ~490.0 K using diamond anvil cell technique to investigate the compression behavior and establish a low-to-high temperature equation of state that can be used as reference when modeling the interior of sulfate-rich icy satellites such as Ganymede. The experimentally determined volume expansivity, α, varies from 7.6 (7) 10-5 K-1 at 0.0001 GPa (from 118.8 to 413.15 K) to 2.6 (3) 10-5 K-1 at 10 GPa (from 313.0 to 453.0 K) with a δα/δP coefficient = -5.6(9)10-6 GPa-1 K-1. The bulk modulus calculated from the least squares fitting of P-V data on the isotherm at 413 K using a second-order Birch - Murnaghan equation of state is 38(5) GPa, which gives the value of δK/δT equal to 0.01(5) GPa K-1. The thermo-baric behavior of blödite appears strongly anisotropic with c lattice parameter being more deformed with respect to a and b. Thermogravimetric analyses performed at ambient pressure showed three endotherms at 413 K, 533 K and 973 K with weight losses of approximately 11%, 11% and 43% caused by partial dehydration, full dehydration and sulfate decomposition respectively. Interestingly, no clear evidence of dehydration was observed up to ~453 K and ~10.4 GPa, suggesting that pressure acts to stabilize the crystalline structure of blödite. The data collected allow to write the following equation of state, V(P, T) = V

  18. Subsurface Ocean Tides in Enceladus and Other Icy Moons

    Science.gov (United States)

    Beuthe, M.

    2016-12-01

    Could tidal dissipation within Enceladus' subsurface ocean account for the observed heat flow? Earthlike models of dynamical tides give no definitive answer because they neglect the influence of the crust. I propose here the first model of dissipative tides in a subsurface ocean, by combining the Laplace Tidal Equations with the membrane approach. For the first time, it is possible to compute tidal dissipation rates within the crust, ocean, and mantle in one go. I show that oceanic dissipation is strongly reduced by the crustal constraint, and thus contributes little to Enceladus' present heat budget. Tidal resonances could have played a role in a forming or freezing ocean less than 100 meters deep. The model is general: it applies to all icy satellites with a thin crust and a shallow or stratified ocean. Scaling rules relate the resonances and dissipation rate of a subsurface ocean to the ones of a surface ocean. If the ocean has low viscosity, the westward obliquity tide does not move the crust. Therefore, crustal dissipation due to dynamical obliquity tides can differ from the static prediction by up to a factor of two.

  19. Two-phase convection in the high-pressure ice layer of the large icy moons: geodynamical implications

    Science.gov (United States)

    Kalousova, K.; Sotin, C.; Tobie, G.; Choblet, G.; Grasset, O.

    2015-12-01

    The H2O layers of large icy satellites such as Ganymede, Callisto, or Titan probably include a liquid water ocean sandwiched between the deep high-pressure ice layer and the outer ice I shell [1]. It has been recently suggested that the high-pressure ice layer could be decoupled from the silicate core by a salty liquid water layer [2]. However, it is not clear whether accumulation of liquids at the bottom of the high-pressure layer is possible due to positive buoyancy of water with respect to high-pressure ice. Numerical simulation of this two-phase (i.e. ice and water) problem is challenging, which explains why very few studies have self-consistently handled the presence and transport of liquids within the solid ice [e.g. 3]. While using a simplified description of water production and transport, it was recently showed in [4] that (i) a significant fraction of the high-pressure layer reaches the melting point and (ii) the melt generation and its extraction to the overlying ocean significantly influence the global thermal evolution and interior structure of the large icy moons.Here, we treat the high-pressure ice layer as a compressible mixture of solid ice and liquid water [5]. Several aspects are investigated: (i) the effect of the water formation on the vigor of solid-state convection and its influence on the amount of heat that is transferred from the silicate mantle to the ocean; (ii) the fate of liquids within the upper thermal boundary layer - whether they freeze or reach the ocean; and (iii) the effect of salts and volatile compounds (potentially released from the rocky core) on the melting/freezing processes. Investigation of these aspects will allow us to address the thermo-chemical evolution of the internal ocean which is crucial to evaluate the astrobiological potential of large icy moons. This work has been performed at the Jet Propulsion Laboratory, California Institute of Technology, under contract to NASA. [1] Hussmann et al. (2007), Treatise of

  20. POST-MAIN SEQUENCE EVOLUTION OF ICY MINOR PLANETS: IMPLICATIONS FOR WATER RETENTION AND WHITE DWARF POLLUTION

    Energy Technology Data Exchange (ETDEWEB)

    Malamud, Uri; Perets, Hagai B., E-mail: uri.mal@tx.technion.ac.il, E-mail: hperets@physics.technion.ac.il [Department of Physics, Technion (Israel)

    2016-12-01

    Most observations of polluted white dwarf atmospheres are consistent with accretion of water-depleted planetary material. Among tens of known cases, merely two involve accretion of objects that contain a considerable mass fraction of water. The purpose of this study is to investigate the relative scarcity of these detections. Based on a new and highly detailed model, we evaluate the retention of water inside icy minor planets during the high-luminosity stellar evolution that follows the main sequence. Our model fully considers the thermal, physical, and chemical evolution of icy bodies, following their internal differentiation as well as water depletion, from the moment of their birth and through all stellar evolution phases preceding the formation of the white dwarf. We also account for different initial compositions and formation times. Our results differ from previous studies, which have either underestimated or overestimated water retention. We show that water can survive in a variety of circumstances and in great quantities, and therefore other possibilities are discussed in order to explain the infrequency of water detection. We predict that the sequence of accretion is such that water accretes earlier, and more rapidly, than the rest of the silicate disk, considerably reducing the chance of its detection in H-dominated atmospheres. In He-dominated atmospheres, the scarcity of water detections could be observationally biased. It implies that the accreted material is typically intrinsically dry, which may be the result of the inside-out depopulation sequence of minor planets.

  1. POST-MAIN SEQUENCE EVOLUTION OF ICY MINOR PLANETS: IMPLICATIONS FOR WATER RETENTION AND WHITE DWARF POLLUTION

    International Nuclear Information System (INIS)

    Malamud, Uri; Perets, Hagai B.

    2016-01-01

    Most observations of polluted white dwarf atmospheres are consistent with accretion of water-depleted planetary material. Among tens of known cases, merely two involve accretion of objects that contain a considerable mass fraction of water. The purpose of this study is to investigate the relative scarcity of these detections. Based on a new and highly detailed model, we evaluate the retention of water inside icy minor planets during the high-luminosity stellar evolution that follows the main sequence. Our model fully considers the thermal, physical, and chemical evolution of icy bodies, following their internal differentiation as well as water depletion, from the moment of their birth and through all stellar evolution phases preceding the formation of the white dwarf. We also account for different initial compositions and formation times. Our results differ from previous studies, which have either underestimated or overestimated water retention. We show that water can survive in a variety of circumstances and in great quantities, and therefore other possibilities are discussed in order to explain the infrequency of water detection. We predict that the sequence of accretion is such that water accretes earlier, and more rapidly, than the rest of the silicate disk, considerably reducing the chance of its detection in H-dominated atmospheres. In He-dominated atmospheres, the scarcity of water detections could be observationally biased. It implies that the accreted material is typically intrinsically dry, which may be the result of the inside-out depopulation sequence of minor planets.

  2. Fulvestrant Injection

    Science.gov (United States)

    ... experienced menopause (change of life; end of monthly menstrual periods) and have not previously been treated with ... buttock).Ask your doctor or pharmacist for a copy of the manufacturer's information for the patient.

  3. Physicochemical Requirements Inferred for Chemical Self-Organization Hardly Support an Emergence of Life in the Deep Oceans of Icy Moons.

    Science.gov (United States)

    Pascal, Robert

    2016-05-01

    An approach to the origin of life, focused on the property of entities capable of reproducing themselves far from equilibrium, has been developed recently. Independently, the possibility of the emergence of life in the hydrothermal systems possibly present in the deep oceans below the frozen crust of some of the moons of Jupiter and Saturn has been raised. The present report is aimed at investigating the mutual compatibility of these alternative views. In this approach, the habitability concept deduced from the limits of life on Earth is considered to be inappropriate with regard to emerging life due to the requirement for an energy source of sufficient potential (equivalent to the potential of visible light). For these icy moons, no driving force would have been present to assist the process of emergence, which would then have had to rely exclusively on highly improbable events, thereby making the presence of life unlikely on these Solar System bodies, that is, unless additional processes are introduced for feeding chemical systems undergoing a transition toward life and the early living organisms. Icy moon-Bioenergetics-Chemical evolution-Habitability-Origin of life. Astrobiology 16, 328-334.

  4. IR reflectance spectroscopy of carbon dioxide clathrate hydrates. Implications for Saturn's icy moons.

    Science.gov (United States)

    Oancea, A.; Grasset, O.; Le Menn, E.; Bezacier, L.; Bollengier, O.; Le Mouélic, S.; Tobie, G.

    2012-04-01

    A CO2 spectral band was discovered by VIMS on the Saturn's satellites Dione, Hyperion, Iapetus and Phoebe [1]. The band position on the three first satellites corresponds to CO2 trapped in a complex material, but no indication exists whether this latter is water ice or some mineral or complex organic compound [1]. On Phoebe, the CO2 spectral band is consistent with solid CO2 or CO2 molecules trapped in the small cages of a clathrate hydrate structure [2]. It is thought that clathrate hydrates could play a significant role in the chemistry of the solar nebula [3] and in the physical evolution of astrophysical objects [4]. But so far, no clathrate hydrate structure has been observed in astrophysical environments. Moreover, identification of molecules trapped in a clathrate hydrate structure is extremely difficult because of the strong IR vibration modes of the water ice matrix. In this work, experimental IR reflectance spectra for CO2 clathrate hydrates are studied on grains and films. Clathrates are synthesized in a high pressure autoclave at low temperatures. IR spectral analysis is made with a low pressure and low temperature cryostat. These experimental conditions - 80 spectrum will be presented. A comparison between the absorption bands of CO2 clathrate hydrates obtained in our lab and CO2 absorption bands as detected by VIMS on the icy satellites of Saturn will be shown. This experimental work confirms that VIMS data are not consistent with the presence of structure I CO2 clathrate hydrates on the surface of the icy moons. Possibility of having metastable structure II still remains unsolved and will be discussed. [1] Dalton et al., Space Sci. Rev. 2010, 153 : 113-154. [2] Cruikshank D.P. et al, Icarus, 2010, 206: 561-572. [3] Mousis O. et al , Ap. J. 2009, 691: 1780-1786. [4] Choukroun M. et al, in Solar System Ices, edited by Castillo-Rogez, J. et al., 2011.

  5. Detection of Deuterium in Icy Surfaces and the D/H Ratio of Icy Objects

    Science.gov (United States)

    Clark, Roger Nelson; Brown, Robert H.; Swayze, Gregg A.; Cruikshank, Dale P.

    2017-10-01

    Water ice in crystalline or amorphous form is orientationally disordered, which results in very broad absorptions. Deuterium in trace amounts goes into an ordered position, so is not broadened like H2O absorptions. The D-O stretch is located at 4.13 microns with a width of 0.027 micron. Laboratory spectral measurements on natural H2O and deuterium doped ice show the absorption is slightly asymmetric and in reflectance the band shifts from 4.132 to 4.137 microns as abundance decreases. We derive a preliminary absorption coefficient of ~ 80,000 cm^-1 for the D-O stretch compared to about 560 cm^-1 in H2O ice at 4.13 microns, enabling the detection of deuterium at levels less than Vienna Standard Mean Ocean Water (VSMOW), depending on S/N. How accurate the D/H ratios can be derived will require additional lab work and radiative transfer modeling to simultaneously derive the grain size distribution, the abundance of any contaminants, and deuterium abundance. To first order, the grain size distribution can be compensated by computing the D-O stretch band depth to 2-micron H2O ice band depth ratio, which we call Dratio. Colorado fresh water (~80% of VSMOW) has a Dratio of 0.036, at a D/H = 0.0005, the Dratio = 0.15, and at a D/H = 0.0025, the Dratio = 0.42. The VSMOW Dratio is ~ 0.045.We have used VIMS data from the Cassini spacecraft to compute large spectral averages to detect the deuterium in the rings and on the icy satellite surfaces. A B-ring, 21,882 pixel average, at 640 ms/pixel, or 3.89 hours of integration time, shows a 3.5% O-D stretch band depth and a Dratio = 0.045, indicating deuterium abundance equal to VSMOW. Rhea, using 1.89 hours of integration time shows Dratio = 0.052, or slightly higher than VSMOW. Phoebe has an unusually deep O-D stretch band of 1.85% considering the high abundance of dark material suppressing the ice absorptions. We measure a Dratio = 0.11, an enhancement of ~2.4 over VSMOW, but detailed radiative transfer modeling is needed to

  6. Lower urinary tract symptoms and metabolic disorders: ICI-RS 2014.

    Science.gov (United States)

    Denys, Marie-Astrid; Anding, Ralf; Tubaro, Andrea; Abrams, Paul; Everaert, Karel

    2016-02-01

    To investigate the link between lower urinary tract symptoms (LUTS) and metabolic disorders. This report results from presentations and subsequent discussions about LUTS and metabolic disorders at the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, 2014. There are common pathophysiological determinants for the onset of LUTS and the metabolic syndrome (MetS). Both conditions are multifactorial, related to disorders in circadian rhythms and share common risk factors. As in men with erectile dysfunction, these potentially modifiable lifestyle factors may be novel targets to prevent and treat LUTS. The link between LUTS and metabolic disorders is discussed by using sleep, urine production and bladder function as underlying mechanisms that need to be further explored during future research. Recent findings indicate a bidirectional relationship between LUTS and the MetS. Future research has to explore underlying mechanisms to explain this relationship, in order to develop new preventive and therapeutic recommendations, such as weight loss and increasing physical activity. The second stage is to determine the effect of these new treatment approaches on the severity of LUTS and each of the components of the MetS. © 2016 Wiley Periodicals, Inc.

  7. A new marine interstitial psammogammarus (Crustacea, Amphipoda, Melitidae) from Gura Ici Island, off western Halmahera (North Moluccas, Indonesia), and an overview of the genus

    NARCIS (Netherlands)

    Vonk, R.; Hoeksema, B.W.; Jaume, D.

    2011-01-01

    Psammogammarus wallacei sp. n. is described from the shallow marine interstitial of a sand and coral rubble beach on the Gura Ici islands (North Moluccas; Indonesia). This is the first record of this circum-tropical genus from SE Asia, with the geographically closest relative inhabiting the Ryukyu

  8. Purification of a Novel Bacteriocin-Like Inhibitory Substance Produced by Enterococcus faecium ICIS 8 and Characterization of Its Mode of Action.

    Science.gov (United States)

    Vasilchenko, Alexey S; Rogozhin, Eugene A; Valyshev, Alexander V

    2017-06-01

    The aim of this work was to purify and characterize a bacteriocin-like antimicrobial substance produced by an antagonistic active strain of Enterococcus faecium. A novel bacteriocin-like inhibitory substance (BLIS) produced by the E. faecium ICIS 8 strain was purified and characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and N-terminal amino acid sequencing revealed the following partial sequence: NH 2 -APKEKCFPKYCV. The proteinaceous nature of purified BLIS was assessed by treatment with proteolytic enzyme. Studies of the action of BLIS using bacteriological and bioluminescence assays revealed a dose-dependent inhibition of Listeria monocytogenes 88BK and Escherichia coli K12 TG1 lac::lux viability. The interaction of the BLIS with the bacterial surface led to the compensation of a negative charge value, as shown by zeta-potential measurements. Assessments of membrane integrity using fluorescent probes and atomic force microscopy revealed the permeabilization of the cellular barrier structures in both L. monocytogenes and E. coli. The novel BLIS from E. faecium ICIS 8 was characterized by a unique primary peptide sequence and exerted bactericidal activity against L. monocytogenes and E. coli by disrupting membrane integrity.

  9. Salt partitioning between water and high-pressure ices. Implication for the dynamics and habitability of icy moons and water-rich planetary bodies

    Science.gov (United States)

    Journaux, Baptiste; Daniel, Isabelle; Petitgirard, Sylvain; Cardon, Hervé; Perrillat, Jean-Philippe; Caracas, Razvan; Mezouar, Mohamed

    2017-04-01

    Water-rich planetary bodies including large icy moons and ocean exoplanets may host a deep liquid water ocean underlying a high-pressure icy mantle. The latter is often considered as a limitation to the habitability of the uppermost ocean because it would limit the availability of nutrients resulting from the hydrothermal alteration of the silicate mantle located beneath the deep ice layer. To assess the effects of salts on the physical properties of high-pressure ices and therefore the possible chemical exchanges and habitability inside H2O-rich planetary bodies, we measured partitioning coefficients and densities in the H2O-RbI system up to 450 K and 4 GPa; RbI standing as an experimentally amenable analog of NaCl in the H2O-salt solutions. We measured the partitioning coefficient of RbI between the aqueous fluid and ices VI and VII, using in-situ Synchrotron X-ray Fluorescence (XRF). With in-situ X-ray diffraction, we measured the unit-cell parameters and the densities of the high-pressure ice phases in equilibrium with the aqueous fluid, at pressures and temperatures relevant to the interior of planetary bodies. We conclude that RbI is strongly incompatible towards ice VI with a partitioning coefficient Kd(VI-L) = 5.0 (± 2.1) ṡ10-3 and moderately incompatible towards ice VII, Kd(VII-L) = 0.12 (± 0.05). RbI significantly increases the unit-cell volume of ice VI and VII by ca. 1%. This implies that RbI-poor ice VI is buoyant compared to H2O ice VI while RbI-enriched ice VII is denser than H2O ice VII. These new experimental results might profoundly impact the internal dynamics of water-rich planetary bodies. For instance, an icy mantle at moderate conditions of pressure and temperature will consist of buoyant ice VI with low concentration of salt, and would likely induce an upwelling current of solutes towards the above liquid ocean. In contrast, a deep and/or thick icy mantle of ice VII will be enriched in salt and hence would form a stable chemical boundary

  10. El receptor de estrógenos alfa como mediador del efecto proliferativo de progestágenos en cáncer de mama

    Directory of Open Access Journals (Sweden)

    Sebastián Giulianelli

    2012-08-01

    Full Text Available En carcinomas mamarios murinos (C4-HD y en células de cáncer de mama humano (T47D observamos que el progestágeno sintético, acetato de medroxiprogesterona (MPA, induce la activación del receptor de estrógenos alfa (REa y su asociación nuclear con el receptor de progesterona (RP. En este trabajo postulamos que dicha interacción a nivel genómico sería fundamental para desarrollar respuestas proliferativas mediadas por progestágenos. Demostramos que el antiestrógeno fulvestrant (FUL, ICI182.780 indujo la regresión completa de tumores C4-HD creciendo con MPA. El progestágeno indujo la expresión temprana de CCND1 y MYC en células T47D y este efecto fue revertido al bloquear el REa. En células tratadas con MPA utilizamos ensayos de inmunoprecipitación de la cromatina (ChIP y corroboramos la colocalización nuclear de RP/REa en los mismos sitios de los promotores de CCND1 y MYC. El ICI no afectó la unión de RP a ambas secuencias regulatorias, pero sí inhibió la unión del REa. Confirmamos la interacción nuclear entre REa y RP en muestras de cáncer de mama humano. Los resultados demuestran que la presencia del REa, interactuando con el RP, en promotores de CCND1 y MYC es fundamental para la transcripción génica y la proliferación celular inducida por el progestágeno.

  11. The StreamCat Dataset: Accumulated Attributes for NHDPlusV2 Catchments (Version 2.1) for the Conterminous United States: Index of Watershed Integrity / Index of Catchment Integrity (IWI/ICI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset represents the Index of Watershed Integrity / Index of Catchment Integrity (IWI/ICI) within individual local NHDPlusV2 catchments and upstream,...

  12. Fluffy dust forms icy planetesimals by static compression

    Science.gov (United States)

    Kataoka, Akimasa; Tanaka, Hidekazu; Okuzumi, Satoshi; Wada, Koji

    2013-09-01

    Context. Several barriers have been proposed in planetesimal formation theory: bouncing, fragmentation, and radial drift problems. Understanding the structure evolution of dust aggregates is a key in planetesimal formation. Dust grains become fluffy by coagulation in protoplanetary disks. However, once they are fluffy, they are not sufficiently compressed by collisional compression to form compact planetesimals. Aims: We aim to reveal the pathway of dust structure evolution from dust grains to compact planetesimals. Methods: Using the compressive strength formula, we analytically investigate how fluffy dust aggregates are compressed by static compression due to ram pressure of the disk gas and self-gravity of the aggregates in protoplanetary disks. Results: We reveal the pathway of the porosity evolution from dust grains via fluffy aggregates to form planetesimals, circumventing the barriers in planetesimal formation. The aggregates are compressed by the disk gas to a density of 10-3 g/cm3 in coagulation, which is more compact than is the case with collisional compression. Then, they are compressed more by self-gravity to 10-1 g/cm3 when the radius is 10 km. Although the gas compression decelerates the growth, the aggregates grow rapidly enough to avoid the radial drift barrier when the orbital radius is ≲6 AU in a typical disk. Conclusions: We propose a fluffy dust growth scenario from grains to planetesimals. It enables icy planetesimal formation in a wide range beyond the snowline in protoplanetary disks. This result proposes a concrete initial condition of planetesimals for the later stages of the planet formation.

  13. -AGAn /-GAn AND -ICI SUFFIXES IN TURKISH AND THEIR USAGE IN SÛDÎ’S ANNOTATION TÜRKÇEDE -AGAn /-GAn VE -ICI EKLERİ VE SÛDÎ ŞERHİNDEKİ KULLANIMLARI

    Directory of Open Access Journals (Sweden)

    Mevlüt ERDEM

    2010-07-01

    Full Text Available The suffixes of -AGAn / -GAn used unfrequently in Modern Turkish exhibit some important features in the development of Turkish. In Karakhanid Turkic, the habitual meaning of the verb is formed with -GAn participle and in some cases with -AGAn. This usage increases gradually in Old Anatolian Turkish and Sudi’s annotation. Sudi utilizes the derivation of -AGAn/-GAn used in his time productively in word formation in order to translate the exact meaning of the Persian words into Turkish, which were called sıfat-ı müşebbehe (an adjective formed from a verb. In these derivations, although the habitual meaning of the verbs is stressed, some of them function as participles. On the other hand, Sudi uses Turkish -IcI suffix in order to substitute Persian agent nouns (ism-i fail. The suffix functions as non-finite verbs in some constructions like -AGAn /-GAn suffixes. Türkiye Türkçesinde işlek olmayan -AGAn/-GAn eki Türkçenin gelişiminde önemli özellikler sergiler. Karahanlı Türkçesinde fiildeki süreklilik anlamı -GAn sıfat-fiiliyle birlikte az da olsa -AGAn ekiyle de sağlanır. Bu kullanım EAT eserlerinde ve Sûdî şerhinde artarak devam eder. Sûdî, döneminde hâlâ işlek olarak kullanıldığını anladığımız -AGAn / -GAn’lı türetimleri Farsça sıfat-ı müşebbehe olan kelimelerin Türkçedeki anlamlarını tam olarak vermek için kullanır. Bu türetimlerde fiilin sürekli yapıldığı vurgulansa da bunların bir kısmı sıfat-fiil işleyişindedir. Sûdî, şerhinde ism-i failleri karşılamak için ise -IcI ekinden yararlanır. Bu ek de -AGAn/-GAn ekleri gibi bazı kullanımlarda bitimsiz fiil işleyişindedir.

  14. When should video and EMG be added to urodynamics in children with lower urinary tract dysfunction and is this justified by the evidence? ICI-RS 2014

    NARCIS (Netherlands)

    Anding, Ralf; Smith, Phillip; de Jong, Tom; Constantinou, Christos; Cardozo, Linda; Rosier, Peter

    AIMS: An ICI-RS Think Tank in 2014 discussed and evaluated the evidence for adding video and EMG to urodynamics (UDS) in children and also highlighted evidence gaps, with the aim of recommending further clinical and research protocols. METHODS: A systematic analysis of the relevant literature for

  15. Gasoline from coal in the state of Illinois: feasibility study. Volume I. Design. [KBW gasification process, ICI low-pressure methanol process and Mobil M-gasoline process

    Energy Technology Data Exchange (ETDEWEB)

    1980-01-01

    Volume 1 describes the proposed plant: KBW gasification process, ICI low-pressure methanol process and Mobil M-gasoline process, and also with ancillary processes, such as oxygen plant, shift process, RECTISOL purification process, sulfur recovery equipment and pollution control equipment. Numerous engineering diagrams are included. (LTN)

  16. Aqueous geochemistry in icy world interiors: Equilibrium fluid, rock, and gas compositions, and fate of antifreezes and radionuclides

    Science.gov (United States)

    Neveu, Marc; Desch, Steven J.; Castillo-Rogez, Julie C.

    2017-09-01

    The geophysical evolution of many icy moons and dwarf planets seems to have provided opportunities for interaction between liquid water and rock (silicate and organic solids). Here, we explore two ways by which water-rock interaction can feed back on geophysical evolution: the production or consumption of antifreeze compounds, which affect the persistence and abundance of cold liquid; and the potential leaching into the fluid of lithophile radionuclides, affecting the distribution of a long-term heat source. We compile, validate, and use a numerical model, implemented with the PHREEQC code, of the interaction of chondritic rock with pure water and with C, N, S-bearing cometary fluid, thought to be the materials initially accreted by icy worlds, and describe the resulting equilibrium fluid and rock assemblages at temperatures, pressures, and water-to-rock ratios of 0-200 ° C, 1-1000 bar, and 0.1-10 by mass, respectively. Our findings suggest that water-rock interaction can strongly alter the nature and amount of antifreezes, resulting in solutions rich in reduced nitrogen and carbon, and sometimes dissolved H2, with additional sodium, calcium, chlorine, and/or oxidized carbon. Such fluids can remain partially liquid down to 176 K if NH3 is present. The prominence of Cl in solution seems to hinge on its primordial supply in ices, which is unconstrained by the meteoritical record. Equilibrium assemblages, rich in serpentine and saponite clays, retain thorium and uranium radionuclides unless U-Cl or U-HCO3 complexing, which was not modeled, significantly enhances U solubility. However, the radionuclide 40 K can be leached at high water:rock ratio and/or low temperature at which K is exchanged with ammonium in minerals. We recommend the inclusion of these effects in future models of the geophysical evolution of ocean-bearing icy worlds. Our simulation products match observations of chloride salts on Europa and Enceladus; CI chondrites mineralogies; the observation of

  17. Bi-directional Reflectance of Icy Surface Analogs: A Dual Approach

    Science.gov (United States)

    Quinones, Juan Manuel; Vides, Christina; Nelson, Robert M.; Boryta, Mark; Mannat, Ken s.

    2018-01-01

    Bi-directional reflectance measurements of analogs for planetary regolith have provided insight into the surface properties of planetary satellites and small bodies. Because Aluminum Oxide (Al2O3) and water ice share a similar hexagonal crystalline structure, the former has been used in laboratory experiments to simulate the regolith of both icy and dusty planetary bodies. By measuring various sizes of well sorted size fractions of Al2O3, the reflectance phase curve and porosity of a planetary regolith can be determined. We have designed an experiment to test the laboratory measurements produced by Nelson et al. (2000). Additionally, we made reflectance measurements for other alkali-halide compounds that could be used for applications beyond astronomy and planetary science.In order to provide an independent check on the Nelson et al. data, we designed an instrument with a different configuration. While both instruments take bidirectional reflectance measurements, our instrument, the Rigid Photometric Goniometer (RPG), is fixed at a phase angle of 5° and detects the scattered light with a photomultiplier tube (PMT). The PMT current is then measured with an electrometer. Following the example of Nelson et al., we measured the bidirectional reflectance of Al2O3 particulate size fractions between 0.1sizes from 20size that provided optimal, or maximum, reflectance for each compound. Our conclusions bring confirmation and clarity to photometric sciences.

  18. Breaking Ice 2: A rift system on the Ross Ice Shelf as an analog for tidal tectonics on icy moons

    Science.gov (United States)

    Brunt, K. M.; Hurford, T., Jr.; Schmerr, N. C.; Sauber, J. M.; MacAyeal, D. R.

    2016-12-01

    Ice shelves are the floating regions of the polar ice sheets. Outside of the influence of the narrow region of their grounding zone, they are fully hydrostatic and strongly influenced by the ocean tides. Recent observational and modeling studies have assessed the effect of tides on ice shelves, including: the tidal influence on the ice-shelf surface height, which changes by as much as 6 to 7 m on the southern extreme of the Ronne-Filchner Ice Shelf; the tidal modulation of the ice-shelf horizontal flow velocities, which changes the mean ice-flow rate by as much as two fold on the Ross Ice Shelf; and the tidal contribution to fracture and rift propagation, which eventually leads to iceberg calving. Here, we present the analysis of 16 days of continuous GPS data from a rift system near the front of the Ross Ice Shelf. While the GPS sites were installed for a different scientific investigation, and not optimized to assess tidal rifting mechanics, they provide a first-order sense of the tidal evolution of the rift system. These analyses can be used as a terrestrial analog for tidal activity on icy satellites, such as Europa and Enceladus, moons of Jupiter and Saturn, respectively. Using remote sensing and modeling of the Ross Ice Shelf rift system, we can investigate the geological processes observed on icy satellites and advance modeling efforts of their tidal-tectonic evolution.

  19. Exploration of Icy Moons in the Outer Solar System: Updated Planetary Protection Requirements for Missions to Enceladus and Europa

    Science.gov (United States)

    Rummel, J. D.; Race, M. S.

    2016-12-01

    Enceladus and Europa are bodies with icy/watery environments and potential habitable conditions for life, making both of great interest in astrobiological studies of chemical evolution and /or origin of life. They are also of significant planetary protection concern for spacecraft missions because of the potential for harmful contamination during exploration. At a 2015 COSPAR colloquium in Bern Switzerland, international scientists identified an urgent need to establish planetary protection requirements for missions proposing to return samples to Earth from Saturn's moon Enceladus. Deliberations at the meeting resulted in recommended policy updates for both forward and back contamination requirements for missions to Europa and Enceladus, including missions sampling plumes originating from those bodies. These recently recommended COSPAR policy revisions and biological contamination requirements will be applied to future missions to Europa and Encealadus, particularly noticeable in those with plans for in situ life detection and sample return capabilities. Included in the COSPAR policy are requirementsto `break the chain of contact' with Europa or Enceladus, to keep pristine returned materials contained, and to complete required biohazard analyses, testing and/or sterilization upon return to Earth. Subsequent to the Bern meeting, additional discussions of Planetary Protection of Outer Solar System bodies (PPOSS) are underway in a 3-year study coordinated by the European Science Foundation and involving multiple international partners, including Japan, China and Russia, along with a US observer. This presentation will provide science and policy updates for those whose research or activities will involve icy moon missions and exploration.

  20. Water Ice Radiolytic O2, H2, and H2O2 Yields for Any Projectile Species, Energy, or Temperature: A Model for Icy Astrophysical Bodies

    Science.gov (United States)

    Teolis, B. D.; Plainaki, C.; Cassidy, T. A.; Raut, U.

    2017-10-01

    O2, H2, and H2O2 radiolysis from water ice is pervasive on icy astrophysical bodies, but the lack of a self-consistent, quantitative model of the yields of these water products versus irradiation projectile species and energy has been an obstacle to estimating the radiolytic oxidant sources to the surfaces and exospheres of these objects. A major challenge is the wide variation of O2 radiolysis yields between laboratory experiments, ranging over 4 orders of magnitude from 5 × 10-7 to 5 × 10-3 molecules/eV for different particles and energies. We revisit decades of laboratory data to solve this long-standing puzzle, finding an inverse projectile range dependence in the O2 yields, due to preferential O2 formation from an 30 Å thick oxygenated surface layer. Highly penetrating projectile ions and electrons with ranges ≳30 Å are therefore less efficient at producing O2 than slow/heavy ions and low-energy electrons (≲ 400 eV) which deposit most energy near the surface. Unlike O2, the H2O2 yields from penetrating projectiles fall within a comparatively narrow range of (0.1-6) × 10-3 molecules/eV and do not depend on range, suggesting that H2O2 forms deep in the ice uniformly along the projectile track, e.g., by reactions of OH radicals. We develop an analytical model for O2, H2, and H2O2 yields from pure water ice for electrons and singly charged ions of any mass and energy and apply the model to estimate possible O2 source rates on several icy satellites. The yields are upper limits for icy bodies on which surface impurities may be present.

  1. Searching for traces of life in subglacial Lake Vostok (Antarctica) in terms of forward contamination: the lessons for exploration of icy environments on Mars

    Science.gov (United States)

    Bulat, S. A.; Alekhina, I. A.; Lipenkov, V. Ya.; Petit, J.-R.

    Bacterial 16S ribosomal gene analysis guarded by criteria for trace DNA analysis and Ancient DNA research clearly testifies for the very low biomass in accretion ice from giant subglacial Lake Vostok buried beneath 4-km thick East Antarctic ice sheet. It seems that the accretion ice is essentially germ-free indicating that the water body should also be hosting a highly sparse life, if any, unless the lake water lost its biological contents during accretion process. Due to this the search for life in Lake Vostok is constrained by a high chance of contamination similar to forward-contamination upon searching for life on Mars and other icy planets. Of 16 bacterial phylotypes initially recovered from the accretion ice the only one was kept with confident relevance to the lake environment while 15 others were presumed to be contaminants on the basis of indexing contaminant criteria developed for Lake Vostok and similar icy environments. The current way to avoid contamination appears to use stringent ice chemistry-based decontamination procedures and comprehensive biological controls including establishment of contemporary contaminant database as a prerequisite to identify and categorize sources of contaminants. More challenge would be to advance cleanliness and sterilization approaches and procedures in order to achieve and measure the level of cleanliness appropriate for tools exploring environments like Lake Vostok. As a guide for searching for life in (sub)glacial environments on Earth or Mars and Jovian's Europa our recommendations can be summarized as follows: (i) apply stringent ice decontamination procedures to meet chemistry and trace DNA analysis standards, (ii) document biological contents of various environments including humans in contact with ice samples (development of contaminant database), (iii) ensure in using relevant methods to cover both known and expected biodiversity and (iv) verify microbial findings through their possible metabolic profiles

  2. Crustal control of dissipative ocean tides in Enceladus and other icy moons

    Science.gov (United States)

    Beuthe, Mikael

    2016-12-01

    Could tidal dissipation within Enceladus' subsurface ocean account for the observed heat flow? Earthlike models of dynamical tides give no definitive answer because they neglect the influence of the crust. I propose here the first model of dissipative tides in a subsurface ocean, by combining the Laplace Tidal Equations with the membrane approach. For the first time, it is possible to compute tidal dissipation rates within the crust, ocean, and mantle in one go. I show that oceanic dissipation is strongly reduced by the crustal constraint, and thus contributes little to Enceladus' present heat budget. Tidal resonances could have played a role in a forming or freezing ocean less than 100 m deep. The model is general: it applies to all icy satellites with a thin crust and a shallow ocean. Scaling rules relate the resonances and dissipation rate of a subsurface ocean to the ones of a surface ocean. If the ocean has low viscosity, the westward obliquity tide does not move the crust. Therefore, crustal dissipation due to dynamical obliquity tides can differ from the static prediction by up to a factor of two.

  3. Production of Oxidants by Ion Bombardment of Icy Moons in the Outer Solar System

    Directory of Open Access Journals (Sweden)

    Philippe Boduch

    2011-01-01

    Full Text Available Our groups in Brazil, France and Italy have been active, among others in the world, in performing experiments on physical-chemical effects induced by fast ions colliding with solids (frozen gases, carbonaceous and organic materials, silicates, etc. of astrophysical interest. The used ions span a very large range of energies, from a few keV to hundreds MeV. Here we present a summary of the results obtained so far on the formation of oxidants (hydrogen peroxide and ozone after ion irradiation of frozen water, carbon dioxide and their mixtures. Irradiation of pure water ice produces hydrogen peroxide whatever is the used ion and at different temperatures. Irradiation of carbon dioxide and water frozen mixtures result in the production of molecules among which hydrogen peroxide and ozone. The experimental results are discussed in the light of the relevance they have to support the presence of an energy source for biosphere on Europa and other icy moons in the outer Solar System.

  4. Fundamentals and clinical perspective of urethral sphincter instability as a contributing factor in patients with lower urinary tract dysfunction--ICI-RS 2014.

    Science.gov (United States)

    Kirschner-Hermanns, Ruth; Anding, Ralf; Rosier, Peter; Birder, Lori; Andersson, Karl Erik; Djurhuus, Jens Christian

    2016-02-01

    Urethral pathophysiology is often neglected in discussions of bladder dysfunction. It has been debated whether "urethral sphincter instability," referred to based on observed "urethral pressure variations," is an important aspect of overactive bladder syndrome (OAB). The purpose of this report is to summarize current urethral pathophysiology evidence and outline directions for future research based on a literature review and discussions during the ICI-RS meeting in Bristol in 2014. Urethral pathophysiology with a focus on urethral pressure variation (UPV) was presented and discussed in a multidisciplinary think tank session at the ICI_R meeting in Bristol 2014. This think tank session was based on collaboration between physicians and basic science researchers. Experimental animal studies or studies performed in clinical series (predominantly symptomatic women) provided insights into UPV, but the findings were inconsistent and incomplete. However, UPV is certainly associated with lower urinary tract symptoms (likely OAB), and thus, future research on this topic is relevant. Future research based on adequately defined clinical (and urodynamic) parameters with precisely defined patient groups might shed better light on the cause of OAB symptoms. Further fundamental investigation of urethral epithelial-neural interactions via the release of mediators should enhance our knowledge and improve the management of patients with OAB. © 2016 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.

  5. Cryo-braking using penetrators for enhanced capabilities for the potential landing of payloads on icy solar system objects

    Science.gov (United States)

    Winglee, R. M.; Robinson, T.; Danner, M.; Koch, J.

    2018-03-01

    The icy moons of Jupiter and Saturn are important astrobiology targets. Access to the surface of these worlds is made difficult by the high ΔV requirements which is typically in the hypervelocity range. Passive braking systems cannot be used due to the lack of an atmosphere, and active braking by rockets significantly adds to the missions costs. This paper demonstrates that a two-stage landing system can overcome these problems and provide significant improvements in the payload fraction that can be landed The first stage involves a hypervelocity impactor which is designed to penetrate to a depth of a few tens of meters. This interaction is the cryo-breaking component and is examined through laboratory experiments, empirical relations and modeling. The resultant ice-particle cloud creates a transient artificial atmosphere that can be used to enable passive braking of the second stage payload dd, with a substantially higher mass payload fraction than possible with a rocket landing system. It is shown that a hollow cylinder design for the impactor can more efficiently eject the material upwards in a solid cone of ice particles relative to solid impactors such as spheres or spikes. The ejected mass is shown to be of the order of 103 to 104 times the mass of the impactor. The modeling indicates that a 10 kg payload with a braking system of 3 m2 (i.e. an areal density of 0.3 kg/m2) is sufficient to allow the landing of the payload with the deceleration limited to less than 2000 g's. Modern electronics can withstand this deceleration and as such the system provides an important alternative to landing payloads on icy solar system objects.

  6. Factors associated with prolonged time to treatment failure with fulvestrant 500 mg in patients with post-menopausal estrogen receptor-positive advanced breast cancer: a sub-group analysis of the JBCRG-C06 Safari study.

    Science.gov (United States)

    Kawaguchi, Hidetoshi; Masuda, Norikazu; Nakayama, Takahiro; Aogi, Kenjiro; Anan, Keisei; Ito, Yoshinori; Ohtani, Shoichiro; Sato, Nobuaki; Saji, Shigehira; Takano, Toshimi; Tokunaga, Eriko; Nakamura, Seigo; Hasegawa, Yoshie; Hattori, Masaya; Fujisawa, Tomomi; Morita, Satoshi; Yamaguchi, Miki; Yamashita, Hiroko; Yamashita, Toshinari; Yamamoto, Yutaka; Yotsumoto, Daisuke; Toi, Masakazu; Ohno, Shinji

    2018-01-01

    The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this sub-group analysis was to further examine data from the Safari study, focusing on ER + and human epidermal growth factor receptor-negative (HER2-) cases. The Safari study (UMIN000015168) was a retrospective, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p < .001), no prior chemotherapy (p < .001), and F500 treatment line (p < .001) were correlated with prolonged TTF (median = 5.39 months). In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

  7. IMPACT OF COHERENT BACKSCATTERING ON THE SPECTRA OF ICY SATELLITES OF SATURN AND THE IMPLICATIONS OF ITS EFFECTS FOR REMOTE SENSING

    International Nuclear Information System (INIS)

    Kolokolova, L.; Buratti, B.; Tishkovets, V.

    2010-01-01

    We have found systematic variations in the spectra of Saturn's icy satellites Rhea and Iapetus obtained by the Cassini Visual and Infrared Mapping Spectrometer (VIMS). The main attribute of these variations is a significantly different depth of the absorption bands at different phase angles. We show that these variations likely result from the coherent backscattering effect (CBE). This effect has been mainly known as the probable reason for a steep opposition spike in brightness observed for some asteroids, moons, and Kuiper Belt Objects at phase angles smaller than 3 deg. The opposition spike has different steepness at different albedos due to the strong dependence of the CBE on the absorption of the material. As a result of this dependence, the impact of the CBE should be different within and outside of the absorption spectral bands. This produces a systematic change in the depth of the absorption bands at different phase angles, as we see in the VIMS spectra of Rhea and Iapetus. Neglecting this effect may result in misinterpretation of the spectra and misleading conclusions about compositional and particle size differences of icy bodies studied at different phase angles. Our computer modeling of the CBE reproduces the observed spectral variations and also shows that they are strongly affected by the size and packing of particles. Thus, the variations in the absorption bands produced by the CBE not only allow us to improve interpretation of the spectra, but also provide a promising approach to study size and packing of the regolith and dust particles.

  8. Descent with Modification: Thermal Reactions of Subsurface H2O2 of Relevance to Icy Satellites and Other Small Bodies

    Science.gov (United States)

    Hudson, Reggie L.; Loefler, Mark J.

    2012-01-01

    Laboratory experiments have demonstrated that magnetospheric radiation in the Jovian system drives reaction chemistry in ices at temperatures relevant to Europa and other icy satellites. Similarly, cosmic radiation (mainly protons) acting on cometary and interstellar ices can promote extensive chemical change. Among the products that have been identified in irradiated H20-ice is hydrogen peroxide (H202), which has been observed on Europa and is suspected on other worlds. Although the infrared spectra and radiation chemistry of H2O2-containing ices are well documented, the thermally-induced solid-phase chemistry of H2O2 is largely unknown. Therefore, in this presentation we report new laboratory results on reactions at 50 - 130 K in ices containing H2O2 and other molecules, both in the presence and absence of H2O. As an example of our results, we find that warming H2O + H2O2 + SO2 ices promotes SO2 oxidation to SO4(2-). We suspect that such redox chemistry may explain some of the observations related to the presence and distribution of H2O2 across Europa's surface as well as the lack of H2O2 on Ganymede and Callisto. If other molecules prove to be just as reactive with frozen H2O2 then it may explain why H2O2 has been absent from surfaces of many of the small icy bodies that are known to be exposed to ionizing radiation. Our results also have implications for the survival of H2O2 as it descends towards a subsurface ocean on Europa.

  9. Carbonic acid as a reserve of carbon dioxide on icy moons: The formation of carbon dioxide (CO2) in a polar environment

    International Nuclear Information System (INIS)

    Jones, Brant M.; Kaiser, Ralf I.; Strazzulla, Giovanni

    2014-01-01

    Carbon dioxide (CO 2 ) has been detected on the surface of several icy moons of Jupiter and Saturn via observation of the ν 3 band with the Near-Infrared Mapping Spectrometer on board the Galileo spacecraft and the Visible-Infrared Mapping Spectrometer on board the Cassini spacecraft. Interestingly, the CO 2 band for several of these moons exhibits a blueshift along with a broader profile than that seen in laboratory studies and other astrophysical environments. As such, numerous attempts have been made in order to clarify this abnormal behavior; however, it currently lacks an acceptable physical or chemical explanation. We present a rather surprising result pertaining to the synthesis of carbon dioxide in a polar environment. Here, carbonic acid was synthesized in a water (H 2 O)-carbon dioxide (CO 2 ) (1:5) ice mixture exposed to ionizing radiation in the form of 5 keV electrons. The irradiated ice mixture was then annealed, producing pure carbonic acid which was then subsequently irradiated, recycling water and carbon dioxide. However, the observed carbon dioxide ν 3 band matches almost exactly with that observed on Callisto; subsequent temperature program desorption studies reveal that carbon dioxide synthesized under these conditions remains in solid form until 160 K, i.e., the sublimation temperature of water. Consequently, our results suggest that carbon dioxide on Callisto as well as other icy moons is indeed complexed with water rationalizing the shift in peak frequency, broad profile, and the solid state existence on these relatively warm moons.

  10. High-resolution CASSINI-VIMS mosaics of Titan and the icy Saturnian satellites

    Science.gov (United States)

    Jaumann, R.; Stephan, K.; Brown, R.H.; Buratti, B.J.; Clark, R.N.; McCord, T.B.; Coradini, A.; Capaccioni, F.; Filacchione, G.; Cerroni, P.; Baines, K.H.; Bellucci, G.; Bibring, J.-P.; Combes, M.; Cruikshank, D.P.; Drossart, P.; Formisano, V.; Langevin, Y.; Matson, D.L.; Nelson, R.M.; Nicholson, P.D.; Sicardy, B.; Sotin, Christophe; Soderbloom, L.A.; Griffith, C.; Matz, K.-D.; Roatsch, Th.; Scholten, F.; Porco, C.C.

    2006-01-01

    The Visual Infrared Mapping Spectrometer (VIMS) onboard the CASSINI spacecraft obtained new spectral data of the icy satellites of Saturn after its arrival at Saturn in June 2004. VIMS operates in a spectral range from 0.35 to 5.2 ??m, generating image cubes in which each pixel represents a spectrum consisting of 352 contiguous wavebands. As an imaging spectrometer VIMS combines the characteristics of both a spectrometer and an imaging instrument. This makes it possible to analyze the spectrum of each pixel separately and to map the spectral characteristics spatially, which is important to study the relationships between spectral information and geological and geomorphologic surface features. The spatial analysis of the spectral data requires the determination of the exact geographic position of each pixel on the specific surface and that all 352 spectral elements of each pixel show the same region of the target. We developed a method to reproject each pixel geometrically and to convert the spectral data into map projected image cubes. This method can also be applied to mosaic different VIMS observations. Based on these mosaics, maps of the spectral properties for each Saturnian satellite can be derived and attributed to geographic positions as well as to geological and geomorphologic surface features. These map-projected mosaics are the basis for all further investigations. ?? 2006 Elsevier Ltd. All rights reserved.

  11. Choline acetyltransferase and TrkA expression, as well as the improvement in cognition produced by E2 and P4 in ovariectomized rats, are blocked by ICI 182 780 and RU486.

    Science.gov (United States)

    Espinosa-Raya, Judith; Cruz-Raya, Ulises; López-Martínez, Margarita; Picazo, Ofir

    2018-01-09

    Treatment with 17-β estradiol and progesterone improves the performance of ovariectomized rats in an autoshaping learning task, representing cognitive improvement. To test whether this is attributable to genomic mechanisms, the antiestrogen ICI 182 780 or antiprogesterone RU486 was injected into ovariectomized animals primed previously with estrogen or progesterone, respectively. Compared with the vehicle control, each hormone administered alone produced an elevated expression of choline acetyltransferase and TrkA, along with an improvement in performance on the behavioral test. E2+ICI reverted the increase in these two proteins. However, RU alone elicited higher ChAT expression. With this exception, there was a clear linear regression between the number of conditioned responses and the level of ChAT and TrkA in the basal forebrain. The results suggest that TrkA may be more important than ChAT for regulating autoshaping learning tasks, and that genomic mechanisms in the basal forebrain could possibly underlie hormonal improvement of cognition.

  12. Iceless Icy Moons: Is the Nice Model In Trouble?

    Science.gov (United States)

    Dones, Henry C. Luke; Levison, H. F.

    2012-05-01

    Nimmo and Korycansky (2012; henceforth NK12) stated that if the outer Solar System underwent a Late Heavy Bombardment (LHB) in the Nice model, the mass striking the icy satellites at speeds up to tens of km/s would have vaporized so much ice that moons such as Mimas, Enceladus, and Miranda would have been devolatilized. NK12's possible explanations of this apparent discrepancy with observations include (1) the mass influx was a factor of 10 less than that in the Nice model; (2) the mass distribution of the impactors was top-heavy, so that luck might have saved some of the moons from suffering large, vapor-removing impacts; or (3) the inner moons formed after the LHB. NK12 calculated the mass influx onto the satellites from the lunar impact rate estimated by Gomes et al. (2005) and scaling factors calculated by Zahnle et al. (1998, 2003; also see Barr and Canup 2010). Production of vapor in hypervelocity impacts is calculated from Kraus et al. (2011). Our preliminary results show that there is about an order-of-magnitude uncertainty in the mass striking the satellites during the LHB, with NK12's estimate at the upper end of the range. We will discuss how the mass influx depends on the velocity and mass distributions of the impactors. The Nice model lives. We thank the NASA Lunar Science Institute (http://lunarscience.nasa.gov/) for support. Barr, A.C., Canup, R.M., Nature Geoscience 3, 164-167 (2010). Gomes, R., Levison, H.F., Tsiganis, K., Morbidelli, A., Nature 435, 466-469 (2005). Kraus, R.G., Senft, L.E., Stewart, S.T., Icarus 214, 724-738 (2011). Nimmo, F., Korycansky, D.G., Icarus, in press, http://www.sciencedirect.com/science/article/pii/S0019103512000310 (2012). Zahnle, K., Dones, L., Levison, H.F., Icarus 136, 202-222 (1998). Zahnle, K., Schenk, P., Levison, H.F., Dones, L., Icarus 163, 263-289 (2003).

  13. Targeting the American market for medicines, ca. 1950s-1970s: ICI and Rhône-Poulenc compared.

    Science.gov (United States)

    Quirke, Viviane

    2014-01-01

    The forces that have shaped American medicine include a wide set of interrelated changes, among them the changing research, development, and marketing practices of the pharmaceutical industry. This article compares the research and development (R&D) and marketing strategies of the British group Imperial Chemical Industries (ICI, whose Pharmaceutical Division was spun off and merged with the Swedish company Astra to form AstraZeneca) and its French counterpart Rhône-Poulenc (now part of Sanofi-Aventis) in dealing with the American medical market. It examines how, in the process, the relationship between R&D and marketing was altered, and the firms themselves were transformed. The article also questions the extent to which their approaches to this market, one of the most significant markets for drugs in general, and for anticancer drugs in particular, became standardized in the period of "scientific marketing."

  14. High pressure study of water-salt systems, phase equilibria, partitioning, thermodynic properties and implication for large icy worlds hydrospheres.

    Science.gov (United States)

    Journaux, B.; Brown, J. M.; Abramson, E.; Petitgirard, S.; Pakhomova, A.; Boffa Ballaran, T.; Collings, I.

    2017-12-01

    Water salt systems are predicted to be present in deep hydrosphere inside water-rich planetary bodies, following water/rock chemical interaction during early differentiation stages or later hydrothermal activity. Unfortunately the current knowledge of the thermodynamic and physical properties of aqueous salt mixtures at high pressure and high temperature is still insufficient to allow realistic modeling of the chemical or dynamic of thick planetary hydrospheres. Recent experimental results have shown that the presence of solutes, and more particularly salts, in equilibrium with high pressure ices have large effects on the stability fields, buoyancy and chemistry of all the phases present at these extreme conditions. Effects currently being investigated by our research group also covers ice melting curve depressions that depend on the salt species and incorporation of solutes inside the crystallographic lattice of high pressure ices. Both of these could have very important implication at the planetary scale, enabling thicker/deeper liquid oceans, and allowing chemical transportation through the high pressure ice layer in large icy worlds. We will present the latest results obtained in-situ using diamond anvil cell, coupled with Synchrotron X-Ray diffraction, Raman Spectroscopy and optical observations, allowing to probe the crystallographic structure, equations of state, partitioning and phase boundary of high pressure ice VI and VII in equilibrium with Na-Mg-SO4-Cl ionic species at high pressures (1-10 GPa). The difference in melting behavior depending on the dissolved salt species was characterized, suggesting differences in ionic speciation at liquidus conditions. The solidus P-T conditions were also measured as well as an increase of lattice volumes interpreted as an outcome of ionic incorporation in HP ice during incongruent crystallization. The measured phase diagrams, lattice volumes and important salt incorporations suggest a more complex picture of the

  15. Formation of Valley Networks in a Cold and Icy Early Mars Climate: Predictions for Erosion Rates and Channel Morphology

    Science.gov (United States)

    Cassanelli, J.

    2017-12-01

    Mars is host to a diverse array of valley networks, systems of linear-to-sinuous depressions which are widely distributed across the surface and which exhibit branching patterns similar to the dendritic drainage patterns of terrestrial fluvial systems. Characteristics of the valley networks are indicative of an origin by fluvial activity, providing among the most compelling evidence for the past presence of flowing liquid water on the surface of Mars. Stratigraphic and crater age dating techniques suggest that the formation of the valley networks occurred predominantly during the early geologic history of Mars ( 3.7 Ga). However, whether the valley networks formed predominantly by rainfall in a relatively warm and wet early Mars climate, or by snowmelt and episodic rainfall in an ambient cold and icy climate, remains disputed. Understanding the formative environment of the valley networks will help distinguish between these warm and cold end-member early Mars climate models. Here we test a conceptual model for channel incision and evolution under cold and icy conditions with a substrate characterized by the presence of an ice-free dry active layer and subjacent ice-cemented regolith, similar to that found in the Antarctic McMurdo Dry Valleys. We implement numerical thermal models, quantitative erosion and transport estimates, and morphometric analyses in order to outline predictions for (1) the precise nature and structure of the substrate, (2) fluvial erosion/incision rates, and (3) channel morphology. Model predictions are compared against morphologic and morphometric observational data to evaluate consistency with the assumed cold climate scenario. In the cold climate scenario, the substrate is predicted to be characterized by a kilometers-thick globally-continuous cryosphere below a 50-100 meter thick desiccated ice-free zone. Initial results suggest that, with the predicted substrate structure, fluvial channel erosion and morphology in a cold early Mars

  16. Estrogen modulates potassium currents and expression of the Kv4.2 subunit in GT1-7 cells.

    Science.gov (United States)

    Farkas, Imre; Varju, Patricia; Liposits, Zsolt

    2007-03-01

    The proper maintenance of reproduction requires the pulsatile secretion of gonadotropin-releasing hormone (GnRH), which is ensured by synchronized periodic firing of multiple GnRH neurons. Both hormone secretion and electrophysiological properties of GnRH cells are influenced by estrogen. The impact of 17beta-estradiol treatment on the function of voltage gated A- and K-type potassium channels, known modulators of firing rate, was therefore examined in our experiments using immortalized GnRH-producing GT1-7 neurons. Whole cell patch clamp recordings showed the absence of the A-type current in GT1-7 cells cultured in estrogen-free medium and after 8h 17beta-estradiol treatment. Exposure of the cells to 17beta-estradiol for 24 and 48 h, respectively, resulted in the appearance of the A-type current. The induction of the A-type current by 17beta-estradiol was dose-related (50 pM to 15 nM range). In contrast, the K-type potassium current was apparent in the estrogen-free environment and 17beta-estradiol administration significantly decreased its amplitude. Co-administration of 17beta-estradiol and estrogen receptor blocker, Faslodex (ICI 182,780; 1 microM) abolished the occurrence of the A-type current. Real-time PCR data demonstrated that expression of the Kv4.2 subunit of the A-type channel was low at 0, 0.5, 2 and 8h, peaked at 24h and diminished at 48 h 17beta-estradiol treatment (15 nM). These data indicate that potassium channels of GT1-7 neurons are regulated by estrogen a mechanism that might contribute to modulation of firing rate and hormone secretion in GnRH neurons.

  17. Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases.

    Science.gov (United States)

    Turner, N C; Finn, R S; Martin, M; Im, S-A; DeMichele, A; Ettl, J; Diéras, V; Moulder, S; Lipatov, O; Colleoni, M; Cristofanilli, M; Lu, D R; Mori, A; Giorgetti, C; Iyer, S; Bartlett, C Huang; Gelmon, K A

    2018-03-01

    This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases. Pre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N = 521) and postmenopausal women untreated for ABC (PALOMA-2; N = 666) were randomized 2 : 1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression-free survival (PFS), safety, and patient-reported quality of life (QoL) were evaluated by prior treatment and visceral involvement. Visceral metastases incidence was higher in patients with prior resistance to ET (58.3%, PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In patients with prior resistance to ET and visceral metastases, median PFS (mPFS) was 9.2 months with palbociclib plus fulvestrant versus 3.4 months with placebo plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35-0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In patients with nonvisceral metastases, mPFS was 16.6 versus 7.3 months, HR 0.53; 95% CI 0.36-0.77. In patients with visceral disease and naive to ET in the advanced disease setting, mPFS was 19.3 months with palbociclib plus letrozole versus 12.9 months with placebo plus letrozole (HR 0.63; 95% CI 0.47-0.85); ORR was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not reached with palbociclib plus letrozole versus 16.8 months with placebo plus letrozole (HR 0.50; 95% CI 0.36-0.70). In patients with prior resistance to ET with visceral metastases, palbociclib plus fulvestrant significantly delayed deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported QoL was maintained with palbociclib plus letrozole in patients naive to endocrine-based therapy for ABC. Palbociclib plus ET prolonged mPFS in

  18. The use of chromatographic indexes to study the biodegradation of crude oil in cold/icy seawater

    International Nuclear Information System (INIS)

    Siron, R.; Pelletier, E.

    1993-01-01

    A group of five protected mesocosms (3.5 m 3 each) was used to study the biodegradation of dispersed crude oil in cold and icy seawater. A wide range of oil concentrations was tested over four experiments lasting two weeks to six months. Various oil treatments were studied with respect to the natural bacterial degradation: chemically dispersed and untreated crude oil; and oil adsorbed on, and released from, an immersed substrate. The study was concerned with oil accommodated in the water column, accumulated in surface (sheens and emulsions), and collected in sediment traps. The oil biodegradation was assessed by means of the following gas chromatographic indexes: C17/pristane; C18/phytane; n-alkanes/isoprenoids; pristane/phytane; naphthalene/phenanthrene; 2-methyl naphthalene/1-methyl naphthalene; and methylnaphthalenes/total substituted naphthalenes. A combined index of biodegradation defined from the most significant hydrocarbon ratios is proposed to evaluate the overall biodegradation of dissolved compounds and oil droplets, involving both aliphatic and aromatic hydrocarbons. Coupled with mesocosm facilities, this approach appears very convenient to determine the potential degradability of crude oils by natural indigenous microflora. 26 refs., 11 figs., 2 tabs

  19. SIZE AND SURFACE AREA OF ICY DUST AGGREGATES AFTER A HEATING EVENT AT A PROTOPLANETARY NEBULA

    Energy Technology Data Exchange (ETDEWEB)

    Sirono, Sin-iti [Earth and Environmental Sciences, Graduate School of Environmental Studies, Nagoya University, Nagoya 464-8601 (Japan)

    2013-03-01

    The activity of a young star rises abruptly during an FU Orionis outburst. This event causes a temporary temperature increase in the protoplanetary nebula. H{sub 2}O icy grains are sublimated by this event, and silicate cores embedded inside the ice are ejected. During the high-temperature phase, the silicate grains coagulate to form silicate core aggregates. After the heating event, the temperature drops, and the ice recondenses onto the aggregates. I determined numerically the size distribution of the ice-covered aggregates. The size of the aggregates exceeds 10 {mu}m around the snow line. Because of the migration of the ice to large aggregates, only a small fraction of the silicate core aggregate is covered with H{sub 2}O ice. After the heating event, the surface of an ice-covered aggregate is totally covered by silicate core aggregates. This might reduce the fragmentation velocity of aggregates when they collide. It is possible that the covering silicate cores shield the UV radiation field which induces photodissociation of H{sub 2}O ice. This effect may cause the shortage of cold H{sub 2}O vapor observed by Herschel.

  20. ICI 56,780 Optimization: Structure-Activity Relationship Studies of 7-(2-Phenoxyethoxy)-4(1H)-quinolones with Antimalarial Activity.

    Science.gov (United States)

    Maignan, Jordany R; Lichorowic, Cynthia L; Giarrusso, James; Blake, Lynn D; Casandra, Debora; Mutka, Tina S; LaCrue, Alexis N; Burrows, Jeremy N; Willis, Paul A; Kyle, Dennis E; Manetsch, Roman

    2016-07-28

    Though malaria mortality rates are down 48% globally since 2000, reported occurrences of resistance against current therapeutics threaten to reverse that progress. Recently, antimalarials that were once considered unsuitable therapeutic agents have been revisited to improve physicochemical properties and efficacy required for selection as a drug candidate. One such compound is 4(1H)-quinolone ICI 56,780, which is known to be a causal prophylactic that also displays blood schizonticidal activity against P. berghei. Rapid induction of parasite resistance, however, stalled its further development. We have completed a full structure-activity relationship study on 4(1H)-quinolones, focusing on the reduction of cross-resistance with atovaquone for activity against the clinical isolates W2 and TM90-C2B, as well as the improvement of microsomal stability. These studies revealed several frontrunner compounds with superb in vivo antimalarial activity. The best compounds were found to be curative with all mice surviving a Plasmodium berghei infection after 30 days.

  1. Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.

    Directory of Open Access Journals (Sweden)

    Mathieu Dalvai

    Full Text Available Antiestrogens are designed to antagonize hormone induced proliferation and ERalpha target gene expression in mammary tumor cells. Commonly used drugs such as OH-Tamoxifen and ICI 182780 (Fulvestrant block cell cycle progression in G0/G1. Inversely, the effect of cell cycle stage on ER regulated gene expression has not been tested directly. We show that in ERalpha-positive breast cancer cells (MCF-7 the estrogen receptor gene and downstream target genes are cell cycle regulated with expression levels varying as much as three-fold between phases of the cell cycle. Steroid free culture conditions commonly used to assess the effect of hormones or antiestrogens on gene expression also block MCF-7 cells in G1-phase when several ERalpha target genes are overexpressed. Thus, cell cycle effects have to be taken into account when analyzing the impact of hormonal treatments on gene transcription. We found that antiestrogens repress transcription of several ERalpha target genes specifically in S phase. This observation corroborates the more rapid and strong impact of antiestrogen treatments on cell proliferation in thymidine, hydroxyurea or aphidicolin arrested cells and correlates with an increase of apoptosis compared to similar treatments in lovastatin or nocodazol treated cells. Hence, cell cycle effects synergize with the action of antiestrogens. An interesting therapeutic perspective could be to enhance the action of anti-estrogens by associating hormone-therapy with specific cell cycle drugs.

  2. Icy Saturnian satellites: Disk-integrated UV-IR characteristics and links to exogenic processes

    Science.gov (United States)

    Hendrix, Amanda R.; Filacchione, Gianrico; Paranicas, Chris; Schenk, Paul; Scipioni, Francesca

    2018-01-01

    Combined Cassini observations obtained at similar observing geometries in the ultraviolet through infrared spectral range, along with additional ultraviolet (UV) data from Hubble Space Telescope where available, are used to study system-wide trends in spectral albedos of the inner icy Saturnian satellites (Mimas, Enceladus, Tethys, Dione, Rhea). We derive UV and visible geometric albedos and UV absorption strengths of the leading and trailing hemispheres and compare with E ring grain flux and charged particle intensities (electrons and ions of varying energies) to those hemispheres. We find that the UV absorption strength on the leading and trailing hemispheres is anti-correlated with E ring grain flux. On the trailing hemispheres, the UV absorption strength is correlated with intensity of electrons in the tens of keV range. We suggest that these relationships could imply links with the organic component of the E ring. Radiolytic processing of organics causes the products to become spectrally redder, increasing the UV absorption strength. Such processing occurs while organic-rich grains are in the E ring, and increases with exposure time in the E ring, such that grains interacting with Rhea are redder (more processed) than those impacting moons closer to Enceladus. Further processing (and associated darkening/reddening) occurs on the trailing hemispheres of the satellites, via radiolysis by electrons in the tens of keV range. Silicates and salts also redden with weathering; however because organics are present in the E ring in significantly greater abundance than salts or silicates, we suggest here that weathering of organics dominates the coloring of the inner Saturnian moons.

  3. Ejection of rocky and icy material from binary star systems: implications for the origin and composition of 1I/`Oumuamua

    Science.gov (United States)

    Jackson, Alan P.; Tamayo, Daniel; Hammond, Noah; Ali-Dib, Mohamad; Rein, Hanno

    2018-06-01

    In single-star systems like our own Solar system, comets dominate the mass budget of bodies ejected into interstellar space, since they form further away and are less tightly bound. However, 1I/`Oumuamua, the first interstellar object detected, appears asteroidal in its spectra and lack of detectable activity. We argue that the galactic budget of interstellar objects like 1I/`Oumuamua should be dominated by planetesimal material ejected during planet formation in circumbinary systems, rather than in single-star systems or widely separated binaries. We further show that in circumbinary systems, rocky bodies should be ejected in comparable numbers to icy ones. This suggests that a substantial fraction of interstellar objects discovered in future should display an active coma. We find that the rocky population, of which 1I/`Oumuamua seems to be a member, should be predominantly sourced from A-type and late B-star binaries.

  4. Studying the Surfaces of the Icy Galilean Satellites With JIMO

    Science.gov (United States)

    Prockter, L.; Schenk, P.; Pappalardo, R.

    2003-12-01

    The Geology subgroup of the Jupiter Icy Moons Orbiter (JIMO) Science Definition Team (SDT) has been working with colleagues within the planetary science community to determine the key outstanding science goals that could be met by the JIMO mission. Geological studies of the Galilean satellites will benefit from the spacecraft's long orbital periods around each satellite, lasting from one to several months. This mission plan allows us to select the optimal viewing conditions to complete global compositional and morphologic mapping at high resolution, and to target geologic features of key scientific interest at very high resolution. Community input to this planning process suggests two major science objectives, along with corresponding measurements proposed to meet them. Objective 1: Determine the origins of surface features and their implications for geological history and evolution. This encompasses investigations of magmatism (intrusion, extrusion, and diapirism), tectonism (isostatic compensation, and styles of faulting, flexure and folding), impact cratering (morphology and distribution), and gradation (erosion and deposition) processes (impact gardening, sputtering, mass wasting and frosts). Suggested measurements to meet this goal include (1) two dimensional global topographic mapping sufficient to discriminate features at a spatial scale of 10 m, and with better than or equal to 1 m relative vertical accuracy, (2) nested images of selected target areas at a range of resolutions down to the submeter pixel scale, (3) global (albedo) mapping at better than or equal to 10 m/pixel, and (4) multispectral global mapping in at least 3 colors at better than or equal to 100 m/pixel, with some subsets at better than 30 m/pixel. Objective 2. Identify and characterize potential landing sites for future missions. A primary component to the success of future landed missions is full characterization of potential sites in terms of their relative age, geological interest, and

  5. Palbociclib: A Novel Cyclin-Dependent Kinase Inhibitor for Hormone Receptor-Positive Advanced Breast Cancer.

    Science.gov (United States)

    Mangini, Neha S; Wesolowski, Robert; Ramaswamy, Bhuvaneswari; Lustberg, Maryam B; Berger, Michael J

    2015-11-01

    To review palbociclib, a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6, and its current place in therapy for the treatment of hormone receptor (HMR)-positive, human epidermal growth factor receptor 2 (Her2)-negative advanced breast cancer. Four phase I trials, 2 phase II trials, and 1 phase III trial were identified from May 2004 to May 2015 using PubMed, American Society of Clinical Oncology (ASCO) abstracts, and European Society of Medical Oncology (ESMO) abstracts. In the first-line setting, the phase II PALbociclib: Ongoing trials in the Management of breast cAncer (PALOMA)-1 trial randomized patients to receive letrozole alone or letrozole plus palbociclib 125 mg daily for 3 weeks, followed by 1 week off, as initial therapy for advanced breast cancer. The investigator-assessed median progression-free survival (PFS) was 20. 2 months for the combination versus 10.2 months for letrozole alone (hazard ratio [HR] = 0.488; 95% CI = 0.319-0.748; 1-sided P = 0.0004). The ensuing Food and Drug Administration approval of palbociclib was given a "breakthrough therapy" designation, where preliminary evidence suggests substantial improvement over existing therapies for a serious or life-threatening disease. A confirmatory phase III trial, PALOMA-2, is under way. In patients who were previously treated with endocrine therapy for advanced breast cancer, the phase III PALOMA-3 trial randomized patients to fulvestrant plus palbociclib versus fulvestrant plus placebo. The investigator-assessed median PFS at the time of a preplanned analysis was 9.2 months with palbociclib-fulvestrant compared with 3.8 months with placebo-fulvestrant (HR = 0.42; 95% CI = 0.32-0.56; P < 0.001). Palbociclib, the first-in-class CDK4/6 inhibitor, significantly extended PFS in combination with endocrine therapy in the first and subsequent lines of treatment for HMR-positive, Her2-negative advanced breast cancer. © The Author(s) 2015.

  6. Between ice and gas: CO2 on the icy satellites of Jupiter and Saturn

    Science.gov (United States)

    Hibbitts, C.

    2010-12-01

    CO2 exists in the surfaces of the icy Galilean and Saturnian satellites [1-6], yet despite its discovery over a decade ago on Ganymede, and five years ago on the Saturnian satellites, its nature is still debated [7]. On the Galilean satellites Callisto and Ganymede, the CO2 that is detected is bound to, or trapped within, the non-ice materials that prevent it from sublimating or otherwise escaping from the surface. On Europa, it resides within both the ice and nonice materials [8,9]. While greater abundances of CO2 may exist in the interiors of these moons, or small amounts may be continually created through particle bombardment of the surface, the observed CO2 is only a trace material, with a few hundred molecules responsible for the deepest absorption features and an estimated molar abundance of 0.1% [2; 10-12]. Yet its presence may provide essential clues to processes that shape the surfaces of the moon [13] and potentially key to understanding the composition of potential oceans in the subsurfaces. We continue measurements of the infrared properties associated with CO2 adsorbed onto nonice materials under pressures and at temperatures relevant to these icy satellites using bidirectional reflectance spectroscopy from ~ 1.5 to 5.5 μm. Previous measurements, using transmission spectroscopy, demonstrated both a compositional and a temperature dependence on the spectral signature of adsorbed CO2 [14]. Bidirectional spectroscopy enables detection of lower concentrations of adsorbate on fine-grained materials such as clays due to their large surface area to volume ratios and thus large surface areas that may be covered by adsorbate [15]. The effectiveness of transmission spectroscopy was also limited by the strong absorption of light within the pressed sample and its impermeability, which limited the coverage by adsorbate to the pellet’s outer surface. All measurements demonstrate that CO2 adsorbs onto montmorillonite clays, possibly due to its quadrupole moment

  7. Experimental Thermodynamics of [Na-Mg-Cl-SO4] Aqueous Solutions at GPa Pressure With Application to Icy Worlds.

    Science.gov (United States)

    Brown, J. M.; Bollengier, O.; Vance, S.

    2017-12-01

    Water competes with silicates as the main constituent of solid bodies in the outer solar system. Ganymede and Titan, the Mercury-sized satellites of Jupiter and Saturn, are made up half of water present as massive hydrospheres where pressure can reach up to 1.5 GPa. Geophysical data and planetary models unequivocally support the existence of global aqueous oceans trapped in these hydrospheres. However, the extent of these oceans and their role in the processes governing the internal structure of these moons remain unresolved. At issue is the poor to non-existent characterization, at the relevant pressures, of the properties of the aqueous fluids of significance to the outer solar system (with notably the Na-Mg-Cl-SO4 salts found in primitive chondrites), forcing current models to rely on pure water only. Our team at the University of Washington has developed an experimental apparatus to acquire the speed of sound of aqueous solutions in the 0 - 0.7 GPa and 250 - 350 K pressure and temperature ranges covering most of the conditions of existence of these extra-terrestrial oceans. Speeds of sound measured over a grid of pressures and temperatures allow calculation of the thermodynamic quantities (G, ρ, μ...) required for planetary science. Early analysis of pure water samples indicates our experimental results are on par with (at lower pressures), or better than, the IAPWS water laboratory standard, with sound speeds determined to 0.02% over our entire pressure range. For the first time at the high pressures of interest for large icy moons, we achieved the exploration of H2O-NaCl, H2O-MgSO4, H2O-Na2SO4 and H2O-MgCl2 solutions, from dilute concentrations to saturation. We are now in the process of acquiring the first data for H2O-NaCl-MgSO4 mixtures. We will briefly present our experimental setup and the underlying sound speed theory, and will then compare our results for the four endmembers, with an emphasis on their different association behavior under pressure as

  8. The urinary microbiome and its contribution to lower urinary tract symptoms; ICI-RS 2015.

    Science.gov (United States)

    Drake, Marcus J; Morris, Nicola; Apostolidis, Apostolos; Rahnama'i, Mohammad S; Marchesi, Julian R

    2017-04-01

    The microbiome is the term used for the symbiotic microbial colonisation of healthy organs. Studies have found bacterial identifiers within voided urine which is apparently sterile on conventional laboratory culture, and accordingly there may be health and disease implications. The International Consultation on Incontinence Research Society (ICI-RS) established a literature review and expert consensus discussion focussed on the increasing awareness of the urinary microbiome, and potential research priorities. The consensus considered the discrepancy between findings of conventional clinical microbiology methods, which generally rely on culture parameters predisposed towards certain "expected" organisms. Discrepancy between selective culture and RNA sequencing to study species-specific 16S ribosomal RNA is increasingly clear, and highlights the possibility that protective or harmful bacteria may be overlooked where microbiological methods are selective. There are now strong signals of the existence of a "core" urinary microbiome for the human urinary tract, particularly emerging with ageing. The consensus reviewed the potential relationship between a patient's microbiome and lower urinary tract dysfunction, whether low-count bacteriuria may be clinically significant and mechanisms which could associate micro-organisms with lower urinary tract symptoms. Key research priorities identified include the need to establish the scope of microbiome across the range of normality and clinical presentations, and gain consensus on testing protocols. Proteomics to study enzymatic and other functions may be necessary, since different bacteria may have overlapping phenotype. Longitudinal studies into risk factors for exposure, cumulative risk, and emergence of disease need to undertaken. Neurourol. Urodynam. 36:850-853, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Physicochemical Requirements Inferred for Chemical Self-Organization Hardly Support an Emergence of Life in the Deep Oceans of Icy Moons

    Science.gov (United States)

    Pascal, Robert

    2016-05-01

    An approach to the origin of life, focused on the property of entities capable of reproducing themselves far from equilibrium, has been developed recently. Independently, the possibility of the emergence of life in the hydrothermal systems possibly present in the deep oceans below the frozen crust of some of the moons of Jupiter and Saturn has been raised. The present report is aimed at investigating the mutual compatibility of these alternative views. In this approach, the habitability concept deduced from the limits of life on Earth is considered to be inappropriate with regard to emerging life due to the requirement for an energy source of sufficient potential (equivalent to the potential of visible light). For these icy moons, no driving force would have been present to assist the process of emergence, which would then have had to rely exclusively on highly improbable events, thereby making the presence of life unlikely on these Solar System bodies, that is, unless additional processes are introduced for feeding chemical systems undergoing a transition toward life and the early living organisms.

  10. Do we need a new definition of the overactive bladder syndrome? ICI-RS 2013.

    Science.gov (United States)

    Drake, Marcus J

    2014-06-01

    Overactive bladder syndrome (OAB) has a symptom-based definition. Following a presentation of issues, the definition was subjected to expert discussion at the International Consultation on Incontinence Research Society to identify key issues. OAB is a widely used term; it is a pragmatic approach to categorizing a recognized group of patients, and is understood by the patients, however, expert opinion suggested several issues for which additional evidence should be sought. Naming an organ (bladder) in the condition may suggest underlying mechanism, when contributory aspects may lie outside the bladder. No severity thresholds are set, which can cause uncertainty. Urgency is prominent in the definition, but may not be prominent in patients whose adaptive behavior reduces their propensity to urgency. OAB can co-exist with other common conditions, such as benign prostate enlargement (BPE), stress incontinence or nocturnal polyuria. Consensus led by the International Continence Society can be attempted for aspects such as "fear of leakage." To develop a new definition, more substantive evidence is needed for key elements, and until such evidence is available, full redefinition is not appropriate. Thus, the medical profession should accept constructive compromise and work supportively. The ICI-RS proposes that the terminology is slightly rephrased as: "overactive bladder syndrome (OAB) is characterized by urinary urgency, with or without urgency urinary incontinence, usually with increased daytime frequency and nocturia, if there is no proven infection or other obvious pathology." More substantive changes would require additional scientific evidence. Strengths, limitations, and practicalities of the definition of OAB were discussed at the ICIRS meeting 2013. Following a presentation of issues, the definition was subjected to expert discussion. © 2014 Wiley Periodicals, Inc.

  11. Estrogen Receptor β (ERβ1) Transactivation Is Differentially Modulated by the Transcriptional Coregulator Tip60 in a cis-Acting Element-dependent Manner*

    Science.gov (United States)

    Lee, Ming-Tsung; Leung, Yuet-Kin; Chung, Irving; Tarapore, Pheruza; Ho, Shuk-Mei

    2013-01-01

    Estrogen receptor (ER) β1 and ERα have overlapping and distinct functions despite their common use of estradiol as the physiological ligand. These attributes are explained in part by their differential utilization of coregulators and ligands. Although Tip60 has been shown to interact with both receptors, its regulatory role in ERβ1 transactivation has not been defined. In this study, we found that Tip60 enhances transactivation of ERβ1 at the AP-1 site but suppresses its transcriptional activity at the estrogen-response element (ERE) site in an estradiol-independent manner. However, different estrogenic compounds can modify the Tip60 action. The corepressor activity of Tip60 at the ERE site is abolished by diarylpropionitrile, genistein, equol, and bisphenol A, whereas its coactivation at the AP-1 site is augmented by fulvestrant (ICI 182,780). GRIP1 is an important tethering mediator for ERs at the AP-1 site. We found that coexpression of GRIP1 synergizes the action of Tip60. Although Tip60 is a known acetyltransferase, it is unable to acetylate ERβ1, and its coregulatory functions are independent of its acetylation activity. In addition, we showed the co-occupancy of ERβ1 and Tip60 at ERE and AP-1 sites of ERβ1 target genes. Tip60 differentially regulates the endogenous expression of the target genes by modulating the binding of ERβ1 to the cis-regulatory regions. Thus, we have identified Tip60 as the first dual-function coregulator of ERβ1. PMID:23857583

  12. Estrogen receptor β (ERβ1) transactivation is differentially modulated by the transcriptional coregulator Tip60 in a cis-acting element-dependent manner.

    Science.gov (United States)

    Lee, Ming-Tsung; Leung, Yuet-Kin; Chung, Irving; Tarapore, Pheruza; Ho, Shuk-Mei

    2013-08-30

    Estrogen receptor (ER) β1 and ERα have overlapping and distinct functions despite their common use of estradiol as the physiological ligand. These attributes are explained in part by their differential utilization of coregulators and ligands. Although Tip60 has been shown to interact with both receptors, its regulatory role in ERβ1 transactivation has not been defined. In this study, we found that Tip60 enhances transactivation of ERβ1 at the AP-1 site but suppresses its transcriptional activity at the estrogen-response element (ERE) site in an estradiol-independent manner. However, different estrogenic compounds can modify the Tip60 action. The corepressor activity of Tip60 at the ERE site is abolished by diarylpropionitrile, genistein, equol, and bisphenol A, whereas its coactivation at the AP-1 site is augmented by fulvestrant (ICI 182,780). GRIP1 is an important tethering mediator for ERs at the AP-1 site. We found that coexpression of GRIP1 synergizes the action of Tip60. Although Tip60 is a known acetyltransferase, it is unable to acetylate ERβ1, and its coregulatory functions are independent of its acetylation activity. In addition, we showed the co-occupancy of ERβ1 and Tip60 at ERE and AP-1 sites of ERβ1 target genes. Tip60 differentially regulates the endogenous expression of the target genes by modulating the binding of ERβ1 to the cis-regulatory regions. Thus, we have identified Tip60 as the first dual-function coregulator of ERβ1.

  13. The Possible Emergence of Life and Differentiation of a Shallow Biosphere on Irradiated Icy Worlds: The Example of Europa.

    Science.gov (United States)

    Russell, Michael J; Murray, Alison E; Hand, Kevin P

    2017-12-01

    Irradiated ice-covered ocean worlds with rocky mafic mantles may provide the conditions needed to drive the emergence and maintenance of life. Alkaline hydrothermal springs-relieving the geophysical, thermal, and chemical disequilibria between oceans and tidally stressed crusts-could generate inorganic barriers to the otherwise uncontrolled and kinetically disfavored oxidation of hydrothermal hydrogen and methane. Ionic gradients imposed across these inorganic barriers, comprising iron oxyhydroxides and sulfides, could drive the hydrogenation of carbon dioxide and the oxidation of methane through thermodynamically favorable metabolic pathways leading to early life-forms. In such chemostatic environments, fuels may eventually outweigh oxidants. Ice-covered oceans are primarily heated from below, creating convection that could transport putative microbial cells and cellular cooperatives upward to congregate beneath an ice shell, potentially giving rise to a highly focused shallow biosphere. It is here where electron acceptors, ultimately derived from the irradiated surface, could be delivered to such life-forms through exchange with the icy surface. Such zones would act as "electron disposal units" for the biosphere, and occupants might be transferred toward the surface by buoyant diapirs and even entrained into plumes. Key Words: Biofilms-Europa-Extraterrestrial life-Hydrothermal systems. Astrobiology 17, 1265-1273.

  14. Post-main-sequence Evolution of Icy Minor Planets. II. Water Retention and White Dwarf Pollution around Massive Progenitor Stars

    Energy Technology Data Exchange (ETDEWEB)

    Malamud, Uri; Perets, Hagai B., E-mail: uri.mal@tx.technion.ac.il, E-mail: hperets@physics.technion.ac.il [Department of Physics, Technion (Israel)

    2017-06-10

    Most studies suggest that the pollution of white dwarf (WD) atmospheres arises from the accretion of minor planets, but the exact properties of polluting material, and in particular the evidence for water in some cases, are not yet understood. Here we study the water retention of small icy bodies in exo-solar planetary systems, as their respective host stars evolve through and off the main sequence and eventually become WDs. We explore, for the first time, a wide range of star masses and metallicities. We find that the mass of the WD progenitor star is of crucial importance for the retention of water, while its metallicity is relatively unimportant. We predict that minor planets around lower-mass WD progenitors would generally retain more water and would do so at closer distances from the WD than compared with high-mass progenitors. The dependence of water retention on progenitor mass and other parameters has direct implications for the origin of observed WD pollution, and we discuss how our results and predictions might be tested in the future as more observations of WDs with long cooling ages become available.

  15. The Possible Emergence of Life and Differentiation of a Shallow Biosphere on Irradiated Icy Worlds: The Example of Europa

    Science.gov (United States)

    Russell, Michael J.; Murray, Alison E.; Hand, Kevin P.

    2017-12-01

    Irradiated ice-covered ocean worlds with rocky mafic mantles may provide the conditions needed to drive the emergence and maintenance of life. Alkaline hydrothermal springs - relieving the geophysical, thermal, and chemical disequilibria between oceans and tidally stressed crusts - could generate inorganic barriers to the otherwise uncontrolled and kinetically disfavored oxidation of hydrothermal hydrogen and methane. Ionic gradients imposed across these inorganic barriers, comprising iron oxyhydroxides and sulfides, could drive the hydrogenation of carbon dioxide and the oxidation of methane through thermodynamically favorable metabolic pathways leading to early life-forms. In such chemostatic environments, fuels may eventually outweigh oxidants. Ice-covered oceans are primarily heated from below, creating convection that could transport putative microbial cells and cellular cooperatives upward to congregate beneath an ice shell, potentially giving rise to a highly focused shallow biosphere. It is here where electron acceptors, ultimately derived from the irradiated surface, could be delivered to such life-forms through exchange with the icy surface. Such zones would act as "electron disposal units" for the biosphere, and occupants might be transferred toward the surface by buoyant diapirs and even entrained into plumes.

  16. Estrogenic effects of fusarielins in human breast cancer cell lines

    DEFF Research Database (Denmark)

    Søndergaard, Teis; Klitgaard, Louise Graabæk; Purup, Stig

    2012-01-01

    without the estrogen receptor-α and MCF-10a cells without estrogen receptors were not stimulated by fusarielins. Furthermore, the stimulation was prevented in MCF-7 cells when fusarielins were incubated in the presence of the estrogen receptor antagonist fulvestrant. These observations suggest...

  17. Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement.

    Science.gov (United States)

    Pritchard, K I; Gelmon, K A; Rayson, D; Provencher, L; Webster, M; McLeod, D; Verma, S

    2013-02-01

    Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

  18. Endocrine therapy for postmenopausal women with hormone receptor–positive her2–negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement

    Science.gov (United States)

    Pritchard, K.I.; Gelmon, K.A.; Rayson, D.; Provencher, L.; Webster, M.; McLeod, D.; Verma, S.

    2013-01-01

    Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2–) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients—efect, sofea, confirm, and bolero-2—have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2– advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient’s age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged. PMID:23443928

  19. Quantum chemical protocols for modeling reactions and spectra in astrophysical ice analogs: the challenging case of the C⁺ + H₂O reaction in icy grain mantles.

    Science.gov (United States)

    Woon, David E

    2015-11-21

    Icy grain mantles that accrete on refractory dust particles in the very cold interstellar medium or beyond the snow line in protoplanetary disks serve as minute incubators for heterogeneous chemistry. Ice mantle chemistry can differ significantly from the gas phase chemistry that occurs in these environments and is often richer. Modeling ices and their chemistry is a challenging task for quantum theoretical methods, but theory promises insight into these systems that is difficult to attain with experiments. Density functional theory (DFT) is predominately employed for modeling reactions in icy grain mantles due to its favorable scalability, but DFT has limitations that risk undercutting its reliability for this task. In this work, basic protocols are proposed for identifying the degree to which DFT methods are able to reproduce experimental or higher level theoretical results for the fundamental interactions upon which ice mantle chemistry depends, including both reactive interactions and non-reactive scaffolding interactions. The exemplar of this study is the reaction of C(+) with H2O, where substantial methodological differences are found in the prediction of gas phase relative energetics for stationary points (about 10 kcal mol(-1) for the C-O bond energy of the H2OC(+) intermediate), which in turn casts doubt about employing it to treat the C(+) + H2O reaction on an ice surface. However, careful explorations demonstrate that B3LYP with small correlation consistent basis sets performs in a sufficiently reliable manner to justify using it to identify plausible chemical pathways, where the dominant products were found to be neutral HOC and the CO(-) anion plus one and two H3O(+) cations, respectively. Predicted vibrational and electronic spectra are presented that would serve to verify or disconfirm the pathways; the latter were computed with time-dependent DFT. Conclusions are compared with those of a recent similar study by McBride and coworkers (J. Phys. Chem

  20. A new marine interstitial Psammogammarus (Crustacea, Amphipoda, Melitidae from Gura Ici Island, off western Halmahera (North Moluccas, Indonesia, and an overview of the genus

    Directory of Open Access Journals (Sweden)

    Ronald Vonk

    2011-09-01

    Full Text Available Psammogammarus wallacei sp. n. is described from the shallow marine interstitial of a sand and coral rubble beach on the Gura Ici islands (North Moluccas; Indonesia. This is the first record of this circum-tropical genus from SE Asia, with the geographically closest relative inhabiting the Ryukyu archipelago in Japan. The new species is highly distinctive by the display of sexual dimorphism on pleopod II, with the medial margin of the male proximal article of exopod provided with a comb of short, blunt curved spinules; no other representative of the genus is known to display sexually-dimorphic appendages aside of the gnathopods. The new species is also noteworthy by the outline of the palm margin of male gnathopod II, hardly excavated, and by showing a carpus broader than long. An overview of the genus Psammogammarus with 14 species to date is provided.

  1. Breast cancer cells can switch between estrogen receptor alpha and ErbB signaling and combined treatment against both signaling pathways postpones development of resistance

    DEFF Research Database (Denmark)

    Sonne-Hansen, Katrine; Norrie, Ida C; Emdal, Kristina Bennet

    2010-01-01

    circumvent development of resistance. Limited effects were observed when targeting EGFR and ErbB2 with the monoclonal antibodies cetuximab, trastuzumab, and pertuzumab, whereas the pan-ErbB inhibitor CI-1033 selectively inhibited growth of fulvestrant resistant cell lines. CI-1033 inhibited Erk but not Akt...

  2. Gonadal steroids differentially modulate neurotoxicity of HIV and cocaine: testosterone and ICI 182,780 sensitive mechanism

    Directory of Open Access Journals (Sweden)

    Mactutus Charles F

    2005-06-01

    Full Text Available Abstract Background HIV Associated Dementia (HAD is a common complication of human immunodeficiency virus (HIV infection that erodes the quality of life for patients and burdens health care providers. Intravenous drug use is a major route of HIV transmission, and drug use is associated with increased HAD. Specific proteins released as a consequence of HIV infection (e.g., gp120, the HIV envelope protein and Tat, the nuclear transactivating protein have been implicated in the pathogenesis of HAD. In primary cultures of human fetal brain tissue, subtoxic doses of gp120 and Tat are capable of interacting with a physiologically relevant dose of cocaine, to produce a significant synergistic neurotoxicity. Using this model system, the neuroprotective potential of gonadal steroids was investigated. Results 17β-Estradiol (17β-E2, but not 17α-estradiol (17α-E2, was protective against this combined neurotoxicity. Progesterone (PROG afforded limited neuroprotection, as did dihydrotestosterone (DHT. The efficacy of 5α-testosterone (T-mediated neuroprotection was robust, similar to that provided by 17β-E2. In the presence of the specific estrogen receptor (ER antagonist, ICI-182,780, T's neuroprotection was completely blocked. Thus, T acts through the ER to provide neuroprotection against HIV proteins and cocaine. Interestingly, cholesterol also demonstrated concentration-dependent neuroprotection, possibly attributable to cholesterol's serving as a steroid hormone precursor in neurons. Conclusion Collectively, the present data indicate that cocaine has a robust interaction with the HIV proteins gp120 and Tat that produces severe neurotoxicity, and this toxicity can be blocked through pretreatment with ER agonists.

  3. One-Dimensional Convective Thermal Evolution Calculation Using a Modified Mixing Length Theory: Application to Saturnian Icy Satellites

    Science.gov (United States)

    Kamata, Shunichi

    2018-01-01

    Solid-state thermal convection plays a major role in the thermal evolution of solid planetary bodies. Solving the equation system for thermal evolution considering convection requires 2-D or 3-D modeling, resulting in large calculation costs. A 1-D calculation scheme based on mixing length theory (MLT) requires a much lower calculation cost and is suitable for parameter studies. A major concern for the MLT scheme is its accuracy due to a lack of detailed comparisons with higher dimensional schemes. In this study, I quantify its accuracy via comparisons of thermal profiles obtained by 1-D MLT and 3-D numerical schemes. To improve the accuracy, I propose a new definition of the mixing length (l), which is a parameter controlling the efficiency of heat transportation due to convection, for a bottom-heated convective layer. Adopting this new definition of l, I investigate the thermal evolution of Saturnian icy satellites, Dione and Enceladus, under a wide variety of parameter conditions. Calculation results indicate that each satellite requires several tens of GW of heat to possess a thick global subsurface ocean suggested from geophysical analyses. Dynamical tides may be able to account for such an amount of heat, though the reference viscosity of Dione's ice and the ammonia content of Dione's ocean need to be very high. Otherwise, a thick global ocean in Dione cannot be maintained, implying that its shell is not in a minimum stress state.

  4. A Submersible, Off-Axis Holographic Microscope for Detection of Microbial Motility and Morphology in Aqueous and Icy Environments.

    Science.gov (United States)

    Lindensmith, Christian A; Rider, Stephanie; Bedrossian, Manuel; Wallace, J Kent; Serabyn, Eugene; Showalter, G Max; Deming, Jody W; Nadeau, Jay L

    2016-01-01

    Sea ice is an analog environment for several of astrobiology's near-term targets: Mars, Europa, Enceladus, and perhaps other Jovian or Saturnian moons. Microorganisms, both eukaryotic and prokaryotic, remain active within brine channels inside the ice, making it unnecessary to penetrate through to liquid water below in order to detect life. We have developed a submersible digital holographic microscope (DHM) that is capable of resolving individual bacterial cells, and demonstrated its utility for immediately imaging samples taken directly from sea ice at several locations near Nuuk, Greenland. In all samples, the appearance and motility of eukaryotes were conclusive signs of life. The appearance of prokaryotic cells alone was not sufficient to confirm life, but when prokaryotic motility occurred, it was rapid and conclusive. Warming the samples to above-freezing temperatures or supplementing with serine increased the number of motile cells and the speed of motility; supplementing with serine also stimulated chemotaxis. These results show that DHM is a useful technique for detection of active organisms in extreme environments, and that motility may be used as a biosignature in the liquid brines that persist in ice. These findings have important implications for the design of missions to icy environments and suggest ways in which DHM imaging may be integrated with chemical life-detection suites in order to create more conclusive life detection packages.

  5. Male bladder outlet obstruction: Time to re-evaluate the definition and reconsider our diagnostic pathway? ICI-RS 2015.

    Science.gov (United States)

    Rademakers, Kevin; Drake, Marcus J; Gammie, Andrew; Djurhuus, Jens C; Rosier, Peter F W M; Abrams, Paul; Harding, Christopher

    2017-04-01

    The diagnosis of bladder outlet obstruction (BOO) in the male is dependent on measurements of pressure and flow made during urodynamic studies. The procedure of urodynamics and the indices used to delineate BOO are well standardized largely as a result of the work of the International Continence Society. The clinical utility of the diagnosis of BOO is however, less well defined and there are several shortcomings and gaps in the currently available medical literature. Consequently the International Consultation on Incontinence Research Society (ICI-RS) held a think tank session in 2015 entitled "Male bladder outlet obstruction: Time to re-evaluate the definition and reconsider our diagnostic pathway?" This manuscript details the discussions that took place within that think tank setting out the pros and cons of the current definition of BOO and exploring alternative clinical tests (alone or in combination) which may be useful in the future investigation of male patients with lower urinary tract symptoms. The think tank panel concluded that pressure-flow studies remain the diagnostic gold-standard for BOO although there is still a lack of high quality evidence. Newer, less invasive, investigations have shown promise in terms of diagnostic accuracy for BOO but similar criticisms can be levelled against these tests. Therefore, the think tank suggests further research with regard to these alternative indicators to determine their clinical utility. © 2017 Wiley Periodicals, Inc.

  6. A Submersible, Off-Axis Holographic Microscope for Detection of Microbial Motility and Morphology in Aqueous and Icy Environments.

    Directory of Open Access Journals (Sweden)

    Christian A Lindensmith

    Full Text Available Sea ice is an analog environment for several of astrobiology's near-term targets: Mars, Europa, Enceladus, and perhaps other Jovian or Saturnian moons. Microorganisms, both eukaryotic and prokaryotic, remain active within brine channels inside the ice, making it unnecessary to penetrate through to liquid water below in order to detect life. We have developed a submersible digital holographic microscope (DHM that is capable of resolving individual bacterial cells, and demonstrated its utility for immediately imaging samples taken directly from sea ice at several locations near Nuuk, Greenland. In all samples, the appearance and motility of eukaryotes were conclusive signs of life. The appearance of prokaryotic cells alone was not sufficient to confirm life, but when prokaryotic motility occurred, it was rapid and conclusive. Warming the samples to above-freezing temperatures or supplementing with serine increased the number of motile cells and the speed of motility; supplementing with serine also stimulated chemotaxis. These results show that DHM is a useful technique for detection of active organisms in extreme environments, and that motility may be used as a biosignature in the liquid brines that persist in ice. These findings have important implications for the design of missions to icy environments and suggest ways in which DHM imaging may be integrated with chemical life-detection suites in order to create more conclusive life detection packages.

  7. COAGULATION CALCULATIONS OF ICY PLANET FORMATION AT 15-150 AU: A CORRELATION BETWEEN THE MAXIMUM RADIUS AND THE SLOPE OF THE SIZE DISTRIBUTION FOR TRANS-NEPTUNIAN OBJECTS

    Energy Technology Data Exchange (ETDEWEB)

    Kenyon, Scott J. [Smithsonian Astrophysical Observatory, 60 Garden Street, Cambridge, MA 02138 (United States); Bromley, Benjamin C., E-mail: skenyon@cfa.harvard.edu, E-mail: bromley@physics.utah.edu [Department of Physics, University of Utah, 201 JFB, Salt Lake City, UT 84112 (United States)

    2012-03-15

    We investigate whether coagulation models of planet formation can explain the observed size distributions of trans-Neptunian objects (TNOs). Analyzing published and new calculations, we demonstrate robust relations between the size of the largest object and the slope of the size distribution for sizes 0.1 km and larger. These relations yield clear, testable predictions for TNOs and other icy objects throughout the solar system. Applying our results to existing observations, we show that a broad range of initial disk masses, planetesimal sizes, and fragmentation parameters can explain the data. Adding dynamical constraints on the initial semimajor axis of 'hot' Kuiper Belt objects along with probable TNO formation times of 10-700 Myr restricts the viable models to those with a massive disk composed of relatively small (1-10 km) planetesimals.

  8. Main Power Distribution Unit for the Jupiter Icy Moons Orbiter (JIMO)

    Science.gov (United States)

    Papa, Melissa R.

    2004-01-01

    Around the year 2011, the Jupiter Icy Moons Orbiter (JIMO) will be launched and on its way to orbit three of Jupiter s planet-sized moons. The mission goals for the JIMO project revolve heavily around gathering scientific data concerning ingredients we, as humans, consider essential: water, energy and necessary chemical elements. The JIM0 is an ambitious mission which will implore propulsion from an ION thruster powered by a nuclear fission reactor. Glenn Research Center is responsible for the development of the dynamic power conversion, power management and distribution, heat rejection and ION thrusters. The first test phase for the JIM0 program concerns the High Power AC Power Management and Distribution (PMAD) Test Bed. The goal of this testing is to support electrical performance verification of the power systems. The test bed will incorporate a 2kW Brayton Rotating Unit (BRU) to simulate the nuclear reactor as well as two ION thrusters. The first module of the PMAD Test Bed to be designed is the Main Power Distribution Unit (MPDU) which relays the power input to the various propulsion systems and scientific instruments. The MPDU involves circuitry design as well as mechanical design to determine the placement of the components. The MPDU consists of fourteen relays of four different variations used to convert the input power into the appropriate power output. The three phase system uses 400 Vo1ts(sub L-L) rms at 1000 Hertz. The power is relayed through the circuit and distributed to the scientific instruments, the ION thrusters and other controlled systems. The mechanical design requires the components to be positioned for easy electrical wiring as well as allowing adequate room for the main buss bars, individual circuit boards connected to each component and power supplies. To accomplish creating a suitable design, AutoCAD was used as a drafting tool. By showing a visual layout of the components, it is easy to see where there is extra room or where the

  9. H-atmospheres of Icy Super-Earths Formed In Situ in the Outer Solar System: An Application to a Possible Planet Nine

    Science.gov (United States)

    Levi, A.; Kenyon, S. J.; Podolak, M.; Prialnik, D.

    2017-04-01

    We examine the possibility that icy super-Earth mass planets, formed over long timescales (0.1-1 Gyr) at large distances (˜200-1000 au) from their host stars, will develop massive H-rich atmospheres. Within the interior of these planets, high pressure converts CH4 into ethane, butane, or diamond and releases H2. Using simplified models that capture the basic physics of the internal structure, we show that the physical properties of the atmosphere depend on the outflux of H2 from the mantle. When this outflux is ≲ {10}10 molec cm-2 s-1, the outgassed atmosphere has a base pressure of ≲1 bar. Larger outflows result in a substantial atmosphere where the base pressure may approach 103-104 bar. For any pressure, the mean density of these planets, 2.4-3 g cm-3, is much larger than the mean density of Uranus and Neptune, 1.3-1.6 g cm-3. Thus, observations can distinguish between a Planet Nine with a primordial H/He-rich atmosphere accreted from the protosolar nebula and one with an atmosphere outgassed from the core.

  10. Assay of Calcium Transients and Synapses in Rat Hippocampal Neurons by Kinetic Image Cytometry and High-Content Analysis: An In Vitro Model System for Postchemotherapy Cognitive Impairment.

    Science.gov (United States)

    McDonough, Patrick M; Prigozhina, Natalie L; Basa, Ranor C B; Price, Jeffrey H

    2017-07-01

    Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days. Kinetic Image Cytometry™ (KIC™) methods were developed to quantify spontaneously occurring intracellular calcium transients representing the activity of the neurons, and high-content analysis (HCA) methods were developed to quantify the expression, colocalization, and puncta formed by synaptic proteins (postsynaptic density protein-95 [PSD-95] and presynaptic protein Synapsin-1 [Syn-1]). As quantified by KIC, FSK increased the occurrence and synchronization of the calcium transients indicating stimulatory effects on RHN activity, whereas TAM had inhibitory effects. As quantified by HCA, FSK also increased PSD-95 puncta and PSD-95:Syn-1 colocalization, whereas ES increased the puncta of both PSD-95 and Syn-1 with little effect on colocalization. The estrogen receptor antagonist FUL also increased PSD-95 puncta. In contrast, TAM reduced Syn-1 and PSD-95:Syn-1 colocalization, consistent with its inhibitory effects on the calcium transients. Thus TAM reduced activity and synapse formation by the RHNs, which may relate to the ability of this agent to cause PCCI. The results illustrate that KIC and HCA can be used to quantify neurotoxic and neuroprotective effects of chemicals in RHNs to investigate mechanisms and potential therapeutics for PCCI.

  11. Effect of in-core instrumentation mounting location on external reactor vessel cooling

    International Nuclear Information System (INIS)

    Suh, Jungsoo; Ha, Huiun

    2017-01-01

    Highlights: • Numerical simulations were conducted for the evaluation of an IVR-ERVC application. • The ULPU-V experiment was simulated for the validation of numerical method. • The effect of ICI mounting location on an IVR-ERVC application was investigated. • TM-ICI is founded to be superior to BM-ICI for successful application of IVR-ERVC. - Abstract: The effect of in-core instrumentation (ICI) mounting location on the application of in-vessel corium retention through external reactor vessel cooling (IVR-ERVC), used to mitigate severe accidents in which the nuclear fuel inside the reactor vessel becomes molten, was investigated. Numerical simulations of the subcooled boiling flow within an advanced pressurized-water reactor (PWR) in IVR-ERVC applications were conducted for the cases of top-mounted ICI (TM-ICI) and bottom-mounted ICI (BM-ICI), using the commercially available computational fluid dynamics (CFD) software ANSYS-CFX. Shear stress transport (SST) and the RPI model were used for turbulence closure and subcooled flow boiling, respectively. To validate the numerical method for IVR applications, numerical simulations of ULPU-V experiments were also conducted. The BM-ICI reactor vessel was modeled using a simplified design of an advanced PWR with BM-ICI; the TM-ICI counterpart was modeled by removing the ICI parts from the original geometry. It was found that TM-ICI was superior to BM-ICI for successful application of IVR-ERVC. For the BM-ICI case, the flow field was complicated because of the existence of ICIs and a significant temperature gradient was observed near the ICI nozzles on the lower part of the reactor vessel, where the ICIs were attached. These observations suggest that the existence of ICI below the reactor vessel hinders reactor vessel cooling.

  12. National assessment of shoreline change—Summary statistics for updated vector shorelines and associated shoreline change data for the north coast of Alaska, U.S.-Canadian Border to Icy Cape

    Science.gov (United States)

    Gibbs, Ann E.; Richmond, Bruce M.

    2017-09-25

    Long-term rates of shoreline change for the north coast of Alaska, from the U.S.-Canadian border to the Icy Cape region of northern Alaska, have been updated as part of the U.S. Geological Survey’s National Assessment of Shoreline Change Project. Short-term shoreline change rates are reported for the first time. Additional shoreline position data were used to compute rates where the previous rate-of-change assessment only included two shoreline positions at a given location. The calculation of uncertainty associated with the long-term average rates has also been updated to match refined methods used in other study regions of the National Assessment of Shoreline Change Project. The average rates of this report have a reduced amount of uncertainty compared to those presented in the first assessment for this region.

  13. A Phase I/Ib Study of Enzalutamide Alone and in Combination with Endocrine Therapies in Women with Advanced Breast Cancer.

    Science.gov (United States)

    Schwartzberg, Lee S; Yardley, Denise A; Elias, Anthony D; Patel, Manish; LoRusso, Patricia; Burris, Howard A; Gucalp, Ayca; Peterson, Amy C; Blaney, Martha E; Steinberg, Joyce L; Gibbons, Jacqueline A; Traina, Tiffany A

    2017-08-01

    Purpose: Several lines of evidence support targeting the androgen signaling pathway in breast cancer. Enzalutamide is a potent inhibitor of androgen receptor signaling. Preclinical data in estrogen-expressing breast cancer models demonstrated activity of enzalutamide monotherapy and enhanced activity when combined with various endocrine therapies (ET). Enzalutamide is a strong cytochrome P450 3A4 (CYP3A4) inducer, and ETs are commonly metabolized by CYP3A4. The pharmacokinetic (PK) interactions, safety, and tolerability of enzalutamide monotherapy and in combination with ETs were assessed in this phase I/Ib study. Experimental Design: Enzalutamide monotherapy was assessed in dose-escalation and dose-expansion cohorts of patients with advanced breast cancer. Additional cohorts examined effects of enzalutamide on anastrozole, exemestane, and fulvestrant PK in patients with estrogen receptor-positive/progesterone receptor-positive (ER + /PgR + ) breast cancer. Results: Enzalutamide monotherapy ( n = 29) or in combination with ETs ( n = 70) was generally well tolerated. Enzalutamide PK in women was similar to prior data on PK in men with prostate cancer. Enzalutamide decreased plasma exposure to anastrozole by approximately 90% and exemestane by approximately 50%. Enzalutamide did not significantly affect fulvestrant PK. Exposure of exemestane 50 mg/day given with enzalutamide was similar to exemestane 25 mg/day alone. Conclusions: These results support a 160 mg/day enzalutamide dose in women with breast cancer. Enzalutamide can be given in combination with fulvestrant without dose modifications. Exemestane should be doubled from 25 mg/day to 50 mg/day when given in combination with enzalutamide; this combination is being investigated in a randomized phase II study in patients with ER + /PgR + breast cancer. Clin Cancer Res; 23(15); 4046-54. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. Development of cell-cycle checkpoint therapy for solid tumors.

    Science.gov (United States)

    Tamura, Kenji

    2015-12-01

    Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Inherited chromosomally integrated human herpesvirus 6 as a predisposing risk factor for the development of angina pectoris.

    Science.gov (United States)

    Gravel, Annie; Dubuc, Isabelle; Morissette, Guillaume; Sedlak, Ruth H; Jerome, Keith R; Flamand, Louis

    2015-06-30

    Inherited chromosomally integrated human herpesvirus-6 (iciHHV-6) results in the germ-line transmission of the HHV-6 genome. Every somatic cell of iciHHV-6+ individuals contains the HHV-6 genome integrated in the telomere of chromosomes. Whether having iciHHV-6 predisposes humans to diseases remains undefined. DNA from 19,597 participants between 40 and 69 years of age were analyzed by quantitative PCR (qPCR) for the presence of iciHHV-6. Telomere lengths were determined by qPCR. Medical records, hematological, biochemical, and anthropometric measurements and telomere lengths were compared between iciHHV-6+ and iciHHV-6- subjects. The prevalence of iciHHV-6 was 0.58%. Two-way ANOVA with a Holm-Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on continuous outcomes. Two-way logistic regression with a Holm-Bonferroni correction was used to determine the effects of iciHHV6, sex, and their interaction on disease prevalence. Of 50 diseases monitored, a single one, angina pectoris, is significantly elevated (3.3×) in iciHHV-6+ individuals relative to iciHHV-6- subjects (P = 0.017; 95% CI, 1.73-6.35). When adjusted for potential confounding factors (age, body mass index, percent body fat, and systolic blood pressure), the prevalence of angina remained three times greater in iciHHV-6+ subjects (P = 0.015; 95%CI, 1.23-7.15). Analyses of telomere lengths between iciHHV-6- without angina, iciHHV-6- with angina, and iciHHV-6+ with angina indicate that iciHHV-6+ with angina have shorter telomeres than age-matched iciHHV-6- subjects (P = 0.006). Our study represents, to our knowledge, the first large-scale analysis of disease association with iciHHV-6. Our results are consistent with iciHHV-6 representing a risk factor for the development of angina.

  16. Estrogen regulates estrogen receptors and antioxidant gene expression in mouse skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Kristen A Baltgalvis

    Full Text Available BACKGROUND: Estrogens are associated with the loss of skeletal muscle strength in women with age. Ovarian hormone removal by ovariectomy in mice leads to a loss of muscle strength, which is reversed with 17beta-estradiol replacement. Aging is also associated with an increase in antioxidant stress, and estrogens can improve antioxidant status via their interaction with estrogen receptors (ER to regulate antioxidant gene expression. The purpose of this study was to determine if ER and antioxidant gene expression in skeletal muscle are responsive to changes in circulating estradiol, and if ERs regulate antioxidant gene expression in this tissue. METHODOLOGY/PRINCIPAL FINDINGS: Adult C57BL/6 mice underwent ovariectomies or sham surgeries to remove circulating estrogens. These mice were implanted with placebo or 17beta-estradiol pellets acutely or chronically. A separate experiment examined mice that received weekly injections of Faslodex to chronically block ERs. Skeletal muscles were analyzed for expression of ER genes and proteins and antioxidant genes. ERalpha was the most abundant, followed by Gper and ERbeta in both soleus and EDL muscles. The loss of estrogens through ovariectomy induced ERalpha gene and protein expression in the soleus, EDL, and TA muscles at both the acute and chronic time points. Gpx3 mRNA was also induced both acutely and chronically in all 3 muscles in mice receiving 17beta-estradiol. When ERs were blocked using Faslodex, Gpx3 mRNA was downregulated in the soleus muscle, but not the EDL and TA muscles. CONCLUSIONS/SIGNIFICANCE: These data suggest that Gpx3 and ERalpha gene expression are sensitive to circulating estrogens in skeletal muscle. ERs may regulate Gpx3 gene expression in the soleus muscle, but skeletal muscle regulation of Gpx3 via ERs is dependent upon muscle type. Further work is needed to determine the indirect effects of estrogen and ERalpha on Gpx3 expression in skeletal muscle, and their importance in the

  17. Descent Without Modification? The Thermal Chemistry of H2O2 on Europa and Other Icy Worlds

    Science.gov (United States)

    Loeffler, Mark Josiah; Hudson, Reggie Lester

    2015-01-01

    The strong oxidant H2O2 is known to exist in solid form on Europa and is suspected to exist on several other Solar System worlds at temperatures below 200 K. However, little is known of the thermal chemistry that H2O2 might induce under these conditions. Here, we report new laboratory results on the reactivity of solid H2O2 with eight different compounds in H2O-rich ices. Using infrared spectroscopy, we monitored compositional changes in ice mixtures during warming. The compounds CH4 (methane), C3H4 (propyne), CH3OH (methanol), and CH3CN (acetonitrile) were unaltered by the presence of H2O2 in ices, showing that exposure to either solid H2O2 or frozen H2O+H2O2 at cryogenic temperatures will not oxidize these organics, much less convert them to CO2. This contrasts strongly with the much greater reactivity of organics with H2O2 at higher temperatures, and particularly in the liquid and gas phases. Of the four inorganic compounds studied, CO, H2S, NH3, and SO2, only the last two reacted in ices containing H2O2, NH3 making NHþ 4 and SO2 making SO2 4 by H+ and e - transfer, respectively. An important astrobiological conclusion is that formation of surface H2O2 on Europa and that molecule's downward movement with H2O-ice do not necessarily mean that all organics encountered in icy subsurface regions will be destroyed by H2O2 oxidation.

  18. Development and Testing of a Laser-Powered Cryobot for Outer Planet Icy Moon Exploration

    Science.gov (United States)

    Siegel, V.; Stone, W.; Hogan, B.; Lelievre, S.; Flesher, C.

    2013-12-01

    Project VALKYRIE (Very-deep Autonomous Laser-powered Kilowatt-class Yo-yoing Robotic Ice Explorer) is a NASA-funded effort to develop the first laser powered cryobot - a self-contained intelligent ice penetrator capable of delivering science payloads through ice caps of the outer planet icy moons. The long range objective is to enable a full-scale Europa lander mission in which an autonomous life-searching underwater vehicle is transported by the cryobot and launched into the sub-surface Europan ocean. Mission readiness testing will involve an Antarctic sub-glacial lake cryobot sample return through kilometers of ice cap thickness. A key element of VALKYRIE's design is the use of a high energy laser as the primary power source. 1070 nm laser light is transmitted at a power level of 5 kW from a surface-based laser and injected into a custom-designed optical waveguide that is spooled out from the descending cryobot. Light exits the downstream end of the fiber, travels through diverging optics, and strikes a beam dump, which channels thermal power to hot water jets that melt the descent hole. Some beam energy is converted, via photovoltaic cells, to electricity for running onboard electronics and jet pumps. Since the vehicle can be sterilized prior to deployment and the melt path freezes behind it, preventing forward contamination, expansions on VALKYRIE concepts may enable cleaner and faster access to sub-glacial Antarctic lakes. Testing at Stone Aerospace between 2010 and 2013 has already demonstrated high power optical energy transfer over relevant (kilometer scale) distances as well as the feasibility of a vehicle-deployed optical waveguide (through which the power is transferred). The test vehicle is equipped with a forward-looking synthetic aperture radar (SAR) that can detect obstacles out to 1 kilometer from the vehicle. The initial ASTEP test vehicle will carry a science payload consisting of a DUV flow cytometer and a water sampling sub-system that will be

  19. Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30) in lung cancer

    International Nuclear Information System (INIS)

    Jala, Venkatakrishna Rao; Radde, Brandie N; Haribabu, Bodduluri; Klinge, Carolyn M

    2012-01-01

    G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17β-estradiol (E 2 ), tamoxifen, and ICI 182,780 (fulvestrant) and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors α and β (ERα and ERβ), the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer. The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels), Western blot and immunohistochemistry (IHC) methods (at protein levels). The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues) were performed. Analysis by real-time PCR and Western blotting revealed a significantly higher expression of GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC) lines relative to immortalized normal lung bronchial epithelial cells (HBECs). The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue. The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression

  20. THE EFFECTS OF CRACKING ON THE SURFACE POTENTIAL OF ICY GRAINS IN SATURN’S E-RING: LABORATORY STUDIES

    Energy Technology Data Exchange (ETDEWEB)

    Bu, Caixia; Bahr, David A.; Dukes, Catherine A.; Baragiola, Raúl A., E-mail: cb8nw@virginia.edu [Laboratory for Astrophysics and Surface Physics, Materials Science and Engineering, University of Virginia, Charlottesville, VA 22904 (United States)

    2016-07-10

    Within Saturn's E-ring, dust grains are coated by water vapor co-released with ice grains from the geyser-like eruptions of Enceladus. These ice-coated grains have intrinsic surface potential and interact synergistically with the ions and electrons of Saturn's magnetospheric plasmas. We perform laboratory experiments to investigate the effects of water-ice growth on the surface potential, using amorphous solid water (ASW) films. We estimate the growth of the surface potential to be ∼ 2.5 mV (Earth) yr{sup 1} and 112 mV yr{sup 1} for E-ring grains at ∼4.5 R {sub s} and 3.95 R {sub s} outside Enceladus’s plume, respectively. In addition, our measurements show that the linear relationship between the surface potential and the film thickness, as described in previous studies, has an upper limit, where the film spontaneously cracks above a porosity-dependent critical thickness. Heating of the cracked films with (and without) deposited charge shows that significant positive (and negative) surface potentials are retained at temperatures above 110 K, contrary to the minimal values (roughly zero) for thin, transparent ASW films. The significant surface potentials observed on micron-scale cracked ice films after thermal cycling, (5–20) V, are consistent with Cassini measurements, which indicate a negative charge of up to 5 V for E-ring dust particles at ∼5 R {sub s}. Therefore, the native grain surface potential resulting from water-vapor coating must be included in modeling studies of interactions between E-ring icy surfaces and Saturn's magnetospheric plasma.

  1. "Balancing on Skates on the Icy Surface of Work": a metasynthesis of work participation for persons with psychiatric disabilities.

    Science.gov (United States)

    Kinn, Liv Grethe; Holgersen, Helge; Aas, Randi W; Davidson, Larry

    2014-03-01

    To explore how persons with psychiatric disabilities experience facilitators of and barriers to participation in paid work in transitional, supported, and open employment settings, in order to provide guidance for efforts to attract and retain these persons in gainful employment as a key dimension of recovery and community life. A metasynthesis was conducted using 16 qualitative studies published between 1990 and 2011. Ten themes, two phases, and an overarching metaphor were identified. The first five themes describe facilitators of and impediments to getting a job (getting off the bench): (1) fighting inertia; (2) taking control; (3) encouraging peers; (4) disruptions related to the illness; (5) lack of opportunities and supports. The next five themes represent facilitators of and impediments to working (skating on the ice); (6) going mainstream; (7) social cohesion; (8) clarity in role and responsibilities; (9) environmental factors; (10) managing self-disclosure. We chose as our overarching metaphor "Balancing on Skates on the Icy Surface of Work," as we view both iceskaters and workers with psychiatric disabilities as needing to achieve and maintain their balance while being "on the edge" between various extremities. We have shown that, for persons with psychiatric disabilities to "get off the bench" and "onto the ice" of employment, they may need to be supported in finding and maintaining their balance in new situations through a combination of learning new skills and competencies (learning how to skate) while receiving in vivo assistance from empathic and knowledgeable supporters (being coached while on the ice).

  2. How does lower urinary tract dysfunction (LUTD) affect sexual function in men and women? ICI-RS 2015-Part 2.

    Science.gov (United States)

    Apostolidis, Apostolos; Rantell, Angie; Anding, Ralf; Kirschner-Hermanns, Ruth; Cardozo, Linda

    2017-04-01

    To discuss available data on the links between LUTD and sexual dysfunction, what is still unknown about the causative effect of disease processes on sexual function (SF), and to suggest proposals for further research. At the 2015 International Consultation on Incontinence-Research Society (ICI-RS), a multi-disciplinary group presented a literature search of what is known about the effect of LUTD on SF in men and women. Wider discussions regarding knowledge gaps, and ideal research methodology ensued and are presented. The underlying mechanisms of the impact of LUTD on SF remain largely unknown. Risk factors for the metabolic syndrome may cause both LUTS and ED in men, and their improvement may improve both conditions. In women, neurovascular changes may be common in LUTD and FSD. Successful LUTS management results in FSD improvement, but the mechanisms are ill understood. Gaps in standardization of sexual dysfunction terminology, variations of assessment, and treatment in clinical practice and research make most studies not comparable. The sensitive knowledge and subjective nature of the problem present challenges and often result in neglecting it. Neurovascular and hormonal factors, but also indirect effects may link LUTD to SD in both sexes, but the evidence is not robust and the mechanisms unclear. There is a need for defining the terminology and standardizing outcomes assessed in clinical trials. The multifactorial nature of SF in both sexes makes trial design challenging and "real world" studies may prove more beneficial for patients' outcomes and clinicians' understanding. © 2017 Wiley Periodicals, Inc.

  3. Evaluation of I and C architecture alternatives required for the jupiter Icy moons orbiter (JIMO) reactor

    International Nuclear Information System (INIS)

    Muhlheim, M. D.; Wood, R. T.; Bryan, W. L.; Wilson Jr, T. L.; Holcomb, D. E.; Korsah, K.; Jagadish, U.

    2006-01-01

    This paper discusses alternative architectural considerations for instrumentation and control (I and C) systems in high-reliability applications to support remote, autonomous, inaccessible nuclear reactors, such as a space nuclear power plant (SNPP) for mission electrical power and space exploration propulsion. This work supported the pre-conceptual design of the reactor control system for the Jupiter Icy Moons Orbiter (JIMO) mission. Long-term continuous operation without intermediate maintenance cycles forces consideration of alternatives to commonly used active, N-multiple redundancy techniques for high-availability systems. Long space missions, where mission duration can exceed the 50% reliability limit of constituent components, can make active, N-multiple redundant systems less reliable than simplex systems. To extend a control system lifetime beyond the 50% reliability limits requires incorporation of passive redundancy of functions. Time-dependent availability requirements must be factored into the use of combinations of active and passive redundancy techniques for different mission phases. Over the course of a 12 to 20-year mission, reactor control, power conversion, and thermal management system components may fail, and the I and C system must react and adjust to accommodate these failures and protect non-failed components to continue the mission. This requires architectural considerations to accommodate partial system failures and to adapt to multiple control schemes according to the state of non-failed components without going through a complete shutdown and restart cycle. Relevant SNPP I and C architecture examples provide insights into real-time fault tolerance and long-term reliability and availability beyond time periods normally associated with terrestrial power reactor I and C systems operating cycles. I and C architectures from aerospace systems provide examples of highly reliable and available control systems associated with short- and long

  4. ERR Gamma: Does an Orphan Nuclear Receptor Link Steroid Hormone Biogenesis to Endocrine Resistance?

    Science.gov (United States)

    2007-09-01

    the mammary gland develops normally until puberty. However, several abnormalities are apparent during pregnancy and lactation, including incomplete...contribute to the protection conferred by pregnancy and lactation against breast cancer. Several reports describe a loss of ERb during car- cinogenesis (for...fulvestrant as antagonists, it has been shown that ERb can uti - lize these compounds as agonists when associated R.B. Riggins et al. / Cancer Letters

  5. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Boér K

    2016-10-01

    Full Text Available Katalin Boér Department of Medical Oncology, Szent Margit Hospital, Budapest, Hungary Abstract: Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years. In 2012, a new molecularly targeted therapeutic strategy, inhibition of mammalian target of rapamycin with everolimus, was introduced into clinical practice. Everolimus, in combination with a steroidal aromatase inhibitor, exemestane, resulted in an increase in progression-free survival, but not overall survival in patients with estrogen receptor (ER+ve advanced disease who had progressed on hormone therapy. In 2015, the first cyclin-dependent kinases 4/6 (CDK4/6 inhibitor, palbociclib, received accelerated US Food and Drug Administration approval for use in combination with letrozole for the treatment of postmenopausal ER+ve/HER2-ve advanced breast cancer as initial, endocrine-based therapy. The addition of palbociclib to endocrine therapy resulted in longer progression-free survival than letrozole alone. One year later, palbociclib received a new indication, use in combination with fulvestrant, in both premenopausal and postmenopausal females with advanced breast cancer of the same subtype with disease progression following endocrine therapy. Adding palbociclib to fulvestrant resulted in a significantly increased median progression-free survival compared to fulvestrant

  6. Seçici Özellikteki Farklı Besiyerlerinin bazı Mayaların Meyveli Yoğurttan Geri Kazanımları Amacı ile Karşılaştırılmaları (İngilizce)

    OpenAIRE

    Şule Şenses Ergül; Z. Yeşim Özbaş

    2015-01-01

    Bu çalışmada, yapay olarak aşılanan meyveli yoğurt örneklerinden bazı mayaların izolasyonu için kullanılabilecek farklı besiyerleri karşılaştırılmıştır. Bu amaçla, kontrol besiyeri olarak malt extract agar ve beş farklı seçici besiyeri kullanılmıştır. Bu besiyerleri; malt extract yeast extract %50 fructose glucose agar, malt extract yeast extract %40 sucrose agar, malt extract yeast extract glucose %0.8 peptone agar, malt extract yeast extract glucose %0.1 peptone agar and potato dextrose %50...

  7. Progesterone receptor modulators in breast cancer

    OpenAIRE

    WIEHLE, Ronald D.

    2015-01-01

    Breast cancer has been treated successfully with selective estrogen receptor antagonists (SERMs) such as tamoxifen, receptor-depleting agents such as fulvestrant, and aromatase inhibitors such as anastrozole. Selective progesterone receptor modulators (SPRMs or PRMs) have not been studied as much and are currently under investigation for inhibition of mammary carcinogenesis in animal models and breast cancer prevention trials in women. They might follow tamoxifen and aromatase inhibitors in t...

  8. Slush Fund: The Multiphase Nature of Oceanic Ices and Its Role in Shaping Europa's Icy Shell

    Science.gov (United States)

    Buffo, J.; Schmidt, B. E.; Huber, C.

    2017-12-01

    shell thickness, and ocean-surface interaction rates. Moreover, this work aims to shed light on the important role microscale physics plays in determining the macroscale properties of icy worlds by highlighting and adapting successful multiphase reactive transport sea ice models utilized in large scale Earth systems science simulations.

  9. Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer.

    Science.gov (United States)

    Kim, Esther S; Scott, Lesley J

    2017-06-01

    Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates. Neutropenia was the most commonly reported any-grade and grade ≥ 3 adverse event. It was infrequently associated with febrile neutropenia (<2%) and generally manageable with a palbociclib dose delay, interruption or reduction, without the routine use of growth factors, and without affecting efficacy. In conclusion, oral palbociclib combination therapy is a valuable emerging option for use in patients with HR-positive, HER2-negative advanced or metastatic breast cancer.

  10. Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    BACKGROUND: Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women. METHODS: Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically. RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.

  11. Outcomes of hematopoietic cell transplantation using donors or recipients with inherited chromosomally integrated HHV-6.

    Science.gov (United States)

    Hill, Joshua A; Magaret, Amalia S; Hall-Sedlak, Ruth; Mikhaylova, Anna; Huang, Meei-Li; Sandmaier, Brenda M; Hansen, John A; Jerome, Keith R; Zerr, Danielle M; Boeckh, Michael

    2017-08-24

    Human herpesvirus 6 (HHV-6) species have a unique ability to integrate into chromosomal telomeres. Mendelian inheritance via gametocyte integration results in HHV-6 in every nucleated cell. The epidemiology and clinical effect of inherited chromosomally integrated HHV-6 (iciHHV-6) in hematopoietic cell transplant (HCT) recipients is unclear. We identified 4319 HCT donor-recipient pairs (8638 subjects) who received an allogeneic HCT and had archived pre-HCT peripheral blood mononuclear cell samples. We screened these samples for iciHHV-6 and compared characteristics of HCT recipients and donors with iciHHV-6 with those of recipients and donors without iciHHV-6, respectively. We calculated Kaplan-Meier probability estimates and Cox proportional hazards models for post-HCT outcomes based on recipient and donor iciHHV-6 status. We identified 60 HCT recipients (1.4%) and 40 donors (0.9%) with iciHHV-6; both recipient and donor harbored iciHHV-6 in 13 HCTs. Thus, there were 87 HCTs (2%) in which the recipient, donor, or both harbored iciHHV-6. Acute graft-versus-host disease (GVHD) grades 2-4 was more frequent when recipients or donors had iciHHV-6 (adjusted hazard ratios, 1.7-1.9; P = .004-.001). Cytomegalovirus viremia (any and high-level) was more frequent among recipients with iciHHV-6 (adjusted HRs, 1.7-3.1; P = .001-.040). Inherited ciHHV-6 status did not significantly affect risk for chronic GVHD, hematopoietic cell engraftment, overall mortality, or nonrelapse mortality. Screening for iciHHV-6 could guide donor selection and post-HCT risk stratification and treatment. Further study is needed to replicate these findings and identify potential mechanisms. © 2017 by The American Society of Hematology.

  12. Post-main-sequence Evolution of Icy Minor Planets. III. Water Retention in Dwarf Planets and Exomoons and Implications for White Dwarf Pollution

    Energy Technology Data Exchange (ETDEWEB)

    Malamud, Uri; Perets, Hagai B., E-mail: uri.mal@tx.technion.ac.il, E-mail: hperets@physics.technion.ac.il [Department of Physics, Technion (Israel)

    2017-11-01

    Studies suggest that the pollution of white dwarf (WD) atmospheres arises from the accretion of minor planets, but the exact properties of polluting material, and in particular the evidence for water in some cases are not yet understood. Several previous works studied the possibility of water surviving inside minor planets around evolving stars. However, they all focused on small, comet-sized to moonlet-sized minor planets, when the inferred mass inside the convection zones of He-dominated WDs could actually be compatible with much more massive minor planets. Here we explore for the first time, the water retention inside exoplanetary dwarf planets, or moderate-sized moons, with radii of the order of hundreds of kilometers. This paper concludes a series of papers that has now covered nearly the entire potential mass range of minor planets, in addition to the full mass range of their host stars. We find that water retention is (a) affected by the mass of the WD progenitor, and (b) it is on average at least 5%, irrespective of the assumed initial water composition, if it came from a single accretion event of an icy dwarf planet or moon. The latter prediction strengthens the possibility of habitability in WD planetary systems, and it may also be used in order to distinguish between pollution originating from multiple small accretion events and singular large accretion events. To conclude our work, we provide a code that calculates ice and water retention by interpolation and may be freely used as a service to the community.

  13. « Nous le verrons plus bas », « voir ci-dessus », « je ne reviens pas ici » : retours sur les propriétés de la langue écrite

    Directory of Open Access Journals (Sweden)

    Lefebvre Julie

    2014-07-01

    Full Text Available La présente communication porte sur des séquences du type de « je ne reviens pas ici sur » ou encore « nous verrons plus loin que » qui, comportant un syntagme adverbial soutenant un repérage spatial de type déictique, se présentent comme des suites ordonnées de termes constituant un tout sous le rapport d’une activité de type métadiscursif. Ces séquences prennent pour objet le dire en train de se faire en tant qu’il est écrit et que, en tant que tel, il a des propriétés singulières qui sont celles de la « langue écrite » (Vachek (1939, Catach (éd. (1988, Anis (1988. La nature de l’activité réflexive à l’œuvre dans ces séquences est principalement abordée à travers l’analyse des propriétés de l’emploi déictique de l’adverbe « ici » à l’écrit. L’examen de cette activité est complété par une amorce de description des composés « ci-dessus » et « ci-dessous », des groupes adverbiaux « plus haut », « plus bas » et « plus loin », et des adverbes latins « infra » et « supra ». Enfin, à travers quelques exemples, on montre quelles perspectives ouvre, pour l’analyse des textes et des discours, l’attention portée aux « postures énonciatives » (Authier-Revuz, 1995/2012 qui se dessinent dans ces séquences témoignant du rapport du locuteur — scripteur, en l’occurrence — à son « dire écrit ».

  14. SoundScapes - Exploring the Human Interactive Kinesphere

    DEFF Research Database (Denmark)

    Lewis Brooks, Anthony (aka Tony)

    2005-01-01

    About ICIS ICIS; The International Centre for Creativity, Innovation and Sustainability promotes literacy of what sustainable development is and how it contributes to the improvement of life conditions for all. ICIS' VISION is environmental, economic and social wellbeing of individuals, groups of...

  15. Simulating Extraterrestrial Ices in the Laboratory

    Science.gov (United States)

    Berisford, D. F.; Carey, E. M.; Hand, K. P.; Choukroun, M.

    2017-12-01

    Several ongoing experiments at JPL attempt to simulate the ice environment for various regimes associated with icy moons. The Europa Penitent Ice Experiment (EPIX) simulates the surface environment of an icy moon, to investigate the physics of ice surface morphology growth. This experiment features half-meter-scale cryogenic ice samples, cryogenic radiative sink environment, vacuum conditions, and diurnal cycling solar simulation. The experiment also includes several smaller fixed-geometry vacuum chambers for ice simulation at Earth-like and intermediate temperature and vacuum conditions for development of surface morphology growth scaling relations. Additionally, an ice cutting facility built on a similar platform provides qualitative data on the mechanical behavior of cryogenic ice with impurities under vacuum, and allows testing of ice cutting/sampling tools relevant for landing spacecraft. A larger cutting facility is under construction at JPL, which will provide more quantitative data and allow full-scale sampling tool tests. Another facility, the JPL Ice Physics Laboratory, features icy analog simulant preparation abilities that range icy solar system objects such as Mars, Ceres and the icy satellites of Saturn and Jupiter. In addition, the Ice Physics Lab has unique facilities for Icy Analog Tidal Simulation and Rheological Studies of Cryogenic Icy Slurries, as well as equipment to perform thermal and mechanical properties testing on icy analog materials and their response to sinusoidal tidal stresses.

  16. International cooperative initiatives and the United Nations Framework Convention on Climate Change

    DEFF Research Database (Denmark)

    Bakhtiari, Fatemeh

    2017-01-01

    International cooperative initiatives (ICIs) are multi-country, multi-actor non-state actions that have the potential to reduce emissions of greenhouse gases. The article summarizes the literature on estimates of emission reduction potentials attributed to ICIs. This summary highlights three key ...... efforts under the UNFCCC is uncertain, but believed to be quite large. •The UNFCCC is arguably ill suited to coordinate and strengthen the accountability of international cooperative initiatives.......International cooperative initiatives (ICIs) are multi-country, multi-actor non-state actions that have the potential to reduce emissions of greenhouse gases. The article summarizes the literature on estimates of emission reduction potentials attributed to ICIs. This summary highlights three key...... transparent performance monitoring and reporting mechanisms. The article concludes with two considerations. Firstly, it advocates for the United Nations Environment Programme as one entity that could bring much-needed coordination among ICIs, and between ICIs and national government-led efforts to mitigate...

  17. Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer's disease.

    Science.gov (United States)

    Bagheri, Maryam; Joghataei, Mohammad-Taghi; Mohseni, Simin; Roghani, Mehrdad

    2011-03-01

    Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by increased β-amyloid (Aβ) deposition and neuronal dysfunction leading to impaired learning and recall. Ageing, heredity, and induced oxidative stress are among proposed risk factors. The increased frequency of the disease in women also suggests a role for estrogen in development of AD. In the present study, effects of the phytoestrogen genistein (10mg/kg) on learning and memory impairments was assessed in intrahippocampal Aβ(1-40)-injected rats. The estrogen receptor antagonist fulvestrant was injected intracerebroventricularly in a group of Aβ-lesioned rats. The Aβ-injected animals exhibited the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in the RAM task. Genistein, but not genistein and fulvestrant, significantly improved most of these parameters. Measurements of oxidative stress markers in hippocampal tissue of Aβ-injected rats showed an elevation of malondialdehyde (MDA) and nitrite content, and a reduction of superoxide dismutase (SOD) activity. Genistein significantly attenuated the increased MDA content but did not affect the nitrite content or SOD activity. These results indicate that genistein pretreatment ameliorates Aβ-induced impairment of short-term spatial memory in rats through an estrogenic pathway and by inducing attenuation of oxidative stress. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Dicty_cDB: VSA387 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ---HLKELRTELSSLRVAQVKSPNPSKLAKIGTVRKAIARVLTVFNQTQKNHLRAVYSKK SSSKIPTDLRYKKTRAIRRRLTNKQXKVVTLRVSKTATNFPQRVFAVKA*ici*milk...QVKSPNPSKLAKIGTVRKAIARVLTVFNQTQKNHLRAVYSKK SSSKIPTDLRYKKTRAIRRRLTNKQXKVVTLRVSKTATNFPQRVFAVKA*ici*milknk iy*k

  19. Titan's icy scar

    Science.gov (United States)

    Griffith, C. A.; Penteado, P. F.; Turner, J. D.; Neish, C. D.; Mitri, G.; Montiel, M. J.; Schoenfeld, A.; Lopes, R. M. C.

    2017-09-01

    We conduct a Principal Components Analysis (PCA) of Cassini/VIMS [1] infrared spectral windows to identify and quantify weak surface features, with no assumptions on the haze and surface characteris- tics. This study maps the organic sediments, supplied by past atmospheres, as well as ice-rich regions that constitute Titan's bedrock.

  20. Late Noachian Icy Highlands climate model: Exploring the possibility of transient melting and fluvial/lacustrine activity through peak annual and seasonal temperatures

    Science.gov (United States)

    Palumbo, Ashley M.; Head, James W.; Wordsworth, Robin D.

    2018-01-01

    The nature of the Late Noachian climate of Mars remains one of the outstanding questions in the study of the evolution of martian geology and climate. Despite abundant evidence for flowing water (valley networks and open/closed basin lakes), climate models have had difficulties reproducing mean annual surface temperatures (MAT) > 273 K in order to generate the ;warm and wet; climate conditions presumed to be necessary to explain the observed fluvial and lacustrine features. Here, we consider a ;cold and icy; climate scenario, characterized by MAT ∼225 K and snow and ice distributed in the southern highlands, and ask: Does the formation of the fluvial and lacustrine features require continuous ;warm and wet; conditions, or could seasonal temperature variation in a ;cold and icy; climate produce sufficient summertime ice melting and surface runoff to account for the observed features? To address this question, we employ the 3D Laboratoire de Météorologie Dynamique global climate model (LMD GCM) for early Mars and (1) analyze peak annual temperature (PAT) maps to determine where on Mars temperatures exceed freezing in the summer season, (2) produce temperature time series at three valley network systems and compare the duration of the time during which temperatures exceed freezing with seasonal temperature variations in the Antarctic McMurdo Dry Valleys (MDV) where similar fluvial and lacustrine features are observed, and (3) perform a positive-degree-day analysis to determine the annual volume of meltwater produced through this mechanism, estimate the necessary duration that this process must repeat to produce sufficient meltwater for valley network formation, and estimate whether runoff rates predicted by this mechanism are comparable to those required to form the observed geomorphology of the valley networks. When considering an ambient CO2 atmosphere, characterized by MAT ∼225 K, we find that: (1) PAT can exceed the melting point of water (>273 K) in

  1. Blocking beta 2-adrenergic receptor inhibits dendrite ramification in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Wu, Qin; Sun, Jin-Xia; Song, Xiang-He; Wang, Jing; Xiong, Cun-Quan; Teng, Fei-Xiang; Gao, Cui-Xiang

    2017-09-01

    Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer's disease (AD), although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β 2 -adrenergic receptor antagonist, ICI 118551 (ICI), on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic (TG) mice treated with ICI (AD-TG/ICI) was significantly poorer compared with NaCl-treated AD-TG mice (AD-TG/NaCl), suggesting that β 2 -adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β 2 -adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β 2 -adrenergic receptor increased amyloid-β accumulation by downregulating hippocampal α-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β 2 -adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.

  2. Dicty_cDB: VSC875 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available NKTQLLEHLKELRTELSSLRVAQVKSPNPSKLAKIGTVRKAIARVLTVF NQTQKNHLRAVYSKKSSSKIPTDLRYKKTRAIRRRFTNKQSKVVTLRVSKTATNFPQRVF AVKA*ici*milk...YSKKSSSKIPTDLRYKKTRAIRRRFTNKQSKVVTLRVSKTATNFPQRVF AVKA*ici*milknkiy* Frame C: kklkllnsepktrlnylntsrnselssqv*

  3. MO-FG-BRA-04: Leveraging the Abscopal Effect Via New Design Radiotherapy Biomaterials Loaded with Immune Checkpoint Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Y; Cifter, G; Altundal, Y; Moreau, M; Sajo, E [Univ Massachusetts Lowell, Lowell, MA (United States); Sinha, N [Wentworth Institute of Technology, Boston, MA (United States); Makrigiorgos, G [Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Ngwa, W [Univ Massachusetts Lowell, Lowell, MA (United States); Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

    2015-06-15

    Purpose: Studies show that stereotactic body radiation therapy (SBRT) of a primary tumor in combination with immune checkpoint inhibitors (ICI) could Result in an immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However toxicities due to repeated systematic administration of ICI have been shown to be a major obstacle in clinical trials. Towards overcoming these toxicity limitations, we investigate a potential new approach whereby the ICI are administered via sustained in-situ release from radiotherapy (RT) biomaterials (e.g. fiducials) coated with a polymer containing the ICI. Methods: New design RT biomaterials were prepared by coating commercially available spacers/fiducials with a biocompatible polymer (PLGA) film containing fluorescent nanoparticles of size needed to load the ICI. The release of the nanoparticles was investigated in-vitro. Meanwhile, an experimentally determined in- vivo nanoparticle diffusion coefficient was employed in analytic calculations based on Fick’s second law to estimate the time for achieving the concentrations of ICI in the tumor draining lymph node (TDLN) that are needed to engender the abscopal effect during SBRT. The ICI investigated here was anti-CTLA-4 antibody (ipilimumab) at approved FDA concentrations. Results: Our in -vitro study results showed that RT biomaterials could be designed to achieve burst release of nanoparticles within one day. Meanwhile, our calculations indicate that for a 2 to 4 cm tumor it would take 4–22 days, respectively, following burst release, for the required concentration of ICI nanoparticles to accumulate in the TDLN during SBRT. Conclusion: Current investigations combining RT and immunotherapy involve repeated intravenous administration of ICI leading to significant systemic toxicities. Our preliminary results highlight a potential new approach for sustained in-situ release of the ICI from new design RT biomaterials. These results

  4. MO-FG-BRA-04: Leveraging the Abscopal Effect Via New Design Radiotherapy Biomaterials Loaded with Immune Checkpoint Inhibitors

    International Nuclear Information System (INIS)

    Hao, Y; Cifter, G; Altundal, Y; Moreau, M; Sajo, E; Sinha, N; Makrigiorgos, G; Ngwa, W

    2015-01-01

    Purpose: Studies show that stereotactic body radiation therapy (SBRT) of a primary tumor in combination with immune checkpoint inhibitors (ICI) could Result in an immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However toxicities due to repeated systematic administration of ICI have been shown to be a major obstacle in clinical trials. Towards overcoming these toxicity limitations, we investigate a potential new approach whereby the ICI are administered via sustained in-situ release from radiotherapy (RT) biomaterials (e.g. fiducials) coated with a polymer containing the ICI. Methods: New design RT biomaterials were prepared by coating commercially available spacers/fiducials with a biocompatible polymer (PLGA) film containing fluorescent nanoparticles of size needed to load the ICI. The release of the nanoparticles was investigated in-vitro. Meanwhile, an experimentally determined in- vivo nanoparticle diffusion coefficient was employed in analytic calculations based on Fick’s second law to estimate the time for achieving the concentrations of ICI in the tumor draining lymph node (TDLN) that are needed to engender the abscopal effect during SBRT. The ICI investigated here was anti-CTLA-4 antibody (ipilimumab) at approved FDA concentrations. Results: Our in -vitro study results showed that RT biomaterials could be designed to achieve burst release of nanoparticles within one day. Meanwhile, our calculations indicate that for a 2 to 4 cm tumor it would take 4–22 days, respectively, following burst release, for the required concentration of ICI nanoparticles to accumulate in the TDLN during SBRT. Conclusion: Current investigations combining RT and immunotherapy involve repeated intravenous administration of ICI leading to significant systemic toxicities. Our preliminary results highlight a potential new approach for sustained in-situ release of the ICI from new design RT biomaterials. These results

  5. Dicty_cDB: VSE856 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available LRTKNKTQLLEHLKELRTELSSLRVAQVKSPNPSKLAKIGTVRKAIARVLTVFN QTQKNHLRAVYSKKSSSKIPTDLRYKKTRAIRRRLTNKQSKVVTLRVSKTATNFPQRVFA VKA*ici*milk...KNHLRAVYSKKSSSKIPTDLRYKKTRAIRRRLTNKQSKVVTLRVSKTATNFPQRVFA VKA*ici*milknkiy*kk Frame C: klkllnsepktrlnylntsrn

  6. Dicty_cDB: VSG811 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available NHLRAVYSKKSSSKIPTDLRYKKTRAIRRRLTNKQSKVVTLRVSKTATN FPQRVFAVKA*ici*milknkiy*kkekx--- Translated Amino Acid seq...LAKIGTVRKAIA RVLTVFNQTQKNHLRAVYSKKSSSKIPTDLRYKKTRAIRRRLTNKQSKVVTLRVSKTATN FPQRVFAVKA*ici*milk

  7. Dicty_cDB: VSA330 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available QKNHLRAVYSKKSSSKIPTDLRYKKTRAIRRRFTNKQSKVVTLRVSKTATNFPQRVF AVKA*ici*milknkiy*kkekkkkkkkkkkkkkkk Translated Am...TRAIRRRFTNKQSKVVTLRVSKTATNFPQRVF AVKA*ici*milknkiy*kkekkkkkkkkkkkkkkk Frame C: kklkllnsepktrlnylntsrnselssqv

  8. Dicty_cDB: VSC664 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available RRRFTNKQFKVVTLRVSKTATNFPQRVF AVKA*ici*milknkiy*kkekkkkk Translated Amino Acid sequence (All Frames) Frame A:...RVAQVKSPNPSKLAKIGTVRKAIARVLTVF NQTQKNHXRAVYSKKSSSKIPTDLRYKKTRAIRRRFTNKQFKVVTLRVSKTATNFPQRVF AVKA*ici*milknki

  9. Dicty_cDB: VSC307 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available LTNKQSKVVTLRVSKTATN FPQRVFAVKA*ici*milknkiy Translated Amino Acid sequence (All Frames) Frame A: QNFNMAEKTKA...FELRTKNKTQLLEHLKELRTELSSLRVAQVKSPNPSKLAKIGTVRKAIA RVLTVFNQTQKNHLRAVYSKKSSSKIPTDLRYKKTRAIRRRLTNKQSKVVTLRVSKTATN FPQRVFAVKA*ici*milk

  10. Dicty_cDB: VSC838 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available AIRRRFTNKQSKVVTLRVSKTATNFPQRV FAVKA*ici*milknkiy*kkekkkk Translated Amino Acid sequence (All Frames) Frame A...SSLRVAQVKSPNPSKLAKIGTVRKAIARVLTV FNQTQKNHFRAVYSKKSSSKIPTDLRYKKTRAIRRRFTNKQSKVVTLRVSKTATNFPQRV FAVKA*ici*milk

  11. The effect of nursing participation in the design of a critical care information system: a case study in a Chinese hospital.

    Science.gov (United States)

    Qin, Yanhong; Zhou, Ranyun; Wu, Qiong; Huang, Xiaodi; Chen, Xinli; Wang, Weiwei; Wang, Xun; Xu, Hua; Zheng, Jing; Qian, Siyu; Bai, Changqing; Yu, Ping

    2017-12-06

    Intensive care information systems (ICIS) are continuously evolving to meet the ever changing information needs of intensive care units (ICUs), providing the backbone for a safe, intelligent and efficient patient care environment. Although beneficial for the international advancement in building smart environments to transform ICU services, knowledge about the contemporary development of ICIS worldwide, their usage and impacts is limited. This study aimed to fill this knowledge gap by researching the development and implementation of an ICIS in a Chinese hospital, nurses' use of the system, and the impact of system use on critical care nursing processes and outcomes. This descriptive case study was conducted in a 14-bed Respiratory ICU in a tertiary hospital in Beijing. Participative design was the method used for ICU nurses, hospital IT department and a software company to collaboratively research and develop the ICIS. Focus group discussions were conducted to understand the subjective perceptions of the nurses toward the ICIS. Nursing documentation time and quality were compared before and after system implementation. ICU nursing performance was extracted from the annual nursing performance data collected by the hospital. A participative design process was followed by the nurses in the ICU, the hospital IT staff and the software engineers in the company to develop and implement a highly useful ICIS. Nursing documentation was fully digitized and was significantly improved in quality and efficiency. The wrong data, missing data items and calculation errors were significantly reduced. Nurses spent more time on direct patient care after the introduction of the ICIS. The accuracy and efficiency of medication administration was also improved. The outcome was improvement in ward nursing performance as measured by ward management, routine nursing practices, disinfection and isolation, infection rate and mortality rate. Nurses in this ICU unit in China actively

  12. Roll-to-Roll sputtered ITO/Cu/ITO multilayer electrode for flexible, transparent thin film heaters and electrochromic applications.

    Science.gov (United States)

    Park, Sung-Hyun; Lee, Sang-Mok; Ko, Eun-Hye; Kim, Tae-Ho; Nah, Yoon-Chae; Lee, Sang-Jin; Lee, Jae Heung; Kim, Han-Ki

    2016-09-22

    We fabricate high-performance, flexible, transparent electrochromic (EC) films and thin film heaters (TFHs) on an ITO/Cu/ITO (ICI) multilayer electrode prepared by continuous roll-to-roll (RTR) sputtering of ITO and Cu targets. The RTR-sputtered ICI multilayer on a 700 mm wide PET substrate at room temperature exhibits a sheet resistance of 11.8 Ω/square and optical transmittance of 73.9%, which are acceptable for the fabrication of flexible and transparent EC films and TFHs. The effect of the Cu interlayer thickness on the electrical and optical properties of the ICI multilayer was investigated in detail. The bending and cycling fatigue tests demonstrate that the RTR-sputtered ICI multilayer was more flexible than a single ITO film because of high strain failure of the Cu interlayer. The flexible and transparent EC films and TFHs fabricated on the ICI electrode show better performances than reference EC films and TFHs with a single ITO electrode. Therefore, the RTR-sputtered ICI multilayer is the best substitute for the conventional ITO film electrode in order to realize flexible, transparent, cost-effective and large-area EC devices and TFHs that can be used as flexible and smart windows.

  13. Dicty_cDB: VSB406 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available GTVRKAIARVLTVFNQTQKNHLR XVYSKKSSSKIPTDLRYKKTRAIRRRLTNKQSKVVTLRVSKTATNFPQRVFAVKA*ici* milknkiy Translated Ami...RRLTNKQSKVVTLRVSKTATNFPQRVFAVKA*ici* milknkiy Homology vs CSM-cDNA Score E Sequences producing significant a

  14. Formation of an ultracarbonaceous Antarctic micrometeorite through minimal aqueous alteration in a small porous icy body

    Science.gov (United States)

    Yabuta, Hikaru; Noguchi, Takaaki; Itoh, Shoichi; Nakamura, Tomoki; Miyake, Akira; Tsujimoto, Shinichi; Ohashi, Noriaki; Sakamoto, Naoya; Hashiguchi, Minako; Abe, Ken-ichi; Okubo, Aya; Kilcoyne, A. L. David; Tachibana, Shogo; Okazaki, Ryuji; Terada, Kentaro; Ebihara, Mitsuru; Nagahara, Hiroko

    2017-10-01

    have been necessary for the formation of the UCAMM. The GEMS grains depleted in Mg and S in the UCAMM prove a very weak degree of aqueous alteration; weaker than that of carbonaceous chondrites. Short-duration weak alteration probably caused by planetesimal shock locally melted cometary ice grains and released water that dissolved the organics; the fluid would likely have not mobilized because of the very low thermal conductivity of the porous icy body. This event allowed the formation of the large organic puddle of the UCAMM, as well as organic matter sulfurization, formation of thin membrane-like layers of minerals, and deformation of organic nanoglobules.

  15. Estrogen receptor alpha is cell cycle-regulated and regulates the cell cycle in a ligand-dependent fashion.

    Science.gov (United States)

    JavanMoghadam, Sonia; Weihua, Zhang; Hunt, Kelly K; Keyomarsi, Khandan

    2016-06-17

    Estrogen receptor alpha (ERα) has been implicated in several cell cycle regulatory events and is an important predictive marker of disease outcome in breast cancer patients. Here, we aimed to elucidate the mechanism through which ERα influences proliferation in breast cancer cells. Our results show that ERα protein is cell cycle-regulated in human breast cancer cells and that the presence of 17-β-estradiol (E2) in the culture medium shortened the cell cycle significantly (by 4.5 hours, P cycle duration were observed in the S and G2/M phases, whereas the G1 phase was indistinguishable under liganded and unliganded conditions. In addition, ERα knockdown in MCF-7 cells accelerated mitotic exit, whereas transfection of ERα-negative MDA-MB-231 cells with exogenous ERα significantly shortened the S and G2/M phases (by 9.1 hours, P cycle progression through the S and G2/M phases than fulvestrant does, presumably because of the destabilizing effect of fulvestrant on ERα protein. Together, these results show that ERα modulates breast cancer cell proliferation by regulating events during the S and G2/M phases of the cell cycle in a ligand-dependent fashion. These results provide the rationale for an effective treatment strategy that includes a cell cycle inhibitor in combination with a drug that lowers estrogen levels, such as an aromatase inhibitor, and an antiestrogen that does not result in the degradation of ERα, such as tamoxifen.

  16. The Parallel Algorithm Based on Genetic Algorithm for Improving the Performance of Cognitive Radio

    Directory of Open Access Journals (Sweden)

    Liu Miao

    2018-01-01

    Full Text Available The intercarrier interference (ICI problem of cognitive radio (CR is severe. In this paper, the machine learning algorithm is used to obtain the optimal interference subcarriers of an unlicensed user (un-LU. Masking the optimal interference subcarriers can suppress the ICI of CR. Moreover, the parallel ICI suppression algorithm is designed to improve the calculation speed and meet the practical requirement of CR. Simulation results show that the data transmission rate threshold of un-LU can be set, the data transmission quality of un-LU can be ensured, the ICI of a licensed user (LU is suppressed, and the bit error rate (BER performance of LU is improved by implementing the parallel suppression algorithm. The ICI problem of CR is solved well by the new machine learning algorithm. The computing performance of the algorithm is improved by designing a new parallel structure and the communication performance of CR is enhanced.

  17. Immune-related adverse effects of cancer immunotherapy- Implications for rheumatology

    OpenAIRE

    Cappelli, Laura C.; Shah, Ami A.; Bingham, Clifton O.

    2016-01-01

    Immune checkpoint inhibitors (ICIs) are being increasingly studied and used as therapy for a growing number of malignancies. ICIs work by blocking inhibitory pathways of T-cell activation, leading to an immune response directed against tumors. Such nonspecific immunologic activation can lead to immune-related adverse events (IRAE). Some IRAE including inflammatory arthritis, sicca syndrome, myositis and vasculitis are of special interest to rheumatologists. As use of ICIs increases, recogniti...

  18. Dicty_cDB: VSA850 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available IRRRLTNKQSKVVTLRVSKTATN FPQRVFAVKA*ici*milknkiy*k Translated Amino Acid sequence (All Frames) Frame A: QNFNM...RVSKTATN FPQRVFAVKA*ici*milknkiy*k Frame B: kistwpkklkllnsepktrlnylntsrnselssqv*e...AEKTKAFELRTKNKTQLLEHLKELRTELSSLRVAQVKSPNPSKLAKIGTVRKAIA RVLTVFNQTQKNHLRAVYSKKSSSKIPTDLRYKKTRAIRRRLTNKQSKVVTL

  19. The Feasibility and Safety of Surgery in Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Alexandra W. Elias

    2017-06-01

    Full Text Available Immune checkpoint inhibitors (ICI are revolutionizing care for cancer patients. The list of malignancies for which the Food and Drug Administration is granting approval is rapidly increasing. Furthermore, there is a concomitant increase in clinical trials incorporating ICI. However, the safety of ICI in patients undergoing surgery remains unclear. Herein, we assessed the safety of ICI in the perioperative setting at a single center. We conducted a retrospective review of patients who underwent planned surgery while receiving ICI in the perioperative setting from 2012 to 2016. We collected 30-day postoperative morbidity and mortality utilizing the Clavien–Dindo classification system. We identified 17 patients who received perioperative ICI in 22 operations. Patients were diagnosed with melanoma (n = 14, renal cell carcinoma (n = 2, and urothelial carcinoma (n = 1. Therapies included pembrolizumab (n = 10, ipilimumab (n = 5, atezolizumab (n = 5, and ipilimumab/nivolumab (n = 2. Procedures included cutaneous/subcutaneous resection (n = 6, lymph node resection (n = 5, small bowel resection (n = 5, abdominal wall resection (n = 3, other abdominal surgery (n = 3, orthopedic surgery (n = 1, hepatic resection (n = 1, and neurosurgery (n = 2. There were no Grade III–IV Clavien–Dindo complications. There was one death secondary to ventricular fibrillation in the setting of coronary artery disease. ICI appear safe in the perioperative setting, involving multiple different types of surgery, and likely do not need to be stopped in the perioperative setting. Further studies are warranted to confirm these findings.

  20. The Effects of Fat Structures and Ice Cream Mix Viscosity on Physical and Sensory Properties of Ice Cream.

    Science.gov (United States)

    Amador, Julia; Hartel, Rich; Rankin, Scott

    2017-08-01

    The purpose of this work was to investigate iciness perception and other sensory textural attributes of ice cream due to ice and fat structures and mix viscosity. Two studies were carried out varying processing conditions and mix formulation. In the 1st study, ice creams were collected at -3, -5, and -7.5 °C draw temperatures. These ice creams contained 0%, 0.1%, or 0.2% emulsifier, an 80:20 blend of mono- and diglycerides: polysorbate 80. In the 2nd study, ice creams were collected at -3 °C draw temperature and contained 0%, 0.2%, or 0.4% stabilizer, a blend of guar gum, locust bean gum, and carrageenan. Multiple linear regressions were used to determine relationships between ice crystal size, destabilized fat, and sensory iciness. In the ice and fat structure study, an inverse correlation was found between fat destabilization and sensory iciness. Ice creams with no difference in ice crystal size were perceived to be less icy with increasing amounts of destabilized fat. Destabilized fat correlated inversely with drip-through rate and sensory greasiness. In the ice cream mix viscosity study, an inverse correlation was found between mix viscosity and sensory iciness. Ice creams with no difference in ice crystal size were perceived to be less icy when formulated with higher mix viscosity. A positive correlation was found between mix viscosity and sensory greasiness. These results indicate that fat structures and mix viscosity have significant effects on ice cream microstructure and sensory texture including the reduction of iciness perception. © 2017 Institute of Food Technologists®.

  1. Layout of PWR in-core instrumentation system tubing and support structure with Bechtel 3D-CADD

    International Nuclear Information System (INIS)

    Ichikawa, T.; Pfeifer, B.W.; Mulay, J.N.

    1987-01-01

    The optimization study of the PWR In-Core Instrumentation System (ICIS) tubing layout and support structure presented an opportunity to utilize the Bechtel 3D-CADD program to perform this task. This paper provides a brief summary of the Bechtel 3D-CADD program development and capabilities and outlines the process of developing and optimizing the ICIS tube layout. Specific aspects relating to the ICIS tube layout criteria, support, alignment, electronic interference check and erection sequence are provided. (orig.)

  2. Scalp Hematoma Characteristics Associated With Intracranial Injury in Pediatric Minor Head Injury.

    Science.gov (United States)

    Burns, Emma C M; Grool, Anne M; Klassen, Terry P; Correll, Rhonda; Jarvis, Anna; Joubert, Gary; Bailey, Benoit; Chauvin-Kimoff, Laurel; Pusic, Martin; McConnell, Don; Nijssen-Jordan, Cheri; Silver, Norm; Taylor, Brett; Osmond, Martin H

    2016-05-01

    Minor head trauma accounts for a significant proportion of pediatric emergency department (ED) visits. In children younger than 24 months, scalp hematomas are thought to be associated with the presence of intracranial injury (ICI). We investigated which scalp hematoma characteristics were associated with increased odds of ICI in children less than 17 years who presented to the ED following minor head injury and whether an underlying linear skull fracture may explain this relationship. This was a secondary analysis of 3,866 patients enrolled in the Canadian Assessment of Tomography of Childhood Head Injury (CATCH) study. Information about scalp hematoma presence (yes/no), location (frontal, temporal/parietal, occipital), and size (small and localized, large and boggy) was collected by emergency physicians using a structured data collection form. ICI was defined as the presence of an acute brain lesion on computed tomography. Logistic regression analyses were adjusted for age, sex, dangerous injury mechanism, irritability on examination, suspected open or depressed skull fracture, and clinical signs of basal skull fracture. ICI was present in 159 (4.1%) patients. The presence of a scalp hematoma (n = 1,189) in any location was associated with significantly greater odds of ICI (odds ratio [OR] = 4.4, 95% confidence interval [CI] = 3.06 to 6.02), particularly for those located in temporal/parietal (OR = 6.0, 95% CI = 3.9 to 9.3) and occipital regions (OR = 5.6, 95% CI = 3.5 to 8.9). Both small and localized and large and boggy hematomas were significantly associated with ICI, although larger hematomas conferred larger odds (OR = 9.9, 95% CI = 6.3 to 15.5). Although the presence of a scalp hematoma was associated with greater odds of ICI in all age groups, odds were greatest in children aged 0 to 6 months (OR = 13.5, 95% CI = 1.5 to 119.3). Linear skull fractures were present in 156 (4.0%) patients. Of the 111 patients with scalp hematoma and ICI, 57 (51%) patients had

  3. Exobiology of icy satellites

    Science.gov (United States)

    Simakov, M. B.

    At the beginning of 2004 the total number of discovered planets near other stars was 119 All of them are massive giants and met practically in all orbits In a habitable zone from 0 8 up to 1 1 AU at less 11 planets has been found starting with HD 134987 and up to HD 4203 It would be naive to suppose existence of life in unique known to us amino-nucleic acid form on the gas-liquid giant planets Nevertheless conditions for onset and evolutions of life can be realized on hypothetical satellites extrasolar planets All giant planets of the Solar system have a big number of satellites 61 of Jupiter 52 of Saturn known in 2003 A small part of them consist very large bodies quite comparable to planets of terrestrial type but including very significant share of water ice Some from them have an atmosphere E g the mass of a column of the Titan s atmosphere exceeds 15 times the mass of the Earth atmosphere column Formation or capture of satellites is a natural phenomenon and satellite systems definitely should exist at extrasolar planets A hypothetical satellite of the planet HD 28185 with a dense enough atmosphere and hydrosphere could have biosphere of terrestrial type within the limits of our notion about an origin of terrestrial biosphere As an example we can see on Titan the largest satellite of Saturn which has a dense nitrogen atmosphere and a large quantity of liquid water under ice cover and so has a great exobiological significance The most recent models of the Titan s interior lead to the conclusion that a substantial liquid layer

  4. Emerging biomarkers for cancer immunotherapy in melanoma.

    Science.gov (United States)

    Axelrod, Margaret L; Johnson, Douglas B; Balko, Justin M

    2017-09-14

    The treatment and prognosis of metastatic melanoma has changed substantially since the advent of novel immune checkpoint inhibitors (ICI), agents that enhance the anti-tumor immune response. Despite the success of these agents, clinically actionable biomarkers to aid patient and regimen selection are lacking. Herein, we summarize and review the evidence for candidate biomarkers of response to ICIs in melanoma. Many of these candidates can be examined as parts of a known molecular pathway of immune response, while others are clinical in nature. Due to the ability of ICIs to illicit dramatic and durable responses, well-validated biomarkers that can be effectively implemented in the clinic will require strong negative predictive values that do not limit patients with who may benefit from ICI therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Downregulation of TXNIP leads to high proliferative activity and estrogen-dependent cell growth in breast cancer.

    Science.gov (United States)

    Park, Jun Won; Lee, Su Hyung; Woo, Gye-Hyung; Kwon, Hyo-Jung; Kim, Dae-Yong

    2018-04-06

    TXNIP is a potent tumor suppressor with reduced expression in various types of human cancer. The prognostic and predictive power of TXNIP has been recognized in human breast cancer. The aim of this study is to investigate the clinical relevance and functional roles of TXNIP downregulation in breast cancer. We examined TXNIP expression at the protein level in tissue microarray (TMA)-based human breast cancers and its correlation with clinical parameters and molecular markers on immunohistochemistry (IHC). Compared with normal tissues, TXNIP expression was significantly decreased in human breast cancer tissues and animal mammary tumors, along with tumor progression. TXNIP was restored immediately after histone deacetylase inhibitor treatment in breast cancer cells, implying transcriptional regulation of TXNIP by histone modification. Decreased TXNIP protein levels were more common in tumors showing high proliferative activity, such as high Ki-67 labeling indexes and low p27 expression. TXNIP knockdown led to increased in vitro and in vivo breast cancer cell growth accompanied by p27 reduction and GLUT1 induction. Interestingly, estrogen receptor (ER)-positive breast cancer samples showed higher TXNIP expression compared to ER-negative samples. TXNIP expression decreased when ER signaling was activated by estradiol, while its expression increased under ER blockage by anti-estrogen fulvestrant. In addition, TXNIP knockdown in breast cancer cells caused significant reduction in the cell-growth inhibitory effect of anti-estrogen fulvestrant. In conclusion, our data demonstrated that TXNIP functions to suppress high proliferative activity and estrogen-dependent cell growth in breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Testing Consent Order for Sodium Cyanide

    Science.gov (United States)

    This document announces that EPA has signed an enforceable testing Consent Order with E.I. du Pont de Nemours and Company (DuPont), FMC Corporation (FMC), Degussa Corporation (Degussa), ICI Americas Incorporated (ICI), and Cyanco Company (Cyanco).

  7. Conférence extérieure - Université de Genève: La modélisation numérique des extrêmes climatiques: Projections pour l'Europe et la Suisse d'ici 2100 - French version only

    CERN Document Server

    2006-01-01

    Université de Genève Ecole de physique 24 quai Ernest Ansermet 1211 Genève 4 Tél : + 41 22 379 63 83 (secrétariat) Tél : + 41 22 379 62 56 (réception) Fax: + 41 22 379 69 22 Lundi 15 janvier 2007 17 heures - Auditoire Stueckelberg La modélisation numérique des extrêmes climatiques: Projections pour l'Europe et la Suisse d'ici 2100 Prof. Martin Beniston / Chaire de Climatologie de l'Université de Genève Les nombreuses catastrophes liées au climat (canicule 2003 en Europe; inondations en Suisse en 2005; sécheresse en Australie; ouragans Katrina, etc.) donnent l'impression que les catastrophes climatiques qui touchent de nombreuses parties du monde sont la preuve du réchauffement climatique. A voir... Pourtant, les changements climatiques représentent l'un des thèmes de préoccupation majeure de ce début du 21e siècle, du moins pour les scientifiques sinon pour le monde politique. Car si l'ampleur, et surtout la rapidité du changement, sont aussi importants que ce que laissent entrevoi...

  8. Reversão dos efeitos da história de incontrolabilidade sob contingências de variação comportamental Reversión de los efectos de la historia de incontrolabilidad bajo contingencias de variación comportamental Reversing the effects of a history of uncontrollability under behavior variation contingencies

    Directory of Open Access Journals (Sweden)

    Karina de Guimarães Souto e Motta

    2007-12-01

    Full Text Available A exposição a eventos incontroláveis produz dificuldade na aprendizagem de novos comportamentos. O presente estudo investigou o papel da instrução e da exposição à controlabilidade na reversão dos efeitos da história de incontrolabilidade. No treino, estudantes universitários foram expostos à controlabilidade (grupo CC ou à incontrolabilidade (grupos IC, ICi, II, IIi. Na "terapia", os grupos CC, IC e ICi foram expostos à controlabilidade, enquanto os grupos II e IIi continuaram expostos à incontrolabilidade. Os grupos ICi e IIi receberam uma instrução de incontrolabilidade/controlabilidade. No teste, todos os grupos foram expostos a controlabilidade. Os participantes expostos apenas à incontrolabilidade (grupos II e IIi apresentaram maior persistência do responder do que aqueles expostos à "terapia" (grupos IC e ICi, os quais não diferiram dos participantes expostos apenas à controlabilidade (Grupo CC, a despeito da instrução. O procedimento de "terapia", portanto, foi mais efetivo do que a instrução para reverter os efeitos da história de incontrolabilidade.La exposición a eventos incontrolables produce dificultad en el aprendizaje de nuevos comportamientos. El presente estudio investigó el rol de la instrucción y de la exposición a la controlabilidad en la reversión de los efectos de la historia de incontrolabilidad. En el entrenamiento, estudiantes universitarios fueron expuestos a la controlabilidad (grupo CC o a la incontrolabilidad (grupos IC, ICi, II, IIi. En la "terapia", los grupos CC, IC y ICi fueron expuestos a la controlabilidad, mientras que los grupos II y IIi siguieron expuestos a la incontrolabilidad. Los grupos ICi y IIi recibieron una instrucción de incontrolabilidad/controlabilidad. En el test, todos los grupos fueron expuestos a la controlabilidad. Los participantes expuestos sólo a la incontrolabilidad (grupos II y IIi presentaron mayor persistencia del responder, comparados a aquellos

  9. Clinical feasibility of combined intracavitary/interstitial brachytherapy in locally advanced cervical cancer employing MRI with a tandem/ring applicator in situ and virtual preplanning of the interstitial component

    International Nuclear Information System (INIS)

    Fokdal, Lars; Tanderup, Kari; Hokland, Steffen Bjerre; Røhl, Lisbeth; Pedersen, Erik Morre; Nielsen, Søren Kynde; Paludan, Merete; Lindegaard, Jacob Christian

    2013-01-01

    Purpose: To investigate the reproducibility of virtually planned needles, changes in DVH parameters and clinical feasibility of combined intracavitary/interstitial (IC/IS) pulsed dose rate brachytherapy (PDR-BT) for locally advanced cervical cancer based on 3D MRI preplanning. Material and methods: Fifty-eight consecutively patients accrued in the EMBRACE study were included. Treatment was initiated with external beam radiotherapy and cisplatin. Three BT implants and MRI with the applicator in situ were performed in all patients, i.e. week 5 (BT0), week 6 (BT1) and week 7 (BT2) of the treatment. BT0 was only used for preplanning of subsequent implantations, whereas BT1 and BT2 comprised 2 equal sized fractions of PDR BT. Results: Based on BT0, 24 patients (41%) were selected for a combined IC/IS implant at BT1 and BT2. Patients treated with IC/IS BT had significantly larger tumours compared with patients treated with IC BT only (p < 0.03). Additional time in general anaesthesia for the IC/IS component was on average 16 min. The number of preplanned virtual needles was 5.3 ± 2.7 compared to 5.3 ± 2.9 and 5.4 ± 3.0 needles implanted at BT1 and BT2, respectively (p = 0.72). Planned needle implantation depth was 33 ± 15 mm compared to 30 ± 10 mm at BT1 and 29 ± 11 mm at BT2 (p = 0.04). In the 24 patients selected for IC/IS BT both the virtual IC/IS plan (BT0) and the actually delivered plan (BT1 + BT2) significantly increased D90 and D100 for HR CTV (p < 0.01) and reduced D2cc for sigmoid (p < 0.01) and bowel (p = 0.04) compared to the optimised IC preplan (BT0). IC/IS BT was only associated with minor morbidity, which was resolved at a 3-month follow up. Conclusion: Combined IC/IS BT based on full 3D MRI preplanning is clinically feasible. The virtual preplanned needle positions are reproducible at subsequent BT applications leading to significantly improved DVH parameters and a clinically feasible and fast implant procedure

  10. 77 FR 56244 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing of...

    Science.gov (United States)

    2012-09-12

    ... America (``BDA''), Government Finance Officers Association (``GFOA''), Investment Company Institute (``ICI... comment will be considered with any other comments received at that time. BDA, ICI, SIFMA and Stifel Nicolaus stated opposition to eliminating the practice of masking large trade sizes. BDA stated that...

  11. The Longevity of Water Ice on Ganymedes and Europas around Migrated Giant Planets

    International Nuclear Information System (INIS)

    Lehmer, Owen R.; Catling, David C.; Zahnle, Kevin J.

    2017-01-01

    The gas giant planets in the Solar System have a retinue of icy moons, and we expect giant exoplanets to have similar satellite systems. If a Jupiter-like planet were to migrate toward its parent star the icy moons orbiting it would evaporate, creating atmospheres and possible habitable surface oceans. Here, we examine how long the surface ice and possible oceans would last before being hydrodynamically lost to space. The hydrodynamic loss rate from the moons is determined, in large part, by the stellar flux available for absorption, which increases as the giant planet and icy moons migrate closer to the star. At some planet–star distance the stellar flux incident on the icy moons becomes so great that they enter a runaway greenhouse state. This runaway greenhouse state rapidly transfers all available surface water to the atmosphere as vapor, where it is easily lost from the small moons. However, for icy moons of Ganymede’s size around a Sun-like star we found that surface water (either ice or liquid) can persist indefinitely outside the runaway greenhouse orbital distance. In contrast, the surface water on smaller moons of Europa’s size will only persist on timescales greater than 1 Gyr at distances ranging 1.49–0.74 au around a Sun-like star for Bond albedos of 0.2 and 0.8, where the lower albedo becomes relevant if ice melts. Consequently, small moons can lose their icy shells, which would create a torus of H atoms around their host planet that might be detectable in future observations.

  12. The nature and origin of nucleus-like intracellular inclusions in Paleoproterozoic eukaryote microfossils.

    Science.gov (United States)

    Pang, K; Tang, Q; Schiffbauer, J D; Yao, J; Yuan, X; Wan, B; Chen, L; Ou, Z; Xiao, S

    2013-11-01

    The well-known debate on the nature and origin of intracellular inclusions (ICIs) in silicified microfossils from the early Neoproterozoic Bitter Springs Formation has recently been revived by reports of possible fossilized nuclei in phosphatized animal embryo-like fossils from the Ediacaran Doushantuo Formation of South China. The revisitation of this discussion prompted a critical and comprehensive investigation of ICIs in some of the oldest indisputable eukaryote microfossils-the ornamented acritarchs Dictyosphaera delicata and Shuiyousphaeridium macroreticulatum from the Paleoproterozoic Ruyang Group of North China-using a suite of characterization approaches: scanning electron microscopy (SEM), transmission electron microscopy (TEM), and focused ion beam scanning electron microscopy (FIB-SEM). Although the Ruyang acritarchs must have had nuclei when alive, our data suggest that their ICIs represent neither fossilized nuclei nor taphonomically condensed cytoplasm. We instead propose that these ICIs likely represent biologically contracted and consolidated eukaryotic protoplasts (the combination of the nucleus, surrounding cytoplasm, and plasma membrane). As opposed to degradational contraction of prokaryotic cells within a mucoidal sheath-a model proposed to explain the Bitter Springs ICIs-our model implies that protoplast condensation in the Ruyang acritarchs was an in vivo biologically programmed response to adverse conditions in preparation for encystment. While the discovery of bona fide nuclei in Paleoproterozoic acritarchs would be a substantial landmark in our understanding of eukaryote evolution, the various processes (such as degradational and biological condensation of protoplasts) capable of producing nuclei-mimicking structures require that interpretation of ICIs as fossilized nuclei be based on comprehensive investigations. © 2013 John Wiley & Sons Ltd.

  13. The Longevity of Water Ice on Ganymedes and Europas around Migrated Giant Planets

    Energy Technology Data Exchange (ETDEWEB)

    Lehmer, Owen R.; Catling, David C. [Dept. of Earth and Space Sciences/Astrobiology Program, University of Washington, Seattle, WA (United States); Zahnle, Kevin J., E-mail: olehmer@gmail.com [NASA Ames Research Center, Moffett Field, CA (United States)

    2017-04-10

    The gas giant planets in the Solar System have a retinue of icy moons, and we expect giant exoplanets to have similar satellite systems. If a Jupiter-like planet were to migrate toward its parent star the icy moons orbiting it would evaporate, creating atmospheres and possible habitable surface oceans. Here, we examine how long the surface ice and possible oceans would last before being hydrodynamically lost to space. The hydrodynamic loss rate from the moons is determined, in large part, by the stellar flux available for absorption, which increases as the giant planet and icy moons migrate closer to the star. At some planet–star distance the stellar flux incident on the icy moons becomes so great that they enter a runaway greenhouse state. This runaway greenhouse state rapidly transfers all available surface water to the atmosphere as vapor, where it is easily lost from the small moons. However, for icy moons of Ganymede’s size around a Sun-like star we found that surface water (either ice or liquid) can persist indefinitely outside the runaway greenhouse orbital distance. In contrast, the surface water on smaller moons of Europa’s size will only persist on timescales greater than 1 Gyr at distances ranging 1.49–0.74 au around a Sun-like star for Bond albedos of 0.2 and 0.8, where the lower albedo becomes relevant if ice melts. Consequently, small moons can lose their icy shells, which would create a torus of H atoms around their host planet that might be detectable in future observations.

  14. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates and models temporal suppression of click-evoked otoacoustic emissions (CEOAEs). This suppression-effect is created when a suppressor-click is presented close in time to a test-click. The analysis was carried out for short time-frames of short- and long-latency CEOAEs...... suppression is present in all CEOAEs for inter-click intervals (ICIs) less than 8 ms. The long-latency CEOAEs showed augmentation (i.e., negative suppression) for ICIs of 6-7 ms which was not reported for the short-latency CEOAE at these ICIs. A phenomenological approach is adopted here to explain both...

  15. Mechanisms of immune regulation by norepinephrine and cholera toxin

    International Nuclear Information System (INIS)

    Campbell, K.S.

    1988-01-01

    Norepinephrine has previously been demonstrated by this laboratory to potentiate the in vitro T-dependent antibody response through the stimulation of β-adrenergic receptors. The role of β-adrenergic receptor subtypes in norepinephrine-induced potentiation of the antibody responses was examined with selective β-adrenergic antagonists. The antagonists were metoprolol (β 1 -selective), ICI 118-551 (β 2 -selective), and propranolol (β-non-selective). Both propranolol and ICI 118-551 blocked norepinephrine-induced potentiation of the antibody response, but metoprolol was ineffective. Receptor binding competition of antagonists with the radioligant, [ 3 H]CGP-12177 was examined and results were analyzed with the computer program, LIGAND. Competition by ICI 118-551 identified 75% β 2 - and 25% β 1 -adrenergic receptors on splenic mononuclear cells. Enriched T lymphocytes exhibited 75% β 2 -adrenergic receptors, while enriched B lymphocytes contained 90% β 2 -adrenergic receptors as identified by ICI 118-551. Greater than twice as many total receptors were identified on B lymphocytes than T lymphocytes. A T cell lymphoma contained about 60% β 2 -receptors, while 100% were β 2 receptors on a B cell lymphoma, as assessed by ICI 118-551. Results support a heterogeneous β-adrenergic receptor population on T lymphocytes and a more homogeneous β 2 -population on B lymphocytes

  16. Immunosenescence and immunecheckpoint inhibitors in non-small cell lung cancer patients: Does age really matter?

    Science.gov (United States)

    Ferrara, Roberto; Mezquita, Laura; Auclin, Edouard; Chaput, Nathalie; Besse, Benjamin

    2017-11-01

    Immunotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer (NSCLC), extending overall survival, with a favorable safety profile. However, there is still a gap of knowledge about the efficacy of immune checkpoint inhibitors (ICIs) in elderly patients. Data from randomized clinical trials testing ICIs are conflicting and often lack adequate statistical power. Although two large meta-analyses suggested an absence of a significant survival benefit in patients older than 75years, expanded access programs and retrospective cohort studies of ICIs in the real-life setting, showed comparable survival outcomes and safety profiles between older and younger patients. In this complex scenario, a further unresolved issue is the potential correlation between older age and immunotherapy primary resistance, a phenomenon probably linked to the continuous and progressive remodeling of immune functions with ageing, known as immunosenescence. Defining the role of ICIs in elderly NSCLC patients and exploring the molecular mechanisms underlying a possible lack of benefit or even accelerated tumor growth during immunotherapy are two major challenges for future research in this field of cancer treatment. In this review, we describe the major hallmarks of immunosenescence and we summarize the existing clinical data of ICIs in elderly NSCLC patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  17. Results from the Two-Year Infrared Cloud Imager Deployment at ARM's NSA Observatory in Barrow, Alaska

    Science.gov (United States)

    Shaw, J. A.; Nugent, P. W.

    2016-12-01

    Ground-based longwave-infrared (LWIR) cloud imaging can provide continuous cloud measurements in the Arctic. This is of particular importance during the Arctic winter when visible wavelength cloud imaging systems cannot operate. This method uses a thermal infrared camera to observe clouds and produce measurements of cloud amount and cloud optical depth. The Montana State University Optical Remote Sensor Laboratory deployed an infrared cloud imager (ICI) at the Atmospheric Radiation Monitoring North Slope of Alaska site at Barrow, AK from July 2012 through July 2014. This study was used to both understand the long-term operation of an ICI in the Arctic and to study the consistency of the ICI data products in relation to co-located active and passive sensors. The ICI was found to have a high correlation (> 0.92) with collocated cloud instruments and to produce an unbiased data product. However, the ICI also detects thin clouds that are not detected by most operational cloud sensors. Comparisons with high-sensitivity actively sensed cloud products confirm the existence of these thin clouds. Infrared cloud imaging systems can serve a critical role in developing our understanding of cloud cover in the Arctic by provided a continuous annual measurement of clouds at sites of interest.

  18. Dielectric properties of Jovian satellite ice analogs for subsurface radar exploration: A review

    Science.gov (United States)

    Pettinelli, Elena; Cosciotti, Barbara; Di Paolo, Federico; Lauro, Sebastian Emanuel; Mattei, Elisabetta; Orosei, Roberto; Vannaroni, Giuliano

    2015-09-01

    The first European mission dedicated to the exploration of Jupiter and its icy moons (JUpiter ICy moons Explorer—JUICE) will be launched in 2022 and will reach its final destination in 2030. The main goals of this mission are to understand the internal structure of the icy crusts of three Galilean satellites (Europa, Ganymede, and Callisto) and, ultimately, to detect Europa's subsurface ocean, which is believed to be the closest to the surface among those hypothesized to exist on these moons. JUICE will be equipped with the 9 MHz subsurface-penetrating radar RIME (Radar for Icy Moon Exploration), which is designed to image the ice down to a depth of 9 km. Moreover, a parallel mission to Europa, which will host onboard REASON (Radar for Europa Assessment and Sounding: Ocean to Near-surface) equipped with 9MHz and 60MHz antennas, has been recently approved by NASA. The success of these experiments strongly relies on the accurate prediction of the radar performance and on the optimal processing and interpretation of radar echoes that, in turn, depend on the dielectric properties of the materials composing the icy satellite crusts. In the present review we report a complete range of potential ice types that may occur on these icy satellites to understand how they may affect the results of the proposed missions. First, we discuss the experimental results on pure and doped water ice in the framework of the Jaccard theory, highlighting the critical aspects in terms of a lack of standard laboratory procedures and inconsistency in data interpretation. We then describe the dielectric behavior of extraterrestrial ice analogs like hydrates and icy mixtures, carbon dioxide ice and ammonia ice. Building on this review, we have selected the most suitable data to compute dielectric attenuation, velocity, vertical resolution, and reflection coefficients for such icy moon environments, with the final goal being to estimate the potential capabilities of the radar missions as a

  19. Near-Infrared Intraoperative Chemiluminescence Imaging

    KAUST Repository

    Bü chel, Gabriel E.; Carney, Brandon; Shaffer, Travis M.; Tang, Jun; Austin, Christine; Arora, Manish; Zeglis, Brian M.; Grimm, Jan; Eppinger, Jö rg; Reiner, Thomas

    2016-01-01

    Intraoperative imaging technologies recently entered the operating room, and their implementation is revolutionizing how physicians plan, monitor, and perform surgical interventions. In this work, we present a novel surgical imaging reporter system: intraoperative chemiluminescence imaging (ICI). To this end, we have leveraged the ability of a chemiluminescent metal complex to generate near-infrared light upon exposure to an aqueous solution of Ce4+ in the presence of reducing tissue or blood components. An optical camera spatially resolves the resulting photon flux. We describe the construction and application of a prototype imaging setup, which achieves a detection limit as low as 6.9pmolcm-2 of the transition-metal-based ICI agent. As a proof of concept, we use ICI for the invivo detection of our transition metal tracer following both systemic and subdermal injections. The very high signal-to-noise ratios make ICI an interesting candidate for the development of new intraoperative imaging technologies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Near-Infrared Intraoperative Chemiluminescence Imaging

    KAUST Repository

    Büchel, Gabriel E.

    2016-08-03

    Intraoperative imaging technologies recently entered the operating room, and their implementation is revolutionizing how physicians plan, monitor, and perform surgical interventions. In this work, we present a novel surgical imaging reporter system: intraoperative chemiluminescence imaging (ICI). To this end, we have leveraged the ability of a chemiluminescent metal complex to generate near-infrared light upon exposure to an aqueous solution of Ce4+ in the presence of reducing tissue or blood components. An optical camera spatially resolves the resulting photon flux. We describe the construction and application of a prototype imaging setup, which achieves a detection limit as low as 6.9pmolcm-2 of the transition-metal-based ICI agent. As a proof of concept, we use ICI for the invivo detection of our transition metal tracer following both systemic and subdermal injections. The very high signal-to-noise ratios make ICI an interesting candidate for the development of new intraoperative imaging technologies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. A Framework for Uplink Intercell Interference Modeling with Channel-Based Scheduling

    KAUST Repository

    Tabassum, Hina

    2012-12-29

    This paper presents a novel framework for modeling the uplink intercell interference(ICI) in a multiuser cellular network. The proposed framework assists in quantifying the impact of various fading channel models and state-of-the-art scheduling schemes on the uplink ICI. Firstly, we derive a semianalytical expression for the distribution of the location of the scheduled user in a given cell considering a wide range of scheduling schemes. Based on this, we derive the distribution and moment generating function (MGF) of the uplink ICI considering a single interfering cell. Consequently, we determine the MGF of the cumulative ICI observed from all interfering cells and derive explicit MGF expressions for three typical fading models. Finally, we utilize the obtained expressions to evaluate important network performance metrics such as the outage probability, ergodic capacity, and average fairness numerically. Monte-Carlo simulation results are provided to demonstrate the efficacy of the derived analytical expressions.

  2. Blood pressure reduction induced by low dose of epinephrine via different routes in rats.

    Science.gov (United States)

    Wu, Jing; Ji, Mu-Huo; Wang, Zhong-Yun; Zhu, Wei; Yang, Jian-Jun; Peng, Yong G

    2013-09-01

    Epinephrine was recently shown to induce a hypotension episode. Activation of β₂-adrenoceptors with smooth muscle relaxation may be the underlying mechanism. This study investigated the effects of ICI 118551, a β₂-adrenoceptors antagonist, on epinephrine-induced blood pressure reduction via different administration routes in rats. A total of 144 Sprague Dawley rats were equally randomized into 3 groups (intranasal, intravenous, and intra-arterial administration), each with 4 subgroups: saline + saline, ICI 118551 + saline, saline + epinephrine, and ICI 118551 + epinephrine. All rats were anesthetized while spontaneously breathing. Epinephrine was administered at doses of 5 μg/kg via nose, 0.25 μg/kg via femoral vein, and 0.1 μg/kg via aorta. Mean arterial pressure and heart rate were monitored. Mean arterial pressure decreased in all 3 saline + epinephrine subgroups after administration (P blood pressure reduction can be prevented by ICI 118551 in rats, suggesting that the activation of β₂-adrenoceptors contributes to blood pressure reduction.

  3. Estrogen provides neuroprotection against brain edema and blood brain barrier disruption through both estrogen receptors α and β following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Vida Naderi

    2015-02-01

    Full Text Available Objective(s:Estrogen (E2 has neuroprotective effects on blood-brain-barrier (BBB after traumatic brain injury (TBI. In order to investigate the roles of estrogen receptors (ERs in these effects, ER-α antagonist (MPP and, ER-β antagonist (PHTPP, or non-selective estrogen receptors antagonist (ICI 182780 were administered. Materials and Methods: Ovariectomized rats were divided into 10 groups, as follows: Sham, TBI, E2, oil, MPP+E2, PHTPP+E2, MPP+PHTPP+E2, ICI+E2, MPP, and DMSO. E2 (33.3 µg/Kg or oil were administered 30 min after TBI. 1 dose (150 µg/Kg of each of MPP, PHTPP, and (4 mg/kg ICI182780 was injected two times, 24 hr apart, before TBI and estrogen treatment. BBB disruption (Evans blue content and brain edema (brain water content evaluated 5 hr and 24 hr after the TBI were evaluated, respectively. Results: The results showed that E2 reduced brain edema after TBI compared to vehicle (P

  4. Radioiodinated cholesteryl ester analogs as residualizing tracers of lipoproteins disposition

    International Nuclear Information System (INIS)

    DeForge, L.E.

    1989-01-01

    Due to the importance of low density lipoprotein (LDL) in lipid metabolism and atherosclerosis, efforts were made to incorporate 125 I-cholesteryl iopanoate ( 125 I-CI), a residualizing cholesteryl ester (CE) analog, into the lipid core of LDL. This preparation is potentially useful as a scintigraphically detectable tracer of LDL uptake into atheroma and tissues such as the adrenal and liver. Initial studies using a cholesterol-fed rabbit model of atherosclerosis validated the use of 125 I-CI as a tracer of CE deposition. However, scintigraphy revealed considerable nonspecific 125 I-CI uptake due to tissue cholesterol loading. An alternative animal model was the guinea pig, which responds moderately to cholesterol feeding and carries the plasma cholesterol predominantly as LDL. Dietary fat and cholesterol, coupled with chronic aortic injury caused by an indwelling catheter, resulted in lipid containing, smooth muscle cell proliferative lesions in many animals. However, further studies are necessary to fully characterize this model. In additional studies, in vitro methods for incorporating 125 I-CI into LDL were examined. These included a reconstitution procedure described by Krieger et al. and a procedure involving incubation of detergent (Tween 20)-solubilized 125 I-CI with plasma. Although both LDL preparations were taken up normally by cultured fibroblasts, the plasma clearance rate of reconstituted LDL was markedly abnormal in guinea pigs. In contrast, LDL labeled by the detergent method cleared from the plasma identically to a radioiodinated LDL control. Therefore, this latter procedure was also used to incorporate two novel radioiodinated cholesteryl ether analogs 125 I-CI cholesteryl m-iodobenzyl ether [ 125 I-CIDE] and 125 I-cholesteryl 12-(miodophenyl)dodecyl ether [ 125 I-CIDE] into LDL

  5. Characteristics of elderly fall patients with baseline mental status: high-risk features for intracranial injury.

    Science.gov (United States)

    Hamden, Khalief; Agresti, Darin; Jeanmonod, Rebecca; Woods, Dexter; Reiter, Mark; Jeanmonod, Donald

    2014-08-01

    Falls are a major cause of morbidity in the elderly. We describe the low-acuity elderly fall population and study which historical and clinical features predict traumatic intracranial injuries (ICIs). This is a prospective observational study of patients at least 65 years old presenting with fall to a tertiary care facility. Patients were eligible if they were at baseline mental status and were not triaged to the trauma bay. At presentation, a data form was completed by treating physicians regarding mechanism and position of fall, history of head strike, headache, loss of consciousness (LOC), and signs of head trauma. Radiographic imaging was obtained at the discretion of treating physicians. Medical records were subsequently reviewed to determine imaging results. All patients were called in follow-up at 30 days to determine outcome in those not imaged. The study was institutional review board approved. A total of 799 patients were enrolled; 79.5% of patients underwent imaging. Twenty-seven had ICIs (3.4%). Fourteen had subdural hematoma, 7 had subarachnoid hemorrhage, 3 had cerebral contusion, and 3 had a combination of injuries. Logistic regression demonstrated 2 study variables that were associated with ICIs: LOC (odds ratio, 2.8; confidence interval, 1.2-6.3) and signs of head trauma (odds ratio, 13.2; confidence interval, 2.7-64.1). History of head strike, mechanism and position, headache, and anticoagulant and antiplatelet use were not associated with ICIs. Elderly fall patients who are at their baseline mental status have a low incidence of ICIs. The best predictors of ICIs are physical findings of trauma to the head and history of LOC. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Statistical-mechanics approach to wide-band digital communication.

    Science.gov (United States)

    Efraim, Hadar; Peleg, Yitzhak; Kanter, Ido; Shental, Ori; Kabashima, Yoshiyuki

    2010-12-01

    The emerging popular scheme of fourth generation wireless communication, orthogonal frequency-division multiplexing, is mapped onto a variant of a random field Ising Hamiltonian and results in an efficient physical intercarrier interference (ICI) cancellation decoding scheme. This scheme is based on Monte Carlo (MC) dynamics at zero temperature as well as at the Nishimori temperature and demonstrates improved bit error rate (BER) and robust convergence time compared to the state of the art ICI cancellation decoding scheme. An optimal BER performance is achieved with MC dynamics at the Nishimori temperature but with a substantial computational cost overhead. The suggested ICI cancellation scheme also supports the transmission of biased signals.

  7. Mechanisms of immune regulation by norepinephrine and cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, K.S.

    1988-01-01

    Norepinephrine has previously been demonstrated by this laboratory to potentiate the in vitro T-dependent antibody response through the stimulation of {beta}-adrenergic receptors. The role of {beta}-adrenergic receptor subtypes in norepinephrine-induced potentiation of the antibody responses was examined with selective {beta}-adrenergic antagonists. The antagonists were metoprolol ({beta}{sub 1}-selective), ICI 118-551 ({beta}{sub 2}-selective), and propranolol ({beta}-non-selective). Both propranolol and ICI 118-551 blocked norepinephrine-induced potentiation of the antibody response, but metoprolol was ineffective. Receptor binding competition of antagonists with the radioligant, ({sup 3}H)CGP-12177 was examined and results were analyzed with the computer program, LIGAND. Competition by ICI 118-551 identified 75% {beta}{sub 2}- and 25% {beta}{sub 1}-adrenergic receptors on splenic mononuclear cells. Enriched T lymphocytes exhibited 75% {beta}{sub 2}-adrenergic receptors, while enriched B lymphocytes contained 90% {beta}{sub 2}-adrenergic receptors as identified by ICI 118-551. Greater than twice as many total receptors were identified on B lymphocytes than T lymphocytes. A T cell lymphoma contained about 60% {beta}{sub 2}-receptors, while 100% were {beta}{sub 2} receptors on a B cell lymphoma, as assessed by ICI 118-551. Results support a heterogeneous {beta}-adrenergic receptor population on T lymphocytes and a more homogeneous {beta}{sub 2}-population on B lymphocytes.

  8. Studies of Behavior Melting Temperature Characteristics for Multi Thermocouple In-Core Instrument Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Donghyup; Chae, Myoungeun; Kim, Sungjin; Lee, Kyulim [Woojin inc, Hwasung (Korea, Republic of)

    2015-05-15

    Bottom-up type in-core instruments (ICIs) are used for the pressurized water reactors of OPR-1000, APR- 1400 in order to measure neutron flux and temperature in the reactor. It is a well-known technique and a proven design using years in the nuclear field. ICI consists of one pair of K-type thermocouple, five self-powered neutron detectors (SPNDs) and one back ground detector. K-type thermocouple's purpose is to measure the core exit temperature (CET) in the reactor. The CET is a very important factor for operating nuclear power plants and it is 327 .deg. C when generally operating the reactor in the nuclear power plant(NPP) in case of OPR- 1000. If the CET will exceed 650 .deg. C, Operators in the main control room should be considered to be an accident situation in accordance with a severe accident management guidance(SAMG). The Multi Thermocouple ICI is a new designed ICI assuming severe accident conditions. It consists of four more thermocouples than the existing design, so it has five Ktype thermocouples besides the thermocouple measuring CET is located in the same elevation as the ICI. Each thermocouple is able to be located in the desired location as required. The Multi Thermocouple ICI helps to measure the temperature distribution of the entire reactor. In addition, it will measure certain point of melted core because of the in-vessel debris of nuclear fuel when an accident occurs more seriously. In this paper, to simulate a circumstance such as a nuclear reactor severe accident was examined. In this study, the K-type thermocouples of Multi Thermocouple ICI was confirmed experimentally to be able to measure up to 1370 .deg. C before the thermocouples have been melted. And after the thermocouples were melted by debris, it was able to be monitored that the signal of EMF directed the infinite value of voltage. Therefore through the results of the test, it can be assumed that if any EMF data among the Multi Thermocouple ICI will direct the infinite value

  9. Studies of Behavior Melting Temperature Characteristics for Multi Thermocouple In-Core Instrument Assembly

    International Nuclear Information System (INIS)

    Shin, Donghyup; Chae, Myoungeun; Kim, Sungjin; Lee, Kyulim

    2015-01-01

    Bottom-up type in-core instruments (ICIs) are used for the pressurized water reactors of OPR-1000, APR- 1400 in order to measure neutron flux and temperature in the reactor. It is a well-known technique and a proven design using years in the nuclear field. ICI consists of one pair of K-type thermocouple, five self-powered neutron detectors (SPNDs) and one back ground detector. K-type thermocouple's purpose is to measure the core exit temperature (CET) in the reactor. The CET is a very important factor for operating nuclear power plants and it is 327 .deg. C when generally operating the reactor in the nuclear power plant(NPP) in case of OPR- 1000. If the CET will exceed 650 .deg. C, Operators in the main control room should be considered to be an accident situation in accordance with a severe accident management guidance(SAMG). The Multi Thermocouple ICI is a new designed ICI assuming severe accident conditions. It consists of four more thermocouples than the existing design, so it has five Ktype thermocouples besides the thermocouple measuring CET is located in the same elevation as the ICI. Each thermocouple is able to be located in the desired location as required. The Multi Thermocouple ICI helps to measure the temperature distribution of the entire reactor. In addition, it will measure certain point of melted core because of the in-vessel debris of nuclear fuel when an accident occurs more seriously. In this paper, to simulate a circumstance such as a nuclear reactor severe accident was examined. In this study, the K-type thermocouples of Multi Thermocouple ICI was confirmed experimentally to be able to measure up to 1370 .deg. C before the thermocouples have been melted. And after the thermocouples were melted by debris, it was able to be monitored that the signal of EMF directed the infinite value of voltage. Therefore through the results of the test, it can be assumed that if any EMF data among the Multi Thermocouple ICI will direct the infinite value

  10. Current status of ion source development

    International Nuclear Information System (INIS)

    Ishikawa, Junzo

    2001-01-01

    In this report, the current status of ion source development will be discussed. In September 2001, the 9th International Conference on Ion Sources (ICIS01) was held in Oakland, U.S.A. Referring the talks presented at ICIS01, recent topics in the ion source research fields will be described. (author)

  11. High rate of complete responses to immune checkpoint inhibitors in patients with relapsed or refractory Hodgkin lymphoma previously exposed to epigenetic therapy

    Directory of Open Access Journals (Sweden)

    Lorenzo Falchi

    2016-11-01

    Full Text Available Abstract Options for patients with relapsed or refractory (R/R classical Hodgkin lymphoma (cHL after brentuximab vedotin (Bv and autologous stem cell transplantation (ASCT are limited. Immune checkpoint inhibitors (ICI are active in this population but rarely induce complete response (CR. Ten patients with R/R cHL after ASCT and Bv received pembrolizumab (n = 8 or nivolumab (n = 2. Five had been previously exposed to 5-azacitidine on a phase 1 study. Among nine evaluable patients, seven (78% achieved CR, one partial response, and one reduction of tumor burden. All five patients who had received 5-azacitidine prior to ICI achieved CR, while only two of four who did not receive prior 5-azacitidine achieved CR. At a median follow-up of 9.9 months [0.5–14.3], eight patients are alive and five are still receiving treatment. We documented an unprecedented CR rate after ICI in patients with R/R cHL. We hypothesize that hypomethylating agents might have an immune priming effect and enhance the efficacy of ICI.

  12. Independence Between Two Channels of Surface Electromyogram Signal to Measure the Loss of Motor Units

    Directory of Open Access Journals (Sweden)

    Arjunan Sridhar P.

    2015-06-01

    Full Text Available This study has investigated the relationship in the connectivity of motor units in surface electromyogram (sEMG of biceps brachii muscle. It is hypothesized that with ageing, there is reduction/loss in number of motor units, leading to reduction in the independence between the channels of the recorded muscle activity. Two channels of sEMG were recorded during three levels of isometric muscle contraction: 50 %, 75 % and 100 % maximal voluntary contraction (MVC. 73 subjects (age range 20-70 participated in the experiments. The independence in channel index (ICI between the two sEMG recording locations was computed using the independent components and Frobenius norm. ANOVA Statistical analysis was performed to test the effect of age (loss of motor units and level of contraction on ICI. The results show that the ICI among the older cohort was significantly lower compared with the younger adults. This research study has shown that the reduction in number of motor units is reflected by the reduction in the ICI of the sEMG signal.

  13. Influence of Inter Carrier Interference on Link Adaptation Algorithms in OFDM Systems

    DEFF Research Database (Denmark)

    Das, Suvra S.; Rahman, Muhammad Imadur; Wang, Yuanye

    2007-01-01

    The performance of Link Adaptation (LA) under the influence of inter carrier interference (ICI), which is cause by carrier frequency offset (CFO) and Doppler frequency spread due to mobility, in orthogonal frequency division multiplexing (OFDM) based wireless systems is analyzed in this work. LA...... maximizes throughput while maintaining a target bit error rate (BER)or Block Error Rate (BLER) at the receiver using the signal to noise ratio (SNR) fed back from the receiver to the transmitter. Since ICI power is proportional to the signal strength, the implications of such an impairment on LA OFDM...... can over the problem. It is also noted that ICI severely reduces the spectral efficiency of OFDM systems even when LA is used....

  14. Response evaluation in nuclear medicine. Criteria, results and pitfalls; Nuklearmedizinische Responsebeurteilung. Kriterien, Ergebnisse und Pitfalls

    Energy Technology Data Exchange (ETDEWEB)

    Hoffend, J. [Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Onkologische Diagnostik/PET-CT, Zentralinstitut fuer diagnostische und interventionelle Radiologie, Ludwigshafen (Germany); Sachpekidis, C. [Deutsches Krebsforschungszentrum Heidelberg, Klinische Kooperationseinheit Nuklearmedizin, Forschungsschwerpunkt Bildgebung und Radiologie, Heidelberg (Germany); Deutsches Krebsforschungszentrum Heidelberg, Abteilung Radiologie, Forschungsschwerpunkt Bildgebung und Radiologie, Heidelberg (Germany); Dimitrakopoulou-Strauss, A. [Deutsches Krebsforschungszentrum Heidelberg, Klinische Kooperationseinheit Nuklearmedizin, Forschungsschwerpunkt Bildgebung und Radiologie, Heidelberg (Germany)

    2017-10-15

    Established criteria to categorize metabolic tumor response to cytotoxic chemotherapies may not be suited to capture the effects of therapy with immune checkpoint inhibitors (ICI) or with kinase inhibitors (KI), such as BRAF or MEK inhibitors. To assess the metabolic response to cytotoxic chemotherapy by positron emission tomography (PET) with {sup 18}F-fluorodeoxyglucose (FDG), the criteria of the European Organization for Research and Treatment of Cancer (EORTC) and the positron emission tomography response criteria in solid tumors (PERCIST) were conceived. The salient features of both criteria are detailed in a comparative way. To date only retrospective data exist for the evaluation of therapies with either ICI or KI. They show that response to ICI cannot be reliably determined using the established criteria. Employing the EORTC criteria the responses to KI can be adequately ascertained so that the metabolic tumor response in FDG-PET is regarded as a surrogate marker for the efficacy of these drugs. Tumor response to therapy with ICI cannot at present be assessed with FDG-PET. Responses to BRAF and MEK inhibitors are, however, assessable using the criteria that were originally developed to evaluate responses to cytotoxic chemotherapy. (orig.) [German] Bisherige Kriterien, welche das metabolische Ansprechen von Tumoren auf zytotoxische Chemotherapien klassifizieren, lassen sich moeglicherweise nur bedingt verwenden, um ein Ansprechen auf Immuncheckpointinhibitoren (ICI) und Kinasehemmer (KI) wie BRAF- und MEK-Inhibitoren zu erfassen. Um das Ansprechen unter Chemotherapie durch die Positronenemissionstomographie (PET) mit {sup 18}F-Fluordesoxyglukose (FDG) zu erfassen, wurden Kriterien der European Organization for Research and Treatment of Cancer (EORTC) und die Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) entwickelt. Die wesentlichen Merkmale beider Kriterien werden vergleichend beschrieben. Bisher liegen sowohl fuer ICI als auch KI

  15. Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

    Directory of Open Access Journals (Sweden)

    Athanassios Argiris

    2017-05-01

    Full Text Available The major development of the past decade in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy (CT, followed by maintenance cetuximab (the “EXTREME” regimen. This regimen is supported by a phase 3 randomized trial and subsequent observational studies, and it confers well-documented survival benefits, with median survival ranging between approximately 10 and 14 months, overall response rates between 36 and 44%, and disease control rates of over 80%. Furthermore, as indicated by patient-reported outcome measures, the addition of cetuximab to platinum-based CT leads to a significant reduction in pain and problems with social eating and speech. Conversely, until very recently, there has been a lack of evidence-based second-line treatment options, and the therapies that have been available have shown low response rates and poor survival outcomes. Presently, a promising new treatment option in R/M SCCHN has emerged: immune checkpoint inhibitors (ICIs, which have demonstrated favorable results in second-line clinical trials. Nivolumab and pembrolizumab are the first two ICIs that were approved by the US Food and Drug Administration. We note that the trials that showed benefit with ICIs included not only patients who previously received ≥1 platinum-based regimens for R/M SCCHN but also patients who experienced recurrence within 6 months after combined modality therapy with a platinum agent for locally advanced disease. In this review, we outline the available clinical and observational evidence for the EXTREME regimen and the initial results from clinical trials for ICIs in patients with R/M SCCHN. We propose that these treatment options can be integrated into a new continuum of care paradigm, with first-line EXTREME regimen followed by second-line ICIs. A number of ongoing clinical trials

  16. A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer.

    Science.gov (United States)

    Bilgin, Burak; Sendur, Mehmet A N; Şener Dede, Didem; Akıncı, Muhammed Bülent; Yalçın, Bülent

    2017-09-01

    Resistance to endocrine treatment generally occurs over time, especially in the metastatic stage. In this paper, we aimed to review the mechanisms of cyclin-dependent kinase (CDK) 4/6 inhibition and clinical usage of new agents in the light of recent literature updates. A literature search was carried out using PubMed, Medline and ASCO and ESMO annual-meeting abstracts by using the following search keywords; "palbociclib", "abemaciclib", "ribociclib", "cyclin-dependent kinase inhibitors" and "CDK 4/6" in metastatic breast cancer (MBC). The last search was on 10 June 2017. CDKs and cyclins are two molecules that have a key role in cell cycle progression. Today, there are three highly selective CDK4/6 inhibitors in clinical development - palbociclib, ribociclib and abemaciclib. Palbociclib and ribociclib were recently approved by the US FDA in combination with letrozole for the treatment of MBC in a first-line setting, as well as palbociclib in combination with fulvestrant for hormone-receptor (HR)-positive MBC that had progressed while on previous endocrine therapy according to the PALOMA-1, MONALEESA-2 and PALOMA-3 trials, respectively. In the recently published randomized phase III MONARCH 2 trial, abemaciclib plus letrozole had longer progression-free survival and higher objective response rates with less serious adverse events in advanced HR-positive breast cancer previously treated with hormonal treatment. CDK4/6 inhibition is a new and promising target for patients with hormone-receptor-positive MBC. Both palbociclib and ribociclib showed significant additive benefit for patients receiving first-line treatment for HR-positive, epidermal growth factor receptor-2-negative advanced breast cancer. Palbociclib and abemaciclib also had significant activity in combination with fulvestrant for patients with MBC that progressed on previous endocrine therapy.

  17. An integrative analysis of cellular contexts, miRNAs and mRNAs reveals network clusters associated with antiestrogen-resistant breast cancer cells

    Directory of Open Access Journals (Sweden)

    Nam Seungyoon

    2012-12-01

    Full Text Available Abstract Background A major goal of the field of systems biology is to translate genome-wide profiling data (e.g., mRNAs, miRNAs into interpretable functional networks. However, employing a systems biology approach to better understand the complexities underlying drug resistance phenotypes in cancer continues to represent a significant challenge to the field. Previously, we derived two drug-resistant breast cancer sublines (tamoxifen- and fulvestrant-resistant cell lines from the MCF7 breast cancer cell line and performed genome-wide mRNA and microRNA profiling to identify differential molecular pathways underlying acquired resistance to these important antiestrogens. In the current study, to further define molecular characteristics of acquired antiestrogen resistance we constructed an “integrative network”. We combined joint miRNA-mRNA expression profiles, cancer contexts, miRNA-target mRNA relationships, and miRNA upstream regulators. In particular, to reduce the probability of false positive connections in the network, experimentally validated, rather than prediction-oriented, databases were utilized to obtain connectivity. Also, to improve biological interpretation, cancer contexts were incorporated into the network connectivity. Results Based on the integrative network, we extracted “substructures” (network clusters representing the drug resistant states (tamoxifen- or fulvestrant-resistance cells compared to drug sensitive state (parental MCF7 cells. We identified un-described network clusters that contribute to antiestrogen resistance consisting of miR-146a, -27a, -145, -21, -155, -15a, -125b, and let-7s, in addition to the previously described miR-221/222. Conclusions By integrating miRNA-related network, gene/miRNA expression and text-mining, the current study provides a computational-based systems biology approach for further investigating the molecular mechanism underlying antiestrogen resistance in breast cancer cells. In

  18. Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation.

    Science.gov (United States)

    Lewis, Joan S; Meeke, Kathleen; Osipo, Clodia; Ross, Eric A; Kidawi, Noman; Li, Tianyu; Bell, Eric; Chandel, Navdeep S; Jordan, V Craig

    2005-12-07

    We previously developed an estrogen receptor (ER)-positive breast cancer cell line (MCF-7:5C) that is resistant to long-term estrogen deprivation and undergoes rapid and complete apoptosis in the presence of physiologic concentrations of 17beta-estradiol. Here, we investigated the role of the mitochondrial apoptotic pathway in this process. Apoptosis in MCF-7:5C cells treated with estradiol, fulvestrant, or vehicle (control) was investigated by annexin V-propidium iodide double staining and 4',6-diamidino-2-phenylindole (DAPI) staining. Apoptosis was also analyzed in MCF-7:5C cells transiently transfected with small interfering RNAs (siRNAs) to apoptotic pathway components. Expression of apoptotic pathway intermediates was measured by western blot analysis. Mitochondrial transmembrane potential (psim) was determined by rhodamine-123 retention assay. Mitochondrial pathway activity was determined by cytochrome c release and cleavage of poly(ADP-ribose) polymerase (PARP) protein. Tumorigenesis was studied in ovariectomized athymic mice that were injected with MCF-7:5C cells. Differences between the treatment groups and control group were determined by two-sample t test or one-factor analysis of variance. All statistical tests were two-sided. MCF-7:5C cells treated with estradiol underwent apoptosis and showed increased expression of proapoptotic proteins, decreased psim, enhanced cytochrome c release, and PARP cleavage compared with cells treated with fulvestrant or vehicle. Blockade of Bax, Bim, and p53 mRNA expression by siRNA reduced estradiol-induced apoptosis relative to control by 76% [95% confidence interval (CI) = 73% to 79%, P estradiol-induced apoptosis in long-term estrogen-deprived breast cancer cells. Physiologic concentrations of estradiol could potentially be used to induce apoptosis and tumor regression in tumors that have developed resistance to aromatase inhibitors.

  19. Rapid effects of phytoestrogens on human colonic smooth muscle are mediated by oestrogen receptor beta.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    Epidemiological studies have correlated consumption of dietary phytoestrogens with beneficial effects on colon, breast and prostate cancers. Genomic and non-genomic mechanisms are responsible for anti-carcinogenic effects but, until now, the effect on human colon was assumed to be passive and remote. No direct effect on human colonic smooth muscle has previously been described. Institutional research board approval was granted. Histologically normal colon was obtained from the proximal resection margin of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended under 1g of tension in organ baths containing oxygenated Krebs solution at 37 degrees C. After an equilibration period, tissues were exposed to diarylpropionitrile (DPN) (ER beta agonist) and 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (ER alpha agonist) or to the synthetic phytoestrogen compounds genistein (n=8), daidzein (n=8), fisetin (n=8) and quercetin (n=8) in the presence or absence of fulvestrant (oestrogen receptor antagonist). Mechanism of action was investigated by inhibition of downstream pathways. The cholinergic agonist carbachol was used to induce contractile activity. Tension was recorded isometrically. Phytoestrogens inhibit carbachol-induced colonic contractility. In keeping with a non-genomic, rapid onset direct action, the effect was within minutes, reversible and similar to previously described actions of 17 beta oestradiol. No effect was seen in the presence of fulvestrant indicating receptor modulation. While the DPN exerted inhibitory effects, PPT did not. The effect appears to be reliant on a p38\\/mitogen activated protein kinase mediated induction of nitric oxide production in colonic smooth muscle. The present data set provides the first description of a direct effect of genistein, daidzein, fisetin and quercetin on human colonic smooth muscle. The presence of ER in colonic smooth muscle has been functionally proven and the beta

  20. The nature of cometary materials

    International Nuclear Information System (INIS)

    Stephens, J.

    1989-01-01

    Because cometary surfaces are likely to be far colder and of a different composition than planetary surfaces, there are some new considerations that must be examined in regards to placing instrumented packages or sample return devices on their surfaces. The qualitative analysis of the problem of attaching hardware to a comet and not being ejected back into space can be divided into two parts. The first problem is to pierce the mantle and obtain access to the icy core. Drilling through the mantle requires that the drilling forces be reacted. Reacting such forces probably requires attachment to the icy core below. Therefore, some kinetic impact piercing device is likely to be required as the first act of attachment. The second problem for a piercing device to overcome is the force produced by the impact kinetic energy that tries to eject the piercing device back into space. The mantle and icy core can absorb some of the impact kinetic energy in the form of fracture formation and friction energy. The energy that is not absorbed in these two ways is stored by the core as elastic deformation of the mantle and icy core. It is concluded that because the cometary materials are almost certainly brittle and the icy core is likely to be self lubricating, the elastic rebound and gas pressure expulsion forces must be counteracted by forces greater than those that may be provided by a piercing device or its capture devices (barbs)

  1. Brief Report: Cancer Immunotherapy in Patients With Preexisting Rheumatic Disease: The Mayo Clinic Experience.

    Science.gov (United States)

    Richter, Michael D; Pinkston, Olga; Kottschade, Lisa A; Finnes, Heidi D; Markovic, Svetomir N; Thanarajasingam, Uma

    2018-03-01

    To determine the risk of rheumatic disease flare and adverse effects in patients with preexisting rheumatic disease who were receiving immune checkpoint inhibitor (ICI) therapy. A retrospective medical record review was performed to identify all patients who received ICI therapy at Mayo Clinic in Rochester, Minnesota between 2011 and 2016 (~700 patients). Those with a preexisting rheumatic disease were identified using specific diagnostic codes. Sixteen patients were identified (81% female, median age 68.5 years). The most common rheumatic diseases were rheumatoid arthritis (n = 5), polymyalgia rheumatica (n = 5), Sjögren's syndrome (n = 2), and systemic lupus erythematosus (n = 2). Seven patients were receiving immunosuppressive therapy or glucocorticoids for their rheumatic disease at the time of initiation of the ICI. The primary malignancies were melanoma (n = 10), pulmonary (n = 4), or hematologic (n = 2). In most cases, ICIs were offered only after failure of several other therapies. Immune-related adverse effects (IRAEs) occurred in 6 patients, and all were treated successfully with glucocorticoids and discontinuation of the ICI therapy. There were no significant differences in time from cancer diagnosis to immunotherapy, duration of immunotherapy, age, or sex between the patients with and those without IRAEs. To our knowledge, this represents the largest single-center cohort of patients with rheumatic diseases who were exposed to modern cancer immunotherapy. Only a minority of these patients experienced a flare of their preexisting rheumatic disease or any other IRAE. © 2017, American College of Rheumatology.

  2. Seçici Özellikteki Farklı Besiyerlerinin bazı Mayaların Meyveli Yoğurttan Geri Kazanımları Amacı ile Karşılaştırılmaları (İngilizce

    Directory of Open Access Journals (Sweden)

    Şule Şenses Ergül

    2015-02-01

    Full Text Available Bu çalışmada, yapay olarak aşılanan meyveli yoğurt örneklerinden bazı mayaların izolasyonu için kullanılabilecek farklı besiyerleri karşılaştırılmıştır. Bu amaçla, kontrol besiyeri olarak malt extract agar ve beş farklı seçici besiyeri kullanılmıştır. Bu besiyerleri; malt extract yeast extract %50 fructose glucose agar, malt extract yeast extract %40 sucrose agar, malt extract yeast extract glucose %0.8 peptone agar, malt extract yeast extract glucose %0.1 peptone agar and potato dextrose %50 sucrose glucose agar’dır. Maya suşları olarak; Zygosaccharomyces rouxii IFO 0487, Zygosaccharomyces bailii IFO 0488 ve Saccharomyces cerevisiae IFO 2359 kullanılmıştır. Uygun inkübasyon süreleri sonunda, besiyerlerinin geri kazanım özellikleri belirlenmiştir. Yapılan istatistiksel değerlendirmeler ve bazı öznel verilere göre, malt extract yeast extract %40 sucrose agar besiyerinin test edilen suşlar için daha iyi sonuç verdiği tespit edilmiştir.

  3. Iterative Overlap FDE for Multicode DS-CDMA

    Science.gov (United States)

    Takeda, Kazuaki; Tomeba, Hiromichi; Adachi, Fumiyuki

    Recently, a new frequency-domain equalization (FDE) technique, called overlap FDE, that requires no GI insertion was proposed. However, the residual inter/intra-block interference (IBI) cannot completely be removed. In addition to this, for multicode direct sequence code division multiple access (DS-CDMA), the presence of residual interchip interference (ICI) after FDE distorts orthogonality among the spreading codes. In this paper, we propose an iterative overlap FDE for multicode DS-CDMA to suppress both the residual IBI and the residual ICI. In the iterative overlap FDE, joint minimum mean square error (MMSE)-FDE and ICI cancellation is repeated a sufficient number of times. The bit error rate (BER) performance with the iterative overlap FDE is evaluated by computer simulation.

  4. A mean-field approach for an intercarrier interference canceller for OFDM

    International Nuclear Information System (INIS)

    Sakata, A; Kabashima, Y; Peleg, Y

    2012-01-01

    The similarity of the mathematical description of random-field spin systems to the orthogonal frequency-division multiplexing (OFDM) scheme for wireless communication is exploited in an intercarrier interference (ICI) canceller used in the demodulation of OFDM. The translational symmetry in the Fourier domain generically concentrates the major contribution of ICI from each subcarrier in the subcarrier’s neighbourhood. This observation in conjunction with the mean-field approach leads to the development of an ICI canceller whose necessary cost of computation scales linearly with respect to the number of subcarriers. It is also shown that the dynamics of the mean-field canceller are well captured by a discrete map of a single macroscopic variable, without taking the spatial and time correlations of estimated variables into account. (paper)

  5. Mimas: Tectonic structure and geologic history

    Science.gov (United States)

    Croft, Steven K.

    1991-01-01

    Mimas, the innermost of the major saturnian satellites, occupies an important place in comparative studies of icy satellites. It is the smallest icy satellite known to have a mostly spherical shape. Smaller icy objects like Hyperion and Puck are generally irregular in shape, while larger ones like Miranda and Enceladus are spherical. Thus Mimas is near the diameter where the combination of increasing surface gravity and internal heating begin to have a significant effect on global structure. The nature and extent of endogenic surface features provide important constraints on the interior structure and history of this transitional body. The major landforms on Mimas are impact craters. Mimas has one of the most heavily cratered surfaces in the solar system. The most prominent single feature on Mimas is Herschel, an unrelaxed complex crater 130 km in diameter. The only other recognized landforms on Mimas are tectonic grooves and lineaments. Groove locations were mapped by Schenk, but without analysis of groove structures or superposition relationships. Mimas' tectonic structures are remapped here in more detail than previously has been done, as part of a general study of tectonic features on icy satellites.

  6. The impact of personality on person-centred care: a study of care staff in Swedish nursing homes.

    Science.gov (United States)

    Elfstrand Corlin, Tinna; Kajonius, Petri J; Kazemi, Ali

    2017-06-01

    In this study, we explore how personal and situational factors relate to the provision of person-centred care (PCC) in nursing homes. Specifically, we focus on the relationship between the care staff's personality traits and provision of PCC and to what extent perceptions of the working environment influences this relationship. The ultimate goal of elderly care is to meet the older person's needs and individual preferences (PCC). Interpersonal aspects of care and the quality of relationship between the care staff and the older person are therefore central in PCC. A cross-sectional Swedish sample of elderly care staff (N = 322) completed an electronic survey including measures of personality (Mini-IPIP) and person-centred care (Individualized Care Inventory, ICI). A principal component analysis was conducted on the ICI-data to separate the user orientation (process quality) of PCC from the preconditions (structure quality) of PCC. Among the five factors of personality, neuroticism was the strongest predictor of ICI user orientation. ICI preconditions significantly mediated this relationship, indicating the importance of a supportive working environment. In addition, stress was introduced as a potential explanation and was shown to mediate the impact of neuroticism on ICI preconditions. Personality traits have a significant impact on user orientation, and the perception of a supportive and stress free working environment is an important prerequisite for achieving high-quality person-centred elderly care. Understanding how personality is linked to the way care staff interacts with the older person adds a new perspective on provision of person-centred elderly care. © 2016 John Wiley & Sons Ltd.

  7. Androgen receptor or estrogen receptor-beta blockade alters DHEA-, DHT-, and E(2)-induced proliferation and PSA production in human prostate cancer cells.

    Science.gov (United States)

    Arnold, Julia T; Liu, Xunxian; Allen, Jeffrey D; Le, Hanh; McFann, Kimberly K; Blackman, Marc R

    2007-08-01

    Dehydroepiandrosterone (DHEA) is an endogenous steroid that is metabolized to androgens and/or estrogens in the human prostate. DHEA levels decline with age, and use of DHEA supplements to retard the aging process is of unproved effectiveness and safety. LNCaP and LAPC-4 prostate cancer cells were used to determine whether DHEA-modulated proliferation and prostate specific antigen (PSA) production were mediated via the androgen receptor (AR) and/or ERbeta. Cells were treated with DHEA, DHT, or E(2) and antagonists to AR (Casodex-bicalutamide) or ER (ICI 182,780) or siRNA to the respective receptors. Proliferation was assessed by MTT assay and PSA mRNA and protein secretion were measured by quantitative real-time PCR and ELISA. Associations of AR and ERbeta were analyzed by co-immunoprecipitation studies and fluorescent confocal microscopy. DHEA-, T-, and E(2)-induced proliferation of LNCaP cells was blunted by Casodex but not by ICI treatment. In LNCaP cells, Casodex and ICI suppressed hormone-induced PSA production. In LAPC-4 cells, DHT-stimulated PSA mRNA was inhibited by Casodex and ICI, and the minimal stimulation by DHEA was inhibited by ICI. Use of siRNAs confirmed involvement of AR and ERbeta in hormone-induced PSA production while AR-ERbeta co-association was suggested by immunoprecipitation and nuclear co-localization. These findings support involvement of both AR and ERbeta in mediating DHEA-, DHT-, and E(2)-induced PSA expression in prostate cancer cells. (c) 2007 Wiley-Liss, Inc.

  8. Guidelines to Avoid Biocontamination of Antarctic Subglacial Aquatic Environments: Forward Contamination Concerns, Environmental Management and Scientific Stewardship of Icy analogue environments

    Science.gov (United States)

    Race, M. S.; Hobbie, J.; et al.

    2007-12-01

    For more than a decade, scientists and space mission planners have recognized the importance of collaborative information exchange with the Antarctic research community to address their many shared exploration challenges, from drilling methods, remote sample collection, and data interpretation, to concerns about cross contamination that could adversely impact both the environment and interpretation of scientific data. Another shared concern exists in the regulatory realm; both the Antarctic and outer space environments are subject to separate international treaties that impose regulatory controls and oversight with serious implications for exploration planning. In recent years, both communities have faced the need to adjust their regulatory controls in light of fast-paced advances in scientific understanding of extreme environments, particularly related to potential microbial life. Both communities have sought and received advice from the National Research Council (NRC) through studies that suggested ways to update their respective oversight and regulatory systems while allowing for continued scientific exploration. A recently completed NRC study "Exploration of Antarctic Subglacial Aquatic Environments: Environmental and Scientific Stewardship" provided a suite of recommendations to address1) 'cleanliness' levels necessary for equipment and devices used in exploration of subglacial aquatic environments, as well as 2) the scientific basis for contamination standards, and 3) the steps for defining an overall exploration strategy conducive to sound environmental management and scientific stewardship. This talk will present the findings of the recent multinational NRC study, which is likely to translate into useful information for analogue studies that proceed to test techniques and capabilities for exploring an Europan ocean, other icy celestial locations, and related science targets on Earth. As the science and exploration of subglacial environments grows beyond its

  9. Naloxone and the Inner City Youth Experience (NICYE): a community-based participatory research study examining young people's perceptions of the BC take home naloxone program.

    Science.gov (United States)

    Mitchell, Keren; Durante, S Elise; Pellatt, Katrina; Richardson, Chris G; Mathias, Steve; Buxton, Jane A

    2017-06-07

    Take home naloxone (THN) programs reduce mortality by training bystanders to respond to opioid overdoses. Clinical observation by the health care team at the Inner City Youth (ICY) program indicated that young adults appeared to enthusiastically participate in the THN program and developed improved relationships with staff after THN training. However, we found a dearth of literature exploring the experiences of young adults with THN programs. This study set out to address this gap and identify suggestions from the young adults for program improvement. The primary research question was "How do street-involved young people experience the THN Program in Vancouver, BC?" The study was undertaken at the ICY Program. Two peer researchers with lived experience of THN were recruited from ICY and were involved in all phases of the study. The peer researchers and a graduate student facilitated two focus groups and five individual interviews with ICY program participants using a semi-structured interview guide. Audio recordings were transcribed verbatim. The cut-up-and-put-in-folders approach was used to identify emerging themes. The themes that emerged were perceptions of risk, altruism, strengthening relationship with staff, access to training, empowerment, and confidence in ability to respond, and suggestions for youth-friendly training. These themes were then situated within the framework of the health belief model to provide additional context. Participants viewed themselves as vulnerable to overdose and spoke of the importance of expanding access to THN training. Following training, participants reported an increase in internal locus of control, an improved sense of safety among the community of people who use drugs, improved self-esteem, and strengthened relationships with ICY staff. Overall, participants found THN training engaging, which appeared to enhance participation in other ICY programming. Young people perceived THN training as a positive experience that

  10. Crude extract and purified components isolated from the stems of Tinospora crispa exhibit positive inotropic effects on the isolated left atrium of rats

    DEFF Research Database (Denmark)

    Praman, Siwaporn; Mulvany, Michael J.; Williams, David E.

    2013-01-01

    of 5 bioactive compounds: higenamine, salsolinol, tyramine, adenosine and uridine. Higenamine, salsolinol (at low concentration) and tyramine acted via the adrenergic receptors to increase the force of the atrial contraction, whereas a high concentration of salsolinol acted indirectly by stimulating...... an increase in the force of contraction of the electrical field stimulated left atrium. This effect was inhibited by propranolol, atenolol, ICI-118,551, phentolamine and atropine. The positive inotropic effect on the reserpenized isolated left atrium of the Tinospora crispa extract was significantly inhibited...... by propranolol, atenolol and ICI-118,551. Phentolamine, on the other hand, caused potentiation and the effect was inhibited when propranolol was also added. Higenamine caused an increase in the force of contraction of the electrical field stimulated left atrium and this effect was significantly inhibited by ICI...

  11. PLUMEX I: Coincident Radar and Rocket Observations of Equatorial Spread-F.

    Science.gov (United States)

    1980-03-17

    SCLmS1RESTOw, VA. 2n"g fIC? ArTN PIm KIM L10I@ICY ATN W14~ PAT C~aSIc ? A T T N C O D E A k io J A MCS A T. O sI w a C LA R K wATNOS .JISU NL# ICY...AG CY SICY ATTN OYC CAPT J. MARY PT. NqtD~ulr.J 07703 SICY ATTN DoC JOH A. 9Aq SICY ATTN OCCUENT CONTROL SICY ATTN OTT CAT HAM A. PRY SICY ATTN DES IAJ...CA 9550 OC T ATTN A. B. IAZZARI 0iCr ATTN OX: CON POP TEO IW OEPT OICY ATTN DOC CON POP L-309 R. OTT EADQUARTERS ICY A"T DOC CON FO L-51 I

  12. La L.O.L.F. et les projets annuels de performance (P.A.P.) : Elaboration des figures du citoyen, de l'usager, du contribuable et du service public

    OpenAIRE

    Eyraud, Corine

    2006-01-01

    Nous nous intéresserons ici à la fois aux questions de la mesure des effets de l'action publique - ici l'action publique éducative universitaire -, aux dispositifs qui « construisent » les figures de l'usager (en tant que client ?), du citoyen, du contribuable et du service public, et aux nouvelles formes de démocratie que ces dispositifs génèrent (ou pas).

  13. Partnerships in the Middle East: Interventionist Endeavors?

    DEFF Research Database (Denmark)

    Aarøe Jørgensen, Jakob

    2014-01-01

    This chapter aims to analyse NATO’s two Middle Eastern and North African (MENA)1 partnership programmes – the Mediterranean Dialogue (MD) and the Istanbul Cooperation Initiative (ICI). The chapter aims to answer the questions: (1) why does NATO engage with MENA partners; (2) what are the obstacles...... that MD and ICI face, and; (3) is the new flexible partnership policy a step towards more constructive Middle Eastern partnerships?...

  14. Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: Harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation.

    Science.gov (United States)

    Ferris, Robert L; Lenz, Heinz-Josef; Trotta, Anna Maria; García-Foncillas, Jesús; Schulten, Jeltje; Audhuy, François; Merlano, Marco; Milano, Gerard

    2018-02-01

    Immunoglobulin (Ig) G1 antibodies stimulate antibody-dependent cell-mediated cytotoxicity (ADCC). Cetuximab, an IgG1 isotype monoclonal antibody, is a standard-of-care treatment for locally advanced and recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal cancer (CRC). Here we review evidence regarding the clinical relevance of cetuximab-mediated ADCC and other immune functions and provide a biological rationale concerning why this property positions cetuximab as an ideal partner for immune checkpoint inhibitors (ICIs) and other emerging immunotherapies. We performed a nonsystematic review of available preclinical and clinical data involving cetuximab-mediated immune activity and combination approaches of cetuximab with other immunotherapies, including ICIs, in SCCHN and CRC. Indeed, cetuximab mediates ADCC activity in the intratumoral space and primes adaptive and innate cellular immunity. However, counterregulatory mechanisms may lead to immunosuppressive feedback loops. Accordingly, there is a strong rationale for combining ICIs with cetuximab for the treatment of advanced tumors, as targeting CTLA-4, PD-1, and PD-L1 can ostensibly overcome these immunosuppressive counter-mechanisms in the tumor microenvironment. Moreover, combining ICIs (or other immunotherapies) with cetuximab is a promising strategy for boosting immune response and enhancing response rates and durability of response. Cetuximab immune activity-including, but not limited to, ADCC-provides a strong rationale for its combination with ICIs or other immunotherapies to synergistically and fully mobilize the adaptive and innate immunity against tumor cells. Ongoing prospective studies will evaluate the clinical effect of these combination regimens and their immune effect in CRC and SCCHN and in other indications. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Ion Formation Resulting from Freezing, Thawing, and Collisional Processes in Plumes Emitted from Planetary Bodies: Implications for Plume Chemistry and the Detection of Trace Organics Present in Enceladus Geysers

    Science.gov (United States)

    Beauchamp, J. L.; Wiley, J. S.; Thomas, D. A.

    2014-12-01

    Icy plumes emitted into space from Enceladus and other planetary bodies offer the intriguing possibility of sampling the composition of subsurface liquid reservoirs that may comprise habitable zones of particular astrobiological significance in our solar system. Mass spectrometric sampling of plume materials enables the detection of molecules that facilitate an assessment of the extent of chemical and biological evolution that may have occurred in a subsurface sea. In laboratory experiments we have investigated the physical and chemical processes that occur in the complex plume environment that lead to ionization of trace organic constituents, both as a result of the freezing of liquid droplets and the thawing of icy particles. We also demonstrate that collisions between icy particles lead to triboelectric charging. Subsequent discharges between oppositely charged particles result not only in the ionization of trace organics but to chemical reactions between molecular components present in the particles. For example, nitriles react with water to form amides and acids. In particular, icy particles doped with small amounts of aminoacetonitrile and water lead to the formation of the simplest amino acid glycine. The implications which these observations may have for sampling plume composition from orbit in a future mission to Enceladus will be discussed.

  16. On the statistics of uplink inter-cell interference with greedy resource allocation

    KAUST Repository

    Tabassum, Hina

    2012-10-03

    In this paper, we introduce a new methodology to model the uplink inter-cell interference (ICI) in wireless cellular networks. The model takes into account both the effect of channel statistics (i.e., path loss, shadowing, fading) and the resource allocation scheme in the interfering cells. Firstly, we derive a semi-analytical expression for the distribution of the locations of the allocated user in a given cell considering greedy resource allocation with maximum signal-to-noise ratio (SNR) criterion. Based on this, we derive the distribution of the uplink ICI from one neighboring cell. Next, we compute the moment generating function (MGF) of the cumulative ICI observed from all neighboring cells and discuss some examples. Finally, we utilize the derived expressions to evaluate the outage probability in the network. In order to validate the accuracy of the developed semi-analytical expressions, we present comparison results with Monte Carlo simulations. The major benefit of the proposed mechanism is that it helps in estimating the distribution of ICI without the knowledge of instantaneous resource allocations in the neighbor cells. The proposed methodology applies to any shadowing and fading distributions. Moreover, it can be used to evaluate important network performance metrics numerically without the need for time-consuming Monte Carlo simulations. © 2011 IEEE.

  17. On the statistics of uplink inter-cell interference with greedy resource allocation

    KAUST Repository

    Tabassum, Hina; Yilmaz, Ferkan; Dawy, Zaher; Alouini, Mohamed-Slim

    2012-01-01

    In this paper, we introduce a new methodology to model the uplink inter-cell interference (ICI) in wireless cellular networks. The model takes into account both the effect of channel statistics (i.e., path loss, shadowing, fading) and the resource allocation scheme in the interfering cells. Firstly, we derive a semi-analytical expression for the distribution of the locations of the allocated user in a given cell considering greedy resource allocation with maximum signal-to-noise ratio (SNR) criterion. Based on this, we derive the distribution of the uplink ICI from one neighboring cell. Next, we compute the moment generating function (MGF) of the cumulative ICI observed from all neighboring cells and discuss some examples. Finally, we utilize the derived expressions to evaluate the outage probability in the network. In order to validate the accuracy of the developed semi-analytical expressions, we present comparison results with Monte Carlo simulations. The major benefit of the proposed mechanism is that it helps in estimating the distribution of ICI without the knowledge of instantaneous resource allocations in the neighbor cells. The proposed methodology applies to any shadowing and fading distributions. Moreover, it can be used to evaluate important network performance metrics numerically without the need for time-consuming Monte Carlo simulations. © 2011 IEEE.

  18. Antibodies against glucan, chitin, and Saccharomyces cerevisiae mannan as new biomarkers of Candida albicans infection that complement tests based on C. albicans mannan.

    Science.gov (United States)

    Sendid, B; Dotan, N; Nseir, S; Savaux, C; Vandewalle, P; Standaert, A; Zerimech, F; Guery, B P; Dukler, A; Colombel, J F; Poulain, D

    2008-12-01

    Antibodies against Saccharomyces cerevisiae mannan (ASCA) and antibodies against synthetic disaccharide fragments of glucans (ALCA) and chitin (ACCA) are biomarkers of Crohn's disease (CD). We previously showed that Candida albicans infection generates ASCA. Here, we explored ALCA and ACCA as possible biomarkers of invasive C. albicans infection (ICI). ASCA, ALCA, ACCA, and Candida mannan antigen and antibody detection tests were performed on 69 sera obtained sequentially from 18 patients with ICIs proven by blood culture, 59 sera from CD patients, 47 sera from hospitalized subjects colonized by Candida species (CZ), and 131 sera from healthy controls (HC). ASCA, ALCA, and ACCA levels in CD and ICI patients were significantly different from those in CZ and HC subjects (PACCA, and Platelia Candida tests, 100% of ICIs were detected, with the kinetics of the antibody response depending on the patient during the time course of infection. A large number of sera presented with more than three positive tests. This is the first evidence that the detection of antibodies against chitin and glucans has diagnostic value in fungal infections and that these tests can complement more specific tests. Future trials are necessary to assess the value of these tests in multiparametric analysis, as well as their pathophysiological relevance.

  19. TRUMP’S ELECTED SHOCK EFFECT IN INDONESIAN STOCK MARKET

    Directory of Open Access Journals (Sweden)

    Vietha Devia Sagita

    2017-05-01

    Full Text Available It is inevitable that the presidential election in the United States can caused stock market fluctuations both in the United States alone as well as in other countries, for example Indonesia. Using regression method and chow test this study aimed at the effects before and after the election of Donald Trump as president of the United States on November 8, 2016. Using the data series shares the value of DJIA and ICI, this study analyzes the emergence of shock due to the change of president in United Staten share prices at the stock market in Indonesia. Based on the chow test result, the election of Donald Trump can provide a shock effect on ICI as well as DJIA, because the value of 6.917956 F count is larger than the value of 3,93 F table. DJIA positive influence on the value of ICI shares due to the election of Donald Trump is significantly below 5% at 1855.782. Meanwhile, before the election of Donald Trump DJIA has a negative influence on the ICI for - 1407.59. Based on that we can conclude that the election of Donald Trump bring a good impact on the growth of the Indonesian stock market.

  20. Quick, save the ozone

    International Nuclear Information System (INIS)

    Weber, J.

    1993-01-01

    Last December, after an all-out, nearly $500 million development effort, an Imperial Chemical Industries (ICI) plant in Louisiana was the first world-scale US facility to start pumping out HFC 134a, an alternative to CFC12, the chemical that accounts for more than 50% of CFC use. The saga of 134a is an object lesson in how a global crisis can compel governments and companies to transform technology far faster than either thought possible. With deadlines for phasing out CFCs closing in, ICI and its rivals, Du Pont and Elf, developed technology speedily by constructing factories even while their choice molecules were still being tested. ICI slashed the time it takes to commercialize a technology from the industry norm of more than a decade to only five years. If companies are forced to act on environmental issues, they do it

  1. On the modeling of uplink inter-cell interference based on proportional fair scheduling

    KAUST Repository

    Tabassum, Hina

    2012-10-03

    We derive a semi-analytical expression for the uplink inter-cell interference (ICI) assuming proportional fair scheduling (with a maximum normalized signal-to-noise ratio (SNR) criterion) deployed in the cellular network. The derived expression can be customized for different models of channel statistics that can capture path loss, shadowing, and fading. Firstly, we derive an expression for the distribution of the locations of the allocated user in a given cell. Then, we derive the distribution and moment generating function of the uplink ICI from one interfering cell. Finally, we determine the moment generating function of the cumulative uplink ICI from all interfering cells. The derived expression is utilized to evaluate important network performance metrics such as outage probability and fairness among users. The accuracy of the derived expressions is verified by comparing the obtained results to Monte Carlo simulations. © 2012 IEEE.

  2. A Statistical Model for Uplink Intercell Interference with Power Adaptation and Greedy Scheduling

    KAUST Repository

    Tabassum, Hina

    2012-10-03

    This paper deals with the statistical modeling of uplink inter-cell interference (ICI) considering greedy scheduling with power adaptation based on channel conditions. The derived model is implicitly generalized for any kind of shadowing and fading environments. More precisely, we develop a generic model for the distribution of ICI based on the locations of the allocated users and their transmit powers. The derived model is utilized to evaluate important network performance metrics such as ergodic capacity, average fairness and average power preservation numerically. Monte-Carlo simulation details are included to support the analysis and show the accuracy of the derived expressions. In parallel to the literature, we show that greedy scheduling with power adaptation reduces the ICI, average power consumption of users, and enhances the average fairness among users, compared to the case without power adaptation. © 2012 IEEE.

  3. Immunotherapy-Induced Colitis: An Emerging Problem for the Hospitalist.

    Science.gov (United States)

    Marin-Acevedo, Julian A; Harris, Dana M; Burton, M Caroline

    2018-06-01

    Since their introduction for melanoma treatment, the use of immune checkpoint inhibitors (ICIs) has rapidly expanded. Though their impact on survival is irrefutable, these medications have been associated with autoimmune-like adverse events related to their ability to induce the immune system. One of the most commonly affected organ systems is the gastrointestinal (GI) tract, in which manifestations range from mild diarrhea to severe colitis with intestinal perforation. Because of the increased use of ICIs, hospitalists are caring for an increasing number of patients experiencing their adverse events. We present a case-oriented review of the GI adverse events associated with the use of ICIs to familiarize the hospitalist with their mechanism of action and potential complications and to emphasize the importance of early diagnosis and treatment to decrease morbidity and mortality. © 2018 Society of Hospital Medicine.

  4. Waste management practices in Ontario`s workplaces: An emerging industrial ecology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-09-01

    Describes a study commissioned to evaluate employee attitudes and behaviours with respect to participation in workplace initiatives in waste diversion/reduction, to examine management initiatives related to waste diversion and reduction/recycling/reuse, and to report on Ontario Ministry of Environment & Energy activities related to industrial, commercial, and institutional (ICI) waste diversion activities. Linkages between management and employees, management and government, and ICI activities and government were also studied. The study methodology included a literature review, a series of interviews with key stakeholders, industry associations, and waste management companies, and a series of 12 case studies spanning major industrial sectors in Ontario. Issues addressed in the study include the factors that trigger waste diversion activities by ICI establishments, barriers to the initiation of waste diversion practices, and the social aspects of waste reduction/recycling/reuse practices.

  5. A Statistical Model for Uplink Intercell Interference with Power Adaptation and Greedy Scheduling

    KAUST Repository

    Tabassum, Hina; Yilmaz, Ferkan; Dawy, Zaher; Alouini, Mohamed-Slim

    2012-01-01

    This paper deals with the statistical modeling of uplink inter-cell interference (ICI) considering greedy scheduling with power adaptation based on channel conditions. The derived model is implicitly generalized for any kind of shadowing and fading environments. More precisely, we develop a generic model for the distribution of ICI based on the locations of the allocated users and their transmit powers. The derived model is utilized to evaluate important network performance metrics such as ergodic capacity, average fairness and average power preservation numerically. Monte-Carlo simulation details are included to support the analysis and show the accuracy of the derived expressions. In parallel to the literature, we show that greedy scheduling with power adaptation reduces the ICI, average power consumption of users, and enhances the average fairness among users, compared to the case without power adaptation. © 2012 IEEE.

  6. On the modeling of uplink inter-cell interference based on proportional fair scheduling

    KAUST Repository

    Tabassum, Hina; Yilmaz, Ferkan; Dawy, Zaher; Alouini, Mohamed-Slim

    2012-01-01

    We derive a semi-analytical expression for the uplink inter-cell interference (ICI) assuming proportional fair scheduling (with a maximum normalized signal-to-noise ratio (SNR) criterion) deployed in the cellular network. The derived expression can be customized for different models of channel statistics that can capture path loss, shadowing, and fading. Firstly, we derive an expression for the distribution of the locations of the allocated user in a given cell. Then, we derive the distribution and moment generating function of the uplink ICI from one interfering cell. Finally, we determine the moment generating function of the cumulative uplink ICI from all interfering cells. The derived expression is utilized to evaluate important network performance metrics such as outage probability and fairness among users. The accuracy of the derived expressions is verified by comparing the obtained results to Monte Carlo simulations. © 2012 IEEE.

  7. EPA Facility Registry Service (FRS): ICIS

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  8. Plate Tectonics and Europa's Icy Shell

    Indian Academy of Sciences (India)

    defence of his theory with the 1915 publication of The Origin of Continents and Oceans. Wegener .... is one of the most promising places in our solar system to search .... Universe, Paperback Edition, Copernicus Books, pp.191–216, 2003.

  9. NIMPH - Nano Icy Moons Propellant Harvester

    Data.gov (United States)

    National Aeronautics and Space Administration — The latest Decadal Survey lists multiple sample return missions to the Moon, Mars and Jovian moons as high priority goals. In particular, a mission to Jupiter's...

  10. Structure and petroleum potential of the continental margin between Cross Sound and Icy Bay, northern Gulf of Alaska

    Science.gov (United States)

    Bruns, T.R.

    1982-01-01

    Major structural features of the Yakutat segment, the segment of the continental margin between Cross Sound and Icy Bay, northern Gulf of Alaska, are delineated by multichannel seismic reflection data. A large structural high is centered on Fairweather Ground and lies generally at the edge of the shelf from Cross Sound to west of the Alsek Valley. A basement uplift, the Dangerous River zone, along which the seismic acoustic basement shallows by up to two kilometers, extends north from the western edge of Fairweather Ground towards the mouth of the Dangerous River. The Dangerous River zone separates the Yakutat segment into two distinct subbasins. The eastern subbasin has a maximum sediment thickness of about 4 km, and the axis of the basin is near and parallel to the coast. Strata in this basin are largely of late Cenozoic age (Neogene and Quaternary) and approximately correlate with the onshore Yakataga Formation. The western subbasin has a maximum of at least 9 km of sediment, comprised of a thick (greater than 4.5 km) Paleogene section overlain by late Cenozoic strata. The Paleogene section is truncated along the Dangerous River zone by a combination of erosion, faulting, and onlap onto the acoustic basement. Within the western subbasin, the late Cenozoic basin axis is near and parallel to the coast, but the Paleogene basin axis appears to trend in a northwest direction diagonally across the shelf. Sedimentary strata throughout the Yakutat shelf show regional subsidence and only minor deformation except in the vicinity of the Fairweather Ground structural high, near and along the Dangerous River zone, and at the shoreline near Lituya Bay. Seismic data across the continental slope and adjacent deep ocean show truncation at the continental slope of Paleogene strata, the presence of a thick (to 6 km) undeformed or mildly deformed abyssal sedimentary section at the base of the slope that in part onlaps the slope, and a relatively narrow zone along the slope or at

  11. La théorie du chaos vers une nouvelle science

    CERN Document Server

    Gleick, James

    1989-01-01

    Là où commence le chaos s'arrêtait jusqu'ici la science. Or, dans les années 70, quelques scientifiques français et américains ont commencé à explorer le chaos. A la surprise générale celui-ci s'est révélé gouverné par un ordre dynamique qui a permis d'expliquer bien des phénomènes naturels jusqu'ici totalement incompréhensibles.

  12. Efficient Sequence Detection of Multicarrier Transmissions over Doubly Dispersive Channels

    Directory of Open Access Journals (Sweden)

    Hwang Sung-Jun

    2006-01-01

    Full Text Available We propose a high-spectral-efficiency multicarrier system for communication over the doubly dispersive (DD channel which yields very low frame error rate (FER, with quadratic (in the frame length receiver complexity. To accomplish this, we combine a non-(biorthogonal multicarrier modulation (MCM scheme recently proposed by the authors with novel sequence detection (SD and channel estimation (CE algorithms. In particular, our MCM scheme allows us to accurately represent the DD channels otherwise complicated intercarrier interference (ICI and intersymbol interference (ISI response with a relatively small number of coefficients. The SD and CE algorithms then leverage this sparse ICI/ISI structure for low-complexity operation. Our SD algorithm combines a novel adaptive breadth-first search procedure with a new fast MMSE-GDFE preprocessor, while our CE algorithm uses a rank-reduced pilot-aided Wiener technique to estimate only the significant ICI/ISI coefficients.

  13. Current Diagnosis and Management of Immune Related Adverse Events (irAEs Induced by Immune Checkpoint Inhibitor Therapy

    Directory of Open Access Journals (Sweden)

    Vivek Kumar

    2017-02-01

    Full Text Available The indications of immune checkpoint inhibitors (ICIs are set to rise further with the approval of newer agent like atezolimumab for use in patients with advanced stage urothelial carcinoma. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs. The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems. There are new safety data accumulating on ICIs in patients with previously diagnosed autoimmune conditions. It is challenging for clinicians to continuously update their working knowledge to diagnose and manage these events successfully. If diagnosed timely, the majority of events are completely reversible, and temporary immunosuppression with glucocorticoids, infliximab or other agents is warranted only in the most severe grade illnesses. The same principles of management will possibly apply as newer anti- cytotoxic T lymphocytes-associated antigen 4 (CTLA-4 and programmed cell death protein 1 (PD-1/PD-L1 antibodies are introduced. The current focus of research is for prophylaxis and for biomarkers to predict the onset of these toxicities. In this review we summarize the irAEs of ICIs and emphasize their growing spectrum and their management algorithms, to update oncology practitioners.

  14. Instrumentation, Control, and Intelligent Systems

    International Nuclear Information System (INIS)

    Not Available

    2005-01-01

    Abundant and affordable energy is required for U.S. economic stability and national security. Advanced nuclear power plants offer the best near-term potential to generate abundant, affordable, and sustainable electricity and hydrogen without appreciable generation of greenhouse gases. To that end, Idaho National Laboratory (INL) has been charged with leading the revitalization of nuclear power in the U.S. The INL vision is to become the preeminent nuclear energy laboratory with synergistic, world-class, multi-program capabilities and partnerships by 2015. The vision focuses on four essential destinations: (1) Be the preeminent internationally-recognized nuclear energy research, development, and demonstration laboratory; (2) Be a major center for national security technology development and demonstration; (3) Be a multi-program national laboratory with world-class capabilities; (4) Foster academic, industry, government, and international collaborations to produce the needed investment, programs, and expertise. Crucial to that effort is the inclusion of research in advanced instrumentation, control, and intelligent systems (ICIS) for use in current and advanced power and energy security systems to enable increased performance, reliability, security, and safety. For nuclear energy plants, ICIS will extend the lifetime of power plant systems, increase performance and power output, and ensure reliable operation within the system's safety margin; for national security applications, ICIS will enable increased protection of our nation's critical infrastructure. In general, ICIS will cost-effectively increase performance for all energy security systems

  15. Cell Selection Game for Densely-Deployed Sensor and Mobile Devices In 5G Networks Integrating Heterogeneous Cells and the Internet of Things.

    Science.gov (United States)

    Wang, Lusheng; Wang, Yamei; Ding, Zhizhong; Wang, Xiumin

    2015-09-18

    With the rapid development of wireless networking technologies, the Internet of Things and heterogeneous cellular networks (HCNs) tend to be integrated to form a promising wireless network paradigm for 5G. Hyper-dense sensor and mobile devices will be deployed under the coverage of heterogeneous cells, so that each of them could freely select any available cell covering it and compete for resource with others selecting the same cell, forming a cell selection (CS) game between these devices. Since different types of cells usually share the same portion of the spectrum, devices selecting overlapped cells can experience severe inter-cell interference (ICI). In this article, we study the CS game among a large amount of densely-deployed sensor and mobile devices for their uplink transmissions in a two-tier HCN. ICI is embedded with the traditional congestion game (TCG), forming a congestion game with ICI (CGI) and a congestion game with capacity (CGC). For the three games above, we theoretically find the circular boundaries between the devices selecting the macrocell and those selecting the picocells, indicated by the pure strategy Nash equilibria (PSNE). Meanwhile, through a number of simulations with different picocell radii and different path loss exponents, the collapse of the PSNE impacted by severe ICI (i.e., a large number of picocell devices change their CS preferences to the macrocell) is profoundly revealed, and the collapse points are identified.

  16. Upregulation of ER signaling as an adaptive mechanism of cell survival in HER2-positive breast tumors treated with anti-HER2 therapy

    Science.gov (United States)

    Giuliano, Mario; Hu, Huizhong; Wang, Yen-Chao; Fu, Xiaoyong; Nardone, Agostina; Herrera, Sabrina; Mao, Sufeng; Contreras, Alejandro; Gutierrez, Carolina; Wang, Tao; Hilsenbeck, Susan G.; De Angelis, Carmine; Wang, Nicholas J.; Heiser, Laura M.; Gray, Joe W.; Lopez-Tarruella, Sara; Pavlick, Anne C.; Trivedi, Meghana V.; Chamness, Gary C.; Chang, Jenny C.; Osborne, C. Kent; Rimawi, Mothaffar F.; Schiff, Rachel

    2015-01-01

    Purpose To investigate the direct effect and therapeutic consequences of epidermal growth factor receptor 2 (HER2)-targeting therapy on expression of estrogen receptor (ER) and Bcl2 in preclinical models and clinical tumor samples. Experimental design Archived xenograft tumors from two preclinical models (UACC812 and MCF7/HER2-18) treated with ER and HER2-targeting therapies, and also HER2+ clinical breast cancer specimens collected in a lapatinib neoadjuvant trial (baseline and week 2 post treatment), were used. Expression levels of ER and Bcl2 were evaluated by immunohistochemistry and western blot. The effects of Bcl2 and ER inhibition, by ABT-737 and fulvestrant respectively, were tested in parental versus lapatinib-resistant UACC812 cells in vitro. Results Expression of ER and Bcl2 was significantly increased in xenograft tumors with acquired resistance to anti-HER2 therapy, compared with untreated tumors, in both preclinical models (UACC812: ER p=0.0014; Bcl2 p<0.001. MCF7/HER2-18: ER p=0.0007; Bcl2 p=0.0306). In the neoadjuvant clinical study, lapatinib treatment for two weeks was associated with parallel upregulation of ER and Bcl2 (Spearman’s coefficient: 0.70; p=0.0002). Importantly, 18% of tumors originally ER-negative (ER−) converted to ER+ upon anti-HER2 therapy. In ER−/HER2+ MCF7/HER2-18 xenografts, ER re-expression was primarily observed in tumors responding to potent combination of anti-HER2 drugs. Estrogen deprivation added to this anti-HER2 regimen significantly delayed tumor progression (p=0.018). In the UACC812 cells, fulvestrant, but not ABT-737, was able to completely inhibit anti-HER2-resistant growth (p<0.0001). Conclusion HER2 inhibition can enhance or restore ER expression with parallel Bcl2 upregulation, representing an ER-dependent survival mechanism potentially leading to anti-HER2 resistance. PMID:26015514

  17. Membrane Stability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Hobbs, D.T. [Westinghouse Savannah River Company, AIKEN, SC (United States)

    1997-09-30

    The Electrosynthesis Co. Inc. (ESC) was contracted by the Westinghouse Savannah River Company to investigate the long term performance and durability of cell components (anode, membrane, cathode) in an electrochemical caustic recovery process using a simulated SRC liquid waste as anolyte solution. This report details the results of two long-term studies conducted using an ICI FM01 flow cell. This cell is designed and has previously been demonstrated to scale up directly into the commercial scale ICI FM21 cell.

  18. Carboplatin treatment of antiestrogen-resistant breast cancer cells

    DEFF Research Database (Denmark)

    Larsen, Mathilde S; Yde, Christina Westmose; Christensen, Ib J

    2012-01-01

    Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen‑resistant breast cancer cell lines have increased...... sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant...... to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen‑resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression...

  19. Ovulation induction by antiestrogens in an Indian tropical vespertillionid bat, Scotophilus heathi.

    Science.gov (United States)

    Pakrasi, Pranab Lal; Tiwari, Anjana

    2006-11-02

    The ovulation induction property of ICI 182,780 a pure antiestrogen and enclomiphene citrate (ENC) was carried out in Scotophilus heathi, an Indian tropical vespertillionid bat, during December to February i.e., preovulatory period. This bat ovulates two ova naturally and shows ovulatory asynchrony. The study showed that 100 ìg of ENC followed by 10 IU hCG resulted in significantly lower number of ovulation. Whereas, the pure antiestrogen ICI 182,780 at a dose of 100 ìg followed by 10 IU hCG resulted in ovulation induction (4.2 +/- 0.4), which is significantly different in comparison to other groups. This is possibly the first report of ovulation induction using this pure antiestrogen i.e., ICI 182,780 in any bat as well as in any animal model that exhibits temporary anovulation similar to polycystic ovary disease (PCOD). This antiestrogen may be useful to induce ovulation in PCOD patients.

  20. Measuring the level and content of consciousness during epileptic seizures: the Ictal Consciousness Inventory.

    Science.gov (United States)

    Cavanna, A E; Mula, M; Servo, S; Strigaro, G; Tota, G; Barbagli, D; Collimedaglia, L; Viana, M; Cantello, R; Monaco, F

    2008-07-01

    Ictal alterations of the level of general awareness and subjective content of consciousness play a pivotal role in the clinical phenomenology of epilepsy, and reflect the pathological involvement of different neurobiological substrates. However, no self-reported measures have been proposed for patients experiencing altered conscious states during seizures. This study describes the development and validation of a new scale for the quantitative assessment of the level and content of ictal consciousness, the Ictal Consciousness Inventory (ICI). The ICI is a 20-item questionnaire generated on the basis of interviews with patients, literature review, and consultation with experts. It was tested on a sample of 110 patients attending three different epilepsy clinics in Northern Italy, who also completed standardized clinical scales. Standard psychometric methods were used to demonstrate that this scale satisfies criteria for acceptability, reliability, and validity. The ICI is proposed as a user-friendly and clinically sound instrument for the measurement of ictal alterations of consciousness in patients with epilepsy.

  1. Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer.

    Science.gov (United States)

    Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

    2016-05-10

    Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette-Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.

  2. Image guided adaptive brachytherapy with combined intracavitary and interstitial technique improves the therapeutic ratio in locally advanced cervical cancer: Analysis from the retroEMBRACE study

    DEFF Research Database (Denmark)

    LU, Fokdal; Sturdza, Alina; Mazeron, Renaud

    2016-01-01

    Background and purpose Image guided adaptive brachytherapy (IGABT) using intracavitary applicators (IC) has led to a significant improvement of local control in locally advanced cervical cancer (LACC). Further improvement has been obtained with combined intracavitary/interstitial (IC/IS) applicat...... IC/IS brachytherapy improves the therapeutic ratio in LACC by enabling a tumour specific dose escalation resulting in significantly higher local control in large tumours without adding treatment related late morbidity.......Background and purpose Image guided adaptive brachytherapy (IGABT) using intracavitary applicators (IC) has led to a significant improvement of local control in locally advanced cervical cancer (LACC). Further improvement has been obtained with combined intracavitary/interstitial (IC....../IS) applicators. The aim of this analysis was to evaluate the impact on local control and late morbidity of application of combined IS/IC brachytherapy in a large multicentre population. Material/methods 610 patients with LACC from the retroEMBRACE study were included. Patients were divided into an IC group (N...

  3. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol

    OpenAIRE

    CRUZ, PAMELA; TORRES, CRISTIAN; RAMÍREZ, MARÍA EUGENIA; EPUÑÁN, MARÍA JOSÉ; VALLADARES, LUIS EMILIO; SIERRALTA, WALTER DANIEL

    2010-01-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E2) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E2, and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27O...

  4. Instrumentation, Control, and Intelligent Systems

    Energy Technology Data Exchange (ETDEWEB)

    2005-09-01

    Abundant and affordable energy is required for U.S. economic stability and national security. Advanced nuclear power plants offer the best near-term potential to generate abundant, affordable, and sustainable electricity and hydrogen without appreciable generation of greenhouse gases. To that end, Idaho National Laboratory (INL) has been charged with leading the revitalization of nuclear power in the U.S. The INL vision is to become the preeminent nuclear energy laboratory with synergistic, world-class, multi-program capabilities and partnerships by 2015. The vision focuses on four essential destinations: (1) Be the preeminent internationally-recognized nuclear energy research, development, and demonstration laboratory; (2) Be a major center for national security technology development and demonstration; (3) Be a multi-program national laboratory with world-class capabilities; (4) Foster academic, industry, government, and international collaborations to produce the needed investment, programs, and expertise. Crucial to that effort is the inclusion of research in advanced instrumentation, control, and intelligent systems (ICIS) for use in current and advanced power and energy security systems to enable increased performance, reliability, security, and safety. For nuclear energy plants, ICIS will extend the lifetime of power plant systems, increase performance and power output, and ensure reliable operation within the system's safety margin; for national security applications, ICIS will enable increased protection of our nation's critical infrastructure. In general, ICIS will cost-effectively increase performance for all energy security systems.

  5. Cell Selection Game for Densely-Deployed Sensor and Mobile Devices In 5G Networks Integrating Heterogeneous Cells and the Internet of Things

    Science.gov (United States)

    Wang, Lusheng; Wang, Yamei; Ding, Zhizhong; Wang, Xiumin

    2015-01-01

    With the rapid development of wireless networking technologies, the Internet of Things and heterogeneous cellular networks (HCNs) tend to be integrated to form a promising wireless network paradigm for 5G. Hyper-dense sensor and mobile devices will be deployed under the coverage of heterogeneous cells, so that each of them could freely select any available cell covering it and compete for resource with others selecting the same cell, forming a cell selection (CS) game between these devices. Since different types of cells usually share the same portion of the spectrum, devices selecting overlapped cells can experience severe inter-cell interference (ICI). In this article, we study the CS game among a large amount of densely-deployed sensor and mobile devices for their uplink transmissions in a two-tier HCN. ICI is embedded with the traditional congestion game (TCG), forming a congestion game with ICI (CGI) and a congestion game with capacity (CGC). For the three games above, we theoretically find the circular boundaries between the devices selecting the macrocell and those selecting the picocells, indicated by the pure strategy Nash equilibria (PSNE). Meanwhile, through a number of simulations with different picocell radii and different path loss exponents, the collapse of the PSNE impacted by severe ICI (i.e., a large number of picocell devices change their CS preferences to the macrocell) is profoundly revealed, and the collapse points are identified. PMID:26393617

  6. Cell Selection Game for Densely-Deployed Sensor and Mobile Devices In 5G Networks Integrating Heterogeneous Cells and the Internet of Things

    Directory of Open Access Journals (Sweden)

    Lusheng Wang

    2015-09-01

    Full Text Available With the rapid development of wireless networking technologies, the Internet of Things and heterogeneous cellular networks (HCNs tend to be integrated to form a promising wireless network paradigm for 5G. Hyper-dense sensor and mobile devices will be deployed under the coverage of heterogeneous cells, so that each of them could freely select any available cell covering it and compete for resource with others selecting the same cell, forming a cell selection (CS game between these devices. Since different types of cells usually share the same portion of the spectrum, devices selecting overlapped cells can experience severe inter-cell interference (ICI. In this article, we study the CS game among a large amount of densely-deployed sensor and mobile devices for their uplink transmissions in a two-tier HCN. ICI is embedded with the traditional congestion game (TCG, forming a congestion game with ICI (CGI and a congestion game with capacity (CGC. For the three games above, we theoretically find the circular boundaries between the devices selecting the macrocell and those selecting the picocells, indicated by the pure strategy Nash equilibria (PSNE. Meanwhile, through a number of simulations with different picocell radii and different path loss exponents, the collapse of the PSNE impacted by severe ICI (i.e., a large number of picocell devices change their CS preferences to the macrocell is profoundly revealed, and the collapse points are identified.

  7. Clinical Use of the Utrecht Applicator for Combined Intracavitary/Interstitial Brachytherapy Treatment in Locally Advanced Cervical Cancer

    International Nuclear Information System (INIS)

    Nomden, Christel N.; Leeuw, Astrid A.C. de; Moerland, Marinus A.; Roesink, Judith M.; Tersteeg, Robbert J.H.A.; Jürgenliemk-Schulz, Ina Maria

    2012-01-01

    Purpose: The aims of this study were to investigate the benefit of the Utrecht interstitial CT/MR applicator for combined intracavitary/interstitial (IC/IS) approach, using magnetic resonance imaging—guided brachytherapy, over the intracavitary approach alone in patients with locally advanced cervical cancer and to analyze the clinical use of needles. Methods and Materials: This study includes the first 20 patients treated with the new applicator. Brachytherapy consisted of two pulsed dose rate applications, and the second application was performed with the IC/IS approach. The number of needles, chosen guiding holes through the ovoids, and insertion depths were based on the dose distribution and dosimetric shortcomings of the first application (IC alone). We investigated the dosimetric gain by comparing the clinical interstitial optimized plan (IC/IS clinical ) with an additionally generated optimized plan without needle use (IC study ). Furthermore, we studied the relation of the inserted needles and their source loading patterns with the high-risk clinical target volume (HR-CTV). Results: A total of 54 needles (range, 1–6 per application) were applied with an average depth of 25 mm. The chosen needle positions corresponded with the location of the HR-CTV extensions. The total and individual needle treatment times per application were on average 19% (range, 4–35%) and 7% (range, 2–14%) of the implant treatment time, respectively. The total (external-beam radiotherapy + brachytherapy) D90 HR-CTV for the IC study and the IC/IS clinical were on average 79.5 (SD 7.4) Gy α/β10 and 83.9 (SD 6.7) Gy α/β10 , respectively, with an average gain of 4.4 (SD 2.3) Gy α/β10 for the second application. Conclusions: Needle placement was feasible in all patients and resulted in a gain in dose and better coverage of HR-CTV. Defining the location of HR-CTV protrusions and analyzing the associated needles has given us deeper understanding of the possibilities in magnetic

  8. A Study of the Behavior Characteristics for K-type Thermocouple

    International Nuclear Information System (INIS)

    Ye, Songhae; Kim, Yongsik; Lee, Sooill; Kim, Sungjin; Lyou, Jooon

    2014-01-01

    K-type thermocouple is widely used in nuclear power plants (NPP) and they provide reliable service. Generally, the thermocouple assembly is the finished product and usually only nondestructive tests are performed on the assembly, whereas destructive tests are confined to selected bulk cable specimens. This K-type thermocouple has been used representatively in the In-Core Instrument Assembly (ICI) in the nuclear power plants. The ICI consists of five rhodium emitter detectors that provide information on the thermal power for the core and one K-type thermocouple made with two cables (Chromel-Alumel) that provides the temperature of core exit (CET). Generally, the quantity of the ICI is absolutely different according to the number of fuel assemblies in the NPP. In the case of SKN 3 and 4, they were designed to the 61 ICI to provide information on the core cooling to the inadequate core cooling monitoring system (ICCMS). This measured temperature could be also used to check the entry condition of severe accidents. The technology of the TFDR is a generic skill to detect the fault position of the cable. In-core Instruments (ICIs) were used to detect the Core Exit Temperature (CET) in a reactor. This measured temperature was also used to check the entry condition of severe accidents. However, if a serious accident occurs, the upper portion of the core is damaged. This instrument has not been available. This paper illustrates the estimation possibility for the status of molten core through the high-temperature characteristics test of k-type thermocouple. It turns out that it is possible to measure the k-type thermocouple up to 1350 .deg. C degrees before melting during insertion into the melting furnace. Additionally, in order to measure a high temperature of 2000 .deg. C or more, the replacement possibility of k-type thermocouple was evaluated. However the tungsten-rhenium thermocouple is impossible to use in the detection of temperature at the in-core because of the

  9. ASSESSMENT OF RELEASE RATES FOR RADIONUCLIDES IN ACTIVATED CONCRETE.

    Energy Technology Data Exchange (ETDEWEB)

    SULLIVAN,T.M.

    2003-08-23

    The Maine Yankee (MY) nuclear power plant is undergoing the process of decontamination and decommissioning (D&D). Part of the process requires analyses that demonstrate that any radioactivity that remains after D&D will not cause exposure to radioactive contaminants to exceed acceptable limits. This requires knowledge of the distribution of radionuclides in the remaining material and their potential release mechanisms from the material to the contacting groundwater. In this study the concern involves radionuclide contamination in activated concrete in the ICI Sump below the containment building. Figures 1-3 are schematic representations of the ICI Sump. Figure 2 and 3 contain the relevant dimensions needed for the analysis. The key features of Figures 2 and 3 are the 3/8-inch carbon steel liner that isolates the activated concrete from the pit and the concrete wall, which is between 7 feet and 7 feet 2 inches thick. During operations, a small neutron flux from the reactor activated the carbon steel liner and the concrete outside the liner. Current MY plans call for filling the ICI sump with compacted sand.

  10. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.

    Science.gov (United States)

    Cruz, Pamela; Torres, Cristian; Ramírez, María Eugenia; Epuñán, María José; Valladares, Luis Emilio; Sierralta, Walter Daniel

    2010-05-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.

  11. The method to Certify Performance of Long-Lived In-Core Instrumentation

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Kyung-ho; Cha, Kyoon-ho; Moon, Sang-rae [KHNP CRI, Daejeon (Korea, Republic of)

    2015-10-15

    Rh ICI (In-Core Instrumentation) used in OPR1000 generates the relatively large signal but its lifetime is below 6 years. Rh ICI consists of 5 detectors which is a type of SPND (Self Powered Neutron Detector), a couple of thermo-couple, one background wire and several fillers. The short lifetime of Rh detector causes increase of procurement price and space shortage of spent fuel pool. Also, it makes operators be exposed by more radiations. KHNP (Korea Hydro and Nuclear Power Co., Ltd.) CRI (Central Research Institute) is developing the LLICI (Long-Lived In-Core Instrumentation) based on vanadium to solve these problems. LLICI is the detector which is a type of SPND based on Vanadium and has the lifetime of about 10 years. The short lifetime of OPR1000's Rh ICI and long cycle operation strategy cause increase of procurement price, space shortage of spent fuel pool and more radiation exposed to operators. KHNP (Korea Hydro and Nuclear Power Co., Ltd.) CRI (Central Research Institute) is developing the LLICI (Long-Lived In-Core Instrumentation) to solve these problems.

  12. Assessment of block height for satisfactory spinal anaesthesia for caesarean section.

    Science.gov (United States)

    Ousley, R; Egan, C; Dowling, K; Cyna, A M

    2012-12-01

    We investigated block heights that anaesthetists considered adequate for caesarean section to proceed under spinal anaesthesia. During 3 months, 15 obstetric anaesthetists recorded block height to touch, pinprick or cold when spinal anaesthesia was considered satisfactory for caesarean section to proceed. Median (IQR [range]) block height for touch, pinprick, first cold and icy were: T10 (T7-T12 [T3-L1]); T5 (T4-T6 [C7-L1]); T5 (T4-T6 [C7-L1]); and T3 (T2-T4 [C7-L1]), respectively. Modalities were significantly correlated for: touch and cold, p = 0.0001; touch and icy, p = 0.0007; touch and pinprick, p = 0.0018; cold and icy, p satisfactory anaesthesia despite 76 (81%) having a block to touch below T6. Single modality assessment of block height, particularly using touch, may erroneously indicate inadequate anaesthesia for caesarean section. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  13. The role of neratinib in HER2-driven breast cancer.

    Science.gov (United States)

    Cherian, Mathew A; Ma, Cynthia X

    2017-06-30

    Up to 25% of patients with early-stage HER2+ breast cancer relapse despite adjuvant trastuzumab-based regimens and virtually all patients with metastatic disease eventually die from resistance to existing treatment options. In addition, recent studies indicate that activating HER2 mutations without gene amplification could drive tumor growth in a subset of HER2-ve breast cancer that is not currently eligible for HER2-targeted agents. Neratinib is an irreversible HER kinase inhibitor with activity as extended adjuvant therapy following standard trastuzumab-based adjuvant treatment in a Phase III trial. Phase II trials of neratinib demonstrate promising activity in combination with cytotoxic agents in trastuzumab resistant metastatic HER2+ breast cancer, and either as monotherapy or in combination with fulvestrant for HER2-mutated breast cancers. We anticipate a potential role for neratinib in the therapy of these patient populations.

  14. Journey to the Center of Icy Moons

    Data.gov (United States)

    National Aeronautics and Space Administration — In Jules Verne's classic science fiction, Journey to the Center of the Earth, Professor Otto Lidenbrock and his company descend into an Icelandic volcano to explore...

  15. Vital Signs: Seismology of Icy Ocean Worlds.

    Science.gov (United States)

    Vance, Steven D; Kedar, Sharon; Panning, Mark P; Stähler, Simon C; Bills, Bruce G; Lorenz, Ralph D; Huang, Hsin-Hua; Pike, W T; Castillo, Julie C; Lognonné, Philippe; Tsai, Victor C; Rhoden, Alyssa R

    2018-01-01

    Ice-covered ocean worlds possess diverse energy sources and associated mechanisms that are capable of driving significant seismic activity, but to date no measurements of their seismic activity have been obtained. Such investigations could reveal the transport properties and radial structures, with possibilities for locating and characterizing trapped liquids that may host life and yielding critical constraints on redox fluxes and thus on habitability. Modeling efforts have examined seismic sources from tectonic fracturing and impacts. Here, we describe other possible seismic sources, their associations with science questions constraining habitability, and the feasibility of implementing such investigations. We argue, by analogy with the Moon, that detectable seismic activity should occur frequently on tidally flexed ocean worlds. Their ices fracture more easily than rocks and dissipate more tidal energy than the worlds also should create less thermal noise due to their greater distance and consequently smaller diurnal temperature variations. They also lack substantial atmospheres (except in the case of Titan) that would create additional noise. Thus, seismic experiments could be less complex and less susceptible to noise than prior or planned planetary seismology investigations of the Moon or Mars. Key Words: Seismology-Redox-Ocean worlds-Europa-Ice-Hydrothermal. Astrobiology 18, 37-53.

  16. Administration of a selective β2 adrenergic receptor antagonist exacerbates neuropathology and cognitive deficits in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Branca, Caterina; Wisely, Elena V; Hartman, Lauren K; Caccamo, Antonella; Oddo, Salvatore

    2014-12-01

    Currently, there are no available approaches to cure or slow down the progression of Alzheimer's disease (AD), which is characterized by the accumulation of extracellular amyloid-β (Aβ) deposits and intraneuronal tangles that comprised hyperphosphorylated tau. The β2 adrenergic receptors (β2ARs) are expressed throughout the cortex and hippocampus and play a key role in cognitive functions. Alterations in the function of these receptors have been linked to AD; however, these data remain controversial as apparent contradicting reports have been published. Given the current demographics of growing elderly population and the high likelihood of concurrent β-blocker use for other chronic conditions, more studies into the role of this receptor in AD animal models are needed. Here, we show that administration of ICI 118,551 (ICI), a selective β2AR antagonist, exacerbates cognitive deficits in a mouse model of AD, the 3xTg-AD mice. Neuropathologically, ICI increased Aβ levels and Aβ plaque burden. Concomitantly, ICI-treated 3xTg-AD mice showed an increase in tau phosphorylation and accumulation. Mechanistically, these changes were linked to an increase in amyloidogenic amyloid precursor protein processing. These results suggest that under the conditions used here, selective pharmacologic inhibition of β2ARs has detrimental effects on AD-like pathology in mice. Overall, these studies strengthen the notion that the link between β2ARs and AD is likely highly complex and suggest caution in generalizing the beneficial effects of β blockers on AD. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Stability of Sulphur Dimers (S2) in Cometary Ices

    International Nuclear Information System (INIS)

    Mousis, O.; Ronnet, T.; Ozgurel, O.; Pauzat, F.; Markovits, A.; Ellinger, Y.; Lunine, J. I.; Luspay-Kuti, A.

    2017-01-01

    S 2 has been observed for decades in comets, including comet 67P/Churyumov–Gerasimenko. Despite the fact that this molecule appears ubiquitous in these bodies, the nature of its source remains unknown. In this study, we assume that S 2 is formed by irradiation (photolysis and/or radiolysis) of S-bearing molecules embedded in the icy grain precursors of comets and that the cosmic ray flux simultaneously creates voids in ices within which the produced molecules can accumulate. We investigate the stability of S 2 molecules in such cavities, assuming that the surrounding ice is made of H 2 S or H 2 O. We show that the stabilization energy of S 2 molecules in such voids is close to that of the H 2 O ice binding energy, implying that they can only leave the icy matrix when this latter sublimates. Because S 2 has a short lifetime in the vapor phase, we derive that its formation in grains via irradiation must occur only in low-density environments such as the ISM or the upper layers of the protosolar nebula, where the local temperature is extremely low. In the first case, comets would have agglomerated from icy grains that remained pristine when entering the nebula. In the second case, comets would have agglomerated from icy grains condensed in the protosolar nebula and that would have been efficiently irradiated during their turbulent transport toward the upper layers of the disk. Both scenarios are found consistent with the presence of molecular oxygen in comets.

  18. Stability of Sulphur Dimers (S{sub 2}) in Cometary Ices

    Energy Technology Data Exchange (ETDEWEB)

    Mousis, O.; Ronnet, T. [Aix Marseille Université, CNRS, LAM (Laboratoire d’Astrophysique de Marseille) UMR 7326, F-13388, Marseille (France); Ozgurel, O.; Pauzat, F.; Markovits, A.; Ellinger, Y. [Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC Univ. Paris 06, CNRS UMR 7616, F-75252 Paris CEDEX 05 (France); Lunine, J. I. [Department of Astronomy and Carl Sagan Institute, Space Sciences Building Cornell University, Ithaca, NY 14853 (United States); Luspay-Kuti, A., E-mail: olivier.mousis@lam.fr [Department of Space Research, Southwest Research Institute, 6220 Culebra Road, San Antonio, TX 78228 (United States)

    2017-02-01

    S{sub 2} has been observed for decades in comets, including comet 67P/Churyumov–Gerasimenko. Despite the fact that this molecule appears ubiquitous in these bodies, the nature of its source remains unknown. In this study, we assume that S{sub 2} is formed by irradiation (photolysis and/or radiolysis) of S-bearing molecules embedded in the icy grain precursors of comets and that the cosmic ray flux simultaneously creates voids in ices within which the produced molecules can accumulate. We investigate the stability of S{sub 2} molecules in such cavities, assuming that the surrounding ice is made of H{sub 2}S or H{sub 2}O. We show that the stabilization energy of S{sub 2} molecules in such voids is close to that of the H{sub 2}O ice binding energy, implying that they can only leave the icy matrix when this latter sublimates. Because S{sub 2} has a short lifetime in the vapor phase, we derive that its formation in grains via irradiation must occur only in low-density environments such as the ISM or the upper layers of the protosolar nebula, where the local temperature is extremely low. In the first case, comets would have agglomerated from icy grains that remained pristine when entering the nebula. In the second case, comets would have agglomerated from icy grains condensed in the protosolar nebula and that would have been efficiently irradiated during their turbulent transport toward the upper layers of the disk. Both scenarios are found consistent with the presence of molecular oxygen in comets.

  19. Potential role of recombinant secretory leucoprotease inhibitor in the prevention of neutrophil mediated matrix degradation.

    Science.gov (United States)

    Llewellyn-Jones, C G; Lomas, D A; Stockley, R A

    1994-06-01

    Neutrophil elastase is able to degrade connective tissue matrices and is thought to be involved in the pathogenesis of destructive lung diseases. The ability of recombinant secretory leucoprotease inhibitor (rSLPI) to inhibit neutrophil mediated degradation of fibronectin in vitro is demonstrated and its efficacy compared with native alpha-1-proteinase inhibitor (n alpha 1-PI), recombinant alpha-1-proteinase inhibitor (r alpha 1-PI), and the chemical elastase inhibitor ICI 200,355. When preincubated with neutrophils both rSLPI and r alpha 1-PI were effective inhibitors of fibronectin degradation although n alpha 1-PI and ICI 200,355 were less effective. Recombinant SLPI was the most effective inhibitor when the cells were allowed to adhere to fibronectin before the addition of the inhibitors. Preincubation of rSLPI (0.1 mumol/l) with the fibronectin plate resulted in almost total inhibition of fibronectin degradation (reduced to 3.3 (SE 0.9)% of control). Pretreating the fibronectin plate with 1 mumol/l rSLPI, r alpha 1-PI and ICI 200,355 followed by thorough washing before the addition of cells resulted in no inhibition of fibronectin degradation with r alpha 1-PI and the ICI inhibitor, but rSLPI retained its inhibitory effect. This effect could be reduced by adding rSLPI in high pH buffer or 2 mol/1 NaCl. It is postulated that rSLPI binds to fibronectin to form a protective layer which prevents its degradation by neutrophil elastase. It may prove to be the most useful therapeutic agent in the prevention of neutrophil mediated lung damage.

  20. Satellites

    International Nuclear Information System (INIS)

    Burns, J.A.; Matthews, M.S.

    1986-01-01

    The present work is based on a conference: Natural Satellites, Colloquium 77 of the IAU, held at Cornell University from July 5 to 9, 1983. Attention is given to the background and origins of satellites, protosatellite swarms, the tectonics of icy satellites, the physical characteristics of satellite surfaces, and the interactions of planetary magnetospheres with icy satellite surfaces. Other topics include the surface composition of natural satellites, the cratering of planetary satellites, the moon, Io, and Europa. Consideration is also given to Ganymede and Callisto, the satellites of Saturn, small satellites, satellites of Uranus and Neptune, and the Pluto-Charon system

  1. Développement d'immunoessais associés aux électrodes sérigraphies: des particules superparamagnétiques aux nanobodies

    OpenAIRE

    Patris, Stéphanie

    2014-01-01

    Cette thèse a pour vocation de contribuer au développement de différents immunocapteurs ampérométriques associés aux électrodes sérigraphiées (SPE). Les immunocapteurs sont des dispositifs simples associant un anticorps ou un antigène qui assurent la sélectivité à un transducteur (ici une SPE) ;ce dernier transforme la liaison anticorps/antigène en un signal mesurable (ici ampérométrique). Le travail est divisé en deux volets principaux. Le premier est consacré à la mise en œuvre de dif...

  2. Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Sacdalan DB

    2018-02-01

    Full Text Available Danielle Benedict Sacdalan,1 Josephine Anne Lucero,2 Dennis Lee Sacdalan1 1Section of Medical Oncology, Department of Medicine, University of the Philippines Manila and Philippine General Hospital, Manila, Philippines; 2Department of Medicine, University of the Philippines Manila and Philippine General Hospital, Manila, Philippines Introduction: Systemic inflammation is associated with prognosis in solid tumors. The neutrophil-to-lymphocyte ratio (NLR is a marker for the general immune response to various stress stimuli. Studies have shown correlation of NLR to outcomes in immune checkpoint blockade, peripheral neutrophil count to intratumor neutrophil population, and NLR to intratumoral levels of myeloid-derived suppressor cells. Studies have shown elevated peripheral blood regulator T cells accompanied by elevated NLR are associated with poor outcomes further highlighting the importance of inflammation in the prognosis of cancer patients.Methods: We performed a meta-analysis of published articles on the utility of baseline NLR in predicting outcomes in patients treated with immune checkpoint inhibitors (ICIs using Review Manager, version 5.3. Seven studies on the prognostic utility of NLR in ICI treatment were included in this analysis. For outcomes of interest, the hazard ratios (HRs were computed. Subgroup analyses were planned based on type of malignancy and type of immune checkpoint inhibitor.Results/discussion: A high NLR resulted in worse overall survival (OS (HR, 1.92; 95% CI, 1.29–2.87; p=0.001 and progression-free survival (PFS; HR, 1.66; 95% CI, 1.38–2.01; p<0.00001 across types of malignancies studied (melanoma, non-small-cell lung cancer, and genitourinary cancer. Subgroup analysis across different types of malignancies treated with ICI showed similar results for OS and PFS. The single study on genitourinary cancers also showed worse OS and PFS (OS: HR, 1.82; 95% CI, 1.29–2.87; p=0.001 and PFS: HR, 1.83; 95% CI, 0.97–3

  3. Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors

    Energy Technology Data Exchange (ETDEWEB)

    Madureira, Tânia Vieira, E-mail: tvmadureira@icbas.up.pt [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Institute of Biomedical Sciences Abel Salazar, U.Porto (ICBAS)—University of Porto, Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto (Portugal); Malhão, Fernanda; Pinheiro, Ivone; Lopes, Célia; Ferreira, Nádia [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Institute of Biomedical Sciences Abel Salazar, U.Porto (ICBAS)—University of Porto, Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto (Portugal); Urbatzka, Ralph [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Castro, L. Filipe C. [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Faculty of Sciences (FCUP), U.Porto—University of Porto, Department of Biology, Rua do Campo Alegre, P 4169-007 Porto (Portugal); Rocha, Eduardo [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Institute of Biomedical Sciences Abel Salazar, U.Porto (ICBAS)—University of Porto, Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto (Portugal)

    2015-12-15

    Highlights: • Evidence of crosstalk between estrogens and peroxisomal pathways in brown trout. • VtgA and ERα mRNA levels increased after 1, 10 and 50 μM of ethinylestradiol (EE2). • ERβ-1, catalase and urate oxidase mRNA levels decreased after estrogenic stimuli. • Estrogenic effects in VtgA, ERα and Uox mRNA levels were reverted by ICI 182,780. • Immunofluorescence/electron microscopy shows smaller peroxisomes after 50 μM of EE2. - Abstract: Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96 h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol—EE2) at 1, 10 and 50 μM; (2) an ER antagonist (ICI 182,780) at 10 and 50 μM; and (3) mixtures of both (Mix I—10 μM EE2 and 50 μM ICI; Mix II—1 μM EE2 and 10 μM ICI and Mix III—1 μM EE2 and 50 μM ICI). The mRNA levels of the estrogenic targets (ERα, ERβ-1 and vitellogenin A—VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase—Uox, 17β-hydroxysteroid dehydrogenase 4—17β-HSD4, peroxin 11α—Pex11α and PPARα) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50 μM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERα m

  4. Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors

    International Nuclear Information System (INIS)

    Madureira, Tânia Vieira; Malhão, Fernanda; Pinheiro, Ivone; Lopes, Célia; Ferreira, Nádia; Urbatzka, Ralph; Castro, L. Filipe C.; Rocha, Eduardo

    2015-01-01

    Highlights: • Evidence of crosstalk between estrogens and peroxisomal pathways in brown trout. • VtgA and ERα mRNA levels increased after 1, 10 and 50 μM of ethinylestradiol (EE2). • ERβ-1, catalase and urate oxidase mRNA levels decreased after estrogenic stimuli. • Estrogenic effects in VtgA, ERα and Uox mRNA levels were reverted by ICI 182,780. • Immunofluorescence/electron microscopy shows smaller peroxisomes after 50 μM of EE2. - Abstract: Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96 h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol—EE2) at 1, 10 and 50 μM; (2) an ER antagonist (ICI 182,780) at 10 and 50 μM; and (3) mixtures of both (Mix I—10 μM EE2 and 50 μM ICI; Mix II—1 μM EE2 and 10 μM ICI and Mix III—1 μM EE2 and 50 μM ICI). The mRNA levels of the estrogenic targets (ERα, ERβ-1 and vitellogenin A—VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase—Uox, 17β-hydroxysteroid dehydrogenase 4—17β-HSD4, peroxin 11α—Pex11α and PPARα) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50 μM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERα m

  5. The Enceladus Ionizing Radiation Environment: Implications for Biomolecules

    Science.gov (United States)

    Teodoro, L. A.; Elphic, R. C.; Davila, A. F.; McKay, C.; Dartnell, L.

    2016-12-01

    Enceladus' subsurface ocean is a possible abode for life, but it is inaccessible with current technology. However, icy particles and vapor are being expelled into space through surface fractures known as Tiger Stripes, forming a large plume centered in the South Polar Terrains. Direct chemical analyses by Cassini have revealed salts and organic compounds in a significant fraction of plume particles, which suggests that the subsurface ocean is the main source of materials in the plume (i.e. frozen ocean spray). While smaller icy particles in the plume reach escape velocity and feed Saturn's E-ring, larger particles fall back on the moon's surface, where they accumulate as icy mantling deposits at practically all latitudes. The organic content of these fall-out materials could be of great astrobiological relevance. Galactic Cosmic Rays (GCRs) that strike both Enceladus' surface and the lofted icy particles produce ionizing radiation in the form of high-energy electrons, protons, gamma rays, neutrons and muons. An additional source of ionizing radiation is the population of energetic charged particles in Saturn's magnetosphere. The effects of ionizing radiation in matter always involve the destruction of chemical bonds and the creation of free radicals. Both affect organic matter, and can damage or destroy biomarkers over time. Using ionizing radiation transport codes, we recreated the radiation environment on the surface of Enceladus, and evaluated its possible effects on organic matter (including biomarkers) in the icy mantling deposits. Here, we present full Monte-Carlo simulations of the nuclear reactions induced by the GCRs hitting Enceladus's surface using a code based on the GEANT-4 toolkit for the transport of particles. To model the GCR primary spectra for Z= 1-26 (protons to iron nuclei) we assumed the CREAME96 model under solar minimum, modified to take into account Enceladus' location. We considered bulk compositions of: i) pure water ice, ii) water ice

  6. Mechanical stimulation enhanced estrogen receptor expression and callus formation in diaphyseal long bone fracture healing in ovariectomy-induced osteoporotic rats.

    Science.gov (United States)

    Chow, S K H; Leung, K S; Qin, J; Guo, A; Sun, M; Qin, L; Cheung, W H

    2016-10-01

    Estrogen receptor (ER) in ovariectomy-induced osteoporotic fracture was reported to exhibit delayed expression. Mechanical stimulation enhanced ER-α expression in osteoporotic fracture callus at the tissue level. ER was also found to be required for the effectiveness of vibrational mechanical stimulation treatment in osteoporotic fracture healing. Estrogen receptor(ER) is involved in mechanical signal transduction in bone metabolism. Its expression was reported to be delayed in osteoporotic fracture healing. The purpose of this study was to investigate the roles played by ER during osteoporotic fracture healing enhanced with mechanical stimulation. Ovariectomy-induced osteoporotic SD rats that received closed femoral fractures were divided into five groups, (i) SHAM, (ii) SHAM-VT, (iii) OVX, (iv) OVX-VT, and (v) OVX-VT-ICI, where VT stands for whole-body vibration treatment and ICI for ER antagonization by ICI 182,780. Callus formation and gene expression were assessed at 2, 4, and 8 weeks postfracture. In vitro osteoblastic differentiation, mineralization, and ER-α expression were assessed. The delayed ER expression was found to be enhanced by vibration treatment. Callus formation enhancement was shown by callus morphometry and micro-CT analysis. Enhancement effects by vibration were partially abolished when ER was modulated by ICI 182,780, in terms of callus formation capacity at 2-4 weeks and ER gene and protein expression at all time points. In vitro, ER expression in osteoblasts was not enhanced by VT treatment, but osteoblastic differentiation and mineralization were enhanced under estrogen-deprived condition. When osteoblastic cells were modulated by ICI 182,780, enhancement effects of VT were eliminated. Vibration was able to enhance ER expression in ovariectomy-induced osteoporotic fracture healing. ER was essential in mechanical signal transduction and enhancement in callus formation effects during osteoporotic fracture healing enhanced by vibration

  7. Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors.

    Science.gov (United States)

    Madureira, Tânia Vieira; Malhão, Fernanda; Pinheiro, Ivone; Lopes, Célia; Ferreira, Nádia; Urbatzka, Ralph; Castro, L Filipe C; Rocha, Eduardo

    2015-12-01

    Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol-EE2) at 1, 10 and 50μM; (2) an ER antagonist (ICI 182,780) at 10 and 50μM; and (3) mixtures of both (Mix I-10μM EE2 and 50μM ICI; Mix II-1μM EE2 and 10μM ICI and Mix III-1μM EE2 and 50μM ICI). The mRNA levels of the estrogenic targets (ERα, ERβ-1 and vitellogenin A-VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase-Uox, 17β-hydroxysteroid dehydrogenase 4-17β-HSD4, peroxin 11α-Pex11α and PPARα) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50μM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERα mRNA increased after all EE2 treatments, while ERβ-1 had an inverse pattern. The EE2 action was reversed by ICI 182,780 in a concentration-dependent manner, for VtgA, ERα and Uox. Overall, our data show the great value of primary brown trout hepatocytes to study the effects of estrogenic/anti-estrogenic inputs in peroxisome kinetics and in ER and PPARα signaling, backing the still open hypothesis of crosstalk interactions between these pathways and calling for more mechanistic

  8. Water and Volatiles in the Outer Solar System

    Science.gov (United States)

    Grasset, O.; Castillo-Rogez, J.; Guillot, T.; Fletcher, L. N.; Tosi, F.

    2017-10-01

    Space exploration and ground-based observations have provided outstanding evidence of the diversity and the complexity of the outer solar system. This work presents our current understanding of the nature and distribution of water and water-rich materials from the water snow line to the Kuiper Belt. This synthesis is timely, since a thorough exploration of at least one object in each region of the outer solar system has now been achieved. Next steps, starting with the Juno mission now in orbit around Jupiter, will be more focused on understanding the processes at work than on describing the general characteristics of each giant planet systems. This review is organized in three parts. First, the nature and the distribution of water and volatiles in giant and intermediary planets are described from their inner core to their outer envelopes. A special focus is given to Jupiter and Saturn, which are much better understood than the two ice giants (Uranus and Neptune) thanks to the Galileo and Cassini missions. Second, the icy moons will be discussed. Space missions and ground-based observations have revealed the variety of icy surfaces in the outer system. While Europa, Enceladus, and maybe Titan present past or even active tectonic and volcanic activities, many other moons have been dead worlds for more than 3 billion years. Ice compositions found at these bodies are also complex and it is now commonly admitted that icy surfaces are never composed of pure ices. A detailed review of the distribution of non-ice materials on the surfaces and in the tenuous atmospheres of the moons is proposed, followed by a more focused discussion on the nature and the characteristics of the liquid layers trapped below the cold icy crusts that have been suggested in the icy Galilean moons, and in Enceladus, Dione, and Titan at Saturn. Finally, the recent observations collected by Dawn at Ceres and New Horizons at Pluto, as well as the state of knowledge of other transneptunian objects

  9. Biological assessment and streambed-sediment chemistry of streams in the Indianapolis metropolitan area, Indiana, 2003–2008

    Science.gov (United States)

    Voelker, David C.

    2012-01-01

    During 2003–2008, the U.S. Geological Survey sampled 13 sites in the Indianapolis metropolitan area in Indiana for benthic invertebrates, fish communities, and streambed-sediment chemistry. Data from seven White River sites and six tributary sites complement surface-water chemistry data collected by the Indianapolis Department of Public Works. The information is being used to assess changes in water quality in conjunction with the City's programs to reduce combined sewer overflows and other point and nonpoint sources of pollution in the Indianapolis area. During the study, 233 benthic-invertebrate taxa were identified from which the Ephemeroptera, Plecoptera, and Trichoptera (EPT) Index, the Hilsenhoff Biotic Index (HBI), and the Invertebrate Community Index (ICI) were calculated. EPT index scores ranged from 2 to 16 on the White River and from 2 to 17 on the tributaries. EPT index scores indicate that these pollution-intolerant taxa are more prevalent upstream from and away from the combined-sewer areas of Indianapolis. HBI scores from sites on the White River ranged from 4.67 (good) to 9.55 (very poor), whereas on the tributaries, scores ranged from 4.21 (very good) to 8.14 (poor). Lower HBI scores suggest that less organic pollution was present and, like the EPT scores, indicate better conditions where combined-sewer overflows (CSOs) are not present. Similarly, ICI scores indicated better conditions upstream from the CSO outfalls on the White River. White River scores ranged from 12 to 46, where higher ICI scores indicate better conditions in the benthic-invertebrate community. ICI scores at the tributary sites ranged from 12 to 52, with the highest scores on streams without CSOs.

  10. Gene expression profiling in Ishikawa cells: A fingerprint for estrogen active compounds

    International Nuclear Information System (INIS)

    Boehme, Kathleen; Simon, Stephanie; Mueller, Stefan O.

    2009-01-01

    Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (Diethylstilbestrol, Genistein, Zearalenone, Resveratrol, Bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused by these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, Bisphenol A, o,p'-DDT, Zearalenone, Genistein and Resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of Resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals Bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects

  11. A statistical model of uplink inter-cell interference with slow and fast power control mechanisms

    KAUST Repository

    Tabassum, Hina; Yilmaz, Ferkan; Dawy, Zaher; Alouini, Mohamed-Slim

    2013-01-01

    Uplink power control is in essence an interference mitigation technique that aims at minimizing the inter-cell interference (ICI) in cellular networks by reducing the transmit power levels of the mobile users while maintaining their target received signal quality levels at base stations. Power control mechanisms directly impact the interference dynamics and, thus, affect the overall achievable capacity and consumed power in cellular networks. Due to the stochastic nature of wireless channels and mobile users' locations, it is important to derive theoretical models for ICI that can capture the impact of design alternatives related to power control mechanisms. To this end, we derive and verify a novel statistical model for uplink ICI in Generalized-K composite fading environments as a function of various slow and fast power control mechanisms. The derived expressions are then utilized to quantify numerically key network performance metrics that include average resource fairness, average reduction in power consumption, and ergodic capacity. The accuracy of the derived expressions is validated via Monte-Carlo simulations. Results are generated for multiple network scenarios, and insights are extracted to assess various power control mechanisms as a function of system parameters. © 1972-2012 IEEE.

  12. A statistical model of uplink inter-cell interference with slow and fast power control mechanisms

    KAUST Repository

    Tabassum, Hina

    2013-09-01

    Uplink power control is in essence an interference mitigation technique that aims at minimizing the inter-cell interference (ICI) in cellular networks by reducing the transmit power levels of the mobile users while maintaining their target received signal quality levels at base stations. Power control mechanisms directly impact the interference dynamics and, thus, affect the overall achievable capacity and consumed power in cellular networks. Due to the stochastic nature of wireless channels and mobile users\\' locations, it is important to derive theoretical models for ICI that can capture the impact of design alternatives related to power control mechanisms. To this end, we derive and verify a novel statistical model for uplink ICI in Generalized-K composite fading environments as a function of various slow and fast power control mechanisms. The derived expressions are then utilized to quantify numerically key network performance metrics that include average resource fairness, average reduction in power consumption, and ergodic capacity. The accuracy of the derived expressions is validated via Monte-Carlo simulations. Results are generated for multiple network scenarios, and insights are extracted to assess various power control mechanisms as a function of system parameters. © 1972-2012 IEEE.

  13. Presynaptic beta-adrenoceptors in guinea pig papillary muscle: evidence for adrenaline-mediated positive feedback on noradrenergic transmission

    International Nuclear Information System (INIS)

    Valenta, B.; Singer, E.A.

    1991-01-01

    Guinea pig papillary muscles were preincubated in the presence of 5 x 10 - 9 mol/L unlabeled noradrenaline or adrenaline then incubated with ( 3 H)-noradrenaline and superfused. Electrical field stimulation with 180 pulses delivered at 1 or 3 Hz was used to induce overflow of radioactivity. Comparison of the effects of preexposure of the tissue to adrenaline or noradrenaline revealed that adrenaline incubation caused an enhancement of stimulation-evoked overflow of ( 3 H)noradrenaline and a reduction of the effect of exogenously added isoprenaline. Furthermore, the selective beta 2-adrenoceptor antagonist ICI 118,551 (10 - 7 mol/L), but not the selective beta 1-adrenoceptor antagonist ICI 89,406 (10 - 7 mol/L), reduced electrically evoked overflow of ( 3 H)noradrenaline in tissue preincubated with adrenaline but not in tissue preincubated with noradrenaline. The overflow-reducing effect of ICI 118.551 occurred at stimulation with 3 Hz but not at stimulation with 1 Hz. The present results support the hypothesis that noradrenergic transmission in guinea pig papillary muscle is facilitated via beta 2-adrenoceptors, and that adrenaline may serve as transmitter in this positive feedback mechanism after its incorporation into sympathetic nerves

  14. Remediation by in-situ solidification/stabilisation of Ardeer landfill, Scotland

    International Nuclear Information System (INIS)

    Wyllie, M.; Esnault, A.; Barker, P.

    1997-01-01

    The Ardeer Landfill site at ICI Explosives factory on the west coast of Scotland had been a repository for waste from the site for 40 years. In order to safeguard the local environment ICI Explosives, with approval of Local Authorities and the Clyde River Purification Board put into action a programme of investigation and planning which culminated in the in-situ treatment of 10,000 m3 of waste within the landfill by a deep mixing method using the open-quotes Colmixclose quotes system. The paper describes in varying degrees of detail the remediation from investigation to the execution of the in-situ stabilisation and presents the post construction monitoring results

  15. United States Air Force Statistical Digest, Fiscal Year 1980. Thirty-Fifth Edition

    Science.gov (United States)

    1981-03-15

    11832 90.b =en 2 11052 11352 10 .... 7 en’""’"" 3 1 U503 10146 96.6= ~’:Id4 10158 101.7 =:z ’+ :zr- r--< 9903 -<TOTAL 4376’+ 43489 T-,)3 A 1 102b4 ’Hb...34’""’" 76.8 == .. 1498 .1.151::ICI ::ICI= TOTAL ~. iSO 457:>3 ’i5.1 ="’""’" :::!:!"’"Si e:.- 6-c;7C 252r- 51123F 1 r- c: 2 221 c:en 3 231 en"’""’" 4 0:::31= !iZ

  16. Search for bacterial waste as a possible signature of life on Europa

    International Nuclear Information System (INIS)

    Bhattacherjee, A.B.; Chela-Flores, J.

    2004-07-01

    Observations of the icy Jovian moon Europa by the Galileo spacecraft served to stimulate conceptual planning for missions to Europa to search for signs of life in the volcanically-heated ocean presumed to underlie its thick icy surface. Liquid water is thought to be an essential ingredient for life, so the existence of a second water ocean in the solar system would be of paramount importance in any search for life beyond earth. In-situ measurements will be needed to directly explore the Europan ocean. The wide range of thermal and pressure environments expected on Europa provide a considerable challenge in designing an instrument package. (author)

  17. Éthique de la différence dans Il padre e lo straniero de Giancarlo De Cataldo

    OpenAIRE

    Le Gouez, Brigitte

    2012-01-01

    Ce sont ici des notes de lecture que nous proposons, plus qu’une analyse véritablement aboutie. En effet, Il padre e lo straniero de Giancarlo De Cataldo est un roman qui peut susciter quelque perplexité. Le texte pourrait lui-même apparaître comme inabouti, à moins qu’il ne manifeste, précisément, une volonté d’inachèvement. Ce sont ces questionnements du lecteur que nous avons résolu d’exposer ici. Le récit oscille entre « giallo » et « noir », double coloration à laquelle nous avait déjà h...

  18. L’ethnologue aux prises avec les archives - Introduction

    Directory of Open Access Journals (Sweden)

    Marie-Dominique Mouton

    2008-08-01

    Full Text Available Les textes présentés ici invitent à une réflexion sur les matériaux de terrain et plus largement sur la relation qui unit l’ethnologue aux archives, qu’il s’agisse des siennes, données vivantes, inspiratrices de sa recherche, de celles de ses aînés, devenues objets d’étude après leur dépôt dans une institution, ou de toutes les autres archives, constituées et rassemblées, à différentes époques, dans des perspectives administratives, juridiques, historiques ou religieuses, envisagées ici au tr...

  19. Magnetic field fluctuations measurement onboard ESA/JUICE mission by search-coil magnetometer: SCM instrument as a part of RPWI consortium

    Science.gov (United States)

    Retinò, A.; Chust, T.; Mansour, M.; Canu, P.; Sahraoui, F.; Le Contel, O.; Alison, D.; Sou, G.; Varizat, L.; Techer, J.-D.; Jeandet, A.; Geyskens, N.; Chariet, M.; Cecconi, B.; Bergman, J.; Wahlund, J.-E.; Santolik, O.; Soucek, J.; Dougherty, M.

    2017-09-01

    The JUpiter ICy moons Explorer (JUICE) mission is planned for launch in 2022 with arrival at Jupiter in 2029 and will spend at least three years making detailed observations of Jupiter's system. The Radio and Plasma Wave Investigation (RPWI) consortium will carry the most advanced set of electric and magnetic fields sensors ever flown therein, which will allow to characterize the plasma wave environment and the radio emission of Jupiter and its icy moons in great detail. The Search Coil Magnetometer (SCM) will provide high-quality measurements of the magnetic field fluctuations' vector for RPWI. Here we present the technical features of the SCM instrument and we discuss its scientific objectives.

  20. Développement d'immunoessais associés aux électrodes sérigraphiées: des particules superparamagnétiques aux nanobodies

    OpenAIRE

    Patris, Stéphanie

    2014-01-01

    Cette thèse a pour vocation de contribuer au développement de différents immunocapteurs ampérométriques associés aux électrodes sérigraphiées (SPE). Les immunocapteurs sont des dispositifs simples associant un anticorps ou un antigène qui assurent la sélectivité à un transducteur (ici une SPE) ;ce dernier transforme la liaison anticorps/antigène en un signal mesurable (ici ampérométrique).Le travail est divisé en deux volets principaux.Le premier est consacré à la mise en œuvre de différents ...

  1. Polarimetry of stars and planetary systems

    National Research Council Canada - National Science Library

    Kolokolova, Ludmilla; Hough, James; Levasseur-Regourd, Anny-Chantal

    2015-01-01

    ... fields of polarimetric exploration, including proto-planetary and debris discs, icy satellites, transneptunian objects, exoplanets and the search for extraterrestrial life -- unique results produced...

  2. Proceedings of the International Cancer Imaging Society (ICIS 16th Annual Teaching Course

    Directory of Open Access Journals (Sweden)

    Dow-Mu Koh

    2016-10-01

    Full Text Available Table of contents O1 Tumour heterogeneity: what does it mean? Dow-Mu Koh O2 Skeletal sequelae in adult survivors of childhood cancer Sue Creviston Kaste O3 Locoregional effects of breast cancer treatment Sarah J Vinnicombe O4 Imaging of cancer therapy-induced CNS toxicity Giovanni Morana, Andrea Rossi O5 Screening for lung cancer Christian J. Herold O6Risk stratification of lung nodules Theresa C. McLoud O7 PET imaging of pulmonary nodules Kirk A Frey O8 Transarterial tumour therapy Bernhard Gebauer O9 Interventional radiology in paediatric oncology Derek Roebuck O10 Image guided prostate interventions Jurgen J. Fütterer O11 Imaging cancer predisposition syndromes Alexander J. Towbin O12Chest and chest wall masses Thierry AG Huisman O13 Abdominal masses: good or bad? Anne MJB Smets O14 Hepatobiliary MR contrast: enhanced liver MRI for HCC diagnosis and management Giovanni Morana O15 Role of US elastography and multimodality fusion for managing patients with chronic liver disease and HCC Jeong Min Lee O16 Opportunities and challenges in imaging metastatic disease Hersh Chandarana O17 Diagnosis, treatment monitoring, and follow-up of lymphoma Marius E. Mayerhoefer, Markus Raderer, Alexander Haug O18 Managing high-risk and advanced prostate cancer Matthias Eiber O19 Immunotherapy: imaging challenges Bernhard Gebauer O20 RECIST and RECIST 1.1 Andrea Rockall O21 Challenges of RECIST in oncology imaging basics for the trainee and novice Aslam Sohaib O22 Lymphoma: PET for interim and end of treatment response assessment: a users’ guide to the Deauville Score Victoria S Warbey O23 Available resources Hebert Alberto Vargas O24 ICIS e-portal and the online learning community Dow-Mu Koh O25 Benign lesions that mimic pancreatic cancer Jay P Heiken O26 Staging and reporting pancreatic malignancies Isaac R Francis, Mahmoud, M Al-Hawary, Ravi K Kaza O27 Intraductal papillary mucinous neoplasm Giovanni Morana O28 Cystic pancreatic tumours Mirko D’Onofrio O

  3. Estrogen-Induced Maldevelopment of the Penis Involves Down-Regulation of Myosin Heavy Chain 11 (MYH11) Expression, a Biomarker for Smooth Muscle Cell Differentiation1

    Science.gov (United States)

    Okumu, L.A.; Bruinton, Sequoia; Braden, Tim D.; Simon, Liz; Goyal, Hari O.

    2012-01-01

    ABSTRACT Cavernous smooth muscle cells are essential components in penile erection. In this study, we investigated effects of estrogen exposure on biomarkers for smooth muscle cell differentiation in the penis. Neonatal rats received diethylstilbestrol (DES), with or without the estrogen receptor (ESR) antagonist ICI 182,780 (ICI) or the androgen receptor (AR) agonist dihydrotestosterone (DHT), from Postnatal Days 1 to 6. Tissues were collected at 7, 10, or 21 days of age. The smooth muscle cell biomarker MYH11 was studied in depth because microarray data showed it was significantly down-regulated, along with other biomarkers, in DES treatment. Quantitative real time-PCR and Western blot analyses showed 50%–80% reduction (P ≤ 0.05) in Myh11 expression in DES-treated rats compared to that in controls; and ICI and DHT coadministration mitigated the decrease. Temporally, from 7 to 21 days of age, Myh11 expression was onefold increased (P ≥ 0.05) in DES-treated rats versus threefold increased (P ≤ 0.001) in controls, implying the long-lasting inhibitory effect of DES on smooth muscle cell differentiation. Immunohistochemical localization of smooth muscle alpha actin, another biomarker for smooth muscle cell differentiation, showed fewer cavernous smooth muscle cells in DES-treated animals than in controls. Additionally, DES treatment significantly up-regulated Esr1 mRNA expression and suppressed the neonatal testosterone surge by 90%, which was mitigated by ICI coadministration but not by DHT coadministration. Collectively, results provided evidence that DES treatment in neonatal rats inhibited cavernous smooth muscle cell differentiation, as shown by down-regulation of MYH11 expression at the mRNA and protein levels and by reduced immunohistochemical staining of smooth muscle alpha actin. Both the ESR and the AR pathways probably mediate this effect. PMID:22976277

  4. Final report on Thermally Modified Sand demonstration project

    Energy Technology Data Exchange (ETDEWEB)

    1994-09-23

    The use of salt and salt/sand mixtures on icy roadway surfaces has dramatically increased during the past 30 years. Despite extensive documentation on salt related damage to the roadway improvements, vehicles and the environment, road maintenance departments have continued to rely on this practice. Road maintenance departments in northern climate areas have long recognized the safety benefits for public mobility on icy roadways from the use of sand. As an abrasive material, the sand improves the surface traction that results in more drivable and less hazardous road conditions during the winter months. Stockpiles of pure sand stored during the winter months oftentimes freeze into large unworkable, monolithic piles. To maintain a free-flowing condition, it has been found to be necessary to add salt to the sand. The addition of salt in amounts ranging from 5 to 10 percent to that of sand, is usually sufficient to provide relatively free-flowing abrasive material that could be stored in stockpiles and applied to icy road surfaces with conventional sand spreading trucks. Another alternative for winter storage of pure sand to maintain a free-flowing condition is in humidity-controlled, heated buildings. As would be expected, this method has high capital and operating costs. and not cost effective for general highway maintenance use. The invention demonstrated herein is a method of thermally modifying pure sand that will remain in a free-flowing state throughout the winter season without the need for the salt additive. The thermally modified sand provides an abrasive material that when applied to icy roads does not cause environmental and corrosive damage as done by the application of sand with salt. By employing a very simple process of freezing screened sand particles by forced air convection under subfreezing conditions, the invention creates a product that has significant value in terms of economic and environmental benefits.

  5. Remote Sensing Observations and Numerical Simulation for Martian Layered Ejecta Craters

    Science.gov (United States)

    Li, L.; Yue, Z.; Zhang, C.; Li, D.

    2018-04-01

    To understand past Martian climates, it is important to know the distribution and nature of water ice on Mars. Impact craters are widely used ubiquitous indicators for the presence of subsurface water or ice on Mars. Remote sensing observations and numerical simulation are powerful tools for investigating morphological and topographic features on planetary surfaces, and we can use the morphology of layered ejecta craters and hydrocode modeling to constrain possible layering and impact environments. The approach of this work consists of three stages. Firstly, the morphological characteristics of the Martian layered ejecta craters are performed based on Martian images and DEM data. Secondly, numerical modeling layered ejecta are performed through the hydrocode iSALE (impact-SALE). We present hydrocode modeling of impacts onto targets with a single icy layer within an otherwise uniform basalt crust to quantify the effects of subsurface H2O on observable layered ejecta morphologies. The model setup is based on a layered target made up of a regolithic layer (described by the basalt ANEOS), on top an ice layer (described by ANEOS equation of H2O ice), in turn on top of an underlying basaltic crust. The bolide is a 0.8 km diameter basaltic asteroid hitting the Martian surface vertically at a velocity of 12.8 km/s. Finally, the numerical results are compared with the MOLA DEM profile in order to analyze the formation mechanism of Martian layered ejecta craters. Our simulations suggest that the presence of an icy layer significantly modifies the cratering mechanics, and many of the unusual features of SLE craters may be explained by the presence of icy layers. Impact cratering on icy satellites is significantly affected by the presence of subsurface H2O.

  6. Controlling feeding behavior by chemical or gene-directed targeting in the brain: What’s so spatial about our methods?

    Directory of Open Access Journals (Sweden)

    Arshad M Khan

    2013-12-01

    Full Text Available Intracranial chemical injection (ICI methods have been used to identify the locations in the brain where feeding behavior can be controlled acutely. Scientists conducting ICI studies often document their injection site locations, thereby leaving kernels of valuable location data for others to use to further characterize feeding control circuits. Unfortunately, this rich dataset has not yet been formally contextualized with other published neuroanatomical data. In particular, axonal tracing studies have delineated several neural circuits originating in the same areas where ICI injection feeding-control sites have been documented, but it remains unclear whether these circuits participate in feeding control. However, comparing injection sites with other types of location data requires careful anatomical registration between the datasets. Here, a conceptual framework is presented for how such anatomical registration efforts can be performed. For example, by using a simple atlas alignment tool, a hypothalamic locus sensitive to the orexigenic effects of neuropeptide Y (NPY can be aligned accurately with the locations of neurons labeled by anterograde tracers or those known to express NPY receptors or feeding-related peptides. This approach can also be applied to those intracranial gene-directed injection (IGI methods (e.g., site-specific recombinase methods, RNA expression or interference, optogenetics and pharmacosynthetics that involve viral injections to targeted neuronal populations. Spatial alignment efforts can be accelerated if location data from ICI/IGI methods are mapped to stereotaxic brain atlases to allow powerful neuroinformatics tools to overlay different types of data in the same reference space. Atlas-based mapping will be critical for community-based sharing of location data for feeding control circuits, and will accelerate our understanding of structure-function relationships in the brain for mammalian models of obesity and

  7. EPA Enforcement and Compliance History Online: Water Discharge Monitoring Report Data Sets for FY2013

    Data.gov (United States)

    U.S. Environmental Protection Agency — Integrated Compliance Information System (ICIS) National Pollutant Discharge Elimination System (NPDES) Discharge Monitoring Report (DMR) data sets for Clean Water...

  8. EPA Enforcement and Compliance History Online: Water Discharge Monitoring Report Data Sets for FY2010

    Data.gov (United States)

    U.S. Environmental Protection Agency — Integrated Compliance Information System (ICIS) National Pollutant Discharge Elimination System (NPDES) Discharge Monitoring Report (DMR) data sets for Clean Water...

  9. EPA Enforcement and Compliance History Online: Water Discharge Monitoring Report Data Sets for FY2015

    Data.gov (United States)

    U.S. Environmental Protection Agency — Integrated Compliance Information System (ICIS) National Pollutant Discharge Elimination System (NPDES) Discharge Monitoring Report (DMR) data sets for Clean Water...

  10. EPA Enforcement and Compliance History Online: Water Discharge Monitoring Report Data Sets for FY2014

    Data.gov (United States)

    U.S. Environmental Protection Agency — Integrated Compliance Information System (ICIS) National Pollutant Discharge Elimination System (NPDES) Discharge Monitoring Report (DMR) data sets for Clean Water...

  11. EPA Enforcement and Compliance History Online: Water Discharge Monitoring Report Data Sets for FY2009

    Data.gov (United States)

    U.S. Environmental Protection Agency — Integrated Compliance Information System (ICIS) National Pollutant Discharge Elimination System (NPDES) Discharge Monitoring Report (DMR) data sets for Clean Water...

  12. EPA Enforcement and Compliance History Online: Water Discharge Monitoring Report Data Sets for FY2016

    Data.gov (United States)

    U.S. Environmental Protection Agency — Integrated Compliance Information System (ICIS) National Pollutant Discharge Elimination System (NPDES) Discharge Monitoring Report (DMR) data sets for Clean Water...

  13. Carlo Ginzburg, Peur, révérence, terreur. Quatre essais d’iconographie politique

    OpenAIRE

    Font-Réaulx, Dominique de

    2015-01-01

    Les quatre essais réunis ici ont été publiés, séparément, entre 2000 et 2009, par Carlo Ginzburg. Leur rassemblement n’a pas été guidé par leur thème – fort différent, du Leviathan de Thomas Hobbes au Guernica de Pablo Picasso en passant par La Mort de Marat de Jacques-Louis David et au Your country needs you ! de lord Kitchener –, ni par la chronologie des événements. Le philosophe cherche à montrer ici la pertinence de sa méthode d’analyse des images. Il la place, de manière originale et sé...

  14. J.M. Barrie : Les masques de Jacobus Hook Partie I/II : Le Capitaine Hook à Eton ou Le Solitaire1

    OpenAIRE

    Faivre, Céline-Albin

    2013-01-01

    Cette causerie n’aurait pas lieu si le Doyen ne m’avait pas lancé un défi. Je me trouvai ici le 4 juin dernier, lorsque, pendant le déjeuner, au beau milieu de son discours, le Doyen me mit au défi de réfuter cette terrible accusation : « James Hook, le Capitaine pirate, était un grand mais non pas un bon Etonien. » Or, à mon avis, Hook était un bon mais non pas un grand Etonien ; et c’est cette envie de vous en convaincre qui m’a poussé à venir ici cet après-midi, tout en sachant néanmoins q...

  15. Adoptive cell therapy and modulation of the tumour microenvironment: new insights from ASCO 2016

    Science.gov (United States)

    Khoja, Leila; Gyawali, Bishal

    2016-01-01

    Abstract Immuno-oncology has changed the landscape of cancer treatment in recent years. Immune checkpoint inhibitors (ICI) have shown survival advantage with long term remissions in a variety of cancers. However, there is another approach to harnessing the power of the immune system in combating cancer: the adoptive cell therapy (ACT) strategy. Although ACT is restricted to small specialized centres and has yet to deliver as much success as ICI, some important results were presented at this year’s ASCO meeting. Important lessons have been learned from these studies, including the prospects and challenges ahead. In this editorial, we summarize the important studies on ACT presented at the ASCO 2016 meeting and discuss the way forward. PMID:27610200

  16. Du rapport entre le harcèlement et l’hégémonie intellectuelle

    OpenAIRE

    Berger, Vincent

    2015-01-01

    Mesdames, Messieurs, Chers collègues, Je suis très heureux que mon tout dernier discours ici à la Présidence de Paris Diderot – la fin même de cette intervention sera l’occasion pour moi de prononcer mes derniers mots de Président – le soit sur le thème des relations entre les hommes et les femmes à l’Université. Vous êtes ici dans  un  lieu  universitaire  engagé  sur  la  thématique de l’égalité entre les femmes et les hommes. Le harcèlement entre personnels me semble  un  problème  relat...

  17. ICIS-NPDES DMR Summary and Data Element Dictionary ...

    Science.gov (United States)

    ECHO, Enforcement and Compliance History Online, provides compliance and enforcement information for approximately 800,000 EPA-regulated facilities nationwide. ECHO includes permit, inspection, violation, enforcement action, and penalty information about facilities regulated under the Clean Air Act (CAA) Stationary Source Program, Clean Water Act (CWA) National Pollutant Elimination Discharge System (NPDES), and/or Resource Conservation and Recovery Act (RCRA). Information also is provided on surrounding demographics when available.

  18. ICIS-NPDES Limit Summary and Data Element Dictionary ...

    Science.gov (United States)

    ECHO, Enforcement and Compliance History Online, provides compliance and enforcement information for approximately 800,000 EPA-regulated facilities nationwide. ECHO includes permit, inspection, violation, enforcement action, and penalty information about facilities regulated under the Clean Air Act (CAA) Stationary Source Program, Clean Water Act (CWA) National Pollutant Elimination Discharge System (NPDES), and/or Resource Conservation and Recovery Act (RCRA). Information also is provided on surrounding demographics when available.

  19. Extensional and compressional instabilities in icy satellite lithospheres

    International Nuclear Information System (INIS)

    Herrick, D.L.; Stevenson, D.J.

    1990-01-01

    The plausibility of invoking a lithospheric instability mechanism to account for the grooved terrains on Ganymede, Encedalus, and Miranda is presently evaluated in light of the combination of a simple mechanical model of planetary lithospheres and asthenospheres with recent experimental data for the brittle and ductile deformation of ice. For Ganymede, high surface gravity and warm temperatures render the achievement of an instability sufficiently great for the observed topographic relief virtually impossible; an instability of sufficient strength, however, may be able to develop on such smaller, colder bodies as Encedalus and Miranda. 15 refs

  20. ICIS-Air Download Summary and Data Element Dictionary ...

    Science.gov (United States)

    ECHO, Enforcement and Compliance History Online, provides compliance and enforcement information for approximately 800,000 EPA-regulated facilities nationwide. ECHO includes permit, inspection, violation, enforcement action, and penalty information about facilities regulated under the Clean Air Act (CAA) Stationary Source Program, Clean Water Act (CWA) National Pollutant Elimination Discharge System (NPDES), and/or Resource Conservation and Recovery Act (RCRA). Information also is provided on surrounding demographics when available.

  1. Ion irradiation of CH4-containing icy mixtures

    International Nuclear Information System (INIS)

    Baratta, G.A.; Domingo, M.; Ferini, G.; Leto, G.; Palumbo, M.E.; Satorre, M.A.; Strazzulla, G.

    2003-01-01

    We have studied by infrared absorption spectroscopy the effects of ion irradiation with 60 keV Ar 2+ ions on pure methane (CH 4 ) ice at 12 K and mixtures with water (H 2 O) and nitrogen (N 2 ). Ion irradiation, among other effects, causes the rupture of original molecular bonds and the formation of molecular species not present in the initial ice. Here we present the experimental results and discuss their astrophysical relevance

  2. Interactions of planetary magnetospheres with icy satellite surfaces

    International Nuclear Information System (INIS)

    Cheng, A.F.; Haff, P.K.; Johnson, R.E.; Lanzerotti, L.J.

    1986-01-01

    When natural satellites and ring particles are embedded within magnetospheric plasmas, the charged particles interact with the surfaces of these solid bodies. These interactions have important implications for the surface, the atmosphere of the parent body, and the magnetosphere as a whole. Significant erosion of the surface by sputtering, as well as redeposition of sputter ejecta, can occur over geologic time. The surface can also be chemically modified. Sputter ejecta can make important contributions to the atmosphere; sputtering provides a lower limit to the atmospheric column density even for arbitrarily cold satellite surfaces. Sputter ejecta escaping from the parent body can form extensive neutral clouds within the magnetosphere. Ionization and dissociation within these neutral clouds can be dominant sources of low-energy plasma. The importance of these processes is discussed for the satellites and magnetospheres of Jupiter, Saturn and Uranus

  3. Microbial Growth in the Magnesium- Chloride - Sodium- Sulphate Ion System: Implications for Habitability in Terrestrial and Extraterrestrial Salts

    Science.gov (United States)

    Loudon, C. M.; Aka, S.; Cockell, C. S.

    2017-12-01

    Icy moons in the outer solar system are key targets in the search for extra-terrestrial life as there is evidence that they harbour subsurface oceans. Observational evidence of icy moons such as Europa suggest that these likely brine oceans should be composed of chloride and sulphate salts. The effects of the ions that compose these salts on biology and how the interactions between them can create geochemical and geophysical barriers to life are poorly understood. Here we present an in depth study of four microorganisms grown in solutions with varying combinations of the magnesium- chloride- sodium- sulphate ions. We find that the ion composition of the brine solution can have a large effect on growth. Whilst the water activity must be permissible for growth we found that this alone could not predict the effects of the ions on growth, chaotropic effects and ion specific effects influenced by the specific physiology of organisms are also evident. For this reason we conclude that simply knowing which salts are present on icy moons is not sufficient information to determine their potential habitibility. A full sample of any brine ocean would need to be studied to fully determine the potential for biology on these outer solar system satellites.

  4. A Multistage Decision-Feedback Receiver Design for LTE Uplink in Mobile Time-Variant Environments

    Directory of Open Access Journals (Sweden)

    Juinn-Horng Deng

    2012-01-01

    Full Text Available Single-carrier-frequency division multiple access (SC-FDMA has recently become the preferred uplink transmission scheme in long-term evolution (LTE systems. Similar to orthogonal frequency division multiple access (OFDMA, SC-FDMA is highly sensitive to frequency offsets caused by oscillator inaccuracies and Doppler spread, which lead to intercarrier interference (ICI. This work proposes a multistage decision-feedback structure to mitigate the ICI effect and enhance system performance in time-variant environments. Based on the block-type pilot arrangement of the LTE uplink type 1 frame structure, the time-domain least squares (TDLS method and polynomial-based curve-fitting algorithm are employed for channel estimation. Instead of using a conventional equalizer, this work uses a group frequency-domain equalizer (GFDE to reduce computational complexity. Furthermore, this work utilizes a dual iterative structure of group parallel interference cancellation (GPIC and frequency-domain group parallel interference cancellation (FPIC to mitigate the ICI effect. Finally, to optimize system performance, this work applies a novel error-correction scheme. Simulation results demonstrate the bit error rate (BER performance is markedly superior to that of the conventional full-size receiver based on minimum mean square error (MMSE. This structure performs well and is a flexible choice in mobile environments using the SC-FDMA scheme.

  5. OFDM with Index Modulation for Asynchronous mMTC Networks.

    Science.gov (United States)

    Doğan, Seda; Tusha, Armed; Arslan, Hüseyin

    2018-04-21

    One of the critical missions for next-generation wireless communication systems is to fulfill the high demand for massive Machine-Type Communications (mMTC). In mMTC systems, a sporadic transmission is performed between machine users and base station (BS). Lack of coordination between the users and BS in time destroys orthogonality between the subcarriers, and causes inter-carrier interference (ICI). Therefore, providing services to asynchronous massive machine users is a major challenge for Orthogonal Frequency Division Multiplexing (OFDM). In this study, OFDM with index modulation (OFDM-IM) is proposed as an eligible solution to alleviate ICI caused by asynchronous transmission in uncoordinated mMTC networks. In OFDM-IM, data transmission is performed not only by modulated subcarriers but also by the indices of active subcarriers. Unlike classical OFDM, fractional subcarrier activation leads to less ICI in OFDM-IM technology. A novel subcarrier mapping scheme (SMS) named as Inner Subcarrier Activation is proposed to further alleviate adjacent user interference in asynchronous OFDM-IM-based systems. ISA reduces inter-user interference since it gives more activation priority to inner subcarriers compared with the existing SMS-s. The superiority of the proposed SMS is shown through both theoretical analysis and computer-based simulations in comparison to existing mapping schemes for asynchronous systems.

  6. Phytoestrogens Enhance the Vascular Actions of the Endocannabinoid Anandamide in Mesenteric Beds of Female Rats

    Directory of Open Access Journals (Sweden)

    Roxana N. Peroni

    2012-01-01

    Full Text Available In rat isolated mesenteric beds that were contracted with NA as an in vitro model of the vascular adrenergic hyperactivity that usually precedes the onset of primary hypertension, the oral administration (3 daily doses of either 10 mg/kg genistein or 20 mg/kg daidzein potentiated the anandamide-induced reduction of contractility to NA in female but not in male rats. Oral treatment with phytoestrogens also restored the vascular effects of anandamide as well as the mesenteric content of calcitonin gene-related peptide (CGRP that were reduced after ovariectomy. The enhancement of anandamide effects caused by phytoestrogens was prevented by the concomitant administration of the estrogen receptor antagonist fulvestrant (2.5 mg/kg, s.c., 3 daily doses. It is concluded that, in the vasculature of female rats, phytoestrogens produced an estrogen-receptor-dependent enhancement of the anandamide-vascular actions that involves the modulation of CGRP levels and appears to be relevant whenever an adrenergic hyperactivity occurs.

  7. Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity

    Directory of Open Access Journals (Sweden)

    Bruno M. Simões

    2015-09-01

    Full Text Available Breast cancers (BCs typically express estrogen receptors (ERs but frequently exhibit de novo or acquired resistance to hormonal therapies. Here, we show that short-term treatment with the anti-estrogens tamoxifen or fulvestrant decrease cell proliferation but increase BC stem cell (BCSC activity through JAG1-NOTCH4 receptor activation both in patient-derived samples and xenograft (PDX tumors. In support of this mechanism, we demonstrate that high ALDH1 predicts resistance in women treated with tamoxifen and that a NOTCH4/HES/HEY gene signature predicts for a poor response/prognosis in 2 ER+ patient cohorts. Targeting of NOTCH4 reverses the increase in Notch and BCSC activity induced by anti-estrogens. Importantly, in PDX tumors with acquired tamoxifen resistance, NOTCH4 inhibition reduced BCSC activity. Thus, we establish that BCSC and NOTCH4 activities predict both de novo and acquired tamoxifen resistance and that combining endocrine therapy with targeting JAG1-NOTCH4 overcomes resistance in human breast cancers.

  8. EPA Facility Registry Service (FRS): Wastewater Treatment Plants

    Data.gov (United States)

    U.S. Environmental Protection Agency — This GIS dataset contains data on wastewater treatment plants, based on EPA's Facility Registry Service (FRS), EPA's Integrated Compliance Information System (ICIS)...

  9. Mobile In-Situ Mars Water Extractor (MISME), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Extracting water and volatiles from icy soils requires excavating and manipulating those soils as feedstock, but the Phoenix mission demonstrated some of the...

  10. Dicty_cDB: VSK121 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available **fef*fl*fl*xxvlqehvxmav*mvvpviqixnvxalixgl xxiaqlxgskfiqfs Translated Amino Acid sequence (All Frames) Frame A: *inkfkkknee...*rx*sdflwlvhskfsnfylnwksnlysnpcyy*sn*m*ywcw*w ckgyfnhsswlylvfskll*icy*tnhscklsnkllk*rllwcwsl--- ---g*inxfkkknee

  11. Technology Readiness Level Elevation of the Enceladus Organic Analyzer (EOA) for Outer-Planetary in situ Organic Analysis

    Data.gov (United States)

    National Aeronautics and Space Administration — Outer-planetary icy moons like Enceladus and Europa have become enticing targets for future space exploration due to their subsurface oceans and hydrothermal vent...

  12. Studies of small-scale plasma inhomogeneities in the cusp ionosphere using sounding rocket data

    Science.gov (United States)

    Chernyshov, Alexander A.; Spicher, Andres; Ilyasov, Askar A.; Miloch, Wojciech J.; Clausen, Lasse B. N.; Saito, Yoshifumi; Jin, Yaqi; Moen, Jøran I.

    2018-04-01

    Microprocesses associated with plasma inhomogeneities are studied on the basis of data from the Investigation of Cusp Irregularities (ICI-3) sounding rocket. The ICI-3 rocket is devoted to investigating a reverse flow event in the cusp F region ionosphere. By numerical stability analysis, it is demonstrated that inhomogeneous-energy-density-driven (IEDD) instability can be a mechanism for the excitation of small-scale plasma inhomogeneities. The Local Intermittency Measure (LIM) method also applied the rocket data to analyze irregular structures of the electric field during rocket flight in the cusp. A qualitative agreement between high values of the growth rates of the IEDD instability and the regions with enhanced LIM is observed. This suggests that IEDD instability is connected to turbulent non-Gaussian processes.

  13. Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

    Science.gov (United States)

    2018-04-06

    Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  14. Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor α signalling and results in tamoxifen insensitive proliferation

    International Nuclear Information System (INIS)

    Moerkens, Marja; Zhang, Yinghui; Wester, Lynn; Water, Bob van de; Meerman, John HN

    2014-01-01

    Tamoxifen resistance is a major problem in the treatment of estrogen receptor (ER) α -positive breast cancer patients. Although the mechanisms behind tamoxifen resistance are still not completely understood, clinical data suggests that increased expression of receptor tyrosine kinases is involved. Here, we studied the estrogen and anti-estrogen sensitivity of human breast cancer MCF7 cells that have a moderate, retroviral-mediated, ectopic expression of epidermal growth factor receptor (MCF7-EGFR). Proliferation of MCF7-EGFR and parental cells was induced by 17β-estradiol (E2), epidermal growth factor (EGF) or a combination of these. Inhibition of proliferation under these conditions was investigated with 4-hydroxy-tamoxifen (TAM) or fulvestrant at 10 -12 to 10 -6 M. Cells were lysed at different time points to determine the phosphorylation status of EGFR, MAPK 1/3 , AKT and the expression of ERα. Knockdown of target genes was established using smartpool siRNAs. Transcriptomics analysis was done 6 hr after stimulation with growth factors using Affymetrix HG-U133 PM array plates. While proliferation of parental MCF7 cells could only be induced by E2, proliferation of MCF7-EGFR cells could be induced by either E2 or EGF. Treatment with TAM or fulvestrant did significantly inhibit proliferation of MCF7-EGFR cells stimulated with E2 alone. EGF treatment of E2/TAM treated cells led to a marked cell proliferation thereby overruling the anti-estrogen-mediated inhibition of cell proliferation. Under these conditions, TAM however did still inhibit ERα- mediated transcription. While siRNA-mediated knock-down of EGFR inhibited the EGF- driven proliferation under TAM/E2/EGF condition, knock down of ERα did not. The TAM resistant cell proliferation mediated by the conditional EGFR-signaling may be dependent on the PI3K/Akt pathway but not the MEK/MAPK pathway, since a MEK inhibitor (U0126), did not block the proliferation. Transcriptomic analysis under the various E2/TAM

  15. Synthesis of substrates for gene therapy monitoring of HSV1-TK system

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Tae Hyun; Ahn, Soon Hyuk; Choi, Chang Woon; Lim, Sang Moo; Awh, Ok Doo [College of Medicine, Yonsei Univ., Wonju (Korea, Republic of)

    2002-04-01

    In gene therapy, tumor cells expressing the herpes simplex virus thymidine kinase are sensitive to prodrugs. Potential prodrugs IVDU and IVFRU were synthesized and radiolabeled with radioiodine for noninvasive imaging of herpes simplex virus type 1 gene expression. 5-(2-trimethysilyl) vinyl-2'-deoxyuridine and 5-t(2-trimethylsilyl)vinyl-2'-fluoro-2'-deoxyuridine, precursors of 5-(2-iodo)viny 1-2'-deoxy uridine(IVDU) and 5-(2-iodo)-2'-vinyl-2'-deoxy-2'-fluorotibofuranosyl uracil(IVFRU), were synthesized from reaction of trans-1-trimethylsillyl-2-tri-n-butylstannylethylene with 5-iodo-2'-deoxyuridine and 5-iodo-2'-fluoro-2'-deoxyuridine, respectively, on the condition of Pd catalyst. These precursors were separated from reaction mixture by silica gel column chromatography method. Each precursor was radioiodinated with radioiodine by mixing with ICI oxidizing agent. These radioiodinated compounds were purified with HPLC. Radiohalogen exchange has been shown to be effective for the synthesis of products with lower specific activity. Similarly, carrier-added and high specific activity products have been isolated in respectable radiochemical yields using ICI method. Synthetic yield of precursors, IVDU and IVFRU were 43% and 18%, respectively. Radiochemical purity of both compunds was over 98%. We synthesized precursors of IVDU and IVFRU for monitoring of HSV1-tk gene expression. Radiotracers were radioiodinated with high radiolabeling yield by ICI method.

  16. ORIGIN OF MOLECULAR OXYGEN IN COMET 67P/CHURYUMOV–GERASIMENKO

    Energy Technology Data Exchange (ETDEWEB)

    Mousis, O.; Ronnet, T.; Brugger, B.; Vernazza, P. [Aix Marseille Université, CNRS, LAM (Laboratoire d’Astrophysique de Marseille) UMR 7326, F-13388, Marseille (France); Ozgurel, O.; Pauzat, F.; Ellinger, Y.; Markovits, A. [Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC Univ. Paris 06, CNRS UMR 7616, F-75252 Paris CEDEX 05 (France); Maggiolo, R. [Royal Institute for Space Aeronomy, 3 Avenue Circulaire, Brussels (Belgium); Wurz, P.; Altwegg, K.; Bieler, A.; Rubin, M. [Physikalisches Institut, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland); Lunine, J. I. [Department of Astronomy and Carl Sagan Institute, Space Sciences Building Cornell University, Ithaca, NY 14853 (United States); Luspay-Kuti, A.; Mandt, K. E., E-mail: olivier.mousis@lam.fr [Department of Space Research, Southwest Research Institute, 6220 Culebra Rd., San Antonio, TX 78228 (United States)

    2016-06-01

    Molecular oxygen has been detected in the coma of comet 67P/Churyumov–Gerasimenko with abundances in the 1%–10% range by the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis-Double Focusing Mass Spectrometer instrument on board the Rosetta spacecraft. Here we find that the radiolysis of icy grains in low-density environments such as the presolar cloud may induce the production of large amounts of molecular oxygen. We also show that molecular oxygen can be efficiently trapped in clathrates formed in the protosolar nebula (PSN), and that its incorporation as crystalline ice is highly implausible, because this would imply much larger abundances of Ar and N{sub 2} than those observed in the coma. Assuming that radiolysis has been the only O{sub 2} production mechanism at work, we conclude that the formation of comet 67P/Churyumov–Gerasimenko is possible in a dense and early PSN in the framework of two extreme scenarios: (1) agglomeration from pristine amorphous icy grains/particles formed in ISM and (2) agglomeration from clathrates that formed during the disk’s cooling. The former scenario is found consistent with the strong correlation between O{sub 2} and H{sub 2}O observed in comet 67P/Churyumov-Gerasimenko’s coma while the latter scenario requires that clathrates formed from ISM icy grains that crystallized when entering the PSN.

  17. ORIGIN OF MOLECULAR OXYGEN IN COMET 67P/CHURYUMOV–GERASIMENKO

    International Nuclear Information System (INIS)

    Mousis, O.; Ronnet, T.; Brugger, B.; Vernazza, P.; Ozgurel, O.; Pauzat, F.; Ellinger, Y.; Markovits, A.; Maggiolo, R.; Wurz, P.; Altwegg, K.; Bieler, A.; Rubin, M.; Lunine, J. I.; Luspay-Kuti, A.; Mandt, K. E.

    2016-01-01

    Molecular oxygen has been detected in the coma of comet 67P/Churyumov–Gerasimenko with abundances in the 1%–10% range by the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis-Double Focusing Mass Spectrometer instrument on board the Rosetta spacecraft. Here we find that the radiolysis of icy grains in low-density environments such as the presolar cloud may induce the production of large amounts of molecular oxygen. We also show that molecular oxygen can be efficiently trapped in clathrates formed in the protosolar nebula (PSN), and that its incorporation as crystalline ice is highly implausible, because this would imply much larger abundances of Ar and N_2 than those observed in the coma. Assuming that radiolysis has been the only O_2 production mechanism at work, we conclude that the formation of comet 67P/Churyumov–Gerasimenko is possible in a dense and early PSN in the framework of two extreme scenarios: (1) agglomeration from pristine amorphous icy grains/particles formed in ISM and (2) agglomeration from clathrates that formed during the disk’s cooling. The former scenario is found consistent with the strong correlation between O_2 and H_2O observed in comet 67P/Churyumov-Gerasimenko’s coma while the latter scenario requires that clathrates formed from ISM icy grains that crystallized when entering the PSN.

  18. A possible answer to the mysterious non-detection of hydroxylamine in space: the thermal desorption mechanism

    Science.gov (United States)

    Jonusas, Mindaugas; Krim, Lahouari

    2016-06-01

    The presence of NH2OH, one of the main precursors in the formation of amino-acids, on dust grain mantles, may be the most obvious elucidation for the creation of large pre-biotic molecules in the interstellar medium. However, while many laboratory experimental studies, to simulate the icy grain chemistry in space, found that NH2OH molecules may be easily formed in solid phase with high abundances and then they should desorb, through a temperature-induced desorption into the gas phase, with the same high abundances; all the spatial observations conclude that NH2OH is not detected in gas phase within any of the explored astronomical sources. Such inconsistencies between laboratory experiment simulations and spatial observations lead our investigations towards this experimental study to see if there is any chemical transformation of NH2OH, occurring in the solid phase before the desorption processes of NH2OH from the mantle of interstellar icy grains. Our experimental results show that the heating of NH2OH-H2O ices lead to a decomposition of NH2OH into HNO, NH3 and O2, even before reaching its desorption temperature. We show through this work that the NH2OH non-detection from previous examined astronomical sources could mainly due to its high reactivity in solid phase on the icy interstellar grains.

  19. HABEBEE: habitability of eyeball-exo-Earths.

    Science.gov (United States)

    Angerhausen, Daniel; Sapers, Haley; Citron, Robert; Bergantini, Alexandre; Lutz, Stefanie; Queiroz, Luciano Lopes; da Rosa Alexandre, Marcelo; Araujo, Ana Carolina Vieira

    2013-03-01

    Extrasolar Earth and super-Earth planets orbiting within the habitable zone of M dwarf host stars may play a significant role in the discovery of habitable environments beyond Earth. Spectroscopic characterization of these exoplanets with respect to habitability requires the determination of habitability parameters with respect to remote sensing. The habitable zone of dwarf stars is located in close proximity to the host star, such that exoplanets orbiting within this zone will likely be tidally locked. On terrestrial planets with an icy shell, this may produce a liquid water ocean at the substellar point, one particular "Eyeball Earth" state. In this research proposal, HABEBEE: exploring the HABitability of Eyeball-Exo-Earths, we define the parameters necessary to achieve a stable icy Eyeball Earth capable of supporting life. Astronomical and geochemical research will define parameters needed to simulate potentially habitable environments on an icy Eyeball Earth planet. Biological requirements will be based on detailed studies of microbial communities within Earth analog environments. Using the interdisciplinary results of both the physical and biological teams, we will set up a simulation chamber to expose a cold- and UV-tolerant microbial community to the theoretically derived Eyeball Earth climate states, simulating the composition, atmosphere, physical parameters, and stellar irradiation. Combining the results of both studies will enable us to derive observable parameters as well as target decision guidance and feasibility analysis for upcoming astronomical platforms.

  20. Indicadores de calidad de las harinas de trigo: índice de calidad industrial y su relación con ensayos predictivos

    Directory of Open Access Journals (Sweden)

    A.E. de la Horra

    2012-12-01

    Full Text Available El objetivo de este trabajo fue estudiar y evaluar la capacidad de diferentes parámetros para predecir la calidad de las harinas de trigo, analizando las relaciones existentes entre éstos y el índice de calidad industrial (ICI. Se utilizaron siete muestras de harina de trigo provistas por la CEI Barrow. Se determinaron parámetros relacionados con la calidad del grano de trigo, la molienda y la composición de las harinas. Además, se llevaron a cabo ensayos relacionados con el comportamiento de las masas (ensayo farinográfico y alveográfico y se elaboró pan. Se calculó el ICI para cada una de las muestras y se estudió su relación con pruebas de predicción y ensayos de calidad. El ICI mostró correlaciones significativas y positivas con el contenido de macropolímero de glutenina, la extensibilidad alveográfica y el tiempo de desarrollo de la masa. Estas relaciones podrían resultar beneficiosas en la evaluación de la aptitud de las harinas para la elaboración de diferentes productos panificados, ya que constituyen determinaciones más sencillas y no requieren de equipamiento de alta tecnología ni grandes cantidades de muestra.

  1. Testosterone-induced modulation of peroxisomal morphology and peroxisome-related gene expression in brown trout (Salmo trutta f. fario) primary hepatocytes.

    Science.gov (United States)

    Lopes, Célia; Malhão, Fernanda; Guimarães, Cláudia; Pinheiro, Ivone; Gonçalves, José F; Castro, L Filipe C; Rocha, Eduardo; Madureira, Tânia V

    2017-12-01

    Disruption of androgenic signaling has been linked to possible cross-modulation with other hormone-mediated pathways. Therefore, our objective was to explore effects caused by testosterone - T (1, 10 and 50μM) in peroxisomal signaling of brown trout hepatocytes. To study the underlying paths involved, several co-exposure conditions were tested, with flutamide - F (anti-androgen) and ICI 182,780 - ICI (anti-estrogen). Molecular and morphological approaches were both evaluated. Peroxisome proliferator-activated receptor alpha (PPARα), catalase and urate oxidase were the selected targets for gene expression analysis. The vitellogenin A gene was also included as a biomarker of estrogenicity. Peroxisome relative volumes were estimated by immunofluorescence, and transmission electron microscopy was used for qualitative morphological control. The single exposures of T caused a significant down-regulation of urate oxidase (10 and 50μM) and a general up-regulation of vitellogenin. A significant reduction of peroxisome relative volumes and smaller peroxisome profiles were observed at 50μM. Co-administration of T and ICI reversed the morphological modifications and vitellogenin levels. The simultaneous exposure of T and F caused a significant and concentration-dependent diminishing in vitellogenin expression. Together, the findings suggest that in the tested model, T acted via both androgen and estrogen receptors to shape the peroxisomal related targets. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Macula on Europa

    Science.gov (United States)

    1997-01-01

    This image of Europa, an icy satellite of Jupiter about the size of the Earth's Moon, was obtained from a range of 7415 miles (11933 kilometers) by the Galileo spacecraft during its fourth orbit around Jupiter and its first close pass of Europa. The image spans 30 miles by 57 miles (48 km by 91 km) and shows features as small as 800 feet (240 meters) across. The large circular feature centered in the upper middle of the image is called a macula, and could be the scar of a large meteorite impact. The surface of Europa is composed mostly of water ice, so large impact craters on Europa could look different from large bowl-shaped depressions formed by impact into rock, such as on the Moon. On Europa's icy surface, the original impact crater has been modified into a central zone of rugged topography surrounded by circular fractures which reflect adjustments to stress in the surrounding icy crust.The Jet Propulsion Laboratory, Pasadena, CA manages the mission for NASA's Office of Space Science, Washington, DC.This image and other images and data received from Galileo are posted on the Galileo mission home page on the World Wide Web at http://galileo.jpl.nasa.gov. Background information and educational context for the images can be found at URL http://www.jpl.nasa.gov/galileo/sepo

  3. Steroidal regulation of Ihh and Gli1 expression in the rat uterus.

    Science.gov (United States)

    Kubota, Kaiyu; Yamauchi, Nobuhiko; Yamagami, Kazuki; Nishimura, Sho; Gobaru, Takafumi; Yamanaka, Ken-ichi; Wood, Chris; Soh, Tomoki; Takahashi, Masashi; Hattori, Masa-aki

    2010-05-01

    Ovarian steroid hormones, progesterone (P4), and estradiol (E2) strictly regulate the endometrial tissue remodeling required for successful embryo implantation. Indian hedgehog (Ihh) is up-regulated by P4 and critically mediates uterine receptivity in the mouse. However, the regulation of Ihh expression during the implantation period still remains unclear. The present study was conducted to elucidate the mechanism of the steroidal regulation in the expression of Ihh and Gli1, the mediator of the Ihh pathway. Ihh mRNA was expressed in the rat uterus on 3.5-5.5 days post-coitus (dpc), while Gli1 expression transiently increased at 3.5 dpc but decreased significantly on 5.5 dpc (P Ihh was induced by the implantation-induced E2 treatment in the primed rat uterus. In contrast, expression of Gli1 was significantly decreased by E2 treatment (P = 0.016). In the case of ICI182.780 (ICI) treatment, Ihh expression was eliminated by ICI, whilst Gli1 expression increased. These results suggest that Ihh expression is maintained at a high level until the initiation of implantation, while the expression of Gli1 is decreased just prior to the initiation of implantation depending on the E2 action. This observation aids in the understanding of the Ihh signaling pathway mediating uterine remodeling for implantation.

  4. Plasma analysis of inductively coupled impulse sputtering of Cu, Ti and Ni

    Science.gov (United States)

    Loch, D. A. L.; Aranda Gonzalvo, Y.; Ehiasarian, A. P.

    2017-06-01

    Inductively coupled impulse sputtering (ICIS) is a new development in the field of highly ionised pulsed PVD processes. For ICIS the plasma is generated by an internal inductive coil, replacing the need for a magnetron. To understand the plasma properties, measurements of the current and voltage waveforms at the cathode were conducted. The ion energy distribution functions (IEDFs) were measured by energy resolved MS and plasma chemistry was analysed by OES and then compared to a model. The target was operated in pulsed DC mode and the coil was energised by pulsed RF power, with a duty cycle of 7.5%. At a constant pressure (14 Pa) the set peak RF power was varied from 1000-4000 W. The DC voltage to the target was kept constant at 1900 V. OES measurements have shown a monotonic increase in intensity with increasing power. Excitation and ionisation processes were single step for ICIS of Ti and Ni and multi-step for Cu. The latter exhibited an unexpectedly steep rise in ionisation efficiency with power. The IEDFs measured by MS show the material- and time-dependant plasma potential in the range of 10-30 eV, ideal for increased surface mobility without inducing lattice defects. A lower intensity peak, of high energetic ions, is visible at 170 eV during the pulse.

  5. Advanced in-core monitoring system for high-power reactors

    International Nuclear Information System (INIS)

    Mitin, V.I.; Alekseev, A.N.; Golovanov, M.N.; Zorin, A.V.; Kalinushkin, A.E.; Kovel, A.I.; Milto, N.V.; Musikhin, A.M.; Tikhonova, N.V.; Filatov, V.P.

    2006-01-01

    This paper encompasses such section as objective, conception and engineering solution for construction of advanced in-core instrumentation system for high power reactor, including WWER-1000. The ICIS main task is known to be an on-line monitoring of power distribution and functionals independently of design programs to avoid a common cause error. This paper shows in what way the recovery of power distribution has been carried out using the signals from in-core neutron detectors or temperature sensors. On the basis of both measured and processed data, the signals of preventive and emergency protection on local parameters (linear power of the maximum intensive fuel rods, departure from nucleate boiling ratio peaking factor) have been automatically generated. The paper presents a detection technology and processing methods for signals from SPNDs and TCs, ICIS composition and structure, computer hardware, system and applied software. Structure, composition and the taken decisions allow combining class IE and class B and C tasks in accordance with international standards of separation and safety category realization. Nowadays, ICIS-M is a system that is capable to ensure: monitoring, safety, information display and diagnostics function, which allow securing actual increase of quality, reliability and safety in operation of nuclear fuel and power units. Meanwhile, it reduce negative influence of human factor on thermal technical reliability in the operational process (Authors)

  6. Adrenergic beta 2-selective blocker in isoprenaline-enhanced essential tremor.

    Science.gov (United States)

    Teräväinen, H; Huttunen, J

    1987-01-01

    A beta 2-selective adrenergic-receptor-blocking drug, ICI 118.551, 150 mg/day, prevented almost as effectively as the nonselective antagonist propranolol, 240 mg/day, the isoprenaline enhancement of essential tremor amplitude.

  7. Study of Geological Analogues for Understanding the Radar Sounder Response of the RIME Targets

    Science.gov (United States)

    Thakur, S.; Bruzzone, L.

    2017-12-01

    Radar for Icy Moon Exploration (RIME), the radar sounder onboard the Jupiter Icy Moons Explorer (JUICE), is aimed at characterizing the ice shells of the Jovian moons - Ganymede, Europa and Callisto. RIME is optimized to operate at 9 MHz central frequency with bandwidth of 1 MHz and 2.7 MHz to achieve a penetration depth up to 9 km through ice. We have developed an approach to the definition of a database of simulated RIME radargrams by leveraging the data available from airborne and orbital radar sounder acquisitions over geological analogues of the expected icy moon features. These simulated radargrams are obtained by merging real radar sounder data with models of the subsurface of the Jupiter icy moons. They will be useful for geological interpretation of the RIME radargrams and for better predicting the performance of RIME. The database will also be useful in developing pre-processing and automatic feature extraction algorithms to support data analysis during the mission phase of RIME. Prior to the JUICE mission exploring the Jovian satellites with RIME, there exist radar sounders such as SHARAD (onboard MRO) and MARSIS (onboard MEX) probing Mars, the LRS (onboard SELENE) probing the Moon, and many airborne sounders probing the polar regions of Earth. Analogues have been identified in these places based on similarity in geo-morphological expression. Moreover, other analogues have been identified on the Earth for possible dedicated acquisition campaigns before the RIME operations. By assuming that the subsurface structure of the RIME targets is approximately represented in the analogue radargrams, the difference in composition is accounted for by imposing different dielectric and subsurface attenuation models. The RIME radargrams are simulated from the analogue radargrams using the radar equation and the RIME processing chain and accounting for different possible scenarios in terms of subsurface structure, dielectric properties and instrument parameters. For

  8. Investigation of Secondary Craters in the Saturnian System

    Science.gov (United States)

    Hoogenboom, T.; Schenk, P.; White, O. L.

    2012-03-01

    To derive accurate ages using impact craters, the impact source must be determined. We investigate secondary crater size, frequency, distribution, formation, and crater chain formation on icy satellites throughout the Jupiter and Saturn systems.

  9. Methyl salicylate overdose

    Science.gov (United States)

    ... used to relieve sore muscles and joints (Ben Gay, Icy Hot) Oil of wintergreen Solutions for vaporizers ... breathing problems, and other symptoms Activated charcoal Laxative Tube through the mouth into the stomach if vomiting ...

  10. Working in the Cold

    Centers for Disease Control (CDC) Podcasts

    During the winter, many workers are outdoors, working in cold, wet, icy, or snowy conditions. Learn how to identify symptoms that tell you there may be a problem and protect yourself from cold stress.

  11. Research reactor back-end options - decommissioning: a necessary consideration

    International Nuclear Information System (INIS)

    England, M.R.; Parry, D.R.; Smith, C.

    1998-01-01

    Decommissioning is a challenge, which all radioactive site licensees eventually need to face and research reactors are no exception. BNFL has completed numerous major decommissioning projects at its own operational sites and has undertaken similar works at customers' sites including the decommissioning of the Universities Research Reactor (URR), Risley and the ICI TRIGA 1-Mk I Reactor at Billingham. Based on the execution of such projects BNFL has gained an understanding of the variety of customer requirements and the effectiveness of specific decommissioning techniques for research reactors. This paper addresses factors to be considered when reviewing the way forward following shut down and how these affect the final decisions for fuel management and the extent of decommissioning. Case studies are described from BNFL's recent experience decommissioning both the URR and ICI TRIGA reactors. (author)

  12. Mathematical model of rhodium self-powered detectors and algorithms for correction of their time delay

    International Nuclear Information System (INIS)

    Bur'yan, V.I.; Kozlova, L.V.; Kuzhil', A.S.; Shikalov, V.F.

    2005-01-01

    The development of algorithms for correction of self-powered neutron detector (SPND) inertial is caused by necessity to increase the fast response of the in-core instrumentation systems (ICIS). The increase of ICIS fast response will permit to monitor in real time fast transient processes in the core, and in perspective - to use the signals of rhodium SPND for functions of emergency protection by local parameters. In this paper it is proposed to use mathematical model of neutron flux measurements by means of SPND in integral form for creation of correction algorithms. This approach, in the case, is the most convenient for creation of recurrent algorithms for flux estimation. The results of comparison for estimation of neutron flux and reactivity by readings of ionization chambers and SPND signals, corrected by proposed algorithms, are presented [ru

  13. Comparison of delay-interferometer and time-lens-based all-optical OFDM demultiplexers

    DEFF Research Database (Denmark)

    Lillieholm, Mads; Mulvad, Hans Christian Hansen; Galili, Michael

    2015-01-01

    ) based on time lenses. In the former scheme, cascaded delay-interferometers (DIs) are used to perform the O-DFT, with subsequent active optical gating to remove the intercarrier interference (ICI). Here a reduced-complexity partial O-DFT, realized by replacing a number of DIs with optical bandpass......In this paper we present the first detailed numerical comparison of two promising all-optical schemes to demultiplex orthogonal frequency-division multiplexing (OFDM) signals. The investigated schemes are the optical discrete Fourier transformation (O-DFT) and the optical spectral magnification (SM...... filters, is investigated. In the latter scheme the OFDM spectrum is magnified, allowing for simple optical bandpass filtering of the individual subcarriers with reduced ICI. Ideally only a single unit consisting of two time lenses is needed, reducing the complexity and potentially the energy consumption...

  14. Comparison of Delay-Interferometer and Time- Lens-Based All-Optical OFDM Demultiplexers

    DEFF Research Database (Denmark)

    Lillieholm, Mads; Mulvad, Hans Christian Hansen; Galili, Michael

    2015-01-01

    (SM) based on time lenses. In the former scheme, cascaded delay-interferometers (DIs) are used to perform the O-DFT, with subsequent active optical gating to remove the intercarrier interference (ICI). Here, a reduced-complexity partial O-DFT, realized by replacing a number of DIs with optical......In this letter, we present the first detailed numerical comparison of two promising all-optical schemes to demultiplex orthogonal frequency-division multiplexing (OFDM) signals. The investigated schemes are the optical discrete Fourier transformation (O-DFT) and the optical spectral magnification...... bandpass filters, is investigated. In the latter scheme, the OFDM spectrum is magnified, allowing for simple optical bandpass filtering of the individual subcarriers with reduced ICI. Ideally, only a single unit consisting of two time lenses is needed, reducing the complexity and potentially the energy...

  15. Mercury analysis in hair

    DEFF Research Database (Denmark)

    Esteban, Marta; Schindler, Birgit K; Jiménez-Guerrero, José A

    2015-01-01

    Human biomonitoring (HBM) is an effective tool for assessing actual exposure to chemicals that takes into account all routes of intake. Although hair analysis is considered to be an optimal biomarker for assessing mercury exposure, the lack of harmonization as regards sampling and analytical...... assurance program (QAP) for assessing mercury levels in hair samples from more than 1800 mother-child pairs recruited in 17 European countries. To ensure the comparability of the results, standard operating procedures (SOPs) for sampling and for mercury analysis were drafted and distributed to participating...... laboratories. Training sessions were organized for field workers and four external quality-assessment exercises (ICI/EQUAS), followed by the corresponding web conferences, were organized between March 2011 and February 2012. ICI/EQUAS used native hair samples at two mercury concentration ranges (0...

  16. Using a field radiometer to estimate instantaneous sky clearness Radiômetro de campo para cálculo da clareza instantânea do céu

    Directory of Open Access Journals (Sweden)

    Eduardo G. Souza

    2006-06-01

    Full Text Available Reflectance measurements of crop plants and canopies show promise for guiding within-season, variable-rate nitrogen (N application. Most research results have been obtained around solar noon with clear skies. However, for practical application, the system must work under cloudy skies or away from solar noon. The objective of this work was to assess the effect of cloud conditions on reflectance measurements of a corn canopy. The approach was to estimate an instantaneous sky clearness index (ICI which could be used to correct field radiometer data for variations in cloud cover, such that the same reflectance reading would be obtained (and the same N recommendation made for the same plants regardless of cloud conditions. Readings were taken from morning until night over 11 days with a range of sky conditions (sunny, overcast, partly cloudy. Data from clear days were used to estimate the theoretical expected spectral global radiation incident on a horizontal surface. The ICI was calculated as the ratio between the actual spectral global radiation and the corresponding theoretical global radiation. Analysis of the ICI for each band showed that the influence of cloudiness was different for each band. Thus, the cloud effect could not be compensated by the use of a band ratio or vegetation index.Medidas da reflectância das folhas das plantas mostram-se promissoras para a aplicação de nitrogênio a taxa variável; entretanto, a maioria dos resultados de pesquisa foi obtida ao redor do meio-dia solar e com céu aberto, porém para aplicações práticas um sistema tem que trabalhar debaixo de céu nublado e fora do meio-dia solar. O objetivo deste trabalho foi avaliar o efeito de condições de nuvem em medidas de reflectância de milho. A abordagem foi calcular um índice instantâneo de clareza do céu (ICI que pode ser usado para corrigir dados de radiômetros de campo para variações em cobertura de nuvem, tal que essas reflectâncias seriam

  17. SLUSH: Europa Hybrid Deep Drill, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — There are at least two fundamental design approaches one could use when trying to penetrate the icy shell on Europa and other planetary bodies: a melt probe and an...

  18. Atmospheric Modeling of the Martian Polar Regions: CRISM EPF Coverage During the South Polar Spring Recession

    Science.gov (United States)

    Brown, A. J.; McGuire, P.; Wolff, M. J.

    2008-03-01

    We describe efforts to model dust and ice aerosols content and soils and icy surface reflectance in the Martian southern polar region during spring recession (Ls = 152-320) using CRISM emission phase function (EPF) observations.

  19. PREBIOTIC HYDROCARBON SYNTHESIS IN IMPACTING REDUCED ASTROPHYSICAL ICY MIXTURES

    International Nuclear Information System (INIS)

    Koziol, Lucas; Goldman, Nir

    2015-01-01

    We present results of prebiotic organic synthesis in shock-compressed reducing mixtures of simple ices from quantum molecular dynamics simulations extended to close to chemical equilibrium timescales. Given the relative abundance of carbon in reduced forms in astrophysical ices as well as the tendency of these mixtures to form complex hydrocarbons under the presence of external stimuli, it is possible that cometary impacts on a planetary surface could have yielded a larger array of prebiotic organic compounds than previously investigated. We find that the high pressures and temperatures due to shock compression yield a large assortment of carbon- and nitrogen-bonded extended structures that are highly reactive with short molecular lifetimes. Expansion and cooling causes these materials to break apart and form a wide variety of stable, potentially life-building compounds, including long-chain linear and branched hydrocarbons, large heterocyclic compounds, and a variety of different amines and exotic amino acids. Our results help provide a bottom-up understanding of hydrocarbon impact synthesis on the early Earth and its role in producing life-building molecules from simple starting materials

  20. The drive to life on wet and icy worlds.

    Science.gov (United States)

    Russell, Michael J; Barge, Laura M; Bhartia, Rohit; Bocanegra, Dylan; Bracher, Paul J; Branscomb, Elbert; Kidd, Richard; McGlynn, Shawn; Meier, David H; Nitschke, Wolfgang; Shibuya, Takazo; Vance, Steve; White, Lauren; Kanik, Isik

    2014-04-01

    This paper presents a reformulation of the submarine alkaline hydrothermal theory for the emergence of life in response to recent experimental findings. The theory views life, like other self-organizing systems in the Universe, as an inevitable outcome of particular disequilibria. In this case, the disequilibria were two: (1) in redox potential, between hydrogen plus methane with the circuit-completing electron acceptors such as nitrite, nitrate, ferric iron, and carbon dioxide, and (2) in pH gradient between an acidulous external ocean and an alkaline hydrothermal fluid. Both CO2 and CH4 were equally the ultimate sources of organic carbon, and the metal sulfides and oxyhydroxides acted as protoenzymatic catalysts. The realization, now 50 years old, that membrane-spanning gradients, rather than organic intermediates, play a vital role in life's operations calls into question the idea of "prebiotic chemistry." It informs our own suggestion that experimentation should look to the kind of nanoengines that must have been the precursors to molecular motors-such as pyrophosphate synthetase and the like driven by these gradients-that make life work. It is these putative free energy or disequilibria converters, presumably constructed from minerals comprising the earliest inorganic membranes, that, as obstacles to vectorial ionic flows, present themselves as the candidates for future experiments. Key Words: Methanotrophy-Origin of life. Astrobiology 14, 308-343. The fixation of inorganic carbon into organic material (autotrophy) is a prerequisite for life and sets the starting point of biological evolution. (Fuchs, 2011 ) Further significant progress with the tightly membrane-bound H(+)-PPase family should lead to an increased insight into basic requirements for the biological transport of protons through membranes and its coupling to phosphorylation. (Baltscheffsky et al., 1999 ).

  1. PREBIOTIC HYDROCARBON SYNTHESIS IN IMPACTING REDUCED ASTROPHYSICAL ICY MIXTURES

    Energy Technology Data Exchange (ETDEWEB)

    Koziol, Lucas; Goldman, Nir, E-mail: lucas.koziol@exxonmobil.com, E-mail: ngoldman@llnl.gov [Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States)

    2015-04-20

    We present results of prebiotic organic synthesis in shock-compressed reducing mixtures of simple ices from quantum molecular dynamics simulations extended to close to chemical equilibrium timescales. Given the relative abundance of carbon in reduced forms in astrophysical ices as well as the tendency of these mixtures to form complex hydrocarbons under the presence of external stimuli, it is possible that cometary impacts on a planetary surface could have yielded a larger array of prebiotic organic compounds than previously investigated. We find that the high pressures and temperatures due to shock compression yield a large assortment of carbon- and nitrogen-bonded extended structures that are highly reactive with short molecular lifetimes. Expansion and cooling causes these materials to break apart and form a wide variety of stable, potentially life-building compounds, including long-chain linear and branched hydrocarbons, large heterocyclic compounds, and a variety of different amines and exotic amino acids. Our results help provide a bottom-up understanding of hydrocarbon impact synthesis on the early Earth and its role in producing life-building molecules from simple starting materials.

  2. Pluto’s non-icy component: a close-in analysis

    Science.gov (United States)

    Dalle Ore, Cristina M.; Protopapa, Silvia; Cruikshank, Dale P.; Grundy, William M.; Stern, S. Alan; Ennico, Kimberly; Olkin, Catherine; Reuter, Dennie; Young, Leslie; Weaver, Harold A.; New Horizons Composition Theme Team

    2017-10-01

    The understanding of the origin and evolution of Pluto, and, by extension, that of a vast number of similar sized and smaller bodies in the Third Zone of the solar system, are closely tied to their atmosphere and surface chemistry. In turn, a major role in the composition and coloration (from dark red to yellow) of the surface -and indirectly the atmosphere- of Pluto is played by non-ice components presumed to be organic compounds known as tholins. While some of these compounds have been reproduced in the laboratory by irradiation of native materials found in Pluto’s atmosphere and surface, the number of kinds of tholins on the surface of Pluto, and the processes responsible for their formation and distribution is still subject of investigation. We make use of Pluto data from the New Horizons Ralph instrument consisting of a multicolor/panchromatic mapper (MVIC) and mapping infrared (IR) composition spectrometer (LEISA). For this study we have adopted a set of scans at high spatial resolution (on average 2.7 km/pixel), spectroscopically analyzed for the first time. Our preliminary analysis shows different signatures for the dark red material that could be attributed to either grain size or composition/nature of the darkening agent. We characterize and inter-compare the potentially different tholins aiming at understanding its/their history and chemical evolution.

  3. Astrobiological Aspects of Radiation Chemistry in Europa's Icy Regolith

    Science.gov (United States)

    Carlson, R. W.; Hand, K. P.

    2006-05-01

    Jupiter's moon Europa, with its likely subsurface ocean and young, active surface, is a promising habitat for life. Europa orbits in the heart of Jupiter's powerful magnetosphere and suffers intense energetic particle bombardment, producing both positive and negative aspects for astrobiology at Europa. Ionizing radiation can produce oxidants that could support a radiation-driven ecology as proposed by Chyba. On the other hand, biomolecular evidence for life that may be upwelled to the surface is rapidly altered by irradiation, complicating astrobiological searches for evidence of life. We present an overview of laboratory work performed at JPL and elsewhere and observational results related to these two aspects. The oxidants hydrogen peroxide and molecular oxygen are known to exist on Europa and the radiolytic production of these species has been studied in the laboratory for both electron and ion irradiation. Laboratory- measured equilibrium concentrations of H2O2, where production and destruction rates are equal, are in general agreement with the observed 0.1% molar abundance on Europa. The shape of Europa's peroxide band is consistent with the line shapes observed in radiolysis and with H2O2 dispersed in water ice rather than occurring as H2O2 aggregates. Surprisingly, molecular oxygen may be even more abundant on Europa even though O2 is extremely volatile ande would be expected to escape from the ice surface. Radiolysis can produce molecular oxygen and appears to simultaneously alter the ice matrix, trapping the O2. Other species observed on Europa are CO2 and SO2, and laboratory radiolysis of these species in H2O ice produces carbonic and sulfuric acid, respectively. We are studying the radiolytic degradation of biomarkers in ice at Europa temperatures by studying both simple organics and more complex biomolecules, including microorganisms. Hydrocarbon radiolysis yields carbon dioxide and methane, which can escape the system and results in loss of carbon. In addition, polymerization produces brown, high-molecular weight residues with complex mass spectra. Radiolysis of microorganisms shows the loss of amine, amide, methyl, and methylene groups, and production of carbon dioxide, carbon monoxide, nitriles, and isocyanates. Work is continuing to establish useful biosignatures that may persist in the complex mass spectra of irradiated microorganisms.

  4. ICIS-FE&C Download Summary and Data Element Dictionary ...

    Science.gov (United States)

    ECHO, Enforcement and Compliance History Online, provides compliance and enforcement information for approximately 800,000 EPA-regulated facilities nationwide. ECHO includes permit, inspection, violation, enforcement action, and penalty information about facilities regulated under the Clean Air Act (CAA) Stationary Source Program, Clean Water Act (CWA) National Pollutant Elimination Discharge System (NPDES), and/or Resource Conservation and Recovery Act (RCRA). Information also is provided on surrounding demographics when available.

  5. Exit this way; Par ici la sortie du nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    This paper aims to inform the public on the nuclear power phaseout necessity. The fist part presents the hazards bound the nuclear activities, from the uranium mines to the radioactive wastes disposal and the reasons of a necessary phaseout. The second part recalls the historical aspects of the nuclear power implementation in the french energy policy and the today government attitude to value its choice. The last part presents the advantages of other energies sources and scenario of nuclear power phaseout. (A.L.B.)

  6. A Framework for Uplink Intercell Interference Modeling with Channel-Based Scheduling

    KAUST Repository

    Tabassum, Hina; Yilmaz, Ferkan; Dawy, Zaher; Alouini, Mohamed-Slim

    2012-01-01

    This paper presents a novel framework for modeling the uplink intercell interference(ICI) in a multiuser cellular network. The proposed framework assists in quantifying the impact of various fading channel models and state-of-the-art scheduling

  7. Vers de profonds bouleversements demographiques. 2040, la Suisse en vases communicants

    CERN Multimedia

    2004-01-01

    "Geneve, Fribourg et Zurich seront les grands beneficiaires des changements demographiques spectaculaires qui devraient affecter la Suisse d'ici a 2040, selon des chiffres inedits publies vendredi par l'Office federal de la statistique (OFS)" (1 page)

  8. High salt loading induces urinary storage dysfunction via upregulation of epithelial sodium channel alpha in the bladder epithelium in Dahl salt-sensitive rats

    Directory of Open Access Journals (Sweden)

    Seiji Yamamoto

    2017-11-01

    Full Text Available We aimed to investigate whether high salt intake affects bladder function via epithelial sodium channel (ENaC by using Dahl salt-resistant (DR and salt-sensitive (DS rats. Bladder weight of DR + high-salt diet (HS, 8% NaCl and DS + HS groups were significantly higher than those of DR + normal-salt diet (NS, 0.3% NaCl and DS + NS groups after one week treatment. We thereafter used only DR + HS and DS + HS group. Systolic and diastolic blood pressures were significantly higher in DS + HS group than in DR + HS group after the treatment period. Cystometrogram showed the intercontraction intervals (ICI were significantly shorter in DS + HS group than in DR + HS group during infusion of saline. Subsequent infusion of amiloride significantly prolonged ICI in DS + HS group, while no intra-group difference in ICI was observed in DR + HS group. No intra- or inter-group differences in maximum intravesical pressure were observed. Protein expression levels of ENaCα in the bladder were significantly higher in DS + HS group than in DR + HS group. ENaCα protein was localized at bladder epithelium in both groups. In conclusion, high salt intake is considered to cause urinary storage dysfunction via upregulation of ENaC in the bladder epithelium with salt-sensitive hypertension, suggesting that ENaC might be a candidate for therapeutic target for urinary storage dysfunction.

  9. Une carte du feu

    Directory of Open Access Journals (Sweden)

    Sylvie RIMBERT

    1991-12-01

    Full Text Available L’un des apports majeurs de l’informatisation à la cartographie est de faciliter la simulation spatiale. On propose ici un exemple de diffusion d’incendie, simulée sur micro-ordinateur bas de gamme.

  10. AFSC/ABL: Southeast Coastal Monitoring Survey (SECM)-juvenile salmon and associated epipelagic ichthyofauna in the marine waters of Southeast Alaska

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — SECM research was initiated in the spring of 1997, just prior to the onset of a strong El Nio event, and has continued annually. SECM sampling occurs around Icy...

  11. Splenectomy in children with idiopathic thrombocytopenic purpura : A prospective study of 134 children from the Intercontinental Childhood ITP Study Group

    NARCIS (Netherlands)

    Kuehne, Thomas; Blanchette, Victor; Buchanan, George R.; Ramenghi, Ugo; Donato, Hugo; Tamminga, Rienk Y. J.; Rischewski, Johannes; Berchtold, Willi; Imbach, Paul

    2007-01-01

    Background. Splenectomy is an effective procedure for children and adults with severe or refractory idiopathic thrombocytopenic purpura (ITP). Data regarding pediatric patients are limited. Procedure. Sixty-eight Intercontinental Childhood ITP Study Group (ICIS) investigators from 57 institutions in

  12. Europa the ocean moon : search for an alien biosphere

    CERN Document Server

    Greenberg, Richard

    2004-01-01

    Europa - The Ocean Moon tells the story of the Galileo spacecraft probe to Jupiter's moon, Europa. It provides a detailed description of the physical processes, including the dominating tidal forces that operate on Europa, and includes a comprehensive tour of Europa using images taken by Galileo's camera. The book reviews and evaluates the interpretative work carried out to date, providing a philosophical discussion of the scientific process of analyzing results and the pitfalls that accompany it. It also examines the astrobiological constraints on this possible biosphere, and implications for future research, exploration and planetary biological protection. Europa - The Ocean Moon provides a unique understanding of the Galileo images of Europa, discusses the theory of tidal processes that govern its icy ridged and disrupted surface, and examines in detail the physical setting that might sustain extra-terrestrial life in Europa's ocean and icy crust.

  13. Frequency offset estimation in OFDM systems using Bayesian filtering

    Science.gov (United States)

    Yu, Yihua

    2011-10-01

    Orthogonal frequency division multiplexing (OFDM) is sensitive to carrier frequency offset (CFO) that causes inter-carrier interference (ICI). In this paper, we present two schemes for the CFO estimation, which are based on rejection sampling (RS) and a form of particle filtering (PF) called kernel smoothing technique, respectively. The first scheme is offline estimation, where the observations contained in the OFDM training symbol are treated in the batch mode. The second scheme is online estimation, where the observations in the OFDM training symbol are treated in the sequential manner. Simulations are provided to illustrate the performances of the schemes. Performance comparisons of the two schemes and with other Bayesian methods are provided. Simulation results show that the two schemes are effective when estimating the CFO and can effectively combat the effect of ICI in OFDM systems.

  14. Thermal Regeneration of Sulfuric Acid Hydrates after Irradiation

    Science.gov (United States)

    Loeffler, Mark J.; Hudson, Reggie L.

    2012-01-01

    In an attempt to more completely understand the surface chemistry of the jovian icy satellites, we have investigated the effect of heating on two irradiated crystalline sulfuric acid hydrates, H2SO4 4H2O and H2SO4 H2O. At temperatures relevant to Europa and the warmer jovian satellites, post-irradiation heating recrystallized the amorphized samples and increased the intensities of the remaining hydrate's infrared absorptions. This thermal regeneration of the original hydrates was nearly 100% efficient, indicating that over geological times, thermally-induced phase transitions enhanced by temperature fluctuations will reform a large fraction of crystalline hydrated sulfuric acid that is destroyed by radiation processing. The work described is the first demonstration of the competition between radiation-induced amorphization and thermally-induced recrystallization in icy ionic solids relevant to the outer Solar System.

  15. 17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells.

    KAUST Repository

    Ren, Jian

    2013-04-01

    Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication (GJIC) remain obscure. We found that 17β estradiol (E2) up-regulated Cx43, and enhanced GJIC in osteocyte-like MLO-Y4 cells in fluorescence recovery after photobleaching (FRAP) assay. Combination of E2 pre-treatment and oscillating fluid flow (OFF) further enhanced Cx43 expression and mitogen-activated protein kinase (MAPK) phosphorylation, comparing to E2 or OFF treatment alone. Both blocking of classical estrogen receptors (ERα/β) by fulvestrant and ERα knockdown by small interfering RNA inhibited E2-mediated Cx43 increase, while a GPR30-specific agonist G-1 failed to promote Cx43 expression. Our results suggest that the presence of E2 enhanced Cx43-based GJIC mainly via ERα/β pathway, and sensitized osteocytes to mechanical loading. © 2012 Elsevier Inc. All rights reserved.

  16. Inde : Quand les villes grandissent trop vite | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    , par le fait même, de transformer le pays. « Ici, le climat n'est pas la seule chose qui change. Tout change! » explique Veena Srinivasan, sociohydrologiste au Ashoka Trust for Research in Ecology and the Environment ...

  17. IlOTI-OPERATION AL INSTRtJCTION .f\\.I... SYSTEMS MODEL

    African Journals Online (AJOL)

    Navy and. R. F. Mager's. Criteria. Referenced. Instruction. Model for Analysis. Design and ... Naval educational pol icy of the U.S Navy and of .... skills or abilities which are required as the entry .... development provides for a self correcting, self.

  18. Interlaboratory comparison of four in vitro assays for assessing androgenic and antiandrogenic activity of environmental chemicals

    DEFF Research Database (Denmark)

    Körner, Wolfgang; Vinggaard, Anne; Terouanne, B.

    2004-01-01

    steroidal androgens, two antiandrogens, an androgenic control, 5alpha-dihydrotestosterone (DHT), and an antiandrogenic control, bicalutamide (ICI 176,334). All laboratories correctly detected the androgenic activity of 4-androsten-3,17-dione and 17alpha-methyl-testosterone. For both compounds...

  19. Cine militante:Del internacionalismo a la política sensible neoliberal / Militant Cinema: From Internationalism to Neoliberal Sensible Politics

    Directory of Open Access Journals (Sweden)

    Irmgard Emmelhainz

    2017-02-01

    Full Text Available En los años sesenta, el cine militante buscó compartir y expandir estrategias y herramientas para la lucha política alrededor del mundo. Ici et ailleurs (1969- 1974, la película que Godard filmó con Jean-Pierre Gorin bajo el marco del Grupo Dziga Vertov y editó con Anne-Marie Miéville, no es solo un ejemplo de cine político de vanguardia, sino un recuento auto-reflexivo del resultado de las revoluciones aquí y en otro lado, del devenir de la militancia y el cine comprometido y de su repudio a mediados de los años setenta. En este ensayo, me enfoco en tres elementos que forman parte del legado del cine militante en general, y específicamente de Ici et ailleurs: primero, las lecciones que se pueden derivar de las ordalías derivadas de simpatizar, hablar o imaginar procesos políticos de otros, en otros lados. Segundo, el problema que Godard plantea en películas posteriores a Ici et ailleurs, a lo que llamo la «mediatización de la mediación», como la forma de activismo que siguió al rechazo del marxismo-leninismo como depositario de la política progresiva. Tercero, la no poco problemática transformación de la política de la imagen de Godard en la «política sensible» post-política, un nicho en la producción cultural que se ha dado la tarea de codificar actos políticos inestables en formas mediáticas, transformando la acción y enunciación política en cuestión de expresión.Palabras clave: cine militante, Jean-Luc Godard, Palestina, activismo, política sensible, post-política, compromiso político.Abstract:In the 1960s, militant cinema aimed to share and expand strategies and tools for the political struggle around the world. Ici et ailleurs (1969-1974, the film that Godard shot with Jean-Pierre Gorin within the Dziga Vertov’s Group and edited with Anne-Marie Miéville, it is not only an example of avant-garde political cinema, but also an auto-reflexive account of the outcome of revolutions here and elsewhere, of

  20. Medically inoperable stage I endometrial carcinoma: a few dilemmas in radiotherapeutic management

    International Nuclear Information System (INIS)

    Chao, Clifford K. S.; Grigsby, Perry W.; Perez, Carlos A.; Mutch, David G.; Herzog, Thomas; Camel, H. Marvin

    1996-01-01

    Purpose: The aggressiveness of radiation therapy for patients with medically inoperable endometrial carcinoma is controversial. Patients may die of their underlining medical disease before succumbing to cancer. We try to identify certain subgroup of patients who might benefit most from an aggressive approach and also investigate the impact of residual tumor present in dilatation and curettage (D and C) specimen obtained in second intracavitary implant (ICI). Methods and Materials: From 1965 to 1990, 101 patients were treated for clinical clinical Stage I endometrial carcinoma with RT alone due to medical problems. Ages ranged from 39 to 94 years (median 71 years). There were 18 patients with clinical Stage IA and 83 with clinical Stage IB disease. Histology included 44 well-differentiated, 37 moderately differentiated, and 20 poorly differentiated tumors. Radiation therapy consisted of external beam only in 3 patients, ICI alone in 26, whole pelvis plus ICI in 10, and whole pelvis plus split field plus ICI in 62. A second D and C was performed on 26 patients at the time of the second ICI. Minimum follow-up was 2 years (median, 6.3 years). Results: The 5-year actuarial disease-free survival (DFS) for the studied cohort is comparable to the expected survival of an age-matched population. Pelvic control was 100% for Stage IA and 88% for Stage IB with 5-year disease-free survivals of 80 and 84%, respectively. We also observed a greater disassociation of DFS and overall survival among patients older than 75 years (84 and 55%, respectively) than in younger patients (84 and 78%, respectively). This is mainly because older patients succumbed to their medical illness. Well-differentiated disease demonstrated the trend toward a better outcome than moderately or poorly differentiated lesions in Stage IB patients (p 0.05), but not in Stage IA patients. Aggressive radiation therapy approach showed the trend toward a better result in Stage IB patients 75 years of age or younger

  1. Anti-Inflammatory Effects of Tanshinone IIA on Atherosclerostic Vessels of Ovariectomized ApoE-/- Mice are Mediated by Estrogen Receptor Activation and Through the ERK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xin Liu

    2015-03-01

    Full Text Available Aims: Estrogen plays a protective role in atherosclerosis. Our preliminary work demonstrated that the active conformation of Tanshinone IIA(TanIIA is similar to the 17ß-estradiol and it can bind to the estrogen receptor. Here, we hypothesized that Tanshinone IIA might have anti-inflammatory and anti-oxidative effects in atherosclerosis, mediated through estrogen receptor activation. Methods: Subjects for this study were 120 apoE-/- female mice and 20 C57/BL female mice. The apoE-/- mice were ovariectomized (OVX and the C57/BL mice were sham ovariectomized. The sham OVX mice were maintained on a normal diet (NOR group. The OVX apoE-/- mice were fed a high fat diet and randomly divided into 6 groups: Model (MOD group which was fed a high fat diet only, E2 group were given estrogen (E2 0.13mg/kg/d; E2+ICI group were given E2:0.13mg/kg/d and ICI182780:65mg/kg/m; TLD group (TanIIA low dose were given TanIIA: 30mg/kg/d; THD group (TanIIA high dose were given TanIIA:60mg/kg/d; and TLD+ICI group were given TanIIA 30mg/kg/d and ICI182780 65mg/kg/m. After three months of treatment, the aorta and the blood of the mice from each group was collected. The aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE and oil red O staining and for testing the expression of p-ERK1/2 by Western blot. The blood was used for testing the serum cholesterol, superoxide dismutase (SOD, methane dicarboxylic aldehyde (MDA, nuclear factor kappa (NF-κB, soluble intercellular cell adhesion molecule-1 (sICAM-1, activating protein-1 (AP-1, E-selectin and 17ß-estradiol in serum. Results: Tanshinone IIA significantly reduced the lipid deposition in aorta, decreased the levels of total cholesterol (TC, triglyceride (TG, low density lipoprotein (LDL, very low density lipoprotein (VLDL, MDA, NF-κB, sICAM-1, AP-1, and E-selectin in serum but increased the levels of high density lipoprotein (HDL and SOD in serum. Tanshinone IIA also suppressed the

  2. Constitution d’un Corpus de Français Langue Etrangère destiné aux Apprenants Allemands

    Directory of Open Access Journals (Sweden)

    Fauth Camille

    2014-07-01

    Nationale de la Recherche et Deutsche Forschungsgemeinschaft attribué à l’équipe Parole du LORIA UMR 7503, Nancy – France et à l’Equipe de Linguistique Computationnelle et de Phonétique FR 4.7 de l’Université de la Sarre Sarrebruck – Allemagne dans lequel le français et l’allemand sont des langues cibles. Pour la paire allemand-français, peu de corpus parallèles sont disponibles. Nous présentons ici l’élaboration d’un corpus de productions orales de locuteurs natifs et non natifs pour la paire allemand-français. Notre corpus entend mettre au jour les déviations phonétiques et phonologiques que les locuteurs allemands produisent lorsqu’ils apprennent le français. Ce travail s’insère dans un projet plus global, Ce projet entend étudier les difficultés que les locuteurs français rencontrent lorsqu’ils apprennent l’allemand, et réciproquement. Aussi, cinquante locuteurs allemands seront recrutés dans des milieux universitaires et scolaires (niveau lycée en Allemagne et cinquante locuteurs français dans les mêmes milieux en France. Il s’agit pour les deux populations de produire d’une part le corpus en langue étrangère (en langue française pour les locuteurs allemands et en langue allemande pour les locuteurs français mais également le corpus en langue maternelle (en allemand pour les allemands et en français pour les français. Les corpus ainsi obtenus devraient nous permettre d’identifier les difficultés que les locuteurs allemands ou français rencontrent lorsqu’ils apprennent le français ou l’allemand. Les données de contrôle sont doubles puisque l’on pourra à la fois se référer aux productions des apprenants dans leur langue maternelle (ici l’allemand, mais également à celles de locuteurs natifs (ici germanophones. Nous ne présenterons ici que la constitution du corpus en français.

  3. Relation nappe-rivière dans le bassin versant du Bandama en ...

    African Journals Online (AJOL)

    Dr gatsin

    'Information Géographique (SIG). Traitement des images. L'objectif ici est de ..... effluents des ouvrages d'assainissement). Une faible connexion entre ces deux aquifères qui ralentirait la continuité hydraulique et donc un mélange de ces deux ...

  4. Building a Geologic Map of Neptune's Moon Triton

    Science.gov (United States)

    Martin, E. S.; Patthoff, D. A.; Bland, M. T.; Watters, T. R.; Collins, G. C.; Becker, T.

    2018-06-01

    Triton serves as a bridge between KBOs and icy satellites, and characterization of its terrains is important for advancing comparative planetological studies. We aim to create a geologic map of the Neptune-facing side of Triton at a scale of 1:5M.

  5. Anti-icing and de-icing superhydrophobic concrete to improve the safety on critical elements on roadway pavements.

    Science.gov (United States)

    2013-09-01

    Icy roads lead to treacherous driving conditions in regions of the U.S. resulting in over 450 fatalities per year. Deicing chemicals, such as rock salt help to reduce ice formation on roadways to an extent, however also result in detrimental effects ...

  6. Comparison of short-term estrogenicity tests for identification of hormone-disrupting chemicals

    DEFF Research Database (Denmark)

    Andersen, H R; Andersson, A M; Arnold, S F

    1999-01-01

    induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n...

  7. Community Languages in Europe : Challenges and Opportunities

    NARCIS (Netherlands)

    McPake, J.; Martyniuk, W.; Aarts, R.; Broeder, Peter; Latomaa, Sirkku; Mijares, Laura; Tinsley, Teresa

    2004-01-01

    This paper reviews issues affecting school students’ learning of community languages across Europe, with the aim of identifying both challenges and opportunities inherent in the current context. Language education pol icy has become more inclusive of late, addressing the full range of languages

  8. 75 FR 52793 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

    Science.gov (United States)

    2010-08-27

    ...''); Joseph S. Fichera, Saber Partners, LLC, New York, New York (``Saber Partners''), dated April 12, 2010 (``Saber Letter''); Heather Traeger, Associate Counsel, Investment Company Institute (``ICI''), dated April... the lack of transparency creates the opportunity for manipulation and unfair dealing. \\10\\ See Saber...

  9. Clathrates - An Exploration of the Chemistry of Caged Compounds

    Indian Academy of Sciences (India)

    also found on the icy moons of our solar system, at Saturn and .... This mineral loses water rapidly on heating and seemed ... The prototype of clathrate-I structure for gas hydrate has a .... Useful for studies of air pollution, process control and.

  10. Oligochètes

    NARCIS (Netherlands)

    Cognetti de Martiis, L.

    1913-01-01

    La collection qui forme le sujet de ce travail se compose de huit espèces, dont quatre sont nouvelles. A mr. le Docteur L. F. de Beaufort, qui a bien voulu me la communiquer, j’exprime ici mes sentiments de gratitude.

  11. Winter Safety Tips for Older Adults

    Science.gov (United States)

    ... checked and changed if necessary. • Remember your cell phone when you drive in bad weather, and always let someone know where you are going and when you should be expected back. • Avoid driving on icy roads, and be especially careful driving ...

  12. The Radio & Plasma Wave Investigation (RPWI) for JUICE

    Science.gov (United States)

    Wahlund, J.-E.

    2013-09-01

    We present the Radio & Plasma Waves Investigation (RPWI) selected for implementation on the JUICE mission. RPWI consists of a highly integrated instrument package that provides a whole set of plasma and fields measurements. The RPWI instrument has outstanding new capabilities not previously available to outer planet missions, and that would address many fundamental planetary science objectives. Specifically, RPWI would be able to study the electro-dynamic influence of the Jovian magnetosphere on the exospheres, surfaces and conducting oceans of Ganymede, Europa and Callisto. RPWI would also be able to monitor the sources of radio emissions from auroral regions of Ganymede and Jupiter, and possibly also from lightning activity in Jupiter's clouds. Moreover, RPWI will search for exhaust plumes from cracks on the icy moons, as well as μm-sized dust and related dust-plasmasurface interaction processes occurring near the icy moons of Jupiter.

  13. Linearly interpolated sub-symbol optical phase noise suppression in CO-OFDM system.

    Science.gov (United States)

    Hong, Xuezhi; Hong, Xiaojian; He, Sailing

    2015-02-23

    An optical phase noise suppression algorithm, LI-SCPEC, based on phase linear interpolation and sub-symbol processing is proposed for CO-OFDM system. By increasing the temporal resolution of carrier phase tracking through dividing one symbol into several sub-blocks, i.e., sub-symbols, inter-carrier-interference (ICI) mitigation is achieved in the proposed algorithm. Linear interpolation is employed to obtain a reliable temporal reference for sub-symbol phase estimation. The new algorithm, with only a few number of sub-symbols (N(B) = 4), can provide a considerably larger laser linewidth tolerance than several other ICI mitigation algorithms as demonstrated by Monte-Carlo simulations. Numerical analysis verifies that the best performance is achieved with an optimal and moderate number of sub-symbols. Complexity analysis shows that the required number of complex-valued multiplications is independent of the number of sub-symbols used in the proposed algorithm.

  14. Une histoire des mathématiques routes et dédales

    CERN Document Server

    Dahan-Dalmedico, Amy

    1986-01-01

    L'histoire des mathématiques est celle des conjectures, des hésitations, des impasses, des modèles concurrents, des intuitions fulgurantes, des synthèses théoriques... La naissance et le développement de l'activité mathématique sont ici replacés dans leur contexte historique et leur environnement culturel, économique et institutionnel. Le cadre est ainsi fixé pour l'étude précise de différents thèmes : équations, espace, limite, fonctions, lois, opérations ; notions fondamentales auxquelles tout élève, étudiant, enseignant est confronté. Les mathématiques ne se présentent pas, ici, comme un corps figé d'axiomes, théorèmes, lemmes et corollaires ; elles tissent une toile en devenir qui suscite bien des curiosités.

  15. Gene expression changes in rat prostate after activation or blocking of the androgen and estrogen receptor

    DEFF Research Database (Denmark)

    Nellemann, Christine Lydia; Dalgaard, Majken; Holst, Bjørn

    2005-01-01

    responsive genes (complement C3, ER alpha, ER beta, AR, TRPM-2, PBPC3, ODC, and IGF-1 mRNA) was analyzed in rat ventral prostate by real time RT-PCR. Administration of estradiol benzoate (EB) to castrated testosterone-treated rats had no effect on reproductive organ weights or gene expression levels...... reversed by ICI 182780, and affected TRPM-2, PBP C3, ODC, IGF-1, AR, and ERa mRNA levels. AR expression in the prostate seemed to be under regulation of both estrogens and androgens, as ICI 182780 inhibited the testosterone-induced AR expression, and flutamide inhibited the EB-induced AR expression...... administration abolished the effects of EB. First choice of gene expression profiles in the Hershberger assay to study androgenic or anti-androgenic effects would be the traditional, TRPNI-2 and PBP C3, supplemented with the new complement C3....

  16. Joint Frequency-Domain Equalization and Despreading for Multi-Code DS-CDMA Using Cyclic Delay Transmit Diversity

    Science.gov (United States)

    Yamamoto, Tetsuya; Takeda, Kazuki; Adachi, Fumiyuki

    Frequency-domain equalization (FDE) based on the minimum mean square error (MMSE) criterion can provide a better bit error rate (BER) performance than rake combining. To further improve the BER performance, cyclic delay transmit diversity (CDTD) can be used. CDTD simultaneously transmits the same signal from different antennas after adding different cyclic delays to increase the number of equivalent propagation paths. Although a joint use of CDTD and MMSE-FDE for direct sequence code division multiple access (DS-CDMA) achieves larger frequency diversity gain, the BER performance improvement is limited by the residual inter-chip interference (ICI) after FDE. In this paper, we propose joint FDE and despreading for DS-CDMA using CDTD. Equalization and despreading are simultaneously performed in the frequency-domain to suppress the residual ICI after FDE. A theoretical conditional BER analysis is presented for the given channel condition. The BER analysis is confirmed by computer simulation.

  17. Experimental Results of Network-Assisted Interference Suppression Scheme Using Adaptive Beam-Tilt Switching

    Directory of Open Access Journals (Sweden)

    Tomoki Murakami

    2017-01-01

    Full Text Available This paper introduces a network-assisted interference suppression scheme using beam-tilt switching per frame for wireless local area network systems and its effectiveness in an actual indoor environment. In the proposed scheme, two access points simultaneously transmit to their own desired station by adjusting angle of beam-tilt including transmit power assisted from network server for the improvement of system throughput. In the conventional researches, it is widely known that beam-tilt is effective for ICI suppression in the outdoor scenario. However, the indoor effectiveness of beam-tilt for ICI suppression has not yet been indicated from the experimental evaluation. Thus, this paper indicates the effectiveness of the proposed scheme by analyzing multiple-input multiple-output channel matrices from experimental measurements in an office environment. The experimental results clearly show that the proposed scheme offers higher system throughput than the conventional scheme using just transmit power control.

  18. Initiatives for the energy renovation of single-family houses inDenmark evaluated on the basis of barriers and motivators

    DEFF Research Database (Denmark)

    Grøn Bjørneboe, Matilde; Svendsen, Svend; Heller, Alfred

    2018-01-01

    The renovation of single-family houses in Denmark is progressing only slowly. Changes in current pol-icy are needed if the political goal of a fossil-free building sector as part of a fossil-free society is to beachieved. Known barriers and motivators for energy renovation are identified, and arr......The renovation of single-family houses in Denmark is progressing only slowly. Changes in current pol-icy are needed if the political goal of a fossil-free building sector as part of a fossil-free society is to beachieved. Known barriers and motivators for energy renovation are identified......, suggestions are madefor improvement in four areas: (1) focus on non-energy benefits rather than investment, (2) enhance-ment of subsidy system, (3) including relevant renovation plans in the energy performance certificate(EPC), and (4) long-term regulation on the maximum allowed energy consumption of houses....

  19. A note on the possible origin of comets in an interstellar gas cloud

    International Nuclear Information System (INIS)

    Yabushita, S.; Hasegawa, I.

    1978-01-01

    A possible origin of comets in an interstellar gas cloud is discussed in relation to the two recent results on cometary research. First, among 200 long-period comets whose original incoming orbits were recently calculated, seven have definitely and 14 have probably negative values of 1/a, where 1/a is twice the binding energy (positive a corresponds to an elliptic orbit) with respect to the solar system barycentre. Second, it has been shown how an aggregate of dust grains embedded in an icy matrix of gaseous compounds could form in an interstellar gas cloud, which could be identified with the icy nucleus of a comet. Again, of about 20 comets whose original 1/a values are negative, seven are transformed into future elliptic orbits by planetary perturbation. Thus, a comet which originated in an interstellar cloud could be captured by the solar system

  20. SILICON AND OXYGEN ABUNDANCES IN PLANET-HOST STARS

    International Nuclear Information System (INIS)

    Brugamyer, Erik; Dodson-Robinson, Sarah E.; Cochran, William D.; Sneden, Christopher

    2011-01-01

    The positive correlation between planet detection rate and host star iron abundance lends strong support to the core accretion theory of planet formation. However, iron is not the most significant mass contributor to the cores of giant planets. Since giant planet cores are thought to grow from silicate grains with icy mantles, the likelihood of gas giant formation should depend heavily on the oxygen and silicon abundance of the planet formation environment. Here we compare the silicon and oxygen abundances of a set of 76 planet hosts and a control sample of 80 metal-rich stars without any known giant planets. Our new, independent analysis was conducted using high resolution, high signal-to-noise data obtained at McDonald Observatory. Because we do not wish to simply reproduce the known planet-metallicity correlation, we have devised a statistical method for matching the underlying [Fe/H] distributions of our two sets of stars. We find a 99% probability that planet detection rate depends on the silicon abundance of the host star, over and above the observed planet-metallicity correlation. We do not detect any such correlation for oxygen. Our results would thus seem to suggest that grain nucleation, rather than subsequent icy mantle growth, is the important limiting factor in forming giant planets via core accretion. Based on our results and interpretation, we predict that planet detection should correlate with host star abundance for refractory elements responsible for grain nucleation and that no such trends should exist for the most abundant volatile elements responsible for icy mantle growth.

  1. Modulatory role of androgenic and estrogenic neurosteroids in determining the direction of synaptic plasticity in the CA1 hippocampal region of male rats.

    Science.gov (United States)

    Pettorossi, Vito Enrico; Di Mauro, Michela; Scarduzio, Mariangela; Panichi, Roberto; Tozzi, Alessandro; Calabresi, Paolo; Grassi, Silvarosa

    2013-12-01

    Estrogenic and androgenic neurosteroids can rapidly modulate synaptic plasticity in the brain through interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used electrophysiological recordings in slices of young and adolescent male rats to explore the influence of sex neurosteroids on synaptic plasticity in the CA1 hippocampal region, by blocking ARs or ERs during induction of long-term depression (LTD) and depotentiation (DP) by low-frequency stimulation (LFS) and long-term potentiation (LTP) by high-frequency stimulation (HFS). We found that LTD and DP depend on ARs, while LTP on ERs in both age groups. Accordingly, the AR blocker flutamide affected induction of LTD reverting it into LTP, and prevented DP, while having no effect on HFS-dependent LTP. Conversely, ER blockade with ICI 182,780 (ICI) markedly reduced LTP, but did not influence LTD and DP. However, the receptor blockade did not affect the maintenance of either LTD or LTP. Moreover, we found that similar to LTP and LTD induced in control condition, the LTP unveiled by flutamide during LFS and residual LTP induced by HFS under ICI depended on N-methyl-d aspartate receptor (NMDAR) activation. Furthermore, as the synaptic paired-pulse facilitation (PPF) was not affected by either AR or ER blockade, we suggest that sex neurosteroids act primarily at a postsynaptic level. This study demonstrates for the first time the crucial role of estrogenic and androgenic neurosteroids in determining the sign of hippocampal synaptic plasticity in male rat and the activity-dependent recruitment of androgenic and estrogenic pathways leading to LTD and LTP, respectively.

  2. The costo-uterine muscle of the rat contains a homogeneous population of beta-adrenoceptors.

    Science.gov (United States)

    Hartley, M. L.; Pennefather, J. N.

    1985-01-01

    The effects of two selective beta-adrenoceptor antagonists on the inhibitory responses to some sympathomimetic amines of electrically-stimulated preparations of costo-uterine muscle, taken from virgin rats, have been examined quantitatively. pA2 values for the antagonist, atenolol (beta 1-selective) and ICI 118,551 (beta 2-selective) were obtained using as agonists, fenoterol (beta 2-selective agonist) and noradrenaline (alpha- and beta-adrenoceptor agonist, beta 1-selective); and in addition, with ICI 118,551 only, isoprenaline (beta-agonist, non-selective) and adrenaline (alpha- and beta-adrenoceptor agonist, beta 2-selective). Catecholamine uptake mechanisms and alpha-adrenoceptors were not blocked in any of these experiments. Atenolol competitively antagonized the effects of fenoterol and noradrenaline to a similar extent, the pA2 values being 5.4 and 5.7, respectively. ICI 118,551 competitively antagonized the effects of fenoterol, isoprenaline, adrenaline and noradrenaline to a similar extent; pA2 values ranged from 8.7 with noradrenaline to 9.1 with isoprenaline. These results extend our previous observations which indicated that the adrenoceptors mediating inhibition of electrically-evoked contractions of costo-uterine muscle of the virgin rat are homogeneous and of the beta 2-subtype. The potency of the beta 1-selective agonist RO 363 in producing inhibition of electrically-evoked contractions of this tissue was also examined. RO 363 was 200 times less potent than isoprenaline but was a full agonist. This indicates that there is efficient coupling between beta 2-adrenoceptor activation and tissue response in this non-innervated preparation. PMID:2858239

  3. A comparison of the treatment recommendations for neurogenic lower urinary tract dysfunction in the national institute for health and care excellence, European Association of Urology and international consultations on incontinence guidelines.

    Science.gov (United States)

    Jaggi, Ashley; Drake, Marcus; Siddiqui, Emad; Fatoye, Francis

    2018-04-17

    Healthcare guidelines are an important vehicle in establishing up-to-date evidence based medicine (EBM) in clinical practice. Due to varying development processes, clinical guidelines created by different institutions can often contain contrasting recommendations. This can have implications for optimal and standardized patient care across management settings. The similarities and differences of treatment recommendations made in the National Institute for Health and Care Excellence (NICE), The European Association of Urology (EAU), and the International Consultation on Continence (ICI) guidelines for neurogenic lower urinary tract dysfunction (NLUTD) were assessed. The guidelines generally agree on their approach to conservative management, including behavioral therapies, and catheterization techniques. There was discrepancy on the benefit of using an alpha blocker in NLUTD and bladder outlet obstruction (BOO) and administering Botulinum toxin A (Onabotulinum-A) in NLUTD. The highest degree of divergence was seen in recommendations for surgical treatments, where the EAU made gender-specific recommendations, and gave continent urinary diversion higher preference than given in the NICE and ICI guidelines. In the absence of high-quality clinical evidence, many of the recommendations made across all three guidelines are based on expert opinion. NICE, the EAU and ICI have similarities but they place differing emphasis on costs and expert opinion, which translated in notably different recommendations. It is evident that increased research efforts, possibly in the form of prospective registries, pragmatic trials, and resource utilization studies are necessary to improve the underlying evidence base for NLUTD, and subsequently the strength and concordance of recommendations across guidelines. © 2018 Wiley Periodicals, Inc.

  4. Micrometer-sized Water Ice Particles for Planetary Science Experiments: Influence of Surface Structure on Collisional Properties

    Energy Technology Data Exchange (ETDEWEB)

    Gärtner, S.; Fraser, H. J. [School of Physical Sciences, The Open University, Walton Hall, Milton Keynes MK7 6AA (United Kingdom); Gundlach, B.; Ratte, J.; Blum, J. [Institut für Geophysik und extraterrestrische Physik, TU Braunschweig, Mendelssohnstr. 3, D-38106 Braunschweig (Germany); Headen, T. F.; Youngs, T. G. A.; Bowron, D. T. [ISIS Facility, STFC Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0QX (United Kingdom); Oesert, J.; Gorb, S. N., E-mail: sabrina.gaertner@stfc.ac.uk, E-mail: helen.fraser@open.ac.uk [Zoologisches Institut, Christian-Albrechts-Universität zu Kiel, Am Botanischen Garten 1-9, D-24118 Kiel (Germany)

    2017-10-20

    Models and observations suggest that ice-particle aggregation at and beyond the snowline dominates the earliest stages of planet formation, which therefore is subject to many laboratory studies. However, the pressure–temperature gradients in protoplanetary disks mean that the ices are constantly processed, undergoing phase changes between different solid phases and the gas phase. Open questions remain as to whether the properties of the icy particles themselves dictate collision outcomes and therefore how effectively collision experiments reproduce conditions in protoplanetary environments. Previous experiments often yielded apparently contradictory results on collision outcomes, only agreeing in a temperature dependence setting in above ≈210 K. By exploiting the unique capabilities of the NIMROD neutron scattering instrument, we characterized the bulk and surface structure of icy particles used in collision experiments, and studied how these structures alter as a function of temperature at a constant pressure of around 30 mbar. Our icy grains, formed under liquid nitrogen, undergo changes in the crystalline ice-phase, sublimation, sintering and surface pre-melting as they are heated from 103 to 247 K. An increase in the thickness of the diffuse surface layer from ≈10 to ≈30 Å (≈2.5 to 12 bilayers) proves increased molecular mobility at temperatures above ≈210 K. Because none of the other changes tie-in with the temperature trends in collisional outcomes, we conclude that the surface pre-melting phenomenon plays a key role in collision experiments at these temperatures. Consequently, the pressure–temperature environment, may have a larger influence on collision outcomes than previously thought.

  5. The Effects of Sex Hormonal Fluctuations during Menstrual Cycle on Cortical Excitability and Manual Dexterity (a Pilot Study.

    Directory of Open Access Journals (Sweden)

    Maryam Zoghi

    Full Text Available To investigate whether hormonal fluctuations during the menstrual cycle affect corticospinal excitability, intracortical inhibition (ICI or facilitation (ICF in primary motor cortex, and also whether the hormonal fluctuations have any effect on manual dexterity in neurologically intact women.Twenty volunteers (10 Female, 10 Male were included in this study. The levels of progesterone and estradiol were measured from saliva during the women's menstrual follicular, ovulation and mid-luteal phases. Motor evoked potentials were recorded from the right first dorsal interosseous muscle. Single and paired-pulse Transcranial Magnetic Stimulation (TMS were delivered in a block of 20 stimuli. With paired-pulse technique, 3ms and 10ms inter-stimulus intervals were used to assess ICI and ICF, respectively. The Grooved Pegboard Test (GPT was completed in each session before the TMS assessments. Male participants were tested at similar time intervals as female participants.Mixed design ANOVA revealed that GPT score in female participants was significantly lower at the mid-luteal phase compared to the ovulation phase (p = 0.017. However, it was not correlated with progesterone or estrogen fluctuations during the menstrual cycle. The results also showed that the effect of phase, sex and the interaction of phase by sex for resting motor threshold, ICI or ICF were not significant (p > 0.05.Manual dexterity performance fluctuates during the menstrual cycle in neurologically intact women, which might be due to the balance of the neuromodulatory effects of P4 and E2 in the motor cortex during different phases.

  6. European Scientific Notes. Volume 37, Number 6.

    Science.gov (United States)

    1983-06-30

    Univ. voir membrane systems or with specially of Mainz, West Germany). shaped devices, essentially linear Dr. F.G. Hutchinson (ICI Pharma - release can...languages, such as Course- of the printing press. writer, TUTOR , and PILOT, are themselves software systems that help educators write courseware. According

  7. Résultats de recherche | Page 106 | CRDI - Centre de recherches ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Centre d'innovation pour la résilience de l'Afrique de l'Est. D'ici 2025, la pauvreté sera essentiellement concentrée dans les pays africains à faible revenu touchés par des conflits et de la violence. Projet.

  8. Jeux de cartes

    Directory of Open Access Journals (Sweden)

    Pierre GENTELLE

    1986-09-01

    Full Text Available Dans la grande tradition de la science-fiction et des lieux imaginaires traduits ici en «jeux» de cartes, l'auteur bouleverse quelques localisations au prix de mouvements tectoniques imprévus et en prévoit quelques conséquences.

  9. Les baobabs de Madagascar : quel cadre régle- mentaire pour leur ...

    African Journals Online (AJOL)

    1 juin 2014 ... dont trois 'En Danger' sur la liste rouge de l'UICN et trois ... With lemurs, baobabs are the most emblematic species of. Madagascar internationally. .... (CDB 2010) stipulant que 'd'ici à 2020, l'extinction d'espèces menacées ...

  10. How to Have a Healthy Winter | Poster

    Science.gov (United States)

    Without a doubt, winter is here. Between the icy weather and the recent hustle and bustle of the holidays, everyone is at an increased risk of getting sick. With that in mind, Occupational Health Services has a few simple tips for staying healthy this winter.

  11. Industrial and commercial applications for a Triga reactor

    International Nuclear Information System (INIS)

    Green, D.

    1986-01-01

    The Physics and Radioisotope Services Group of ICI operates a Triga Reactor in support of a commercial, Industrial Radioisotope Technology Service. The technical and commercial development of this business is discussed in the context of operating a Triga Reactor in an Industrial Environment. (author)

  12. Iterative equalization for OFDM systems over wideband Multi-Scale Multi-Lag channels

    NARCIS (Netherlands)

    Xu, T.; Tang, Z.; Remis, R.; Leus, G.

    2012-01-01

    OFDM suffers from inter-carrier interference (ICI) when the channel is time varying. This article seeks to quantify the amount of interference resulting from wideband OFDM channels, which are assumed to follow the multi-scale multi-lag (MSML) model. The MSML channel model results in full channel

  13. Pharmacological treatment of overactive bladder: report from the International Consultation on Incontinence

    NARCIS (Netherlands)

    Andersson, Karl-Erik; Chapple, Christopher R.; Cardozo, Linda; Cruz, Francisco; Hashim, Hashim; Michel, Martin C.; Tannenbaum, Cara; Wein, Alan J.

    2009-01-01

    Purpose of review Treatment options for the overactive bladder were recently discussed at the 4th International Consultation on Incontinence (ICI) held in Paris, 5-8 July 2008. This article will overview current thoughts on the pharmacological and clinical basis for the different classes of drugs

  14. Sadhana | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    The ICI technique is based on a consistency measure across confidence intervals corresponding to different window lengths. An approximate asymptotic analysis to determine the optimal confidence interval width shows that the asymptotic expressions are the same irrespective of whether one starts with a uniform sampling ...

  15. FERTILTTY IN COWS AF-TER SYNCHRONISATION OF OESTRUS ...

    African Journals Online (AJOL)

    REFERENCES. COOPER, M.J., 1974. Control of oestrous cycles of heifen with a synthetic prostaglandin analogue. Vet. Rec. 95,240. COOPER, MJ. and JACKSON, P.S., 1975. Control of the bovine oestrous cycle with a synthetic prostaglandin analogue, I.C.I.80996 - preliminary field experiencesinlactatingbeef cattle. hoc.

  16. 78 FR 46005 - NPDES Electronic Reporting Rule

    Science.gov (United States)

    2013-07-30

    .... B. Does this action apply to me? Entities potentially affected by this action would include all... Compliance System (ICIS-NPDES) is the transmission of eXtensible Markup Language (XML) data files through a... system that allocates points against various factors including flow, pollutant loadings, and water...

  17. Popnädal. Billboard 200 Albumid Top 20 / Jaan Tamm

    Index Scriptorium Estoniae

    Tamm, Jaan

    2002-01-01

    Ansambli The Smiths 20. sünnipäeva puhul ilmunud joonisfilmist. Jennifer Lopezist filmis "Enough". Peter Gabrieli albumist "Up". Duo Elton John ja Bernie autasustamisest Music Industry Trust galal. Duubelplaadist Yann Tiersen "C'Etait ICI". Filmist muusiku Gram Parsoni elust. Iiri poistebändist Westlife

  18. Shining light on interstellar matter : a laboratory study

    NARCIS (Netherlands)

    Paardekooper, D.M.

    2016-01-01

    In recent years it has become clear that the space in between the stars, contains a remarkable amount of highly diverse molecules, ranging from simple diatomics to large complex species. Astronomical observations and dedicated laboratory experiments show that icy dust grains play a prominent role in

  19. 40 CFR 89.612 - Prohibited acts; penalties.

    Science.gov (United States)

    2010-07-01

    ... years may be adjusted based on the Consumer Price Index. The specific regulatory provisions for changing... govern any decision to suspend, revoke, or refuse to issue certificates of conformity under this subpart... revocation, the ICI demonstrates to the Administrator's satisfaction that the decision to initiate suspension...

  20. From ice to gas : constraining the desorption processes of interstellar ices

    NARCIS (Netherlands)

    Fayolle, Edith Carine

    2013-01-01

    The presence of icy mantles on interstellar dust grains play a key role in the formation of molecules observed at all stages of star formation. This thesis addresses thermal and UV-induced ice sublimation. Using state of the art laboratory experiments and synchrotron-based UV radiation, the