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Sample records for zd6474 vandetanib zactima

  1. Determination of vandetanib in human plasma and cerebrospinal fluid by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).

    Science.gov (United States)

    Bai, Feng; Johnson, Jennifer; Wang, Fan; Yang, Lei; Broniscer, Alberto; Stewart, Clinton F

    2011-09-01

    A sensitive and precise LC-ESI-MS/MS method for the determination of vandetanib (ZD6474) in human plasma and cerebrospinal fluid (CSF) using [(13)C,d(3)]-ZD6474 as an internal standard (ISTD) was developed and validated. Sample preparation consisted of a simple liquid-liquid extraction with tert-butyl methyl ether containing 0.1% or 0.5% ammonium hydroxide. ZD6474 and ISTD were separated on a Kinetex C18 column (2.6 μm, 50 mm × 2.1 mm) at ambient temperature with an isocratic mobile phase (acetonitrile/10mM ammonium formate=50/50, v/v, at pH 5.0) delivered at 0.11 mL/min. The retention time of both compounds was at 1.60 min in a runtime of three min. Detection was achieved by an API-3200 LC-MS/MS system, monitoring m/z 475.1/112.1 and m/z 479.1/116.2 for vandetanib and ISTD, respectively. The method was linear in the range of 0.25-50 ng/mL (R(2) ≥ 0.990) for the CSF curve and from 1.0 to 3000 ng/mL (R(2) ≥ 0.992) for the plasma curve. The mean recovery for vandetanib was 80%. Within-day and between-day precisions were ≤ 8.8% and ≤ 5.9% for CSF and plasma, respectively. Within-day and between-day accuracies ranged from 95.0 to 98.5% for CSF, and from 104.0 to 108.5% for plasma. Analysis of plasma from six different sources showed no matrix effect for vandetanib (MF=0.98, %CV ≤ 4.97, n=6). This method was successfully applied to the analysis of pharmacokinetic samples from children with brain tumors treated with oral vandetanib. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Clinical utility of vandetanib in the treatment of patients with advanced medullary thyroid cancer

    Directory of Open Access Journals (Sweden)

    Deshpande H

    2011-12-01

    Full Text Available Hari Deshpande1,3, Vicky Marler3, Julie Ann Sosa2,31Department of Medicine, 2Department of Surgery, Yale University School of Medicine, 3Yale Cancer Center, New Haven, CT, USAAbstract: Vandetanib (ZD6474 became the first systemic agent to be approved for the treatment of metastatic or locally advanced medullary thyroid cancer. It was a proof of principle, because it is an orally bioavailable medication that targets the growth factors felt to be important in the pathogenesis of this disease, ie, the rearranged during transfection proto-oncogene and vascular endothelial growth factor receptor. It was tested initially in two Phase II studies at doses of 100 mg and 300 mg daily. Although activity was seen at both doses, the higher dose was chosen for a randomized, placebo-controlled Phase II study. This trial, which accrued more than 300 patients, showed a statistically significant benefit for the group taking vandetanib compared with those taking placebo medication. Progression-free survival for the vandetanib arm has not been reached, compared with 19 months for the placebo arm. The main toxicity appears to be diarrhea, although some patients experienced significant side effects, including torsades de pointes and sudden cardiac death. Therefore, it is now necessary for practitioners to enroll in a Risk Evaluation Mitigation Strategy before being allowed to prescribe this medication, to reduce the risk of serious side effects occurring.Keywords: ZD6474, medullary thyroid cancer, vandetanib

  3. Phase I study of cetuximab, irinotecan, and vandetanib (ZD6474 as therapy for patients with previously treated metastastic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Meyerhardt

    Full Text Available BACKGROUND: To determine the maximum tolerated dose (MTD and safety, and explore efficacy and biomarkers of vandetanib with cetuximab and irinotecan in second-line metastatic colorectal cancer. METHODS: Vandetanib (an orally bioavailable VEGFR-2 and EGFR tyrosine kinases inhibitor was combined at 100 mg, 200 mg, or 300 mg daily with standard dosed cetuximab and irinotecan (3+3 dose-escalation design. Ten patients were treated at the MTD and plasma angiogenesis biomarkers (VEGF, PlGF, bFGF, sVEGFR1, sVEGFR2, IL-1β, IL-6, IL-8, TNF-α, SDF1α were measured before and after treatment. RESULTS: Twenty-seven patients were enrolled at 4 dose levels and the MTD. Two dose-limiting toxicities (grade 3 QTc prolongation and diarrhea were detected at 300 mg of vandetanib with cetuximab and irinotecan resulting in 200 mg being the MTD. Seven percent of patients had a partial response, 59% stable disease and 34% progressed. Median progression-free survival was 3.6 months (95% CI, 3.2-5.6 and median overall survival was 10.5 months (95% CI, 5.1-20.7. Toxicities were fairly manageable with grade 3 or 4 diarrhea being most prominent (30%. Vandetanib and cetuximab treatment induced a sustained increase in plasma PlGF and a transient decrease in plasma sVEGFR1, but no changes in plasma VEGF and sVEGFR2. CONCLUSIONS: Vandetanib can be safely combined with cetuximab and irinotecan for metastatic colorectal cancer. Exploratory biomarker analyses suggest differential effects on certain plasma biomarkers for VEGFR inhibition when combined with EGFR blockade and a potential correlation between baseline sVEGFR1 and response. However, while the primary endpoint was safety, the observed efficacy raises concern for moving forward with this combination. TRIAL REGISTRATION: Clinicaltrials.gov NCT00436072.

  4. Vandetanib in advanced medullary thyroid cancer: review of adverse event management strategies

    DEFF Research Database (Denmark)

    Grande, Enrique; Kreissl, Michael C; Filetti, Sebastiano

    2013-01-01

    Vandetanib has recently demonstrated clinically meaningful benefits in patients with unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). Given the potential for long-term vandetanib therapy in this setting, in addition to treatment for disease-related symptoms, effective...

  5. ZD6126: A novel small molecule vascular targeting agent

    International Nuclear Information System (INIS)

    Blakey, David C.; Ashton, Susan E.; Westwood, F. Russell; Walker, Mike; Ryan, Anderson J.

    2002-01-01

    Purpose: The aim of these studies was to evaluate factors that contribute to the selectivity of the novel vascular targeting agent ZD6126. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with ZD6126 phenol, and effects on morphology, detachment, and cytotoxicity (sulforhodamine-B dye incorporation) were determined. Hras5-transformed mouse 3T3 fibroblasts were implanted s.c. in athymic nude rats, and effects on the tumor were assessed after either i.v. bolus or 24-h minipump infusion of ZD6126. Results: In vitro, ZD6126 phenol (∼0.1 μm) rapidly (<40 min) destabilized the tubulin cytoskeleton of proliferating endothelial cells, resulting in cell shape change ('rounding up') and cell detachment at noncytotoxic drug concentrations. In vivo, in rats, an i.v. bolus dose of ZD6126 (20 mg/kg) was rapidly broken down to ZD6126 phenol, which has a short plasma elimination half-life (∼1 h). Peak plasma levels of ZD6126 phenol were well above the level required to induce HUVEC morphology changes in vitro, but cytotoxic concentrations were not maintained. A single i.v. bolus dose (50 and 20 mg/kg) of ZD6126 was well tolerated and resulted in extensive central tumor necrosis in the Hras5 model. Administration of ZD6126 using a 24-h s.c. minipump resulted in decreased (∼30-fold) peak plasma levels, but maintained cytotoxic drug levels over 24 h. Infusion of 50 mg/kg ZD6126 over 24 h was not tolerated. Infusion of 20 mg/kg ZD6126 resulted in increased toxicity compared with the i.v. bolus doses of ZD6126 and did not result in any increased tumor necrosis after 24 h. Conclusion: ZD6126 phenol induces rapid morphologic changes in HUVECs at noncytotoxic drug levels. These rapid morphologic effects combined with the rapid elimination of ZD6126 phenol contribute to the selective effects of ZD6126 on tumor vasculature at well-tolerated doses

  6. Effect of an Outreach Programme on Vandetanib Safety in Medullary Thyroid Cancer

    DEFF Research Database (Denmark)

    Bastholt, Lars; Kreissl, Michael C; Führer, Dagmar

    2016-01-01

    OBJECTIVES: Effective management of adverse events (AEs) following vandetanib treatment is important to maximize clinical benefits. We examined whether more frequent contact with vandetanib-treated patients reduced AEs of CTCAE grade 2 or higher. STUDY DESIGN: In this open-label, multicentre, pha...

  7. Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.

    Science.gov (United States)

    Robinson, Bruce G; Paz-Ares, Luis; Krebs, Annetta; Vasselli, James; Haddad, Robert

    2010-06-01

    Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.

  8. Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model

    International Nuclear Information System (INIS)

    Wachsberger, Phyllis; Burd, Randy; Ryan, Anderson; Daskalakis, Constantine; Dicker, Adam P.

    2009-01-01

    Purpose: The tumor growth kinetics of the human LoVo colorectal xenograft model was assessed in response to vandetanib, an orally available receptor tyrosine kinase inhibitor, radiotherapy (RT), or irinotecan (CPT-11), as single therapies and in combination. Methods and Materials: LoVo cells were injected subcutaneously into the right hind limb (5x10 6 cells in 100μL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm 3 before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3x3 Gy) on Days 1, 2, and 3. CPT-11 was given at 15 mg/kg intraperitoneally on Days 1 and 3. Tumor volumes were measured on a daily basis and calculated by measuring tumor diameters with digital calipers in two orthogonal dimensions. Results: All three single treatments (vandetanib, CPT-11, and radiation) significantly slowed LoVo colorectal tumor growth. Vandetanib significantly increased the antitumor effects of CPT-11 and radiation when given in combination with either of these treatments. These treatment combinations resulted in a slow tumor growth rate during the 2 weeks of vandetanib administration. The triple combination of vandetanib, CPT-11, and radiation produced the most marked improvement in response as observed by measurable shrinkage of tumors during the first week of treatment. Conclusions: The tumor growth delay kinetics observed in this study of the LoVo colorectal model suggest concurrent and sustained post-sequencing of vandetanib with cytotoxic therapy may be beneficial in tumors of this type.

  9. ZD-I intelligent scaler

    International Nuclear Information System (INIS)

    Zhen Zhihao; Zhou Weimin

    1999-01-01

    The ZD-I Intelligent Scaler is a new kind of high-powered scaler using high-speed CMOS96 series single chip processor. Besides the normal timing and counting functions, it can also supply 0-2000 V high voltage, store or print measuring data, communicate with PC by RS232 interface, and transfer measuring data. There is essential improvements on the panel. Keyboard without dialing switches and rheostats can perform all the operations, and the setting parameters would not lose when the scaler is switched off. So the ZD-I Intelligent Scaler is a perfect up-to-date production of the NIM-style scaler and the HV-generator

  10. Phase I study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma.

    Science.gov (United States)

    Papadimitrakopoulou, Vasiliki A; Frank, Steven J; Cohen, Ezra W; Hirsch, Fred R; Myers, Jeffrey N; Heymach, John V; Lin, Heather; Tran, Hai T; Chen, Changhu R; Jimeno, Antonio; Nedzi, Lucien; Vasselli, Joseph R; Lowe, Elizabeth S; Raben, David

    2016-03-01

    Vandetanib, added to cisplatin and radiation therapy (RT) overcomes chemoradiation therapy (CRT) and epidermal growth factor receptor (EGFR) inhibitor resistance in head and neck squamous cell carcinoma (HNSCC) lines and models. Patients with previously untreated HNSCC received vandetanib daily for 14 days (starting dose 100 mg) and then vandetanib + RT (2.2 Gy/day, 5 days/week) for 6 weeks (regimen 1) or vandetanib + RT (2 Gy/day, 5 days/week) + cisplatin (30 mg/m(2) weekly) for 7 weeks (regimen 2). The primary objective was the maximum tolerated dose (MTD) of vandetanib with RT +/- cisplatin. Of 33 treated patients, 30 completed therapy (regimen 1, n = 12; regimen 2, n = 18). MTD in regimen 2 was 100 mg (3 dose limiting toxicities [DLTs] at 200 mg), whereas regimen 1 was stopped because of poor recruitment (1 DLT at 200 mg). Most common grade ≥3 adverse events (AEs) were dysphagia (30%), stomatitis (33%), and mucosal inflammation (27%). Five patients discontinued vandetanib because of AEs. Vandetanib with CRT was feasible. © 2015 Wiley Periodicals, Inc.

  11. Augmentation of radiation response with the vascular targeting agent ZD6126

    International Nuclear Information System (INIS)

    Hoang Tien; Huang Shyhmin; Armstrong, Eric; Eickhoff, Jens C.; Harari, Paul M.

    2006-01-01

    Purpose: To examine the antivascular and antitumor activity of the vascular targeting agent ZD6126 in combination with radiation in lung and head-and-neck (H and N) cancer models. The overall hypothesis was that simultaneous targeting of tumor cells (radiation) and tumor vasculature (ZD6126) might enhance tumor cell killing. Methods and Materials: A series of in vitro studies using human umbilical vein endothelial cells (HUVEC) and in vivo studies in athymic mice bearing human lung (H226) and H and N (squamous cell carcinoma [SCC]1, SCC6) tumor xenografts treated with ZD6126 and/or radiation were performed. Results: ZD6126 inhibited the capillary-like network formation in HUVEC. Treatment of HUVEC with ZD6126 resulted in cell cycle arrest in G2/M, with decrease of cells in S phase and proliferation inhibition in a dose-dependent manner. ZD6126 augmented the cell-killing effect of radiation and radiation-induced apoptosis in HUVEC. The combination of ZD6126 and radiation further decreased tumor vascularization in an in vivo Matrigel angiogenesis assay. In tumor xenografts, ZD6126 enhanced the antitumor activity of radiation, resulting in tumor growth delay. Conclusions: These preclinical studies suggest that ZD6126 can augment the radiation response of proliferating endothelial H and N and lung cancer cells. These results complement recent reports suggesting the potential value of combining radiation with vascular targeting/antiangiogenic agents

  12. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial.

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    Wells, Samuel A; Robinson, Bruce G; Gagel, Robert F; Dralle, Henning; Fagin, James A; Santoro, Massimo; Baudin, Eric; Elisei, Rossella; Jarzab, Barbara; Vasselli, James R; Read, Jessica; Langmuir, Peter; Ryan, Anderson J; Schlumberger, Martin J

    2012-01-10

    There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC. Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments. Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; P < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (P < .001), disease control rate (P = .001), and biochemical response (P < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%). Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).

  13. Vandetanib in locally advanced or metastatic differentiated thyroid cancer

    DEFF Research Database (Denmark)

    Leboulleux, Sophie; Bastholt, Lars; Krause, Thomas

    2012-01-01

    No effective standard treatment exists for patients with radioiodine-refractory, advanced differentiated thyroid carcinoma. We aimed to assess efficacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting....

  14. ZD0473 pharmacokinetics in Japanese patients: a Phase I dose-escalation study.

    Science.gov (United States)

    Murakami, H; Tamura, T; Yamada, Y; Yamamoto, N; Ueda, Y; Shimoyama, T; Saijo, N

    2002-12-01

    ZD0473 is new platinum agent that was rationally designed to circumvent platinum resistance and reduce the potential for nephro-and neurotoxicity. This Phase I dose-escalating study investigated the pharmacokinetics, tolerability and efficacy of ZD0473 in Japanese patients with solid, refractory tumours. ZD0473 was administered as a 1-h intravenous infusion every 3 weeks. Nine patients received a total of 16 cycles of ZD0473 (median 1 cycle/patient), with 3 patients treated at each of 3 doses (60, 90, 120 mg/m2). The maximum plasma concentration (C(max)) and the area under the concentration-time curve to infinity (AUC(0-infinity)) increased with dose in a linear fashion for both total platinum and ZD0473 in plasma ultrafiltrate, suggesting that the pharmacokinetics of ZD0473 are linear. Haematological and non-haematological toxicities such as nausea and vomiting were mild (grade 1 or 2) and transient. No clinically significant nephro-, oto- or neurotoxicity was observed. Dose-limiting toxicity (DLT) was not observed and the maximum tolerated dose (MTD) was not identified. ZD0473 treatment showed evidence of disease stabilisation in 3 patients (33%). In conclusion, ZD0473 appears to have linear pharmacokinetics, and an acceptable tolerability profile at doses up to 120 mg/m2 in Japanese patients with refractory solid malignancies. Following evaluation of the data from all the Western trials, the ZD0473 development programme changed and this Japanese trial was stopped.

  15. Novel Platinum (Pt)-Vandetanib Hybrid Compounds: Design, Synthesis and Investigation of Anti-cancer Activity and Mechanism of Action

    Science.gov (United States)

    Fei, Rong

    Purpose: Lung cancer is one of the most common cancers and non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancers. 70% of individuals with NSCLC harboring somatic mutations in exons of the epidermal growth factor receptor (EGFR) gene that encode tyrosine kinase domain. EGFR tyrosine kinase inhibitors (TKIs) are promising molecular targeted therapy for NSCLC with sensitizing EGFR mutations. However, secondary mutation of EGFR after treatment of TKIs develops resistance. Vandetanib is introduced to overcome erlotinib resistance as a multi-targeted TKI. However, its anticancer effect is still compromised by EGFR T790M mutation. Therefore, new molecular anticancer strategies are necessarily needed. In this study, vandetanib is incorporated with Pt-based anticancer agents as hybrid compounds, aiming to circumvent TKI resistance. Furthermore, hybrid compounds are investigated in cisplatin resistant problem to expect to overcome resistance by introduction of vandetanib. Methods: Three novel Pt-vandetanib hybrid compounds were synthesized and its physicochemical properties were characterized. Anticancer activity and cytotoxicity were evaluated by sulforhodamine B assay and lactate dehydrogenase release. Docking simulation was performed to investigate the interaction of compounds with EGFR harboring different mutations. Inhibition efficacy of hybrids to kinases was evaluated by kinase inhibition profiling service and cell-free kinase inhibition assay. Mechanistic studies on cytotoxicity activity of the hybrid compounds were carried out. DNA damage response of hybrid compounds was further investigated in KB cells. The cytotoxicity of hybrids was tested in cisplatin resistant KB CP20 cells. Mechanistic of anticancer activity was studied to test inhibition on oncoprotein CIP2Aand DNA damage. Results: Platinum-vandetanib hybrid compounds were synthesized and test to be stable under extracellular condition. Hybrids reacted with 5'-GMP2- and glutathione, and both

  16. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies.

    Science.gov (United States)

    Platt, Adam; Morten, John; Ji, Qunsheng; Elvin, Paul; Womack, Chris; Su, Xinying; Donald, Emma; Gray, Neil; Read, Jessica; Bigley, Graham; Blockley, Laura; Cresswell, Carl; Dale, Angela; Davies, Amanda; Zhang, Tianwei; Fan, Shuqiong; Fu, Haihua; Gladwin, Amanda; Harrod, Grace; Stevens, James; Williams, Victoria; Ye, Qingqing; Zheng, Li; de Boer, Richard; Herbst, Roy S; Lee, Jin-Soo; Vasselli, James

    2015-03-23

    To determine the prevalence of RET rearrangement genes, RET copy number gains and expression in tumor samples from four Phase III non-small-cell lung cancer (NSCLC) trials of vandetanib, a selective inhibitor of VEGFR, RET and EGFR signaling, and to determine any association with outcome to vandetanib treatment. Archival tumor samples from the ZODIAC ( NCT00312377 , vandetanib ± docetaxel), ZEAL ( NCT00418886 , vandetanib ± pemetrexed), ZEPHYR ( NCT00404924 , vandetanib vs placebo) and ZEST ( NCT00364351 , vandetanib vs erlotinib) studies were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in 944 and 1102 patients. The prevalence of RET rearrangements by FISH was 0.7% (95% CI 0.3-1.5%) among patients with a known result. Seven tumor samples were positive for RET rearrangements (vandetanib, n = 3; comparator, n = 4). 2.8% (n = 26) of samples had RET amplification (innumerable RET clusters, or ≥7 copies in > 10% of tumor cells), 8.1% (n = 76) had low RET gene copy number gain (4-6 copies in ≥40% of tumor cells) and 8.3% (n = 92) were RET expression positive (signal intensity ++ or +++ in >10% of tumor cells). Of RET-rearrangement-positive patients, none had an objective response in the vandetanib arm and one patient responded in the comparator arm. Radiologic evidence of tumor shrinkage was observed in two patients treated with vandetanib and one treated with comparator drug. The objective response rate was similar in the vandetanib and comparator arms for patients positive for RET copy number gains or RET protein expression. We have identified prevalence for three RET biomarkers in a population predominated by non-Asians and smokers. RET rearrangement prevalence was lower than previously reported. We found no evidence of a differential benefit for efficacy by IHC and RET gene copy number gains. The low prevalence of RET rearrangements (0.7%) prevents firm conclusions regarding association of vandetanib treatment with

  17. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer.

    Science.gov (United States)

    Wells, Samuel A; Gosnell, Jessica E; Gagel, Robert F; Moley, Jeffrey; Pfister, David; Sosa, Julie A; Skinner, Michael; Krebs, Annetta; Vasselli, James; Schlumberger, Martin

    2010-02-10

    PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. METHODS Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at >/= 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). CONCLUSION In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.

  18. The anti-neoplastic activity of Vandetanib against high-risk medulloblastoma variants is profoundly enhanced by additional PI3K inhibition.

    Science.gov (United States)

    Craveiro, Rogerio B; Ehrhardt, Michael; Velz, Julia; Olschewski, Martin; Goetz, Barbara; Pietsch, Torsten; Dilloo, Dagmar

    2017-07-18

    Medulloblastoma is comprised of at least four molecular subgroups with distinct clinical outcome (WHO classification 2016). SHH-TP53-mutated as well as MYC-amplified Non-WNT/Non-SHH medulloblastoma show the worst prognosis.Here we present evidence that single application of the multi-kinase inhibitor Vandetanib displays anti-neoplastic efficacy against cell lines derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/Non-SHH medulloblastoma. The narrow target spectrum of Vandetanib along with a favourable toxicity profile renders this drug ideal for multimodal treatment approaches. In this context our investigation documents that Vandetanib in combination with the clinically available PI3K inhibitor GDC-0941 leads to enhanced cytotoxicity against MYC-amplified and SHH-TP53-mutated medulloblastoma. In line with these findings we show for MYC-amplified medulloblastoma a profound reduction in activity of the oncogenes STAT3 and AKT. Furthermore, we document that Vandetanib and the standard chemotherapeutic Etoposide display additive anti-neoplastic efficacy in the investigated medulloblastoma cell lines that could be further enhanced by PI3K inhibition. Of note, the combination of Vandetanib, GDC-0941 and Etoposide results in MYC-amplified and SHH-TP53-mutated cell lines in complete loss of cell viability. Our findings therefore provide a rational to further evaluate Vandetanib in combination with PI3K inhibitors as well as standard chemotherapeutics in vivo for the treatment of most aggressive medulloblastoma variants.

  19. To be or not to be a poly(3-hydroxybutyrate) (PHB) depolymerase: PhaZd1 (PhaZ6) and PhaZd2 (PhaZ7) of Ralstonia eutropha, highly active PHB depolymerases with no detectable role in mobilization of accumulated PHB.

    Science.gov (United States)

    Sznajder, Anna; Jendrossek, Dieter

    2014-08-01

    The putative physiological functions of two related intracellular poly(3-hydroxybutyrate) (PHB) depolymerases, PhaZd1 and PhaZd2, of Ralstonia eutropha H16 were investigated. Purified PhaZd1 and PhaZd2 were active with native PHB granules in vitro. Partial removal of the proteinaceous surface layer of native PHB granules by trypsin treatment or the use of PHB granules isolated from ΔphaP1 or ΔphaP1-phaP5 mutant strains resulted in increased specific PHB depolymerase activity, especially for PhaZd2. Constitutive expression of PhaZd1 or PhaZd2 reduced or even prevented the accumulation of PHB under PHB-permissive conditions in vivo. Expression of translational fusions of enhanced yellow fluorescent protein (EYFP) with PhaZd1 and PhaZd2 in which the active-site serines (S190 and Ser193) were replaced with alanine resulted in the colocalization of only PhaZd1 fusions with PHB granules. C-terminal fusions of inactive PhaZd2(S193A) with EYFP revealed the presence of spindle-like structures, and no colocalization with PHB granules was observed. Chromosomal deletion of phaZd1, phaZd2, or both depolymerase genes had no significant effect on PHB accumulation and mobilization during growth in nutrient broth (NB) or NB-gluconate medium. Moreover, neither proteome analysis of purified native PHB granules nor lacZ fusion studies gave any indication that PhaZd1 or PhaZd2 was detectably present in the PHB granule fraction or expressed at all during growth on NB-gluconate medium. In conclusion, PhaZd1 and PhaZd2 are two PHB depolymerases with a high capacity to degrade PHB when artificially expressed but are apparently not involved in PHB mobilization in the wild type. The true in vivo functions of PhaZd1 and PhaZd2 remain obscure. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  20. Antitumor activity of ZD6126, a novel vascular-targeting agent, is enhanced when combined with ZD1839, an epidermal growth factor receptor tyrosine kinase inhibitor, and potentiates the effects of radiation in a human non-small cell lung cancer xenograft model.

    Science.gov (United States)

    Raben, David; Bianco, Cataldo; Damiano, Vincenzo; Bianco, Roberto; Melisi, Davide; Mignogna, Chiara; D'Armiento, Francesco Paolo; Cionini, Luca; Bianco, A Raffaele; Tortora, Giampaolo; Ciardiello, Fortunato; Bunn, Paul

    2004-08-01

    Targeting the tumor vasculature may offer an alternative or complementary therapeutic approach to targeting growth factor signaling in lung cancer. The aim of these studies was to evaluate the antitumor effects in vivo of the combination of ZD6126, a tumor-selective vascular-targeting agent; ZD1839 (gefitinib, Iressa), an epidermal growth factor receptor tyrosine kinase inhibitor; and ionizing radiation in the treatment of non-small cell lung cancer xenograft model. Athymic nude mice with established flank A549 human non-small cell lung cancer xenograft model xenografts were treated with fractionated radiation therapy, ZD6126, ZD1839, or combinations of each treatment. ZD6126 (150 mg/kg) was given i.p. the day after each course of radiation. Animals treated with ZD1839 received 100 mg/kg per dose per animal, 5 or 7 days/wk for 2 weeks. Immunohistochemistry was done to evaluate the effects on tumor growth using an anti-Ki67 monoclonal antibody. Effects on tumor-induced vascularization were quantified using an anti-factor VIII-related antigen monoclonal antibody. ZD6126 attenuated the growth of human A549 flank xenografts compared with untreated animals. Marked antitumor effects were observed when animals were treated with a combination of ZD6126 and fractionated radiation therapy with protracted tumor regression. ZD6126 + ZD1839 resulted in a greater tumor growth delay than either agent alone. Similar additive effects were seen with ZD1839 + fractionated radiation. Finally, the addition of ZD6126 to ZD1839 and radiation therapy seemed to further improve tumor growth control, with a significant tumor growth delay compared with animals treated with single agent or with double combinations. Immunohistochemistry showed that ZD1839 induced a marked reduction in A549 tumor cell proliferation. Both ZD1839 and ZD6126 treatment substantially reduced tumor-induced angiogenesis. ZD6126 caused marked vessel destruction through loss of endothelial cells and thrombosis

  1. PET imaging of early response to the tyrosine kinase inhibitor ZD4190

    International Nuclear Information System (INIS)

    Yang, Min; Gao, Haokao; Yan, Yongjun; Sun, Xilin; Chen, Kai; Quan, Qimeng; Lang, Lixin; Kiesewetter, Dale; Niu, Gang; Chen, Xiaoyuan

    2011-01-01

    We evaluated noninvasive positron emission tomography (PET) imaging for monitoring tumor response to the VEGFR-2 tyrosine kinase (TK) inhibitor ZD4190 during cancer therapy. Orthotopic MDA-MB-435 tumor-bearing mice were treated with ZD4190 (100 mg/kg orally per day for three consecutive days). Tumor growth was monitored by caliper measurement. During the therapeutic period, longitudinal PET scans were acquired using 18 F-FDG, 18 F-FLT and 18 F-FPPRGD2 as imaging tracers to evaluate tumor glucose metabolism, tumor cell proliferation, and angiogenesis, respectively. Imaging metrics were validated by immunohistochemical analysis of Ki67, GLUT-1, F4/80, CD31, murine integrin β3, and human integrin αvβ3. Three consecutive daily oral administrations of 100 mg/kg of ZD4190 were effective in delaying MDA-MB-435 tumor growth. A significant difference in tumor volume was observed on day 7 between the treatment group and the control group (p 18 F-FPPRGD2 uptake was stable between days 0 and 7. In ZD4190-treated tumors, 18 F-FPPRGD2 uptake had decreased significantly relative to baseline by 26.74±8.12% (p 18 F-FLT had also decreased on both day 1 and day 3 after initiation of ZD4190 treatment. No significant change in 18 F-FDG uptake in ZD4190-treated tumors was observed, however, compared with the control group. All of the imaging findings were supported by ex vivo analysis of related biomarkers. The longitudinal imaging results demonstrated the usefulness of quantitative 18 F-FLT and 18 F-FPPRGD2 PET imaging in evaluating the early antiproliferative and antiangiogenic effects of ZD4190. The quantification data from the PET imaging were consistent with the pattern of initial growth inhibition with treatment, followed by tumor relapse after treatment cessation. (orig.)

  2. Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer.

    Science.gov (United States)

    Heymach, John V; Paz-Ares, Luis; De Braud, Filippo; Sebastian, Martin; Stewart, David J; Eberhardt, Wilfried E E; Ranade, Anantbhushan A; Cohen, Graham; Trigo, Jose Manuel; Sandler, Alan B; Bonomi, Philip D; Herbst, Roy S; Krebs, Annetta D; Vasselli, James; Johnson, Bruce E

    2008-11-20

    Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC). All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention. VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.

  3. Biotransformation of trans-1-chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd)

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Tobias [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany); Bertermann, Rüdiger [Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg (Germany); Rusch, George M.; Tveit, Ann [Honeywell, P.O. Box 1057, Morristown, NJ 07962-1057 (United States); Dekant, Wolfgang, E-mail: dekant@toxi.uni-wuerzburg.de [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany)

    2013-05-01

    trans-1-Chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd) is a novel foam blowing and precision cleaning agent with a very low impact for global warming and ozone depletion. trans-HCFO-1233zd also has a low potential for toxicity in rodents and is negative in genotoxicity testing. The biotransformation of trans-HCFO-1233zd and kinetics of metabolite excretion with urine were assessed in vitro and in animals after inhalation exposures. For in vitro characterization, liver microsomes from rats, rabbits and humans were incubated with trans-HCFO-1233zd. Male Sprague Dawley rats and female New Zealand White rabbits were exposed to 2,000, 5,000 and 10,000 ppm for 6 h and urine was collected for 48 h after the end of the exposure. Study specimens were analyzed for metabolites using {sup 19}F NMR, LC-MS/MS and GC/MS. S-(3,3,3-trifluoro-trans-propenyl)-glutathione was identified as predominant metabolite of trans-HCFO-1233zd in all microsomal incubation experiments in the presence of glutathione. Products of the oxidative biotransformation of trans-HCFO-1233zd were only minor metabolites when glutathione was present. In rats, both 3,3,3-trifluorolactic acid and N-acetyl-(3,3,3-trifluoro-trans-propenyl)-L-cysteine were observed as major urinary metabolites. 3,3,3-Trifluorolactic acid was not detected in the urine of rabbits. Quantitation showed rapid excretion of both metabolites in both species (t{sub 1/2} < 6 h) and the extent of biotransformation of trans-HCFO-1233zd was determined as approximately 0.01% of received dose in rabbits and approximately 0.002% in rats. trans-HCFO-1233zd undergoes both oxidative biotransformation and glutathione conjugation at very low rates. The low extent of biotransformation and the rapid excretion of metabolites formed are consistent with the very low potential for toxicity of trans-HCFO-1233zd in mammals. - Highlights: ► No lethality and clinical signs were observed. ► Glutathione S-transferase and cytochrome P-450 dependent

  4. Incidence and risk of QTc interval prolongation among cancer patients treated with vandetanib: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jiajie Zang

    Full Text Available Vandetanib is a multikinase inhibitor that is under assessment for the treatment of various cancers. QTc interval prolongation is one of the major adverse effects of this drug, but the reported incidence varies substantially among clinical trials. We performed a systematic review and meta-analysis to obtain a better understanding in the risk of QTc interval prolongation among cancer patients administered vandetanib.Eligible studies were phase II and III prospective clinical trials that involved cancer patients who were prescribed vandetanib 300 mg/d and that included data on QTc interval prolongation. The overall incidence and risk of QTc interval prolongation were calculated using random-effects or fixed-effects models, depending on the heterogeneity of the included studies. Nine trials with 2,188 patients were included for the meta-analysis. The overall incidence of all-grade and high-grade QTc interval prolongation was 16.4% (95% CI, 8.1-30.4% and 3.7% (8.1-30.4%, respectively, among non-thyroid cancer patients, and 18.0% (10.7-28.6% and 12.0% (4.5-28.0%, respectively, among thyroid cancer patients. Patients with thyroid cancer who had longer treatment duration also had a higher incidence of high-grade events, with a relative risk of 3.24 (1.57-6.71, than patients who had non-thyroid cancer. Vandetanib was associated with a significantly increased risk of all-grade QTc interval prolongation with overall Peto odds ratios of 7.26 (4.36-12.09 and 5.70 (3.09-10.53 among patients with non-thyroid cancer and thyroid cancer, respectively, compared to the controls.Treatment with vandetanib is associated with a significant increase in the overall incidence and risk of QTc interval prolongation. Different cancer types and treatment durations may affect the risk of developing high-grade QTc interval prolongation.

  5. RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt.

    Science.gov (United States)

    Gupta, Avinash; Roberts, Corran; Tysoe, Finn; Goff, Matthew; Nobes, Jenny; Lester, James; Marshall, Ernie; Corner, Carie; Wolstenholme, Virginia; Kelly, Charles; Wise, Adelyn; Collins, Linda; Love, Sharon; Woodward, Martha; Salisbury, Amanda; Middleton, Mark R

    2016-11-08

    Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI: 0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area.

  6. Biotransformation of trans-1-chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd)

    International Nuclear Information System (INIS)

    Schmidt, Tobias; Bertermann, Rüdiger; Rusch, George M.; Tveit, Ann; Dekant, Wolfgang

    2013-01-01

    trans-1-Chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd) is a novel foam blowing and precision cleaning agent with a very low impact for global warming and ozone depletion. trans-HCFO-1233zd also has a low potential for toxicity in rodents and is negative in genotoxicity testing. The biotransformation of trans-HCFO-1233zd and kinetics of metabolite excretion with urine were assessed in vitro and in animals after inhalation exposures. For in vitro characterization, liver microsomes from rats, rabbits and humans were incubated with trans-HCFO-1233zd. Male Sprague Dawley rats and female New Zealand White rabbits were exposed to 2,000, 5,000 and 10,000 ppm for 6 h and urine was collected for 48 h after the end of the exposure. Study specimens were analyzed for metabolites using 19 F NMR, LC-MS/MS and GC/MS. S-(3,3,3-trifluoro-trans-propenyl)-glutathione was identified as predominant metabolite of trans-HCFO-1233zd in all microsomal incubation experiments in the presence of glutathione. Products of the oxidative biotransformation of trans-HCFO-1233zd were only minor metabolites when glutathione was present. In rats, both 3,3,3-trifluorolactic acid and N-acetyl-(3,3,3-trifluoro-trans-propenyl)-L-cysteine were observed as major urinary metabolites. 3,3,3-Trifluorolactic acid was not detected in the urine of rabbits. Quantitation showed rapid excretion of both metabolites in both species (t 1/2 1/2 < 6 h). ► Glutathione adduct as predominant in vitro metabolite in all tested species. ► Toxic metabolites could not be detected in any great extent

  7. RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases – results and lessons learnt

    Science.gov (United States)

    Gupta, Avinash; Roberts, Corran; Tysoe, Finn; Goff, Matthew; Nobes, Jenny; Lester, James; Marshall, Ernie; Corner, Carie; Wolstenholme, Virginia; Kelly, Charles; Wise, Adelyn; Collins, Linda; Love, Sharon; Woodward, Martha; Salisbury, Amanda; Middleton, Mark R

    2016-01-01

    Background: Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. Methods: In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. Results: Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6–5.6) in the vandetanib group and 2.5 months (90% CI: 0.2–4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6–6.3) and 2.5 months (90% CI: 0.2–7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. Conclusions: The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area. PMID:27711083

  8. Universal quantum computing using (Zd) 3 symmetry-protected topologically ordered states

    Science.gov (United States)

    Chen, Yanzhu; Prakash, Abhishodh; Wei, Tzu-Chieh

    2018-02-01

    Measurement-based quantum computation describes a scheme where entanglement of resource states is utilized to simulate arbitrary quantum gates via local measurements. Recent works suggest that symmetry-protected topologically nontrivial, short-ranged entangled states are promising candidates for such a resource. Miller and Miyake [npj Quantum Inf. 2, 16036 (2016), 10.1038/npjqi.2016.36] recently constructed a particular Z2×Z2×Z2 symmetry-protected topological state on the Union Jack lattice and established its quantum-computational universality. However, they suggested that the same construction on the triangular lattice might not lead to a universal resource. Instead of qubits, we generalize the construction to qudits and show that the resulting (d -1 ) qudit nontrivial Zd×Zd×Zd symmetry-protected topological states are universal on the triangular lattice, for d being a prime number greater than 2. The same construction also holds for other 3-colorable lattices, including the Union Jack lattice.

  9. ZD-I intelligent scaler

    International Nuclear Information System (INIS)

    Chen Zhihao

    2001-01-01

    The ZD-I Intelligent Scaler is a new kind of high-powered scaler using high-speed CMOS96 series single chip processor. It not only has the normal timing, counting functions, but also can supply 0-2000 V high voltage, storage or print measuring data, communicate with PC by RS232 interface, transfer measuring data. And there is essentially improvement on the panel. Keyboard without dialing switches and rheostats can perform all the operations, and the setting parameters wouldn't lose when you shut down the scaler. So the ZE-I Intelligent Scaler is a perfect updating production of the NIM-style scaler and the HV-generator

  10. The vascular disrupting agent ZD6126 shows increased antitumor efficacy and enhanced radiation response in large, advanced tumors

    International Nuclear Information System (INIS)

    Siemann, Dietmar W.; Rojiani, Amyn M.

    2005-01-01

    Purpose: ZD6126 is a vascular-targeting agent that induces selective effects on the morphology of proliferating and immature endothelial cells by disrupting the tubulin cytoskeleton. The efficacy of ZD6126 was investigated in large vs. small tumors in a variety of animal models. Methods and Materials: Three rodent tumor models (KHT, SCCVII, RIF-1) and three human tumor xenografts (Caki-1, KSY-1, SKBR3) were used. Mice bearing leg tumors ranging in size from 0.1-2.0 g were injected intraperitoneally with a single 150 mg/kg dose of ZD6126. The response was assessed by morphologic and morphometric means as well as an in vivo to in vitro clonogenic cell survival assay. To examine the impact of tumor size on the extent of enhancement of radiation efficacy by ZD6126, KHT sarcomas of three different sizes were irradiated locally with a range of radiation doses, and cell survival was determined. Results: All rodent tumors and human tumor xenografts evaluated showed a strong correlation between increasing tumor size and treatment effect as determined by clonogenic cell survival. Detailed evaluation of KHT sarcomas treated with ZD6126 showed a reduction in patent tumor blood vessels that was ∼20% in small ( 90% in large (>1.0 g) tumors. Histologic assessment revealed that the extent of tumor necrosis after ZD6126 treatment, although minimal in small KHT sarcomas, became more extensive with increasing tumor size. Clonogenic cell survival after ZD6126 exposure showed a decrease in tumor surviving fraction from approximately 3 x 10 -1 to 1 x 10 -4 with increasing tumor size. When combined with radiotherapy, ZD6126 treatment resulted in little enhancement of the antitumor effect of radiation in small (<0.3 g) tumors but marked increases in cell kill in tumors larger than 1.0 g. Conclusions: Because bulky neoplastic disease is typically the most difficult to manage, the present findings provide further support for the continued development of vascular disrupting agents such as

  11. Vascular Targeting in Pancreatic Cancer: The Novel Tubulin-Binding Agent ZD6126 Reveals Antitumor Activity in Primary and Metastatic Tumor Models

    Directory of Open Access Journals (Sweden)

    Axel Kleespies

    2005-10-01

    Full Text Available ZD6126 is a novel vascular-targeting agent that acts by disrupting the tubulin cytoskeleton of an immature tumor endothelium, leading to an occlusion of tumor blood vessels and a subsequent tumor necrosis. We wanted to evaluate ZD6126 in primary and metastatic tumor models of human pancreatic cancer. Nude mice were injected orthotopically with L3.6pl pancreatic cancer cells. In single and multiple dosing experiments, mice received ZD6126, gemcitabine, a combination of both agents, or no treatment. For the induction of metastatic disease, additional groups of mice were injected with L3.6pl cells into the spleen. Twenty-four hours after a single-dose treatment, ZD6126 therapy led to an extensive central tumor necrosis, which was not seen after gemcitabine treatment. Multiple dosing of ZD6126 resulted in a significant growth inhibition of primary tumors and a marked reduction of spontaneous liver and lymph node metastases. Experimental metastatic disease could be significantly controlled by a combination of ZD6126 and gemcitabine, as shown by a reduction of the number and size of established liver metastases. As shown by additional in vitro and in vivo experiments, possible mechanisms involve antivascular activities and subsequent antiproliferative and proapoptotic effects of ZD6126 on tumor cells, whereas direct activities against tumor cells seem unlikely. These data highlight the antitumor and antimetastatic effects of ZD6126 in human pancreatic cancer and reveal benefits of adding ZD6126 to standard gemcitabine therapy.

  12. Antitumor efficacy of conventional anticancer drugs is enhanced by the vascular targeting agent ZD6126

    International Nuclear Information System (INIS)

    Siemann, Dietmar W.; Rojiani, Amyn M.

    2002-01-01

    Purpose: The present report reviews the preclinical data on combined chemotherapy/vascular targeting agent treatments. Basic principles are illustrated in studies evaluating the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) when combined with the anticancer drug cisplatin in experimental rodent (KHT sarcoma) and human renal (Caki-1) tumor models. Methods and Materials: C3H/HeJ and NCR/nu-nu mice bearing i.m. tumors were injected i.p. with ZD6126 (0-150 mg/kg) or cisplatin (0-20 mg/kg) either alone or in combination. Tumor response to treatment was assessed by clonogenic cell survival. Results: Treatment with ZD6126 was found to damage existing neovasculature, leading to a rapid vascular shutdown. Histologic evaluation showed dose-dependent morphologic damage of tumor cells within a few hours after drug exposure, followed by extensive central tumor necrosis and neoplastic cell death as a result of prolonged ischemia. ZD6126 doses that led to pathophysiologic effects also enhanced the tumor cell killing of cisplatin when administered either 24 h before or 1-24 h after chemotherapy. In both tumor models, the administration of a 150 mg/kg dose of ZD6126 1 h after a range of doses of cisplatin resulted in an increase in tumor cell kill 10-500-fold greater than that seen with chemotherapy alone. In contrast, the inclusion of the antivascular agent did not increase bone marrow stem cell toxicity associated with this anticancer drug. Conclusion: The results obtained in the KHT and Caki-1 tumor models indicate that ZD6126 effectively enhanced the antitumor effects of cisplatin therapy. These findings are representative of the marked enhancements generally observed when vascular targeting agents are combined with chemotherapy in solid tumor therapy

  13. Assessment of vandetanib as an inhibitor of various human renal transporters: inhibition of multidrug and toxin extrusion as a possible mechanism leading to decreased cisplatin and creatinine clearance.

    Science.gov (United States)

    Shen, Hong; Yang, Zheng; Zhao, Weiping; Zhang, Yueping; Rodrigues, A David

    2013-12-01

    Vandetanib was evaluated as an inhibitor of human organic anion transporter 1 (OAT1), OAT3, organic cation transporter 2 (OCT2), and multidrug and toxin extrusion (MATE1 and MATE2K) transfected (individually) into human embryonic kidney 293 cells (HEK293). Although no inhibition of OAT1 and OAT3 was observed, inhibition of OCT2-mediated uptake of 1-methyl-4-phenylpyridinium (MPP(+)) and metformin was evident (IC(50) of 73.4 ± 14.8 and 8.8 ± 1.9 µM, respectively). However, vandetanib was an even more potent inhibitor of MATE1- and MATE2K-mediated uptake of MPP(+) (IC(50) of 1.23 ± 0.05 and 1.26 ± 0.06 µM, respectively) and metformin (IC(50) of 0.16 ± 0.05 and 0.30 ± 0.09 µM, respectively). Subsequent cytotoxicity studies demonstrated that transport inhibition by vandetanib (2.5 µM) significantly decreased the sensitivity [right shift in concentration of cisplatin giving rise to 50% cell death; IC(50(CN))] of MATE1-HEK and MATE2K-HEK cells to cisplatin [IC(50(CN)) of 1.12 ± 0.13 versus 2.39 ± 0.44 µM; 0.85 ± 0.09 versus 1.99 ± 0.16 µM; P cisplatin nephrotoxicity (reduced cisplatin clearance), in some subjects receiving vandetanib therapy.

  14. Model ZD-I paper base weight measuring and controlling system

    International Nuclear Information System (INIS)

    Li Nianzu; Song Debin; Wu Guoliang; Hou Yaoxin; Li Dazhen

    1988-01-01

    Model ZD-I Base Weight Measuring and Controlling System has been developed for the automation process in paper-making industry. A single-board microprocessor is installed in the system. The mass thickness can be controlled within 1 g/m 2 if the changing range of concentration and water content is less than 10%

  15. 34 CFR 647.4 - What activities and services may a project provide?

    Science.gov (United States)

    2010-07-01

    ... PROGRAM General § 647.4 What activities and services may a project provide? A McNair project may provide... activities designed to prepare participants for doctoral study. (d) Tutoring. (e) Academic counseling. (f... programs. (g) Mentoring programs involving faculty members or students at institutions of higher education...

  16. The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy

    Directory of Open Access Journals (Sweden)

    Basetti Madhu

    2006-07-01

    Full Text Available The response of radiation-induced fibrosarcoma1 (RIF-1 tumors treated with the vascular-disrupting agent (VDA ZD6126 was assessed by in vivo and ex vivo1H magnetic resonance spectroscopy (MRS methods. Tumors treated with 200 mg/kg ZD6126 showed a significant reduction in total choline (tCho in vivo 24 hours after treatment, whereas control tumors showed a significant increase in tCho. This response was investigated further within both ex vivo unprocessed tumor tissues and tumor tissue metabolite extracts. Ex vivo high-resolution magic angle spinning (HRMAS and 1H MRS of metabolite extracts revealed a significant reduction in phosphocholine and glycerophosphocholine in biopsies of ZD6126-treated tumors, confirming in vivo tCho response. ZD6126-induced reduction in choline compounds is consistent with a reduction in cell membrane turnover associated with necrosis and cell death following disruption of the tumor vasculature. In vivo tumor tissue water diffusion and lactate measurements showed no significant changes in response to ZD6126. Spin-spin relaxation times (T2 of water and metabolites also remained unchanged. Noninvasive 1H MRS measurement of tCho in vivo provides a potential biomarker of tumor response to VDAs in RIF-1 tumors.

  17. Targeting the EGFR pathway for cancer therapy

    DEFF Research Database (Denmark)

    Johnston, JB; Navaratnam, S; Pitz, MW

    2006-01-01

    .g.: Trastuzumab/Herceptin, Pertuzumab/Omnitarg/rhuMab-2C4, Cetuximab/Erbitux/IMC-C225, Panitumumab/Abenix/ABX-EGF, and also ZD6474). In addition, we summarize, both current therapy development driven by antibody-based targeting of the EGFR-dependent signaling pathways, and furthermore, we provide a background...

  18. Pollen developmental defects in ZD-CMS rice line explored by cytological, molecular and proteomic approaches.

    Science.gov (United States)

    Yan, Junjie; Tian, Han; Wang, Shuzhen; Shao, Jinzhen; Zheng, Yinzhen; Zhang, Hongyuan; Guo, Lin; Ding, Yi

    2014-08-28

    Cytoplasmic male sterility (CMS) is a widely observed phenomenon, which is especially useful in hybrid seed production. Meixiang A (MxA) is a new rice CMS line derived from a pollen-free sterile line named Yunnan ZidaoA (ZD-CMS). In this study, a homologous WA352 gene with variation in two nucleotides was identified in MxA. Cytological analysis revealed that MxA was aborted in the early uninucleate stage. The protein expression profiles of MxA and its maintainer line MeixiangB (MxB) were systematically compared using iTRAQ-based quantitative proteomics technology using young florets at the early uninucleate stage. A total of 688 proteins were quantified in both rice lines, and 45 of these proteins were found to be differentially expressed. Bioinformatics analysis indicated a large number of the proteins involved in carbohydrate metabolism or the stress response were downregulated in MxA, suggesting that these metabolic processes had been hindered during pollen development in MxA. The ROS (reactive oxygen species) level was increased in the mitochondrion of MxA, and further ultrastructural analysis showed the mitochondria with disrupted cristae in the rice CMS line MxA. These findings substantially contribute to our knowledge of pollen developmental defects in ZD-CMS rice line. MeixiangA (MxA) is a new type of rice CMS line, which is derived from pollen-free sterile line Yunnan ZidaoA. In this study, the cytological, molecular and proteomic approaches were used to study the characteristics of this new CMS line. Cytological study indicates the CMS line is aborted at the early uninucleate stage. A potential sterile gene ZD352 is identified in MxA, the protein product of which is mainly accumulated at the MMC/Meiotic stage. iTRAQ based proteomic analysis is performed to study the relevant proteins involved in the CMS occurance, 45 proteins are found to be significant differentially expressed and these proteins are involved in many cellular processes such as

  19. The ideal harvest time for seeds of hybrid maize (Zea mays L.) XY335 and ZD958 produced in multiple environments.

    Science.gov (United States)

    Gu, Riliang; Li, Li; Liang, Xiaolin; Wang, Yanbo; Fan, Tinglu; Wang, Ying; Wang, Jianhua

    2017-12-13

    To identify the ideal harvest time (IHT) for the seed production of XY335 and ZD958, six seed-related traits were evaluated in seeds harvested at 11 harvest stages in 8 environments. Standard germination (SG), accelerated aging germination (AAG) and cold test germination (CTG) were vigor traits; hundred-seed weight (HSW) and seed moisture content (SMC) were physiological traits; and ≥10 °C accumulated temperature from pollination to harvest (AT10 ph ) was an ecological trait. All the traits were significantly affected by harvest stage. The responses of SG, AAG, CTG and HSW to postponing harvest stage fit quadratic models, while SMC and AT10 ph fit linear models. The IHT (indicated by the last date to reach maximum SG, AAG and CTG) were 57.97 DAP and 56.80 DAP for XY335 and ZD958, respectively. SMC and AT10 ph at IHT were 33.15% and 1234 °C for XY335, and 34.98% and 1226 °C for ZD958, respectively. The period to reach the maximum HSW was 5 days later than the IHT. Compared to HSW and SMC, AT10 ph had a closer relationship to the seed vigor traits. Together with the fact that AT10 ph was less affected by environment, these results suggested that AT10 ph may be a novel indicator for determining the IHT.

  20. Enhanced vesicular stomatitis virus (VSVΔ51 targeting of head and neck cancer in combination with radiation therapy or ZD6126 vascular disrupting agent

    Directory of Open Access Journals (Sweden)

    Alajez Nehad M

    2012-06-01

    Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC is the 5th most common cancer worldwide. Locally advanced HNSCC are treated with either radiation or chemo-radiotherapy, but still associated with high mortality rate, underscoring the need to develop novel therapies. Oncolytic viruses have been garnering increasing interest as anti-cancer agents due to their preferential killing of transformed cells. In this study, we evaluated the therapeutic potential of mutant vesicular stomatitis virus (VSVΔ51 against the human hypopharyngeal FaDu tumour model in vitro and in vivo. Results Our data demonstrated high toxicity of the virus against FaDu cells in vitro, which was associated with induction of apoptosis. In vivo, systemic injection of 1 × 109 pfu had minimal effect on tumour growth; however, when combined with two doses of ionizing radiation (IR; 5 Gy each or a single injection of the vascular disrupting agent (ZD6126, the virus exhibited profound suppression of tumour growth, which translated to a prolonged survival in the treated mice. Concordantly, VSVΔ51 combined with ZD6126 led to a significant increase in viral replication in these tumours. Conclusions Our data suggest that the combinations of VSVΔ51 with either IR or ZD6126 are potentially novel therapeutic opportunities for HNSCC.

  1. Are the brightest Lyman Alpha Emitters at zD5.7 primeval galaxies?

    Science.gov (United States)

    Lidman, Christopher; Hayes, Matthew; Jones, Heath; Meisenheimer, Klaus; Tapken, Christian; Westra, Eduard

    2009-04-01

    Wide-field, narrow-band surveys have proven to be effective at finding very high redshift galaxies that emit brightly in the Lyman alpha line - the so-called Lyman alpha emitters (LAEs). It was through this technique that the most distant spectroscopically confirmed galaxy, a galaxy at zD6.96 (Iye et al. 2006), was discovered. Considerable effort is currently being spent on discovering these galaxies at ever higher redshifts by extending this technique into the near-IR. In contrast to this effort, there has been relatively little work on understanding these galaxies. In particular, how do LAEs relate to other high redshift galaxies, such as those discovered through drop out techniques, and, more importantly, what role LAEs play in re-ionising the universe, if any. We recently discovered two extremely luminous LAEs at zD5.7. These LAEs are among the brightest LAEs ever discovered at this redshift. In a recent paper by Mao et al. (2007), the brightest LAEs are associated to the most massive halos. One of these targets was successfully observed with the IRAC 3.6 micron imager on Spitzer during cycle 5. These data, when combined with constraints that we derive from our deep ground-based spectroscopic data, indicate that the bulk of the flux at 3.6 microns comes from a stellar population that is considserably older than the stars that dominate the flux in the UV. We propose to complete the project and image the second target. These data will enable us to estimate the age and mass of the stellar burst that produces the Lyman alpha line, to estimate the contribution from an older stellar population and to estimate the fraction of Lyman continuum photons that escape the galaxy and are thus available to re-ionise the universe.

  2. Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance.

    Science.gov (United States)

    Hegedüs, Csilla; Truta-Feles, Krisztina; Antalffy, Géza; Várady, György; Német, Katalin; Ozvegy-Laczka, Csilla; Kéri, György; Orfi, László; Szakács, Gergely; Settleman, Jeffrey; Váradi, András; Sarkadi, Balázs

    2012-08-01

    Human ABCG2 is a plasma membrane glycoprotein that provides physiological protection against xenobiotics. ABCG2 also significantly influences biodistribution of drugs through pharmacological tissue barriers and confers multidrug resistance to cancer cells. Moreover, ABCG2 is the molecular determinant of the side population that is characteristically enriched in normal and cancer stem cells. Numerous tumors depend on unregulated EGFR signaling, thus inhibition of this receptor by small molecular weight inhibitors such as gefitinib, and the novel second generation agents vandetanib, pelitinib and neratinib, is a promising therapeutic option. In the present study, we provide detailed biochemical characterization regarding the interaction of these EGFR inhibitors with ABCG2. We show that ABCG2 confers resistance to gefitinib and pelitinib, whereas the intracellular action of vandetanib and neratinib is unaltered by the presence of the transporter. At higher concentrations, however, all these EGFR inhibitors inhibit ABCG2 function, thereby promoting accumulation of ABCG2 substrate drugs. We also report enhanced expression of ABCG2 in gefitinib-resistant non-small cell lung cancer cells, suggesting potential clinical relevance of ABCG2 in acquired drug resistance. Since ABCG2 has important impact on both the pharmacological properties and anti-cancer efficiencies of drugs, our results regarding the novel EGFR inhibitors should provide useful information about their therapeutic applicability against ABCG2-expressing cancer cells depending on EGFR signaling. In addition, the finding that these EGFR inhibitors efficiently block ABCG2 function may help to design novel drug-combination therapeutic strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. The ideal harvest time for seeds of hybrid maize (Zea mays L.) XY335 and ZD958 produced in multiple environments

    OpenAIRE

    Gu, Riliang; Li, Li; Liang, Xiaolin; Wang, Yanbo; Fan, Tinglu; Wang, Ying; Wang, Jianhua

    2017-01-01

    To identify the ideal harvest time (IHT) for the seed production of XY335 and ZD958, six seed-related traits were evaluated in seeds harvested at 11 harvest stages in 8 environments. Standard germination (SG), accelerated aging germination (AAG) and cold test germination (CTG) were vigor traits; hundred-seed weight (HSW) and seed moisture content (SMC) were physiological traits; and ≥10 °C accumulated temperature from pollination to harvest (AT10ph) was an ecological trait. All the traits wer...

  4. A Study on Some Chemical Constituents of Ganoderma Lucidum Leyss. Ex. Fr. p. Karst (vifZD; rId) from Pyin-Oo-Lwin Area

    International Nuclear Information System (INIS)

    Khine Kyi Oo; Aye Aye Tun

    2005-10-01

    A study on some chemical constituents G. Lucidum (vifZD ;) which grows throughout Myanmar has been undertaken. Two compounds, Ergosterol and its ester from mushroom body have been isolated by solvent extraction followed by column chomatography. Isolated compounds were identified by spectroscopic techniques. Lingzhi is traditionally utilized for lowering bllod cholestrol, regulate blood pressure, prevent heart disease, and regulated blood suger in diabetic patients and increase body immunity

  5. Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Pitoia Fabian; Bueno, Fernanda; Schmidt, Angelica; Lucas, Sabrina; Cross, Graciela, E-mail: fpitoia@intramed.net [Division de Endocrinologia, Hospital de Clinicas, Universidad de Buenos Aires Buenos Aires (Argentina)

    2015-08-15

    Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of followup developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up. (author)

  6. Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome

    International Nuclear Information System (INIS)

    Pitoia Fabian; Bueno, Fernanda; Schmidt, Angelica; Lucas, Sabrina; Cross, Graciela

    2015-01-01

    Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of followup developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up. (author)

  7. Vandetanib

    Science.gov (United States)

    ... your doctor and pharmacist if you are taking chloroquine (Aralen); clarithromycin (Biaxin, in Prevpac); haloperidol (Haldol); medications ... of plain, non-carbonated drinking water. Do not use any other liquid to dissolve the tablet. Stir ...

  8. A three-dimensional model of the atmospheric chemistry of E and Z-CF3CH=CHCl (HCFO-1233(zd) (E/Z))

    Science.gov (United States)

    Sulbaek Andersen, Mads P.; Schmidt, Johan A.; Volkova, Aleksandra; Wuebbles, Donald J.

    2018-04-01

    Using a 3-dimensional global atmospheric chemistry and transport model we investigated the atmospheric degradation of HCFO-1233zd(E), E-CF3CH=CHCl, a commercially important, new hydrofluorocarbon replacement compound. Atmospheric degradation of E-CF3CH=CHCl is initiated by reaction with OH radicals, which leads to several chemical oxidation products. Dissemination of these oxidation products to the environment is of concern due to the possible formation of trifluoroacetic acid (TFA) as a degradation product. The model indicates that the average global yield of TFA from atmospheric processing of E-CF3CH=CHCl is approximately 2%. The annually averaged atmospheric lifetime of E-CF3CH=CHCl was found to be approximately 36 days (12 days for Z-CF3CH=CHCl). As E-CF3CH=CHCl is short lived, by far the majority of its Cl atoms will be released and deposited in the lower atmosphere, and the impact on stratospheric ozone is insignificant. An Ozone Depletion Potential of 0.00030 was determined. The Photochemical Ozone Creation Potential was evaluated and a value of 3.6 determined. Finally, we derive a Global Warming Potential for E-CF3CH=CHCl for a 100 year time horizon of model.

  9. Management of treatment-related toxicities in advanced medullary thyroid cancer.

    Science.gov (United States)

    Brose, Marcia S; Bible, Keith C; Chow, Laura Q M; Gilbert, Jill; Grande, Carolyn; Worden, Francis; Haddad, Robert

    2018-04-22

    Progress in the treatment of advanced medullary thyroid cancer (MTC) has resulted from the approval of 2 drugs within the past 5 years, vandetanib and cabozantinib. These multikinase inhibitors (MKIs) possess overlapping specificities for multiple kinase targets implicated in the progression of MTC. Both drugs are associated with toxicities, including hypertension, hemorrhage/perforation, diarrhea and other gastrointestinal events, several dermatologic events, and hypothyroidism. In addition, vandetanib is uniquely associated with QTc prolongation through interaction with myocardial potassium channels, and cabozantinib is uniquely associated with hand-foot skin reaction. Treatment-related toxicities occur frequently and can be severe or life-threatening, and patients undergoing long-term treatment will likely experience adverse events (AEs). Here we offer specific practical recommendations for managing AEs commonly occurring with vandetanib and cabozantinib. The recommended approach relies on early recognition and palliation of symptoms, dose interruption, and dose reduction as necessary in order for the patient to maintain the highest tolerable dose for as long as possible and optimal quality of life. Treatment guidelines do not specify a recommended sequence for treating with vandetanib and cabozantinib; however, most patients will receive both drugs during their lifetime. The choice for first-line therapy is individualized after a risk-benefit assessment and depends on physician preference and patient-related factors, such as comorbid conditions. Because most generalist practices may not be familiar with the intricacies of agents such as vandetanib and cabozantinib, we commend that patients with advanced MTC be managed and treated by a thyroid cancer specialist with coordination of care within a multidisciplinary team. Copyright © 2018. Published by Elsevier Ltd.

  10. Mitochondria-Targeted Nitroxide, Mito-CP, Suppresses Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo

    Science.gov (United States)

    Starenki, Dmytro

    2013-01-01

    Context: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the RET proto-oncogene. For MTC therapy, the U.S. Food and Drug Administration recently approved vandetanib and cabozantinib, multikinase inhibitors targeting RET and other tyrosine kinase receptors of vascular endothelial growth factor, epidermal growth factor, or hepatocyte growth factor. Nevertheless, not all patients with the progressive MTC respond to these drugs, requiring the development of additional therapeutic modalities that have distinct activity. Objective: We aimed to evaluate mitochondria-targeted carboxy-proxyl (Mito-CP), a mitochondria-targeted redox-sensitive agent, for its tumor-suppressive efficacy against MTC. Design: In vitro cultures of 2 human MTC cell lines, TT and MZ-CRC-1, and TT xenografts in mice were treated with Mito-CP in comparison with vandetanib. The effects on cell survival/death, RET expression, mitochondrial integrity, and oxidative stress were determined. Results: Contrary to vandetanib, Mito-CP induced RET downregulation and strong cytotoxic effects in both cell lines in vitro, including caspase-dependent apoptosis. These effects were accompanied by mitochondrial membrane depolarization, decreased oxygen consumption, and increased oxidative stress in cells. Intriguingly, Mito-CP–induced cell death, but not RET downregulation, was partially inhibited by the reactive oxygen species scavenger, N-acetyl-cysteine, indicating that Mito-CP mediates tumor-suppressive effects via redox-dependent as well as redox-independent mechanisms. Orally administered Mito-CP effectively suppressed TT xenografts in mice, with an efficacy comparable to vandetanib and relatively low toxicity to animals. Conclusion: Our results suggest that Mito-CP can effectively suppress MTC cell growth/survival via a mechanism distinct from vandetanib effects. Mitochondrial targeting may be a potential strategy for MTC therapy. PMID:23509102

  11. Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models

    International Nuclear Information System (INIS)

    Marino, Ana-Maria; Sofiadis, Anastasios; Baryawno, Ninib; Johnsen, John Inge; Larsson, Catharina; Vukojevic, Vladana; Ekstroem, Tomas J.

    2011-01-01

    Highlights: → The histone deacetylase inhibitor 4-phenylbutyrate substantially enhance efficacy of the receptor tyrosine kinase inhibitors gefitinib or vandetanib in glioma and medulloblastoma cell lines. → Cell death increases and clonogenic survival is reduced in the combination treatments, over mono-therapy. → Combination treatments with these drugs may improve clinical outcome for cancer therapy. -- Abstract: We have investigated in vitro effects of anticancer therapy with the histone deacetylase inhibitor (HDACi) 4-phenylbutyrate (4-PB) combined with receptor tyrosine kinase inhibitors (RTKi) gefitinib or vandetanib on the survival of glioblastoma (U343MGa) and medulloblastoma (D324Med) cells. In comparison with individual effects of these drugs, combined treatment with gefitinib/4-PB or vandetanib/4-PB resulted in enhanced cell killing and reduced clonogenic survival in both cell lines. Our results suggest that combined treatment using HDACi and RTKi may beneficially affect the outcome of cancer therapy.

  12. Influence of zinc on growth, somatomedin, and glycosaminoglycan metabolism in rats

    International Nuclear Information System (INIS)

    Bolze, M.S.; Reeves, R.D.; Lindbeck, F.E.; Elders, M.J.

    1987-01-01

    Weanling male rats were fed control ad libitum, zinc-deficient (ZD, 1 ppm zinc) or pair-fed (PF) control diets for 13 days. Rats subsequently were refed control diets for up to 8 days and serially killed. ZD and PF diets significantly decreased growth rate, feed intake, and feed efficiency compared to controls. Body weight and feed efficiency, but not feed intake, were significantly less in ZD compared to PF. Bone zinc was 315, 286, and 109 μg/g for control, PF, and ZD at the end of depletion. 35 SO 4 uptake by glycosaminoglycans (GAG) was significantly less in ZD compared to either control ad libitum or PF rats. Xylosyltransferase activity was decreased significantly below PF and control by ZD, suggesting depressed enzyme activity and/or decreased GAG acceptor sites. Bioassayable somatomedin (Sm) activity was 0.81, 0.42 and 0.33 +/- 0.09 relative activity for control, PF and ZD at the end of depletion. Sm was statistically less in ZD compared to PF at day 2 and 5 of refeeding, but not at the end of depletion. Sm activity and GAG metabolism returned to normal after refeeding for 2-5 days in PF and for 5-8 days in ZD rats. Serum insulin but not glucose was significantly depressed by ZD and PF diets. Thus, zinc deficiency depressed growth and cartilage metabolism and was associated with decreased Sm activity and insulin levels. Some of these changes could be attributed to decreased feed intake as a result of ZD

  13. Search for new light gauge bosons in Higgs boson decays to four-lepton final states in $pp$ collisions at $\\sqrt{s}=8$TeV with the ATLAS detector at the LHC

    CERN Document Server

    Aad, Georges; Abdallah, Jalal; Abdinov, Ovsat; Aben, Rosemarie; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Affolder, Tony; Agatonovic-Jovin, Tatjana; Aguilar-Saavedra, Juan Antonio; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akerstedt, Henrik; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albrand, Solveig; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexopoulos, Theodoros; Alhroob, Muhammad; Alimonti, Gianluca; Alio, Lion; Alison, John; Alkire, Steven Patrick; Allbrooke, Benedict; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Altheimer, Andrew David; Alvarez Gonzalez, Barbara; Άlvarez Piqueras, Damián; Alviggi, Mariagrazia; Amadio, Brian Thomas; Amako, Katsuya; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amram, Nir; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anders, John Kenneth; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Angelidakis, Stylianos; Angelozzi, Ivan; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Arce, Ayana; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; Auerbach, Benjamin; Augsten, Kamil; Aurousseau, Mathieu; Avolio, Giuseppe; Axen, Bradley; Ayoub, Mohamad Kassem; Azuelos, Georges; Baak, Max; Baas, Alessandra; Bacci, Cesare; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Bagiacchi, Paolo; Bagnaia, Paolo; Bai, Yu; Bain, Travis; Baines, John; Baker, Oliver Keith; Balek, Petr; Balestri, Thomas; Balli, Fabrice; Banas, Elzbieta; Banerjee, Swagato; Bannoura, Arwa A E; Bansil, Hardeep Singh; Barak, Liron; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barisonzi, Marcello; Barklow, Timothy; Barlow, Nick; Barnes, Sarah Louise; Barnett, Bruce; Barnett, Michael; Barnovska, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Basalaev, Artem; Bassalat, Ahmed; Basye, Austin; Bates, Richard; Batista, Santiago Juan; Batley, Richard; Battaglia, Marco; Bauce, Matteo; Bauer, Florian; Bawa, Harinder Singh; Beacham, James Baker; Beattie, Michael David; Beau, Tristan; Beauchemin, Pierre-Hugues; Beccherle, Roberto; Bechtle, Philip; Beck, Hans Peter; Becker, Anne Kathrin; Becker, Maurice; Becker, Sebastian; Beckingham, Matthew; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bednyakov, Vadim; Bee, Christopher; Beemster, Lars; Beermann, Thomas; Begel, Michael; Behr, Janna Katharina; Belanger-Champagne, Camille; Bell, William; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belotskiy, Konstantin; Beltramello, Olga; Benary, Odette; Benchekroun, Driss; Bender, Michael; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez Garcia, Jorge-Armando; Benjamin, Douglas; Bensinger, James; Bentvelsen, Stan; Beresford, Lydia; Beretta, Matteo; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Berghaus, Frank; Beringer, Jürg; Bernard, Clare; Bernard, Nathan Rogers; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertoli, Gabriele; Bertolucci, Federico; Bertsche, Carolyn; Bertsche, David; Besana, Maria Ilaria; Besjes, Geert-Jan; Bessidskaia Bylund, Olga; Bessner, Martin Florian; Besson, Nathalie; Betancourt, Christopher; Bethke, Siegfried; Bevan, Adrian John; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianchini, Louis; Bianco, Michele; Biebel, Otmar; Bieniek, Stephen Paul; Biglietti, Michela; Bilbao De Mendizabal, Javier; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Black, Curtis; Black, James; Black, Kevin; Blackburn, Daniel; Blair, Robert; Blanchard, Jean-Baptiste; Blanco, Jacobo Ezequiel; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blum, Walter; Blumenschein, Ulrike; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Bock, Christopher; Boehler, Michael; Bogaerts, Joannes Andreas; Bogdanchikov, Alexander; Bohm, Christian; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Boldyrev, Alexey; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Borroni, Sara; Bortfeldt, Jonathan; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boudreau, Joseph; Bouffard, Julian; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozic, Ivan; Bracinik, Juraj; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brazzale, Simone Federico; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Lydia; Brenner, Richard; Bressler, Shikma; Bristow, Kieran; Bristow, Timothy Michael; Britton, Dave; Britzger, Daniel; Brochu, Frederic; Brock, Ian; Brock, Raymond; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Brown, Jonathan; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Buchholz, Peter; Buckley, Andrew; Buda, Stelian Ioan; Budagov, Ioulian; Buehrer, Felix; Bugge, Lars; Bugge, Magnar Kopangen; Bulekov, Oleg; Bullock, Daniel; Burckhart, Helfried; Burdin, Sergey; Burghgrave, Blake; Burke, Stephen; Burmeister, Ingo; Busato, Emmanuel; Büscher, Daniel; Büscher, Volker; Bussey, Peter; Butler, John; Butt, Aatif Imtiaz; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Buzykaev, Aleksey; Cabrera Urbán, Susana; Caforio, Davide; Cairo, Valentina; Cakir, Orhan; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Caloba, Luiz; Calvet, David; Calvet, Samuel; Camacho Toro, Reina; Camarda, Stefano; Camarri, Paolo; Cameron, David; Caminada, Lea Michaela; Caminal Armadans, Roger; Campana, Simone; Campanelli, Mario; Campoverde, Angel; Canale, Vincenzo; Canepa, Anadi; Cano Bret, Marc; Cantero, Josu; Cantrill, Robert; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Caputo, Regina; Cardarelli, Roberto; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Sascha; Carquin, Edson; Carrillo-Montoya, German D; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Casolino, Mirkoantonio; Castaneda-Miranda, Elizabeth; Castelli, Angelantonio; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catastini, Pierluigi; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Caudron, Julien; Cavaliere, Viviana; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Cerio, Benjamin; Cerny, Karel; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cerv, Matevz; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chalupkova, Ina; Chang, Philip; Chapleau, Bertrand; Chapman, John Derek; Charlton, Dave; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Karen; Chen, Liming; Chen, Shenjian; Chen, Xin; Chen, Ye; Cheng, Hok Chuen; Cheng, Yangyang; Cheplakov, Alexander; Cheremushkina, Evgenia; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Chevalier, Laurent; Chiarella, Vitaliano; Childers, John Taylor; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chitan, Adrian; Chizhov, Mihail; Choi, Kyungeon; Chouridou, Sofia; Chow, Bonnie Kar Bo; Christodoulou, Valentinos; Chromek-Burckhart, Doris; Chu, Ming-Lee; Chudoba, Jiri; Chuinard, Annabelle Julia; Chwastowski, Janusz; Chytka, Ladislav; Ciapetti, Guido; Ciftci, Abbas Kenan; Cinca, Diane; Cindro, Vladimir; Cioara, Irina Antonela; Ciocio, Alessandra; Citron, Zvi Hirsh; Ciubancan, Mihai; Clark, Allan G; Clark, Brian Lee; Clark, Philip James; Clarke, Robert; Cleland, Bill; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coffey, Laurel; Cogan, Joshua Godfrey; Cole, Brian; Cole, Stephen; Colijn, Auke-Pieter; Collot, Johann; Colombo, Tommaso; Compostella, Gabriele; Conde Muiño, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Consonni, Sofia Maria; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Corso-Radu, Alina; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Côté, David; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Crispin Ortuzar, Mireia; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; D'Auria, Saverio; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Dandoy, Jeffrey Rogers; Dang, Nguyen Phuong; Daniells, Andrew Christopher; Danninger, Matthias; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Davey, Will; David, Claire; Davidek, Tomas; Davies, Eleanor; Davies, Merlin; Davison, Peter; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dedovich, Dmitri; Deigaard, Ingrid; Del Peso, Jose; Del Prete, Tarcisio; Delgove, David; Deliot, Frederic; Delitzsch, Chris Malena; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Domenico, Antonio; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaconu, Cristinel; Diamond, Miriam; Dias, Flavia; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Diglio, Sara; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; Barros do Vale, Maria Aline; Dobos, Daniel; Dobre, Monica; Doglioni, Caterina; Dohmae, Takeshi; Dolejsi, Jiri; Dolezal, Zdenek; Dolgoshein, Boris; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Drechsler, Eric; Dris, Manolis; Dubreuil, Emmanuelle; Duchovni, Ehud; Duckeck, Guenter; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Duflot, Laurent; Duguid, Liam; Dührssen, Michael; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dyndal, Mateusz; Eckardt, Christoph; Ecker, Katharina Maria; Edgar, Ryan Christopher; Edson, William; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Endo, Masaki; Erdmann, Johannes; Ereditato, Antonio; Ernis, Gunar; Ernst, Jesse; Ernst, Michael; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Esposito, Bellisario; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Fabbri, Laura; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Faucci Giannelli, Michele; Favareto, Andrea; Fayard, Louis; Federic, Pavol; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Fernandez Martinez, Patricia; Fernandez Perez, Sonia; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Adam; Fischer, Cora; Fischer, Julia; Fisher, Wade Cameron; Fitzgerald, Eric Andrew; Flechl, Martin; Fleck, Ivor; Fleischmann, Philipp; Fleischmann, Sebastian; Fletcher, Gareth Thomas; Fletcher, Gregory; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Formica, Andrea; Forti, Alessandra; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Francis, David; Franconi, Laura; Franklin, Melissa; Fraternali, Marco; Freeborn, David; French, Sky; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Gao, Jun; Gao, Yanyan; Gao, Yongsheng; Garay Walls, Francisca; Garberson, Ford; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gatti, Claudio; Gaudiello, Andrea; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Geisler, Manuel Patrice; Gemme, Claudia; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghazlane, Hamid; Giacobbe, Benedetto; Giagu, Stefano; Giangiobbe, Vincent; Giannetti, Paola; Gibbard, Bruce; Gibson, Stephen; Gilchriese, Murdock; Gillam, Thomas; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giorgi, Filippo Maria; Giorgi, Francesco Michelangelo; Giraud, Pierre-Francois; Giromini, Paolo; Giugni, Danilo; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Goblirsch-Kolb, Maximilian; Goddard, Jack Robert; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Goujdami, Driss; Goussiou, Anna; Govender, Nicolin; Grabas, Herve Marie Xavier; Graber, Lars; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Gray, Heather; Graziani, Enrico; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grivaz, Jean-Francois; Grohs, Johannes Philipp; Grohsjean, Alexander; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Guan, Liang; Guenther, Jaroslav; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Gupta, Shaun; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Haefner, Petra; Hageböck, Stephan; Hajduk, Zbigniew; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Hall, David; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamer, Matthias; Hamilton, Andrew; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Hanke, Paul; Hanna, Remie; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Maike Christina; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harrington, Robert; Harrison, Paul Fraser; Hartjes, Fred; Hasegawa, Makoto; Hasegawa, Satoshi; Hasegawa, Yoji; Hasib, A; Hassani, Samira; Haug, Sigve; Hauser, Reiner; Hauswald, Lorenz; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Lukas; Hejbal, Jiri; Helary, Louis; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, James; Henderson, Robert; Heng, Yang; Hengler, Christopher; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Hernández Jiménez, Yesenia; Herrberg-Schubert, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hetherly, Jeffrey Wayne; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hinman, Rachel Reisner; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hohlfeld, Marc; Hohn, David; Holmes, Tova Ray; Homann, Michael; Hong, Tae Min; Hooft van Huysduynen, Loek; Hopkins, Walter; Horii, Yasuyuki; Horton, Arthur James; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Catherine; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Qipeng; Hu, Xueye; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hülsing, Tobias Alexander; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Ideal, Emma; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikematsu, Katsumasa; Ikeno, Masahiro; Ilchenko, Iurii; Iliadis, Dimitrios; Ilic, Nikolina; Inamaru, Yuki; Ince, Tayfun; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Ivarsson, Jenny; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jabbar, Samina; Jackson, Brett; Jackson, Matthew; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Jansky, Roland; Janssen, Jens; Janus, Michel; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Jeanty, Laura; Jejelava, Juansher; Jeng, Geng-yuan; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Yi; Jiggins, Stephen; Jimenez Pena, Javier; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Joergensen, Morten Dam; Johansson, Per; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Ju, Xiangyang; Jung, Christian; Jussel, Patrick; Juste Rozas, Aurelio; Kaci, Mohammed; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kahn, Sebastien Jonathan; Kajomovitz, Enrique; Kalderon, Charles William; Kama, Sami; Kamenshchikov, Andrey; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karamaoun, Andrew; Karastathis, Nikolaos; Kareem, Mohammad Jawad; Karnevskiy, Mikhail; Karpov, Sergey; Karpova, Zoya; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Katre, Akshay; Katzy, Judith; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keller, John; Kempster, Jacob Julian; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Keyes, Robert; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharlamov, Alexey; Khoo, Teng Jian; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hee Yeun; Kim, Hyeon Jin; Kim, Shinhong; Kim, Young-Kee; Kimura, Naoki; Kind, Oliver Maria; King, Barry; King, Matthew; King, Robert Steven Beaufoy; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kiss, Florian; Kiuchi, Kenji; Kivernyk, Oleh; Kladiva, Eduard; Klein, Matthew Henry; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klioutchnikova, Tatiana; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Aine; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolanoski, Hermann; Koletsou, Iro; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; König, Sebastian; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Kortner, Oliver; Kortner, Sandra; Kosek, Tomas; Kostyukhin, Vadim; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitriy; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kreiss, Sven; Kretz, Moritz; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Krizka, Karol; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Krumnack, Nils; Krumshteyn, Zinovii; Kruse, Amanda; Kruse, Mark; Kruskal, Michael; Kubota, Takashi; Kucuk, Hilal; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuger, Fabian; Kuhl, Andrew; Kuhl, Thorsten; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kurashige, Hisaya; Kurochkin, Yurii; Kurumida, Rie; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwan, Tony; Kyriazopoulos, Dimitrios; La Rosa, Alessandro; La Rosa Navarro, Jose Luis; La Rotonda, Laura; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Lambourne, Luke; Lammers, Sabine; Lampen, Caleb; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lange, J örn Christian; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Menedeu, Eve; LeBlanc, Matthew Edgar; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Claire Alexandra; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehan, Allan; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leight, William Axel; Leisos, Antonios; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Leontsinis, Stefanos; Leroy, Claude; Lester, Christopher; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Adrian; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Haifeng; Li, Ho Ling; Li, Lei; Li, Liang; Li, Shu; Li, Yichen; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Liblong, Aaron; Lichard, Peter; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Lin, Simon; Lin, Tai-Hua; Linde, Frank; Lindquist, Brian Edward; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Dong; Liu, Jian; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loginov, Andrey; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Long, Brian Alexander; Long, Jonathan; Long, Robin Eamonn; Looper, Kristina Anne; Lopes, Lourenco; Lopez Mateos, David; Lopez Paredes, Brais; Lopez Paz, Ivan; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lösel, Philipp Jonathan; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lu, Nan; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Lynn, David; Lysak, Roman; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Macdonald, Calum Michael; Machado Miguens, Joana; Macina, Daniela; Madaffari, Daniele; Madar, Romain; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeland, Steffen; Maeno, Tadashi; Maevskiy, Artem; Magradze, Erekle; Mahboubi, Kambiz; Mahlstedt, Joern; Maiani, Camilla; Maidantchik, Carmen; Maier, Andreas Alexander; Maier, Thomas; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mamuzic, Judita; Mancini, Giada; Mandelli, Beatrice; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Manfredini, Alessandro; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mantifel, Rodger; Mantoani, Matteo; Mapelli, Livio; March, Luis; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marjanovic, Marija; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian Thomas; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Mario; Martin-Haugh, Stewart; Martoiu, Victor Sorin; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massa, Lorenzo; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Mattmann, Johannes; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazza, Simone Michele; Mazzaferro, Luca; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McPherson, Robert; Medinnis, Michael; Meehan, Samuel; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mergelmeyer, Sebastian; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Middleton, Robin; Miglioranzi, Silvia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milesi, Marco; Milic, Adriana; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mochizuki, Kazuya; Mohapatra, Soumya; Mohr, Wolfgang; Molander, Simon; Moles-Valls, Regina; Mönig, Klaus; Monini, Caterina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Morinaga, Masahiro; Morisbak, Vanja; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Mortensen, Simon Stark; Morton, Alexander; Morvaj, Ljiljana; Mosidze, Maia; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Muanza, Steve; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Klemens; Mueller, Ralph Soeren Peter; Mueller, Thibaut; Muenstermann, Daniel; Mullen, Paul; Munwes, Yonathan; Murillo Quijada, Javier Alberto; Murray, Bill; Musheghyan, Haykuhi; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nackenhorst, Olaf; Nadal, Jordi; Nagai, Koichi; Nagai, Ryo; Nagai, Yoshikazu; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nagy, Elemer; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Nef, Pascal Daniel; Negri, Andrea; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen, Duong Hai; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolopoulos, Konstantinos; Nilsen, Jon Kerr; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nomachi, Masaharu; Nomidis, Ioannis; Nooney, Tamsin; Norberg, Scarlet; Nordberg, Markus; Novgorodova, Olga; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; Nuti, Francesco; O'Brien, Brendan Joseph; O'grady, Fionnbarr; O'Neil, Dugan; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Ochoa-Ricoux, Juan Pedro; Oda, Susumu; Odaka, Shigeru; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okamura, Wataru; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Owen, Rhys Edward; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagáčová, Martina; Pagan Griso, Simone; Paganis, Efstathios; Pahl, Christoph; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Palma, Alberto; Pan, Yibin; Panagiotopoulou, Evgenia; Pandini, Carlo Enrico; Panduro Vazquez, William; Pani, Priscilla; Panitkin, Sergey; Pantea, Dan; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Michael Andrew; Parker, Kerry Ann; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Fernanda; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Pauly, Thilo; Pearce, James; Pearson, Benjamin; Pedersen, Lars Egholm; Pedersen, Maiken; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Pelikan, Daniel; Peng, Haiping; Penning, Bjoern; Penwell, John; Perepelitsa, Dennis; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petrolo, Emilio; Petrucci, Fabrizio; Pettersson, Nora Emilia; Pezoa, Raquel; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Pickering, Mark Andrew; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pina, João Antonio; Pinamonti, Michele; Pinfold, James; Pingel, Almut; Pinto, Belmiro; Pires, Sylvestre; Pitt, Michael; Pizio, Caterina; Plazak, Lukas; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Plucinski, Pawel; Pluth, Daniel; Poettgen, Ruth; Poggioli, Luc; Pohl, David-leon; Polesello, Giacomo; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Prell, Soeren; Price, Darren; Price, Lawrence; Primavera, Margherita; Prince, Sebastien; Proissl, Manuel; Prokofiev, Kirill; Prokoshin, Fedor; Protopapadaki, Eftychia-sofia; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Ptacek, Elizabeth; Puddu, Daniele; Pueschel, Elisa; Puldon, David; Purohit, Milind; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Quarrie, David; Quayle, William; Queitsch-Maitland, Michaela; Quilty, Donnchadha; Raddum, Silje; Radeka, Veljko; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Rajagopalan, Srinivasan; Rammensee, Michael; Rangel-Smith, Camila; Rauscher, Felix; Rave, Stefan; Ravenscroft, Thomas; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Rehnisch, Laura; Reisin, Hernan; Relich, Matthew; Rembser, Christoph; Ren, Huan; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter, Stefan; Richter-Was, Elzbieta; Ricken, Oliver; Ridel, Melissa; Rieck, Patrick; Riegel, Christian Johann; Rieger, Julia; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Ristić, Branislav; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Roda, Chiara; Roe, Shaun; Røhne, Ole; Rolli, Simona; Romaniouk, Anatoli; Romano, Marino; Romano Saez, Silvestre Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Peyton; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Rachel; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rubinskiy, Igor; Rud, Viacheslav; Rudolph, Christian; Rudolph, Matthew Scott; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Ruschke, Alexander; Russell, Heather; Rutherfoord, John; Ruthmann, Nils; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Saavedra, Aldo; Sabato, Gabriele; Sacerdoti, Sabrina; Saddique, Asif; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Saimpert, Matthias; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salamon, Andrea; Saleem, Muhammad; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sampsonidis, Dimitrios; Sanchez, Arturo; Sánchez, Javier; Sanchez Martinez, Victoria; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sannino, Mario; Sansoni, Andrea; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Santoyo Castillo, Itzebelt; Sapp, Kevin; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; Sasaki, Osamu; Sasaki, Yuichi; Sato, Koji; Sauvage, Gilles; Sauvan, Emmanuel; Savage, Graham; Savard, Pierre; Sawyer, Craig; Sawyer, Lee; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Scarcella, Mark; Scarfone, Valerio; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schaefer, Ralph; Schaeffer, Jan; Schaepe, Steffen; Schaetzel, Sebastian; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R~Dean; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Schiavi, Carlo; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmidt, Evelyn; Schmieden, Kristof; Schmitt, Christian; Schmitt, Sebastian; Schmitt, Stefan; Schneider, Basil; Schnellbach, Yan Jie; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schopf, Elisabeth; Schorlemmer, Andre Lukas; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schramm, Steven; Schreyer, Manuel; Schroeder, Christian; Schuh, Natascha; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwanenberger, Christian; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schwegler, Philipp; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Schwindt, Thomas; Schwoerer, Maud; Sciacca, Gianfranco; Scifo, Estelle; Sciolla, Gabriella; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekhon, Karishma; Sekula, Stephen; Selbach, Karoline Elfriede; Seliverstov, Dmitry; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Serre, Thomas; Sessa, Marco; Seuster, Rolf; Severini, Horst; Sfiligoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Shaw, Savanna Marie; Shcherbakova, Anna; Shehu, Ciwake Yusufu; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shiyakova, Mariya; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Shojaii, Seyedruhollah; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Shushkevich, Stanislav; Sicho, Petr; Sidiropoulou, Ourania; Sidorov, Dmitri; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, José; Silver, Yiftah; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simon, Dorian; Simoniello, Rosa; Sinervo, Pekka; Sinev, Nikolai; Siragusa, Giovanni; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skinner, Malcolm Bruce; Skottowe, Hugh Philip; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smestad, Lillian; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Matthew; Smith, Russell; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snidero, Giacomo; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Soh, Dart-yin; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Song, Hong Ye; Soni, Nitesh; Sood, Alexander; Sopczak, Andre; Sopko, Bruno; Sopko, Vit; Sorin, Veronica; Sosa, David; Sosebee, Mark; Sotiropoulou, Calliope Louisa; Soualah, Rachik; Soueid, Paul; Soukharev, Andrey; South, David; Sowden, Benjamin; Spagnolo, Stefania; Spalla, Margherita; Spanò, Francesco; Spearman, William Robert; Spettel, Fabian; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; Spreitzer, Teresa; St Denis, Richard Dante; Staerz, Steffen; Stahlman, Jonathan; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stanitzki, Marcel Michael; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staszewski, Rafal; Stavina, Pavel; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Subramaniam, Rajivalochan; Succurro, Antonella; Sugaya, Yorihito; Suhr, Chad; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Shota; Suzuki, Yu; Svatos, Michal; Swedish, Stephen; Swiatlowski, Maximilian; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Taccini, Cecilia; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tam, Jason; Tan, Kong Guan; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Shuji; Tannenwald, Benjamin Bordy; Tannoury, Nancy; Tapprogge, Stefan; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teischinger, Florian Alfred; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Tepel, Fabian-Phillipp; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Emily; Thompson, Paul; Thompson, Ray; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thun, Rudolf; Tibbetts, Mark James; Ticse Torres, Royer Edson; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tiouchichine, Elodie; Tipton, Paul; Tisserant, Sylvain; Todorov, Theodore; Todorova-Nova, Sharka; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tollefson, Kirsten; Tolley, Emma; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; True, Patrick; Truong, Loan; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tudorache, Alexandra; Tudorache, Valentina; Tuna, Alexander Naip; Tupputi, Salvatore; Turchikhin, Semen; Turecek, Daniel; Turra, Ruggero; Turvey, Andrew John; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Tyndel, Mike; Ueda, Ikuo; Ueno, Ryuichi; Ughetto, Michael; Ugland, Maren; Uhlenbrock, Mathias; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Unverdorben, Christopher; Urban, Jozef; Urquijo, Phillip; Urrejola, Pedro; Usai, Giulio; Usanova, Anna; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Valderanis, Chrysostomos; Valencic, Nika; Valentinetti, Sara; Valero, Alberto; Valery, Loic; Valkar, Stefan; Valladolid Gallego, Eva; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; Van Den Wollenberg, Wouter; Van Der Deijl, Pieter; van der Geer, Rogier; van der Graaf, Harry; Van Der Leeuw, Robin; van Eldik, Niels; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vanguri, Rami; Vaniachine, Alexandre; Vannucci, Francois; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vazeille, Francois; Vazquez Schroeder, Tamara; Veatch, Jason; Veloce, Laurelle Maria; Veloso, Filipe; Velz, Thomas; Veneziano, Stefano; Ventura, Andrea; Ventura, Daniel; Venturi, Manuela; Venturi, Nicola; Venturini, Alessio; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigne, Ralph; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Vivarelli, Iacopo; Vives Vaque, Francesc; Vlachos, Sotirios; Vladoiu, Dan; Vlasak, Michal; Vogel, Marcelo; Vokac, Petr; Volpi, Guido; Volpi, Matteo; von der Schmitt, Hans; von Radziewski, Holger; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Voss, Rudiger; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vuillermet, Raphael; Vukotic, Ilija; Vykydal, Zdenek; Wagner, Peter; Wagner, Wolfgang; Wahlberg, Hernan; Wahrmund, Sebastian; Wakabayashi, Jun; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wang, Chao; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Kuhan; Wang, Rui; Wang, Song-Ming; Wang, Tan; Wang, Xiaoxiao; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Warsinsky, Markus; Washbrook, Andrew; Wasicki, Christoph; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Samuel; Weber, Michele; Weber, Stefan Wolf; Webster, Jordan S; Weidberg, Anthony; Weinert, Benjamin; Weingarten, Jens; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Wessels, Martin; Wetter, Jeffrey; Whalen, Kathleen; Wharton, Andrew Mark; White, Andrew; White, Martin; White, Ryan; White, Sebastian; Whiteson, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wildauer, Andreas; Wilkens, Henric George; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, Alan; Wilson, John; Wingerter-Seez, Isabelle; Winklmeier, Frank; Winter, Benedict Tobias; Wittgen, Matthias; Wittkowski, Josephine; Wollstadt, Simon Jakob; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wu, Mengqing; Wu, Miles; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xu, Da; Xu, Lailin; Yabsley, Bruce; Yacoob, Sahal; Yakabe, Ryota; Yamada, Miho; Yamaguchi, Yohei; Yamamoto, Akira; Yamamoto, Shimpei; Yamanaka, Takashi; Yamauchi, Katsuya; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Yi; Yao, Liwen; Yao, Weiming; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yeletskikh, Ivan; Yen, Andy L; Yildirim, Eda; Yorita, Kohei; Yoshida, Rikutaro; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Youssef, Saul; Yu, David Ren-Hwa; Yu, Jaehoon; Yu, Jiaming; Yu, Jie; Yuan, Li; Yurkewicz, Adam; Yusuff, Imran; Zabinski, Bartlomiej; Zaidan, Remi; Zaitsev, Alexander; Zalieckas, Justas; Zaman, Aungshuman; Zambito, Stefano; Zanello, Lucia; Zanzi, Daniele; Zeitnitz, Christian; Zeman, Martin; Zemla, Andrzej; Zengel, Keith; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Jinlong; Zhang, Lei; Zhang, Ruiqi; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Xiandong; Zhao, Yongke; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Chen; Zhou, Lei; Zhou, Li; Zhou, Ning; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhukov, Konstantin; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Stephanie; Zinonos, Zinonas; Zinser, Markus; Ziolkowski, Michael; Živković, Lidija; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zurzolo, Giovanni; Zwalinski, Lukasz

    2015-11-03

    This paper presents a search for Higgs bosons decaying to four leptons, either electrons or muons, via one or two light exotic gauge bosons $Z_d$, $H\\to Z Z_d \\to 4\\ell$ or $H\\to Z_d Z_d \\to 4\\ell$. The search was performed using $pp$ collision data corresponding to an integrated luminosity of about 20 fb$^{-1}$ at the center-of-mass energy of $\\sqrt{s}=8 $TeV recorded with the ATLAS detector at the Large Hadron Collider. The observed data are well described by the Standard Model prediction. Upper bounds on the branching ratio of $H\\to Z Z_d \\to 4\\ell$ and on the kinetic mixing parameter between the $Z_d$ and the Standard Model hypercharge gauge boson are set in the range $(1$--$9)\\times10^{-5}$ and $(4$--$17)\\times10^{-2}$ respectively, at 95% confidence level assuming the Standard Model branching ratio of $H\\to Z Z^* \\to 4\\ell$, for $Z_d$ masses between 15 and 55 GeV. Upper bounds on the effective mass mixing parameter between the $Z$ and the $Z_d$ are also set using the branching ratio limits in the $H \\to...

  14. Zero-determinant strategy: An underway revolution in game theory

    International Nuclear Information System (INIS)

    Hao Dong; Rong Zhi-Hai; Zhou Tao

    2014-01-01

    Repeated games describe situations where players interact with each other in a dynamic pattern and make decisions according to outcomes of previous stage games. Very recently, Press and Dyson have revealed a new class of zero-determinant (ZD) strategies for the repeated games, which can enforce a fixed linear relationship between expected payoffs of two players, indicating that a smart player can control her unwitting co-player's payoff in a unilateral way [Proc. Acad. Natl. Sci. USA 109, 10409 (2012)]. The theory of ZD strategies provides a novel viewpoint to depict interactions among players, and fundamentally changes the research paradigm of game theory. In this brief survey, we first introduce the mathematical framework of ZD strategies, and review the properties and constrains of two specifications of ZD strategies, called pinning strategies and extortion strategies. Then we review some representative research progresses, including robustness analysis, cooperative ZD strategy analysis, and evolutionary stability analysis. Finally, we discuss some significant extensions to ZD strategies, including the multi-player ZD strategies, and ZD strategies under noise. Challenges in related research fields are also listed. (topical review - statistical physics and complex systems)

  15. Zhang functions and various models

    CERN Document Server

    Zhang, Yunong

    2015-01-01

    This book focuses on solving different types of time-varying problems. It presents various Zhang dynamics (ZD) models by defining various Zhang functions (ZFs) in real and complex domains. It then provides theoretical analyses of such ZD models and illustrates their results. It also uses simulations to substantiate their efficacy and show the feasibility of the presented ZD approach (i.e., different ZFs leading to different ZD models), which is further applied to the repetitive motion planning (RMP) of redundant robots, showing its application potential.

  16. The effect of a moderate zinc deficiency and dietary fat source on the activity and expression of the Δ(3)Δ (2)-enoyl-CoA isomerase in the liver of growing rats.

    Science.gov (United States)

    Justus, Jennifer; Weigand, Edgar

    2014-06-01

    Auxiliary enzymes participate in β-oxidation of unsaturated fatty acids. The objective of the study was to investigate the impact of a moderate zinc deficiency and a high intake of polyunsaturated fat on Δ(3)Δ(2)-enoyl-CoA isomerase (ECI) in the liver and other tissues. Five groups of eight weanling rats each were fed moderately zinc-deficient (ZD) or zinc-adequate (ZA) semisynthetic diets (7 or 50 mg Zn/kg) enriched with 22 % cocoa butter (CB) or 22 % safflower oil (SO) for 4 weeks: (1) ZD-CB, fed free choice; (2) ZA-CBR, ZA-CB diet fed in equivalent amounts consumed by the ZD-CB group; (3) ZD-SO, fed free choice; (4) ZA-SOR, ZA-SO diet fed in equivalent amounts consumed by the ZD-SO group; and (5) ZA-SO, fed free choice. Growth and Zn status markers were markedly reduced in the ZD groups. ECI activity in the liver of the animals fed the ZD- and ZA-SO diets were significantly higher (approximately 2- and 3-fold, respectively) as compared with the CB-fed animals, whereas activities in extrahepatic tissues (kidneys, heart, skeletal muscle, testes, adipose tissue) were not altered by dietary treatments. Transcript levels of the mitochondrial Eci gene in the liver did not significantly differ between ZD and ZA rats, but were 1.6-fold higher in the ZA-SO- than in the ZD-CB-fed animals (P safflower oil as a source high in linoleic acid induce markedly increased hepatic ECI activities and that a moderate Zn deficiency does not affect transcription of the mitochondrial Eci gene in the liver.

  17. Extortion under uncertainty: Zero-determinant strategies in noisy games

    Science.gov (United States)

    Hao, Dong; Rong, Zhihai; Zhou, Tao

    2015-05-01

    Repeated game theory has been one of the most prevailing tools for understanding long-running relationships, which are the foundation in building human society. Recent works have revealed a new set of "zero-determinant" (ZD) strategies, which is an important advance in repeated games. A ZD strategy player can exert unilateral control on two players' payoffs. In particular, he can deterministically set the opponent's payoff or enforce an unfair linear relationship between the players' payoffs, thereby always seizing an advantageous share of payoffs. One of the limitations of the original ZD strategy, however, is that it does not capture the notion of robustness when the game is subjected to stochastic errors. In this paper, we propose a general model of ZD strategies for noisy repeated games and find that ZD strategies have high robustness against errors. We further derive the pinning strategy under noise, by which the ZD strategy player coercively sets the opponent's expected payoff to his desired level, although his payoff control ability declines with the increase of noise strength. Due to the uncertainty caused by noise, the ZD strategy player cannot ensure his payoff to be permanently higher than the opponent's, which implies dominant extortions do not exist even under low noise. While we show that the ZD strategy player can still establish a novel kind of extortions, named contingent extortions, where any increase of his own payoff always exceeds that of the opponent's by a fixed percentage, and the conditions under which the contingent extortions can be realized are more stringent as the noise becomes stronger.

  18. Teacher self-efficacy in instruction and in parent involvement

    Directory of Open Access Journals (Sweden)

    Peter Gavora

    2012-06-01

    Full Text Available The study investigated self-efficacy of a sample of Slovak primary schoolteachers in two areas: area of instruction and area of parent involvement. Twoinstruments were used: the 16-item Slovak version of Teacher Efficacy Scale ofGibson and Dembo, and ZdUR, a 24-item scale to measure self-efficacy of teacherin parents’ involvement, developed by authors of the present study. The correlation between scores of personal teaching efficacy dimension of TES and ZdUR was 0.58 and between general teaching efficacy of TES and ZdUR was only 0.01. Teachers inthis sample had better scores in all dimensions of ZdUR than those of TES, with theexception of engaging parents in school activities. Scores of four teachers in TES andZdUR were analysed to document the possibility of making the individual profiles ofteacher self-efficacy.

  19. E1B-attenuated onco lytic adenovirus enhances antitumor effect of radionuclide therapy by P53-independent way: cellular basic for radionuclide-viral therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhenwei, Zhang [Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Hua, Wu; Xuemei, Zhang [Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xinyuan, Liu [Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai (China)

    2004-07-01

    Purpose: Chemotherapy or external radiation therapy can potentiate the therapeutic effect of E1 B-attenuated oncolytic adenovirus. In this study, the antitumor efficacy of oncolytic adenovirus combined with internal radionuclide therapy was evaluated. Methods: Firstly, viral replication was examined by plaque assay and Southern blotting, after oncolytic adenovirus, ZD55, was exposed to iodine-131. Cell viability was evaluated qualitatively by crystal violet staining and quantitatively by MTT assay. FACS analysis was performed to determine the synergic proapoptotic effect of iodine-131 combined with ZD55. Results: Irradiation of iodine-131 does not influence ZD55 viral DNA replication. In combination with ZD55, iodine-131 can efficiently kill tumor cells in a p53-independent model. ZD55 augments the proapoptotic effect of iodine-131. Conclusion: Radionuclide-viral therapy might be a novel tool for treatment of hepatocarcinoma. (authors)

  20. [Recurrent subareolar non puerperal abscess of breast with fistules of lactiferous ducts (Zuskas disease)].

    Science.gov (United States)

    Móricová, P; Žúbor, P; Kapustová, I; Švecová, I; Danko, J

    2013-09-01

    Zuskas disease (ZD) is an illness also known as the recurrent subareolar non-puerperal abscess of breast with fistulas of lactiferous ducts or as a periductal mastitis. ZD is rare, but painful chronic disease of breast characterized by local inflammation and evacuation of viscous content from abscess around the nipple. We present a rare form of the non-puerperal mastitis in patients with recurrence of this disease and with the description of management and treatment. The treatment of ZD is often inadequate and it leads to the recurrence of ZD and retraction of the nipple. Definitive treatment of ZD is surgical excision of the fistulation, removing of whole retroareolar fibroglandular tissue, abscess cavity and ductal tissue inside the nipple, including the obstructed ducts. The ratio of patients cured by this method is high, as well as their satisfaction with the final cosmetic effect of the nipple and breast.

  1. Feasibility and usefulness of using swallow contrast-enhanced ultrasound to diagnose Zenker's diverticulum: preliminary results.

    Science.gov (United States)

    Cui, Xin-Wu; Ignee, Andre; Baum, Ulrich; Dietrich, Christoph F

    2015-04-01

    Zenker's diverticulum (ZD) may be misdiagnosed on conventional ultrasound as a thyroid nodule or other lesion. A barium esophagram is usually used to confirm the diagnosis; however, this procedure exposes the patient to radiation. The aim of this study was to evaluate the feasibility of using swallow contrast-enhanced ultrasound (swallow-CEUS) to diagnose ZD. Ten consecutive patients with ZD (7 men and 3 women, aged 67 ± 11 y) were included in the study. In 4 patients, ZD was incidentally found on head and neck ultrasound, and in 6 patients, ZD was suspected because of dysphagia. All lesions could be detected on conventional ultrasound before swallow-CEUS. Ten healthy volunteers (8 men and 2 women, aged 60 ± 12 y) were chosen as a control group. Written informed consent was obtained. With the patient in the sitting or upright position, conventional ultrasound was performed first to image the lesion, then the patient was asked to swallow ultrasound contrast agent (UCA) (2-4 drops of SonoVue diluted with about 200 mL of tap water). Transity of the contrast agent in the esophagus was imaged with CEUS. Retention of the UCA in the diverticulum was monitored for at least 3 min. All patients underwent a barium esophagram as the gold standard. Swallow-CEUS revealed that in all patients (100%), the UCA was transported from the pharynx to the esophagus while the patient swallowed. ZD appeared as a pouch-shaped structure at the posterior pharyngo-esophageal junction that retained UCA longer than 3 min. The barium esophagram confirmed the diagnosis of ZD in all patients. For the 10 volunteers, no abnormal structure (retaining UCA) was detected during or after swallowing of UCA. With the advantages of no radiation and bedside availability, swallow-CEUS may become a method of choice in confirmation of the diagnosis of ZD, especially when ZD is suspected on conventional ultrasound. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier

  2. Targeted Therapy Shows Benefit in Rare Type of Thyroid Cancer

    Science.gov (United States)

    Treatment with the multitargeted agent vandetanib (Caprelsa) improved progression-free survival in patients with medullary thyroid cancer (MTC), according to findings from a randomized clinical trial.

  3. Increased suppression of oncolytic adenovirus carrying mutant k5 on colorectal tumor

    International Nuclear Information System (INIS)

    Fan Junkai; Xiao Tian; Gu Jinfa; Wei Na; He Lingfeng; Ding Miao; Liu Xinyuan

    2008-01-01

    Angiogenesis plays a key role in the development of a wide variety of malignant tumors. The approach of targeting antiangiogenesis has become an important field of cancer gene therapy. In this study, the antiangiogenesis protein K5 (the kringle 5 of human plasminogen) has been mutated by changing leucine71 to arginine to form mK5. Then the ZD55-mK5, which is an oncolytic adenovirus expressing mK5, was constructed. It showed stronger inhibition on proliferation of human umbilical vein endothelial cell. Moreover, in tube formation and embryonic chorioallantoic membrane assay, ZD55-mK5 exhibited more effective antiangiogenesis than ZD55-K5. In addition, ZD55-mK5 generated obvious suppression on the growth of colorectal tumor xenografts and prolonged the life span of nude mice. These results indicate that ZD55-mK5 is a potent agent for inhibiting the tumor angiogenesis and tumor growth

  4. Drugs Approved for Thyroid Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) Doxorubicin ...

  5. Long-term results using LigaSure™ 5 mm instrument for treatment of Zenker's diverticulum

    DEFF Research Database (Denmark)

    Andersen, Michelle Fog; Trolle, Waldemar; Anthonsen, Kristian

    2017-01-01

    The purpose of the present study was to evaluate the long-term results and patient's satisfaction of a new approach using the LigaSure™ 5 mm instrument for treatment of Zenker's diverticulum (ZD) and to compare with other long-term results using traditional treatment modalities. Between December ...... to traditional endoscopic techniques and is now the standard treatment method for ZD in our departments.......The purpose of the present study was to evaluate the long-term results and patient's satisfaction of a new approach using the LigaSure™ 5 mm instrument for treatment of Zenker's diverticulum (ZD) and to compare with other long-term results using traditional treatment modalities. Between December......%) reported no symptoms at all. Our results suggest that endoscopic management of ZD with the LigaSure™ 5 mm instrument is a minimally invasive, fast and safe method with solid long-term outcome with relief of symptoms and patient satisfaction. This new operative instrument was not found inferior...

  6. A traditional Chinese medicine formula extracts stimulate proliferation and inhibit mineralization of human mesenchymal stem cells in vitro

    DEFF Research Database (Denmark)

    Chen, Muwan; Feng, Wenzhou; Cao, Hui

    2009-01-01

    AIM OF THE STUDY: To investigate the effects of a traditional Chinese medicine (TCM) formula extract, named as ZD-I, on the proliferation and osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro. MATERIALS AND METHODS: When hMSCs cultivated in the basal medium with ZD-I, cell...

  7. The role of the Zn(II binding domain in the mechanism of E. coli DNA topoisomerase I

    Directory of Open Access Journals (Sweden)

    Tse-Dinh Yuk-Ching

    2002-05-01

    Full Text Available Abstract Background Escherichia coli DNA topoisomerase I binds three Zn(II with three tetracysteine motifs which, together with the 14 kDa C-terminal region, form a 30 kDa DNA binding domain (ZD domain. The 67 kDa N-terminal domain (Top67 has the active site tyrosine for DNA cleavage but cannot relax negatively supercoiled DNA. We analyzed the role of the ZD domain in the enzyme mechanism. Results Addition of purified ZD domain to Top67 partially restored the relaxation activity, demonstrating that covalent linkage between the two domains is not necessary for removal of negative supercoils from DNA. The two domains had similar affinities to ssDNA. However, only Top67 could bind dsDNA with high affinity. DNA cleavage assays showed that the Top67 had the same sequence and structure selectivity for DNA cleavage as the intact enzyme. DNA rejoining also did not require the presence of the ZD domain. Conclusions We propose that during relaxation of negatively supercoiled DNA, Top67 by itself can position the active site tyrosine near the junction of double-stranded and single-stranded DNA for cleavage. However, the interaction of the ZD domain with the passing single-strand of DNA, coupled with enzyme conformational change, is needed for removal of negative supercoils.

  8. Atmospheric chemistry of short-chain haloolefins: photochemical ozone creation potentials (POCPs), global warming potentials (GWPs), and ozone depletion potentials (ODPs).

    Science.gov (United States)

    Wallington, T J; Sulbaek Andersen, M P; Nielsen, O J

    2015-06-01

    Short-chain haloolefins are being introduced as replacements for saturated halocarbons. The unifying chemical feature of haloolefins is the presence of a CC double bond which causes the atmospheric lifetimes to be significantly shorter than for the analogous saturated compounds. We discuss the atmospheric lifetimes, photochemical ozone creation potentials (POCPs), global warming potentials (GWPs), and ozone depletion potentials (ODPs) of haloolefins. The commercially relevant short-chain haloolefins CF3CFCH2 (1234yf), trans-CF3CHCHF (1234ze(Z)), CF3CFCF2 (1216), cis-CF3CHCHCl (1233zd(Z)), and trans-CF3CHCHCl (1233zd(E)) have short atmospheric lifetimes (days to weeks), negligible POCPs, negligible GWPs, and ODPs which do not differ materially from zero. In the concentrations expected in the environment their atmospheric degradation products will have a negligible impact on ecosystems. CF3CFCH2 (1234yf), trans-CF3CHCHF (1234ze(Z)), CF3CFCF2 (1216), cis-CF3CHCHCl (1233zd(Z)), and trans-CF3CHCHCl (1233zd(E)) are environmentally acceptable. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. A double-regulated oncolytic adenovirus with improved safety for adenocarcinoma therapy

    International Nuclear Information System (INIS)

    Wei, Na; Fan, Jun Kai; Gu, Jin Fa; He, Ling Feng; Tang, Wen Hao; Cao, Xin; Liu, Xin Yuan

    2009-01-01

    Safety and efficiency are equally important to be considered in developing oncolytic adenovirus. Previously, we have reported that ZD55, an oncolytic adenovirus with the deletion of E1B-55K gene, exhibited potent antitumor activity. In this study, to improve the safety of ZD55, we utilized MUC1 promoter to replace the native promoter of E1A on the basis of ZD55, and generated a double-regulated adenovirus, named MUD55. Our data demonstrated that the expression of early and late genes of MUD55 was both reduced in MUC1-negative cells, resulting in its stricter glandular-tumor selective progeny production. The cytopathic effect of MUD55 was about 10-fold lower than mono-regulated adenovirus ZD55 or Ad.MUC1 in normal cells and not obviously attenuated in glandular tumor cells. Moreover, MUD55 showed the least liver toxicity when administrated by intravenous injection in nude mice. These results indicate that MUD55 could be a promising candidate for the treatment of adenocarcinoma.

  10. Contribution to the asymptotic estimation of the global error of single step numerical integration methods. Application to the simulation of electric power networks; Contribution a l'estimation asymptotique de l'erreur globale des methodes d'integration numerique a un pas. Application a la simulation des reseaux electriques

    Energy Technology Data Exchange (ETDEWEB)

    Aid, R.

    1998-01-07

    This work comes from an industrial problem of validating numerical solutions of ordinary differential equations modeling power systems. This problem is solved using asymptotic estimators of the global error. Four techniques are studied: Richardson estimator (RS), Zadunaisky's techniques (ZD), integration of the variational equation (EV), and Solving for the correction (SC). We give some precisions on the relative order of SC w.r.t. the order of the numerical method. A new variant of ZD is proposed that uses the Modified Equation. In the case of variable step-size, it is shown that under suitable restriction, on the hypothesis of the step-size selection, ZD and SC are still valid. Moreover, some Runge-Kutta methods are shown to need less hypothesis on the step-sizes to exhibit a valid order of convergence for ZD and SC. Numerical tests conclude this analysis. Industrial cases are given. Finally, an algorithm to avoid the a priori specification of the integration path for complex time differential equations is proposed. (author)

  11. Zrozeni z hvězd

    Czech Academy of Sciences Publication Activity Database

    Borovička, Jan

    2014-01-01

    Roč. 27, [2.8.2014] (2014), s. 21-21 ISSN 0862-5921 Institutional support: RVO:67985831 Keywords : chemistry * geochemistry * cosmochemistry * chemical elements * Sun * universe * Earth Subject RIV: DD - Geochemistry

  12. Delayed plasma clearance and hepatic uptake of lymph chylomicron 14C-cholesterol in marginally zinc-deficient rats

    International Nuclear Information System (INIS)

    Koo, S.I.; Algilani, K.; Norvell, J.E.; Henderson, D.A.

    1986-01-01

    Previously, chylomicrons from marginally zinc-deficient rats were shown to be abnormally large, with markedly reduced levels of apoproteins C and E. In the present study, effects of such changes on the plasma clearance and hepatic uptake of chylomicron cholesterol were investigated in rats fed 3 ppm of zinc (ZD), as compared with those fed 30 ppm of zinc (CT). The rate of plasma clearance was determined by plasma 14C-radioactivity at different intervals after intravenous injection of lymph chylomicrons labeled in vivo with 14C-cholesterol. The 14C-clearance curves were nonlinear, consisting of an initial rapid phase followed by a slow phase of clearance. The initial 14C-clearance was significantly (p less than 0.05) delayed whether the labeled chylomicrons from ZD donors were injected into ZD or CT recipients. The hepatic 14C-recovery in extracted lipids was also significantly lower in ZD rats. The present data provide first evidence that a marginal level of zinc deficiency produces a significant delay in the plasma clearance and hepatic uptake of chylomicron cholesterol. This may be attributable in part to the molecular alterations of chylomicrons induced by zinc deficiency

  13. Prevalence of prenatal zinc deficiency and its association with socio-demographic, dietary and health care related factors in Rural Sidama, Southern Ethiopia: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Gebremedhin Samson

    2011-11-01

    Full Text Available Abstract Background Several studies witnessed that prenatal zinc deficiency (ZD predisposes to diverse pregnancy complications. However, scientific evidences on the determinants of prenatal ZD are scanty and inconclusive. The purpose of the present study was to assess the prevalence and determinants of prenatal ZD in Sidama zone, Southern Ethiopia. Methods A community based, cross-sectional study was conducted in Sidama zone in January and February 2011. Randomly selected 700 pregnant women were included in the study. Data on potential determinants of ZD were gathered using a structured questionnaire. Serum zinc concentration was measured using Atomic Absorption Spectrometry. Statistical analysis was done using logistic regression and linear regression. Results The mean serum zinc concentration was 52.4 (+/-9.9 μg/dl (95% CI: 51.6-53.1 μg/dl. About 53.0% (95% CI: 49.3-56.7% of the subjects were zinc deficient. The majority of the explained variability of serum zinc was due to dietary factors like household food insecurity level, dietary diversity and consumption of animal source foods. The risk of ZD was 1.65 (95% CI: 1.02-2.67 times higher among women from maize staple diet category compared to Enset staple diet category. Compared to pregnant women aged 15-24 years, those aged 25-34 and 35-49 years had 1.57 (95% CI: 1.04-2.34 and 2.18 (95% CI: 1.25-3.63 times higher risk of ZD, respectively. Women devoid of self income had 1.74 (95% CI: 1.11-2.74 time increased risk than their counterparts. Maternal education was positively associated to zinc status. Grand multiparas were 1.74 (95% CI: 1.09-3.23 times more likely to be zinc deficient than nulliparas. Frequency of coffee intake was negatively association to serum zinc level. Positive association was noted between serum zinc and hemoglobin concentrations. Altitude, history of iron supplementation, maternal workload, physical access to health service, antenatal care and nutrition education were

  14. Establishment for Nuclear Equipment -Overview

    International Nuclear Information System (INIS)

    Pracz, J.

    2006-01-01

    Research and development works conducted in the Establishment for Nuclear Equipment (ZdAJ) were focused around 3 subject areas: an accelerator for cancer treatment, therapeutical tables, systems and methods for controlling objects that cross international borders. The new, medium energy accelerator for cancer therapy cases is being designed in the Establishment for several years. In 2005 progress was achieved. A physical part, containing an electron beam has been completed and the parameters of that beam make it useful for therapeutical purposes. Consequently, the work on designing and testing of beam control systems, ensuring its high stability, repetition of irradiation parameters and accuracy of dosage have been started. Results of these tests make it very probable that 2006 will be the final year of scientific works and in 2007 the new apparatus will be ready for sales. Therapeutical tables have become a leading product of ZdAJ IPJ. Their technical parameters, reliability and universality in uses are appreciated by many customers of ZdAJ. In 2005, the table Polkam 16 was registered by the national Office for Registration of Medical Equipment as the first product of ZdAJ that meets all technical and formal requirements of the safety mark CE. This allows sales of the product on the market of the European Union. The research and development part of designing a therapeutical table for uses in the total body irradiation technique was also concluded in 2005. After the September 11 terrorist attacks on WTC a matter of controlling international borders have become a priority for many countries. In 2005 in ZdAJ IPJ, we conducted many preliminary calculations and experiments analyzing systems of irradiation sources, both photon and neutron as well as systems of detection and designing of signals triggered by controlling objects crossing the border. The results so far have enabled us to formulate a research project which has been positively evaluated by experts and found

  15. Generalized shift-invariant systems and frames for subspaces

    DEFF Research Database (Denmark)

    Christensen, Ole; Eldar, Y.C.

    2005-01-01

    Let T-k denote translation by k is an element of Z(d). Given countable collections of functions {phi(j)}(j is an element of J), {(phi) over bar (j)}(j is an element of J) subset of L-2(R-d) and assuming that {T(k)phi(j)}(j is an element of J,k is an element of Z)(d) and {T-k(phi) over bar (j)} (d...

  16. Entangling transformations in composite finite quantum systems

    International Nuclear Information System (INIS)

    Vourdas, A

    2003-01-01

    Phase space methods are applied in the context of finite quantum systems. 'Galois quantum systems' (with a dimension which is a power of a prime number) are considered, and symplectic Sp(2,Z(d)) transformations are studied. Composite systems comprising two finite quantum systems are also considered. Symplectic Sp(4,Z(d)) transformations are classified into local and entangling ones and the necessary matrices which perform such transformations are calculated numerically

  17. Anti-cancer effect of oncolytic adenovirus-armed shRNA targeting MYCN gene on doxorubicin-resistant neuroblastoma cells.

    Science.gov (United States)

    Li, Yuan; Zhuo, Baobiao; Yin, Yiyu; Han, Tao; Li, Shixian; Li, Zhengwei; Wang, Jian

    2017-09-09

    Chemotherapy is one of the few effective choices for patients with neuroblastoma. However, the development of muti-drug resistance (MDR) to chemotherapy is a major obstacle to the effective treatment of advanced or recurrent neuroblastoma. The muti-drug resistance-associated protein (MRP), which encodes a transmembrane glycoprotein, is a key regulator of MDR. The expression of MRP is a close correlation with MYCN oncogene in neuroblastoma. We have recently shown ZD55-shMYCN (oncolytic virus armed with shRNA against MYCN) can down-regulate MYCN to inhibit tumor cells proliferation and induce apoptosis in neuroblastoma. Here we further report ZD55-shMYCN re-sensitized doxorubicin-resistant cells to doxorubicin (as shown by reduced proliferation, increased apoptosis, and inhibited cell migration), and reduced the in vivo growth rate of neuroblastoma xenografts by down-regulation of MRP expression. Sequential therapy with doxorubicin did not affect the replication of ZD55-shMYCN in doxorubicin-resistant neuroblastoma cells, but decreased the expression of Bcl-2, Bcl-X L , MMP-1. Thus, this synergistic effect of ZD55-shMYCN in combination with doxorubicin provides a novel therapy strategy for doxorubicin-resistant neuroblastoma, and is a promising approach for further clinical development. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Marginal bone-level alterations of loaded zirconia and titanium dental implants: an experimental study in the dog mandible.

    Science.gov (United States)

    Thoma, Daniel S; Benic, Goran I; Muñoz, Fernando; Kohal, Ralf; Sanz Martin, Ignacio; Cantalapiedra, Antonio G; Hämmerle, Christoph H F; Jung, Ronald E

    2016-04-01

    The aim was to test whether or not the marginal bone-level alterations of loaded zirconia implants are similar to the bone-level alterations of a grade 4 titanium one-piece dental implant. In six dogs, all premolars and the first molars were extracted in the mandible. Four months later, three zirconia implants (BPI, VC, ZD) and a control titanium one-piece (STM) implant were randomly placed in each hemimandible and left for transmucosal healing (baseline). Six months later, CAD/CAM crowns were cemented. Sacrifice was scheduled at 6-month postloading. Digital X-rays were taken at implant placement, crowns insertion, and sacrifice. Marginal bone-level alterations were calculated, and intra- and intergroup comparisons performed adjusted by confounding factors. Implants were successfully placed. Until crown insertion, two implants were fractured (one VC, one ZD). At sacrifice, 5 more implants were (partly) fractured (one BPI, four ZD), and one lost osseointegration (VC). No decementation of crowns occurred. All implant systems demonstrated a statistically significant (except VC) loss of marginal bone between baseline and crown insertion ranging from 0.29 mm (VC; P = 0.116) to 0.80 mm (ZD; P = 0.013). The estimated marginal bone loss between baseline and 6 months of loading ranged between 0.19 mm (BPI) and 1.11 mm (VC), being statistically significant for STM and VC only (P implants and control implants (STM vs. BPI P = 0.007; vs. VC P = 0.001; vs. ZD P = 0.011). Zirconia implants were more prone to fracture prior to and after loading with implant-supported crowns compared to titanium implants. Individual differences and variability in the extent of the bone-level changes during the 12-month study period were found between the different implant types and materials. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. THROUGH THE LOOKING GLASS: BRIGHT, HIGHLY MAGNIFIED GALAXY CANDIDATES AT z {approx} 7 BEHIND A1703

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, L. D.; Coe, D. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Bouwens, R. J.; Smit, R. [Leiden Observatory, Leiden University, Postbus 9513, 2300 RA Leiden (Netherlands); Zitrin, A. [School of Physics and Astronomy, Tel Aviv University, Tel Aviv 69978 (Israel); Ford, H. C.; Zheng, W. [Department of Physics and Astronomy, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States); Illingworth, G. D. [UCO/Lick Observatory, Department of Astronomy and Astrophysics, University of California Santa Cruz, Santa Cruz, CA 95064 (United States); Benitez, N. [Instituto de Astrofisica de Andalucia (CSIC), C/Camino Bajo de Huetor 24, Granada 18008 (Spain); Broadhurst, T. J. [Department of Theoretical Physics, University of Basque Country UPV/EHU, Leioa (Spain)

    2012-03-01

    We report the discovery of seven strongly lensed Lyman-break galaxy (LBG) candidates at z {approx} 7 detected in Hubble Space Telescope Wide Field Camera 3 (WFC3) imaging of A1703. The brightest candidate, called A1703-zD1, has an observed (lensed) magnitude of 24.0 AB (26{sigma}) in the WFC3/IR F160W band, making it 0.2 mag brighter than the z{sub 850}-dropout candidate recently reported behind the Bullet Cluster and 0.7 mag brighter than the previously brightest known z {approx} 7.6 galaxy, A1689-zD1. With a cluster magnification of {approx}9, this source has an intrinsic magnitude of H{sub 160} = 26.4 AB, a strong z{sub 850} - J{sub 125} break of 1.7 mag, and a photometric redshift of z {approx} 6.7. Additionally, we find six other bright LBG candidates with H{sub 160}-band magnitudes of 24.9-26.4, photometric redshifts z {approx} 6.4 - 8.8, and magnifications {mu} {approx} 3-40. Stellar population fits to the Advanced Camera for Surveys, WFC3/IR, and Spitzer/Infrared Array Camera data for A1703-zD1 and A1703-zD4 yield stellar masses (0.7 - 3.0) Multiplication-Sign 10{sup 9} M{sub Sun }, stellar ages 5-180 Myr, and star formation rates {approx}7.8 M{sub Sun} yr{sup -1}, and low reddening with A{sub V} {<=} 0.7. The source-plane reconstruction of the exceptionally bright candidate A1703-zD1 exhibits an extended structure, spanning {approx}4 kpc in the z {approx} 6.7 source plane, and shows three resolved star-forming knots of radius r {approx} 0.4 kpc.

  20. Zenker's Diverticulum: Diagnostic Approach and Surgical Management

    Directory of Open Access Journals (Sweden)

    Carlos M. Nuño-Guzmán

    2014-11-01

    Full Text Available Zenker's diverticulum (ZD, also known as cricopharyngeal, pharyngoesophageal or hypopharyngeal diverticulum, is a rare condition characterized by an acquired outpouching of the mucosal and submucosal layers originating from the pharyngoesophageal junction. This false and pulsion diverticulum occurs dorsally at the pharyngoesophageal wall between the inferior pharyngeal constrictor and the cricopharyngeus muscle. The pathophysiology of ZD involves altered compliance of the cricopharyngeus muscle and raised intrabolus pressure. Decreased compliance of the upper esophageal sphincter and failure to open completely for effective bolus clearance both lead to an increase in the hypopharyngeal pressure gradient. Different open surgical techniques and transoral endoscopic approaches have been described for the management of ZD, although there is no consensus about the best option. We report the case of a 61-year-old patient with a 7-year history of dysphagia and odynophagia for solid food, which after 2 months progressed to dysphagia for liquids and after 4 months to regurgitation 2-6 h after meals. The patient experienced a 12-kg weight loss. Diagnosis was established by esophagogram, which showed a diverticulum through the posterior pharyngeal wall, suggestive of a ZD. Esophagogastroduodenoscopy showed a pouch with erythematous mucosa. Under general anesthesia, diverticulectomy and myotomy were performed. After an uneventful recovery and adequate oral intake, the patient remains free of symptoms at 4 months of follow-up.

  1. Teacher self-efficacy in instruction and in parent involvement

    OpenAIRE

    Peter Gavora; Jana Majerčíková

    2012-01-01

    The study investigated self-efficacy of a sample of Slovak primary schoolteachers in two areas: area of instruction and area of parent involvement. Twoinstruments were used: the 16-item Slovak version of Teacher Efficacy Scale ofGibson and Dembo, and ZdUR, a 24-item scale to measure self-efficacy of teacherin parents’ involvement, developed by authors of the present study. The correlation between scores of personal teaching efficacy dimension of TES and ZdUR was 0.58 and between general teach...

  2. Comparison of the rhizosphere bacterial communities of Zigongdongdou soybean and a high-methionine transgenic line of this cultivar.

    Directory of Open Access Journals (Sweden)

    Jingang Liang

    Full Text Available Previous studies have shown that methionine from root exudates affects the rhizosphere bacterial population involved in soil nitrogen fixation. A transgenic line of Zigongdongdou soybean cultivar (ZD91 that expresses Arabidopsis cystathionine γ-synthase resulting in an increased methionine production was examined for its influence to the rhizosphere bacterial population. Using 16S rRNA gene-based pyrosequencing analysis of the V4 region and DNA extracted from bacterial consortia collected from the rhizosphere of soybean plants grown in an agricultural field at the pod-setting stage, we characterized the populational structure of the bacterial community involved. In total, 87,267 sequences (approximately 10,908 per sample were analyzed. We found that Acidobacteria, Proteobacteria, Bacteroidetes, Actinobacteria, Chloroflexi, Planctomycetes, Gemmatimonadetes, Firmicutes, and Verrucomicrobia constitute the dominant taxonomic groups in either the ZD91 transgenic line or parental cultivar ZD, and that there was no statistically significant difference in the rhizosphere bacterial community structure between the two cultivars.

  3. Dynamical systems of algebraic origin

    CERN Document Server

    Schmidt, Klaus

    1995-01-01

    Although much of classical ergodic theory is concerned with single transformations and one-parameter flows, the subject inherits from statistical mechanics not only its name, but also an obligation to analyze spatially extended systems with multidimensional symmetry groups. However, the wealth of concrete and natural examples which has contributed so much to the appeal and development of classical dynamics, is noticeably absent in this more general theory. The purpose of this book is to help remedy this scarcity of explicit examples by introducing a class of continuous Zd-actions diverse enough to exhibit many of the new phenomena encountered in the transition from Z to Zd, but which nevertheless lends itself to systematic study: the Zd-actions by automorphisms of compact, abelian groups. One aspect of these actions, not surprising in itself but quite striking in its extent and depth nonetheless, is the connection with commutative algebra and arithmetical algebraic geometry. The algebraic framework resulting...

  4. Kepercayaan Diri Ditinjau dari Pola Asuh Orang Tua pada Siswa Kelas VII (Studi Kasus

    Directory of Open Access Journals (Sweden)

    Danti Marta Dewi

    2013-12-01

    Full Text Available Penelitian ini bertujuan mengetahui tingkat kepercayaan diri siswa yang ditinjau dari pola asuh orang tua. Metode penelitian dengan penelitian kualitatif, pendekatannya studi kasus. Peneliti menentukan empat orang siswa sebagai subjek penelitian, DS dan MR, siswa dengan kepercayaan tinggi dan YB dan ZD, siswa dengan kepercayaan diri rendah. Menggunakan instrumen wawancara, obervasi, dokumentasi. Hasil penelitian menunjukkan bahwa subjek penelitian DS dan MR mempunyai tingkat kepercayaan diri yang tinggi, ditandai dengan tenang dalam mengerjakan suatu hal, memiliki kemampuan sosialisasi yang baik, memiliki pandangan positif terhadap diri sendiri, berpandangan positif terhadap orang lain, berpandangan positif terhadap kemampuan yang dimiliki dan berusaha untuk menghadapi kegagalan. YB dan ZD mempunyai tingkat kepercayaan diri rendah ditandai dengan gugup dalam melakukan suatu, kemampuan sosialisasinya rendah, berpandangan negatif terhadap dirinya sendiri, memandang orang lain memiliki banyak kelebihan dan dia mempunyai banyak kekurangan, tetapi sudah bisa menghadapi kegagalan dengan cukup baik. orang tua DS dan MR menerapkan pola asuh yang cenderung kepada pola asuh tipe demokratis, YB diasuh dengan pola asuh yang cenderung kepada pola asuh otoriter, ZD diasuh dengan pola asuh yang cenderung kepada pola asuh Permissive-indulgent. Dapat disimpulkan bahwa seorang seorang anak yang diasuh dengan kecenderungan tipe otoritatif atau demokratis akan mempunyai kepercayaan diri yang lebih tinggi.   The purpose of this research to determine students in term of parenting style. This research is qualitative research methods with a case study approach. Researchers determined the four students as research subjects, two students with high self confidence (DS and MR and two students with low self confidence (YB and ZD. Instruments used interviews, observation, documentation. The results showed that  DS and MR had a high level of confidence, which is

  5. Scaling properties of charged particle multiplicity distributions in oxygen induced emulsion interactions at 14.6, 60 and 200 A GeV

    International Nuclear Information System (INIS)

    Adamovich, M.I.; Aggarwal, M.M.; Arora, R.

    1988-12-01

    The multiplicity distributions of shower particles (n s ) are measured in inclusive inelastic oxygen emulsion interactions. Scaling in observed in the normalized variable n s / ave.(n s ) for 14.6, 60 and 200 A GeV. The dependence of ave. (n s ) on the charge flow in the forward direction (Q ZD ) and the distribution of the number of participating projectile protons is examined. The normalized multiplicities as a function of Q ZD seem also to be independent of incident energies. A comparison with the Lund Model Fritiof yields satisfactory agreement. (authors)

  6. Zinc deficiency leads to lipofuscin accumulation in the retinal pigment epithelium of pigmented rats.

    Directory of Open Access Journals (Sweden)

    Sylvie Julien

    Full Text Available BACKGROUND: Age-related macular degeneration (AMD is associated with lipofuscin accumulation whereas the content of melanosomes decreases. Melanosomes are the main storage of zinc in the pigmented tissues. Since the elderly population, as the most affected group for AMD, is prone to zinc deficit, we investigated the chemical and ultrastructural effects of zinc deficiency in pigmented rat eyes after a six-month zinc penury diet. METHODOLOGY/PRINCIPAL FINDINGS: Adult Long Evans (LE rats were investigated. The control animals were fed with a normal alimentation whereas the zinc-deficiency rats (ZD-LE were fed with a zinc deficient diet for six months. Quantitative Energy Dispersive X-ray (EDX microanalysis yielded the zinc mole fractions of melanosomes in the retinal pigment epithelium (RPE. The lateral resolution of the analysis was 100 nm. The zinc mole fractions of melanosomes were significantly smaller in the RPE of ZD-LE rats as compared to the LE control rats. Light, fluorescence and electron microscopy, as well as immunohistochemistry were performed. The numbers of lipofuscin granules in the RPE and of infiltrated cells (Ø>3 µm found in the choroid were quantified. The number of lipofuscin granules significantly increased in ZD-LE as compared to control rats. Infiltrated cells bigger than 3 µm were only detected in the choroid of ZD-LE animals. Moreover, the thickness of the Bruch's membrane of ZD-LE rats varied between 0.4-3 µm and thin, rangy ED1 positive macrophages were found attached at these sites of Bruch's membrane or even inside it. CONCLUSIONS/SIGNIFICANCE: In pigmented rats, zinc deficiency yielded an accumulation of lipofuscin in the RPE and of large pigmented macrophages in the choroids as well as the appearance of thin, rangy macrophages at Bruch's membrane. Moreover, we showed that a zinc diet reduced the zinc mole fraction of melanosomes in the RPE and modulated the thickness of the Bruch's membrane.

  7. Through the Looking Glass: Bright, Highly Magnified Galaxy Candidates at z ~ 7 behind A1703

    Science.gov (United States)

    Bradley, L. D.; Bouwens, R. J.; Zitrin, A.; Smit, R.; Coe, D.; Ford, H. C.; Zheng, W.; Illingworth, G. D.; Benítez, N.; Broadhurst, T. J.

    2012-03-01

    We report the discovery of seven strongly lensed Lyman-break galaxy (LBG) candidates at z ~ 7 detected in Hubble Space Telescope Wide Field Camera 3 (WFC3) imaging of A1703. The brightest candidate, called A1703-zD1, has an observed (lensed) magnitude of 24.0 AB (26σ) in the WFC3/IR F160W band, making it 0.2 mag brighter than the z 850-dropout candidate recently reported behind the Bullet Cluster and 0.7 mag brighter than the previously brightest known z ~ 7.6 galaxy, A1689-zD1. With a cluster magnification of ~9, this source has an intrinsic magnitude of H 160 = 26.4 AB, a strong z 850 - J 125 break of 1.7 mag, and a photometric redshift of z ~ 6.7. Additionally, we find six other bright LBG candidates with H 160-band magnitudes of 24.9-26.4, photometric redshifts z ~ 6.4 - 8.8, and magnifications μ ~ 3-40. Stellar population fits to the Advanced Camera for Surveys, WFC3/IR, and Spitzer/Infrared Array Camera data for A1703-zD1 and A1703-zD4 yield stellar masses (0.7 - 3.0) × 109 M ⊙, stellar ages 5-180 Myr, and star formation rates ~7.8 M ⊙ yr-1, and low reddening with AV Universities for Research in Astronomy under NASA contract NAS5-26555. Based on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology under NASA contract 1407.

  8. Stability of wavelet frames with matrix dilations

    DEFF Research Database (Denmark)

    Christensen, Ole; Sun, Wenchang

    2006-01-01

    (j,k) are perturbed. As a special case of our result, we obtain that if {Tau(A(j), A(j)Bn)psi} (j is an element of Z, n is an element of Zd) is a frame for an expansive matrix A and an invertible matrix B, then {Tau(A'(j), A(j)B lambda(n))psi}(j is an element of Z,) (n is an element of) (Zd) is a frame if vertical...... bar vertical bar A(-j)A'(j) - I vertical bar vertical bar(2) lambda(n) - n vertical bar vertical bar infinity 0....

  9. Soybean seeds expressing feedback-insensitive cystathionine γ-synthase exhibit a higher content of methionine.

    Science.gov (United States)

    Song, Shikui; Hou, Wensheng; Godo, Itamar; Wu, Cunxiang; Yu, Yang; Matityahu, Ifat; Hacham, Yael; Sun, Shi; Han, Tianfu; Amir, Rachel

    2013-04-01

    Soybean seeds provide an excellent source of protein for human and livestock nutrition. However, their nutritional quality is hampered by a low concentration of the essential sulfur amino acid, methionine (Met). In order to study factors that regulate Met synthesis in soybean seeds, this study used the Met-insensitive form of Arabidopsis cystathionine γ-synthase (AtD-CGS), which is the first committed enzyme of Met biosynthesis. This gene was expressed under the control of a seed-specific promoter, legumin B4, and used to transform the soybean cultivar Zigongdongdou (ZD). In three transgenic lines that exhibited the highest expression level of AtD-CGS, the level of soluble Met increased significantly in developing green seeds (3.8-7-fold). These seeds also showed high levels of other amino acids. This phenomenon was more prominent in two transgenic lines, ZD24 and ZD91. The total Met content, which including Met incorporated into proteins, significantly increased in the mature dry seeds of these two transgenic lines by 1.8- and 2.3-fold, respectively. This elevation was accompanied by a higher content of other protein-incorporated amino acids, which led to significantly higher total protein content in the seeds of these two lines. However, in a third transgenic line, ZD01, the level of total Met and the level of other amino acids did not increase significantly in the mature dry seeds. This line also showed no significant change in protein levels. This suggests a positive connection between high Met content and the synthesis of other amino acids that enable the synthesis of more seed proteins.

  10. Endoscopic needle-knife treatment for symptomatic esophageal Zenker's diverticulum: A meta-analysis and systematic review.

    Science.gov (United States)

    Li, Lian Yong; Yang, Yong Tao; Qu, Chang Min; Liang, Shu Wen; Zhong, Chang Qing; Wang, Xiao Ying; Chen, Yan; Spandorfer, Robert M; Christofaro, Sarah; Cai, Qiang

    2018-04-01

    The aim of this study was to assess the efficacy and safety following endoscopic management of Zenker's diverticulum (ZD) using a needle-knife technique. A systematic search of PubMed, Embase and Cochrane library databases was performed. All original studies reporting efficacy and safety of needle-knife technique for treatment of ZD were included. Pooled event rates across studies were expressed with summative statistics. Main outcomes, such as rates of immediate symptomatic response (ISR), adverse events and recurrence, were extracted, pooled and analyzed. Heterogeneity among studies was assessed using the R statistic. The random effects model was used and results were expressed with forest plots and summative statistics. Thirteen studies included 589 patients were enrolled. Pooled event rates for ISR, overall complication, bleeding and perforation were 88% (95% confidence interval [CI] 79-94%), 13% (95% CI 8-22%), 5% (95% CI 3-10%) and 7% (95% CI 4-12%), respectively. The pooled data demonstrated an overall recurrence rate of 14% (95% CI 9-21%). Diverticulum size of at least 4 cm and less than 4 cm demonstrated pooled adverse event rates of 17% (95% CI 10-27%) and 7% (95% CI 2-18%), respectively. When using diverticuloscope as an accessory, pooled ISR and adverse events rates were 84% (95% CI 58-95%) and 10% (95% CI 3-26%), respectively. Flexible endoscopic procedures using needle-knife offers a relatively safe and effective treatment of symptomatic ZD, especially for ZD of <4 cm in diameter. © 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  11. Stage and season effects on cell cycle and apoptotic activities of germ cells and Sertoli cells during spermatogenesis in the spiny dogfish (Squalus acanthias).

    Science.gov (United States)

    McClusky, L M

    2005-01-01

    To understand the processes involved in the spatial and temporal maturation of testicular cells in Squalus acanthias, we used standard morphometry, proliferating-cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) immunohistochemistry. Except for immature spermatocysts (germinal zone, GZ; early-stage pre-meiotic, E-PrM), the number of cysts in all subsequent stages and the total number of cysts in the spermatogenic progression varied seasonally. The spermatogenic cycle spans about 2 years and is interrupted by germcell clone deletion via apoptosis at the mitosis-meiosis transition in April/May, manifesting as a zone of degeneration (ZD). Rate of displacement of the ZD across the testis diameter indicates that late-stage premeiotic (L-PrM) generations 12-13 require 9-10 months to reach the mature-spermatid stage. Also, the number of cysts completing spermatogenesis is approximately 4-5-fold less than the number that entered spermatogenesis proper 2 years earlier. Pronounced gonocytogenesis in the germinal ridge was coincident with ZD formation in April/May, but it was absent in the fall when mature spermatogonial and meiotic activities had resumed. Whereas strong Sertoli cell PCNA immunoreactivity dominated the GZ cyst cell-cycle activities throughout the year, except during the spring/summer months, the spermatogonial- and Sertoli-cell PCNA indices in E-PrM cysts were inversely related. PCNA immunoreactivity in spermatocytes was seasonal and dependent on the stage of meiosis. TUNEL labelling was limited to spermatogonia and increased stage-dependently in the PrM region (L-PrM = mid-stage PrM >E-PrM >GZ), correlating with ZD formation, in a season-dependent manner. Results imply that effects of normal regulatory factors in Squalus are stage- and process-specific.

  12. Zapping Zenker’s Diverticulum: Gastroscopic Treatment

    Directory of Open Access Journals (Sweden)

    Chris JJ Mulder

    1999-01-01

    Full Text Available Zenker’s diverticulum (ZD is a common cause of dysphagia in the elderly. Many symptomatic elderly are poor candidates for surgery and/or ear, nose and throat treatment. The author’s first experiences with gastroscopic treatment by cutting the Zenker bridge to allow an overflow have recently been published. Only patients with contraindications for general anesthesia were accepted to the pilot group. However, the author now treats all ZD patients in this manner. One hundred and twenty-five patients (male to female ratio 1.6 were referred for treatment from 1993 to 1997. After introduction of the gastroscope into the esophagus, a nasogastric tube was positioned to treat a ZD bridge with a height of less than 1 cm. The ZD bridge was divided by argon plasma coagulation, if necessary, in combination with monopolar forceps, Savary dilator and/or precut needle. All patients received antibiotics, topical anesthesia to the throat, if necessary, and intravenous midazolam, if possible. Radiography was performed after treatment. Normalization of the diet was allowed when the x-ray showed no signs of leakage. All patients referred for treatment were treated successfully. The median age was 77 years (range 41 to 100 years. Symptomatic improvement was seen in all patients after treatment. Complications included subcutaneous emphysema (n=17, mediastinal emphysema (n=5 and bleeding (n=2. One patient (95 years of age died in her nursing home 27 days after treatment due to massive pulmonary embolism. The thirty-day mortality rate was otherwise zero. Three patients had been previously treated by surgeons and 12 by ear, nose and throat physicians, without sufficient improvement; all were adequately treated by the author. The mean number of treatment sessions was 1.8. This approach seems safe and effective. Treatment of every patient was possible and was carried out, even in patients in very poor condition, without general anesthesia.

  13. Biological responses of the coral Montastraea annularis to the removal of filamentous turf algae.

    Directory of Open Access Journals (Sweden)

    Neidy P Cetz-Navarro

    Full Text Available Coral reef degradation increases coral interactions with filamentous turf algae (FTA and macroalgae, which may result in chronic stress for the corals. We evaluated the effects of short (2.5 month and long (10 month periods of FTA removal on tissue thickness (TT, zooxanthellae density (ZD, mitotic index (MI, and concentration of chlorophyll a (Chl a in Montastraea annularis at the beginning and end of gametogenesis. Ramets (individual lobes within a colony consistently surrounded by FTA and ramets surrounded by crustose coralline algae (CCA were used as controls. FTA removal reduced coral stress, indicated by increased TT and ZD and lower MI. The measured effects were similar in magnitude for the short and long periods of algal removal. Ramets were more stressed at the end of gametogenesis compared with the beginning, with lower ZD and Chl a cm(-2, and higher MI. However, it was not possible to distinguish the stress caused by the presence of FTA from that caused by seasonal changes in seawater temperature. Ramets surrounded by CCA showed less stress in comparison with ramets surrounded by FTA: with higher TT, Chl a cm(-2 and ZD, and lower MI values. Coral responses indicated that ramets with FTA suffered the most deleterious effects and contrasted with those measured in ramets surrounded by CCA. According to published studies and our observations, there could be at least six mechanisms associated to FTA in the stress caused to M. annularis by FTA. Owing to the high cover of FTA (in contrast to macroalgae and CCA in the Caribbean, the chronic stress, the overgrowth and mortality that this functional algal group can cause on M. annularis species complex, a further decline of this important reef-building coral in the Caribbean is expected.

  14. Biological Responses of the Coral Montastraea annularis to the Removal of Filamentous Turf Algae

    Science.gov (United States)

    Cetz-Navarro, Neidy P.; Espinoza-Avalos, Julio; Hernández-Arana, Héctor A.; Carricart-Ganivet, Juan P.

    2013-01-01

    Coral reef degradation increases coral interactions with filamentous turf algae (FTA) and macroalgae, which may result in chronic stress for the corals. We evaluated the effects of short (2.5 month) and long (10 month) periods of FTA removal on tissue thickness (TT), zooxanthellae density (ZD), mitotic index (MI), and concentration of chlorophyll a (Chl a) in Montastraea annularis at the beginning and end of gametogenesis. Ramets (individual lobes within a colony) consistently surrounded by FTA and ramets surrounded by crustose coralline algae (CCA) were used as controls. FTA removal reduced coral stress, indicated by increased TT and ZD and lower MI. The measured effects were similar in magnitude for the short and long periods of algal removal. Ramets were more stressed at the end of gametogenesis compared with the beginning, with lower ZD and Chl a cm−2, and higher MI. However, it was not possible to distinguish the stress caused by the presence of FTA from that caused by seasonal changes in seawater temperature. Ramets surrounded by CCA showed less stress in comparison with ramets surrounded by FTA: with higher TT, Chl a cm−2 and ZD, and lower MI values. Coral responses indicated that ramets with FTA suffered the most deleterious effects and contrasted with those measured in ramets surrounded by CCA. According to published studies and our observations, there could be at least six mechanisms associated to FTA in the stress caused to M. annularis by FTA. Owing to the high cover of FTA (in contrast to macroalgae and CCA) in the Caribbean, the chronic stress, the overgrowth and mortality that this functional algal group can cause on M. annularis species complex, a further decline of this important reef-building coral in the Caribbean is expected. PMID:23372774

  15. The impact of urbanization on wind speed and surface aerodynamic characteristics in Beijing during 1991-2011

    Science.gov (United States)

    Liu, Junkai; Gao, Zhiqiu; Wang, Linlin; Li, Yubin; Gao, Chloe Y.

    2018-06-01

    Urbanization has a significant influence on climate and meteorological conditions through altering surface aerodynamic characteristics. Based on observational data collected at 15 levels on a 325 m meteorological tower in Beijing during 1991-2011, changes in wind speed, vertical profile, aerodynamic roughness length (z0), and zero-plane displacement height (zd) were analyzed. Decreasing trends were observed predominantly during this period, especially for levels between 65 and 140 m where the largest decreasing rates often occur. The annual and seasonal (spring, summer, autumn, and winter) mean wind speeds at 15 levels all present decreasing trends with average rates of 0.029, 0.024, 0.023, 0.040, and 0.019 m s-1 a-1, respectively. The decreases in strong wind categories contribute most to the reduction of mean wind speed. Furthermore, in 2005-2011, the diurnal maximum wind speeds at lower levels tend to appear earlier as compared to those in 1991-1997, while the patterns of diurnal cycle between different levels become more similar in these periods. Besides, the phenomena of "kink" in wind profiles are visible in various atmospheric stabilities, and the average height of a kink has increased from about 40 m to nearly 80 m associated with urbanization during 1991-2011. In addition, the results of z0 and zd calculated using the wind profile method vary with wind directions due to surface heterogeneity and that larger values often occur along with southerly winds. Both z0 and zd show increasing trends in different sectors during 1991-2011, and the annual mean z0 and zd have increased from less than 1 m to greater than 2 m, and from less than 10 m to greater than 20 m, respectively.

  16. Z-dark search with the ATLAS detector

    CERN Document Server

    INSPIRE-00212108

    2016-01-01

    The search of the "hidden sector" via new neutral light bosons Z-dark ($Z_{d}$) could be revealed by the study of the decay of the discovered Higgs-like boson or any other undiscovered Higgs boson. After the LHC concluded a successful first period of running, the ATLAS Collaboration published its latest results on the $H\\rightarrow Z_{d}Z_{d}\\rightarrow 4l$ analysis using up to 20 fb$^{-1}$ of integrated luminosity at $\\sqrt{s}=8$ TeV. In this proceeding I present a summary of the recent results on the search of the $Z_{d}$ in the signature $H\\rightarrow Z_{d}Z_{d}\\rightarrow 4l$ with the ATLAS detector at the LHC.

  17. Morphological, functional and metabolic imaging biomarkers: assessment of vascular-disrupting effect on rodent liver tumours

    International Nuclear Information System (INIS)

    Wang, Huaijun; Li, Junjie; Keyzer, Frederik De; Yu, Jie; Feng, Yuanbo; Marchal, Guy; Ni, Yicheng; Chen, Feng; Nuyts, Johan

    2010-01-01

    To evaluate effects of a vascular-disrupting agent on rodent tumour models. Twenty rats with liver rhabdomyosarcomas received ZD6126 intravenously at 20 mg/kg, and 10 vehicle-treated rats were used as controls. Multiple sequences, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) with the microvascular permeability constant (K), were acquired at baseline, 1 h, 24 h and 48 h post-treatment by using 1.5-T MRI. [ 18 F]fluorodeoxyglucose micro-positron emission tomography ( 18 F-FDG μPET) was acquired pre- and post-treatment. The imaging biomarkers including tumour volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient (ADC) and K from MRI, and maximal standardised uptake value (SUV max ) from FDG μPET were quantified and correlated with postmortem microangiography and histopathology. In the ZD6126-treated group, tumours grew slower with higher necrosis ratio at 48 h (P max dropped at 24 h (P < 0.01). Relative K of tumour versus liver at 48 h correlated with relative vascular density on microangiography (r = 0.93, P < 0.05). The imaging biomarkers allowed morphological, functional and metabolic quantifications of vascular shutdown, necrosis formation and tumour relapse shortly after treatment. A single dose of ZD6126 significantly diminished tumour blood supply and growth until 48 h post-treatment. (orig.)

  18. Scaling Limit of Symmetric Random Walk in High-Contrast Periodic Environment

    Science.gov (United States)

    Piatnitski, A.; Zhizhina, E.

    2017-11-01

    The paper deals with the asymptotic properties of a symmetric random walk in a high contrast periodic medium in Z^d, d≥1. From the existing homogenization results it follows that under diffusive scaling the limit behaviour of this random walk need not be Markovian. The goal of this work is to show that if in addition to the coordinate of the random walk in Z^d we introduce an extra variable that characterizes the position of the random walk inside the period then the limit dynamics of this two-component process is Markov. We describe the limit process and observe that the components of the limit process are coupled. We also prove the convergence in the path space for the said random walk.

  19. Correlation of MRI Biomarkers with Tumor Necrosis in Hras5 Tumor Xenograft in Athymic Rats

    Directory of Open Access Journals (Sweden)

    Daniel P. Bradley

    2007-05-01

    Full Text Available Magnetic resonance imaging (MRI can measure the effects of therapies targeting the tumor vasculature and has demonstrated that vascular-damaging agents (VDA induce acute vascular shutdown in tumors in human and animal models. However, at subtherapeutic doses, blood flow may recover before the induction of significant levels of necrosis. We present the relationship between changes in MRI biomarkers and tumor necrosis. Multiple MRI measurements were taken at 4.7 T in athymic rats (n = 24 bearing 1.94 ± 0.2-cm3 subcutaneous Hras5 tumors (ATCC 41000 before and 24 hours after clinically relevant doses of the VDA, ZD6126 (0-10 mg/kg, i.v.. We measured effective transverse relaxation rate (R2*, initial area under the gadolinium concentration-time curve (IAUGC60/150, equivalent enhancing fractions (EHF60/150, time constant (Ktrans, proportion of hypoperfused voxels as estimated from fit failures in Ktrans analysis, and signal intensity (SI in T2-weighted MRI (T2W. ZD6126 treatment induced < 90% dose-dependent tumor necrosis at 10 mg/kg; correspondingly, SI changes were evident from T2W MRI. Although R2* did not correlate, other MRI biomarkers significantly correlated with necrosis at doses of ≥ 5 mg/kg ZD6126. These data on Hras5 tumors suggest that the quantification of hypoperfused voxels might provide a useful biomarker of tumor necrosis.

  20. Synthesis of geopolymer composites from a mixture of volcanic scoria and metakaolin

    Directory of Open Access Journals (Sweden)

    J.N.Y. Djobo

    2014-12-01

    Full Text Available The aim of this work is to valorize volcanic scoria by using them as starting material for geopolymers production. Nevertheless, volcanic scoria possesses low reactivity. Various amounts of metakaolin (5%, 10%, 15%, 20% and 25% were added into two volcanic scoria (ZD and ZG in order to improve their reactivity. Two alkaline solutions were used to activate the aluminosilicate materials. The starting materials were characterized by particle size distribution, specific surface area, chemical and mineralogical composition. The geopolymers were characterized by the setting time, XRD, FTIR, SEM and compressive strength. The results indicated that volcanic scoria have low specific surface area (2.3 m2/g for ZD, 15.7 m2/g for ZG, high average particle size (d50 = 13.08 μm and 10.68 μm for ZD and for ZG respectively and low glass phase contents. Metakaolin have a smaller average particle size (d50 = 9.95 μm and high specific surface (20.5 m2/g. The compressive strength of geopolymers increased in the ranges of 23–68 MPa and 39–64 MPa for geopolymers from ZD–MK and ZG–MK respectively. This study shows that despite the low reactivity of volcanic scoria it can still be used to synthesize geopolymers with good physical and mechanical properties.

  1. β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Darimont Christian

    2004-08-01

    Full Text Available Abstract Background Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114 could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet. Methods Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study. Results In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG and diacylglycerol (DAG accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet. Conclusions These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.

  2. A new spectrofluorimetric assay method for vandetanib in tablets ...

    African Journals Online (AJOL)

    556. 7. Balwani G, Joseph E, Reddi S, Nagpal V, Saha RN. Rapid, Simple, and Sensitive Spectrofluorimetric Method for the Estimation of Ganciclovir in Bulk and. Pharmaceutical Formulations. J Spectrosc 2013;. 2013:1-5. 8. Bai F, Johnson J, ...

  3. Digitalis toxicity

    Science.gov (United States)

    ... Concepts and Clinical Practice . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 152. Goldberger AL, Goldberger ZD, ... Electrocardiography: A Simplified Approach . 8th ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 18. Nelson LS, Ford MD. ...

  4. The Impact of Wine Style and Sugar Addition in liqueur d’expedition (dosage Solutions on Traditional Method Sparkling Wine Composition

    Directory of Open Access Journals (Sweden)

    Belinda Kemp

    2017-01-01

    Full Text Available The purpose of this study was to investigate the effect of wine style and cane sugar addition in the liqueur d’expedition (dosage solution on volatile aroma compounds (VOCs in traditional method sparkling wine. There were 24 bottles of each treatment produced. Treatments were sparkling wine zero dosage (ZD; NV sparkling wine + sugar (BS; unoaked still Chardonnay wine + sugar (UC; Pinot noir 2009 sparkling wine + sugar (PN; Niagara produced Brandy + sugar (B and Icewine (IW. The control treatment in the sensory analysis was an oaked still Chardonnay wine + sugar (OC because the zero-dosage wine was not suitable for a difference test that compared wines with sugar to one without. Standard wine chemical parameters were analysed before disgorging and after liqueur d’expedition was added and included; pH, titratable acidity (TA g/L, alcohol (v/v %, residual sugar (RS g/L, free and total SO2 and total phenolics (A.U.. Volatile aroma compounds (VOCs analysed by Headspace Solid- Phase Micro-Extraction Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS included two alcohols, and six ethyl esters. ZD wines had the highest foam height and highest dissolved oxygen level. Sugar affected VOC concentrations in all treatments at five weeks post-disgorging, but by 15 weeks after liqueur d’expedition addition, the wine with added sugar had similar VOC concentrations to the ZD wines. The type of wines used in the dosage solutions had more influence on VOC concentrations than sugar addition.

  5. Local distribution of wall static pressure and heat transfer on a rough flat plate impinged by a slot air jet

    Science.gov (United States)

    Meda, Adimurthy; Katti, Vadiraj V.

    2017-08-01

    The present work experimentally investigates the local distribution of wall static pressure and the heat transfer coefficient on a rough flat plate impinged by a slot air jet. The experimental parameters include, nozzle-to-plate spacing (Z /D h = 0.5-10.0), axial distance from stagnation point ( x/D h ), size of detached rib ( b = 4-12 mm) and Reynolds number ( Re = 2500-20,000). The wall static pressure on the surface is recorded using a Pitot tube and a differential pressure transmitter. Infrared thermal imaging technique is used to capture the temperature distribution on the target surface. It is observed that, the maximum wall static pressure occurs at the stagnation point ( x/D h = 0) for all nozzle-to-plate spacing ( Z/D h ) and rib dimensions studied. Coefficient of wall static pressure ( C p ) decreases monotonically with x/D h . Sub atmospheric pressure is evident in the detached rib configurations for jet to plate spacing up to 6.0 for all ribs studied. Sub atmospheric region is stronger at Z/D h = 0.5 due to the fluid accelerating under the rib. As nozzle to plate spacing ( Z/D h ) increases, the sub-atmospheric region becomes weak and vanishes gradually. Reasonable enhancement in both C p as well as Nu is observed for the detached rib configuration. Enhancement is found to decrease with the increase in the rib width. The results of the study can be used in optimizing the cooling system design.

  6. The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the hippocampus.

    Science.gov (United States)

    Hu, Yan-Dan; Pang, Wei; He, Cong-Cong; Lu, Hao; Liu, Wei; Wang, Zi-Yu; Liu, Yan-Qiang; Huang, Cheng-Yu; Jiang, Yu-Gang

    2017-11-01

    This study was carried out to understand the effects of zinc deficiency in rats aged 0∼2 months on learning and memory, and the brain-derived neurotrophic factor (BDNF) gene methylation status in the hippocampus. The lactating mother rats were randomly divided into three groups (n = 12): zinc-adequate group (ZA: zinc 30 mg/kg diet), zinc-deprived group (ZD: zinc 1 mg/kg diet), and a pair-fed group (PF: zinc 30 mg/kg diet), in which the rats were pair-fed to those in the ZD group. After weaning (on day 23), offspring were fed the same diets as their mothers. After 37 days, the zinc concentrations in the plasma and hippocampus were measured, and the behavioral function of the offspring rats was measured using the passive avoidance performance test. We then assessed the DNA methylation patterns of the exon IX of BDNF by methylation-specific quantitative real-time PCR and the mRNA expression of BDNF in the hippocampus by RT-PCR. Compared with the ZA and PF groups, rats in the ZD group had shorter latency period, lower zinc concentrations in the plasma and hippocampus (P zinc-deficient diet during 0∼2 month period. Furthermore, this work supports the speculative notion that altered DNA methylation of BDNF in the hippocampus is one of the main causes of cognitive impairment by zinc deficiency.

  7. Two dimensional conformal supergravity and critical behavior

    International Nuclear Information System (INIS)

    Abdalla, E.; Abdalla, M.C.B.; Zadra, A.

    1988-01-01

    A recent construction of Z-D gravity is generalized to the supersymmetric case. Anomalous dimensions are found. A super Kac-Moody SL (Z,R) algebra is obtained as a starting point using the anomaly equation for the graviton/gravitino system. (authors) [pt

  8. A Dynamic Model of Heavy Ion 7Li Irradiation Mutagenesis Based on Maize Inbred Line Nutrition Difference

    Science.gov (United States)

    Hu, Jin-Shan; Geng, Jin-Peng; Li, Duo-Fang; Sui, Li; Zhan, Yong

    2018-04-01

    Not Available Supported by the National Natural Science Foundation of China under Grant No 11735006, the Hebei Natural Science Foundation of China under Grant No B2014209314, and the Hebei Science and Technology Research Project of Higher Education under Grant No ZD2017023.

  9. Emulsion Polymerization of MMA/BA in the Presence of Ionic Surface Active Monomers(Ⅰ)--Syntheses and Polymerization Reactivities of the Surfmers%离子型表面活性单体存在下的MMA/BA乳液聚合(Ⅰ)--表面活性单体的合成及其(共)聚合活性

    Institute of Scientific and Technical Information of China (English)

    张茂根; 翁志学; 黄志明; 毛昕; 潘祖仁

    1999-01-01

    合成了两种离子型表面活性单体(Surfmer)--磺化-十二醇-烯丙基甘油-丁二酸酯钠盐(ZC-L)和磺化-十二醇-甲基丙烯酰甘油-丁二酸酯钠盐(ZD-L).着重研究了ZC-L的结构、表面张力行为、均聚及共聚能力.实验结果表明,不同Surfmer用量以及不同固含量下,MMA/BA/Surfmer,MMA/Surfmer及BA/Surfmer共聚乳液的表面张力较高,说明Surfmer已通过共聚结合在乳胶粒上,乳液中残留甚少.对MMA/BA体系,ZC-L的共聚性能比ZD-L好.

  10. On the Tannaka-Artin problem

    International Nuclear Information System (INIS)

    Mahdavi Hezavehi, M.

    1995-05-01

    Let D be a division ring of index n over its centre F. Denote by RN(D * ) and N(D * ) the images of D * = D - {0} under the reduced norm functions of D to F, respectively. Algebraic properties of the Abelian factor group G(D) := D * /RN(D * )D', where D' is the derived group of D * , are investigated. It is shown that there is a group homormorphism φ : G(D) → H(D), where H(D) := RN(D * )/N(D * ), whose kernel is a homormophic image of the reduced Whitehead group SK 1 (D). Using this result, it is proved that SK 1 (D) = {1} if and only if Ω = Z(D') and φ is an isomorphism, where Ω is the subgroup of the existing n-th roots of unity in F and Z(D') is the centre of the derived group of D * . (author). 8 refs

  11. Constitutive expression of feedback-insensitive cystathionine γ-synthase increases methionine levels in soybean leaves and seeds

    Institute of Scientific and Technical Information of China (English)

    YU Yang; HOU Wen-sheng; YaeI Hacham; SUN Shi; WU Cun-xiang; Ifat Matityahu; SONG Shikui; RacheI Amir; HAN Tian-fu

    2018-01-01

    Soybean (Glycine max (L.) Merr.) is a major crop that provides plant-origin protein and oil for humans and livestock. Although the soybean vegetative tissues and seeds provide a major source of high-quality protein, they suffer from low concentration of an essential sulfur-containing amino acid, methionine, which significantly limits their nutritional quality. The level of methionine is mainly controlled by the first unique enzyme of methionine synthesis, cystathione γ-synthase (CGS). Aiming to elevate methionine level in vegetative tissues and seeds, we constitutively over-expressed a feedback-insensitive Arabidopsis CGS (AtD-CGS) in soybean cultivars, Zigongdongdou (ZD) and Jilinxiaoli 1 (JX). The levels of soluble methionine increased remarkably in leaves of transgenic soybeans compared to wild-type plants (6.6- and 7.3-fold in two transgenic ZD lines, and 3.7-fold in one transgenic JX line). Furthermore, the total methionine contents were significantly increased in seeds of the transgenic ZD lines (1.5- to 4.8-fold increase) and the transgenic JX lines (1.3- to 2.3-fold increase) than in the wild type. The protein contents of the transgenic soybean seeds were significantly elevated compared to the wild type, suggesting that the scarcity of methionine in soybeans may limit protein accumulation in soybean seeds. The increased protein content did not alter the profile of major storage proteins in the seeds. Generally, this study provides a promising strategy to increase the levels of methionine and protein in soybean through the breeding programs.

  12. Contribution of presynaptic HCN channels to excitatory inputs of spinal substantia gelatinosa neurons.

    Science.gov (United States)

    Peng, S-C; Wu, J; Zhang, D-Y; Jiang, C-Y; Xie, C-N; Liu, T

    2017-09-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pathological pain-associated voltage-gated ion channels. They are widely expressed in central nervous system including spinal lamina II (also named the substantia gelatinosa, SG). Here, we examined the distribution of HCN channels in glutamatergic synaptic terminals as well as their role in the modulation of synaptic transmission in SG neurons from SD rats and glutamic acid decarboxylase-67 (GAD67)-GFP mice. We found that the expression of the HCN channel isoforms was varied in SG. The HCN4 isoform showed the highest level of co-localization with VGLUT2 (23±3%). In 53% (n=21/40 neurons) of the SG neurons examined in SD rats, application of HCN channel blocker, ZD7288 (10μM), decreased the frequency of spontaneous (s) and miniature (m) excitatory postsynaptic currents (EPSCs) by 37±4% and 33±4%, respectively. Consistently, forskolin (FSK) (an activator of adenylate cyclase) significantly increased the frequency of mEPSCs by 225±34%, which could be partially inhibited by ZD7288. Interestingly, the effects of ZD7288 and FSK on sEPSC frequency were replicated in non-GFP-expressing neurons, but not in GFP-expressing GABAergic SG neurons, in GAD67-GFP transgenic C57/BL6 mice. In summary, our results represent a previously unknown cellular mechanism by which presynaptic HCN channels, especially HCN4, regulate the glutamate release from presynaptic terminals that target excitatory, but not inhibitory SG interneurons. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Urban roughness mapping validation techniques and some first results

    NARCIS (Netherlands)

    Bottema, M; Mestayer, PG

    1998-01-01

    Because of measuring problems related to evaluation of urban roughness parameters, a new approach using a roughness mapping tool has been tested: evaluation of roughness length z(o) and zero displacement z(d) from cadastral databases. Special attention needs to be given to the validation of the

  14. De la circulation des "locis sanctis" - le Mons Sion a Prague

    Czech Academy of Sciences Publication Activity Database

    Benešovská, Klára

    2014-01-01

    Roč. 1, č. 1 (2014), s. 50-62 ISSN 2336-3452 R&D Projects: GA ČR GA13-39192S Institutional support: RVO:68378033 Keywords : Mons Sion * Jindřich Zdík * Strahov * pilgrimage * Jerusalem * Holy Sepulchre Subject RIV: AL - Art, Architecture, Cultural Heritage

  15. Hard disks with SCSI interface

    CERN Document Server

    Denisov, O Yu

    1999-01-01

    The testing of 20 models of hard SCSI-disks is carried out: the Fujitsu MAE3091LP; the IBM DDRS-39130, DGHS-318220, DNES-318350, DRHS-36V and DRVS-18V; the Quantum Atlas VI 18.2; the Viking 11 9.1; the Seagate ST118202LW, ST118273LW, ST118273W, ST318203LW, ST318275LW, ST34520W, ST39140LW and ST39173W; and the Western Digital WDE9100-0007, WDE9100-AV0016, WDE9100-AV0030 and WDE9180-0048. All tests ran under the Windows NT 4.0 workstation operating system with Service Pack 4, under video mode with 1024*768 pixel resolution, 32- bit colour depth and V-frequency equal to 85 Hz. The detailed description and characteristics of SCSI stores are presented. Test results (ZD Winstone 99 and ZD WinBench 99 tests) are given in both table and diagram (disk transfer rate) forms. (0 refs).

  16. The effects of chilling stress after anthesis on the physicochemical properties of rice (Oryza sativa L) starch.

    Science.gov (United States)

    Zhu, Dawei; Wei, Haiyan; Guo, Baowei; Dai, Qigen; Wei, Cunxu; Gao, Hui; Hu, Yajie; Cui, Peiyuan; Li, Min; Huo, Zhongyang; Xu, Ke; Zhang, Hongcheng

    2017-12-15

    This study investigates the effect of chilling stress, over a period of three days after anthesis, on the physicochemical properties of starches derived from six rice cultivars. Chilling stress significantly affected the grain characteristics and physicochemical properties of rice starches, except for those of two varieties, NJ 9108 and ZD 18. In the other four rice cultivars subjected to chilling stress, the content of medium, and large sized granules showed a decrease, and an increase, respectively. Amylose content increased as a result of chilling stress, thereby resulting in starch with a lower swelling power, water solubility, and higher retrogradation enthalpy and gelatinization temperature. Chilling stress led to deterioration of cooked rice quality as determined by the pasting properties of starch. This study indicated that among the cultivars studied, the two rice varieties most resistant to chilling stress after rice anthesis were NJ 9108 and ZD 18. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Higher-Order Inhomogeneous Generalized Heisenberg Supermagnetic Model

    Science.gov (United States)

    Yan, Zhao-Wen; Zhang, Mei-Na; Cui, Ji-Feng

    2018-05-01

    Not Available Supported by the National Natural Science Foundation of China under Grant Nos 11605096 and 11601247, the Science Research Project of Inner Mongolia University of Technology under Grant No ZD201613, and the Innovation Foundation of Inner Mongolia University for the College Students under Grant No 201711208.

  18. Search Results | Page 82 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2010-01-01

    Results 811 - 820 of 8491 ... IPv6 deployment. Published date. January 1, 2010. Studies. -. Welcome address by Prof. Z.D. Kadzamira, Chairman, UA, at the UbuntuNet Connect 2010. Published date. January 1, 2010. Studies. -. CHAIN project and prospects for Sub Saharan Africa. Published date. January 1, 2010. Pages.

  19. Foliar urea application affects nitric oxide burst and glycine betaine metabolism in two maize cultivars under drought

    International Nuclear Information System (INIS)

    Zhang, L.; Zhang, X.; Wang, K.; Zhao, Y.; Zhai, Y.; Gao, M.

    2011-01-01

    Foliar urea has been proved to act a better role in alleviation of the negative effects of drought stress (DS). However, the modulation mechanism of foliar urea are not conclusive in view of nitric oxide (NO) burst and glycine betaine metabolism and their relationship. Two maize ( Zea mays L.) cultivars (Zhengdan 958, JD958, Jundan 20, ZD20) were grown in hydroponic medium, which were treated with spraying of urea concentration of 15 g L/sup -1/ and two water regimes (non-stress and DS simulated by the addition of polyethylene glycol (PEG, 15% w/v, MW 6000). The ten-day DS treatment increased betaine aldehyde dehydrogenase (BADH) activity, choline content and nitric oxide (NO) content acted as the key enzyme, initial substrate and a nitrogenous signal substance respectively in GB synthesis metabolism, thus, induced to great GB accumulation. The accumulation of NO reached the summit earlier than that of GB. The more positive/less negative responses were recorded in JD958 as compared with ZD20 to DS. Addition of foliar ur ea could increase accumulation of choline and BADH activity as well as NO content, thereby, increase GB accumulation under DS. These positive effects of urea applying foliarly on all parameters measured were more pronounced in cultivar JD20 than those in ZD958 under drought. It is, therefore, concluded that increases of both BADH activity and choline content possibly resulted in enhancement of GB accumulation. Foliar urea application could provoke better GB accumulation by modulation of GB metabolism, possibly mediating by NO burst as a signal molecule during drought, especially in the drought sensitive maize cultivar. (author)

  20. Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2

    NARCIS (Netherlands)

    Hooijberg, J. H.; Broxterman, H. J.; Kool, M.; Assaraf, Y. G.; Peters, G. J.; Noordhuis, P.; Scheper, R. J.; Borst, P.; Pinedo, H. M.; Jansen, G.

    1999-01-01

    Transfection of multidrug resistance proteins (MRPs) MRP1 and MRP2 in human ovarian carcinoma 2008 cells conferred a marked level of resistance to short-term (1-4 h) exposure to the polyglutamatable antifolates methotrexate (MTX; 21-74-fold), ZD1694 (4-138-fold), and GW1843 (101-156-fold). Evidence

  1. 78 FR 11101 - Air Quality: Revision to Definition of Volatile Organic Compounds-Exclusion of trans

    Science.gov (United States)

    2013-02-15

    ... Review of Solstice\\TM\\ 1233zd(E) D. Significant New Alternatives Policy Program Review of Solstice\\TM... compounds creates an incentive for industry to use negligibly reactive compounds in place of more highly reactive compounds that are regulated as VOCs. The EPA lists compounds that it has determined to be...

  2. 78 FR 53029 - Air Quality: Revision to Definition of Volatile Organic Compounds-Exclusion of trans

    Science.gov (United States)

    2013-08-28

    ..., is subject to restrictions under the Significant New Alternatives Policy (SNAP) program (CAA Sec. 612; 40 CFR part 82 subpart G). The SNAP program has issued final approvals for Solstice TM 1233zd(E) as a... incentive for industry to use negligibly reactive compounds in place of more highly reactive compounds that...

  3. Scintigraphic evaluation of Zenker's diverticulum

    Energy Technology Data Exchange (ETDEWEB)

    Valenza, Venanzio; Perotti, Germano; Di Giuda, Daniela [Institute of Nuclear Medicine, Policlinico A. Gemelli, Catholic University of Sacred Heart, Largo Gemelli 8, 00168, Rome (Italy); Castrucci, Gioacchino [Department of Surgery, Bel Colle Hospital, Viterbo (Italy); Celi, Giuseppe; Restaino, Gennaro [Institute of Radiology, Catholic University of Sacred Heart, Rome (Italy)

    2003-12-01

    Zenker's diverticulum (ZD) is a rare pathology, with a prevalence of between 0.01% and 0.11%. Definitive diagnosis of ZD can be accomplished by contrast radiographic examination (barium oesophagogram, BE); oesophageal manometry (ME) is recommended mainly for those patients suffering from dysphagia and/or gastro-oesophageal reflux. The aims of the present study were to assess whether oropharyngo-oesophageal scintigraphy (OPES) is able (a) to visualise ZD and (2) to demonstrate the corresponding alteration in the swallowing phases. We studied 16 patients (nine male, seven female, mean age 67.4 years), and 17 healthy volunteers (ten male, seven female, mean age 53 years) as a control group. All the patients underwent ME, BE and OPES. Nine patients underwent surgery and six of them were re-evaluated after 6 months. We administered 10 ml of water with 37 MBq of technetium-99m colloid through a straw, acquiring 480 sequential images (0.125 s/frame for a total of 60 s) with the patient standing in front of the gamma camera in the 80 right anterior oblique position. Two static images were performed at the end of the dynamic phase, before and after ingestion of 100 ml of unlabelled water to evaluate the presence of inflammation (persistence of radioactivity in the diverticulum or oesophagus). Study of the sequential scintigraphic images and time-activity curves permitted both qualitative (diverticulum visualisation, multiple deglutitions, reflux, presence of inflammation) and quantitative analyses [oral, pharyngeal and oesophageal transit times and retention indexes, tracheal aspiration percentage] of swallowing disorders. OPES showed a good correlation with the results of other diagnostic techniques usually performed in patients with this pathology, and especially with ME in the evaluation of oropharyngeal phase disorders. Furthermore, OPES is a sensitive and simple technique that is well tolerated and entails a low irradiation dose for patients. (orig.)

  4. An Analysis of Elliptic Grid Generation Techniques Using an Implicit Euler Solver.

    Science.gov (United States)

    1986-06-09

    at M. =0.90 and a=00 is when interpolating for the radius of curvature obtained. One expects the computed shock strength (r), a second examination is...solver to yield accurate second-order, ... v.s zd solutions. References Snn, .:-P.. Flr.e ’rference Methods In Z, .tational Fluid DinamIcs , to he published

  5. Linkage Map of the Long Arm of Barley Chromosome 3 Using C-Bands and Marker Genes

    DEFF Research Database (Denmark)

    Linde-Laursen, Ib

    1982-01-01

    locations. No recombination was observed between the two proximal C-band locations whereas the two distal locations recombined with a frequency of 12 2 per cent. The three C-band locations were linked with loci cer-zd, uz, and cer-zn, but not with the tightly linked loci Est-1 and Est-4. The order...

  6. The rational maps Fλ(z)

    Indian Academy of Sciences (India)

    It is proved that the rational maps in the family {z → zm +λ/zd : λ ∈ C\\{0}} for integers m, d ≥ 2 ... The problem of the existence of Herman rings of a rational map has been studied by. Lyubich in [9] ..... Surveys 41(4) (1986) 35–95. [10] Milnor J ...

  7. Establishing quality control ranges for antimicrobial susceptibility testing of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus: a cornerstone to develop reference strains for Korean clinical microbiology laboratories.

    Science.gov (United States)

    Hong, Sung Kuk; Choi, Seung Jun; Shin, Saeam; Lee, Wonmok; Pinto, Naina; Shin, Nari; Lee, Kwangjun; Hong, Seong Geun; Kim, Young Ah; Lee, Hyukmin; Kim, Heejung; Song, Wonkeun; Lee, Sun Hwa; Yong, Dongeun; Lee, Kyungwon; Chong, Yunsop

    2015-11-01

    Quality control (QC) processes are being performed in the majority of clinical microbiology laboratories to ensure the performance of microbial identification and antimicrobial susceptibility testing by using ATCC strains. To obtain these ATCC strains, some inconveniences are encountered concerning the purchase cost of the strains and the shipping time required. This study was focused on constructing a database of reference strains for QC processes using domestic bacterial strains, concentrating primarily on antimicrobial susceptibility testing. Three strains (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) that showed legible results in preliminary testing were selected. The minimal inhibitory concentrations (MICs) and zone diameters (ZDs) of eight antimicrobials for each strain were determined according to the CLSI M23. All resulting MIC and ZD ranges included at least 95% of the data. The ZD QC ranges obtained by using the CLSI method were less than 12 mm, and the MIC QC ranges extended no more than five dilutions. This study is a preliminary attempt to construct a bank of Korean QC strains. With further studies, a positive outcome toward cost and time reduction can be anticipated.

  8. The Higgs as a portal to the hidden sector via an analysis of $H\\to Zd_d Z_d \\to 4l$ using the ATLAS detector

    CERN Document Server

    Unwuchola, D A

    2015-01-01

    The Standard Model (SM) has well known deciencies, and there is clearly need for new physics beyond the SM. The particles manifesting the new physics would interact at most weakly with the SM particles, and hence they are termed dark. The Higgs boson is potentially a favourable route for the production of the dark particles. There are a large class of theories where couplings or mixings at the Higgs level leads to exotic Higgs decays, which nonetheless do not signicantly disturb the known physics below the Higgs level. This is therefore a signicant potential discovery opportunity. We present the motivation and progress made in the studies which have been carried out as part of designing the search for the exotic decay of the SM Higgs which proceeds via a dark force back to SM four leptons, H $\\to$ Z$_d$Z$_d$ $\\to$ 4l from the LHC run 1 data using the ATLAS detector.

  9. Fulltext PDF

    Indian Academy of Sciences (India)

    https://www.youtube.com/watch?v=zdKX9qO9BpQ. Suggestions. We now suggest a few experiments which the reader may wish to attempt. Experiment 1: Interaction of a Vortex Ring With a Wall. The experiment discussed above may be repeated in a shallow glass beaker. When the vortex ring approaches the bottom of the.

  10. Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells

    Science.gov (United States)

    To evaluate the influence of resveratrol on cellular zinc status, normal human prostate epithelial (NHPrE) cells were treated with 6 levels of resveratrol (0, 0.5, 1, 2.5, 5 and 10 microM) and 4 levels of zinc [0, 4, 16, and 32 microM for zinc-deficient (ZD), zinc-normal (ZN), zinc-adequate (ZA), an...

  11. Quasi-symmetric Conjugacy of Blaschke Products on the unit Circle

    DEFF Research Database (Denmark)

    Petersen, Carsten Lunde

    2007-01-01

    Let B be a Blaschke product for which the restriction to the unit circle 1 is a degree d > 1 covering. We prove that B is quasi-symmetrically conjugate to z zd on 1, if all its periodic points in 1 are repelling and if 1 does not intersect the -limit set of any recurrent critical point for B....

  12. An essential representation for a product system over a finitely ...

    Indian Academy of Sciences (India)

    25

    2017-10-06

    An essential representation for a product system over a finitely generated subsemigroup of Z d. S.P. Murugan and S. Sundar. October 6, 2017. Abstract. Let S ⊂ Zd be a finitely generated subsemigroup. Let E be a product system over S. We show that there exists an infinite dimensional separable Hilbert space. H and a ...

  13. Hvězdářství krále Jana

    Science.gov (United States)

    Černá, Alena M.; Hadrava, Petr; Hadravová, Alena; Stluka, Martin

    The critical edition of the collection "King John's Astronomy" is based on the Old Czech manuscript written at the beginning of the 15th century which is preserved at the Library of the National Museum in Prague (ms. II F 14). The collection consists of several separate parts - first of all it contains astronomical and astrological treatises refering to Ptolemy's works. Explanations on the impact of the seven planets and twelve zodiacal signs on the fate of man, who was born under their influence, prevail in the texts. The texts which are connected with Hippocrates and Galenos' doctrines about humoral physiology and humoral pathology are another subject. They are supplemented by a treatise on blood-letting and by pharmaceutical instructions on different weight units. Another treatise deals with God, God's acts and with human fate. The manuscript also contains calendar tools for the calculation of Easter and other feasts during the year. The origin of this Old Czech text coincides with the period of the development of national languages as languages of science. Vocabulary contained in the manuscript is rich. It yields evidence about the formation of terminological systems in various fields involved in the collection. The Old Czech language of this literary monument exhibits unexpectedly archaic features. The present edition is a result of interdisciplinary collaboration of researchers from the fields of diachronic Bohemistics, classical philology, and astronomy. The publication is completed with the critical apparatus, indices, vocabulary, by a list of the chosen literature and other related supplements.

  14. Characterisations of Partition of Unities Generated by Entire Functions in Cd

    DEFF Research Database (Denmark)

    Christensen, Ole; Kim, Hong Oh; Kim, Rae Young

    2017-01-01

    Collections of functions forming a partition of unity play an important role in analysis. In this paper we characterise for any N∈N the entire functions P for which the partition of unity condition ∑n∈ZdP(x+n)χ[0,N]d(x+n)=1 holds for all x∈Rd. The general characterisation leads to various easy wa...

  15. Symmetry and asymmetry rogue waves in two-component coupled nonlinear Schrödinger equations

    Science.gov (United States)

    Li, Zai-Dong; Huo, Cong-Zhe; Li, Qiu-Yan; He, Peng-Bin; Xu, Tian-Fu

    2018-04-01

    Not Available Project supported by the National Natural Science Foundation of China (Grant Nos. 11304270 and 61774001), the Key Project of Scientific and Technological Research of Hebei Province, China (Grant No. ZD2015133), the Construction Project of Graduate Demonstration Course of Hebei Province, China (Grant No. 94/220079), and the Natural Science Foundation of Hunan Province, China (Grant No. 2017JJ2045).

  16. (Non-) Gibbsianness and Phase Transitions in Random Lattice Spin Models

    NARCIS (Netherlands)

    Külske, C.

    1999-01-01

    We consider disordered lattice spin models with finite-volume Gibbs measures µΛ[η](dσ). Here σ denotes a lattice spin variable and η a lattice random variable with product distribution P describing the quenched disorder of the model. We ask: when will the joint measures limΛ↑Zd P(dη)µΛ[η](dσ) be

  17. Optimize the thermoelectric performance of CdO ceramics by doping Zn

    Science.gov (United States)

    Zha, Xin-Yu; Gao, Lin-Jie; Bai, Hong-Chang; Wang, Jiang-Long; Wang, Shu-Fang

    2017-09-01

    Not Available Project supported by the National Natural Science Foundation of China (Grant No. 51372064), the Natural Science Foundation of Hebei Province, China (Grant Nos. A2014201176 and E2017201209), the Outstanding Doctoral Cultivation Project of Hebei University (Grant No. YB201502), and the Hebei Province Universities Science and Technology Program funded by the Hebei Provincial Education Department, China (Grant Nos. ZD2014018 and QN2017017).

  18. 鱆雉韶 鱆鞅鞣鞜恊 触

    Indian Academy of Sciences (India)

    RANJEET

    @ias.ernet.in lekpkj if=dk vdkneh osclkbV www.ias.ac.in/patrika/ esa miyC/k gSA lekpkj if=dk dh fu;fer izfr izkIr djus ds fy,] d`i;k vdkneh ds dk;Zdkjh lfpo dks fy[ksa. ¼chandra@ias.ernet.in½. iPphloha v)Z&okf'kZd cSBd] csaxywj. 4&5 tqykbZ 2014.

  19. Cognitive Engineering of Advanced Information Technology for Air Force Systems Design and Deployment: Prototype for Air Defense Intelligence and Operations

    Science.gov (United States)

    1989-10-01

    defines decision problems according to their location along decision time, threat and awareness continuua, as suggested in Figure 2.16. Biddle (1989...4NKqC9, a, LWL 4. 3, 111M tts t vI3031t:V Zd LAC. NIC - Zii oe> ~~4c Zo t -- C , -C >-- 3050 IA , 6j~ I. I.. 04 306 I IC I I 307 14C A- tbt * N * IW

  20. Biological Activity of Peanut (Arachis hypogaea) Phytoalexins and Selected Natural and Synthetic Stilbenoids

    Science.gov (United States)

    2011-02-11

    prenylated flavonoids have been identified as constituents in plants, and display biological activities, such as anticancer, antiandrogen, anti-Leishmania, and...to opioid receptors was examined. ’MATERIALS AND METHODS General Experimental Procedures. HPLC -grade solvents used in the preparation of mobile phases...were obtained from Fisher (Suwanee, GA). HPLC -grade H2Owas prepared with a ZD20 four-bowl Milli-Q water system (Millipore). Deuterium oxide (99.9 atom

  1. On the formal series Witt transform

    NARCIS (Netherlands)

    Moree, P.

    2005-01-01

    Given a formal power series f(z)∈C〚z〛f(z)∈C〚z〛 we define, for any positive integer r, its r th Witt transform, Wf(r), by Wf(r)(z)=1r∑d|rμ(d)f(zd)r/d, where μμ denotes the Möbius function. The Witt transform generalizes the necklace polynomials, M(α;n)M(α;n), that occur in the cyclotomic identity

  2. Cumulative Distributions and Flow Structure of Two-Passage Shear Coaxial Injector with Various Gas Injection Ratio

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Inchul; Kim, Dohun; Koo, Jaye [Korea Aerospace Univ., Goyang (Korea, Republic of)

    2013-07-15

    To verify the effect of inner- and outer-stage gas jets, a shear coaxial injector was designed to analyze the axial velocity profile and breakup phenomenon with an increase in the measurement distance. When the measurement position was increased to Z/d=100, the axial flow showed a fully developed shape due to the momentum transfer, aerodynamic drag effect, and viscous mixing. An inner gas injection, which induces a higher momentum flux ratio near the nozzle, produces the greater shear force on atomization than an outer gas injection. Inner- and Outer-stage gas injection do not affect the mixing between the inner and outer gas flow below Z/d=5. The experiment results showed that the main effect of liquid jet breakup was governed by the gas jet of an inner stage. As the nozzle exit of the outer-stage was located far from the liquid column, shear force and turbulence breaking up of the liquid jets do not fully affect the liquid column. In the case of an inner-stage gas injection momentum flux ratio within 0.84, with the increase in the outer gas momentum flux ratio, the Smd decreases. However, at an inner-stage gas jet momentum flux ratio over 1.38, the Smd shows the similar distribution.

  3. प्राचीन सभ्यता के विकास एवं विनाश मे जलवायु का योगदान: पुरातात्विक अवशेषो पर आधारित एक अध्ययन

    Digital Repository Service at National Institute of Oceanography (India)

    Gaur, A.S.

    Zme ‘| Obdm`w H$m `moJXmZ… nwamVmpËdH$ Adeofm| na AmYm[aV EH$ AÜ``Z E A{ZéÕ {g§h Jm¡a gmam§e Obdm`w n[adV©Z EH$ {Za§Va à{H«$`m h¡ Am¡a Bgr {gÕm§V na AmYm[aV h¢ X¡{ZH$ Ed§ dm{f©H$ n[adV©Z & bo{H$Z `h n[adV©Z n¥Ïdr na ahZo dmbo Ord-OÝVw {OZ...§ {dXoer gm{hË`m| ‘| {H$gr ‘mZd g§ñH¥${V Ho$ {dZme Ho$ {ddaU {‘bVo h¢ Am¡a CgH$o à‘wI H$maU Ho$ ê$n ‘| n¥Ïdr na Am`r ^`§H$a àb` H$m C„oI {H$`m J`m h¡& H$hm OmVm h¡ {H$ n¥Ïdr na BVZm A{YH$ nmZr ~‹T> J`m Wm {H$ Am{X ‘mZd H$mo {h‘mb` ‘| eaU boZr n‹S>r Wr...

  4. Report of the Defense Science Board Task Force on Military System Applications of Superconductors

    Science.gov (United States)

    1988-10-01

    LTS materials. A superconducting homopolar D.C. motor of 40,000 h.p., employing superconducting shield- ing, could be built at about one fourth the...ENERGY STORAGE .................... 2-17 Figure 2-9 - MOTOR /GENERATOR APPLICATIONS ............... 2-19 Figure 2-10 - MAGNETICALLY ASSISTED HYPERSONIC...sensitivity increases over current scan- ning IR sensors, # W’W Ana/&_ and U/tin-Fast Di sia$zd W Pfor radar and optical sen- sors; W’Ujh Power Motors

  5. Amplified Cold Transduction in Native Nociceptors by M-Channel Inhibition

    Czech Academy of Sciences Publication Activity Database

    Vetter, I.; Hein, A.; Sattler, S.; Hessler, S.; Touška, Filip; Bressan, E.; Parra, A.; Hager, U.; Leffler, A.; Boukalová, Štěpána; Nissen, M.; Lewis, R. J.; Belmonte, C.; Alzheimer, Ch.; Huth, T.; Vlachová, Viktorie; Reeh, P. W.; Zimmermann, K.

    2013-01-01

    Roč. 33, č. 42 (2013), s. 16627-16641 ISSN 0270-6474 Institutional support: RVO:67985823 Keywords : nociceptor * channels of HEK293T * receptor TRPM8 Subject RIV: ED - Physiology Impact factor: 6.747, year: 2013

  6. Zinc deficiency with reduced mastication impairs spatial memory in young adult mice.

    Science.gov (United States)

    Kida, Kumiko; Tsuji, Tadataka; Tanaka, Susumu; Kogo, Mikihiko

    2015-12-01

    Sufficient oral microelements such as zinc and fully chewing of foods are required to maintain cognitive function despite aging. No knowledge exists about the combination of factors such as zinc deficiency and reduced mastication on learning and memory. Here we show that tooth extraction only in 8-week-old mice did not change the density of glial fibrillary acidic protein-labeled astrocytes in the hippocampus or spatial memory parameters. However, tooth extraction followed by zinc deprivation strongly impaired spatial memory and led to an increase in astrocytic density in the hippocampal CA1 region. The impaired spatial performance in the zinc-deficient only (ZD) mice also coincided well with the increase in the astrocytic density in the hippocampal CA1 region. After switching both zinc-deficient groups to a normal diet with sufficient zinc, spatial memory recovered, and more time was spent in the quadrant with the goal in the probe test in the mice with tooth extraction followed by zinc deprivation (EZD) compared to the ZD mice. Interestingly, we found no differences in astrocytic density in the CA1 region among all groups at 22 weeks of age. Furthermore, the escape latency in a visible probe test at all times was longer in zinc-deficient groups than the others and demonstrated a negative correlation with body weight. No significant differences in escape latency were observed in the visible probe test among the ZD, EZD, and normal-fed control at 4 weeks (CT4w) groups in which body weight was standardized to that of the EZD group, or in the daily reduction in latency between the normal-fed control and CT4w groups. Our data showed that zinc-deficient feeding during a young age impairs spatial memory performance and leads to an increase in astrocytic density in the hippocampal CA1 region and that zinc-sufficient feeding is followed by recovery of the impaired spatial memory along with changes in astrocytic density. The combination of the two factors, zinc deficiency

  7. Variation and Inter-relationship ,Between Yield aJld,SQQl

    African Journals Online (AJOL)

    'fh~~;m(;JC(iztj~ii of.v~'n.'ails 'trails with'}rield.· The a;riWinediDz~lysis over two yeafs was used to estif11!lte genetic. Ycir.lance!~:I{e!irabjjit}/ dJ;zd,e'xpected ... J.e~ semrd.":aIf vanet~e~ has n~t .. ', f' Id' '~". " b S 1.",-. Af'. 'th. Been successfulm Tanzama due to poor gram major Ie 'crops.~m;su: aUd.lan: _ n.£C! ,\\Yl. an.,. . .....

  8. Spatial birth-and-death processes in random environment

    OpenAIRE

    Fernandez, Roberto; Ferrari, Pablo A.; Guerberoff, Gustavo R.

    2004-01-01

    We consider birth-and-death processes of objects (animals) defined in ${\\bf Z}^d$ having unit death rates and random birth rates. For animals with uniformly bounded diameter we establish conditions on the rate distribution under which the following holds for almost all realizations of the birth rates: (i) the process is ergodic with at worst power-law time mixing; (ii) the unique invariant measure has exponential decay of (spatial) correlations; (iii) there exists a perfect-simulation algorit...

  9. Rapid Activation of Plasticity-Associated Gene Transcription in Hippocampal Neurons Provides a Mechanism for Encoding of One-Trial Experience

    Czech Academy of Sciences Publication Activity Database

    Miyashita, T.; Kubík, Štěpán; Haghighi, N.; Steward, O.; Guzowski, J. F.

    2009-01-01

    Roč. 29, č. 4 (2009), s. 898-906 ISSN 0270-6474 Institutional research plan: CEZ:AV0Z50110509 Keywords : hippocampus * one-trial learning * Arc Subject RIV: FH - Neuro logy Impact factor: 7.178, year: 2009

  10. Gamma Oscillations and Spontaneous Network Activity in the Hippocampus Are Highly Sensitive to Decreases in pO2 and Concomitant Changes in Mitochondrial Redox State

    Czech Academy of Sciences Publication Activity Database

    Huchzermeyer, Ch.; Albus, K.; Gabriel, H.-J.; Otáhal, Jakub; Taubenberger, N.; Heinemann, U.; Kovács, R.; Kann, O.

    2008-01-01

    Roč. 28, č. 5 (2008), s. 1153-1162 ISSN 0270-6474 Institutional research plan: CEZ:AV0Z50110509 Keywords : gamma oscillations * pO2 * hippocampus Subject RIV: FH - Neurology Impact factor: 7.452, year: 2008

  11. Phencyclidine Discoordinates Hippocampal Network Activity But Not Place Fields

    Czech Academy of Sciences Publication Activity Database

    Kao, H. Y.; Dvořák, D.; Park, E.; Kenney, Jana; Kelemen, E.; Fenton, A.A.

    2017-01-01

    Roč. 37, č. 49 (2017), s. 12031-12049 ISSN 0270-6474 Institutional support: RVO:61388963 Keywords : gamma * neural discoordination * NMDA antagonist * oscillations Subject RIV: FH - Neurology OBOR OECD: Neuroscience s (including psychophysiology Impact factor: 5.988, year: 2016

  12. Endogenous Nitric Oxide Is a Key Promoting Factor for Initiation of Seizure-Like Events in Hippocampal and Entorhinal Cortex Slices

    Czech Academy of Sciences Publication Activity Database

    Kovács, R.; Rabanus, A.; Otáhal, Jakub; Patzak, A.; Kardos, J.; Albus, K.; Heinemann, U.; Kann, O.

    2009-01-01

    Roč. 29, č. 26 (2009), s. 8565-8577 ISSN 0270-6474 Institutional research plan: CEZ:AV0Z50110509 Keywords : neuro nal nitric oxide synthase * epilepsy * fluorescence imaging Subject RIV: FH - Neuro logy Impact factor: 7.178, year: 2009

  13. Prescriptions and universalizability: a defence of Harean ethical theory

    OpenAIRE

    Elstein, Daniel Y.

    2014-01-01

    ZD-44370 R.M. Hare had an ambitious scheme of providing a unified account of meta-ethics and normative ethics by combining expressivism with Kantianism and utilitarianism. The project of this thesis is to defend Hare’s theory in its most ambitious form. This means not just showing how the expressivist, Kantian and utilitarian elements are consistent, or that the three are each correct, but also that they are interdependent. The only defensible form of expressivism is Kantian; the only defe...

  14. The Impact of the Demonstration Project on Managers at the Naval Weapons Center, China Lake.

    Science.gov (United States)

    1983-06-01

    oooo 03CJ6-" MMMMM I MMMMMMMMMM I I I I I I I I HHHHHH I I I T-ova^ t r»*o • • t i in • oo© i *»«» © I *o I in »fcH...I 1 <« cjw to HhHHHH •1HHMHHHHHH -I > Zd Z * CD CM* mm t 1 1 1 t I 1 1 w O « 13C0 M * 3 * 33

  15. IMIS as an information engineering system

    International Nuclear Information System (INIS)

    Leeb, H.

    1992-01-01

    A precondition for the functionality of the decentrally organized system IMIS-IT is the clear-cut distribution of tasks and competences in an operational concept. It distinguishes between task areas which are handled centrally by the Federal Office of Radiation Protection, in particular by the ZdB and task areas which are handled decentrally by Land data centers, federal authorities and Land state measuring points. An overview of the IMIS-IT network with its hardware and software components is provided. (DG) [de

  16. Phencyclidine Discoordinates Hippocampal Network Activity But Not Place Fields

    Czech Academy of Sciences Publication Activity Database

    Kao, H. Y.; Dvořák, D.; Park, E.; Kenney, Jana; Kelemen, E.; Fenton, A.A.

    2017-01-01

    Roč. 37, č. 49 (2017), s. 12031-12049 ISSN 0270-6474 Institutional support: RVO:67985823 Keywords : gamma * neural discoordination * NMDA antagonist * oscillations * place cell * theta Subject RIV: FH - Neurology OBOR OECD: Neuroscience s (including psychophysiology Impact factor: 5.988, year: 2016

  17. Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development

    DEFF Research Database (Denmark)

    Robdrup Tinning, Anne; Jensen, Boye L; Johnsen, Iben

    2016-01-01

    Postnatal inhibition or deletion of angiotensin II (ANG II) AT1 receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary....... In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg·kg(-1)·day(-1)) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria...... for the development of the renal medullary microcirculation. Endothelial cell-specific immunolabeling of kidney sections from rats showed immature vascular bundles at postnatal day (P) 10 with subsequent expansion of bundles until P21. Medullary VEGF protein abundance coincided with vasa recta bundle formation...

  18. Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

    Science.gov (United States)

    Kasturi, Kannan; Fernandes, Lucas; Quezado, Martha; Eid, Mary; Marcus, Leigh; Chittiboina, Prashant; Rappaport, Mark; Stratakis, Constantine A; Widemann, Brigitte; Lodish, Maya

    2017-06-01

    Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.

  19. Nrdp1-Mediated ErbB3 Increase during Androgen Ablation and its Contribution to Androgen-Independence

    Science.gov (United States)

    2013-04-01

    Matar P, Albanell J, Guzman M, Rojo F, Arribas J, et al.: ZD1839, a specifi c epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor...or AR cDNA whose protein product contains a Thr→ Ala muta- tion at the 877 residual position isolated from LNCaP cells (24). pCDNA-HER2 and pCDNA3...Scaltriti M, Verma C, Guzman M, Jimenez J, Parra JL, Pedersen K, Smith DJ, Landolfi S, Ramon y Cajal S, Arribas J, Baselga J. Lapatinib, a HER2 tyrosine

  20. Outcome of status epilepticus in immature rats varies according to the paraldehyde treatment

    Czech Academy of Sciences Publication Activity Database

    Kubová, Hana; Rejchrtová, Jana; Redkozubova, Olga; Mareš, Pavel

    2005-01-01

    Roč. 46, Suppl. 5 (2005), s. 38-42 ISSN 0013-9580 R&D Projects: GA MZd(CZ) NF6474 Institutional research plan: CEZ:AV0Z5011922 Keywords : status epilepticus * paraldehyde * long-term consequences Subject RIV: ED - Physiology Impact factor: 3.227, year: 2005

  1. 76 FR 39259 - Manual Requirements

    Science.gov (United States)

    2011-07-06

    ... established new requirements for the certification, operation, and maintenance of light-sport aircraft under...-6474; e-mail [email protected] . SUPPLEMENTARY INFORMATION: The FAA published a final rule entitled ``Certification of Aircraft and Airmen for the Operation of Light-Sport Aircraft,'' in the Federal...

  2. Beyond memory, navigation, and inhibition: behavioral evidence for hippocampus-dependent cognitive coordination in the rat

    Czech Academy of Sciences Publication Activity Database

    Wesierska, M.; Dockery, Colleen; Fenton, André Antonio

    2005-01-01

    Roč. 25, č. 9 (2005), s. 2413-2419 ISSN 0270-6474 Grant - others:European Commission(XE) QLG3-CT-1999-00192 Institutional research plan: CEZ:AV0Z5011922 Keywords : cognition * hippocampus * cognitive disorganization Subject RIV: FH - Neurology Impact factor: 7.506, year: 2005

  3. Investigation of the turbulent swirl flow in pipe generated by axial fans using PIV and LDA methods

    Directory of Open Access Journals (Sweden)

    Čantrak Đorđe S.

    2015-01-01

    Full Text Available In this paper is presented experimental investigation of the turbulent swirl flow in pipe generated by axial fans. Two various models of industrial axial fans are used. One of these is axial fan W30, model AP 400, Minel, Serbia and has seven blades and outer diameter 0.397m. Second axial fan SP30 is model TGT/2-400-6, S&P, Spain, has six blades and outer diameter 0.386m. This results with greater clearance in the second case. Blades were adjusted for both fans at the angle of 30° at the outer diameter. Test rig length is 27.74-D, where D is average inner diameter app. 0.4 m. Measurements are performed in two measuring sections downstream the axial fans (z/D = 3.35 and z/D = 26.31 with one-component laser Doppler anemometry (LDA system and stereo particle image velocimetry (SPIV. Obtained Reynolds numbers, calculated on the basis of the average axial velocity (Um in the first measuring section are for fan SP30 Re = 226757, while for fan W30 Re = 254010. Integral flow parameters are determined such as average circulation and swirl number. Significant downstream axial velocity transformation occurs for both fans, while circumferential velocity is decreased, but non-dimensional velocity profile remains the same. Circumferential velocity distribution for both fans in the central zone corresponds to the solid body, while in r/R > 0.4, where D = 2R, distribution is more uniform. Radial velocity in the case of fan SP30 has almost zero values in the measuring section z/D = 3.35, while its values are significantly increased in the downstream section with the maximum in the vortex core region. On the contrary radial velocity decreases downstream for fan W30 and has also maximum value in the vortex core region for both measuring sections. Level of turbulence, skewness and flatness factors are calculated on the basis of the experimental data. The highest levels of turbulence for circumferential velocity are reached in the vortex core region for both fans

  4. Dynamic changes of status epilepticus-induced neuronal degeneration in the mediodorsal nucleus of the thalamus during postnatal development of the rat

    Czech Academy of Sciences Publication Activity Database

    Kubová, Hana; Druga, Rastislav; Haugvicová, Renata; Suchomelová, Lucie; Pitkanen, A.

    2002-01-01

    Roč. 43, Suppl. 5 (2002), s. 54-60 ISSN 0013-9580 R&D Projects: GA MZd NF6474; GA ČR GA309/01/0285 Institutional research plan: CEZ:AV0Z5011922 Keywords : status epilepticus Subject RIV: FH - Neurology Impact factor: 3.530, year: 2002

  5. Behavioral deficits in adult rats treated neonatally with glutamate

    Czech Academy of Sciences Publication Activity Database

    Hliňák, Zdeněk; Gandalovičová, D.; Krejčí, I.

    2005-01-01

    Roč. 27, č. 3 (2005), s. 465-473 ISSN 0892-0362 R&D Projects: GA MZd(CZ) NF6474 Institutional research plan: CEZ:AV0Z5011922 Keywords : neonatal treatment * monosodium glutamate * long-term effect Subject RIV: ED - Physiology Impact factor: 1.940, year: 2005

  6. Consistency maintenance for constraint in role-based access control model

    Institute of Scientific and Technical Information of China (English)

    韩伟力; 陈刚; 尹建伟; 董金祥

    2002-01-01

    Constraint is an important aspect of role-based access control and is sometimes argued to be the principal motivation for role-based access control (RBAC). But so far few authors have discussed consistency maintenance for constraint in RBAC model. Based on researches of constraints among roles and types of inconsistency among constraints, this paper introduces corresponding formal rules, rule-based reasoning and corresponding methods to detect, avoid and resolve these inconsistencies. Finally, the paper introduces briefly the application of consistency maintenance in ZD-PDM, an enterprise-oriented product data management (PDM) system.

  7. Consistency maintenance for constraint in role-based access control model

    Institute of Scientific and Technical Information of China (English)

    韩伟力; 陈刚; 尹建伟; 董金祥

    2002-01-01

    Constraint is an important aspect of role-based access control and is sometimes argued to be the principal motivation for role-based access control (RBAC). But so far'few authors have discussed consistency maintenance for constraint in RBAC model. Based on researches of constraints among roles and types of inconsistency among constraints, this paper introduces correaponding formal rules, rulebased reasoning and corresponding methods to detect, avoid and resolve these inconsistencies. Finally,the paper introduces briefly the application of consistency maintenance in ZD-PDM, an enterprise-ori-ented product data management (PDM) system.

  8. The Effect of Load Factor on Aircraft Handling Qualities.

    Science.gov (United States)

    1984-08-10

    sideslip, rudder and aileron deflection are calculated in the AMAT and BMAT program using data frcon this program and solving the side force, yawing and...0 PP = 0 RI = I NY = 8 GOTO 4530 4520 00 = 0 PP = 0 :RI = 8 NY = 8 4538 REM CHANGES EXISTING ELEMENTS OF AMAT & BMAT FOR CO NT AUG - ON & OFF 4540...IN POUNDS ;E 5670 A(9,9) = L4 * A(3,9) - L5 * ZD(5) - 16 5680 GOSUB 5716 5696 GOTO 5590 5706 RETURN 5710 REM SUBROUTINE FOR STORING AMAT & BMAT TO

  9. Department of the Navy Justification of Estimates for Fiscal Year 1988/1989 Submitted to Congress. Procurement. Other Procurement, Navy.

    Science.gov (United States)

    1987-01-01

    7 7ZD- AISI 9721 PffARTMENT OF THE NAVY JUffjA~j HFC S A FO L/L U I (NAUil) WASHINC ON C JAN&LNCLASS IFI ED F/G 5/1 NL I M2 I12 5 coo~ LIFJ -I LII...0 4 4)-s.. -4 4J C: 00 + ,. LI0a 4)00&.4. 00a 4)CA.V f0 4- > 1 - 1 404- 4JLA. 0- =. i.- >, 0h0 a0 cn 4 (40 s.4 > 4 24*~ (-A *.eZ---. 0. .. ., tv 4140

  10. A Monotonicity Result for the Range of a Perturbed Random Walk

    OpenAIRE

    Chen, Lung-Chi; Sun, Rongfeng

    2012-01-01

    We consider a discrete time simple symmetric random walk on Z^d, d>=1, where the path of the walk is perturbed by inserting deterministic jumps. We show that for any time n and any deterministic jumps that we insert, the expected number of sites visited by the perturbed random walk up to time n is always larger than or equal to that for the unperturbed walk. This intriguing problem arises from the study of a particle among a Poisson system of moving traps with sub-diffusive trap motion. In pa...

  11. Novel hole transport layer of nickel oxide composite with carbon for high-performance perovskite solar cells

    Science.gov (United States)

    Sajid; Elseman, A. M.; Ji, Jun; Dou, Shangyi; Huang, Hao; Cui, Peng; Wei, Dong; Li, Meicheng

    2018-01-01

    Not Available Project supported by the National High-tech Research and Development Program of China (Grant No. 2015AA034601), the National Natural Science Foundation of China (Grant Nos. 51772096, 91333122, 51372082, 51402106, and 11504107), the Ph.D. Programs Foundation of Ministry of Education of China (Grant No. 20130036110012), the Par-Eu Scholars Program, Beijing Municipal Science and Technology Project, China (Grant No. Z161100002616039), and the Fundamental Research Funds for the Central Universities of China (Grant Nos. 2016JQ01, 2015ZZD03, 2015ZD07, and 2017ZZD02).

  12. Elsevier’s approach to the bioCADDIE 2016 Dataset Retrieval Challenge

    Science.gov (United States)

    Scerri, Antony; Kuriakose, John; Deshmane, Amit Ajit; Stanger, Mark; Moore, Rebekah; Naik, Raj; de Waard, Anita

    2017-01-01

    Abstract We developed a two-stream, Apache Solr-based information retrieval system in response to the bioCADDIE 2016 Dataset Retrieval Challenge. One stream was based on the principle of word embeddings, the other was rooted in ontology based indexing. Despite encountering several issues in the data, the evaluation procedure and the technologies used, the system performed quite well. We provide some pointers towards future work: in particular, we suggest that more work in query expansion could benefit future biomedical search engines. Database URL: https://data.mendeley.com/datasets/zd9dxpyybg/1 PMID:29220454

  13. High-Frequency Network Activity, Global Increase in Neuronal Activity, and Synchrony Expansion Precede Epileptic Seizures in Vitro

    Czech Academy of Sciences Publication Activity Database

    Jiruška, P.; Csicsvari, J.; Powell, A.V.; Fox, J.E.; Chang, W.C.; Vreugdenhil, M.; Li, X.; Paluš, Milan; Bujan, A.F.; Dearden, R.W.; Jefferys, J. G. R.

    2010-01-01

    Roč. 30, č. 16 (2010), s. 5690-5701 ISSN 0270-6474 Institutional research plan: CEZ:AV0Z10300504 Keywords : mammalian hippocampus invitro * temporal - lobe epilepsy * nonsynaptic epileptogenesis * spatiotemporal dynamics * after-discharges * pyramidal cells * oscillations * rat * calcium * slice Subject RIV: FH - Neurology Impact factor: 7.271, year: 2010

  14. File list: His.Emb.05.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.05.AllAg.Mitotic_cycle_12-14 dm3 Histone Embryo Mitotic cycle 12-14 SRX6474...41,SRX647443,SRX647442,SRX647440 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/His.Emb.05.AllAg.Mitotic_cycle_12-14.bed ...

  15. Objev vápenců s rohovci v Boskovické brázdě

    Czech Academy of Sciences Publication Activity Database

    Krmíček, Lukáš; Bartík, J.; Bubík, M.

    2014-01-01

    Roč. 99, č. 2 (2014), s. 73-84 ISSN 1211-8796 Institutional support: RVO:67985831 Keywords : South Moravia * Boskovice Furrow * micritic-peloidal/oolitic limestone * dark chert * sabkha environment Subject RIV: DB - Geology ; Mineralogy

  16. Noninvasive diagnostics of mitochondrial disorders in isolated lymphocytes with high resolution respirometry

    Czech Academy of Sciences Publication Activity Database

    Pecina, Petr; Houšťková, H.; Mráček, Tomáš; Pecinová, Alena; Nůsková, Hana; Tesařová, M.; Hansíková, H.; Janota, J.; Zeman, J.; Houštěk, Josef

    2014-01-01

    Roč. 2, Dec (2014), s. 62-71 ISSN 2214-6474 R&D Projects: GA MZd(CZ) NT12370; GA ČR(CZ) GAP303/11/0970; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : lymphocytes * respirometry * oxidative phosphorylation * mitochondrial diseases * diagnostics Subject RIV: FG - Pediatrics

  17. 75 FR 65711 - High School Equivalency Program and College Assistance Migrant Program, The Federal TRIO Programs...

    Science.gov (United States)

    2010-10-26

    ... Math and Science (UBMS), and Veterans Upward Bound (VUB)) Sec. 646.4 (SSS), and Sec. 647.4 (McNair) to... school after the cohort completes the last grade level offered by the school at which the cohort began to... whom English is a second language, individuals pursing science, technology, engineering and math...

  18. Status epilepticus in immature rats leads to behavioural and cognitive impairment and epileptogenesis

    Czech Academy of Sciences Publication Activity Database

    Kubová, Hana; Mareš, Pavel; Suchomelová, Lucie; Brožek, Gustav; Druga, Rastislav; Pitkanen, A.

    2004-01-01

    Roč. 19, č. 12 (2004), s. 3255-3265 ISSN 0953-816X R&D Projects: GA MZd NF6474; GA ČR GA309/01/0285 Institutional research plan: CEZ:AV0Z5011922 Keywords : epilepsy * elevated plus-maze * Morris water-maze Subject RIV: FH - Neurology Impact factor: 3.820, year: 2004

  19. Neelima Shrikhande

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. Neelima Shrikhande. Articles written in Resonance – Journal of Science Education. Volume 2 Issue 2 February 1997 pp 64-74 General Article. Internet and The World Wide Web · Neelima Shrikhande · More Details Fulltext PDF. Volume 4 Issue 6 June 1999 pp ...

  20. Internet and The World Wide Web

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 2. Internet and The World Wide Web. Neelima Shrikhande. General Article Volume 2 Issue 2 February 1997 pp 64-74. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/002/02/0064-0074 ...

  1. A specific type of membrane microdomains is involved in the maintenance and translocation of kinase active Lck to lipid rafts

    Czech Academy of Sciences Publication Activity Database

    Ballek, Ondřej; Broučková, Adéla; Manning, Jasper; Filipp, Dominik

    2012-01-01

    Roč. 142, 1-2 (2012), s. 64-74 ISSN 0165-2478 R&D Projects: GA ČR GA310/09/2084 Institutional research plan: CEZ:AV0Z50520514 Keywords : pY394Lck * T-cell proximal signaling * membrane microdomains Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.337, year: 2012

  2. An English-French-German-Spanish Word Frequency Dictionary: A Correlation of the First Six Thousand Words in Four Single-Language Frequency Lists.

    Science.gov (United States)

    Eaton, Helen S., Comp.

    This semantic frequency list for English, French, German, and Spanish correlates 6,474 concepts represented by individual words in an order of diminishing occurrence. Designed as a research tool, the work is segmented into seven comparative "Thousand Concepts" lists with 115 sectional subdivisions, each of which begins with the key English word…

  3. Precise Orbit Solution for Swarm Using Space-Borne GPS Data and Optimized Pseudo-Stochastic Pulses

    Directory of Open Access Journals (Sweden)

    Bingbing Zhang

    2017-03-01

    Full Text Available Swarm is a European Space Agency (ESA project that was launched on 22 November 2013, which consists of three Swarm satellites. Swarm precise orbits are essential to the success of the above project. This study investigates how well Swarm zero-differenced (ZD reduced-dynamic orbit solutions can be determined using space-borne GPS data and optimized pseudo-stochastic pulses under high ionospheric activity. We choose Swarm space-borne GPS data from 1–25 October 2014, and Swarm reduced-dynamic orbits are obtained. Orbit quality is assessed by GPS phase observation residuals and compared with Precise Science Orbits (PSOs released by ESA. Results show that pseudo-stochastic pulses with a time interval of 6 min and a priori standard deviation (STD of 10−2 mm/s in radial (R, along-track (T and cross-track (N directions are optimized to Swarm ZD reduced-dynamic precise orbit determination (POD. During high ionospheric activity, the mean Root Mean Square (RMS of Swarm GPS phase residuals is at 9–11 mm, Swarm orbit solutions are also compared with Swarm PSOs released by ESA and the accuracy of Swarm orbits can reach 2–4 cm in R, T and N directions. Independent Satellite Laser Ranging (SLR validation indicates that Swarm reduced-dynamic orbits have an accuracy of 2–4 cm. Swarm-B orbit quality is better than those of Swarm-A and Swarm-C. The Swarm orbits can be applied to the geomagnetic, geoelectric and gravity field recovery.

  4. Ambiguity resolution in precise point positioning with hourly data for global single receiver

    Science.gov (United States)

    Zhang, Xiaohong; Li, Pan; Guo, Fei

    2013-01-01

    Integer ambiguity resolution (IAR) can improve precise point positioning (PPP) performance significantly. IAR for PPP became a highlight topic in global positioning system (GPS) community in recent years. More and more researchers focus on this issue. Progress has been made in the latest years. In this paper, we aim at investigating and demonstrating the performance of a global zero-differenced (ZD) PPP IAR service for GPS users by providing routine ZD uncalibrated fractional offsets (UFOs) for wide-lane and narrow-lane. Data sets from all IGS stations collected on DOY 1, 100, 200 and 300 of 2010 are used to validate and demonstrate this global service. Static experiment results show that an accuracy better than 1 cm in horizontal and 1-2 cm in vertical could be achieved in ambiguity-fixed PPP solution with only hourly data. Compared with PPP float solution, an average improvement reaches 58.2% in east, 28.3% in north and 23.8% in vertical for all tested stations. Results of kinematic experiments show that the RMS of kinematic PPP solutions can be improved from 21.6, 16.6 and 37.7 mm to 12.2, 13.3 and 34.3 mm for the fixed solutions in the east, north and vertical components, respectively. Both static and kinematic experiments show that wide-lane and narrow-lane UFO products of all satellites can be generated and provided in a routine way accompanying satellite orbit and clock products for the PPP user anywhere around the world, to obtain accurate and reliable ambiguity-fixed PPP solutions.

  5. Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint.

    Science.gov (United States)

    Hatch, R J; Jennings, E A; Ivanusic, J J

    2013-08-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih ) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system. © 2012 European Federation of International Association for the Study of Pain Chapters.

  6. Performance Prediction of Centrifugal Compressor for Drop-In Testing Using Low Global Warming Potential Alternative Refrigerants and Performance Test Codes

    Directory of Open Access Journals (Sweden)

    Joo Hoon Park

    2017-12-01

    Full Text Available As environmental regulations to stall global warming are strengthened around the world, studies using newly developed low global warming potential (GWP alternative refrigerants are increasing. In this study, substitute refrigerants, R-1234ze (E and R-1233zd (E, were used in the centrifugal compressor of an R-134a 2-stage centrifugal chiller with a fixed rotational speed. Performance predictions and thermodynamic analyses of the centrifugal compressor for drop-in testing were performed. A performance prediction method based on the existing ASME PTC-10 performance test code was proposed. The proposed method yielded the expected operating area and operating point of the centrifugal compressor with alternative refrigerants. The thermodynamic performance of the first and second stages of the centrifugal compressor was calculated as the polytropic state. To verify the suitability of the proposed method, the drop-in test results of the two alternative refrigerants were compared. The predicted operating range based on the permissible deviation of ASME PTC-10 confirmed that the temperature difference was very small at the same efficiency. Because the drop-in test of R-1234ze (E was performed within the expected operating range, the centrifugal compressor using R-1234ze (E is considered well predicted. However, the predictions of the operating point and operating range of R-1233zd (E were lower than those of the drop-in test. The proposed performance prediction method will assist in understanding thermodynamic performance at the expected operating point and operating area of a centrifugal compressor using alternative gases based on limited design and structure information.

  7. Caída de s en griego antiguo y fenómenos concomitantes

    Directory of Open Access Journals (Sweden)

    J. Vara

    1984-12-01

    Full Text Available In old Greek the sound s is lost as a consequence of the pressure of the system on the sequence of the apicals. It follows a chain of phenomena, analysed in this paper, which could be summarized like this: 1. A general assibilation occurs in some dialects; as a result of it ti becomes si, the place of the sound s in the system being empty on account of its former disappearance. In other dialects the assibilation does not occur. 2. In the dialects which have undergone the general assibilation, ts becomes ss, on the analogy of the assibilation of ti into si; while in those dialects in which the assibilation has not occurred, ts changes into ti. 3. Further changes occur due to the extensive working of analogy: in the dialects in which ts has become ss, zd changes into zz, by analogy to ss. On the other hand, in those dialects which have undergone the change of ts into tt, zd becomes dd, on the analogy of tt. 4. Later on, the place of ti in the paradigm being empty in the former dialects because of its having become si, it is replaced by the labial velar ku̯i, which finally becomes ti, however anomalous this change may seem. While in the dialects in which te is preserved, not having become se, the labial-velar ku̯i usually results in pe, not te. The logic underlying this theory and its formulation will be found in the whole paper.

  8. Establishment for Nuclear Equipment: Overview

    International Nuclear Information System (INIS)

    Pracz, J.

    2001-01-01

    Full text: The activity of ZdAJ in 2000 was focused on realisation of the Government-Ordered Project - 6/15 MeV Accelerator. The realisation was accomplished in two stages: - stage I should result in deriving principal operational parameters of the accelerator - stage 2 will result in full implementation of the control system providing optimum control of the equipment and automatic maintaining of its parameters. Within the frames of the first stage, a klystron modulator panel was finished and the design documentation of the mechanical supporting structure, the arm, accelerating structure, collimator and control panel were advanced. Manufacturing of the above sub-units in the workshop has started. In the frames of the Specific Project of the State Committee for Scientific Research, the improvement of Neptun lOPC accelerator was undertaken. The read-out of the monitor dose with atmospheric pressure and ambient temperature compensation has been introduced. New filters for equalising the photon and electron beam and new wedge filters have been designed. Changes in programming have been introduced, which improve the patient's safety by eliminating possible personnel errors and increase the accuracy of radiation fields read-out. In 2000 ZdAJ progressed in development of the Quality System conforming EN-ISO 9001 Standard by including the provisions of EN 46001 Standard. The Standard EN 46001: ''Quality Systems - Medical Equipment''. Detailed requirements related to application of EN ISO 9001 is an European Quality Standard extending the provisions of EN ISO 9001 Standard over the manufacturers of medical equipment. (author)

  9. Behavioral evidence that segregation and representation are dissociable hippocampal functions

    Czech Academy of Sciences Publication Activity Database

    Kubík, Štěpán; Fenton, André Antonio

    2005-01-01

    Roč. 25, č. 40 (2005), s. 9205-9212 ISSN 0270-6474 Grant - others:European Commission(XE) QLG3-CT-1999-00192; McDonnell Foundation(US) 98-38-CNS-QUA.05 Institutional research plan: CEZ:AV0Z5011922 Keywords : acquisition * retention * pattern separation Subject RIV: FH - Neurology Impact factor: 7.506, year: 2005

  10. Diffusion model analyses of the experimental data of 12C+27Al, 40Ca dissipative collisions

    International Nuclear Information System (INIS)

    SHEN Wen-qing; QIAO Wei-min; ZHU Yong-tai; ZHAN Wen-long

    1985-01-01

    Assuming that the intermediate system decays with a statistical lifetime, the general behavior of the threefold differential cross section d 3 tau/dZdEdtheta in the dissipative collisions of 68 MeV 12 C+ 27 Al and 68.6 MeV 12 C+ 40 Ca system is analyzed in the diffusion model framework. The lifetime of the intermediate system and the separation distance for the completely damped deep-inelastic component are obtained. The calculated results and the experimental data of the angular distributions and Wilczynski plots are compared. The probable reasons for the differences between them are briefly discussed

  11. Global optimization numerical strategies for rate-independent processes

    Czech Academy of Sciences Publication Activity Database

    Benešová, Barbora

    2011-01-01

    Roč. 50, č. 2 (2011), s. 197-220 ISSN 0925-5001 R&D Projects: GA ČR GAP201/10/0357 Grant - others:GA MŠk(CZ) LC06052 Program:LC Institutional research plan: CEZ:AV0Z20760514 Keywords : rate-independent processes * numerical global optimization * energy estimates based algorithm Subject RIV: BA - General Mathematics Impact factor: 1.196, year: 2011 http://math.hnue.edu.vn/portal/rss.viewpage.php?id=0000037780&ap=L3BvcnRhbC9ncmFiYmVyLnBocD9jYXRpZD0xMDEyJnBhZ2U9Mg==

  12. Defense Science Board 1986 Summer Study: Use of Commercial Components in Military Equipment

    Science.gov (United States)

    1987-01-01

    I 0 LU 0L c/) LU C- 0.. < o 0. Ui LU C FL/ zD 5 aZz z o C.0 0 cc U ~ ’ 4 i i 0 U-4 ZZ .J •-• go--’ E c : L -- 4 L- u z V 0 acca )0 V f.z ?A 4. CV...Guidebook Certify and Audit IC Suppliers Yes-Who? and Processes Use Industrial Plastic Encap- Partial sulated ICs in Selected Application Remove MIL...removal of precedence between IC selections. The first question concerns certification/ audit , specifically, who performs this function -- the

  13. An experimental analysis of flow boiling and pressure drop in a brazed plate heat exchanger for organic Rankine cycle power systems

    DEFF Research Database (Denmark)

    Desideri, Adriano; Zhang, Ji; Kærn, Martin Ryhl

    2017-01-01

    Organic Rankine cycle power systems for low quality waste heat recovery applications can play a major role in achieving targets of increasing industrial processes efficiency and thus reducing the emissions of greenhouse gases. Low capacity organic Rankine cycle systems are equipped with brazed...... and pressure drop during vaporization at typical temperatures for low quality waste heat recovery organic Rankine cycle systems are presented for the working fluids HFC-245fa and HFO-1233zd. The experiments were carried out at saturation temperatures of 100°C, 115°C and 130°C and inlet and outlet qualities...

  14. Electronic and Solid State Sciences. Program Summary, FY 1979.

    Science.gov (United States)

    1979-01-01

    34, A. Kahn, D. Kanani, P. Mark, P. Chye , C. Su, I. Lindau and W. Spicer, Surface Science 87 (1979) 325. 15. "Order-Disorder Effect in GaAs(l1O)-Oxygen...3, z-D"..o) by Qunu-elLuminescence", R. Chin , 71. Ho-lonyak, Jr. , 21 rchoefer, .- bs an. F. A. De.zek, AprlI. Phys. l~t 7 (-6 (09 *"Ph n.-,n-Assiste...Recombination in ai 𔃾ultiple QunumWllTPS TnP-l jx(_7a, ie ter,-structiirc Laser", !]. A. Rezek, R. Chin , !:. 5s,! nyak, Jr, . Sand R. ’.’. Kolbas

  15. Individual particles of cryoconite deposited on the mountain glaciers of the Tibetan Plateau: Insights into chemical composition and sources

    Science.gov (United States)

    Dong, Zhiwen; Qin, Dahe; Kang, Shichang; Liu, Yajun; Li, Yang; Huang, Jie; Qin, Xiang

    2016-08-01

    Cryoconite deposited on mountain glacier surfaces is significant for understanding regional atmospheric environments, which could influence the albedo and energy balance of the glacier basins, and maintain the glacial microbiology system. Field observations were conducted on the glaciers of western China, including Laohugou Glacier No.12 (LHG), Tanggula Dongkemadi Glacier (TGL), Zhadang Glacier (ZD), and Baishui Glacier No.1 in the Yulong Mountains (YL), as well as Urumqi Glacier No.1 in the Tianshan Mountains (TS) for comparison with locations in the Tibetan Plateau, in addition to laboratory TEM-EDX analysis of the individual cryoconite particles filtered on lacey carbon (LC) and calcium-coated carbon (Ca-C) TEM grids. This work provided information on the morphology and chemical composition, as well as a unique record of the particle's physical state, of cryoconite deposition on the Tibetan Plateau. The result showed that there is a large difference in the cryoconite particle composition between various locations on the Tibetan Plateau. In total, mineral dust particles were dominant (>50%) in the cryoconite at all locations. However, more anthropogenic particles (e.g., black carbon (BC) and fly ash) were found in YL (38%) and ZD (22%) in the Ca-C grids in the southern locations. In TGL, many NaCl and MCS particles (>10%), as well as few BC and biological particles (<5%), were found in cryoconite in addition to mineral dust. In TS, the cryoconite is composed primarily of mineral dust, as well as BC (<5%). Compared with other sites, the LHG cryoconite shows a more complex composition of atmospheric deposition with sufficient NaCl, BC, fly ash and biological particles (6% in LC grid). The higher ratio of anthropogenic particles in the southern Tibetan Plateau is likely caused by atmospheric pollutant transport from the south Asia to the Tibetan Plateau. Cryoconite in the northern locations (e.g., TGL, LHG, and TS) with higher dust and salt particle ratio are

  16. Equilibrative nucleoside transporter 2 regulates olfactory memory and synaptic function in Drosophila

    Czech Academy of Sciences Publication Activity Database

    Knight, D.; Harvey, P. J.; Iliadi, K. G.; Klose, M. K.; Iliadi, N.; Doleželová, Eva; Charlton, M. P.; Žurovec, Michal; Boulianne, G. L.

    2010-01-01

    Roč. 30, č. 14 (2010), s. 5047-5057 ISSN 0270-6474 R&D Projects: GA MŠk(CZ) LC06077 Grant - others:Canadian Institutes of Health Research(CA) MOP 14143; Canadian Institutes of Health Research(CA) MOP 67130 Institutional research plan: CEZ:AV0Z50070508 Keywords : Drosophila Subject RIV: ED - Physiology Impact factor: 7.271, year: 2010

  17. The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4

    Czech Academy of Sciences Publication Activity Database

    Li, Y.; Adámek, Pavel; Zhang, H.; Tatsui, C. E.; Rhines, L. D.; Mrózková, Petra; Li, Q.; Kosturakis, A. K.; Cassidy, R. M.; Harrison, D. S.; Cata, J. P.; Sapire, K.; Zhang, HM.; Kennamer-Chapman, R. M.; Jawad, A. B.; Ghetti, A.; Yan, J.; Paleček, Jiří; Dougherty, P. M.

    2015-01-01

    Roč. 35, č. 39 (2015), s. 13487-13500 ISSN 0270-6474 R&D Projects: GA MŠk(CZ) LH12058; GA MŠk(CZ) EE2.3.30.0025; GA ČR(CZ) GA15-11138S Institutional support: RVO:67985823 Keywords : cancer * dorsal horn * DRG * neuropathy Subject RIV: FH - Neurology Impact factor: 5.924, year: 2015

  18. KCTD Hetero-oligomers Confer Unique Kinetic Properties on Hippocampal GABA(B) Receptor-Induced K+ Currents

    Czech Academy of Sciences Publication Activity Database

    Fritzius, T.; Tureček, Rostislav; Seddik, R.; Kobayashi, H.; Tiao, J.; Rem, P.D.; Metz, M.; Králíková, Michaela; Bouvier, M.; Gassmann, M.; Bettler, B.

    2017-01-01

    Roč. 37, č. 5 (2017), s. 1162-1175 ISSN 0270-6474 R&D Projects: GA ČR(CZ) GA14-28334S Institutional support: RVO:68378041 Keywords : G-protein coupled receptor * GABA-B * GPCR Subject RIV: FH - Neurology OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 5.988, year: 2016

  19. Cognitive disorganization in hippocampus: a physiological model of the disorganization in psychosis

    Czech Academy of Sciences Publication Activity Database

    Olypher, Andrej Vadimovich; Klement, Daniel; Fenton, André Antonio

    2006-01-01

    Roč. 26, č. 1 (2006), s. 158-168 ISSN 0270-6474 R&D Projects: GA MŠk(CZ) LC554 Grant - others:European Commission(XE) QLG3-CT-1999-00192 Institutional research plan: CEZ:AV0Z5011922 Keywords : cognitive disorganization * reversible lesion * parasitic attractor Subject RIV: FH - Neurology Impact factor: 7.453, year: 2006

  20. Pure Absolutely Continuous Spectrum for Random Operators on $l^2(Z^d)$ at Low Disorder

    CERN Document Server

    Grinshpun, V

    2006-01-01

    Absence of singular continuous component, with probability one, in the spectra of random perturbations of multidimensional finite-difference Hamiltonians, is for the first time rigorously established under certain conditions ensuring either absence of point component, or absence of absolutely continuous component in the corresponding regions of spectra. The main technical tool involved is the rank-one perturbation theory of singular spectra. The respective new result (the non-mixing property) is applied to establish existence and bounds of the (non-empty) pure absolutely continuous component in the spectrum of the Anderson model with bounded random potential in dimension d=2 at low disorder (similar proof holds for d>4). The new result implies, via the trace-class perturbation analysis, Anderson model with the unbounded random potential having only pure point spectrum (complete system of localized wave-functions) with probability one in arbitrary dimension. The basic idea is to establish absence of the mixed,...

  1. [Effects of sowing depth on seedling traits and root characteristics of summer maize].

    Science.gov (United States)

    Cao, Hui-ying; Wang, Ding-bo; Shi, Jian-guo; Zhu, Kun-lun; Dong, Shu-ting; Liu, Peng; Zhao, Bin; Zhang, Ji-wang

    2015-08-01

    Two summer maize hybrids, Zhengdan 958 (ZD958) and Xianyu 335 (XY335), were used as experimental materials. 4 sowing depths (3, 5, 7 and 9 cm) and uneven sowing depth (CK) were designed under sand culture and field experiments to investigate the effects of sowing depth on seedling traits and root characteristics of summer maize. The results showed that the seedling emergence rate gradually decreased and seedling emergence time gradually lengthened as the sowing depth increased. Compared with the sowing depth of 3 cm, the seedling emergence rates of ZD958 and XY335 sown at the depth of 9 cm were reduced by 9.4% and 11.8%, respectively, and the seedling emergence duration was prolonged 1.5 d. With the increasing sowing depth, the seedling length and uniformity decreased significantly, the mesocotyl length increased significantly, while the coleoptile length had no significant difference; the primary radicle length gradually decreased, the total length of secondary radicle gradually increased, and the total root length had no significant difference; the total dry mass of seedling and mesocotyl increased significantly, and the total root dry mass had no significant difference. With the increasing sowing depth, the soluble sugar content in each part of seedling increased and the amount of nutritional consumption of germinating seeds increased, the seedling root growth rate increased, but the root activity decreased, and the number of total nodal root and nodal layers increased. With the increasing sowing depth, harvested ears per unit area were reduced by decreased seedling emergence rate and seedling vigor, thus influenced the yield. In addition, uniform sowing depth could improve the canopy uniformity and relative characteristics, then increase the yield.

  2. THE TAIWAN ECDFS NEAR-INFRARED SURVEY: VERY BRIGHT END OF THE LUMINOSITY FUNCTION AT z > 7

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Bau-Ching; Wang, Wei-Hao; Lin, Lihwai; Lim, Jeremy; Ho, Paul T. P. [Institute of Astrophysics and Astronomy, Academia Sinica, P.O. Box 23-141, Taipei 106, Taiwan (China); Yan, Haojing [Department of Physics and Astronomy, University of Missouri, Columbia, MO 65211 (United States); Karoji, Hiroshi [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Tsai, Chao-Wei [Infrared Processing and Analysis Center, California Institute of Technology, 770 South Wilson Avenue, Pasadena, CA 91125 (United States)

    2012-04-10

    The primary goal of the Taiwan ECDFS Near-Infrared Survey (TENIS) is to find well-screened galaxy candidates at z > 7 (z' dropout) in the Extended Chandra Deep Field-South (ECDFS). To this end, TENIS provides relatively deep J and K{sub s} data ({approx}25.3 ABmag, 5{sigma}) for an area of 0.5 Multiplication-Sign 0.5 deg. Leveraged with existing data at mid-infrared to optical wavelengths, this allows us to screen for the most luminous high-z objects, which are rare and thus require a survey over a large field to be found. We introduce new color selection criteria to select a z > 7 sample with minimal contaminations from low-z galaxies and Galactic cool stars; to reduce confusion in the relatively low angular resolution Infrared Array Camera (IRAC) images, we introduce a novel deconvolution method to measure the IRAC fluxes of individual sources. Illustrating perhaps the effectiveness at which we screen out interlopers, we find only one z > 7 candidate, TENIS-ZD1. The candidate has a weighted z{sub phot} of 7.8, and its colors and luminosity indicate a young (45M years old) starburst galaxy with a stellar mass of 3.2 Multiplication-Sign 10{sup 10} M{sub Sun }. The result matches with the observational luminosity function analysis and the semianalytic simulation result based on the Millennium Simulations, which may over predict the volume density for high-z massive galaxies. The existence of TENIS-ZD1, if confirmed spectroscopically to be at z > 7, therefore poses a challenge to current theoretical models for how so much mass can accumulate in a galaxy at such a high redshift.

  3. Discovery of a Very Bright Strongly Lensed Galaxy Candidate at z ≈ 7.6

    Science.gov (United States)

    Bradley, L. D.; Bouwens, R. J.; Ford, H. C.; Illingworth, G. D.; Jee, M. J.; Benítez, N.; Broadhurst, T. J.; Franx, M.; Frye, B. L.; Infante, L.; Motta, V.; Rosati, P.; White, R. L.; Zheng, W.

    2008-05-01

    Using Hubble Space Telescope (HST) and Spitzer IRAC imaging, we report the discovery of a very bright strongly lensed Lyman break galaxy (LBG) candidate at z ~ 7.6 in the field of the massive galaxy cluster Abell 1689 (z = 0.18). The galaxy candidate, which we refer to as A1689-zD1, shows a strong z850 - J110 break of at least 2.2 mag and is completely undetected (= 25). A1689-zD1 has an observed (lensed) magnitude of 24.7 AB (8 σ) in the NICMOS H160 band and is ~1.3 mag brighter than the brightest known z850-dropout galaxy. When corrected for the cluster magnification of ~9.3 at z ~ 7.6, the candidate has an intrinsic magnitude of H160 = 27.1 AB, or about an L* galaxy at z ~ 7.6. The source-plane deprojection shows that the star formation is occurring in compact knots of size lesssim300 pc. The best-fit stellar population synthesis models yield a median redshift of 7.6, stellar masses (1.6-3.9) × 109 M⊙, stellar ages 45-320 Myr, star formation rates lesssim7.6 M⊙ yr-1, and low reddening with AV 7.0 galaxy candidate found to date. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy under NASA contract NAS5-26555. Based on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology under NASA contract 1407.

  4. Cellular Signaling Pathway Alterations and Potential Targeted Therapies for Medullary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Serena Giunti

    2013-01-01

    Full Text Available Parafollicular C-cell-derived medullary thyroid cancer (MTC comprises 3% to 4% of all thyroid cancers. While cytotoxic treatments have been shown to have limited efficacy, targeted molecular therapies that inhibit rearranged during transfection (RET and other tyrosine kinase receptors that are mainly involved in angiogenesis have shown great promise in the treatment of metastatic or locally advanced MTC. Multi-tyrosine kinase inhibitors such as vandetanib, which is already approved for the treatment of progressive MTC, and cabozantinib have shown distinct advantages with regard to rates of disease response and control. However, these types of tyrosine kinase inhibitor compounds are able to concurrently block several types of targets, which limits the understanding of RET as a specific target. Moreover, important resistances to tyrosine kinase inhibitors can occur, which limit the long-term efficacy of these treatments. Deregulated cellular signaling pathways and genetic alterations in MTC, particularly the activation of the RAS/mammalian target of rapamycin (mTOR cascades and RET crosstalk signaling, are now emerging as novel and potentially promising therapeutic treatments for aggressive MTC.

  5. Proceedings of the DOD (Department of Defense) Standardization and Data Management Conference Supporting the Acquisition Process Held in Linthicum, Maryland on August 22-24, 1988

    Science.gov (United States)

    1988-01-01

    of markets to U.S. firms, such as when foreign competitors are producing competing products in non-metric units." The Production Manager for Textron...rz1 >4 E-4rzl4 * VJCI) H Ucg W U) U) O HU) 0U VL) P~U OH H 1z1 u1U)4 z~> ~ z E-4 -4 W ) 13 lidH to 1 - U)- >4 E- QW Z-D4 0 04 VIT-9 A Metric America - A...INCREASINGLY COMPETITIVE EUROPEAN MARKET PLACE. HOWEVER, WITH THE GOVERNMENT’S "NEW WAY" OF DOING BUSINESS - -" WITH CORPORATE * CONTRIBUTION AND INCREASED

  6. Bral1: Its Role in Diffusion Barrier Formation and Conduction Velocity in the CNS

    Czech Academy of Sciences Publication Activity Database

    Bekku, Y.; Vargová, Lýdia; Goto, Y.; Voříšek, Ivan; Dmytrenko, Lesia; Narasaki, M.; Ohtsuka, A.; Fässler, R.; Ninomiya, Y.; Syková, Eva; Oohashi, T.

    2010-01-01

    Roč. 30, č. 8 (2010), s. 3113-3123 ISSN 0270-6474 R&D Projects: GA ČR GA309/09/1597 Grant - others:GA MŠk(CZ) 1M0538; GA MZd(CZ) NS9915 Program:1M Institutional research plan: CEZ:AV0Z50390512 Keywords : Bral1 * central nervous system * brain development Subject RIV: FH - Neurology Impact factor: 7.271, year: 2010

  7. Medical Surveillance Monthly Report (MSMR). Volume 18, Number 01, January 2011

    Science.gov (United States)

    2011-01-01

    conditions (ICD-9-CM: 287), or malaria complicating pregnancy (ICD-9-CM: 647.4) in any diagnostic position; or (5) a hospitalization record with a...4) a hospitalization record with a non- primary diagnosis of malaria plus a diagnosis of anemia (ICD-9-CM: 280-285), thrombocyctopenia and related ...publication of the Armed Forces Health Surveillance Center Update: Malaria , U.S. Armed Forces, 2010 _______________________________________2 Diagnoses of

  8. Effects of shading on the photosynthetic characteristics and mesophyll cell ultrastructure of summer maize.

    Science.gov (United States)

    Ren, Baizhao; Cui, Haiyan; Camberato, James J; Dong, Shuting; Liu, Peng; Zhao, Bin; Zhang, Jiwang

    2016-08-01

    A field experiment was conducted to study the effects of shading on the photosynthetic characteristics and mesophyll cell ultrastructure of two summer maize hybrids Denghai605 (DH605) and Zhengdan958 (ZD958). The ambient sunlight treatment was used as control (CK) and shading treatments (40 % of ambient sunlight) were applied at different growth stages from silking (R1) to physiological maturity (R6) (S1), from the sixth leaf stage (V6) to R1 (S2), and from seeding to R6 (S3), respectively. The net photosynthetic rate (P n) was significantly decreased after shading. The greatest reduction of P n was found at S3 treatment, followed by S1 and S2 treatments. P n of S3 was decreased by 59 and 48 % for DH605, and 39 and 43 % for ZD958 at tasseling and milk-ripe stages, respectively, compared to that of CK. Additionally, leaf area index (LAI) and chlorophyll content decreased after shading. In terms of mesophyll cell ultrastructure, chloroplast configuration of mesophyll cells dispersed, and part of chloroplast swelled and became circular. Meanwhile, the major characteristics of chloroplasts showed poorly developed thylakoid structure at the early growth stage, blurry lamellar structure, loose grana, and a large gap between slices and warping granum. Then, plasmolysis occurred in mesophyll cells and the endomembrane system was destroyed, which resulted in the dissolution of cell membrane, karyotheca, mitochondria, and some membrane structures. The damaged mesophyll cell ultrastructure led to the decrease of photosynthetic capacity, and thus resulted in significant yield reduction by 45, 11, and 84 % in S1, S2, and S3 treatments, respectively, compared to that of CK.

  9. Response to "Comment on `Solitonic and chaotic behaviors for the nonlinear dust-acoustic waves in a magnetized dusty plasma'" [Phys. Plasmas 24, 094701 (2017)

    Science.gov (United States)

    Zhen, Hui-Ling; Tian, Bo; Xie, Xi-Yang; Wu, Xiao-Yu; Wen, Xiao-Yong

    2018-02-01

    On our previous construction [H. L. Zhen et al., Phys. Plasmas 23, 052301 (2016)] of the soliton solutions of a model describing the dynamics of the dust particles in a weakly ionized, collisional dusty plasma comprised of the negatively charged cold dust particles, hot ions, hot electrons, and stationary neutrals in the presence of an external static magnetic field, Ali et al. [Phys. Plasmas 24, 094701 (2017)] have commented that there exists a different form of Eq. (4) from that shown in Zhen et al. [Phys. Plasmas 23, 052301 (2016)] and that certain interesting phenomena with the dust neutral collision frequency ν0>0 are ignored in Zhen et al. [Phys. Plasmas 23, 052301 (2016)]. In this Reply, according to the transformation given by the Ali et al. [Phys. Plasmas 24, 094701 (2017)] comment, we present some one-, two-, and N-soliton solutions which have not been obtained in the Ali et al. [Phys. Plasmas 24, 094701 (2017)] comment. We point out that our previous solutions in Zhen et al. [Phys. Plasmas 23, 052301 (2016)] are still valid because of the similarity between the two dispersion relations of previous solutions in Zhen et al. [Phys. Plasmas 23, 052301 (2016)] and the solutions presented in this Reply. Based on our soliton solutions in this Reply, it is found that the soliton amplitude is inversely related to Zd and B0, but positively related to md and α, where α refers to the coefficient of the nonlinear term, Zd and md are the charge number and mass of a dust particle, respectively, B0 represents the strength of the external static magnetic field. We also find that the two solitons are always in parallel during the propagation.

  10. Exogenous 5-aminolevulenic acid promotes seed germination in Elymus nutans against oxidative damage induced by cold stress.

    Directory of Open Access Journals (Sweden)

    Juanjuan Fu

    Full Text Available The protective effects of 5-aminolevulenic acid (ALA on germination of Elymus nutans Griseb. seeds under cold stress were investigated. Seeds of E. nutans (Damxung, DX and Zhengdao, ZD were pre-soaked with various concentrations (0, 0.1, 0.5, 1, 5, 10 and 25 mg l(-1 of ALA for 24 h before germination under cold stress (5°C. Seeds of ZD were more susceptible to cold stress than DX seeds. Both seeds treated with ALA at low concentrations (0.1-1 mg l(-1 had higher final germination percentage (FGP and dry weight at 5°C than non-ALA-treated seeds, whereas exposure to higher ALA concentrations (5-25 mg l(-1 brought about a dose dependent decrease. The highest FGP and dry weight of germinating seeds were obtained from seeds pre-soaked with 1 mg l(-1 ALA. After 5 d of cold stress, pretreatment with ALA provided significant protection against cold stress in the germinating seeds, significantly enhancing seed respiration rate and ATP synthesis. ALA pre-treatment also increased reduced glutathione (GSH, ascorbic acid (AsA, total glutathione, and total ascorbate concentrations, and the activities of superoxide dismutase (SOD, catalase (CAT, ascorbate peroxidase (APX and glutathione reductase (GR, whereas decreased the contents of malondialdehyde (MDA and hydrogen peroxide (H2O2, and superoxide radical (O2•- release in both germinating seeds under cold stress. In addition, application of ALA increased H+-ATPase activity and endogenous ALA concentration compared with cold stress alone. Results indicate that ALA considered as an endogenous plant growth regulator could effectively protect E. nutans seeds from cold-induced oxidative damage during germination without any adverse effect.

  11. Comparative proteome analysis reveals four novel polyhydroxybutyrate (PHB) granule-associated proteins in Ralstonia eutropha H16.

    Science.gov (United States)

    Sznajder, Anna; Pfeiffer, Daniel; Jendrossek, Dieter

    2015-03-01

    Identification of proteins that were present in a polyhydroxybutyrate (PHB) granule fraction isolated from Ralstonia eutropha but absent in the soluble, membrane, and membrane-associated fractions revealed the presence of only 12 polypeptides with PHB-specific locations plus 4 previously known PHB-associated proteins with multiple locations. None of the previously postulated PHB depolymerase isoenzymes (PhaZa2 to PhaZa5, PhaZd1, and PhaZd2) and none of the two known 3-hydroxybutyrate oligomer hydrolases (PhaZb and PhaZc) were significantly present in isolated PHB granules. Four polypeptides were found that had not yet been identified in PHB granules. Three of the novel proteins are putative α/β-hydrolases, and two of those (A0671 and B1632) have a PHB synthase/depolymerase signature. The third novel protein (A0225) is a patatin-like phospholipase, a type of enzyme that has not been described for PHB granules of any PHB-accumulating species. No function has been ascribed to the fourth protein (A2001), but its encoding gene forms an operon with phaB2 (acetoacetyl-coenzyme A [CoA] reductase) and phaC2 (PHB synthase), and this is in line with a putative function in PHB metabolism. The localization of the four new proteins at the PHB granule surface was confirmed in vivo by fluorescence microscopy of constructed fusion proteins with enhanced yellow fluorescent protein (eYFP). Deletion of A0671 and B1632 had a minor but detectable effect on the PHB mobilization ability in the stationary growth phase of nutrient broth (NB)-gluconate cells, confirming the functional involvement of both proteins in PHB metabolism. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Momentum, sensible heat and CO2 correlation coefficient variability: what can we learn from 20 years of continuous eddy covariance measurements?

    Science.gov (United States)

    Hurdebise, Quentin; Heinesch, Bernard; De Ligne, Anne; Vincke, Caroline; Aubinet, Marc

    2017-04-01

    Long-term data series of carbon dioxide and other gas exchanges between terrestrial ecosystems and atmosphere become more and more numerous. Long-term analyses of such exchanges require a good understanding of measurement conditions during the investigated period. Independently of climate drivers, measurements may indeed be influenced by measurement conditions themselves subjected to long-term variability due to vegetation growth or set-up changes. The present research refers to the Vielsalm Terrestrial Observatory (VTO) an ICOS candidate site located in a mixed forest (beech, silver fir, Douglas fir, Norway spruce) in the Belgian Ardenne. Fluxes of momentum, carbon dioxide and sensible heat have been continuously measured there by eddy covariance for more than 20 years. During this period, changes in canopy height and measurement height occurred. The correlation coefficients (for momemtum, sensible heat and CO2) and the normalized standard deviations measured for the past 20 years at the Vielsalm Terrestrial Observatory (VTO) were analysed in order to define how the fluxes, independently of climate conditions, were affected by the surrounding environment evolution, including tree growth, forest thinning and tower height change. A relationship between canopy aerodynamic distance and the momentum correlation coefficient was found which is characteristic of the roughness sublayer, and suggests that momentum transport processes were affected by z-d. In contrast, no relationship was found for sensible heat and CO2 correlation coefficients, suggesting that the z-d variability observed did not affect their turbulent transport. There were strong differences in these coefficients, however, between two wind sectors, characterized by contrasted stands (height differences, homogeneity) and different hypotheses were raised to explain it. This study highlighted the importance of taking the surrounding environment variability into account in order to ensure the spatio

  13. Potentiation of Inhibitory Synaptic Transmission by Extracellular ATP in Rat Suprachiasmatic Nuclei

    Czech Academy of Sciences Publication Activity Database

    Bhattacharya, Anirban; Vávra, Vojtěch; Svobodová, Irena; Bendová, Z.; Vereb, G.; Zemková, Hana

    2013-01-01

    Roč. 33, č. 18 (2013), s. 8035-8044 ISSN 0270-6474 R&D Projects: GA AV ČR(CZ) IAA500110910; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : suprachiasmatic nucleus * P2X receptors * P2Y receptors * ATP * GABA * spontaneous inhibitory synaptic currents Subject RIV: ED - Physiology Impact factor: 6.747, year: 2013

  14. Medical Surveillance Monthly Report (MSMR). Volume 19, Number 1, January 2012

    Science.gov (United States)

    2012-01-01

    conditions (ICD-9-CM: 287), or malaria complicating pregnancy (ICD- 9-CM: 647.4) in any diagnostic position; or (5) a hospitalization record with a non...variability of estimates of case counts of malaria in relation to characteristics of sur- veillance case defi nitions. In particular, the report...subsequent diagnostic positions (with no malaria -specifi c or associated diagno- ses in the primary diagnostic position); ii) records of malaria - related

  15. Absolutely continuous measures and compact composition operator on spaces of Cauchy transforms

    Directory of Open Access Journals (Sweden)

    Yusuf Abu Muhanna

    2004-01-01

    Full Text Available The analytic self-map of the unit disk D, φ is said to induce a composition operator Cφ from the Banach space X to the Banach space Y if Cφ(f=f∘φ∈Y for all f∈X. For z∈D and α>0, the families of weighted Cauchy transforms Fα are defined by f(z=∫TKxα(zdμ(x, where μ(x is complex Borel measure, x belongs to the unit circle T, and the kernel Kx(z=(1−x¯z−1. In this paper, we will explore the relationship between the compactness of the composition operator Cφ acting on Fα and the complex Borel measures μ(x.

  16. Hotel na Vysočině

    OpenAIRE

    Machatka, Petr

    2013-01-01

    Diplomová práce s názvem Hotel na Vysočině řeší projektovou dokumentaci ve stupni pro provedení stavby. Hotel má tři nadzemní podlaží. Objekt je nepodsklepený. Zastřešení je provedeno plochou a šikmou střechou. Zdící systém POROTHERM s kontaktním zateplením expandovaným polystyrenem EPS -F. The master thesis named Hotel at Vysočina solves project documentation in the degree for building construction. The hotel has three floors. The object is without a cellar. As roofing is used a flat and ...

  17. Contribution of the putative inner-pore region to the gating of the Transient Receptor Potential Vanilloid Subtype 1 Channel (TRPV1)

    Czech Academy of Sciences Publication Activity Database

    Sušánková, Klára; Ettrich, Rüdiger; Vyklický st., Ladislav; Teisinger, Jan; Vlachová, Viktorie

    2007-01-01

    Roč. 27, č. 28 (2007), s. 7578-7585 ISSN 0270-6474 R&D Projects: GA ČR(CZ) GA305/06/0319; GA ČR(CZ) GA303/07/0915; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA MŠk LC06010 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z60870520 Keywords : capsaicin * vanilloid receptor * TRP channels Subject RIV: ED - Physiology Impact factor: 7.490, year: 2007

  18. Hyperpolarization-activated current (I(h)) in vestibular calyx terminals: characterization and role in shaping postsynaptic events.

    Science.gov (United States)

    Meredith, Frances L; Benke, Tim A; Rennie, Katherine J

    2012-12-01

    Calyx afferent terminals engulf the basolateral region of type I vestibular hair cells, and synaptic transmission across the vestibular type I hair cell/calyx is not well understood. Calyces express several ionic conductances, which may shape postsynaptic potentials. These include previously described tetrodotoxin-sensitive inward Na(+) currents, voltage-dependent outward K(+) currents and a K(Ca) current. Here, we characterize an inwardly rectifying conductance in gerbil semicircular canal calyx terminals (postnatal days 3-45), sensitive to voltage and to cyclic nucleotides. Using whole-cell patch clamp, we recorded from isolated calyx terminals still attached to their type I hair cells. A slowly activating, noninactivating current (I(h)) was seen with hyperpolarizing voltage steps negative to the resting potential. External Cs(+) (1-5 mM) and ZD7288 (100 μM) blocked the inward current by 97 and 83 %, respectively, confirming that I(h) was carried by hyperpolarization-activated, cyclic nucleotide gated channels. Mean half-activation voltage of I(h) was -123 mV, which shifted to -114 mV in the presence of cAMP. Activation of I(h) was well described with a third order exponential fit to the current (mean time constant of activation, τ, was 190 ms at -139 mV). Activation speeded up significantly (τ=136 and 127 ms, respectively) when intracellular cAMP and cGMP were present, suggesting that in vivo I(h) could be subject to efferent modulation via cyclic nucleotide-dependent mechanisms. In current clamp, hyperpolarizing current steps produced a time-dependent depolarizing sag followed by either a rebound afterdepolarization or an action potential. Spontaneous excitatory postsynaptic potentials (EPSPs) became larger and wider when I(h) was blocked with ZD7288. In a three-dimensional mathematical model of the calyx terminal based on Hodgkin-Huxley type ionic conductances, removal of I(h) similarly increased the EPSP, whereas cAMP slightly decreased simulated EPSP size

  19. Impact of surrounding environment evolution on long-term gas flux measurements in a temperate mixed forest

    Science.gov (United States)

    Hurdebise, Quentin; Rixen, Toma; De Ligne, Anne; Vincke, Caroline; Heinesch, Bernard; Aubinet, Marc

    2016-04-01

    With the development of eddy covariance networks like Fluxnet, ICOS or NEON, long-term data series of carbon dioxide, water vapor and other gas exchanges between terrestrial ecosystems and atmosphere will become more and more numerous. However, long-term analyses of such exchanges require a good understanding of measurement conditions during the investigated period. Independently of climate drivers, measurements may indeed be influenced by measurement conditions themselves subjected to long-term variability due to vegetation growth or set-up changes. The present research refers to the Vielsalm Terrestrial Observatory (VTO) where fluxes of momentum, carbon dioxide, latent and sensible heat have been continuously measured by eddy covariance during twenty years. VTO is an ICOS site installed in a mixed forest (beech, silver fir, Douglas fir, Norway spruce) in the Belgian Ardennes. A multidisciplinary approach was developed in order to investigate the spatial and temporal evolution of several site characteristics: -displacement height (d) and relative measurement height (z-d) were determined using a spectral approach that compared observed and theoretical cospectra; -turbulence statistics were analyzed in the context of Monin-Obukhov similarity theory; -tree height during the measurement period was obtained by combining tree height inventories, a LIDAR survey and tree growth models; -measurement footprint was determined by using a footprint model. A good agreement was found between the three first approaches. Results show notably that z-d was subjected to both temporal and spatial evolution. Temporal evolution resulted from continuous tree growth as well as from a tower raise, achieved in 2009. Spatial evolution, due to canopy heterogeneity, was also observed. The impacts of these changes on measurements are investigated. In particular, it was shown that they affect measurement footprint, flux spectral corrections and flux quality. All these effects must be taken into

  20. HCN channels segregate stimulation‐evoked movement responses in neocortex and allow for coordinated forelimb movements in rodents

    Science.gov (United States)

    Farrell, Jordan S.; Palmer, Laura A.; Singleton, Anna C.; Pittman, Quentin J.; Teskey, G. Campbell

    2016-01-01

    Key points The present study tested whether HCN channels contribute to the organization of motor cortex and to skilled motor behaviour during a forelimb reaching task.Experimental reductions in HCN channel signalling increase the representation of complex multiple forelimb movements in motor cortex as assessed by intracortical microstimulation.Global HCN1KO mice exhibit reduced reaching accuracy and atypical movements during a single‐pellet reaching task relative to wild‐type controls.Acute pharmacological inhibition of HCN channels in forelimb motor cortex decreases reaching accuracy and increases atypical movements during forelimb reaching. Abstract The mechanisms by which distinct movements of a forelimb are generated from the same area of motor cortex have remained elusive. Here we examined a role for HCN channels, given their ability to alter synaptic integration, in the expression of forelimb movement responses during intracortical microstimulation (ICMS) and movements of the forelimb on a skilled reaching task. We used short‐duration high‐resolution ICMS to evoke forelimb movements following pharmacological (ZD7288), experimental (electrically induced cortical seizures) or genetic approaches that we confirmed with whole‐cell patch clamp to substantially reduce I h current. We observed significant increases in the number of multiple movement responses evoked at single sites in motor maps to all three experimental manipulations in rats or mice. Global HCN1 knockout mice were less successful and exhibited atypical movements on a skilled‐motor learning task relative to wild‐type controls. Furthermore, in reaching‐proficient rats, reaching accuracy was reduced and forelimb movements were altered during infusion of ZD7288 within motor cortex. Thus, HCN channels play a critical role in the separation of overlapping movement responses and allow for successful reaching behaviours. These data provide a novel mechanism for the encoding of multiple

  1. Rodinný dům ve svahu

    OpenAIRE

    Hrubý, Libor

    2013-01-01

    Bakalářská práce, zabývající se projektovou dokumentací stavební části ve stupni pro provedení stavby na novostavbu samostatně stojícího rodinného domu ve svahu. Objekt je dvoupodlažní, podsklepený. Svislé konstrukce z vápenopískového zdícího systému KM Beta Sendwix. Stropní konstrukce z předpjatých stropních panelů Spiroll. Zastřešení provedeno pultovou vegetační střechou se sklonem 10%, plochou střechou s terasovou úpravou a plochou vegetační střechou. Dispozičně je objekt rozdělen na klido...

  2. Interaction of the electromagnetic waves and non-magnetized plasmas

    International Nuclear Information System (INIS)

    Sun Aiping; Qiu Xiaoming; Dong Yuying; Li Liqiong

    2002-01-01

    The propagation of electromagnetic waves with 0.5 - 10 GHz in a non-magnetized collisional plasma slab is studied numerically. The change in the absorbed power, reflected power and transmitted power of the electromagnetic wave with collisional frequency of electrons and neutral atoms in plasma from 0.1 - 10 GHz, is calculated, in the condition of the uniform plasma with density of 10 10 or 10 11 cm -3 and depth of 10 cm, and the non-uniform plasma with density distribution of n = n 0 exp[2(z/d-1)] and depth of 10 cm, respectively. The results show that the absorbed power in either uniform or non-uniform plasma is large when the plasma density is large and collision frequency is high, and the peak value is 90%

  3. Structural and robustness properties of smart-city transportation networks

    Science.gov (United States)

    Zhang, Zhen-Gang; Ding, Zhuo; Fan, Jing-Fang; Meng, Jun; Ding, Yi-Min; Ye, Fang-Fu; Chen, Xiao-Song

    2015-09-01

    The concept of smart city gives an excellent resolution to construct and develop modern cities, and also demands infrastructure construction. How to build a safe, stable, and highly efficient public transportation system becomes an important topic in the process of city construction. In this work, we study the structural and robustness properties of transportation networks and their sub-networks. We introduce a complementary network model to study the relevance and complementarity between bus network and subway network. Our numerical results show that the mutual supplement of networks can improve the network robustness. This conclusion provides a theoretical basis for the construction of public traffic networks, and it also supports reasonable operation of managing smart cities. Project supported by the Major Projects of the China National Social Science Fund (Grant No. 11 & ZD154).

  4. Závislost fotometrických parametrů hvězd na orbitálních parametrech exoplanet

    Czech Academy of Sciences Publication Activity Database

    Pintr, Pavel

    2012-01-01

    Roč. 57, 11-12 (2012), s. 317-320 ISSN 0447-6441. [OaM 2012 International Conference on Optics and Measurement. Liberec, 16.10.2012-18.10.2012] Institutional research plan: CEZ:AV0Z20430508 Keywords : Exoplanets * regression analyse * stellar luminosity * stellar irradiance * effective temperature * orbital parameters Subject RIV: BH - Optics, Masers, Lasers

  5. Advances and controversies in the management of medullary thyroid carcinoma.

    Science.gov (United States)

    Maia, Ana Luiza; Wajner, Simone Magagnin; Vargas, Carla Vaz Ferreira

    2017-01-01

    Medullary thyroid carcinoma (MTC) comprises approximately 4% of all malignant thyroid neoplasms. Although the majority of patients have a good prognosis, a subgroup of patients develops progressive disease and requires systemic therapy. Here, we focused on the current MTC therapeutic approaches and discussed the advantages and disadvantages of molecular targeted therapies. Targeted molecular therapies that inhibit RET and other tyrosine kinase receptors involved in angiogenesis have been shown to improve progression-free survival in patients with advanced MTC. Two drugs, vandetanib and cabozantinib, have been approved for the treatment of progressive or symptomatic MTC, and several others have exhibited variable efficacy. No tyrosine kinase inhibitor has been shown to improve survival. Although no definitive recommendation can currently be made, cumulative data indicate that knowledge of the tumor mutational profile may facilitate improvements in targeted therapy for MTC. Tyrosine kinase inhibitors are effective therapeutic agents for the treatment of progressive MTC. Nevertheless, it is not clear who will benefit the most from therapy, and the decision regarding when and how to initiate the treatment should be made based on the patient's medical history and tumor behavior. Hopefully, in the near future, molecular profiling of MTC can be used to determine the most effective molecular therapeutic target.

  6. Targeted Therapy for Medullary Thyroid Cancer: A Review

    Directory of Open Access Journals (Sweden)

    S. R. Priya

    2017-10-01

    Full Text Available Medullary thyroid cancers (MTCs constitute between 2 and 5% of all thyroid cancers. The 10-year overall survival (OS rate of patients with localized disease is around 95% while that of patients with regional stage disease is about 75%. Only 20% of patients with distant metastases at diagnosis survive 10 years which is significantly lower than for differentiated thyroid cancers. Cases with regional metastases at presentation have high recurrence rates. Adjuvant external radiation confers local control but not improved OS. The management of residual, recurrent, or metastatic disease till a few years ago was re-surgery with local measures such as radiation. Chemotherapy was used with marginal benefit. The development of targeted therapy has brought in a major advantage in management of such patients. Two drugs—vandetanib and cabozantinib—have been approved for use in progressive or metastatic MTC. In addition, several drugs acting on other steps of the molecular pathway are being investigated with promising results. Targeted radionuclide therapy also provides an effective treatment option with good quality of life. This review covers the rationale of targeted therapy for MTC, present treatment options, drugs and methods under investigation, as well as an outline of the adverse effects and their management.

  7. Drug therapy for hereditary cancers

    Directory of Open Access Journals (Sweden)

    Imyanitov Evgeny N

    2011-08-01

    Full Text Available Abstract Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose polymerase (PARP. Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC. Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC patients; studies involving non-selected (i.e., both sporadic and hereditary CRC with high-level microsatellite instability (MSI-H suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP. Hereditary medullary thyroid cancers (MTC have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.

  8. Preferential Inhibition of Tonically over Phasically Activated NMDA Receptors by Pregnane Derivatives

    Czech Academy of Sciences Publication Activity Database

    Vyklický, Vojtěch; Smejkalová, Tereza; Krausová, Barbora; Balík, Aleš; Kořínek, Miloslav; Borovská, Jiřina; Horák, Martin; Chvojková, Markéta; Kletečková, Lenka; Valeš, Karel; Černý, Jiří; Nekardová, Michaela; Chodounská, Hana; Kudová, Eva; Vyklický ml., Ladislav

    2016-01-01

    Roč. 36, č. 7 (2016), s. 2161-2175 ISSN 0270-6474 R&D Projects: GA ČR(CZ) GAP303/12/1464; GA ČR(CZ) GBP304/12/G069; GA TA ČR(CZ) TE01020028; GA ČR(CZ) GBP208/12/G016; GA MŠk(CZ) EE2.3.30.0025; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 ; RVO:61388963 Keywords : memantine * neuroprotection * neurosteroid * NMDA receptor * pregnanolone sulfate * synaptic transmission Subject RIV: ED - Physiology Impact factor: 5.988, year: 2016

  9. Three-Dimensional Propagation and Scattering Around a Conical Seamount

    Science.gov (United States)

    2007-06-01

    s) Td . I or, 71 IT +~ f E [ai’D+l + 153j n 1JDJ+Iil (rj) r7 1 ql(Z)Xpij+l[, = ZL ,i2nH1., (,)+ 1, ,, )1 k --f , 1(z) Mll qjk)I,p4z)d1. (4.45) 102...F,t )-I (DH-ljC,,,+’. flj + Ihj ,Cb+’DfIIlj ) f + (Fj) -’ (DIlh,,C a+ lj 7’+1 -, !/,.-fI/’jiC+1lDjJ I) b-’,,+ REJ+ 1 anj+ 1 + Jl R3r, ’ 1,(4|.55...80 , li ,c൓ 400 400 ; :l 200 I/10 0 0 200 -400 -400 -00fO d00 50 50 (a) Td Los, dg) C-SNAP J 0 7 - os s (M), C-SNAP Jx 33 12012 600 110 600 110 400

  10. VizieR Online Data Catalog: Identifications of Sonneberg variables (Kinnunen+, 1999-2000)

    Science.gov (United States)

    Kinnunen, T.; Skiff, B. A.

    2002-09-01

    The list below is a continuation of a series providing accurate positions and identifications for variables appearing on the MVS charts (Hoffmeister, 1957, Mitt. Verdander. Sterne, No. 245). The variables here were first described by Hoffmeister (1949, Astron. Abh. Ergaenzungshefte z.d. Astron. Nach., 12, no. 1, A3) in the difficult-to-find ``Ergaenzungshefte'' to the Astronomische Nachrichten, and are the first group from a collection of some 1440 variables from this publication. Details about the identification procedure and table layout are contained in the first report of our series (Kinnunen & Skiff, 2000IBVS.4862....1K). We are grateful to librarians Antoinette Beiser (Lowell) and Brenda Corbin (U. S. Naval Observatory, Washington) for providing a photocopy of the Hoffmeister survey; ``bibliothecaire extraordinaire'' Suzanne Laloe (Obs. Paris-Meudon) advised on how this obscure journal should be cited. (3 data files).

  11. İneklerde embriyo transferinde farklı prostaglandin F2α protokolleri ile taşıyıcı senkronizasyonu

    OpenAIRE

    Kırbaş, Mesut; Dursun, Şükrü; Köse, Mehmet; Bülbül, Bülent; Çolak, Mehmet; Mutlu, Hasan

    2010-01-01

    Amaç: Çalışmada, dondurulmuş çözdürülmüş embriyo transferi amacıyla taşıyıcı senkronizasyonunda kullanılan farklı prostaglandin F2α protokolleri karşılaştırıldı. Gereç ve Yöntem: Toplam 46 İsviçre Esmeri inek rastgele üç gruba ayrıldı. Grup I (n=15)’deki ineklere östrüs siklusunun herhangi bir döneminde i.m. yoldan tek doz 0.150 mg kloprostenol enjekte edildi. Enjeksiyonları takiben beş gün boyunca östrüsler takip edildi. Diğer ineklere ise 11 (Grup II, n=15) ya da 14 (Grup III, n=16) gün ara...

  12. Business komunikace v poštovních službách

    OpenAIRE

    Becková, Helena

    2016-01-01

    Příspěvek se zabývá problematikou komunikace, se zaměřením na business komunikaci. Nejprve zdůrazňuje význam business komunikace pro úspěšnost podnikání. V rámci obecných principů komunikace se věnuje komunikačním dovednostem, pravidlům, která vedou k efektivní komunikaci, a jejich využití v business komunikaci. V následující části jsou zmíněny další aspekty business komunikace, jako jsou komunikační typy, komunikační styly, vyjednávání či konflikty. V příspěvku je vysvětlena důležitost busin...

  13. Pattern formation in superdiffusion Oregonator model

    Science.gov (United States)

    Feng, Fan; Yan, Jia; Liu, Fu-Cheng; He, Ya-Feng

    2016-10-01

    Pattern formations in an Oregonator model with superdiffusion are studied in two-dimensional (2D) numerical simulations. Stability analyses are performed by applying Fourier and Laplace transforms to the space fractional reaction-diffusion systems. Antispiral, stable turing patterns, and travelling patterns are observed by changing the diffusion index of the activator. Analyses of Floquet multipliers show that the limit cycle solution loses stability at the wave number of the primitive vector of the travelling hexagonal pattern. We also observed a transition between antispiral and spiral by changing the diffusion index of the inhibitor. Project supported by the National Natural Science Foundation of China (Grant Nos. 11205044 and 11405042), the Research Foundation of Education Bureau of Hebei Province, China (Grant Nos. Y2012009 and ZD2015025), the Program for Young Principal Investigators of Hebei Province, China, and the Midwest Universities Comprehensive Strength Promotion Project.

  14. Describing the urban form: morphometric indexes = Describiendo la forma urbana: índices morfométricos

    Directory of Open Access Journals (Sweden)

    Nicolás Ramírez

    2017-08-01

    Full Text Available Characterizing the urban form of cities from an aerodynamic point of view is essential to forecast pollutant dispersion, to implement and understand natural ventilation strategies or to enhance outdoor thermal comfort and pedestrian wind environment, to name a few. Nonetheless, accurate results make use, normally, of Computational Fluid Dynamic (CFD simulations, wind tunnel experiments and/or field measurements. However, these methodologies are expensive, time consuming and sometimes impossible to carry out. Therefore, simplified ways of characterizing a city aerodynamically must be put forward to bridge this gap. Two of the most common aerodynamic parameters, namely z0 (roughness length and zd (zero displacement length, can be related to the morphometry of the urban shape through simple morphometric indexes. This paper explores and analyses these indexes, and suggests an alternative and improved definition that might achieve more accurate results. Resumen Caracterizar la forma urbana de las ciudades desde un punto de vista aerodinámico es esencial para poder prever la dispersión de contaminantes, para implementar y comprender las estrategias de ventilación natural o para mejorar el control térmico en exteriores o el ambiente de viento peatonal, por citar sólo algunos casos. Para cualquiera de estos análisis, si se desea disponer de valores de cierta precisión es habitual emplear simulaciones mediante dinámica de fluidos computacional (CFD, experimentos en túnel de viento y/o tomas de datos de campo. Estos métodos, sin embargo, implican una inversión económica y temporal que en ocasiones no es posible realizar. El empleo de métodos simplificados para caracterizar la ciudad desde un punto de vista aerodinámico puede ayudar a hacer más sencillos estos procesos. Dos de los parámetros aerodinámicos más habituales, z0 (rugosidad superficial y zd (longitud desplazamiento cero pueden ponerse en relación con la morfometría de la

  15. Identification of selective inhibitors of RET and comparison with current clinical candidates through development and validation of a robust screening cascade [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Amanda J. Watson

    2016-05-01

    Full Text Available RET (REarranged during Transfection is a receptor tyrosine kinase, which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activation of RET is a mechanism of oncogenesis in medullary thyroid carcinomas where both germline and sporadic activating somatic mutations are prevalent.   At present, there are no known specific RET inhibitors in clinical development, although many potent inhibitors of RET have been opportunistically identified through selectivity profiling of compounds initially designed to target other tyrosine kinases. Vandetanib and cabozantinib, both multi-kinase inhibitors with RET activity, are approved for use in medullary thyroid carcinoma, but additional pharmacological activities, most notably inhibition of vascular endothelial growth factor - VEGFR2 (KDR, lead to dose-limiting toxicity. The recent identification of RET fusions present in ~1% of lung adenocarcinoma patients has renewed interest in the identification and development of more selective RET inhibitors lacking the toxicities associated with the current treatments.   In an earlier publication [Newton et al, 2016; 1] we reported the discovery of a series of 2-substituted phenol quinazolines as potent and selective RET kinase inhibitors. Here we describe the development of the robust screening cascade which allowed the identification and advancement of this chemical series.  Furthermore we have profiled a panel of RET-active clinical compounds both to validate the cascade and to confirm that none display a RET-selective target profile.

  16. Tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptor (VEGFR) have distinct cutaneous toxicity profiles: a meta-analysis and review of the literature.

    Science.gov (United States)

    Massey, Paul R; Okman, Jonathan S; Wilkerson, Julia; Cowen, Edward W

    2015-06-01

    Inhibition of the vascular endothelial growth factor receptor (VEGFR) with tyrosine kinase inhibitors (TKIs) is associated with cutaneous adverse effects that increase patient morbidity. Our objective was to examine the skin toxicity profile of anti-VEGFR TKIs and determine the changing incidence in clinical trials. PubMed was queried for phase II or III trials of anti-VEGFR TKIs between 2000 and 2013 involving ≥50 patients. Adverse events were abstracted, with results presented in both fixed and random effects models. Odds ratios (OR) and 95 % confidence intervals (CIs) were estimated for studies with at least two arms. Across 82 included studies, all grades rash (OR, 2.68; 95 % CI, 2.45-2.94), hand-foot skin reaction (HFSR) (OR, 2.70; 95 % CI, 2.43-3.00), and pruritus (OR, 1.25; 95 % CI, 1.12-1.39) were associated with anti-VEGFR TKIs. Vandetanib had the highest incidence of rash (41 %), while sorafenib was most commonly associated with HFSR (37 %) and pruritus (14 %). The incidence of HFSR from 2000 to 2013 showed an upward trend (r (2) = 0.042, p = 0.10) and in sunitinib therapy increased significantly (r (2) = 0.237, p = 0.04). The incidence of HFSR, rash, and pruritus varies considerably by drug. Our data suggest a continued need to address skin toxicities and improve reporting strategies.

  17. Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review.

    Science.gov (United States)

    Chen, Li-Tzong; Oh, Do-Youn; Ryu, Min-Hee; Yeh, Kun-Huei; Yeo, Winnie; Carlesi, Roberto; Cheng, Rebecca; Kim, Jongseok; Orlando, Mauro; Kang, Yoon-Koo

    2017-10-01

    Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

  18. Fatigue associated with newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: an up-to-date meta-analysis.

    Science.gov (United States)

    Li, Jing; Gu, Jian

    2017-10-01

    The fatigue associated with five newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) is poorly understood. We conducted this systematic review to fully investigate the fatigue associated with these VEGFR-TKIs in cancer patients. Relevant studies of randomized controlled trials in cancer patients treated with the five VEGFR-TKIs were retrieved and a systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until March 2017. Thirteen randomized controlled trials and 4395 patients were included. The current analysis suggested that the use of five newly approved VEGFR-TKIs increased the risk of all-grade fatigue (1.43; 95% CI 1.23-1.66; p fatigue (1.97; 95% CI1.44-2.70; p fatigue varied significantly within drug type, but high-grade fatigue did not. The RR of all-grade and high-grade fatigue did not vary significantly according to cancer type, treatment line, and treatment duration. The risk of high-grade fatigue may vary with treatment duration, whereas all-grade fatigue may not. The available data suggest that the use of the five newly approved VEGFR-TKIs is associated with a significantly increased risk of fatigue in cancer patients. Physicians should be aware of this adverse effect and should monitor cancer patients receiving these drugs.

  19. Establishment for Nuclear Equipment: Overview

    International Nuclear Information System (INIS)

    Pracz, J.

    1999-01-01

    Full text: In 1998 ZdAJ was mainly involved in the production of accelerators, simulators and tables ordered by the domestic market or destined for export. ZDAJ produced 28 POLKAM 15 therapeutic tables, 7 SIMAX X-ray simulators, 2 Coline soft accelerators and 2 Neptun accelerators. In addition 2D ALFARD treatment planning system was introduced for sale and five planning systems were installed in Polish hospitals. An order was received for the delivery of target chambers for the Isolde experiment carried out by CERN European Laboratory in Geneva. It is noteworthy that we got 1998 ''Teraz Polska'' prize, a reward for the best industrial product of the year based on Polish technical solutions, for the SACON cancer treatment therapeutic range. The SACON therapeutic range includes SMIAX diagnostic simulator with POLKAM 15 table, ALFARD treatment planning system, as well as Coline and Neptun accelerators. (author)

  20. Universality for 1d Random Band Matrices: Sigma-Model Approximation

    Science.gov (United States)

    Shcherbina, Mariya; Shcherbina, Tatyana

    2018-02-01

    The paper continues the development of the rigorous supersymmetric transfer matrix approach to the random band matrices started in (J Stat Phys 164:1233-1260, 2016; Commun Math Phys 351:1009-1044, 2017). We consider random Hermitian block band matrices consisting of W× W random Gaussian blocks (parametrized by j,k \\in Λ =[1,n]^d\\cap Z^d ) with a fixed entry's variance J_{jk}=δ _{j,k}W^{-1}+β Δ _{j,k}W^{-2} , β >0 in each block. Taking the limit W→ ∞ with fixed n and β , we derive the sigma-model approximation of the second correlation function similar to Efetov's one. Then, considering the limit β , n→ ∞, we prove that in the dimension d=1 the behaviour of the sigma-model approximation in the bulk of the spectrum, as β ≫ n , is determined by the classical Wigner-Dyson statistics.

  1. Novostavba rodinného domu s projekční kanceláří

    OpenAIRE

    Kopecká, Andrea

    2014-01-01

    Tato bakalářská práce zpracovává návrh novostavby rodinného domu s projekční kanceláří na území obce Boršov. Jedná se o dvoupodlažní stavbu s jednou obytnou buňkou pro 4 osoby a s provozovnou kanceláře. Dům je navržen ze zděného systému a jeho střecha je řešena jako plochá. Střecha nad kanceláří je rozdělena na pochozí terasu a vegetační střechu. Projektová dokumentace je zpracovaná v souladu s aktuálně platnými zákony, vyhláškami a normami. This thesis describes of design a new building f...

  2. Dicty_cDB: Contig-U16187-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CI 5 ALP Hydra magnipapill... 62 2e-14 2 ( AW719233 ) LjNEST1e12r Lotus japonicus nodule library, matur... 5... 17ACDHMS_UP_015_C09_27OCT2004_075 Brassica napus ... 50 2e-09 3 ( EX123282 ) BR107112 mature green leaf cDNA library...a rapa sub... 50 2e-09 3 ( EX125217 ) BR109047 mature green leaf cDNA library KHLM Bras... 50 2e-09 3 ( EV161608 ) 0085470 Brassic...ETGS6H_UP_013_E04_15NOV2004_024 Brassica napus 6... 50 3e-08 3 ( CV515629 ) 0048P0010Z_H11_T7 Mimulus guttatus library 1 Mimu...E543256 ) 9RDBNGA_UP_037_C07_03DEC2003_059 Brassica napus -... 50 3e-08 3 ( CV515401 ) 0048P0009Z_D01_T7 Mimulus guttatus library

  3. Experimental investigation of vector static magnetic field detection using an NV center with a single first-shell 13C nuclear spin in diamond

    Science.gov (United States)

    Jiang, Feng-Jian; Ye, Jian-Feng; Jiao, Zheng; Jiang, Jun; Ma, Kun; Yan, Xin-Hu; Lv, Hai-Jiang

    2018-05-01

    We perform a proof-of-principle experiment that uses a single negatively charged nitrogen–vacancy (NV) color center with a nearest neighbor 13C nuclear spin in diamond to detect the strength and direction (including both polar and azimuth angles) of a static vector magnetic field by optical detection magnetic resonance (ODMR) technique. With the known hyperfine coupling tensor between an NV center and a nearest neighbor 13C nuclear spin, we show that the information of static vector magnetic field could be extracted by observing the pulsed continuous wave (CW) spectrum. Project supported by the National Natural Science Foundation of China (Grant Nos. 11305074, 11135002, and 11275083), the Key Program of the Education Department Outstanding Youth Foundation of Anhui Province, China (Grant No. gxyqZD2017080), and the Education Department Natural Science Foundation of Anhui Province, China (Grant No. KJHS2015B09).

  4. One-group Perturbation Theory Applied to Substitution Measurements with Void

    Energy Technology Data Exchange (ETDEWEB)

    Persson, R

    1962-06-15

    Formulas suitable for evaluating substitution measurements or single-rod experiments by means of one-group perturbation theory are derived. The diffusion coefficient may depend on direction and position. By using the buckling concept the expressions derived are quite simple and the perturbed flux can be taken into account in a comparatively simple way. By using an unconventional definition of cells a transition region is introduced quite logically. Experiments with voids around metal rods, diam. 3.05 cm, have been analysed. The agreement between extrapolated and directly measured buckling values is excellent, the buckling difference between lattices with water-filled and voided shrouds being 0.263 {+-} 0.015/m{sup 2} and 0.274 {+-} 0.005 /m{sup 2} resp. The differences between diffusion coefficients are also determined, {delta}D{sub r}/D = 0.083 {+-} 0.004 and {delta}D{sub z}/D = 0.120 {+-} 0.018.

  5. On Properties of Impurity Spectrum in the Disordered Exactly Solvable Model

    CERN Document Server

    Grinshpun, V

    2006-01-01

    The random point interaction Hamiltonian (H) is considered on L^2(R^d), d=2, or d=3. Existence and certain bounds of the non-empty pure point component and exponential decay of the corresponding eigenfunctions with probability 1, within region of impurity spectrum of H, are rigorously established. In order to prove the localization result, the structure of the generalized eigenfunctions of H is explicitly described, and the relation between its spectral properties, and the properties of spectra of finite-difference infinite-order operators on l^2(Z^d), is established. The multiscale analysis scheme is applied to investigate the point spectrum of finite-difference operators. In addition, the generalized spectral theorem, and absolute continuity of the integrated density of states of H at the negative (impurity) part of the spectrum, rigorously proved. Applications of the new approximation scheme include straightforward analysis of absolutely continuous conductivity spectrum, subject to a possible separate publ...

  6. Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces Apoptosis

    Directory of Open Access Journals (Sweden)

    J. Bolnick

    2011-01-01

    Full Text Available We identified a major peptide signaling target of EGF/EGFR pathway and explored the consequences of blocking or activating this pathway in the first trimester extravillous trophoblast cells, HTR-8/SVneo. A global analysis of protein phosphorylation was undertaken using novel technology (Kinexus Kinetworks that utilizes SDS-polyacrylamide minigel electrophoresis and multi-lane immunoblotting to permit specific and semiquantitative detection of multiple phosphoproteins. Forty-seven protein phosphorylation sites were queried, and the results reported based on relative phosphorylation at each site. EGF- and Iressa-(gefitinib, ZD1839, an inhibitor of EGFR treated HTR-8/SVneo cells were subjected to immunoblotting and flow cytometry to confirm the phosphoprotein screen and to assess the effects of EGF versus Iressa on cell cycle and apoptosis. EGFR mediates the phosphorylation of important signaling proteins, including PKBα/AKT. This pathway is likely to be central to EGFR-mediated trophoblast survival. Furthermore, EGF treatment induces proliferation and inhibits apoptosis, while Iressa induces apoptosis.

  7. A Continuous Family of Equilibria in Ferromagnetic Media are Ground States

    Science.gov (United States)

    Su, Xifeng; de la Llave, Rafael

    2017-09-01

    We show that a foliation of equilibria (a continuous family of equilibria whose graph covers all the configuration space) in ferromagnetic transitive models are ground states. The result we prove is very general, and it applies to models with long range and many-body interactions. As an application, we consider several models of networks of interacting particles including models of Frenkel-Kontorova type on Z^d and one-dimensional quasi-periodic media. The result above is an analogue of several results in the calculus of variations (fields of extremals) and in PDE's. Since the models we consider are discrete and long range, new proofs need to be given. We also note that the main hypothesis of our result (the existence of foliations of equilibria) is the conclusion (using KAM theory) of several recent papers. Hence, we obtain that the KAM solutions recently established are minimizers when the interaction is ferromagnetic and transitive (these concepts are defined later).

  8. Rodinný dům s ateliérem, Roztoky u Prahy

    OpenAIRE

    Degr, Luboš

    2013-01-01

    Předmětem této bakalářské práce je novostavba rodinného domu s ateliérem v Roztokách u Prahy. Objekt se dělí na dvě části. První - obytná část je dvoupodlažní a je izolována od komunikace druhou částí. Druhá část je jednopodlažní s otevřeným pracovním prostorem, oddělenou kanceláří a zasedací místností. Objekt je navržen jako zděný z broušených cihelných bloků s keramickou stropní konstrukcí. Střecha objektu je plochá a na jednopodlažní části domu slouží zároveň jako terasa. Stavební pozemek ...

  9. Search for Higgs boson decays to beyond-the-Standard-Model light bosons in four-lepton events with the ATLAS detector at $\\sqrt{s}=13$ TeV

    CERN Document Server

    Aaboud, Morad; ATLAS Collaboration; Abbott, Brad; Abdinov, Ovsat; Abeloos, Baptiste; Abidi, Syed Haider; AbouZeid, Ossama; Abraham, Nicola; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adachi, Shunsuke; Adamczyk, Leszek; Adelman, Jahred; Adersberger, Michael; Adye, Tim; Affolder, Tony; Afik, Yoav; Agatonovic-Jovin, Tatjana; Agheorghiesei, Catalin; Aguilar-Saavedra, Juan Antonio; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akatsuka, Shunichi; Akerstedt, Henrik; {\\AA}kesson, Torsten Paul Ake; Akilli, Ece; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albicocco, Pietro; Alconada Verzini, Maria Josefina; Alderweireldt, Sara; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexopoulos, Theodoros; Alhroob, Muhammad; Ali, Babar; Aliev, Malik; Alimonti, Gianluca; Alison, John; Alkire, Steven Patrick; Allbrooke, Benedict; Allen, Benjamin William; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Alshehri, Azzah Aziz; Alstaty, Mahmoud; Alvarez Gonzalez, Barbara; \\'{A}lvarez Piqueras, Dami\\'{a}n; Alviggi, Mariagrazia; Amadio, Brian Thomas; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amoroso, Simone; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, John Kenneth; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Angelidakis, Stylianos; Angelozzi, Ivan; Angerami, Aaron; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antel, Claire; Antonelli, Mario; Antonov, Alexey; Antrim, Daniel Joseph; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Araujo Ferraz, Victor; Arce, Ayana; Ardell, Rose Elisabeth; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Armitage, Lewis James; Arnaez, Olivier; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Artz, Sebastian; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; Augsten, Kamil; Avolio, Giuseppe; Axen, Bradley; Ayoub, Mohamad Kassem; Azuelos, Georges; Baas, Alessandra; Baca, Matthew John; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Bagnaia, Paolo; Bahmani, Marzieh; Bahrasemani, Sina; Baines, John; Bajic, Milena; Baker, Oliver Keith; Bakker, Pepijn Johannes; Baldin, Evgenii; Balek, Petr; Balli, Fabrice; Balunas, William Keaton; Banas, Elzbieta; Bandyopadhyay, Anjishnu; Banerjee, Swagato; Bannoura, Arwa A E; Barak, Liron; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barisits, Martin-Stefan; Barkeloo, Jason Tyler Colt; Barklow, Timothy; Barlow, Nick; Barnes, Sarah Louise; Barnett, Bruce; Barnett, Michael; Barnovska-Blenessy, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barranco Navarro, Laura; Barreiro, Fernando; Barreiro Guimar\\~{a}es da Costa, Jo\\~{a}o; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Basalaev, Artem; Bassalat, Ahmed; Bates, Richard; Batista, Santiago Juan; Batley, Richard; Battaglia, Marco; Bauce, Matteo; Bauer, Florian; Bawa, Harinder Singh; Beacham, James; Beattie, Michael David; Beau, Tristan; Beauchemin, Pierre-Hugues; Bechtle, Philip; Beck, Hans~Peter; Beck, Helge Christoph; Becker, Kathrin; Becker, Maurice; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bednyakov, Vadim; Bedognetti, Matteo; Bee, Christopher; Beermann, Thomas; Begalli, Marcia; Begel, Michael; Behr, Janna Katharina; Bell, Andrew Stuart; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belotskiy, Konstantin; Beltramello, Olga; Belyaev, Nikita; Benary, Odette; Benchekroun, Driss; Bender, Michael; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez, Jose; Benjamin, Douglas; Benoit, Mathieu; Bensinger, James; Bentvelsen, Stan; Beresford, Lydia; Beretta, Matteo; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Beringer, J\\"urg; Berlendis, Simon; Bernard, Nathan Rogers; Bernardi, Gregorio; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertoli, Gabriele; Bertram, Iain Alexander; Bertsche, Carolyn; Bertsche, David; Besjes, Geert-Jan; Bessidskaia Bylund, Olga; Bessner, Martin Florian; Besson, Nathalie; Bethani, Agni; Bethke, Siegfried; Betti, Alessandra; Bevan, Adrian John; Beyer, Julien-christopher; Bianchi, Riccardo-Maria; Biebel, Otmar; Biedermann, Dustin; Bielski, Rafal; Bierwagen, Katharina; Biesuz, Nicolo Vladi; Biglietti, Michela; Billoud, Thomas Remy Victor; Bilokon, Halina; Bindi, Marcello; Bingul, Ahmet; Bini, Cesare; Biondi, Silvia; Bisanz, Tobias; Bittrich, Carsten; Bjergaard, David Martin; Black, James; Black, Kevin; Blair, Robert; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blue, Andrew; Blumenschein, Ulrike; Blunier, Sylvain; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Bock, Christopher; Boehler, Michael; Boerner, Daniela; Bogavac, Danijela; Bogdanchikov, Alexander; Bohm, Christian; Boisvert, Veronique; Bokan, Petar; Bold, Tomasz; Boldyrev, Alexey; Bolz, Arthur Eugen; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Bortfeldt, Jonathan; Bortoletto, Daniela; Bortolotto, Valerio; Boscherini, Davide; Bosman, Martine; Bossio Sola, Jonathan David; Boudreau, Joseph; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Boutle, Sarah Kate; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozson, Adam James; Bracinik, Juraj; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Braren, Frued; Bratzler, Uwe; Brau, Benjamin; Brau, James; Breaden Madden, William Dmitri; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Lydia; Brenner, Richard; Bressler, Shikma; Briglin, Daniel Lawrence; Bristow, Timothy Michael; Britton, Dave; Britzger, Daniel; Brochu, Frederic; Brock, Ian; Brock, Raymond; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Broughton, James; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruni, Alessia; Bruni, Graziano; Bruni, Lucrezia Stella; Bruno, Salvatore; Brunt, Benjamin; Bruschi, Marco; Bruscino, Nello; Bryant, Patrick; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Buchholz, Peter; Buckley, Andrew; Budagov, Ioulian; Buehrer, Felix; Bugge, Magnar Kopangen; Bulekov, Oleg; Bullock, Daniel; Burch, Tyler James; Burdin, Sergey; Burgard, Carsten Daniel; Burger, Angela Maria; Burghgrave, Blake; Burka, Klaudia; Burke, Stephen; Burmeister, Ingo; Burr, Jonathan Thomas Peter; Busato, Emmanuel; B\\"uscher, Daniel; B\\"uscher, Volker; Bussey, Peter; Butler, John; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Buzykaev, Aleksey; C-Q, Changqiao; Cabrera Urb\\'an, Susana; Caforio, Davide; Cai, Huacheng; Cairo, Valentina; Cakir, Orhan; Calace, Noemi; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Callea, Giuseppe; Caloba, Luiz; Calvente Lopez, Sergio; Calvet, David; Calvet, Samuel; Calvet, Thomas Philippe; Camacho Toro, Reina; Camarda, Stefano; Camarri, Paolo; Cameron, David; Caminal Armadans, Roger; Camincher, Clement; Campana, Simone; Campanelli, Mario; Camplani, Alessandra; Campoverde, Angel; Canale, Vincenzo; Cano Bret, Marc; Cantero, Josu; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Carbone, Ryne Michael; Cardarelli, Roberto; Cardillo, Fabio; Carli, Ina; Carli, Tancredi; Carlino, Gianpaolo; Carlson, Benjamin Taylor; Carminati, Leonardo; Carney, Rebecca; Caron, Sascha; Carquin, Edson; Carr\\'a, Sonia; Carrillo-Montoya, German D; Casadei, Diego; Casado, Maria Pilar; Casha, Albert Francis; Casolino, Mirkoantonio; Casper, David William; Castelijn, Remco; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Caudron, Julien; Cavaliere, Viviana; Cavallaro, Emanuele; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Celebi, Emre; Ceradini, Filippo; Cerda Alberich, Leonor; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chan, Stephen Kam-wah; Chan, Wing Sheung; Chan, Yat Long; Chang, Philip; Chapman, John Derek; Charlton, David; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Che, Siinn; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Cheng; Chen, Chunhui; Chen, Hucheng; Chen, Jing; Chen, Shenjian; Chen, Shion; Chen, Xin; Chen, Ye; Cheng, Hok Chuen; Cheng, Huajie; Cheplakov, Alexander; Cheremushkina, Evgeniya; Cherkaoui El Moursli, Rajaa; Cheu, Elliott; Cheung, Kingman; Chevalier, Laurent; Chiarella, Vitaliano; Chiarelli, Giorgio; Chiodini, Gabriele; Chisholm, Andrew; Chitan, Adrian; Chiu, Yu Him Justin; Chizhov, Mihail; Choi, Kyungeon; Chomont, Arthur Rene; Chouridou, Sofia; Chow, Yun Sang; Christodoulou, Valentinos; Chu, Ming Chung; Chudoba, Jiri; Chuinard, Annabelle Julia; Chwastowski, Janusz; Chytka, Ladislav; Ciftci, Abbas Kenan; Cinca, Diane; Cindro, Vladimir; Cioar\\u{a}, Irina Antonela; Ciocio, Alessandra; Cirotto, Francesco; Citron, Zvi Hirsh; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Brian Lee; Clark, Michael; Clark, Philip James; Clarke, Robert; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Colasurdo, Luca; Cole, Brian; Colijn, Auke-Pieter; Collot, Johann; Colombo, Tommaso; Conde Mui\\~no, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Constantinescu, Serban; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper-Sarkar, Amanda; Cormier, Felix; Cormier, Kyle James Read; Corradi, Massimo; Corriveau, Francois; Cortes-Gonzalez, Arely; Costa, Giuseppe; Costa, Mar\\'ia Jos\\'e; Costanzo, Davide; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Crawley, Samuel Joseph; Creager, Rachael; Cree, Graham; Cr\\'ep\\'e-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cueto, Ana; Cuhadar Donszelmann, Tulay; Cukierman, Aviv Ruben; Cummings, Jane; Curatolo, Maria; C\\'uth, Jakub; Czekierda, Sabina; Czodrowski, Patrick; D'amen, Gabriele; D'Auria, Saverio; D'eramo, Louis; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dado, Tomas; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Dandoy, Jeffrey; Daneri, Maria Florencia; Dang, Nguyen Phuong; Daniells, Andrew Christopher; Dann, Nicholas Stuart; Danninger, Matthias; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Daubney, Thomas; Davey, Will; David, Claire; Davidek, Tomas; Davis, Douglas; Davison, Peter; Dawe, Edmund; Dawson, Ian; De, Kaushik; de Asmundis, Riccardo; De Benedetti, Abraham; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Maria, Antonio; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vasconcelos Corga, Kevin; De Vivie De Regie, Jean-Baptiste; Debbe, Ramiro; Debenedetti, Chiara; Dedovich, Dmitri; Dehghanian, Nooshin; Deigaard, Ingrid; Del Gaudio, Michela; Del Peso, Jose; Delgove, David; Deliot, Frederic; Delitzsch, Chris Malena; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delporte, Charles; Delsart, Pierre-Antoine; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Denysiuk, Denys; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Dette, Karola; Devesa, Maria Roberta; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Bello, Francesco Armando; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Clemente, William Kennedy; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Micco, Biagio; Di Nardo, Roberto; Di Petrillo, Karri Folan; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaconu, Cristinel; Diamond, Miriam; Dias, Flavia; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; D\\'iez Cornell, Sergio; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; Barros do Vale, Maria Aline; Dobos, Daniel; Dobre, Monica; Dodsworth, David; Doglioni, Caterina; Dolejsi, Jiri; Dolezal, Zdenek; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Drechsler, Eric; Dris, Manolis; Du, Yanyan; Duarte-Campderros, Jorge; Dubinin, Filipp; Dubreuil, Arnaud; Duchovni, Ehud; Duckeck, Guenter; Ducourthial, Audrey; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Dudder, Andreas Christian; Duffield, Emily Marie; Duflot, Laurent; D\\"uhrssen, Michael; Dulsen, Carsten; Dumancic, Mirta; Dumitriu, Ana Elena; Duncan, Anna Kathryn; Dunford, Monica; Duperrin, Arnaud; Duran Yildiz, Hatice; D\\"uren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dutta, Baishali; Duvnjak, Damir; Dyndal, Mateusz; Dziedzic, Bartosz Sebastian; Eckardt, Christoph; Ecker, Katharina Maria; Edgar, Ryan Christopher; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; El Kosseifi, Rima; Ellajosyula, Venugopal; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Ennis, Joseph Stanford; Epland, Matthew Berg; Erdmann, Johannes; Ereditato, Antonio; Ernst, Michael; Errede, Steven; Escalier, Marc; Escobar, Carlos; Esposito, Bellisario; Estrada Pastor, Oscar; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Ezzi, Mohammed; Fabbri, Federica; Fabbri, Laura; Fabiani, Veronica; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farina, Christian; Farina, Edoardo Maria; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Faucci Giannelli, Michele; Favareto, Andrea; Fawcett, William James; Fayard, Louis; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Fenton, Michael James; Fenyuk, Alexander; Feremenga, Last; Fernandez Martinez, Patricia; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Fiedler, Frank; Filip\\v{c}i\\v{c}, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Fischer, Adam; Fischer, Cora; Fischer, Julia; Fisher, Wade Cameron; Flaschel, Nils; Fleck, Ivor; Fleischmann, Philipp; Fletcher, Rob Roy MacGregor; Flick, Tobias; Flierl, Bernhard Matthias; Flores Castillo, Luis; Flowerdew, Michael; Forcolin, Giulio Tiziano; Formica, Andrea; F\\"orster, Fabian Alexander; Forti, Alessandra; Foster, Andrew Geoffrey; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Franchino, Silvia; Francis, David; Franconi, Laura; Franklin, Melissa; Frate, Meghan; Fraternali, Marco; Freeborn, David; Fressard-Batraneanu, Silvia; Freund, Benjamin; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fusayasu, Takahiro; Fuster, Juan; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gach, Grzegorz; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Louis Guillaume; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Ganguly, Sanmay; Gao, Yanyan; Gao, Yongsheng; Garay Walls, Francisca; Garc\\'ia, Carmen; Garc\\'ia Navarro, Jos\\'e Enrique; Garc\\'ia Pascual, Juan Antonio; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gascon Bravo, Alberto; Gasnikova, Ksenia; Gatti, Claudio; Gaudiello, Andrea; Gaudio, Gabriella; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Gee, Norman; Geisen, Jannik; Geisen, Marc; Geisler, Manuel Patrice; Gellerstedt, Karl; Gemme, Claudia; Genest, Marie-H\\'el\\`ene; Geng, Cong; Gentile, Simonetta; Gentsos, Christos; George, Simon; Gerbaudo, Davide; Ge\\ss{}ner, Gregor; Ghasemi, Sara; Ghneimat, Mazuza; Giacobbe, Benedetto; Giagu, Stefano; Giangiacomi, Nico; Giannetti, Paola; Gibson, Stephen; Gignac, Matthew; Gilchriese, Murdock; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giordani, MarioPaolo; Giorgi, Filippo Maria; Giraud, Pierre-Francois; Giromini, Paolo; Giugliarelli, Gilberto; Giugni, Danilo; Giuli, Francesco; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, B{\\o}rge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gkountoumis, Panagiotis; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Goblirsch-Kolb, Maximilian; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gon\\c calo, Ricardo; Goncalves Gama, Rafael; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Giulia; Gonella, Laura; Gongadze, Alexi; Gonski, Julia; Gonz\\'alez de la Hoz, Santiago; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gori\\v{s}ek, Andrej; Goshaw, Alfred; G\\"ossling, Claus; Gostkin, Mikhail Ivanovitch; Gottardo, Carlo Alberto; Goudet, Christophe Raymond; Goujdami, Driss; Goussiou, Anna; Govender, Nicolin; Gozani, Eitan; Grabowska-Bold, Iwona; Gradin, Per Olov Joakim; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Gratchev, Vadim; Gravila, Paul Mircea; Gray, Chloe; Gray, Heather; Greenwood, Zeno Dixon; Grefe, Christian; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Grevtsov, Kirill; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grivaz, Jean-Francois; Groh, Sabrina; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Grummer, Aidan; Guan, Liang; Guan, Wen; Guenther, Jaroslav; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Gui, Bin; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Guo, Wen; Guo, Yicheng; Gupta, Ruchi; Gurbuz, Saime; Gustavino, Giuliano; Gutelman, Benjamin Jacque; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guyot, Claude; Guzik, Marcin Pawel; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Hadef, Asma; Hageb\\"ock, Stephan; Hagihara, Mutsuto; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamilton, Andrew; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Han, Shuo; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Handl, David Michael; Haney, Bijan; Hanke, Paul; Hansen, J{\\o}rgen Beck; Hansen, Jorn Dines; Hansen, Maike Christina; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harrison, Paul Fraser; Hartmann, Nikolai Marcel; Hasegawa, Yoji; Hasib, Ahmed; Hassani, Samira; Haug, Sigve; Hauser, Reiner; Hauswald, Lorenz; Havener, Laura Brittany; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hayakawa, Daiki; Hayden, Daniel; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heer, Sebastian; Heidegger, Kim Katrin; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Jochen Jens; Heinrich, Lukas; Heinz, Christian; Hejbal, Jiri; Helary, Louis; Held, Alexander; Hellman, Sten; Helsens, Clement; Henderson, Robert; Heng, Yang; Henkelmann, Steffen; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Herde, Hannah; Herget, Verena; Hern\\'andez Jim\\'enez, Yesenia; Herr, Holger; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Herwig, Theodor Christian; Hesketh, Gavin Grant; Hessey, Nigel; Hetherly, Jeffrey Wayne; Higashino, Satoshi; Hig\\'on-Rodriguez, Emilio; Hildebrand, Kevin; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hils, Maximilian; Hinchliffe, Ian; Hirose, Minoru; Hirschbuehl, Dominic; Hiti, Bojan; Hladik, Ondrej; Hlaluku, Dingane Reward; Hoad, Xanthe; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hohn, David; Holmes, Tova Ray; Holzbock, Michael; Homann, Michael; Honda, Shunsuke; Honda, Takuya; Hong, Tae Min; Hooberman, Benjamin Henry; Hopkins, Walter; Horii, Yasuyuki; Horton, Arthur James; Hostachy, Jean-Yves; Hostiuc, Alexandru; Hou, Suen; Hoummada, Abdeslam; Howarth, James; Hoya, Joaquin; Hrabovsky, Miroslav; Hrdinka, Julia; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Qipeng; Hu, Shuyang; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Huhtinen, Mika; Hunter, Robert Francis Holub; Huo, Peng; Huseynov, Nazim; Huston, Joey; Huth, John; Hyneman, Rachel; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikeno, Masahiro; Ilchenko, Yuriy; Iliadis, Dimitrios; Ilic, Nikolina; Iltzsche, Franziska; Introzzi, Gianluca; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Isacson, Max Fredrik; Ishijima, Naoki; Ishino, Masaya; Ishitsuka, Masaki; Issever, Cigdem; Istin, Serhat; Ito, Fumiaki; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jabbar, Samina; Jackson, Paul; Jacobs, Ruth Magdalena; Jain, Vivek; Jakobi, Katharina Bianca; 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Kimura, Naoki; Kind, Oliver Maria; King, Barry; Kirchmeier, David; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kitali, Vincent; Kivernyk, Oleh; Kladiva, Eduard; Klapdor-Kleingrothaus, Thorwald; Klein, Matthew Henry; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klingl, Tobias; Klioutchnikova, Tatiana; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Aine; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; K\\"ohler, Nicolas Maximilian; Koi, Tatsumi; Kolb, Mathis; Koletsou, Iro; Komar, Aston; Kondo, Takahiko; Kondrashova, Nataliia; K\\"oneke, Karsten; K\\"onig, Adriaan; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; 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Kuprash, Oleg; Kurashige, Hisaya; Kurchaninov, Leonid; Kurochkin, Yurii; Kurth, Matthew Glenn; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwan, Tony; Kyriazopoulos, Dimitrios; La Rosa, Alessandro; La Rosa Navarro, Jose Luis; La Rotonda, Laura; La Ruffa, Francesco; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lack, David Philip John; Lacker, Heiko; Lacour, Didier; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lai, Stanley; Lammers, Sabine; Lampl, Walter; Lan\\c con, Eric; Landgraf, Ulrich; Landon, Murrough; Lanfermann, Marie Christine; Lang, Valerie Susanne; Lange, J \\"{o}rn Christian; Langenberg, Robert Johannes; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Lanza, Agostino; Lapertosa, Alessandro; Laplace, Sandrine; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Lau, Tak Shun; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Lazovich, Tomo; Lazzaroni, Massimo; Le, Brian; Le Dortz, Olivier; Le Guirriec, Emmanuel; 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Luzi, Pierre Marc; Lynn, David; Lysak, Roman; Lytken, Else; Lyu, Feng; Lyubushkin, Vladimir; Ma, Hong; Ma, Lian Liang; Ma, Yanhui; Maccarrone, Giovanni; Macchiolo, Anna; Macdonald, Calum Michael; Ma\\v{c}ek, Bo\\v{s}tjan; Machado Miguens, Joana; Madaffari, Daniele; Madar, Romain; Mader, Wolfgang; Madsen, Alexander; Madysa, Nico; Maeda, Junpei; Maeland, Steffen; Maeno, Tadashi; Maevskiy, Artem; Magerl, Veronika; Maiani, Camilla; Maidantchik, Carmen; Maier, Thomas; Maio, Am\\'elia; Majersky, Oliver; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Claire; Maltezos, Stavros; Malyukov, Sergei; Mamuzic, Judita; Mancini, Giada; Mandi\\'{c}, Igor; Maneira, Jos\\'e; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mankinen, Katja Hannele; Mann, Alexander; Manousos, Athanasios; Mansoulie, Bruno; Mansour, Jason Dhia; Mantifel, Rodger; Mantoani, Matteo; Manzoni, Stefano; Mapelli, Livio; Marceca, Gino; March, Luis; Marchese, Luigi; Marchiori, Giovanni; Marcisovsky, Michal; Marin Tobon, Cesar Augusto; Marjanovic, Marija; Marley, Daniel; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Martensson, Mikael; Marti-Garcia, Salvador; Martin, Christopher Blake; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Mario; Martinez Outschoorn, Verena; Martin-Haugh, Stewart; Martoiu, Victor Sorin; Martyniuk, Alex; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Mason, Lara Hannan; Massa, Lorenzo; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; M\\"attig, Peter; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Maznas, Ioannis; Mazza, Simone Michele; Mc Fadden, Neil Christopher; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Thomas; McClymont, Laurie; McDonald, Emily; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McNamara, Peter Charles; McNicol, Christopher John; McPherson, Robert; Meehan, Samuel; Megy, Theo Jean; Mehlhase, Sascha; Mehta, Andrew; Meideck, Thomas; Meier, Karlheinz; Meirose, Bernhard; Melini, Davide; Mellado Garcia, Bruce Rafael; Mellenthin, Johannes Donatus; Melo, Matej; Meloni, Federico; Melzer, Alexander; Menary, Stephen Burns; Meng, Lingxin; Meng, Xiangting; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mergelmeyer, Sebastian; Merlassino, Claudia; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer Zu Theenhausen, Hanno; Miano, Fabrizio; Middleton, Robin; Miglioranzi, Silvia; Mijovi\\'{c}, Liza; Mikenberg, Giora; Mikestikova, Marcela; Miku\\v{z}, Marko; Milesi, Marco; Milic, Adriana; Millar, Declan Andrew; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Minegishi, Yuji; Ming, Yao; Mir, Lluisa-Maria; Mirto, Alessandro; Mistry, Khilesh; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mizukami, Atsushi; Mj\\"ornmark, Jan-Ulf; Mkrtchyan, Tigran; Mlynarikova, Michaela; Moa, Torbjoern; Mochizuki, Kazuya; Mogg, Philipp; Mohapatra, Soumya; Molander, Simon; Moles-Valls, Regina; Mondragon, Matthew Craig; M\\"onig, Klaus; Monk, James; Monnier, Emmanuel; Montalbano, Alyssa; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Ll\\'acer, Mar\\'ia; Morettini, Paolo; Morgenstern, Stefanie; Mori, Daniel; Mori, Tatsuya; Morii, Masahiro; Morinaga, Masahiro; Morisbak, Vanja; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morvaj, Ljiljana; Moschovakos, Paris; Mosidze, Maia; Moss, Harry James; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Moyse, Edward; Muanza, Steve; Mueller, Felix; Mueller, James; Mueller, Ralph Soeren Peter; Muenstermann, Daniel; Mullen, Paul; Mullier, Geoffrey; Munoz Sanchez, Francisca Javiela; Murray, Bill; Musheghyan, Haykuhi; Mu\\v{s}kinja, Miha; Myagkov, Alexey; Myska, Miroslav; Nachman, Benjamin Philip; Nackenhorst, Olaf; Nagai, Koichi; Nagai, Ryo; Nagano, Kunihiro; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nagy, Elemer; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Narrias Villar, Daniel Isaac; Naryshkin, Iouri; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nelson, Michael Edward; Nemecek, Stanislav; Nemethy, Peter; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Newman, Paul; Ng, Tsz Yu; Ng, Sam Yanwing; Nguyen Manh, Tuan; Nickerson, Richard; Nicolaidou, Rosy; Nielsen, Jason; Nikiforou, Nikiforos; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolopoulos, Konstantinos; Nilsen, Jon Kerr; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nishu, Nishu; Nisius, Richard; Nitsche, Isabel; Nitta, Tatsumi; Nobe, Takuya; Noguchi, Yohei; Nomachi, Masaharu; Nomidis, Ioannis; Nomura, Marcelo Ayumu; Nooney, Tamsin; Nordberg, Markus; Norjoharuddeen, Nurfikri; Novgorodova, Olga; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nurse, Emily; Nuti, Francesco; O'connor, Kelsey; O'Neil, Dugan; O'Rourke, Abigail Alexandra; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Ochoa-Ricoux, Juan Pedro; Oda, Susumu; Odaka, Shigeru; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Oleiro Seabra, Luis Filipe; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, Ant\\'onio; Onogi, Kouta; Onyisi, Peter; Oppen, Henrik; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Owen, Mark; Owen, Rhys Edward; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Pacheco Rodriguez, Laura; Padilla Aranda, Cristobal; Pagan Griso, Simone; Paganini, Michela; Paige, Frank; Palacino, Gabriel; Palazzo, Serena; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Panagiotopoulou, Evgenia; Panagoulias, Ilias; Pandini, Carlo Enrico; Panduro Vazquez, William; Pani, Priscilla; Panitkin, Sergey; Pantea, Dan; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Adam Jackson; Parker, Michael Andrew; Parker, Kerry Ann; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pascuzzi, Vincent; Pasner, Jacob Martin; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Francesca; Pataraia, Sophio; Pater, Joleen; Pauly, Thilo; Pearson, Benjamin; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Penc, Ondrej; Peng, Cong; Peng, Haiping; Penwell, John; Peralva, Bernardo; Perego, Marta Maria; Perepelitsa, Dennis; Peri, Francesco; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petroff, Pierre; Petrolo, Emilio; Petrov, Mariyan; Petrucci, Fabrizio; Pettersson, Nora Emilia; Peyaud, Alan; Pezoa, Raquel; Phillips, Forrest Hays; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Pickering, Mark Andrew; Piegaia, Ricardo; Pilcher, James; Pilkington, Andrew; Pinamonti, Michele; Pinfold, James; Pirumov, Hayk; Pitt, Michael; Plazak, Lukas; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Pluth, Daniel; Podberezko, Pavel; Poettgen, Ruth; Poggi, Riccardo; Poggioli, Luc; Pogrebnyak, Ivan; Pohl, David-leon; Pokharel, Ishan; Polesello, Giacomo; Poley, Anne-luise; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pomm\\`es, Kathy; Ponomarenko, Daniil; Pontecorvo, Ludovico; Popeneciu, Gabriel Alexandru; Portillo Quintero, Dilia Mar\\'ia; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potti, Harish; Poulsen, Trine; Poveda, Joaquin; Pozo Astigarraga, Mikel Eukeni; Pralavorio, Pascal; Pranko, Aliaksandr; Prell, Soeren; Price, Darren; Primavera, Margherita; Prince, Sebastien; Proklova, Nadezda; Prokofiev, Kirill; Prokoshin, Fedor; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Puri, Akshat; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Queitsch-Maitland, Michaela; Quilty, Donnchadha; Raddum, Silje; Radeka, Veljko; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Raine, John Andrew; Rajagopalan, Srinivasan; Rangel-Smith, Camila; Rashid, Tasneem; Raspopov, Sergii; Ratti, Maria Giulia; Rauch, Daniel; Rauscher, Felix; Rave, Stefan; Ravinovich, Ilia; Rawling, Jacob Henry; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Reale, Marilea; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reed, Robert; Reeves, Kendall; Rehnisch, Laura; Reichert, Joseph; Reiss, Andreas; Rembser, Christoph; Ren, Huan; Rescigno, Marco; Resconi, Silvia; Resseguie, Elodie Deborah; Rettie, Sebastien; Reynolds, Elliot; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter, Stefan; Richter-Was, Elzbieta; Ricken, Oliver; Ridel, Melissa; Rieck, Patrick; Riegel, Christian Johann; Rieger, Julia; Rifki, Othmane; Rijssenbeek, Michael; Rimoldi, Adele; Rimoldi, Marco; Rinaldi, Lorenzo; Ripellino, Giulia; Risti\\'{c}, Branislav; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Rizzi, Chiara; Roberts, Rhys Thomas; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Rocco, Elena; Roda, Chiara; Rodina, Yulia; Rodriguez Bosca, Sergi; Rodriguez Perez, Andrea; Rodriguez Rodriguez, Daniel; Roe, Shaun; Rogan, Christopher Sean; R{\\o}hne, Ole; Roloff, Jennifer; Romaniouk, Anatoli; Romano, Marino; Romano Saez, Silvestre Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Rosati, Stefano; Rosbach, Kilian; Rose, Peyton; Rosien, Nils-Arne; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Jonatan; Rosten, Rachel; Rotaru, Marina; Rothberg, Joseph; Rousseau, David; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; R\\"uhr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Russell, Heather; Rutherfoord, John; Ruthmann, Nils; R{\\"u}ttinger, Elias Michael; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryu, Soo; Ryzhov, Andrey; Rzehorz, Gerhard Ferdinand; Saavedra, Aldo; Sabato, Gabriele; Sacerdoti, Sabrina; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Saha, Puja; Sahinsoy, Merve; Saimpert, Matthias; Saito, Masahiko; Saito, Tomoyuki; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salazar Loyola, Javier Esteban; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, Jos\\'e; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sammel, Dirk; Sampsonidis, Dimitrios; Sampsonidou, Despoina; S\\'anchez, Javier; Sanchez Martinez, Victoria; Sanchez Pineda, Arturo Rodolfo; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Christian Oliver; Sandhoff, Marisa; Sandoval, Carlos; Sankey, Dave; Sannino, Mario; Sano, Yuta; Sansoni, Andrea; Santoni, Claudio; Santos, Helena; Santoyo Castillo, Itzebelt; Sapronov, Andrey; Saraiva, Jo\\~ao; Sarrazin, Bjorn; Sasaki, Osamu; Sato, Koji; Sauvan, Emmanuel; Savage, Graham; Savard, Pierre; Savic, Natascha; Sawyer, Craig; Sawyer, Lee; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Schaarschmidt, Jana; Schacht, Peter; Schachtner, Balthasar Maria; Schaefer, Douglas; Schaefer, Leigh; Schaefer, Ralph; Schaeffer, Jan; Schaepe, Steffen; Schaetzel, Sebastian; Sch\\"afer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R Dean; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Schiavi, Carlo; Schier, Sheena; Schildgen, Lara Katharina; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmidt-Sommerfeld, Korbinian Ralf; Schmieden, Kristof; Schmitt, Christian; Schmitt, Stefan; Schmitz, Simon; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schopf, Elisabeth; Schott, Matthias; Schouwenberg, Jeroen; Schovancova, Jaroslava; Schramm, Steven; Schuh, Natascha; Schulte, Alexandra; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schweiger, Hansdieter; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Sciandra, Andrea; Sciolla, Gabriella; Scornajenghi, Matteo; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seixas, Jos\\'e; Sekhniaidze, Givi; Sekhon, Karishma; Sekula, Stephen; Semprini-Cesari, Nicola; Senkin, Sergey; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Sessa, Marco; Seuster, Rolf; Severini, Horst; \\v{S}filigoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shaikh, Nabila Wahab; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Shaw, Savanna Marie; Shcherbakova, Anna; Shehu, Ciwake Yusufu; Shen, Yu-Ting; Sherafati, Nima; Sherman, Alexander David; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shipsey, Ian Peter Joseph; Shirabe, Shohei; Shiyakova, Mariya; Shlomi, Jonathan; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Shojaii, Seyed Ruhollah; Shope, David Richard; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Sicho, Petr; Sickles, Anne Marie; Sidebo, Per Edvin; Sideras Haddad, Elias; Sidiropoulou, Ourania; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, Jos\\'e; Silverstein, Samuel; Simak, Vladislav; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simon, Manuel; Sinervo, Pekka; Sinev, Nikolai; Sioli, Maximiliano; Siragusa, Giovanni; Siral, Ismet; Sivoklokov, Serguei; Sj\\"{o}lin, J\\"{o}rgen; Skinner, Malcolm Bruce; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Slovak, Radim; Smakhtin, Vladimir; Smart, Ben; Smiesko, Juraj; Smirnov, Nikita; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Joshua Wyatt; Smith, Matthew; Smith, Russell; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snyder, Ian Michael; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; S{\\o}gaard, Andreas; Soh, Dart-yin; Sokhrannyi, Grygorii; Solans Sanchez, Carlos; Solar, Michael; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Son, Hyungsuk; Sopczak, Andre; Sosa, David; Sotiropoulou, Calliope Louisa; Sottocornola, Simone; Soualah, Rachik; Soukharev, Andrey; South, David; Sowden, Benjamin; Spagnolo, Stefania; Spalla, Margherita; Spangenberg, Martin; Span\\`o, Francesco; Sperlich, Dennis; Spettel, Fabian; Spieker, Thomas Malte; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; St Denis, Richard Dante; Stabile, Alberto; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanitzki, Marcel Michael; Stapf, Birgit Sylvia; Stapnes, Steinar; Starchenko, Evgeny; Stark, Giordon; Stark, Jan; Stark, Simon Holm; Staroba, Pavel; Starovoitov, Pavel; St\\"arz, Steffen; Staszewski, Rafal; Stegler, Martin; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stevenson, Thomas James; Stewart, Graeme; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strauss, Michael; Strizenec, Pavol; Str\\"ohmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Suchek, Stanislav; Sugaya, Yorihito; Suk, Michal; Sulin, Vladimir; Sultan, D M S; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Suruliz, Kerim; Suster, Carl; Sutton, Mark; Suzuki, Shota; Svatos, Michal; Swiatlowski, Maximilian; Swift, Stewart Patrick; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Tahirovic, Elvedin; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takasugi, Eric Hayato; Takeda, Kosuke; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tanaka, Junichi; Tanaka, Masahiro; Tanaka, Reisaburo; Tanaka, Shuji; Tanioka, Ryo; Tannenwald, Benjamin Bordy; Tapia Araya, Sebastian; Tapprogge, Stefan; Tarem, Shlomit; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Aaron; Taylor, Alan James; Taylor, Geoffrey; Taylor, Pierre Thor Elliot; Taylor, Wendy; Teixeira-Dias, Pedro; Temple, Darren; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Tepel, Fabian-Phillipp; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Thais, Savannah Jennifer; Theveneaux-Pelzer, Timoth\\'ee; Thiele, Fabian; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Paul; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Tian, Yun; Tibbetts, Mark James; Ticse Torres, Royer Edson; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tipton, Paul; Tisserant, Sylvain; Todome, Kazuki; Todorova-Nova, Sharka; Todt, Stefanie; Tojo, Junji; Tok\\'ar, Stanislav; Tokushuku, Katsuo; Tolley, Emma; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Tong, Baojia(Tony); Tornambe, Peter; Torrence, Eric; Torres, Heberth; Torr\\'o Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Treado, Colleen Jennifer; Trefzger, Thomas; Tresoldi, Fabio; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocm\\'e, Benjamin; Trofymov, Artur; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; Truong, Loan; Trzebinski, Maciej; Trzupek, Adam; Tsang, Ka Wa; Tseng, Jeffrey; Tsiareshka, Pavel; Tsipolitis, Georgios; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tu, Yanjun; Tudorache, Alexandra; Tudorache, Valentina; Tulbure, Traian Tiberiu; Tuna, Alexander Naip; Turchikhin, Semen; Turgeman, Daniel; Turk Cakir, Ilkay; Turra, Ruggero; Tuts, Michael; Ucchielli, Giulia; Ueda, Ikuo; Ughetto, Michael; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Uno, Kenta; Unverdorben, Christopher; Urban, Jozef; Urquijo, Phillip; Urrejola, Pedro; Usai, Giulio; Usui, Junya; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Vadla, Knut Oddvar Hoie; Vaidya, Amal; Valderanis, Chrysostomos; Valdes Santurio, Eduardo; Valente, Marco; Valentinetti, Sara; Valero, Alberto; Val\\'ery, Lo\\"ic; Valkar, Stefan; Vallier, Alexis; Valls Ferrer, Juan Antonio; Van Den Wollenberg, Wouter; van der Graaf, Harry; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vaniachine, Alexandre; Vankov, Peter; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varni, Carlo; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vasquez, Jared Gregory; Vasquez, Gerardo; Vazeille, Francois; Vazquez Furelos, David; Vazquez Schroeder, Tamara; Veatch, Jason; Veeraraghavan, Venkatesh; Veloce, Laurelle Maria; Veloso, Filipe; Veneziano, Stefano; Ventura, Andrea; Venturi, Manuela; Venturi, Nicola; Venturini, Alessio; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Ambrosius Thomas; Vermeulen, Jos; Vetterli, Michel; Viaux Maira, Nicolas; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigani, Luigi; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Vishwakarma, Akanksha; Vittori, Camilla; Vivarelli, Iacopo; Vlachos, Sotirios; Vogel, Marcelo; Vokac, Petr; Volpi, Guido; von der Schmitt, Hans; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Voss, Rudiger; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vuillermet, Raphael; Vukotic, Ilija; Wagner, Peter; Wagner, Wolfgang; Wagner-Kuhr, Jeannine; Wahlberg, Hernan; Wahrmund, Sebastian; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wallangen, Veronica; Wang, Chao; Wang, Chao; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Qing; Wang, Renjie; Wang, Rongkun; Wang, Rui; Wang, Song-Ming; Wang, Tingting; Wang, Wei; Wang, Wenxiao; Wang, Zirui; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Washbrook, Andrew; Watkins, Peter; Watson, Alan; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Aaron Foley; Webb, Samuel; Weber, Michele; Weber, Sebastian Mario; Weber, Stefan Wolf; Weber, Stephen; Webster, Jordan S; Weidberg, Anthony; Weinert, Benjamin; Weingarten, Jens; Weirich, Marcel; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Michael David; Werner, Per; Wessels, Martin; Weston, Thomas; Whalen, Kathleen; Whallon, Nikola Lazar; Wharton, Andrew Mark; White, Aaron; White, Andrew; White, Martin; White, Ryan; Whiteson, Daniel; Whitmore, Ben William; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wildauer, Andreas; Wilk, Fabian; Wilkens, Henric George; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, John; Wingerter-Seez, Isabelle; Winkels, Emma; Winklmeier, Frank; Winston, Oliver James; Winter, Benedict Tobias; Wittgen, Matthias; Wobisch, Markus; Wolf, Tim Michael Heinz; Wolff, Robert; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wong, Vincent Wai Sum; Woods, Natasha Lee; Worm, Steven; Wosiek, Barbara; Wotschack, Jorg; Wozniak, Krzysztof; Wu, Miles; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xi, Zhaoxu; Xia, Ligang; Xu, Da; Xu, Lailin; Xu, Tairan; Xu, Wenhao; Yabsley, Bruce; Yacoob, Sahal; Yamaguchi, Daiki; Yamaguchi, Yohei; Yamamoto, Akira; Yamamoto, Shimpei; Yamanaka, Takashi; Yamane, Fumiya; Yamatani, Masahiro; Yamazaki, Tomohiro; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Yi; Yang, Zongchang; Yao, Weiming; Yap, Yee Chinn; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yeletskikh, Ivan; Yigitbasi, Efe; Yildirim, Eda; Yorita, Kohei; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Yu, Jaehoon; Yu, Jie; Yuen, Stephanie P; Yusuff, Imran; Zabinski, Bartlomiej; Zacharis, Georgios; Zaidan, Remi; Zaitsev, Alexander; Zakharchuk, Nataliia; Zalieckas, Justas; Zaman, Aungshuman; Zambito, Stefano; Zanzi, Daniele; Zeitnitz, Christian; Zemaityte, Gabija; Zemla, Andrzej; Zeng, Jian Cong; Zeng, Qi; Zenin, Oleg; \\v{Z}eni\\v{s}, Tibor; Zerwas, Dirk; Zhang, Dengfeng; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Guangyi; Zhang, Huijun; Zhang, Jinlong; Zhang, Lei; Zhang, Liqing; Zhang, Matt; Zhang, Peng; Zhang, Rui; Zhang, Ruiqi; Zhang, Xueyao; Zhang, Yu; Zhang, Zhiqing; Zhao, Xiandong; Zhao, Yongke; Zhao, Zhengguo; Zhemchugov, Alexey; Zhou, Bing; Zhou, Chen; Zhou, Li; Zhou, Maosen; Zhou, Mingliang; Zhou, Ning; Zhou, You; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhukov, Konstantin; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Stephanie; Zinonos, Zinonas; Zinser, Markus; Ziolkowski, Michael; \\v{Z}ivkovi\\'{c}, Lidija; Zobernig, Georg; Zoccoli, Antonio; Zou, Rui; zur Nedden, Martin; Zwalinski, Lukasz

    2018-01-01

    A search is conducted for a new beyond-the-Standard-Model boson using events where a Higgs boson with mass 125 GeV decays to four leptons ($\\ell =$ $e$ or $\\mu$). This decay is presumed to occur via an intermediate state which contains one or two on-shell, promptly decaying bosons: $H\\rightarrow ZX/XX \\rightarrow 4\\ell$, where $X$ is a new vector boson $Z_d$ or pseudoscalar $a$ with mass between 1 and 60 GeV. The search uses $pp$ collision data collected with the ATLAS detector at the LHC with an integrated luminosity of 36.1 fb$^{-1}$ at a centre-of-mass energy $\\sqrt{s}=13$ TeV. No significant excess of events above Standard Model background predictions is observed; therefore, upper limits at 95% confidence level are set on model-independent fiducial cross-sections, and on the Higgs boson decay branching ratios to vector and pseudoscalar bosons in two benchmark models.

  10. Post-Endüstriyel İyimserlikten Hegemonik Despotizme: 21. Yüzyılın İlk Çeyreğinde Taşeron Çalışma

    OpenAIRE

    Nurol, Bahadır

    2017-01-01

    Taşeronluksistemi 1980’lerin sonlarından bu yana günümüz firmalarının maliyet düşürmestratejilerinin bir parçası olagelmiştir. Ancak sistemin teorik meşruiyeti,yirminci yüzyılın son çeyreğinde popülerlik kazanan post-endüstriyel toplumteorilerine dayanmaktadır. Bu teoriler taşeron çalışmasını bağımsız, yaratıcıve hayli yüksek vasıflı profesyonellere özgü bir iş olarak ele aldılar. Ancakson on yıl içinde taşeronluk sistemi neredeyse bütün iş alanlarına sızdı veemekçi sınıfların artan güvencesi...

  11. A dusty, normal galaxy in the epoch of reionization

    DEFF Research Database (Denmark)

    Watson, Darach; Christensen, Lise; Knudsen, Kirsten Kraiberg

    2015-01-01

    Candidates for the modest galaxies that formed most of the stars in the early universe, at redshifts $z > 7$, have been found in large numbers with extremely deep restframe-UV imaging. But it has proved difficult for existing spectrographs to characterise them in the UV. The detailed properties...... of these galaxies could be measured from dust and cool gas emission at far-infrared wavelengths if the galaxies have become sufficiently enriched in dust and metals. So far, however, the most distant UV-selected galaxy detected in dust emission is only at $z = 3.25$, and recent results have cast doubt on whether...... dust and molecules can be found in typical galaxies at this early epoch. Here we report thermal dust emission from an archetypal early universe star-forming galaxy, A1689-zD1. We detect its stellar continuum in spectroscopy and determine its redshift to be $z = 7.5\\pm0.2$ from a spectroscopic detection...

  12. Free Eenergy as a Dynamical and Geometric Invariant (or Can You Hear the Shape of a Potential?)

    CERN Document Server

    Pollicott, M

    2003-01-01

    The lattice gas provides an important and illuminating family of models in statistical physics. An interaction $\\Phi$ on a lattice $L \\subset \\Bbb Z^d$ determines an idealized lattice gas system with potential $A_\\Phi$. The pressure $P(A_\\Phi)$ and free energy $F_{A_\\Phi}(\\beta)= -(1/\\beta) P(\\beta A_\\Phi)$ are fundamental characteristics of the system. However, even for the simplest lattice systems, the information about the potential that the free energy captures is subtle and poorly understood. We study whether, or to what extent, potentials for certain model systems are determined by their free energy. In particular, we show that for a one-dimensional lattice gas, the free energy of finite range interactions typically determines the potential, up to natural equivalence, and there is always at most a finite ambiguity; we exhibit exceptional potentials where uniqueness fails; and we establish deformation rigidity for the free energy. The proofs use a combination of thermodynamic formalism, algebraic geometr...

  13. Localised surface plasmon-like resonance generated by microwave electromagnetic waves in pipe defects

    Science.gov (United States)

    Alobaidi, Wissam M.; Nima, Zeid A.; Sandgren, Eric

    2018-01-01

    Localised surface plasmon (LSP)-like resonance phenomena were simulated in COMSOL Multiphysics™, and the electric field enhancement was evaluated in eight pipe defects using the microwave band from 1.80 to 3.00 GHz and analysed by finite element analysis (FEA). The simulation was carried out, in each defect case, on a pipe that has 762 mm length and 152.4 mm inner diameter, and 12.7 mm pipe wall thickness. Defects were positioned in the middle of the pipe and were named as follows; SD: Square Defect, FCD: fillet corner defect, FD: fillet defect, HCD: half circle defect, TCD: triangle corner defect, TD: triangle defect, ZD: zigzag defect, GD: gear defect. The LSP electric field, and scattering parametric (S21, and S11) waves were evaluated in all cases and found to be strongly dependent on the size and the shape of the defect rather than the pipe and or the medium materials.

  14. Detrended cross-correlation coefficient: Application to predict apoptosis protein subcellular localization.

    Science.gov (United States)

    Liang, Yunyun; Liu, Sanyang; Zhang, Shengli

    2016-12-01

    Apoptosis, or programed cell death, plays a central role in the development and homeostasis of an organism. Obtaining information on subcellular location of apoptosis proteins is very helpful for understanding the apoptosis mechanism. The prediction of subcellular localization of an apoptosis protein is still a challenging task, and existing methods mainly based on protein primary sequences. In this paper, we introduce a new position-specific scoring matrix (PSSM)-based method by using detrended cross-correlation (DCCA) coefficient of non-overlapping windows. Then a 190-dimensional (190D) feature vector is constructed on two widely used datasets: CL317 and ZD98, and support vector machine is adopted as classifier. To evaluate the proposed method, objective and rigorous jackknife cross-validation tests are performed on the two datasets. The results show that our approach offers a novel and reliable PSSM-based tool for prediction of apoptosis protein subcellular localization. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Establishment for Nuclear Equipment: Overview

    International Nuclear Information System (INIS)

    Pracz, J.

    2000-01-01

    Full text: The main objective of the activity of the Establishment for Nuclear Equipment (ZdAJ) in 1999 was to obtain the ISO 9001 certificate. Work on this problem has been successfully completed. The changes introduced in agreement with requirements of ISO in supervising the construction, manufacturing and servicing eliminate possible deficiencies of our products and will pay in the future. Two new important ventures have been undertaken: design of an accelerator with two photon energies and a reconstruction of simulator directed towards better geometrical parameters. The completion of the improvements in accelerator is foreseen for the year 2002. The changes comprise almost all sub-assemblies of the device. The modernized simulator will be installed in the hospital already in the year 2000 - the ameliorations concern mainly the arm of the apparatus, collimator, driving gears and control system. Of course - apart from this, the routine production activity of the Establishment was continued in 1999. (author)

  16. In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma.

    Directory of Open Access Journals (Sweden)

    Susanna J E Veringa

    Full Text Available Pediatric high-grade gliomas (pHGG, including diffuse intrinsic pontine gliomas (DIPG, are the leading cause of cancer-related death in children. While it is clear that surgery (if possible, and radiotherapy are beneficial for treatment, the role of chemotherapy for these tumors is still unclear. Therefore, we performed an in vitro drug screen on primary glioma cells, including three DIPG cultures, to determine drug sensitivity of these tumours, without the possible confounding effect of insufficient drug delivery. This screen revealed a high in vitro cytotoxicity for melphalan, doxorubicine, mitoxantrone, and BCNU, and for the novel, targeted agents vandetanib and bortezomib in pHGG and DIPG cells. We subsequently determined the expression of the drug efflux transporters P-gp, BCRP1, and MRP1 in glioma cultures and their corresponding tumor tissues. Results indicate the presence of P-gp, MRP1 and BCRP1 in the tumor vasculature, and expression of MRP1 in the glioma cells themselves. Our results show that pediatric glioma and DIPG tumors per se are not resistant to chemotherapy. Treatment failure observed in clinical trials, may rather be contributed to the presence of drug efflux transporters that constitute a first line of drug resistance located at the blood-brain barrier or other resistance mechanism. As such, we suggest that alternative ways of drug delivery may offer new possibilities for the treatment of pediatric high-grade glioma patients, and DIPG in particular.

  17. The evolving field of kinase inhibitors in thyroid cancer.

    Science.gov (United States)

    Marotta, V; Sciammarella, C; Vitale, M; Colao, A; Faggiano, A

    2015-01-01

    Most of the genetic events implicated in the pathogenesis of thyroid cancer (TC) involve genes with kinase activity. Thus, kinase inhibitors (KIs) are very relevant in this field. KIs are considered the most suitable treatment for patients with iodine-refractory differentiated TC; these patients comprise the subgroup with the poorer prognosis. To date, only sorafenib has been approved for this indication, but promising results have been reported with several other KIs. In particular, lenvatinib has demonstrated excellent efficacy, with both progression-free survival and objective tumour response being better than with sorafenib. Despite being considered to be well tolerated, both sorafenib and lenvatinib have shown a remarkable toxicity, which has led to dose reductions in the majority of patients and to treatment discontinuation in a significant proportion of cases. The role of KIs in differentiated TC may be revolutionised by the finding that selumetinib may restore a clinical response to radioactive iodine (RAI). Vandetanib and cabozantinib have been approved for the treatment of advanced, progressive medullary TC (MTC). Nevertheless, the toxicity of both compounds suggests their selective use in those patients with strong disease progression. Treatment with the mTOR-inhibitor everolimus, alone or in combination with somatostatin analogues, should be studied in metastatic MTC patients with slow progression of disease, these representing the vast majority of patients. KIs did not significantly impact on the clinical features of anaplastic TC (ATC). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Thermal-hydraulic process for cooling, heating and power production with low-grade heat sources in residential sector

    International Nuclear Information System (INIS)

    Borgogno, R.; Mauran, S.; Stitou, D.; Marck, G.

    2017-01-01

    Highlights: • Assessment of solar thermal-hydraulic process for tri-generation application. • Choice of the most suitable working fluid pair (R1234yf/R1233zd). • Evaluation of the global annual performance in Mediterranean climate. • Global annual COP and heat amplification achieving 0.24 and 1.2 respectively. • Global annual performance achieving an electric efficiency of 3.7%. - Abstract: A new process based on thermal-hydraulic conversion actuated by low-grade thermal energy is investigated. Input thermal energy can be provided by the means of solar collectors, as well as other low temperature energy sources. In the following article, “thermo-hydraulic” term refers to a process involving an incompressible fluid used as an intermediate medium to transfer work hydraulically between different thermal operated components or sub-systems. The system aims at providing trigeneration energy features for the residential sector, that is providing heating, cooling and electrical power for meeting the energy needs of domestic houses. This innovative system is made of two dithermal processes (working at two different levels of temperatures) and featuring two different working fluids. The first process is able to directly supply either electrical energy generated by an hydraulic turbine or drives the second process thanks to the incompressible fluid, which is similar to a heat pump effect for heating or cooling purposes. The innovative aspect of this process relies on the use of an hydraulic transfer fluid to transfer the work between each sub-system and therefore simplifying the conversion chain. A model, assuming steady-state operation, is developed to assess the energy performances of different variants of this thermo-hydraulic process with various heat source temperatures (80–110 °C) or heat sinks (0–30 °C), as well as various pairs of working fluids. For instance, in the frame of a single-family home, located in the Mediterranean region, the working

  19. Analisis dan Optimalisasi Potensi Lahan Pertanian Sebagai Kajian Dampak Positif Erupsi Gunungapi Kelud 2014

    Directory of Open Access Journals (Sweden)

    Syamsul Bachri

    2017-12-01

    Full Text Available Abstract The 2014 eruption of Kelud Volcano has brought various effects on the surrounding agriculture. Aside from negative impact, it affected the potentials of agricultural land positively. This research analyzed the optimization of eruption-affected land using several steps. The first step was land suitability analysis with multicriteria assessment and Geographic Information System (GIS technology. In addition to the physical analysis, Focus Group Discussion (FGD was performed in the second step to identify the community’s perception of the eruption impact. The research produced land suitability maps consisting of the following classification: S1 (64.74%, S2 (31.51%, and S3 (3.75%. The maps revealed that the majority of the land in Kelud Volcano had the potentials for agricultural development. These findings were supported by the perception of the local community, which argued that they could significantly benefit from the positive impact of the eruption. Abstrak Erupsi gunungapi Kelud pada tahun 2014 membawa dampak yang beragam terhadap kondisi pertanian di sekitarnya. Selain dampak negatif, erupsi gunungapi Kelud membawa dampak positif khususnya pada potensi lahan terdampak yang perlu dioptimalkan. Melalui penelitian ini, kajian optimalisasi potensi lahan terdampak erupsi dilakukan dengan beberapa tahapan. Tahap pertama berupa analisis kesesuaian lahan melalui penilaian multikriteria dan teknologi Sistem Informasi geografis (SIG. Selain kajian fisik, kegiatan Focus Group Discussion (FGD merupakan tahapan kedua yang dilakukan untuk mengetahui bagaimana persepsi masyarakat terkait dengan dampak erupsi Gunungapi Kelud. Hasil penelitian menghasilkan peta kesesuaian dengan kelas kesesuaian S1 (64,74%, S2 (31,51%, S3 (3,75%. Berdasarkan hasil pemetaan ini, sebagian besar wilayah Gunungapi Kelud berpotensi untuk pengembangan pertanian. Hal ini didukung dengan persepsi masyarakat kawasan Gunungapi Kelud yang berpendapat bahwa dampak positif

  20. Moderní hebrejština: kukaččí mládě v semitském hnízdě?

    Czech Academy of Sciences Publication Activity Database

    Fottová, Magdaléna

    2017-01-01

    Roč. 10, č. 40 (2017), s. 70-71 ISSN 1803-8077 Institutional support: RVO:68378068 Keywords : Hebrew * Semitic language s * Slavic language s * language ideology Subject RIV: AJ - Letters, Mass-media, Audiovision OBOR OECD: Specific literatures

  1. Experience Modulates the Effects of Histone Deacetylase Inhibitors on Gene and Protein Expression in the Hippocampus: Impaired Plasticity in Aging.

    Science.gov (United States)

    Sewal, Angila S; Patzke, Holger; Perez, Evelyn J; Park, Pul; Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G; Fletcher, Bonnie R; Long, Jeffrey M; Rapp, Peter R

    2015-08-19

    The therapeutic potential of histone deacetylase inhibitor (HDACi) treatment has attracted considerable attention in the emerging area of cognitive neuroepigenetics. The possibility that ongoing cognitive experience importantly regulates the cell biological effects of HDACi administration, however, has not been systematically examined. In an initial experiment addressing this issue, we tested whether water maze training influences the gene expression response to acute systemic HDACi administration in the young adult rat hippocampus. Training powerfully modulated the response to HDACi treatment, increasing the total number of genes regulated to nearly 3000, including many not typically linked to neural plasticity, compared with neuroepigenetics. Copyright © 2015 the authors 0270-6474/15/3511730-14$15.00/0.

  2. Effects of Arbuscular Mycorrhiza on Osmotic Adjustment and Photosynthetic Physiology of Maize Seedlings in Black Soils Region of Northeast China

    Directory of Open Access Journals (Sweden)

    Hongwen Xu

    Full Text Available ABSTRACT To investigate the effect of arbuscular mycorrhiza fungi on maize growth, osmoregulation substances and photosynthetic physiology, a popular maize variety ZD 958 was measured under potted condition. Arbuscular mycorrhiza (AM symbiosis promoted plant growth, and enhanced plant height, leaf length, mean leaf width and dry weight. Higher soluble sugar and protein, but lower proline concentrations were detected in AM seedlings than corresponding non-AM seedlings. Quantum yield of PSII photochemistry and potential photochemical efficiency increased by arbuscular mycorrhiza fungi, meanwhile, AM plants had lower primary fluorescence but higher maximal fluorescence and variable fluorescence than non-AM plants. AM enhanced apparent quantum efficiency, maximum net photosynthetic rate, dark respiration rate and light saturation point, but reduced light compensation point. The conclusion was that, after the seedling inoculated with Glomus. tortuosum, AM symbioses could protect cell from being hurt through regulating substances related to osmotic adjustment, besides, the efficiency of light utilization, the capacity of using low light and the capacity of fitting and using high light were all increased by AM symbiosis.

  3. Wellness hotel

    OpenAIRE

    Bambas, Vratislav

    2013-01-01

    Novostavba Wellness hotelu. Objekt je částečně podsklepen. Hotel se skládá ze tří částí. Střední trakt je železobetonový skelet a má pět nadzemních podlaží. Tato část slouží jako vstupní hala a hlavní schodiště. Boční trakty mají čtyři nadzemní podlaží a jejich nosný systém je příčný stěnový, zděný, ze systému Porotherm. V suterénu se nachází zázemí hotelu a bazén. Do přízemí je umístěno restaurační zařízení. Ve druhém patře se nacházejí pokoje, posilovna a služby. V posledním patře jsou pouz...

  4. One-Group Perturbation Theory Applied to Measurements with Void

    Energy Technology Data Exchange (ETDEWEB)

    Persson, Rolf

    1966-09-15

    Formulas suitable for evaluating progressive as well as single rod substitution measurements are derived by means of one-group perturbation theory. The diffusion coefficient may depend on direction and position. By using the buckling concept one can derive expressions which are quite simple and the perturbed flux can be taken into account in a comparatively simple way. By using an unconventional definition of cells a transition region is introduced quite logically. Experiments with voids around metal rods, diam. 3.05 cm, have been analysed. The agreement between extrapolated and directly measured buckling values is excellent, the buckling difference between lattices with water-filled and voided shrouds being 0. 263 {+-} 0.015/m{sup 2} and 0.267 {+-} 0.005/m{sup 2} resp. From single-rod experiments differences between diffusion coefficients are determined to {delta}D{sub r}/D = 0.083 {+-} 0.004 and {delta}D{sub z}/D = 0.120 {+-} 0.018. With air-filled shrouds there is consequently anisotropy in the neutron diffusion and we have (D{sub z}/D{sub r}){sub air} = 1.034 {+-} 0.020.

  5. Zlepšení dispergace křemičitého úletu ve vysokohodnotných betonech

    OpenAIRE

    Janča, Martin

    2017-01-01

    Cílem této práce bylo vytvořit metodu pro zlepšení dispergace křemičitých úletů pro použití ve vysokohodnotných betonech. Tradiční metody použité pro návrh a výrobu vysokohodnotných betonů zdůrazňují odstranění hrubých agregátů. Využívají se speciálně tříděné jemné agregáty při relativně nízkých dávkách, superplastifikátory a křemičitý úlet. Nízkého obsahu záměsové vody bylo dosaženo pomocí použití superplastifikátorů na polykarboxylátové bázi. K samotné dispergaci křemičitého úletu byla vybr...

  6. Interfacial area transport of vertical upward air-water two-phase flow in an annulus at elevated pressures

    International Nuclear Information System (INIS)

    Ozar, Basar; Hibiki, Takashi; Ishii, Mamoru; Euh, Dong-Jin

    2009-01-01

    The interfacial area transport of vertical, upward, air-water two-phase flows in an annular channel has been investigated at different system pressures. The inner and outer diameters of the annular channel were 19.1 mm and 38.1 mm, respectively. Twenty three inlet flow conditions were selected, which coverED bubbly, cap-slug, and churn-turbulent flows. These flow conditions also overlapped with twelve conditions of our previous study for comparison. The local flow parameters, such as void fractions, interfacial area concentrations (IAC), and bubble interface velocities, were measured at nine radial positions for the three axial locations (z/D h =52, 149 and 230) and converted into area-averaged parameters. The axial evolutions of local flow structure was interpreted in terms of bubble coalescence, breakup, expansion of the gas-phase due to pressure drop and system pressure. An assessment of interfacial area transport equation (IATE) was made and compared with the experimental data. A discussion of the comparison between model prediction and the experimental results were made. (author)

  7. Annealed scaling for a charged polymer in dimensions two and higher

    Science.gov (United States)

    Berger, Q.; den Hollander, F.; Poisat, J.

    2018-02-01

    This paper considers an undirected polymer chain on {Z}d , d ≥slant 2 , with i.i.d. random charges attached to its constituent monomers. Each self-intersection of the polymer chain contributes an energy to the interaction Hamiltonian that is equal to the product of the charges of the two monomers that meet. The joint probability distribution for the polymer chain and the charges is given by the Gibbs distribution associated with the interaction Hamiltonian. The object of interest is the annealed free energy per monomer in the limit as the length n of the polymer chain tends to infinity. We show that there is a critical curve in the parameter plane spanned by the charge bias and the inverse temperature separating an extended phase from a collapsed phase. We derive the scaling of the critical curve for small and for large charge bias and the scaling of the annealed free energy for small inverse temperature. We argue that in the collapsed phase the polymer chain is subdiffusive, namely, on scale \

  8. Laboratorní měření předpjatého zdiva

    OpenAIRE

    Stará, Marie; Čajka, Radim; Matečková, Pavlína; Janulíková, Martina

    2012-01-01

    Předpínání zdiva je jednou z nejpoužívanějších a současně nejúčinějších metod sanace u staticky porušených objektů. Na stavební fakultě bylo vyrobeno laboratorní zařízení právě pro bližší zkoumání chování předpínaného zdiva. A to konkrétně pro měření deformací zděného rohu především v okolí kotevních desek, které slouží pro přenos předpínacích sil do zdiva. Měření bylo provedeno pro dvě hodnoty předpínacích sil. Předpětí bylo instalováno v obou směrech. Dále je zde okrajově poj...

  9. Phosphoproteomic fingerprinting of epidermal growth factor signaling and anticancer drug action in human tumor cells.

    Science.gov (United States)

    Lim, Yoon-Pin; Diong, Lang-Shi; Qi, Robert; Druker, Brian J; Epstein, Richard J

    2003-12-01

    Many proteins regulating cancer cell growth are tyrosine phosphorylated. Using antiphosphotyrosine affinity chromatography, thiourea protein solubilization, two-dimensional PAGE, and mass spectrometry, we report here the characterization of the epidermal growth factor (EGF)-induced phosphoproteome in A431 human epidermoid carcinoma cells. Using this approach, more than 50 distinct tyrosine phosphoproteins are identifiable within five main clusters-cytoskeletal proteins, signaling enzymes, SH2-containing adaptors, chaperones, and focal adhesion proteins. Comparison of the phosphoproteomes induced in vitro by transforming growth factor-alpha and platelet-derived growth factor demonstrates the pathway- and cell-specific nature of the phosphoproteomes induced. Elimination of both basal and ligand-dependent phosphoproteins by cell exposure to the EGF receptor catalytic inhibitor gefitinib (Iressa, ZD1839) suggests either an autocrine growth loop or the presence of a second inhibited kinase in A431 cells. By identifying distinct patterns of phosphorylation involving novel signaling substrates, and by clarifying the mechanism of action of anticancer drugs, these findings illustrate the potential of immunoaffinity-based phosphoproteomics for guiding the discovery of new drug targets and the rational utilization of pathway-specific chemotherapies.

  10. First law of entanglement rates from holography

    Science.gov (United States)

    O'Bannon, Andy; Probst, Jonas; Rodgers, Ronnie; Uhlemann, Christoph F.

    2017-09-01

    For a perturbation of the state of a conformal field theory (CFT), the response of the entanglement entropy is governed by the so-called "first law" of entanglement entropy, in which the change in entanglement entropy is proportional to the change in energy. Whether such a first law holds for other types of perturbations, such as a change to the CFT Lagrangian, remains an open question. We use holography to study the evolution in time t of entanglement entropy for a CFT driven by a t -linear source for a conserved U (1 ) current or marginal scalar operator. We find that although the usual first law of entanglement entropy may be violated, a first law for the rates of change of entanglement entropy and energy still holds. More generally, we prove that this first law for rates holds in holography for any asymptotically (d +1 )-dimensional anti-de Sitter metric perturbation whose t dependence first appears at order zd in the Fefferman-Graham expansion about the boundary at z =0 .

  11. Flow-driven simulation on variation diameter of counter rotating wind turbines rotor

    Directory of Open Access Journals (Sweden)

    Littik Y. Fredrika

    2018-01-01

    Full Text Available Wind turbines model in this paper developed from horizontal axis wind turbine propeller with single rotor (HAWT. This research aims to investigating the influence of front rotor diameter variation (D1 with rear rotor (D2 to the angular velocity optimal (ω and tip speed ratio (TSR on counter rotating wind turbines (CRWT. The method used transient 3D simulation with computational fluid dynamics (CFD to perform the aerodynamics characteristic of rotor wind turbines. The counter rotating wind turbines (CRWT is designed with front rotor diameter of 0.23 m and rear rotor diameter of 0.40 m. In this research, the wind velocity is 4.2 m/s and variation ratio between front rotor and rear rotor (D1/D2 are 0.65; 0.80; 1.20; 1.40; and 1.60 with axial distance (Z/D2 0.20 m. The result of this research indicated that the variation diameter on front rotor influence the aerodynamics performance of counter rotating wind turbines.

  12. An advanced SEU tolerant latch based on error detection

    Science.gov (United States)

    Xu, Hui; Zhu, Jianwei; Lu, Xiaoping; Li, Jingzhao

    2018-05-01

    This paper proposes a latch that can mitigate SEUs via an error detection circuit. The error detection circuit is hardened by a C-element and a stacked PMOS. In the hold state, a particle strikes the latch or the error detection circuit may cause a fault logic state of the circuit. The error detection circuit can detect the upset node in the latch and the fault output will be corrected. The upset node in the error detection circuit can be corrected by the C-element. The power dissipation and propagation delay of the proposed latch are analyzed by HSPICE simulations. The proposed latch consumes about 77.5% less energy and 33.1% less propagation delay than the triple modular redundancy (TMR) latch. Simulation results demonstrate that the proposed latch can mitigate SEU effectively. Project supported by the National Natural Science Foundation of China (Nos. 61404001, 61306046), the Anhui Province University Natural Science Research Major Project (No. KJ2014ZD12), the Huainan Science and Technology Program (No. 2013A4011), and the National Natural Science Foundation of China (No. 61371025).

  13. Understanding carbon regulation in aquatic systems - Bacteriophages as a model [v1; ref status: indexed, http://f1000r.es/4zd

    Directory of Open Access Journals (Sweden)

    Swapnil Sanmukh

    2015-06-01

    Full Text Available The bacteria and their phages are the most abundant constituents of the aquatic environment, and so represent an ideal model for studying carbon regulation in an aquatic system. The microbe-mediated interconversion of bioavailable organic carbon (OC into dissolved organic carbon (DOC by the microbial carbon pump (MCP has been suggested to have the potential to revolutionize our view of carbon sequestration. It is estimated that DOC is the largest pool of organic matter in the ocean and, though a major component of the global carbon cycle, its source is not yet well understood. A key element of the carbon cycle is the microbial conversion of DOC into inedible forms. The primary aim of this study is to understand the phage conversion from organic to inorganic carbon during phage-host interactions. Time studies of phage-host interactions under controlled conditions reveal their impact on the total carbon content of the samples and their interconversion of organic and inorganic carbon compared to control samples. A total organic carbon (TOC analysis showed an increase in inorganic carbon content by 15-25 percent in samples with bacteria and phage compared to samples with bacteria alone. Compared to control samples, the increase in inorganic carbon content was 60-70-fold in samples with bacteria and phage, and 50-55-fold for samples with bacteria alone. This study indicates the potential impact of phages in regulating the carbon cycle of aquatic systems.

  14. Gateways to clinical trials.

    Science.gov (United States)

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    , Uracil, Ustekinumab; V-260, Vandetanib, Vatalanib succinate, Vernakalant hydrochloride, Vorinostat; YM-155; Zileuton, Zoledronic acid monohydrate.

  15. The treatment landscape in thyroid cancer: a focus on cabozantinib

    Directory of Open Access Journals (Sweden)

    Weitzman SP

    2015-08-01

    Full Text Available Steven P Weitzman, Maria E Cabanillas Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Although patients with thyroid cancer generally fare well, there is a subset for which this is not necessarily true. Progress in understanding the molecular aberrations in thyroid cancer has led to a change in the management of these cases. Since 2011, four multikinase inhibitors (MKIs have been approved by the US Food and Drug Administration for thyroid cancer – cabozantinib and vandetanib for medullary thyroid cancer and sorafenib and lenvatinib for differentiated thyroid cancer. This change in the treatment landscape has raised challenges for practitioners who may not be familiar with the use of MKIs or with the treatment and natural history of advanced thyroid cancer in general. This article reviews the epidemiology, molecular drivers, and initial treatment of patients with thyroid cancer and offers practical guidance to assist with the determination of when to appropriately start an MKI. As an example, cabozantinib and its efficacy are discussed in detail. Close monitoring is required for all patients on targeted agents to assess for adverse effects and response to therapy. An approach to managing drug-related adverse events is detailed. Since these drugs are not curative and have not yet proven to prolong overall survival, it is critical to weigh the risks and benefits of treatment at every visit. The potential value of changing to a different agent following failure of an MKI is also addressed. Keywords: chemotherapy, adverse event, targeted therapy, kinase inhibitor, VEGF, RET

  16. Gateways to clinical trials.

    Science.gov (United States)

    Tomillero, A; Moral, M A

    2010-01-01

    , Tiotropium bromide, TIV, Trabectedin, Tremelimumab, TRU-016; Vadimezan, Val8-GLP-1(7-37)OH, Vandetanib, Vernakalant hydrochloride, Voreloxin, Voriconazole, Vorinostat, Yttrium 90 (90Y) ibritumomab tiuxetan; Zeaxanthin, Ziprasidone hydrochloride, Zosuquidar trihydrochloride. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  17. Marcadores tumorais no câncer de pulmão: um caminho para a terapia biológica Tumor markers in lung cancer: a pathway to biological therapy

    Directory of Open Access Journals (Sweden)

    FERNANDO AZEVEDO PACHECO

    2002-06-01

    Full Text Available Os avanços recentes na genética e na biologia molecular permitiram a identificação de genes e proteínas produzidos ou superexpressados pelos tumores. Tais produtos, os chamados marcadores tumorais, antes utilizados apenas como ferramentas de diagnóstico e prognóstico, vêm atualmente tomando papel importante no desenvolvimento de novas modalidades de tratamento, direcionadas a quebrar o ciclo biológico da progressão tumoral. Neste artigo, revisa-se o papel de alguns marcadores tumorais tradicionalmente conhecidos (CEA, p53, NSE, K-ras, e descrevem-se a prevalência e a função da superexpressão do receptor do fator de crescimento epidérmico (EGFR e do seu produto protéico (p185neu. Novos agentes têm sido desenvolvidos baseando-se no bloqueio da sinalização iniciada pelo EGFR. Destes, destaca-se o ZD1839 (Iressa, uma droga via oral que inibe de modo reversível e seletivo a atividade tirosina-quinase do EGFR, e que vem demonstrando bons resultados tanto isoladamente quanto em combinação com outros agentes quimioterápicos. Tais avanços devem contribuir de modo significativo no tratamento do câncer, principalmente no carcinoma de pulmão do tipo não-pequenas células.Recent advances in genetics and molecular biology lead to the identification of genes and protein products overexpressed by tumors. Such products, called tumor markers, were previously used only as diagnostic and prognostic tools, but are currently being the target of extensive research, with growing evidence that some of them may have an important role in the development of new treatment modalities, targeting the tumor cell biological cycle. In this article, the authors review the role of some of the traditionally known tumor markers (CEA, p53, NSE, K-ras, and describe the prevalence and the role of the epidermal growth factor receptor (EGFR overexpression and its protein product, p185neu. New drugs have been developed, aiming at the blockade of the signaling

  18. Game Dilemma Analysis and Optimization of PoW Consensus Algorithm%PoW共识算法中的博弈困境分析与优化

    Institute of Scientific and Technical Information of China (English)

    唐长兵; 杨珍; 郑忠龙; 陈中育; 李翔

    2017-01-01

    Blockchain is a new decentralized distributed system with the prevalence of Bitcoin and other cryptocurrencies,whose characteristics include decentralization,time-series data,collective maintenance,programmability,security,and so on.Currently,blockchain has attracted intensive attention from governments,financial institutions,high-tech enterprises,and capital markets.Under the framework of this decentralized distributed system,one of the key research issues is how to reach a consensus effectively.In this paper,we analyze the Nash equilibria existence of the miner's strategy choice in the process of proof of work (PoW) consensus algorithm.Besides,we apply the zero determinant (ZD) strategy to optimize the strategy choosing of the miner,and verify the effectiveness of the optimization algorithm through numerical simulation.In brief,this work contributes understanding and analyzeing the PoW consensus algorithm,and provides a new idea and method for the design of consensus algorithm based on the game theory.%区块链是随着比特币等数字加密货币逐渐兴起而盛行的一种新型去中心化分布式系统,具有去中心化、时序数据、集体维护、可编程和安全可信等特点.目前,区块链已引起政府部门、金融机构、科技企业和资本市场的高度重视与广泛关注.如何在一个去中心化的分布式系统中高效地达成共识是区块链技术研究的重要问题.本文从工作量证明(Proof of work,PoW)共识算法的挖矿困境入手,分析PoW共识过程中矿工策略选择的纳什均衡存在条件.利用零行列式(Zero determinant,ZD)策略对矿工策略选择进行优化,并通过数值仿真来验证优化算法的有效性.概括来说,本文从博弈论角度来理解和剖析PoW共识算法,为进一步设计基于博弈论的共识算法提供新的思路和方法.

  19. New opinion on the subtypes of poststroke depression in Chinese stroke survivors

    Directory of Open Access Journals (Sweden)

    Yue Y

    2017-03-01

    Full Text Available Yingying Yue,1,2 Rui Liu,3 Yin Cao,4 Yanfeng Wu,5 Shining Zhang,6 Huajie Li,7 Jijun Zhu,8 Wenhao Jiang,1,2 Aiqin Wu,9 Yonggui Yuan1,2 1Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 2Institute of Psychosomatics, Medical school of Southeast university, Nanjing, 3School of Information Science and Engineering, Southeast University, Nanjing, 4Department of Neurology, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, Changzhou, 5Department of Neurology, The Second Affiliated Hospital of Nanjing Medical University, 6Department of Psychiatry, Nanjing Brain Hospital of Nanjing Medical University, Nanjing, 7Department of Neurology, Changzhou First People’s Hospital, Changzhou, 8Department of Neurology, Yancheng Third People’s Hospital, Yancheng, 9Department of Psychosomatics, The Affiliated First Hospital of Suzhou University, Suzhou, People’s Republic of China Aim: Poststroke depression (PSD is the most common complication of stroke. However, some stroke survivors with depression cannot meet the diagnostic criteria of PSD. The aim of this study was to propose the new conception of stroke patients with depression and then make them to receive reasonable diagnosis and treatment. Methods: We first put forward the opinion that the general PSD should consist of PSD disorder (PSDD and PSD symptoms (PSDS according to the Diagnostic and Statistical Manual of Mental Disorder – Fifth Edition (DSM-5 and ZhongDa diagnostic criteria – first edition (ZD-1, respectively. The ZD-1 was established based on the suggestions of 65 Chinese chief doctors considering that the symptoms of PSDS might be different from those of PSDD and the duration of DSM-5 was too strict. Then, 166 stroke inpatients were recruited, and the study was conducted using the diagnosis and classification of PSD to verify the new concept. Results: A total of 24 (14.46% and 80 (48.19% stroke

  20. The Role of Epigenetic Mechanisms in the Regulation of Gene Expression in the Nervous System.

    Science.gov (United States)

    Cholewa-Waclaw, Justyna; Bird, Adrian; von Schimmelmann, Melanie; Schaefer, Anne; Yu, Huimei; Song, Hongjun; Madabhushi, Ram; Tsai, Li-Huei

    2016-11-09

    Neuroepigenetics is a newly emerging field in neurobiology that addresses the epigenetic mechanism of gene expression regulation in various postmitotic neurons, both over time and in response to environmental stimuli. In addition to its fundamental contribution to our understanding of basic neuronal physiology, alterations in these neuroepigenetic mechanisms have been recently linked to numerous neurodevelopmental, psychiatric, and neurodegenerative disorders. This article provides a selective review of the role of DNA and histone modifications in neuronal signal-induced gene expression regulation, plasticity, and survival and how targeting these mechanisms could advance the development of future therapies. In addition, we discuss a recent discovery on how double-strand breaks of genomic DNA mediate the rapid induction of activity-dependent gene expression in neurons. Copyright © 2016 the authors 0270-6474/16/3611427-08$15.00/0.

  1. Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system.

    Science.gov (United States)

    Plog, Benjamin A; Dashnaw, Matthew L; Hitomi, Emi; Peng, Weiguo; Liao, Yonghong; Lou, Nanhong; Deane, Rashid; Nedergaard, Maiken

    2015-01-14

    The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity. Copyright © 2015 the authors 0270-6474/15/350518-09$15.00/0.

  2. Experimentální ověření odezvy zděné valené klenby na dynamické účinky

    Czech Academy of Sciences Publication Activity Database

    Witzany, J.; Zigler, R.; Kroftová, K.; Urushadze, Shota; Pospíšil, Stanislav

    2014-01-01

    Roč. 23, 9/10 (2014), s. 131-135 ISSN 1805-2576 Institutional support: RVO:68378297 Keywords : non-reinforced barrel vault * seismic risks * dynamic experiments Subject RIV: JN - Civil Engineering http://www.civilengineeringjournal.cz/archive/issues/2014/so_9-10/so_05_14_witzany_I.pdf

  3. Extracting dimer structures from simulations of organic-based materials using QM/MM methods

    Energy Technology Data Exchange (ETDEWEB)

    Pérez-Jiménez, A.J., E-mail: aj.perez@ua.es; Sancho-García, J.C., E-mail: jc.sancho@ua.es

    2015-09-28

    Highlights: • DFT geometries of isolated dimers in organic crystals differ from experimental ones. • This can be corrected using QM/MM geometry optimizations. • The QM = B3LYP–D3(ZD)/cc-pVDZ and MM = GAFF combination works reasonably well. - Abstract: The functionality of weakly bound organic materials, either in Nanoelectronics or in Materials Science, is known to be strongly affected by their morphology. Theoretical predictions of the underlying structure–property relationships are frequently based on calculations performed on isolated dimers, but the optimized structure of the latter may significantly differ from experimental data even when dispersion-corrected methods are used for it. Here, we address this problem on two organic crystals, namely coronene and 5,6,11,12-tetrachlorotetracene, concluding that it is caused by the absence of the surrounding monomers present in the crystal, and that it can be efficiently cured when the dimer is embedded into a general Quantum Mechanics/Molecular Mechanics (QM/MM) geometry optimization scheme. We also investigate how the size of the MM region affects the results. These findings may be helpful for the simulation of the morphology of active materials in crystalline or glassy samples.

  4. Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place, Fiscal Year 1987. Part 11. Kodet Architectural Group-Mantech Field Engineering.

    Science.gov (United States)

    1987-01-01

    8217’ C4J C >)> Cm (0 C’) C- ir40 0 -4-4N (4 0 0 .- .>’ .- . ~ - - C 4NL.4- N04.. (0 M’) C -00)0 N U C -(D tD C ,’ m0 0- r, O N N 0 V I- CNFL O4 .0 U 0...10 0646I 0- -I WN 0 Z-D0 I-C’ C-C’) 01 O 6-0 C’)’ C’) 0 ’-40 0l11 0 0 CD C’)U CC C ) TD N0l 06 N- 0.60 00 00000 on 00 0, C. C 000 00 00 000) _𔃺 -’l) U...W LJ "- C C :34 N m4 1 0 w 4 n-it un w N nN r, v 3- 4bD )n0wt400 040 cCO 0n 00 V cl 00a) C)O0LA m-4 I4 N 0413 4 VMPP,?-0V VN 4 (D W 04 4O(D0) 00 cc -4

  5. Empirical description of the element production cross sections in dissipative heavy-ion collisions

    International Nuclear Information System (INIS)

    Wollersheim, H.J.

    1984-06-01

    Correlations between experimental observables yield analytical expressions for the energy dsigma/dE and element distributions dsigma/dZ, d 2 sigma/dZdE in dissipative collisions. These empirical formulas are applied to twelve heavy ion systems at bombarding energies well above the Coulomb barrier. The element production can be calculated for all kinetic energies of the reaction fragments from the quasi-elastic region down to a minimum total kinetic energy Vsub(c)sup(def) which is the result of the Coulomb repulsion of two deformed nuclei prior to scission. In cases where the dissipative collisions are the dominant part of the reaction process, the deformed Coulomb energy can also be deduced from the total reaction cross section. For these heavy ion systems the empirical formulas depend only on quantities of the ingoing channels. Especially, the normalization of the Gaussian shaped element distributions indicates that the reminiscence on the entrance channel is not completely lost in dissipative collisions. For the 209 Bi + 136 Xe reaction at a laboratory bombarding energy of 1130 MeV the energy and element distributions are calculated which show an excellent agreement with the experimental data. (orig.)

  6. Antipsychotic potential of quinazoline ErbB1 inhibitors in a schizophrenia model established with neonatal hippocampal lesioning.

    Science.gov (United States)

    Mizuno, Makoto; Iwakura, Yuriko; Shibuya, Masako; Zheng, Yingjun; Eda, Takeyoshi; Kato, Taisuke; Takasu, Yohei; Nawa, Hiroyuki

    2010-01-01

    Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in the pathophysiology of schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In the present study, we used an animal model of schizophrenia established by neonatal hippocampal lesioning and evaluated the neurobehavioral consequences of ErbB1-inhibitor treatment. Subchronic administration of the ErbB1 inhibitor ZD1839 to the cerebroventricle of rats receiving neonatal hippocampal lesioning ameliorated deficits in prepulse inhibition as well as those in the latent inhibition of tone-dependent fear learning. There were no apparent adverse effects on basal learning scores or locomotor activity, however. The administration of other ErbB1 inhibitors, PD153035 and OSI-774, similarly attenuated the prepulse inhibition impairment of this animal model. In parallel, there were decreases in ErbB1 phosphorylation in animals treated with ErbB1 inhibitors. These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel therapeutic targets for schizophrenia or its related psychotic symptoms.

  7. Pathogenicity of Shigella in chickens.

    Science.gov (United States)

    Shi, Run; Yang, Xia; Chen, Lu; Chang, Hong-tao; Liu, Hong-ying; Zhao, Jun; Wang, Xin-wei; Wang, Chuan-qing

    2014-01-01

    Shigellosis in chickens was first reported in 2004. This study aimed to determine the pathogenicity of Shigella in chickens and the possibility of cross-infection between humans and chickens. The pathogenicity of Shigella in chickens was examined via infection of three-day-old SPF chickens with Shigella strain ZD02 isolated from a human patient. The virulence and invasiveness were examined by infection of the chicken intestines and primary chicken intestinal epithelial cells. The results showed Shigella can cause death via intraperitoneal injection in SPF chickens, but only induce depression via crop injection. Immunohistochemistry and transmission electron microscopy revealed the Shigella can invade the intestinal epithelia. Immunohistochemistry of the primary chicken intestinal epithelial cells infected with Shigella showed the bacteria were internalized into the epithelial cells. Electron microscopy also confirmed that Shigella invaded primary chicken intestinal epithelia and was encapsulated by phagosome-like membranes. Our data demonstrate that Shigella can invade primary chicken intestinal epithelial cells in vitro and chicken intestinal mucosa in vivo, resulting in pathogenicity and even death. The findings suggest Shigella isolated from human or chicken share similar pathogenicity as well as the possibility of human-poultry cross-infection, which is of public health significance.

  8. Three-dimensional susceptibility-weighted imaging and two-dimensional T2*-weighted gradient-echo imaging of intratumoral hemorrhages in pediatric diffuse intrinsic pontine glioma

    International Nuclear Information System (INIS)

    Loebel, Ulrike; Sedlacik, Jan; Sabin, Noah D.; Hillenbrand, Claudia M.; Patay, Zoltan; Kocak, Mehmet; Broniscer, Alberto

    2010-01-01

    We compared the sensitivity and specificity of T2*-weighted gradient-echo imaging (T2*-GRE) and susceptibility-weighted imaging (SWI) in determining prevalence and cumulative incidence of intratumoral hemorrhages in children with diffuse intrinsic pontine glioma (DIPG) undergoing antiangiogenic and radiation therapy. Patients were recruited from an institutional review board-approved prospective phase I trial of vandetanib administered in combination with radiation therapy. Patient consent was obtained before enrollment. Consecutive T2*-GRE and SWI exams of 17 patients (F/M: 9/8; age 3-17 years) were evaluated. Two reviewers (R1 and R2) determined the number and size of hemorrhages at baseline and multiple follow-ups (92 scans, mean 5.4/patient). Statistical analyses were performed using descriptive statistics, graphical tools, and mixed-effects Poisson regression models. Prevalence of hemorrhages at diagnosis was 41% and 47%; the cumulative incidences of hemorrhages at 6 months by T2*-GRE and SWI were 82% and 88%, respectively. Hemorrhages were mostly petechial; 9.7% of lesions on T2*-GRE and 5.2% on SWI were hematomas (>5 mm). SWI identified significantly more hemorrhages than T2*-GRE did. Lesions were missed or misinterpreted in 36/39 (R1/R2) scans by T2*-GRE and 9/3 scans (R1/R2) by SWI. Hemorrhages had no clinically significant neurological correlates in patients. SWI is more sensitive than T2*-GRE in detecting hemorrhages and differentiating them from calcification, necrosis, and artifacts. Also, petechial hemorrhages are more common in DIPG at diagnosis than previously believed and their number increases during the course of treatment; hematomas are rare. (orig.)

  9. Isolation and characterization of a cDNA clone coding for a glutathione S-transferase class delta enzyme from the biting midge Culicoides variipennis sonorensis Wirth and Jones.

    Science.gov (United States)

    Abdallah, M A; Pollenz, R S; Droog, F N; Nunamaker, R A; Tabachnick, W J; Murphy, K E

    2000-12-01

    Culicoides variipennis sonorensis is the primary vector of bluetongue viruses in North America. Glutathione S-transferases (GSTs) are enzymes that catalyze nucleophilic substitutions, converting reactive lipophilic molecules into soluble conjugates. Increased GST activity is associated with development of insecticide resistance. Described here is the isolation of the first cDNA encoding a C. variipennis GST. The clone consists of 720 translated bases encoding a protein with a M(r) of approximately 24,800 composed of 219 amino acids. The deduced amino acid sequence is similar (64%-74%) to class Delta (previously named Theta) GSTs from the dipteran genera Musca, Drosophila, Lucilia and Anopheles. The cDNA was subcloned into pET-11b, expressed in Epicurian coli BL21 (DE3) and has a specific activity of approximately 28,000 units/mg for the substrate 1-chloro-2,4-dinitrobenzene.

  10. Persistent pain after spinal cord injury is maintained by primary afferent activity.

    Science.gov (United States)

    Yang, Qing; Wu, Zizhen; Hadden, Julia K; Odem, Max A; Zuo, Yan; Crook, Robyn J; Frost, Jeffrey A; Walters, Edgar T

    2014-08-06

    Chronic pain caused by insults to the CNS (central neuropathic pain) is widely assumed to be maintained exclusively by central mechanisms. However, chronic hyperexcitablility occurs in primary nociceptors after spinal cord injury (SCI), suggesting that SCI pain also depends upon continuing activity of peripheral sensory neurons. The present study in rats (Rattus norvegicus) found persistent upregulation after SCI of protein, but not mRNA, for a voltage-gated Na(+) channel, Nav1.8, that is expressed almost exclusively in primary afferent neurons. Selectively knocking down Nav1.8 after SCI suppressed spontaneous activity in dissociated dorsal root ganglion neurons, reversed hypersensitivity of hindlimb withdrawal reflexes, and reduced ongoing pain assessed by a conditioned place preference test. These results show that activity in primary afferent neurons contributes to ongoing SCI pain. Copyright © 2014 the authors 0270-6474/14/3410765-05$15.00/0.

  11. Slack channels expressed in sensory neurons control neuropathic pain in mice.

    Science.gov (United States)

    Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

    2015-01-21

    Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

  12. Molecular targeted therapies of aggressive thyroid cancer

    Directory of Open Access Journals (Sweden)

    Silvia Martina eFerrari

    2015-11-01

    Full Text Available Differentiated thyroid carcinomas (DTC that arise from follicular cells account > 90% of thyroid cancer (TC [papillary thyroid cancer (PTC 90%, follicular thyroid cancer (FTC 10%], while medullary thyroid cancer (MTC accounts < 5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts towards the development of new drugs.Several genetic alterations in different molecular pathways in TC have been shown in the last decades, associated with TC development and progression. Rearranged during transfection (RET/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the above-mentioned molecular pathways involved in growth, angiogenesis, local and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC and anaplastic thyroid cancer (ATC, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds, and to personalize

  13. Validated LC-MS/MS Method for the Quantification of Ponatinib in Plasma: Application to Metabolic Stability.

    Directory of Open Access Journals (Sweden)

    Adnan A Kadi

    Full Text Available In the current work, a rapid, specific, sensitive and validated liquid chromatography tandem mass-spectrometric method was developed for the quantification of ponatinib (PNT in human plasma and rat liver microsomes (RLMs with its application to metabolic stability. Chromatographic separation of PNT and vandetanib (IS were accomplished on Agilent eclipse plus C18 analytical column (50 mm × 2.1 mm, 1.8 μm particle size maintained at 21±2°C. Flow rate was 0.25 mLmin-1 with run time of 4 min. Mobile phase consisted of solvent A (10 mM ammonium formate, pH adjusted to 4.1 with formic acid and solvent B (acetonitrile. Ions were generated by electrospray (ESI and multiple reaction monitoring (MRM was used as basis for quantification. The results revealed a linear calibration curve in the range of 5-400 ngmL-1 (r2 ≥ 0.9998 with lower limit of quantification (LOQ and lower limit of detection (LOD of 4.66 and 1.53 ngmL-1 in plasma, 4.19 and 1.38 ngmL-1 in RLMs. The intra- and inter-day precision and accuracy in plasma ranged from1.06 to 2.54% and -1.48 to -0.17, respectively. Whereas in RLMs ranged from 0.97 to 2.31% and -1.65 to -0.3%. The developed procedure was applied for quantification of PNT in human plasma and RLMs for study metabolic stability of PNT. PNT disappeared rapidly in the 1st 10 minutes of RLM incubation and the disappearance plateaued out for the rest of the incubation. In vitro half-life (t1/2 was 6.26 min and intrinsic clearance (CLin was 15.182± 0.477.

  14. लक्षद्वीप समूह: भारत का समुद्री पुरातत्व

    Digital Repository Service at National Institute of Oceanography (India)

    Tripati, S.; Sharma, R.

    ‘wÐr nwamVËd E {gbm {Ìn{V E amHo$e e‘m© gmam§e bjÛrn g‘yh nyd© Am¡a A’«$sH$s Xoem| go Xya X{jU E{e`m Ho$ g‘wÐr ‘mJ© na AdpñWV h¡ & ì`mnma ‘mJ© hmoZo Ho$ ZmVo Zmdm| Am¡a OhmOm| Ûmam VmµOm nmZr boZo Ho$ {bE amñVo H$m EH$ R>hamd Ho... nma OhmOm| Ho$ Sy>~Zo H$m AÝdofU ^r em{‘b h¡& Bg XñVmdoµO H$m {ddaU bjÛrn ‘¢ àma§{^H$ ‘mZd OZdgVr Am¡a g‘wÐr g§nH©$ Am¡a Sy>~o hþE OhmOm| Ho$ nwamVpËdH$ ImoO Ho$ g§X^© ‘¢ h¡ & à‘wI eãX :~m¡Õ Y‘© ,bjÛrn ,g‘wÐr ì`mnma ,~V©Z ,Zï> Ob`mZ ,àñVa b...

  15. Directed Abelian algebras and their application to stochastic models.

    Science.gov (United States)

    Alcaraz, F C; Rittenberg, V

    2008-10-01

    With each directed acyclic graph (this includes some D-dimensional lattices) one can associate some Abelian algebras that we call directed Abelian algebras (DAAs). On each site of the graph one attaches a generator of the algebra. These algebras depend on several parameters and are semisimple. Using any DAA, one can define a family of Hamiltonians which give the continuous time evolution of a stochastic process. The calculation of the spectra and ground-state wave functions (stationary state probability distributions) is an easy algebraic exercise. If one considers D-dimensional lattices and chooses Hamiltonians linear in the generators, in finite-size scaling the Hamiltonian spectrum is gapless with a critical dynamic exponent z=D. One possible application of the DAA is to sandpile models. In the paper we present this application, considering one- and two-dimensional lattices. In the one-dimensional case, when the DAA conserves the number of particles, the avalanches belong to the random walker universality class (critical exponent sigma_(tau)=32 ). We study the local density of particles inside large avalanches, showing a depletion of particles at the source of the avalanche and an enrichment at its end. In two dimensions we did extensive Monte-Carlo simulations and found sigma_(tau)=1.780+/-0.005 .

  16. Experimental comparison of the optical measurements of a cross-flow in a rod bundle with mixing vanes

    International Nuclear Information System (INIS)

    Chang, Seok Kyu; Choo, Yeon Jun; Kim, Bok Deuk; Song, Chul Hwa

    2008-01-01

    The lateral crossflow on subchannels in a rod bundle array was investigated to understand the flow characteristics related to the mixing vane types on a spacer grid by using the PIV technique. For more measurement resolutions, a 5x5 rod bundle was fabricated a 2.6 times larger than the real rod bundle size in a pressurized water reactor. A rod-embedded optic array was specially designed and used for the illumination of the inner subchannels. The crossflow field in a subchannel was characterized by the type and the arrangement of the mixing vanes. At a near downstream location from the spacer grid (z/D h =1) in the case of the split type, a couple of small vortices were generated diagonally in a subchannel. On the other hand, in the case of the swirl type, there was a large elliptic vortex generated in the center of a subchannel. The measurement results were compared with the experimental results which had been performed with the LDV technique at the same test facility. The magnitudes of the flow velocity and the vorticity in PIV results were less than those in LDV measurement results. It was shown that the instantaneous flow fields in a subchannel frequently have quite different shapes from the averaged one

  17. KAM for the non-linear Schroedinger equation

    CERN Document Server

    Eliasson, L H

    2006-01-01

    We consider the $d$-dimensional nonlinear Schr\\"o\\-dinger equation under periodic boundary conditions:-i\\dot u=\\Delta u+V(x)*u+\\ep|u|^2u;\\quad u=u(t,x),\\;x\\in\\T^dwhere $V(x)=\\sum \\hat V(a)e^{i\\sc{a,x}}$ is an analytic function with $\\hat V$ real. (This equation is a popular model for the `real' NLS equation, where instead of the convolution term $V*u$ we have the potential term $Vu$.) For $\\ep=0$ the equation is linear and has time--quasi-periodic solutions $u$,u(t,x)=\\sum_{s\\in \\AA}\\hat u_0(a)e^{i(|a|^2+\\hat V(a))t}e^{i\\sc{a,x}}, \\quad 0<|\\hat u_0(a)|\\le1,where $\\AA$ is any finite subset of $\\Z^d$. We shall treat $\\omega_a=|a|^2+\\hat V(a)$, $a\\in\\AA$, as free parameters in some domain $U\\subset\\R^{\\AA}$. This is a Hamiltonian system in infinite degrees of freedom, degenerate but with external parameters, and we shall describe a KAM-theory which, in particular, will have the following consequence: \\smallskip {\\it If $|\\ep|$ is sufficiently small, then there is a large subset $U'$ of $U$ such that for all $...

  18. KAM for the non-linear Schroedinger equation a short presentation

    CERN Document Server

    Eliasson, H L

    2006-01-01

    We consider the $d$-dimensional nonlinear Schr\\"o\\-dinger equation under periodic boundary conditions:-i\\dot u=\\Delta u+V(x)*u+\\ep \\frac{\\p F}{\\p \\bar u}(x,u,\\bar u) ;\\quad u=u(t,x),\\;x\\in\\T^dwhere $V(x)=\\sum \\hat V(a)e^{i\\sc{a,x}}$ is an analytic function with $\\hat V$ real and $F$ is a real analytic function in $\\Re u$, $\\Im u$ and $x$. (This equation is a popular model for the `real' NLS equation, where instead of the convolution term $V*u$ we have the potential term $Vu$.) For $\\ep=0$ the equation is linear and has time--quasi-periodic solutions $u$,u(t,x)=\\sum_{s\\in \\AA}\\hat u_0(a)e^{i(|a|^2+\\hat V(a))t}e^{i\\sc{a,x}}, \\quad 0<|\\hat u_0(a)|\\le1,where $\\AA$ is any finite subset of $\\Z^d$. We shall treat $\\omega_a=|a|^2+\\hat V(a)$, $a\\in\\AA$, as free parameters in some domain $U\\subset\\R^{\\AA}$. This is a Hamiltonian system in infinite degrees of freedom, degenerate but with external parameters, and we shall describe a KAM-theory which, in particular, will have the following consequence: \\smallskip {\\it ...

  19. Production of biodiesel from palm oil using modified Malaysian natural dolomites

    International Nuclear Information System (INIS)

    Shajaratun Nur, Z.A.; Taufiq-Yap, Y.H.; Rabiah Nizah, M.F.; Teo, Siow Hwa; Syazwani, O.N.; Islam, Aminul

    2014-01-01

    Highlights: • Transesterification was carried out using modified Malaysian natural dolomite catalyst. • Characterizations of the catalyst were performed by using XRD, TPD-CO 2 , BET and SEM. • Maximum biodiesel conversion of 100% was achieved from SnO 2 /dolomite catalyst. • The yield was affected by the surface are as well as the basicity of catalyst. • The transesterification reaction gave significant conversion with relatively lower amount of catalyst. - Abstract: Calcined dolomite (AD), produced by calcination of Malaysian dolomite (UD) promotes a potential natural catalyst for biodiesel production from palm oil with the conversion of 99.98%. The catalysts were characterized by using X-ray Diffractometer (XRD), Brunauer–Emmet–Teller (BET) surface area, Scanning Electron Microscopy (SEM) and Temperature Programmed Desorption (TPD) of CO 2 . All catalysts were then employed for transesterification reaction under different conditions (time, methanol to oil molar ratio and amount of catalyst). SnO 2 doped on activated dolomite (SD) shows an optimum conversion (99.98%) at conditions, i.e. 15:1 methanol to oil molar ratio in 4 h compared to ZnO doped on activated dolomite (ZD) and AD. The catalytic activities of these catalysts were found to be depending on the basicity as well as the surface area of the catalyst used

  20. Příběh zdánlivě obyčejného venkovského domu č.p.17 v Petrovicích

    Czech Academy of Sciences Publication Activity Database

    Hůrková, Ludmila

    -, č. 13 (2015), s. 39-47 ISSN 1802-8128. [Specializovaná konference stavebně historického průzkumu /13./. Slaný, 17.06.2014-20.06.2014] Institutional support: RVO:68378033 Keywords : Prague-Petrovice * country building * late Middle Ages * late baroque or classicist outbuilding * architecture in the country in the 20th century Subject RIV: AL - Art, Architecture, Cultural Heritage

  1. Hrázděné stěny v podkrovích českých a moravských zámků

    Czech Academy of Sciences Publication Activity Database

    Bláha, Jiří

    2016-01-01

    Roč. 14, č. 1 (2016), s. 255-270 ISSN 1802-8128 R&D Projects: GA MŠk(CZ) LO1219 Keywords : built heritage * chateaux and castles * timber framed constructions * half–timbered walls * roof timber frames * attics Subject RIV: AL - Art, Architecture, Cultural Heritage OBOR OECD: History (history of science and technology to be 6.3, history of specific sciences to be under the respective headings)

  2. Division of Information Technology - Overview

    International Nuclear Information System (INIS)

    Szlachciak, J.

    2010-01-01

    Physics and Technology and Accelerator Physics and Technology are located. The network speed was upgraded to gigabit Ethernet in this LAN segment. The second achievement was the inclusion of the originally independent network of the ZdAJ Production Unit in the global LAN infrastructure in Swierk. Together with this task we migrated all ZdAJ users to the main computer domain. The migration included moving of their mailboxes located on external servers. In order to improve security and management of our desktop computers we implemented the following software: · Microsoft Windows Server Update Services for automatic distribution of updates and upgrades for Microsoft products; · ESET Nod32 business edition for protection against viruses: this software replaced Symantec antivirus products used in the past; · GFI MailSecurity for e-mail protection against viruses. Implemented at the end of 2006. the Scientific Activity Database continued its operation and was extended by several useful reports and fields containing important information. One of the main extensions was a development of the subsystem for financial bonuses for scientists by implementation of a scientific publication score system based on rating introduced by the Ministry of Science and Higher Education. (author)

  3. Auditory cortical processing in real-world listening: the auditory system going real.

    Science.gov (United States)

    Nelken, Israel; Bizley, Jennifer; Shamma, Shihab A; Wang, Xiaoqin

    2014-11-12

    The auditory sense of humans transforms intrinsically senseless pressure waveforms into spectacularly rich perceptual phenomena: the music of Bach or the Beatles, the poetry of Li Bai or Omar Khayyam, or more prosaically the sense of the world filled with objects emitting sounds that is so important for those of us lucky enough to have hearing. Whereas the early representations of sounds in the auditory system are based on their physical structure, higher auditory centers are thought to represent sounds in terms of their perceptual attributes. In this symposium, we will illustrate the current research into this process, using four case studies. We will illustrate how the spectral and temporal properties of sounds are used to bind together, segregate, categorize, and interpret sound patterns on their way to acquire meaning, with important lessons to other sensory systems as well. Copyright © 2014 the authors 0270-6474/14/3415135-04$15.00/0.

  4. Computational substrates of social value in interpersonal collaboration.

    Science.gov (United States)

    Fareri, Dominic S; Chang, Luke J; Delgado, Mauricio R

    2015-05-27

    Decisions to engage in collaborative interactions require enduring considerable risk, yet provide the foundation for building and maintaining relationships. Here, we investigate the mechanisms underlying this process and test a computational model of social value to predict collaborative decision making. Twenty-six participants played an iterated trust game and chose to invest more frequently with their friends compared with a confederate or computer despite equal reinforcement rates. This behavior was predicted by our model, which posits that people receive a social value reward signal from reciprocation of collaborative decisions conditional on the closeness of the relationship. This social value signal was associated with increased activity in the ventral striatum and medial prefrontal cortex, which significantly predicted the reward parameters from the social value model. Therefore, we demonstrate that the computation of social value drives collaborative behavior in repeated interactions and provide a mechanistic account of reward circuit function instantiating this process. Copyright © 2015 the authors 0270-6474/15/358170-11$15.00/0.

  5. Deep Neural Networks Reveal a Gradient in the Complexity of Neural Representations across the Ventral Stream.

    Science.gov (United States)

    Güçlü, Umut; van Gerven, Marcel A J

    2015-07-08

    Converging evidence suggests that the primate ventral visual pathway encodes increasingly complex stimulus features in downstream areas. We quantitatively show that there indeed exists an explicit gradient for feature complexity in the ventral pathway of the human brain. This was achieved by mapping thousands of stimulus features of increasing complexity across the cortical sheet using a deep neural network. Our approach also revealed a fine-grained functional specialization of downstream areas of the ventral stream. Furthermore, it allowed decoding of representations from human brain activity at an unsurpassed degree of accuracy, confirming the quality of the developed approach. Stimulus features that successfully explained neural responses indicate that population receptive fields were explicitly tuned for object categorization. This provides strong support for the hypothesis that object categorization is a guiding principle in the functional organization of the primate ventral stream. Copyright © 2015 the authors 0270-6474/15/3510005-10$15.00/0.

  6. Noradrenaline and dopamine neurons in the reward/effort trade-off: a direct electrophysiological comparison in behaving monkeys.

    Science.gov (United States)

    Varazzani, Chiara; San-Galli, Aurore; Gilardeau, Sophie; Bouret, Sebastien

    2015-05-20

    Motivation determines multiple aspects of behavior, including action selection and energization of behavior. Several components of the underlying neural systems have been examined closely, but the specific role of the different neuromodulatory systems in motivation remains unclear. Here, we compare directly the activity of dopaminergic neurons from the substantia nigra pars compacta and noradrenergic neurons from the locus coeruleus in monkeys performing a task manipulating the reward/effort trade-off. Consistent with previous reports, dopaminergic neurons encoded the expected reward, but we found that they also anticipated the upcoming effort cost in connection with its negative influence on action selection. Conversely, the firing of noradrenergic neurons increased with both pupil dilation and effort production in relation to the energization of behavior. Therefore, this work underlines the contribution of dopamine to effort-based decision making and uncovers a specific role of noradrenaline in energizing behavior to face challenges. Copyright © 2015 the authors 0270-6474/15/357866-12$15.00/0.

  7. Quantifying the microvascular origin of BOLD-fMRI from first principles with two-photon microscopy and an oxygen-sensitive nanoprobe.

    Science.gov (United States)

    Gagnon, Louis; Sakadžić, Sava; Lesage, Frédéric; Musacchia, Joseph J; Lefebvre, Joël; Fang, Qianqian; Yücel, Meryem A; Evans, Karleyton C; Mandeville, Emiri T; Cohen-Adad, Jülien; Polimeni, Jonathan R; Yaseen, Mohammad A; Lo, Eng H; Greve, Douglas N; Buxton, Richard B; Dale, Anders M; Devor, Anna; Boas, David A

    2015-02-25

    The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences. Copyright © 2015 the authors 0270-6474/15/353663-13$15.00/0.

  8. Long-term memory stabilized by noise-induced rehearsal.

    Science.gov (United States)

    Wei, Yi; Koulakov, Alexei A

    2014-11-19

    Cortical networks can maintain memories for decades despite the short lifetime of synaptic strengths. Can a neural network store long-lasting memories in unstable synapses? Here, we study the effects of ongoing spike-timing-dependent plasticity (STDP) on the stability of memory patterns stored in synapses of an attractor neural network. We show that certain classes of STDP rules can stabilize all stored memory patterns despite a short lifetime of synapses. In our model, unstructured neural noise, after passing through the recurrent network connections, carries the imprint of all memory patterns in temporal correlations. STDP, combined with these correlations, leads to reinforcement of all stored patterns, even those that are never explicitly visited. Our findings may provide the functional reason for irregular spiking displayed by cortical neurons and justify models of system memory consolidation. Therefore, we propose that irregular neural activity is the feature that helps cortical networks maintain stable connections. Copyright © 2014 the authors 0270-6474/14/3415804-12$15.00/0.

  9. Delineating the Diversity of Spinal Interneurons in Locomotor Circuits.

    Science.gov (United States)

    Gosgnach, Simon; Bikoff, Jay B; Dougherty, Kimberly J; El Manira, Abdeljabbar; Lanuza, Guillermo M; Zhang, Ying

    2017-11-08

    Locomotion is common to all animals and is essential for survival. Neural circuits located in the spinal cord have been shown to be necessary and sufficient for the generation and control of the basic locomotor rhythm by activating muscles on either side of the body in a specific sequence. Activity in these neural circuits determines the speed, gait pattern, and direction of movement, so the specific locomotor pattern generated relies on the diversity of the neurons within spinal locomotor circuits. Here, we review findings demonstrating that developmental genetics can be used to identify populations of neurons that comprise these circuits and focus on recent work indicating that many of these populations can be further subdivided into distinct subtypes, with each likely to play complementary functions during locomotion. Finally, we discuss data describing the manner in which these populations interact with each other to produce efficient, task-dependent locomotion. Copyright © 2017 the authors 0270-6474/17/3710835-07$15.00/0.

  10. The olfactory tubercle encodes odor valence in behaving mice.

    Science.gov (United States)

    Gadziola, Marie A; Tylicki, Kate A; Christian, Diana L; Wesson, Daniel W

    2015-03-18

    Sensory information acquires meaning to adaptively guide behaviors. Despite odors mediating a number of vital behaviors, the components of the olfactory system responsible for assigning meaning to odors remain unclear. The olfactory tubercle (OT), a ventral striatum structure that receives monosynaptic input from the olfactory bulb, is uniquely positioned to transform odor information into behaviorally relevant neural codes. No information is available, however, on the coding of odors among OT neurons in behaving animals. In recordings from mice engaged in an odor discrimination task, we report that the firing rate of OT neurons robustly and flexibly encodes the valence of conditioned odors over identity, with rewarded odors evoking greater firing rates. This coding of rewarded odors occurs before behavioral decisions and represents subsequent behavioral responses. We predict that the OT is an essential region whereby odor valence is encoded in the mammalian brain to guide goal-directed behaviors. Copyright © 2015 the authors 0270-6474/15/354515-13$15.00/0.

  11. Stress induces pain transition by potentiation of AMPA receptor phosphorylation.

    Science.gov (United States)

    Li, Changsheng; Yang, Ya; Liu, Sufang; Fang, Huaqiang; Zhang, Yong; Furmanski, Orion; Skinner, John; Xing, Ying; Johns, Roger A; Huganir, Richard L; Tao, Feng

    2014-10-08

    Chronic postsurgical pain is a serious issue in clinical practice. After surgery, patients experience ongoing pain or become sensitive to incident, normally nonpainful stimulation. The intensity and duration of postsurgical pain vary. However, it is unclear how the transition from acute to chronic pain occurs. Here we showed that social defeat stress enhanced plantar incision-induced AMPA receptor GluA1 phosphorylation at the Ser831 site in the spinal cord and greatly prolonged plantar incision-induced pain. Interestingly, targeted mutation of the GluA1 phosphorylation site Ser831 significantly inhibited stress-induced prolongation of incisional pain. In addition, stress hormones enhanced GluA1 phosphorylation and AMPA receptor-mediated electrical activity in the spinal cord. Subthreshold stimulation induced spinal long-term potentiation in GluA1 phosphomimetic mutant mice, but not in wild-type mice. Therefore, spinal AMPA receptor phosphorylation contributes to the mechanisms underlying stress-induced pain transition. Copyright © 2014 the authors 0270-6474/14/3413737-10$15.00/0.

  12. Exercise, energy intake, glucose homeostasis, and the brain.

    Science.gov (United States)

    van Praag, Henriette; Fleshner, Monika; Schwartz, Michael W; Mattson, Mark P

    2014-11-12

    Here we summarize topics covered in an SFN symposium that considered how and why exercise and energy intake affect neuroplasticity and, conversely, how the brain regulates peripheral energy metabolism. This article is not a comprehensive review of the subject, but rather a view of how the authors' findings fit into a broader context. Emerging findings elucidate cellular and molecular mechanisms by which exercise and energy intake modify the plasticity of neural circuits in ways that affect brain health. By enhancing neurogenesis, synaptic plasticity and neuronal stress robustness, exercise and intermittent energy restriction/fasting may optimize brain function and forestall metabolic and neurodegenerative diseases. Moreover, brain-centered glucoregulatory and immunomodulating systems that mediate peripheral health benefits of intermittent energetic challenges have recently been described. A better understanding of adaptive neural response pathways activated by energetic challenges will enable the development and optimization of interventions to reduce the burden of disease in our communities. Copyright © 2014 the authors 0270-6474/14/3415139-11$15.00/0.

  13. Successful treatment of persistent bronchorrhea by gefitinib in a case with Recurrent Bronchioloalveolar Carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Shimono Takatsugu

    2003-07-01

    Full Text Available Abstract Background Bronchorrhea is one of late complaints in patients with bronchioloalveolar carcinoma (BAC and hampers their quality of life. Although an effective treatment for bronchorrhea in these patients has not been established, recently we have treated effectively one case of persistent bronchorrhea associated with clinical recurrent BAC with gefitinib (ZD1839, 'Iressa™'; AstraZeneca Japan; Osaka, Japan. Case Presentation A 63-year-old Japanese female had undergone left pneumonectomy with radical lymph node dissection (ND2a for diffuse type bronchioloalveolar carcinoma originated in left lower lobe. Multiple pulmonary metastases in right lung were found one year after operation. Pulmonary metastatic lesion has grown and she complained of progressive symptoms of massive watery sputum and dyspnea, four years after operation. Although her symptom was getting worse in spite of routine treatment, it completely disappeared within 2 weeks of starting oral gefitinib. Thereafter, she has been symptom-free and shows good partial response on repeat scan after 9 months of oral gefitinib. Conclusions The dramatic remission of persistent bronchorrhea by gefitinib in the presented case suggests that gefitinib might be a promising option for bronchioloalveolar carcinoma, particularly in cases with severe bronchorrhea. Although it is not possible to comment on whether the improvement came from tumor cell death itself or suppressive effect of mucin synthesis by the epidermal growth factor receptor-tyrosine kinase inhibitory action.

  14. Swirling Combustor Energy Converter: H2/Air Simulations of Separated Chambers

    Directory of Open Access Journals (Sweden)

    Angelo Minotti

    2015-09-01

    Full Text Available This work reports results related to the “EU-FP7-HRC-Power” project aiming at developing micro-meso hybrid sources of power. One of the goals of the project is to achieve surface temperatures up to more than 1000 K, with a ∆T ≤ 100 K, in order to be compatible with a thermal/electrical conversion by thermo-photovoltaic cells. The authors investigate how to reach that goal adopting swirling chambers integrated in a thermally-conductive and emitting element. The converter consists of a small parallelepiped brick inside two separated swirling meso-combustion chambers, which heat up the parallelepiped, emitting material by the combustion of H2 and air at ambient pressure. The overall dimension is of the order of cm. Nine combustion simulations have been carried out assuming detailed chemistry, several length/diameter ratios (Z/D = 3, 5 and 11 and equivalence ratios (0.4, 0.7 and 1; all are at 400 W of injected chemical power. Among the most important results are the converter surfaces temperatures, the heat loads, provided to the environment, and the chemical efficiency. The high chemical efficiency, h > 99.9%, is due to the relatively long average gas residence time coupled with the fairly good mixing due to the swirl motion and the impinging air/fuel jets that provide heat and radicals to the flame.

  15. Dietary zinc deficiency effects dorso-lateral and ventral prostate of Wistar rats: histological, biochemical and trace element study.

    Science.gov (United States)

    Joshi, Sangeeta; Nair, Neena; Bedwal, R S

    2014-10-01

    Zinc deficiency has become a global problem affecting the developed and developing countries due to inhibitors in the diet which prevents its absorption or due to a very low concentration of bioavailable zinc in the diet. Being present in high concentration in the prostate and having diverse biological function, we investigated the effects of dietary zinc deficiency for 2 and 4 weeks on dorso-lateral and ventral prostate. Sixty prepubertal rats were divided into three groups: zinc control (ZC), pair fed (PF) and zinc deficient (ZD) and fed on 100 μg/g (zinc control and pair fed groups) and 1 μg/g (zinc deficient) diet. Zinc deficiency was associated with degenerative changes in dorso-lateral and ventral prostate as made evident by karyolysis, karyorhexis, cytoplasmolysis, loss of cellularisation, decreased intraluminar secretion and degeneration of fibromuscular stroma. In response, protein carbonyl, nitric oxide, acid phosphatase, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase increased, exhibiting variable level of significance. Total protein and total zinc concentration in dorso-lateral and ventral prostate as well as in serum decreased (P dorso-lateral and ventral prostate after dietary zinc deficiency as well as impairment of metabolic and secretory activity, reduced gonadotropin levels by hypothalamus -hypophysial system which is indicative of a critical role of zinc in maintaining the prostate integrity.

  16. Potential role for epidermal growth factor receptor inhibitors in combined-modality therapy for non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Choy, Hak

    2004-01-01

    There has been a surge of interest in the translation of discoveries in molecular biology into clinically relevant therapies in the field of hematology/oncology. The epidermal growth factor receptor (EGFR) has been a molecular target of significant interest and investigation, and preclinical and clinical studies support a role for targeted therapy in a variety of cancers, including non-small-cell lung cancer (NSCLC) via compounds that specifically inhibit EGFR. ZD1839, IMC-C225, and OSI-774 are the most clinically developed of these compounds. Interestingly, preclinical studies have demonstrated that EGFR inhibitors may have radiation-sensitizing properties, as well as increased cytotoxic activity in combination with chemotherapeutic agents, suggesting a potential role for EGFR inhibitors as an adjunct to the current combined-modality approach for therapy of Stage III NSCLC. Therefore, clinical trials have been proposed and initiated to address the issue of determining the impact of the addition of EGFR inhibitors to the standard combined-modality regimen (chemotherapy/radiation therapy ± surgery) for Stage III NSCLC. This article reviews preclinical and clinical data supporting the role for EGFR inhibitors alone or in combination with chemotherapy/radiation therapy for locally advanced NSCLC. Also, it will provide an overview of ongoing and proposed clinical studies investigating the potential role for EGFR inhibitors in Stage III NSCLC

  17. Experimental assessment of blade tip immersion depth from free surface on average power and thrust coefficients of marine current turbine

    Science.gov (United States)

    Lust, Ethan; Flack, Karen; Luznik, Luksa

    2014-11-01

    Results from an experimental study on the effects of marine current turbine immersion depth from the free surface are presented. Measurements are performed with a 1/25 scale (diameter D = 0.8m) two bladed horizontal axis turbine towed in the large towing tank at the U.S. Naval Academy. Thrust and torque are measured using a dynamometer, mounted in line with the turbine shaft. Shaft rotation speed and blade position are measured using a shaft position indexing system. The tip speed ratio (TSR) is adjusted using a hysteresis brake which is attached to the output shaft. Two optical wave height sensors are used to measure the free surface elevation. The turbine is towed at 1.68 m/s, resulting in a 70% chord based Rec = 4 × 105. An Acoustic Doppler Velocimeter (ADV) is installed one turbine diameter upstream of the turbine rotation plane to characterize the inflow turbulence. Measurements are obtained at four relative blade tip immersion depths of z/D = 0.5, 0.4, 0.3, and 0.2 at a TSR value of 7 to identify the depth where free surface effects impact overall turbine performance. The overall average power and thrust coefficient are presented and compared to previously conducted baseline tests. The influence of wake expansion blockage on the turbine performance due to presence of the free surface at these immersion depths will also be discussed.

  18. Renormalization in quantum field theory and the Riemann-Hilbert problem. I. Hopf algebra structure of graphs and the main theorem

    International Nuclear Information System (INIS)

    Connes, A.; Kreimer, D.

    2000-01-01

    This paper gives a complete selfcontained proof of our result (1999) showing that renormalization in quantum field theory is a special instance of a general mathematical procedure of extraction of finite values based on the Riemann-Hilbert problem. We shall first show that for any quantum field theory, the combinatorics of Feynman graphs gives rise to a Hopf algebra H which is commutative asan algebra. It is the dual Hopf algebra of the enveloping algebra of a Lie algebra G whose basis is labelled by the one particle irreducible Feynman graphs. The Lie bracket of two such graphs is computed from insertions of one graph in the other and vice versa. The corresponding Lie group G is the group of characters of H. We show then that, using dimensional regularization, the bare (unrenormalized) theory gives rise to a loop γ(z) element of G, z element of C, where C is a small circle of complex dimensions around the integer dimension D of space-time. Our main result is that the renormalized theory is just the evaluation at z=D of the holomorphic part γ + of the Birkhoff decomposition of γ. We begin to analyse the group G and show that it is a semi-direct product of an easily understood abelian group by a highly non-trivial group closely tied up with groups of diffeomorphisms. (orig.)

  19. On turbulence structure in vertical pipe flow of fiber suspensions [refractivity, flow measurement, turbulent flow, glass fibers, fluid flow

    International Nuclear Information System (INIS)

    Steen, M.

    1989-01-01

    A suspension of glass fibers in alcohol has been used to investigate a upward vertical developing pipe flow. The refractive index of the alcohol was matched to that of the glass fibers, making the whole suspension transparent. Laser Doppler Anemometry (LDA) was applied, and fluid velocities could then be measured for consistencies up to c = 12 g/l. Radial profiles of axial U-velocity and turbulence spectra have been recorded at various positions (z/D = 2, 5, 36) downstream of an orifice (step) with 64% open area. Measurements were taken for different consistencies (c = 1.2, 12 g/l), fiber lengths (l = 1, 3 mm) and Reynolds numbers (R e = 8.5 ⋅ 10 3 , 6.5 ⋅ 10 4 ). The fiber crowding factor (n f ) has been used to discuss the observed effects of the present fibers on momentum transfer and turbulence structure. The results show both an increase (l= 1 mm, c= 1.2 g/l) and decrease (l=3 mm, c = 12 g/l) in turbulence levels in the presence of fibers. Suspensions with long fibers at the highest consistency show plug flow in parts of the core. This causes damping of the turbulence mainly at smaller length scales. For short fibers at low consistency, the increased turbulent energy was mainly observed at small length scales in the spectrum. (author)

  20. Afterheat usage from cooling facilities in ORC processes

    International Nuclear Information System (INIS)

    Theede, Florian; Luke, Andrea

    2016-01-01

    In the course of the reduction of climate warming an energy-efficient lay-out of processes is necessary. A possibility for the efficiency increasement is the usage of afterheat currents for instance in ORC processes. Connected with the limitation of refrigerants with high greenhouse potential it comes to the increased application of transcritical cooling facilities with carbon dioxide (CO_2) as refrigerant. By the high pressures after the compression arise here new afterheat sources on a temperature level of about 100 C. An alternative for the simple back-cooling or the heating support and drinking-water heating represents the current production in an ORC process. Great challenges for the lay-out of such an ORC process are the selection of the working fluid as well as the lay-out of the heat exchangers. Established refrigerants in the low-temperature like R245fa for ORC facilities will be in forseeable future no more available. For the study of the possible replacement by alternative refrigerants a simulation model has been developed. By means of this model different refrigerants are analyzed regarding their performance and simultaneously the effects on process and other components studied. The results show that in the temperature range two hydrofluoroolefines R1233zd[E] and R1234ze[Z] as well as the hadron carbon butane can thermodynamically form an alternative.

  1. Afterheat usage from cooling facilities in ORC processes; Abwaermenutzung aus Kaelteanlagen in ORC-Prozessen

    Energy Technology Data Exchange (ETDEWEB)

    Theede, Florian; Luke, Andrea [Kassel Univ. (Germany). Technische Themodynamik

    2016-07-01

    In the course of the reduction of climate warming an energy-efficient lay-out of processes is necessary. A possibility for the efficiency increasement is the usage of afterheat currents for instance in ORC processes. Connected with the limitation of refrigerants with high greenhouse potential it comes to the increased application of transcritical cooling facilities with carbon dioxide (CO{sub 2}) as refrigerant. By the high pressures after the compression arise here new afterheat sources on a temperature level of about 100 C. An alternative for the simple back-cooling or the heating support and drinking-water heating represents the current production in an ORC process. Great challenges for the lay-out of such an ORC process are the selection of the working fluid as well as the lay-out of the heat exchangers. Established refrigerants in the low-temperature like R245fa for ORC facilities will be in forseeable future no more available. For the study of the possible replacement by alternative refrigerants a simulation model has been developed. By means of this model different refrigerants are analyzed regarding their performance and simultaneously the effects on process and other components studied. The results show that in the temperature range two hydrofluoroolefines R1233zd[E] and R1234ze[Z] as well as the hadron carbon butane can thermodynamically form an alternative.

  2. Imaging auditory representations of song and syllables in populations of sensorimotor neurons essential to vocal communication.

    Science.gov (United States)

    Peh, Wendy Y X; Roberts, Todd F; Mooney, Richard

    2015-04-08

    Vocal communication depends on the coordinated activity of sensorimotor neurons important to vocal perception and production. How vocalizations are represented by spatiotemporal activity patterns in these neuronal populations remains poorly understood. Here we combined intracellular recordings and two-photon calcium imaging in anesthetized adult zebra finches (Taeniopygia guttata) to examine how learned birdsong and its component syllables are represented in identified projection neurons (PNs) within HVC, a sensorimotor region important for song perception and production. These experiments show that neighboring HVC PNs can respond at markedly different times to song playback and that different syllables activate spatially intermingled PNs within a local (~100 μm) region of HVC. Moreover, noise correlations were stronger between PNs that responded most strongly to the same syllable and were spatially graded within and between classes of PNs. These findings support a model in which syllabic and temporal features of song are represented by spatially intermingled PNs functionally organized into cell- and syllable-type networks within local spatial scales in HVC. Copyright © 2015 the authors 0270-6474/15/355589-17$15.00/0.

  3. Chemical composition and physicochemical properties of tropical red seaweed, Gracilaria changii.

    Science.gov (United States)

    Chan, Pei Teng; Matanjun, Patricia

    2017-04-15

    A study on the proximate composition, minerals, vitamins, carotenoids, amino acids, fatty acids profiles and some physicochemical properties of freeze dried Gracilaria changii was conducted. It was discovered that this seaweed was high in dietary fibre (64.74±0.82%), low in fat (0.30±0.02%) and Na/K ratio (0.12±0.02). The total amino acid content was 91.90±7.70% mainly essential amino acids (55.87±2.15mgg -1 ) which were comparable to FAO/WHO requirements. The fatty acid profiles were dominated by the polyunsaturated fatty acids particularly docosahexaenoic (48.36±6.76%) which led to low ω6/ω3, atherogenic, and thrombogenic index. The physicochemical properties of this seaweed namely the water holding and the swelling capacity were comparable to some commercial fibre rich products. This study suggested that G. changii could be potentially used as ingredients to improve nutritive value and texture of functional foods for human consumption. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Epigenetic Etiology of Intellectual Disability.

    Science.gov (United States)

    Iwase, Shigeki; Bérubé, Nathalie G; Zhou, Zhaolan; Kasri, Nael Nadif; Battaglioli, Elena; Scandaglia, Marilyn; Barco, Angel

    2017-11-08

    Intellectual disability (ID) is a prevailing neurodevelopmental condition associated with impaired cognitive and adaptive behaviors. Many chromatin-modifying enzymes and other epigenetic regulators have been genetically associated with ID disorders (IDDs). Here we review how alterations in the function of histone modifiers, chromatin remodelers, and methyl-DNA binding proteins contribute to neurodevelopmental defects and altered brain plasticity. We also discuss how progress in human genetics has led to the generation of mouse models that unveil the molecular etiology of ID, and outline the direction in which this field is moving to identify therapeutic strategies for IDDs. Importantly, because the chromatin regulators linked to IDDs often target common downstream genes and cellular processes, the impact of research in individual syndromes goes well beyond each syndrome and can also contribute to the understanding and therapy of other IDDs. Furthermore, the investigation of these disorders helps us to understand the role of chromatin regulators in brain development, plasticity, and gene expression, thereby answering fundamental questions in neurobiology. Copyright © 2017 the authors 0270-6474/17/3710773-10$15.00/0.

  5. The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a.

    Science.gov (United States)

    Cánovas, José; Berndt, F Andrés; Sepúlveda, Hugo; Aguilar, Rodrigo; Veloso, Felipe A; Montecino, Martín; Oliva, Carlos; Maass, Juan C; Sierralta, Jimena; Kukuljan, Manuel

    2015-05-13

    The acquisition of distinct neuronal fates is fundamental for the function of the cerebral cortex. We find that the development of subcerebral projections from layer 5 neurons in the mouse neocortex depends on the high levels of expression of the transcription factor CTIP1; CTIP1 is coexpressed with CTIP2 in neurons that project to subcerebral targets and with SATB2 in those that project to the contralateral cortex. CTIP1 directly represses Tbr1 in layer 5, which appears as a critical step for the acquisition of the subcerebral fate. In contrast, lower levels of CTIP1 in layer 6 are required for TBR1 expression, which directs the corticothalamic fate. CTIP1 does not appear to play a critical role in the acquisition of the callosal projection fate in layer 5. These findings unravel a key step in the acquisition of cell fate for closely related corticofugal neurons and indicate that differential dosages of transcriptions factors are critical to specify different neuronal identities. Copyright © 2015 the authors 0270-6474/15/357552-13$15.00/0.

  6. MET receptor tyrosine kinase controls dendritic complexity, spine morphogenesis, and glutamatergic synapse maturation in the hippocampus.

    Science.gov (United States)

    Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

    2014-12-03

    The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. Copyright © 2014 the authors 0270-6474/14/3416166-14$15.00/0.

  7. Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine.

    Science.gov (United States)

    Navarro, Gemma; Quiroz, César; Moreno-Delgado, David; Sierakowiak, Adam; McDowell, Kimberly; Moreno, Estefanía; Rea, William; Cai, Ning-Sheng; Aguinaga, David; Howell, Lesley A; Hausch, Felix; Cortés, Antonio; Mallol, Josefa; Casadó, Vicent; Lluís, Carme; Canela, Enric I; Ferré, Sergi; McCormick, Peter J

    2015-04-29

    Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target σ1 receptor (σ1R) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the σ1R-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking. Copyright © 2015 the authors 0270-6474/15/356639-15$15.00/0.

  8. EOL-1, the homolog of the mammalian Dom3Z, regulates olfactory learning in C. elegans.

    Science.gov (United States)

    Shen, Yu; Zhang, Jiangwen; Calarco, John A; Zhang, Yun

    2014-10-01

    Learning is an essential function of the nervous system. However, our understanding of molecular underpinnings of learning remains incomplete. Here, we characterize a conserved protein EOL-1 that regulates olfactory learning in Caenorhabditis elegans. A recessive allele of eol-1 (enhanced olfactory learning) learns better to adjust its olfactory preference for bacteria foods and eol-1 acts in the URX sensory neurons to regulate learning. The mammalian homolog of EOL-1, Dom3Z, which regulates quality control of pre-mRNAs, can substitute the function of EOL-1 in learning regulation, demonstrating functional conservation between these homologs. Mutating the residues of Dom3Z that are critical for its enzymatic activity, and the equivalent residues in EOL-1, abolishes the function of these proteins in learning. Together, our results provide insights into the function of EOL-1/Dom3Z and suggest that its activity in pre-mRNA quality control is involved in neural plasticity. Copyright © 2014 the authors 0270-6474/14/3413364-07$15.00/0.

  9. Dynamic divisive normalization predicts time-varying value coding in decision-related circuits.

    Science.gov (United States)

    Louie, Kenway; LoFaro, Thomas; Webb, Ryan; Glimcher, Paul W

    2014-11-26

    Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding. Copyright © 2014 the authors 0270-6474/14/3416046-12$15.00/0.

  10. Disruption of Fgf13 causes synaptic excitatory-inhibitory imbalance and genetic epilepsy and febrile seizures plus.

    Science.gov (United States)

    Puranam, Ram S; He, Xiao Ping; Yao, Lijun; Le, Tri; Jang, Wonjo; Rehder, Catherine W; Lewis, Darrell V; McNamara, James O

    2015-06-10

    We identified a family in which a translocation between chromosomes X and 14 was associated with cognitive impairment and a complex genetic disorder termed "Genetic Epilepsy and Febrile Seizures Plus" (GEFS(+)). We demonstrate that the breakpoint on the X chromosome disrupted a gene that encodes an auxiliary protein of voltage-gated Na(+) channels, fibroblast growth factor 13 (Fgf13). Female mice in which one Fgf13 allele was deleted exhibited hyperthermia-induced seizures and epilepsy. Anatomic studies revealed expression of Fgf13 mRNA in both excitatory and inhibitory neurons of hippocampus. Electrophysiological recordings revealed decreased inhibitory and increased excitatory synaptic inputs in hippocampal neurons of Fgf13 mutants. We speculate that reduced expression of Fgf13 impairs excitability of inhibitory interneurons, resulting in enhanced excitability within local circuits of hippocampus and the clinical phenotype of epilepsy. These findings reveal a novel cause of this syndrome and underscore the powerful role of FGF13 in control of neuronal excitability. Copyright © 2015 the authors 0270-6474/15/358866-16$15.00/0.

  11. Neural dynamics underlying attentional orienting to auditory representations in short-term memory.

    Science.gov (United States)

    Backer, Kristina C; Binns, Malcolm A; Alain, Claude

    2015-01-21

    Sounds are ephemeral. Thus, coherent auditory perception depends on "hearing" back in time: retrospectively attending that which was lost externally but preserved in short-term memory (STM). Current theories of auditory attention assume that sound features are integrated into a perceptual object, that multiple objects can coexist in STM, and that attention can be deployed to an object in STM. Recording electroencephalography from humans, we tested these assumptions, elucidating feature-general and feature-specific neural correlates of auditory attention to STM. Alpha/beta oscillations and frontal and posterior event-related potentials indexed feature-general top-down attentional control to one of several coexisting auditory representations in STM. Particularly, task performance during attentional orienting was correlated with alpha/low-beta desynchronization (i.e., power suppression). However, attention to one feature could occur without simultaneous processing of the second feature of the representation. Therefore, auditory attention to memory relies on both feature-specific and feature-general neural dynamics. Copyright © 2015 the authors 0270-6474/15/351307-12$15.00/0.

  12. Correlations in V1 are reduced by stimulation outside the receptive field.

    Science.gov (United States)

    Snyder, Adam C; Morais, Michael J; Kohn, Adam; Smith, Matthew A

    2014-08-20

    The trial-to-trial response variability of nearby cortical neurons is correlated. These correlations may strongly influence population coding performance. Numerous studies have shown that correlations can be dynamically modified by attention, adaptation, learning, and potent stimulus drive. However, the mechanisms that influence correlation strength remain poorly understood. Here we test whether correlations are influenced by presenting stimuli outside the classical receptive field (RF) of visual neurons, where they recruit a normalization signal termed surround suppression. We recorded simultaneously the activity of dozens of cells using microelectrode arrays implanted in the superficial layers of V1 in anesthetized, paralyzed macaque monkeys. We presented annular stimuli that encircled--but did not impinge upon--the RFs of the recorded cells. We found that these "extra-classical" stimuli reduced correlations in the absence of stimulation of the RF, closely resembling the decorrelating effects of stimulating the RFs directly. Our results suggest that normalization signals may be an important mechanism for modulating correlations. Copyright © 2014 the authors 0270-6474/14/3411222-06$15.00/0.

  13. Phrenic long-term facilitation requires PKCθ activity within phrenic motor neurons.

    Science.gov (United States)

    Devinney, Michael J; Fields, Daryl P; Huxtable, Adrianne G; Peterson, Timothy J; Dale, Erica A; Mitchell, Gordon S

    2015-05-27

    Acute intermittent hypoxia (AIH) induces a form of spinal motor plasticity known as phrenic long-term facilitation (pLTF); pLTF is a prolonged increase in phrenic motor output after AIH has ended. In anesthetized rats, we demonstrate that pLTF requires activity of the novel PKC isoform, PKCθ, and that the relevant PKCθ is within phrenic motor neurons. Whereas spinal PKCθ inhibitors block pLTF, inhibitors targeting other PKC isoforms do not. PKCθ is highly expressed in phrenic motor neurons, and PKCθ knockdown with intrapleural siRNAs abolishes pLTF. Intrapleural siRNAs targeting PKCζ, an atypical PKC isoform expressed in phrenic motor neurons that underlies a distinct form of phrenic motor plasticity, does not affect pLTF. Thus, PKCθ plays a critical role in spinal AIH-induced respiratory motor plasticity, and the relevant PKCθ is localized within phrenic motor neurons. Intrapleural siRNA delivery has considerable potential as a therapeutic tool to selectively manipulate plasticity in vital respiratory motor neurons. Copyright © 2015 the authors 0270-6474/15/358107-11$15.00/0.

  14. Dissociating movement from movement timing in the rat primary motor cortex.

    Science.gov (United States)

    Knudsen, Eric B; Powers, Marissa E; Moxon, Karen A

    2014-11-19

    Neural encoding of the passage of time to produce temporally precise movements remains an open question. Neurons in several brain regions across different experimental contexts encode estimates of temporal intervals by scaling their activity in proportion to the interval duration. In motor cortex the degree to which this scaled activity relies upon afferent feedback and is guided by motor output remains unclear. Using a neural reward paradigm to dissociate neural activity from motor output before and after complete spinal transection, we show that temporally scaled activity occurs in the rat hindlimb motor cortex in the absence of motor output and after transection. Context-dependent changes in the encoding are plastic, reversible, and re-established following injury. Therefore, in the absence of motor output and despite a loss of afferent feedback, thought necessary for timed movements, the rat motor cortex displays scaled activity during a broad range of temporally demanding tasks similar to that identified in other brain regions. Copyright © 2014 the authors 0270-6474/14/3415576-11$15.00/0.

  15. Identification of cellular targets involved in cardiac failure caused by PKI in oncology: an approach combining pharmacovigilance and pharmacodynamics.

    Science.gov (United States)

    Patras de Campaigno, Emilie; Bondon-Guitton, Emmanuelle; Laurent, Guy; Montastruc, Francois; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse; Despas, Fabien

    2017-07-01

    The aims of the present study were to evaluate the risk of cardiac failure (CF) associated with 15 anticancer protein kinase inhibitors (PKIs) through a case/noncase analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. In order to evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the World Health Organization safety report database (VigiBase®). We realised a literature review to identify 21 protein kinases (PKs) that were possibly involved in CF caused by PKIs. Pearson correlation coefficients (r) between aRORs and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely to be involved in PKI-induced CF. A total of 141 601 individual case safety reports (ICSRs) were extracted from VigiBase® for the following PKIs: afatinib, axitinib, bosutinib, crizotinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, pazopanib, ruxolitinib, sorafenib, sunitinib and vandetanib. Among them, 2594 ICSRs concerned CF. The disproportionality analysis revealed that, for dasatinib, imatinib, bosutinib, sunitinib and nilotinib, disproportionality for CF was significantly higher than for other PKIs, with aRORs of 2.52 [95% CI 2.26, 2.82], 1.79 (95% CI 1.57, 2.03), 1.73 (95% CI 1.18, 2.54), 1.67 (95% CI 1.51, 1.84) and 1.38 (95% CI 1.18, 1.61), respectively. Significant values for correlation coefficients between the product of dissociation constant (pKd) and aROR were observed for two non-receptor protein kinases: ABL1 (non-phosphorylated and phosphorylated forms) and ABL2 protein kinases, with values of r = 0.83 (P = 0.0001), r = 0.75 (P = 0.0014) and r = 0.78 (P = 0.0006), respectively. We observed a higher disproportionality for CF with dasatinib, imatinib, bosutinib, sunitinib and nilotinib than with other PKIs. In addition, the study highlighted the role of ABL tyrosine kinases in CF caused by anticancer PKIs. © 2017 The British

  16. Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Colquhoun, AJ; Mchugh, LA; Tulchinsky, E.; Kriajevska, M.; Mellon, JK

    2007-01-01

    External beam radiotherapy (EBRT) is the principal bladder-preserving monotherapy for muscle-invasive bladder cancer. Seventy percent of muscle-invasive bladder cancers express epidermal growth factor receptor (EGFR), which is associated with poor prognosis. Ionising radiation (IR) stimulates EGFR causing activation of cytoprotective signalling cascades and thus may be an underlying cause of radioresistance in bladder tumours. We assessed the ability of IR to activate EGFR in bladder cancer cells and the effect of the anti-EGFR therapy, gefitinib on potential radiation-induced activation. Subsequently we assessed the effect of IR on signalling pathways downstream of EGFR. Finally we assessed the activity of gefitinib as a monotherapy, and in combination with IR, using clonogenic assay in vitro, and a murine model in vivo. IR activated EGFR and gefitinib partially inhibited this activation. Radiation-induced activation of EGFR activated the MAPK and Akt pathways. Gefitinib partially inhibited activation of the MAPK pathway but not the Akt pathway. Treatment with combined gefitinib and IR significantly inhibited bladder cancer cell colony formation more than treatment with gefitinib alone (p=0.001-0.03). J82 xenograft tumours treated with combined gefitinib and IR showed significantly greater growth inhibition than tumours treated with IR alone (p=0.04). Combining gefitinib and IR results in significantly greater inhibition of invasive bladder cancer cell colony formation in vitro and significantly greater tumour growth inhibition in vivo. Given the high frequency of EGFR expression by bladder tumours and the low toxicity of gefitinib there is justification to translate this work into a clinical trial. (author)

  17. GLOBAL STABILITY AND PERIODIC SOLUTION OF A VIRAL DYNAMIC MODEL

    Directory of Open Access Journals (Sweden)

    Erhan COŞKUN

    2009-02-01

    Full Text Available Abstract:In this paper, we consider the classical viral dynamic mathematical model. Global dynamics of the model is rigorously established. We prove that, if the basic reproduction number, the HIV infection is cleared from the T-cell population; if , the HIV infection persists. For an open set of parameter values, the chronic-infection equilibrium can be unstable and periodic solutions may exist. We establish parameter regions for which is globally stable. Keywords: Global stability, HIV infection; CD4+ T cells; Periodic solution Mathematics Subject Classifications (2000: 65L10, 34B05 BİR VİRAL DİNAMİK MODELİN GLOBAL KARARLILIĞI VE PERİYODİK ÇÖZÜMÜ Özet: Bu makalede klasik viral dinamik modeli ele aldık. Modelin global dinamikleri oluşturuldu. Eğer temel üretim sayısı olur ise HIV enfeksiyonu T hücre nüfusundan çıkartılır, eğer olursa HIV enfeksiyonu çıkartılamaz. Parametre değerlerinin açık bir kümesi için kronik enfeksiyon dengesi kararsızdır ve periyodik çözüm oluşabilir. ın global kararlı olduğu parametre bölgeleri oluşturuldu. Anahtar Kelimeler: Global Kararlılık, HIV enfeksiyon, CD4+ T hücreler, Periyodik çözüm

  18. Fibre Concrete 2017

    Science.gov (United States)

    2017-09-01

    9th international conference on fibre reinforced concretes (FRC), textile reinforced concretes (TRC) and ultra-high performance concretes (UHPC) Preface The Fibre Concrete Conference series is held biennially to provide a platform to share knowledge on fibre reinforced concretes, textile concretes and ultra-high performance concretes regarding material properties and behaviour, technology procedures, topics of long-term behaviour, creep, durability; sustainable aspects of concrete including utilisation of waste materials in concrete production and recycling of concrete. The tradition of Fibre Concrete Conferences started in eighties of the last century. Nowadays the conference is organized by the Department of Concrete and Masonry Structures of the Czech Technical University in Prague, Faculty of Civil Engineering. The 9th International Conference Fibre Concrete 2017 had 109 participants from 27 countries all over the world. 55 papers were presented including keynote lectures of Professor Bažant, Professor Bartoš and Dr. Broukalová. The conference program covered wide range of topics from scientific research to practical applications. The presented contributions related to performance and behaviour of cement based composites, their long-term behaviour and durability, sustainable aspects, advanced analyses of structures from these composites and successful applications. This conference was organized also to honour Professor Zděnek P. Bažant on the occasion of his jubilee and to appreciate his merits and discoveries in the field of fibre reinforced composites, structural mechanics and engineering.

  19. Reduced Hyperpolarization-Activated Current Contributes to Enhanced Intrinsic Excitability in Cultured Hippocampal Neurons from PrP(-/-) Mice.

    Science.gov (United States)

    Fan, Jing; Stemkowski, Patrick L; Gandini, Maria A; Black, Stefanie A; Zhang, Zizhen; Souza, Ivana A; Chen, Lina; Zamponi, Gerald W

    2016-01-01

    Genetic ablation of cellular prion protein (PrP(C)) has been linked to increased neuronal excitability and synaptic activity in the hippocampus. We have previously shown that synaptic activity in hippocampi of PrP-null mice is increased due to enhanced N-methyl-D-aspartate receptor (NMDAR) function. Here, we focused on the effect of PRNP gene knock-out (KO) on intrinsic neuronal excitability, and in particular, the underlying ionic mechanism in hippocampal neurons cultured from P0 mouse pups. We found that the absence of PrP(C) profoundly affected the firing properties of cultured hippocampal neurons in the presence of synaptic blockers. The membrane impedance was greater in PrP-null neurons, and this difference was abolished by the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288 (100 μM). HCN channel activity appeared to be functionally regulated by PrP(C). The amplitude of voltage sag, a characteristic of activating HCN channel current (I h), was decreased in null mice. Moreover, I h peak current was reduced, along with a hyperpolarizing shift in activation gating and slower kinetics. However, neither HCN1 nor HCN2 formed a biochemical complex with PrP(C). These results suggest that the absence of PrP downregulates the activity of HCN channels through activation of a cell signaling pathway rather than through direct interactions. This in turn contributes to an increase in membrane impedance to potentiate neuronal excitability.

  20. Tracing of Zinc Nanocrystals in the Anterior Pituitary of Zinc-Deficient Wistar Rats.

    Science.gov (United States)

    Kuldeep, Anjana; Nair, Neena; Bedwal, Ranveer Singh

    2017-06-01

    The aim of this study was to trace zinc nanocrystals in the anterior pituitary of zinc-deficient Wistar rats by using autometallographic technique. Male Wistar rats (30-40 days of age, pre-pubertal period) of 40-50 g body weight were divided into the following: the ZC (zinc control) group-fed with 100 ppm zinc in diet, the ZD (zinc-deficient) group-fed with zinc-deficient (1.00 ppm) diet and the PF (pair-fed) group-received 100 ppm zinc in diet. The experiments were set for 2 and 4 weeks. Pituitary was removed and processed for the autometallographic technique. The control and pair-fed groups retained their normal morphological features. However, male Wistar rats fed on zinc-deficient diet for 2 and 4 weeks displayed a wide range of symptoms such as significant (P zinc nanocrystals in the nuclei. The present findings suggest that the dietary zinc deficiency causes decreased intensity of zinc nanocrystals localization and their distribution in the pituitary thereby contributing to the dysfunction of the pituitary of the male Wistar rats. The severity of zinc deficiency symptoms progressed after the second week of the experiment. Decreased intensity of zinc nanocrystals attenuates the pituitary function which would exert its affect on other endocrine organs impairing their functions indicating that the metabolic regulation of pituitary is mediated to a certain extent by zinc and/or hypothalamus-hypophysial system which also reflects its essentiality during the period of growth.

  1. Non-Markovianity Measure Based on Brukner-Zeilinger Invariant Information for Unital Quantum Dynamical Maps

    Science.gov (United States)

    He, Zhi; Zhu, Lie-Qiang; Li, Li

    2017-03-01

    A non-Markovianity measure based on Brukner-Zeilinger invariant information to characterize non-Markovian effect of open systems undergoing unital dynamical maps is proposed. The method takes advantage of non-increasing property of the Brukner-Zeilinger invariant information under completely positive and trace-preserving unital maps. The simplicity of computing the Brukner-Zeilinger invariant information is the advantage of the proposed measure because of mainly depending on the purity of quantum state. The measure effectively captures the characteristics of non-Markovianity of unital dynamical maps. As some concrete application, we consider two typical non-Markovian noise channels, i.e., the phase damping channel and the random unitary channel to show the sensitivity of the proposed measure. By investigation, we find that the conditions of detecting the non-Markovianity for the phase damping channel are consistent with the results of existing measures for non-Markovianity, i.e., information flow, divisibility and quantum mutual information. However, for the random unitary channel non-Markovian conditions are same to that of the information flow, but is different from that of the divisibility and quantum mutual information. Supported by the National Natural Science Foundation of China under Grant No. 61505053, the Natural Science Foundation of Hunan Province under Grant No. 2015JJ3092, the Research Foundation of Education Bureau of Hunan Province, China under Grant No. 16B177, the School Foundation from the Hunan University of Arts and Science under Grant No. 14ZD01

  2. Quantitative proteomic analyses of the microbial degradation of estrone under various background nitrogen and carbon conditions.

    Science.gov (United States)

    Du, Zhe; Chen, Yinguang; Li, Xu

    2017-10-15

    Microbial degradation of estrogenic compounds can be affected by the nitrogen source and background carbon in the environment. However, the underlying mechanisms are not well understood. The objective of this study was to elucidate the molecular mechanisms of estrone (E1) biodegradation at the protein level under various background nitrogen (nitrate or ammonium) and carbon conditions (no background carbon, acetic acid, or humic acid as background carbon) by a newly isolated bacterial strain. The E1 degrading bacterial strain, Hydrogenophaga atypica ZD1, was isolated from river sediments and its proteome was characterized under various experimental conditions using quantitative proteomics. Results show that the E1 degradation rate was faster when ammonium was used as the nitrogen source than with nitrate. The degradation rate was also faster when either acetic acid or humic acid was present in the background. Proteomics analyses suggested that the E1 biodegradation products enter the tyrosine metabolism pathway. Compared to nitrate, ammonium likely promoted E1 degradation by increasing the activities of the branched-chain-amino-acid aminotransferase (IlvE) and enzymes involved in the glutamine synthetase-glutamine oxoglutarate aminotransferase (GS-GOGAT) pathway. The increased E1 degradation rate with acetic acid or humic acid in the background can also be attributed to the up-regulation of IlvE. Results from this study can help predict and explain E1 biodegradation kinetics under various environmental conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Dependent Human Error Probability Assessment

    International Nuclear Information System (INIS)

    Simic, Z.; Mikulicic, V.; Vukovic, I.

    2006-01-01

    This paper presents an assessment of the dependence between dynamic operator actions modeled in a Nuclear Power Plant (NPP) PRA and estimate the associated impact on Core damage frequency (CDF). This assessment was done improve HEP dependencies implementation inside existing PRA. All of the dynamic operator actions modeled in the NPP PRA are included in this assessment. Determining the level of HEP dependence and the associated influence on CDF are the major steps of this assessment. A decision on how to apply the results, i.e., should permanent HEP model changes be made, is based on the resulting relative CDF increase. Some CDF increase was selected as a threshold based on the NPP base CDF value and acceptance guidelines from the Regulatory Guide 1.174. HEP dependence resulting in a CDF increase of > 5E-07 would be considered potential candidates for specific incorporation into the baseline model. The approach used to judge the level of dependence between operator actions is based on dependency level categories and conditional probabilities developed in the Handbook of Human Reliability Analysis with Emphasis on Nuclear Power Plant Applications NUREG/CR-1278. To simplify the process, NUREG/CR-1278 identifies five levels of dependence: ZD (zero dependence), LD (low dependence), MD (moderate dependence), HD (high dependence), and CD (complete dependence). NUREG/CR-1278 also identifies several qualitative factors that could be involved in determining the level of dependence. Based on the NUREG/CR-1278 information, Time, Function, and Spatial attributes were judged to be the most important considerations when determining the level of dependence between operator actions within an accident sequence. These attributes were used to develop qualitative criteria (rules) that were used to judge the level of dependence (CD, HD, MD, LD, ZD) between the operator actions. After the level of dependence between the various HEPs is judged, quantitative values associated with the

  4. Mapping the Hypocretin/Orexin Neuronal System: An Unexpectedly Productive Journey.

    Science.gov (United States)

    Peyron, Christelle; Kilduff, Thomas S

    2017-03-01

    Early in 1998, we (de Lecea et al., 1998) and others (Sakurai et al., 1998) described the same hypothalamic neuropeptides, respectively called the hypocretins or orexins, which were discovered using two different approaches. In December of that year, we published the subject of this commentary in the Journal of Neuroscience : a highly detailed anatomical description of the extensive axonal projections of the hypocretin/orexin neurons. Although the function of this system was unknown at the time, a large body of literature today attests that the hypocretin/orexin neuropeptides play important roles in multiple physiological functions, particularly in sleep/wake regulation. Neuroanatomical studies are rarely frontline news, but the citation rate of this paper underscores the critical nature of such basic research. Based in part on this detailed description, the hypocretin/orexin neuropeptides have since been studied in many different areas of neuroscience research, including sleep/wake regulation, feeding, addiction, reward and motivation, anxiety and depression, cardiovascular regulation, pain, migraine, and neuroendocrine regulation, including reproduction. Thus, this paper has had a surprisingly broad impact on neuroscience research, particularly since it was originally rejected by the Journal ! Copyright © 2017 the authors 0270-6474/17/372268-05$15.00/0.

  5. Temporal-pattern similarity analysis reveals the beneficial and detrimental effects of context reinstatement on human memory.

    Science.gov (United States)

    Staudigl, Tobias; Vollmar, Christian; Noachtar, Soheyl; Hanslmayr, Simon

    2015-04-01

    A powerful force in human memory is the context in which memories are encoded (Tulving and Thomson, 1973). Several studies suggest that the reinstatement of neural encoding patterns is beneficial for memory retrieval (Manning et al., 2011; Staresina et al., 2012; Jafarpour et al., 2014). However, reinstatement of the original encoding context is not always helpful, for instance, when retrieving a memory in a different contextual situation (Smith and Vela, 2001). It is an open question whether such context-dependent memory effects can be captured by the reinstatement of neural patterns. We investigated this question by applying temporal and spatial pattern similarity analysis in MEG and intracranial EEG in a context-match paradigm. Items (words) were tagged by individual dynamic context stimuli (movies). The results show that beta oscillatory phase in visual regions and the parahippocampal cortex tracks the incidental reinstatement of individual context trajectories on a single-trial level. Crucially, memory benefitted from reinstatement when the encoding and retrieval contexts matched but suffered from reinstatement when the contexts did not match. Copyright © 2015 the authors 0270-6474/15/355373-12$15.00/0.

  6. Adolescence and Reward: Making Sense of Neural and Behavioral Changes Amid the Chaos.

    Science.gov (United States)

    Walker, Deena M; Bell, Margaret R; Flores, Cecilia; Gulley, Joshua M; Willing, Jari; Paul, Matthew J

    2017-11-08

    Adolescence is a time of significant neural and behavioral change with remarkable development in social, emotional, and cognitive skills. It is also a time of increased exploration and risk-taking (e.g., drug use). Many of these changes are thought to be the result of increased reward-value coupled with an underdeveloped inhibitory control, and thus a hypersensitivity to reward. Perturbations during adolescence can alter the developmental trajectory of the brain, resulting in long-term alterations in reward-associated behaviors. This review highlights recent developments in our understanding of how neural circuits, pubertal hormones, and environmental factors contribute to adolescent-typical reward-associated behaviors with a particular focus on sex differences, the medial prefrontal cortex, social reward, social isolation, and drug use. We then introduce a new approach that makes use of natural adaptations of seasonally breeding species to investigate the role of pubertal hormones in adolescent development. This research has only begun to parse out contributions of the many neural, endocrine, and environmental changes to the heightened reward sensitivity and increased vulnerability to mental health disorders that characterize this life stage. Copyright © 2017 the authors 0270-6474/17/3710855-12$15.00/0.

  7. β-Secretase BACE1 regulates hippocampal and reconstituted M-currents in a β-subunit-like fashion.

    Science.gov (United States)

    Hessler, Sabine; Zheng, Fang; Hartmann, Stephanie; Rittger, Andrea; Lehnert, Sandra; Völkel, Meike; Nissen, Matthias; Edelmann, Elke; Saftig, Paul; Schwake, Michael; Huth, Tobias; Alzheimer, Christian

    2015-02-25

    The β-secretase BACE1 is widely known for its pivotal role in the amyloidogenic pathway leading to Alzheimer's disease, but how its action on transmembrane proteins other than the amyloid precursor protein affects the nervous system is only beginning to be understood. We report here that BACE1 regulates neuronal excitability through an unorthodox, nonenzymatic interaction with members of the KCNQ (Kv7) family that give rise to the M-current, a noninactivating potassium current with slow kinetics. In hippocampal neurons from BACE1(-/-) mice, loss of M-current enhanced neuronal excitability. We relate the diminished M-current to the previously reported epileptic phenotype of BACE1-deficient mice. In HEK293T cells, BACE1 amplified reconstituted M-currents, altered their voltage dependence, accelerated activation, and slowed deactivation. Biochemical evidence strongly suggested that BACE1 physically associates with channel proteins in a β-subunit-like fashion. Our results establish BACE1 as a physiologically essential constituent of regular M-current function and elucidate a striking new feature of how BACE1 impacts on neuronal activity in the intact and diseased brain. Copyright © 2015 the authors 0270-6474/15/353298-14$15.00/0.

  8. A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia.

    Science.gov (United States)

    Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn; Munir, Jared; Chandler-Militello, Devin; Wang, Su; Goldman, Steven A

    2014-11-26

    Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiation of the donor cells is influenced by the host environment, such that more donor cells differentiated as oligodendrocytes in the hypomyelinated shiverer brain than in myelin wild-types, in which hGPCs were more likely to remain as progenitors. Yet in each recipient, both the number and relative proportion of mouse GPCs fell as a function of time, concomitant with the mitotic expansion and spread of donor hGPCs. By a year after neonatal xenograft, the forebrain GPC populations of implanted mice were largely, and often entirely, of human origin. Thus, neonatally implanted hGPCs outcompeted and ultimately replaced the host population of mouse GPCs, ultimately generating mice with a humanized glial progenitor population. These human glial chimeric mice should permit us to define the specific contributions of glia to a broad variety of neurological disorders, using human cells in vivo. Copyright © 2014 the authors 0270-6474/14/3416153-09$15.00/0.

  9. Landslides triggered by Hurricane Hugo in eastern Puerto Rico, September 1989

    Science.gov (United States)

    Larsen, Matthew C.; Torres-Sanchez, Angel J.

    1992-01-01

    On the morning of September 18, 1989, a category-four hurricane struck eastern Puerto Rico with a sustained wind speed in excess of 46 m/s. The 24-h rainfall accumulation from the hurricane ranged from 100 to 339 mm. Average rainfall intensities ranging from 34 to 39 mm/h were calculated for 4 and 6 h periods, respectively, at a rain gage equipped with satellite telemetry, and at an observer station. The hurricane rainfall triggered more than 400 landslides in the steeply sloping, highly dissected mountains of eastern Puerto Rico. Of these landslides, 285 were mapped from aerial photography which covered 6474 ha. Many of the mapped landslides were on northeast- and northwest-facing slopes at the eastern terminus of the mountains, nearest the hurricane path. The surface area of individual landslides ranged from 18 m2 to 4500 m2, with a median size of 148 m2. The 285 landslides disturbed 0.11% of the land surface in the area covered by aerial photographs. An approximate denudation rate of 164 mm/1000 y was calculated from the volume of material eroded by landsliding and the 10-y rainfall recurrence interval.

  10. Explicit and Implicit Processes Constitute the Fast and Slow Processes of Sensorimotor Learning.

    Science.gov (United States)

    McDougle, Samuel D; Bond, Krista M; Taylor, Jordan A

    2015-07-01

    A popular model of human sensorimotor learning suggests that a fast process and a slow process work in parallel to produce the canonical learning curve (Smith et al., 2006). Recent evidence supports the subdivision of sensorimotor learning into explicit and implicit processes that simultaneously subserve task performance (Taylor et al., 2014). We set out to test whether these two accounts of learning processes are homologous. Using a recently developed method to assay explicit and implicit learning directly in a sensorimotor task, along with a computational modeling analysis, we show that the fast process closely resembles explicit learning and the slow process approximates implicit learning. In addition, we provide evidence for a subdivision of the slow/implicit process into distinct manifestations of motor memory. We conclude that the two-state model of motor learning is a close approximation of sensorimotor learning, but it is unable to describe adequately the various implicit learning operations that forge the learning curve. Our results suggest that a wider net be cast in the search for the putative psychological mechanisms and neural substrates underlying the multiplicity of processes involved in motor learning. Copyright © 2015 the authors 0270-6474/15/359568-12$15.00/0.

  11. Should a Few Null Findings Falsify Prefrontal Theories of Conscious Perception?

    Science.gov (United States)

    Odegaard, Brian; Knight, Robert T; Lau, Hakwan

    2017-10-04

    Is activity in prefrontal cortex (PFC) critical for conscious perception? Major theories of consciousness make distinct predictions about the role of PFC, providing an opportunity to arbitrate between these views empirically. Here we address three common misconceptions: (1) PFC lesions do not affect subjective perception; (2) PFC activity does not reflect specific perceptual content; and (3) PFC involvement in studies of perceptual awareness is solely driven by the need to make reports required by the experimental tasks rather than subjective experience per se. These claims are incompatible with empirical findings, unless one focuses only on studies using methods with limited sensitivity. The literature highlights PFC's essential role in enabling the subjective experience in perception, contra the objective capacity to perform visual tasks; conflating the two can also be a source of confusion. Dual Perspectives Companion Paper: Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence, by Melanie Boly, Marcello Massimini, Naotsugu Tsuchiya, Bradley R. Postle, Christof Koch, and Giulio Tononi. Copyright © 2017 the authors 0270-6474/17/379593-10$15.00/0.

  12. The role of an ancestral hyperpolarization-activated cyclic nucleotide-gated K+ channel in branchial acid-base regulation in the green crab, Carcinus maenas.

    Science.gov (United States)

    Fehsenfeld, Sandra; Weihrauch, Dirk

    2016-03-01

    Numerous electrophysiological studies on branchial K(+) transport in brachyuran crabs have established an important role for potassium channels in osmoregulatory ion uptake and ammonia excretion in the gill epithelium of decapod crustaceans. However, hardly anything is known of the actual nature of these channels in crustaceans. In the present study, the identification of a hyperpolarization-activated cyclic nucleotide-gated potassium channel (HCN) in the transcriptome of the green crab Carcinus maenas and subsequent performance of quantitative real-time PCR revealed the ubiquitous expression of this channel in this species. Even though mRNA expression levels in the cerebral ganglion were found to be approximately 10 times higher compared with all other tissues, posterior gills still expressed significant levels of HCN, indicating an important role for this transporter in branchial ion regulation. The relatively unspecific K(+)-channel inhibitor Ba(2+), as well as the HCN-specific blocker ZD7288, as applied in gill perfusion experiments and electrophysiological studies employing the split gill lamellae revealed the presence of at least two different K(+)/NH4(+)-transporting structures in the branchial epithelium of C. maenas. Furthermore, HCN mRNA levels in posterior gill 7 decreased significantly in response to the respiratory or metabolic acidosis that was induced by acclimation of green crabs to high environmental PCO2 and ammonia, respectively. Consequently, the present study provides first evidence that HCN-promoted NH4(+) epithelial transport is involved in both branchial acid-base and ammonia regulation in an invertebrate. © 2016. Published by The Company of Biologists Ltd.

  13. Aquaporin Expression and Water Transport Pathways inside Leaves Are Affected by Nitrogen Supply through Transpiration in Rice Plants

    Directory of Open Access Journals (Sweden)

    Lei Ding

    2018-01-01

    Full Text Available The photosynthetic rate increases under high-N supply, resulting in a large CO2 transport conductance in mesophyll cells. It is less known that water movement is affected by nitrogen supply in leaves. This study investigated whether the expression of aquaporin and water transport were affected by low-N (0.7 mM and high-N (7 mM concentrations in the hydroponic culture of four rice varieties: (1 Shanyou 63 (SY63, a hybrid variant of the indica species; (2 Yangdao 6 (YD6, a variant of indica species; (3 Zhendao 11 (ZD11, a hybrid variant of japonica species; and (4 Jiuyou 418 (JY418, another hybrid of the japonica species. Both the photosynthetic and transpiration rate were increased by the high-N supply in the four varieties. The expressions of aquaporins, plasma membrane intrinsic proteins (PIPs, and tonoplast membrane intrinsic protein (TIP were higher in high-N than low-N leaves, except in SY63. Leaf hydraulic conductance (Kleaf was lower in high-N than low-N leaves in SY63, while Kleaf increased under high-N supply in the YD6 variant. Negative correlations were observed between the expression of aquaporin and the transpiration rate in different varieties. Moreover, there was a significant negative correlation between transpiration rate and intercellular air space. In conclusion, the change in expression of aquaporins could affect Kleaf and transpiration. A feedback effect of transpiration would regulate aquaporin expression. The present results imply a coordination of gas exchange with leaf hydraulic conductance.

  14. A perturbation method to the tent map based on Lyapunov exponent and its application

    Science.gov (United States)

    Cao, Lv-Chen; Luo, Yu-Ling; Qiu, Sen-Hui; Liu, Jun-Xiu

    2015-10-01

    Perturbation imposed on a chaos system is an effective way to maintain its chaotic features. A novel parameter perturbation method for the tent map based on the Lyapunov exponent is proposed in this paper. The pseudo-random sequence generated by the tent map is sent to another chaos function — the Chebyshev map for the post processing. If the output value of the Chebyshev map falls into a certain range, it will be sent back to replace the parameter of the tent map. As a result, the parameter of the tent map keeps changing dynamically. The statistical analysis and experimental results prove that the disturbed tent map has a highly random distribution and achieves good cryptographic properties of a pseudo-random sequence. As a result, it weakens the phenomenon of strong correlation caused by the finite precision and effectively compensates for the digital chaos system dynamics degradation. Project supported by the Guangxi Provincial Natural Science Foundation, China (Grant No. 2014GXNSFBA118271), the Research Project of Guangxi University, China (Grant No. ZD2014022), the Fund from Guangxi Provincial Key Laboratory of Multi-source Information Mining & Security, China (Grant No. MIMS14-04), the Fund from the Guangxi Provincial Key Laboratory of Wireless Wideband Communication & Signal Processing, China (Grant No. GXKL0614205), the Education Development Foundation and the Doctoral Research Foundation of Guangxi Normal University, the State Scholarship Fund of China Scholarship Council (Grant No. [2014]3012), and the Innovation Project of Guangxi Graduate Education, China (Grant No. YCSZ2015102).

  15. Monitoring of spotted eagles in Estonia in 1994–2014: Stability of the lesser spotted eagle (Aquila pomarina and decline of the greater spotted eagle (A. clanga

    Directory of Open Access Journals (Sweden)

    Väli Ülo

    2015-06-01

    Full Text Available Populacné trendy orla kriklavého a hrubozobého v Estónsku boli odhadnuté z údajov získaných v rokoch 1994 - 2014 v rámci monitoringu bežných druhov dravcov a tiež zo špeciálnych plôch na monitoring týchto dvoch druhov orlov. Oba metodické prístupy majú svoje klady a zápory, avšak z ich údajov vypocítané populacné trendy sú si podobné. Pocetnost orla kriklavého v posledných dvoch desatrociach mierne kolísala, celkový trend je ale stabilný; velkost jeho populácie sa v súcasnosti odhaduje na 600 - 700 párov. Pocet hniezdnych teritórií orla hrubozobého (cisté aj zmiešané páry významne poklesol, napr. v rokoch 2004 až 2010 o 14 % za rok, v posledných rokoch sa ich pocet zdá byt stabilizovaný na kriticky nízkej úrovni. Pokles pocetnosti cistých párov bol prudší než u zmiešaných párov, ich podiel sa znížil z tretiny na štvrtinu z hniezdnych teritórií orla hrubozobého. Dnes je v Estónsku možné nájst 5 - 10 hniezdnych teritórií tohto druhu orla.

  16. Objev nové ELL proměnné hvězdy v souhvězdí Kentaura a možnost detekce nových exoplanet pomocí dalekohledu FRAM

    Czech Academy of Sciences Publication Activity Database

    Pintr, Pavel; Vápenka, David; Mašek, M.

    2015-01-01

    Roč. 60, č. 2 (2015), s. 65-68 ISSN 0447-6441 R&D Projects: GA MŠk(CZ) LO1206; GA ČR GA13-10365S Institutional support: RVO:61389021 Keywords : variable star * light curve * FRAM * period analysis * exoplanet transit Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics http://jmo.fzu.cz/

  17. Tyrosine and aurora kinase inhibitors diminish transport function of multidrug resistance-associated protein (MRP 4 and breast cancer resistance protein (BCRP

    Directory of Open Access Journals (Sweden)

    Rhiannon N. Hardwick

    2016-12-01

    BCRP was much more extensive and included alisertib, barasertib, danusertib, enzastaurin, erlotinib, gefitinib, imatinib, neratinib, nilotinib, pazopanib, selumetinib, sorafenib, sunitinib, tozasertib, and vandetanib. These findings indicate the significant potential for TKI/AKIs to inhibit multiple ABC efflux transporters. The resulting inhibition data could provide insight regarding the clinical interpretation of pharmacokinetic/pharmacodynamic outcomes when TKI/AKIs are administered concomitantly with additional chemotherapeutic agents.

  18. Metacognitive mechanisms underlying lucid dreaming.

    Science.gov (United States)

    Filevich, Elisa; Dresler, Martin; Brick, Timothy R; Kühn, Simone

    2015-01-21

    Lucid dreaming is a state of awareness that one is dreaming, without leaving the sleep state. Dream reports show that self-reflection and volitional control are more pronounced in lucid compared with nonlucid dreams. Mostly on these grounds, lucid dreaming has been associated with metacognition. However, the link to lucid dreaming at the neural level has not yet been explored. We sought for relationships between the neural correlates of lucid dreaming and thought monitoring. Human participants completed a questionnaire assessing lucid dreaming ability, and underwent structural and functional MRI. We split participants based on their reported dream lucidity. Participants in the high-lucidity group showed greater gray matter volume in the frontopolar cortex (BA9/10) compared with those in the low-lucidity group. Further, differences in brain structure were mirrored by differences in brain function. The BA9/10 regions identified through structural analyses showed increases in blood oxygen level-dependent signal during thought monitoring in both groups, and more strongly in the high-lucidity group. Our results reveal shared neural systems between lucid dreaming and metacognitive function, in particular in the domain of thought monitoring. This finding contributes to our understanding of the mechanisms enabling higher-order consciousness in dreams. Copyright © 2015 the authors 0270-6474/15/351082-07$15.00/0.

  19. Effects of hydrophobic drug-polyesteric core interactions on drug loading and release properties of poly(ethylene glycol)-polyester-poly(ethylene glycol) triblock core-shell nanoparticles

    International Nuclear Information System (INIS)

    Khoee, Sepideh; Hassanzadeh, Salman; Goliaie, Bahram

    2007-01-01

    BAB amphiphilic triblock copolymers consisting of poly(ethylene glycol) (B) (PEG) as the hydrophilic segment and different polyesters (A) as the hydrophobic block were prepared by a polycondensation reaction as efficient model core-shell nanoparticles to assay the effect of interactions between the hydrophobic drug and the polyesteric core in terms of drug loading content and release profile. PEG-poly(hexylene adipate)-PEG (PEG-PHA-PEG) and PEG-poly(butylene adipate)-PEG (PEG-PBA-PEG) to PEG-poly(ethylene adipate)-PEG (PEG-PEA-PEG) core-shell type nanoparticles entrapping quercetin (an anticarcinogenic, allergy inhibitor and antibacterial agent), were prepared by a nanoprecipitation method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and x-ray diffraction (XRD) techniques. It was found that the obtained nanoparticles showed a smooth surface and spherical shape with controllable sizes in the range of 64-74 nm, while drug loading varied from 7.24% to 19% depending on the copolymer composition and the preparation conditions. The in vitro release behaviour exhibited a sustained release and was affected by the polymer-drug interactions. UV studies revealed the presence of hydrogen bonding as the main existing interaction between quercetin and polyesters in the nanosphere cores

  20. Goal-congruent default network activity facilitates cognitive control.

    Science.gov (United States)

    Spreng, R Nathan; DuPre, Elizabeth; Selarka, Dhawal; Garcia, Juliana; Gojkovic, Stefan; Mildner, Judith; Luh, Wen-Ming; Turner, Gary R

    2014-10-15

    Substantial neuroimaging evidence suggests that spontaneous engagement of the default network impairs performance on tasks requiring executive control. We investigated whether this impairment depends on the congruence between executive control demands and internal mentation. We hypothesized that activation of the default network might enhance performance on an executive control task if control processes engage long-term memory representations that are supported by the default network. Using fMRI, we scanned 36 healthy young adult humans on a novel two-back task requiring working memory for famous and anonymous faces. In this task, participants (1) matched anonymous faces interleaved with anonymous face, (2) matched anonymous faces interleaved with a famous face, or (3) matched a famous faces interleaved with an anonymous face. As predicted, we observed a facilitation effect when matching famous faces, compared with anonymous faces. We also observed greater activation of the default network during these famous face-matching trials. The results suggest that activation of the default network can contribute to task performance during an externally directed executive control task. Our findings provide evidence that successful activation of the default network in a contextually relevant manner facilitates goal-directed cognition. Copyright © 2014 the authors 0270-6474/14/3414108-07$15.00/0.

  1. Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aβ accumulation.

    Science.gov (United States)

    Tong, Leslie M; Djukic, Biljana; Arnold, Christine; Gillespie, Anna K; Yoon, Seo Yeon; Wang, Max M; Zhang, Olivia; Knoferle, Johanna; Rubenstein, John L R; Alvarez-Buylla, Arturo; Huang, Yadong

    2014-07-16

    Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity in the hippocampal dentate gyrus in AD-related mouse models and humans, leading to learning and memory deficits. To determine whether replacing the lost or impaired interneurons rescues neuronal signaling and behavioral deficits, we transplanted embryonic interneuron progenitors into the hippocampal hilus of aged apoE4 knock-in mice without or with Aβ accumulation. In both conditions, the transplanted cells developed into mature interneurons, functionally integrated into the hippocampal circuitry, and restored normal learning and memory. Thus, restricted hilar transplantation of inhibitory interneurons restores normal cognitive function in two widely used AD-related mouse models, highlighting the importance of interneuron impairments in AD pathogenesis and the potential of cell replacement therapy for AD. More broadly, it demonstrates that excitatory and inhibitory balance are crucial for learning and memory, and suggests an avenue for investigating the processes of learning and memory and their alterations in healthy aging and diseases. Copyright © 2014 the authors 0270-6474/14/349506-10$15.00/0.

  2. The representation of order information in auditory-verbal short-term memory.

    Science.gov (United States)

    Kalm, Kristjan; Norris, Dennis

    2014-05-14

    Here we investigate how order information is represented in auditory-verbal short-term memory (STM). We used fMRI and a serial recall task to dissociate neural activity patterns representing the phonological properties of the items stored in STM from the patterns representing their order. For this purpose, we analyzed fMRI activity patterns elicited by different item sets and different orderings of those items. These fMRI activity patterns were compared with the predictions made by positional and chaining models of serial order. The positional models encode associations between items and their positions in a sequence, whereas the chaining models encode associations between successive items and retain no position information. We show that a set of brain areas in the postero-dorsal stream of auditory processing store associations between items and order as predicted by a positional model. The chaining model of order representation generates a different pattern similarity prediction, which was shown to be inconsistent with the fMRI data. Our results thus favor a neural model of order representation that stores item codes, position codes, and the mapping between them. This study provides the first fMRI evidence for a specific model of order representation in the human brain. Copyright © 2014 the authors 0270-6474/14/346879-08$15.00/0.

  3. Circadian Activators Are Expressed Days before They Initiate Clock Function in Late Pacemaker Neurons from Drosophila.

    Science.gov (United States)

    Liu, Tianxin; Mahesh, Guruswamy; Houl, Jerry H; Hardin, Paul E

    2015-06-03

    Circadian pacemaker neurons in the Drosophila brain control daily rhythms in locomotor activity. These pacemaker neurons can be subdivided into early or late groups depending on whether rhythms in period (per) and timeless (tim) expression are initiated at the first instar (L1) larval stage or during metamorphosis, respectively. Because CLOCK-CYCLE (CLK-CYC) heterodimers initiate circadian oscillator function by activating per and tim transcription, a Clk-GFP transgene was used to mark when late pacemaker neurons begin to develop. We were surprised to see that CLK-GFP was already expressed in four of five clusters of late pacemaker neurons during the third instar (L3) larval stage. CLK-GFP is only detected in postmitotic neurons from L3 larvae, suggesting that these four late pacemaker neuron clusters are formed before the L3 larval stage. A GFP-cyc transgene was used to show that CYC, like CLK, is also expressed exclusively in pacemaker neurons from L3 larval brains, demonstrating that CLK-CYC is not sufficient to activate per and tim in late pacemaker neurons at the L3 larval stage. These results suggest that most late pacemaker neurons develop days before novel factors activate circadian oscillator function during metamorphosis. Copyright © 2015 the authors 0270-6474/15/358662-10$15.00/0.

  4. Sleep restriction impairs blood-brain barrier function.

    Science.gov (United States)

    He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J; Wang, Yuping; Pan, Weihong

    2014-10-29

    The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. Copyright © 2014 the authors 0270-6474/14/3414697-10$15.00/0.

  5. Sex-dependent dissociation between emotional appraisal and memory: a large-scale behavioral and fMRI study.

    Science.gov (United States)

    Spalek, Klara; Fastenrath, Matthias; Ackermann, Sandra; Auschra, Bianca; Coynel, David; Frey, Julia; Gschwind, Leo; Hartmann, Francina; van der Maarel, Nadine; Papassotiropoulos, Andreas; de Quervain, Dominique; Milnik, Annette

    2015-01-21

    Extensive evidence indicates that women outperform men in episodic memory tasks. Furthermore, women are known to evaluate emotional stimuli as more arousing than men. Because emotional arousal typically increases episodic memory formation, the females' memory advantage might be more pronounced for emotionally arousing information than for neutral information. Here, we report behavioral data from 3398 subjects, who performed picture rating and memory tasks, and corresponding fMRI data from up to 696 subjects. We were interested in the interaction between sex and valence category on emotional appraisal, memory performances, and fMRI activity. The behavioral results showed that females evaluate in particular negative (p pictures, as emotionally more arousing (pinteraction recall females outperformed males not only in positive (p picture recall (p pictures (pinteraction memory advantage during free recall was absent in a recognition setting. We identified activation differences in fMRI, which corresponded to the females' stronger appraisal of especially negative pictures, but no activation differences that reflected the interaction effect in the free recall memory task. In conclusion, females' valence-category-specific memory advantage is only observed in a free recall, but not a recognition setting and does not depend on females' higher emotional appraisal. Copyright © 2015 the authors 0270-6474/15/350920-16$15.00/0.

  6. Simultaneous recordings from the primary visual cortex and lateral geniculate nucleus reveal rhythmic interactions and a cortical source for γ-band oscillations.

    Science.gov (United States)

    Bastos, Andre M; Briggs, Farran; Alitto, Henry J; Mangun, George R; Usrey, W Martin

    2014-05-28

    Oscillatory synchronization of neuronal activity has been proposed as a mechanism to modulate effective connectivity between interacting neuronal populations. In the visual system, oscillations in the gamma-frequency range (30-100 Hz) are thought to subserve corticocortical communication. To test whether a similar mechanism might influence subcortical-cortical communication, we recorded local field potential activity from retinotopically aligned regions in the lateral geniculate nucleus (LGN) and primary visual cortex (V1) of alert macaque monkeys viewing stimuli known to produce strong cortical gamma-band oscillations. As predicted, we found robust gamma-band power in V1. In contrast, visual stimulation did not evoke gamma-band activity in the LGN. Interestingly, an analysis of oscillatory phase synchronization of LGN and V1 activity identified synchronization in the alpha (8-14 Hz) and beta (15-30 Hz) frequency bands. Further analysis of directed connectivity revealed that alpha-band interactions mediated corticogeniculate feedback processing, whereas beta-band interactions mediated geniculocortical feedforward processing. These results demonstrate that although the LGN and V1 display functional interactions in the lower frequency bands, gamma-band activity in the alert monkey is largely an emergent property of cortex. Copyright © 2014 the authors 0270-6474/14/347639-06$15.00/0.

  7. Oscillatory neuronal activity reflects lexical-semantic feature integration within and across sensory modalities in distributed cortical networks.

    Science.gov (United States)

    van Ackeren, Markus J; Schneider, Till R; Müsch, Kathrin; Rueschemeyer, Shirley-Ann

    2014-10-22

    Research from the previous decade suggests that word meaning is partially stored in distributed modality-specific cortical networks. However, little is known about the mechanisms by which semantic content from multiple modalities is integrated into a coherent multisensory representation. Therefore we aimed to characterize differences between integration of lexical-semantic information from a single modality compared with two sensory modalities. We used magnetoencephalography in humans to investigate changes in oscillatory neuronal activity while participants verified two features for a given target word (e.g., "bus"). Feature pairs consisted of either two features from the same modality (visual: "red," "big") or different modalities (auditory and visual: "red," "loud"). The results suggest that integrating modality-specific features of the target word is associated with enhanced high-frequency power (80-120 Hz), while integrating features from different modalities is associated with a sustained increase in low-frequency power (2-8 Hz). Source reconstruction revealed a peak in the anterior temporal lobe for low-frequency and high-frequency effects. These results suggest that integrating lexical-semantic knowledge at different cortical scales is reflected in frequency-specific oscillatory neuronal activity in unisensory and multisensory association networks. Copyright © 2014 the authors 0270-6474/14/3314318-06$15.00/0.

  8. Prying into the Prion Hypothesis for Parkinson's Disease.

    Science.gov (United States)

    Brundin, Patrik; Melki, Ronald

    2017-10-11

    In Parkinson's disease, intracellular α-synuclein inclusions form in neurons. We suggest that prion-like behavior of α-synuclein is a key component in Parkinson's disease pathogenesis. Although multiple molecular changes are involved in the triggering of the disease process, we propose that neuron-to-neuron transfer is a crucial event that is essential for Lewy pathology to spread from one brain region to another. In this review, we describe key findings in human postmortem brains, cultured cells, and animal models of disease that support the idea that α-synuclein can act as a prion. We consider potential triggers of the α-synuclein misfolding and why the aggregates escape cellular degradation under disease conditions. We also discuss whether different strains of α-synuclein fibrils can underlie differences in cellular and regional distribution of aggregates in different synucleinopathies. Our conclusion is that α-synuclein probably acts as a prion in human diseases, and a deeper understanding of this step in the pathogenesis of Parkinson's disease can facilitate the development of disease-modifying therapies in the future. Dual Perspectives Companion Paper: Parkinson's Disease Is Not Simply a Prion Disorder, by D. James Surmeier, José A. Obeso, and Glenda M. Halliday. Copyright © 2017 the authors 0270-6474/17/379808-11$15.00/0.

  9. Improvement of the Quality and the Shelf Life of the High Oxygen Modified Atmosphere Packaged Veal by Superficial Spraying with Dihydroquercetin Solution

    Directory of Open Access Journals (Sweden)

    Stefan Georgiev Dragoev

    2014-01-01

    Full Text Available The improvement of quality and the shelf life of veal by combination of 80%O2/20%CO2 modified atmosphere packaging and superficial spraying with 0.02% dihydroquercetin solutions was studied. The control samples C, air packaged only, D, air packaged sprayed by 0.02% dihydroquercetin solution, MAP, modified atmosphere packaging only, BMAP, modified atmosphere packaging sprayed by 0.02% butylated hydroxytoluene solution, and DMAP, modified atmosphere packaging sprayed by 0.02% dihydroquercetin solution, were measured. The best results were obtained in modified atmosphere packaging sprayed by 0.02% dihydroquercetin solution. Comparisons with control samples were expressed as reduction in acid value with 27.72%, peroxide value with 64.74%, 2-thiobarbituric acid reactive substances (TBARS with 65.71%, and the pH with 6.18%. The acid and peroxide values, TBARS, and pH were decreased linearly in response when applying the combination of 80%O2/20%CO2 modified atmosphere packaging and superficial spraying with 0.02% dihydroquercetin solutions (P0.05. According to results obtained it was concluded that 80%O2/20%CO2 modified atmosphere packaged veal stored at 0±0.5°C after 0.02% dihydroquercetin solution treatment can preserve its quality and shelf life to 15 d postmortem.

  10. MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels.

    Science.gov (United States)

    Lu, Yunqi; Hu, Zhongyi; Mangala, Lingegowda S; Stine, Zachary E; Hu, Xiaowen; Jiang, Dahai; Xiang, Yan; Zhang, Youyou; Pradeep, Sunila; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; DeMarzo, Angelo M; Sood, Anil K; Zhang, Lin; Dang, Chi V

    2018-01-01

    The MYC oncogene broadly promotes transcription mediated by all nuclear RNA polymerases, thereby acting as a positive modifier of global gene expression. Here, we report that MYC stimulates the transcription of DANCR, a long noncoding RNA (lncRNA) that is widely overexpressed in human cancer. We identified DANCR through its overexpression in a transgenic model of MYC-induced lymphoma, but found that it was broadly upregulated in many human cancer cell lines and cancers, including most notably in prostate and ovarian cancers. Mechanistic investigations indicated that DANCR limited the expression of cell-cycle inhibitor p21 (CDKN1A) and that the inhibitory effects of DANCR loss on cell proliferation could be partially rescued by p21 silencing. In a xenograft model of human ovarian cancer, a nanoparticle-mediated siRNA strategy to target DANCR in vivo was sufficient to strongly inhibit tumor growth. Our observations expand knowledge of how MYC drives cancer cell proliferation by identifying DANCR as a critical lncRNA widely overexpressed in human cancers. Significance: These findings expand knowledge of how MYC drives cancer cell proliferation by identifying an oncogenic long noncoding RNA that is widely overexpressed in human cancers. Cancer Res; 78(1); 64-74. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. Auditory properties in the parabelt regions of the superior temporal gyrus in the awake macaque monkey: an initial survey.

    Science.gov (United States)

    Kajikawa, Yoshinao; Frey, Stephen; Ross, Deborah; Falchier, Arnaud; Hackett, Troy A; Schroeder, Charles E

    2015-03-11

    The superior temporal gyrus (STG) is on the inferior-lateral brain surface near the external ear. In macaques, 2/3 of the STG is occupied by an auditory cortical region, the "parabelt," which is part of a network of inferior temporal areas subserving communication and social cognition as well as object recognition and other functions. However, due to its location beneath the squamous temporal bone and temporalis muscle, the STG, like other inferior temporal regions, has been a challenging target for physiological studies in awake-behaving macaques. We designed a new procedure for implanting recording chambers to provide direct access to the STG, allowing us to evaluate neuronal properties and their topography across the full extent of the STG in awake-behaving macaques. Initial surveys of the STG have yielded several new findings. Unexpectedly, STG sites in monkeys that were listening passively responded to tones with magnitudes comparable to those of responses to 1/3 octave band-pass noise. Mapping results showed longer response latencies in more rostral sites and possible tonotopic patterns parallel to core and belt areas, suggesting the reversal of gradients between caudal and rostral parabelt areas. These results will help further exploration of parabelt areas. Copyright © 2015 the authors 0270-6474/15/354140-11$15.00/0.

  12. The amygdala and basal forebrain as a pathway for motivationally guided attention.

    Science.gov (United States)

    Peck, Christopher J; Salzman, C Daniel

    2014-10-08

    Visual stimuli associated with rewards attract spatial attention. Neurophysiological mechanisms that mediate this process must register both the motivational significance and location of visual stimuli. Recent neurophysiological evidence indicates that the amygdala encodes information about both of these parameters. Furthermore, the firing rate of amygdala neurons predicts the allocation of spatial attention. One neural pathway through which the amygdala might influence attention involves the intimate and bidirectional connections between the amygdala and basal forebrain (BF), a brain area long implicated in attention. Neurons in the rhesus monkey amygdala and BF were therefore recorded simultaneously while subjects performed a detection task in which the stimulus-reward associations of visual stimuli modulated spatial attention. Neurons in BF were spatially selective for reward-predictive stimuli, much like the amygdala. The onset of reward-predictive signals in each brain area suggested different routes of processing for reward-predictive stimuli appearing in the ipsilateral and contralateral fields. Moreover, neurons in the amygdala, but not BF, tracked trial-to-trial fluctuations in spatial attention. These results suggest that the amygdala and BF could play distinct yet inter-related roles in influencing attention elicited by reward-predictive stimuli. Copyright © 2014 the authors 0270-6474/14/3413757-11$15.00/0.

  13. Genetic Diversity and Taxonomic Studies of Allium Akaka and A. Elburzense Native to Iran Using Morphological Characters

    Directory of Open Access Journals (Sweden)

    Jafari Sajad

    2017-06-01

    Full Text Available Two Allium species (A. akaka S.G. Gmelin and A. elburzense W. native to Iran are used locally as the fresh vegetables and in medical therapy. They are not cultivated, but are collected from the wild, thus, will soon be threatened with extinction. In this study, the diversity of 15 wild accessions (4 accessions of A. elburzense endemic of Iran and 11 accessions of A. akaka collected from the north-western part of Iran were evaluated with the use of 16 qualitative and 16 quantitative characteristics. The morphological characters with high heritability included leaf length, flower number in umbel, inflorescence diameter, leaf dry weight, bulb fresh weight, weight of 100 seeds, seed length and seed length/width. Results of the principal component analysis indicated that 92.52% of the observed variability was explained by the first six components. The first two components explained about 64.74% of the total observed variability. The first and third hierarchical cluster analysis included all accessions of A. akaka. The accessions of A. elburzense, except one, were placed in a separate cluster. These morphological descriptors can successfully apply for evaluating morphological diversity of Allium wild accessions and can help in horticultural usage.

  14. [Tribological properties of carbon fiber-reinforced plastic. Experimental and clinical results].

    Science.gov (United States)

    Früh, H J; Ascherl, R; Hipp, E

    1997-02-01

    Wear of the articulating components (especially PE-UHMW) of total hip endoprostheses is the most important technical factor limiting the functional lifetime. To minimize wear debris, ceramic heads, according to ISO 6474 (Al2O3), have been used, from 1969 paired with Al2O3 and since 1975 paired with PE-UHMW. Al2O3 balls articulating with cups made from CFRP have been in clinical use since 1988. Laboratory experiments and in-vivo testing showed minimized wear debris and mild biological response to wear products using CFRP (carbon fiber reinforced plastic) instead of PE-UHMW as the cup material. The articulating surfaces of retrieved ceramic heads (Al2O3-Biolox) and cementless CFRP cups (carbon fiber reinforced plastic, Caproman) were compared using sphericity measurement techniques, scanning electron microscopy (SEM) and roughness measurements (including advanced roughness parameters Rvk or Rpk according to ISO 4287). Altogether, the first results of the clinical study showed that the combination Al2O3-ball/CFRP-cup came up to the expected lower wear rates compared with the conventional combinations. The wear rates are comparable with the combination Al2O3/Al2O3 without the material-related problems of ceramic components in all ceramic combinations.

  15. Audio-vocal interaction in single neurons of the monkey ventrolateral prefrontal cortex.

    Science.gov (United States)

    Hage, Steffen R; Nieder, Andreas

    2015-05-06

    Complex audio-vocal integration systems depend on a strong interconnection between the auditory and the vocal motor system. To gain cognitive control over audio-vocal interaction during vocal motor control, the PFC needs to be involved. Neurons in the ventrolateral PFC (VLPFC) have been shown to separately encode the sensory perceptions and motor production of vocalizations. It is unknown, however, whether single neurons in the PFC reflect audio-vocal interactions. We therefore recorded single-unit activity in the VLPFC of rhesus monkeys (Macaca mulatta) while they produced vocalizations on command or passively listened to monkey calls. We found that 12% of randomly selected neurons in VLPFC modulated their discharge rate in response to acoustic stimulation with species-specific calls. Almost three-fourths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of vocalization. Based on these audio-vocal interactions, the VLPFC might be well positioned to combine higher order auditory processing with cognitive control of the vocal motor output. Such audio-vocal integration processes in the VLPFC might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2015 the authors 0270-6474/15/357030-11$15.00/0.

  16. Assembling a Cellular User Manual for the Brain.

    Science.gov (United States)

    Sloan, Steven A; Barres, Ben A

    2018-03-28

    For many years, efforts to decipher the various cellular components that comprise the CNS were stymied by a lack of technical strategies for isolating and profiling the brain's resident cell types. The advent of transcriptional profiling, combined with powerful new purification schemes, changed this reality and transformed our understanding of the macroglial populations within the brain. Here, we chronicle the historical context and scientific setting for our efforts to transcriptionally profile neurons, astrocytes, and oligodendrocytes, and highlight some of the profound discoveries that were cultivated by these data.Following a lengthy battle with pancreatic cancer, Ben Barres passed away during the writing of this Progression piece. Among Ben's innumerable contributions to the greater scientific community, his addition of publicly available transcriptome databases of CNS cell types will forever remain a relic of his generous spirit and boundless scientific curiosity. Although he had impressively committed a majority of these enormous gene lists to memory, Ben could oftentimes be spotted at meetings buried in his cell phone on the Barres RNAseq database. Perhaps the only thing he enjoyed more than exploring these data himself, was knowing how useful these contributions had been (and will hopefully continue to be) to his scientific peers. Copyright © 2018 the authors 0270-6474/18/383149-05$15.00/0.

  17. Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.

    Science.gov (United States)

    Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P

    2017-10-04

    Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. Copyright © 2017 the authors 0270-6474/17/379705-10$15.00/0.

  18. Structural, functional, and evolutionary analysis of moeZ, a gene encoding an enzyme required for the synthesis of the Pseudomonas metabolite, pyridine-2,6-bis(thiocarboxylic acid

    Directory of Open Access Journals (Sweden)

    Crawford Ronald L

    2002-04-01

    Full Text Available Abstract Background Pyridine-2,6-bis(thiocarboxylic acid (pdtc is a small secreted metabolite that has a high affinity for transition metals, increases iron uptake efficiency by 20% in Pseudomonas stutzeri, has the ability to reduce both soluble and mineral forms of iron, and has antimicrobial activity towards several species of bacteria. Six GenBank sequences code for proteins similar in structure to MoeZ, a P. stutzeri protein necessary for the synthesis of pdtc. Results Analysis of sequences similar to P. stutzeri MoeZ revealed that it is a member of a superfamily consisting of related but structurally distinct proteins that are members of pathways involved in the transfer of sulfur-containing moieties to metabolites. Members of this family of enzymes are referred to here as MoeB, MoeBR, MoeZ, and MoeZdR. MoeB, the molybdopterin synthase activating enzyme in the molybdopterin cofactor biosynthesis pathway, is the most characterized protein from this family. Remarkably, lengths of greater than 73% nucleic acid homology ranging from 35 to 486 bp exist between Pseudomonas stutzeri moeZ and genomic sequences found in some Mycobacterium, Mesorhizobium, Pseudomonas, Streptomyces, and cyanobacteria species. Conclusions The phylogenetic relationship among moeZ sequences suggests that P. stutzeri may have acquired moeZ through lateral gene transfer from a donor more closely related to mycobacteria and cyanobacteria than to proteobacteria. The importance of this relationship lies in the fact that pdtc, the product of the P. stutzeri pathway that includes moeZ, has an impressive set of capabilities, some of which could make it a potent pathogenicity factor.

  19. Hyperpolarization-activated current (In is reduced in hippocampal neurons from Gabra5-/- mice.

    Directory of Open Access Journals (Sweden)

    Robert P Bonin

    Full Text Available Changes in the expression of γ-aminobutyric acid type A (GABAA receptors can either drive or mediate homeostatic alterations in neuronal excitability. A homeostatic relationship between α5 subunit-containing GABAA (α5GABAA receptors that generate a tonic inhibitory conductance, and HCN channels that generate a hyperpolarization-activated cation current (Ih was recently described for cortical neurons, where a reduction in Ih was accompanied by a reciprocal increase in the expression of α5GABAA receptors resulting in the preservation of dendritosomatic synaptic function. Here, we report that in mice that lack the α5 subunit gene (Gabra5-/-, cultured embryonic hippocampal pyramidal neurons and ex vivo CA1 hippocampal neurons unexpectedly exhibited a decrease in Ih current density (by 40% and 28%, respectively, compared with neurons from wild-type (WT mice. The resting membrane potential and membrane hyperpolarization induced by blockade of Ih with ZD-7288 were similar in cultured WT and Gabra5-/- neurons. In contrast, membrane hyperpolarization measured after a train of action potentials was lower in Gabra5-/- neurons than in WT neurons. Also, membrane impedance measured in response to low frequency stimulation was greater in cultured Gabra5-/- neurons. Finally, the expression of HCN1 protein that generates Ih was reduced by 41% in the hippocampus of Gabra5-/- mice. These data indicate that loss of a tonic GABAergic inhibitory conductance was followed by a compensatory reduction in Ih. The results further suggest that the maintenance of resting membrane potential is preferentially maintained in mature and immature hippocampal neurons through the homeostatic co-regulation of structurally and biophysically distinct cation and anion channels.

  20. Analyzing the optimization of an organic Rankine cycle system for recovering waste heat from a large marine engine containing a cooling water system

    International Nuclear Information System (INIS)

    Yang, Min-Hsiung; Yeh, Rong-Hua

    2014-01-01

    Highlights: • Employing the thermodynamic analysis and a heat-transfer method, an ORC optimization is presented. • An optimal objective parameter evaluation of six working fluids is presented. • Refrigerants with superior thermodynamic properties do not necessary have excellent performance. • Cylinder jacket water temperature strongly affects optimal evaporation temperature. - Abstract: In this study, six working fluids with zero ozone depletion potential and low global warming potential are used in an organic Rankine cycle (ORC) system to recover waste heat from cylinder jacket water of large marine diesel engines. Thermodynamic analysis and a finite-temperature-difference heat-transfer method are developed to evaluate the thermal efficiency, total heat-exchanger area, objective parameter, and exergy destruction of the ORC system. The optimal evaporation and condensation temperatures for achieving the maximal objective parameter, the ratio of net power output to the total heat-transfer area of heat exchangers, of an ORC system are investigated. The results show that, among the working fluids, R600a performs the best in the optimal objective parameter evaluation followed by R1234ze, R1234yf, R245fa, R245ca, and R1233zd at evaporation temperatures ranging from 58 °C to 68 °C and condensation temperatures ranging from 35 °C to 45 °C. The optimal operating temperatures and corresponding thermal efficiency and exergy destruction are proposed. Furthermore, the influences of inlet temperatures on cylinder jacket water and cooling water in the ORC are presented for recovering waste heat. The results of this work were verified with theoretical solutions and experimental results in the literature and it was revealed that they were consistent with them

  1. Preliminary study of the specific endothelin a receptor antagonist zibotentan in combination with docetaxel in patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Trump, Donald L; Payne, Heather; Miller, Kurt; de Bono, Johann S; Stephenson, Joe; Burris, Howard A; Nathan, Faith; Taboada, Maria; Morris, Thomas; Hubner, Andreas

    2011-09-01

    This two-part study assessed the safety and tolerability of combined treatment with zibotentan (ZD4054), a specific endothelin A receptor antagonist, plus docetaxel in patients with metastatic castration-resistant prostate cancer. Part A was an open-label, dose-finding phase to determine the safety and toxicity profile of zibotentan in combination with docetaxel. Patients received once-daily oral zibotentan 10 mg (initial cohort) or 15 mg in combination with docetaxel 75 mg/m(2) (administered on day 1 of each 21-day cycle) for up to 10 cycles. Part B was a double-blind phase which evaluated the safety and preliminary activity of zibotentan plus docetaxel. Patients were randomized 2:1 to receive zibotentan (at the highest tolerated dose identified in part A) plus docetaxel or placebo plus docetaxel. Six patients were enrolled in part A (n  = 3, zibotentan 10 mg; n = 3, zibotentan 15 mg). No dose-limiting toxicity was observed, thus zibotentan 15 mg in combination with docetaxel was evaluated in part B (n = 20, zibotentan plus docetaxel; n = 11, placebo plus docetaxel). CTCAE grade ≥3, most commonly neutropenia or leucopenia, were reported in 10 (50%) and nine (82%) patients in the zibotentan and placebo groups, respectively. One (17%) patient receiving placebo achieved complete response, two (22%) patients receiving zibotentan achieved partial response and stable disease occurred in six (67%) and three (50%) patients receiving zibotentan and placebo, respectively. The tolerability of zibotentan plus docetaxel was consistent with the known profiles of each drug. Sufficient preliminary activity was seen with this combination to merit continued development. Copyright © 2011 Wiley-Liss, Inc.

  2. Importance of polypyrrole in constructing 3D hierarchical carbon nanotube@MnO2 perfect core-shell nanostructures for high-performance flexible supercapacitors

    Science.gov (United States)

    Zhou, Jinyuan; Zhao, Hao; Mu, Xuemei; Chen, Jiayi; Zhang, Peng; Wang, Yaling; He, Yongmin; Zhang, Zhenxing; Pan, Xiaojun; Xie, Erqing

    2015-08-01

    This study reports the preparation of 3D hierarchical carbon nanotube (CNT) @MnO2 core-shell nanostructures under the assistance of polypyrrole (PPy). The as-prepared CNT@PPy@MnO2 core-shell structures show a perfect coating of MnO2 on each CNT and, more importantly, a robust bush-like pseudocapacitive shell to effectively increase the specific surface area and enhance the ion accessibility. As expected, a high specific capacity of 490-530 F g-1 has been achieved from CNT@PPy@MnO2 single electrodes. And about 98.5% of the capacity is retained after 1000 charge/discharge cycles at a current density of 5 A g-1. Furthermore, the assembled asymmetric CNT@PPy@MnO2//AC capacitors show the maximum energy density of 38.42 W h kg-1 (2.24 mW h cm-3) at a power density of 100 W kg-1 (5.83 mW cm-3), and they maintain 59.52% of the initial value at 10 000 W kg-1 (0.583 W cm-3). In addition, the assembled devices show high cycling stabilities (89.7% after 2000 cycles for asymmetric and 87.2% for symmetric), and a high bending stability (64.74% after 200 bending tests). This ability to obtain high energy densities at high power rates while maintaining high cycling stability demonstrates that this well-designed structure could be a promising electrode material for high-performance supercapacitors.This study reports the preparation of 3D hierarchical carbon nanotube (CNT) @MnO2 core-shell nanostructures under the assistance of polypyrrole (PPy). The as-prepared CNT@PPy@MnO2 core-shell structures show a perfect coating of MnO2 on each CNT and, more importantly, a robust bush-like pseudocapacitive shell to effectively increase the specific surface area and enhance the ion accessibility. As expected, a high specific capacity of 490-530 F g-1 has been achieved from CNT@PPy@MnO2 single electrodes. And about 98.5% of the capacity is retained after 1000 charge/discharge cycles at a current density of 5 A g-1. Furthermore, the assembled asymmetric CNT@PPy@MnO2//AC capacitors show the

  3. Toward an autonomous brain machine interface: integrating sensorimotor reward modulation and reinforcement learning.

    Science.gov (United States)

    Marsh, Brandi T; Tarigoppula, Venkata S Aditya; Chen, Chen; Francis, Joseph T

    2015-05-13

    For decades, neurophysiologists have worked on elucidating the function of the cortical sensorimotor control system from the standpoint of kinematics or dynamics. Recently, computational neuroscientists have developed models that can emulate changes seen in the primary motor cortex during learning. However, these simulations rely on the existence of a reward-like signal in the primary sensorimotor cortex. Reward modulation of the primary sensorimotor cortex has yet to be characterized at the level of neural units. Here we demonstrate that single units/multiunits and local field potentials in the primary motor (M1) cortex of nonhuman primates (Macaca radiata) are modulated by reward expectation during reaching movements and that this modulation is present even while subjects passively view cursor motions that are predictive of either reward or nonreward. After establishing this reward modulation, we set out to determine whether we could correctly classify rewarding versus nonrewarding trials, on a moment-to-moment basis. This reward information could then be used in collaboration with reinforcement learning principles toward an autonomous brain-machine interface. The autonomous brain-machine interface would use M1 for both decoding movement intention and extraction of reward expectation information as evaluative feedback, which would then update the decoding algorithm as necessary. In the work presented here, we show that this, in theory, is possible. Copyright © 2015 the authors 0270-6474/15/357374-14$15.00/0.

  4. The Effect of Early Visual Deprivation on the Neural Bases of Auditory Processing.

    Science.gov (United States)

    Guerreiro, Maria J S; Putzar, Lisa; Röder, Brigitte

    2016-02-03

    Transient congenital visual deprivation affects visual and multisensory processing. In contrast, the extent to which it affects auditory processing has not been investigated systematically. Research in permanently blind individuals has revealed brain reorganization during auditory processing, involving both intramodal and crossmodal plasticity. The present study investigated the effect of transient congenital visual deprivation on the neural bases of auditory processing in humans. Cataract-reversal individuals and normally sighted controls performed a speech-in-noise task while undergoing functional magnetic resonance imaging. Although there were no behavioral group differences, groups differed in auditory cortical responses: in the normally sighted group, auditory cortex activation increased with increasing noise level, whereas in the cataract-reversal group, no activation difference was observed across noise levels. An auditory activation of visual cortex was not observed at the group level in cataract-reversal individuals. The present data suggest prevailing auditory processing advantages after transient congenital visual deprivation, even many years after sight restoration. The present study demonstrates that people whose sight was restored after a transient period of congenital blindness show more efficient cortical processing of auditory stimuli (here speech), similarly to what has been observed in congenitally permanently blind individuals. These results underscore the importance of early sensory experience in permanently shaping brain function. Copyright © 2016 the authors 0270-6474/16/361620-11$15.00/0.

  5. Size and synchronization of auditory cortex promotes musical, literacy, and attentional skills in children.

    Science.gov (United States)

    Seither-Preisler, Annemarie; Parncutt, Richard; Schneider, Peter

    2014-08-13

    Playing a musical instrument is associated with numerous neural processes that continuously modify the human brain and may facilitate characteristic auditory skills. In a longitudinal study, we investigated the auditory and neural plasticity of musical learning in 111 young children (aged 7-9 y) as a function of the intensity of instrumental practice and musical aptitude. Because of the frequent co-occurrence of central auditory processing disorders and attentional deficits, we also tested 21 children with attention deficit (hyperactivity) disorder [AD(H)D]. Magnetic resonance imaging and magnetoencephalography revealed enlarged Heschl's gyri and enhanced right-left hemispheric synchronization of the primary evoked response (P1) to harmonic complex sounds in children who spent more time practicing a musical instrument. The anatomical characteristics were positively correlated with frequency discrimination, reading, and spelling skills. Conversely, AD(H)D children showed reduced volumes of Heschl's gyri and enhanced volumes of the plana temporalia that were associated with a distinct bilateral P1 asynchrony. This may indicate a risk for central auditory processing disorders that are often associated with attentional and literacy problems. The longitudinal comparisons revealed a very high stability of auditory cortex morphology and gray matter volumes, suggesting that the combined anatomical and functional parameters are neural markers of musicality and attention deficits. Educational and clinical implications are considered. Copyright © 2014 the authors 0270-6474/14/3410937-13$15.00/0.

  6. Persistent discharges in dentate gyrus perisoma-inhibiting interneurons require hyperpolarization-activated cyclic nucleotide-gated channel activation.

    Science.gov (United States)

    Elgueta, Claudio; Köhler, Johannes; Bartos, Marlene

    2015-03-11

    Parvalbumin (PV)-expressing perisoma-inhibiting interneurons (PIIs) of the dentate gyrus integrate rapidly correlated synaptic inputs and generate short-duration action potentials that propagate along the axon to their output synapses, supporting fast inhibitory signaling onto their target cells. Here we show that PV-PIIs in rat and mouse dentate gyrus (DG) integrate their intrinsic activity over time and can turn into a persistent firing mode characterized by the ability to generate long-lasting trains of action potentials at ∼50 Hz in the absence of additional inputs. Persistent firing emerges in the axons remote from the axon initial segment and markedly depends on hyperpolarization-activated cyclic nucleotide-gated channel (HCNC) activation. Persistent firing properties are modulated by intracellular Ca(2+) levels and somatic membrane potential. Detailed computational single-cell PIIs models reveal that HCNC-mediated conductances can contribute to persistent firing during conditions of a shift in their voltage activation curve to more depolarized potentials. Paired recordings from PIIs and their target granule cells show that persistent firing supports strong inhibitory output signaling. Thus, persistent firing may emerge during conditions of intense activation of the network, thereby providing silencing to the circuitry and the maintenance of sparse activity in the dentate gyrus. Copyright © 2015 the authors 0270-6474/15/354131-09$15.00/0.

  7. The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxicity and Increase TDP-43 Levels.

    Science.gov (United States)

    Salazar, Dominique A; Butler, Victoria J; Argouarch, Andrea R; Hsu, Tsung-Yuan; Mason, Amanda; Nakamura, Ayumi; McCurdy, Helen; Cox, David; Ng, Rachel; Pan, Gloria; Seeley, William W; Miller, Bruce L; Kao, Aimee W

    2015-06-24

    Mutations in the human progranulin gene resulting in protein haploinsufficiency cause frontotemporal lobar degeneration with TDP-43 inclusions. Although progress has been made in understanding the normal functions of progranulin and TDP-43, the molecular interactions between these proteins remain unclear. Progranulin is proteolytically processed into granulins, but the role of granulins in the pathogenesis of neurodegenerative disease is unknown. We used a Caenorhabditis elegans model of neuronal TDP-43 proteinopathy to specifically interrogate the contribution of granulins to the neurodegenerative process. Complete loss of the progranulin gene did not worsen TDP-43 toxicity, whereas progranulin heterozygosity did. Interestingly, expression of individual granulins alone had little effect on behavior. In contrast, when granulins were coexpressed with TDP-43, they exacerbated its toxicity in a variety of behaviors including motor coordination. These same granulins increased TDP-43 levels via a post-translational mechanism. We further found that in human neurodegenerative disease subjects, granulin fragments accumulated specifically in diseased regions of brain. To our knowledge, this is the first demonstration of a toxic role for granulin fragments in a neurodegenerative disease model. These studies suggest that presence of cleaved granulins, rather than or in addition to loss of full-length progranulin, may contribute to disease in TDP-43 proteinopathies. Copyright © 2015 the authors 0270-6474/15/359315-14$15.00/0.

  8. Cerebellar direct current stimulation enhances on-line motor skill acquisition through an effect on accuracy.

    Science.gov (United States)

    Cantarero, Gabriela; Spampinato, Danny; Reis, Janine; Ajagbe, Loni; Thompson, Tziporah; Kulkarni, Kopal; Celnik, Pablo

    2015-02-18

    The cerebellum is involved in the update of motor commands during error-dependent learning. Transcranial direct current stimulation (tDCS), a form of noninvasive brain stimulation, has been shown to increase cerebellar excitability and improve learning in motor adaptation tasks. Although cerebellar involvement has been clearly demonstrated in adaptation paradigms, a type of task that heavily relies on error-dependent motor learning mechanisms, its role during motor skill learning, a behavior that likely involves error-dependent as well as reinforcement and strategic mechanisms, is not completely understood. Here, in humans, we delivered cerebellar tDCS to modulate its activity during novel motor skill training over the course of 3 d and assessed gains during training (on-line effects), between days (off-line effects), and overall improvement. We found that excitatory anodal tDCS applied over the cerebellum increased skill learning relative to sham and cathodal tDCS specifically by increasing on-line rather than off-line learning. Moreover, the larger skill improvement in the anodal group was predominantly mediated by reductions in error rate rather than changes in movement time. These results have important implications for using cerebellar tDCS as an intervention to speed up motor skill acquisition and to improve motor skill accuracy, as well as to further our understanding of cerebellar function. Copyright © 2015 the authors 0270-6474/15/353285-06$15.00/0.

  9. Utility-based early modulation of processing distracting stimulus information.

    Science.gov (United States)

    Wendt, Mike; Luna-Rodriguez, Aquiles; Jacobsen, Thomas

    2014-12-10

    Humans are selective information processors who efficiently prevent goal-inappropriate stimulus information to gain control over their actions. Nonetheless, stimuli, which are both unnecessary for solving a current task and liable to cue an incorrect response (i.e., "distractors"), frequently modulate task performance, even when consistently paired with a physical feature that makes them easily discernible from target stimuli. Current models of cognitive control assume adjustment of the processing of distractor information based on the overall distractor utility (e.g., predictive value regarding the appropriate response, likelihood to elicit conflict with target processing). Although studies on distractor interference have supported the notion of utility-based processing adjustment, previous evidence is inconclusive regarding the specificity of this adjustment for distractor information and the stage(s) of processing affected. To assess the processing of distractors during sensory-perceptual phases we applied EEG recording in a stimulus identification task, involving successive distractor-target presentation, and manipulated the overall distractor utility. Behavioral measures replicated previously found utility modulations of distractor interference. Crucially, distractor-evoked visual potentials (i.e., posterior N1) were more pronounced in high-utility than low-utility conditions. This effect generalized to distractors unrelated to the utility manipulation, providing evidence for item-unspecific adjustment of early distractor processing to the experienced utility of distractor information. Copyright © 2014 the authors 0270-6474/14/3416720-06$15.00/0.

  10. Fast gamma oscillations are generated intrinsically in CA1 without the involvement of fast-spiking basket cells.

    Science.gov (United States)

    Craig, Michael T; McBain, Chris J

    2015-02-25

    Information processing in neuronal networks relies on the precise synchronization of ensembles of neurons, coordinated by the diverse family of inhibitory interneurons. Cortical interneurons can be usefully parsed by embryonic origin, with the vast majority arising from either the caudal or medial ganglionic eminences (CGE and MGE). Here, we examine the activity of hippocampal interneurons during gamma oscillations in mouse CA1, using an in vitro model where brief epochs of rhythmic activity were evoked by local application of kainate. We found that this CA1 KA-evoked gamma oscillation was faster than that in CA3 and, crucially, did not appear to require the involvement of fast-spiking basket cells. In contrast to CA3, we also found that optogenetic inhibition of pyramidal cells in CA1 did not significantly affect the power of the oscillation, suggesting that excitation may not be essential for gamma genesis in this region. We found that MGE-derived interneurons were generally more active than CGE interneurons during CA1 gamma, although a group of CGE-derived interneurons, putative trilaminar cells, were strongly phase-locked with gamma oscillations and, together with MGE-derived axo-axonic and bistratified cells, provide attractive candidates for being the driver of this locally generated, predominantly interneuron-driven model of gamma oscillations. Copyright © 2015 the authors 0270-6474/15/353616-09$15.00/0.

  11. Development of an LC–MS/MS method for the quantitation of deoxyglycychloxazol in rat plasma and its application in pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Rongshan Li

    2016-06-01

    Full Text Available Deoxyglycychloxazol (TY501 is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C8 column with the mobile phase consisting of methanol and 10 mM ammonium formate (containing 0.1% of formic acid (90:10, v/v. The selected reaction monitoring (SRM transitions were performed at m/z 647.4→191.2 for TY501 and m/z 473.3→143.3 for astragaloside aglycone (IS in the positive ion mode with atmospheric pressure chemical ionization (APCI source. Calibration curve was linear over the concentration range of 5–5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra- and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within ±1.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.

  12. Cholinergic stimulation enhances Bayesian belief updating in the deployment of spatial attention.

    Science.gov (United States)

    Vossel, Simone; Bauer, Markus; Mathys, Christoph; Adams, Rick A; Dolan, Raymond J; Stephan, Klaas E; Friston, Karl J

    2014-11-19

    The exact mechanisms whereby the cholinergic neurotransmitter system contributes to attentional processing remain poorly understood. Here, we applied computational modeling to psychophysical data (obtained from a spatial attention task) under a psychopharmacological challenge with the cholinesterase inhibitor galantamine (Reminyl). This allowed us to characterize the cholinergic modulation of selective attention formally, in terms of hierarchical Bayesian inference. In a placebo-controlled, within-subject, crossover design, 16 healthy human subjects performed a modified version of Posner's location-cueing task in which the proportion of validly and invalidly cued targets (percentage of cue validity, % CV) changed over time. Saccadic response speeds were used to estimate the parameters of a hierarchical Bayesian model to test whether cholinergic stimulation affected the trial-wise updating of probabilistic beliefs that underlie the allocation of attention or whether galantamine changed the mapping from those beliefs to subsequent eye movements. Behaviorally, galantamine led to a greater influence of probabilistic context (% CV) on response speed than placebo. Crucially, computational modeling suggested this effect was due to an increase in the rate of belief updating about cue validity (as opposed to the increased sensitivity of behavioral responses to those beliefs). We discuss these findings with respect to cholinergic effects on hierarchical cortical processing and in relation to the encoding of expected uncertainty or precision. Copyright © 2014 the authors 0270-6474/14/3415735-08$15.00/0.

  13. Frequency of intestinal parasites and socioeconomic conditions of São Marcos city-RS schoolchildren

    Directory of Open Access Journals (Sweden)

    Scheila Cristina Rech

    2016-11-01

    Full Text Available The present study assess the frequency of intestinal parasites in São Marcos city-RS elementary and middle school children, from March to October 2015. A questionnaire was applied to asses students' knowledge on pathways for parasite transmission and on sanitation facilities in the city. Stool samples were collected from eighth-grade students of nine different schools and were analyzed/processed by spontaneous sedimentation. Of the 190 students who participated in the study, most were female (51.58% and the mean age of the students was 7.99 ± 3.23 years. 5.79% of the samples were positive for parasites, being 3.16% of cysts of Entamoeba coli, 1.58% of Endolimax nana and 1.05% of Giardia lamblia. As for the students’ knowledge on parasites, 73.16% reported knowing what parasites are and what damage they can cause, 68.42% are aware of the transmission pathways, however 41.58% consider there is insufficient information available to the public. Related to the health issues to which they are exposed, 94.21% reported consuming potable water and 64.74% reported having sewage collection and treatment. The present study has shown a low prevalence of parasitic infections, which could be explained by the knowledge of parents and guardians about topic, favorable sanitary conditions, and the high percentage (78.95% of students who have already been treated with antiparasitic drugs.

  14. Network structure shapes spontaneous functional connectivity dynamics.

    Science.gov (United States)

    Shen, Kelly; Hutchison, R Matthew; Bezgin, Gleb; Everling, Stefan; McIntosh, Anthony R

    2015-04-08

    The structural organization of the brain constrains the range of interactions between different regions and shapes ongoing information processing. Therefore, it is expected that large-scale dynamic functional connectivity (FC) patterns, a surrogate measure of coordination between brain regions, will be closely tied to the fiber pathways that form the underlying structural network. Here, we empirically examined the influence of network structure on FC dynamics by comparing resting-state FC (rsFC) obtained using BOLD-fMRI in macaques (Macaca fascicularis) to structural connectivity derived from macaque axonal tract tracing studies. Consistent with predictions from simulation studies, the correspondence between rsFC and structural connectivity increased as the sample duration increased. Regions with reciprocal structural connections showed the most stable rsFC across time. The data suggest that the transient nature of FC is in part dependent on direct underlying structural connections, but also that dynamic coordination can occur via polysynaptic pathways. Temporal stability was found to be dependent on structural topology, with functional connections within the rich-club core exhibiting the greatest stability over time. We discuss these findings in light of highly variable functional hubs. The results further elucidate how large-scale dynamic functional coordination exists within a fixed structural architecture. Copyright © 2015 the authors 0270-6474/15/355579-10$15.00/0.

  15. Functional Organization of the Parahippocampal Cortex: Dissociable Roles for Context Representations and the Perception of Visual Scenes.

    Science.gov (United States)

    Baumann, Oliver; Mattingley, Jason B

    2016-02-24

    The human parahippocampal cortex has been ascribed central roles in both visuospatial and mnemonic processes. More specifically, evidence suggests that the parahippocampal cortex subserves both the perceptual analysis of scene layouts as well as the retrieval of associative contextual memories. It remains unclear, however, whether these two functional roles can be dissociated within the parahippocampal cortex anatomically. Here, we provide evidence for a dissociation between neural activation patterns associated with visuospatial analysis of scenes and contextual mnemonic processing along the parahippocampal longitudinal axis. We used fMRI to measure parahippocampal responses while participants engaged in a task that required them to judge the contextual relatedness of scene and object pairs, which were presented either as words or pictures. Results from combined factorial and conjunction analyses indicated that the posterior section of parahippocampal cortex is driven predominantly by judgments associated with pictorial scene analysis, whereas its anterior section is more active during contextual judgments regardless of stimulus category (scenes vs objects) or modality (word vs picture). Activation maxima associated with visuospatial and mnemonic processes were spatially segregated, providing support for the existence of functionally distinct subregions along the parahippocampal longitudinal axis and suggesting that, in humans, the parahippocampal cortex serves as a functional interface between perception and memory systems. Copyright © 2016 the authors 0270-6474/16/362536-07$15.00/0.

  16. β oscillations are linked to the initiation of sensory-cued movement sequences and the internal guidance of regular tapping in the monkey.

    Science.gov (United States)

    Bartolo, Ramón; Merchant, Hugo

    2015-03-18

    β oscillations in the basal ganglia have been associated with interval timing. We recorded the putaminal local field potentials (LFPs) from monkeys performing a synchronization-continuation task (SCT) and a serial reaction-time task (RTT), where the animals produced regularly and irregularly paced tapping sequences, respectively. We compared the activation profile of β oscillations between tasks and found transient bursts of β activity in both the RTT and SCT. During the RTT, β power was higher at the beginning of the task, especially when LFPs were aligned to the stimuli. During the SCT, β was higher during the internally driven continuation phase, especially for tap-aligned LFPs. Interestingly, a set of LFPs showed an initial burst of β at the beginning of the SCT, similar to the RTT, followed by a decrease in β oscillations during the synchronization phase, to finally rebound during the continuation phase. The rebound during the continuation phase of the SCT suggests that the corticostriatal circuit is involved in the control of internally driven motor sequences. In turn, the transient bursts of β activity at the beginning of both tasks suggest that the basal ganglia produce a general initiation signal that engages the motor system in different sequential behaviors. Copyright © 2015 the authors 0270-6474/15/354635-06$15.00/0.

  17. Visual categorization of natural movies by rats.

    Science.gov (United States)

    Vinken, Kasper; Vermaercke, Ben; Op de Beeck, Hans P

    2014-08-06

    Visual categorization of complex, natural stimuli has been studied for some time in human and nonhuman primates. Recent interest in the rodent as a model for visual perception, including higher-level functional specialization, leads to the question of how rodents would perform on a categorization task using natural stimuli. To answer this question, rats were trained in a two-alternative forced choice task to discriminate movies containing rats from movies containing other objects and from scrambled movies (ordinate-level categorization). Subsequently, transfer to novel, previously unseen stimuli was tested, followed by a series of control probes. The results show that the animals are capable of acquiring a decision rule by abstracting common features from natural movies to generalize categorization to new stimuli. Control probes demonstrate that they did not use single low-level features, such as motion energy or (local) luminance. Significant generalization was even present with stationary snapshots from untrained movies. The variability within and between training and test stimuli, the complexity of natural movies, and the control experiments and analyses all suggest that a more high-level rule based on more complex stimulus features than local luminance-based cues was used to classify the novel stimuli. In conclusion, natural stimuli can be used to probe ordinate-level categorization in rats. Copyright © 2014 the authors 0270-6474/14/3410645-14$15.00/0.

  18. A single-system model predicts recognition memory and repetition priming in amnesia.

    Science.gov (United States)

    Berry, Christopher J; Kessels, Roy P C; Wester, Arie J; Shanks, David R

    2014-08-13

    We challenge the claim that there are distinct neural systems for explicit and implicit memory by demonstrating that a formal single-system model predicts the pattern of recognition memory (explicit) and repetition priming (implicit) in amnesia. In the current investigation, human participants with amnesia categorized pictures of objects at study and then, at test, identified fragmented versions of studied (old) and nonstudied (new) objects (providing a measure of priming), and made a recognition memory judgment (old vs new) for each object. Numerous results in the amnesic patients were predicted in advance by the single-system model, as follows: (1) deficits in recognition memory and priming were evident relative to a control group; (2) items judged as old were identified at greater levels of fragmentation than items judged new, regardless of whether the items were actually old or new; and (3) the magnitude of the priming effect (the identification advantage for old vs new items) overall was greater than that of items judged new. Model evidence measures also favored the single-system model over two formal multiple-systems models. The findings support the single-system model, which explains the pattern of recognition and priming in amnesia primarily as a reduction in the strength of a single dimension of memory strength, rather than a selective explicit memory system deficit. Copyright © 2014 the authors 0270-6474/14/3410963-12$15.00/0.

  19. Neurogenin3 restricts serotonergic neuron differentiation to the hindbrain.

    Science.gov (United States)

    Carcagno, Abel L; Di Bella, Daniela J; Goulding, Martyn; Guillemot, Francois; Lanuza, Guillermo M

    2014-11-12

    The development of the nervous system is critically dependent on the production of functionally diverse neuronal cell types at their correct locations. In the embryonic neural tube, dorsoventral signaling has emerged as a fundamental mechanism for generating neuronal diversity. In contrast, far less is known about how different neuronal cell types are organized along the rostrocaudal axis. In the developing mouse and chick neural tube, hindbrain serotonergic neurons and spinal glutamatergic V3 interneurons are produced from ventral p3 progenitors, which possess a common transcriptional identity but are confined to distinct anterior-posterior territories. In this study, we show that the expression of the transcription factor Neurogenin3 (Neurog3) in the spinal cord controls the correct specification of p3-derived neurons. Gain- and loss-of-function manipulations in the chick and mouse embryo show that Neurog3 switches ventral progenitors from a serotonergic to V3 differentiation program by repressing Ascl1 in spinal p3 progenitors through a mechanism dependent on Hes proteins. In this way, Neurog3 establishes the posterior boundary of the serotonergic system by actively suppressing serotonergic specification in the spinal cord. These results explain how equivalent p3 progenitors within the hindbrain and the spinal cord produce functionally distinct neuron cell types. Copyright © 2014 the authors 0270-6474/14/3415223-11$15.00/0.

  20. The Rubber Tail Illusion as Evidence of Body Ownership in Mice.

    Science.gov (United States)

    Wada, Makoto; Takano, Kouji; Ora, Hiroki; Ide, Masakazu; Kansaku, Kenji

    2016-10-26

    The ownership of one's body parts represents a fundamental aspect of self-consciousness. Accumulating empirical evidence supports the existence of this concept in humans and nonhuman primates, but it is unclear whether nonprimate mammals experience similar feelings. Therefore, the present study used rubber tails to investigate body ownership in rodents. When the real tails and rubber tails were synchronously stroked, the mice responded as if their own tails were touched when the rubber tails were grasped. In contrast, when the stimuli were delivered asynchronously, there was a significantly lower mean response rate when the rubber tail was grasped. These findings suggest that mice may experience body ownership of their tails, suggestive of the rubber hand illusion in humans. To explore the manner in which the ownership of body parts is experienced, this study specifically used the rubber hand illusion (RHI), in which self-consciousness can be extended out of one's own body. Accumulating empirical evidence supports the existence of this concept in humans and nonhuman primates, but it remains unclear whether nonprimate mammals experience similar feelings. This study demonstrated for the first time that mice may experience body ownership of their tails, which is suggestive of the RHI in humans and provides evidence that may highlight how humans experience the ownership of body parts. Copyright © 2016 the authors 0270-6474/16/3611133-05$15.00/0.

  1. Benchmarking Experimental and Computational Thermochemical Data: A Case Study of the Butane Conformers.

    Science.gov (United States)

    Barna, Dóra; Nagy, Balázs; Csontos, József; Császár, Attila G; Tasi, Gyula

    2012-02-14

    Due to its crucial importance, numerous studies have been conducted to determine the enthalpy difference between the conformers of butane. However, it is shown here that the most reliable experimental values are biased due to the statistical model utilized during the evaluation of the raw experimental data. In this study, using the appropriate statistical model, both the experimental expectation values and the associated uncertainties are revised. For the 133-196 and 223-297 K temperature ranges, 668 ± 20 and 653 ± 125 cal mol(-1), respectively, are recommended as reference values. Furthermore, to show that present-day quantum chemistry is a favorable alternative to experimental techniques in the determination of enthalpy differences of conformers, a focal-point analysis, based on coupled-cluster electronic structure computations, has been performed that included contributions of up to perturbative quadruple excitations as well as small correction terms beyond the Born-Oppenheimer and nonrelativistic approximations. For the 133-196 and 223-297 K temperature ranges, in exceptional agreement with the corresponding revised experimental data, our computations yielded 668 ± 3 and 650 ± 6 cal mol(-1), respectively. The most reliable enthalpy difference values for 0 and 298.15 K are also provided by the computational approach, 680.9 ± 2.5 and 647.4 ± 7.0 cal mol(-1), respectively.

  2. Hemispheric Asymmetries in Striatal Reward Responses Relate to Approach-Avoidance Learning and Encoding of Positive-Negative Prediction Errors in Dopaminergic Midbrain Regions.

    Science.gov (United States)

    Aberg, Kristoffer Carl; Doell, Kimberly C; Schwartz, Sophie

    2015-10-28

    Some individuals are better at learning about rewarding situations, whereas others are inclined to avoid punishments (i.e., enhanced approach or avoidance learning, respectively). In reinforcement learning, action values are increased when outcomes are better than predicted (positive prediction errors [PEs]) and decreased for worse than predicted outcomes (negative PEs). Because actions with high and low values are approached and avoided, respectively, individual differences in the neural encoding of PEs may influence the balance between approach-avoidance learning. Recent correlational approaches also indicate that biases in approach-avoidance learning involve hemispheric asymmetries in dopamine function. However, the computational and neural mechanisms underpinning such learning biases remain unknown. Here we assessed hemispheric reward asymmetry in striatal activity in 34 human participants who performed a task involving rewards and punishments. We show that the relative difference in reward response between hemispheres relates to individual biases in approach-avoidance learning. Moreover, using a computational modeling approach, we demonstrate that better encoding of positive (vs negative) PEs in dopaminergic midbrain regions is associated with better approach (vs avoidance) learning, specifically in participants with larger reward responses in the left (vs right) ventral striatum. Thus, individual dispositions or traits may be determined by neural processes acting to constrain learning about specific aspects of the world. Copyright © 2015 the authors 0270-6474/15/3514491-10$15.00/0.

  3. Distinct neuronal interactions in anterior inferotemporal areas of macaque monkeys during retrieval of object association memory.

    Science.gov (United States)

    Hirabayashi, Toshiyuki; Tamura, Keita; Takeuchi, Daigo; Takeda, Masaki; Koyano, Kenji W; Miyashita, Yasushi

    2014-07-09

    In macaque monkeys, the anterior inferotemporal cortex, a region crucial for object memory processing, is composed of two adjacent, hierarchically distinct areas, TE and 36, for which different functional roles and neuronal responses in object memory tasks have been characterized. However, it remains unknown how the neuronal interactions differ between these areas during memory retrieval. Here, we conducted simultaneous recordings from multiple single-units in each of these areas while monkeys performed an object association memory task and examined the inter-area differences in neuronal interactions during the delay period. Although memory neurons showing sustained activity for the presented cue stimulus, cue-holding (CH) neurons, interacted with each other in both areas, only those neurons in area 36 interacted with another type of memory neurons coding for the to-be-recalled paired associate (pair-recall neurons) during memory retrieval. Furthermore, pairs of CH neurons in area TE showed functional coupling in response to each individual object during memory retention, whereas the same class of neuron pairs in area 36 exhibited a comparable strength of coupling in response to both associated objects. These results suggest predominant neuronal interactions in area 36 during the mnemonic processing, which may underlie the pivotal role of this brain area in both storage and retrieval of object association memory. Copyright © 2014 the authors 0270-6474/14/349377-12$15.00/0.

  4. Seeing is not feeling: posterior parietal but not somatosensory cortex engagement during touch observation.

    Science.gov (United States)

    Chan, Annie W-Y; Baker, Chris I

    2015-01-28

    Observing touch has been reported to elicit activation in human primary and secondary somatosensory cortices and is suggested to underlie our ability to interpret other's behavior and potentially empathy. However, despite these reports, there are a large number of inconsistencies in terms of the precise topography of activation, the extent of hemispheric lateralization, and what aspects of the stimulus are necessary to drive responses. To address these issues, we investigated the localization and functional properties of regions responsive to observed touch in a large group of participants (n = 40). Surprisingly, even with a lenient contrast of hand brushing versus brushing alone, we did not find any selective activation for observed touch in the hand regions of somatosensory cortex but rather in superior and inferior portions of neighboring posterior parietal cortex, predominantly in the left hemisphere. These regions in the posterior parietal cortex required the presence of both brush and hand to elicit strong responses and showed some selectivity for the form of the object or agent of touch. Furthermore, the inferior parietal region showed nonspecific tactile and motor responses, suggesting some similarity to area PFG in the monkey. Collectively, our findings challenge the automatic engagement of somatosensory cortex when observing touch, suggest mislocalization in previous studies, and instead highlight the role of posterior parietal cortex. Copyright © 2015 the authors 0270-6474/15/351468-13$15.00/0.

  5. Convergent and reciprocal modulation of a leak K+ current and Ih by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones

    Science.gov (United States)

    Sirois, Jay E; Lynch, Carl; Bayliss, Douglas A

    2002-01-01

    Neurotransmitters and volatile anaesthetics have opposing effects on motoneuronal excitability which appear to reflect contrasting modulation of two types of subthreshold currents. Neurotransmitters increase motoneuronal excitability by inhibiting TWIK-related acid-sensitive K+ channels (TASK) and shifting activation of a hyperpolarization-activated cationic current (Ih) to more depolarized potentials; on the other hand, anaesthetics decrease excitability by activating a TASK-like current and inducing a hyperpolarizing shift in Ih activation. Here, we used whole-cell recording from motoneurones in brainstem slices to test if neurotransmitters (serotonin (5-HT) and noradrenaline (NA)) and an anaesthetic (halothane) indeed compete for modulation of the same ion channels - and we determined which prevails. When applied together under current clamp conditions, 5-HT reversed anaesthetic-induced membrane hyperpolarization and increased motoneuronal excitability. Under voltage clamp conditions, 5-HT and NA overcame most, but not all, of the halothane-induced current. When Ih was blocked with ZD 7288, the neurotransmitters completely inhibited the K+ current activated by halothane; the halothane-sensitive neurotransmitter current reversed at the equilibrium potential for potassium (EK) and displayed properties expected of acid-sensitive, open-rectifier TASK channels. To characterize modulation of Ih in relative isolation, effects of 5-HT and halothane were examined in acidified bath solutions that blocked TASK channels. Under these conditions, 5-HT and halothane each caused their characteristic shift in voltage-dependent gating of Ih. When tested concurrently, however, halothane decreased the neurotransmitter-induced depolarizing shift in Ih activation. Thus, halothane and neurotransmitters converge on TASK and Ih channels with opposite effects; transmitter action prevailed over anaesthetic effects on TASK channels, but not over effects on Ih. These data suggest that

  6. Theoretical studies of molecule surface scattering: Rotationally inelastic diffraction and dissociative dynamics of H2 on metals

    International Nuclear Information System (INIS)

    Cruz Pol, A.J.

    1993-01-01

    The interaction of H 2 and its isotopes with metal surfaces has been the subject of many investigations. The scattering experiments provide data such as the final rotational state distribution, sticking coefficients, kinetic energy distribution, and diffraction data. In the first study of this thesis the author implemented a model for looking at the rotationally inelastic diffraction probabilities for H 2 , HD, and D 2 , as a function of surface temperature. The surface is treated in a quantum mechanical fashion using a recently developed formalism. The center of mass translational motion is treated semiclassically using Gaussian wave packets, and the rotations are described quantum mechanically. The phonon summed rotation-diffraction probabilities as well as the probability distribution for a scattering molecule exchanging an amount of energy ΔE with the surface were computed. In the second and third study of this thesis the author implemented a mixed quantum-classical model to compute the probability for dissociation and rotational excitation for H 2 , HD, and D 2 scattered from Ni(100) dimensionally in dynamics simulations. Of the six degrees of freedom for the dissociative adsorption of a diatomic molecule on a static surface, the author treats Z,d the center of mass distance above the surface plan, r, the internuclear separation, θ, the polar orientation angle, quantum mechanically. The remaining three degrees of freedom, X and Y, the center of mass position on the surface plane, and oe, the azimuthal orientation angle, are treated classically. Probabilities for dissociation and ro-vibrational excitation are computed as a function of incident translational energy. Two sudden approximations are tested, in which either the center of mass translation parallel to the surface or the azimuthal orientation of the molecule are frozen. Comparisons are made between low and high dimensionality results and with fully classical results

  7. Genome-wide analysis of the cellulose synthase-like (Csl) gene family in bread wheat (Triticum aestivum L.).

    Science.gov (United States)

    Kaur, Simerjeet; Dhugga, Kanwarpal S; Beech, Robin; Singh, Jaswinder

    2017-11-03

    Hemicelluloses are a diverse group of complex, non-cellulosic polysaccharides, which constitute approximately one-third of the plant cell wall and find use as dietary fibres, food additives and raw materials for biofuels. Genes involved in hemicellulose synthesis have not been extensively studied in small grain cereals. In efforts to isolate the sequences for the cellulose synthase-like (Csl) gene family from wheat, we identified 108 genes (hereafter referred to as TaCsl). Each gene was represented by two to three homeoalleles, which are named as TaCslXY_ZA, TaCslXY_ZB, or TaCslXY_ZD, where X denotes the Csl subfamily, Y the gene number and Z the wheat chromosome where it is located. A quarter of these genes were predicted to have 2 to 3 splice variants, resulting in a total of 137 putative translated products. Approximately 45% of TaCsl genes were located on chromosomes 2 and 3. Sequences from the subfamilies C and D were interspersed between the dicots and grasses but those from subfamily A clustered within each group of plants. Proximity of the dicot-specific subfamilies B and G, to the grass-specific subfamilies H and J, respectively, points to their common origin. In silico expression analysis in different tissues revealed that most of the genes were expressed ubiquitously and some were tissue-specific. More than half of the genes had introns in phase 0, one-third in phase 2, and a few in phase 1. Detailed characterization of the wheat Csl genes has enhanced the understanding of their structural, functional, and evolutionary features. This information will be helpful in designing experiments for genetic manipulation of hemicellulose synthesis with the goal of developing improved cultivars for biofuel production and increased tolerance against various stresses.

  8. Analýza nestrukturovaných dat z bankovních stránek na sociální síti Facebook

    Directory of Open Access Journals (Sweden)

    Lucie Šperková

    2014-12-01

    Full Text Available Sociální sítě jako novodobý kanál pro sdílení online Word of Mouth představuje pro bankovní společnosti příležitost, jak analyzovat komunikaci a názory svých zákazníků, které zde veřejně sdílejí. Článek ukazuje proces a výsledky pokročilé kontextové analýzy těchto nestrukturovaných dat vybraných veřejných bankovních stránek na sociální síti Facebook. Analýza zákaznických názorů, problémů a přání může hrát významnou roli pro pozici těchto společností na trhu a jejich orientaci na zákazníky. Využity byly metody shlukování a sentiment analýz, výsledky odrážejí stav chování zákazníků a bank na této síti. Článek zdůrazňuje důležitost problematiky Word of Mouth a jeho analýz informačními technologiemi. Zároveň diskutuje, jak analýza kontextu může přenést marketing na další úroveň identifikace zákazníkova chování a jeho vztahu ke společnosti.

  9. Linking γ-aminobutyric acid A receptor to epidermal growth factor receptor pathways activation in human prostate cancer.

    Science.gov (United States)

    Wu, Weijuan; Yang, Qing; Fung, Kar-Ming; Humphreys, Mitchell R; Brame, Lacy S; Cao, Amy; Fang, Yu-Ting; Shih, Pin-Tsen; Kropp, Bradley P; Lin, Hsueh-Kung

    2014-03-05

    Neuroendocrine (NE) differentiation has been attributed to the progression of castration-resistant prostate cancer (CRPC). Growth factor pathways including the epidermal growth factor receptor (EGFR) signaling have been implicated in the development of NE features and progression to a castration-resistant phenotype. However, upstream molecules that regulate the growth factor pathway remain largely unknown. Using androgen-insensitive bone metastasis PC-3 cells and androgen-sensitive lymph node metastasis LNCaP cells derived from human prostate cancer (PCa) patients, we demonstrated that γ-aminobutyric acid A receptor (GABA(A)R) ligand (GABA) and agonist (isoguvacine) stimulate cell proliferation, enhance EGF family members expression, and activate EGFR and a downstream signaling molecule, Src, in both PC-3 and LNCaP cells. Inclusion of a GABA(A)R antagonist, picrotoxin, or an EGFR tyrosine kinase inhibitor, Gefitinib (ZD1839 or Iressa), blocked isoguvacine and GABA-stimulated cell growth, trans-phospohorylation of EGFR, and tyrosyl phosphorylation of Src in both PCa cell lines. Spatial distributions of GABAAR α₁ and phosphorylated Src (Tyr416) were studied in human prostate tissues by immunohistochemistry. In contrast to extremely low or absence of GABA(A)R α₁-positive immunoreactivity in normal prostate epithelium, elevated GABA(A)R α₁ immunoreactivity was detected in prostate carcinomatous glands. Similarly, immunoreactivity of phospho-Src (Tyr416) was specifically localized and limited to the nucleoli of all invasive prostate carcinoma cells, but negative in normal tissues. Strong GABAAR α₁ immunoreactivity was spatially adjacent to the neoplastic glands where strong phospho-Src (Tyr416)-positive immunoreactivity was demonstrated, but not in adjacent to normal glands. These results suggest that the GABA signaling is linked to the EGFR pathway and may work through autocrine or paracine mechanism to promote CRPC progression. Copyright © 2013 Elsevier

  10. Implementation of a one-group interfacial area transport equation in a CFD code for the simulation of upward adiabatic bubbly flow

    International Nuclear Information System (INIS)

    Pellacani, F.; Macian, R.; Chiva, S.; Pena, C.

    2011-01-01

    In this paper upward, isothermal and turbulent bubbly flow in tubes is numerically modeled by using ANSYS CFX 12.1 with the aim of creating a basis for the reliable simulation of the flow along a vertical channel in a nuclear reactor as long term goal. Two approaches based on the mono-dispersed model and on the one-group Interfacial Area Transport Equation (IATE) model are used in order to maintain the computational effort as low as possible. This work represents the necessary step to implement a two-group interfacial area transport equation that will be able to dynamically represent the changes in interfacial structure in the transition region from bubbly to slug flow. The drag coefficient is calculated using the Grace model and the interfacial non-drag forces are also included. The Antal model is used for the calculation of the wall lubrication force coefficient. The lift force coefficient is obtained from the Tomiyama model. The turbulent dispersion force is taken into account and is modeled using the FAD (Favre averaged drag) approach, while the turbulence transfer is simulated with the Sato's model. The liquid velocity is in the range between 0.5 and 2 m/s and the average void fraction varies between 5 and 15%.The source and sink terms for break-up and coalescence needed for the calculation of the implemented Interfacial Area Density are those proposed by Yao and Morel. The model has been checked using experimental results by Mendez. Radial profile distributions of void fraction, interfacial area density and bubble mean diameter are shown at the axial position equivalent to z/D=56. The results obtained by the simulations have a good agreement with the experimental data but show also the need of a better study of the coalescence and breakup phenomena to develop more accurate interaction models. (author)

  11. Novel multifunctional graphene sheets with encased Au/Ag nanoparticles for advanced electrochemical analysis of organic compounds.

    Science.gov (United States)

    Pruneanu, Stela; Biris, Alexandru R; Pogacean, Florina; Lazar, Diana Mihaela; Ardelean, Stefania; Watanabe, Fumyia; Dervishi, Enkeleda; Biris, Alexandru S

    2012-11-12

    This work is the first presentation of the synthesis of few-layer graphene decorated with gold and silver nanoparticles (Gr-Au-Ag) by chemical vapor deposition over a catalytic system formed of bimetallic Au-Ag nanoclusters supported on MgO and with methane used as the source of carbon. The sheetlike morphology of the graphene nanostructures, with mean sizes in the range of hundreds of nanometers, was observed by high-resolution electron microscopy. The distinctive feature found in all the samples was the regular rectangular or square shapes. This multi-component organic-inorganic nanomaterial was used to modify a platinum substrate and subsequently employed for the detection of carbamazepine, an anti-convulsion drug. UV/Vis spectroscopy revealed that a strong hypochromism occurred over time, after mixing solutions of graphene-Au-Ag with carbamazepine. This can be attributed to π-π stacking between the aromatic groups of the two compounds. Linear sweep voltammetry (LCV) provided evidence that the modified platinum substrate presented a significant electrocatalytic reaction toward the oxidation of carbamazepine. The intensity of the current was found to increase by up to 2.5 times, and the oxidation potential shifted from +1.5 to +1.35 V(Ag/AgCl) in comparison with the unmodified electrode. Electrochemical impedance spectroscopy (EIS) was further used to thoroughly assess the activity of the platinum electrode that was modified by the deposition of the Gr-Au-Ag composites in the presence of various concentrations of carbamazepine. The experimental EIS records were used for the generation of an equivalent electrical circuit, based on the charge-transfer resistance (R(ct)), Warburg impedance (Z(D)), solution resistance (R(s)), and a constant phase element (CPE) that characterizes the non-ideal interface capacitive responses. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Quenched Large Deviations for Simple Random Walks on Percolation Clusters Including Long-Range Correlations

    Science.gov (United States)

    Berger, Noam; Mukherjee, Chiranjib; Okamura, Kazuki

    2018-03-01

    We prove a quenched large deviation principle (LDP) for a simple random walk on a supercritical percolation cluster (SRWPC) on {Z^d} ({d ≥ 2}). The models under interest include classical Bernoulli bond and site percolation as well as models that exhibit long range correlations, like the random cluster model, the random interlacement and the vacant set of random interlacements (for {d ≥ 3}) and the level sets of the Gaussian free field ({d≥ 3}). Inspired by the methods developed by Kosygina et al. (Commun Pure Appl Math 59:1489-1521, 2006) for proving quenched LDP for elliptic diffusions with a random drift, and by Yilmaz (Commun Pure Appl Math 62(8):1033-1075, 2009) and Rosenbluth (Quenched large deviations for multidimensional random walks in a random environment: a variational formula. Ph.D. thesis, NYU, arXiv:0804.1444v1) for similar results regarding elliptic random walks in random environment, we take the point of view of the moving particle and prove a large deviation principle for the quenched distribution of the pair empirical measures of the environment Markov chain in the non-elliptic case of SRWPC. Via a contraction principle, this reduces easily to a quenched LDP for the distribution of the mean velocity of the random walk and both rate functions admit explicit variational formulas. The main difficulty in our set up lies in the inherent non-ellipticity as well as the lack of translation-invariance stemming from conditioning on the fact that the origin belongs to the infinite cluster. We develop a unifying approach for proving quenched large deviations for SRWPC based on exploiting coercivity properties of the relative entropies in the context of convex variational analysis, combined with input from ergodic theory and invoking geometric properties of the supercritical percolation cluster.

  13. Numerical Predictions of Enhanced Impingement Jet Cooling with Ribs and Pins in Co-Flow and Cross-Flow Configurations

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    A. M. El-Jummah

    2017-02-01

    Full Text Available Numerical calculations relevant to gas turbine internal wall heat transfer cooling were conducted using conjugate heat transfer (CHT computational Fluid Dynamics (CFD commercial codes. The CHT CFD predictions were carried out for impingement heat transfer with different types of obstacle walls (fins on the target surfaces. A 10 × 10 row of impingement air jet holes (or hole density n of 4306 m-2 was used, which gives ten rows of holes in the cross-flow direction and only one heat transfer enhancement obstacle per impingement jet was investigated. Previously, four different shaped obstacles were investigated experimentally and were used to validate the present predictions. The obstacle walls, which were equally spaced on the centreline between each impingement jet are of the co-flow and cross-flow configurations. The impingement jet pitch X to diameter D, X/D and gap Z to diameter, Z/D ratios were kept constant at 4.66 and 3.06 for X, Z and D of 15.24, 10.00 and 3.27 mm, respectively. The obstacles investigated were ribs and rectangular pin-fins shapes, using two obstacles height H to diameter, H/D ratio of 1.38 and 2.45. Computations were carried out for three different mass flux G of 1.08, 1.48 and 1.94 kg/sm2. Relative pressure loss ∆P/P and surface average heat transfer coefficient (HTC h predictions for the range of G, showed good agreement with the experimental results. The prediction also reveals that obstacles not only increases the turbulent flows, but also takes away most of the cooling heat transfer that produces the regions with highest thermal gradients. It also reduces the impingement gap downstream cross-flow.

  14. Local gas- and liquid-phase measurements for air-water two-phase flows in a rectangular channel

    International Nuclear Information System (INIS)

    Zhou, X.; Sun, X.; Williams, M.; Fu, Y.; Liu, Y.

    2014-01-01

    Local gas- and liquid-phase measurements of various gas-liquid two-phase flows, including bubbly, cap-bubbly, slug, and churn-turbulent flows, were performed in an acrylic vertical channel with a rectangular cross section of 30 mm x 10 mm and height of 3.0 m. All the measurements were carried out at three measurement elevations along the flow channel, with z/D h = 9, 72, and 136, respectively, to study the flow development. The gas-phase velocity, void fraction, and bubble number frequency were measured using a double-sensor conductivity probe. A high-speed imaging system was utilized to perform the flow regime visualization and to provide additional quantitative information of the two-phase flow structure. An image processing scheme was developed to obtain the gas-phase velocity, void fraction, Sauter mean diameter, bubble number density, and interfacial area concentration. The liquid-phase velocity and turbulence measurements were conducted using a particle image velocimetry-planar laser-induced fluorescence (PIV-PLIF) system, which enables whole-field and high-resolution data acquisition. An optical phase separation method, which uses fluorescent particles and optical filtration technique, is adopted to extract the velocity information of the liquid phase. An image pre-processing scheme is imposed on the raw PIV images acquired to remove noises due to the presence of bubble residuals and optically distorted particles in the images captured by the PIV-PLIF system. Due to the better light access and less bubble distortion in the narrow rectangular channel, the PIV-PLIF system were able to perform reasonably well in flows of even higher void fractions as compared to the situations with circular pipe test sections. The flow conditions being studied covered various flow regime transitions, void fractions, and liquid-phase flow Reynolds numbers. The obtained experimental data can also be used to validate two-phase CFD results. (author)

  15. Measurement of subcooled boiling pressure drop and local heat transfer coefficient in horizontal tube under LPLF conditions

    International Nuclear Information System (INIS)

    Baburajan, P.K.; Bisht, G.S.; Gupta, S.K.; Prabhu, S.V.

    2013-01-01

    Highlights: ► Measured subcooled boiling pressure drop and local heat transfer coefficient in horizontal tubes. ► Infra-red thermal imaging is used for wall temperature measurement. ► Developed correlations for pressure drop and local heat transfer coefficient. -- Abstract: Horizontal flow is commonly encountered in boiler tubes, refrigerating equipments and nuclear reactor fuel channels of pressurized heavy water reactors (PHWR). Study of horizontal flow under low pressure and low flow (LPLF) conditions is important in understanding the nuclear core behavior during situations like LOCA (loss of coolant accidents). In the present work, local heat transfer coefficient and pressure drop are measured in a horizontal tube under LPLF conditions of subcooled boiling. Geometrical parameters covered in this study are diameter (5.5 mm, 7.5 mm and 9.5 mm) and length (550 mm, 750 mm and 1000 mm). The operating parameters varied are mass flux (450–935 kg/m 2 s) and inlet subcooling (29 °C, 50 °C and 70 °C). Infra-red thermography is used for the measurement of local wall temperature to estimate the heat transfer coefficient in single phase and two phase flows with water as the working medium at atmospheric pressure. Correlation for single phase diabatic pressure drop ratio (diabatic to adiabatic) as a function of viscosity ratio (wall temperature to fluid temperature) is presented. Correlation for pressure drop under subcooled boiling conditions as a function of Boiling number (Bo) and Jakob number (Ja) is obtained. Correlation for single phase heat transfer coefficient in the thermal developing region is presented as a function of Reynolds number (Re), Prandtl number (Pr) and z/d (ratio of axial length of the test section to diameter). Correlation for two phase heat transfer coefficient under subcooled boiling condition is developed as a function of boiling number (Bo), Jakob number (Ja) and Prandtl number (Pr)

  16. HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.

    Directory of Open Access Journals (Sweden)

    Geoffrey C Horwitz

    Full Text Available The molecular composition of the hair cell transduction channel has not been identified. Here we explore the novel hypothesis that hair cell transduction channels include HCN subunits. The HCN family of ion channels includes four members, HCN1-4. They were originally identified as the molecular correlates of the hyperpolarization-activated, cyclic nucleotide gated ion channels that carry currents known as If, IQ or Ih. However, based on recent evidence it has been suggested that HCN subunits may also be components of the elusive hair cell transduction channel. To investigate this hypothesis we examined expression of mRNA that encodes HCN1-4 in sensory epithelia of the mouse inner ear, immunolocalization of HCN subunits 1, 2 and 4, uptake of the transduction channel permeable dye, FM1-43 and electrophysiological measurement of mechanotransduction current. Dye uptake and transduction current were assayed in cochlear and vestibular hair cells of wildtype mice exposed to HCN channel blockers or a dominant-negative form of HCN2 that contained a pore mutation and in mutant mice that lacked HCN1, HCN2 or both. We found robust expression of HCNs 1, 2 and 4 but little evidence that localized HCN subunits in hair bundles, the site of mechanotransduction. Although high concentrations of the HCN antagonist, ZD7288, blocked 50-70% of the transduction current, we found no reduction of transduction current in either cochlear or vestibular hair cells of HCN1- or HCN2- deficient mice relative to wild-type mice. Furthermore, mice that lacked both HCN1 and HCN2 also had normal transduction currents. Lastly, we found that mice exposed to the dominant-negative mutant form of HCN2 had normal transduction currents as well. Taken together, the evidence suggests that HCN subunits are not required for mechanotransduction in hair cells of the mouse inner ear.

  17. High-pass filtering of input signals by the Ih current in a non-spiking neuron, the retinal rod bipolar cell.

    Directory of Open Access Journals (Sweden)

    Lorenzo Cangiano

    Full Text Available Hyperpolarization-activated cyclic nucleotide-sensitive (HCN channels mediate the I(f current in heart and I(h throughout the nervous system. In spiking neurons I(h participates primarily in different forms of rhythmic activity. Little is known, however, about its role in neurons operating with graded potentials as in the retina, where all four channel isoforms are expressed. Intriguing evidence for an involvement of I(h in early visual processing are the side effects reported, in dim light or darkness, by cardiac patients treated with HCN inhibitors. Moreover, electroretinographic recordings indicate that these drugs affect temporal processing in the outer retina. Here we analyzed the functional role of HCN channels in rod bipolar cells (RBCs of the mouse. Perforated-patch recordings in the dark-adapted slice found that RBCs exhibit I(h, and that this is sensitive to the specific blocker ZD7288. RBC input impedance, explored by sinusoidal frequency-modulated current stimuli (0.1-30 Hz, displays band-pass behavior in the range of I(h activation. Theoretical modeling and pharmacological blockade demonstrate that high-pass filtering of input signals by I(h, in combination with low-pass filtering by passive properties, fully accounts for this frequency-tuning. Correcting for the depolarization introduced by shunting through the pipette-membrane seal, leads to predict that in darkness I(h is tonically active in RBCs and quickens their responses to dim light stimuli. Immunohistochemistry targeting candidate subunit isoforms HCN1-2, in combination with markers of RBCs (PKC and rod-RBC synaptic contacts (bassoon, mGluR6, Kv1.3, suggests that RBCs express HCN2 on the tip of their dendrites. The functional properties conferred by I(h onto RBCs may contribute to shape the retina's light response and explain the visual side effects of HCN inhibitors.

  18. Vividness of Visual Imagery Depends on the Neural Overlap with Perception in Visual Areas.

    Science.gov (United States)

    Dijkstra, Nadine; Bosch, Sander E; van Gerven, Marcel A J

    2017-02-01

    Research into the neural correlates of individual differences in imagery vividness point to an important role of the early visual cortex. However, there is also great fluctuation of vividness within individuals, such that only looking at differences between people necessarily obscures the picture. In this study, we show that variation in moment-to-moment experienced vividness of visual imagery, within human subjects, depends on the activity of a large network of brain areas, including frontal, parietal, and visual areas. Furthermore, using a novel multivariate analysis technique, we show that the neural overlap between imagery and perception in the entire visual system correlates with experienced imagery vividness. This shows that the neural basis of imagery vividness is much more complicated than studies of individual differences seemed to suggest. Visual imagery is the ability to visualize objects that are not in our direct line of sight: something that is important for memory, spatial reasoning, and many other tasks. It is known that the better people are at visual imagery, the better they can perform these tasks. However, the neural correlates of moment-to-moment variation in visual imagery remain unclear. In this study, we show that the more the neural response during imagery is similar to the neural response during perception, the more vivid or perception-like the imagery experience is. Copyright © 2017 the authors 0270-6474/17/371367-07$15.00/0.

  19. Responses of prefrontal multisensory neurons to mismatching faces and vocalizations.

    Science.gov (United States)

    Diehl, Maria M; Romanski, Lizabeth M

    2014-08-20

    Social communication relies on the integration of auditory and visual information, which are present in faces and vocalizations. Evidence suggests that the integration of information from multiple sources enhances perception compared with the processing of a unimodal stimulus. Our previous studies demonstrated that single neurons in the ventrolateral prefrontal cortex (VLPFC) of the rhesus monkey (Macaca mulatta) respond to and integrate conspecific vocalizations and their accompanying facial gestures. We were therefore interested in how VLPFC neurons respond differentially to matching (congruent) and mismatching (incongruent) faces and vocalizations. We recorded VLPFC neurons during the presentation of movies with congruent or incongruent species-specific facial gestures and vocalizations as well as their unimodal components. Recordings showed that while many VLPFC units are multisensory and respond to faces, vocalizations, or their combination, a subset of neurons showed a significant change in neuronal activity in response to incongruent versus congruent vocalization movies. Among these neurons, we typically observed incongruent suppression during the early stimulus period and incongruent enhancement during the late stimulus period. Incongruent-responsive VLPFC neurons were both bimodal and nonlinear multisensory, fostering their ability to respond to changes in either modality of a face-vocalization stimulus. These results demonstrate that ventral prefrontal neurons respond to changes in either modality of an audiovisual stimulus, which is important in identity processing and for the integration of multisensory communication information. Copyright © 2014 the authors 0270-6474/14/3411233-11$15.00/0.

  20. Mouse visual neocortex supports multiple stereotyped patterns of microcircuit activity.

    Science.gov (United States)

    Sadovsky, Alexander J; MacLean, Jason N

    2014-06-04

    Spiking correlations between neocortical neurons provide insight into the underlying synaptic connectivity that defines cortical microcircuitry. Here, using two-photon calcium fluorescence imaging, we observed the simultaneous dynamics of hundreds of neurons in slices of mouse primary visual cortex (V1). Consistent with a balance of excitation and inhibition, V1 dynamics were characterized by a linear scaling between firing rate and circuit size. Using lagged firing correlations between neurons, we generated functional wiring diagrams to evaluate the topological features of V1 microcircuitry. We found that circuit connectivity exhibited both cyclic graph motifs, indicating recurrent wiring, and acyclic graph motifs, indicating feedforward wiring. After overlaying the functional wiring diagrams onto the imaged field of view, we found properties consistent with Rentian scaling: wiring diagrams were topologically efficient because they minimized wiring with a modular architecture. Within single imaged fields of view, V1 contained multiple discrete circuits that were overlapping and highly interdigitated but were still distinct from one another. The majority of neurons that were shared between circuits displayed peri-event spiking activity whose timing was specific to the active circuit, whereas spike times for a smaller percentage of neurons were invariant to circuit identity. These data provide evidence that V1 microcircuitry exhibits balanced dynamics, is efficiently arranged in anatomical space, and is capable of supporting a diversity of multineuron spike firing patterns from overlapping sets of neurons. Copyright © 2014 the authors 0270-6474/14/347769-09$15.00/0.

  1. Angular Gyrus Involvement at Encoding and Retrieval Is Associated with Durable But Less Specific Memories.

    Science.gov (United States)

    van der Linden, Marieke; Berkers, Ruud M W J; Morris, Richard G M; Fernández, Guillén

    2017-09-27

    After consolidation, information belonging to a mental schema is better remembered, but such memory can be less specific when it comes to details. A neuronal mechanism consistent with this behavioral pattern could result from a dynamic interaction that entails mediation by a specific cortical network with associated hippocampal disengagement. We now report that, in male and female adult human subjects, encoding and later consolidation of a series of objects embedded in a semantic schema was associated with a buildup of activity in the angular gyrus (AG) that predicted memory 24 h later. In parallel, the posterior hippocampus became less involved as schema objects were encoded successively. Hippocampal disengagement was related to an increase in falsely remembering objects that were not presented at encoding. During both encoding and retrieval, the AG and lateral occipital complex (LOC) became functionally connected and this interaction was beneficial for successful retrieval. Therefore, a network including the AG and LOC enhances the overnight retention of schema-related memories and their simultaneous detachment from the hippocampus reduces the specificity of the memory. SIGNIFICANCE STATEMENT This study provides the first empirical evidence on how the hippocampus and the neocortex interact dynamically when acquiring and then effectively retaining durable knowledge that is associated to preexisting knowledge, but they do so at the cost of memory specificity. This interaction is a fundamental mnemonic operation that has thus far been largely overlooked in memory research. Copyright © 2017 the authors 0270-6474/17/379474-12$15.00/0.

  2. Optogenetic excitation of central amygdala amplifies and narrows incentive motivation to pursue one reward above another.

    Science.gov (United States)

    Robinson, Mike J F; Warlow, Shelley M; Berridge, Kent C

    2014-12-10

    Choosing one reward above another is important for achieving adaptive life goals. Yet hijacked into excessive intensity in disorders such as addiction, single-minded pursuit becomes maladaptive. Here, we report that optogenetic channelrhodopsin stimulation of neurons in central nucleus of amygdala (CeA), paired with earning a particular sucrose reward in rats, amplified and narrowed incentive motivation to that single reward target. Therefore, CeA rats chose and intensely pursued only the laser-paired sucrose reward while ignoring an equally good sucrose alternative. In contrast, reward-paired stimulation of basolateral amygdala did not hijack choice. In a separate measure of incentive motivation, CeA stimulation also increased the progressive ratio breakpoint or level of effort exerted to obtain sucrose reward. However, CeA stimulation by itself failed to support behavioral self-stimulation in the absence of any paired external food reward, suggesting that CeA photo-excitation specifically transformed the value of its external reward (rather than adding an internal reinforcement state). Nor did CeA stimulation by itself induce any aversive state that motivated escape. Finally, CeA stimulation also failed to enhance 'liking' reactions elicited by sucrose taste and did not simply increase the general motivation to eat. This pattern suggests that CeA photo-excitation specifically enhances and narrows incentive motivation to pursue an associated external reward at the expense of another comparable reward. Copyright © 2014 the authors 0270-6474/14/3416567-14$15.00/0.

  3. Neural activity in the medial temporal lobe reveals the fidelity of mental time travel.

    Science.gov (United States)

    Kragel, James E; Morton, Neal W; Polyn, Sean M

    2015-02-18

    Neural circuitry in the medial temporal lobe (MTL) is critically involved in mental time travel, which involves the vivid retrieval of the details of past experience. Neuroscientific theories propose that the MTL supports memory of the past by retrieving previously encoded episodic information, as well as by reactivating a temporal code specifying the position of a particular event within an episode. However, the neural computations supporting these abilities are underspecified. To test hypotheses regarding the computational mechanisms supported by different MTL subregions during mental time travel, we developed a computational model that linked a blood oxygenation level-dependent signal to cognitive operations, allowing us to predict human performance in a memory search task. Activity in the posterior MTL, including parahippocampal cortex, reflected how strongly one reactivates the temporal context of a retrieved memory, allowing the model to predict whether the next memory will correspond to a nearby moment in the study episode. A signal in the anterior MTL, including perirhinal cortex, indicated the successful retrieval of list items, without providing information regarding temporal organization. A hippocampal signal reflected both processes, consistent with theories that this region binds item and context information together to form episodic memories. These findings provide evidence for modern theories that describe complementary roles of the hippocampus and surrounding parahippocampal and perirhinal cortices during the retrieval of episodic memories, shaping how humans revisit the past. Copyright © 2015 the authors 0270-6474/15/352914-13$15.00/0.

  4. Role of the dorsal medial habenula in the regulation of voluntary activity, motor function, hedonic state, and primary reinforcement.

    Science.gov (United States)

    Hsu, Yun-Wei A; Wang, Si D; Wang, Shirong; Morton, Glenn; Zariwala, Hatim A; de la Iglesia, Horacio O; Turner, Eric E

    2014-08-20

    The habenular complex in the epithalamus consists of distinct regions with diverse neuronal populations. Past studies have suggested a role for the habenula in voluntary exercise motivation and reinforcement of intracranial self-stimulation but have not assigned these effects to specific habenula subnuclei. Here, we have developed a genetic model in which neurons of the dorsal medial habenula (dMHb) are developmentally eliminated, via tissue-specific deletion of the transcription factor Pou4f1 (Brn3a). Mice with dMHb lesions perform poorly in motivation-based locomotor behaviors, such as voluntary wheel running and the accelerating rotarod, but show only minor abnormalities in gait and balance and exhibit normal levels of basal locomotion. These mice also show deficits in sucrose preference, but not in the forced swim test, two measures of depression-related phenotypes in rodents. We have also used Cre recombinase-mediated expression of channelrhodopsin-2 and halorhodopsin to activate dMHb neurons or silence their output in freely moving mice, respectively. Optical activation of the dMHb in vivo supports intracranial self-stimulation, showing that dMHb activity is intrinsically reinforcing, whereas optical silencing of dMHb outputs is aversive. Together, our findings demonstrate that the dMHb is involved in exercise motivation and the regulation of hedonic state, and is part of an intrinsic reinforcement circuit. Copyright © 2014 the authors 0270-6474/14/3411366-19$15.00/0.

  5. Reactivation of Reward-Related Patterns from Single Past Episodes Supports Memory-Based Decision Making.

    Science.gov (United States)

    Wimmer, G Elliott; Büchel, Christian

    2016-03-09

    Rewarding experiences exert a strong influence on later decision making. While decades of neuroscience research have shown how reinforcement gradually shapes preferences, decisions are often influenced by single past experiences. Surprisingly, relatively little is known about the influence of single learning episodes. Although recent work has proposed a role for episodes in decision making, it is largely unknown whether and how episodic experiences contribute to value-based decision making and how the values of single episodes are represented in the brain. In multiple behavioral experiments and an fMRI experiment, we tested whether and how rewarding episodes could support later decision making. Participants experienced episodes of high reward or low reward in conjunction with incidental, trial-unique neutral pictures. In a surprise test phase, we found that participants could indeed remember the associated level of reward, as evidenced by accurate source memory for value and preferences to re-engage with rewarded objects. Further, in a separate experiment, we found that high-reward objects shown as primes before a gambling task increased financial risk taking. Neurally, re-exposure to objects in the test phase led to significant reactivation of reward-related patterns. Importantly, individual variability in the strength of reactivation predicted value memory performance. Our results provide a novel demonstration that affect-related neural patterns are reactivated during later experience. Reactivation of value information represents a mechanism by which memory can guide decision making. Copyright © 2016 the authors 0270-6474/16/362868-13$15.00/0.

  6. Typical and Atypical Development of Functional Connectivity in the Face Network.

    Science.gov (United States)

    Song, Yiying; Zhu, Qi; Li, Jingguang; Wang, Xu; Liu, Jia

    2015-10-28

    Extensive studies have demonstrated that face recognition performance does not reach adult levels until adolescence. However, there is no consensus on whether such prolonged improvement stems from development of general cognitive factors or face-specific mechanisms. Here, we used behavioral experiments and functional magnetic resonance imaging (fMRI) to evaluate these two hypotheses. With a large cohort of children (n = 379), we found that the ability of face-specific recognition in humans increased with age throughout childhood and into late adolescence in both face memory and face perception. Neurally, to circumvent the potential problem of age differences in task performance, attention, or cognitive strategies in task-state fMRI studies, we measured the resting-state functional connectivity (RSFC) between the occipital face area (OFA) and fusiform face area (FFA) in human brain and found that the OFA-FFA RSFC increased until 11-13 years of age. Moreover, the OFA-FFA RSFC was selectively impaired in adults with developmental prosopagnosia (DP). In contrast, no age-related changes or differences between DP and normal adults were observed for RSFCs in the object system. Finally, the OFA-FFA RSFC matured earlier than face selectivity in either the OFA or FFA. These results suggest the critical role of the OFA-FFA RSFC in the development of face recognition. Together, our findings support the hypothesis that prolonged development of face recognition is face specific, not domain general. Copyright © 2015 the authors 0270-6474/15/3514624-12$15.00/0.

  7. Development of thalamocortical connectivity during infancy and its cognitive correlations.

    Science.gov (United States)

    Alcauter, Sarael; Lin, Weili; Smith, J Keith; Short, Sarah J; Goldman, Barbara D; Reznick, J Steven; Gilmore, John H; Gao, Wei

    2014-07-02

    Although commonly viewed as a sensory information relay center, the thalamus has been increasingly recognized as an essential node in various higher-order cognitive circuits, and the underlying thalamocortical interaction mechanism has attracted increasing scientific interest. However, the development of thalamocortical connections and how such development relates to cognitive processes during the earliest stages of life remain largely unknown. Leveraging a large human pediatric sample (N = 143) with longitudinal resting-state fMRI scans and cognitive data collected during the first 2 years of life, we aimed to characterize the age-dependent development of thalamocortical connectivity patterns by examining the functional relationship between the thalamus and nine cortical functional networks and determine the correlation between thalamocortical connectivity and cognitive performance at ages 1 and 2 years. Our results revealed that the thalamus-sensorimotor and thalamus-salience connectivity networks were already present in neonates, whereas the thalamus-medial visual and thalamus-default mode network connectivity emerged later, at 1 year of age. More importantly, brain-behavior analyses based on the Mullen Early Learning Composite Score and visual-spatial working memory performance measured at 1 and 2 years of age highlighted significant correlations with the thalamus-salience network connectivity. These results provide new insights into the understudied early functional brain development process and shed light on the behavioral importance of the emerging thalamocortical connectivity during infancy. Copyright © 2014 the authors 0270-6474/14/349067-09$15.00/0.

  8. Activity in human visual and parietal cortex reveals object-based attention in working memory.

    Science.gov (United States)

    Peters, Benjamin; Kaiser, Jochen; Rahm, Benjamin; Bledowski, Christoph

    2015-02-25

    Visual attention enables observers to select behaviorally relevant information based on spatial locations, features, or objects. Attentional selection is not limited to physically present visual information, but can also operate on internal representations maintained in working memory (WM) in service of higher-order cognition. However, only little is known about whether attention to WM contents follows the same principles as attention to sensory stimuli. To address this question, we investigated in humans whether the typically observed effects of object-based attention in perception are also evident for object-based attentional selection of internal object representations in WM. In full accordance with effects in visual perception, the key behavioral and neuronal characteristics of object-based attention were observed in WM. Specifically, we found that reaction times were shorter when shifting attention to memory positions located on the currently attended object compared with equidistant positions on a different object. Furthermore, functional magnetic resonance imaging and multivariate pattern analysis of visuotopic activity in visual (areas V1-V4) and parietal cortex revealed that directing attention to one position of an object held in WM also enhanced brain activation for other positions on the same object, suggesting that attentional selection in WM activates the entire object. This study demonstrated that all characteristic features of object-based attention are present in WM and thus follows the same principles as in perception. Copyright © 2015 the authors 0270-6474/15/353360-10$15.00/0.

  9. Feedforward and feedback motor control abnormalities implicate cerebellar dysfunctions in autism spectrum disorder.

    Science.gov (United States)

    Mosconi, Matthew W; Mohanty, Suman; Greene, Rachel K; Cook, Edwin H; Vaillancourt, David E; Sweeney, John A

    2015-02-04

    Sensorimotor abnormalities are common in autism spectrum disorder (ASD) and among the earliest manifestations of the disorder. They have been studied far less than the social-communication and cognitive deficits that define ASD, but a mechanistic understanding of sensorimotor abnormalities in ASD may provide key insights into the neural underpinnings of the disorder. In this human study, we examined rapid, precision grip force contractions to determine whether feedforward mechanisms supporting initial motor output before sensory feedback can be processed are disrupted in ASD. Sustained force contractions also were examined to determine whether reactive adjustments to ongoing motor behavior based on visual feedback are altered. Sustained force was studied across multiple force levels and visual gains to assess motor and visuomotor mechanisms, respectively. Primary force contractions of individuals with ASD showed greater peak rate of force increases and large transient overshoots. Individuals with ASD also showed increased sustained force variability that scaled with force level and was more severe when visual gain was highly amplified or highly degraded. When sustaining a constant force level, their reactive adjustments were more periodic than controls, and they showed increased reliance on slower feedback mechanisms. Feedforward and feedback mechanism alterations each were associated with more severe social-communication impairments in ASD. These findings implicate anterior cerebellar circuits involved in feedforward motor control and posterior cerebellar circuits involved in transforming visual feedback into precise motor adjustments in ASD. Copyright © 2015 the authors 0270-6474/15/352015-11$15.00/0.

  10. Motion makes sense: an adaptive motor-sensory strategy underlies the perception of object location in rats.

    Science.gov (United States)

    Saraf-Sinik, Inbar; Assa, Eldad; Ahissar, Ehud

    2015-06-10

    Tactile perception is obtained by coordinated motor-sensory processes. We studied the processes underlying the perception of object location in freely moving rats. We trained rats to identify the relative location of two vertical poles placed in front of them and measured at high resolution the motor and sensory variables (19 and 2 variables, respectively) associated with this whiskers-based perceptual process. We found that the rats developed stereotypic head and whisker movements to solve this task, in a manner that can be described by several distinct behavioral phases. During two of these phases, the rats' whiskers coded object position by first temporal and then angular coding schemes. We then introduced wind (in two opposite directions) and remeasured their perceptual performance and motor-sensory variables. Our rats continued to perceive object location in a consistent manner under wind perturbations while maintaining all behavioral phases and relatively constant sensory coding. Constant sensory coding was achieved by keeping one group of motor variables (the "controlled variables") constant, despite the perturbing wind, at the cost of strongly modulating another group of motor variables (the "modulated variables"). The controlled variables included coding-relevant variables, such as head azimuth and whisker velocity. These results indicate that consistent perception of location in the rat is obtained actively, via a selective control of perception-relevant motor variables. Copyright © 2015 the authors 0270-6474/15/358777-13$15.00/0.

  11. Combinatorial mutagenesis of the voltage-sensing domain enables the optical resolution of action potentials firing at 60 Hz by a genetically encoded fluorescent sensor of membrane potential.

    Science.gov (United States)

    Piao, Hong Hua; Rajakumar, Dhanarajan; Kang, Bok Eum; Kim, Eun Ha; Baker, Bradley J

    2015-01-07

    ArcLight is a genetically encoded fluorescent voltage sensor using the voltage-sensing domain of the voltage-sensing phosphatase from Ciona intestinalis that gives a large but slow-responding optical signal in response to changes in membrane potential (Jin et al., 2012). Fluorescent voltage sensors using the voltage-sensing domain from other species give faster yet weaker optical signals (Baker et al., 2012; Han et al., 2013). Sequence alignment of voltage-sensing phosphatases from different species revealed conserved polar and charged residues at 7 aa intervals in the S1-S3 transmembrane segments of the voltage-sensing domain, suggesting potential coil-coil interactions. The contribution of these residues to the voltage-induced optical signal was tested using a cassette mutagenesis screen by flanking each transmembrane segment with unique restriction sites to allow for the testing of individual mutations in each transmembrane segment, as well as combinations in all four transmembrane segments. Addition of a counter charge in S2 improved the kinetics of the optical response. A double mutation in the S4 domain dramatically reduced the slow component of the optical signal seen in ArcLight. Combining that double S4 mutant with the mutation in the S2 domain yielded a probe with kinetics voltage-sensing domain could potentially lead to fluorescent sensors capable of optically resolving neuronal inhibition and subthreshold synaptic activity. Copyright © 2015 the authors 0270-6474/15/350372-15$15.00/0.

  12. The Puzzle of Visual Development: Behavior and Neural Limits.

    Science.gov (United States)

    Kiorpes, Lynne

    2016-11-09

    The development of visual function takes place over many months or years in primate infants. Visual sensitivity is very poor near birth and improves over different times courses for different visual functions. The neural mechanisms that underlie these processes are not well understood despite many decades of research. The puzzle arises because research into the factors that limit visual function in infants has found surprisingly mature neural organization and adult-like receptive field properties in very young infants. The high degree of visual plasticity that has been documented during the sensitive period in young children and animals leaves the brain vulnerable to abnormal visual experience. Abnormal visual experience during the sensitive period can lead to amblyopia, a developmental disorder of vision affecting ∼3% of children. This review provides a historical perspective on research into visual development and the disorder amblyopia. The mismatch between the status of the primary visual cortex and visual behavior, both during visual development and in amblyopia, is discussed, and several potential resolutions are considered. It seems likely that extrastriate visual areas further along the visual pathways may set important limits on visual function and show greater vulnerability to abnormal visual experience. Analyses based on multiunit, population activity may provide useful representations of the information being fed forward from primary visual cortex to extrastriate processing areas and to the motor output. Copyright © 2016 the authors 0270-6474/16/3611384-10$15.00/0.

  13. Zic-Proteins Are Repressors of Dopaminergic Forebrain Fate in Mice and C. elegans.

    Science.gov (United States)

    Tiveron, Marie-Catherine; Beclin, Christophe; Murgan, Sabrina; Wild, Stefan; Angelova, Alexandra; Marc, Julie; Coré, Nathalie; de Chevigny, Antoine; Herrera, Eloisa; Bosio, Andreas; Bertrand, Vincent; Cremer, Harold

    2017-11-01

    In the postnatal forebrain regionalized neural stem cells along the ventricular walls produce olfactory bulb (OB) interneurons with varying neurotransmitter phenotypes and positions. To understand the molecular basis of this region-specific variability we analyzed gene expression in the postnatal dorsal and lateral lineages in mice of both sexes from stem cells to neurons. We show that both lineages maintain transcription factor signatures of their embryonic site of origin, the pallium and subpallium. However, additional factors, including Zic1 and Zic2, are postnatally expressed in the dorsal stem cell compartment and maintained in the lineage that generates calretinin-positive GABAergic neurons for the OB. Functionally, we show that Zic1 and Zic2 induce the generation of calretinin-positive neurons while suppressing dopaminergic fate in the postnatal dorsal lineage. We investigated the evolutionary conservation of the dopaminergic repressor function of Zic proteins and show that it is already present in C. elegans SIGNIFICANCE STATEMENT The vertebrate brain generates thousands of different neuron types. In this work we investigate the molecular mechanisms underlying this variability. Using a genomics approach we identify the transcription factor signatures of defined neural stem cells and neuron populations. Based thereon we show that two related transcription factors, Zic1 and Zic2, are essential to control the balance between two defined neuron types in the postnatal brain. We show that this mechanism is conserved in evolutionary very distant species. Copyright © 2017 the authors 0270-6474/17/3710611-13$15.00/0.

  14. Neural mechanisms of human perceptual choice under focused and divided attention.

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    Wyart, Valentin; Myers, Nicholas E; Summerfield, Christopher

    2015-02-25

    Perceptual decisions occur after the evaluation and integration of momentary sensory inputs, and dividing attention between spatially disparate sources of information impairs decision performance. However, it remains unknown whether dividing attention degrades the precision of sensory signals, precludes their conversion into decision signals, or dampens the integration of decision information toward an appropriate response. Here we recorded human electroencephalographic (EEG) activity while participants categorized one of two simultaneous and independent streams of visual gratings according to their average tilt. By analyzing trial-by-trial correlations between EEG activity and the information offered by each sample, we obtained converging behavioral and neural evidence that dividing attention between left and right visual fields does not dampen the encoding of sensory or decision information. Under divided attention, momentary decision information from both visual streams was encoded in slow parietal signals without interference but was lost downstream during their integration as reflected in motor mu- and beta-band (10-30 Hz) signals, resulting in a "leaky" accumulation process that conferred greater behavioral influence to more recent samples. By contrast, sensory inputs that were explicitly cued as irrelevant were not converted into decision signals. These findings reveal that a late cognitive bottleneck on information integration limits decision performance under divided attention, and places new capacity constraints on decision-theoretic models of information integration under cognitive load. Copyright © 2015 the authors 0270-6474/15/353485-14$15.00/0.

  15. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults.

    Science.gov (United States)

    Witte, A Veronica; Kerti, Lucia; Margulies, Daniel S; Flöel, Agnes

    2014-06-04

    Dietary habits such as caloric restriction or nutrients that mimic these effects may exert beneficial effects on brain aging. The plant-derived polyphenol resveratrol has been shown to increase memory performance in primates; however, interventional studies in older humans are lacking. Here, we tested whether supplementation of resveratrol would enhance memory performance in older adults and addressed potential mechanisms underlying this effect. Twenty-three healthy overweight older individuals that successfully completed 26 weeks of resveratrol intake (200 mg/d) were pairwise matched to 23 participants that received placebo (total n = 46, 18 females, 50-75 years). Before and after the intervention/control period, subjects underwent memory tasks and neuroimaging to assess volume, microstructure, and functional connectivity (FC) of the hippocampus, a key region implicated in memory functions. In addition, anthropometry, glucose and lipid metabolism, inflammation, neurotrophic factors, and vascular parameters were assayed. We observed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p = 0.038). In addition, resveratrol led to significant increases in hippocampal FC, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p memory performance in association with improved glucose metabolism and increased hippocampal FC in older adults. Our findings offer the basis for novel strategies to maintain brain health during aging. Copyright © 2014 the authors 0270-6474/14/347862-09$15.00/0.

  16. DCDC2 polymorphism is associated with left temporoparietal gray and white matter structures during development.

    Science.gov (United States)

    Darki, Fahimeh; Peyrard-Janvid, Myriam; Matsson, Hans; Kere, Juha; Klingberg, Torkel

    2014-10-22

    Three genes, DYX1C1, DCDC2, and KIAA0319, have been previously associated with dyslexia, neuronal migration, and ciliary function. Three polymorphisms within these genes, rs3743204 (DYX1C1), rs793842 (DCDC2), and rs6935076 (KIAA0319) have also been linked to normal variability of left temporoparietal white matter volume connecting the middle temporal cortex to the angular and supramarginal gyri. Here, we assessed whether these polymorphisms are also related to the cortical thickness of the associated regions during childhood development using a longitudinal dataset of 76 randomly selected children and young adults who were scanned up to three times each, 2 years apart. rs793842 in DCDC2 was significantly associated with the thickness of left angular and supramarginal gyri as well as the left lateral occipital cortex. The cortex was significantly thicker for T-allele carriers, who also had lower white matter volume and lower reading comprehension scores. There was a negative correlation between white matter volume and cortical thickness, but only white matter volume predicted reading comprehension 2 years after scanning. These results show how normal variability in reading comprehension is related to gene, white matter volume, and cortical thickness in the inferior parietal lobe. Possibly, the variability of gray and white matter structures could both be related to the role of DCDC2 in ciliary function, which affects both neuronal migration and axonal outgrowth. Copyright © 2014 the authors 0270-6474/14/3414455-08$15.00/0.

  17. Characteristics of polypoid lesions in patients undergoing microsurgery of the larynx

    Directory of Open Access Journals (Sweden)

    Ido Filho, Jorge Massaaki

    2014-01-01

    Full Text Available Introduction: Dysphonia is the main symptom of lesions that affect the vocal tract. Many of those lesions may require surgical treatment. Polyps are one of the most common forms of vocal cord lesions and the most prevalent indication for laryngeal microsurgery. There are different types of polyps, and their different characteristics can indicate different prognosis and treatments. Aim: To conduct a comparative study of polypoid lesions (angiomatous and gelatinous in patients undergoing laryngeal microsurgery via an electronic protocol. Method: We prospectively evaluated 93 patients diagnosed with vocal fold polyps; the polyps were classified as angiomatous or gelatinous. Results: In total, 93 patients undergoing laryngeal microsurgery were diagnosed with vocal fold polyps. Of these, 63 (64.74% had angiomatous and 30 (32.26% gelatinous polyps. Most patients with angiomatous polyps were men; their polyps were frequently of medium size, positioned in the middle third of the vocal fold, and accompanied by minimal structural alterations (MSA. In contrast, the majority of patients with gelatinous polyps were women; their polyps were smaller, positioned in the middle and posterior third of the vocal fold, and were not accompanied by MSA. Both types of polyps were more frequently located on the right vocal fold. Conclusion: Angiomatous polyps were more frequently encountered than gelatinous polyps. In addition, correlations between polyp type and sex, polyp size, position, location, and the presence of MSA were observed. Different surgical techniques were used, but the postoperative results were similar and satisfactory after speech therapy.

  18. Disturbed neuronal ER-Golgi sorting of unassembled glycine receptors suggests altered subcellular processing is a cause of human hyperekplexia.

    Science.gov (United States)

    Schaefer, Natascha; Kluck, Christoph J; Price, Kerry L; Meiselbach, Heike; Vornberger, Nadine; Schwarzinger, Stephan; Hartmann, Stephanie; Langlhofer, Georg; Schulz, Solveig; Schlegel, Nadja; Brockmann, Knut; Lynch, Bryan; Becker, Cord-Michael; Lummis, Sarah C R; Villmann, Carmen

    2015-01-07

    Recent studies on the pathogenic mechanisms of recessive hyperekplexia indicate disturbances in glycine receptor (GlyR) α1 biogenesis. Here, we examine the properties of a range of novel glycine receptor mutants identified in human hyperekplexia patients using expression in transfected cell lines and primary neurons. All of the novel mutants localized in the large extracellular domain of the GlyR α1 have reduced cell surface expression with a high proportion of receptors being retained in the ER, although there is forward trafficking of glycosylated subpopulations into the ER-Golgi intermediate compartment and cis-Golgi compartment. CD spectroscopy revealed that the mutant receptors have proportions of secondary structural elements similar to wild-type receptors. Two mutants in loop B (G160R, T162M) were functional, but none of those in loop D/β2-3 were. One nonfunctional truncated mutant (R316X) could be rescued by coexpression with the lacking C-terminal domain. We conclude that a proportion of GlyR α1 mutants can be transported to the plasma membrane but do not necessarily form functional ion channels. We suggest that loop D/β2-3 is an important determinant for GlyR trafficking and functionality, whereas alterations to loop B alter agonist potencies, indicating that residues here are critical elements in ligand binding. Copyright © 2015 the authors 0270-6474/15/350422-16$15.00/0.

  19. Developmental profiles of the intrinsic properties and synaptic function of auditory neurons in preterm and term baboon neonates.

    Science.gov (United States)

    Kim, Sei Eun; Lee, Seul Yi; Blanco, Cynthia L; Kim, Jun Hee

    2014-08-20

    The human fetus starts to hear and undergoes major developmental changes in the auditory system during the third trimester of pregnancy. Although there are significant data regarding development of the auditory system in rodents, changes in intrinsic properties and synaptic function of auditory neurons in developing primate brain at hearing onset are poorly understood. We performed whole-cell patch-clamp recordings of principal neurons in the medial nucleus of trapezoid body (MNTB) in preterm and term baboon brainstem slices to study the structural and functional maturation of auditory synapses. Each MNTB principal neuron received an excitatory input from a single calyx of Held terminal, and this one-to-one pattern of innervation was already formed in preterm baboons delivered at 67% of normal gestation. There was no difference in frequency or amplitude of spontaneous excitatory postsynaptic synaptic currents between preterm and term MNTB neurons. In contrast, the frequency of spontaneous GABA(A)/glycine receptor-mediated inhibitory postsynaptic synaptic currents, which were prevalent in preterm MNTB neurons, was significantly reduced in term MNTB neurons. Preterm MNTB neurons had a higher input resistance than term neurons and fired in bursts, whereas term MNTB neurons fired a single action potential in response to suprathreshold current injection. The maturation of intrinsic properties and dominance of excitatory inputs in the primate MNTB allow it to take on its mature role as a fast and reliable relay synapse. Copyright © 2014 the authors 0270-6474/14/3411399-06$15.00/0.

  20. Impacts of pulsed electric field and heat treatment on quality and sensory properties and microbial inactivation of pomegranate juice.

    Science.gov (United States)

    Evrendilek, Gulsun A

    2017-12-01

    Synergistic effects of pulsed electric field+mild heat on quality properties of pomegranate juice were modeled using the best-fit multiple (non-) linear regression models with inactivation kinetics parameters of Escherichia coli O157:H7 and Staphylococcus aureus. No significant difference was detected between the control and the treated samples in terms of pH; °Brix; total antioxidant capacity; total monomeric anthocyanin content; total ascorbic acid concentration; and the sensory properties of flavor, taste, aftertaste, and overall acceptance ( p > 0.05). An exposure of 65.3 J and 40 ℃ caused an increase on conductivity; titratable acidity; L*, a*, and b* values; and a decrease of browning index, total phenolic content, total antioxidant capacity, total monomeric anthocyanin content, total ascorbic acid concentration, and in the sensory properties of color and sourness in pomegranate juice. The goodness-of-fit for the best-fit multiple (non-) linear regression models in descending order belonged to E. coli O157:H7 (92.98%), S. aureus (84.06%), color a* (83.9%), titratable acidity (81.3%), color L* (78.5%), color b* (78.3%), conductivity (74.8%), total phenolic content (74.1%), and total ascorbic acid concentration (64.74%), respectively. D e and z e values for E. coli O157:H7 and S. aureus ranged from 105.64 to 1093.25 and from 79.18 to 1057.73 µs with 27.39 and 30.80 J, consequently.

  1. Different Roles of Direct and Indirect Frontoparietal Pathways for Individual Working Memory Capacity.

    Science.gov (United States)

    Ekman, Matthias; Fiebach, Christian J; Melzer, Corina; Tittgemeyer, Marc; Derrfuss, Jan

    2016-03-09

    The ability to temporarily store and manipulate information in working memory is a hallmark of human intelligence and differs considerably across individuals, but the structural brain correlates underlying these differences in working memory capacity (WMC) are only poorly understood. In two separate studies, diffusion MRI data and WMC scores were collected for 70 and 109 healthy individuals. Using a combination of probabilistic tractography and network analysis of the white matter tracts, we examined whether structural brain network properties were predictive of individual WMC. Converging evidence from both studies showed that lateral prefrontal cortex and posterior parietal cortex of high-capacity individuals are more densely connected compared with low-capacity individuals. Importantly, our network approach was further able to dissociate putative functional roles associated with two different pathways connecting frontal and parietal regions: a corticocortical pathway and a subcortical pathway. In Study 1, where participants were required to maintain and update working memory items, the connectivity of the direct and indirect pathway was predictive of WMC. In contrast, in Study 2, where participants were required to maintain working memory items without updating, only the connectivity of the direct pathway was predictive of individual WMC. Our results suggest an important dissociation in the circuitry connecting frontal and parietal regions, where direct frontoparietal connections might support storage and maintenance, whereas subcortically mediated connections support the flexible updating of working memory content. Copyright © 2016 the authors 0270-6474/16/362894-10$15.00/0.

  2. Elucidating the role of AII amacrine cells in glutamatergic retinal waves.

    Science.gov (United States)

    Firl, Alana; Ke, Jiang-Bin; Zhang, Lei; Fuerst, Peter G; Singer, Joshua H; Feller, Marla B

    2015-01-28

    Spontaneous retinal activity mediated by glutamatergic neurotransmission-so-called "Stage 3" retinal waves-drives anti-correlated spiking in ON and OFF RGCs during the second week of postnatal development of the mouse. In the mature retina, the activity of a retinal interneuron called the AII amacrine cell is responsible for anti-correlated spiking in ON and OFF α-RGCs. In mature AIIs, membrane hyperpolarization elicits bursting behavior. Here, we postulated that bursting in AIIs underlies the initiation of glutamatergic retinal waves. We tested this hypothesis by using two-photon calcium imaging of spontaneous activity in populations of retinal neurons and by making whole-cell recordings from individual AIIs and α-RGCs in in vitro preparations of mouse retina. We found that AIIs participated in retinal waves, and that their activity was correlated with that of ON α-RGCs and anti-correlated with that of OFF α-RGCs. Though immature AIIs lacked the complement of membrane conductances necessary to generate bursting, pharmacological activation of the M-current, a conductance that modulates bursting in mature AIIs, blocked retinal wave generation. Interestingly, blockade of the pacemaker conductance Ih, a conductance absent in AIIs but present in both ON and OFF cone bipolar cells, caused a dramatic loss of spatial coherence of spontaneous activity. We conclude that during glutamatergic waves, AIIs act to coordinate and propagate activity generated by BCs rather than to initiate spontaneous activity. Copyright © 2015 the authors 0270-6474/15/351675-12$15.00/0.

  3. A combined variable temperature 600 MHz NMR/MD study of the calcium release agent cyclic adenosine diphosphate ribose (cADPR): Structure, conformational analysis, and thermodynamics of the conformational equilibria.

    Science.gov (United States)

    Javornik, Uroš; Plavec, Janez; Wang, Baifan; Graham, Steven M

    2018-01-02

    A combined variable temperature 600 MHz NMR/molecular dynamics study of the Ca 2+ -release agent cyclic adenosine 5'-diphosphate ribose (cADPR) was conducted. In addition to elucidating the major and minor orientations of the conformationally flexible furanose rings, γ- (C4'-C5'), and β- (C5'-O5') bonds, the thermodynamics (ΔH o , ΔS o ) associated with each of these conformational equilibria were determined. Both furanose rings were biased towards a south conformation (64-74%) and both β-bonds heavily favored trans conformations. The R-ring γ-bond was found to exist almost exclusively as the γ + conformer, whereas the A-ring γ-bond was a mixture of the γ + and γ t conformers, with the trans conformer being slightly favored. Enthalpic factors accounted for most of the observed conformational preferences, although the R-ring furanose exists as its major conformation based solely on entropic factors. There was excellent agreement between the NMR and MD results, particularly with regard to the conformer identities, but the MD showed a bias towards γ + conformers. The MD results showed that both N-glycosidic χ-bonds are exclusively syn. Collectively the data allowed for the construction of a model for cADPR in which many of the conformationally flexible units in fact effectively adopt single orientations and where most of the conformational diversity resides in its A-ring furanose and γ-bond. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Recency, repetition, and the multidimensional basis of recognition memory.

    Science.gov (United States)

    Buchsbaum, Bradley R; Lemire-Rodger, Sabrina; Bondad, Ashley; Chepesiuk, Alexander

    2015-02-25

    Recency and repetition are two factors that have large effects on human memory performance. One way of viewing the beneficial impact of these variables on recognition memory is to assume that both factors modulate a unidimensional memory trace strength. Although previous functional neuroimaging studies have indicated that recency and repetition may modulate similar brain structures, particularly in the region of the inferior parietal cortex, there is extensive behavioral evidence that human subjects can make independent and accurate recognition memory judgments about both an item's recency and its frequency. In the present study, we used fMRI to examine patterns of brain activity during recognition memory for auditory-verbal stimuli that were parametrically and orthogonally manipulated in terms of recency and number of repetitions. We found in a continuous recognition paradigm that the lateral inferior parietal cortex, a region that has previously been associated with recollective forms of memory, is highly sensitive to recency but not repetition. In a multivariate analysis of whole-brain activation patterns, we found orthogonal components that dissociated recency and repetition variables, indicating largely independent neural bases underlying these two factors. The results demonstrate that although both recency and repetition dramatically improve recognition memory performance, the neural bases for this improvement are dissociable, and thus are difficult to explain in terms of access to a unitary memory trace. Copyright © 2015 the authors 0270-6474/15/353544-11$15.00/0.

  5. The neural code for face orientation in the human fusiform face area.

    Science.gov (United States)

    Ramírez, Fernando M; Cichy, Radoslaw M; Allefeld, Carsten; Haynes, John-Dylan

    2014-09-03

    Humans recognize faces and objects with high speed and accuracy regardless of their orientation. Recent studies have proposed that orientation invariance in face recognition involves an intermediate representation where neural responses are similar for mirror-symmetric views. Here, we used fMRI, multivariate pattern analysis, and computational modeling to investigate the neural encoding of faces and vehicles at different rotational angles. Corroborating previous studies, we demonstrate a representation of face orientation in the fusiform face-selective area (FFA). We go beyond these studies by showing that this representation is category-selective and tolerant to retinal translation. Critically, by controlling for low-level confounds, we found the representation of orientation in FFA to be compatible with a linear angle code. Aspects of mirror-symmetric coding cannot be ruled out when FFA mean activity levels are considered as a dimension of coding. Finally, we used a parametric family of computational models, involving a biased sampling of view-tuned neuronal clusters, to compare different face angle encoding models. The best fitting model exhibited a predominance of neuronal clusters tuned to frontal views of faces. In sum, our findings suggest a category-selective and monotonic code of face orientation in the human FFA, in line with primate electrophysiology studies that observed mirror-symmetric tuning of neural responses at higher stages of the visual system, beyond the putative homolog of human FFA. Copyright © 2014 the authors 0270-6474/14/3412155-13$15.00/0.

  6. Sleep spindles and intelligence: evidence for a sexual dimorphism.

    Science.gov (United States)

    Ujma, Péter P; Konrad, Boris Nikolai; Genzel, Lisa; Bleifuss, Annabell; Simor, Péter; Pótári, Adrián; Körmendi, János; Gombos, Ferenc; Steiger, Axel; Bódizs, Róbert; Dresler, Martin

    2014-12-03

    Sleep spindles are thalamocortical oscillations in nonrapid eye movement sleep, which play an important role in sleep-related neuroplasticity and offline information processing. Sleep spindle features are stable within and vary between individuals, with, for example, females having a higher number of spindles and higher spindle density than males. Sleep spindles have been associated with learning potential and intelligence; however, the details of this relationship have not been fully clarified yet. In a sample of 160 adult human subjects with a broad IQ range, we investigated the relationship between sleep spindle parameters and intelligence. In females, we found a positive age-corrected association between intelligence and fast sleep spindle amplitude in central and frontal derivations and a positive association between intelligence and slow sleep spindle duration in all except one derivation. In males, a negative association between intelligence and fast spindle density in posterior regions was found. Effects were continuous over the entire IQ range. Our results demonstrate that, although there is an association between sleep spindle parameters and intellectual performance, these effects are more modest than previously reported and mainly present in females. This supports the view that intelligence does not rely on a single neural framework, and stronger neural connectivity manifesting in increased thalamocortical oscillations in sleep is one particular mechanism typical for females but not males. Copyright © 2014 the authors 0270-6474/14/3416358-11$15.00/0.

  7. Attention Determines Contextual Enhancement versus Suppression in Human Primary Visual Cortex.

    Science.gov (United States)

    Flevaris, Anastasia V; Murray, Scott O

    2015-09-02

    Neural responses in primary visual cortex (V1) depend on stimulus context in seemingly complex ways. For example, responses to an oriented stimulus can be suppressed when it is flanked by iso-oriented versus orthogonally oriented stimuli but can also be enhanced when attention is directed to iso-oriented versus orthogonal flanking stimuli. Thus the exact same contextual stimulus arrangement can have completely opposite effects on neural responses-in some cases leading to orientation-tuned suppression and in other cases leading to orientation-tuned enhancement. Here we show that stimulus-based suppression and enhancement of fMRI responses in humans depends on small changes in the focus of attention and can be explained by a model that combines feature-based attention with response normalization. Neurons in the primary visual cortex (V1) respond to stimuli within a restricted portion of the visual field, termed their "receptive field." However, neuronal responses can also be influenced by stimuli that surround a receptive field, although the nature of these contextual interactions and underlying neural mechanisms are debated. Here we show that the response in V1 to a stimulus in the same context can either be suppressed or enhanced depending on the focus of attention. We are able to explain the results using a simple computational model that combines two well established properties of visual cortical responses: response normalization and feature-based enhancement. Copyright © 2015 the authors 0270-6474/15/3512273-08$15.00/0.

  8. Reason's Enemy Is Not Emotion: Engagement of Cognitive Control Networks Explains Biases in Gain/Loss Framing.

    Science.gov (United States)

    Li, Rosa; Smith, David V; Clithero, John A; Venkatraman, Vinod; Carter, R McKell; Huettel, Scott A

    2017-03-29

    In the classic gain/loss framing effect, describing a gamble as a potential gain or loss biases people to make risk-averse or risk-seeking decisions, respectively. The canonical explanation for this effect is that frames differentially modulate emotional processes, which in turn leads to irrational choice behavior. Here, we evaluate the source of framing biases by integrating functional magnetic resonance imaging data from 143 human participants performing a gain/loss framing task with meta-analytic data from >8000 neuroimaging studies. We found that activation during choices consistent with the framing effect were most correlated with activation associated with the resting or default brain, while activation during choices inconsistent with the framing effect was most correlated with the task-engaged brain. Our findings argue against the common interpretation of gain/loss framing as a competition between emotion and control. Instead, our study indicates that this effect results from differential cognitive engagement across decision frames. SIGNIFICANCE STATEMENT The biases frequently exhibited by human decision makers have often been attributed to the presence of emotion. Using a large fMRI sample and analysis of whole-brain networks defined with the meta-analytic tool Neurosynth, we find that neural activity during frame-biased decisions was more significantly associated with default behaviors (and the absence of executive control) than with emotion. These findings point to a role for neuroscience in shaping long-standing psychological theories in decision science. Copyright © 2017 the authors 0270-6474/17/373588-11$15.00/0.

  9. Fast but fleeting: adaptive motor learning processes associated with aging and cognitive decline.

    Science.gov (United States)

    Trewartha, Kevin M; Garcia, Angeles; Wolpert, Daniel M; Flanagan, J Randall

    2014-10-01

    Motor learning has been shown to depend on multiple interacting learning processes. For example, learning to adapt when moving grasped objects with novel dynamics involves a fast process that adapts and decays quickly-and that has been linked to explicit memory-and a slower process that adapts and decays more gradually. Each process is characterized by a learning rate that controls how strongly motor memory is updated based on experienced errors and a retention factor determining the movement-to-movement decay in motor memory. Here we examined whether fast and slow motor learning processes involved in learning novel dynamics differ between younger and older adults. In addition, we investigated how age-related decline in explicit memory performance influences learning and retention parameters. Although the groups adapted equally well, they did so with markedly different underlying processes. Whereas the groups had similar fast processes, they had different slow processes. Specifically, the older adults exhibited decreased retention in their slow process compared with younger adults. Within the older group, who exhibited considerable variation in explicit memory performance, we found that poor explicit memory was associated with reduced retention in the fast process, as well as the slow process. These findings suggest that explicit memory resources are a determining factor in impairments in the both the fast and slow processes for motor learning but that aging effects on the slow process are independent of explicit memory declines. Copyright © 2014 the authors 0270-6474/14/3413411-11$15.00/0.

  10. Revisiting the evidence for collapsing boundaries and urgency signals in perceptual decision-making.

    Science.gov (United States)

    Hawkins, Guy E; Forstmann, Birte U; Wagenmakers, Eric-Jan; Ratcliff, Roger; Brown, Scott D

    2015-02-11

    For nearly 50 years, the dominant account of decision-making holds that noisy information is accumulated until a fixed threshold is crossed. This account has been tested extensively against behavioral and neurophysiological data for decisions about consumer goods, perceptual stimuli, eyewitness testimony, memories, and dozens of other paradigms, with no systematic misfit between model and data. Recently, the standard model has been challenged by alternative accounts that assume that less evidence is required to trigger a decision as time passes. Such "collapsing boundaries" or "urgency signals" have gained popularity in some theoretical accounts of neurophysiology. Nevertheless, evidence in favor of these models is mixed, with support coming from only a narrow range of decision paradigms compared with a long history of support from dozens of paradigms for the standard theory. We conducted the first large-scale analysis of data from humans and nonhuman primates across three distinct paradigms using powerful model-selection methods to compare evidence for fixed versus collapsing bounds. Overall, we identified evidence in favor of the standard model with fixed decision boundaries. We further found that evidence for static or dynamic response boundaries may depend on specific paradigms or procedures, such as the extent of task practice. We conclude that the difficulty of selecting between collapsing and fixed bounds models has received insufficient attention in previous research, calling into question some previous results. Copyright © 2015 the authors 0270-6474/15/352476-09$15.00/0.

  11. Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat.

    Science.gov (United States)

    Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Saletin, Jared M; Walker, Matthew P

    2015-07-15

    Facial expressions represent one of the most salient cues in our environment. They communicate the affective state and intent of an individual and, if interpreted correctly, adaptively influence the behavior of others in return. Processing of such affective stimuli is known to require reciprocal signaling between central viscerosensory brain regions and peripheral-autonomic body systems, culminating in accurate emotion discrimination. Despite emerging links between sleep and affective regulation, the impact of sleep loss on the discrimination of complex social emotions within and between the CNS and PNS remains unknown. Here, we demonstrate in humans that sleep deprivation impairs both viscerosensory brain (anterior insula, anterior cingulate cortex, amygdala) and autonomic-cardiac discrimination of threatening from affiliative facial cues. Moreover, sleep deprivation significantly degrades the normally reciprocal associations between these central and peripheral emotion-signaling systems, most prominent at the level of cardiac-amygdala coupling. In addition, REM sleep physiology across the sleep-rested night significantly predicts the next-day success of emotional discrimination within this viscerosensory network across individuals, suggesting a role for REM sleep in affective brain recalibration. Together, these findings establish that sleep deprivation compromises the faithful signaling of, and the "embodied" reciprocity between, viscerosensory brain and peripheral autonomic body processing of complex social signals. Such impairments hold ecological relevance in professional contexts in which the need for accurate interpretation of social cues is paramount yet insufficient sleep is pervasive. Copyright © 2015 the authors 0270-6474/15/3510135-11$15.00/0.

  12. Atomic physics and quantum optics using superconducting circuits: from the Dynamical Casimir effect to Majorana fermions

    Science.gov (United States)

    Nori, Franco

    2012-02-01

    This talk will present an overview of some of our recent results on atomic physics and quantum optics using superconducting circuits. Particular emphasis will be given to photons interacting with qubits, interferometry, the Dynamical Casimir effect, and also studying Majorana fermions using superconducting circuits.[4pt] References available online at our web site:[0pt] J.Q. You, Z.D. Wang, W. Zhang, F. Nori, Manipulating and probing Majorana fermions using superconducting circuits, (2011). Arxiv. J.R. Johansson, G. Johansson, C.M. Wilson, F. Nori, Dynamical Casimir effect in a superconducting coplanar waveguide, Phys. Rev. Lett. 103, 147003 (2009). [0pt] J.R. Johansson, G. Johansson, C.M. Wilson, F. Nori, Dynamical Casimir effect in superconducting microwave circuits, Phys. Rev. A 82, 052509 (2010). [0pt] C.M. Wilson, G. Johansson, A. Pourkabirian, J.R. Johansson, T. Duty, F. Nori, P. Delsing, Observation of the Dynamical Casimir Effect in a superconducting circuit. Nature, in press (Nov. 2011). P.D. Nation, J.R. Johansson, M.P. Blencowe, F. Nori, Stimulating uncertainty: Amplifying the quantum vacuum with superconducting circuits, Rev. Mod. Phys., in press (2011). [0pt] J.Q. You, F. Nori, Atomic physics and quantum optics using superconducting circuits, Nature 474, 589 (2011). [0pt] S.N. Shevchenko, S. Ashhab, F. Nori, Landau-Zener-Stuckelberg interferometry, Phys. Reports 492, 1 (2010). [0pt] I. Buluta, S. Ashhab, F. Nori. Natural and artificial atoms for quantum computation, Reports on Progress in Physics 74, 104401 (2011). [0pt] I.Buluta, F. Nori, Quantum Simulators, Science 326, 108 (2009). [0pt] L.F. Wei, K. Maruyama, X.B. Wang, J.Q. You, F. Nori, Testing quantum contextuality with macroscopic superconducting circuits, Phys. Rev. B 81, 174513 (2010). [0pt] J.Q. You, X.-F. Shi, X. Hu, F. Nori, Quantum emulation of a spin system with topologically protected ground states using superconducting quantum circuit, Phys. Rev. A 81, 063823 (2010).

  13. Mesospheric dust and its secondary effects as observed by the ESPRIT payload

    Directory of Open Access Journals (Sweden)

    O. Havnes

    2009-03-01

    Full Text Available The dust detector on the ESPRIT rocket detected two extended dust/aerosol layers during the launch on 1 July 2006. The lower layer at height ~81.5–83 km coincided with a strong NLC and PMSE layer. The maximum dust charge density was ~−3.5×109 e m−3 and the dust layer was characterized by a few strong dust layers where the dust charge density at the upper edges changed by factors 2–3 over a distance of ≲10 m, while the same change at their lower edges were much more gradual. The upper edge of this layer is also sharp, with a change in the probe current from zero to IDC=−10−11 A over ~10 m, while the same change at the low edge occurs over ~500 m. The second dust layer at ~85–92 km was in the height range of a comparatively weak PMSE layer and the maximum dust charge density was ~−108 e m−3. This demonstrates that PMSE can be formed even if the ratio of the dust charge density to the electron density P=NdZd /n_e≲0.01. In spite of the dust detector being constructed to reduce possible secondary charging effects from dust impacts, it was found that they were clearly present during the passage through both layers. The measured secondary charging effects confirm recent results that dust in the NLC and PMSE layers can be very effective in producing secondary charges with up to ~50 to 100 electron charges being rubbed off by one impacting large dust particle, if the impact angle is θi≳20–35°. This again lends support to the suggested model for NLC and PMSE dust particles (Havnes and Næsheim, 2007 as a loosely bound water-ice clump interspersed with a considerable number of sub-nanometer-sized meteoric smoke particles, possibly also contaminated with meteoric atomic species.

  14. Mesospheric dust and its secondary effects as observed by the ESPRIT payload

    Science.gov (United States)

    Havnes, O.; Surdal, L. H.; Philbrick, C. R.

    2009-03-01

    The dust detector on the ESPRIT rocket detected two extended dust/aerosol layers during the launch on 1 July 2006. The lower layer at height ~81.5-83 km coincided with a strong NLC and PMSE layer. The maximum dust charge density was ~-3.5×109 e m-3 and the dust layer was characterized by a few strong dust layers where the dust charge density at the upper edges changed by factors 2-3 over a distance of ≲10 m, while the same change at their lower edges were much more gradual. The upper edge of this layer is also sharp, with a change in the probe current from zero to IDC=-10-11 A over ~10 m, while the same change at the low edge occurs over ~500 m. The second dust layer at ~85-92 km was in the height range of a comparatively weak PMSE layer and the maximum dust charge density was ~-108 e m-3. This demonstrates that PMSE can be formed even if the ratio of the dust charge density to the electron density P=NdZd /n_e≲0.01. In spite of the dust detector being constructed to reduce possible secondary charging effects from dust impacts, it was found that they were clearly present during the passage through both layers. The measured secondary charging effects confirm recent results that dust in the NLC and PMSE layers can be very effective in producing secondary charges with up to ~50 to 100 electron charges being rubbed off by one impacting large dust particle, if the impact angle is θi≳20-35°. This again lends support to the suggested model for NLC and PMSE dust particles (Havnes and Næsheim, 2007) as a loosely bound water-ice clump interspersed with a considerable number of sub-nanometer-sized meteoric smoke particles, possibly also contaminated with meteoric atomic species.

  15. Current and simulated structure, growth parameters and regeneration of beech forests with different game management in the Lány Game Enclosure / Struktura, růstové parametry, obnova a modelový vývoj bukových porostů s odlišným způsobem mysliveckého hospodaření v podmínkách Lánské obory

    Directory of Open Access Journals (Sweden)

    Ambrož Robin

    2015-06-01

    Full Text Available V příspěvku jsou prezentovány výsledky studia struktury a dynamiky vývoje bukových porostů v Lánské oboře, která se nachází v Chráněné krajinné oblasti Křivoklátsko v České republice. Výzkum se uskutečnil v dospělém bukovém porostu na dvou trvalých výzkumných plochách (TVP, každá o velikosti 0,25 ha s použitím technologie FieldMap. Typologické, půdní, fytocenologické i porostní charakteristiky obou porovnávaných TVP jsou srovnatelné, odlišují se pouze způsobem ochrany proti zvěři. Výsledky ukázaly, že limitujícím faktorem zdárného vývoje přirozené obnovy buku (Fagus sylvatica L. je vysoká zvěř, a to jelen evropský (Cervus elaphus L. - 300 ks, jelen sika (Cervus nippon nippon Temm. - 300 ks, muflon (Ovis musimon Pallas - 250 ks a daněk skvrnitý (Dama dama L. - 300 ks. Přirozená obnova na TVP 1 s černou zvěří (Sus scrofa L. - 150 ks je dostatečná vzhledem ke stanovištním a porostním poměrům. Naproti tomu na TVP 2 s ostatními druhy zvěře se obnova nevyskytuje. Z výsledků biometrických měření a následných vizualizací pomocí simulátoru biodynamiky lesa Sibyla vyplývá, že se jedná o nevýrazně strukturované, dospělé, produktivní bukové porosty s absencí jedinců spodního stromového patra.

  16. AĞ TOPLUMUNUN İLETİŞİMİ EKSENİNDE YEREL YÖNETİMLERİN SOSYAL MEDYA KULLANIM DÜZEYİ: KADIKÖY BELEDİYESİ ÖRNEĞİ

    Directory of Open Access Journals (Sweden)

    Alper DEĞERLİ

    2016-08-01

    Full Text Available Yeni iletişim ortamlarının sunduğu sayısız olanaklar sayesinde ağ toplumu formunda yeniden şekillenen insanoğlu, bu yeni yapıdaki ilişkiler düzeninin değişimine de tanıklık etmektedir. Etki bağlamındaki kitle iletişim yorumlamalarından etkileşimin ön planda olduğu yatay iletişime doğru bir yol alıştır bu. Bu noktada kamusal iletişimin bu değişimden bağımsız kalacağını düşünmek olanaksızdır. Parasosyal etkileşimin yeniden tanımlandığı, kitle iletişimin monolojik yapısından diyalojik iletişime doğru geçildiği bu yeni kamu-yönetim ilişkisinde kamunun rolü de edilgenden etkene doğru evrilmektedir. Ağ toplumunun kamusal alanları olarak karşımıza çıkan sosyal ağlar vasıtasıyla yönetim ile kamu arasındaki ilişki yeniden yorumlanmakta, kamu kısıtlı da olsa erişebilirlik ve hesap sorabilirlik hakkına yeniden yaklaşabilmektedir.Bu çalışma kapsamında; bireylerde çok daha hızlı gerçeklesen bu zihinsel dönüşümün kamu kurumları açısından doğru yorumlanıp yorumlanmadığı sorusuna, Twitter sosyal ağı üzerinde İstanbul ilçe belediyeleri arasında açık ara en fazla takipçiye sahip belediye olan Kadıköy belediyesi özelinde cevaplar aranmaya çalışılmıştır.

  17. Extended Remediation of Sleep Deprived-Induced Working Memory Deficits Using fMRI-guided Transcranial Magnetic Stimulation

    Science.gov (United States)

    Luber, Bruce; Steffener, Jason; Tucker, Adrienne; Habeck, Christian; Peterchev, Angel V.; Deng, Zhi-De; Basner, Robert C.; Stern, Yaakov; Lisanby, Sarah H.

    2013-01-01

    Study Objectives: We attempted to prevent the development of working memory (WM) impairments caused by sleep deprivation using fMRI-guided repetitive transcranial magnetic stimulation (rTMS). Novel aspects of our fMRI-guided rTMS paradigm included the use of sophisticated covariance methods to identify functional networks in imaging data, and the use of fMRI-targeted rTMS concurrent with task performance to modulate plasticity effects over a longer term. Design: Between-groups mixed model. Setting: TMS, MRI, and sleep laboratory study. Participants: 27 subjects (13 receiving Active rTMS, and 14 Sham) completed the sleep deprivation protocol, with another 21 (10 Active, 11 Sham) non-sleep deprived subjects run in a second experiment. Interventions: Our previous covariance analysis had identified a network, including occipital cortex, which demonstrated individual differences in resilience to the deleterious effects of sleep deprivation on WM performance. Five Hz rTMS was applied to left lateral occipital cortex while subjects performed a WM task during 4 sessions over the course of 2 days of total sleep deprivation. Measurements and Results: At the end of the sleep deprivation period, Sham sleep deprived subjects exhibited degraded performance in the WM task. In contrast, those receiving Active rTMS did not show the slowing and lapsing typical in sleep deprivation, and instead performed similarly to non- sleep deprived subjects. Importantly, the Active sleep deprivation group showed rTMS-induced facilitation of WM performance a full 18 hours after the last rTMS session. Conclusions: Over the course of sleep deprivation, these results indicate that rTMS applied concurrently with WM task performance affected neural circuitry involved in WM to prevent its full impact. Citation: Luber B; Steffener J; Tucker A; Habeck C; Peterchev AV; Deng ZD; Basner RC; Stern Y; Lisanby SH. Extended remediation of sleep deprived-induced working memory deficits using f

  18. z ~ 7-10 Galaxies Behind Lensing Clusters: Contrast with Field Search Results

    Science.gov (United States)

    Bouwens, Rychard J.; Illingworth, Garth D.; Bradley, Larry D.; Ford, Holland; Franx, Marijn; Zheng, Wei; Broadhurst, Tom; Coe, Dan; Jee, M. James

    2009-01-01

    We conduct a search for z gsim 7 dropout galaxies behind 11 massive lensing clusters using 21 arcmin2 of deep Hubble Space Telescope NICMOS, ACS, and WFPC2 image data. In total, over this entire area, we find only one robust z ~ 7 z-dropout candidate (previously reported around Abell 1689). Four less robust z-dropout and J-dropout candidates are also found. The nature of the four weaker candidates could not be precisely determined due to the limited depth of the available optical data, but detailed simulations suggest that all four are likely to be low-redshift interlopers. By contrast, we estimate that our robust candidate A1689-zD1 has dropouts and 0.3 z ~ 9 J-dropouts over our cluster search area, in reasonable agreement with our observational results, given the small numbers. The number of z gsim 7 candidates we find in the present search is much lower than that which has been reported in several previous studies of the prevalence of z gsim 7 galaxies behind lensing clusters. To understand these differences, we examined z gsim 7 candidates in other studies and conclude that only a small fraction are likely to be z gsim 7 galaxies. Our findings support models that show that gravitational lensing from clusters is of the most value for detecting galaxies at magnitudes brighter than L* (H lsim 27) where the LF is expected to be very steep. Use of these clusters to constrain the faint-end slope or determine the full LF is likely of less value due to the shallower effective slope measured for the LF at fainter magnitudes, as well as significant uncertainties introduced from modeling both the gravitational lensing and incompleteness. Based on observations made with the NASA/ESA Hubble Space Telescope, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with programs #5352, 5935, 6488, 8249, 8882, 9289, 9452, 9717, 10150, 10154, 10200, 10325, 10504, 10863, 10996.

  19. ΔF = 2 observables and fine-tuning in a warped extra dimension with custodial protection

    International Nuclear Information System (INIS)

    Blanke, Monika; Buras, Andrzej J.; Duling, Bjoern; Gori, Stefania; Weiler, Andreas

    2009-01-01

    We present a complete study of ΔS = 2 and ΔB = 2 processes in a warped extra dimensional model with a custodial protection of Zb L b-bar L , including ε K , ΔM K , ΔM s , ΔM d , A SL q , ΔΓ q , A CP (B d →ψK S ) and A CP (B s →ψφ). These processes are affected by tree level contributions from Kaluza-Klein gluons, the heavy KK photon, new heavy electroweak gauge bosons Z H and Z', and in principle by tree level Z contributions. We confirm recent findings that the fully anarchic approach where all the hierarchies in quark masses and weak mixing angles are geometrically explained seems implausible and we confirm that the KK mass scale M KK generically has to be at least ∼ 20 TeV to satisfy the ε K constraint. We point out, however, that there exist regions in parameter space with only modest fine-tuning in the 5D Yukawa couplings which satisfy all existing ΔF = 2 and electroweak precision constraints for scales M KK ≅ 3 TeV in reach of the LHC. Simultaneously we find that A CP (B s → ψφ) and A s SL can be much larger than in the SM as indicated by recent results from CDF and DOe data. We point out that for B d,s physics ΔF = 2 observables the complex (Z H ,Z') can compete with KK gluons, while the tree level Z and KK photon contributions are very small. In particular we point out that the Zd i L d-bar j L couplings are protected by the custodial symmetry. As a by-product we show the relation of the RS flavour model to the Froggatt-Nielsen mechanism and we provide analytic formulae for the effective flavour mixing matrices in terms of the fundamental 5D parameters.

  20. The galaxy major merger fraction to {z} 1

    Science.gov (United States)

    López-Sanjuan, C.; Balcells, M.; Pérez-González, P. G.; Barro, G.; García-Dabó, C. E.; Gallego, J.; Zamorano, J.

    2009-07-01

    Aims: The importance of disc-disc major mergers in galaxy evolution remains uncertain. We study the major merger fraction in a SPITZER/IRAC-selected catalogue in the GOODS-S field up to z 1 for luminosity- and mass-limited samples. Methods: We select disc-disc merger remnants on the basis of morphological asymmetries/distortions, and address three main sources of systematic errors: (i) we explicitly apply morphological K-corrections; (ii) we measure asymmetries in galaxies artificially redshifted to zd = 1.0 to deal with loss of morphological information with redshift; and (iii) we take into account the observational errors in z and A, which tend to overestimate the merger fraction, though use of maximum likelihood techniques. Results: We obtain morphological merger fractions (f_m^mph) below 0.06 up to z 1. Parameterizing the merger fraction evolution with redshift as f_m^mph(z) = f_m^mph(0) (1+z)^m, we find that m = 1.8 ± 0.5 for MB ≤ -20 galaxies, while m = 5.4 ± 0.4 for Mstar ≥ 1010 M⊙ galaxies. When we translate our merger fractions to merger rates (Re_m^mph), their evolution, parameterized as Re_m^mph(z) = Re_m^mph(0) (1+z)^n, is quite similar in both cases: n = 3.3 ± 0.8 for MB ≤ -20 galaxies, and n = 3.5 ± 0.4 for Mstar ≥ 1010 M⊙ galaxies. Conclusions: Our results imply that only 8% of today's Mstar ≥ 1010 M⊙ galaxies have undergone a disc-disc major merger since z 1. In addition, 21% of Mstar ≥ 1010 M⊙ galaxies at z 1 have undergone one of these mergers since z 1.5. This suggests that disc-disc major mergers are not the dominant process in the evolution of Mstar ≥ 1010 M⊙ galaxies since z 1, with only 0.2 disc-disc major mergers per galaxy, but may be an important process at z > 1, with ˜1 merger per galaxy at 1 < z < 3.

  1. Population responses in V1 encode different figures by response amplitude.

    Science.gov (United States)

    Gilad, Ariel; Slovin, Hamutal

    2015-04-22

    The visual system simultaneously segregates between several objects presented in a visual scene. The neural code for encoding different objects or figures is not well understood. To study this question, we trained two monkeys to discriminate whether two elongated bars are either separate, thus generating two different figures, or connected, thus generating a single figure. Using voltage-sensitive dyes, we imaged at high spatial and temporal resolution V1 population responses evoked by the two bars, while keeping their local attributes similar among the two conditions. In the separate condition, unlike the connected condition, the population response to one bar is enhanced, whereas the response to the other is simultaneously suppressed. The response to the background remained unchanged between the two conditions. This divergent pattern developed ∼200 ms poststimulus onset and could discriminate well between the separate and connected single trials. The stimulus separation saliency and behavioral report were highly correlated with the differential response to the bars. In addition, the proximity and/or the specific location of the connectors seemed to have only a weak effect on this late activity pattern, further supporting the involvement of top-down influences. Additional neural codes were less informative about the separate and connected conditions, with much less consistency and discriminability compared with a response amplitude code. We suggest that V1 is involved in the encoding of each figure by different neuronal response amplitude, which can mediate their segregation and perception. Copyright © 2015 the authors 0270-6474/15/356335-15$15.00/0.

  2. Changes in Purkinje cell simple spike encoding of reach kinematics during adaption to a mechanical perturbation.

    Science.gov (United States)

    Hewitt, Angela L; Popa, Laurentiu S; Ebner, Timothy J

    2015-01-21

    The cerebellum is essential in motor learning. At the cellular level, changes occur in both the simple spike and complex spike firing of Purkinje cells. Because simple spike discharge reflects the main output of the cerebellar cortex, changes in simple spike firing likely reflect the contribution of the cerebellum to the adapted behavior. Therefore, we investigated in Rhesus monkeys how the representation of arm kinematics in Purkinje cell simple spike discharge changed during adaptation to mechanical perturbations of reach movements. Monkeys rapidly adapted to a novel assistive or resistive perturbation along the direction of the reach. Adaptation consisted of matching the amplitude and timing of the perturbation to minimize its effect on the reach. In a majority of Purkinje cells, simple spike firing recorded before and during adaptation demonstrated significant changes in position, velocity, and acceleration sensitivity. The timing of the simple spike representations change within individual cells, including shifts in predictive versus feedback signals. At the population level, feedback-based encoding of position increases early in learning and velocity decreases. Both timing changes reverse later in learning. The complex spike discharge was only weakly modulated by the perturbations, demonstrating that the changes in simple spike firing can be independent of climbing fiber input. In summary, we observed extensive alterations in individual Purkinje cell encoding of reach kinematics, although the movements were nearly identical in the baseline and adapted states. Therefore, adaption to mechanical perturbation of a reaching movement is accompanied by widespread modifications in the simple spike encoding. Copyright © 2015 the authors 0270-6474/15/351106-19$15.00/0.

  3. Unilateral prefrontal lesions impair memory-guided comparisons of contralateral visual motion.

    Science.gov (United States)

    Pasternak, Tatiana; Lui, Leo L; Spinelli, Philip M

    2015-05-06

    The contribution of the lateral prefrontal cortex (LPFC) to working memory is the topic of active debate. On the one hand, it has been argued that the persistent delay activity in LPFC recorded during some working memory tasks is a reflection of sensory storage, the notion supported by some lesion studies. On the other hand, there is emerging evidence that the LPFC plays a key role in the maintenance of sensory information not by storing relevant visual signals but by allocating visual attention to such stimuli. In this study, we addressed this question by examining the effects of unilateral LPFC lesions during a working memory task requiring monkeys to compare directions of two moving stimuli, separated by a delay. The lesions resulted in impaired thresholds for contralesional stimuli at longer delays, and these deficits were most dramatic when the task required rapid reallocation of spatial attention. In addition, these effects were equally pronounced when the remembered stimuli were at threshold or moved coherently. The contralesional nature of the deficits points to the importance of the interactions between the LPFC and the motion processing neurons residing in extrastriate area MT. Delay-specificity of the deficit supports LPFC involvement in the maintenance stage of the comparison task. However, because this deficit was independent of stimulus features giving rise to the remembered direction and was most pronounced during rapid shifts of attention, its role is more likely to be attending and accessing the preserved motion signals rather than their storage. Copyright © 2015 the authors 0270-6474/15/357095-11$15.00/0.

  4. Reward-dependent modulation of movement variability.

    Science.gov (United States)

    Pekny, Sarah E; Izawa, Jun; Shadmehr, Reza

    2015-03-04

    Movement variability is often considered an unwanted byproduct of a noisy nervous system. However, variability can signal a form of implicit exploration, indicating that the nervous system is intentionally varying the motor commands in search of actions that yield the greatest success. Here, we investigated the role of the human basal ganglia in controlling reward-dependent motor variability as measured by trial-to-trial changes in performance during a reaching task. We designed an experiment in which the only performance feedback was success or failure and quantified how reach variability was modulated as a function of the probability of reward. In healthy controls, reach variability increased as the probability of reward decreased. Control of variability depended on the history of past rewards, with the largest trial-to-trial changes occurring immediately after an unrewarded trial. In contrast, in participants with Parkinson's disease, a known example of basal ganglia dysfunction, reward was a poor modulator of variability; that is, the patients showed an impaired ability to increase variability in response to decreases in the probability of reward. This was despite the fact that, after rewarded trials, reach variability in the patients was comparable to healthy controls. In summary, we found that movement variability is partially a form of exploration driven by the recent history of rewards. When the function of the human basal ganglia is compromised, the reward-dependent control of movement variability is impaired, particularly affecting the ability to increase variability after unsuccessful outcomes. Copyright © 2015 the authors 0270-6474/15/354015-10$15.00/0.

  5. The Quest for the FFA and Where It Led.

    Science.gov (United States)

    Kanwisher, Nancy

    2017-02-01

    This article tells the story behind our first paper on the fusiform face area (FFA): how we chose the question, developed the methods, and followed the data to find the FFA and subsequently many other functionally specialized cortical regions. The paper's impact had less to do with the particular findings in the paper itself and more to do with the method that it promoted and the picture of the human mind and brain that it led to. The use of a functional localizer to define a candidate region in each subject individually enabled us not just to make pictures of brain activation, but also to ask principled, hypothesis-driven questions about a thing in nature. This method enabled stronger and more extensive tests of the function of each cortical region than had been possible before in humans and, as a result, has produced a large body of evidence that the human cortex contains numerous regions that are specifically engaged in particular mental processes. The growing inventory of cortical regions with distinctive and often very specific functions can be seen as an initial sketch of the basic components of the human mind. This sketch also serves as a roadmap into the vast and exciting new landscape of questions about the computations, structural connections, time course, development, plasticity, and evolution of each of these regions, as well as the hardest question of all: how do these regions work together to produce human intelligence? Copyright © 2017 the authors 0270-6474/17/371056-06$15.00/0.

  6. Evaluating the Role of Prophylactic Gastrostomy Tube Placement Prior to Definitive Chemoradiotherapy for Head and Neck Cancer

    International Nuclear Information System (INIS)

    Chen, Allen M.; Li Baoqing; Lau, Derick H.; Farwell, D. Gregory; Luu, Quang; Stuart, Kerri; Newman, Kathleen; Purdy, James A.; Vijayakumar, Srinivasan M.D.

    2010-01-01

    Purpose: To determine the effect of prophylactic gastrostomy tube (GT) placement on acute and long-term outcome for patients treated with definitive chemoradiotherapy for locally advanced head and neck cancer. Methods and Materials: One hundred twenty consecutive patients were treated with chemoradiotherapy for Stage III/IV head and neck cancer to a median dose of 70 Gy (range, 64-74 Gy). The most common primary site was the oropharynx (66 patients). Sixty-seven patients (56%) were treated using intensity-modulated radiotherapy (IMRT). Seventy patients (58%) received prophylactic GT placement at the discretion of the physician before initiation of chemoradiotherapy. Results: Prophylactic GT placement significantly reduced weight loss during radiation therapy from 43 pounds (range, 0 to 76 pounds) to 19 pounds (range, 0 to 51 pounds), which corresponded to a net change of -14% (range, 0% to -30%) and -8% (range, +1% to -22%) from baseline, respectively (p < 0.001). However, the proportion of patients who were GT-dependent at 6- and 12-months after treatment was 41% and 21%, respectively, compared with 8% and 0%, respectively, for those with and without prophylactic GT (p < 0.001). Additionally, prophylactic GT was associated with a significantly higher incidence of late esophageal stricture compared with those who did not have prophylactic GT (30% vs. 6%, p < 0.001). Conclusions: Although prophylactic GT placement was effective at preventing acute weight loss and the need for intravenous hydration, it was also associated with significantly higher rates of late esophageal toxicity. The benefits of this strategy must be balanced with the risks.

  7. Developmental Changes in Brain Network Hub Connectivity in Late Adolescence.

    Science.gov (United States)

    Baker, Simon T E; Lubman, Dan I; Yücel, Murat; Allen, Nicholas B; Whittle, Sarah; Fulcher, Ben D; Zalesky, Andrew; Fornito, Alex

    2015-06-17

    The human brain undergoes substantial development throughout adolescence and into early adulthood. This maturational process is thought to include the refinement of connectivity between putative connectivity hub regions of the brain, which collectively form a dense core that enhances the functional integration of anatomically distributed, and functionally specialized, neural systems. Here, we used longitudinal diffusion magnetic resonance imaging to characterize changes in connectivity between 80 cortical and subcortical anatomical regions over a 2 year period in 31 adolescents between the ages of 15 and 19 years. Connectome-wide analysis indicated that only a small subset of connections showed evidence of statistically significant developmental change over the study period, with 8% and 6% of connections demonstrating decreased and increased structural connectivity, respectively. Nonetheless, these connections linked 93% and 90% of the 80 regions, respectively, pointing to a selective, yet anatomically distributed pattern of developmental changes that involves most of the brain. Hub regions showed a distinct tendency to be highly connected to each other, indicating robust "rich-club" organization. Moreover, connectivity between hubs was disproportionately influenced by development, such that connectivity between subcortical hubs decreased over time, whereas frontal-subcortical and frontal-parietal hub-hub connectivity increased over time. These findings suggest that late adolescence is characterized by selective, yet significant remodeling of hub-hub connectivity, with the topological organization of hubs shifting emphasis from subcortical hubs in favor of an increasingly prominent role for frontal hub regions. Copyright © 2015 the authors 0270-6474/15/359078-10$15.00/0.

  8. White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging.

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    Kranz, Georg S; Hahn, Andreas; Kaufmann, Ulrike; Küblböck, Martin; Hummer, Allan; Ganger, Sebastian; Seiger, Rene; Winkler, Dietmar; Swaab, Dick F; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

    2014-11-12

    Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects' sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development. Copyright © 2014 the authors 0270-6474/14/3415466-10$15.00/0.

  9. Synaptic properties of SOM- and CCK-expressing cells in dentate gyrus interneuron networks.

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    Savanthrapadian, Shakuntala; Meyer, Thomas; Elgueta, Claudio; Booker, Sam A; Vida, Imre; Bartos, Marlene

    2014-06-11

    Hippocampal GABAergic cells are highly heterogeneous, but the functional significance of this diversity is not fully understood. By using paired recordings of synaptically connected interneurons in slice preparations of the rat and mouse dentate gyrus (DG), we show that morphologically identified interneurons form complex neuronal networks. Synaptic inhibitory interactions exist between cholecystokinin (CCK)-expressing hilar commissural associational path (HICAP) cells and among somatostatin (SOM)-containing hilar perforant path-associated (HIPP) interneurons. Moreover, both interneuron types inhibit parvalbumin (PV)-expressing perisomatic inhibitory basket cells (BCs), whereas BCs and HICAPs rarely target HIPP cells. HICAP and HIPP cells produce slow, weak, and unreliable inhibition onto postsynaptic interneurons. The time course of inhibitory signaling is defined by the identity of the presynaptic and postsynaptic cell. It is the slowest for HIPP-HIPP, intermediately slow for HICAP-HICAP, but fast for BC-BC synapses. GABA release at interneuron-interneuron synapses also shows cell type-specific short-term dynamics, ranging from multiple-pulse facilitation at HICAP-HICAP, biphasic modulation at HIPP-HIPP to depression at BC-BC synapses. Although dendritic inhibition at HICAP-BC and HIPP-BC synapses appears weak and slow, channelrhodopsin 2-mediated excitation of SOM terminals demonstrates that they effectively control the activity of target interneurons. They markedly reduce the discharge probability but sharpen the temporal precision of action potential generation. Thus, dendritic inhibition seems to play an important role in determining the activity pattern of GABAergic interneuron populations and thereby the flow of information through the DG circuitry. Copyright © 2014 the authors 0270-6474/14/348197-13$15.00/0.

  10. Juvenile obesity enhances emotional memory and amygdala plasticity through glucocorticoids.

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    Boitard, Chloé; Maroun, Mouna; Tantot, Frédéric; Cavaroc, Amandine; Sauvant, Julie; Marchand, Alain; Layé, Sophie; Capuron, Lucile; Darnaudery, Muriel; Castanon, Nathalie; Coutureau, Etienne; Vouimba, Rose-Marie; Ferreira, Guillaume

    2015-03-04

    In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence during adolescence is particularly alarming since recent evidence indicates that obesity can affect hippocampal function during this developmental period. Adolescence is a decisive period for maturation of the amygdala and the hypothalamic-pituitary-adrenal (HPA) stress axis, both required for lifelong cognitive and emotional processing. However, little data are available on the impact of obesity during adolescence on amygdala function. Herein, we therefore evaluate in rats whether juvenile high-fat diet (HFD)-induced obesity alters amygdala-dependent emotional memory and whether it depends on HPA axis deregulation. Exposure to HFD from weaning to adulthood, i.e., covering adolescence, enhances long-term emotional memories as assessed by odor-malaise and tone-shock associations. Juvenile HFD also enhances emotion-induced neuronal activation of the basolateral complex of the amygdala (BLA), which correlates with protracted plasma corticosterone release. HFD exposure restricted to adulthood does not modify all these parameters, indicating adolescence is a vulnerable period to the effects of HFD-induced obesity. Finally, exaggerated emotional memory and BLA synaptic plasticity after juvenile HFD are alleviated by a glucocorticoid receptor antagonist. Altogether, our results demonstrate that juvenile HFD alters HPA axis reactivity leading to an enhancement of amygdala-dependent synaptic and memory processes. Adolescence represents a period of increased susceptibility to the effects of diet-induced obesity on amygdala function. Copyright © 2015 the authors 0270-6474/15/354092-12$15.00/0.

  11. The impact of parent-child interaction on brain structures: cross-sectional and longitudinal analyses.

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    Takeuchi, Hikaru; Taki, Yasuyuki; Hashizume, Hiroshi; Asano, Kohei; Asano, Michiko; Sassa, Yuko; Yokota, Susumu; Kotozaki, Yuka; Nouchi, Rui; Kawashima, Ryuta

    2015-02-04

    There is a vast amount of evidence from psychological studies that the amount of parent-child interaction affects the development of children's verbal skills and knowledge. However, despite the vast amount of literature, brain structural development associated with the amount of parent-child interaction has never been investigated. In the present human study, we used voxel-based morphometry to measure regional gray matter density (rGMD) and examined cross-sectional correlations between the amount of time spent with parents and rGMD among 127 boys and 135 girls. We also assessed correlations between the amount of time spent with parents and longitudinal changes that occurred a few years later among 106 boys and 102 girls. After correcting for confounding factors, we found negative effects of spending time with parents on rGMD in areas in the bilateral superior temporal gyrus (STG) via cross-sectional analyses as well as in the contingent areas of the right STG. We also confirmed positive effects of spending time with parents on the Verbal Comprehension score in cross-sectional and longitudinal analyses. rGMD in partly overlapping or contingent areas of the right STG was negatively correlated with age and the Verbal Comprehension score in cross-sectional analyses. Subsequent analyses revealed verbal parent-child interactions have similar effects on Verbal Comprehension scores and rGMD in the right STG in both cross-sectional and longitudinal analyses. These findings indicate that parent-child interactions affect the right STG, which ma