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Sample records for composite microdose adaptive

  1. A composite microdose Adaptive Response (AR) and Bystander Effect (BE) model-application to low LET and high LET AR and BE data.

    Science.gov (United States)

    Leonard, Bobby E

    2008-08-01

    It has been suggested that Adaptive Response (AR) may reduce risk of adverse health effects due to ionizing radiation. But very low dose Bystander Effects (BE) may impose dominant deleterious human risks. These conflicting behaviors have stimulated controversy regarding the Linear No-Threshold human risk model. A dose and dose rate-dependent microdose model, to examine AR behavior, was developed in prior work. In the prior work a number of in vitro and in vivo dose response data were examined with the model. Recent new data show AR behavior with some evidence of very low dose BE. The purpose of this work is to supplement the microdose model to encompass the Brenner and colleagues BaD (Bystander and Direct Damage) model and apply this composite model to obtain new knowledge regarding AR and BE and illustrate the use of the model to plan radio-biology experiments. The biophysical composite AR and BE Microdose Model quantifies the accumulation of hits (Poisson distributed, microdose specific energy depositions) to cell nucleus volumes. This new composite AR and BE model provides predictions of dose response at very low dose BE levels, higher dose AR levels and even higher dose Direct (linear-quadratic) Damage radiation levels. We find good fits of the model to both BE data from the Columbia University microbeam facility and combined AR and BE data for low Linear Energy Transfer (LET) and high LET data. A Bystander Factor of about 27,000 and an AR protection factor of 0.61 are obtained for the low LET in vivo mouse spleen exposures. A Bystander Factor of 317 and an AR protection factor of 0.53 are obtained for high LET radon alpha particles in human lymphocytes. In both cases the AR is activated at most by one or two radiation induced charged particle traversals through the cell nucleus. The results of the model analysis is consistent with a premise that both Bystander damage and Adaptive Response radioprotection can occur in the same cell type, derived from the same

  2. A review: Development of a microdose model for analysis of adaptive response and bystander dose response behavior.

    Science.gov (United States)

    Leonard, Bobby E

    2008-02-27

    Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type (125)I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite

  3. Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E

    2003-07-01

    In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

  4. Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

    International Nuclear Information System (INIS)

    Feinendegen, L.E.

    2003-01-01

    In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

  5. Use of microdose phenotyping to individualise dosing of patients.

    Science.gov (United States)

    Hohmann, Nicolas; Haefeli, Walter E; Mikus, Gerd

    2015-09-01

    Administering the right amount of the right drug at the right time is a key mission of clinical medicine. This comprises dose adaptation according to a patient's intrinsic and extrinsic factors influencing drug disposition. Several biomarkers are available for dose adaptation; still, prediction of individual drug disposition may be improved. Phenotyping is the quantification of drug metabolism with probe substrates specific to drug-metabolising enzymes. This allows measurement of baseline metabolism and changes after modulation of drug metabolism. This article explores the concept of phenotyping using pharmacologically ineffective microdoses of probe substrates to obtain information on drug metabolism. Several probe drugs such as midazolam for cytochrome P450 3A have already been used, but validation of other microdosed probe drugs, analytical procedures and drug formulations still face some challenges that have to be overcome. Since microdosed probe drugs have no risk of adverse drug reactions or interference with therapy, more widespread use is possible. This allows drug-drug interaction data to be safely obtained during first-in-man studies, enhancing the clinical safety of human healthy volunteers and patients in clinical trials, and, most importantly, allows determination of the drug-metabolising phenotype in severely ill patients. With harmless probe drugs at hand quantifying drug metabolism and adapting the dose accordingly, a phenotyping-based dosing strategy could become reality, offering the possibility of individualised drug therapy with reduced adverse effects and fewer therapeutic failures.

  6. Microdose fluorescence imaging of ABY-029 on an operating microscope adapted by custom illumination and imaging modules.

    Science.gov (United States)

    Elliott, Jonathan T; Dsouza, Alisha V; Marra, Kayla; Pogue, Brian W; Roberts, David W; Paulsen, Keith D

    2016-09-01

    Fluorescence guided surgery has the potential to positively impact surgical oncology; current operating microscopes and stand-alone imaging systems are too insensitive or too cumbersome to maximally take advantage of new tumor-specific agents developed through the microdose pathway. To this end, a custom-built illumination and imaging module enabling picomolar-sensitive near-infrared fluorescence imaging on a commercial operating microscope is described. The limits of detection and system specifications are characterized, and in vivo efficacy of the system in detecting ABY-029 is evaluated in a rat orthotopic glioma model following microdose injections, showing the suitability of the device for microdose phase 0 clinical trials.

  7. Microdosing and drug development: past, present and future

    Science.gov (United States)

    Lappin, Graham; Noveck, Robert; Burt, Tal

    2015-01-01

    Introduction Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date. Areas covered The authors define and distinguish the concept of microdosing from similar approaches. The authors review the ability of microdosing to provide exploratory pharmacokinetics (concentration-time data) but exclude microdosing using positron emission tomography. The article provides a comprehensive review of data within the peer-reviewed literature as well as the latest applications and a look into the future, towards where microdosing may be headed. Expert opinion Evidence so far suggests that microdosing may be a better predictive tool of human pharmacokinetics than alternative methods and combination with physiologically based modelling may lead to much more reliable predictions in the future. The concept has also been applied to drug-drug interactions, polymorphism and assessing drug concentrations over time at its site of action. Microdosing may yet have more to offer in unanticipated directions and provide benefits that have not been fully realised to date. PMID:23550938

  8. Novel strategies for microdose studies using non-radiolabeled compounds.

    Science.gov (United States)

    Maeda, Kazuya; Sugiyama, Yuichi

    2011-06-19

    Microdose studies using non-radiolabeled compounds enable assessment of the clinical pharmacokinetics of drug candidates in humans without the need to synthesize radiolabeled compounds. We have demonstrated that the quantification limits of many drugs measured by LC-MS/MS are low enough to allow estimation of their pharmacokinetic parameters following administration of a microdose. Our previous microdose studies with LC-MS/MS demonstrated the linear pharmacokinetics of fexofenadine between microdoses and therapeutic doses. We also obtained time profiles of plasma concentrations of nicardipine and its multiple metabolites following administration of a microdose. A significant advantage of using non-radiolabeled compounds is the ability to perform cassette microdose studies. By administering multiple drug candidates to the same subject, we can select compounds with appropriate pharmacokinetic properties simultaneously. We can also clarify major factors dominating the pharmacokinetics of drug candidates by cocktail microdosing of the test compounds and probe substrates with or without specific inhibitors for enzymes/transporters. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Micro-dosing for early biokinetic studies in humans

    International Nuclear Information System (INIS)

    Stenstroem, K.; Sydoff, M.; Mattsson, S.

    2010-01-01

    Micro-dosing is a new concept in drug development that-if implemented in the pharmaceutical industry-would mean that new drugs can be tested earlier in humans than done today. The human micro-dosing concept-or 'Phase 0'-may offer improved candidate selection, reduced failure rates in the drug development line and a reduction in the use of laboratory animals in early drug development, factors which will help to speed up drug development and also reduce the costs. Micro-dosing utilises sub-pharmacological amounts of the substance to open opportunities for early studies in man. Three technologies are used for micro-dosing: accelerator mass spectrometry (AMS), positron emission tomography and liquid chromatography-tandem mass spectrometry. This paper focuses on the principle of AMS and discusses the current status of micro-dosing with AMS. (authors)

  10. Ethical, legal, and social implications (ELSI) of microdose clinical trials.

    Science.gov (United States)

    Kurihara, Chieko

    2011-06-19

    A "microdose clinical trial" (microdosing) is one kind of early phase exploratory clinical trial, administering the compound at doses estimated to have no pharmacological or toxicological effects, aimed at screening candidates for further clinical development. This article's objective is to clarify the ethical, legal, and social implications (ELSI) of such an exploratory minimum-risk human trial. The definition and non-clinical study requirements for microdosing have been harmonized among the European Union (EU), United States (US), and Japan. Being conducted according to these regulations, microdosing seems to be ethically well justified in terms of respect for persons, beneficence, justice, human dignity, and animal welfare. Three big projects have been demonstrating the predictability of therapeutic dose pharmacokinetics from microdosing. The article offers suggestions as how microdosing can become a more useful and socially accepted strategy. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Approaches using molecular imaging technology -- use of PET in clinical microdose studies.

    Science.gov (United States)

    Wagner, Claudia C; Langer, Oliver

    2011-06-19

    Positron emission tomography (PET) imaging uses minute amounts of radiolabeled drug tracers and thereby meets the criteria for clinical microdose studies. The advantage of PET, when compared to other analytical methods used in microdose studies, is that the pharmacokinetics (PK) of a drug can be determined in the tissue targeted for drug treatment. PET microdosing already offers interesting applications in clinical oncology and in the development of central nervous system pharmaceuticals and is extending its range of application to many other fields of pharmaceutical medicine. Although requirements for preclinical safety testing for microdose studies have been cut down by regulatory authorities, radiopharmaceuticals increasingly need to be produced under good manufacturing practice (GMP) conditions, which increases the costs of PET microdosing studies. Further challenges in PET microdosing include combining PET with other ultrasensitive analytical methods, such as accelerator mass spectrometry (AMS), to gain plasma PK data of drugs, beyond the short PET examination periods. Finally, conducting clinical PET studies with radiolabeled drugs both at micro- and therapeutic doses is encouraged to answer the question of dose linearity in clinical microdosing. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Pediatric microdose and microtracer studies using 14C in Europe.

    Science.gov (United States)

    Turner, M A; Mooij, M G; Vaes, W H J; Windhorst, A D; Hendrikse, N H; Knibbe, C A J; Kõrgvee, L T; Maruszak, W; Grynkiewicz, G; Garner, R C; Tibboel, D; Park, B K; de Wildt, S N

    2015-09-01

    Important information gaps remain on the efficacy and safety of drugs in children. Pediatric drug development encounters several ethical, practical, and scientific challenges. One barrier to the evaluation of medicines for children is a lack of innovative methodologies that have been adapted to the needs of children. This article presents our successful experience of pediatric microdose and microtracer studies using (14) C-labeled probes in Europe to illustrate the strengths and limitations of these approaches. © 2015 ASCPT.

  13. Microdosing: Concept, application and relevance

    Directory of Open Access Journals (Sweden)

    Tushar Tewari

    2010-01-01

    Full Text Available The use of microdose pharmacokinetic studies as an essential tool in drug development is still to catch on. While this approach promises potential cost savings and a quantum leap in efficiencies of the drug development process, major hurdles still need to be overcome before the technique becomes commonplace and part of routine practice. Clear regulations in Europe and the USA have had an enabling effect. The lack of enabling provisions for microdosing studies in Indian regulation, despite low risk and manifest relevance for the local drug development industry, is inconsistent with the country′s aspirations to be among the leaders in pharmaceutical research.

  14. A clinical pharmacokinetic microdosing study of docetaxel with Japanese patients with cancer.

    Science.gov (United States)

    Fujita, Ken-ichi; Yoshino, Etsuko; Kawara, Kaori; Maeda, Kazuya; Kusuhara, Hiroyuki; Sugiyama, Yuichi; Yokoyama, Taro; Kaneta, Toshikado; Ishida, Hiroo; Sasaki, Yasutsuna

    2015-10-01

    Whether microdosing studies can be used to evaluate the human pharmacokinetics of new anticancer drugs remains unclear. The disposition of docetaxel in cancer patients is linear in terms of dose proportionality. We examined whether the pharmacokinetics of docetaxel in a clinically relevant therapeutic dose could be predicted from the pharmacokinetics of a microdose of docetaxel in Japanese patients with cancer. A microdose of docetaxel (100 μg/patient) was given by 5-min intravenous infusion on day 1, followed by a therapeutic dose of docetaxel (60-75 mg m(-2)), given by 1-h intravenous infusion on day 8. Plasma docetaxel was analyzed by liquid chromatography-tandem mass spectrometry. A two-compartment pharmacokinetic model was used to calculate the area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf). Nine patients received both a microdose and therapeutic dose of docetaxel. The AUC0-inf after microdosing was 3640 ± 1150 ng h L(-1), while that after therapeutic dosing adjusted to 100 mg/patient was 2230 ± 757 µg h L(-1). The ratio of docetaxel clearance in therapeutic dose to that in microdose was 1.8 (P = 0.0041). Plasma α1-acid glycoprotein concentrations negatively correlated with docetaxel clearance at therapeutic dose, whereas the trend was weak at microdose. Docetaxel clearance showed marginal nonlinearity between microdose and therapeutic dose, presumably because of saturation of plasma protein binding; however, the magnitude was within twofold, allowing practically acceptable extrapolation.

  15. Approaches using molecular imaging technology - use of PET in clinical microdose studies§

    Science.gov (United States)

    Wagner, Claudia C; Langer, Oliver

    2013-01-01

    Positron emission tomography (PET) imaging uses minute amounts of radiolabeled drug tracers and thereby meets the criteria for clinical microdose studies. The advantage of PET, when compared to other analytical methods used in microdose studies, is that the pharmacokinetics (PK) of a drug can be determined in the tissue targeted for drug treatment. PET microdosing already offers interesting applications in clinical oncology and in the development of central nervous system pharmaceuticals and is extending its range of application to many other fields of pharmaceutical medicine. Although requirements for preclinical safety testing for microdose studies have been cut down by regulatory authorities, radiopharmaceuticals increasingly need to be produced under good manufacturing practice (GMP) conditions, which increases the costs of PET microdosing studies. Further challenges in PET microdosing include combining PET with other ultrasensitive analytical methods, such as accelerator mass spectrometry (AMS), to gain plasma PK data of drugs, beyond the short PET examination periods. Finally, conducting clinical PET studies with radiolabeled drugs both at micro- and therapeutic doses is encouraged to answer the question of dose linearity in clinical microdosing. PMID:20887762

  16. Fertilizer micro-dosing

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

    Localized application of small quantities of fertilizer (micro-dosing), combined with improved planting pits for rainwater harvesting, has generated greater profits and food security for women farmers in the Sahel. • Women are 25% more likely to use combined applications, and have expanded areas of food crops (cowpea,.

  17. [Microdose clinical trial--impact of PET molecular imaging].

    Science.gov (United States)

    Yano, Tsuneo; Watanabe, Yasuyoshi

    2010-10-01

    Microdose (MD) clinical trial and exploratory IND study including sub-therapeutic dose and therapeutic dose which are higher than microdoses are expected to bring about innovations in drug development. The outlines of guidances for microdose clinical trial and ICH-M3 (R2) issued by the MHLW in June, 2008, and February, 2010, are first explained, respectively, and some examples of their application to clinical developments of therapeutic drugs in the infection and cancer fields are introduced. Especially, thanks to the progress of molecular imaging research, a new field of drug development is explored by using imaging biomarkers for efficacy or safety evaluation which visualize biomarkers by PET imaging agents. Finally, the roadmap for drug development in infection and cancer fields utilizing PET molecular imaging is discussed.

  18. Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics.

    Science.gov (United States)

    Wilkes, Denise M; Orillosa, Susan J; Hustak, Erik C; Williams, Courtney G; Doulatram, Gulshan R; Solanki, Daneshvari R; Garcia, Eduardo A; Huang, Li-Yen M

    2017-06-13

    The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine microdose method involves a pretrial reduction or elimination of systemic opioids followed by a period of abstinence. Intrathecal (IT) morphine is then started at doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued after pump implant and IT morphine monotherapy. Retrospective review of medical records. Private and academic pain clinic practices. Chronic noncancer pain patients. We reviewed the charts of 60 patients who had completed a microdose regimen and had an IT pump implanted between June 11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain scores, side effects, max dose, and duration were recorded. The majority of patients (35/60, 58%) were successfully managed solely on morphine microdose monotherapy. These patients did not require additional oral therapy. There was a significant reduction in mean pain scores, from 7.4 ± 0.32 before microdose therapy to 4.8 ± 0.3 after microdose therapy. Microdose therapy achieved analgesia, improved safety, and avoided systemic side effects. The safety of IT therapy was increased by using a lower concentration (2 mg/mL) and lower daily doses (microdose therapy was feasible, safe, and cost-effective in the outpatient setting. 2017 American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.

  19. Human Lung Cancer Risks from Radon – Part II – Influence from Combined Adaptive Response and Bystander Effects – A Microdose Analysis

    Science.gov (United States)

    Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

    2010-01-01

    In the prior Part I, the potential influence of the low level alpha radiation induced bystander effect (BE) on human lung cancer risks was examined. Recent analysis of adaptive response (AR) research results with a Microdose Model has shown that single low LET radiation induced charged particles traversals through the cell nucleus activates AR. We have here conducted an analysis based on what is presently known about adaptive response and the bystander effect (BE) and what new research is needed that can assist in the further evaluation human cancer risks from radon. We find that, at the UNSCEAR (2000) worldwide average human exposures from natural background and man-made radiations, the human lung receives about a 25% adaptive response protection against the radon alpha bystander damage. At the UNSCEAR (2000) minimum range of background exposure levels, the lung receives minimal AR protection but at higher background levels, in the high UNSCEAR (2000) range, the lung receives essentially 100% protection from both the radon alpha damage and also the endogenic, spontaneously occurring, potentially carcinogenic, lung cellular damage. PMID:22461760

  20. [Impact of microdose clinical trials in the preclinical stage].

    Science.gov (United States)

    Kim, Soonih

    2014-01-01

    A microdose clinical trial may be useful as a safe early-phase exploratory study using doses as low as 100 μg or less for determination of the disposition of a candidate compound in humans in a short period of time. This may increase confidence in candidate compounds, especially those for which it is difficult to predict disposition based on the results of in vitro or preclinical studies. In this study, we examined microdose trials performed in the preclinical stage for two first-in-class compounds with a new mechanism of action. These compounds showed species difference in first pass metabolism in the digestive tract and liver, causing uncertainty in prediction of disposition in humans. For this reason, first-in-human microdose clinical trials were performed. The results showed that the two compounds had effective blood concentrations after oral administration at a dose of 100 mg qd. Administration of an extremely small dose of one (14)C-labeled compound permitted identification of major metabolites. No toxic metabolites were detected. The preclinical toxic dose was determined based on prediction of blood exposure at the estimated maximum clinical dose. For the other candidate compound, the findings of the microdose trial indicated a high bioavailability after oral administration and low hepatic clearance after intravenous administration. These results suggested only a small risk of a change in disposition in patients with hepatic disorder. The data obtained for the two compounds suggest that microdose clinical trials can be useful for improving the process of candidate selection in the preclinical stage.

  1. Approaches using molecular imaging technology - use of PET in clinical microdose studies§

    OpenAIRE

    Wagner, Claudia C.; Langer, Oliver

    2011-01-01

    Positron emission tomography (PET) imaging uses minute amounts of radiolabeled drug tracers and thereby meets the criteria for clinical microdose studies. The advantage of PET, when compared to other analytical methods used in microdose studies, is that the pharmacokinetics (PK) of a drug can be determined in the tissue targeted for drug treatment. PET microdosing already offers interesting applications in clinical oncology and in the development of central nervous system pharmaceuticals and ...

  2. Dose, image quality and spine modeling assessment of biplanar EOS micro-dose radiographs for the follow-up of in-brace adolescent idiopathic scoliosis patients.

    Science.gov (United States)

    Morel, Baptiste; Moueddeb, Sonia; Blondiaux, Eleonore; Richard, Stephen; Bachy, Manon; Vialle, Raphael; Ducou Le Pointe, Hubert

    2018-05-01

    The aim of this study was to compare the radiation dose, image quality and 3D spine parameter measurements of EOS low-dose and micro-dose protocols for in-brace adolescent idiopathic scoliosis (AIS) patients. We prospectively included 25 consecutive patients (20 females, 5 males) followed for AIS and undergoing brace treatment. The mean age was 12 years (SD 2 years, range 8-15 years). For each patient, in-brace biplanar EOS radiographs were acquired in a standing position using both the conventional low-dose and micro-dose protocols. Dose area product (DAP) was systematically recorded. Diagnostic image quality was qualitatively assessed by two radiologists for visibility of anatomical structures. The reliability of 3D spine modeling between two operators was quantitatively evaluated for the most clinically relevant 3D radiological parameters using intraclass correlation coefficient (ICC). The mean DAP for the posteroanterior and lateral acquisitions was 300 ± 134 and 433 ± 181 mGy cm 2 for the low-dose radiographs, and 41 ± 19 and 81 ± 39 mGy cm 2 for micro-dose radiographs. Image quality was lower with the micro-dose protocol. The agreement was "good" to "very good" for all measured clinical parameters when comparing the low-dose and micro-dose protocols (ICC > 0.73). The micro-dose protocol substantially reduced the delivered dose (by a factor of 5-7 compared to the low-dose protocol) in braced children with AIS. Although image quality was reduced, the micro-dose protocol proved to be adapted to radiological follow-up, with adequate image quality and reliable clinical measurements. These slides can be retrieved under Electronic Supplementary Material.

  3. Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability.

    Science.gov (United States)

    Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Houston, Brian; Oosterhuis, Berend; Bjerrum, Ole J; Rowland, Malcolm; Garner, Colin

    2010-05-12

    A human pharmacokinetic study was performed to assess the ability of a microdose to predict the pharmacokinetics of a therapeutic dose of fexofenadine and to determine its absolute oral bioavailability. Fexofenadine was chosen to represent an unmetabolized transporter substrate (P-gP and OATP). Fexofenadine was administered to 6 healthy male volunteers in a three way cross-over design. A microdose (100microg) of (14)C-drug was administered orally (period 1) and intravenously by 30min infusion (period 2). In period 3 an intravenous tracer dose (100microg) of (14)C-drug was administered simultaneously with an oral unlabelled therapeutic dose (120mg). Plasma was collected from all 3 periods and analysed for both total (14)C content and parent drug by accelerator mass spectrometry (AMS). For period 3, plasma samples were also analysed using HPLC-fluorescence to determine total drug concentration. Urine was collected and analysed for total (14)C. Good concordance between the microdose and therapeutic dose pharmacokinetics was observed. Microdose: CL 13L/h, CL(R) 4.1L/h, V(ss) 54L, t(1/2) 16h; therapeutic dose: CL 16L/h, CL(R) 6.2L/h, V(ss) 64L, t(1/2) 12h. The absolute oral bioavailability of fexofenadine was 0.35 (microdose 0.41, therapeutic dose 0.30). Despite a 1200-fold difference in dose of fexofenadine, the microdose predicted well the pharmacokinetic parameters following a therapeutic dose for this transporter dependent compound.

  4. Microdose study of a P-glycoprotein substrate, fexofenadine, using a non-radioisotope-labelled drug and LC/MS/MS.

    Science.gov (United States)

    Yamazaki, A; Kumagai, Y; Yamane, N; Tozuka, Z; Sugiyama, Y; Fujita, T; Yokota, S; Maeda, M

    2010-04-01

    Fexofenadine is a P-glycoprotein substrate of low bioavailability. It is primarily excreted into faeces as a parent drug via biliary excretion. The predictability from microdose data for the drug absorbed via transporters such as P-glycoprotein is not known. Therefore, this study assessed the predictability of therapeutic-dose pharmacokinetics of fexofenadine from microdosing data using non-radioisotope-labelled drug and liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). In a single dose, randomized, two-way crossover study, eight subjects received a microdose (100 microg) or a therapeutic dose (60 mg) of fexofenadine. Blood samples were collected until 12 h after dosing, and assayed using LC/MS/MS. Plasma concentration-time curves of fexofenadine between microdose and therapeutic dose were similar. The mean +/- SD of C(max) normalized to 60 mg dose after microdose and therapeutic dose were 379 +/- 147 and 275 +/- 145 ng/mL respectively. The mean AUC(last) normalized to 60 mg dose after microdose and therapeutic dose were 1914 +/- 738 and 1431 +/- 432 ng/h/mL respectively. The mean dose-adjusted C(max) and AUC(last) after microdose were higher compared with those after therapeutic dose. Individual plots of C(max) and AUC(last) normalized to 60 mg dose, were similar for microdose and therapeutic dose. None of the pharmacokinetic parameters were statistically different using anova. Overall, the microdose pharmacokinetics profile was similar to, and hence predictive of, that of the therapeutic dose. For the P-glycoprotein substrate fexofenadine, the predictability of therapeutic-dose pharmacokinetics from microdose data was good. A microdose study using a non-radioisotope-labelled drug and LC/MS/MS is convenient, and has the potential to aid the early selection of drug candidates.

  5. High-precision piezo-ejection ocular microdosing: Phase II study on local and systemic effects of topical phenylephrine.

    Science.gov (United States)

    Ianchulev, Tsontcho; Weinreb, Robert; Tsai, James C; Lin, Shan; Pasquale, Louis R

    2018-01-01

    Conventional eyedropper-delivered volumes (25-50 µl) exceed the eye's usual tear-film volume (7 µl) and precorneal reservoir capacity, risking overflow and ocular/systemic complications. Piezoelectric high-precision microdosing may circumvent these limitations. Results & methodology: In this masked, nonrandomized, cross-over study, subjects (n = 12) underwent pupil dilation with topical phenylephrine (PE) administered by 32-µl eyedropper (2.5% or 10% formulation) and 8-µl electronic microdosing (10% formulation). Microdosing with PE-10% achieved comparable peak dilation as 10% eyedropper-delivery and superior dilation to 2.5% eyedropper-delivery (p = 0.009) at 75 min. Microdosing significantly reduced 20-min plasma PE levels versus PE10% eyedropper; neither treatment altered heart rate/blood pressure. Eye irritation occurred significantly less frequently with microdosing than PE10% eyedrops. Piezo-ejection PE microdosing achieves comparable biological effect as eyedropper dosing; reduced systemic absorption may decrease risk of systemic side effects.

  6. Microdose analysis of ion strikes on SRAM cells

    Science.gov (United States)

    Scheick, L.

    2003-12-01

    A method of measuring the effect from exposure to highly localized ionizing radiation on microstructures is described. The voltage at which a commercial SRAM cell cannot hold a programmed state changes with microdose. The microdose distribution across the array, in addition to the analysis of the occurrence of anomalous shifts in operating bias due to rare, large energy-deposition events is studied. The effect of multiple hits on a SRAM cell is presented. A general theory on multiple hits from which basic device parameters can be extracted is presented. SPICE, as well as analysis of basic device physics, is used to analyze the damage to individual transistors and the response of a SRAM cell.

  7. Microdosimetry computation code of internal sources - MICRODOSE 1

    International Nuclear Information System (INIS)

    Li Weibo; Zheng Wenzhong; Ye Changqing

    1995-01-01

    This paper describes a microdosimetry computation code, MICRODOSE 1, on the basis of the following described methods: (1) the method of calculating f 1 (z) for charged particle in the unit density tissues; (2) the method of calculating f(z) for a point source; (3) the method of applying the Fourier transform theory to the calculation of the compound Poisson process; (4) the method of using fast Fourier transform technique to determine f(z) and, giving some computed examples based on the code, MICRODOSE 1, including alpha particles emitted from 239 Pu in the alveolar lung tissues and from radon progeny RaA and RAC in the human respiratory tract. (author). 13 refs., 6 figs

  8. Microdose fluorescence imaging of ABY-029 on an operating microscope adapted by custom illumination and imaging modules

    OpenAIRE

    Elliott, Jonathan T.; Dsouza, Alisha V.; Marra, Kayla; Pogue, Brian W.; Roberts, David W.; Paulsen, Keith D.

    2016-01-01

    Fluorescence guided surgery has the potential to positively impact surgical oncology; current operating microscopes and stand-alone imaging systems are too insensitive or too cumbersome to maximally take advantage of new tumor-specific agents developed through the microdose pathway. To this end, a custom-built illumination and imaging module enabling picomolar-sensitive near-infrared fluorescence imaging on a commercial operating microscope is described. The limits of detection and system spe...

  9. Spatial dose and microdose distribution in tissues. Ionization, nuclear reactions, multiple scattering simulation of beam transport

    International Nuclear Information System (INIS)

    Jacquot, C.

    1976-01-01

    Computer simulation and nuclear emulsion and gelatin techniques enabled to give the total elastic and inelastic cross sections and to forecast the spatial microdose distributions in cells, nuclei and molecules. For this purpose, the transport of a beam into tissues having a given composition is calculated, the nuclear reactions are generated and the energy depositions in standard planes perpendicular to the beam are recorded

  10. Charge deposition model for investigating SE-microdose effect in trench power MOSFETs

    Science.gov (United States)

    Xin, Wan; Weisong, Zhou; Daoguang, Liu; Hanliang, Bo; Jun, Xu

    2015-05-01

    It was demonstrated that heavy ions can induce large current—voltage (I-V) characteristics shift in commercial trench power MOSFETs, named single event microdose effect (SE-microdose effect). A model is presented to describe this effect. This model calculates the charge deposition by a single heavy ion hitting oxide and the subsequent charge transport under an electric field. Holes deposited at the SiO2/Si interface by a Xe ion are calculated by using this model. The calculated results were then used in Sentaurus TCAD software to simulate a trench power MOSFET's I-V curve shift after a Xe ion has hit it. The simulation results are consistent with the related experiment's data. In the end, several factors which affect the SE-microdose effect in trench power MOSFETs are investigated by using this model.

  11. Sensitivity and proportionality assessment of metabolites from microdose to high dose in rats using LC-MS/MS.

    Science.gov (United States)

    Ni, Jinsong; Ouyang, Hui; Seto, Carmai; Sakuma, Takeo; Ellis, Robert; Rowe, Josh; Acheampong, Andrew; Welty, Devin; Szekely-Klepser, Gabriella

    2010-03-01

    The objective of this study was to evaluate the sensitivity requirement for LC-MS/MS as an analytical tool to characterize metabolites in plasma and urine at microdoses in rats and to investigate proportionality of metabolite exposure from a microdose of 1.67 µg/kg to a high dose of 5000 µg/kg for atorvastatin, ofloxacin, omeprazole and tamoxifen. Only the glucuronide metabolite of ofloxacin, the hydroxylation metabolite of omeprazole and the hydration metabolite of tamoxifen were characterized in rat plasma at microdose by LC-MS/MS. The exposure of detected metabolites of omeprazole and tamoxifen appeared to increase in a nonproportional manner with increasing doses. Exposure of ortho- and para-hydroxyatorvastatin, but not atorvastatin and lactone, increased proportionally with increasing doses. LC-MS/MS has demonstrated its usefulness for detecting and characterizing the major metabolites in plasma and urine at microdosing levels in rats. The exposure of metabolites at microdose could not simply be used to predict their exposure at higher doses.

  12. Charge deposition model for investigating SE-microdose effect in trench power MOSFETs

    International Nuclear Information System (INIS)

    Wan Xin; Zhou Weisong; Liu Daoguang; Bo Hanliang; Xu Jun

    2015-01-01

    It was demonstrated that heavy ions can induce large current—voltage (I–V) characteristics shift in commercial trench power MOSFETs, named single event microdose effect (SE-microdose effect). A model is presented to describe this effect. This model calculates the charge deposition by a single heavy ion hitting oxide and the subsequent charge transport under an electric field. Holes deposited at the SiO 2 /Si interface by a Xe ion are calculated by using this model. The calculated results were then used in Sentaurus TCAD software to simulate a trench power MOSFET's I–V curve shift after a Xe ion has hit it. The simulation results are consistent with the related experiment's data. In the end, several factors which affect the SE-microdose effect in trench power MOSFETs are investigated by using this model. (paper)

  13. Drug-drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer.

    Science.gov (United States)

    Park, Gab-Jin; Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Min-Ho; Shin, Seok-Ho; Shin, Young G; Yim, Dong-Seok

    2017-01-01

    A microdose drug-drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2-9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (C max ) and area under the curve to the last measurement (AUC t ) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for C max , and 4.07 (micro), 4.33 (regular) for AUC t . For the induction study, they were 0.26 (micro) and 0.21 (regular) for C max , and 0.16 (micro) and 0.15 (regular) for AUC t . There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes.

  14. Intra?Target Microdosing ? A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans

    OpenAIRE

    Burt, T; MacLeod, D; Lee, K; Santoro, A; DeMasi, DK; Hawk, T; Feinglos, M; Rowland, M; Noveck, RJ

    2017-01-01

    Intra-target microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first-in-human (FIH) testing of new molecular entities (NMEs). ITM combines intra-target drug delivery and "microdosing," the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic-level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers receive...

  15. A human microdose study of the antimalarial drug GSK3191607 in healthy volunteers.

    Science.gov (United States)

    Okour, Malek; Derimanov, Geo; Barnett, Rodger; Fernandez, Esther; Ferrer, Santiago; Gresham, Stephanie; Hossain, Mohammad; Gamo, Francisco-Javier; Koh, Gavin; Pereira, Adrian; Rolfe, Katie; Wong, Deborah; Young, Graeme; Rami, Harshad; Haselden, John

    2018-03-01

    GSK3191607, a novel inhibitor of the Plasmodium falciparum ATP4 (PfATP4) pathway, is being considered for development in humans. However, a key problem encountered during the preclinical evaluation of the compound was its inconsistent pharmacokinetic (PK) profile across preclinical species (mouse, rat and dog), which prevented reliable prediction of PK parameters in humans and precluded a well-founded assessment of the potential for clinical development of the compound. Therefore, an open-label microdose (100 μg, six subjects) first time in humans study was conducted to assess the human PK of GSK3191607 following intravenous administration of [14C]-GSK3191607. A human microdose study was conducted to investigate the clinical PK of GSK3191607 and enable a Go/No Go decision on further progression of the compound. The PK disposition parameters estimated from the microdose study, combined with preclinical in vitro and in vivo pharmacodynamic parameters, were all used to estimate the potential efficacy of various oral dosing regimens in humans. The PK profile, based on the microdose data, demonstrated a half-life (~17 h) similar to other antimalarial compounds currently in clinical development. However, combining the microdose data with the pharmacodynamic data provided results that do not support further clinical development of the compound for a single dose cure. The information generated by this study provides a basis for predicting the expected oral PK profiles of GSK3191607 in man and supports decisions on the future clinical development of the compound. © 2017 The British Pharmacological Society.

  16. Observational infant exploratory [14C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis

    Science.gov (United States)

    Garner, Colin R; Park, Kevin B; French, Neil S; Earnshaw, Caroline; Schipani, Alessandro; Selby, Andrew M; Byrne, Lindsay; Siner, Sarah; Crawley, Francis P; Vaes, Wouter H J; van Duijn, Esther; deLigt, Rianne; Varendi, Heili; Lass, Jane; Grynkiewicz, Grzegorz; Maruszak, Wioletta; Turner, Mark A

    2015-01-01

    Aims The aims of the study were to compare [14C]-paracetamol ([14C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0–2 year old age group. Methods [14C]-PARA concentrations in 10–15 µl plasma samples were measured after enteral or i.v. administration of a single [14C]-PARA microdose or mixed in with therapeutic dose in infants receiving PARA as part of their therapeutic regimen. Results Thirty-four infants were included in the PARA PK analysis for this study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6) and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in parentheses) for these dosed groups were 1.46 (1.00) l h–1, 1.76 (1.07) l h–1, 2.93 (2.08) l h–1 and 2.72 (3.10) l h–1, t1/2 values 2.65 h, 2.55 h, 8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l–1 h) values were 0.90 (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). Conclusions All necessary ethical, scientific, clinical and regulatory procedures were put in place to conduct PK studies using enteral and systemic microdosing in two European centres. The pharmacokinetics of a therapeutic dose (mg kg–1) and a microdose (ng kg–1) in babies between 35 to 127 weeks post-menstrual age. [14C]-PARA pharmacokinetic parameters were within a two-fold range after a therapeutic dose or a microdose. Exploratory studies using doses significantly less than therapeutic doses may offer ethical and safety advantages with increased bionalytical sensitivity in selected exploratory paediatric pharmacokinetic studies. PMID:25619398

  17. Observational infant exploratory [(14)C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis.

    Science.gov (United States)

    Garner, Colin R; Park, Kevin B; French, Neil S; Earnshaw, Caroline; Schipani, Alessandro; Selby, Andrew M; Byrne, Lindsay; Siner, Sarah; Crawley, Francis P; Vaes, Wouter H J; van Duijn, Esther; deLigt, Rianne; Varendi, Heili; Lass, Jane; Grynkiewicz, Grzegorz; Maruszak, Wioletta; Turner, Mark A

    2015-07-01

    The aims of the study were to compare [(14)C]-paracetamol ([(14)C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0-2 year old age group. [(14)C]-PARA concentrations in 10-15 µl plasma samples were measured after enteral or i.v. administration of a single [(14)C]-PARA microdose or mixed in with therapeutic dose in infants receiving PARA as part of their therapeutic regimen. Thirty-four infants were included in the PARA PK analysis for this study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6) and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in parentheses) for these dosed groups were 1.46 (1.00) l h(-1), 1.76 (1.07) l h(-1), 2.93 (2.08) l h(-1) and 2.72 (3.10) l h(-1), t(1/2) values 2.65 h, 2.55 h, 8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l(-1) h) values were 0.90 (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). All necessary ethical, scientific, clinical and regulatory procedures were put in place to conduct PK studies using enteral and systemic microdosing in two European centres. The pharmacokinetics of a therapeutic dose (mg kg(-1)) and a microdose (ng kg(-1)) in babies between 35 to 127 weeks post-menstrual age. [(14)C]-PARA pharmacokinetic parameters were within a two-fold range after a therapeutic dose or a microdose. Exploratory studies using doses significantly less than therapeutic doses may offer ethical and safety advantages with increased bionalytical sensitivity in selected exploratory paediatric pharmacokinetic studies. © 2015 The British Pharmacological Society.

  18. Drug–drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer

    Science.gov (United States)

    Park, Gab-jin; Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Min-Ho; Shin, Seok-Ho; Shin, Young G; Yim, Dong-Seok

    2017-01-01

    Purpose A microdose drug–drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Patients and methods Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2–9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. Results The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (Cmax) and area under the curve to the last measurement (AUCt) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for Cmax, and 4.07 (micro), 4.33 (regular) for AUCt. For the induction study, they were 0.26 (micro) and 0.21 (regular) for Cmax, and 0.16 (micro) and 0.15 (regular) for AUCt. There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Conclusion Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes. PMID:28408803

  19. Drug–drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer

    Directory of Open Access Journals (Sweden)

    Park G

    2017-03-01

    Full Text Available Gab-jin Park,1 Soo Hyeon Bae,1 Wan-Su Park,1 Seunghoon Han,1 Min-Ho Park,2 Seok-Ho Shin,2 Young G Shin,2 Dong-Seok Yim1,2 1Department of Clinical Pharmacology and Therapeutics, Seoul St Mary’s Hospital, PIPET (Pharmacometrics Institute for Practical Education and Training, College of Medicine, Catholic University of Korea, Seoul, South Korea; 2College of Pharmacy, Chungnam National University, Daejeon, South Korea Purpose: A microdose drug–drug interaction (DDI study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Patients and methods: Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim and known perpetrators: fluconazole (inhibitor and rifampin (inducer. For both studies, the microdose (100 µg, cold compound and the regular dose (20 mg of omeprazole were given at days 0 and 1, respectively. On days 2–9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. Results: The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only of maximum concentration (Cmax and area under the curve to the last measurement (AUCt of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro and 2.68 (regular for Cmax, and 4.07 (micro, 4.33 (regular for AUCt. For the induction study, they were 0.26 (micro and 0.21 (regular for Cmax, and 0.16 (micro and 0.15 (regular for AUCt. There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Conclusion: Our results may be

  20. Microdose clinical trial: quantitative determination of nicardipine and prediction of metabolites in human plasma.

    Science.gov (United States)

    Yamane, Naoe; Takami, Tomonori; Tozuka, Zenzaburo; Sugiyama, Yuichi; Yamazaki, Akira; Kumagai, Yuji

    2009-01-01

    A sample treatment procedure and high-sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for quantitative determination of nicardipine in human plasma were developed for a microdose clinical trial with nicardipine, a non-radioisotope labeled drug. The calibration curve was linear in the range of 1-500 pg/mL using 1 mL of plasma. Analytical method validation for the clinical dose, for which the calibration curve was linear in the range of 0.2-100 ng/mL using 20 microL of plasma, was also conducted. Each method was successfully applied to making determinations in plasma using LC/MS/MS after administration of a microdose (100 microg) and clinical dose (20 mg) to each of six healthy volunteers. We tested new approaches in the search for metabolites in plasma after microdosing. In vitro metabolites of nicardipine were characterized using linear ion trap-fourier transform ion cyclotron resonance mass spectrometry (LIT-FTICRMS) and the nine metabolites predicted to be in plasma were analyzed using LC/MS/MS. There is a strong possibility that analysis of metabolites by LC/MS/MS may advance to utilization in microdose clinical trials with non-radioisotope labeled drugs.

  1. Clinical relevance of liquid chromatography tandem mass spectrometry as an analytical method in microdose clinical studies.

    Science.gov (United States)

    Yamane, Naoe; Tozuka, Zenzaburo; Kusama, Makiko; Maeda, Kazuya; Ikeda, Toshihiko; Sugiyama, Yuichi

    2011-08-01

    To investigate the potency of LC-MS/MS by means of sensitivity and the applicability for cassette dosing in microdose clinical trials. Thirty one top-selling 31 drugs were spiked to human plasma, extracted, and analyzed by LC-MS/MS. The lower limits of quantification for each drug varied from 0.08 to 50 pg/mL, and were lower than one eighth of the assumed maximum plasma concentration at microdose in all drugs except for losartan, indicating the high performance in acquisition of full pharmacokinetic profiles at microdose. We also succeeded in simultaneous analysis of multiple compounds, assuming a situation of cassette dosing in which multiple drug candidates would be administrated simultaneously. Together with the features of LC-MS/MS, such as immediate verification, the utilization of non-radiolabeled drugs and no special facilities, we suppose that LC-MS/MS analysis would be widely applicable in conducting microdose clinical studies.

  2. Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions.

    Science.gov (United States)

    de Souza, Ana Luiza Ribeiro; Marra, Kayla; Gunn, Jason; Samkoe, Kimberley S; Hoopes, P Jack; Feldwisch, Joachim; Paulsen, Keith D; Pogue, Brian W

    2017-02-01

    Fluorescence guidance in surgical oncology provides the potential to realize enhanced molecular tumor contrast with dedicated targeted tracers, potentially with a microdose injection level. For most glioma tumors, the blood brain barrier is compromised allowing some exogenous drug/molecule delivery and accumulation for imaging. The aberrant overexpression and/or activation of epidermal growth factor receptor (EGFR) is associated with many types of cancers, including glioblastoma, and so the use of a near-infrared (NIR) fluorescent molecule targeted to the EGFR receptor provides the potential for improving tumor contrast during surgery. Fluorescently labeled affibody molecule (ABY-029) has high EGFR affinity and high potential specificity with reasonably fast plasma clearance. In this study, ABY-29 was evaluated in glioma versus normal brain uptake from intravenous injection at a range of doses, down to a microdose injection level. Nude rats were inoculated with the U251 human glioma cell line in the brain. Tumors were allowed to grow for 3-4 weeks. ABY-029 fluorescence ex vivo imaging of brain slices was acquired at different time points (1-48 h) and varying injection doses from 25 to 122 μg/kg (from human protein microdose equivalent to five times microdose levels). The tumor was most clearly visualized at 1-h post-injection with 8- to 16-fold average contrast relative to normal brain. However, the tumor still could be identified after 48 h. In all cases, the ABY-029 fluorescence appeared to localize preferentially in EGFR-positive regions. Increasing the injected dose from a microdose level to five times, a microdose level increased the signal by 10-fold, and the contrast was from 8 to 16, showing that there was value in doses slightly higher than the microdose restriction. Normal tissue uptake was found to be affected by the tumor size, indicating that edema was a likely factor affecting the expected tumor to normal tissue contrast. These results suggest

  3. Lung nodule detection by microdose CT versus chest radiography (standard and dual-energy subtracted).

    Science.gov (United States)

    Ebner, Lukas; Bütikofer, Yanik; Ott, Daniel; Huber, Adrian; Landau, Julia; Roos, Justus E; Heverhagen, Johannes T; Christe, Andreas

    2015-04-01

    The purpose of this study was to investigate the feasibility of microdose CT using a comparable dose as for conventional chest radiographs in two planes including dual-energy subtraction for lung nodule assessment. We investigated 65 chest phantoms with 141 lung nodules, using an anthropomorphic chest phantom with artificial lung nodules. Microdose CT parameters were 80 kV and 6 mAs, with pitch of 2.2. Iterative reconstruction algorithms and an integrated circuit detector system (Stellar, Siemens Healthcare) were applied for maximum dose reduction. Maximum intensity projections (MIPs) were reconstructed. Chest radiographs were acquired in two projections with bone suppression. Four blinded radiologists interpreted the images in random order. A soft-tissue CT kernel (I30f) delivered better sensitivities in a pilot study than a hard kernel (I70f), with respective mean (SD) sensitivities of 91.1%±2.2% versus 85.6%±5.6% (p=0.041). Nodule size was measured accurately for all kernels. Mean clustered nodule sensitivity with chest radiography was 45.7%±8.1% (with bone suppression, 46.1%±8%; p=0.94); for microdose CT, nodule sensitivity was 83.6%±9% without MIP (with additional MIP, 92.5%±6%; pmicrodose CT for readers 1, 2, 3, and 4 were 84.3%, 90.7%, 68.6%, and 45.0%, respectively. Sensitivities with chest radiography for readers 1, 2, 3, and 4 were 42.9%, 58.6%, 36.4%, and 90.7%, respectively. In the per-phantom analysis, respective sensitivities of microdose CT versus chest radiography were 96.2% and 75% (pmicrodose CT, the applied dose was 0.1323 mSv. Microdose CT is better than the combination of chest radiography and dual-energy subtraction for the detection of solid nodules between 5 and 12 mm at a lower dose level of 0.13 mSv. Soft-tissue kernels allow better sensitivities. These preliminary results indicate that microdose CT has the potential to replace conventional chest radiography for lung nodule detection.

  4. Efficacy determinants of subcutaneous microdose glucagon during closed-loop control.

    Science.gov (United States)

    Russell, Steven J; El-Khatib, Firas H; Nathan, David M; Damiano, Edward R

    2010-11-01

    During a previous clinical trial of a closed-loop blood glucose (BG) control system that administered insulin and microdose glucagon subcutaneously, glucagon was not uniformly effective in preventing hypoglycemia (BGMicrodose glucagon administration was relatively ineffective in preventing hypoglycemia when plasma insulin levels exceeded the controller's online estimate by >60%. After the algorithm PK parameters were globally adjusted, insulin dosing was more conservative and microdose glucagon administration was very effective in reducing hypoglycemia while maintaining normal plasma glucagon levels. Improvements in the accuracy of the controller's online estimate of plasma insulin levels could be achieved if ultrarapid-acting insulin formulations could be developed with faster absorption and less intra- and intersubject variability than the current insulin analogs available today. © 2010 Diabetes Technology Society.

  5. Microdose transdermal estrogen therapy for relief of vulvovaginal symptoms in postmenopausal women.

    Science.gov (United States)

    Bachmann, Gloria A; Schaefers, Matthias; Uddin, Alkaz; Utian, Wulf H

    2009-01-01

    The aim of this study was to investigate the effectiveness of microdose transdermal 17beta-estradiol (E2) therapy in postmenopausal women with moderate to severe vulvovaginal symptoms. This report is based on a subset of 121 women who reported most bothersome moderate or severe vulvovaginal symptoms at baseline, from a previous randomized, double-blind, placebo-controlled, multicenter study of 425 healthy, symptomatic, postmenopausal women. Recruits had experienced at least 7 moderate or severe hot flushes daily for at least 1 week or at least 50 moderate or severe hot flushes per week for at least 1 week. Effects on coprimary efficacy variables have been reported previously. Participants received low-dose transdermal E2 plus levonorgestrel (n = 43; nominal delivery 0.023 mg/d E2/0.0075 mg/d levonorgestrel), microdose E2 (n = 42; nominal delivery 0.014 mg/d), or placebo (n = 36) for 12 weeks. Secondary efficacy variables reported herein include mean change from baseline in vaginal pH and vaginal maturation index, the proportion of women with symptoms of vulvar and vaginal atrophy at baseline and week 12, and the proportion of women with moderate-to-severe symptoms of vulvar and vaginal atrophy. Microdose transdermal E2 treatment was associated with a consistent benefit versus placebo in women with vulvovaginal atrophy. There was a statistically significant difference between both E2 versus placebo for changes in vaginal pH and vaginal maturation index. Microdose transdermal E2 offers a useful addition to the therapeutic armamentarium for postmenopausal women in whom vulvovaginal symptoms are particularly troublesome.

  6. Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration.

    Science.gov (United States)

    Wang, Guan; Durussel, Jérôme; Shurlock, Jonathan; Mooses, Martin; Fuku, Noriyuki; Bruinvels, Georgie; Pedlar, Charles; Burden, Richard; Murray, Andrew; Yee, Brendan; Keenan, Anne; McClure, John D; Sottas, Pierre-Edouard; Pitsiladis, Yannis P

    2017-11-14

    Recombinant human erythropoietin (rHuEpo) can improve human performance and is therefore frequently abused by athletes. As a result, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) as an indirect method to detect blood doping. Despite this progress, challenges remain to detect blood manipulations such as the use of microdoses of rHuEpo. Forty-five whole-blood transcriptional markers of rHuEpo previously derived from a high-dose rHuEpo administration trial were used to assess whether microdoses of rHuEpo could be detected in 14 trained subjects and whether these markers may be confounded by exercise (n = 14 trained subjects) and altitude training (n = 21 elite runners and n = 4 elite rowers, respectively). Differential gene expression analysis was carried out following normalisation and significance declared following application of a 5% false discovery rate (FDR) and a 1.5 fold-change. Adaptive model analysis was also applied to incorporate these markers for the detection of rHuEpo. ALAS2, BCL2L1, DCAF12, EPB42, GMPR, SELENBP1, SLC4A1, TMOD1 and TRIM58 were differentially expressed during and throughout the post phase of microdose rHuEpo administration. The CD247 and TRIM58 genes were significantly up- and down-regulated, respectively, immediately following exercise when compared with the baseline both before and after rHuEpo/placebo. No significant gene expression changes were found 30 min after exercise in either rHuEpo or placebo groups. ALAS2, BCL2L1, DCAF12, SLC4A1, TMOD1 and TRIM58 tended to be significantly expressed in the elite runners ten days after arriving at altitude and one week after returning from altitude (FDR > 0.059, fold-change varying from 1.39 to 1.63). Following application of the adaptive model, 15 genes showed a high sensitivity (≥ 93%) and specificity (≥ 71%), with BCL2L1 and CSDA having the highest sensitivity (93%) and specificity (93%). Current results provide further evidence that

  7. Microdose computed tomographic cardiac angiography in normal cats.

    Science.gov (United States)

    Rodriguez, Kiira T; O'Brien, Mauria A; Hartman, Susan K; Mulherin, Allison C; McReynolds, Casie J; McMichael, Maureen; Rapoport, Gregg; O'Brien, Robert T

    2014-03-01

    To determine if microdose contrast-enhanced multi-detector computed tomographic angiography (MDCTA) allows characterization of cardiac chambers in lightly sedated normal cats. Seven healthy domestic cats. Lightly sedated normal cats were imaged pre-contrast and with microdose (0.22 ml/kg of non-ionic iodinated contrast medium, 300 mg I/ml) triple-phase MDCTA in a motion restriction device. On pre-contrast images, the aorta (median: 52.43 Hounsfield units [HU], range 27.35-76.74 HU) was outlined by significantly (p = 0.015) lower attenuating periaortic fat (-66.16 HU, -42.62 to -92.77 HU). On post-contrast images, median peak contrast enhancement in the right ventricle (111.77 HU, 36.09-141.60 HU) was achieved in 3.1 s (range 2.9-7.3 s), in the aorta (149.30 HU, 99.43-319.60 HU) and left atrium (180.83 HU, 88.53-266.84 HU) in 6.4 s (range 5.6-7.7 s) and in the left ventricle (147.89 HU, 57.23-245.77 HU) in 7.10 s (range 6.2-11.2 s). Significantly higher attenuation was measured between all chambers and walls, the right ventricular lumen and interventricular septum (median ratio 53.78 HU, range 0.21-83.20 HU), left ventricular lumen and left ventricular free wall (89.32 HU, 38.81-185.95 HU) and aorta and periaortic fat (190.43 HU, 143.22-425.44 HU) on post-contrast images. Sufficient biological contrast is available on survey CT to discriminate between the aorta and the left atrium, and microdose MDCTA provides sufficient contrast enhancement for adequate visualization of the heart chambers in normal cats. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Oral contraceptive pretreatment does not improve outcome in microdose gonadotrophin-releasing hormone agonist protocol among poor responder intracytoplasmic sperm injection patients.

    Science.gov (United States)

    Duvan, Candan Iltemir; Berker, Bulent; Turhan, Nilgun Ozturk; Satiroglu, Hakan

    2008-01-01

    To compare oral contraceptive (OC) pretreatment plus microdose GnRH-a in flare-up protocol and non-OC microdose GnRH-a in flare-up protocol among poor responder ICSI patients. A retrospective analysis of poor responder ICSI patients. Patients were divided into two groups according to used microdose protocol. Precycle treatment with OC followed by follicular phase administration of 40 microg s.c. leuprolide acetate (LA) every 12 h beginning on after 2 day pill-free period and rFSH administration was begun on the third day of LA administration (OC-Group, n=26). Alternatively on day 2 after menses, patients were administered similar stimulation regime (non-OC Group, n=27). There were no significant differences between groups in the number of oocytes, peak estradiol levels, endometrial thickness, fertilization rates and embryo quality. Implantations and pregnancy rates per embryo transfer were similar. OC pretreatment plus microdose GnRHa in flare-up protocol does not offer advantages over non-OC microdose GnRHa in flare-up protocol among poor responder ICSI patients.

  9. Fertilizer micro-dosing: a profitable innovation for Sahelian women ...

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

    2016-06-06

    Jun 6, 2016 ... The localized application of small quantities of fertilizer (micro-dosing), combined with improved planting pits for rainwater harvesting, has generated greater profits and food security for women farmers in the Sahel. Women have taken to the new methods developed by West African and Canadian ...

  10. Intra‐Target Microdosing – A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans

    Science.gov (United States)

    MacLeod, D; Lee, K; Santoro, A; DeMasi, DK; Hawk, T; Feinglos, M; Rowland, M; Noveck, RJ

    2017-01-01

    Abstract Intra‐Target Microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first‐in‐human (FIH) testing of new molecular entities (NMEs). ITM combines intra‐target drug delivery and “microdosing,” the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic‐level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers received insulin microdose into the radial artery or full therapeutic dose intravenously in separate visits. Insulin and glucose levels were similar between systemic administration and ITM administration in the ipsilateral hand, and glucose levels demonstrated a reduction in the ipsilateral hand but not in the contralateral hand. Positron emission tomography (PET) imaging of 18F‐fluorodeoxyglucose (FDG) uptake demonstrated differences between the ipsilateral and contralateral arms. The procedures were safe and well‐tolerated. Results are consistent with ITM proof‐of‐concept (POC) and demonstrate the ethical, regulatory, and logistical feasibility of the approach. PMID:28689370

  11. Intra-Target Microdosing - A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans.

    Science.gov (United States)

    Burt, T; MacLeod, D; Lee, K; Santoro, A; DeMasi, D K; Hawk, T; Feinglos, M; Rowland, M; Noveck, R J

    2017-09-01

    Intra-Target Microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first-in-human (FIH) testing of new molecular entities (NMEs). ITM combines intra-target drug delivery and "microdosing," the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic-level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers received insulin microdose into the radial artery or full therapeutic dose intravenously in separate visits. Insulin and glucose levels were similar between systemic administration and ITM administration in the ipsilateral hand, and glucose levels demonstrated a reduction in the ipsilateral hand but not in the contralateral hand. Positron emission tomography (PET) imaging of 18 F-fluorodeoxyglucose (FDG) uptake demonstrated differences between the ipsilateral and contralateral arms. The procedures were safe and well-tolerated. Results are consistent with ITM proof-of-concept (POC) and demonstrate the ethical, regulatory, and logistical feasibility of the approach. © 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  12. Assessment of two-dimensional (2D) and three-dimensional (3D) lower limb measurements in adults: Comparison of micro-dose and low-dose biplanar radiographs

    International Nuclear Information System (INIS)

    Rosskopf, Andrea B.; Pfirrmann, Christian W.A.; Buck, Florian M.

    2016-01-01

    To evaluate reliability of 2D and 3D lower limb measurements in adults using micro-dose compared to low-dose biplanar radiographs(BPR). One hundred patients (mean 54.9 years) were examined twice using micro-dose and low-dose BPR. Length and mechanical axis of lower limbs were measured on the antero-posterior(ap) micro-dose and low-dose images by two independent readers. Femoral and tibial torsions of 50 patients were measured by two independent readers using reconstructed 3D-models based on the micro-dose and low-dose BPR. Intermethod and interreader agreements were calculated using descriptive statistics, intraclass-correlation-coefficient(ICC), and Bland-Altman analysis. Mean interreader-differences on micro-dose were 0.3 cm(range 0-1.0)/ 0.7 (0-2.9) for limb length/axis and 0.4 cm (0-1.0)/0.8 (0-3.3) on low-dose BPR. Mean intermethod-difference was 0.04 cm ± 0.2/0.04 ± 0.6 for limb length/axis. Interreader-ICC for limb length/axis was 0.999/0.991 on micro-dose and 0.999/0.987 on low-dose BPR. Interreader-ICC for micro-dose was 0.879/0.826 for femoral/tibial torsion, for low-dose BPR was 0.924/0.909. Mean interreader-differences on micro-dose/low-dose BPR were 3 (0-13 )/2 (0 -12 ) for femoral and 4 (0-18 )/3 (0 -10 ) for tibial torsion. Mean intermethod-difference was -0.1 ± 5.0/-0.4 ± 2.9 for femoral/tibial torsion. Mean dose-area-product was significantly lower (9.9 times;p < 0.001) for micro-dose BPR. 2D-and 3D-measurements of lower limbs based on micro-dose BPR are reliable and provide a 10-times lower radiation dose. (orig.)

  13. Microdose clinical trial by use of radioisotope and perspective of its possible utilization in drug development

    International Nuclear Information System (INIS)

    Yano, Tsuneo; Watanabe, Yasuyoshi

    2009-01-01

    Many promising PET tracers have been developed by the progress of molecular imaging research, and new era could be opened by clinical trials using investigational products labeled by RI. Guidance for microdose clinical trial issued by MHLW in June, 2008, is the regulatory basis to develop PET tracer under clinical trial by the pharmaceutical affairs law. In this review, the discussion from the aspect of regulatory science is highlighted, particularly, on the topics of guidance for microdose and exploratory IND study including sub-therapeutic dose (type II) and therapeutic dose (type III), the revised GMP for investigational product including RI-labeled product, and to ward guidance for microdose clinical trial for biological product. Finally, the US FDA guidance developing medical imaging drug including biological product is introduced, and then perspective of possible utilization of in vivo radiopharmaceutical agents in drug development is discussed. (author)

  14. Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects.

    Science.gov (United States)

    Kusuhara, H; Ito, S; Kumagai, Y; Jiang, M; Shiroshita, T; Moriyama, Y; Inoue, K; Yuasa, H; Sugiyama, Y

    2011-06-01

    A microdose study of metformin was conducted to investigate the predictability of drug-drug interactions at the therapeutic dose (ThD). Healthy subjects received a microdose (100 µg) or ThD (250 mg) of metformin orally, with or without a potent and competitive multidrug and toxin extrusion (MATE) inhibitor, pyrimethamine (50 mg, p.o.), in a crossover fashion. Pyrimethamine significantly reduced the renal clearance of metformin by 23 and 35% at the microdose and ThD, respectively. At ThD, but not at microdose, it caused significant increases in the maximum concentration (C(max)) and area under the plasma concentration-time curve (AUC) of metformin (142 and 139% of control values, respectively). Human canalicular membrane vesicles showed pyrimethamine-inhibitable metformin uptake. Pyrimethamine did not affect plasma lactate/pyruvate after ThD of metformin but significantly reduced the renal clearance of creatinine, thereby causing elevation of plasma creatinine level. This microdose study quantitatively predicted a drug-drug interaction involving the renal clearance of metformin at ThD by pyrimethamine. Pyrimethamine is a useful in vivo inhibitor of MATE proteins.

  15. Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers.

    Science.gov (United States)

    Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Brian Houston, J; Oosterhuis, Berend; Bjerrum, Ole J; Grynkiewicz, Grzegorz; Alder, Jane; Rowland, Malcolm; Garner, Colin

    2011-06-14

    A clinical study was conducted to assess the ability of a microdose (100 μg) to predict the human pharmacokinetics (PK) following a therapeutic dose of clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen) and phenobarbital, both within the study and by reference to the existing literature on these compounds and to explore the source of any nonlinearity if seen. For each drug, 6 healthy male volunteers were dosed with 100 μg (14)C-labelled compound. For clarithromycin, sumatriptan, and propafenone this labelled dose was administered alone, i.e. as a microdose, orally and intravenously (iv) and as an iv tracer dose concomitantly with an oral non-labelled therapeutic dose, in a 3-way cross over design. The oral therapeutic doses were 250, 50, and 150 mg, respectively. Paracetamol was given as the labelled microdose orally and iv using a 2-way cross over design, whereas phenobarbital was given only as the microdose orally. Plasma concentrations of total (14)C and parent drug were measured using accelerator mass spectrometry (AMS) or HPLC followed by AMS. Plasma concentrations following non-(14)C-labelled oral therapeutic doses were measured using either HPLC-electrochemical detection (clarithromycin) or HPLC-UV (sumatriptan, propafenone). For all five drugs an oral microdose predicted reasonably well the PK, including the shape of the plasma profile, following an oral therapeutic dose. For clarithromycin, sumatriptan, and propafenone, one parameter, oral bioavailability, was marginally outside of the normally acceptable 2-fold prediction interval around the mean therapeutic dose value. For clarithromycin, sumatriptan and propafenone, data obtained from an oral and iv microdose were compared within the same cohort of subjects used in the study, as well as those reported in the literature. For paracetamol (oral and iv) and phenobarbital (oral), microdose data were compared with those reported in the literature only. Where 100 μg iv (14)C-doses were

  16. Human microdose evaluation of the novel EP1 receptor antagonist GSK269984A.

    Science.gov (United States)

    Ostenfeld, Thor; Beaumont, Claire; Bullman, Jonathan; Beaumont, Maria; Jeffrey, Phillip

    2012-12-01

    The primary objective was to evaluate the pharmacokinetics (PK) of the novel EP(1) antagonist GSK269984A in human volunteers after a single oral and intravenous (i.v.) microdose (100 µg). GSK269984A was administered to two groups of healthy human volunteers as a single oral (n= 5) or i.v. (n= 5) microdose (100 µg). Blood samples were collected for up to 24 h and the parent drug concentrations were measured in separated plasma using a validated high pressure liquid chromatography-tandem mass spectrometry method following solid phase extraction. Following the i.v. microdose, the geometric mean values for clearance (CL), steady-state volume of distribution (V(ss) ) and terminal elimination half-life (t(1/2) ) of GSK269984A were 9.8 l h(-1) , 62.8 l and 8.2 h. C(max) and AUC(0,∞) were 3.2 ng ml(-1) and 10.2 ng ml(-1)  h, respectively; the corresponding oral parameters were 1.8 ng ml(-1) and 9.8 ng ml(-1)  h, respectively. Absolute oral bioavailability was estimated to be 95%. These data were inconsistent with predictions of human PK based on allometric scaling of in vivo PK data from three pre-clinical species (rat, dog and monkey). For drug development programmes characterized by inconsistencies between pre-clinical in vitro metabolic and in vivo PK data, and where uncertainty exists with respect to allometric predictions of the human PK profile, these data support the early application of a human microdose study to facilitate the selection of compounds for further clinical development. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  17. Assessment of micro-dose biplanar radiography in lower limb measurements in children

    International Nuclear Information System (INIS)

    Lerisson, Heloise; Amzallag-Bellenger, Elisa; Cebulski-Delebarre, Aurelie; Boutry, Nathalie; Nectoux, Eric; Herbaux, Bernard; Desmulliez, Geoffrey; Duhamel, Alain; Drumez, Elodie

    2018-01-01

    To evaluate in children microdose protocol compared with low dose for lower limb alignment (LLA) measurements on biplanar radiography. Children 6 years or older were included. Height, weight and hip width were measured prior to imaging. Hip width allowed classifying children into morphotype M1 (width <25 cm), M2 (25-35 cm) or M3 (>35 cm) corresponding to predefined acquisition parameters (kV, mA, tube speed). Micro- and low-dose protocols were used alternately, with simultaneous acquisition of frontal and lateral radiographs. LLA measurements were performed by two independent observers (n = 526). In 15 children per morphotype, a third observer performed measurements twice (n = 180). Intraclass correlation coefficients and the dose (delivered, absorbed) were calculated. 100 girls and 160 boys (mean age = 11.7 years) were investigated: 74 M1 (mean BMI, 15.7kg/m 2 ), 149 M2 (19.8 kg/m 2 ) and 40 M3 (30.2 kg/m 2 ). With microdose, inter- and intra-observer agreement was >0.90 for lengths whatever the morphotype, 0.75-0.90 (M1) and >0.90 (M2, M3) for valgus/varus and flexion/hyperextension deviations. Dose reduction reached a factor of 8.5 and 5.4 for the delivered and absorbed dose respectively. Microdose could be used for LLA measurements in children and permits a significant dose reduction. (orig.)

  18. Pediatric microdose study of [(14)C]paracetamol to study drug metabolism using accelerated mass spectrometry: proof of concept.

    Science.gov (United States)

    Mooij, Miriam G; van Duijn, Esther; Knibbe, Catherijne A J; Windhorst, Albert D; Hendrikse, N Harry; Vaes, Wouter H J; Spaans, Edwin; Fabriek, Babs O; Sandman, Hugo; Grossouw, Dimitri; Hanff, Lidwien M; Janssen, Paul J J M; Koch, Birgit C P; Tibboel, Dick; de Wildt, Saskia N

    2014-11-01

    Pediatric drug development is hampered by practical, ethical, and scientific challenges. Microdosing is a promising new method to obtain pharmacokinetic data in children with minimal burden and minimal risk. The use of a labeled oral microdose offers the added benefit to study intestinal and hepatic drug disposition in children already receiving an intravenous therapeutic drug dose for clinical reasons. The objective of this study was to present pilot data of an oral [(14)C]paracetamol [acetaminophen (AAP)] microdosing study as proof of concept to study developmental pharmacokinetics in children. In an open-label microdose pharmacokinetic pilot study, infants (0-6 years of age) received a single oral [(14)C]AAP microdose (3.3 ng/kg, 60 Bq/kg) in addition to intravenous therapeutic doses of AAP (15 mg/kg intravenous every 6 h). Blood samples were taken from an indwelling catheter. AAP blood concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and [(14)C]AAP and metabolites ([(14)C]AAP-Glu and [(14)C]AAP-4Sul) were measured by accelerator mass spectrometry. Ten infants (aged 0.1-83.1 months) were included; one was excluded as he vomited shortly after administration. In nine patients, [(14)C]AAP and metabolites in blood samples were detectable at expected concentrations: median (range) maximum concentration (C max) [(14)C]AAP 1.68 (0.75-4.76) ng/L, [(14)C]AAP-Glu 0.88 (0.34-1.55) ng/L, and [(14)C]AAP-4Sul 0.81 (0.29-2.10) ng/L. Dose-normalized oral [(14)C]AAP C max approached median intravenous average concentrations (C av): 8.41 mg/L (3.75-23.78 mg/L) and 8.87 mg/L (3.45-12.9 mg/L), respectively. We demonstrate the feasibility of using a [(14)C]labeled microdose to study AAP pharmacokinetics, including metabolite disposition, in young children.

  19. Use of Microdosing and Accelerator Mass Spectrometry To Evaluate the Pharmacokinetic Linearity of a Novel Tricyclic GyrB/ParE Inhibitor in Rats

    Science.gov (United States)

    Lao, Victoria; Ramos, Courtney L.; Ong, Voon S.; Turteltaub, Kenneth W.

    2014-01-01

    Determining the pharmacokinetics (PKs) of drug candidates is essential for understanding their biological fate. The ability to obtain human PK information early in the drug development process can help determine if future development is warranted. Microdosing was developed to assess human PKs, at ultra-low doses, early in the drug development process. Microdosing has also been used in animals to confirm PK linearity across subpharmacological and pharmacological dose ranges. The current study assessed the PKs of a novel antimicrobial preclinical drug candidate (GP-4) in rats as a step toward human microdosing studies. Dose proportionality was determined at 3 proposed therapeutic doses (3, 10, and 30 mg/kg of body weight), and PK linearity between a microdose and a pharmacological dose was assessed in Sprague-Dawley rats. Plasma PKs over the 3 pharmacological doses were proportional. Over the 10-fold dose range, the maximum concentration in plasma and area under the curve (AUC) increased 9.5- and 15.8-fold, respectively. PKs from rats dosed with a 14C-labeled microdose versus a 14C-labeled pharmacological dose displayed dose linearity. In the animals receiving a microdose and the therapeutically dosed animals, the AUCs from time zero to infinity were 2.6 ng · h/ml and 1,336 ng · h/ml, respectively, and the terminal half-lives were 5.6 h and 1.4 h, respectively. When the AUC values were normalized to a dose of 1.0 mg/kg, the AUC values were 277.5 ng · h/ml for the microdose and 418.2 ng · h/ml for the pharmacological dose. This 1.5-fold difference in AUC following a 300-fold difference in dose is considered linear across the dose range. On the basis of the results, the PKs from the microdosed animals were considered to be predictive of the PKs from the therapeutically dosed animals. PMID:25136019

  20. Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A.

    Science.gov (United States)

    Prueksaritanont, T; Tatosian, D A; Chu, X; Railkar, R; Evers, R; Chavez-Eng, C; Lutz, R; Zeng, W; Yabut, J; Chan, G H; Cai, X; Latham, A H; Hehman, J; Stypinski, D; Brejda, J; Zhou, C; Thornton, B; Bateman, K P; Fraser, I; Stoch, S A

    2017-04-01

    A microdose cocktail containing midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin has been established to allow simultaneous assessment of a perpetrator impact on the most common drug metabolizing enzyme, cytochrome P450 (CYP)3A, and the major transporters organic anion-transporting polypeptides (OATP)1B, breast cancer resistance protein (BCRP), and MDR1 P-glycoprotein (P-gp). The clinical utility of these microdose cocktail probe substrates was qualified by conducting clinical drug interaction studies with three inhibitors with different in vitro inhibitory profiles (rifampin, itraconazole, and clarithromycin). Generally, the pharmacokinetic profiles of the probe substrates, in the absence and presence of the inhibitors, were comparable to their reported corresponding pharmacological doses, and/or in agreement with theoretical expectations. The exception was dabigatran, which resulted in an approximately twofold higher magnitude for microdose compared to conventional dosing, and, thus, can be used to flag a worst-case scenario for P-gp. Broader application of the microdose cocktail will facilitate a more comprehensive understanding of the roles of drug transporters in drug disposition and drug interactions. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  1. A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects.

    Science.gov (United States)

    Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

    2009-03-01

    To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). Five H(1) receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. The median clearance (CL), apparent volume of distribution (V(d)) and apparent terminal elimination half-life (t(1/2)) of diphenhydramine after an i.v. microdose were 24.7 l h(-1), 302 l and 9.3 h, and the oral C(max) and AUC(0-infinity) were 0.195 ng ml(-1) and 1.52 ng h ml(-1), respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection.

  2. A pharmacokinetic evaluation of five H1 antagonists after an oral and intravenous microdose to human subjects

    Science.gov (United States)

    Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

    2009-01-01

    AIMS To evaluate the pharmacokinetics (PK) of five H1 receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). METHODS Five H1 receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. RESULTS The median clearance (CL), apparent volume of distribution (Vd) and apparent terminal elimination half-life (t1/2) of diphenhydramine after an i.v. microdose were 24.7 l h−1, 302 l and 9.3 h, and the oral Cmax and AUC0–∞ were 0.195 ng ml−1 and 1.52 ng h ml−1, respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. CONCLUSIONS Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection. PMID:19523012

  3. Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study.

    Science.gov (United States)

    Berker, Bülent; Duvan, Candan İltemir; Kaya, Cemil; Aytaç, Ruşen; Satıroğlu, Hakan

    2010-01-01

    To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI.

  4. The antiaging activity and cerebral protection of rapamycin at micro-doses.

    Science.gov (United States)

    Qi, Haiyan; Su, Feng-Yun; Wan, Shan; Chen, Yongjie; Cheng, Yan-Qiong; Liu, Ai-Jun

    2014-11-01

    The immunosuppressant drug rapamycin was reported to have an antiaging activity, which was attributed to the TORC1 inhibition that inhibits cell proliferation and increases autophagy. However, rapamycin also exhibits a number of harmful adverse effects. Whether rapamycin can be developed into an antiaging agent remains unclear. We demonstrated that rapamycin at micro-doses (below the TORC1 inhibiting concentration) exhibits a cell-protective activity: (1) It protects cultured neurons against neurotoxin MPP(+) and H2O2. (2) It increases survival time of neuron in culture. (3) It maintains the nonproliferative state of cultured senescent human fibroblasts and prevents cell death induced by telomere dysfunction. (4) In animal models, it decreased the cerebral infarct sizes induced by acute ischemia and dramatically extended the life span of stroke prone spontaneously hypertensive rats (SHR-SPs). We propose that rapamycin at micro-dose can be developed into an antiaging agent with a novel mechanism. © 2014 John Wiley & Sons Ltd.

  5. Comparison of microdose flare-up and antagonist multiple-dose protocols for poor-responder patients: a randomized study.

    Science.gov (United States)

    Demirol, Aygul; Gurgan, Timur

    2009-08-01

    To compare the efficacy of the microdose flare-up and multiple-dose antagonist protocols for poor-responder patients in intracytoplasmic sperm injection-ET cycles. A randomized, prospective study. Center for assisted reproductive technology in Turkey. Ninety patients with poor ovarian response in a minimum of two previous IVF cycles. All women were prospectively randomized into two groups by computer-assisted randomization. The patients in group 1 were stimulated according to the microdose flare-up protocol (n = 45), while the patients in group 2 were stimulated according to antagonist multiple-dose protocol (n = 45). The mean number of mature oocytes retrieved was the primary outcome measure, and fertilization rate, implantation rate per embryo, and clinical pregnancy rates were secondary outcome measures. The mean age of the women, the mean duration of infertility, basal FSH level, and the number of previous IVF cycles were similar in both groups. The total gonadotropin dose used was significantly higher in group 2, while the number of oocytes retrieved was significantly greater in group 1. Although the fertilization and clinical pregnancy rates were nonsignificantly higher in group 1 compared with group 2, the implantation rate was significantly higher in the microdose flare-up group than in the multiple-dose antagonist group (22% vs. 11%). The microdose flare-up protocol seems to have a better outcome in poor-responder patients, with a significantly higher mean number of mature oocytes retrieved and higher implantation rate.

  6. Ultrasensitive liquid chromatography-tandem mass spectrometric methodologies for quantification of five HIV-1 integrase inhibitors in plasma for a microdose clinical trial.

    Science.gov (United States)

    Sun, Li; Li, Hankun; Willson, Kenneth; Breidinger, Sheila; Rizk, Matthew L; Wenning, Larissa; Woolf, Eric J

    2012-10-16

    HIV-1 integrase strand transfer inhibitors are an important class of compounds targeted for the treatment of HIV-1 infection. Microdosing has emerged as an attractive tool to assist in drug candidate screening for clinical development, but necessitates extremely sensitive bioanalytical assays, typically in the pg/mL concentration range. Currently, accelerator mass spectrometry is the predominant tool for microdosing support, which requires a specialized facility and synthesis of radiolabeled compounds. There have been few studies attempted to comprehensively assess a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach in the context of microdosing applications. Herein, we describe the development of automated LC-MS/MS methods to quantify five integrase inhibitors in plasma with the limits of quantification at 1 pg/mL for raltegravir and 2 pg/mL for four proprietary compounds. The assays involved double extractions followed by UPLC coupled with negative ion electrospray MS/MS analysis. All methods were fully validated to the rigor of regulated bioanalysis requirements, with intraday precision between 1.20 and 14.1% and accuracy between 93.8 and 107% at the standard curve concentration range. These methods were successfully applied to a human microdose study and demonstrated to be accurate, reproducible, and cost-effective. Results of the study indicate that raltegravir displayed linear pharmacokinetics between a microdose and a pharmacologically active dose.

  7. 14C sample preparation for AMS microdosing studies at Lund University using online combustion and septa-sealed vials

    Science.gov (United States)

    Sydoff, Marie; Stenström, Kristina

    2010-04-01

    The Department of Physics at Lund University is participating in a European Union project called EUMAPP (European Union Microdose AMS Partnership Programme), in which sample preparation and accelerator mass spectrometry (AMS) measurements of biological samples from microdosing studies have been made. This paper describes a simplified method of converting biological samples to solid graphite for 14C analysis with AMS. The method is based on online combustion of the samples, and reduction of CO 2 in septa-sealed vials. The septa-sealed vials and disposable materials are used to eliminate sample cross-contamination. Measurements of ANU and Ox I standards show deviations of 2% and 3%, respectively, relative to reference values. This level of accuracy is sufficient for biological samples from microdosing studies. Since the method has very few handling steps from sample to graphite, the risk of failure during the sample preparation process is minimized, making the method easy to use in routine preparation of samples.

  8. 14C sample preparation for AMS microdosing studies at Lund University using online combustion and septa-sealed vials

    International Nuclear Information System (INIS)

    Sydoff, Marie; Stenstroem, Kristina

    2010-01-01

    The Department of Physics at Lund University is participating in a European Union project called EUMAPP (European Union Microdose AMS Partnership Programme), in which sample preparation and accelerator mass spectrometry (AMS) measurements of biological samples from microdosing studies have been made. This paper describes a simplified method of converting biological samples to solid graphite for 14 C analysis with AMS. The method is based on online combustion of the samples, and reduction of CO 2 in septa-sealed vials. The septa-sealed vials and disposable materials are used to eliminate sample cross-contamination. Measurements of ANU and Ox I standards show deviations of 2% and 3%, respectively, relative to reference values. This level of accuracy is sufficient for biological samples from microdosing studies. Since the method has very few handling steps from sample to graphite, the risk of failure during the sample preparation process is minimized, making the method easy to use in routine preparation of samples.

  9. The microdose rapid 14C urea breath test compares well with the original rapid 14 breath test

    International Nuclear Information System (INIS)

    Bellon, M.S.; Bartholomeusz, F.D.L.; Chatterton, B.E.

    2000-01-01

    Full text: The 14 C urea breath test (CUBT) is a sensitive test used in the detection of H. pylori infection. The rapid 14 CUBT using 185 KBq of 14 C urea showed a sensitivity of 100% when tested in 36 patients. The aim of this study was to compare the results of the 14 CUBT performed following the ingestion of 37KBq microdose 14 C urea capsule (Bicapsule, Trimed) with the earlier method which uses 185 KBq 14 C urea. 19 patients (nine female age 21-52 yrs) were studied. All subjects first underwent a 14 CUBT with the microdose capsule and a single 15 minute post ingestion sample. An hour later the test was repeated but with a dose of 185 KBq 14 C urea in liquid form. A normal result was taken as 2 = 0.92). This is shown above. The Rapid 14 CUBT performed following the microdose capsule whilst reducing patient radiation exposure is an accurate test for the detection of H. pylori. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  10. Chronic Microdose Lithium Treatment Prevented Memory Loss and Neurohistopathological Changes in a Transgenic Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Nunes, Marielza Andrade; Schöwe, Natalia Mendes; Monteiro-Silva, Karla Cristina; Baraldi-Tornisielo, Ticiana; Souza, Suzzanna Ingryd Gonçalves; Balthazar, Janaina; Albuquerque, Marilia Silva; Caetano, Ariadiny Lima; Viel, Tania Araujo; Buck, Hudson Sousa

    2015-01-01

    The use of lithium is well established in bipolar disorders and the benefits are being demonstrated in neurodegenerative disorders. Recently, our group showed that treatment with microdose lithium stabilized the cognitive deficits observed in Alzheimer's disease (AD) patients. In order to verify the lithium microdose potential in preventing the disease development, the aim of this work was to verify the effects of chronic treatment with microdose lithium given before and after the appearance of symptoms in a mouse model of a disease similar to AD. Transgenic mice (Cg-Tg(PDGFB-APPSwInd)20Lms/2J) and their non-transgenic litter mate genetic controls were treated with lithium carbonate (0.25mg/Kg/day in drinking water) for 16 or 8 months starting at two and ten months of age, respectively [corrected]. Similar groups were treated with water. At the end of treatments, both lithium treated transgenic groups and non-transgenic mice showed no memory disruption, different from what was observed in the water treated transgenic group. Transgenic mice treated with lithium since two months of age showed decreased number of senile plaques, no neuronal loss in cortex and hippocampus and increased BDNF density in cortex, when compared to non-treated transgenic mice. It is suitable to conclude that these data support the use of microdose lithium in the prevention and treatment of Alzheimer's disease, once the neurohistopathological characteristics of the disease were modified and the memory of transgenic animals was maintained.

  11. Chronic Microdose Lithium Treatment Prevented Memory Loss and Neurohistopathological Changes in a Transgenic Mouse Model of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Marielza Andrade Nunes

    Full Text Available The use of lithium is well established in bipolar disorders and the benefits are being demonstrated in neurodegenerative disorders. Recently, our group showed that treatment with microdose lithium stabilized the cognitive deficits observed in Alzheimer's disease (AD patients. In order to verify the lithium microdose potential in preventing the disease development, the aim of this work was to verify the effects of chronic treatment with microdose lithium given before and after the appearance of symptoms in a mouse model of a disease similar to AD. Transgenic mice (Cg-Tg(PDGFB-APPSwInd20Lms/2J and their non-transgenic litter mate genetic controls were treated with lithium carbonate (0.25mg/Kg/day in drinking water for 16 or 8 months starting at two and ten months of age, respectively [corrected]. Similar groups were treated with water. At the end of treatments, both lithium treated transgenic groups and non-transgenic mice showed no memory disruption, different from what was observed in the water treated transgenic group. Transgenic mice treated with lithium since two months of age showed decreased number of senile plaques, no neuronal loss in cortex and hippocampus and increased BDNF density in cortex, when compared to non-treated transgenic mice. It is suitable to conclude that these data support the use of microdose lithium in the prevention and treatment of Alzheimer's disease, once the neurohistopathological characteristics of the disease were modified and the memory of transgenic animals was maintained.

  12. {sup 14}C sample preparation for AMS microdosing studies at Lund University using online combustion and septa-sealed vials

    Energy Technology Data Exchange (ETDEWEB)

    Sydoff, Marie, E-mail: marie.sydoff@med.lu.s [Department of Clinical Sciences, Medical Radiation Physics, Malmo University Hospital, SE-205 02 Malmoe (Sweden); Lund University, Department of Physics, Division of Nuclear Physics, P.O. Box 118, SE-221 00 Lund (Sweden); Stenstroem, Kristina [Lund University, Department of Physics, Division of Nuclear Physics, P.O. Box 118, SE-221 00 Lund (Sweden)

    2010-04-15

    The Department of Physics at Lund University is participating in a European Union project called EUMAPP (European Union Microdose AMS Partnership Programme), in which sample preparation and accelerator mass spectrometry (AMS) measurements of biological samples from microdosing studies have been made. This paper describes a simplified method of converting biological samples to solid graphite for {sup 14}C analysis with AMS. The method is based on online combustion of the samples, and reduction of CO{sub 2} in septa-sealed vials. The septa-sealed vials and disposable materials are used to eliminate sample cross-contamination. Measurements of ANU and Ox I standards show deviations of 2% and 3%, respectively, relative to reference values. This level of accuracy is sufficient for biological samples from microdosing studies. Since the method has very few handling steps from sample to graphite, the risk of failure during the sample preparation process is minimized, making the method easy to use in routine preparation of samples.

  13. Biphasic Elimination of Tenofovir Diphosphate and Nonlinear Pharmacokinetics of Zidovudine Triphosphate in a Microdosing Study

    Science.gov (United States)

    Chen, Jianmeng; Flexner, Charles; Liberman, Rosa G.; Skipper, Paul L.; Louissaint, Nicolette; Tannenbaum, Steven R.; Hendrix, Craig; Fuchs, Edward

    2012-01-01

    Objective Phase 0 studies can provide initial pharmacokinetics (PK) data in humans and help to facilitate early drug development, but their predictive value for standard dosing is controversial. To evaluate the prediction of microdosing for active intracellular drug metabolites, we compared the PK profile of two antiretroviral drugs, zidovudine (ZDV) and tenofovir (TFV), in microdose and standard dosing regimens. Study Design We administered a microdose (100 μg) of 14C-labeled drug (ZDV or tenofovir disoproxil fumarate (TDF)) with or without a standard unlabelled dose (300 mg) to healthy volunteers. Both the parent drug in plasma and the active metabolite, ZDV-triphosphate (ZDV-TP) or TFV-diphosphate (TFV-DP) in PBMCs and CD4+ cells were measured by AMS. Results The intracellular ZDV-TP concentration increased less than proportionally over the dose range studied (100 μg to 300 mg), while the intracellular TFV-DP PK were linear over the same dose range. ZDV-TP concentrations were lower in CD4+ cells versus total peripheral blood mononuclear cells (PBMCs), while TFV-DP concentrations were not different in CD4+ cells and PBMCs. Conclusion Our data were consistent with a rate-limiting step in the intracellular phosphorylation of ZDV but not TFV. AMS shows promise for predicting the PK of active intracellular metabolites of nucleosides, but nonlinearity of PK may be seen with some drugs. PMID:23187888

  14. Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development.

    Science.gov (United States)

    Chung, Karine; Fogle, Robin; Bendikson, Kristin; Christenson, Kamilee; Paulson, Richard

    2011-01-01

    Because the effectiveness of the "microdose flare" stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  15. The research progress of microdose effect in semiconductor devices

    International Nuclear Information System (INIS)

    Yan Yihua; Fan Ruyu; Guo Xiaoqiang; Lin Dongsheng; Guo Hongxia; Zhang Fengqi; Chen Wei

    2012-01-01

    The localized dose deposited around the track of a heavy ion can be high enough to induce a permanent failure in the semiconductor devices, such as the stuck bit error or functional failure. In this paper, progresses in studies on microdose effect are reviewed. Two basic failure mechanisms, i.e. the localized total dose effect and the strong coulomb repulsive force effect, are discussed. Typical failure modes in several types of devices, and the main impact factors, are discussed, too. (authors)

  16. Cumulative effective dose and cancer risk for pediatric population in repetitive full spine follow-up imaging: How micro dose is the EOS microdose protocol?

    Science.gov (United States)

    Law, Martin; Ma, Wang-Kei; Lau, Damian; Cheung, Kenneth; Ip, Janice; Yip, Lawrance; Lam, Wendy

    2018-04-01

    To evaluate and to obtain analytic formulation for the calculation of the effective dose and associated cancer risk using the EOS microdose protocol for scoliotic pediatric patients undergoing full spine imaging at different age of exposure; to demonstrate the microdose protocol capable of delivering lesser radiation dose and hence of further reducing cancer risk induction when compared with the EOS low dose protocol; to obtain cumulative effective dose and cancer risk for both genders scoliotic pediatrics of US and Hong Kong population using the microdose protocol. Organ absorbed doses of full spine exposed scoliotic pediatric patients have been simulated with the use of EOS microdose protocol imaging parameters input to the Monte Carlo software PCXMC. Gender and age specific effective dose has been calculated with the simulated organ absorbed dose using the ICRP-103 approach. The associated radiation induced cancer risk, expressed as lifetime attributable risk (LAR), has been estimated according to the method introduced in the Biological Effects of Ionizing Radiation VII report. Values of LAR have been estimated for scoliotic patients exposed repetitively during their follow up period at different age for US and Hong Kong population. The effective doses of full spine imaging with simultaneous posteroanterior and lateral projection for patients exposed at the age between 5 and 18 years using the EOS microdose protocol have been calculated within the range of 2.54-14.75 μSv. The corresponding LAR for US and Hong Kong population was ranged between 0.04 × 10 -6 and 0.84 × 10 -6 . Cumulative effective dose and cancer risk during follow-up period can be estimated using the results and are of information to patients and their parents. With the use of computer simulation and analytic formulation, we obtained the cumulative effective dose and cancer risk at any age of exposure for pediatric patients of US and Hong Kong population undergoing repetitive

  17. Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A activity in humans.

    Science.gov (United States)

    Hohmann, Nicolas; Kocheise, Franziska; Carls, Alexandra; Burhenne, Jürgen; Haefeli, Walter E; Mikus, Gerd

    2015-02-01

    We aimed to establish a method to assess systemic and pre-systemic cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam. In an open, one sequence, crossover study, 16 healthy participants received intravenous and oral midazolam at microgram (0.001 mg intravenous and 0.003 mg oral) and regular milligram (1 mg intravenous and 3 mg oral) doses to assess the linearity of plasma and urine pharmacokinetics. Dose-normalized AUC and Cmax were 37.1 ng ml(-1 ) h [95% CI 35.5, 40.6] and 39.1 ng ml(-1) [95% CI 30.4, 50.2] for the microdose and 39.0 ng ml(-1 ) h [95% CI 36.1, 42.1] and 37.1 ng ml(-1) [95% CI 26.9, 51.3] for the milligram dose. CLmet was 253 ml min(-1) [95% CI 201, 318] vs. 278 ml min(-1) [95% CI 248, 311] for intravenous doses and 1880 ml min(-1) [95% CI 1590, 2230] vs. 2050 ml min(-1) [95% CI 1720, 2450] for oral doses. Oral bioavailability of a midazolam microdose was 23.4% [95% CI 20.0, 27.3] vs. 20.9% [95% CI 17.1, 25.5] after the regular dose. Hepatic and gut extraction ratios for microgram doses were 0.44 [95% CI 0.39, 0.49] and 0.53 [95% CI 0.45, 0.63] and compared well with those for milligram doses (0.43 [95% CI 0.37, 0.49] and 0.61 [95% CI 0.53, 0.70]). The pharmacokinetics of an intravenous midazolam microdose is linear to the applied regular doses and can be used to assess safely systemic CYP3A activity and, in combination with oral microdoses, pre-systemic CYP3A activity. © 2014 The British Pharmacological Society.

  18. Cost-effectiveness analysis of microdose clinical trials in drug development.

    Science.gov (United States)

    Yamane, Naoe; Igarashi, Ataru; Kusama, Makiko; Maeda, Kazuya; Ikeda, Toshihiko; Sugiyama, Yuichi

    2013-01-01

    Microdose (MD) clinical trials have been introduced to obtain human pharmacokinetic data early in drug development. Here we assessed the cost-effectiveness of microdose integrated drug development in a hypothetical model, as there was no such quantitative research that weighed the additional effectiveness against the additional time and/or cost. First, we calculated the cost and effectiveness (i.e., success rate) of 3 types of MD integrated drug development strategies: liquid chromatography-tandem mass spectrometry, accelerator mass spectrometry, and positron emission tomography. Then, we analyzed the cost-effectiveness of 9 hypothetical scenarios where 100 drug candidates entering into a non-clinical toxicity study were selected by different methods as the conventional scenario without MD. In the base-case, where 70 drug candidates were selected without MD and 30 selected evenly by one of the three MD methods, incremental cost-effectiveness ratio per one additional drug approved was JPY 12.7 billion (US$ 0.159 billion), whereas the average cost-effectiveness ratio of the conventional strategy was JPY 24.4 billion, which we set as a threshold. Integrating MD in the conventional drug development was cost-effective in this model. This quantitative analytical model which allows various modifications according to each company's conditions, would be helpful for guiding decisions early in clinical development.

  19. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease.

    Science.gov (United States)

    Nunes, Marielza Andrade; Viel, Tania Araujo; Buck, Hudson Sousa

    2013-01-01

    A lower incidence of dementia in bipolar patients treated with lithium has been described. This metal inhibits the phosphorylation of glycogen-synthase-kinase 3-α and β, which are related to amyloid precursor protein processing and tau hyperphosphorylation in pathological conditions, respectively. Following the same rationale, a group just found that lithium has disease-modifying properties in amnestic mild cognitive impairment with potential clinical implications for the prevention of Alzheimer's Disease (AD) when a dose ranging from 150 to 600 mg is used. As lithium is highly toxic in regular doses, our group evaluated the effect of a microdose of 300 μg, administered once daily on AD patients for 15 months. In the evaluation phase, the treated group showed no decreased performance in the mini-mental state examination test, in opposition to the lower scores observed for the control group during the treatment, with significant differences starting three months after the beginning of the treatment, and increasing progressively. This data suggests the efficacy of a microdose lithium treatment in preventing cognitive loss, reinforcing its therapeutic potential to treat AD using very low doses.

  20. Calculation and mitigation of isotopic interferences in liquid chromatography-mass spectrometry/mass spectrometry assays and its application in supporting microdose absolute bioavailability studies.

    Science.gov (United States)

    Gu, Huidong; Wang, Jian; Aubry, Anne-Françoise; Jiang, Hao; Zeng, Jianing; Easter, John; Wang, Jun-sheng; Dockens, Randy; Bifano, Marc; Burrell, Richard; Arnold, Mark E

    2012-06-05

    A methodology for the accurate calculation and mitigation of isotopic interferences in liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) assays and its application in supporting microdose absolute bioavailability studies are reported for the first time. For simplicity, this calculation methodology and the strategy to minimize the isotopic interference are demonstrated using a simple molecule entity, then applied to actual development drugs. The exact isotopic interferences calculated with this methodology were often much less than the traditionally used, overestimated isotopic interferences simply based on the molecular isotope abundance. One application of the methodology is the selection of a stable isotopically labeled internal standard (SIL-IS) for an LC-MS/MS bioanalytical assay. The second application is the selection of an SIL analogue for use in intravenous (i.v.) microdosing for the determination of absolute bioavailability. In the case of microdosing, the traditional approach of calculating isotopic interferences can result in selecting a labeling scheme that overlabels the i.v.-dosed drug or leads to incorrect conclusions on the feasibility of using an SIL drug and analysis by LC-MS/MS. The methodology presented here can guide the synthesis by accurately calculating the isotopic interferences when labeling at different positions, using different selective reaction monitoring (SRM) transitions or adding more labeling positions. This methodology has been successfully applied to the selection of the labeled i.v.-dosed drugs for use in two microdose absolute bioavailability studies, before initiating the chemical synthesis. With this methodology, significant time and cost saving can be achieved in supporting microdose absolute bioavailability studies with stable labeled drugs.

  1. Characterization of microdose damage caused by single heavy ion observed in trench type power MOSFETs

    International Nuclear Information System (INIS)

    Ikeda, Naomi; Kuboyama, Satoshi; Maru, Akifumi; Tamura, Takashi; Hirao, Toshio; Abe, Hiroshi

    2010-01-01

    It was demonstrated that anomalously large degradation observed in power MOSFETs was caused by a single heavy ion. It was identified as a microdose effect and successfully characterized by several parameters extracted from experimental data. (author)

  2. To Apply Microdosing or Not? Recommendations to Single Out Compounds with Non-Linear Pharmacokinetics

    NARCIS (Netherlands)

    Bosgra, S.; Vlaming, M.L.H.; Vaes, W.H.J.

    2015-01-01

    Non-linearities occur no more frequently between microdose and therapeutic dose studies than in therapeutic range ascending-dose studies. Most non-linearities are due to known saturable processes, and can be foreseen by integrating commonly available preclinical data. The guidance presented here may

  3. Successful Use of [14C]Paracetamol Microdosing to Elucidate Developmental Changes in Drug Metabolism

    NARCIS (Netherlands)

    M.G. Mooij (Miriam); E. van Duijn (Esther); C.A.J. Knibbe (Catherijne); K.M. Allegaert (Karel); J. Windhorst (Judith); J.M. van Rosmalen (Joost); N.H. Hendrikse (N. Harry); D. Tibboel (Dick); W.H.J. Vaes (Wouter H. J.); S.N. de Wildt (Saskia)

    2017-01-01

    textabstractBackground: We previously showed the practical and ethical feasibility of using [14C]-microdosing for pharmacokinetic studies in children. We now aimed to show that this approach can be used to elucidate developmental changes in drug metabolism, more specifically, glucuronidation and

  4. Successful Use of [(14)C]Paracetamol Microdosing to Elucidate Developmental Changes in Drug Metabolism

    NARCIS (Netherlands)

    Mooij, M.G.; Duijn, E. van; Knibbe, C.A.; Allegaert, K.; Windhorst, A.D.; Rosmalen, J. van; Hendrikse, N.H.; Tibboel, D.; Vaes, W.H.; Wildt, S.N. de

    2017-01-01

    BACKGROUND: We previously showed the practical and ethical feasibility of using [(14)C]-microdosing for pharmacokinetic studies in children. We now aimed to show that this approach can be used to elucidate developmental changes in drug metabolism, more specifically, glucuronidation and sulfation,

  5. Microdose gonadotropin-releasing hormone agonist flare-up protocol versus multiple dose gonadotropin-releasing hormone antagonist protocol in poor responders undergoing intracytoplasmic sperm injection-embryo transfer cycle.

    Science.gov (United States)

    Kahraman, Korhan; Berker, Bulent; Atabekoglu, Cem Somer; Sonmezer, Murat; Cetinkaya, Esra; Aytac, Rusen; Satiroglu, Hakan

    2009-06-01

    To compare the efficacy of microdose GnRH agonist (GnRH-a) flare-up and multiple dose GnRH antagonist protocols in patients who have a poor response to a long luteal GnRH-a protocol. Prospective, randomized, clinical study. University hospital. Forty-two poor responder patients undergoing intracytoplasmic sperm injection (ICSI)-embryo transfer cycle. Twenty-one patients received microdose leuprolide acetate (LA) (50 microg twice daily) starting on the second day of withdrawal bleeding. The other 21 patients received 0.25 mg of cetrorelix daily when the leading follicle reached 14 mm in diameter. Serum E(2) levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate and pregnancy rate (PR). The mean serum E(2) concentration on the day of hCG administration was significantly higher in the microdose GnRH-a group than in the GnRH antagonist group (1,904 vs. 1,362 pg/mL). The clinical PRs per started cycle of microdose GnRH-a and GnRH antagonist groups were 14.2% and 9.5%, respectively. There were no statistically significant differences in the other ovulation induction characteristics, fertilization and implantation rates. Microdose GnRH-a flare-up protocol and multiple dose GnRH antagonist protocol seem to have similar efficacy in improving treatment outcomes of poor responder patients.

  6. EOS microdose protocol for the radiological follow-up of adolescent idiopathic scoliosis.

    Science.gov (United States)

    Ilharreborde, Brice; Ferrero, Emmanuelle; Alison, Marianne; Mazda, Keyvan

    2016-02-01

    Imaging plays a key role in adolescent idiopathic scoliosis (AIS) to determine the prognosis and accordingly define the best therapeutic strategy to follow. Conventional radiographs with ionizing radiation have been associated with 1-2 % increased lifetime risk of developing cancer in children, and physicians, therefore, need a sensitive but harmless way to explore patients at risk, according to the "as low as reasonably achievable" concept. The EOS system (EOS imaging, Paris, France) is available in routine clinical use since 2007, and allows 3D reconstructions of the trunk in standing position with significant radiation reduction. With recent technical advances, further dose reduction can be obtained, but at the cost of image quality that might alter the reliability of 3D reconstructions. The aim of the present study was to analyze the reproducibility of a "microdose" protocol, and evaluate its use in clinical practice. 32 consecutive patients followed for AIS were prospectively included. Biplanar radiographs were obtained with the EOS system according to the new microdose protocol. From the microdose images obtained, three experienced operators performed 3D reconstructions, two times for each subject in a random order (total, 192 reconstructions). The intraoperator repeatability and interoperator reproducibility were evaluated, as recommended by the International Organization for Standardization, for the most clinically relevant 3D radiological parameters. The identification of the required anatomical landmarks for the "fast spine" reconstruction process was possible in all cases. None of the patients required a second acquisition for 3D analysis. Mean time for reconstruction was 5 ± 2 min. The intraoperator repeatability was better than interoperator reproducibility for all parameters, with values ranging between 3° and 8° for frontal and sagittal spinal parameters, and between 1° and 8° for pelvic measurements. The agreement was very good for all clinical

  7. What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?

    Science.gov (United States)

    Berkkanoglu, Murat; Ozgur, Kemal

    2010-07-01

    To find out the optimum maximal dosage of recombinant follicle stimulating hormone (rFSH) in microdose gonadotropin-releasing hormone analog (GnRH-a) flare cycles in poor responders. Prospective randomized study. Private infertility clinic. A total of 119 women were taken into the study. The study group underwent a microdose protocol with a GnRH-agonist followed by rFSH administration. On the third day of GnRH-a administration, 119 patients were randomized in three groups to receive daily fixed doses of 300 IU of rFSH (group A, n = 38), or 450 IU of rFSH (group B, n = 39), or 600 IU of rFSH (group C, n = 42). Peak E(2) levels, days of stimulation with rFSH, total rFSH dosage, total number of oocytes retrieved, M2 oocytes retrieved, total number of embryos, number of embryos transferred, number of Grade-1 embryos transferred, clinical pregnancy rate (positive fetal cardiac activity), and cancellation rates of stimulation and embryo transfer. Clinical pregnancy rates were 13.1%, 15.3%, and 16.1% for group A, group B, and group C, respectively. There were no significant differences in the age, peak serum E(2) concentration, days of stimulation with rFSH, total number of M2 oocytes retrieved, number of embryos transferred, clinical pregnancy rates, and cancellation rates of stimulation and embryo transfer between the three groups except for total rFSH dosage. There is no need to use doses above 300 IU of rFSH to increase the pregnancy rate in microdose cycles. In addition, because the duration of stimulation does not differ between the groups, the usage of 300 IU rFSH in microdose cycles results in less total amount of rFSH consumed in a cycle compared with higher dosages, and this would obviously cost less money to the patients. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Ethical and social significance of microdose clinical trial. Background of guidance draw-up

    International Nuclear Information System (INIS)

    Kurihara, Chieko

    2008-01-01

    Microdose clinical trial (MCT) aims to elucidate only the mass balance (pharmacokinetics, PK) in human of a new drug candidate compound before the first Phase I trial and is going to be approved by the authority MHLW in Japan. In MCT, the compound is administered in human in an extremely small amount (microdose) that is unexpected to exert its pharmacological effect ( 14 C) labeled compound is administered, LC/MS/MS with non-isotopic compound and positron emission tomography (PET) with compound labeled by positron emitter like 11 C, 13 N, etc. Under promotions by support and demand of related scientific societies and corporations in Japan as well as by ICH agreement, MHLW has defined MCT as one of clinical trials linked with GMP standard of drug candidate for clinical trials, with concept for assessment of internal radiation exposure, and with consistency with handling of radioisotopes, because of ethical consideration for volunteers to be enrolled. MCT can expectedly improve the cost- and time-effectiveness of new drug development, which ultimately leads to earlier supply of superior medicines. (R.T.)

  9. A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil.

    Science.gov (United States)

    Wagner, Claudia C; Simpson, Marie; Zeitlinger, Markus; Bauer, Martin; Karch, Rudolf; Abrahim, Aiman; Feurstein, Thomas; Schütz, Matthias; Kletter, Kurt; Müller, Markus; Lappin, Graham; Langer, Oliver

    2011-02-01

    In microdose studies, the pharmacokinetic profile of a drug in blood after administration of a dose up to 100 μg is measured with sensitive analytical techniques, such as accelerator mass spectrometry (AMS). As most drugs exert their effect in tissue rather than blood, methodology is needed for extending pharmacokinetic analysis to different tissue compartments. In the present study, we combined, for the first time, AMS analysis with positron emission tomography (PET) in order to determine the pharmacokinetic profile of the model drug verapamil in plasma and brain of humans. In order to assess pharmacokinetic dose linearity of verapamil, data were acquired and compared after administration of an intravenous microdose and after an intravenous microdose administered concomitantly with an oral therapeutic dose. Six healthy male subjects received an intravenous microdose [0.05 mg] (period 1) and an intravenous microdose administered concomitantly with an oral therapeutic dose [80 mg] of verapamil (period 2) in a randomized, crossover, two-period study design. The intravenous dose was a mixture of (R/S)-[14C]verapamil and (R)-[11C]verapamil and the oral dose was unlabelled racaemic verapamil. Brain distribution of radioactivity was measured with PET whereas plasma pharmacokinetics of (R)- and (S)-verapamil were determined with AMS. PET data were analysed by pharmacokinetic modelling to estimate the rate constants for transfer (k) of radioactivity across the blood-brain barrier. Most pharmacokinetic parameters of (R)- and (S)-verapamil as well as parameters describing exchange of radioactivity between plasma and brain (influx rate constant [K(1)] = 0.030 ± 0.003 and 0.031 ± 0.005 mL/mL/min and efflux rate constant [k(2)] = 0.099 ± 0.006 and 0.095 ± 0.008 min-1 for period 1 and 2, respectively) were not statistically different between the two periods although there was a trend for nonlinear pharmacokinetics for the (R)-enantiomer. On the other hand, all

  10. Effets de la microdose sur la production du niébé, du mil et du ...

    African Journals Online (AJOL)

    Effets de la microdose sur la production du niébé, du mil et du sorgho en fonction la toposéquence. Fatimata Saba, Sibiri Jean Baptiste Taonda, Idriss Serme, Alimata A. Bandaogo, Augustin P. Sourwema, Adama Kabre ...

  11. Comparison of estradiol and progesterone priming/antagonist/letrozole and microdose flare-up protocols for poor responders undergoing intracytoplasmic sperm injection.

    Science.gov (United States)

    Yucel, Oguz; Ekin, Murat; Cengiz, Hüseyin; Zebitay, Ali Galip; Yalcinkaya, Sener; Karahuseyinoglu, Sercin

    2014-09-01

    To compare the effect of the GnRH antagonist/letrozole/gonadotropin protocol with the microdose GnRH agonist flare-up protocol in poor ovarian responders for intracytoplasmic sperm injection. One hundred twenty-one consecutive patients suspected of having or with a history of poor ovarian response between January 2009 and June 2010, who were undergoing ICSI were enrolled. The microdose flareup (MF) protocol was used in 79 patients and the estradiol + progesterone/letrozole + gonadotropin and GnRH antagonist (EP/ALG) protocol was used in 42 patients. Age of the patients, duration of infertility, basal FSH, the total gonadotropin consumption, duration of stimulation, E2 level on the day of hCG administration, the number of embryo transferred, the fertilization rate, implantation rate, clinical pregnancy rate and the live birth rate were not statistically different (p > 0.05). Only the number of oocytes retrieved was significantly higher in the EP/LGA group (1.7 ± 0.7 versus 2.6 ± 0.6). The EP/LGA protocol has no significant improvement against the microdose flare-up protocol in poor responder patients.

  12. Ultra-sensitive LC-MS/MS method for the quantification of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine in human plasma for a microdose clinical trial.

    Science.gov (United States)

    van Nuland, M; Hillebrand, M J X; Rosing, H; Burgers, J A; Schellens, J H M; Beijnen, J H

    2018-03-20

    In microdose clinical trials a maximum of 100 μg of drug substance is administered to participants, in order to determine the pharmacokinetic properties of the agents. Measuring low plasma concentrations after administration of a microdose is challenging and requires the use of ulta-sensitive equipment. Novel liquid chromatography-mass spectrometry (LC-MS/MS) platforms can be used for quantification of low drug plasma levels. Here we describe the development and validation of an LC-MS/MS method for quantification of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in the low picogram per milliliter range to support a microdose trial. The validated assay ranges from 2.5-500 pg/mL for gemcitabine and 250-50,000 pg/mL for dFdU were linear, with a correlation coefficient (r 2 ) of 0.996 or better. Sample preparation with solid phase extraction provided a good and reproducible recovery. All results were within the acceptance criteria of the latest US FDA guidance and EMA guidelines. In addition, the method was successfully applied to measure plasma concentrations of gemcitabine in a patient after administration of a microdose of gemcitabine. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Intraarterial Microdosing, a Novel Drug Development Approach, Proof-of-Concept PET Study in Rats

    Science.gov (United States)

    Burt, Tal; Rouse, Douglas C.; Lee, Kihak; Wu, Huali; Layton, Anita T.; Hawk, Thomas C.; Weitzel, Douglas H.; Chin, Bennett B.; Cohen-Wolkowiez, Michael; Chow, Shein-Chung; Noveck, Robert J.

    2016-01-01

    Intraarterial microdosing (IAM) is a novel drug development approach combining intraarterial drug delivery and microdosing. We aimed to demonstrate that IAM leads to target exposure similar to that of systemic full-dose administration but with minimal systemic exposure. IAM could enable the safe, inexpensive, and early study of novel drugs at the first-in-human stage and the study of established drugs in vulnerable populations. Methods Insulin was administered intraarterially (ipsilateral femoral artery) or systemically to 8 CD IGS rats just before blood sampling or 60-min 18F-FDG uptake PET imaging of ipsilateral and contralateral leg muscles (lateral gastrocnemius) and systemic muscles (spinotrapezius). The 18F-FDG uptake slope analysis was used to compare the interventions. Plasma levels of insulin and glucose were compared using area under the curve calculated by the linear trapezoidal method. A physiologically based computational pharmacokinetics/pharmacodynamics model was constructed to simulate the relationship between the administered dose and response over time. Results 18F-FDG slope analysis found no difference between IAM and systemic full-dose slopes (0.0066 and 0.0061, respectively; 95% confidence interval [CI], −0.024 to 0.029; P = 0.7895), but IAM slope was statistically significantly greater than systemic microdose (0.0018; 95% CI, −0.045 to −0.007; P = 0.0147) and sham intervention (−0.0015; 95% CI, 0.023–0.058; P = 0.0052). The pharmacokinetics/pharmacodynamics data were used to identify model parameters that describe membrane insulin binding and glucose–insulin dynamics. Conclusion Target exposure after IAM was similar to systemic full dose administration but with minimal systemic effects. The computational pharmacokinetics/pharmacodynamics model can be generalized to predict whole-body response. Findings should be validated in larger, controlled studies in animals and humans using a range of targets and classes of drugs. PMID

  14. Stochastic Threshold Microdose Model for Cell Killing by Insoluble Metallic Nanomaterial Particles

    Science.gov (United States)

    Scott, Bobby R.

    2010-01-01

    This paper introduces a novel microdosimetric model for metallic nanomaterial-particles (MENAP)-induced cytotoxicity. The focus is on the engineered insoluble MENAP which represent a significant breakthrough in the design and development of new products for consumers, industry, and medicine. Increased production is rapidly occurring and may cause currently unrecognized health effects (e.g., nervous system dysfunction, heart disease, cancer); thus, dose-response models for MENAP-induced biological effects are needed to facilitate health risk assessment. The stochastic threshold microdose (STM) model presented introduces novel stochastic microdose metrics for use in constructing dose-response relationships for the frequency of specific cellular (e.g., cell killing, mutations, neoplastic transformation) or subcellular (e.g., mitochondria dysfunction) effects. A key metric is the exposure-time-dependent, specific burden (MENAP count) for a given critical target (e.g., mitochondria, nucleus). Exceeding a stochastic threshold specific burden triggers cell death. For critical targets in the cytoplasm, the autophagic mode of death is triggered. For the nuclear target, the apoptotic mode of death is triggered. Overall cell survival is evaluated for the indicated competing modes of death when both apply. The STM model can be applied to cytotoxicity data using Bayesian methods implemented via Markov chain Monte Carlo. PMID:21191483

  15. Clinical Effects of a Microdose GnRH Agonist Flare Regimen Administered to Poor Responders Undergoing ART Cycles

    Directory of Open Access Journals (Sweden)

    Aflatoonian Abbas

    2009-10-01

    Full Text Available The microdose GnRH agonist (GnRH-a flare protocol may have a particular value for previously poor responders in whom it has been observed to stimulate dramatic increases in serum FSH. The Purpose of this study was to determine the effects of microdose GnRH-a in poor responders. This is a clinical trial with before and after design. This study was done in Research and Clinical Center for Infertility (Shahid Sadoughi University, Yazd, Iran and Madar Hospital, Yazd, Iran. In this study, 61 poor responders volunteered for in vitro fertilization (IVF or intracytoplacmic sperm injection (ICSI. The volunteers were divided into two age groups (group A, 20 - 34; group B, 35 - 40 and received low dose oral contraceptive pills for 21 days, then 40µg of subcutaneous buserelin 2 times/day from day 3 of the cycle and human menopausal gonadotropin (hMG 3 ampoules/day from day 5. Main Outcome measures were number of follicles, oocytes and embryos, and pregnancy rate (PR. These measures were then compared with those of the previous cycle. There were significant differences in all parameters (P < 0.05. Pregnancy occurred in 3 women (5%. There was no significant difference in number of follicles, oocytes and embryo between two age groups (P > 0.05. Use of microdose GnRH-a plus HMG for controlled ovarian hyperstimulation in IVF or ICSI cycles can lead to formation of more follicles, oocyte and embryo in poor responders.

  16. Observational infant exploratory [14C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis

    NARCIS (Netherlands)

    Garner, C.R.; Park, K.B.; French, N.S.; Earnshaw, C.; Schipani, A.; Selby, A.M.; Byrne, L.; Siner, S.; Crawley, F.P.; Vaes, W.H.J.; Duijn, E. van; ligt, R. de; Varendi, H.; Lass, J.; Grynkiewicz, G.; Maruszak, W.; Turner, M.A.

    2015-01-01

    Aims The aims of the study were to compare [14C]-paracetamol ([14C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0-2 year old age group.

  17. Fabrication of metal-matrix composites and adaptive composites using ultrasonic consolidation process

    International Nuclear Information System (INIS)

    Kong, C.Y.; Soar, R.C.

    2005-01-01

    Ultrasonic consolidation (UC) has been used to embed thermally sensitive and damage intolerant fibres within aluminium matrix structures using high frequency, low amplitude, mechanical vibrations. The UC process can induce plastic flow in the metal foils being bonded, to allow the embedding of fibres at typically 25% of the melting temperature of the base metal and at a fraction of the clamping force when compared to fusion processes. To date, the UC process has successfully embedded Sigma silicon carbide (SiC) fibres, shape memory alloy wires and optical fibres, which are presented in this paper. The eventual aim of this research is targeted at the fabrication of adaptive composite structures having the ability to measure external stimuli and respond by adapting their structure accordingly, through the action of embedded active and passive functional fibres within a freeform fabricated metal-matrix structure. This paper presents the fundamental studies of this research to identify embedding methods and working range for the fabrication of adaptive composite structures. The methods considered have produced embedded fibre specimens in which large amounts of plastic flow have been observed, within the matrix, as it is deformed around the fibres, resulting in fully consolidated specimens without damage to the fibres. The microscopic observation techniques and macroscopic functionality tests confirms that the UC process could be applied to the fabrication of metal-matrix composites and adaptive composites, where fusion techniques are not feasible and where a 'cold' process is necessary

  18. Effets de la microdose sur la production du niébé, du mil et du ...

    African Journals Online (AJOL)

    respectivement pour le sorgho, le mil et le niébé comparativement au témoin. La microdose a été .... Les prix utilisés sont celui du marché local au moment des semis pour les engrais soit 17500 FCFA pour NPK et ..... Projet « Transfert de la.

  19. BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology.

    Science.gov (United States)

    Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

    2017-08-01

    Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD.

  20. A microdose study of ¹⁴C-AR-709 in healthy men: pharmacokinetics, absolute bioavailability and concentrations in key compartments of the lung.

    Science.gov (United States)

    Lappin, G; Boyce, M J; Matzow, T; Lociuro, S; Seymour, M; Warrington, S J

    2013-09-01

    To explore, in a microdose (phase-0) study, the pharmacokinetics, bioavailability and concentrations in key compartments of the lung, of AR-709, a novel diaminopyrimidine antibiotic for the treatment of respiratory infection. Four healthy men each received two single, 100 μg microdoses of ¹⁴C-AR-709, 7 days apart: the first was administered intravenously (IV), the second orally. Plasma pharmacokinetics of ¹⁴C and unchanged AR-709 were obtained by high-performance liquid chromatography and accelerator mass spectrometry (AMS). Next, 15 healthy men received a single, 100 μg microdose of ¹⁴C-AR-709 IV. Plasma, bronchoalveolar lavage fluid, alveolar macrophages and bronchial mucosal biopsy samples were analysed by AMS. After IV administration, clearance of AR-709 was 496 mL/min, volume of distribution was 1,700 L and the absolute oral bioavailability was 2.5 %. Excretion in urine was negligible. At 8-12 h after IV dosing, ¹⁴C concentrations in lung samples were 15- (bronchial mucosa) to 200- (alveolar macrophages) fold higher than in plasma. In alveolar macrophages, ¹⁴C was still mostly associated with AR-709 at 12 h after dosing. The results of this microdose study indicate that AR-709 attains concentrations appreciably higher within the lung than in plasma. Its low oral bioavailability however, precludes oral administration. Although IV administration would appear to be an effective route of administration, this would limit the use of AR-709 to a clinical setting and would therefore be economically unsustainable. If further clinical development were to be undertaken, therefore, an alternative route of administration would be necessary.

  1. Comparison of mild and microdose GnRH agonist flare protocols on IVF outcome in poor responders.

    Science.gov (United States)

    Karimzadeh, Mohammad Ali; Mashayekhy, Mehri; Mohammadian, Farnaz; Moghaddam, Fatemeh Mansoori

    2011-05-01

    To compare the IVF outcome of clomiphene citrate/gonadotropin/antagonist (mild protocol) and microdose GnRH agonist flare protocols for poor responders undergoing in vitro fertilization. 159 poor responder patients were randomized and ovarian stimulation was performed with clomiphene citrate, gonadotropin and antagonist (group I) or microdose GnRH agonist flare (group II) protocols. Main outcome was clinical pregnancy rate and secondary outcomes were doses of gonadotropin administration and duration of stimulation. There were no significant differences in age, causes of infertility, basal FSH, BMI, duration of infertility, E(2) level on the day of hCG injection in both groups. Although the cancellation, fertilization, and clinical pregnancy rates were similar in both groups, the endometrial thickness, number of retrieved oocytes, mature oocytes and implantation rate were significantly higher in mild protocol. The doses of gonadotropin administration and duration of stimulation were significantly lower in mild protocol. We recommend mild protocol in assisted reproductive technology cycles for poor responders based on our results regarding less doses of used gonadotropin and a shorter duration of stimulation.

  2. Compatibility study of a parenteral microdose polyethylene glycol formulation in medical devices and identification of degradation impurity by 2D-LC/MS.

    Science.gov (United States)

    Dai, Lulu; Yeh, Geoffrey K; Ran, Yingqing; Yehl, Peter; Zhang, Kelly

    2017-04-15

    Polyethylene glycol (PEG) based formulation and polyvinylchloride (PVC) tubing are frequently used for drug delivery and administration. The compatibility of a parenteral drug microdose formulation in intravenous infusion (IV) devices was studied to support the clinical determination of absolute bioavailability by the microdosing method. The investigational microdose formulation containing PEG was found prone to significant loss of potency within hours of storage in the PVC IV tubing due to degradation. Degradation occurred only when both PEG and PVC tubing were present. The degradation product could not be detected by LC/MS due to the significant interference from the high concentration of PEG (4%) matrix and the extremely low level of drug (0.6ppm). To obtain structural information of the degradation impurity and understand the cause of the degradation, a simple heart-cutting 2D-LC/MS approach was utilized to effectively separate the impurity from the complex PEG oligomers and overcome the matrix interference, enabling mass spectrometric analysis of the impurity. An oxidation- dominated mechanism was proposed in which the combination of PEG auto-oxidation and dehydrochlorination of the PVC tubing yielded an oxidative environment that enhanced radical propagation and accelerated degradation of the investigational parent drug. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Microdose pharmacogenetic study of ¹⁴C-tolbutamide in healthy subjects with accelerator mass spectrometry to examine the effects of CYP2C9∗3 on its pharmacokinetics and metabolism.

    Science.gov (United States)

    Ikeda, Toshihiko; Aoyama, Shinsuke; Tozuka, Zenzaburo; Nozawa, Kohei; Hamabe, Yoshimi; Matsui, Takao; Kainuma, Michiko; Hasegawa, Setsuo; Maeda, Kazuya; Sugiyama, Yuichi

    2013-07-16

    Microdose study enables us to understand the pharmacokinetic profiles of drugs in humans prior to the conventional clinical trials. The advantage of microdose study is that the unexpected pharmacological/toxicological effects of drugs caused by drug interactions or genetic polymorphisms of metabolic enzymes/transporters can be avoided due to the limited dose. With a combination use of accelerator mass spectrometry (AMS) and (14)C-labaled compounds, the pharmacokinetics of both parent drug and its metabolites can be sensitively monitored. Thus, to demonstrate the usability of microdose study with AMS for the prediction of the impact of genetic polymorphisms of CYP enzyme on the pharmacokinetics of unchanged drugs and metabolites, we performed microdose pharmacogenetic study using tolbutamide as a CYP2C9 probe drug. A microdose of (14)C-tolbutamide (100 μg) was administered orally to healthy volunteers with the CYP2C9(∗)1/(∗)1 or CYP2C9(∗)1/(∗)3 diplotype. Area under the plasma concentration-time curve for the (14)C-radioactivity, determined by AMS, or that for the parent drug, determined by liquid chromatography/mass spectrometry, was about 1.6 times or 1.7 times greater in the CYP2C9(∗)1/(∗)3 than in the CYP2C9(∗)1/(∗)1 group, which was comparable to the previous reports at therapeutic dose. In the plasma and urine, tolbutamide, carboxytolbutamide, and 4-hydroxytolbutamide were detected and practically no other metabolites could be found in both diplotype groups. The fraction of metabolites in plasma radioactivity was slightly lower in the CYP2C9(∗)1/(∗)3 group. Microdose study can be used for the prediction of the effects of genetic polymorphisms of enzymes on the pharmacokinetics and metabolic profiles of drugs with minimal care of their pharmacological/toxicological effects. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Detection of recombinant EPO in blood and urine samples with EPO WGA MAIIA, IEF and SAR-PAGE after microdose injections.

    Science.gov (United States)

    Dehnes, Yvette; Shalina, Alexandra; Myrvold, Linda

    2013-01-01

    The misuse of microdoses of performance enhancing drugs like erythropoietin (EPO) constitutes a major challenge in doping analysis. When injected intravenously, the half-life of recombinant human EPO (rhEPO) like epoetin alfa, beta, and zeta is only a few hours and hence, the window for direct detection of rhEPO in urine is small. In order to investigate the detection window for rhEPO directly in blood and urine with a combined affinity chromatography and lateral flow immunoassay (EPO WGA MAIIA), we recruited nine healthy people who each received six intravenously injected microdoses (7.5 IU/kg) of NeoRecormon (epoetin beta) over a period of three weeks. Blood and urine samples were collected in the days following the injections and analyzed with EPO WGA MAIIA as well as the current validated methods for rhEPO; isoelectric focusing (IEF) and sarcosyl polyacrylamide gel electrophoresis (SAR-PAGE). For samples collected 18 h after a microdose, the sensitivity of the EPO WGA MAIIA assay was 100% in plasma and 87.5% in urine samples at the respective 98% specificity threshold levels. In comparison, the sensitivity in plasma and urine was 75% and 100%, respectively, with IEF, and 87.5% in plasma and 100% in urine when analyzed with SAR-PAGE. We conclude that EPO WGA MAIIA is a sensitive assay for the detection of rhEPO, with the potential of being a fast, supplemental screening assay for use in doping analysis.

  5. Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders--an observational pilot study.

    Science.gov (United States)

    Mitri, Frederic; Behan, Lucy Ann; Murphy, Courtney A; Hershko-Klement, Anat; Casper, Robert F; Bentov, Yaakov

    2016-01-01

    To investigate whether temporarily withholding FSH and adding androgen could improve follicular response during a microdose flare protocol in women with slow follicular growth or asynchronous follicular development. Observational pilot study. University-affiliated private fertility center. Twenty-six women aged 34-47 years with poor response to stimulation or a previous cancelled IVF cycle and with slow or asynchronous follicular growth during a microdose flare cycle. For 13 women, after initiation of ovarian stimulation using the microdose flare protocol, gonadotropin administration was interrupted and transdermal testosterone gel was added for several days (4.4 ± 1.2 d) starting after cycle day 7 (mean cycle day 10 ± 2.6). FSH, E2, follicular growth, and total number of mature oocytes retrieved were determined for all of the patients. Cycle cancellation rate as well as pregnancy rate following embryo transfer were also documented when applicable. FSH levels declined (25.2 ± 6.5 to 6.8 ± 3.2 IU/L), E2 levels increased (896 ± 687 to 2,163 ± 1,667 pmol/L), and follicular growth improved significantly during gonadotropin interruption and were tracked for 2 days during this time frame. The average number of oocytes retrieved was 5.3 ± 2.6, and the ratio of mature to total oocytes was 4:5. Four of the 13 women in the interruption group conceived following frozen embryo transfer, whereas none in the control group did. The androgen-interrupted FSH protocol may improve follicular response to gonadotropins in cycles that might otherwise be cancelled. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Adaptive neuro-fuzzy control of ionic polymer metal composite actuators

    International Nuclear Information System (INIS)

    Thinh, Nguyen Truong; Yang, Young-Soo; Oh, Il-Kwon

    2009-01-01

    An adaptive neuro-fuzzy controller was newly designed to overcome the degradation of the actuation performance of ionic polymer metal composite actuators that show highly nonlinear responses such as a straightening-back problem under a step excitation. An adaptive control algorithm with the merits of fuzzy logic and neural networks was applied for controlling the tip displacement of the ionic polymer metal composite actuators. The reference and actual displacements and the change of the error with the electrical inputs were recorded to generate the training data. These data were used for training the adaptive neuro-fuzzy controller to find the membership functions in the fuzzy control algorithm. Software simulation and real-time experiments were conducted by using the Simulink and dSPACE environments. Present results show that the current adaptive neuro-fuzzy controller can be successfully applied to the reliable control of the ionic polymer metal composite actuator for which the performance degrades under long-time actuation

  7. Marginal adaptation of composite resins under two adhesive techniques.

    Science.gov (United States)

    Dačić, Stefan; Veselinović, Aleksandar M; Mitić, Aleksandar; Nikolić, Marija; Cenić, Milica; Dačić-Simonović, Dragica

    2016-11-01

    In the present research, different adhesive techniques were used to set up fillings with composite resins. After the application of etch and rinse or self etch adhesive technique, marginal adaptation of composite fillings was estimated by the length of margins without gaps, and by the microretention of resin in enamel and dentin. The study material consisted of 40 extracted teeth. Twenty Class V cavities were treated with 35% phosphorous acid and restored after rinsing by Adper Single Bond 2 and Filtek Ultimate-ASB/FU 3M ESPE composite system. The remaining 20 cavities were restored by Adper Easy One-AEO/FU 3M ESPE composite system. Marginal adaptation of composite fillings was examined using a scanning electron microscope (SEM). The etch and rinse adhesive technique showed a significantly higher percentage of margin length without gaps (in enamel: 92.5%, in dentin: 57.3%), compared with the self-etch technique with lower percentage of margin length without gaps, in enamel 70.4% (p resin tugs in interprismatic spaces of enamel, while the dentin microretention was composed of adhesive and hybrid layers with resin tugs in dentin canals. In the second technique, resin tugs were rarely seen and a microgap was dominant along the border of restoration margins. The SEM analysis showed a better marginal adaptation of composite resin to enamel and dentin with better microretention when the etch and rinse adhesive procedure was applied. © 2016 Wiley Periodicals, Inc.

  8. Microdose Induced Drain Leakage Effects in Power Trench MOSFETs: Experiment and Modeling

    Science.gov (United States)

    Zebrev, Gennady I.; Vatuev, Alexander S.; Useinov, Rustem G.; Emeliyanov, Vladimir V.; Anashin, Vasily S.; Gorbunov, Maxim S.; Turin, Valentin O.; Yesenkov, Kirill A.

    2014-08-01

    We study experimentally and theoretically the micro-dose induced drain-source leakage current in the trench power MOSFETs under irradiation with high-LET heavy ions. We found experimentally that cumulative increase of leakage current occurs by means of stochastic spikes corresponding to a strike of single heavy ion into the MOSFET gate oxide. We simulate this effect with the proposed analytic model allowing to describe (including Monte Carlo methods) both the deterministic (cumulative dose) and stochastic (single event) aspects of the problem. Based on this model the survival probability assessment in space heavy ion environment with high LETs was proposed.

  9. AdaFF: Adaptive Failure-Handling Framework for Composite Web Services

    Science.gov (United States)

    Kim, Yuna; Lee, Wan Yeon; Kim, Kyong Hoon; Kim, Jong

    In this paper, we propose a novel Web service composition framework which dynamically accommodates various failure recovery requirements. In the proposed framework called Adaptive Failure-handling Framework (AdaFF), failure-handling submodules are prepared during the design of a composite service, and some of them are systematically selected and automatically combined with the composite Web service at service instantiation in accordance with the requirement of individual users. In contrast, existing frameworks cannot adapt the failure-handling behaviors to user's requirements. AdaFF rapidly delivers a composite service supporting the requirement-matched failure handling without manual development, and contributes to a flexible composite Web service design in that service architects never care about failure handling or variable requirements of users. For proof of concept, we implement a prototype system of the AdaFF, which automatically generates a composite service instance with Web Services Business Process Execution Language (WS-BPEL) according to the users' requirement specified in XML format and executes the generated instance on the ActiveBPEL engine.

  10. Pollinator adaptation and the evolution of floral nectar sugar composition.

    Science.gov (United States)

    Abrahamczyk, S; Kessler, M; Hanley, D; Karger, D N; Müller, M P J; Knauer, A C; Keller, F; Schwerdtfeger, M; Humphreys, A M

    2017-01-01

    A long-standing debate concerns whether nectar sugar composition evolves as an adaptation to pollinator dietary requirements or whether it is 'phylogenetically constrained'. Here, we use a modelling approach to evaluate the hypothesis that nectar sucrose proportion (NSP) is an adaptation to pollinators. We analyse ~ 2100 species of asterids, spanning several plant families and pollinator groups (PGs), and show that the hypothesis of adaptation cannot be rejected: NSP evolves towards two optimal values, high NSP for specialist-pollinated and low NSP for generalist-pollinated plants. However, the inferred adaptive process is weak, suggesting that adaptation to PG only provides a partial explanation for how nectar evolves. Additional factors are therefore needed to fully explain nectar evolution, and we suggest that future studies might incorporate floral shape and size and the abiotic environment into the analytical framework. Further, we show that NSP and PG evolution are correlated - in a manner dictated by pollinator behaviour. This contrasts with the view that a plant necessarily has to adapt its nectar composition to ensure pollination but rather suggests that pollinators adapt their foraging behaviour or dietary requirements to the nectar sugar composition presented by the plants. Finally, we document unexpectedly sucrose-poor nectar in some specialized nectarivorous bird-pollinated plants from the Old World, which might represent an overlooked form of pollinator deception. Thus, our broad study provides several new insights into how nectar evolves and we conclude by discussing why maintaining the conceptual dichotomy between adaptation and constraint might be unhelpful for advancing this field. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  11. Adaptive, tolerant and efficient composite structures

    Energy Technology Data Exchange (ETDEWEB)

    Wiedemann, Martin; Sinapius, Michael (eds.) [German Aerospace Center DLR, Braunschweig (Germany). Inst. of Composite Structures and Adaptive Systems

    2013-07-01

    Polymer composites offer the possibility for functional integration since the material is produced simultaneously with the product. The efficiency of composite structures raises through functional integration. The specific production processes of composites offer the possibility to improve and to integrate more functions thus making the structure more valuable. Passive functions can be improved by combination of different materials from nano to macro scale, i.e. strength, toughness, bearing strength, compression after impact properties or production tolerances. Active functions can be realized by smart materials, i.e. morphing, active vibration control, active structure acoustic control or structure health monitoring. The basis is a comprehensive understanding of materials, simulation, design methods, production technologies and adaptronics. These disciplines together deliver advanced lightweight solutions for applications ranging from mechanical engineering to vehicles, airframe and space structures along the complete process chain. The book provides basics as well as inspiring ideas for engineers working in the field of adaptive, tolerant and robust composite structures.

  12. Effect of microdose transdermal 17beta-estradiol compared with raloxifene in the prevention of bone loss in healthy postmenopausal women: a 2-year, randomized, double-blind trial.

    Science.gov (United States)

    Schaefers, Matthias; Muysers, Christoph; Alexandersen, Peter; Christiansen, Claus

    2009-01-01

    Declining estrogen levels after menopause result in bone loss and increased fracture risk. This study investigated whether transdermal microdose 17beta-estradiol (E2) has efficacy and safety comparable to those of raloxifene, a selective estrogen-receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis. This study involved a multicenter, randomized, double-blind, active-controlled, noninferiority trial in 500 osteopenic postmenopausal women comparing transdermal microdose E2 (0.014 mg/d) versus oral raloxifene (60 mg/d), administered for 2 years. Percent change from baseline in bone mineral density at the lumbar spine was measured after 2 years of treatment. Secondary endpoints included proportion of women with no loss of bone mineral density in lumbar spine, change in bone mineral density at hip, biochemical markers of bone turnover, and safety parameters. In the per protocol set, lumbar spine bone mineral density increased by 2.4% (95% CI, 1.9-2.9) with microdose E2 versus 3.0% (95% CI, 2.5-3.5) with raloxifene after 2 years; 77.3% of E2 recipients and 80.5% of those taking raloxifene had no bone loss in the lumbar spine. Both treatments were well tolerated. Most women (99% in the E2 group and 100% in the raloxifene group) showed no histological evidence of endometrial stimulation after 2 years. Mean dense area in breast mammograms was 19.8% in the E2 group versus 19.0% in the raloxifene group after 2 years. Transdermal microdose E2 was similarly effective as raloxifene in preventing bone loss at the lumbar spine. Both treatments were well tolerated, with no clinically significant effect on endometrium or breast density.

  13. Laboratory tests for assessing adaptability and stickiness of dental composites.

    Science.gov (United States)

    Rosentritt, Martin; Buczovsky, Sebastian; Behr, Michael; Preis, Verena

    2014-09-01

    Handling (stickiness, adaptability) of a dental composite does strongly influence quality and success of a dental restoration. The purpose was to develop an in vitro test, which allows for evaluating adaptability and stickiness. 15 dentists were asked for providing individual assessment (school scores 1-6) of five dental composites addressing adaptability and stickiness. Composites were applied with a dental plugger (d=1.8 mm) in a class I cavity (human tooth 17). The tooth was fixed on a force gauge for simultaneous determination of application forces with varying storage (6/25°C) and application temperatures (6/25°C). On basis of these data tensile tests were performed with a dental plugger (application force 1N/2N; v=35 mm/min) on PMMA- or human tooth plates. Composite was dosed onto the tip of the plugger and applied. Application and unplugging was performed once and unplugging forces (UF) and length of the adhesive flags (LAF) were determined at different storage (6/25°C) and application temperatures (25/37°C). Unplugging work (UW) was calculated from area of UF and LAF data. The individual assessment revealed significantly different temperature-dependent application forces between 0.58 N and 2.23 N. Adaptability was assessed between 2.1 and 2.8 school scores. Stickiness varied significantly between the materials (scores: 2-3.2). UW differed significantly between the materials with values between 3.20 N mm and 37.83 N mm. Between PMMA substrate or tooth slides and between 1N or 2N application force only small UW differences were found. The presented in vitro unplugging work allows for an in vitro estimation of the handling parameters adaptability and stickiness. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  14. Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer's disease mouse model.

    Science.gov (United States)

    Zhao, Lei; Gong, Neng; Liu, Meng; Pan, Xiaoli; Sang, Shaoming; Sun, Xiaojing; Yu, Zhe; Fang, Qi; Zhao, Na; Fei, Guoqiang; Jin, Lirong; Zhong, Chunjiu; Xu, Tianle

    2014-12-01

    Alzheimer's disease (AD) is a complicated, neurodegenerative disorder involving multifactorial pathogeneses and still lacks effective clinical treatment. Recent studies show that lithium exerts disease-modifying effects against AD. However, the intolerant side effects at conventional effective dosage limit the clinical use of lithium in treating AD. To explore a novel AD treatment strategy with microdose lithium, we designed and synthesized a new chemical, tri-lithium pyrroloquinoline quinone (Li3PQQ), to study the synergistic effects of low-dose lithium and pyrroloquinoline quinone, a native compound with powerful antioxidation and mitochondrial amelioration. The results showed that Li3PQQ at a relative low dose (6 and 12 mg/kg) exhibited more powerful effects in restoring the impairment of learning and memory, facilitating hippocampal long-term potentiation, and reducing cerebral amyloid deposition and phosphorylated tau level in APP/PS1 transgenic mice than that of lithium chloride at both low and high dose (5 and 100 mg/kg). We further found that Li3PQQ inhibited the activity of glycogen synthase kinase-3 and increased the activity of β-amyloid-binding alcohol dehydrogenase, which might underlie the beneficial effects of Li3PQQ on APP/PS1 transgenic mice. Our study demonstrated the efficacy of a novel AD therapeutic strategy targeting at multiple disease-causing mechanisms through the synergistic effects of microdose lithium and pyrroloquinoline quinone. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Topology optimization of compliant adaptive wing leading edge with composite materials

    Directory of Open Access Journals (Sweden)

    Tong Xinxing

    2014-12-01

    Full Text Available An approach for designing the compliant adaptive wing leading edge with composite material is proposed based on the topology optimization. Firstly, an equivalent constitutive relationship of laminated glass fiber reinforced epoxy composite plates has been built based on the symmetric laminated plate theory. Then, an optimization objective function of compliant adaptive wing leading edge was used to minimize the least square error (LSE between deformed curve and desired aerodynamics shape. After that, the topology structures of wing leading edge of different glass fiber ply-orientations were obtained by using the solid isotropic material with penalization (SIMP model and sensitivity filtering technique. The desired aerodynamics shape of compliant adaptive wing leading edge was obtained based on the proposed approach. The topology structures of wing leading edge depend on the glass fiber ply-orientation. Finally, the corresponding morphing experiment of compliant wing leading edge with composite materials was implemented, which verified the morphing capability of topology structure and illustrated the feasibility for designing compliant wing leading edge. The present paper lays the basis of ply-orientation optimization for compliant adaptive wing leading edge in unmanned aerial vehicle (UAV field.

  16. New insights for identification of doping with recombinant human erythropoietin micro-doses after high hydration

    DEFF Research Database (Denmark)

    Martin, L.; Ashenden, M; Bejder, Jacob

    2016-01-01

    To minimize the chances of being caught after doping with recombinant human erythropoietins (rhEPO), athletes have turned to new practices using micro-doses and excess fluid ingestion to accelerate elimination and decrease the probability of detection. Our objective was to test the sensitivity...... subjects. After an injection in the evening, urine and plasma samples were collected the following morning. Half of the subjects then drank a bolus of water and new samples were collected 80 min later. Interestingly, rhEPO was detected in 100% of the samples even after water ingestion. A second similar...

  17. A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders.

    Science.gov (United States)

    DiLuigi, Andrea J; Engmann, Lawrence; Schmidt, David W; Benadiva, Claudio A; Nulsen, John C

    2011-06-30

    We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Human Lung Cancer Risks from Radon – Part I - Influence from Bystander Effects - A Microdose Analysis

    Science.gov (United States)

    Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

    2010-01-01

    Since the publication of the BEIR VI report in 1999 on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, at low domestic and workplace radon levels, in particular the Bystander Effect (BE) and the Adaptive Response radio-protection (AR). We analyzed the microbeam and broadbeam alpha particle data of Miller et al. (1995, 1999), Zhou et al. (2001, 2003, 2004), Nagasawa and Little (1999, 2002), Hei et al. (1999), Sawant et al. (2001a) and found that the shape of the cellular response to alphas is relatively independent of cell species and LET of the alphas. The same alpha particle traversal dose response behavior should be true for human lung tissue exposure to radon progeny alpha particles. In the Bystander Damage Region of the alpha particle response, there is a variation of RBE from about 10 to 35. There is a transition region between the Bystander Damage Region and Direct Damage Region of between one and two microdose alpha particle traversals indicating that perhaps two alpha particle “hits” are necessary to produce the direct damage. Extrapolation of underground miners lung cancer risks to human risks at domestic and workplace levels may not be valid. PMID:21731539

  19. Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

    Science.gov (United States)

    Corcoran, T E; Venkataramanan, R; Hoffman, R M; George, M P; Petrov, A; Richards, T; Zhang, S; Choi, J; Gao, Y Y; Oakum, C D; Cook, R O; Donahoe, M

    2013-02-01

    Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

  20. Micro-dose hCG as luteal phase support without exogenous progesterone administration

    DEFF Research Database (Denmark)

    Andersen, C Yding; Fischer, R; Giorgione, V

    2016-01-01

    RHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple......For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the Gn...... corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential...

  1. Drug–drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer

    OpenAIRE

    Park G; Bae SH; Park W; Han S; Park M; Shin S; Shin YG; Yim DS

    2017-01-01

    Gab-jin Park,1 Soo Hyeon Bae,1 Wan-Su Park,1 Seunghoon Han,1 Min-Ho Park,2 Seok-Ho Shin,2 Young G Shin,2 Dong-Seok Yim1,2 1Department of Clinical Pharmacology and Therapeutics, Seoul St Mary’s Hospital, PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, Catholic University of Korea, Seoul, South Korea; 2College of Pharmacy, Chungnam National University, Daejeon, South Korea Purpose: A microdose drug–drug interaction (DDI) study may be a ...

  2. An intravenous microdose of bevacizumab for the treatment of pigment epithelial detachment associated to age-related macular degeneration refractory to intravitreal bevacizumab: a case report.

    Science.gov (United States)

    Wu, Lihteh; Evans, Teodoro

    2011-01-01

    The purpose of this study was to report the visual and anatomical outcomes of an intravenous microdose of 10 mg of bevacizumab in a patient with a vascularized pigment epithelial detachment (PED) associated with exudative age-related macular degeneration refractory to several intravitreal bevacizumab injections. Interventional case report and literature review. A 62-year-old female patient with a PED secondary to age-related macular degeneration was treated with 9 consecutive intravitreal injections of 2.5 mg of bevacizumab. Despite an initial response where the PED decreased in size, the subretinal fluid reabsorbed and the visual acuity improved; after the seventh injection, the PED started to grow in size again causing a drop in visual acuity. After an intravenous injection of 10 mg of bevacizumab, the patient experienced an improvement in visual acuity and a flattening of her PED. An intravenous injection of a microdose of bevacizumab appears to have resolved the PED with a sustained improvement of visual acuity.

  3. The comparison of microdose flare-up and multiple dose antagonist protocols based on hCG day estradiol (E2), progesterone (P) and P/E2 ratio among poor responder patients in ICSI-ET cycles.

    Science.gov (United States)

    Cicek, M N; Kahyaoglu, I; Kahyaoglu, S

    2015-02-01

    Elevated progesterone levels surpassing exact treshold values impede endometrial receptivity and decrease clinical pregnancy rates in different responder patients during assisted reproductive techniques. A progesterone (P): estradiol (E2) ratio of > 1 on the day of hCG administration has also been suggested to be a manifestation of low ovarian reserve. The clinical significance of P/E2 ratio on the day of hCG administration was investigated among poor responder patients. Based on the ESHRE Bologna consensus criteria related to poor ovarian response diagnosis, 48 poor responder patients were treated with the microdose flare-up regimen and 34 patients were treated with the multiple-dose GnRH antagonist protocol. All patients were destined to perform a ICSI-ET procedure at the end of the stimulation protocols. Progesterone levels and P/E2 ratios have been detected during controlled ovarian hyperstimulation. In the microdose flare-up group; the duration of stimulation, total gonadotropin dose used and hCG day E2 levels were significantly higher than the multiple dose antagonist group. However, the mean hCG day P/E2 rate in the microdose flare-up group was less than that in the multiple-dose antagonist group. The clinical pregnancy rates were non significantly higher in the multiple dose antagonist protocol group than in microdose flare-up group. Impaired endometrial receptivity caused by elevated P levels results with lower pregnancy rates. Regardless of the selected stimulation protocol, poor responder patients are not prone to exhibit high P and E2 secretion. Increased P/E2 ratio of > 1 on hCG day has limited value to predict cycle outcomes in poor responder patients because of ovarian follicle depletion.

  4. High-sensitive LC-MS/MS method for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma: application to microdose clinical trials of mirodenafil.

    Science.gov (United States)

    Cho, Doo-Yeoun; Bae, Soo Hyeon; Shon, Ji-Hong; Bae, Soo Kyung

    2013-03-01

    A high-sensitivity LC/MS/MS method was developed and validated for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma. Mirodenafil, SK-3541, and udenafil as an internal standard were extracted from plasma samples with methyl tert-butyl ether. Chromatographic separation was performed on a Luna phenyl-hexyl column (100 × 2.0 mm) with an isocratic mobile phase consisting of 5 mM ammonium formate and ACN (23:77, v/v) at a flow rate of 0.35 mL/min. Detection and quantification were performed using a mass spectrometer in selected reaction monitoring mode with positive ESI at m/z 532.3 → 296.1 for mirodenafil, m/z 488.1 → 296.1 for SK-3541, and m/z 517.3 → 283.2 for udenafil. The calibration curves were linear over a concentration range of 2-500 pg/mL using 0.5 mL plasma for the microdose of mirodenafil (100 μg). Analytical method validation of the clinical dose (100 mg), with a calibration curve range of 2-500 ng/mL using 0.025-mL plasma, was also conducted. The other LC-MS/MS conditions were similar to those used for the microdosing. Each method was applied successfully to pharmacokinetic studies after a microdose or clinical dose of mirodenafil to six healthy Korean male volunteers. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Grid adaptation using chimera composite overlapping meshes

    Science.gov (United States)

    Kao, Kai-Hsiung; Liou, Meng-Sing; Chow, Chuen-Yen

    1994-01-01

    The objective of this paper is to perform grid adaptation using composite overlapping meshes in regions of large gradient to accurately capture the salient features during computation. The chimera grid scheme, a multiple overset mesh technique, is used in combination with a Navier-Stokes solver. The numerical solution is first converged to a steady state based on an initial coarse mesh. Solution-adaptive enhancement is then performed by using a secondary fine grid system which oversets on top of the base grid in the high-gradient region, but without requiring the mesh boundaries to join in any special way. Communications through boundary interfaces between those separated grids are carried out using trilinear interpolation. Application to the Euler equations for shock reflections and to shock wave/boundary layer interaction problem are tested. With the present method, the salient features are well-resolved.

  6. The comparision of effect of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients.

    Science.gov (United States)

    Ozcan Cenksoy, Pinar; Ficicioglu, Cem; Kizilkale, Ozge; Suhha Bostanci, Mehmet; Bakacak, Murat; Yesiladali, Mert; Kaspar, Cigdem

    2014-07-01

    To compare the effects of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients. Of 225 patients, 83 patients were in microdose flare-up group (Group 1), 70 patients were in GnRH antagonist/letrozole group (Group 2) and 72 patients were in GnRH antagonist/clomiphene citrate group (Group 3). Demographic and endocrine characteristics, the total number of oocytes retrieved, cancellation rate and clinical pregnancy rate were collected Results: Total dosage of gonadotropins (p=0.002) and serum E2 levels on the day of hCG administration (p=0.010) were significantly higher and duration of stimulations (p=0.03) was significantly longer in group 1. The number of oocytes retrieved was significantly greater in group 1 and 2 when compare to those of group 3 (p=0,000). There was a trend towards increasing cycle cancellation rates with GnRH antagonist/clomiphene citrate and GnRH antagonist/letrozole. Our finding suggest that the results of microdose flare-up protocol are better than other two used treatment protocols, in terms of maximum estradiol levels, number of mature oocytes retrieved, and cancellation rate and it still seems to be superior the ovarian stimulation regime for the poor responder patients.

  7. Tribological properties of adaptive phosphate composite coatings with addition of silver and molybdenum disulfide

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Cancan [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou (China); University of Chinese Academy of Sciences, Beijing (China); Chen, Lei, E-mail: chenlei@lzb.ac.cn [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou (China); Zhou, Jiansong, E-mail: jszhou@licp.cas.cn [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou (China); Zhou, Huidi; Chen, Jianmin [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou (China)

    2014-05-01

    Highlights: • A new kind of adaptive coatings was fabricated using relatively simple spraying techniques. • The tribological properties of Ag/MoS{sub 2} phosphate composite coatings were investigated at the temperature from 20 °C to 700 °C. • The composition and wear mechanisms of Ag/MoS{sub 2} phosphate composite coatings were also discussed. • The Ag/MoS{sub 2} phosphate composite coatings have self-repairing capability in the rubbing process at 700 °C. - Abstract: Adaptive phosphate composite coatings with addition of solid lubricants of molybdenum disulfide (MoS{sub 2}) and silver (Ag) using aluminum chromium phosphate as the binder were fabricated on high-temperature steel. The tribological properties of phosphate composite coatings were evaluated from room temperature (RT) to 700 °C. The phase composition and microstructure were investigated according to the characterization by power X-ray diffraction (XRD), Raman spectroscopy and scanning electron microscopy (SEM). The results show that the composite coating with the Ag/MoS{sub 2} mass ratio of 2:1 exhibits the stable and low friction coefficients from RT to 700 °C and relative low wear rates at all testing temperatures. The tribo-chemical reaction between Ag and MoS{sub 2} occurred in the rubbing process to form silver molybdates compounds lubricating film. The temperature-adaptive tribological properties were attributed to the formation of lubricating films composed of lubricants silver, MoS{sub 2} and silver molybdates phases on the worn surfaces of the composites coatings in a wide-temperature range.

  8. Grid adaption using Chimera composite overlapping meshes

    Science.gov (United States)

    Kao, Kai-Hsiung; Liou, Meng-Sing; Chow, Chuen-Yen

    1993-01-01

    The objective of this paper is to perform grid adaptation using composite over-lapping meshes in regions of large gradient to capture the salient features accurately during computation. The Chimera grid scheme, a multiple overset mesh technique, is used in combination with a Navier-Stokes solver. The numerical solution is first converged to a steady state based on an initial coarse mesh. Solution-adaptive enhancement is then performed by using a secondary fine grid system which oversets on top of the base grid in the high-gradient region, but without requiring the mesh boundaries to join in any special way. Communications through boundary interfaces between those separated grids are carried out using tri-linear interpolation. Applications to the Euler equations for shock reflections and to a shock wave/boundary layer interaction problem are tested. With the present method, the salient features are well resolved.

  9. Minimal stimulation protocol using letrozole versus microdose flare up GnRH agonist protocol in women with poor ovarian response undergoing ICSI.

    Science.gov (United States)

    Mohsen, Iman Abdel; El Din, Rasha Ezz

    2013-02-01

    To compare the IVF outcomes of letrozole/antagonist and microdose GnRH agonist flare up protocols in poor ovarian responders undergoing intracytoplasmic sperm injection. A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which four or less oocytes were retrieved when the gonadotrophin starting dose was at least 300 IU/day. Sixty patients were randomized by computer-generated list to receive either letrozole/antagonist (mild stimulation) n = 30 or GnRH-a protocol (microdose flare) n = 30. Both groups were similar with respect to background and hormonal characteristics (age, duration of infertility, BMI, FSH, LH and E2). The clinical pregnancy rate per cycle was similar in both groups (13.3 vs. 16.6%; OR = 0.769; 95% CI = 0.185, 3.198). The doses of used gonadotropins and the number of stimulation days were significantly lower in the letrozole/antagonist protocol. The peak E2 level on the day of hCG, the endometrial thickness, the retrieved oocytes, the number of fertilized oocytes, the number of transferred embryos and the cancellation rate were statistically similar in both groups. The letrozole/antagonist protocol is a cost-effective and patient-friendly protocol that may be used in poor ovarian responders for IVF/ICSI.

  10. Live birth in a 46-year-old woman using microdose GnRH agonist flare-up protocol combined with GnRH antagonist: a case report.

    Science.gov (United States)

    Zhang, Hong; Liu, Ya-Qiong; Lu, Guang-Xiu; Gong, Fei

    2016-12-01

    Few successful pregnancies after age 45 years with low ovarian reserve have been reported. We report a 46-year-old woman with basal FSH 20.36 mIU/mL and an antral follicle count of four obtained two embryos and delivered a healthy infant with IVF using a microdose GnRH-a flare-up protocol combined with GnRH-ant.

  11. Development of a highly sensitive methodology for quantitative determination of fexofenadine in a microdose study by multiple injection method using ultra-high performance liquid chromatography with tandem mass spectrometry.

    Science.gov (United States)

    Tanaka, Yukari; Yoshikawa, Yutaka; Yasui, Hiroyuki

    2012-01-01

    An ultra high-sensitivity method for quantifying fexofenadine concentration in rat plasma samples by multiple injection method (MIM) was developed for a microdose study. In this study, MIM involved continuous injections of multiple samples containing the single compound into a column of the ultra-HPLC (UHPLC) system, and then, temporary trapping of the analyte at the column head. This was followed by elution of the compound from the column and detection by mass spectrometer. Fexofenadine, used as a model compound in this study, was extracted from the plasma samples by a protein precipitation method. Chromatographic separation was achieved on a reversed-phase C18 column by using a gradient method with 0.1% formic acid and 0.1% formic acid in acetonitrile as the mobile phase. The analyte was quantified in the positive-ion electrospray ionization mode using selected reaction monitoring. In this study, the analytical time per fexofenadine sample was approximately 2 min according to the UHPLC system. The method exhibited the linear dynamic ranges of 5-5000 pg/mL for fexofenadine in rat plasma. The intra-day precisions were from 3.2 to 8.7% and the accuracy range was 95.2-99.3%. The inter-day precisions and accuracies ranged from 3.5 to 8.4% and from 98.6 to 102.6%, respectively. The validated MIM was successfully applied to a microdose study in the rats that received oral administration of 100 µg/kg fexofenadine. We suggest that this method might be beneficial for the quantification of fexofenadine concentrations in a microdose clinical study.

  12. Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes.

    Science.gov (United States)

    Weitzman, Vanessa N; Engmann, Lawrence; DiLuigi, Andrea; Maier, Donald; Nulsen, John; Benadiva, Claudio

    2009-07-01

    To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. Retrospective analysis. University-based IVF center. Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.

  13. Comparison of pharmacokinetics of newly discovered aromatase inhibitors by a cassette microdosing approach in healthy Japanese subjects.

    Science.gov (United States)

    Kusuhara, Hiroyuki; Takashima, Tadayuki; Fujii, Hisako; Takashima, Tsutomu; Tanaka, Masaaki; Ishii, Akira; Tazawa, Shusaku; Takahashi, Kazuhiro; Takahashi, Kayo; Tokai, Hidekichi; Yano, Tsuneo; Kataoka, Makoto; Inano, Akihiro; Yoshida, Suguru; Hosoya, Takamitsu; Sugiyama, Yuichi; Yamashita, Shinji; Hojo, Taisuke; Watanabe, Yasuyoshi

    2017-12-01

    The aim of the present study is to investigate the pharmacokinetics of our newly developed aromatase inhibitors (cetrozole and TMD-322) in healthy subjects by a cassette microdose strategy. A cocktail of cetrozole and TMD-322 was administered intravenously or orally (1.98 μg for each drug) to six healthy volunteers in a crossover fashion. Anastrozole (1.98 μg) was also included in the oral cocktail. Total body clearance and bioavailability were 12.1 ± 7.1 mL/min/kg and 34.9 ± 32.3% for cetrozole, and 16.8 ± 3.5 mL/min/kg and 18.4 ± 12.2% for TMD-322, respectively. The area under the plasma concentration-time curves of cetrozole and TMD-322 after oral administration was markedly lower than that of anastrozole because of their high hepatic clearance. Two subjects out of six exhibited 4- and 17-fold larger exposure of cetrozole than the others following intravenous and oral administration, respectively. Such variation was not observed for TMD-322 and anastrozole. Extensive metabolism of cetrozole and TMD-322 was observed in the CYP2C19 expression system among the test CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). We report the first clinical investigation of our aromatase inhibitors by a cassette microdose strategy in healthy Japanese subjects. This strategy offers an optional approach for candidate selection as a phase zero study in drug development. Copyright © 2017. Published by Elsevier Ltd.

  14. Family Cohesion, Adaptability and Composition in Adolescents from Callao, Peru

    Science.gov (United States)

    Villarreal-Zegarra, David; Paz-Jesús, Angel

    2017-01-01

    The objective of the study was to analyze if there are significant differences between family cohesion and adaptability according to the type of family composition (nuclear, extended, single parent and non-nuclear). This is a non-experimental and empirical research, in which a non-probabilistic, cross-sectional, selective and associative strategy…

  15. Microdosing clinical study: pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the oral microdose and therapeutic dose.

    Science.gov (United States)

    Ieiri, Ichiro; Doi, Yohei; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Hirota, Takeshi; Chiyoda, Takeshi; Miyagawa, Mayuko; Irie, Shin; Iwasaki, Kazuhide; Sugiyama, Yuichi

    2012-07-01

    The authors evaluated the contribution of the SLCO2B1 polymorphism to the pharmacokinetics of celiprolol at a microdose (MD) and therapeutic dose (TD) and compared pharmacokinetic proportionality between the 2 dose forms in 30 SLCO2B1 genotype-matched healthy volunteers. Three drugs (celiprolol, fexofenadine, and atenolol) were orally administered as a cassette dosing following the MD (totally 97.5 µg) and then a TD (100 mg) of celiprolol, with and without grapefruit juice. The mean AUC(0-24) of celiprolol was lower in SLCO2B1*3/*3 individuals (775 ng·h/mL) than in *1/*3 (1097 ng·h/mL) and *1/*1 (1547 ng·h/mL) individuals following the TD, and this was confirmed in population pharmacokinetic analysis with statistical significances; however, SLCO2B1 genotype-dependent differences disappeared following the MD. Dose-normalized AUC of celiprolol at the MD was much lower than that at the TD, explained by the saturation of the efflux transporter. Thus, the effect of SLCO2B1 polymorphism on the AUC of celiprolol clearly observed only at the TD may be due to the saturation of the efflux transport systems.

  16. Marginal adaptation of large adhesive class IV composite restorations before and after artificial aging

    NARCIS (Netherlands)

    Ardu, S.; Stavridakis, M.; Feilzer, A.J.; Krejci, I.; Lefever, D.; Dietschi, D.

    2011-01-01

    Purpose: To test the marginal adaptation of Class IV restorations made of different composite materials designed for anterior use. Materials and Methods: Forty-two extracted caries-free human maxillary central incisors were randomly divided into 7 experimental groups - one per composite tested - for

  17. Using the adaptive SMA composite cylinder concept to reduce radial dilation in composite pressure vessels

    Science.gov (United States)

    Paine, Jeffrey S.; Rogers, Craig A.

    1995-05-01

    Composite materials are widely used in the design of pressurized gas and fluid vessels for applications ranging from underground gasoline storage tanks to rocket motors for the space shuttle. In the design of a high pressure composite vessel (Pi > 12 Ksi), thick-wall (R/h short term dilation and long term creep are not problematic for applications requiring only the containment of the pressurized fluid. In applications where metallic liners are required, however, substantial dilation and creep causes plastic yielding which leads to reduced fatigue life. To applications such as a hydraulic accumulator, where a piston is employed to fit and seal the fluid in the composite cylinder, the dilation and creep may allow leakage and pressure loss around the piston. A concept called the adaptive composite cylinder is experimentally presented. Shape memory alloy wire in epoxy resin is wrapped around or within polymer matrix composite cylinders to reduce radial dilation of the cylinder. Experimental results are presented that demonstrate the ability of the SMA wire layers to reduce radial dilation. Results from experimental testing of the recovery stress fatigue response of nitinol shape memory alloy wires is also presented.

  18. A comparison between r-LH and urinary supplements containing LH activity in patients undergoing the microdose GnRH agonist flare protocol for in-vitro fertilization: a pilot study.

    Science.gov (United States)

    Shavit, Tal; Agdi, Mohammed; Son, Weon Y; Hasson, Josseph; Dahan, Michael H

    2016-08-01

    The aim of this study was to compare pregnancy rates and stimulation parameters in patients with diminished ovarian reserve, who were treated with recombinant human luteinizing hormone (r-LH) or menopausal gonadotropins (hMG), as part of a microdose flare protocol. A retrospective cohort study was performed. Comparisons between the group that was stimulated with r-LH plus follicle stimulating hormone (FSH) to those treated with hMG and FSH, were performed. Measurements included: medication doses, number of oocyte collected, number of embryos obtained, pregnancy and clinical pregnancy rates. Patients in the r-LH group (N.=40) had significant higher clinical pregnancy rates (33% vs. 14%; P=0.04) and used lower dose of LH (1938 IU vs. 2807 IU; P=0.02) compared to patients that were stimulated with hMG (N.=39). r-LH may offer advantages for the treatment of diminished ovarian reserve when performing a microdose flare protocol when compared to hMG. Both larger and prospective studies should be carried out to confirm these findings.

  19. Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

    Science.gov (United States)

    Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

    2010-06-01

    To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Bibliometric study of radiation application on microdose useful for new drug development

    International Nuclear Information System (INIS)

    Komoda, Fumio; Suzuki, Akiko; Inoue, Tomio; Yanagisawa, Kazuaki

    2009-01-01

    In spite of the sharp increase in both private and government R and D fund, the number of newly approved medicines for market had decreased since the 1990s. This is attributed to a large extent to the bottleneck in the critical path arising from the great disparity between animal model in pre-clinical trial and human model in clinical trial. This bottleneck may be expected to be gotten rid of by change in paradigm of drug development based on microdosing, which is enabled by radiation-related imaging technology. However, this is impossible without being accompanied by interdisciplinary joint researches, in which clinical investigators belonging to medical schools or hospitals play the most decisive role. In this article, authors verify based on bibliometrics that Japan has not employed the opportunity for revitalizing drug research activities because Japanese researchers' attitude toward radiation technology may not be so positive in comparison with the United States (US), and because the role which clinical investigators play in the phase of preclinical trial is smaller in Japan than in the US. (author)

  1. Adaptive implicit method for thermal compositional reservoir simulation

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, A.; Tchelepi, H.A. [Society of Petroleum Engineers, Richardson, TX (United States)]|[Stanford Univ., Palo Alto (United States)

    2008-10-15

    As the global demand for oil increases, thermal enhanced oil recovery techniques are becoming increasingly important. Numerical reservoir simulation of thermal methods such as steam assisted gravity drainage (SAGD) is complex and requires a solution of nonlinear mass and energy conservation equations on a fine reservoir grid. The most currently used technique for solving these equations is the fully IMplicit (FIM) method which is unconditionally stable, allowing for large timesteps in simulation. However, it is computationally expensive. On the other hand, the method known as IMplicit pressure explicit saturations, temperature and compositions (IMPEST) is computationally inexpensive, but it is only conditionally stable and restricts the timestep size. To improve the balance between the timestep size and computational cost, the thermal adaptive IMplicit (TAIM) method uses stability criteria and a switching algorithm, where some simulation variables such as pressure, saturations, temperature, compositions are treated implicitly while others are treated with explicit schemes. This presentation described ongoing research on TAIM with particular reference to thermal displacement processes such as the stability criteria that dictate the maximum allowed timestep size for simulation based on the von Neumann linear stability analysis method; the switching algorithm that adapts labeling of reservoir variables as implicit or explicit as a function of space and time; and, complex physical behaviors such as heat and fluid convection, thermal conduction and compressibility. Key numerical results obtained by enhancing Stanford's General Purpose Research Simulator (GPRS) were also presented along with a list of research challenges. 14 refs., 2 tabs., 11 figs., 1 appendix.

  2. Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles

    Directory of Open Access Journals (Sweden)

    Parisa Khani

    2013-01-01

    Full Text Available Background: This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasinghormone (GnRH agonist flare combined with the fixed multidose GnRH antagonistprotocol in poor responders undergoing ovarian stimulation.Materials and Methods: In this randomized clinical trial, 120 women who were candidates forassisted reproductive techniques (ART and had histories of one or more failed in vitro fertilization(IVF cycles with three or fewer retrieved oocytes were prospectively randomized into two groups.Group I (60 patients received the microdose flare-up regimen and group II (60 patients receivedthe ultrashort GnRH agonist combined with fixed GnRH antagonist.Results: There were no significant differences between the groups in the number of used gonadotropinampoules (p=0.591, duration of stimulation (p=0.610, number of retrieved oocytes (p=0.802,fertilization rate (p=0.456, and the number of transferred embryos (p=0.954. The clinical pregnancyrates were statistically similar in group I (10% compared with group II (13.3%, p=0.389.Conclusion: According to our results, there is no significant difference between these protocolsfor improving the ART outcome in poor responders. Additional prospective, randomizedstudies with more patients is necessary to determine the best protocol (Registration Number:IRCT201105096420N1.

  3. Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles.

    Science.gov (United States)

    Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

    2013-01-01

    This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1).

  4. Low-energy impact of adaptive cylindrical piezoelectric-composite shells

    Energy Technology Data Exchange (ETDEWEB)

    Saravanos, D.A. [University of Patras (United Kingdom). Dept. of Mechanical Engineering and Aeronautics; Christoforou, A.P. [Kuwait Univ. (Kuwait). Dept. of Mechanical Engineering

    2002-04-01

    A theoretical framework for analyzing low-energy impacts of laminated shells with active and sensory piezoelectric layers is presented, including impactor dynamics and contact law. The formulation encompasses a coupled piezoelectric shell theory mixing first order shear displacement assumptions and layerwise variation of electric potential. An exact in-plane Ritz solution for the impact of open cylindrical piezoelectric-composite shells is developed and solved numerically using an explicit time integration scheme. The active impact control problem of adaptive cylindrical shells with distributed curved piezoelectric actuators is addressed. The cases of optimized state feedback controllers and output feedback controllers using piezoelectric sensors are analyzed. Numerical results quantify the impact response of cylindrical shells of various curvatures including the signal of curved piezoelectric sensors. Additional numerical studies quantify the impact response of adaptive cylindrical panels and investigate the feasibility of actively reducing the impact force. (author)

  5. Pregnancy outcome in delayed start antagonist versus microdose flare GnRH agonist protocol in poor responders undergoing IVF/ICSI: An RCT

    Directory of Open Access Journals (Sweden)

    Robab Davar

    2018-04-01

    Full Text Available Background: Over the years, many article on different aspects of pathogenesis and management of poor ovarian responders have been published but there is no clear guideline for treating themyet. Objective: This study was designated to compare the effectiveness of a delayed start protocol with gonadotropin-releasing hormone (GnRH antagonist and microdose flare-up GnRH agonist protocol in poor ovarian responders. Materials and Methods: This randomized clinical trial consisted of 100 poor ovarian responder women in assisted reproductive technologies cycles. They were divided randomly in delayed-start antagonist protocol (with estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation and microdose flare-up GnRH agonist protocol. The main outcome was clinical pregnancy rate and second outcome was the number of retrieved oocytes, mature oocytes, 2PN number, fertilization rate, and implantation rate. Results: Fertilization rate, clinical pregnancy rate, and ongoing pregnancy rates were not significantly different between the two studied protocols. Number of retrieved oocytes (5.10±3.41 vs. 3.08±2.51 with p=0.002, mature oocytes (4.32±2.69 vs. 2.34±1.80 with p=0.003, number of 2PN (3.94±1.80 vs. 2.20±1.01 with p=0.001 and implantation rate (19.40% vs. 10.30% with p=0.022 were significantly higher in delayed antagonist group. Conclusion: The delayed-start protocol can improve ovarian response in poor responders by stimulating and synchronizing follicle development

  6. Neural adaptive control for vibration suppression in composite fin-tip of aircraft.

    Science.gov (United States)

    Suresh, S; Kannan, N; Sundararajan, N; Saratchandran, P

    2008-06-01

    In this paper, we present a neural adaptive control scheme for active vibration suppression of a composite aircraft fin tip. The mathematical model of a composite aircraft fin tip is derived using the finite element approach. The finite element model is updated experimentally to reflect the natural frequencies and mode shapes very accurately. Piezo-electric actuators and sensors are placed at optimal locations such that the vibration suppression is a maximum. Model-reference direct adaptive neural network control scheme is proposed to force the vibration level within the minimum acceptable limit. In this scheme, Gaussian neural network with linear filters is used to approximate the inverse dynamics of the system and the parameters of the neural controller are estimated using Lyapunov based update law. In order to reduce the computational burden, which is critical for real-time applications, the number of hidden neurons is also estimated in the proposed scheme. The global asymptotic stability of the overall system is ensured using the principles of Lyapunov approach. Simulation studies are carried-out using sinusoidal force functions of varying frequency. Experimental results show that the proposed neural adaptive control scheme is capable of providing significant vibration suppression in the multiple bending modes of interest. The performance of the proposed scheme is better than the H(infinity) control scheme.

  7. Antifouling composites with self-adaptive controlled release based on an active compound intercalated into layered double hydroxides

    Science.gov (United States)

    Yang, Miaosen; Gu, Lianghua; Yang, Bin; Wang, Li; Sun, Zhiyong; Zheng, Jiyong; Zhang, Jinwei; Hou, Jian; Lin, Cunguo

    2017-12-01

    This paper reports a novel method to prepare the antifouling composites with properties of self-adaptive controlled release (defined as control the release rate autonomously and adaptively according to the change of environmental conditions) by intercalation of sodium paeonolsilate (PAS) into MgAl and ZnAl layered double hydroxide (LDH) with the molar ratio (M2+/M3+) of 2:1 and 3:1, respectively. The powder X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) confirm the intercalation of PAS into the galleries of LDH. The controlled release behavior triggered by temperature for the PAS-LDH composites has been investigated, and the results show that the release rate of all PAS-LDH composites increases as the increase of temperature. However, the MgAl-PAS-LDH composites (Mg2Al-PAS-LDH and Mg3Al-PAS-LDH) exhibit the increased release rate of 0.21 ppm/°C from 15 to 30 °C in 3.5% NaCl solution, more than three times of the ZnAl-PAS-LDH composites (0.06 ppm/°C), owing to the confined microenvironment influenced by metal types in LDH layers. In addition, a possible diffusion-controlled process with surface diffusion, bulk diffusion and heterogeneous flat surface diffusion has been revealed via fitting four kinetic equations. Moreover, to verify the practical application of the PAS-LDH composites, a model coating denoted as Mg2Al-PAS-LDH coating was fabricated. The release result displays that the release rate increases or decreases as temperature altered at 15 and 25 °C alternately, indicating its self-adaptive controlled release behavior with temperature. Moreover, the superior resistance to the settlement of Ulva spores at 15 and 25 °C was observed for the Mg2Al-PAS-LDH coating, as a result of the controllable release of antifoulant. Therefore, this work provides a facile and effective method for the fabrication of antifouling composites with self-adaptive controlled release behavior in response to temperature, which can be used to prolong

  8. The evaluation of composite dose using deformable image registration in adaptive radiotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Hwang, Chul Hwan; Ko, Seong Jin; Kim, Chang Soo; Kim, Jung Hoon; Kim, Dong Hyun; Choi, Seok Yoon; Ye, Soo Young; Kang, Se Sik

    2013-01-01

    In adaptive radiotherapy(ART), generated composite dose of surrounding normal tissue on overall treatment course which is using deformable image registration from multistage images. Also, compared with doses summed by each treatment plan and clinical significance is considered. From the first of May, 2011 to the last of July, 2012. Patients who were given treatment and had the head and neck cancer with 3-dimension conformal radiotherapy or intensity modulated radiotherapy, those who were carried out adaptive radiotherapy cause of tumor shrinkage and weight loss. Generated composite dose of surrounding normal tissue using deformable image registration was been possible, statistically significant difference was showed to mandible(48.95±3.89 vs 49.10±3.55 Gy), oral cavity(36.93±4.03 vs 38.97±5.08 Gy), parotid gland(35.71±6.22 vs 36.12±6.70 Gy) and temporomandibular joint(18.41±9.60 vs 20.13±10.42 Gy) compared with doses summed by each treatment plan. The results of this study show significant difference between composite dose by deformable image registration and doses summed by each treatment plan, composite dose by deformable image registration may generate more exact evaluation to surrounding normal tissue in adaptive radiotherapy

  9. The evaluation of composite dose using deformable image registration in adaptive radiotherapy for head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Chul Hwan; Ko, Seong Jin; Kim, Chang Soo; Kim, Jung Hoon; Kim, Dong Hyun; Choi, Seok Yoon; Ye, Soo Young; Kang, Se Sik [Dept. of Radiological Science, College of Health Sciences, Catholic University of Pusan, Pusan (Korea, Republic of)

    2013-09-15

    In adaptive radiotherapy(ART), generated composite dose of surrounding normal tissue on overall treatment course which is using deformable image registration from multistage images. Also, compared with doses summed by each treatment plan and clinical significance is considered. From the first of May, 2011 to the last of July, 2012. Patients who were given treatment and had the head and neck cancer with 3-dimension conformal radiotherapy or intensity modulated radiotherapy, those who were carried out adaptive radiotherapy cause of tumor shrinkage and weight loss. Generated composite dose of surrounding normal tissue using deformable image registration was been possible, statistically significant difference was showed to mandible(48.95±3.89 vs 49.10±3.55 Gy), oral cavity(36.93±4.03 vs 38.97±5.08 Gy), parotid gland(35.71±6.22 vs 36.12±6.70 Gy) and temporomandibular joint(18.41±9.60 vs 20.13±10.42 Gy) compared with doses summed by each treatment plan. The results of this study show significant difference between composite dose by deformable image registration and doses summed by each treatment plan, composite dose by deformable image registration may generate more exact evaluation to surrounding normal tissue in adaptive radiotherapy.

  10. Microdose-Induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice.

    Science.gov (United States)

    Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong; Lin, Tzu-Yin; Malfatti, Michael; Haack, Kurt; Ognibene, Ted; Yang, Hongyuan; Airhart, Susan; Turteltaub, Kenneth W; Cimino, George D; Tepper, Clifford G; Drakaki, Alexandra; Chamie, Karim; de Vere White, Ralph; Pan, Chong-Xian; Henderson, Paul T

    2017-02-01

    We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [ 14 C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [ 14 C]carboplatin or [ 14 C]gemcitabine and the resulting drug-DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug-DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug-DNA adducts as predictive biomarkers. Mol Cancer Ther; 16(2); 376-87. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Static aeroelastic behavior of an adaptive laminated piezoelectric composite wing

    Science.gov (United States)

    Weisshaar, T. A.; Ehlers, S. M.

    1990-01-01

    The effect of using an adaptive material to modify the static aeroelastic behavior of a uniform wing is examined. The wing structure is idealized as a laminated sandwich structure with piezoelectric layers in the upper and lower skins. A feedback system that senses the wing root loads applies a constant electric field to the piezoelectric actuator. Modification of pure torsional deformaton behavior and pure bending deformation are investigated, as is the case of an anisotropic composite swept wing. The use of piezoelectric actuators to create an adaptive structure is found to alter static aeroelastic behavior in that the proper choice of the feedback gain can increase or decrease the aeroelastic divergence speed. This concept also may be used to actively change the lift effectiveness of a wing. The ability to modify static aeroelastic behavior is limited by physical limitations of the piezoelectric material and the manner in which it is integrated into the parent structure.

  12. Functional adaptation of long bone extremities involves the localized "tuning" of the cortical bone composition; evidence from Raman spectroscopy.

    Science.gov (United States)

    Buckley, Kevin; Kerns, Jemma G; Birch, Helen L; Gikas, Panagiotis D; Parker, Anthony W; Matousek, Pavel; Goodship, Allen E

    2014-01-01

    In long bones, the functional adaptation of shape and structure occurs along the whole length of the organ. This study explores the hypothesis that adaptation of bone composition is also site-specific and that the mineral-to-collagen ratio of bone (and, thus, its mechanical properties) varies along the organ's length. Raman spectroscopy was used to map the chemical composition of long bones along their entire length in fine spatial resolution (1 mm), and then biochemical analysis was used to measure the mineral, collagen, water, and sulfated glycosaminoglycan content where site-specific differences were seen. The results show that the mineral-to-collagen ratio of the bone material in human tibiae varies by 10% toward the flared extremities of the bone. Comparisons with long bones from other large animals (horses, sheep, and deer) gave similar results with bone material composition changing across tens of centimeters. The composition of the bone apatite also varied with the phosphate-to-carbonate ratio decreasing toward the ends of the tibia. The data highlight the complexity of adaptive changes and raise interesting questions about the biochemical control mechanisms involved. In addition to their biological interest, the data provide timely information to researchers developing Raman spectroscopy as a noninvasive tool for measuring bone composition in vivo (particularly with regard to sampling and measurement protocol).

  13. Functional adaptation of long bone extremities involves the localized ``tuning'' of the cortical bone composition; evidence from Raman spectroscopy

    Science.gov (United States)

    Buckley, Kevin; Kerns, Jemma G.; Birch, Helen L.; Gikas, Panagiotis D.; Parker, Anthony W.; Matousek, Pavel; Goodship, Allen E.

    2014-11-01

    In long bones, the functional adaptation of shape and structure occurs along the whole length of the organ. This study explores the hypothesis that adaptation of bone composition is also site-specific and that the mineral-to-collagen ratio of bone (and, thus, its mechanical properties) varies along the organ's length. Raman spectroscopy was used to map the chemical composition of long bones along their entire length in fine spatial resolution (1 mm), and then biochemical analysis was used to measure the mineral, collagen, water, and sulfated glycosaminoglycan content where site-specific differences were seen. The results show that the mineral-to-collagen ratio of the bone material in human tibiae varies by 10% toward the flared extremities of the bone. Comparisons with long bones from other large animals (horses, sheep, and deer) gave similar results with bone material composition changing across tens of centimeters. The composition of the bone apatite also varied with the phosphate-to-carbonate ratio decreasing toward the ends of the tibia. The data highlight the complexity of adaptive changes and raise interesting questions about the biochemical control mechanisms involved. In addition to their biological interest, the data provide timely information to researchers developing Raman spectroscopy as a noninvasive tool for measuring bone composition in vivo (particularly with regard to sampling and measurement protocol).

  14. In vitro marginal adaptation of high-viscosity resin composite restorations bonded to dentin cavities.

    Science.gov (United States)

    Rahiotis, Christos; Tzoutzas, John; Kakaboura, Afrodite

    2004-01-01

    The aim of this study was to evaluate the marginal adaptation of high-viscosity resin composite restoratives bonded to dentin in a cylindrical cavity model. The buccal enamel of 64 human premolars was removed and cylindrical cavities 3 mm in diameter and 1.3 mm in depth were prepared on each dentin surface. The cavities were divided into 8 groups of 8 cavities each and restored according to the manufacturers' instructions with the following adhesive/composite systems: Bond 1/Alert, Stae/Glacier, OptiBond Solo/Prodigy Condensable, One-Step/Pyramid, Solidbond/Solitaire, Prime&Bond NT/Surefil, One Coat Bond/Synergy, and Scotchbond 1/Z250. The composite surfaces were pressed against mylar strips, covered with cover slips, and photopolymerized in a single increment for 40 s. The restorations were polished with wet SiC papers of 320 to 1000 grit size to expose dentin margins. The marginal adaptation was evaluated immediately after photopolymerization and again after 1 week of storage in water at 37 +/- 1 degrees C. Evaluation was performed under a metallographic microscope at 200X magnification by recording the frequency of gap-free restorations (GF), the percentage length of the debonded margins relative to the cavity periphery (DM), the width of the maximum marginal gap (MG), and the marginal index (MI = MG x DM / 100). The results were statistically analyzed with one-way ANOVA and the Mann-Whitney U-test at alpha = 0.05. No incidence of gaps was found in 62.5% of One Coat Bond/Synergy and 37.5% of OptiBond Solo/Prodigy Condensable restorations. All the other restorative systems exhibited restorations with gaps. One Coat Bond/Synergy, Scotchbond 1/Z250, and OptiBond Solo/Prodigy Condensable were the groups with the lowest DM values, while Stae/Glacier showed the highest DM values. One Coat Bond/Synergy and OptiBond Solo/Prodigy Condensable revealed the lowest MI values and Stae/Glacier the highest. No statistically significant differences were recorded between

  15. Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization.

    Science.gov (United States)

    Dunne, Caitlin; Seethram, Ken; Roberts, Jeffrey

    2015-09-01

    Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). The administration of growth hormone during the

  16. Development of rapid multistep carbon-11 radiosynthesis of the myeloperoxidase inhibitor AZD3241 to assess brain exposure by PET microdosing

    International Nuclear Information System (INIS)

    Johnström, Peter; Bergman, Linda; Varnäs, Katarina; Malmquist, Jonas; Halldin, Christer; Farde, Lars

    2015-01-01

    Introduction: The myeloperoxidase inhibitor AZD3241 has been selected as a candidate drug currently being developed to delay progression in patients with neurodegenerative brain disorders. Part of the decision tree for translation of AZD3241 into clinical studies included the need for assessment of brain exposure in non-human primates by PET microdosing. For that purpose a rapid multistep method for 11 C-labeling of AZD3241 was developed. Methods: AZD3241 was labeled in the thio-carbonyl position starting from [ 11 C]potassium cyanide in a 4-step procedure using microwave assisted heating. In the first step [ 11 C]potassium cyanide was converted to [ 11 C]potassium thiocyanate followed by reaction with benzoyl chloride to yield benzoyl [ 11 C]isothiocyanate. The benzoyl [ 11 C]isothiocyanate was subsequently reacted with the precursor ethyl 3-(2-isopropoxyethylamino)-1H-pyrrole-2-carboxylate and the formed intermediate underwent a base catalyzed cyclization to obtain [ 11 C]AZD3241 in the final step. To assess [ 11 C]AZD3241 brain exposure PET measurements were performed in three cynomolgus monkeys. Results: [ 11 C]AZD3241 was produced in good and reproducible radiochemical yield 710 ± 294 MBq (mean ± SD, n = 7). Total time of synthesis was 60 min from end of bombardment. The specific radioactivity was 9 ± 4 GBq/μmol and the radiochemical purity was > 98%. Following iv administration of [ 11 C]AZD3241 there was a rapid presence of radioactivity in brain in each of the three monkeys. The distribution of [ 11 C]AZD3241 to brain was fast and a C max of 1.9 to 2.6% of the injected radioactivity was observed within 1.5 min. [ 11 C]AZD3241 was homogeneously distributed in brain. Conclusion: The MPO inhibitor AZD3241 was successfully labeled with carbon-11 in a challenging 4-step procedure in good radiochemical yield allowing PET microdosing studies in cynomolgus monkey. [ 11 C]AZD3241 rapidly entered brain and confirmed adequate brain exposure to support translation

  17. Comparison of the marginal adaptation of direct and indirect composite inlay restorations with optical coherence tomography.

    Science.gov (United States)

    Türk, Ayşe Gözde; Sabuncu, Metin; Ünal, Sena; Önal, Banu; Ulusoy, Mübin

    2016-01-01

    The purpose of the study was to use the photonic imaging modality of optical coherence tomography (OCT) to compare the marginal adaptation of composite inlays fabricated by direct and indirect techniques. Class II cavities were prepared on 34 extracted human molar teeth. The cavities were randomly divided into two groups according to the inlay fabrication technique. The first group was directly restored on cavities with a composite (Esthet X HD, Dentsply, Germany) after isolating. The second group was indirectly restored with the same composite material. Marginal adaptations were scanned before cementation with an invisible infrared light beam of OCT (Thorlabs), allowing measurement in 200 µm intervals. Restorations were cemented with a self-adhesive cement resin (SmartCem2, Dentsply), and then marginal adaptations were again measured with OCT. Mean values were statistically compared by using independent-samples t-test and paired samples t-test (pmarginal discrepancy values than indirect inlays, before (p=0.00001442) and after (p=0.00001466) cementation. Marginal discrepancy values were increased for all restorations after cementation (p=0.00008839, p=0.000000952 for direct and indirect inlays, respectively). The mean marginal discrepancy value of the direct group increased from 56.88±20.04 µm to 91.88±31.7 µm, whereas the indirect group increased from 107.54±35.63 µm to 170.29±54.83 µm. Different techniques are available to detect marginal adaptation of restorations, but the OCT system can give quantitative information about resin cement thickness and its interaction between tooth and restoration in a nondestructive manner. Direct inlays presented smaller marginal discrepancy than indirect inlays. The marginal discrepancy values were increased for all restorations that refer to cement thickness after cementation.

  18. The influence of FRCs reinforcement on marginal adaptation of CAD/CAM composite resin endocrowns after simulated fatigue loading.

    Science.gov (United States)

    Rocca, Giovanni Tommaso; Saratti, Carlo Massimo; Poncet, Antoine; Feilzer, Albert J; Krejci, Ivo

    2016-05-01

    To evaluate the marginal adaptation of endodontically treated molars restored with CAD/CAM composite resin endocrowns either with or without reinforcement by fibre reinforced composites (FRCs), used in different configurations. 32 human endodontically treated molars were cut 2 mm over the CEJ. Two interproximal boxes were created with the margins located 1 mm below the CEJ (distal box) and 1 mm over the CEJ (mesial box). All specimens were divided in four groups (n = 8). The pulp chamber was filled with: group 1 (control), hybrid resin composite (G-aenial Posterior, GC); group 2, as group 1 but covered by 3 meshes of E-glass fibres (EverStick NET, Stick Tech); group 3, FRC resin (EverX Posterior, GC); group 4, as group 3 but covered by 3 meshes of E-glass fibres. The crowns of all teeth were restored with CAD/CAM composite resin endocrowns (LAVA Ultimate, 3M). All specimens were thermo-mechanically loaded in a computer-controlled chewing machine (600,000 cycles, 1.6 Hz, 49 N and simultaneously 1500 thermo-cycles, 60 s, 5-55 °C). Marginal analysis before and after the loading was carried out on epoxy replicas by SEM at 200× magnification. For all the groups, the percentage values of perfect marginal adaptation after loading were always significantly lower than before loading (p marginal adaptation before and after loading was not significantly different between the experimental groups (p > 0.05). Within the limitations of this in vitro study, the use of FRCs to reinforce the pulp chamber of devitalized molars restored with CAD/CAM composite resin restorations did not significantly influenced their marginal quality.

  19. Imaging of Lymph Flow in Breast Cancer Patients after Microdose Administration of a Near-Infrared Fluorophore: Feasibility Study1

    Science.gov (United States)

    Sevick-Muraca, Eva M.; Sharma, Ruchi; Rasmussen, John C.; Marshall, Milton V.; Wendt, Juliet A.; Pham, Hoang Q.; Bonefas, Elizabeth; Houston, Jessica P.; Sampath, Lakshmi; Adams, Kristen E.; Blanchard, Darlene Kay; Fisher, Ronald E.; Chiang, Stephen B.; Elledge, Richard; Mawad, Michel E.

    2011-01-01

    Purpose To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). Materials and Methods Informed consent was obtained from 24 women (age range, 30–85 years) who received intradermal subcutaneous injections of 0.31–100 μg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. Results Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 μg. When indocyanine green dosages were 10 μg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between “packets” of propelled fluid varied from 14 to 92 seconds. In patients who received 10 μg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of

  20. An integration time adaptive control method for atmospheric composition detection of occultation

    Science.gov (United States)

    Ding, Lin; Hou, Shuai; Yu, Fei; Liu, Cheng; Li, Chao; Zhe, Lin

    2018-01-01

    When sun is used as the light source for atmospheric composition detection, it is necessary to image sun for accurate identification and stable tracking. In the course of 180 second of the occultation, the magnitude of sun light intensity through the atmosphere changes greatly. It is nearly 1100 times illumination change between the maximum atmospheric and the minimum atmospheric. And the process of light change is so severe that 2.9 times per second of light change can be reached. Therefore, it is difficult to control the integration time of sun image camera. In this paper, a novel adaptive integration time control method for occultation is presented. In this method, with the distribution of gray value in the image as the reference variable, and the concepts of speed integral PID control, the integration time adaptive control problem of high frequency imaging. The large dynamic range integration time automatic control in the occultation can be achieved.

  1. A novel adaptive sun tracker for spacecraft solar panel based on hybrid unsymmetric composite laminates

    Science.gov (United States)

    Wu, Zhangming; Li, Hao

    2017-11-01

    This paper proposes a novel adaptive sun tracker which is constructed by hybrid unsymmetric composite laminates. The adaptive sun tracker could be applied on spacecraft solar panels to increase their energy efficiency through decreasing the inclined angle between the sunlight and the solar panel normal. The sun tracker possesses a large rotation freedom and its rotation angle depends on the laminate temperature, which is affected by the light condition in the orbit. Both analytical model and finite element model (FEM) are developed for the sun tracker to predict its rotation angle in different light conditions. In this work, the light condition of the geosynchronous orbit on winter solstice is considered in the numerical prediction of the temperatures of the hybrid laminates. The final inclined angle between the sunlight and the solar panel normal during a solar day is computed using the finite element model. Parametric study of the adaptive sun tracker is conducted to improve its capacity and effectiveness of sun tracking. The improved adaptive sun tracker is lightweight and has a state-of-the-art design. In addition, the adaptive sun tracker does not consume any power of the solar panel, since it has no electrical driving devices. The proposed adaptive sun tracker provides a potential alternative to replace the traditional sophisticated electrical driving mechanisms for spacecraft solar panels.

  2. Marginal adaptation of a low-shrinkage silorane-based composite: A SEM-analysis

    DEFF Research Database (Denmark)

    Schmidt, Malene; Bindslev, Preben Hørsted; Poulsen, Sven

    2012-01-01

    shrinkage, has been marketed. Objective. To investigate whether reduced polymerization shrinkage improves the marginal adaptation of composite restorations. Material and methods. A total of 156 scanning electron microscopy (SEM) pictures (78 baseline, 78 follow-up) of the occlusal part of Class II......-casts of the restorations were used for SEM pictures at x 16 magnification. Pictures from baseline and follow-up (398 days, SD 29 days) were randomized and the examiner was blinded to the material and the age of the restoration. Stereologic measurements were used to calculate the length and the width of the marginal...

  3. A high-throughput FTIR spectroscopy approach to assess adaptive variation in the chemical composition of pollen.

    Science.gov (United States)

    Zimmermann, Boris; Bağcıoğlu, Murat; Tafinstseva, Valeria; Kohler, Achim; Ohlson, Mikael; Fjellheim, Siri

    2017-12-01

    The two factors defining male reproductive success in plants are pollen quantity and quality, but our knowledge about the importance of pollen quality is limited due to methodological constraints. Pollen quality in terms of chemical composition may be either genetically fixed for high performance independent of environmental conditions, or it may be plastic to maximize reproductive output under different environmental conditions. In this study, we validated a new approach for studying the role of chemical composition of pollen in adaptation to local climate. The approach is based on high-throughput Fourier infrared (FTIR) characterization and biochemical interpretation of pollen chemical composition in response to environmental conditions. The study covered three grass species, Poa alpina , Anthoxanthum odoratum , and Festuca ovina . For each species, plants were grown from seeds of three populations with wide geographic and climate variation. Each individual plant was divided into four genetically identical clones which were grown in different controlled environments (high and low levels of temperature and nutrients). In total, 389 samples were measured using a high-throughput FTIR spectrometer. The biochemical fingerprints of pollen were species and population specific, and plastic in response to different environmental conditions. The response was most pronounced for temperature, influencing the levels of proteins, lipids, and carbohydrates in pollen of all species. Furthermore, there is considerable variation in plasticity of the chemical composition of pollen among species and populations. The use of high-throughput FTIR spectroscopy provides fast, cheap, and simple assessment of the chemical composition of pollen. In combination with controlled-condition growth experiments and multivariate analyses, FTIR spectroscopy opens up for studies of the adaptive role of pollen that until now has been difficult with available methodology. The approach can easily be

  4. Average glandular dose in routine mammography screening using a Sectra Microdose Mammography unit

    International Nuclear Information System (INIS)

    Hemdal, B.; Herrnsdorf, L.; Andersson, I.; Bengtsson, G.; Heddson, B.; Olsson, M.

    2005-01-01

    The Sectra MicroDose Mammography system is based on direct photon counting (with a solid-state detector), and a substantially lower dose to the breast than when using conventional system can be expected. In this work absorbed dose measurements have been performed for the first unit used in routine mammography screening (at the Hospitals of Helsingborg (Sweden)). Two European protocols on dosimetry in mammography have been followed. Measurement of half value layer (HVL) cannot be performed as prescribed, but this study has demonstrated than non-invasive measurements of HVL can be performed accurately with a sensitive and well collimated solid-state detector with simultaneous correction for the energy dependence. The average glandular dose for a 50 mm standard breast with 50% glandularity, simulated by 45 mm polymethylmethacrylate, was found to be 0.21 and 0.28 mGy in March and December 2004, respectively. These values are much lower than for any other mammography system on the market today. It has to be stressed that the measurement were made using the current clinical settings and that no systematic optimisation of the relationship between absorbed dose and diagnostic image quality has been performed within the present study. In order to further increase the accuracy of absorbed dose measurements for this unit, the existing dose protocols should be revised to account also for the tungsten/aluminium anode/filter combination, the multi-slit pre-collimator device and the occurrence of a dose profile in the scanning direction. (authors)

  5. Microdose follicular flare: a viable alternative for normal responding patients undergoing in vitro fertilization?

    Science.gov (United States)

    Levens, Eric D.; Whitcomb, Brian W.; Kort, Jonathan D.; Materia-Hoover, Donna; Larsen, Frederick W.

    2009-01-01

    Objective To compare cycle outcomes among normal responding patients ≤30 years receiving microdose follicular flare (MDF) and long-luteal agonist (LL). Design Retrospective cohort study. Setting Military-based ART center. Patients First, autologous ART cycles among 499 women ≤30 years old from 01/1999 to 12/2005. Interventions Following OCP administration prior to cycle start, patients were non-randomly assigned to either LL or MDF for LH surge suppression. LL received 1 mg/d leuprolide acetate (LA) on cycle day 21, which was reduced to 0.25 mg/day 10–14 days later. MDF received LA (40 μg BID) beginning 3 days after discontinuing OCPs. Both groups received a combination of hMG and rFSH. Main Outcome Measures Primary outcomes were implantation, clinical pregnancy and live birth rates; in cycle variables included peak E2, oocytes retrieved, oocyte maturity, and fertilization rate. Results Multivariable models controlling for confounding by treatment indication found no significant differences between groups in implantation (MDF:36%; LL:38%), clinical pregnancy (MDF:53%; LL:56%), and live birth rates (MDF:47%; LL:50%). No differences were observed in peak E2, oocytes retrieved, oocyte maturity, fertilization rate, or embryos transferred. Conclusions MDF use among normal responding ART patients produced no differences in cycle outcome when compared to LL. Resultantly, MDF may be a viable alternative for normal responding patients. PMID:18249365

  6. Composition and adaptation of human myotendinous junction and neighboring muscle fibers to heavy resistance training

    DEFF Research Database (Denmark)

    Jakobsen, Jens R.; Mackey, A L; Knudsen, A B

    2017-01-01

    The myotendinous junction (MTJ) is a common site of strain injury and yet understanding of its composition and ability to adapt to loading is poor. The main aims of this study were to determine the profile of selected collagens and macrophage density in human MTJ and adjoining muscle fibers...... 4 weeks of training may reflect a training-induced protection against strain injuries in this region....

  7. Sex-specific functional adaptation of the femoral diaphysis to body composition.

    Science.gov (United States)

    Lacoste Jeanson, Alizé; Santos, Frédéric; Dupej, Ján; Velemínská, Jana; Brůžek, Jaroslav

    2018-03-24

    The human femoral diaphysis is often used to reconstruct loading histories (mobility, activity, body mass). The proximal femur is known to be differentially affected by changes in total fat-mass (FM), fat-free mass (FFM), and body fat percentage (BF%), but the adaptation of the entire diaphysis to body composition has not been thoroughly characterized to date. Understanding how the femoral diaphysis adapts to body components would benefit biomechanical interpretations of the femoral variation and nutrition-related studies. Combining various methods from clinical nutrition, biological anthropology, and geometric morphometrics, we evaluated the correlation of measures taken on the entire femoral diaphysis with estimated FM, FFM, and BF% from 61 CT scans (17 females, 44 males). The sample was predominantly composed of people with obesity. Cortical area of the cross-sections and local cortical thickness showed high correlation with BF% in particular, in females only. The curvature significantly decreased with FM and BF% in both sexes. The lowest correlations are found with FFM. The observed sexual dimorphism is consistent with differing aging processes; cortical bone decreases in females through endosteal resorption while it remains almost constant in males who compensate for endosteal resorption by periosteal apposition on the diaphyseal surface. The functional adaptation to compressive forces indicates a systemic endosteal apposition of bone material with increased BF% and FM in females only. FM and BF% are linked to a straighter femur in both sexes, suggesting an optimization of the resistance to compressive loads by distributing them more linearly along the entire diaphysis. © 2018 Wiley Periodicals, Inc.

  8. Bridging recommendation and adaptation: Generic Adaptation Framework - Twittomender compliance study

    NARCIS (Netherlands)

    Hannon, J.; Knutov, E.; De Bra, P.M.E.; Pechenizkiy, M.; McCarthy, K.; Smyth, B.; Pechenizkiy, M.; Knutov, E.; Yudelson, M.; Abel, F.; Houben, G.J.P.M.; Herder, E.

    2012-01-01

    In this paper we consider Recommender System (RS) modeling in terms of Adaptive Hypermedia Systems (AHS) and investigate AHS and RS functionality compliance in terms of common features, functionality, building blocks and composition of the system. We bring up complementary aspects of adaptation,

  9. Constitutive modeling of SMA SMP multifunctional high performance smart adaptive shape memory composite

    International Nuclear Information System (INIS)

    Jarali, Chetan S; Raja, S; Upadhya, A R

    2010-01-01

    Materials design involving the thermomechanical constitutive modeling of shape memory alloy (SMA) and shape memory polymer (SMP) composites is a key topic in the development of smart adaptive shape memory composites (SASMC). In this work, a constitutive model for SASMC is developed. First, a one-dimensional SMA model, which can simulate the pseudoelastic (PE) and shape memory effects (SME) is presented. Subsequently, a one-dimensional SMP model able to reproduce the SME is addressed. Both SMA and SMP models are based on a single internal state variable, namely the martensite fraction and the frozen fraction, which can be expressed as a function of temperature. A consistent form of the analytical solution for the SMP model is obtained using the fourth-order Runge–Kutta method. Finally, the SASMC constitutive model is proposed, following two analytical homogenization approaches. One approach is based on an equivalent inclusion method and the other approach is the rule of mixtures. The SMA and SMP constitutive models are validated independently with experimental results. However, the validation of the composite model is performed using the two homogenization approaches and a close agreement in results is observed. Results regarding the isothermal and thermomechanical stress–strain responses are analyzed as a function of SMA volume fraction. Further, it is concluded that the proposed composite model is able to reproduce consistently the overall composite response by taking into consideration not only the phase transformations, variable modulus and transformation stresses in SMA but also the variable modulus, the evolution of stored strain and thermal strain in the SMP

  10. Nitrate decreases ruminal methane production with slight changes to ruminal methanogen composition of nitrate-adapted steers.

    Science.gov (United States)

    Zhao, Liping; Meng, Qingxiang; Li, Yan; Wu, Hao; Huo, Yunlong; Zhang, Xinzhuang; Zhou, Zhenming

    2018-03-20

    This study was conducted to examine effects of nitrate on ruminal methane production, methanogen abundance, and composition. Six rumen-fistulated Limousin×Jinnan steers were fed diets supplemented with either 0% (0NR), 1% (1NR), or 2% (2NR) nitrate (dry matter basis) regimens in succession. Rumen fluid was taken after two-week adaptation for evaluation of in vitro methane production, methanogen abundance, and composition measurements. Results showed that nitrate significantly decreased in vitro ruminal methane production at 6 h, 12 h, and 24 h (P methane reduction was significantly related to Methanobrevibacter and Methanoplanus abundance, and negatively correlated with Methanosphaera and Methanimicrococcus abundance.

  11. Gas composition modeling in a reformed Methanol Fuel Cell system using adaptive Neuro-Fuzzy Inference Systems

    DEFF Research Database (Denmark)

    Justesen, Kristian Kjær; Andreasen, Søren Juhl; Shaker, Hamid Reza

    2013-01-01

    This work presents a method for modeling the gas composition in a Reformed Methanol Fuel Cell system. The method is based on Adaptive Neuro-Fuzzy-Inference-Systems which are trained on experimental data. The developed models are of the H2, CO2, CO and CH3OH mass flows of the reformed gas. The ANFIS......, or fuel cell diagnostics systems....

  12. Development and Design of Next-Generation Head-Mounted Ambulatory Microdose Positron-Emission Tomography (AM-PET) System.

    Science.gov (United States)

    Melroy, Samantha; Bauer, Christopher; McHugh, Matthew; Carden, Garret; Stolin, Alexander; Majewski, Stan; Brefczynski-Lewis, Julie; Wuest, Thorsten

    2017-05-19

    Several applications exist for a whole brain positron-emission tomography (PET) brain imager designed as a portable unit that can be worn on a patient's head. Enabled by improvements in detector technology, a lightweight, high performance device would allow PET brain imaging in different environments and during behavioral tasks. Such a wearable system that allows the subjects to move their heads and walk-the Ambulatory Microdose PET (AM-PET)-is currently under development. This imager will be helpful for testing subjects performing selected activities such as gestures, virtual reality activities and walking. The need for this type of lightweight mobile device has led to the construction of a proof of concept portable head-worn unit that uses twelve silicon photomultiplier (SiPM) PET module sensors built into a small ring which fits around the head. This paper is focused on the engineering design of mechanical support aspects of the AM-PET project, both of the current device as well as of the coming next-generation devices. The goal of this work is to optimize design of the scanner and its mechanics to improve comfort for the subject by reducing the effect of weight, and to enable diversification of its applications amongst different research activities.

  13. Development and Design of Next-Generation Head-Mounted Ambulatory Microdose Positron-Emission Tomography (AM-PET System

    Directory of Open Access Journals (Sweden)

    Samantha Melroy

    2017-05-01

    Full Text Available Several applications exist for a whole brain positron-emission tomography (PET brain imager designed as a portable unit that can be worn on a patient’s head. Enabled by improvements in detector technology, a lightweight, high performance device would allow PET brain imaging in different environments and during behavioral tasks. Such a wearable system that allows the subjects to move their heads and walk—the Ambulatory Microdose PET (AM-PET—is currently under development. This imager will be helpful for testing subjects performing selected activities such as gestures, virtual reality activities and walking. The need for this type of lightweight mobile device has led to the construction of a proof of concept portable head-worn unit that uses twelve silicon photomultiplier (SiPM PET module sensors built into a small ring which fits around the head. This paper is focused on the engineering design of mechanical support aspects of the AM-PET project, both of the current device as well as of the coming next-generation devices. The goal of this work is to optimize design of the scanner and its mechanics to improve comfort for the subject by reducing the effect of weight, and to enable diversification of its applications amongst different research activities.

  14. Adaptable piezoelectric hemispherical composite strips using a scalable groove technique for a self-powered muscle monitoring system.

    Science.gov (United States)

    Alluri, Nagamalleswara Rao; Vivekananthan, Venkateswaran; Chandrasekhar, Arunkumar; Kim, Sang-Jae

    2018-01-18

    Contrary to traditional planar flexible piezoelectric nanogenerators (PNGs), highly adaptable hemispherical shape-flexible piezoelectric composite strip (HS-FPCS) based PNGs are required to harness/measure non-linear surface motions. Therefore, a feasible, cost-effective and less-time consuming groove technique was developed to fabricate adaptable HS-FPCSs with multiple lengths. A single HS-CSPNG generates 130 V/0.8 μA and can also work as a self-powered muscle monitoring system (SP-MMS) to measure maximum human body part movements, i.e., spinal cord, throat, jaw, elbow, knee, foot stress, palm hand/finger force and inhale/exhale breath conditions at a time or at variable time intervals.

  15. Tailored breast cancer screening program with microdose mammography, US, and MR Imaging: short-term results of a pilot study in 40-49-year-old women.

    Science.gov (United States)

    Venturini, Elena; Losio, Claudio; Panizza, Pietro; Rodighiero, Maria Grazia; Fedele, Isabella; Tacchini, Simona; Schiani, Elena; Ravelli, Silvia; Cristel, Giulia; Panzeri, Marta Maria; De Cobelli, Francesco; Del Maschio, Alessandro

    2013-08-01

    To evaluate the feasibility, performance, and cost of a breast cancer screening program aimed at 40-49-year-old women and tailored to their risk profile with supplemental ultrasonography (US) and magnetic resonance (MR) imaging. The institutional review board approved this study, and informed written consent was obtained. A total of 3017 40-49-year-old women were invited to participate. The screening program was tailored to lifetime risk (Gail test) and mammographic density (according to Breast Imaging Reporting and Data Systems [BI-RADS] criteria) with supplemental US or MR imaging and bilateral two-view microdose mammography. The indicators suggested by European guidelines, US incremental cancer detection rate (CDR), and estimated costs were evaluated. A total of 1666 women (67.5% participation rate) were recruited. The average lifetime risk of breast cancer was 11.6%, and nine women had a high risk of breast cancer; 917 women (55.0%) had a high density score (BI-RADS density category 3 or 4). The average glandular dose for screening examinations was 1.49 mGy. Screening US was performed in 835 study participants (50.1%), mostly due to high breast density (800 of 1666 women [48.0%]). Screening MR imaging was performed in nine women (0.5%) at high risk for breast cancer. Breast cancer was diagnosed in 14 women (8.4 cases per 1000 women). Twelve diagnoses were made with microdose mammography, and two were made with supplemental US in dense breasts (2.4 cases per 1000 women). All patients were submitted for surgery, and 10 underwent breast-conserving surgery. The sentinel lymph node was evaluated in 11 patients, resulting in negative findings in six. Pathologic analysis resulted in the diagnosis of four ductal carcinomas in situ and 10 invasive carcinomas (five at stage I). A tailored breast cancer screening program in 40-49-year-old women yielded a greater-than-expected number of cancers, most of which were low-stage disease.

  16. Distributed and self-adaptive vehicle speed estimation in the composite braking case for four-wheel drive hybrid electric car

    Science.gov (United States)

    Zhao, Z.-G.; Zhou, L.-J.; Zhang, J.-T.; Zhu, Q.; Hedrick, J.-K.

    2017-05-01

    Considering the controllability and observability of the braking torques of the hub motor, Integrated Starter Generator (ISG), and hydraulic brake for four-wheel drive (4WD) hybrid electric cars, a distributed and self-adaptive vehicle speed estimation algorithm for different braking situations has been proposed by fully utilising the Electronic Stability Program (ESP) sensor signals and multiple powersource signals. Firstly, the simulation platform of a 4WD hybrid electric car was established, which integrates an electronic-hydraulic composited braking system model and its control strategy, a nonlinear seven degrees-of-freedom vehicle dynamics model, and the Burckhardt tyre model. Secondly, combining the braking torque signals with the ESP signals, self-adaptive unscented Kalman sub-filter and main-filter adaptable to the observation noise were, respectively, designed. Thirdly, the fusion rules for the sub-filters and master filter were proposed herein, and the estimation results were compared with the simulated value of a real vehicle speed. Finally, based on the hardware in-the-loop platform and by picking up the regenerative motor torque signals and wheel cylinder pressure signals, the proposed speed estimation algorithm was tested under the case of moderate braking on the highly adhesive road, and the case of Antilock Braking System (ABS) action on the slippery road, as well as the case of ABS action on the icy road. Test results show that the presented vehicle speed estimation algorithm has not only a high precision but also a strong adaptability in the composite braking case.

  17. Bimetal cup hydroforming of Al/St and Cu/St composites: Adaptive finite element analysis and experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Hashemi, Abbas; Gollo, Mohammad Hoseinpour [Shahid Rajaee Teacher Training University, Tehran (Iran, Islamic Republic of); Seyedkashi, S. M. [University of Birjand, Birjand (Iran, Islamic Republic of)

    2016-05-15

    An adaptive Finite element analysis (FEA) was proposed in this paper for the industrial design of bimetal conical-cylindrical cup hydroforming. Forming circumstances for the perfect and imperfect parts were concluded through adaptive FEA using the ANSYS parametric design language. Effective parameters, including pressure loading path, layer placement order, and thickness ratio, were investigated for hydroforming of Al/St and Cu/St composite sheets. Experimental tests were implemented to validate adaptive finite element results. Rupture failure upon the pressure path occurred on the contact area between the blank and punch tip radius at low pressures and on the transition area of the conical-cylindrical portion at high pressures. The proposed method is applicable for any cylindrical, conical, or cylindrical/conical shapes with different materials and dimensions. Therefore, this method is beneficial as a practical design tool for engineers and researchers working in the process design of hydroformed shell products.

  18. Homeoviscous adaptation and the regulation of membrane lipids

    DEFF Research Database (Denmark)

    Ernst, Robert; Ejsing, Christer S; Antonny, Bruno

    2016-01-01

    Biological membranes are complex and dynamic assemblies of lipids and proteins. Poikilothermic organisms including bacteria, fungi, reptiles, and fish do not control their body temperature and must adapt their membrane lipid composition in order to maintain membrane fluidity in the cold. This ada......Biological membranes are complex and dynamic assemblies of lipids and proteins. Poikilothermic organisms including bacteria, fungi, reptiles, and fish do not control their body temperature and must adapt their membrane lipid composition in order to maintain membrane fluidity in the cold....... This adaptive response was termed homeoviscous adaptation and has been frequently studied with a specific focus on the acyl chain composition of membrane lipids. Massspectrometry-based lipidomics can nowadays provide more comprehensive insights into the complexity of lipid remodeling during adaptive responses...... such as neurons maintain unique lipid compositions with specific physicochemical properties. To date little is known about the sensory mechanisms regulating the acyl chain profile in such specialized cells or during adaptive responses. Here we summarize our current understanding of lipid metabolic networks...

  19. Adaptation of model proteins from cold to hot environments involves continuous and small adjustments of average parameters related to amino acid composition.

    Science.gov (United States)

    De Vendittis, Emmanuele; Castellano, Immacolata; Cotugno, Roberta; Ruocco, Maria Rosaria; Raimo, Gennaro; Masullo, Mariorosario

    2008-01-07

    The growth temperature adaptation of six model proteins has been studied in 42 microorganisms belonging to eubacterial and archaeal kingdoms, covering optimum growth temperatures from 7 to 103 degrees C. The selected proteins include three elongation factors involved in translation, the enzymes glyceraldehyde-3-phosphate dehydrogenase and superoxide dismutase, the cell division protein FtsZ. The common strategy of protein adaptation from cold to hot environments implies the occurrence of small changes in the amino acid composition, without altering the overall structure of the macromolecule. These continuous adjustments were investigated through parameters related to the amino acid composition of each protein. The average value per residue of mass, volume and accessible surface area allowed an evaluation of the usage of bulky residues, whereas the average hydrophobicity reflected that of hydrophobic residues. The specific proportion of bulky and hydrophobic residues in each protein almost linearly increased with the temperature of the host microorganism. This finding agrees with the structural and functional properties exhibited by proteins in differently adapted sources, thus explaining the great compactness or the high flexibility exhibited by (hyper)thermophilic or psychrophilic proteins, respectively. Indeed, heat-adapted proteins incline toward the usage of heavier-size and more hydrophobic residues with respect to mesophiles, whereas the cold-adapted macromolecules show the opposite behavior with a certain preference for smaller-size and less hydrophobic residues. An investigation on the different increase of bulky residues along with the growth temperature observed in the six model proteins suggests the relevance of the possible different role and/or structure organization played by protein domains. The significance of the linear correlations between growth temperature and parameters related to the amino acid composition improved when the analysis was

  20. Microdose flare-up vs. flexible-multidose GnRH antagonist protocols for poor responder patients who underwent ICSI.

    Science.gov (United States)

    Esinler, I

    2014-01-01

    To compare the performance of microdose flare-up (MF) and flexible-multidose gonadotropin-releasing hormone (GnRH) antagonist protocols in poor responder patients who underwent intracytoplasmic sperm injection (ICSI). One hundred and 12 consecutive patients (217 cycles) suspected to have poor ovarian response were enrolled. Group 1 (MF GnRH agonist group) constituted 64 patients (135 cycles) who underwent MF GnRH agonist protocol. Group 2 (flexible-multidose GnRH antagonist group) constituted 48 patients (82 cycles) who underwent flexible-multidose GnRH antagonist protocol. The duration of stimulation (d) (11.5 +/- 2.1 vs. 10.4 +/- 2.7, p or = seven blastomeres and < 10% fragmentation at day 3 (35.9% vs. 65.1%, p < 0.05) were significantly lower in Group 1 when compared to Group 2. The number of embryos transferred (2.2 +/- 1.3 vs. 2.4 +/- 0.9), the clinical pregnancy per embryo transfer (16.3% vs. 25.8%), and the implantation rate (8.6% vs. 12.2%) were comparable between groups. Although the flexible-multidose GnRH antagonist protocol produced better oocyte and embryo parameters, the clinical pregnancy rate and the implantation rates were comparable between the flexible-multidose GnRH antagonist and MF protocols in poor responder patients.

  1. Overcoming bioanalytical challenges in an Onglyza(®) intravenous [(14)C]microdose absolute bioavailability study with accelerator MS.

    Science.gov (United States)

    Xu, Xiaohui Sophia; Dueker, Stephen R; Christopher, Lisa J; Lohstroh, Pete N; Keung, Chi Fung Anther; Cao, Kai Kevin; Bonacorsi, Samuel J; Cojocaru, Laura; Shen, Jim X; Humphreys, W Griffith; Stouffer, Bruce; Arnold, Mark E

    2012-08-01

    An absolute bioavailability study that utilized an intravenous [(14)C]microdose was conducted for saxagliptin (Onglyza(®)), a marketed drug product for the treatment of Type 2 diabetes mellitus. Concentrations of [(14)C]saxagliptin were determined by accelerator MS (AMS) after protein precipitation, chromatographic separation by UPLC and analyte fraction collection. A series of investigative experiments were conducted to maximize the release of the drug from high-affinity receptors and nonspecific adsorption, and to determine a suitable quantitation range. A technique-appropriate validation demonstrated the accuracy, precision, specificity, stability and recovery of the AMS methodology across the concentration range of 0.025 to 15.0 dpm/ml (disintegration per minute per milliliter), the equivalent of 1.91-1144 pg/ml. Based on the study sample analysis, the mean absolute bioavailability of saxagliptin was 50% in the eight subjects with a CV of 6.6%. Incurred sample reanalysis data fell well within acceptable limits. This study demonstrated that the optimized sample pretreatment and chromatographic separation procedures were critical for the successful implementation of an UPLC plus AMS method for [(14)C]saxagliptin. The use of multiple-point standards are useful, particularly during method development and validation, to evaluate and correct for concentration-dependent recovery, if observed, and to monitor and control process loss and operational variations.

  2. Microdose 14C urea breath test for the diagnosis of Helicobacter pylori: a survey in Iranian population

    Directory of Open Access Journals (Sweden)

    Reza Dowlatabadi Bazaz

    2005-01-01

    Full Text Available The carbon -14 urea breath test (UBTis a non-invasive and simple method for the diagnosis of Helicobacter pylori infection. Attempts have been made to use lower doses of 14C-urea in the UBT in order to reduce the radiation risk of the test. The aim of this study was to assess the accuracy of a microdose (1 µCi [37 KBq] 14C-UBT in Iranian population for validation of its diagnostic accuracy against gold standard methods. Eighty and two patients were subjected to upper gastrointestinal endoscopy as well as 14C-UBT in one week. Rapid urease test and histological examinations were used as gold standard. Breath samples were collected 10, 20 and 30 minute after ingestion of 1 µCi of 14C- urea solution and their activities were measured using a scintillation counter and expressed as counts per minute (cpm and disintegration per minute (dpm. Good agreement was observed between the 14C-UBT and gold standard for samples which were collected 20 minutes after 14C-urea administration. The 14CUBT showed 100% sensitivity, 95% specificity, 95.45% positive predictive value, 100% negative predictive value and 97.50% accuracy. The results of this study showed good concordance between the 14C-UBT and invasive methods.

  3. Absolute oral bioavailability and pharmacokinetics of canagliflozin: A microdose study in healthy participants.

    Science.gov (United States)

    Devineni, Damayanthi; Murphy, Joseph; Wang, Shean-Sheng; Stieltjes, Hans; Rothenberg, Paul; Scheers, Ellen; Mamidi, Rao N V S

    2015-07-01

    Absolute oral bioavailability of canagliflozin was assessed by simultaneous oral administration with intravenous [(14) C]-canagliflozin microdose infusion in nine healthy men. Pharmacokinetics of canagliflozin, [(14) C]-canagliflozin, and total radioactivity, and safety and tolerability were assessed at prespecified timepoints. On day 1, single-dose oral canagliflozin (300 mg) followed 105 minutes later by intravenous [(14) C]-canagliflozin (10 µg, 200 nCi) was administered. After oral administration, the mean (SD) Cmax of canagliflozin was 2504 (482) ng/mL at 1.5 hours, AUC∞ 17,375 (3555) ng.h/mL, and t1/2 11.6 (0.70) hours. After intravenous administration, the mean (SD) Cmax of unchanged [(14) C]-canagliflozin was 17,605 (6901) ng/mL, AUC∞ 27,100 (10,778) ng.h/mL, Vdss 83.5 (29.2) L, Vdz 119 (41.6) L, and CL 12.2 (3.79) L/h. Unchanged [(14) C]-canagliflozin and metabolites accounted for about 57% and 43% of the plasma total [(14) C] radioactivity AUC∞ , respectively. For total [(14) C] radioactivity, the mean (SD) Cmax was 15,981 (2721) ng-eq/mL, and AUC∞ 53,755 (15,587) ng-eq.h/mL. Renal (34.5% in urine) and biliary (34.1% in feces) excretions were the major elimination pathways for total [(14) C] radioactivity. The absolute oral bioavailability of canagliflozin was 65% (90% confidence interval: 55.41; 76.07). Overall, oral canagliflozin 300 mg coadministered with intravenous [(14) C]-canagliflozin (10 µg) was generally well-tolerated in healthy men, with no treatment-emergent adverse events. © 2014, The American College of Clinical Pharmacology.

  4. Validation of a liquid chromatography-triple quadrupole mass spectrometric method for the determination of 5-nitro-5'-hydroxy-indirubin-3'-oxime (AGM-130) in human plasma and its application to microdose clinical trial.

    Science.gov (United States)

    Park, Min-Ho; Lee, Yun Young; Cho, Kyung Hee; La, Sookie; Lee, Hee Joo; Yim, Dong-Seok; Ban, Sooho; Park, Moon-Young; Kim, Yong-Chul; Kim, Yoon-Gyoon; Shin, Young G

    2016-03-01

    A liquid chromatography-triple quadrupole mass spectrometric (LC-MS/MS) method was developed and validated for the determination of 5-nitro-5'-hydroxy-indirubin-3'-oxime (AGM-130) in human plasma to support a microdose clinical trial. The method consisted of a liquid-liquid extraction for sample preparation and LC-MS/MS analysis in the positive ion mode using TurboIonSpray(TM) for analysis. d3 -AGM-130 was used as the internal standard. A linear regression (weighted 1/concentration) was used to fit calibration curves over the concentration range of 10-2000 pg/mL for AGM-130. There were no endogenous interference components in the blank human plasma tested. The accuracy at the lower limit of quantitation was 96.6% with a precision (coefficient of variation, CV) of 4.4%. For quality control samples at 30, 160 and 1600 pg/mL, the between run CV was ≤5.0 %. Between-run accuracy ranged from 98.1 to 101.0%. AGM-130 was stable in 50% acetonitrile for 168 h at 4°C and 6 h at room temperature. AGM-130 was also stable in human plasma at room temperature for 6 h and through three freeze-thaw cycles. The variability of selected samples for the incurred sample reanalysis was ≤12.7% when compared with the original sample concentrations. This validated LC-MS/MS method for determination of AGM-130 was used to support a phase 0 microdose clinical trial. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Toward a Theory of Adaptive Transfer: Expanding Disciplinary Discussions of "Transfer" in Second-Language Writing and Composition Studies

    Science.gov (United States)

    DePalma, Michael-John; Ringer, Jeffrey M.

    2011-01-01

    In this paper, we argue that discussions of transfer in L2 writing and composition studies have focused primarily on the reuse of past learning and thus have not adequately accounted for the adaptation of learned writing knowledge in unfamiliar situations. In an effort to expand disciplinary discussions of transfer in L2 writing and composition…

  6. Adaptive, tolerant and efficient composite structures

    CERN Document Server

    Sinapius, Michael

    2013-01-01

    Polymer composites offer the possibility for functional integration since the material is produced simultaneously with the product. The efficiency of composite structures raises through functional integration. The specific production processes of composites offer the possibility to improve and to integrate more functions thus making the structure more valuable. Passive functions can be improved by combination of different materials from nano to macro scale, i.e. strength, toughness, bearing strength, compression after impact properties or production tolerances.  Active functions can be realized by smart materials, i.e. morphing, active vibration control, active structure acoustic control or structure health monitoring. The basis is a comprehensive understanding of materials, simulation, design methods, production technologies and adaptronics. These disciplines together deliver advanced lightweight solutions for applications ranging from mechanical engineering to vehicles, airframe and space structures along ...

  7. How Harmful are Adaptation Restrictions

    OpenAIRE

    Bruin, de, K.C.; Dellink, R.B.

    2009-01-01

    The dominant assumption in economic models of climate policy remains that adaptation will be implemented in an optimal manner. There are, however, several reasons why optimal levels of adaptation may not be attainable. This paper investigates the effects of suboptimal levels of adaptation, i.e. adaptation restrictions, on the composition and level of climate change costs and on welfare. Several adaptation restrictions are identified and then simulated in a revised DICE model, extended with ad...

  8. A novel discrete adaptive sliding-mode-like control method for ionic polymer–metal composite manipulators

    International Nuclear Information System (INIS)

    Sun, Zhiyong; Hao, Lina; Liu, Liqun; Chen, Wenlin; Li, Zhi

    2013-01-01

    Ionic polymer–metal composite (IPMC), also called artificial muscle, is an EAP material which can generate a relatively large deformation with a low driving voltage (generally less than 5 V). Like other EAP materials, IPMC possesses strong nonlinear properties, which can be described as a hybrid of back-relaxation (BR) and hysteresis characteristics, which also vary with water content, environmental temperature and even the usage consumption. Nowadays, many control approaches have been developed to tune the IPMC actuators, among which adaptive methods show a particular striking performance. To deal with IPMCs’ nonlinear problem, this paper represents a robust discrete adaptive inverse (AI) control approach, which employs an on-line identification technique based on the BR operator and Prandtl–Ishlinskii (PI) hysteresis operator hybrid model estimation method. Here the newly formed control approach is called discrete adaptive sliding-mode-like control (DASMLC) due to the similarity of its design method to that of a sliding mode controller. The weighted least mean squares (WLMS) identification method was employed to estimate the hybrid IPMC model because of its advantage of insensitivity to environmental noise. Experiments with the DASMLC approach and a conventional PID controller were carried out to compare and demonstrate the proposed controller’s better performance. (paper)

  9. A New Adaptive Response Surface Model for Reliability Analysis of 2.5D C/SiC Composite Turbine Blade

    Science.gov (United States)

    Chang, Yaning; Sun, Zhigang; Sun, Weiyi; Song, Yingdong

    2017-11-01

    In order to calculate the failure probability of complex structures such as a 2.5D/SiC composites turbine blade and improve the structure safety, a new adaptive model of Response Surface (RS) analysis has been developed in this paper, which can improve the computational efficiency of structural failure problem while ensure the accuracy. The Gaussian Process Regression (GPR) theory was used to establish the RS and reconstruct the performance function of structure. And, an Adaptive Latin hypercube Sampling (ALHS) strategy was adopted in the process of establishing and correcting the RS. Finally the Direct Simulation Monte Carlo(DSMC)was utilized to calculate the failure probability of the performance function replacing the complex structure. Two numerical examples were calculated to validate the accuracy and computational efficiency of the proposed method. Additionally the finite element stress analysis results of 2.5D C/SiC composite turbine blade were used to structural reliability analysis by the proposed method. The approach in this paper provides a new way to evaluate the risk of the complex structures.

  10. Adaptive evolution in ecological communities.

    Directory of Open Access Journals (Sweden)

    Martin M Turcotte

    Full Text Available Understanding how natural selection drives evolution is a key challenge in evolutionary biology. Most studies of adaptation focus on how a single environmental factor, such as increased temperature, affects evolution within a single species. The biological relevance of these experiments is limited because nature is infinitely more complex. Most species are embedded within communities containing many species that interact with one another and the physical environment. To understand the evolutionary significance of such ecological complexity, experiments must test the evolutionary impact of interactions among multiple species during adaptation. Here we highlight an experiment that manipulates species composition and tracks evolutionary responses within each species, while testing for the mechanisms by which species interact and adapt to their environment. We also discuss limitations of previous studies of adaptive evolution and emphasize how an experimental evolution approach can circumvent such shortcomings. Understanding how community composition acts as a selective force will improve our ability to predict how species adapt to natural and human-induced environmental change.

  11. Executive Function and Adaptive Behavior in Muenke Syndrome.

    Science.gov (United States)

    Yarnell, Colin M P; Addissie, Yonit A; Hadley, Donald W; Guillen Sacoto, Maria J; Agochukwu, Nneamaka B; Hart, Rachel A; Wiggs, Edythe A; Platte, Petra; Paelecke, Yvonne; Collmann, Hartmut; Schweitzer, Tilmann; Kruszka, Paul; Muenke, Maximilian

    2015-08-01

    To investigate executive function and adaptive behavior in individuals with Muenke syndrome using validated instruments with a normative population and unaffected siblings as controls. Participants in this cross-sectional study included individuals with Muenke syndrome (P250R mutation in FGFR3) and their mutation-negative siblings. Participants completed validated assessments of executive functioning (Behavior Rating Inventory of Executive Function [BRIEF]) and adaptive behavior skills (Adaptive Behavior Assessment System, Second Edition [ABAS-II]). Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years). For the General Executive Composite scale of the BRIEF, 32.1% of the cohort had scores greater than +1.5 SD, signifying potential clinical significance. For the General Adaptive Composite of the ABAS-II, 28.2% of affected individuals scored in the 3rd-8th percentile of the normative population, and 56.4% were below the average category (General Executive Composite and the ABAS-II General Adaptive Composite. Individuals with Muenke syndrome are at an increased risk for developing adaptive and executive function behavioral changes compared with a normative population and unaffected siblings. Published by Elsevier Inc.

  12. Evaluation of internal adaptation of Class V resin composite restorations using three techniques of polymerization

    Directory of Open Access Journals (Sweden)

    José Carlos Pereira

    2007-02-01

    Full Text Available OBJECTIVE: The purpose of this in vitro study was to evaluate the internal adaptation of Class V composite restorations to the cavity walls using three different techniques of polymerization. METHODS: Standard cavities were prepared on the buccal and lingual surfaces of 24 extracted human third molars with margins located above and below the cementoenamel junction. Restorations were placed in one increment using two restorative systems: 3M Filtek A110/ Single Bond (M and 3M Filtek Z250/ Single Bond (H in the same tooth, randomly in the buccal and lingual surfaces. Resin composites were polymerized using three techniques: Group 1 - Conventional (60 s - 600 mW/cm²; Group 2 - Soft-start (20 s - 200 mW/cm² , 40 s - 600 mW/cm²; Group 3 - Pulse Activation (3 s - 200 mW/cm², 3-min hiatus, 57 s - 600 mW/cm². Buccolingual sections were polished, impressions taken and replicated. Specimens were assessed under scanning electron microscopy up to X1000 magnification. Scores were given for presence or absence of gaps (0 - no gap; 1 - gap in one wall; 2 - gap in two walls; 3 - gap in three walls. RESULTS: The mean scores of the groups were (±SD were: G1M-3.0 (± 0.0; G2M-2.43 (± 0.8; G3M- 1.71 (± 0.9; G1H- 2.14 (± 1.2; G2H- 2.00 (± 0.8; G3H- 1.67 (± 1.1. Data were analyzed using Kruskal-Wallis and Dunnet's tests. No statistically significant difference (p>0.05 was found among groups. Gaps were observed in all groups. CONCLUSIONS: The photocuring technique and the type of resin composite had no influence on the internal adaptation of the material to the cavity walls. A positive effect was observed when the slow polymerization techniques were used.

  13. Effect of dual-cure composite resin as restorative material on marginal adaptation of class 2 restorations.

    Science.gov (United States)

    Bortolotto, Tissiana; Melian, Karla; Krejci, Ivo

    2013-10-01

    The present study attempted to find a simple direct adhesive restorative technique for the restoration of Class 2 cavities. A self-etch adhesive system with a dual-cured core buildup composite resin (paste 1 + paste 2) was evaluated in its ability to restore proximo-occlusal cavities with margins located on enamel and dentin. The groups were: A, cavity filling (cf) with paste 1 (light-curing component) by using a layering technique; B, cf by mixing both pastes, bulk insertion, and dual curing; and C, cf by mixing both pastes, bulk insertion, and chemical curing. Two control groups (D, negative, bulk; and E, positive, layering technique) were included by restoring cavities with a classic three-step etch-and-rinse adhesive and a universal restorative composite resin. SEM margin analysis was performed before and after thermomechanical loading in a chewing simulator. Percentages (mean ± SD) of "continuous margins" were improved by applying the material in bulk and letting it self cure (54 ± 6) or dual cure (59 ± 9), and no significant differences were observed between these two groups and the positive control (44 ± 19). The present study showed that the dual-cured composite resin tested has the potential to be used as bulk filling material for Class 2 restorations. When used as filling materials, dual-cure composite resins placed in bulk can provide marginal adaptation similar to light-cured composites applied with a complex stratification technique.

  14. Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Versus GnRH Antagonist Protocols in Poor Ovarian Responders Undergoing Intracytoplasmic Sperm Injection.

    Science.gov (United States)

    Boza, Aysen; Cakar, Erbil; Boza, Barıs; Api, Murat; Kayatas, Semra; Sofuoglu, Kenan

    2016-01-01

    Microdose flare-up GnRH agonist and GnRH antagonist have become more popular in the management of poor ovarian responders (POR) in recent years; however, the optimal protocol for POR patients undergoing in vitro fertilization has still been a challenge. In this observational study design, two hundred forty four poor ovarian responders were retrospectively evaluated for their response to GnRH agonist protocol (group-1, n=135) or GnRH antagonist protocol (group-2, n=109). Clinical pregnancy rate was the primary end point and was compared between the groups. Student t-test, Mann Whitney U test and χ (2)-test were used to compare the groups. The pmicrodose flare-up protocol has favorable outcomes with respect to the number of oocytes retrieved and implantation rate; nevertheless, the clinical pregnancy rate was found to be similar in comparison to GnRH antagonist protocol in poor ovarian responders. GnRH antagonist protocol appears to be promising with significantly lower gonadotropin requirement and lower treatment cost in poor ovarian responders.

  15. [Change in the lipid composition of the inner mitochondrial membranes in rat organs during adaptation to heat].

    Science.gov (United States)

    Zubareva, E V; Seferova, R I; Denisova, N A

    1991-01-01

    Under conditions of adaptation to heating lipid composition in mitochondrial membranes of rat inner tissues was altered as follows: an increase in relative concentration of plasmalogenous forms of phospholipids (kidney, heart) and in content of saturated fatty acids (liver tissue), a decrease in the index of fatty acids unsaturation and in the ratio of fatty acids omega-3/omega-6. The alterations observed enabled the membranes to keep sufficient amount of liquidity essential for functional activity of mitochondria in heating.

  16. Scanning electron microscopy analysis of marginal adaptation of composite resines to enamel after using of standard and gradual photopolimerization

    Directory of Open Access Journals (Sweden)

    Dačić Stefan

    2014-01-01

    Full Text Available Introduction. Bonding between composite and hard dental tissue is most commonly assessed by measuring bonding strength or absence of marginal gap along the restoration interface. Marginal index (MI is a significant indicator of the efficiency of the bond between material and dental tissue because it also shows the values of width and length of marginal gap. Objective. The aim of this investigation was to estimate quantitative and qualitative features of the bond between composite resin and enamel and to determine the values of MI in enamel after application of two techniques of photopolymerization with two composite systems. Methods. Forty Class V cavities on extracted teeth were prepared and restored for scanning electron microscope (SEM analysis of composite bonding to enamel. Adhesion to enamel was achieved by Adper Single Bond 2 - ASB (3M ESPE, or by Adper Easy One - AEO (3M ESPE. Photopolymerization of Filtek Ultimate - FU (3M ESPE was performed using constant halogen light (HIP or soft start program (SOF. Results. Quantitative and qualitative analysis, showed better mikromorphological bonding with SOF photopolymerization and ASB/FU composite system. Differences in MI between different photopolymerization techniques (HIP: 0.6707; SOF: 0.2395 were statistically significant (p<0.001, as well as differences between the composite systems (ASB/FU: 0.0470; AEO/ FU: 0.8651 (p<0.001 by two-way ANOVA test. Conclusion. Better marginal adaptation of composite to enamel was obtained with SOF photopolymerization in both composite systems.

  17. EDITORIAL Smart materials, multifunctional composites, and morphing structures: selected papers from the 20th International Conference on Adaptive Structures and Technologies (ICAST 2009) Smart materials, multifunctional composites, and morphing structures: selected papers from the 20th International Conference on Adaptive Structures and Technologies (ICAST 2009)

    Science.gov (United States)

    Liao, Wei-Hsin

    2010-12-01

    The 20th International Conference on Adaptive Structures and Technologies (ICAST) was held on 20-22 October 2009 in Hong Kong. This special section of Smart Materials and Structures is derived from the research papers presented at the conference. Of the 106 papers presented at the conference, 11 papers were reviewed and accepted for this special section, following the regular review procedures of the journal. This special section is focused on smart materials, multifunctional composites, and applications on morphing structures. Smart materials. Smart materials are the foundation of adaptive structures and intelligent systems. The development of new materials will lead to significant improvement in various applications. Three articles are focused on the fabrication of new materials and investigation of their behaviors: Barium strontium zirconate titanate ((Ba1-xSrx)(ZrxTi1-x)O3; BSZT, x = 0.25 and 0.75) ceramics with a highly crystalline structure were fabricated using the combustion technique. The microstructure of BSZT powders exhibited an almost-spherical morphology and had a porous agglomerated form. Polyaniline (PANI)/clay nanoparticles with unique core-shell structure were synthesized via Pickering emulsion polymerization. By dispersing PANI/clay nanoparticles in silicone oil, the ER fluid was made. Magnetic field effects were investigated on the deposition rate and surface morphology of chromium nitride coatings deposited by magnetron sputtering for superior hardness, excellent wear and oxidation resistance. The surface morphology of chromium nitride films was also examined by a scanning electron microscope (SEM). Multifunctional composites. Composites are made from two or more constituent materials so they can combine the best properties of different materials. Five papers deal with fabrication, testing, and modeling of various multifunctional composites: A new active structural fiber (ASF) was fabricated by coating a single carbon fiber with a concentric

  18. Functional regulation of Pb-Ti/MoS_2 composite coatings for environmentally adaptive solid lubrication

    International Nuclear Information System (INIS)

    Ren, Siming; Li, Hao; Cui, Mingjun; Wang, Liping; Pu, Jibin

    2017-01-01

    Highlights: • Co-doped Pb-Ti/MoS_2 composite coatings were successfully fabricated by unbalanced magnetron sputtering system. • Co-doped Pb-Ti/MoS_2 composite coatings showed lower friction coefficient and longer wear life in both humid and vacuum environments than that of single-doped ones. • The wear behaviours of Pb-Ti/MoS_2 composite coatings with the increase of Pb content is in accordance with the variation in H/E ratio that higher H/E is corresponding to the lower wear rate of coating. - Abstract: The lubrication of molybdenum disulfide coatings has commonly been limited by the application environments, for instance, the crystal MoS_2 are easily affected by water to form MoO_3 that causes a higher friction coefficient and short lifetime. Therefore, to improve the tribolgical performance of MoS_2 in high humidity condition, the co-doped Pb-Ti/MoS_2 composite coatings are deposited by unbalanced magnetron sputtering system. The design of the co-doping elements in MoS_2-based coatings can not only maintain the characteristic of low humidity-sensitivity as the Ti/MoS_2 coating but also improve the mechanical properties and tribological performance of coatings as a comparison with single-doped ones. Moreover, the ultra-low friction coefficient with a minimum value of 0.006 under the vacuum condition is achieved for Pb-Ti/MoS_2 composite coating containing about 4.6 at.% Pb, depending on the densification structure of coating. Intriguingly, the wear behaviours of Pb-Ti/MoS_2 composite coatings are in accordance with the variation in H/E (hardness to the elastic modulus) ratio that the coating with higher H/E exhibits lower wear rate. These results demonstrate that the lubricating properties of MoS_2 coatings in both humid environment and vacuum condition can be achieved through the Pb and Ti co-doped, which is of great significant for developing MoS_2 coatings as the environmentally adaptive lubricants.

  19. A study of an adaptive replication framework for orchestrated composite web services.

    Science.gov (United States)

    Mohamed, Marwa F; Elyamany, Hany F; Nassar, Hamed M

    2013-01-01

    Replication is considered one of the most important techniques to improve the Quality of Services (QoS) of published Web Services. It has achieved impressive success in managing resource sharing and usage in order to moderate the energy consumed in IT environments. For a robust and successful replication process, attention should be paid to suitable time as well as the constraints and capabilities in which the process runs. The replication process is time-consuming since outsourcing some new replicas into other hosts is lengthy. Furthermore, nowadays, most of the business processes that might be implemented over the Web are composed of multiple Web services working together in two main styles: Orchestration and Choreography. Accomplishing a replication over such business processes is another challenge due to the complexity and flexibility involved. In this paper, we present an adaptive replication framework for regular and orchestrated composite Web services. The suggested framework includes a number of components for detecting unexpected and unhappy events that might occur when consuming the original published web services including failure or overloading. It also includes a specific replication controller to manage the replication process and select the best host that would encapsulate a new replica. In addition, it includes a component for predicting the incoming load in order to decrease the time needed for outsourcing new replicas, enhancing the performance greatly. A simulation environment has been created to measure the performance of the suggested framework. The results indicate that adaptive replication with prediction scenario is the best option for enhancing the performance of the replication process in an online business environment.

  20. Composite adaptive control of belt polishing force for aero-engine blade

    Science.gov (United States)

    Zhsao, Pengbing; Shi, Yaoyao

    2013-09-01

    The existing methods for blade polishing mainly focus on robot polishing and manual grinding. Due to the difficulty in high-precision control of the polishing force, the blade surface precision is very low in robot polishing, in particular, quality of the inlet and exhaust edges can not satisfy the processing requirements. Manual grinding has low efficiency, high labor intensity and unstable processing quality, moreover, the polished surface is vulnerable to burn, and the surface precision and integrity are difficult to ensure. In order to further improve the profile accuracy and surface quality, a pneumatic flexible polishing force-exerting mechanism is designed and a dual-mode switching composite adaptive control(DSCAC) strategy is proposed, which combines Bang-Bang control and model reference adaptive control based on fuzzy neural network(MRACFNN) together. By the mode decision-making mechanism, Bang-Bang control is used to track the control command signal quickly when the actual polishing force is far away from the target value, and MRACFNN is utilized in smaller error ranges to improve the system robustness and control precision. Based on the mathematical model of the force-exerting mechanism, simulation analysis is implemented on DSCAC. Simulation results show that the output polishing force can better track the given signal. Finally, the blade polishing experiments are carried out on the designed polishing equipment. Experimental results show that DSCAC can effectively mitigate the influence of gas compressibility, valve dead-time effect, valve nonlinear flow, cylinder friction, measurement noise and other interference on the control precision of polishing force, which has high control precision, strong robustness, strong anti-interference ability and other advantages compared with MRACFNN. The proposed research achieves high-precision control of the polishing force, effectively improves the blade machining precision and surface consistency, and

  1. Pharmacokinetic and pharmacogenomic profiles of telmisartan after the oral microdose and therapeutic dose.

    Science.gov (United States)

    Ieiri, Ichiro; Nishimura, Chisa; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Chiyoda, Takeshi; Hirota, Tekeshi; Irie, Shin; Shimizu, Hitoshi; Noguchi, Takanori; Yoshida, Kenji; Sugiyama, Yuichi

    2011-08-01

    In this study, we evaluated (a) the contribution of SLCO1B3 and UGT1A polymorphisms to the pharmacokinetics of telmisartan in two forms, a microdose (MD) and a therapeutic dose (TD); (b) linkage disequilibrium (LD) between UGT1A1 and UGT1A3; and (c) linearity in the pharmacokinetics of telmisartan between the two forms. Telmisartan was orally administered at MD condition (100 μg), and then at TD condition (80 mg) to 33 healthy volunteers whose genotypes were prescreened by DMET Plus. Plasma concentrations of telmisartan and its glucuronide were measured by LC-MS/MS, and population pharmacokinetic analysis was performed. No obvious effect of SLCO1B3 polymorphisms (334T>G, 699G>A, and rs11045585) on the pharmacokinetics of telmisartan was observed. The strong LD between UGT1A1*6 and UGT1A3*4a, and between UGT1A1*28 and UGT1A3*2a were observed. After both MD and TD administration, the mean area under the curve0-24 (±standard deviation) of telmisartan was significantly lower and higher in individuals with the UGT1A3*2a (TD, 1701±970 ng hr/ml; MD, 978±537 pg hr/ml) and *4a variants (TD, 5340±1168; MD, 3145±1093), respectively, compared with those in individuals with UGT1A3*1/*1 (TD, 2969±1456; MD, 1669±726). These results were quantitatively confirmed by population pharmacokinetic analysis. Nonlinearity of the dose-exposure relationship was observed between the MD and TD. The haplotypes of UGT1A3 significantly influenced pharmacokinetics of telmisartan and a strong LD between UGT1A1 genotype and UGT1A3 haplotype was observed. These findings are potentially of pharmacological and toxicological importance to the development and clinical use of drugs.

  2. Towing Tank and Flume Testing of Passively Adaptive Composite Tidal Turbine Blades: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Murray, Robynne [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ordonez-Sanchez, Stephanie [University of Strathclyde; Porter, Kate E. [University of Strathclyde; Johnstone, Cameron M. [University of Strathclyde; Doman, Darrel A. [Dalhousie University; Pegg, Michael J. [Dalhousie University

    2017-09-28

    Composite tidal turbine blades with bend-twist (BT) coupled layups allow the blade to self-adapt to local site conditions by passively twisting. Passive feathering has the potential to increase annual energy production and shed thrust loads and power under extreme tidal flows. Decreased hydrodynamic thrust and power during extreme conditions meann that the turbine support structure, generator, and other components can be sized more appropriately, resulting in a higher utilization factor and increased cost effectiveness. This paper presents new experimental data for a small-scale turbine with BT composite blades. The research team tested the turbine in the Kelvin Hydrodynamics Laboratory towing tank at the University of Strathclyde in Glasgow, United Kingdom, and in the recirculating current flume at the l Institut Francais de Recherche pour l Exploitation de la Mer Centre in Boulogne-sur-Mer, France. Tests were also performed on rigid aluminum blades with identical geometry, which yielded baseline test sets for comparison. The results from both facilities agreed closely, supporting the hypothesis that increased blade flexibility can induce load reductions. Under the most extreme conditions tested the turbine with BT blades had up to 11 percent lower peak thrust loads and a 15 percent reduction in peak power compared to the turbine with rigid blades. The load reductions varied as a function of turbine rotational velocity and ambient flow velocity.

  3. Consumable core for manufacture of composite articles and related method

    Science.gov (United States)

    Taxacher, Glenn Curtis; de Diego, Peter; Gray, Paul Edward; Monaghan, Philip Harold

    2017-09-05

    Systems, methods and devices adapted to ease manufacture of composite articles (e.g., ceramic composite articles), particularly composite articles which include a hollow feature are disclosed. In one embodiment, a system includes: a consumable core formed to be disposed within an inner portion of a composite precursor, the consumable core adapted to convert into an infiltrant during a manufacturing process and infiltrate the composite precursor.

  4. Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic-induced toxicity in mice

    Directory of Open Access Journals (Sweden)

    Guha B

    2003-10-01

    Full Text Available Abstract Background Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols. Methods Mice were divided into different sets of control (both positive and negative and treated series (As-intoxicated, As-intoxicated plus drug-fed. Alanine amino transferase (ALT and aspartate amino transferase (AST activities and reduced glutathione (GSH level in liver and blood were analyzed in the different series of mice at six different fixation intervals. Results Both Arsenicum Album-30 and Arsenicum Album-200 ameliorated arsenic-induced toxicity to a considerable extent as compared to various controls. Conclusions The results lend further support to our earlier views that microdoses of potentized Arsenicum Album are capable of combating arsenic intoxication in mice, and thus are strong candidates for possible use in human subjects in arsenic contaminated areas under medical supervision.

  5. How to adapt winemaking practices to modified grape composition under climate change conditions

    Directory of Open Access Journals (Sweden)

    Sylvie Dequin

    2017-05-01

    Full Text Available Aim: In the context of climate change, adaptation of enological practices and implementation of novel techniques are major challenges for winemakers. The potential interventions are linked in particular with the alcohol content and the global acidity of wine. Here, we review current microbiological and technological strategies to overcome such issues. Methods and results: Reducing ethanol concentration poses a number of technical and scientific challenges, in particular looking for specific yeast strains with lower alcohol yield. Several non-genetically modified organism (GMO strains – S. cerevisiae or interspecific hybrids of the Saccharomyces genus – have yet been developed using different strategies, and some of them allow decreasing the final ethanol concentration by up to 1%. Several membrane-based technologies have also been developed not only to reduce the ethanol content of wines but also to increase the acidity and more generally to control the wine pH. New strategies are also proposed to improve the control of winemaking, especially the management of alcoholic fermentation of sugar-rich musts and the control of oxidation during the process. Conclusion: Reducing ethanol of wines  and increasing their acidity are good examples of novel techniques  of interest in the context of climate change. Other strategies are still under study to adapt winemaking practices to changes in grape composition. Significance and impact of the study: [Membrane-based technologies can be used to reduce the ethanol content of wines or to increase the acidity.  Microbiological strategies will also be soon available for winemakers.

  6. Effects of Arachidonic Acid Supplementation on Acute Anabolic Signaling and Chronic Functional Performance and Body Composition Adaptations.

    Directory of Open Access Journals (Sweden)

    Eduardo O De Souza

    Full Text Available The primary purpose of this investigation was to examine the effects of arachidonic acid (ARA supplementation on functional performance and body composition in trained males. In addition, we performed a secondary study looking at molecular responses of ARA supplementation following an acute exercise bout in rodents.Thirty strength-trained males (age: 20.4 ± 2.1 yrs were randomly divided into two groups: ARA or placebo (i.e. CTL. Then, both groups underwent an 8-week, 3-day per week, non-periodized training protocol. Quadriceps muscle thickness, whole-body composition scan (DEXA, muscle strength, and power were assessed at baseline and post-test. In the rodent model, male Wistar rats (~250 g, ~8 weeks old were pre-fed with either ARA or water (CTL for 8 days and were fed the final dose of ARA prior to being acutely strength trained via electrical stimulation on unilateral plantar flexions. A mixed muscle sample was removed from the exercised and non-exercised leg 3 hours post-exercise.Lean body mass (2.9%, p<0.0005, upper-body strength (8.7%, p<0.0001, and peak power (12.7%, p<0.0001 increased only in the ARA group. For the animal trial, GSK-β (Ser9 phosphorylation (p<0.001 independent of exercise and AMPK phosphorylation after exercise (p-AMPK less in ARA, p = 0.041 were different in ARA-fed versus CTL rats.Our findings suggest that ARA supplementation can positively augment strength-training induced adaptations in resistance-trained males. However, chronic studies at the molecular level are required to further elucidate how ARA combined with strength training affect muscle adaptation.

  7. Towards Trustworthy Adaptive Case Management with Dynamic Condition Response Graphs

    DEFF Research Database (Denmark)

    Mukkamala, Raghava Rao; Hildebrandt, Thomas; Slaats, Tijs

    2013-01-01

    We describe how the declarative Dynamic Condition Response (DCR) Graphs process model can be used for trustworthy adaptive case management by leveraging the flexible execution, dynamic composition and adaptation supported by DCR Graphs. The dynamically composed and adapted graphs are verified for...

  8. The Use of rLH, HMG and hCG in Controlled Ovarian Stimulation for Assisted Reproductive Technologies

    Science.gov (United States)

    2012-11-21

    responders involves the use of the microdose flare protocol. This protocol avoids the profound suppression of endogenous LH and FSH in the early...follicular phase normally achieved with long luteal downregulation protocols. Scott and Novat’s initial investigation of the microdose flare found it to...protocol increases live birth rates (113-116). One RCT did not show any benefit to adding either rLH or low-dose rHCG to a microdose flare protocol for

  9. Functional regulation of Pb-Ti/MoS{sub 2} composite coatings for environmentally adaptive solid lubrication

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Siming [Key Laboratory of Marine Materials and Related Technologies, Key Laboratory of Marine Materials and Protective Technologies of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China); University of Chinese Academy of Sciences, Beijing 100039 (China); Li, Hao [Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Cui, Mingjun [Key Laboratory of Marine Materials and Related Technologies, Key Laboratory of Marine Materials and Protective Technologies of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China); University of Chinese Academy of Sciences, Beijing 100039 (China); Wang, Liping, E-mail: wangliping@nimte.ac.cn [Key Laboratory of Marine Materials and Related Technologies, Key Laboratory of Marine Materials and Protective Technologies of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China); Pu, Jibin, E-mail: pujibin@nimte.ac.cn [Key Laboratory of Marine Materials and Related Technologies, Key Laboratory of Marine Materials and Protective Technologies of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China)

    2017-04-15

    Highlights: • Co-doped Pb-Ti/MoS{sub 2} composite coatings were successfully fabricated by unbalanced magnetron sputtering system. • Co-doped Pb-Ti/MoS{sub 2} composite coatings showed lower friction coefficient and longer wear life in both humid and vacuum environments than that of single-doped ones. • The wear behaviours of Pb-Ti/MoS{sub 2} composite coatings with the increase of Pb content is in accordance with the variation in H/E ratio that higher H/E is corresponding to the lower wear rate of coating. - Abstract: The lubrication of molybdenum disulfide coatings has commonly been limited by the application environments, for instance, the crystal MoS{sub 2} are easily affected by water to form MoO{sub 3} that causes a higher friction coefficient and short lifetime. Therefore, to improve the tribolgical performance of MoS{sub 2} in high humidity condition, the co-doped Pb-Ti/MoS{sub 2} composite coatings are deposited by unbalanced magnetron sputtering system. The design of the co-doping elements in MoS{sub 2}-based coatings can not only maintain the characteristic of low humidity-sensitivity as the Ti/MoS{sub 2} coating but also improve the mechanical properties and tribological performance of coatings as a comparison with single-doped ones. Moreover, the ultra-low friction coefficient with a minimum value of 0.006 under the vacuum condition is achieved for Pb-Ti/MoS{sub 2} composite coating containing about 4.6 at.% Pb, depending on the densification structure of coating. Intriguingly, the wear behaviours of Pb-Ti/MoS{sub 2} composite coatings are in accordance with the variation in H/E (hardness to the elastic modulus) ratio that the coating with higher H/E exhibits lower wear rate. These results demonstrate that the lubricating properties of MoS{sub 2} coatings in both humid environment and vacuum condition can be achieved through the Pb and Ti co-doped, which is of great significant for developing MoS{sub 2} coatings as the environmentally adaptive

  10. Evaluation of internal adaptation of dental adhesive restorations using micro-CT

    Directory of Open Access Journals (Sweden)

    Oh-Hyun Kwon

    2012-02-01

    Full Text Available Objectives The internal adaptation of composite restorations with or without resin modified glass ionomer cement (RMGIC was analyzed non-destructively using Microcomputed tomography (micro-CT. Materials and Methods Thirty intact human teeth were used. The specimens were divided into 3 groups. In the control group, the cavities were etched with 10% phosphoric acid for 15 sec. Composite resin was filled into the cavity without adhesive. In group 1, light cured glass ionomer cement (GIC, Fuji II LC, GC was applied as a base. The cavities were then etched, bonded, light cured and filled with composites. In group 2, the cavities were then etched, bonded, light cured and filled with composites without base application. They were immersed in a 25% silver nitrate solution. Micro-CT was performed before and after mechanical loading. One-way ANOVA with Duncan analysis was used to compare the internal adaptation between the groups before or after loading. A paired t-test was used to compare internal adaptation before and after mechanical loading. All statistical inferences were made within the 95% confidence interval. Results The silver nitrate solution successfully penetrated into the dentinal tubules from the pulp spaces, and infiltrated into the gap between restoration and pulpal floor. Group 2 showed a lower adaptation than the control group and group 1 (p < 0.05. There was no significant difference between the control group and group 1. For all groups, there was a significant difference between before and after mechanical loading (p < 0.05. Conclusions The internal adaptation before and after loading was better when composites were bonded to tooth using adhesive than composites based with RMGIC.

  11. Effect of egg composition and oxidoreductase on adaptation of Tibetan chicken to high altitude.

    Science.gov (United States)

    Jia, C L; He, L J; Li, P C; Liu, H Y; Wei, Z H

    2016-07-01

    Tibetan chickens have good adaptation to hypoxic conditions, which can be reflected by higher hatchability than lowland breeds when incubated at high altitude. The objective of this trial was to study changes in egg composition and metabolism with regards the adaptation of Tibetan chickens to high altitude. We measured the dry weight of chicken embryos, egg yolk, and egg albumen, and the activity of lactate dehydrogenase (LDH) and succinic dehydrogenase (SDH) in breast muscle, heart, and liver from embryos of Tibetan chicken and Dwarf chicken (lowland breed) incubated at high (2,900 m) and low (100 m) altitude. We found that growth of chicken embryos was restricted at high altitude, especially for Dwarf chicken embryos. In Tibetan chicken, the egg weight was lighter, but the dry weight of egg yolk was heavier than that of Dwarf chicken. The LDH activities of the three tissues from the high altitude groups were respectively higher than those of the lowland groups from d 15 to hatching, except for breast muscle of Tibetan chicken embryos on d 15. In addition, under the high altitude environment, the heart tissue from Tibetan chicken had lower LDH activity than that from Dwarf chicken at d 15 and 18. The lactic acid content of blood from Tibetan chicken embryos was lower than that of Dwarf chicken at d 12 and 15 of incubation at high altitude. There was no difference in SDH activity in the three tissues between the high altitude groups and the lowland groups except in three tissues of hatchlings and at d 15 of incubation in breast muscle, nor between the two breeds at high altitude except in the heart of hatchlings. Consequently, the adaptation of Tibetan chicken to high altitude may be associated with higher quantities of yolk in the egg and a low metabolic oxygen demand in tissue, which illuminate the reasons that the Tibetan chicken have higher hatchability with lower oxygen transport ability. © 2016 Poultry Science Association Inc.

  12. Effect of gingival fluid on marginal adaptation of Class II resin-based composite restorations.

    Science.gov (United States)

    Spahr, A; Schön, F; Haller, B

    2000-10-01

    To evaluate in vitro the marginal quality of Class II composite restorations at the gingival enamel margins as affected by contamination of the cavities with gingival fluid (GF) during different steps of resin bonding procedures. 70 Class II cavities were prepared in extracted human molars and restored with composite using a multi-component bonding system (OptiBond FL/Herculite XRV; OPTI) or a single-bottle adhesive (Syntac Sprint/Tetric Ceram; SYN). The cavities were contaminated with human GF: C1 after acid etching, C2 after application of the primer (OPTI) or light-curing of the primer-adhesive (SYN), and C3 after light-curing of the resin adhesive (OPTI). Uncontaminated cavities were used as the control (C0). The restored teeth were subjected to thermocycling (TC) and replicated for SEM analysis of marginal gap formation. Microleakage at the gingival margins was determined by dye penetration with basic fuchsin. non-parametric tests (Kruskal-Wallis test, Mann-Whitney test with Bonferroni correction). In both bonding systems, contamination with GF after acid etching (C1) did not impair the marginal quality; the mean percentages of continuous margin/mean depths of dye penetration were: OPTI: C0: 88.5%/0.10 mm, C1: 95.6%/0.04 mm; SYN: C0: 90.9%/0.08 mm, C1: 97.0%/0.05 mm. Marginal adaptation was adversely affected when GF contamination was performed after

  13. What Drives Business Model Adaptation?

    DEFF Research Database (Denmark)

    Saebi, Tina; Lien, Lasse B.; Foss, Nicolai Juul

    2017-01-01

    Business models change as managers not only innovate business models, but also engage in more mundane adaptation in response to external changes, such as changes in the level or composition of demand. However, little is known about what causes such business model adaptation. We employ threat......-rigidity as well as prospect theory to examine business model adaptation in response to external threats and opportunities. Additionally, drawing on the behavioural theory of the firm, we argue that the past strategic orientation of a firm creates path dependencies that influence the propensity of the firm...... to adapt its business model. We test our hypotheses on a sample of 1196 Norwegian companies, and find that firms are more likely to adapt their business model under conditions of perceived threats than opportunities, and that strategic orientation geared towards market development is more conducive...

  14. The use of the spectral method within the fast adaptive composite grid method

    Energy Technology Data Exchange (ETDEWEB)

    McKay, S.M.

    1994-12-31

    The use of efficient algorithms for the solution of partial differential equations has been sought for many years. The fast adaptive composite grid (FAC) method combines an efficient algorithm with high accuracy to obtain low cost solutions to partial differential equations. The FAC method achieves fast solution by combining solutions on different grids with varying discretizations and using multigrid like techniques to find fast solution. Recently, the continuous FAC (CFAC) method has been developed which utilizes an analytic solution within a subdomain to iterate to a solution of the problem. This has been shown to achieve excellent results when the analytic solution can be found. The CFAC method will be extended to allow solvers which construct a function for the solution, e.g., spectral and finite element methods. In this discussion, the spectral methods will be used to provide a fast, accurate solution to the partial differential equation. As spectral methods are more accurate than finite difference methods, the ensuing accuracy from this hybrid method outside of the subdomain will be investigated.

  15. An Adaptive Test Sheet Generation Mechanism Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Huan-Yu Lin

    2012-01-01

    Full Text Available For test-sheet composition systems, it is important to adaptively compose test sheets with diverse conceptual scopes, discrimination and difficulty degrees to meet various assessment requirements during real learning situations. Computation time and item exposure rate also influence performance and item bank security. Therefore, this study proposes an Adaptive Test Sheet Generation (ATSG mechanism, where a Candidate Item Selection Strategy adaptively determines candidate test items and conceptual granularities according to desired conceptual scopes, and an Aggregate Objective Function applies Genetic Algorithm (GA to figure out the approximate solution of mixed integer programming problem for the test-sheet composition. Experimental results show that the ATSG mechanism can efficiently, precisely generate test sheets to meet the various assessment requirements than existing ones. Furthermore, according to experimental finding, Fractal Time Series approach can be applied to analyze the self-similarity characteristics of GA’s fitness scores for improving the quality of the test-sheet composition in the near future.

  16. Preclinical Characterization and Human Microdose Pharmacokinetics of ITMN-8187, a Nonmacrocyclic Inhibitor of the Hepatitis C Virus NS3 Protease.

    Science.gov (United States)

    Rajagopalan, Ravi; Pan, Lin; Schaefer, Caralee; Nicholas, John; Lim, Sharlene; Misialek, Shawn; Stevens, Sarah; Hooi, Lisa; Aleskovski, Natalia; Ruhrmund, Donald; Kossen, Karl; Huang, Lea; Yap, Sophia; Beigelman, Leonid; Serebryany, Vladimir; Liu, Jyanwei; Sastry, Srikonda; Seiwert, Scott; Buckman, Brad

    2017-01-01

    The current paradigm for the treatment of chronic hepatitis C virus (HCV) infection involves combinations of agents that act directly on steps of the HCV life cycle. Here we report the preclinical characteristics of ITMN-8187, a nonmacrocyclic inhibitor of the NS3/4A HCV protease. X-ray crystallographic studies of ITMN-8187 and simeprevir binding to NS3/4A protease demonstrated good agreement between structures. Low nanomolar biochemical potency was maintained against NS3/4A derived from HCV genotypes 1, 2b, 4, 5, and 6. In cell-based potency assays, half-maximal reduction of genotype 1a and 1b HCV replicon RNA was afforded by 11 and 4 nM doses of ITMN-8187, respectively. Combinations of ITMN-8187 with other directly acting antiviral agents in vitro displayed additive antiviral efficacy. A 30-mg/kg of body weight dose of ITMN-8187 administered for 4 days yielded significant viral load reductions through day 5 in a chimeric mouse model of HCV. A 3-mg/kg oral dose administered to rats, dogs, or monkeys yielded concentrations in plasma 16 h after dosing that exceeded the half-maximal effective concentration of ITMN-8187. Human microdose pharmacokinetics showed low intersubject variability and prolonged oral absorption with first-order elimination kinetics compatible with once-daily dosing. These preclinical characteristics compare favorably with those of other NS3/4A inhibitors approved for the treatment of chronic HCV infection. Copyright © 2016 American Society for Microbiology.

  17. ICAN Computer Code Adapted for Building Materials

    Science.gov (United States)

    Murthy, Pappu L. N.

    1997-01-01

    The NASA Lewis Research Center has been involved in developing composite micromechanics and macromechanics theories over the last three decades. These activities have resulted in several composite mechanics theories and structural analysis codes whose applications range from material behavior design and analysis to structural component response. One of these computer codes, the Integrated Composite Analyzer (ICAN), is designed primarily to address issues related to designing polymer matrix composites and predicting their properties - including hygral, thermal, and mechanical load effects. Recently, under a cost-sharing cooperative agreement with a Fortune 500 corporation, Master Builders Inc., ICAN was adapted to analyze building materials. The high costs and technical difficulties involved with the fabrication of continuous-fiber-reinforced composites sometimes limit their use. Particulate-reinforced composites can be thought of as a viable alternative. They are as easily processed to near-net shape as monolithic materials, yet have the improved stiffness, strength, and fracture toughness that is characteristic of continuous-fiber-reinforced composites. For example, particlereinforced metal-matrix composites show great potential for a variety of automotive applications, such as disk brake rotors, connecting rods, cylinder liners, and other hightemperature applications. Building materials, such as concrete, can be thought of as one of the oldest materials in this category of multiphase, particle-reinforced materials. The adaptation of ICAN to analyze particle-reinforced composite materials involved the development of new micromechanics-based theories. A derivative of the ICAN code, ICAN/PART, was developed and delivered to Master Builders Inc. as a part of the cooperative activity.

  18. Parallel Monitors for Self-adaptive Sessions

    Directory of Open Access Journals (Sweden)

    Mario Coppo

    2016-06-01

    Full Text Available The paper presents a data-driven model of self-adaptivity for multiparty sessions. System choreography is prescribed by a global type. Participants are incarnated by processes associated with monitors, which control their behaviour. Each participant can access and modify a set of global data, which are able to trigger adaptations in the presence of critical changes of values. The use of the parallel composition for building global types, monitors and processes enables a significant degree of flexibility: an adaptation step can dynamically reconfigure a set of participants only, without altering the remaining participants, even if the two groups communicate.

  19. MODERN APPROACHES TO ADAPTATION OF FORMULAS FOR INFANTS

    Directory of Open Access Journals (Sweden)

    A. I. Safronova

    2012-01-01

    Full Text Available The questions of adaptations of formulas for infants to protein, lipid, carbohydrate, micro- and macronutrients composition of women breast milk are discussed in this article. The authors consider new functional components, used in production of modern adapted formulas: taurine, long-chain polyunsaturated fatty acids (LCPFA, carotenoids, including lutein, prebiotics etc.

  20. Estradiol and Antagonist Pretreatment Prior to Microdose Leuprolide in in Vitro Fertilization. Does It Improve IVF Outcomes in Poor Responders as Compared to Oral Contraceptive Pill?

    Science.gov (United States)

    Elassar, Alyaa; Nulsen, John; Engmann, Lawrence; Benadiva, Claudio

    2015-01-01

    To compare in vitro fertilization (IVF) outcomes in low responders stimulated with microdose leuprolide protocol (ML) following pretreatment with either oral contraceptive pill (OCP) or luteal estradiol (E2) + GnRH antagonist (E2 + antag) for follicular synchronization prior to controlled ovarian hyperstimulation (COH). This was a retrospective study of 130 women, who were poor responders, undergoing IVF with either OCP/ML or E2+ antag/ML protocols. The main outcome measures were ongoing pregnancy rates, number of oocytes retrieved, and cancellation rate. Both groups were similar in baseline characteristics. There were no significant differences in gonadotropin requirement, cancellation rate, and number of embryos transferred. Ongoing pregnancy rates (40% vs. 15%) were significantly higher in the OCP/ML group. Trends toward greater number of oocytes retrieved (7.7 ± 3.4 vs. 5.9 ± 4.2) and improved implantation rates (20% vs. 12%) were also noted, but these did not reach statistical significance. E2+antag pretreatment does not appear to improve IVF outcomes in ML protocol when compared to the standard OCP in poor responders. Randomized trials with adequate power to study the optimal method of steroid pretreatments appear justified.

  1. New social adaptability index predicts overall mortality.

    Science.gov (United States)

    Goldfarb-Rumyantzev, Alexander; Barenbaum, Anna; Rodrigue, James; Rout, Preeti; Isaacs, Ross; Mukamal, Kenneth

    2011-08-01

    Definitions of underprivileged status based on race, gender and geographic location are neither sensitive nor specific; instead we proposed and validated a composite index of social adaptability (SAI). Index of social adaptability was calculated based on employment, education, income, marital status, and substance abuse, each factor contributing from 0 to 3 points. Index of social adaptability was validated in NHANES-3 by association with all-cause and cause-specific mortality. Weighted analysis of 19,593 subjects demonstrated mean SAI of 8.29 (95% CI 8.17-8.40). Index of social adaptability was higher in Whites, followed by Mexican-Americans and then the African-American population (ANOVA, p adaptability with a strong association with mortality, which can be used to identify underprivileged populations at risk of death.

  2. Molybdenum sealing glass-ceramic composition

    International Nuclear Information System (INIS)

    Eagan, R.J.

    1976-01-01

    A glass-ceramic composition is described having low hydrogen and helium permeability properties, along with high fracture strength, and a thermal coefficient of expansion similar to that of molybdenum. The composition is adaptable for hermetically sealing to molybdenum at temperatures between 900 and about 950 0 C to form a hermetically sealed insulator body

  3. A composition-based cartilage model for the assessment of compositional changes during cartilage damage and adaptation

    NARCIS (Netherlands)

    Wilson, W.; Huyghe, J.M.R.J.; Donkelaar, van C.C.

    2006-01-01

    The composition of articular cartilage changes with progression of osteoarthritis. Since compositional changes are associated with changes in the mechanical properties of the tissue, they are relevant for understanding how mechanical loading induces progression. The objective of this study is to

  4. CT coronary angiography: impact of adapted statistical iterative reconstruction (ASIR) on coronary stenosis and plaque composition analysis.

    Science.gov (United States)

    Fuchs, Tobias A; Fiechter, Michael; Gebhard, Cathérine; Stehli, Julia; Ghadri, Jelena R; Kazakauskaite, Egle; Herzog, Bernhard A; Husmann, Lars; Gaemperli, Oliver; Kaufmann, Philipp A

    2013-03-01

    To assess the impact of adaptive statistical iterative reconstruction (ASIR) on coronary plaque volume and composition analysis as well as on stenosis quantification in high definition coronary computed tomography angiography (CCTA). We included 50 plaques in 29 consecutive patients who were referred for the assessment of known or suspected coronary artery disease (CAD) with contrast-enhanced CCTA on a 64-slice high definition CT scanner (Discovery HD 750, GE Healthcare). CCTA scans were reconstructed with standard filtered back projection (FBP) with no ASIR (0 %) or with increasing contributions of ASIR, i.e. 20, 40, 60, 80 and 100 % (no FBP). Plaque analysis (volume, components and stenosis degree) was performed using a previously validated automated software. Mean values for minimal diameter and minimal area as well as degree of stenosis did not change significantly using different ASIR reconstructions. There was virtually no impact of reconstruction algorithms on mean plaque volume or plaque composition (e.g. soft, intermediate and calcified component). However, with increasing ASIR contribution, the percentage of plaque volume component between 401 and 500 HU decreased significantly (p ASIR, which has been developed for noise reduction in latest high resolution CCTA scans, can be used reliably without interfering with the plaque analysis and stenosis severity assessment.

  5. Adapting fire management to future fire regimes: impacts on boreal forest composition and carbon balance in Canadian National Parks

    Science.gov (United States)

    de Groot, W. J.; Flannigan, M. D.; Cantin, A.

    2009-04-01

    The effects of future fire regimes altered by climate change, and fire management in adaptation to climate change were studied in the boreal forest region of western Canada. Present (1975-90) and future (2080-2100) fire regimes were simulated for several National Parks using data from the Canadian (CGCM1) and Hadley (HadCM3) Global Climate Models (GCM) in separate simulation scenarios. The long-term effects of the different fire regimes on forests were simulated using a stand-level, boreal fire effects model (BORFIRE). Changes in forest composition and biomass storage due to future altered fire regimes were determined by comparing current and future simulation results. This was used to assess the ecological impact of altered fire regimes on boreal forests, and the future role of these forests as carbon sinks or sources. Additional future simulations were run using adapted fire management strategies, including increased fire suppression and the use of prescribed fire to meet fire cycle objectives. Future forest composition, carbon storage and emissions under current and adapted fire management strategies were also compared to determine the impact of various future fire management options. Both of the GCM's showed more severe burning conditions under future fire regimes. This includes fires with higher intensity, greater depth of burn, greater total fuel consumption and shorter fire cycles (or higher rates of annual area burned). The Canadian GCM indicated burning conditions more severe than the Hadley GCM. Shorter fire cycles of future fire regimes generally favoured aspen, birch, and jack pine because it provided more frequent regeneration opportunity for these pioneer species. Black spruce was only minimally influenced by future fire regimes, although white spruce declined sharply. Maintaining representation of pure and mixed white spruce ecosystems in natural areas will be a concern under future fire regimes. Active fire suppression is required in these areas. In

  6. Functional profiling of cyanobacterial genomes and its role in ecological adaptations

    Directory of Open Access Journals (Sweden)

    Ratna Prabha

    2016-09-01

    Full Text Available With the availability of complete genome sequences of many cyanobacterial species, it is becoming feasible to study the broad prospective of the environmental adaptation and the overall changes at transcriptional and translational level in these organisms. In the evolutionary phase, niche-specific competitive forces have resulted in specific features of the cyanobacterial genomes. In this study, functional composition of the 84 different cyanobacterial genomes and their adaptations to different environments was examined by identifying the genomic composition for specific cellular processes, which reflect their genomic functional profile and ecological adaptation. It was identified that among cyanobacterial genomes, metabolic genes have major share over other categories and differentiation of genomic functional profile was observed for the species inhabiting different habitats. The cyanobacteria of freshwater and other habitats accumulate large number of poorly characterized genes. Strain specific functions were also reported in many cyanobacterial members, of which an important feature was the occurrence of phage-related sequences. From this study, it can be speculated that habitat is one of the major factors in giving the shape of functional composition of cyanobacterial genomes towards their ecological adaptations.

  7. Toward prediction of efficacy of chemotherapy: A proof of concept study in lung cancer patients using [11C]docetaxel and positron emission tomography

    NARCIS (Netherlands)

    A.A.M. van der Veldt (Astrid); M. Lubberink (Mark); A.H.J. Mathijssen (Ron); W.J. Loos (Walter); G.J.M. Herder (G. J M); M.J.W. Greuter (Marcel); E.F.I. Comans (Emile); H.B. Rutten (Hugo); J. Eriksson (Joel); A.D. Windhorst (Albert); N.H. Hendrikse (N. Harry); D. Postmus (Douwe); E.F. Smit (Egbert); A.A. Lammertsma (Adriaan)

    2013-01-01

    textabstractPurpose: Pharmacokinetics of docetaxel can be measured in vivo using positron emission tomography (PET) and a microdose of radiolabeled docetaxel ([11C]docetaxel). The objective of this study was to investigate whether a [11C]docetaxel PET microdosing study could predict tumor uptake of

  8. Recent Re-Measurement of Neutron and Gamma-Ray Spectra 1080 Meters from the APRD (Army Pulse Radiation Division) Critical Facility,

    Science.gov (United States)

    1984-01-01

    TISSUE-EQUIVALENT ION CHAMBER GM - GEIGER-MUELLER COUNTER TE-GM - DIFFERENCE BETWEEN TE AND GM DATA MICRODOSE - MICRODOSIMETRY USING 0.5" ROSSI COUNTER...KERMA 4.26+8 1979 APRO NE-213+PR NEUTRON KERMA 4.26+8 1979 WWD NE-213 NEUTRON KERMA 3.10+8 > 550 KEV 1980 DREO MICRODOSE NEUTRON KERMA 4.32+8 1979...APRD GM GAMMA KERMA 3.86+7 1979 WWD NE-213 GAMMA KERMA 4.34+7 > 450 KEV 1980 DREO MICRODOSE GAMMA KERMA 3.90+7 76 1979 APRD TE TOTAL KERMA 4.50+8 50 c.c

  9. Stimulation of the young poor responder: comparison of the luteal estradiol/gonadotropin-releasing hormone antagonist priming protocol versus oral contraceptive microdose leuprolide.

    Science.gov (United States)

    Shastri, Shefali M; Barbieri, Elizabeth; Kligman, Isaac; Schoyer, Katherine D; Davis, Owen K; Rosenwaks, Zev

    2011-02-01

    To evaluate in vitro fertilization (IVF) cycle outcomes in young poor responders treated with a luteal estradiol/gonadotropin-releasing hormone antagonist (E(2)/ANT) protocol versus an oral contraceptive pill microdose leuprolide protocol (OCP-MDL). Retrospective cohort. Academic practice. Poor responders: 186 women, aged <35 years undergoing IVF with either E(2)/ANT or OCP-MDL protocols. None. Clinical pregnancies, oocytes retrieved, cancellation rate. Patients in the E(2)/ANT group had a greater gonadotropin requirement (71.9 ± 22.2 vs. 57.6 ± 25.7) and lower E(2) level (1,178.6 ± 668 vs. 1,627 ± 889), yet achieved similar numbers of oocytes retrieved and fertilized, and a greater number of embryos transferred (2.3 ± 0.9 vs. 2.0 ± 1.1) with a better mean grade (2.14 ± .06 vs. 2.7 ± 1.8) compared with the OCP/MDL group. The E2/ANT group exhibited a trend toward improved implantation rates (30.5% vs. 21.1%) and ongoing pregnancy rates per started cycle: 44 out of 117 (37%) versus 17 out of 69 (25%). Poor responders aged <35 years may be treated with the aggressive E(2)/ANT protocol to improve cycle outcomes. Both protocols remain viable options for this group. Adequately powered, randomized clinical comparison appears justified. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Composite membrane with integral rim

    Science.gov (United States)

    Routkevitch, Dmitri; Polyakov, Oleg G

    2015-01-27

    Composite membranes that are adapted for separation, purification, filtration, analysis, reaction and sensing. The composite membranes can include a porous support structure having elongate pore channels extending through the support structure. The composite membrane also includes an active layer comprising an active layer material, where the active layer material is completely disposed within the pore channels between the surfaces of the support structure. The active layer is intimately integrated within the support structure, thus enabling great robustness, reliability, resistance to mechanical stress and thermal cycling, and high selectivity. Methods for the fabrication of composite membranes are also provided.

  11. Summary of Research 2000: Department of Electrical and Computer Engineering

    Science.gov (United States)

    2001-12-01

    provides promising radiation hardening characteristics but the effect of microdose issues are not understood. As transistors shrink, trapping of small...examines the effects of enacting a microdose single event effect (SEE) upon a thick gate oxide of an SOI MOS capacitor in order to determine the degree

  12. Quantitation of 14C-oxaliplatin concentrations in human serum samples by using accelerator mass spectrometry

    International Nuclear Information System (INIS)

    Kobayashi, Takeshi; Toyoguchi, Teiko; Kato, Kazuhiro; Tokanai, Fuyuki; Shiraishi, Tadashi

    2013-01-01

    The understanding of human pharmacokinetics is important for development of new drugs. Microdosing studies have been proposed as means of obtaining human pharmacokinetics information at early stages of drug development. Accelerator mass spectrometry (AMS) has high detection sensitivity and is expected to play an important role in microdose trials. In this study, we used the AMS microdosing facility at Yamagata University to measure the concentration of 14 C in 14 C-oxaliplatin-spiked serum samples. The calibration curve of 14 C concentration in serum was linear, and the correlation coefficient was 0.9994. The precision, accuracy, and stability values obtained (freeze and thaw cycles, and short- and long-term stability) satisfied the criteria. The mean background 14 C concentrations in samples of 6 healthy Japanese volunteers were 1.635dpm/mL in blood and 0.56dpm/mL in plasma. These results suggest the suitability of AMS-based quantitation for analyzing samples from microdosing studies. (author)

  13. Nanostructural self-organization and dynamic adaptation of metal-polymer tribosystems

    Science.gov (United States)

    Mashkov, Yu. K.

    2017-02-01

    The results of investigating the effect of nanosize modifiers of a polymer matrix on the nanostructural self-organization of polymer composites and dynamic adaptation of metal-polymer tribosystems, which considerably affect the wear resistance of polymer composite materials, have been analyzed. It has been shown that the physicochemical nanostructural self-organization processes are developed in metal-polymer tribosystems with the formation of thermotropic liquid-crystal structures of the polymer matrix, followed by the transition of the system to the stationary state with a negative feedback that ensures dynamic adaptation of the tribosystem to given operating conditions.

  14. Composite Monopack for 120mm Mortar, With Plastic Pallet Adapters on a 42" x 53" Wooden Pallet, MIL-STD-1660 Tests, "Design Criteria for Ammunition Unit Loads", and Extreme Temperature Tests

    National Research Council Canada - National Science Library

    Dugan, Jeffery L

    2005-01-01

    ... (AMSRD-AAR-AIL-P) to conduct MIL-STD-1660 Tests to determine if the composite monopack for the 120MM mortar, with plastic pallet adapters on a 42" x 53" wooden pallet, designed by US Army ARDEC and manufactured...

  15. An Assessment of the Oral Bioavailability of Three Ca-Channel Blockers Using a Cassette-Microdose Study: A New Strategy for Streamlining Oral Drug Development.

    Science.gov (United States)

    Yamashita, Shinji; Kataoka, Makoto; Suzaki, Yuki; Imai, Hiromitsu; Morimoto, Takuya; Ohashi, Kyoichi; Inano, Akihiro; Togashi, Kazutaka; Mutaguchi, Kuninori; Sugiyama, Yuichi

    2015-09-01

    A cassette-microdose (MD) clinical study was performed to demonstrate its usefulness for identifying the most promising compound for oral use. Three Ca-channel blockers (nifedipine, nicardipine, and diltiazem) were chosen as model drugs. In the MD clinical study, a cassette-dose method was employed in which three model drugs were administered simultaneously. Both intravenous (i.v.) and oral (p.o.) administration studies were conducted to calculate the oral bioavailability (BA). For comparison, p.o. studies with therapeutic dose (ThD) levels were also performed. In all studies, blood concentrations of each drug were successfully determined using liquid chromatography-mass spectrometry with the lower limit of quantification of 0.2-2.0 pg/mL. Oral BA of nifedipine in the MD study was approximately 50% and in the same range with that obtained in the ThD study, whereas other two drugs showed significantly lower BA in the MD study, indicating a dose-dependent absorption. In addition, compared with the ThD study, absorption of nicardipine was delayed in the MD study. As a result, nifedipine was considered to be most promising for oral use. In conclusion, a cassette-MD clinical study is of advantage for oral drug development that enables to identify the candidate having desired properties for oral use. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Changes in Rumen Microbial Community Composition during Adaption to an In Vitro System and the Impact of Different Forages.

    Directory of Open Access Journals (Sweden)

    Melanie B Lengowski

    Full Text Available This study examined ruminal microbial community composition alterations during initial adaption to and following incubation in a rumen simulation system (Rusitec using grass or corn silage as substrates. Samples were collected from fermenter liquids at 0, 2, 4, 12, 24, and 48 h and from feed residues at 0, 24, and 48 h after initiation of incubation (period 1 and on day 13 (period 2. Microbial DNA was extracted and real-time qPCR was used to quantify differences in the abundance of protozoa, methanogens, total bacteria, Fibrobacter succinogenes, Ruminococcus albus, Ruminobacter amylophilus, Prevotella bryantii, Selenomonas ruminantium, and Clostridium aminophilum. We found that forage source and sampling time significantly influenced the ruminal microbial community. The gene copy numbers of most microbial species (except C. aminophilum decreased in period 1; however, adaption continued through period 2 for several species. The addition of fresh substrate in period 2 led to increasing copy numbers of all microbial species during the first 2-4 h in the fermenter liquid except protozoa, which showed a postprandial decrease. Corn silage enhanced the growth of R. amylophilus and F. succinogenes, and grass silage enhanced R. albus, P. bryantii, and C. aminophilum. No effect of forage source was detected on total bacteria, protozoa, S. ruminantium, or methanogens or on total gas production, although grass silage enhanced methane production. This study showed that the Rusitec provides a stable system after an adaption phase that should last longer than 48 h, and that the forage source influenced several microbial species.

  17. A Novel Hand-Held Optical Imager with Real-Time Co-Registration Facilities Towards Diagnostic Mammography

    Science.gov (United States)

    2012-01-01

    patients after microdose administration of near-infrared f uorophore: A feasibility study,” Radiol- ogy, vol. 246, no. 3, pp. 734–741, 2008. Sarah J...Adams KE, et al. (2008). Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility

  18. Autonomic Fuselet Specification and Composition

    National Research Council Canada - National Science Library

    Mills, Peter H

    2006-01-01

    ... model for its business logic, and to perform workflow composition from a goal and specifications to executable model in a manner that enables feedback mechanisms that can assess and adapt the process...

  19. Symbiotic Composition and Evolvability

    OpenAIRE

    Watson, Richard A.; Pollack, Jordan B.

    2001-01-01

    Several of the Major Transitions in natural evolution, such as the symbiogenic origin of eukaryotes from prokaryotes, share the feature that existing entities became the components of composite entities at a higher level of organisation. This composition of pre-adapted extant entities into a new whole is a fundamentally different source of variation from the gradual accumulation of small random variations, and it has some interesting consequences for issues of evolvability. In this paper we p...

  20. Using Ontology to Drive an Adaptive Learning Interface

    Directory of Open Access Journals (Sweden)

    Andrew Crapo

    2004-10-01

    Full Text Available Intelligent, adaptive interfaces are a pre-requisite to elevating computer-based applications to the realm of collaborative decision support in complex, relatively open-ended domains such as logistics and planning. This is because the composition and effective presentation of even the most useful information must be tailored to constantly changing circumstances. Our objective is to not only achieve an adaptive human-machine interface, but to imbue the software with a significant portion of the responsibility for effectively controlling the adaptation, freeing the user from unnecessary distraction and making the human-machine relationship more collaborative in nature. The foundational concepts of interface adaptation are discussed and a specific logistics application is described as an example.

  1. Adaptive response of Peruvian Hake to overfishing

    OpenAIRE

    Mendo, C.W.; Carrasco, R.G.

    2000-01-01

    Compensatory mechanisms of the Peruvian hake population (Merluccius gayi peruanus) in response to heavy exploitation and changes in species interaction are discussed. Changes in the rate of cannibalism, diet composition, maximization of fecundity and behavioral adaptation are noted.

  2. Merits and challenges of career adaptability as a tool towards sustainable careers

    NARCIS (Netherlands)

    Buyken, M.B.W.; Klehe, U.-C.; Zikic, J.; van Vianen, A.E.M.; de Vos, A.; van der Heijden, B.I.J.M.

    2015-01-01

    The chapter discusses how career adaptability can be valuable in constructing sustainable careers. Still, the concept faces a number of challenges and unresolved issues. First, we address the conceptualization of career adaptability as a composite construct and argue in particular that the component

  3. Original Research Cross-cultural adaptation, content validation, and ...

    African Journals Online (AJOL)

    study which aimed to cross culturally adapt a composite lifestyle cardiovascular disease (CVD) risk factors ... and a relative lack of access to adequate advice and care. .... meaning different things are distinguished by giving symbols.

  4. Chameleon Coatings: Adaptive Surfaces to Reduce Friction and Wear in Extreme Environments

    Science.gov (United States)

    Muratore, C.; Voevodin, A. A.

    2009-08-01

    Adaptive nanocomposite coating materials that automatically and reversibly adjust their surface composition and morphology via multiple mechanisms are a promising development for the reduction of friction and wear over broad ranges of ambient conditions encountered in aerospace applications, such as cycling of temperature and atmospheric composition. Materials selection for these composites is based on extensive study of interactions occurring between solid lubricants and their surroundings, especially with novel in situ surface characterization techniques used to identify adaptive behavior on size scales ranging from 10-10 to 10-4 m. Recent insights on operative solid-lubricant mechanisms and their dependency upon the ambient environment are reviewed as a basis for a discussion of the state of the art in solid-lubricant materials.

  5. Human Lung Cancer Risks from Radon – Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis

    Science.gov (United States)

    Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

    2012-01-01

    Since the publication of the BEIR VI (1999) report on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005, 2006) and the 8 North American pooled study (Krewski et al 2005, 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m−3 there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid. PMID:22942874

  6. Adaptive structures flight experiments

    Science.gov (United States)

    Martin, Maurice

    The topics are presented in viewgraph form and include the following: adaptive structures flight experiments; enhanced resolution using active vibration suppression; Advanced Controls Technology Experiment (ACTEX); ACTEX program status; ACTEX-2; ACTEX-2 program status; modular control patch; STRV-1b Cryocooler Vibration Suppression Experiment; STRV-1b program status; Precision Optical Bench Experiment (PROBE); Clementine Spacecraft Configuration; TECHSAT all-composite spacecraft; Inexpensive Structures and Materials Flight Experiment (INFLEX); and INFLEX program status.

  7. Robust Adaptive Neural Control of Morphing Aircraft with Prescribed Performance

    Directory of Open Access Journals (Sweden)

    Zhonghua Wu

    2017-01-01

    Full Text Available This study proposes a low-computational composite adaptive neural control scheme for the longitudinal dynamics of a swept-back wing aircraft subject to parameter uncertainties. To efficiently release the constraint often existing in conventional neural designs, whose closed-loop stability analysis always necessitates that neural networks (NNs be confined in the active regions, a smooth switching function is presented to conquer this issue. By integrating minimal learning parameter (MLP technique, prescribed performance control, and a kind of smooth switching strategy into back-stepping design, a new composite switching adaptive neural prescribed performance control scheme is proposed and a new type of adaptive laws is constructed for the altitude subsystem. Compared with previous neural control scheme for flight vehicle, the remarkable feature is that the proposed controller not only achieves the prescribed performance including transient and steady property but also addresses the constraint on NN. Two comparative simulations are presented to verify the effectiveness of the proposed controller.

  8. Adaptive control for accelerators

    International Nuclear Information System (INIS)

    Eaton, L.E.; Jachim, S.P.; Natter, E.F.

    1991-01-01

    This patent describes an adaptive feedforward control loop is provided to stabilize accelerator beam loading of the radio frequency field in an accelerator cavity during successive pulses of the beam into the cavity. A digital signal processor enables an adaptive algorithm to generate a feedforward error correcting signal functionally determined by the feedback error obtained by a beam pulse loading the cavity after the previous correcting signal was applied to the cavity. Each cavity feedforward correcting signal is successively stored in the digital processor and modified by the feedback error resulting from its application to generate the next feedforward error correcting signal. A feedforward error correcting signal is generated by the digital processor in advance of the beam pulse to enable a composite correcting signal and the beam pulse to arrive concurrently at the cavity

  9. Adaptive control for accelerators

    Science.gov (United States)

    Eaton, Lawrie E.; Jachim, Stephen P.; Natter, Eckard F.

    1991-01-01

    An adaptive feedforward control loop is provided to stabilize accelerator beam loading of the radio frequency field in an accelerator cavity during successive pulses of the beam into the cavity. A digital signal processor enables an adaptive algorithm to generate a feedforward error correcting signal functionally determined by the feedback error obtained by a beam pulse loading the cavity after the previous correcting signal was applied to the cavity. Each cavity feedforward correcting signal is successively stored in the digital processor and modified by the feedback error resulting from its application to generate the next feedforward error correcting signal. A feedforward error correcting signal is generated by the digital processor in advance of the beam pulse to enable a composite correcting signal and the beam pulse to arrive concurrently at the cavity.

  10. 30 CFR 36.26 - Composition of exhaust gas.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Composition of exhaust gas. 36.26 Section 36.26... EQUIPMENT Construction and Design Requirements § 36.26 Composition of exhaust gas. (a) Preliminary engine... methane) is a satisfactory substitute for pure methane in these tests. (c) Coupling or adapter. The...

  11. A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF

    Directory of Open Access Journals (Sweden)

    Gayem İnayet Turgay Çelik

    2015-01-01

    Full Text Available Objective. To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF. Study Design. A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET program between January 2006 and November 2012. The groups were compared to the patients’ characteristics, controlled ovarian stimulation (COH results, and laboratory results. Results. Combination protocol was applied to 46 patients (group 1, and a single protocol was applied to 85 patients (group 2. In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%. A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4% or the clinical pregnancy rates (7.1% versus 10.6%. Conclusion. The combination protocol does not provide additional efficacy.

  12. A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF.

    Science.gov (United States)

    Çelik, Gayem İnayet Turgay; Sütçü, Havva Kömür; Akpak, Yaşam Kemal; Akar, Münire Erman

    2015-01-01

    To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients' characteristics, controlled ovarian stimulation (COH) results, and laboratory results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). The combination protocol does not provide additional efficacy.

  13. Protein and DNA sequence determinants of thermophilic adaptation.

    Directory of Open Access Journals (Sweden)

    Konstantin B Zeldovich

    2007-01-01

    Full Text Available There have been considerable attempts in the past to relate phenotypic trait--habitat temperature of organisms--to their genotypes, most importantly compositions of their genomes and proteomes. However, despite accumulation of anecdotal evidence, an exact and conclusive relationship between the former and the latter has been elusive. We present an exhaustive study of the relationship between amino acid composition of proteomes, nucleotide composition of DNA, and optimal growth temperature (OGT of prokaryotes. Based on 204 complete proteomes of archaea and bacteria spanning the temperature range from -10 degrees C to 110 degrees C, we performed an exhaustive enumeration of all possible sets of amino acids and found a set of amino acids whose total fraction in a proteome is correlated, to a remarkable extent, with the OGT. The universal set is Ile, Val, Tyr, Trp, Arg, Glu, Leu (IVYWREL, and the correlation coefficient is as high as 0.93. We also found that the G + C content in 204 complete genomes does not exhibit a significant correlation with OGT (R = -0.10. On the other hand, the fraction of A + G in coding DNA is correlated with temperature, to a considerable extent, due to codon patterns of IVYWREL amino acids. Further, we found strong and independent correlation between OGT and the frequency with which pairs of A and G nucleotides appear as nearest neighbors in genome sequences. This adaptation is achieved via codon bias. These findings present a direct link between principles of proteins structure and stability and evolutionary mechanisms of thermophylic adaptation. On the nucleotide level, the analysis provides an example of how nature utilizes codon bias for evolutionary adaptation to extreme conditions. Together these results provide a complete picture of how compositions of proteomes and genomes in prokaryotes adjust to the extreme conditions of the environment.

  14. Composite membranes and methods for making same

    Science.gov (United States)

    Routkevitch, Dmitri; Polyakov, Oleg G

    2012-07-03

    Composite membranes that are adapted for separation, purification, filtration, analysis, reaction and sensing. The composite membranes can include a porous support structure having elongate pore channels extending through the support structure. The composite membrane also includes an active layer comprising an active layer material, where the active layer material is completely disposed within the pore channels between the surfaces of the support structure. The active layer is intimately integrated within the support structure, thus enabling great robustness, reliability, resistance to mechanical stress and thermal cycling, and high selectivity. Methods for the fabrication of composite membranes are also provided.

  15. Tricolore. A flexible color scale for ternary compositions

    DEFF Research Database (Denmark)

    2018-01-01

    tricolore is an R library providing a flexible color scale for the visualization of three-part/ternary compositions. Its main functionality is to color-code any ternary composition as a mixture of three primary colours and to draw a suitable color-key. tricolore flexibly adapts to different...... visualisation challenges via - discrete and continuous color support - support for unbalanced compositional data via centering - support for data with very narrow range via scaling - hue, chroma and lightness options...

  16. Pick a Color MARIA: Adaptive Sampling Enables the Rapid Identification of Complex Perovskite Nanocrystal Compositions with Defined Emission Characteristics.

    Science.gov (United States)

    Bezinge, Leonard; Maceiczyk, Richard M; Lignos, Ioannis; Kovalenko, Maksym V; deMello, Andrew J

    2018-06-06

    Recent advances in the development of hybrid organic-inorganic lead halide perovskite (LHP) nanocrystals (NCs) have demonstrated their versatility and potential application in photovoltaics and as light sources through compositional tuning of optical properties. That said, due to their compositional complexity, the targeted synthesis of mixed-cation and/or mixed-halide LHP NCs still represents an immense challenge for traditional batch-scale chemistry. To address this limitation, we herein report the integration of a high-throughput segmented-flow microfluidic reactor and a self-optimizing algorithm for the synthesis of NCs with defined emission properties. The algorithm, named Multiparametric Automated Regression Kriging Interpolation and Adaptive Sampling (MARIA), iteratively computes optimal sampling points at each stage of an experimental sequence to reach a target emission peak wavelength based on spectroscopic measurements. We demonstrate the efficacy of the method through the synthesis of multinary LHP NCs, (Cs/FA)Pb(I/Br) 3 (FA = formamidinium) and (Rb/Cs/FA)Pb(I/Br) 3 NCs, using MARIA to rapidly identify reagent concentrations that yield user-defined photoluminescence peak wavelengths in the green-red spectral region. The procedure returns a robust model around a target output in far fewer measurements than systematic screening of parametric space and additionally enables the prediction of other spectral properties, such as, full-width at half-maximum and intensity, for conditions yielding NCs with similar emission peak wavelength.

  17. Multifluid Block-Adaptive-Tree Solar Wind Roe-Type Upwind Scheme: Magnetospheric Composition and Dynamics During Geomagnetic Storms-Initial Results

    Science.gov (United States)

    Glocer, A.; Toth, G.; Ma, Y.; Gombosi, T.; Zhang, J.-C.; Kistler, L. M.

    2009-01-01

    The magnetosphere contains a significant amount of ionospheric O+, particularly during geomagnetically active times. The presence of ionospheric plasma in the magnetosphere has a notable impact on magnetospheric composition and processes. We present a new multifluid MHD version of the Block-Adaptive-Tree Solar wind Roe-type Upwind Scheme model of the magnetosphere to track the fate and consequences of ionospheric outflow. The multifluid MHD equations are presented as are the novel techniques for overcoming the formidable challenges associated with solving them. Our new model is then applied to the May 4, 1998 and March 31, 2001 geomagnetic storms. The results are juxtaposed with traditional single-fluid MHD and multispecies MHD simulations from a previous study, thereby allowing us to assess the benefits of using a more complex model with additional physics. We find that our multifluid MHD model (with outflow) gives comparable results to the multispecies MHD model (with outflow), including a more strongly negative Dst, reduced CPCP, and a drastically improved magnetic field at geosynchronous orbit, as compared to single-fluid MHD with no outflow. Significant differences in composition and magnetic field are found between the multispecies and multifluid approach further away from the Earth. We further demonstrate the ability to explore pressure and bulk velocity differences between H+ and O+, which is not possible when utilizing the other techniques considered

  18. Cultural adaptation of the Latin American version of the World Health Organization Composite International Diagnostic Interview (WHO-CIDI) (v 3.0) for use in Spain.

    Science.gov (United States)

    Navarro-Mateu, Fernando; Morán-Sánchez, Inés; Alonso, Jordi; Tormo, Ma José; Pujalte, Ma Luisa; Garriga, Ascensión; Aguilar-Gaxiola, Sergio; Navarro, Carmen

    2013-01-01

    To develop a Spanish version of the WHO-Composite International Diagnostic Interview (WHO-CIDI) applicable to Spain, through cultural adaptation of its most recent Latin American (LA v 20.0) version. A 1-week training course on the WHO-CIDI was provided by certified trainers. An expert panel reviewed the LA version, identified words or expressions that needed to be adapted to the cultural or linguistic norms for Spain, and proposed alternative expressions that were agreed on through consensus. The entire process was supervised and approved by a member of the WHO-CIDI Editorial Committee. The changes were incorporated into a Computer Assisted Personal Interview (CAPI) format and the feasibility and administration time were pilot tested in a convenience sample of 32 volunteers. A total of 372 questions were slightly modified (almost 7% of approximately 5000 questions in the survey) and incorporated into the CAPI version of the WHO-CIDI. Most of the changes were minor - but important - linguistic adaptations, and others were related to specific Spanish institutions and currency. In the pilot study, the instrument's mean completion administration time was 2h and 10min, with an interquartile range from 1.5 to nearly 3h. All the changes made were tested and officially approved. The Latin American version of the WHO-CIDI was successfully adapted and pilot-tested in its computerized format and is now ready for use in Spain. Copyright © 2012 SESPAS. Published by Elsevier Espana. All rights reserved.

  19. Comparison of microdose GnRH agonist protocol with GnRH antagonist / letrazole protocol in patients with poor ovarian response

    Directory of Open Access Journals (Sweden)

    Yiğit Çakıroğlu

    2013-09-01

    Full Text Available Objective: To compare microdose GnRH agonist (MDL protocol with GnRH antagonist/letrazole (AL protocol in patients with poor ovarian response. Design: Randomised clinical trial. Setting: Kocaeli University Assisted Reproductive Centre Interventions: POR was diagnosed according to ESHRE Bologna criteria in case of presence of 2 out of 3 criteria. In the MDL group (n=27, 40µg/0.2 cc subcutaneous leuprolid acetate was given two times a day starting on the first day of menstrual cycle. On the second day of the cycle, gonadotrophin stimulation was started at 450-600 IU and/or 150 IU human menopausal gonadotrophin (hMG along with leuprolid. In the AL group (n=28, 5 mg letrazole was given for 5 days starting on the second day of the spontaneous cycle and after the 5th day of the cycle, 450-600 IU and/or 150 IU hMG was given. Main Outcome Measures: To compare the outcomes of MDL protocol with AL protocol in patients with poor ovarian response. Results: Stimulation days, total gonadotrophin dose (IU, peak E2 (pg/ml levels, and endometrial thickness were found to be statistically significantly lower in the AL group. While no cases of cycle cancellation was detected in the MDL group, statistically significantly higher rates of cycle cancellation (%35.7, p<0.001 was detected in the AL group. No statistically significant differences were detected in total oocyte numbers (3.7±2.9 vs 2.7±2.2, number of transferred embryos (1.4±0.5 vs 1.4±1.9, pregnancy rates (3/27 (%11.1 vs 2/28 (%7.1 and implantation rates (3/36 (%8.3 vs 2/22 (%9.1 in between the groups. Comment: Although AL protocol is not superior to MDL protocol in poor ovarian response patients, it may be used as an alternative protocol.

  20. Nutrition and training adaptations in aquatic sports.

    Science.gov (United States)

    Mujika, Iñigo; Stellingwerff, Trent; Tipton, Kevin

    2014-08-01

    The adaptive response to training is determined by the combination of the intensity, volume, and frequency of the training. Various periodized approaches to training are used by aquatic sports athletes to achieve performance peaks. Nutritional support to optimize training adaptations should take periodization into consideration; that is, nutrition should also be periodized to optimally support training and facilitate adaptations. Moreover, other aspects of training (e.g., overload training, tapering and detraining) should be considered when making nutrition recommendations for aquatic athletes. There is evidence, albeit not in aquatic sports, that restricting carbohydrate availability may enhance some training adaptations. More research needs to be performed, particularly in aquatic sports, to determine the optimal strategy for periodizing carbohydrate intake to optimize adaptations. Protein nutrition is an important consideration for optimal training adaptations. Factors other than the total amount of daily protein intake should be considered. For instance, the type of protein, timing and pattern of protein intake and the amount of protein ingested at any one time influence the metabolic response to protein ingestion. Body mass and composition are important for aquatic sport athletes in relation to power-to-mass and for aesthetic reasons. Protein may be particularly important for athletes desiring to maintain muscle while losing body mass. Nutritional supplements, such as b-alanine and sodium bicarbonate, may have particular usefulness for aquatic athletes' training adaptation.

  1. Adaptive, Active and Multifunctional Composite and Hybrid Materials Program: Composite and Hybrid Materials ERA

    Science.gov (United States)

    2014-04-01

    590 . SMASIS2011-4934. L. D. Peel, J. Baur, D. Phillips, and A. McClung, “The Effect of Scaling on the Performance of Elastomer Composite Actuators...fragility of the fibers it was also not possible to extract some of them from their adhesive paper mountings without breakage. For Raman ... Raman spectroscopy and microscopy (SEM), the nanocomposites were evaluated for their thermal analytical properties using TGA. Electrical

  2. Self-adapted thermocouple-diagnostic complex

    International Nuclear Information System (INIS)

    Alekseev, S.V.; Grankovskij, K.Eh.; Olejnikov, P.P.; Prijmak, S.V.; Shikalov, V.F.

    2003-01-01

    A self-adapted thermocouple-diagnostic complex (STDC) for obtaining the reliable data on the coolant temperature in the reactors of NPP is described. The STDC in based on the thermal pulse monitoring of a thermocouple in the measuring channel of a reactor. Measurement method and STDC composition are substantiated. It is shown that introduction of the developed STDC ensures realization of precise and reliable temperature monitoring in the reactors of all types [ru

  3. Psychological Adaptation to Extreme Environments: Effects of Team Composition on Individual Adaptation

    Science.gov (United States)

    Wood, J.; Hysong, S. J.; Lugg, D. J.; Harm, D. L.

    1999-01-01

    This study is part of an ongoing program of research examining the psychological effects of isolation and confinement on individual adaptation, productivity and group relations in Antarctic winter personnel. This environment is used as an analogue for long-duration space mission scenarios, such as a space station sojourn, or a mission to Mars. Earlier results from this and other environments have demonstrated that: (1) most changes in psychological well-being are event-related and of relatively short duration; and (2) the greatest problem facing most individuals is interpersonal conflict. Content analysis of responses to open-ended questions has identified the numerous enjoyable aspects of Antarctic living, and confirmed that many of the problems reported were interpersonal in nature, and that problems varied significantly by station. Current work is exploring the effects of team assignment on the self-reported psychological changes and self-evaluations of members of isolated teams. This work includes identifying the dimensions by which subjects determine how well they are functioning. These dimensions (e.g., work, social life, internal emotional state) appear to play an important role in how subjects evaluate many aspects of life in isolation.

  4. A Process Mining Based Service Composition Approach for Mobile Information Systems

    Directory of Open Access Journals (Sweden)

    Chengxi Huang

    2017-01-01

    Full Text Available Due to the growing trend in applying big data and cloud computing technologies in information systems, it is becoming an important issue to handle the connection between large scale of data and the associated business processes in the Internet of Everything (IoE environment. Service composition as a widely used phase in system development has some limits when the complexity of relationship among data increases. Considering the expanding scale and the variety of devices in mobile information systems, a process mining based service composition approach is proposed in this paper in order to improve the adaptiveness and efficiency of compositions. Firstly, a preprocessing is conducted to extract existing service execution information from server-side logs. Then process mining algorithms are applied to discover the overall event sequence with preprocessed data. After that, a scene-based service composition is applied to aggregate scene information and relocate services of the system. Finally, a case study that applied the work in mobile medical application proves that the approach is practical and valuable in improving service composition adaptiveness and efficiency.

  5. A Survey of Service Composition Mechanisms in Ubiquitous Computing

    DEFF Research Database (Denmark)

    Brønsted, Jeppe; Hansen, Klaus Marius; Ingstrup, Mads

    2007-01-01

    Composition of services, i.e., providing new services by combining existing ones, is a pervasive idea in ubiquitous computing. We surveyed the field by looking at what features are actually present in technologies that support service composition in some form. Condensing this into a list...... of features allowed us to discuss the qualitative merits and drawbacks of various approaches to service composition, focusing in particular on usability, adaptability and efficiency. Moreover, we found that further research is needed into quality-of-service assurance of composites and into contingency...... management for composites—one of the concerns differentiating service composition in ubiquitous computing from its counterpart in less dynamic settings....

  6. The 4D Composite Higgs

    CERN Document Server

    De Curtis, Stefania; Tesi, Andrea

    2012-01-01

    We propose a four dimensional description of Composite Higgs Models which represents a complete framework for the physics of the Higgs as a pseudo-Nambu-Goldstone boson. Our setup captures all the relevant features of 5D models and more in general of composite Higgs models with partial compositeness. We focus on the minimal scenario where we include a single multiplet of resonances of the composite sector, as these will be the only degrees of freedom which might be accessible at the LHC. This turns out to be sufficient to compute the effective potential and derive phenomenological consequences of the theory. Moreover our simplified approach is well adapted to simulate these models at the LHC. We also consider the impact of non-minimal terms in the effective lagrangian which do not descend from a 5D theory and could be of phenomenological relevance, for example contributing to the S-parameter.

  7. High-Temperature Graphite/Phenolic Composite

    Science.gov (United States)

    Seal, Ellis C.; Bodepudi, Venu P.; Biggs, Robert W., Jr.; Cranston, John A.

    1995-01-01

    Graphite-fiber/phenolic-resin composite material retains relatively high strength and modulus of elasticity at temperatures as high as 1,000 degrees F. Costs only 5 to 20 percent as much as refractory materials. Fabrication composite includes curing process in which application of full autoclave pressure delayed until after phenolic resin gels. Curing process allows moisture to escape, so when composite subsequently heated in service, much less expansion of absorbed moisture and much less tendency toward delamination. Developed for nose cone of external fuel tank of Space Shuttle. Other potential aerospace applications for material include leading edges, parts of nozzles, parts of aircraft engines, and heat shields. Terrestrial and aerospace applications include structural firewalls and secondary structures in aircraft, spacecraft, and ships. Modified curing process adapted to composites of phenolic with other fiber reinforcements like glass or quartz. Useful as high-temperature circuit boards and electrical insulators.

  8. Behavior of Fiber-Reinforced Smart Soft Composite Actuators According to Material Composition

    Energy Technology Data Exchange (ETDEWEB)

    Han, Min-Woo; Kim, Hyung-Il; Song, Sung-Hyuk; Ahn, Sung-Hoon [Seoul Nat’l Univ., Seoul (Korea, Republic of)

    2017-02-15

    Fiber-reinforced polymer composites, which are made by combining a continuous fiber that acts as reinforcement and a homogeneous polymeric material that acts as a host, are engineering materials with high strength and stiffness and a lightweight structure. In this study, a shape memory alloy(SMA) reinforced composite actuator is presented. This actuator is used to generate large deformations in single lightweight structures and can be used in applications requiring a high degree of adaptability to various external conditions. The proposed actuator consists of numerous individual laminas of the glass-fiber fabric that are embedded in a polymeric matrix. To characterize its deformation behavior, the composition of the actuator was changed by changing the matrix material and the number of the glass-fiber fabric layers. In addition, current of various magnitudes were applied to each actuator to study the effect of the heating of SMA wires on applying current.

  9. Thixotropic gel-like composition and sterile blood-collecting and separating device

    International Nuclear Information System (INIS)

    Semersky, F.E.

    1980-01-01

    A thixotropic gel-like composition comprising liquid polybutadiene and an inorganic inert filler dispersed therein is adapted for use as a sealing barrier between separated phases of differing densities of a fluid in which said composition has at rest a density intermediate said differing densities, said gel-like composition being substantially resistant to sterilizing radiation. There is also disclosed a pre-packaged blood collecting and separating device which contains a mixture of liquid polybutadiene and an inorganic, inert filler, such as silica, as a thixotropic gel adapted at rest to form a sealing barrier between separated blood phases. The device and gel are subjected to sterilizing radiation to form a substantially sterile device, substantially free of backflow contamination without degradation of the physical properties of the gel. (author)

  10. Microleakage of Different Post Systems and a Custom Adapted Fiber Post

    Directory of Open Access Journals (Sweden)

    Farideh Geramipanah

    2013-01-01

    Full Text Available Objective: The effects of closely adapting a prefabricated fiber to the post space remain unknown. The purpose of this study was to quantify the microleakages of a custom adapted fiber-reinforced post, a prefabricated quartz fiber post and a cast post using nondestructive methods.Materials and Methods: Sixty-five extracted human premolars were endodontically treated and randomly divided into three groups (n=15, which were restored using a cast post-and-core, a custom adapted fiber post (Refropost with a microhybrid microfiller resin composite (Gradia, or a prefabricated quartz fiber post (DT light post and two groups of control ( n=10. All groups were cemented using a dual polymerizing resin cement (Panavia F2.0. A composite core (Z100 was used for the fiber posts. The microleakage was calculated for the experimental and control groups before and after thermal cycling and cycling loading using a radiotracer solution (thallium 201 chloride and a gamma counter device. Data were subjected to statistical analysis of ANOVA and Tukey HSD at significant level of P< 0.05.Results: Significantly lower microleakage values were found for the cast post-and-core (mean value =16.04 ×104 and custom adapted fiber post groups (mean value=14.36×104. Thermal cycling and cyclic loading had no significant effect on the microleakage value of any tested group.Conclusion: Post systems with improved adaptation showed similar microleakage to casting post

  11. Alteration of the phospho- or neutral lipid content and fatty acid composition in Listeria monocytogenes due to acid adaptation mechanisms for hydrochloric, acetic and lactic acids at pH 5.5 or benzoic acid at neutral pH.

    Science.gov (United States)

    Mastronicolis, Sofia K; Berberi, Anita; Diakogiannis, Ioannis; Petrova, Evanthia; Kiaki, Irene; Baltzi, Triantafillia; Xenikakis, Polydoros

    2010-10-01

    This study provides a first approach to observe the effects on Listeria monocytogenes of cellular exposure to acid stress at low or neutral pH, notably how phospho- or neutral lipids are involved in this mechanism, besides the fatty acid profile alteration. A thorough investigation of the composition of polar and neutral lipids from L. monocytogenes grown at pH 5.5 in presence of hydrochloric, acetic and lactic acids, or at neutral pH 7.3 in presence of benzoic acid, is described relative to cells grown in acid-free medium. The results showed that only low pH values enhance the antimicrobial activity of an acid. We suggest that, irrespective of pH, the acid adaptation response will lead to a similar alteration in fatty acid composition [decreasing the ratio of branched chain/saturated straight fatty acids of total lipids], mainly originating from the neutral lipid class of adapted cultures. Acid adaptation in L. monocytogenes was correlated with a decrease in total lipid phosphorus and, with the exception of cells adapted to benzoic acid, this change in the amount of phosphorus reflected a higher content of the neutral lipid class. Upon acetic or benzoic acid stress the lipid phosphorus proportion was analysed in the main phospholipids present: cardiolipin, phosphatidylglycerol, phosphoaminolipid and phosphatidylinositol. Interestingly only benzoic acid had a dramatic effect on the relative quantities of these four phospholipids.

  12. Cross-cultural adaptation, content validation, and reliability of the ...

    African Journals Online (AJOL)

    Background: Assessment of lifestyle risk factors must be culturally- and contextually relevant and available in local languages. This paper reports on a study which aimed to cross culturally adapt a composite lifestyle cardiovascular disease (CVD) risk factors questionnaire into an African language (Yoruba) and testing some ...

  13. Layout and composition for animation

    CERN Document Server

    Ghertner, Ed

    2012-01-01

    This essential, hands-on guide is filled with examples of what a composition should look like and example of poorly designed layouts. Spot potential problems before they cost time and money, and adapt creative solutions for your own projects with this invaluable resource for beginner and intermediate artists.  With Beauty and the Beast examples and Simpson character layouts, readers will learn how to develop character layout and background layout as well as strengthen composition  styles with a creative toolset of trick shot examples and inspirational case studies. A companion website will

  14. Aerobic Exercise Training Adaptations Are Increased by Postexercise Carbohydrate-Protein Supplementation

    Directory of Open Access Journals (Sweden)

    Lisa Ferguson-Stegall

    2011-01-01

    Full Text Available Carbohydrate-protein supplementation has been found to increase the rate of training adaptation when provided postresistance exercise. The present study compared the effects of a carbohydrate and protein supplement in the form of chocolate milk (CM, isocaloric carbohydrate (CHO, and placebo on training adaptations occurring over 4.5 weeks of aerobic exercise training. Thirty-two untrained subjects cycled 60 min/d, 5 d/wk for 4.5 wks at 75–80% of maximal oxygen consumption (VO2 max. Supplements were ingested immediately and 1 h after each exercise session. VO2 max and body composition were assessed before the start and end of training. VO2 max improvements were significantly greater in CM than CHO and placebo. Greater improvements in body composition, represented by a calculated lean and fat mass differential for whole body and trunk, were found in the CM group compared to CHO. We conclude supplementing with CM postexercise improves aerobic power and body composition more effectively than CHO alone.

  15. Neural network based adaptive control for nonlinear dynamic regimes

    Science.gov (United States)

    Shin, Yoonghyun

    Adaptive control designs using neural networks (NNs) based on dynamic inversion are investigated for aerospace vehicles which are operated at highly nonlinear dynamic regimes. NNs play a key role as the principal element of adaptation to approximately cancel the effect of inversion error, which subsequently improves robustness to parametric uncertainty and unmodeled dynamics in nonlinear regimes. An adaptive control scheme previously named 'composite model reference adaptive control' is further developed so that it can be applied to multi-input multi-output output feedback dynamic inversion. It can have adaptive elements in both the dynamic compensator (linear controller) part and/or in the conventional adaptive controller part, also utilizing state estimation information for NN adaptation. This methodology has more flexibility and thus hopefully greater potential than conventional adaptive designs for adaptive flight control in highly nonlinear flight regimes. The stability of the control system is proved through Lyapunov theorems, and validated with simulations. The control designs in this thesis also include the use of 'pseudo-control hedging' techniques which are introduced to prevent the NNs from attempting to adapt to various actuation nonlinearities such as actuator position and rate saturations. Control allocation is introduced for the case of redundant control effectors including thrust vectoring nozzles. A thorough comparison study of conventional and NN-based adaptive designs for a system under a limit cycle, wing-rock, is included in this research, and the NN-based adaptive control designs demonstrate their performances for two highly maneuverable aerial vehicles, NASA F-15 ACTIVE and FQM-117B unmanned aerial vehicle (UAV), operated under various nonlinearities and uncertainties.

  16. Tracking error constrained robust adaptive neural prescribed performance control for flexible hypersonic flight vehicle

    Directory of Open Access Journals (Sweden)

    Zhonghua Wu

    2017-02-01

    Full Text Available A robust adaptive neural control scheme based on a back-stepping technique is developed for the longitudinal dynamics of a flexible hypersonic flight vehicle, which is able to ensure the state tracking error being confined in the prescribed bounds, in spite of the existing model uncertainties and actuator constraints. Minimal learning parameter technique–based neural networks are used to estimate the model uncertainties; thus, the amount of online updated parameters is largely lessened, and the prior information of the aerodynamic parameters is dispensable. With the utilization of an assistant compensation system, the problem of actuator constraint is overcome. By combining the prescribed performance function and sliding mode differentiator into the neural back-stepping control design procedure, a composite state tracking error constrained adaptive neural control approach is presented, and a new type of adaptive law is constructed. As compared with other adaptive neural control designs for hypersonic flight vehicle, the proposed composite control scheme exhibits not only low-computation property but also strong robustness. Finally, two comparative simulations are performed to demonstrate the robustness of this neural prescribed performance controller.

  17. Survey of advanced composite material technology; Senshin fukugo zairyo gijutsu ni kansuru chosa

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    Results of functions and examples are investigated and described for more than 190 fiber reinforced composite materials. There should be a new viewpoint for even the same material when changing the point to observe it, and new industries will be expected if the viewpoint is adequate. This report has proposed a new concept of `composite functions.` The development works based on non-strength functions which will differentiate the other materials have been stressed. After describing the brief history of the advanced composite materials and significance of composite functions, the present situations and future possibilities of such functions as heat resistance, electricity-electromagnetism, chemicals-proof, adsorption, vibration-proof and resistance, tribology, erosion, sound, adaptability to living bodies and etc. have been examined based on the practical examples. As the future important subjects, adapting possibility of materials having composite functions to marine structures, and possibility of water cleaning system are described. 59 refs., 4 figs., 10 tabs.

  18. Adaptive plasma for cancer therapy: physics, mechanism and applications

    Science.gov (United States)

    Keidar, Michael

    2017-10-01

    One of the most promising applications of cold atmospheric plasma (CAP) is the cancer therapy. The uniqueness of plasma is in its ability to change composition in situ. Plasma self-organization could lead to formation of coherent plasma structures. These coherent structures tend to modulate plasma chemistry and composition, including reactive species, the electric field and charged particles. Formation of coherent plasma structures allows the plasma to adapt to external boundary conditions, such as different cells types and their contextual tissues. In this talk we will explore possibilities and opportunities that the adaptive plasma therapeutic system might offer. We shall define such an adaptive system as a plasma device that is able to adjust the plasma composition to obtain optimal desirable outcomes through its interaction with cells and tissues. The efficacy of cold plasma in a pre-clinical model of various cancer types such as lung, bladder, breast, head, neck, brain and skin has been demonstrated. Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. Recently mechanism of plasma selectivity based on aquaporin hypothesis has been proposed. Aquaporins (AQPs) are the confirmed membrane channels of H2O2 and other large molecules. We have demonstrated that the anti-cancer capacity of plasma could be inhibited by silencing the expression of AQPs. Additional possible cell feedback mechanism was recently discovered. It is associated with production of reactive species during direct CAP treatment by cancer cells. Selective production of hydrogen peroxide by different cells can lead to adaptation of chemistry at the plasma-cell interface based on the cellular input. In particular we have found that the discharge voltage is an important factor affecting the ratio of reactive oxygen species to reactive nitrogen species in the gas phase and this correlates well with effect of hydrogen peroxide production by cells. This work was

  19. The role of adaptive immunity as an ecological filter on the gut microbiota in zebrafish.

    Science.gov (United States)

    Stagaman, Keaton; Burns, Adam R; Guillemin, Karen; Bohannan, Brendan Jm

    2017-07-01

    All animals live in intimate association with communities of microbes, collectively referred to as their microbiota. Certain host traits can influence which microbial taxa comprise the microbiota. One potentially important trait in vertebrate animals is the adaptive immune system, which has been hypothesized to act as an ecological filter, promoting the presence of some microbial taxa over others. Here we surveyed the intestinal microbiota of 68 wild-type zebrafish, with functional adaptive immunity, and 61 rag1 - zebrafish, lacking functional B- and T-cell receptors, to test the role of adaptive immunity as an ecological filter on the intestinal microbiota. In addition, we tested the robustness of adaptive immunity's filtering effects to host-host interaction by comparing the microbiota of fish populations segregated by genotype to those containing both genotypes. The presence of adaptive immunity individualized the gut microbiota and decreased the contributions of neutral processes to gut microbiota assembly. Although mixing genotypes led to increased phylogenetic diversity in each, there was no significant effect of adaptive immunity on gut microbiota composition in either housing condition. Interestingly, the most robust effect on microbiota composition was co-housing within a tank. In all, these results suggest that adaptive immunity has a role as an ecological filter of the zebrafish gut microbiota, but it can be overwhelmed by other factors, including transmission of microbes among hosts.

  20. High temperature resistant cermet and ceramic compositions

    Science.gov (United States)

    Phillips, W. M. (Inventor)

    1978-01-01

    Cermet compositions having high temperature oxidation resistance, high hardness and high abrasion and wear resistance, and particularly adapted for production of high temperature resistant cermet insulator bodies are presented. The compositions are comprised of a sintered body of particles of a high temperature resistant metal or metal alloy, preferably molybdenum or tungsten particles, dispersed in and bonded to a solid solution formed of aluminum oxide and silicon nitride, and particularly a ternary solid solution formed of a mixture of aluminum oxide, silicon nitride and aluminum nitride. Also disclosed are novel ceramic compositions comprising a sintered solid solution of aluminum oxide, silicon nitride and aluminum nitride.

  1. Keto-adaptation enhances exercise performance and body composition responses to training in endurance athletes.

    Science.gov (United States)

    McSwiney, Fionn T; Wardrop, Bruce; Hyde, Parker N; Lafountain, Richard A; Volek, Jeff S; Doyle, Lorna

    2018-04-01

    Low-carbohydrate diets have recently grown in popularity among endurance athletes, yet little is known about the long-term (>4wk) performance implications of consuming a low-carbohydrate high fat ketogenic diet (LCKD) in well-trained athletes. Twenty male endurance-trained athletes (age 33±11y, body mass 80±11kg; BMI 24.7±3.1kg/m 2 ) who habitually consumed a carbohydrate-based diet, self-selected into a high-carbohydrate (HC) group (n=11, %carbohydrate:protein:fat=65:14:20), or a LCKD group (n=9, 6:17:77). Both groups performed the same training intervention (endurance, strength and high intensity interval training (HIIT)). Prior to and following successful completion of 12-weeks of diet and training, participants had their body composition assessed, and completed a 100km time trial (TT), six second (SS) sprint, and a critical power test (CPT). During post-intervention testing the HC group consumed 30-60g/h carbohydrate, whereas the LCKD group consumed water, and electrolytes. The LCKD group experienced a significantly greater decrease in body mass (HC -0.8kg, LCKD -5.9kg; P=0.006, effect size (ES): 0.338) and percentage body fat percentage (HC -0.7%, LCKD -5.2%; P=0.008, ES: 0.346). Fasting serum beta-hydroxybutyrate (βHB) significantly increased from 0.1 at baseline to 0.5mmol/L in the LCKD group (P=0.011, ES: 0.403) in week 12. There was no significant change in performance of the 100km TT between groups (HC -1.13min·s, LCKD -4.07min·s, P=0.057, ES: 0.196). SS sprint peak power increased by 0.8 watts per kilogram bodyweight (w/kg) in the LCKD group, versus a -0.1w/kg reduction in the HC group (P=0.025, ES: 0.263). CPT peak power decreased by -0.7w/kg in the HC group, and increased by 1.4w/kg in the LCKD group (P=0.047, ES: 0.212). Fat oxidation in the LCKD group was significantly greater throughout the 100km TT. Compared to a HC comparison group, a 12-week period of keto-adaptation and exercise training, enhanced body composition, fat oxidation during

  2. Tracking of multiple objects with time-adjustable composite correlation filters

    Science.gov (United States)

    Ruchay, Alexey; Kober, Vitaly; Chernoskulov, Ilya

    2017-09-01

    An algorithm for tracking of multiple objects in video based on time-adjustable adaptive composite correlation filtering is proposed. For each frame a bank of composite correlation filters are designed in such a manner to provide invariance to pose, occlusion, clutter, and illumination changes. The filters are synthesized with the help of an iterative algorithm, which optimizes the discrimination capability for each object. The filters are adapted to the objects changes online using information from the current and past scene frames. Results obtained with the proposed algorithm using real-life scenes are presented and compared with those obtained with state-of-the-art tracking methods in terms of detection efficiency, tracking accuracy, and speed of processing.

  3. Follicular synchronization using transdermal estradiol patch and GnRH antagonists in the luteal phase; does it increase oocyte yield in poor responders to gonadotropin stimulation for in vitro fertilization (IVF)? A comparative study with microdose flare-up protocol.

    Science.gov (United States)

    Ata, Baris; Zeng, Xing; Son, Weon Y; Holzer, Hananel; Tan, Seang L

    2011-11-01

    The aim of this retrospective study was to compare the oocyte yield with the luteal estradiol patch (LPA) - GnRH antagonist and microdose (MD) flare-up protocols in anticipated poor responders. Fifty-seven women who underwent IVF treatment following stimulation with LPA or MD protocols at McGill Reproductive Centre were matched for age and markers of ovarian reserve. Numbers of oocytes collected (6 vs 7), mature oocytes collected (5 vs 5), and oocyte maturation rates (72% vs 74%) were similar. The numbers of good quality embryos available (2 vs 1) and embryos transferred (3 vs 3) were likewise similar. Embryo implantation rate of 16.7% and clinical pregnancy rate of 38.9% achieved in the LPA group were almost 50% higher than the corresponding figures at 10.3% and 22.2% in the MD group; however, the differences were not statistically significant (p > 0.05 for all comparisons). Although the results do not suggest an increased oocyte yield or follicular synchronization with the LPA protocol, the observed trend toward higher embryo implantation and clinical pregnancy rates requires further research.

  4. Two-year clinical comparison of a flowable-type nano-hybrid composite and a paste-type composite in posterior restoration.

    Science.gov (United States)

    Hirata-Tsuchiya, Shizu; Yoshii, Shinji; Ichimaru-Suematsu, Miki; Washio, Ayako; Saito, Noriko; Urata, Mariko; Hanada, Kaori; Morotomi, Takahiko; Kitamura, Chiaki

    2017-08-01

    The purpose of the present study was to compare the clinical efficacy between a flowable-type nano-hybrid composite and a paste-type composite for posterior restoration. Of 62 posterior teeth in 33 patients (mean age: 34.1 years), 31 were filled with a paste-type composite (Heliomolar [HM] group), and another 31 with a flowable nano-hybrid composite (MI FIL [MI] group). Clinical efficacy was evaluated at 2 years after the restoration. There were no differences for retention, surface texture deterioration, anatomical form change, deterioration of marginal adaptation, and secondary caries, while a statistical difference was found for marginal discoloration, which was significantly greater in the HM group (P < 0.05). Furthermore, color matching in the MI group was superior to that in the HM group immediately after the restoration throughout the study period. The present 2-year clinical evaluation of different composites showed that the flowable nano-hybrid composite could be an effective esthetic material for posterior restoration. © 2016 John Wiley & Sons Australia, Ltd.

  5. Large Neighborhood Search and Adaptive Randomized Decompositions for Flexible Jobshop Scheduling

    DEFF Research Database (Denmark)

    Pacino, Dario; Van Hentenryck, Pascal

    2011-01-01

    This paper considers a constraint-based scheduling approach to the flexible jobshop, a generalization of the traditional jobshop scheduling where activities have a choice of machines. It studies both large neighborhood (LNS) and adaptive randomized de- composition (ARD) schemes, using random...

  6. Durability-Based Design Criteria for a Chopped-Glass-Fiber Automotive Structural Composite; TOPICAL

    International Nuclear Information System (INIS)

    Battiste, R.L.; Corum, J.M.; Ren, W.; Ruggles, M.B.

    1999-01-01

    This report provides recommended durability-based design criteria for a chopped-glass-fiber reinforced polymeric composite for automotive structural applications. The criteria closely follow the framework of an earlier criteria document for a continuous-strand-mat (CSM) glass-fiber reference composite. Together these design criteria demonstrate a framework that can be adapted for future random-glass-fiber composites for automotive structural applications

  7. Prism adaptation does not alter configural processing of faces [v1; ref status: indexed, http://f1000r.es/1wk

    Directory of Open Access Journals (Sweden)

    Janet H. Bultitude

    2013-10-01

    Full Text Available Patients with hemispatial neglect (‘neglect’ following a brain lesion show difficulty responding or orienting to objects and events on the left side of space. Substantial evidence supports the use of a sensorimotor training technique called prism adaptation as a treatment for neglect. Reaching for visual targets viewed through prismatic lenses that induce a rightward shift in the visual image results in a leftward recalibration of reaching movements that is accompanied by a reduction of symptoms in patients with neglect. The understanding of prism adaptation has also been advanced through studies of healthy participants, in whom adaptation to leftward prismatic shifts results in temporary neglect-like performance. Interestingly, prism adaptation can also alter aspects of non-lateralised spatial attention. We previously demonstrated that prism adaptation alters the extent to which neglect patients and healthy participants process local features versus global configurations of visual stimuli. Since deficits in non-lateralised spatial attention are thought to contribute to the severity of neglect symptoms, it is possible that the effect of prism adaptation on these deficits contributes to its efficacy. This study examines the pervasiveness of the effects of prism adaptation on perception by examining the effect of prism adaptation on configural face processing using a composite face task. The composite face task is a persuasive demonstration of the automatic global-level processing of faces: the top and bottom halves of two familiar faces form a seemingly new, unknown face when viewed together. Participants identified the top or bottom halves of composite faces before and after prism adaptation. Sensorimotor adaptation was confirmed by significant pointing aftereffect, however there was no significant change in the extent to which the irrelevant face half interfered with processing. The results support the proposal that the therapeutic effects

  8. Flexible, wearable, and functional graphene-textile composites

    Science.gov (United States)

    Liu, Ying; Zhang, Kun-Ning; Zhang, Ying; Tao, Lu-Qi; Li, Yu-Xing; Wang, Dan-Yang; Yang, Yi; Ren, Tian-Ling

    2017-06-01

    In this paper, a flexible, wearable, and functional graphene-textile composite is demonstrated. Laser scribing technology is applied to fabricate a graphene film. The thin layer of polydimethylsiloxane is covered on the surface of the graphene-textile film evenly, which would improve the abrasive resistance of the film, enhance the ability to adapt to environmental changes, and extend the service life, while maintaining the device's excellent flexibility and comfort. The graphene-textile composite can achieve constant temperature heating by controlling the input voltage, detect the human movement, and perceive the human pulse signal. The composite presents great commercial prospects and a large value in the medical, daily wear, and other areas that are closely related to human lives.

  9. Nyx: Adaptive mesh, massively-parallel, cosmological simulation code

    Science.gov (United States)

    Almgren, Ann; Beckner, Vince; Friesen, Brian; Lukic, Zarija; Zhang, Weiqun

    2017-12-01

    Nyx code solves equations of compressible hydrodynamics on an adaptive grid hierarchy coupled with an N-body treatment of dark matter. The gas dynamics in Nyx use a finite volume methodology on an adaptive set of 3-D Eulerian grids; dark matter is represented as discrete particles moving under the influence of gravity. Particles are evolved via a particle-mesh method, using Cloud-in-Cell deposition/interpolation scheme. Both baryonic and dark matter contribute to the gravitational field. In addition, Nyx includes physics for accurately modeling the intergalactic medium; in optically thin limits and assuming ionization equilibrium, the code calculates heating and cooling processes of the primordial-composition gas in an ionizing ultraviolet background radiation field.

  10. Is adaptation. Truly an adaptation? Is adaptation. Truly an adaptation?

    Directory of Open Access Journals (Sweden)

    Thais Flores Nogueira Diniz

    2008-04-01

    Full Text Available The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition, joined with the study of recycling, remaking, and every form of retelling. The film deals with the attempt by the scriptwriter Charles Kaufman, cast by Nicholas Cage, to adapt/translate a non-fictional book to the cinema, but ends up with a kind of film which is by no means what it intended to be: a film of action in the model of Hollywood productions. During the process of creation, Charles and his twin brother, Donald, undergo a series of adventures involving some real persons from the world of film, the author and the protagonist of the book, all of them turning into fictional characters in the film. In the film, adaptation then signifies something different from itstraditional meaning. The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition

  11. Relationships between Endogenous Plasma Biomarkers of Constitutive Cytochrome P450 3A Activity and Single-Time-Point Oral Midazolam Microdose Phenotype in Healthy Subjects.

    Science.gov (United States)

    Woolsey, Sarah J; Beaton, Melanie D; Choi, Yun-Hee; Dresser, George K; Gryn, Steven E; Kim, Richard B; Tirona, Rommel G

    2016-04-01

    Due to high basal interindividual variation in cytochrome P450 3A (CYP3A) activity and susceptibility to drug interactions, there has been interest in the application of efficient probe drug phenotyping strategies, as well as endogenous biomarkers for assessment of in vivo CYP3A activity. The biomarkers 4β-hydroxycholesterol (4βHC) and 6β-hydroxycortisol (6βHCL) are sensitive to CYP3A induction and inhibition. However, their utility for the assessment of constitutive CYP3A activity remains uncertain. We investigated whether endogenous plasma biomarkers (4βHC and 6βHCL) are associated with basal CYP3A metabolic activity in healthy subjects assessed by a convenient single-time-point oral midazolam (MDZ) phenotyping strategy. Plasma 4βHC and 6βHCL metabolic ratios (MRs) were analysed in 51 healthy adult participants. CYP3A activity was determined after administration of an oral MDZ microdose (100 μg). Simple linear and multiple linear regression analyses were performed to assess relationships between MDZ oral clearance, biomarkers and subject covariates. Among study subjects, basal MDZ oral clearance, 4βHC and 6βHCL MRs ranged 6.5-, 10- and 13-fold, respectively. Participant age and alcohol consumption were negatively associated with MDZ oral clearance (p = 0.03 and p = 0.045, respectively), while weight and female sex were associated with lower plasma 4βHC MR (p = 0.0003 and p = 0.032, respectively). Neither 4βHC nor 6βHCL MRs were associated with MDZ oral clearance. Plasma 4βHC and 6βHCL MRs do not relate to MDZ single-time-point metabolic phenotype in the assessment of constitutive CYP3A activity among healthy individuals. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  12. Effects of Er, Cr:YSGG laser irradiation on external adaptation of restorations in caries-affected cavities

    International Nuclear Information System (INIS)

    Tonetto, Mateus Rodrigues; Saad, José Roberto Cury; Campos, Edson Alves de; Neto, Sizenando de Toledo Porto; De Andrade, Marcelo Ferrarezi; Bandéca, Matheus Coelho; Borges, Alvaro Henrique; Pinto, Shelon Cristina Souza

    2013-01-01

    This study evaluated the effect of Er,Cr:YSGG laser irradiation on the external adaptation of composite resin restorations in caries-affected cavities. Mixed class V cavity preparations were performed in 36 intact human third molars, in half of which caries was artificially induced. Both healthy and carious dentin were etched with 35% phosphoric acid (Ultradent Products Inc., South Jordan, Utah, USA), and the teeth were divided into three groups, i.e., (a) untreated etched dentin, (b) application of the Er, Cr:YSGG laser and (c) use of chlorhexidine as an adjunct in the bonding process. Restorations were fabricated with Z350 XT FiltekTM composite resin (3M ESPE) and subsequently the specimens were subjected to thermocycling to simulate artificial ageing. Quantitative analysis of external adaptation was performed by scanning electron microscopy in both healthy and affected dentin using epoxy resin replicas. It was concluded that the application of laser and chlorhexidine did not affect the percentages of marginal adaptation of class V restorations. Furthermore, thermocycling may influence adaptation values. (letter)

  13. Investigations on the magnetization behavior of magnetic composite particles

    Energy Technology Data Exchange (ETDEWEB)

    Eichholz, Christian [Process Research and Chemical Engineering, BASF SE, Ludwigshafen (Germany); Knoll, Johannes, E-mail: johannes.knoll@kit.edu [Institute of Mechanical Engineering and Mechanics, Karlsruhe Institute of Technology, Karlsruhe (Germany); Lerche, Dietmar [L.U.M. GmbH, Berlin (Germany); Nirschl, Hermann [Institute of Mechanical Engineering and Mechanics, Karlsruhe Institute of Technology, Karlsruhe (Germany)

    2014-11-15

    In life sciences the application of surface functionalized magnetic composite particles is establishing in diagnostics and in downstream processing of modern biotechnology. These magnetic composite particles consist of non-magnetic material, e.g. polystyrene, which serves as a matrix for the second magnetic component, usually colloidal magnetite. Because of the multitude of magnetic cores these magnetic beads show a complex magnetization behavior which cannot be described with the available approaches for homogeneous magnetic material. Therefore, in this work a new model for the magnetization behavior of magnetic composite particles is developed. By introducing an effective magnetization and considering an overall demagnetization factor the deviation of the demagnetization of homogeneously magnetized particles is taken into account. Calculated and experimental results show a good agreement which allows for the verification of the adapted model of particle magnetization. Besides, a newly developed magnetic analyzing centrifuge is used for the characterization of magnetic composite particle systems. The experimental results, also used for the model verification, give both, information about the magnetic properties and the interaction behavior of particle systems. By adding further components to the particle solution, such as salts or proteins, industrial relevant systems can be reconstructed. The analyzing tool can be used to adapt industrial processes without time-consuming preliminary tests with large samples in the process equipments. - Highlights: • New model for magnetizability calculation of magnetic composite particles. • New method for particle bulk characterization relating to their magnetizability. • Model verification due to experimental data.

  14. Investigations on the magnetization behavior of magnetic composite particles

    International Nuclear Information System (INIS)

    Eichholz, Christian; Knoll, Johannes; Lerche, Dietmar; Nirschl, Hermann

    2014-01-01

    In life sciences the application of surface functionalized magnetic composite particles is establishing in diagnostics and in downstream processing of modern biotechnology. These magnetic composite particles consist of non-magnetic material, e.g. polystyrene, which serves as a matrix for the second magnetic component, usually colloidal magnetite. Because of the multitude of magnetic cores these magnetic beads show a complex magnetization behavior which cannot be described with the available approaches for homogeneous magnetic material. Therefore, in this work a new model for the magnetization behavior of magnetic composite particles is developed. By introducing an effective magnetization and considering an overall demagnetization factor the deviation of the demagnetization of homogeneously magnetized particles is taken into account. Calculated and experimental results show a good agreement which allows for the verification of the adapted model of particle magnetization. Besides, a newly developed magnetic analyzing centrifuge is used for the characterization of magnetic composite particle systems. The experimental results, also used for the model verification, give both, information about the magnetic properties and the interaction behavior of particle systems. By adding further components to the particle solution, such as salts or proteins, industrial relevant systems can be reconstructed. The analyzing tool can be used to adapt industrial processes without time-consuming preliminary tests with large samples in the process equipments. - Highlights: • New model for magnetizability calculation of magnetic composite particles. • New method for particle bulk characterization relating to their magnetizability. • Model verification due to experimental data

  15. Fructan metabolism and changes in fructan composition during cold acclimation in perennial ryegrass

    DEFF Research Database (Denmark)

    Abeynayake, Shamila; Etzerodt, Thomas; Jonavičienė, Kristina

    2015-01-01

    . The ecotype ‘Falster’, adapted to cold climates, increased total fructan content and produced more fructans (DP˃7) in the roots than the variety ‘Veyo’, adapted to warmer climates suggesting that accumulation of fructans in roots, especially the high-DP fructans as an adaptive trait for plant recovery after......Perennial ryegrass (Lolium perenne L.) produces high levels of fructans as a mixture of oligomers with different degrees of polymerization (DP). The present study describes the analysis of the compositional changes in the full spectrum of fructan oligomers, fructan distribution between above ground...... biomass (top) and the roots, and the transcription of candidate genes involved in fructan metabolism during cold acclimation in perennial ryegrass variety ‘Veyo’ and ecotype ‘Falster’ from distinct geographical origins. We observed changes in fructan composition and induction of low-DP fructans...

  16. Laboratory evaluation of two x-ray baggage inspection systems

    International Nuclear Information System (INIS)

    Schellenbaum, R.L.

    1979-06-01

    The AS and E Micro-Dose X-ray Baggage Inspection System was designed for high-volume, detailed examination of packages at ultralow x-ray exposure levels. This system is used in airline terminals for the detection of weapons, bombs, and other contraband. It is also employed by security personnel in other facilities to search packages for contraband carried in and out of secured areas. The Micro-Dose system has a unique design concept which includes an Automatic Threat Alert System (ATA) and a zoom display presentation feature

  17. SEM Evaluation of Internal Adaptation of Bases and Liners under Composite Restorations

    Directory of Open Access Journals (Sweden)

    Dimitrios Dionysopoulos

    2014-04-01

    Full Text Available The aim of this study was to evaluate the interfacial microgaps generating between different materials and between materials and dentin after polymerization of the composite restorations, using SEM. Methods: The materials investigated were a composite, an adhesive, a RMGI, and a calcium hydroxide. Thirty third molars were selected and two circular class V cavities (5 mm × 3 mm for each tooth were made. The teeth were randomly assigned into six groups and restored with a combination of the materials. The specimens were subjected to thermocycling and each tooth was sectioned mesiodistally in two halves. Each half was sectioned along the longitudinal axis through the center of the restorations to obtain a slice of 2 mm. The specimens were examined under SEM. The interfaces between the liners, the liners and dentin, and between the liners and the composite were examined for microgaps. Results: The results showed that there was not any significant difference in the mean width of microgaps in the interfaces between Dycal-dentin and Vitrebond-dentin (p>0.05. However, the width of microgaps in the interfaces between dentin-Clearfil Tri-S Bond was significantly smaller (p<0.05. The use of Clearfil Tri-S Bond reduced the possibility of microgap formation between the bonded interface and the materials tested.

  18. Hybrid Decompositional Verification for Discovering Failures in Adaptive Flight Control Systems

    Science.gov (United States)

    Thompson, Sarah; Davies, Misty D.; Gundy-Burlet, Karen

    2010-01-01

    Adaptive flight control systems hold tremendous promise for maintaining the safety of a damaged aircraft and its passengers. However, most currently proposed adaptive control methodologies rely on online learning neural networks (OLNNs), which necessarily have the property that the controller is changing during the flight. These changes tend to be highly nonlinear, and difficult or impossible to analyze using standard techniques. In this paper, we approach the problem with a variant of compositional verification. The overall system is broken into components. Undesirable behavior is fed backwards through the system. Components which can be solved using formal methods techniques explicitly for the ranges of safe and unsafe input bounds are treated as white box components. The remaining black box components are analyzed with heuristic techniques that try to predict a range of component inputs that may lead to unsafe behavior. The composition of these component inputs throughout the system leads to overall system test vectors that may elucidate the undesirable behavior

  19. Material and Social Construction: A Framework for the Adaptation of Buildings

    Directory of Open Access Journals (Sweden)

    Jesse M. Keenan

    2014-12-01

    Full Text Available This article is a formulation of a framework for understanding the nature of change, particularly climate change, as it applies to the scale of a building. Through an exploration of various scientific and social scientific literutre, the article positions the concept of adaptation as the appropriate mode for understanding and managing change. Through the classification of a duality of material and social construction in the ontological composition of a building, various lines of thought relating to adaptive capacity and adaptive cycling within systems theory are appropriated within an integrated framework for adaptation. Specifically, it is theorized that as buildings as objects are developing greater capacities for intergrated operations and management through artificial intelligence, they will possess an ex ante capacity to autonomously adapt in dynamic relation to and with the ex post adaptation of owners and operators. It is argued that this top-down and bottom-up confluence of multi-scalar dynamic change is consistent with the prevailing theory of Panarchy applied in social-ecological systems theory. The article concludes with normative perspectives on the limitations of systems theory in architecture, future directions for research and an alternative positioning of professional practices.

  20. Cross-cultural adaptation, content validation, and reliability of the Nigerian Composite Lifestyle CVD Risk Factors Questionnaire for adolescents among Yoruba rural adolescents in Nigeria.

    Science.gov (United States)

    Odunaiya, Nse A; Louw, Quinette A; Grimmer, Karen

    2017-06-01

    Assessment of lifestyle risk factors must be culturally- and contextually relevant and available in local languages. This paper reports on a study which aimed to cross culturally adapt a composite lifestyle cardiovascular disease (CVD) risk factors questionnaire into an African language (Yoruba) and testing some of its psychometric properties such as content validity and test retest reliability in comparison to the original English version. This study utilized a cross sectional design. Translation of the English version of the questionnaire into Yoruba was undertaken using the guideline by Beaton et al. The translated instrument was presented to 21 rural adolescents to assess comprehensibility and clarity using a sample of convenience. A test retest reliability was conducted among 150 rural adolescents using a purposive sampling. Data was analyzed using intraclass correlation (ICC ) model 3, Cohen kappa statistics and prevalence rates. ICC ranged between 0.4-0.8. The Yoruba version was completed 15-20 minutes and was reported to be culturally appropriate and acceptable for rural Nigerian adolescents. The Yoruba translation of the Nigerian composite lifestyle risk factors questionnaire performs at least as well as the original English version in terms of content validity and reliability. It took a shorter time to complete therefore may be more relevant to rural adolescents.

  1. MgO by injection CVD

    International Nuclear Information System (INIS)

    Abrutis, A.; Kubilius, V.; Teiserkis, A.; Bigelyte, V.; Vengalis, B.; Jukna, A.; Butkute, R.

    1997-01-01

    Epitaxial YBa 2 Cu 3 O 7 layers with 45 in-plane orientation have been grown by injection CVD on MgO substrates polished off-axis to within 1.4-1.9 of the [100] direction. This new single-source CVD process is based on computer-controlled injection of precise microdoses of a metal-organic precursor solution into a CVD reactor. A wide range of solution compositions was tested to investigate compositional effects on phase purity, surface morphology, texturing and superconducting properties of the prepared films. The highest quality films with pure 45 texture had a smooth surface, zero resistance T c (R=0) of 88-89 K, and critical current density J c (77 K) above 10 6 A/cm 2 . (orig.) and critical current density J c (77 K) above 10 6 A/cm 2 . (orig.)

  2. Effects of low-dose recombinant human erythropoietin treatment on cognitive performance

    DEFF Research Database (Denmark)

    Viuff, Søren Lundgaard; Plenge, Ulla; Belhage, Bo

    2017-01-01

    , NUFI or self-reported results between the groups. CONCLUSIONS: In this small study, we found no significant effect of low-dose or micro-dose rhEpo on visual attention, cognitive performance in complex cognitive tasks or self-experienced cognitive performance compared with placebo. FUNDING: The Aase......INTRODUCTION: High-dose recombinant human erythropoietin (rhEpo) has been shown to improve cognitive performance in both healthy volunteers and in patients suffering from diseases affecting the brain. The aim of this study was to examine whether administration of low-dose and even micro-dose rh...

  3. Effects of low-dose recombinant human erythropoietin treatment on cognitive performance

    DEFF Research Database (Denmark)

    Viuff, Søren Lundgaard; Plenge, Ulla; Belhage, Bo

    2017-01-01

    -reported results between the groups. Conclusions: In this small study, we found no significant effect of low-dose or micro-dose rhEpo on visual attention, cognitive performance in complex cognitive tasks or self-experienced cognitive performance compared with placebo. Funding: The Aase and Ejnar Danielsen......Introduction: High-dose recombinant human erythropoietin (rhEpo) has been shown to improve cognitive performance in both healthy volunteers and in patients suffering from diseases affecting the brain. The aim of this study was to examine whether administration of low-dose and even micro-dose rh...

  4. Thermophilic Adaptation in Prokaryotes Is Constrained by Metabolic Costs of Proteostasis

    Science.gov (United States)

    Venev, Sergey V; Zeldovich, Konstantin B

    2018-01-01

    Abstract Prokaryotes evolved to thrive in an extremely diverse set of habitats, and their proteomes bear signatures of environmental conditions. Although correlations between amino acid usage and environmental temperature are well-documented, understanding of the mechanisms of thermal adaptation remains incomplete. Here, we couple the energetic costs of protein folding and protein homeostasis to build a microscopic model explaining both the overall amino acid composition and its temperature trends. Low biosynthesis costs lead to low diversity of physical interactions between amino acid residues, which in turn makes proteins less stable and drives up chaperone activity to maintain appropriate levels of folded, functional proteins. Assuming that the cost of chaperone activity is proportional to the fraction of unfolded client proteins, we simulated thermal adaptation of model proteins subject to minimization of the total cost of amino acid synthesis and chaperone activity. For the first time, we predicted both the proteome-average amino acid abundances and their temperature trends simultaneously, and found strong correlations between model predictions and 402 genomes of bacteria and archaea. The energetic constraint on protein evolution is more apparent in highly expressed proteins, selected by codon adaptation index. We found that in bacteria, highly expressed proteins are similar in composition to thermophilic ones, whereas in archaea no correlation between predicted expression level and thermostability was observed. At the same time, thermal adaptations of highly expressed proteins in bacteria and archaea are nearly identical, suggesting that universal energetic constraints prevail over the phylogenetic differences between these domains of life. PMID:29106597

  5. Parametric recursive system identification and self-adaptive modeling of the human energy metabolism for adaptive control of fat weight.

    Science.gov (United States)

    Őri, Zsolt P

    2017-05-01

    A mathematical model has been developed to facilitate indirect measurements of difficult to measure variables of the human energy metabolism on a daily basis. The model performs recursive system identification of the parameters of the metabolic model of the human energy metabolism using the law of conservation of energy and principle of indirect calorimetry. Self-adaptive models of the utilized energy intake prediction, macronutrient oxidation rates, and daily body composition changes were created utilizing Kalman filter and the nominal trajectory methods. The accuracy of the models was tested in a simulation study utilizing data from the Minnesota starvation and overfeeding study. With biweekly macronutrient intake measurements, the average prediction error of the utilized carbohydrate intake was -23.2 ± 53.8 kcal/day, fat intake was 11.0 ± 72.3 kcal/day, and protein was 3.7 ± 16.3 kcal/day. The fat and fat-free mass changes were estimated with an error of 0.44 ± 1.16 g/day for fat and -2.6 ± 64.98 g/day for fat-free mass. The daily metabolized macronutrient energy intake and/or daily macronutrient oxidation rate and the daily body composition change from directly measured serial data are optimally predicted with a self-adaptive model with Kalman filter that uses recursive system identification.

  6. The adaptive use of recognition in group decision making.

    Science.gov (United States)

    Kämmer, Juliane E; Gaissmaier, Wolfgang; Reimer, Torsten; Schermuly, Carsten C

    2014-06-01

    Applying the framework of ecological rationality, the authors studied the adaptivity of group decision making. In detail, they investigated whether groups apply decision strategies conditional on their composition in terms of task-relevant features. The authors focused on the recognition heuristic, so the task-relevant features were the validity of the group members' recognition and knowledge, which influenced the potential performance of group strategies. Forty-three three-member groups performed an inference task in which they had to infer which of two German companies had the higher market capitalization. Results based on the choice data support the hypothesis that groups adaptively apply the strategy that leads to the highest theoretically achievable performance. Time constraints had no effect on strategy use but did have an effect on the proportions of different types of arguments. Possible mechanisms underlying the adaptive use of recognition in group decision making are discussed. © 2014 Cognitive Science Society, Inc.

  7. Review of natural fiber composites

    Science.gov (United States)

    Rohan, T.; Tushar, B.; T, Mahesha G.

    2018-02-01

    Development of new alternative materials to the existing traditional metals, alloys and synthetic materials is the new buzz in recent research activities at the academic and industrial level taking place all over the world. Earning carbon credits by minimizing the atmospheric pollution is getting an increase in attention by industries. One small step to conserve the atmosphere around us is to use natural resources in making fully bio degradable or partially bio degradable composite materials. Such prepared alternative materials can find applications in interior housing, automotive, marine, domestic, and other applications. Composites made by using appropriate natural fibers as reinforcements is a possibility that ensures such a reality as they can be well received in multiple disciplines of engineering. Results published from various research activities illustrates that natural fiber composites can successfully be adapted for non-structural, moderate load bearing indoor applications. Further, the few deficiencies in the natural fibers can be overcome by subjecting them to morphological changes by various physical or chemical treatment methods. The overall objective of this paper is to provide a comprehensive overview of the property profiles of Natural Fiber Composites.

  8. “Protective Bystander Effects Simulated with the State-Vector Model”—HeLa x Skin Exposure to 137Cs Not Protective Bystander Response But Mammogram and Diagnostic X-Rays Are

    Science.gov (United States)

    Leonard, Bobby E.

    2008-01-01

    The recent Dose Response journal article “Protective Bystander Effects Simulated with the State-Vector Model” (Schollnberger and Eckl 2007) identified the suppressive (below natural occurring, zero primer dose, spontaneous level) dose response for HeLa x skin exposure to 137Cs gamma rays (Redpath et al 2001) as a protective Bystander Effect (BE) behavior. I had previously analyzed the Redpath et al (2001) data with a Microdose Model and conclusively showed that the suppressive response was from Adaptive Response (AR) radio-protection (Leonard 2005, 2007a). The significance of my microdose analysis has been that low LET radiation induced single (i.e. only one) charged particle traversals through a cell can initiate a Poisson distributed activation of AR radio-protection. The purpose of this correspondence is to clarify the distinctions relative to the BE and the AR behaviors for the Redpath groups 137Cs data, show conversely however that the Redpath group data for mammography (Ko et al 2004) and diagnostic (Redpath et al 2003) X-rays do conclusively reflect protective bystander behavior and also herein emphasize the need for radio-biologist to apply microdosimetry in planning and analyzing their experiments for BE and AR. Whether we are adamantly pro-LNT, adamantly anti-LNT or, like most of us, just simple scientists searching for the truth in radio-biology, it is important that we accurately identify our results, especially when related to the LNT hypothesis controversy. PMID:18846260

  9. Hybrid Adaptive Flight Control with Model Inversion Adaptation

    Science.gov (United States)

    Nguyen, Nhan

    2011-01-01

    This study investigates a hybrid adaptive flight control method as a design possibility for a flight control system that can enable an effective adaptation strategy to deal with off-nominal flight conditions. The hybrid adaptive control blends both direct and indirect adaptive control in a model inversion flight control architecture. The blending of both direct and indirect adaptive control provides a much more flexible and effective adaptive flight control architecture than that with either direct or indirect adaptive control alone. The indirect adaptive control is used to update the model inversion controller by an on-line parameter estimation of uncertain plant dynamics based on two methods. The first parameter estimation method is an indirect adaptive law based on the Lyapunov theory, and the second method is a recursive least-squares indirect adaptive law. The model inversion controller is therefore made to adapt to changes in the plant dynamics due to uncertainty. As a result, the modeling error is reduced that directly leads to a decrease in the tracking error. In conjunction with the indirect adaptive control that updates the model inversion controller, a direct adaptive control is implemented as an augmented command to further reduce any residual tracking error that is not entirely eliminated by the indirect adaptive control.

  10. Influence of artificial aging in marginal adaptation of mixed class V cavities.

    Science.gov (United States)

    Tonetto, Mateus Rodrigues; Bandéca, Matheus Coelho; Barud, Hélida Gomes de Oliveira; Pinto, Shelon Cristina Souza; Lima, Darlon Martins; Borges, Alvaro Henrique; de Campos, Edson Alves; de Andrade, Marcelo Ferrarezi

    2013-03-01

    The aim of this study was to investigate whether the artificial aging by thermal cycling had influenced the marginal adaptation of class V restorations with/without chlorhexidine application in the bond process. Twelve intact human third molars were used. Class V cavity preparations were performed on the buccal surface and the teeth received 35% phosphoric acid-etching procedure (Ultradent Products Inc., South Jordan, Utah, USA). Subsequently, the samples were divided in two groups: Untreated acid-etched dentin and chlorhexidine application as an adjunct in the bond process. The adhesive Single Bond 2 (3M ESPE, St. Paul, MN, USA) was used after 2% chlorhexidine application, and the restorations were performed with Filtek™ Z350 XT (3M ESPE) composite resin. The specimens were submitted to artificial aging by thermal cycling with 3,000 cycles. Analyzes were performed on scanning electron microscopy using replicas of marginal adaptation in percentage of continuous margin before and after the artificial aging. The data were analyzed by paired test and the results showed statistically significant differences in the percentage of continuous margin with/without chlorhexidine treatment before and after thermal cycling. This study concluded that the artificial aging by thermal cycling influenced the marginal adaptation of mixed class V composite restorations.

  11. Adaptive Lighting Design – Staged Experiences of Light

    DEFF Research Database (Denmark)

    Søndergaard, Karin; Petersen, Kjell Yngve

    2015-01-01

    involved in the negotiations of how the lighting design unfolds. Each installation stages a specified place, where participants perform their own experiences of being and moving in dynamically changing lighting settings. Through investigative actions participants test the ways that the lighting...... compositions influence their ability to orient themselves within the geography of the space and how the balances in light colours and luminous intensities affect their experience of directionality, distances, and scales. In short, the experience of being present in the space as well as one’s experience......Adaptive Lighting Design – Staged Experiences of Light The two installations, White Cube and White Box, enable experience-based studies as a form of perceptual activity, wherein lighting conditions are examined in a dialectical exchange between the system and the people participating. Adaptive...

  12. Building a Context World for Dynamic Service Composition

    DEFF Research Database (Denmark)

    Yu, Lian; Glenstrup, Arne John; Su, Shuang

    Dynamic service composition requires responding and adapting to changes in the computing environment when orchestrating existing services into one or more new services that fit better to a composite application. This paper abstracts the changes of the environment as a context world to store the p...... and capabilities of goals and services in a concise and editable manner. Goal-driven and planning techniques are used to dynamically implement the service composition according to the domain knowledge and facts in the context world....... the physical contexts of the computing environment, user profiles and computed results of services as well. We use ontology techniques to model the domain concepts of application contexts. Context Condition/Effect Description Language is designed to describe the dynamic semantics of the requirements...

  13. Marginal integrity of resin composite restorations restored with PPD initiatorcontaining resin composite cured by QTH, monowave and polywave LED units.

    Science.gov (United States)

    Bortolotto, Tissiana; Betancourt, Francisco; Krejci, Ivo

    2016-12-01

    This study evaluated the influence of curing devices on marginal adaptation of cavities restored with self-etching adhesive containing CQ and PPD initiators and hybrid composite. Twenty-four class V (3 groups, n=8) with margins located on enamel and dentin were restored with Clearfil S3 Bond and Clearfil APX PLT, light-cured with a monowave LED, multiwave LED and halogen light-curing unit (LCU). Marginal adaptation was evaluated with SEM before/after thermo-mechanical loading (TML). On enamel, significantly lower % continuous margins (74.5±12.6) were found in group cured by multiwave LED when compared to monowave LED (87.6±9.5) and halogen LCU (94.4±9.1). The presence of enamel and composite fractures was significantly higher in the group light-cured with multiwave LED, probably due to an increased materials' friability resulted from an improved degree of cure. The clinician should aware that due to a distinct activation of both initiators, marginal quality may be influenced on the long-term.

  14. Adaptation.

    Science.gov (United States)

    Broom, Donald M

    2006-01-01

    The term adaptation is used in biology in three different ways. It may refer to changes which occur at the cell and organ level, or at the individual level, or at the level of gene action and evolutionary processes. Adaptation by cells, especially nerve cells helps in: communication within the body, the distinguishing of stimuli, the avoidance of overload and the conservation of energy. The time course and complexity of these mechanisms varies. Adaptive characters of organisms, including adaptive behaviours, increase fitness so this adaptation is evolutionary. The major part of this paper concerns adaptation by individuals and its relationships to welfare. In complex animals, feed forward control is widely used. Individuals predict problems and adapt by acting before the environmental effect is substantial. Much of adaptation involves brain control and animals have a set of needs, located in the brain and acting largely via motivational mechanisms, to regulate life. Needs may be for resources but are also for actions and stimuli which are part of the mechanism which has evolved to obtain the resources. Hence pigs do not just need food but need to be able to carry out actions like rooting in earth or manipulating materials which are part of foraging behaviour. The welfare of an individual is its state as regards its attempts to cope with its environment. This state includes various adaptive mechanisms including feelings and those which cope with disease. The part of welfare which is concerned with coping with pathology is health. Disease, which implies some significant effect of pathology, always results in poor welfare. Welfare varies over a range from very good, when adaptation is effective and there are feelings of pleasure or contentment, to very poor. A key point concerning the concept of individual adaptation in relation to welfare is that welfare may be good or poor while adaptation is occurring. Some adaptation is very easy and energetically cheap and

  15. Forest management for mitigation and adaptation: insights from long-term silvicultural experiments

    Science.gov (United States)

    Anthony W. D' Amato; John B. Bradford; Shawn Fraver; Brian J. Palik

    2011-01-01

    Developing management strategies for addressing global climate change has become an increasingly important issue influencing forest management around the globe. Currently, management approaches are being proposed that intend to (1) mitigate climate change by enhancing forest carbon stores and (2) foster adaptation by maintaining compositionally and structurally complex...

  16. The role of tetraether lipid composition in the adaptation of thermophilic archaea to acidity.

    Science.gov (United States)

    Boyd, Eric S; Hamilton, Trinity L; Wang, Jinxiang; He, Liu; Zhang, Chuanlun L

    2013-01-01

    Diether and tetraether lipids are fundamental components of the archaeal cell membrane. Archaea adjust the degree of tetraether lipid cyclization in order to maintain functional membranes and cellular homeostasis when confronted with pH and/or thermal stress. Thus, the ability to adjust tetraether lipid composition likely represents a critical phenotypic trait that enabled archaeal diversification into environments characterized by extremes in pH and/or temperature. Here we assess the relationship between geochemical variation, core- and polar-isoprenoid glycerol dibiphytanyl glycerol tetraether (C-iGDGT and P-iGDGT, respectively) lipid composition, and archaeal 16S rRNA gene diversity and abundance in 27 geothermal springs in Yellowstone National Park, Wyoming. The composition and abundance of C-iGDGT and P-iGDGT lipids recovered from geothermal ecosystems were distinct from surrounding soils, indicating that they are synthesized endogenously. With the exception of GDGT-0 (no cyclopentyl rings), the abundances of individual C-iGDGT and P-iGDGT lipids were significantly correlated. The abundance of a number of individual tetraether lipids varied positively with the relative abundance of individual 16S rRNA gene sequences, most notably crenarchaeol in both the core and polar GDGT fraction and sequences closely affiliated with Candidatus Nitrosocaldus yellowstonii. This finding supports the proposal that crenarchaeol is a biomarker for nitrifying archaea. Variation in the degree of cyclization of C- and P-iGDGT lipids recovered from geothermal mats and sediments could best be explained by variation in spring pH, with lipids from acidic environments tending to have, on average, more internal cyclic rings than those from higher pH ecosystems. Likewise, variation in the phylogenetic composition of archaeal 16S rRNA genes could best be explained by spring pH. In turn, the phylogenetic similarity of archaeal 16S rRNA genes was significantly correlated with the similarity

  17. The Role of Tetraether Lipid Composition in the Adaptation of Thermophilic Archaea to Acidity

    Science.gov (United States)

    Boyd, Eric S.; Hamilton, Trinity L.; Wang, Jinxiang; He, Liu; Zhang, Chuanlun L.

    2013-01-01

    Diether and tetraether lipids are fundamental components of the archaeal cell membrane. Archaea adjust the degree of tetraether lipid cyclization in order to maintain functional membranes and cellular homeostasis when confronted with pH and/or thermal stress. Thus, the ability to adjust tetraether lipid composition likely represents a critical phenotypic trait that enabled archaeal diversification into environments characterized by extremes in pH and/or temperature. Here we assess the relationship between geochemical variation, core- and polar-isoprenoid glycerol dibiphytanyl glycerol tetraether (C-iGDGT and P-iGDGT, respectively) lipid composition, and archaeal 16S rRNA gene diversity and abundance in 27 geothermal springs in Yellowstone National Park, Wyoming. The composition and abundance of C-iGDGT and P-iGDGT lipids recovered from geothermal ecosystems were distinct from surrounding soils, indicating that they are synthesized endogenously. With the exception of GDGT-0 (no cyclopentyl rings), the abundances of individual C-iGDGT and P-iGDGT lipids were significantly correlated. The abundance of a number of individual tetraether lipids varied positively with the relative abundance of individual 16S rRNA gene sequences, most notably crenarchaeol in both the core and polar GDGT fraction and sequences closely affiliated with Candidatus Nitrosocaldus yellowstonii. This finding supports the proposal that crenarchaeol is a biomarker for nitrifying archaea. Variation in the degree of cyclization of C- and P-iGDGT lipids recovered from geothermal mats and sediments could best be explained by variation in spring pH, with lipids from acidic environments tending to have, on average, more internal cyclic rings than those from higher pH ecosystems. Likewise, variation in the phylogenetic composition of archaeal 16S rRNA genes could best be explained by spring pH. In turn, the phylogenetic similarity of archaeal 16S rRNA genes was significantly correlated with the similarity

  18. Beyond cool: adapting upland streams for climate change using riparian woodlands.

    Science.gov (United States)

    Thomas, Stephen M; Griffiths, Siân W; Ormerod, Steve J

    2016-01-01

    Managed adaptation could reduce the risks of climate change to the world's ecosystems, but there have been surprisingly few practical evaluations of the options available. For example, riparian woodland is advocated widely as shade to reduce warming in temperate streams, but few studies have considered collateral effects on species composition or ecosystem functions. Here, we use cross-sectional analyses at two scales (region and within streams) to investigate whether four types of riparian management, including those proposed to reduce potential climate change impacts, might also affect the composition, functional character, dynamics and energetic resourcing of macroinvertebrates in upland Welsh streams (UK). Riparian land use across the region had only small effects on invertebrate taxonomic composition, while stable isotope data showed how energetic resources assimilated by macroinvertebrates in all functional guilds were split roughly 50:50 between terrestrial and aquatic origins irrespective of riparian management. Nevertheless, streams draining the most extensive deciduous woodland had the greatest stocks of coarse particulate matter (CPOM) and greater numbers of 'shredding' detritivores. Stream-scale investigations showed that macroinvertebrate biomass in deciduous woodland streams was around twice that in moorland streams, and lowest of all in streams draining non-native conifers. The unexpected absence of contrasting terrestrial signals in the isotopic data implies that factors other than local land use affect the relative incorporation of allochthonous subsidies into riverine food webs. Nevertheless, our results reveal how planting deciduous riparian trees along temperate headwaters as an adaptation to climate change can modify macroinvertebrate function, increase biomass and potentially enhance resilience by increasing basal resources where cover is extensive (>60 m riparian width). We advocate greater urgency in efforts to understand the ecosystem

  19. Unique biochemical and mineral composition of whale ear bones.

    Science.gov (United States)

    Kim, Sora L; Thewissen, J G M; Churchill, Morgan M; Suydam, Robert S; Ketten, Darlene R; Clementz, Mark T

    2014-01-01

    Abstract Cetaceans are obligate aquatic mammals derived from terrestrial artiodactyls. The defining characteristic of cetaceans is a thick and dense lip (pachyosteosclerotic involucrum) of an ear bone (the tympanic). This unique feature is absent in modern terrestrial artiodactyls and is suggested to be important in underwater hearing. Here, we investigate the mineralogical and biochemical properties of the involucrum, as these may hold clues to the aquatic adaptations of cetaceans. We compared bioapatites (enamel, dentine, cementum, and skeletal bone) of cetaceans with those of terrestrial artiodactyls and pachyosteosclerotic ribs of manatees (Sirenia). We investigated organic, carbonate, and mineral composition as well as crystal size and crystallinity index. In all studied variables, bioapatites of the cetacean involucrum were intermediate in composition and structure between those of tooth enamel on the one hand and those of dentine, cementum, and skeletal bone on the other. We also studied the amino acid composition of the cetacean involucrum relative to that of other skeletal bone. The central involucrum had low glycine and hydroxyproline concentrations but high concentrations of nonessential amino acids, unlike most bone samples but similar to the tympanic of hippos and the (pachyosteosclerotic) ribs of manatees. These amino acid results are evidence of rapid bone development. We hypothesize that the mineralogical and amino acid composition of cetacean bullae differs from that of other bone because of (1) functional modifications for underwater sound reception and (2) structural adaptations related to rapid ossification.

  20. Adaptive Rationality, Adaptive Behavior and Institutions

    Directory of Open Access Journals (Sweden)

    Volchik Vyacheslav, V.

    2015-12-01

    Full Text Available The economic literature focused on understanding decision-making and choice processes reveals a vast collection of approaches to human rationality. Theorists’ attention has moved from absolutely rational, utility-maximizing individuals to boundedly rational and adaptive ones. A number of economists have criticized the concepts of adaptive rationality and adaptive behavior. One of the recent trends in the economic literature is to consider humans irrational. This paper offers an approach which examines adaptive behavior in the context of existing institutions and constantly changing institutional environment. It is assumed that adaptive behavior is a process of evolutionary adjustment to fundamental uncertainty. We emphasize the importance of actors’ engagement in trial and error learning, since if they are involved in this process, they obtain experience and are able to adapt to existing and new institutions. The paper aims at identifying relevant institutions, adaptive mechanisms, informal working rules and practices that influence actors’ behavior in the field of Higher Education in Russia (Rostov Region education services market has been taken as an example. The paper emphasizes the application of qualitative interpretative methods (interviews and discourse analysis in examining actors’ behavior.

  1. Quantitation of anacetrapib, stable-isotope labeled-anacetrapib (microdose), and four metabolites in human plasma using liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Chavez-Eng, C M; Lutz, R W; Li, H; Goykhman, D; Bateman, K P; Woolf, E

    2016-02-01

    An ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of (4S,5R)-5-[3,5-bis (trifluoromethyl)phenyl]-3-{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl] methyl}-4-methyl-1,3-oxazolidin-2-one (anacetrapib, I) and [(13)C5(15)N]-anacetrapib, II in human plasma has been developed to support a clinical study to determine the absolute bioavailability of I. The analytes and the stable-isotope labeled internal standard ([(13)C7(15)N(2)H7]-anacetrapib, III) were extracted from 100μL of human plasma by liquid-liquid extraction using 20/80 isopropyl alcohol/hexane (v/v). The chromatographic separation of the analytes was achieved using Waters BEH Shield RP 18 (50×2.1mm×1.7μm) column and mobile phase gradient of 0.1% formic acid in water (Solvent A) and 0.1% formic acid in acetonitrile (Solvent B) at 0.6mL/min flow rate. The MS/MS detection was performed on AB Sciex 5000 or AB 5500 in positive electrospray ionization mode, operated in selected reaction monitoring mode. The assay was validated in the concentration range 1-2000ng/mL for I; and a lower curve range, 0.025-50ng/mL for II. In addition to the absolute bioavailability determination, it was desired to better elucidate the pharmacokinetic behavior of several hydroxylated metabolites of I. Toward this end, two exploratory assays for the hydroxy metabolites of I were qualified in the concentration range 0.5-500ng/mL. All metabolites were separated on a Supelco Ascentis Express Phenyl-Hexyl (50×2.1mm, 2.7μm) column. Metabolite M4 was analyzed in the negative mode with a mobile phase consisting of a gradient mixture of water (A) and acetonitrile (B). The other three metabolites, M1-M3 were analyzed in the positive mode using a mobile phase gradient of water with 0.1% formic acid (A) and acetonitrile with 0.1% formic acid (B). The assays were utilized to support a clinical study in which a microdosing approach was used to

  2. A novel double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]tofogliflozin after oral administration and concomitant intravenous microdose administration of [13C]tofogliflozin in humans.

    Science.gov (United States)

    Schwab, Dietmar; Portron, Agnes; Backholer, Zoe; Lausecker, Berthold; Kawashima, Kosuke

    2013-06-01

    Human mass balance studies and the assessment of absolute oral bioavailability (F) are usually assessed in separate studies. Intravenous microdose administration of an isotope tracer concomitant to an unlabeled oral dose is an emerging technique to assess F. We report a novel double-tracer approach implemented for tofogliflozin combining oral administration of a radiolabel tracer with concomitant intravenous administration of a stable isotope tracer. Tofogliflozin is a potent and selective sodium/glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus currently in clinical development. The objectives of the present study were to assess the systemic exposure of major circulating metabolites, excretion balance, F and contribution of renal clearance (CLR) to total clearance (CL) of tofogliflozin in healthy subjects within one study applying a novel double-tracer technique. Six healthy male subjects received 20 mg [(12)C/(14)C]tofogliflozin (3.73 MBq) orally and a concomitant microdose of 0.1 mg [(13)C]tofogliflozin intravenously. Pharmacokinetics of tofogliflozin were determined for the oral and intravenous route; the pharmacokinetics of the metabolites M1 and M5 were determined for the oral route. Quantification of [(12)C]tofogliflozin in plasma and urine and [(13)C]tofogliflozin in plasma was performed by selective LC-MS/MS methods. For the pre-selected metabolites of tofogliflozin, M1 and M5, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to plasma and urine samples. Total radioactivity was assessed in plasma, urine and feces. Pharmacokinetic analysis was conducted by non-compartmental methods. The pharmacokinetics of tofogliflozin in healthy subjects were characterized by an F of 97.5 ± 12.3 %, CL of 10.0 ± 1.3 l/h and volume of distribution at steady-state (V(ss)) of 50.6 ± 6.7 l. The main route of elimination of total drug-related material was by excretion into urine (77.0 ± 4.1 % of the dose). The

  3. Carbon Nanotube Enhanced Aerospace Composite Materials A New Generation of Multifunctional Hybrid Structural Composites

    CERN Document Server

    Kostopoulos, V

    2013-01-01

    The well documented increase in the use of high performance composites as structural materials in aerospace components is continuously raising the demands in terms of dynamic performance, structural integrity, reliable life monitoring systems and adaptive actuating abilities. Current technologies address the above issues separately; material property tailoring and custom design practices aim to the enhancement of dynamic and damage tolerance characteristics, whereas life monitoring and actuation is performed with embedded sensors that may be detrimental to the structural integrity of the component. This publication explores the unique properties of carbon nanotubes (CNT) as an additive in the matrix of Fibre Reinforced Plastics (FRP), for producing structural composites with improved mechanical performance as well as sensing/actuating capabilities. The successful combination of the CNT properties and existing sensing actuating technologies leads to the realization of a multifunctional FRP structure. The curre...

  4. Robust Optimal Adaptive Control Method with Large Adaptive Gain

    Science.gov (United States)

    Nguyen, Nhan T.

    2009-01-01

    In the presence of large uncertainties, a control system needs to be able to adapt rapidly to regain performance. Fast adaptation is referred to the implementation of adaptive control with a large adaptive gain to reduce the tracking error rapidly. However, a large adaptive gain can lead to high-frequency oscillations which can adversely affect robustness of an adaptive control law. A new adaptive control modification is presented that can achieve robust adaptation with a large adaptive gain without incurring high-frequency oscillations as with the standard model-reference adaptive control. The modification is based on the minimization of the Y2 norm of the tracking error, which is formulated as an optimal control problem. The optimality condition is used to derive the modification using the gradient method. The optimal control modification results in a stable adaptation and allows a large adaptive gain to be used for better tracking while providing sufficient stability robustness. Simulations were conducted for a damaged generic transport aircraft with both standard adaptive control and the adaptive optimal control modification technique. The results demonstrate the effectiveness of the proposed modification in tracking a reference model while maintaining a sufficient time delay margin.

  5. Spectroscopic analyses of chemical adaptation processes within microalgal biomass in response to changing environments

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, Frank, E-mail: fvogt@utk.edu; White, Lauren

    2015-03-31

    Highlights: • Microalgae transform large quantities of inorganics into biomass. • Microalgae interact with their growing environment and adapt their chemical composition. • Sequestration capabilities are dependent on cells’ chemical environments. • We develop a chemometric hard-modeling to describe these chemical adaptation dynamics. • This methodology will enable studies of microalgal compound sequestration. - Abstract: Via photosynthesis, marine phytoplankton transforms large quantities of inorganic compounds into biomass. This has considerable environmental impacts as microalgae contribute for instance to counter-balancing anthropogenic releases of the greenhouse gas CO{sub 2}. On the other hand, high concentrations of nitrogen compounds in an ecosystem can lead to harmful algae blooms. In previous investigations it was found that the chemical composition of microalgal biomass is strongly dependent on the nutrient availability. Therefore, it is expected that algae’s sequestration capabilities and productivity are also determined by the cells’ chemical environments. For investigating this hypothesis, novel analytical methodologies are required which are capable of monitoring live cells exposed to chemically shifting environments followed by chemometric modeling of their chemical adaptation dynamics. FTIR-ATR experiments have been developed for acquiring spectroscopic time series of live Dunaliella parva cultures adapting to different nutrient situations. Comparing experimental data from acclimated cultures to those exposed to a chemically shifted nutrient situation reveals insights in which analyte groups participate in modifications of microalgal biomass and on what time scales. For a chemometric description of these processes, a data model has been deduced which explains the chemical adaptation dynamics explicitly rather than empirically. First results show that this approach is feasible and derives information about the chemical biomass

  6. Spectroscopic analyses of chemical adaptation processes within microalgal biomass in response to changing environments

    International Nuclear Information System (INIS)

    Vogt, Frank; White, Lauren

    2015-01-01

    Highlights: • Microalgae transform large quantities of inorganics into biomass. • Microalgae interact with their growing environment and adapt their chemical composition. • Sequestration capabilities are dependent on cells’ chemical environments. • We develop a chemometric hard-modeling to describe these chemical adaptation dynamics. • This methodology will enable studies of microalgal compound sequestration. - Abstract: Via photosynthesis, marine phytoplankton transforms large quantities of inorganic compounds into biomass. This has considerable environmental impacts as microalgae contribute for instance to counter-balancing anthropogenic releases of the greenhouse gas CO 2 . On the other hand, high concentrations of nitrogen compounds in an ecosystem can lead to harmful algae blooms. In previous investigations it was found that the chemical composition of microalgal biomass is strongly dependent on the nutrient availability. Therefore, it is expected that algae’s sequestration capabilities and productivity are also determined by the cells’ chemical environments. For investigating this hypothesis, novel analytical methodologies are required which are capable of monitoring live cells exposed to chemically shifting environments followed by chemometric modeling of their chemical adaptation dynamics. FTIR-ATR experiments have been developed for acquiring spectroscopic time series of live Dunaliella parva cultures adapting to different nutrient situations. Comparing experimental data from acclimated cultures to those exposed to a chemically shifted nutrient situation reveals insights in which analyte groups participate in modifications of microalgal biomass and on what time scales. For a chemometric description of these processes, a data model has been deduced which explains the chemical adaptation dynamics explicitly rather than empirically. First results show that this approach is feasible and derives information about the chemical biomass adaptations

  7. Composition and characteristics of Libyan flora

    Directory of Open Access Journals (Sweden)

    Ying Feng

    2013-01-01

    Full Text Available The composition, life forms and the distribution of plants in Libya were studied. The results show that in Libya there are 2103 species that belong to 856 genera and 155 families. The distribution among Libyan seed plants was characterized by a high proportion of herbs (annual to perennial, unlike the low number of woody (tree and shrub species; these have an important influence on the structure of floral composition. The geographic element of the flora was predominantly tropical and Mediterranean. The local plants belong to representative tropical desert flora. The presence and distribution characteristics of flora in Libya show that climate, environmental condition, ecological amplitude and adaptive capacity of the plants have a determinative influence on the floristic stock in the area studies.

  8. Learning to Adapt. Organisational Adaptation to Climate Change Impacts

    International Nuclear Information System (INIS)

    Berkhout, F.; Hertin, J.; Gann, D.M.

    2006-01-01

    Analysis of human adaptation to climate change should be based on realistic models of adaptive behaviour at the level of organisations and individuals. The paper sets out a framework for analysing adaptation to the direct and indirect impacts of climate change in business organisations with new evidence presented from empirical research into adaptation in nine case-study companies. It argues that adaptation to climate change has many similarities with processes of organisational learning. The paper suggests that business organisations face a number of obstacles in learning how to adapt to climate change impacts, especially in relation to the weakness and ambiguity of signals about climate change and the uncertainty about benefits flowing from adaptation measures. Organisations rarely adapt 'autonomously', since their adaptive behaviour is influenced by policy and market conditions, and draws on resources external to the organisation. The paper identifies four adaptation strategies that pattern organisational adaptive behaviour

  9. Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    Science.gov (United States)

    McGill, Anne-Thea

    2014-01-01

    Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome's underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to 'test' this composite unifying theory it is important to show that the hypothesis and sub-theories pertain throughout the whole of human evolution and history up till the current era. Corollaries of the composite unifying theory of MetS are examined with respect to past under-nutrition and malnutrition since agriculture began 10,000 years ago. The effects of man-made pollutants on degenerative change are examined. Projections are then made from current to future patterns on the state of 'insufficient micronutrient and/or unbalanced high energy malnutrition with central obesity and metabolic dysregulation' or 'malnubesity'. Forecasts

  10. Deep Exemplar 2D-3D Detection by Adapting from Real to Rendered Views

    OpenAIRE

    Massa, Francisco; Russell, Bryan; Aubry, Mathieu

    2015-01-01

    This paper presents an end-to-end convolutional neural network (CNN) for 2D-3D exemplar detection. We demonstrate that the ability to adapt the features of natural images to better align with those of CAD rendered views is critical to the success of our technique. We show that the adaptation can be learned by compositing rendered views of textured object models on natural images. Our approach can be naturally incorporated into a CNN detection pipeline and extends the accuracy and speed benefi...

  11. A Compositional Relevance Model for Adaptive Information Retrieval

    Science.gov (United States)

    Mathe, Nathalie; Chen, James; Lu, Henry, Jr. (Technical Monitor)

    1994-01-01

    There is a growing need for rapid and effective access to information in large electronic documentation systems. Access can be facilitated if information relevant in the current problem solving context can be automatically supplied to the user. This includes information relevant to particular user profiles, tasks being performed, and problems being solved. However most of this knowledge on contextual relevance is not found within the contents of documents, and current hypermedia tools do not provide any easy mechanism to let users add this knowledge to their documents. We propose a compositional relevance network to automatically acquire the context in which previous information was found relevant. The model records information on the relevance of references based on user feedback for specific queries and contexts. It also generalizes such information to derive relevant references for similar queries and contexts. This model lets users filter information by context of relevance, build personalized views of documents over time, and share their views with other users. It also applies to any type of multimedia information. Compared to other approaches, it is less costly and doesn't require any a priori statistical computation, nor an extended training period. It is currently being implemented into the Computer Integrated Documentation system which enables integration of various technical documents in a hypertext framework.

  12. Carbon Nano tube Composites for Electronic Packaging Applications: A Review

    International Nuclear Information System (INIS)

    Aryasomayajula, L.; Wolter, K.J.

    2013-01-01

    Composite engineering comprises of metal matrix composites. They have high strength-weight ratio, better stiffness, economical production, and ease of availability of raw materials. The discovery of carbon nano tubes has opened new possibilities to face challenges better. Carbon Nano tubes are known for their high mechanical strength, excellent thermal and electrical properties. Recent research has made progress in fabricating carbon nano tube metal matrix and polymer-based composites. The methods of fabrication of these composites, their properties and possible applications restricted to the field of electronic packaging have been discussed in this paper. Experimental and theoretical calculations have shown improved mechanical and physical properties like tensile stress, toughness, and improved electrical and thermal properties. They have also demonstrated the ease of production of the composites and their adaptability as one can tailor their properties as per the requirement. This paper reviews work reported on fabricating and characterizing carbon- nano tube-based metal matrix and polymer composites. The focus of this paper is mainly to review the importance of these composites in the field of electronics packaging.

  13. Full-Length Venom Protein cDNA Sequences from Venom-Derived mRNA: Exploring Compositional Variation and Adaptive Multigene Evolution.

    Science.gov (United States)

    Modahl, Cassandra M; Mackessy, Stephen P

    2016-06-01

    Envenomation of humans by snakes is a complex and continuously evolving medical emergency, and treatment is made that much more difficult by the diverse biochemical composition of many venoms. Venomous snakes and their venoms also provide models for the study of molecular evolutionary processes leading to adaptation and genotype-phenotype relationships. To compare venom complexity and protein sequences, venom gland transcriptomes are assembled, which usually requires the sacrifice of snakes for tissue. However, toxin transcripts are also present in venoms, offering the possibility of obtaining cDNA sequences directly from venom. This study provides evidence that unknown full-length venom protein transcripts can be obtained from the venoms of multiple species from all major venomous snake families. These unknown venom protein cDNAs are obtained by the use of primers designed from conserved signal peptide sequences within each venom protein superfamily. This technique was used to assemble a partial venom gland transcriptome for the Middle American Rattlesnake (Crotalus simus tzabcan) by amplifying sequences for phospholipases A2, serine proteases, C-lectins, and metalloproteinases from within venom. Phospholipase A2 sequences were also recovered from the venoms of several rattlesnakes and an elapid snake (Pseudechis porphyriacus), and three-finger toxin sequences were recovered from multiple rear-fanged snake species, demonstrating that the three major clades of advanced snakes (Elapidae, Viperidae, Colubridae) have stable mRNA present in their venoms. These cDNA sequences from venom were then used to explore potential activities derived from protein sequence similarities and evolutionary histories within these large multigene superfamilies. Venom-derived sequences can also be used to aid in characterizing venoms that lack proteomic profiles and identify sequence characteristics indicating specific envenomation profiles. This approach, requiring only venom, provides

  14. Influence of different sizes of composite femora on the biomechanical behavior of cementless hip prosthesis.

    Science.gov (United States)

    Schmidutz, Florian; Woiczinski, Mathias; Kistler, Manuel; Schröder, Christian; Jansson, Volkmar; Fottner, Andreas

    2017-01-01

    For the biomechanical evaluation of cementless stems different sizes of composite femurs have been used in the literature. However, the impact of different specimen sizes on test results is unknown. To determine the potential effect of femur size the biomechanical properties of a conventional stem (CLS Spotorno) were examined in 3 different sizes (small, medium and large composite Sawbones®). Primary stability was tested under physiologically adapted dynamic loading conditions measuring 3-dimensional micromotions. For the small composite femur the dynamic load needed to be adapted since fractures occurred when reaching 1700N. Additionally, surface strain distribution was recorded before and after implantation to draw conclusions about the tendency for stress shielding. All tested sizes revealed similar micromotions only reaching a significant different level at one measurement point. The highest micromotions were observed at the tip of the stems exceeding the limit for osseous integration of 150μm. Regarding strain distribution the highest strain reduction after implantation was registered in all sizes at the level of the lesser trochanter. Specimen size seems to be a minor influence factor for biomechanical evaluation of cementless stems. However, the small composite femur is less suitable for biomechanical testing since this size failed under physiological adapted loads. For the CLS Spotorno osseous integration is unlikely at the tip of the stem and the tendency for stress shielding is the highest at the level of the lesser trochanter. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Lack of Exposure in a First-in-Man Study Due to Aldehyde Oxidase Metabolism: Investigated by Use of 14C-microdose, Humanized Mice, Monkey Pharmacokinetics, and In Vitro Methods.

    Science.gov (United States)

    Jensen, Klaus Gjervig; Jacobsen, Anne-Marie; Bundgaard, Christoffer; Nilausen, Dorrit Østergaard; Thale, Zia; Chandrasena, Gamini; Jørgensen, Martin

    2017-01-01

    Inclusion of a microdose of 14 C-labeled drug in the first-in-man study of new investigational drugs and subsequent analysis by accelerator mass spectrometry has become an integrated part of drug development at Lundbeck. It has been found to be highly informative with regard to investigations of the routes and rates of excretion of the drug and the human metabolite profiles according to metabolites in safety testing guidance and also when additional metabolism-related issues needed to be addressed. In the first-in-man study with the NCE Lu AF09535, contrary to anticipated, surprisingly low exposure was observed when measuring the parent compound using conventional bioanalysis. Parallel accelerator mass spectrometry analysis revealed that the low exposure was almost exclusively attributable to extensive metabolism. The metabolism observed in humans was mediated via a human specific metabolic pathway, whereas an equivalent extent of metabolism was not observed in preclinical species. In vitro, incubation studies in human liver cytosol revealed involvement of aldehyde oxidase (AO) in the biotransformation of Lu AF09535. In vivo, substantially lower plasma exposure of Lu AF09535 was observed in chimeric mice with humanized livers compared with control animals. In addition, Lu AF09535 exhibited very low oral bioavailability in monkeys despite relatively low clearance after intravenous administration in contrast to the pharmacokinetics in rats and dogs, both showing low clearance and high bioavailability. The in vitro and in vivo methods applied were proved useful for identifying and evaluating AO-dependent metabolism. Different strategies to integrate these methods for prediction of in vivo human clearance of AO substrates were evaluated. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Driving Meaningful Adaptation Action through an Adaptation Market Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Butzengeiger-Geyer, Sonja; Koehler, Michel; Michaelowa, Axel

    2011-07-01

    Approaches and criteria for allocating adaptation funds vary significantly among current sources - UN-backed funds and bilateral cooperation - and to some extent lack transparency and consistency. Such funding risks being spent in a haphazard way that repeats many of the mistakes made in development assistance over the past decades. An Adaptation Market Mechanism (AMM) could contribute to efficient allocation of adaptation funds, promote adaptation activities by private and public actors through additional financial incentives, and raise additional and reliable adaptation money. This would help to avoid future public criticism of the effectiveness and efficiency of spending adaptation funding.The proposed AMM would specify mandatory adaptation targets, on international, regional or domestic level. Participants who achieve their targets either by generating adaptation units or by buying them in the market would incentivize private, commercial and institutional actors to develop adaptation projects that create verified adaptation units. A universally accepted and verifiable trading unit applicable to all types of adaptation activities would help to maximize the cost reduction potential for the AMM. We suggest applying net present value (NPV) for property saved; Disability Adjusted Life Years Saved (DALYS) for health benefits; and potentially a separate unit to consider the environmental benefits of an adaptation activity.(Author)

  17. Molding apparatus. [for thermosetting plastic compositions

    Science.gov (United States)

    Heier, W. C. (Inventor)

    1974-01-01

    Apparatus for compression molding of thermosetting plastics compositions including interfitting hollow male and female components is reported. The components are adapted to be compressed to form a rocket nozzle in a cavity. A thermal jacket is provided exteriorly adjacent to the female component for circulating a thermal transfer fluid to effect curing of a thermosetting plastics material being molded. Each of the male and female components is provided with suitable inlets and outlets for circulating a thermal transfer fluid.

  18. Robust Adaptive Neural Control of Morphing Aircraft with Prescribed Performance

    OpenAIRE

    Wu, Zhonghua; Lu, Jingchao; Shi, Jingping; Liu, Yang; Zhou, Qing

    2017-01-01

    This study proposes a low-computational composite adaptive neural control scheme for the longitudinal dynamics of a swept-back wing aircraft subject to parameter uncertainties. To efficiently release the constraint often existing in conventional neural designs, whose closed-loop stability analysis always necessitates that neural networks (NNs) be confined in the active regions, a smooth switching function is presented to conquer this issue. By integrating minimal learning parameter (MLP) tech...

  19. Creatine Monohydrate Supplementation Does Not Augment Fitness, Performance, or Body Composition Adaptations in Response to Four Weeks of High-Intensity Interval Training in Young Females.

    Science.gov (United States)

    Forbes, Scott C; Sletten, Nathan; Durrer, Cody; Myette-Côté, Étienne; Candow, D; Little, Jonathan P

    2017-06-01

    High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness, performance, body composition, and insulin sensitivity. Creatine (Cr) supplementation may augment responses to HIIT, leading to even greater physiological adaptations. The purpose of this study was to determine the effects of 4 weeks of HIIT (three sessions/week) combined with Cr supplementation in recreationally active females. Seventeen females (age = 23 ± 4 yrs; BMI = 23.4 ± 2.4) were randomly assigned to either Cr (Cr; 0.3 g・kg -1 ・d -1 for 5 d followed by 0.1 g・kg -1 ・d -1 for 23 days; n = 9) or placebo (PLA; n = 8). Before and after the intervention, VO 2peak , ventilatory threshold (VT), time-trial performance, lean body mass and fat mass, and insulin sensitivity were assessed. HIIT improved VO 2peak (Cr = +10.2%; PLA = +8.8%), VT (Cr = +12.7%; PLA = +9.9%), and time-trial performance (Cr = -11.5%; PLA = -11.6%) with no differences between groups (time main effects, all p body lean mass (Cr = +0.5%; PLA = -0.9%), or insulin resistance (Cr = +3.9%; PLA = +18.7%). In conclusion, HIIT is an effective way to improve cardiorespiratory fitness, VT, and time-trial performance. The addition of Cr to HIIT did not augment improvements in cardiorespiratory fitness, performance or body composition in recreationally active females.

  20. Adaptation, plant evolution, and the fossil record

    Science.gov (United States)

    Knoll, A. H.; Niklas, K. J.

    1987-01-01

    The importance of adaptation in determining patterns of evolution has become an important focus of debate in evolutionary biology. As it pertains to paleobotany, the issue is whether or not adaptive evolution mediated by natural selection is sufficient to explain the stratigraphic distributions of taxa and character states observed in the plant fossil record. One means of addressing this question is the functional evaluation of stratigraphic series of plant organs set in the context of paleoenvironmental change and temporal patterns of floral composition within environments. For certain organ systems, quantitative estimates of biophysical performance can be made on the basis of structures preserved in the fossil record. Performance estimates for plants separated in time or space can be compared directly. Implicit in different hypotheses of the forces that shape the evolutionary record (e.g. adaptation, mass extinction, rapid environmental change, chance) are predictions about stratigraphic and paleoenvironmental trends in the efficacy of functional performance. Existing data suggest that following the evolution of a significant structural innovation, adaptation for improved functional performance can be a major determinant of evolutionary changes in plants; however, there are structural and development limits to functional improvement, and once these are reached, the structure in question may no longer figure strongly in selection until and unless a new innovation evolves. The Silurian-Devonian paleobotanical record is consistent with the hypothesis that the succession of lowland floodplain dominants preserved in the fossil record of this interval was determined principally by the repeated evolution of new taxa that rose to ecological importance because of competitive advantages conferred by improved biophysical performance. This does not seem to be equally true for Carboniferous-Jurassic dominants of swamp and lowland floodplain environments. In these cases

  1. Introducing Biological Microdosimetry for Ionising Radiation

    International Nuclear Information System (INIS)

    Scott, B.R.; Schoellnberger, H.

    2000-01-01

    Microdosimetry is important for radiation protection, for understanding mechanisms of radiation action, and for radiation risk assessment. This article introduces a generic, Monte Carlo based approach to biological microdosimetry for ionising radiation. Our Monte Carlo analyses are carried out with a widely used Crystal Ball software. The approach to biological microdosimetry presented relates to quantal biological effects data (e.g. cell survival, mutagenesis, neoplastic transformation) for which there is an initial linear segment to the dose-response curve. The macroscopic dose data considered were selected such that is could be presumed that the vast majority of cells at risk have radiation dose delivered to their critical target. For cell killing, neoplastic transformation, and mutagenesis, the critical biological target for radiation is presumed to be DNA. Our approach to biological microdosimetry does not require detailed information about the mass, volume, and shape of the critical biological target. Further, one does not have to know what formal distribution function applies to the microdose distribution. However, formal distributions are required for the biological data used to derive the non-parametric microdose distributions. Here, we use the binomial distribution to characterise the variability in the number of cells affected by a fixed macroscopic dose. Assuming this variability to arise from variability in the microscopic dose to the critical biological target, a non-parametric microdose distribution is generated by the standard Monte Carlo method. The non-parametric distribution is then fitted using a set of formal distributions (beta, exponential, extreme value, gamma, logistic, log-normal, normal, Pareto, triangular, uniform, and Weibull). The best fit is then evaluated based on statistical criteria (chi-square test). To demonstrate the application of biological microdosimetry, the standard Monte Carlo method is used with radiobiological data for

  2. Introducing Biological Microdosimetry for Ionising Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Scott, B.R.; Schoellnberger, H

    2000-07-01

    Microdosimetry is important for radiation protection, for understanding mechanisms of radiation action, and for radiation risk assessment. This article introduces a generic, Monte Carlo based approach to biological microdosimetry for ionising radiation. Our Monte Carlo analyses are carried out with a widely used Crystal Ball software. The approach to biological microdosimetry presented relates to quantal biological effects data (e.g. cell survival, mutagenesis, neoplastic transformation) for which there is an initial linear segment to the dose-response curve. The macroscopic dose data considered were selected such that is could be presumed that the vast majority of cells at risk have radiation dose delivered to their critical target. For cell killing, neoplastic transformation, and mutagenesis, the critical biological target for radiation is presumed to be DNA. Our approach to biological microdosimetry does not require detailed information about the mass, volume, and shape of the critical biological target. Further, one does not have to know what formal distribution function applies to the microdose distribution. However, formal distributions are required for the biological data used to derive the non-parametric microdose distributions. Here, we use the binomial distribution to characterise the variability in the number of cells affected by a fixed macroscopic dose. Assuming this variability to arise from variability in the microscopic dose to the critical biological target, a non-parametric microdose distribution is generated by the standard Monte Carlo method. The non-parametric distribution is then fitted using a set of formal distributions (beta, exponential, extreme value, gamma, logistic, log-normal, normal, Pareto, triangular, uniform, and Weibull). The best fit is then evaluated based on statistical criteria (chi-square test). To demonstrate the application of biological microdosimetry, the standard Monte Carlo method is used with radiobiological data for

  3. Fertilizer Use and Management Practices among Maize and Cowpea Smallholder Farmer in Ghana

    Directory of Open Access Journals (Sweden)

    Okebalama, CB.

    2016-01-01

    Full Text Available In most parts of West Africa, poverty contributes immensely to poor fertilizer adoption by smallholder farmers. Fertilizer adoption could be improved with micro-dosing technology. A socio-economic survey was conducted in the semi-deciduous forest zone of Ghana to assess the extent of fertilizer use and management among maize and cowpea smallholder farmers. Oral interview with structured questionnaire was used to interview one hundred farmers each at two locations. The results showed that farmers are aware of the use of fertilizer to increase crop yield. About 65% and 80% of maize and cowpea farmers respectively, identified high cost of fertilizer as a major constraint to fertilizer utilization. Consequently, only 32% maize farmers and 19% cowpea farmers were fertilizer users. In addition, the choice of fertilizer type to use was dependent on the type available on the market. As such, NPK 15:15:15 was mostly used for both maize and cowpea crops. Also, fertilizer application rate was mainly determined by the quantity farmer can purchase. On average, fertilizer application rate for maize and cowpea crops were 18.45 kg/ha and 9.05 kg/ha, respectively. The prevalent fertilizer application method on maize was mostly by point/side placement while ring application was largely used for cowpea. Awareness of fertilizer micro-dosing among the farmers was only 10%. Since the quantity of fertilizer used by the farmers as well as the fertilizer application methods were comparable to fertilizer micro-dosing, dissemination of micro-dosing technology to these farmers could promote fertilizer use and management among smallholder farmers, and ultimately sustain maize and cowpea production.

  4. Adapting Activity and Participation (The ADAPT intervention program)

    DEFF Research Database (Denmark)

    von Bülow, Cecilie

    Præsentation af et ergoterapeutisk gruppebaseret program, ADAPT programmet. ADAPT programmet er designet på baggrund af evidens samt understøttet af ergoterapeutiske teorier og modeller......Præsentation af et ergoterapeutisk gruppebaseret program, ADAPT programmet. ADAPT programmet er designet på baggrund af evidens samt understøttet af ergoterapeutiske teorier og modeller...

  5. Characteristics of adapted hydrogenotrophic community during biomethanation.

    Science.gov (United States)

    Rachbauer, Lydia; Beyer, Reinhard; Bochmann, Günther; Fuchs, Werner

    2017-10-01

    The results presented in this study were carried out as concomitant experiments during the start-up and operation of a biomethanation unit to evaluate the effect of process parameters on carbon conversion, product formation (methane and acetate) and community composition. For that, two different samples were withdrawn from a trickle-bed reactor with immobilized enrichment culture of hydrogenotrophic methanogens adapted from sewage sludge. One sample was taken from the recirculation liquid during start-up phase while the other was withdrawn directly from the carrier material in the reactor. Elevated acid levels especially during start-up were shown to affect the overall carbon conversion. This effect was also seen during the acid tolerance testing reported here. Final acid concentrations of 1.6±0.3g/L resulted in a reduced conversion ratio of only 46%. Without acid addition complete conversion of CO 2 in the headspace was achieved. However, maximum methane production of 0.55±0.02mmol after 4days of incubation was monitored at moderate initial acetate concentration of 0.4g/L. In both analyzed inoculation materials Methanobacterium species were by far the most dominant Archaea with 21.8% in the recirculation liquid during start-up and 84.8% in the enrichment culture immobilized on the carrier material. The microbial composition of the two analyzed samples is in accordance with the results obtained for the carbon conversion and product formation. With approximately 50% of Bacteroidetes and Firmicutes present during reactor start-up the acetic acid production significantly contributed to the overall carbon conversion. In contrast, methane was produced almost exclusively in trials representing continuous operation where acetogenic bacteria accounted only up to 17.5%. In summary, the acid accumulation monitored during reactor start-up of a biomethanation unit is most likely to result from the microbial composition present. Nevertheless, complete adaptation to

  6. A modified thrombolytic scheme for the treatment of thrombosis in anatomically varied cerebral venous sinus

    International Nuclear Information System (INIS)

    Zhao Lin; Li Linfang; Liu Zengpin; Qin Huimin; Wang Tiegang; Zhou Cunhe

    2010-01-01

    Objective: To discuss the curative effect of unremitting pump infusion of microdose urokinase (100000 u / 24 h) into the cerebral venous sinus in treating thrombosis in cerebral venous sinus which had anatomical variation. Methods: Mechanical disruption of the thrombus and unremitting pump infusion of microdose urokinase (100000 u / 24 h) into the cerebral venous sinus for 48-96 hours were employed in 9 patients with thrombosis in anatomically varied cerebral venous sinus. After the procedure the original disorder was actively treated and the anticoagulant therapy was continued for 6 months. A follow-up of 6-12 months (mean 10 months) was conducted. Results: Recanalization of the previously occluded cerebral venous sinus was obtained in all 9 patients. The dose of urokinase was 100 000 u / 24 h in 8 patients. For the remaining one patient the dose of urokinase was 100000 u / 24 h in the first 48 hours, then the dose was increased to 250000 u / 24 h. Excellent result was obtained in all patients. Conclusion: Unremitting pump infusion of microdose urokinase into the cerebral venous sinus can effectively treat the thrombosis in anatomically varied cerebral venous sinus. (authors)

  7. Instruments for radiation measurement in life sciences (4). VI. Use of Accelerator mass spectrometry in studies on drug metabolism and pharmacokinetics

    International Nuclear Information System (INIS)

    Ikeda, Toshihiko

    2005-01-01

    Non-clinical and clinical uses of accelerator mass spectrometry (AMS) are described mainly on studies of drug metabolism and pharmacokinetics from a view of new drug development. AMS is applicable as a highly sensitive method to measure plasma drug concentrations. Measurement of 14 C-labeled compounds less than 1 dpm/sample or of parathyroid hormone-related protein (PTHrP), in combination of AMS and radioimmunoassay without radioactive waste release is described as an example. Cases of measuring DNA-adduct are also described involving human studies using 14 C-mutagen (a quinoxaline derivative derived from burned amino acid, given in a microdose of 304 ng/kg, 4.3 μCi/body). Plasma concentration measurement, mass balance study and metabolite identification of 14 C-GI1817771 (a drug candidate) are a typical AMS application for a pharmacokinetic study in human in a microdose (121 Bq/body). Metabolites of 14 C-compound A in rat platelet are identified by the author. As above, AMS makes it possible to conduct the pharmacokinetic study in human at a microdose with no significant radiation exposure, which will promote the efficient new drug development. (N.I.)

  8. [Breast milk: its nutritional composition and functional properties].

    Science.gov (United States)

    Tackoen, M

    2012-09-01

    Human milk is a complex biological fluid with thousands of components. The milk composition in the mammalian species is specific and adapted to the needs of the offspring. It contains macronutrients (proteins, lipids and carbohydrates), micronutrients (minerals and vitamins) and numerous biologically active substrates. Human milk not only covers the nutritional needs of the newborn but protects the baby against infection, inflammation and oxidative stress. It has immunomodulation properties and confers trophical protection to the intestinal mucosa. The newborn infant is particularly immature: innate immunity, adaptive immunity and intestinal immaturity. Human milk will offer this exogenous protective and immunomodulating source. The development of the composition of the intestinal microflora of the neonate will be impacted by pre- and probiotic components of human milk. Current scientific knowledge of human milk properties highlights interdependency of the different components, ontogeny of the intestinal function, development of the mucosal intestinal immune system, colonization by the intestinal microbiota and protection against pathogens. Quality of these interactions influences the newborn's short and long-term health status. The promotion of breastfeeding with the support of the Baby Friendly Hospital Initiative (BFHI) program and labeling has been shown to have positive impact in public health.

  9. Supporting Adaptive and Adaptable Hypermedia Presentation Semantics

    NARCIS (Netherlands)

    D.C.A. Bulterman (Dick); L. Rutledge (Lloyd); L. Hardman (Lynda); J.R. van Ossenbruggen (Jacco)

    1999-01-01

    textabstractHaving the content of a presentation adapt to the needs, resources and prior activities of a user can be an important benefit of electronic documents. While part of this adaptation is related to the encodings of individual data streams, much of the adaptation can/should be guided by the

  10. Interactive music composition driven by feature evolution.

    Science.gov (United States)

    Kaliakatsos-Papakostas, Maximos A; Floros, Andreas; Vrahatis, Michael N

    2016-01-01

    Evolutionary music composition is a prominent technique for automatic music generation. The immense adaptation potential of evolutionary algorithms has allowed the realisation of systems that automatically produce music through feature and interactive-based composition approaches. Feature-based composition employs qualitatively descriptive music features as fitness landmarks. Interactive composition systems on the other hand, derive fitness directly from human ratings and/or selection. The paper at hand introduces a methodological framework that combines the merits of both evolutionary composition methodologies. To this end, a system is presented that is organised in two levels: the higher level of interaction and the lower level of composition. The higher level incorporates the particle swarm optimisation algorithm, along with a proposed variant and evolves musical features according to user ratings. The lower level realizes feature-based music composition with a genetic algorithm, according to the top level features. The aim of this work is not to validate the efficiency of the currently utilised setup in each level, but to examine the convergence behaviour of such a two-level technique in an objective manner. Therefore, an additional novelty in this work concerns the utilisation of artificial raters that guide the system through the space of musical features, allowing the exploration of its convergence characteristics: does the system converge to optimal melodies, is this convergence fast enough for potential human listeners and is the trajectory to convergence "interesting' and "creative" enough? The experimental results reveal that the proposed methodological framework represents a fruitful and robust, novel approach to interactive music composition.

  11. Flexible Composite-Material Pressure Vessel

    Science.gov (United States)

    Brown, Glen; Haggard, Roy; Harris, Paul A.

    2003-01-01

    A proposed lightweight pressure vessel would be made of a composite of high-tenacity continuous fibers and a flexible matrix material. The flexibility of this pressure vessel would render it (1) compactly stowable for transport and (2) more able to withstand impacts, relative to lightweight pressure vessels made of rigid composite materials. The vessel would be designed as a structural shell wherein the fibers would be predominantly bias-oriented, the orientations being optimized to make the fibers bear the tensile loads in the structure. Such efficient use of tension-bearing fibers would minimize or eliminate the need for stitching and fill (weft) fibers for strength. The vessel could be fabricated by techniques adapted from filament winding of prior composite-material vessels, perhaps in conjunction with the use of dry film adhesives. In addition to the high-bias main-body substructure described above, the vessel would include a low-bias end substructure to complete coverage and react peak loads. Axial elements would be overlaid to contain damage and to control fiber orientation around side openings. Fiber ring structures would be used as interfaces for connection to ancillary hardware.

  12. 75 FR 57859 - Specially Adapted Housing and Special Home Adaptation

    Science.gov (United States)

    2010-09-23

    ... Home Adaptation AGENCY: Department of Veterans Affairs. ACTION: Final rule. SUMMARY: The Department of... specially adapted housing and special home adaptation grants. This final rule incorporates certain... regulations pertaining to eligibility for specially adapted housing (SAH) grants and special home adaptation...

  13. The Role of Tetraether Lipid Composition in the Adaptation of Thermophilic Archaea to Acidity

    Directory of Open Access Journals (Sweden)

    Eric eBoyd

    2013-04-01

    Full Text Available Diether and tetraether lipids are fundamental components of the archaeal cell membrane. Archaea adjust the degree of tetraether lipid cyclization in order to maintain functional membranes and cellular homeostasis when confronted with pH and/or thermal stress. Thus, the ability to adjust tetraether lipid composition likely represents a critical phenotypic trait that enabled archaeal diversification into environments characterized by extremes in pH and/or temperature. Here we assess the relationship between geochemical variation, core- and polar-isoprenoid glycerol dibiphytanyl glycerol tetraether (C-iGDGT and P-iGDGT, respectively lipid composition, and archaeal 16S rRNA gene diversity and abundance in 27 geothermal springs in Yellowstone National Park (YNP, Wyoming. The composition and abundance of C-iGDGT and P-iGDGT lipids recovered from geothermal ecosystems were distinct from surrounding soils, indicating that they are synthesized endogenously. With the exception of GDGT-0 (no cyclopentyl rings, the abundances of individual C-iGDGT and P-iGDGT lipids were significantly correlated. The abundance of a number of individual tetraether lipids varied positively with the relative abundance of individual 16S rRNA gene sequences, most notably crenarchaeol in both the core and polar GDGT fraction and sequences closely affiliated with Candidatus Nitrosocaldus yellowstonii. This finding supports the proposal that crenarchaeol is a biomarker for nitrifying archaea. Variation in the degree of cyclization of C- and P-iGDGT lipids recovered from geothermal mats and sediments could best be explained by variation in spring pH, with lipids from acidic environments tending to have, on average, more internal cyclic rings than those from higher pH ecosystems. Likewise, variation in the phylogenetic composition of archaeal 16S rRNA genes could best be explained by spring pH. In turn, the phylogenetic similarity of archaeal 16S rRNA genes was significantly

  14. Clinical Effect of Dental Adhesive on Marginal Integrity in Class I And Class II Resin-Composite Restorations

    Directory of Open Access Journals (Sweden)

    Manchorova-Veleva Neshka A.

    2015-12-01

    Full Text Available BACKGROUND: Dental adhesives are believed to influence marginal adaptation and marginal discoloration when used under posterior resin-based composite restorations. Studies on the latest adhesive systems reveal that the group of the three-step etch-and-rinse adhesive (3-E&RA and the one-step self-etch adhesive (1-SEA have entirely different bonding mechanisms, as well as different bond strength and resistance to chemical, thermal and mechanical factors. STUDY OBJECTIVES: A hypothesis that a 1-SEA would result in greater enamel marginal discoloration and poorer marginal adaptation than a 3-E&RA was tested. MATERIAL AND METHODS: One hundred restorations were placed with a 1-SEA and 100 restorations with a 3-E&RA. Teeth were restored with Filtek Supreme nanofilled resin-composite and were evaluated for marginal adaptation and marginal discoloration at baseline, and 6 months, 12 months, and 36 months postoperatively. RESULTS: The statistical analysis revealed significant differences in marginal integrity between test groups. The 1-SEA resulted in greater enamel marginal discoloration and poorer marginal adaptation than the 3-E&RA at any recall time. CONCLUSIONS: Marginal adaptation and marginal discoloration depend on the type of dentin adhesive used. The restorations with Filtek Supreme and Scotchbond MP are better than the restorations with Adper Prompt L-Pop with regard to the marginal adaptation and marginal discoloration at 6-, 12- and 36-month evaluations.

  15. Evolution of adaptation mechanisms: Adaptation energy, stress, and oscillating death.

    Science.gov (United States)

    Gorban, Alexander N; Tyukina, Tatiana A; Smirnova, Elena V; Pokidysheva, Lyudmila I

    2016-09-21

    In 1938, Selye proposed the notion of adaptation energy and published 'Experimental evidence supporting the conception of adaptation energy.' Adaptation of an animal to different factors appears as the spending of one resource. Adaptation energy is a hypothetical extensive quantity spent for adaptation. This term causes much debate when one takes it literally, as a physical quantity, i.e. a sort of energy. The controversial points of view impede the systematic use of the notion of adaptation energy despite experimental evidence. Nevertheless, the response to many harmful factors often has general non-specific form and we suggest that the mechanisms of physiological adaptation admit a very general and nonspecific description. We aim to demonstrate that Selye׳s adaptation energy is the cornerstone of the top-down approach to modelling of non-specific adaptation processes. We analyze Selye׳s axioms of adaptation energy together with Goldstone׳s modifications and propose a series of models for interpretation of these axioms. Adaptation energy is considered as an internal coordinate on the 'dominant path' in the model of adaptation. The phenomena of 'oscillating death' and 'oscillating remission' are predicted on the base of the dynamical models of adaptation. Natural selection plays a key role in the evolution of mechanisms of physiological adaptation. We use the fitness optimization approach to study of the distribution of resources for neutralization of harmful factors, during adaptation to a multifactor environment, and analyze the optimal strategies for different systems of factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The morphing properties of a vascular shape memory composite

    International Nuclear Information System (INIS)

    Cortes, P; Kubas, G; Terzak, J; Phillips, D; Baur, J W

    2014-01-01

    This work investigates the fabrication, experimentation, testing, and modeling of shape memory composites consisting of two-way shape memory alloy (SMA) tubes embedded in a shape memory polymer (SMP) matrix. The hybrid system here investigated is thermally activated via internal transport of thermal fluids through the SMA vascular system. The resulting shape memory composite (SMC) combines the high modulus and high specific actuation force of SMAs with the strong shape fixing and variable stiffness of SMPs to create a light-weight composite capable of controllably and rapidly achieving two shape memory states. Specifically, a 25° thermally induced out-of-plane bending state is achieved with a 2% volume fraction of SMA in the composite after 2 min of being activated by an internal thermal fluid. Here, while the thermal structural design of the SMC was not optimized and the thermal cycling was significantly restricted by the low thermal conduction of the SMP, the deflection of the composite was within 20% of the expected value modeled by the thermal–mechanical finite element analysis (FEA) here performed. The close agreement between the experimental performance and the modeled composite response suggests that morphing composites based on SMAs and SMPs are promising structures for adaptive applications. (paper)

  17. The process of organisational adaptation through innovations, and organisational adaptability

    OpenAIRE

    Tikka, Tommi

    2010-01-01

    This study is about the process of organisational adaptation and organisational adaptability. The study generates a theoretical framework about organisational adaptation behaviour and conditions that have influence on success of organisational adaptation. The research questions of the study are: How does an organisation adapt through innovations, and which conditions enhance or impede organisational adaptation through innovations? The data were gathered from five case organisations withi...

  18. From “Crash!” to Crash: Adapting the Adaptation

    Directory of Open Access Journals (Sweden)

    Ljubica Matek

    2017-12-01

    Full Text Available The paper focuses on J.G. Ballard’s various adaptations of his own material related to the issue of the sexual and sensual nature of an automobile crash, and suggests that adaptation is one of the key methods in art and literature which can be used as a means of contemplating and developing various aesthetic and political ideas. Ballard’s short story “Crash!” was first published in the ICA’s (Institute of Contemporary Arts Eventsheet in February 1969, and later became a chapter of his experimental novel The Atrocity Exhibition (1970. At the same time, Ballard adapts the idea into the “Crashed Cars” exhibition (1970 in London. The short story was then adapted into a short film, Crash!, directed by Harley Cokeliss (1971 and starring Ballard himself, to be finally adapted into the novel Crash (1973. Ballard’s adaptation of his initial ideas across literary forms and media testifies to the importance of adaptation as a process and method of creating art. Thus, rather than suggesting that adaptations merely “breathe life” into the written word, the paper points to the conclusion that the form and content are mutually influential and that, in this case, the novel itself is an adaptation, rather than a hypotext (which it becomes in 1996 to David Cronenberg as he adapts it to film. The complexity of the relationship between the source text and its many adaptations has already contributed to the deconstruction, in Derrida’s terms, of the hierarchy (opposition between the original and the copy. Rather, Ballard’s crossmedial and transmedial adaptations of his own ideas show how, as Ray would suggest, an adaptation cites the source and grafts it into a new context, giving it a new function, both aesthetic and political.

  19. Mobilization and Adaptation of a Rural Cradle-to-Career Network

    Directory of Open Access Journals (Sweden)

    Sarah J. Zuckerman

    2016-10-01

    Full Text Available This case study explored the development of a rural cradle-to-career network with a dual focus on the initial mobilization of network members and subsequent adaptations made to maintain mobilization, while meeting local needs. Data sources included interviews with network members, observations of meetings, and documentary evidence. Network-based social capital facilitated mobilization. Where networks were absent and where distrust and different values were evident, mobilization faltered. Three network adaptations were discovered: Special rural community organizing strategies, district-level action planning, and a theory of action focused on out-of-school factors. All three were attributable to the composition of mobilized stakeholders and this network’s rural social geography. These findings illuminate the importance of social geography in the development and advancement of rural cradle-to-career networks.

  20. A Self-adaptive Dynamic Evaluation Model for Diabetes Mellitus, Based on Evolutionary Strategies

    Directory of Open Access Journals (Sweden)

    An-Jiang Lu

    2016-03-01

    Full Text Available In order to evaluate diabetes mellitus objectively and accurately, this paper builds a self-adaptive dynamic evaluation model for diabetes mellitus, based on evolutionary strategies. First of all, on the basis of a formalized description of the evolutionary process of diabetes syndromes, using a state transition function, it judges whether a disease is evolutionary, through an excitation parameter. It then, provides evidence for the rebuilding of the evaluation index system. After that, by abstracting and rebuilding the composition of evaluation indexes, it makes use of a heuristic algorithm to determine the composition of the evolved evaluation index set of diabetes mellitus, It then, calculates the weight of each index in the evolved evaluation index set of diabetes mellitus by building a dependency matrix and realizes the self-adaptive dynamic evaluation of diabetes mellitus under an evolutionary environment. Using this evaluation model, it is possible to, quantify all kinds of diagnoses and treatment experiences of diabetes and finally to adopt ideal diagnoses and treatment measures for different patients with diabetics.

  1. On Adaptive vs. Non-adaptive Security of Multiparty Protocols

    DEFF Research Database (Denmark)

    Canetti, Ran; Damgård, Ivan Bjerre; Dziembowski, Stefan

    2001-01-01

    highlights of our results are: – - According to the definition of Dodis-Micali-Rogaway (which is set in the information-theoretic model), adaptive and non-adaptive security are equivalent. This holds for both honest-but-curious and Byzantine adversaries, and for any number of parties. – - According......Security analysis of multiparty cryptographic protocols distinguishes between two types of adversarialsettings: In the non-adaptive setting, the set of corrupted parties is chosen in advance, before the interaction begins. In the adaptive setting, the adversary chooses who to corrupt during...... the course of the computation. We study the relations between adaptive security (i.e., security in the adaptive setting) and non-adaptive security, according to two definitions and in several models of computation. While affirming some prevailing beliefs, we also obtain some unexpected results. Some...

  2. Methods of preparing and using intravenous nutrient compositions

    International Nuclear Information System (INIS)

    Beigler, M.A.; Koury, A.J.

    1983-01-01

    A method for preparing a stable, dry-packaged, sterile, nutrient composition which upon addition of sterile, pyrogen-free water is suitable for intravenous administration to a mammal, including a human, is described. The method comprises providing the nutrients in a specific dry form and state of physical purity acceptable for intravenous administration, sealing the nutrients in a particular type of container adapted to receive and dispense sterile fluids and subjecting the container and its sealed contents to a sterilizing, nondestructive dose of ionizing radiation. The method results in a packaged, sterile nutrient composition which may be dissolved by the addition of sterile pyrogen-free water. The resulting aqueous intravenous solution may be safely administered to a mammal in need of nutrient therapy. The packaged nutrient compositions of the invention exhibit greatly extended storage life and provide an economical method of providing intravenous solutions which are safe and efficacious for use. (author)

  3. Is adaptation. Truly an adaptation?

    Directory of Open Access Journals (Sweden)

    Thais Flores Nogueira Diniz

    2006-04-01

    Full Text Available The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition, joined with the study of recycling, remaking, and every form of retelling. The film deals with the attempt by the scriptwriter Charles Kaufman, cast by Nicholas Cage, to adapt/translate a non-fictional book to the cinema, but ends up with a kind of film which is by no means what it intended to be: a film of action in the model of Hollywood productions. During the process of creation, Charles and his twin brother, Donald, undergo a series of adventures involving some real persons from the world of film, the author and the protagonist of the book, all of them turning into fictional characters in the film. In the film, adaptation then signifies something different from itstraditional meaning.

  4. Regulation of intestinal homeostasis by innate and adaptive immunity.

    Science.gov (United States)

    Kayama, Hisako; Takeda, Kiyoshi

    2012-11-01

    The intestine is a unique tissue where an elaborate balance is maintained between tolerance and immune responses against a variety of environmental factors such as food and the microflora. In a healthy individual, the microflora stimulates innate and adaptive immune systems to maintain gut homeostasis. However, the interaction of environmental factors with particular genetic backgrounds can lead to dramatic changes in the composition of the microflora (i.e. dysbiosis). Many of the specific commensal-bacterial products and the signaling pathways they trigger have been characterized. The role of T(h)1, T(h)2 and T(h)17 cells in inflammatory bowel disease has been widely investigated, as has the contribution of epithelial cells and subsets of dendritic cells and macrophages. To date, multiple regulatory cells in adaptive immunity, such as regulatory T cells and regulatory B cells, have been shown to maintain gut homeostasis by preventing inappropriate innate and adaptive immune responses to commensal bacteria. Additionally, regulatory myeloid cells have recently been identified that prevent intestinal inflammation by inhibiting T-cell proliferation. An increasing body of evidence has shown that multiple regulatory mechanisms contribute to the maintenance of gut homeostasis.

  5. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial lighting ceases...

  6. Chromostereopsis in "virtual reality" adapters with electrically tuneable liquid lens oculars

    Science.gov (United States)

    Ozolinsh, Maris; Muizniece, Kristine; Berzinsh, Janis

    2016-10-01

    Chromostereopsis can be sight and feel in "Virtual Reality" adapters, that induces the appearance of color dependant depth sense and, finally, combines this sense with the source conceived depth scenario. Present studies are devoted to investigation the induced chromastereopsis when using adapted "Virtual Reality" frame together with mobile devices as smartphones. We did observation of composite visual stimuli presented on the high spatial resolution screen of the mobile phone placed inside a portable "Virtual Reality" adapter. Separated for the left and right eyes stimuli consisted of two areas: a) identical for both eyes color chromostereopsis part, and b) additional conventional color neutral random-dot stereopsis part with a stereodisparity based on the horizontal shift of a random-dot segment in images for the left and right eyes, correspondingly. The observer task was to equalize the depth sense for neutral and colored stimuli areas. Such scheme allows to determine actual observed chromostereopsis disparity value versus eye stimuli color difference. At standard observation conditions for adapter with +2D ocular lenses for mobile red-blue stimuli, the perceptual chromostereopsis depth sensitivity on color difference was linearly approximated with a slope SChS ≈ 2.1[arcmin/(Labcolor difference)] for red-blue pairs. Additional to standard application in adapter the tuneable "Varioptic" liquid lens oculars were incorporated, that allowed stimuli eye magnification, vergence and disparity values control electrically.

  7. Process monitoring of fibre reinforced composites using optical fibre sensors

    Energy Technology Data Exchange (ETDEWEB)

    Fernando, G.F.; Degamber, B.

    2006-04-15

    The deployment of optical fibre based sensor systems for process monitoring of advanced fibre reinforced organic matrix composites is reviewed. The focus is on thermosetting resins and the various optical and spectroscopy-based techniques that can be used to monitor the processing of these materials. Following brief consideration of the manufacturing methods commonly used in the production of thermoset based composites, a discussion is presented on sensor systems that can be used to facilitate real-time chemical process monitoring. Although the focus is on thermosets, the techniques described can be adapted for chemical monitoring of organic species in general. (author)

  8. Vibrational behavior of adaptive aircraft wing structures modelled as composite thin-walled beams

    Science.gov (United States)

    Song, O.; Librescu, L.; Rogers, C. A.

    1992-01-01

    The vibrational behavior of cantilevered aircraft wings modeled as thin-walled beams and incorporating piezoelectric effects is studied. Based on the converse piezoelectric effect, the system of piezoelectric actuators conveniently located on the wing yield the control of its associated vertical and lateral bending eigenfrequencies. The possibility revealed by this study enabling one to increase adaptively the eigenfrequencies of thin-walled cantilevered beams could play a significant role in the control of the dynamic response and flutter of wing and rotor blade structures.

  9. Composite turbine bucket assembly

    Science.gov (United States)

    Liotta, Gary Charles; Garcia-Crespo, Andres

    2014-05-20

    A composite turbine blade assembly includes a ceramic blade including an airfoil portion, a shank portion and an attachment portion; and a transition assembly adapted to attach the ceramic blade to a turbine disk or rotor, the transition assembly including first and second transition components clamped together, trapping said ceramic airfoil therebetween. Interior surfaces of the first and second transition portions are formed to mate with the shank portion and the attachment portion of the ceramic blade, and exterior surfaces of said first and second transition components are formed to include an attachment feature enabling the transition assembly to be attached to the turbine rotor or disk.

  10. High-performance composite chocolate

    Science.gov (United States)

    Dean, Julian; Thomson, Katrin; Hollands, Lisa; Bates, Joanna; Carter, Melvyn; Freeman, Colin; Kapranos, Plato; Goodall, Russell

    2013-07-01

    The performance of any engineering component depends on and is limited by the properties of the material from which it is fabricated. It is crucial for engineering students to understand these material properties, interpret them and select the right material for the right application. In this paper we present a new method to engage students with the material selection process. In a competition-based practical, first-year undergraduate students design, cost and cast composite chocolate samples to maximize a particular performance criterion. The same activity could be adapted for any level of education to introduce the subject of materials properties and their effects on the material chosen for specific applications.

  11. Distinguishing Byproducts from Non-Adaptive Effects of Algorithmic Adaptations

    Directory of Open Access Journals (Sweden)

    Justin H. Park

    2007-01-01

    Full Text Available I evaluate the use of the byproduct concept in psychology, particularly the adaptation-byproduct distinction that is commonly invoked in discussions of psychological phenomena. This distinction can be problematic when investigating algorithmic mechanisms and their effects, because although all byproducts may be functionless concomitants of adaptations, not all incidental effects of algorithmic adaptations are byproducts (although they have sometimes been labeled as such. I call attention to Sperber's (1994 distinction between proper domains and actual domains of algorithmic mechanisms. Extending Sperber's distinction, I propose the terms adaptive effects and non-adaptive effects, which more accurately capture the phenomena of interest to psychologists and prevent fruitless adaptation-versus-byproduct debates.

  12. Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[ def,p ]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Madeen, Erin P.; Ognibene, Ted J.; Corley, Richard A.; McQuistan, Tammie J.; Henderson, Marilyn C.; Baird, William M.; Bench, Graham; Turteltaub, Ken W.; Williams, David E.

    2016-10-17

    Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novel “moving wire” interface between ultra-performance liquid chromatography (UPLC) and AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/-)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Free and conjugated metabolites were detected in urine with [14C]-(+/-)-DBC-11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which were conjugated (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6-12 h pool). [14C]-DBC-11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6-12 h pool). Parent [14C]-DBC was not detected in urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose animal models to humans for translation of environmental health risk assessment.

  13. Climate adaptation

    Science.gov (United States)

    Kinzig, Ann P.

    2015-03-01

    This paper is intended as a brief introduction to climate adaptation in a conference devoted otherwise to the physics of sustainable energy. Whereas mitigation involves measures to reduce the probability of a potential event, such as climate change, adaptation refers to actions that lessen the impact of climate change. Mitigation and adaptation differ in other ways as well. Adaptation does not necessarily have to be implemented immediately to be effective; it only needs to be in place before the threat arrives. Also, adaptation does not necessarily require global, coordinated action; many effective adaptation actions can be local. Some urban communities, because of land-use change and the urban heat-island effect, currently face changes similar to some expected under climate change, such as changes in water availability, heat-related morbidity, or changes in disease patterns. Concern over those impacts might motivate the implementation of measures that would also help in climate adaptation, despite skepticism among some policy makers about anthropogenic global warming. Studies of ancient civilizations in the southwestern US lends some insight into factors that may or may not be important to successful adaptation.

  14. A Composite Agent Architecture for Multi-Agent Simulations

    OpenAIRE

    VanPutte, Michael; Osborn, Brian; Hiles, John

    2002-01-01

    CGF Computer Generated Forces and Behavioral Representation The MOVES Institute’s Computer-Generated Autonomy Group has focused on a research goal of modeling complex and adaptive behavior while at the same time making the behavior easier to create and control. This research has led to several techniques for agent construction, that includes a social and organization relationship management engine, a composite agent architecture, an agent goal apparatus, a structure for capturi...

  15. Understanding climate change adaptation and adaptive capacity: synthesis report

    Energy Technology Data Exchange (ETDEWEB)

    Patino, L. [Policy Research Initiative, Government of Canada, Ottawa, ON (Canada)

    2010-09-15

    In 2007, the Natural Resources Canada (NRCan) Climate Change Impacts and Adaptation Division (CCIAD) offered its support to research projects that were involved in understanding and improving adaptation and adaptive capacity and contributed to climate change decision-making and policy development in Canada. 20 research projects were commissioned by the CCIAD. With the collaboration of NRCan, the principal findings raised by the commissioned projects were synthesized by the Policy Research Initiative (PRI). Common themes and main messages are introduced in this synthesis report, and policy and program aspects that promote adaptive capacity to climate change in Canada are identified. Common themes and important messages emerging from the research projects, as well as the processes and barriers to adaptation and adaptive capacity identified in the commissioned projects, were discussed during a workshop held in Ottawa in 2009. Five main themes and four common barriers to adaptation were found. 25 refs.

  16. A structure-based approach to evaluation product adaptability in adaptable design

    International Nuclear Information System (INIS)

    Cheng, Qiang; Liu, Zhifeng; Cai, Ligang; Zhang, Guojun; Gu, Peihua

    2011-01-01

    Adaptable design, as a new design paradigm, involves creating designs and products that can be easily changed to satisfy different requirements. In this paper, two types of product adaptability are proposed as essential adaptability and behavioral adaptability, and through measuring which respectively a model for product adaptability evaluation is developed. The essential adaptability evaluation proceeds with analyzing the independencies of function requirements and function modules firstly based on axiomatic design, and measuring the adaptability of interfaces secondly with three indices. The behavioral adaptability reflected by the performance of adaptable requirements after adaptation is measured based on Kano model. At last, the effectiveness of the proposed method is demonstrated by an illustrative example of the motherboard of a personal computer. The results show that the method can evaluate and reveal the adaptability of a product in essence, and is of directive significance to improving design and innovative design

  17. Development of bonded composite doublers for the repair of oil recovery equipment.

    Energy Technology Data Exchange (ETDEWEB)

    Roach, David W.; Rackow, Kirk A.

    2005-06-01

    An unavoidable by-product of a metallic structure's use is the appearance of crack and corrosion flaws. Economic barriers to the replacement of these structures have created an aging infrastructure and placed even greater demands on efficient and safe repair methods. In the past decade, an advanced composite repair technology has made great strides in commercial aviation use. Extensive testing and analysis, through joint programs between the Sandia Labs FAA Airworthiness Assurance Center and the aviation industry, have proven that composite materials can be used to repair damaged aluminum structure. Successful pilot programs have produced flight performance history to establish the durability of bonded composite patches as a permanent repair on commercial aircraft structures. With this foundation in place, this effort is adapting bonded composite repair technology to civil structures. The use of bonded composite doublers has the potential to correct the difficulties associated with current repair techniques and the ability to be applied where there are no rehabilitation options. It promises to be cost-effective with minimal disruption to the users of the structure. This report concludes a study into the application of composite patches on thick steel structures typically used in mining operations. Extreme fatigue, temperature, erosive, and corrosive environments induce an array of equipment damage. The current weld repair techniques for these structures provide a fatigue life that is inferior to that of the original plate. Subsequent cracking must be revisited on a regular basis. The use of composite doublers, which do not have brittle fracture problems such as those inherent in welds, can help extend the structure's fatigue life and reduce the equipment downtime. Two of the main issues for adapting aircraft composite repairs to civil applications are developing an installation technique for carbon steel and accommodating large repairs on extremely thick

  18. Considerations about expected a posteriori estimation in adaptive testing: adaptive a priori, adaptive correction for bias, and adaptive integration interval.

    Science.gov (United States)

    Raiche, Gilles; Blais, Jean-Guy

    2009-01-01

    In a computerized adaptive test, we would like to obtain an acceptable precision of the proficiency level estimate using an optimal number of items. Unfortunately, decreasing the number of items is accompanied by a certain degree of bias when the true proficiency level differs significantly from the a priori estimate. The authors suggest that it is possible to reduced the bias, and even the standard error of the estimate, by applying to each provisional estimation one or a combination of the following strategies: adaptive correction for bias proposed by Bock and Mislevy (1982), adaptive a priori estimate, and adaptive integration interval.

  19. PRAGMATICS DRIVEN LAND COVER SERVICE COMPOSITION UTILIZING BEHAVIOR-INTENTION MODEL

    Directory of Open Access Journals (Sweden)

    H. Wu

    2016-06-01

    Full Text Available Web service composition is one of the key issues to develop a global land cover (GLC information service portal. Aiming at the defect that traditional syntax and semantic service compositionare difficult to take pragmatic information into account, the paper firstly analyses three tiers of web service language and their succession relations, discusses the conceptual model of pragmatic web service, and proposes the idea of pragmatics-oriented adaptive composition method based on the analysis of some examples. On this basis it puts forward the pragmatic web service model based on Behavior-Intention through presetting and expression of service usability, users' intention, and other pragmatic information, develops the on-demand assembly method based on the agent theory and matching and reconstruction method on heterogeneous message, solves the key technological issue of algorithm applicability and heterogeneous message transformation in the process of covering web service composition on the ground, applies these methods into service combination, puts forward the pragmatic driven service composition method based on behavior-intention model, and effectively settles the issue of coordination and interaction of composite service invocation.

  20. ALE-PSO: An Adaptive Swarm Algorithm to Solve Design Problems of Laminates

    Directory of Open Access Journals (Sweden)

    Paolo Vannucci

    2009-04-01

    Full Text Available This paper presents an adaptive PSO algorithm whose numerical parameters can be updated following a scheduled protocol respecting some known criteria of convergence in order to enhance the chances to reach the global optimum of a hard combinatorial optimization problem, such those encountered in global optimization problems of composite laminates. Some examples concerning hard design problems are provided, showing the effectiveness of the approach.

  1. Evaluation of the efficacy of flowable composite as lining material on microleakage of composite resin restorations: A systematic review and meta-analysis.

    Science.gov (United States)

    Boruziniat, Alireza; Gharaee, Samineh; Sarraf Shirazi, Alireza; Majidinia, Sara; Vatanpour, Mehdi

    2016-02-01

    The efficacy of flowable composite in improving marginal adaptation or reducing microleakage is not fully understood. The purpose of this study was to systematically evaluate existing evidence to verify whether an application of flowable composite as a liner provided less microleakage in Class 2 composite restorations. PubMed, ISI (Web of Science), and Scopus databases were searched according to the selected keywords, up to 15 Feb 2015, without any restriction on date or language. Full texts of published articles that seemed to meet primary criteria for inclusion in this research were obtained. Data of studies were extracted if they were assessed as high or moderate level of evidence. Due to the variation of methods used in different studies, they were divided into five groups: groups 1 and 2, studies that evaluated the effect of flowable composite as a liner on dentinal or enamel margins and applied flowable composite on all of the cavity wall margins; groups 3 and 4, studies that evaluated the effect of flowable composite as a liner on dentinal and enamel margins and applied flowable composite only on gingival margin; and group 5, clinical studies. The initial search yielded 1,370 publications. After hand searching, six extra studies were included in the review. The abstracts of all were read independently by AB and SG. After methodologic assessment and evaluation of the level of evidence, 18 studies were selected for this study. The results of this study indicate that flowable composite liners have no significant effect on microleakage of composite restorations in all of five groups. Application of flowable composite as a liner in composite restorations cannot reduce microleakage or improve clinical performance.

  2. Nectar sugar composition of European Caryophylloideae (Caryophyllaceae) in relation to flower length, pollination biology and phylogeny.

    Science.gov (United States)

    Witt, T; Jürgens, A; Gottsberger, G

    2013-10-01

    Floral nectar composition has been explained as an adaptation to factors that are either directly or indirectly related to pollinator attraction. However, it is often unclear whether the sugar composition is a direct adaptation to pollinator preferences. Firstly, the lower osmolality of sucrose solutions means that they evaporate more rapidly than hexose solutions, which might be one reason why sucrose-rich nectar is typically found in flowers with long tubes (adapted to long-tongued pollinators), where it is better protected from evaporation than in open or short-tubed flowers. Secondly, it can be assumed that temperature-dependent evaporation is generally lower during the night than during the day so that selection pressure to secrete nectar with high osmolality (i.e. hexose-rich solutions) is relaxed for night-active flowers pollinated at night. Thirdly, the breeding system may affect selection pressure on nectar traits; that is, for pollinator-independent, self-pollinated plants, a lower selective pressure on nectar traits can be assumed, leading to a higher variability of nectar sugar composition independent of pollinator preferences, nectar accessibility and nectar protection. To analyse the relations between flower tube length, day vs. night pollination and self-pollination, the nectar sugar composition was investigated in 78 European Caryophylloideae (Caryophyllaceae) with different pollination modes (diurnal, nocturnal, self-pollination) using high-performance liquid chromatography (HPLC). All Caryophylleae species (Dianthus and relatives) were found to have nectar with more than 50% sucrose, whereas the sugar composition of Sileneae species (Silene and relatives) ranged from 0% to 98.2%. In the genus Silene, a clear dichotomous distribution of sucrose- and hexose-dominant nectars is evident. We found a positive correlation between the flower tube length and sucrose content in Caryophylloideae, particularly in day-flowering species, using both conventional

  3. Factors influencing the aroma composition of Chardonnay wines.

    Science.gov (United States)

    Gambetta, Joanna M; Bastian, Susan E P; Cozzolino, Daniel; Jeffery, David W

    2014-07-16

    Chardonnay is one of the oldest and most widely distributed wine grape cultivars and is of commercial importance for the world's wine-producing nations. It is an extremely flexible variety that has adapted to different regions with varied weather and soil characteristics. Somewhat uniquely among white wines, Chardonnay lends itself to a wide variety of production styles, which can be tailored to the target market. Techniques such as skin maceration, barrel and stainless steel fermentation, use of selected or indigenous yeasts, malolactic fermentation, and aging in barrels with or without lees are all applicable and lead to different compositional outcomes. A number of research papers have been published with a view to understanding Chardonnay composition and quality as well as the impact of different enological techniques on the final product. This review summarizes current knowledge, explaining the influence of viticultural and production techniques on aroma composition, and poses directions for further research into Chardonnay wines.

  4. Modeling adaptive and non-adaptive responses to environmental change

    DEFF Research Database (Denmark)

    Coulson, Tim; Kendall, Bruce E; Barthold, Julia A.

    2017-01-01

    , with plastic responses being either adaptive or non-adaptive. We develop an approach that links quantitative genetic theory with data-driven structured models to allow prediction of population responses to environmental change via plasticity and adaptive evolution. After introducing general new theory, we...... construct a number of example models to demonstrate that evolutionary responses to environmental change over the short-term will be considerably slower than plastic responses, and that the rate of adaptive evolution to a new environment depends upon whether plastic responses are adaptive or non-adaptive....... Parameterization of the models we develop requires information on genetic and phenotypic variation and demography that will not always be available, meaning that simpler models will often be required to predict responses to environmental change. We consequently develop a method to examine whether the full...

  5. The life of a dead ant: the expression of an adaptive extended phenotype.

    Science.gov (United States)

    Andersen, Sandra B; Gerritsma, Sylvia; Yusah, Kalsum M; Mayntz, David; Hywel-Jones, Nigel L; Billen, Johan; Boomsma, Jacobus J; Hughes, David P

    2009-09-01

    Specialized parasites are expected to express complex adaptations to their hosts. Manipulation of host behavior is such an adaptation. We studied the fungus Ophiocordyceps unilateralis, a locally specialized parasite of arboreal Camponotus leonardi ants. Ant-infecting Ophiocordyceps are known to make hosts bite onto vegetation before killing them. We show that this represents a fine-tuned fungal adaptation: an extended phenotype. Dead ants were found under leaves, attached by their mandibles, on the northern side of saplings approximately 25 cm above the soil, where temperature and humidity conditions were optimal for fungal growth. Experimental relocation confirmed that parasite fitness was lower outside this manipulative zone. Host resources were rapidly colonized and further secured by extensive internal structuring. Nutritional composition analysis indicated that such structuring allows the parasite to produce a large fruiting body for spore production. Our findings suggest that the osmotrophic lifestyle of fungi may have facilitated novel exploitation strategies.

  6. Electrically Conductive TPU Nanofibrous Composite with High Stretchability for Flexible Strain Sensor

    Science.gov (United States)

    Tong, Lu; Wang, Xiao-Xiong; He, Xiao-Xiao; Nie, Guang-Di; Zhang, Jun; Zhang, Bin; Guo, Wen-Zhe; Long, Yun-Ze

    2018-03-01

    Highly stretchable and electrically conductive thermoplastic polyurethane (TPU) nanofibrous composite based on electrospinning for flexible strain sensor and stretchable conductor has been fabricated via in situ polymerization of polyaniline (PANI) on TPU nanofibrous membrane. The PANI/TPU membrane-based sensor could detect a strain from 0 to 160% with fast response and excellent stability. Meanwhile, the TPU composite has good stability and durability. Besides, the composite could be adapted to various non-flat working environments and could maintain opportune conductivity at different operating temperatures. This work provides an easy operating and low-cost method to fabricate highly stretchable and electrically conductive nanofibrous membrane, which could be applied to detect quick and tiny human actions.

  7. Processing of Aluminum-Graphite Particulate Metal Matrix Composites by Advanced Shear Technology

    Science.gov (United States)

    Barekar, N.; Tzamtzis, S.; Dhindaw, B. K.; Patel, J.; Hari Babu, N.; Fan, Z.

    2009-12-01

    To extend the possibilities of using aluminum/graphite composites as structural materials, a novel process is developed. The conventional methods often produce agglomerated structures exhibiting lower strength and ductility. To overcome the cohesive force of the agglomerates, a melt conditioned high-pressure die casting (MC-HPDC) process innovatively adapts the well-established, high-shear dispersive mixing action of a twin screw mechanism. The distribution of particles and properties of composites are quantitatively evaluated. The adopted rheo process significantly improved the distribution of the reinforcement in the matrix with a strong interfacial bond between the two. A good combination of improved ultimate tensile strength (UTS) and tensile elongation (ɛ) is obtained compared with composites produced by conventional processes.

  8. Reorganization of Azospirillum brasilense cell membrane is mediated by lipid composition adjustment to maintain optimal fluidity during water deficit.

    Science.gov (United States)

    Cesari, A B; Paulucci, N S; Biasutti, M A; Reguera, Y B; Gallarato, L A; Kilmurray, C; Dardanelli, M S

    2016-01-01

    We study the Azospirillum brasilense tolerance to water deficit and the dynamics of adaptive process at the level of the membrane. Azospirillum brasilense was exposed to polyethylene glycol (PEG) growth and PEG shock. Tolerance, phospholipids and fatty acid (FA) composition and membrane fluidity were determined. Azospirillum brasilense was able to grow in the presence of PEG; however, its viability was reduced. Cells grown with PEG showed membrane fluidity similar to those grown without, the lipid composition was modified, increasing phosphatidylcholine and decreasing phosphatidylethanolamine amounts. The unsaturation FAs degree was reduced. The dynamics of the adaptive response revealed a decrease in fluidity 20 min after the addition of PEG, indicating that the PEG has a fluidizing effect on the hydrophobic region of the cell membrane. Fluidity returned to initial values after 60 min of PEG exposure. Azospirillum brasilense is able to perceive osmotic changes by changing the membrane fluidity. This effect is offset by changes in the composition of membrane phospholipid and FA, contributing to the homeostasis of membrane fluidity under water deficit. This knowledge can be used to develop new Azospirillum brasilense formulations showing an adapted membrane to water deficit. © 2015 The Society for Applied Microbiology.

  9. Coupling internal cerebellar models enhances online adaptation and supports offline consolidation in sensorimotor tasks.

    Science.gov (United States)

    Passot, Jean-Baptiste; Luque, Niceto R; Arleo, Angelo

    2013-01-01

    The cerebellum is thought to mediate sensorimotor adaptation through the acquisition of internal models of the body-environment interaction. These representations can be of two types, identified as forward and inverse models. The first predicts the sensory consequences of actions, while the second provides the correct commands to achieve desired state transitions. In this paper, we propose a composite architecture consisting of multiple cerebellar internal models to account for the adaptation performance of humans during sensorimotor learning. The proposed model takes inspiration from the cerebellar microcomplex circuit, and employs spiking neurons to process information. We investigate the intrinsic properties of the cerebellar circuitry subserving efficient adaptation properties, and we assess the complementary contributions of internal representations by simulating our model in a procedural adaptation task. Our simulation results suggest that the coupling of internal models enhances learning performance significantly (compared with independent forward and inverse models), and it allows for the reproduction of human adaptation capabilities. Furthermore, we provide a computational explanation for the performance improvement observed after one night of sleep in a wide range of sensorimotor tasks. We predict that internal model coupling is a necessary condition for the offline consolidation of procedural memories.

  10. Coupling internal cerebellar models enhances online adaptation and supports offline consolidation in sensorimotor tasks

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste ePassot

    2013-07-01

    Full Text Available The cerebellum is thought to mediate sensorimotor adaptation through the acquisition of internal models of the body–environment interaction. These representations can be of two types, identified as forward and inverse models. The first predicts the sensory consequences of actions, while the second provides the correct commands to achieve desired state transitions. In this paper, we propose a composite architecture consisting of multiple cerebellar internal models to account for the adaptation performance of humans during sensorimotor learning. The proposed model takes inspiration from the cerebellar microcomplex circuit, and employs spiking neurons to process information. We investigate the intrinsic properties of the cerebellar circuitry subserving efficient adaptation properties, and we assess the complementary contributions of internal representations by simulating our model in a procedural adaptation task. Our simulation results suggest that the coupling of internal models enhances learning performance significantly (compared with independent forward and inverse models, and it allows for the reproduction of human adaptation capabilities. Furthermore, we provide a computational explanation for the performance improvement observed after one night of sleep in a wide range of sensorimotor tasks. We predict that internal model coupling is a necessary condition for the offline consolidation of procedural memories.

  11. Quantum Logic with Composite Pulse Sequences on Sr^+

    Science.gov (United States)

    Shewmon, Ruth; Labaziewicz, Jaroslaw; Ge, Yufei; Wang, Shannon; Chuang, Isaac L.

    2008-03-01

    The optical 5S1/2->4D1/2 transition in Sr^+ is an attractive qubit because it can be addressed by diode lasers, which are relatively inexpensive and easy to operate. We characterize single-qubit rotations as well as a CNOT gate on a Sr^+ ion in a surface electrode Paul trap. To improve these operations, the frequency of the clock laser is stabilized to a high-finesse optical cavity. The resulting linewidth of the laser is approximately 300Hz. Composite pulse sequences, a technique adapted from NMR, have been shown to reduce the effects of systematic errors in a variety of quantum systems. We demonstrate several composite sequences that improve the fidelity of quantum logic operations on Sr^+.

  12. Adaptation research meets adaptation decision-making. Second Nordic international conference on climate change adaption. Programme and abstracts

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    Nearly two years have passed since a small team of researchers began a new chapter in Nordic co-operation on climate change by organising a conference in Stockholm, Sweden. The conference, entitled Climate Adaptation in the Nordic Countries - Science, Practice, Policy, co-ordinated by the Stockholm Environment Institute and hosted by Stockholm University in November 2010, was the first of its kind in the Nordic region. Since the European Commission adopted its White Paper on adaptation to climate change in 2009, many of that document's 33 actions have been implemented, a climate change adaptation platform, Climate-ADAPT, was launched at the European Environment Agency in March this year, and just a week before this conference the Commission concluded a public consultation of stakeholders and experts in member states designed to feed into the preparation of a European Union adaptation strategy. The 2012 conference therefore presents an ideal opportunity to take stock of ongoing efforts and to consider how adaptation research efforts are keeping pace with policy demands as well as the needs of public and private decision-makers operating at a range of scales. It brings together researchers, public and private decision- makers, as well as those who plan and realize adaptation plans. Session themes include, among others: national and local adaptation plans, climate portals and climate services, adaptation in developing countries, legal aspects of adaptation, economic appraisal of adaptation, analysing and handling risk and uncertainty, urban planning and scenarios. The contributors have very diverse backgrounds, ranging from biosciences to social sciences, economics to geo-sciences, and engineering to architecture. Interest in climate change adaptation in the Nordic region is clearly high, with over 70% of our participants drawn from the five Nordic countries, but the conference has also managed to attract participation from further afield, with registrations

  13. Adaptive steganography

    Science.gov (United States)

    Chandramouli, Rajarathnam; Li, Grace; Memon, Nasir D.

    2002-04-01

    Steganalysis techniques attempt to differentiate between stego-objects and cover-objects. In recent work we developed an explicit analytic upper bound for the steganographic capacity of LSB based steganographic techniques for a given false probability of detection. In this paper we look at adaptive steganographic techniques. Adaptive steganographic techniques take explicit steps to escape detection. We explore different techniques that can be used to adapt message embedding to the image content or to a known steganalysis technique. We investigate the advantages of adaptive steganography within an analytical framework. We also give experimental results with a state-of-the-art steganalysis technique demonstrating that adaptive embedding results in a significant number of bits embedded without detection.

  14. Adaptive versus Non-Adaptive Security of Multi-Party Protocols

    DEFF Research Database (Denmark)

    Canetti, Ran; Damgård, Ivan Bjerre; Dziembowski, Stefan

    2004-01-01

    Security analysis of multi-party cryptographic protocols distinguishes between two types of adversarial settings: In the non-adaptive setting the set of corrupted parties is chosen in advance, before the interaction begins. In the adaptive setting the adversary chooses who to corrupt during...... the course of the computation. We study the relations between adaptive security (i.e., security in the adaptive setting) and nonadaptive security, according to two definitions and in several models of computation....

  15. Effects of cooking methods on starch and sugar composition of sweetpotato storage roots

    Science.gov (United States)

    Sweet potato has rich nutrition, good ecological adaptability and high yield. There was a lack of knowledge about the relationship among cooking methods, sugar components and cultivars. The objective of this study was to determine sugar composition of four sweet potato cultivars under three cooking ...

  16. Adapt

    Science.gov (United States)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  17. Resilience through adaptation.

    Directory of Open Access Journals (Sweden)

    Guus A Ten Broeke

    Full Text Available Adaptation of agents through learning or evolution is an important component of the resilience of Complex Adaptive Systems (CAS. Without adaptation, the flexibility of such systems to cope with outside pressures would be much lower. To study the capabilities of CAS to adapt, social simulations with agent-based models (ABMs provide a helpful tool. However, the value of ABMs for studying adaptation depends on the availability of methodologies for sensitivity analysis that can quantify resilience and adaptation in ABMs. In this paper we propose a sensitivity analysis methodology that is based on comparing time-dependent probability density functions of output of ABMs with and without agent adaptation. The differences between the probability density functions are quantified by the so-called earth-mover's distance. We use this sensitivity analysis methodology to quantify the probability of occurrence of critical transitions and other long-term effects of agent adaptation. To test the potential of this new approach, it is used to analyse the resilience of an ABM of adaptive agents competing for a common-pool resource. Adaptation is shown to contribute positively to the resilience of this ABM. If adaptation proceeds sufficiently fast, it may delay or avert the collapse of this system.

  18. Resilience through adaptation.

    Science.gov (United States)

    Ten Broeke, Guus A; van Voorn, George A K; Ligtenberg, Arend; Molenaar, Jaap

    2017-01-01

    Adaptation of agents through learning or evolution is an important component of the resilience of Complex Adaptive Systems (CAS). Without adaptation, the flexibility of such systems to cope with outside pressures would be much lower. To study the capabilities of CAS to adapt, social simulations with agent-based models (ABMs) provide a helpful tool. However, the value of ABMs for studying adaptation depends on the availability of methodologies for sensitivity analysis that can quantify resilience and adaptation in ABMs. In this paper we propose a sensitivity analysis methodology that is based on comparing time-dependent probability density functions of output of ABMs with and without agent adaptation. The differences between the probability density functions are quantified by the so-called earth-mover's distance. We use this sensitivity analysis methodology to quantify the probability of occurrence of critical transitions and other long-term effects of agent adaptation. To test the potential of this new approach, it is used to analyse the resilience of an ABM of adaptive agents competing for a common-pool resource. Adaptation is shown to contribute positively to the resilience of this ABM. If adaptation proceeds sufficiently fast, it may delay or avert the collapse of this system.

  19. Science of adaptation to climate change and science for adaptation

    Directory of Open Access Journals (Sweden)

    Rob eSwart

    2014-07-01

    Full Text Available Adaptation to climate change has gained a prominent place next to mitigation on global, national and local policy agendas. However, while an abundance of adaptation strategies, plans and programmes have been developed, progress in turning these into action has been slow. The development of a sound knowledge basis to support adaptation globally is suggested to accelerate progress, but has lagged behind. The emphasis in both current and newly proposed programmes is very much on practice-oriented research with strong stakeholder participation. This paper supports such practice-oriented research, but argues that this is insufficient to support adaptation policy and practice in a productive manner. We argue that there is not only a need for science for adaptation, but also a science of adaptation. The paper argues that participatory, practice-oriented research is indeed essential, but has to be complemented by and connected to more fundamental inquiry and concept development, which takes into account knowledge that has been developed in disciplinary sciences and on issues other than climate change adaptation. At the same time, the level and method of participation in science for adaptation should be determined on the basis of the specific project context and goals. More emphasis on science of adaptation can lead to improved understanding of the conditions for successful science for adaptation.

  20. Expressing Adaptation Strategies Using Adaptation Patterns

    Science.gov (United States)

    Zemirline, N.; Bourda, Y.; Reynaud, C.

    2012-01-01

    Today, there is a real challenge to enable personalized access to information. Several systems have been proposed to address this challenge including Adaptive Hypermedia Systems (AHSs). However, the specification of adaptation strategies remains a difficult task for creators of such systems. In this paper, we consider the problem of the definition…

  1. Novelty, Adaptive Capacity, and Resilience

    Directory of Open Access Journals (Sweden)

    Craig R. Allen

    2010-09-01

    Full Text Available We present a conceptual framework that explores some of the forces creating innovation and novelty in complex systems. Understanding the sources of variability and novelty may help us better understand complex systems. Understanding complex phenomena such as invasions, migration, and nomadism may provide insight into the structure of ecosystems and other complex systems, and aid our attempts to cope with and mitigate these phenomena, in the case of invasions, and better understand and or predict them. Our model is broadly applicable to ecological theory, including community ecology, resilience, restoration, and policy. Characterizing the link between landscape change and the composition of species communities may help policymakers in their decision-making processes. Understanding how variability is related to system structure, and how that generates novelty, may help us understand how resilience is generated. We suggest that there are three primary opportunities for the generation of novelty into complex systems. These sources of novelty are inherent in the cross-scale structure of complex systems, and are critical for creating adaptive capacity. Novelty originates from the inherent variability present in cross scale structures, within scale reorganization associated with adaptive cycles, and whole-scale transformations resulting from regime shifts. Although speculative, our ideas are grounded in research and observation, and they may provide insight into the evolution of complex systems.

  2. Generic adaptation framework for unifying adaptive web-based systems

    NARCIS (Netherlands)

    Knutov, E.

    2012-01-01

    The Generic Adaptation Framework (GAF) research project first and foremost creates a common formal framework for describing current and future adaptive hypermedia (AHS) and adaptive webbased systems in general. It provides a commonly agreed upon taxonomy and a reference model that encompasses the

  3. Comparison of Two Methods for Speeding Up Flash Calculations in Compositional Simulations

    DEFF Research Database (Denmark)

    Belkadi, Abdelkrim; Yan, Wei; Michelsen, Michael Locht

    2011-01-01

    Flash calculation is the most time consuming part in compositional reservoir simulations and several approaches have been proposed to speed it up. Two recent approaches proposed in the literature are the shadow region method and the Compositional Space Adaptive Tabulation (CSAT) method. The shadow...... region method reduces the computation time mainly by skipping stability analysis for a large portion of compositions in the single phase region. In the two-phase region, a highly efficient Newton-Raphson algorithm can be employed with initial estimates from the previous step. The CSAT method saves...... and the tolerance set for accepting the feed composition are the key parameters in this method since they will influence the simulation speed and the accuracy of simulation results. Inspired by CSAT, we proposed a Tieline Distance Based Approximation (TDBA) method to get approximate flash results in the twophase...

  4. Plant sulfolipid. III. Role in adaptation

    Directory of Open Access Journals (Sweden)

    Taran N. Yu.

    2009-04-01

    Full Text Available The quality and/or relative content of plant sulfoquinovosyl diacylglycerol (SQDG change in response to a stress action. Various types of stress action induce two types of response – more general to the oxidative stress and specific – to a concrete stress factor. Besides, two types of reaction take place in photosynthesizing and non-photosynthesizing tissues. SQDG molecules take part in the adaptation reaction being cytochrome oxidase, CF1, F1, ATPase regulators, protectors and stabilizing agents for D1/D2 dimers and LHC II. This compound in non-photosynthesising tissues could be connected with negative charge domination required for lipoprotein complex stabilisation. SQDG quantitative changes and acyl composition shifts take place at both abiotic and biotic factors impact.

  5. Influence of light energy density on heat generation during photoactivation of dental composites with different dentin and composite thickness

    Directory of Open Access Journals (Sweden)

    Ricardo Danil Guiraldo

    2009-08-01

    Full Text Available OBJECTIVE: The aim of this study was to determine the influence of different energy densities on the heat generated during photoactivation of Filtek Z250 (3M/ESPE and Z100 (3M/ESPE composite resins with different dentin and composite thickness. MATERIAL AND METHODS: The temperature increase was registered with a type-K thermocouple connected to a digital thermometer (Iopetherm 46. A chemically polymerized acrylic resin base was prepared to serve as a guide for the thermocouple and as a support for 0.5-, 1.0-, and 1.5-mm-thick bovine dentin discs. Circular elastomer molds (1.0 mm-height x 3.0-mm diameter or 2.0-mm height x 3.0-mm diameter were adapted on the acrylic resin base to standardize the composite resin thickness. A conventional halogen light-curing unit (XL 2500, 3M/ESPE was used with light intensity of 700 mW/cm². Energy density was calculated by the light intensity applied during a certain time with values of 28 J/cm² for Z100 and 14 J/cm² for Filtek Z250. The temperature change data were subjected to three-way ANOVA and Tukey's test at 5% level. RESULTS: The higher energy density (Z100 promoted greater temperature increase (p<0.05 than the lower energy density (Filtek Z250. For both composites and all composite thicknesses, the lowest dentin thickness (0.5 mm yielded significantly higher (p<0.05 temperature increase than the other two dentin thicknesses. The 1-mm-thick composite resin layer yielded significantly higher (p<0.05 temperature changes for both composites and all dentin thicknesses. CONCLUSIONS: Temperature increase was influenced by higher energy density and dentin/composite thickness.

  6. Learning to adapt: Organisational adaptation to climate change impacts

    NARCIS (Netherlands)

    Berkhout, F.G.H.; Hertin, J.; Gann, D.M.

    2006-01-01

    Analysis of human adaptation to climate change should be based on realistic models of adaptive behaviour at the level of organisations and individuals. The paper sets out a framework for analysing adaptation to the direct and indirect impacts of climate change in business organisations with new

  7. PAQ: Persistent Adaptive Query Middleware for Dynamic Environments

    Science.gov (United States)

    Rajamani, Vasanth; Julien, Christine; Payton, Jamie; Roman, Gruia-Catalin

    Pervasive computing applications often entail continuous monitoring tasks, issuing persistent queries that return continuously updated views of the operational environment. We present PAQ, a middleware that supports applications' needs by approximating a persistent query as a sequence of one-time queries. PAQ introduces an integration strategy abstraction that allows composition of one-time query responses into streams representing sophisticated spatio-temporal phenomena of interest. A distinguishing feature of our middleware is the realization that the suitability of a persistent query's result is a function of the application's tolerance for accuracy weighed against the associated overhead costs. In PAQ, programmers can specify an inquiry strategy that dictates how information is gathered. Since network dynamics impact the suitability of a particular inquiry strategy, PAQ associates an introspection strategy with a persistent query, that evaluates the quality of the query's results. The result of introspection can trigger application-defined adaptation strategies that alter the nature of the query. PAQ's simple API makes developing adaptive querying systems easily realizable. We present the key abstractions, describe their implementations, and demonstrate the middleware's usefulness through application examples and evaluation.

  8. Disturbance and productivity interactions mediate stability of forest composition and structure

    Science.gov (United States)

    Christopher D. O' Connor; Donald A. Falk; Ann M. Lynch; Thomas W. Swetnam; Craig P. Wilcox

    2017-01-01

    Fire is returning to many conifer-dominated forests where species composition and structure have been altered by fire exclusion. Ecological effects of these fires are influenced strongly by the degree of forest change during the fire-free period. Response of fire-adapted species assemblages to extended fire-free intervals is highly variable, even in communities with...

  9. Adaptive Modular Playware

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Þorsteinsson, Arnar Tumi

    2011-01-01

    In this paper, we describe the concept of adaptive modular playware, where the playware adapts to the interaction of the individual user. We hypothesize that there are individual differences in user interaction capabilities and styles, and that adaptive playware may adapt to the individual user...

  10. Adaptation

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

    building skills, knowledge or networks on adaptation, ... the African partners leading the AfricaAdapt network, together with the UK-based Institute of Development Studies; and ... UNCCD Secretariat, Regional Coordination Unit for Africa, Tunis, Tunisia .... 26 Rural–urban Cooperation on Water Management in the Context of.

  11. Resilience through adaptation

    NARCIS (Netherlands)

    Broeke, ten Guus; Voorn, van George A.K.; Ligtenberg, Arend; Molenaar, Jaap

    2017-01-01

    Adaptation of agents through learning or evolution is an important component of the resilience of Complex Adaptive Systems (CAS). Without adaptation, the flexibility of such systems to cope with outside pressures would be much lower. To study the capabilities of CAS to adapt, social simulations

  12. Uncertainty in adaptive capacity; Incertitudes dans la capacite d'adaptation

    Energy Technology Data Exchange (ETDEWEB)

    Neil Adger, W.; Vincent, K. [East Anglia Univ., Tyndall Centre for Climate Change Research, School of Environmental Sciences, Norwich (United Kingdom)

    2005-03-01

    The capacity to adapt is a critical element of the process of adaptation: it is the vector of resources that represent the asset base from which adaptation actions can be made. Adaptive capacity can in theory be identified and measured at various scales, from the individual to the nation. The assessment of uncertainty within such measures comes from the contested knowledge domain and theories surrounding the nature of the determinants of adaptive capacity and the human action of adaptation. While generic adaptive capacity at the national level, for example, is often postulated as being dependent on health, governance and political rights, and literacy, and economic well-being, the determinants of these variables at national levels are not widely understood. We outline the nature of this uncertainty for the major elements of adaptive capacity and illustrate these issues with the example of a social vulnerability index for countries in Africa. (authors)

  13. Marginal and internal fit of CAD-CAM-fabricated composite resin and ceramic crowns scanned by 2 intraoral cameras.

    Science.gov (United States)

    de Paula Silveira, Alessandra C; Chaves, Sacha B; Hilgert, Leandro A; Ribeiro, Ana Paula D

    2017-03-01

    The precision of fit of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) complete crowns is affected by digital impression and restorative material. The purpose of this in vitro study was to evaluate by microcomputed tomography (μCT) the marginal and internal adaptation of composite resin and ceramic complete crowns fabricated with 2 different intraoral cameras and 2 restorative materials. Ten extracted human third molars received crown preparations. For each prepared molar, 2 digital impressions were made with different intraoral cameras of the CEREC system, Bluecam and Omnicam. Four groups were formed: LB (Lava Ultimate+Bluecam), EB (Emax+Bluecam), LO (Lava Ultimate+Omnicam), and EO (Emax+Omnicam). Before measuring the precision of fit, all crowns were stabilized with a silicone material. Each unit (crown + prepared tooth) was imaged with μCT, and marginal and internal discrepancies were analyzed. For the 2D analysis, 120 measurements were made of each crown for marginal adaptation, 20 for marginal discrepancy (MD), and 20 for absolute marginal discrepancy (AMD); and for internal adaptation, 40 for axial space (AS) and 40 for occlusal space (OS). After reconstructing the 3D images, the average internal space (AIS) was calculated by dividing the total volume of the internal space by the contact surface. Data were analyzed with 2-way ANOVA and quantile regression. Regarding marginal adaptation, no significant differences were observed among groups. For internal adaptation measured in the 2D evaluation, a significant difference was observed between LO and EO for the AS variable (Mann-Whitney test; POmnicam, and composite resin crowns showed less discrepancy than did ceramic crowns. The marginal adaptations assessed in all groups showed values within the clinically accepted range. Moreover, the composite resin blocks associated with the Bluecam intraoral camera demonstrated the best results for AIS compared with those of the other groups

  14. An Optimal Control Modification to Model-Reference Adaptive Control for Fast Adaptation

    Science.gov (United States)

    Nguyen, Nhan T.; Krishnakumar, Kalmanje; Boskovic, Jovan

    2008-01-01

    This paper presents a method that can achieve fast adaptation for a class of model-reference adaptive control. It is well-known that standard model-reference adaptive control exhibits high-gain control behaviors when a large adaptive gain is used to achieve fast adaptation in order to reduce tracking error rapidly. High gain control creates high-frequency oscillations that can excite unmodeled dynamics and can lead to instability. The fast adaptation approach is based on the minimization of the squares of the tracking error, which is formulated as an optimal control problem. The necessary condition of optimality is used to derive an adaptive law using the gradient method. This adaptive law is shown to result in uniform boundedness of the tracking error by means of the Lyapunov s direct method. Furthermore, this adaptive law allows a large adaptive gain to be used without causing undesired high-gain control effects. The method is shown to be more robust than standard model-reference adaptive control. Simulations demonstrate the effectiveness of the proposed method.

  15. An overview of the development, testing, and application of composite absorbers

    International Nuclear Information System (INIS)

    Sebesta, F.; John, J.

    1995-02-01

    Although inorganic exchangers offer many advantages for removing selected elements from radioactive waste streams, few of these materials are suitable for use in packed-bed columns. We review various adaptations of inorganic exchangers for use in columns, which include granular forms of the intrinsic absorbers, absorber compounds supported on other materials, and composite absorbers that use organic or inorganic binders. An organic binding polymer of polyacrylonitrile (PAN), developed at the Czech Technical University, has been demonstrated to offer advantages. We describe general methods for preparing inorganic exchange materials, which then are incorporated into PAN-based composites. Such PAN composites have been used to remove selected radionuclides from a variety of liquid waste streams. Sixteen different PAN composites were prepared for testing at Los Alamos National Laboratory (LANL) as part of an evaluation of potential partitioning agents for remediating the liquid waste in underground storage tanks at the Hanford site near Richland, Washington. Our collaboration with LANL is expected to continue for another 2 years

  16. An overview of the development, testing, and application of composite absorbers

    Energy Technology Data Exchange (ETDEWEB)

    Sebesta, F. [Czech Technical Univ., Brehova (Czech Republic); John, J. [Los Alamos National Lab., NM (United States)

    1995-02-01

    Although inorganic exchangers offer many advantages for removing selected elements from radioactive waste streams, few of these materials are suitable for use in packed-bed columns. We review various adaptations of inorganic exchangers for use in columns, which include granular forms of the intrinsic absorbers, absorber compounds supported on other materials, and composite absorbers that use organic or inorganic binders. An organic binding polymer of polyacrylonitrile (PAN), developed at the Czech Technical University, has been demonstrated to offer advantages. We describe general methods for preparing inorganic exchange materials, which then are incorporated into PAN-based composites. Such PAN composites have been used to remove selected radionuclides from a variety of liquid waste streams. Sixteen different PAN composites were prepared for testing at Los Alamos National Laboratory (LANL) as part of an evaluation of potential partitioning agents for remediating the liquid waste in underground storage tanks at the Hanford site near Richland, Washington. Our collaboration with LANL is expected to continue for another 2 years.

  17. Longitudinal trajectories of intellectual and adaptive functioning in adolescents and adults with Williams syndrome.

    Science.gov (United States)

    Fisher, M H; Lense, M D; Dykens, E M

    2016-10-01

    Williams syndrome (WS) is associated with a distinct cognitive-behavioural phenotype including mild to moderate intellectual disability, visual-spatial deficits, hypersociability, inattention and anxiety. Researchers typically characterise samples of individuals with WS by their intellectual functioning and adaptive behaviour. Because of the low prevalence of the syndrome, researchers often include participants with WS across a broad age range throughout childhood and adulthood and assume participants demonstrate consistent cognitive development across ages. Indeed, IQ scores are generally stable for children and adolescents with WS, although there are significant individual differences. It is less clear whether this pattern of stable intellectual ability persists into adulthood. Furthermore, while adaptive behaviour is an important indicator of an individual's ability to apply their conceptual skills to everyday functioning, conflicting findings on the trajectories of adaptive behaviour in adolescents and adults with WS have been reported. The current study examined longitudinal profiles of cognitive and adaptive functioning in adolescents and adults with WS. To examine cognitive functioning, participants included 52 individuals with WS (51.9% men) who were assessed with the Kaufman Brief Intelligence Test, 2nd edition (KBIT-2) between two and seven times. At their first assessment, participants had a mean age of 25.4 years (SD = 8.4), ranging in age from 14.2 to 48.9 years. To assess adaptive behaviour, participants included a subset of 28 individuals with WS whose parents completed the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II) between two and five times. At their initial administration, participants ranged from 17.1-40.2 years of age, with a mean age of 26.5 years (SD = 7.3). A series of multilevel models were used to examine changes in KBIT-2 Composite IQ, Verbal IQ and Nonverbal IQ standard scores over time, as well as the

  18. Multivariate refined composite multiscale entropy analysis

    International Nuclear Information System (INIS)

    Humeau-Heurtier, Anne

    2016-01-01

    Multiscale entropy (MSE) has become a prevailing method to quantify signals complexity. MSE relies on sample entropy. However, MSE may yield imprecise complexity estimation at large scales, because sample entropy does not give precise estimation of entropy when short signals are processed. A refined composite multiscale entropy (RCMSE) has therefore recently been proposed. Nevertheless, RCMSE is for univariate signals only. The simultaneous analysis of multi-channel (multivariate) data often over-performs studies based on univariate signals. We therefore introduce an extension of RCMSE to multivariate data. Applications of multivariate RCMSE to simulated processes reveal its better performances over the standard multivariate MSE. - Highlights: • Multiscale entropy quantifies data complexity but may be inaccurate at large scale. • A refined composite multiscale entropy (RCMSE) has therefore recently been proposed. • Nevertheless, RCMSE is adapted to univariate time series only. • We herein introduce an extension of RCMSE to multivariate data. • It shows better performances than the standard multivariate multiscale entropy.

  19. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    the investigations of lighting scenarios carried out in two test installations: White Cube and White Box. The test installations are discussed as large-scale experiential instruments. In these test installations we examine what could potentially occur when light using LED technology is integrated and distributed......Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial lighting ceases...

  20. Prediction of strength of wood composite materials using ultrasonic

    International Nuclear Information System (INIS)

    Mahmoud, M.K.; Emam, A.

    2005-01-01

    Wood is a biological material integrating a very large variability of its mechanical properties (tensile and compressive), on the two directional longitudinal and transverse Ultrasonic method has been utilized to measure both wood physical and / or wood mechanical properties. The aim of this article is to show the development of ultrasonic technique for quality evaluation of trees, wood material and wood based composites. For quality assessment of these products we discuss the nondestructive evaluation of different factors such as: moisture content, temperature, biological degradation induced by bacterial attack and fungal attack. These techniques were adapted for trees, timber and wood based composites. The present study discusses the prediction of tensile and compressive strength of wood composite materials using ultrasonic testing. Empirical relationships between the tensile properties, compression strength and ultrasonic were proposed. The experimental results indicate the possibility of establishing a relationship between tensile strength and compression values. Moreover, the fractures in tensile and compressive are discussed by photographic

  1. The composition of cell walls from grape skin in Vitis vinifera intraspecific hybrids.

    Science.gov (United States)

    Apolinar-Valiente, Rafael; Gómez-Plaza, Encarna; Terrier, Nancy; Doco, Thierry; Ros-García, José María

    2017-09-01

    Monastrell is a red grape cultivar adapted to the dry environmental conditions of Murcia, SE Spain. Its berries seem to be characterized by a rigid cell wall structure, which could make difficult the winemaking process. Cabernet Sauvignon cultivar is used to complement Monastrell wines in this region owing to its high phenolic content with high extractability. This study explores the skin cell wall composition of grapes from plants resulting from intraspecific crosses of Vitis vinifera cultivars Monastrell × Cabernet Sauvignon. Moreover, the morphology of the cell wall material (CWM) from some representative samples was visualized by transmission optical microscopy. The total sugar content of CWM from nine out of ten genotypes of the progeny was lower than that from Monastrell. Seven out of ten genotypes showed lower phenolic content than Cabernet Sauvignon. The CWM from nine out of ten hybrids presented lower protein content than that from Monastrell. This study confirms that skin cell walls from Monastrell × Cabernet Sauvignon hybrid grapes presented major differences in composition compared with their parents. These data could help in the development of new cultivars adapted to the dry conditions of SE Spain and with a cell wall composition favouring extractability. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  2. A 4-year clinical evaluation of direct composite build-ups for space closure after orthodontic treatment.

    Science.gov (United States)

    Demirci, Mustafa; Tuncer, Safa; Öztaş, Evren; Tekçe, Neslihan; Uysal, Ömer

    2015-12-01

    To evaluate the medium-term clinical performance of direct composite build-ups for diastema closures and teeth recontouring using a nano and a nanohybrid composite in combination with three- or two-step etch-and-rinse adhesives following treatment with fixed orthodontic appliances. A total of 30 patients (mean age, 19.5 years) received 147 direct composite additions for teeth recontouring and diastema closures. A nano and a nanohybrid composite (Filtek Supreme XT and CeramX Duo) were bonded to tooth structure by using a three-step (Scotchbond Multipurpose) or a two-step (XP Bond) etch and rinse adhesive. Ten out of 147 composite build-ups (composite addition) constituted tooth recontouring cases, and the remaining 137 constituted diastema closure cases. The restorations were evaluated by two experienced, calibrated examiners according to modified Ryge criteria at the following time intervals: baseline, 1, 2, 3, and 4 years. The 4-year survival rates were 92.8 % for Filtek Supreme XT/Scotchbond Multi-Purpose Plus and 93 % for CeramX Duo/XP Bond. Only ten restorations failed (5 Filtek Supreme XT and 5 CeramX Duo). Statistical analysis revealed no significant differences between the two composite-adhesive combinations with respect to color match, marginal discoloration, wear/loss of anatomical form, caries formation, marginal adaptation, and surface texture on comparing the five time periods (baseline, 1, 2, 3, and 4 years) The 4-year survival rates in the present study were favorable. The restorations exhibited excellent scores with regard to color match, marginal adaptation, surface texture, marginal discoloration, wear/loss of anatomical form, and caries formation, after 4 years of clinical evaluation. Clinical relevance An alternative clinical approach for correcting discrepancies in tooth size and form, such as performing direct composite restorations following fixed orthodontic treatment, may be an excellent and minimally invasive treatment.

  3. 3D printing-assisted interphase engineering of polymer composites: Concept and feasibility

    Directory of Open Access Journals (Sweden)

    G. Szebenyi

    2017-07-01

    Full Text Available We introduced a general concept to create smart, (multifunctional interphases in polymer composites with layered reinforcements, making use of 3D printing. The concept can be adapted for both thermoplastic and thermoset matrix-based composites with either thermoplastic- or thermoset-enriched interphases. We showed feasibility using an example of a composite containing a thermoset matrix/thermoplastic interphase. Carbon fiber unidirectional reinforcing layers were patterned with poly(ε-caprolactone (PCL through 3D printing, then infiltrated with an amine-cured epoxy (EP. The corresponding composites were subjected to static and dynamic flexure tests. The PCL-rich interphase markedly improved the ductility in static tests without deteriorating the flexural properties. Its effect was marginal in Charpy impact tests, which can be explained with effects of specimen and PCL pattern sizes. The PCL-rich interphase ensured self-healing when triggered by heat treatment above the melting temperature of PCL.

  4. Integrating adaptive governance and participatory multicriteria methods: a framework for climate adaptation governance

    Directory of Open Access Journals (Sweden)

    Stefania Munaretto

    2014-06-01

    Full Text Available Climate adaptation is a dynamic social and institutional process where the governance dimension is receiving growing attention. Adaptive governance is an approach that promises to reduce uncertainty by improving the knowledge base for decision making. As uncertainty is an inherent feature of climate adaptation, adaptive governance seems to be a promising approach for improving climate adaptation governance. However, the adaptive governance literature has so far paid little attention to decision-making tools and methods, and the literature on the governance of adaptation is in its infancy in this regard. We argue that climate adaptation governance would benefit from systematic and yet flexible decision-making tools and methods such as participatory multicriteria methods for the evaluation of adaptation options, and that these methods can be linked to key adaptive governance principles. Moving from these premises, we propose a framework that integrates key adaptive governance features into participatory multicriteria methods for the governance of climate adaptation.

  5. The effects of whey protein with or without carbohydrates on resistance training adaptations

    OpenAIRE

    Hulmi, Juha; Laakso, Mia; Mero, Antti; Häkkinen, Keijo; Ahtiainen, Juha; Peltonen, Heikki

    2015-01-01

    Background: Nutrition intake in the context of a resistance training (RT) bout may affect body composition and muscle strength. However, the individual and combined effects of whey protein and carbohydrates on long-term resistance training adaptations are poorly understood. Methods: A four-week preparatory RT period was conducted in previously untrained males to standardize the training background of the subjects. Thereafter, the subjects were randomized into three groups: 30 g of...

  6. Greenlandic Inuit show genetic signatures of diet and climate adaptation

    DEFF Research Database (Denmark)

    Fumagalli, Matteo; Moltke, Ida; Grarup, Niels

    2015-01-01

    The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes......, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs....

  7. Adaptive Multimedia Retrieval: Semantics, Context, and Adaptation

    DEFF Research Database (Denmark)

    This book constitutes the thoroughly refereed post-conference proceedings of the 10th International Conference on Adaptive Multimedia Retrieval, AMR 2012, held in Copenhagen, Denmark, in October 2012. The 17 revised full papers presented were carefully reviewed and selected from numerous submissi......This book constitutes the thoroughly refereed post-conference proceedings of the 10th International Conference on Adaptive Multimedia Retrieval, AMR 2012, held in Copenhagen, Denmark, in October 2012. The 17 revised full papers presented were carefully reviewed and selected from numerous...... submissions. The papers cover topics of state of the art contributions, features and classification, location context, language and semantics, music retrieval, and adaption and HCI....

  8. Possibilities to improve the adaptation quality of calculated material substitutes

    Energy Technology Data Exchange (ETDEWEB)

    Geske, G.

    1981-04-01

    In calculating the composition of material substitutes by a system of simultaneous equations it is possible, by using a so called quality index, to find out of the set of solutions which generally exists that solution which possesses the best adaptation quality. Further improvement is often possible by describing coherent scattering and photoelectric interaction by an own material parameter for each effect. The exact formulation of these quantities as energy indepedent functions is, however, impossible. Using a set of attenuation coefficients at suitably chosen energies as coefficients for the system of equations the best substitutes are found. The solutions for the investigated example are identical with the original relative to its chemical composition. Such solutions may be of use in connection with neutrons, protons, heavy ions and negative pions. The components taken into consideration must, of course, permit such solutions. These facts are discussed in detail by two examples.

  9. Novel nanohybrid MTA compositions

    DEFF Research Database (Denmark)

    Lovschall, Henrik; Ranjkesh, Bahram

    Original Mineral Trioxide Aggregate (MTA) has been recommended for various uses in endodontics. MTA is a calcia, silica, alumina containing hydraulic cement with long setting time, calcium hydroxide release, and high pH. It possesses antibacterial and sealing properties. Interestingly, recent...... studies describe hydroxyapatite crystals form over MTA when it comes in contact with simulated physiological tissue fluid. On the basis of available evidence it appears that MTA efficiently develop superior marginal adaptation in humid environments. Observations suggest MTA is suitable material for pulp...... modified calcia-silica-alumina-sulphate composition with soluble fluorides, radiocontrast material, and nanosilicate. iMTA thereby demonstrate a remarkably high compressive strength in comparison to several commonly used dental cements. Reduction of iMTA setting time to 2-10 min with either flowable...

  10. Numerical Tools for Composite Woven Fabric Preforming

    Directory of Open Access Journals (Sweden)

    Abel Cherouat

    2013-01-01

    Full Text Available An important step in the manufacturing processes of thin composite components is the layingup of the reinforcement onto the mould surface. The prediction of the angular distortion of the reinforcement during draping and the changes in fibre orientation are essential for the understanding of the manufacture process and the evaluation of the mechanical properties of the composite structures. This paper presents an optimization-based method for the simulation of the forming processes of woven fabric reinforced composites. Two different approaches are proposed for the simulation of the draping of woven fabric onto complex geometries: geometrical and mechanical approaches. The geometrical approach is based on a fishnet model. It is well adapted to predimensioning fabrics and to give a suitable quantification of the resulting flat patterns. The mechanical approach is based on a mesostructural model. It allows us to take into account the mechanical properties of fibres and resin and the various dominating mode of deformation of woven fabrics during the forming process. Some numerical simulations of the forming process are proposed and compared with the experimental results in order to demonstrate the efficiency of our approaches.

  11. ARABIC TRANSLATION AND ADAPTATION OF THE HOSPITAL CONSUMER ASSESSMENT OF HEALTHCARE PROVIDERS AND SYSTEMS (HCAHPS) PATIENT SATISFACTION SURVEY INSTRUMENT.

    Science.gov (United States)

    Dockins, James; Abuzahrieh, Ramzi; Stack, Martin

    2015-01-01

    To translate and adapt an effective, validated, benchmarked, and widely used patient satisfaction measurement tool for use with an Arabic-speaking population. Translation of survey's items, survey administration process development, evaluation of reliability, and international benchmarking Three hundred-bed tertiary care hospital in Jeddah, Saudi Arabia. 645 patients discharged during 2011 from the hospital's inpatient care units. INTERVENTIONS; The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) instrument was translated into Arabic, a randomized weekly sample of patients was selected, and the survey was administered via telephone during 2011 to patients or their relatives. Scores were compiled for each of the HCAHPS questions and then for each of the six HCAHPS clinical composites, two non-clinical items, and two global items. Clinical composite scores, as well as the two non-clinical and two global items were analyzed for the 645 respondents. Clinical composites were analyzed using Spearman's correlation coefficient and Cronbach's alpha to demonstrate acceptable internal consistency for these items and scales demonstrated acceptable internal consistency for the clinical composites. (Spearman's correlation coefficient = 0.327 - 0.750, P quarterly to US national averages with results that closely paralleled the US benchmarks. . The Arabic translation and adaptation of the HCAHPS is a valid, reliable, and feasible tool for evaluation and benchmarking of inpatient satisfaction in Arabic speaking populations.

  12. Morphing of geometric composites via residual swelling.

    Science.gov (United States)

    Pezzulla, Matteo; Shillig, Steven A; Nardinocchi, Paola; Holmes, Douglas P

    2015-08-07

    Understanding and controlling the shape of thin, soft objects has been the focus of significant research efforts among physicists, biologists, and engineers in the last decade. These studies aim to utilize advanced materials in novel, adaptive ways such as fabricating smart actuators or mimicking living tissues. Here, we present the controlled growth-like morphing of 2D sheets into 3D shapes by preparing geometric composite structures that deform by residual swelling. The morphing of these geometric composites is dictated by both swelling and geometry, with diffusion controlling the swelling-induced actuation, and geometric confinement dictating the structure's deformed shape. Building on a simple mechanical analog, we present an analytical model that quantitatively describes how the Gaussian and mean curvatures of a thin disk are affected by the interplay among geometry, mechanics, and swelling. This model is in excellent agreement with our experiments and numerics. We show that the dynamics of residual swelling is dictated by a competition between two characteristic diffusive length scales governed by geometry. Our results provide the first 2D analog of Timoshenko's classical formula for the thermal bending of bimetallic beams - our generalization explains how the Gaussian curvature of a 2D geometric composite is affected by geometry and elasticity. The understanding conferred by these results suggests that the controlled shaping of geometric composites may provide a simple complement to traditional manufacturing techniques.

  13. E-CAI: a novel server to estimate an expected value of Codon Adaptation Index (eCAI

    Directory of Open Access Journals (Sweden)

    Garcia-Vallvé Santiago

    2008-01-01

    Full Text Available Abstract Background The Codon Adaptation Index (CAI is a measure of the synonymous codon usage bias for a DNA or RNA sequence. It quantifies the similarity between the synonymous codon usage of a gene and the synonymous codon frequency of a reference set. Extreme values in the nucleotide or in the amino acid composition have a large impact on differential preference for synonymous codons. It is thence essential to define the limits for the expected value of CAI on the basis of sequence composition in order to properly interpret the CAI and provide statistical support to CAI analyses. Though several freely available programs calculate the CAI for a given DNA sequence, none of them corrects for compositional biases or provides confidence intervals for CAI values. Results The E-CAI server, available at http://genomes.urv.es/CAIcal/E-CAI, is a web-application that calculates an expected value of CAI for a set of query sequences by generating random sequences with G+C and amino acid content similar to those of the input. An executable file, a tutorial, a Frequently Asked Questions (FAQ section and several examples are also available. To exemplify the use of the E-CAI server, we have analysed the codon adaptation of human mitochondrial genes that codify a subunit of the mitochondrial respiratory chain (excluding those genes that lack a prokaryotic orthologue and are encoded in the nuclear genome. It is assumed that these genes were transferred from the proto-mitochondrial to the nuclear genome and that its codon usage was then ameliorated. Conclusion The E-CAI server provides a direct threshold value for discerning whether the differences in CAI are statistically significant or whether they are merely artifacts that arise from internal biases in the G+C composition and/or amino acid composition of the query sequences.

  14. Adaptivity in GRAPPLE: Adaptation in any way you like (Poster)

    NARCIS (Netherlands)

    De Bra, P.M.E.; Smits, D.; Pechenizkiy, M.; Vasilyeva, E.; Bonk, C.J.; et al., xx

    2008-01-01

    GRAPPLE is an EU funded IST FP7 project that brings together a group of researchers into adaptive learning technology and environments and developers of learning management systems (LMSs), in order to offer adaptive learning as a standard feature of future LMSs. This paper presents the adaptation

  15. Measurements and modeling for examination of magnitudes and thresholds and transitions of cellular radio-protective mechanisms

    International Nuclear Information System (INIS)

    Leonard, B.

    2007-01-01

    Complete text of publication follows. Purpose: To provide results of dose and dose rate measurements, modeling and analysis for the high Radon 'inverse' dose-rate effect (IDRE), adaptive response (AR) , Bystander Effects (BE), Hyper-radiosensitivity and dose induced radioresistance (HRS/IRR) and the low LET IDRE. Methods: Radon progeny particle diameters decrease at high Radon levels, due to increased neutralization rates. Underground miners data are used to confirm lung dose effects. An adaptive response Microdose Model formulated from the microdose concepts of Feinendegen and his cohorts, is extended to include BE and applied to IDRE, AR and BE experimental data. Results: Analysis of underground miners data conclusively supports a factor of 4.3 in lung dose from increased deposition in the nasel passages, negating BE as cause of the Lubin et al (1995) high Radon lung cancer IDRE. This negates support of BE as major concern at domestic Radon levels and high LET galactic radiations for manned Mars mission. AR Microdose Model use for mammography X-rays shows single Specific Energy Hits, at very low dose rates to the cell nucleus, activates AR protection against spontaneous neoplastic transformations of a factor of 2 further supporting Redpath (2007) of no deleterious cancer risk from mammography X-rays and a dose/dose-rate coupling. IRR in HRS/IRR is from increased repair capability 'triggered' at a very low dose of 15 cGy. The 'triggering' is shown in low LET IDRE with G2/M checkpoint arrest. The correlation suggest IRR in both HRS/IRR and low LET IDRE dose and dose rate radio-protection are from the activation of same increased repair rate protective mechanisms i.e. dose/dose-rate coupling. In examination of LDR Brachytherapy, it's plausible the high excess post-treatment complications, especially for cervix cancer, compared to HDR Brachytherapy is from a high-radiosensitivity for the decaying permanent implant sources below the IDRE threshold with a possible

  16. Lamb Wave Response of Fatigued Composite Samples

    Science.gov (United States)

    Seale, Michael; Smith, Barry T.; Prosser, William H.; Masters, John E.

    1994-01-01

    Composite materials are being more widely used today by aerospace, automotive, sports equipment, and a number of other commercial industries because of their advantages over conventional metals. Composites have a high strength-to-weight ratio and can be constructed to meet specific design needs. Composite structures are already in use in secondary parts of the Douglas MD-11 and are planned to be used in the new MD-12X. Plans also exist for their use in primary and secondary structures on the Boeing 777. Douglas proposed MD-XX may also incorporate composite materials into primary structures such as the wings and tail. Use of composites in these structures offers weight savings, corrosion resistance, and improved aerodynamics. Additionally, composites have been used to repair cracks in many B-1Bs where traditional repair techniques were not very effective. Plans have also been made to reinforce all of the remaining B-1s with composite materials. Verification of the structural integrity of composite components is needed to insure safe operation of these aerospace vehicles. One aspect of the use of these composites is their response to fatigue. To track this progression of fatigue in aerospace structures, a convenient method to nondestructively monitor this damage needs to be developed. Traditional NDE techniques used on metals are not easily adaptable to composites due to the inhomogeneous and anisotropic nature of these materials. Finding an effective means of nondestructively monitoring fatigue damage is extremely important to the safety and reliability of such structures. Lamb waves offer one method of evaluating these composite materials. As a material is fatigued, the modulus degrades. Since the Lamb wave velocity can be related to the modulus of the material, an effective tool can be developed to monitor fatigue damage in composites by measuring the velocity of these waves. In this work, preliminary studies have been conducted which monitor fatigue damage in

  17. Thermotolerant Yeast Strains Adapted by Laboratory Evolution Show Trade-Off at Ancestral Temperatures and Preadaptation to Other Stresses

    DEFF Research Database (Denmark)

    Caspeta, Luis; Nielsen, Jens

    2015-01-01

    adaptive laboratory evolution, we previously isolated seven Saccharomyces cerevisiae strains with improved growth at 40°C. Here, we show that genetic adaptations to high temperature caused a growth trade-off at ancestral temperatures, reduced cellular functions, and improved tolerance of other stresses...... in the ancestral strain. The latter is an advantageous attribute for acquiring thermotolerance and correlates with the reduction of yeast functions associated with loss of respiration capacity. This trait caused glycerol overproduction that was associated with the growth trade-off at ancestral temperatures....... In combination with altered sterol composition of cellular membranes, glycerol overproduction was also associated with yeast osmotolerance and improved tolerance of high concentrations of glucose and ethanol. Our study shows that thermal adaptation of yeast is suitable for improving yeast resistance...

  18. Fibre-reinforced composite structures based on thermoplastic matrices with embedded piezoceramic modules

    International Nuclear Information System (INIS)

    Hufenbach, Werner A; Modler, Niels; Winkler, Anja; Ilg, Juergen; Rupitsch, Stefan J

    2014-01-01

    The paper presents recent developments for the integration of piezoceramic modules into fibre-reinforced composite structures based on thermoplastic matrices. An adapted hot pressing technology is conceptualized that allows for material homogeneous integration of the active modules. The main focus of this contribution is on the development of a robust and continuous manufacturing process of such novel active composites as well as on the operational testing of the produced samples. Therefore, selected specimens are manufactured as bending beams and investigated by means of electrical impedance measurements, modal analysis and structural excitation tests. In particular, the functionality of representative specimens is characterized based on frequency as well as spatially resolved deflection measurements. Moreover, the mentioned samples are compared to non-integrated piezoceramic modules and to equivalent passive reinforced composite structures. (paper)

  19. Association between the availability of environmental resources and the atomic composition of organismal proteomes: Evidence from Prochlorococcus strains living at different depths

    International Nuclear Information System (INIS)

    Lv Jie; Li Ning; Niu Dengke

    2008-01-01

    The cyanobacteria Prochlorococcus is a cyanbacterial genus, with some strains adapted to sea surface environments, which are poor in nutrients and have high-light intensity, and some strains adapted to deep sea conditions, which have relatively higher concentrations of nitrogen and phosphorus and lower light intensity. Here, we report pairwise comparisons between strains isolated from different depths of the same sea, which reveal a close association between atomic composition of the proteome and the availability nitrogen and phosphorus in the environment. The atomic composition of proteomes differs significantly among Prochlorococcus strains with different supplies of nitrogen in vivo; these different supplies result from different capacities for nitrogen assimilation. We repeated our whole-proteome analysis with the core proteomes of Prochlorococcus and obtained similar results. Our findings indicate that the elemental composition of proteomes is shaped by the availability of resources in the environment

  20. Adaptation of polystyrene/multi-wall carbon nanotube composite properties in respect of its thermal stability

    Czech Academy of Sciences Publication Activity Database

    Slobodian, P.; Králová, Daniela; Lengálová, A.; Novotný, R.; Sáha, P.

    2010-01-01

    Roč. 31, č. 3 (2010), s. 452-458 ISSN 0272-8397 Institutional research plan: CEZ:AV0Z40500505 Keywords : electrical conductivity * polymer composites * miniemulsion polymerization Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.998, year: 2010

  1. Film Adaptation as Translation: An Analysis of Adaptation Shifts in Silver Linings Playbook

    Directory of Open Access Journals (Sweden)

    Katerina Perdikaki

    2017-12-01

    Full Text Available The purpose of this paper is to approach film adaptation as a modality of translation and to provide a systematic analysis of the changes occurring in the adaptation of a novel for the big screen. These changes, i.e. adaptation shifts, are examined by means of a model that consists of a descriptive/comparative component and an interpretive component. The model is derived from combining insights from adaptation and translation studies and thus builds on the interdisciplinary nature of adaptation studies so as to offer a comprehensive methodological tool for the analysis of adaptations. As processes and products, adaptation and translation involve an act of communication between a source and a target text within a new sociocultural context. In this light, adaptation can be examined as a case of intersemiotic translation in that it involves the transfer of meaning between two different media; in the case of film adaptation, more specifically, meaning is transferred from book to film and the dynamics between the source novel and adaptation is juxtaposed with that between a source text and its translation. The adaptation model is applied to the film adaptation Silver Linings Playbook with an aim to understand the aspects in which the adaptation differs from the source novel and the rationale behind the adaptation shifts. Finally, it is argued that such an analysis from a descriptive as well as an interpretive perspective can lead to a more holistic understanding of adaptation as a cultural phenomenon in the contemporary creative industries.

  2. Five-year evaluation of a low-shrinkage Silorane resin composite material: a randomized clinical trial.

    Science.gov (United States)

    Schmidt, Malene; Dige, Irene; Kirkevang, Lise-Lotte; Vaeth, Michael; Hørsted-Bindslev, Preben

    2015-03-01

    The aim of the present study was to investigate the clinical performance of a low-shrinkage silorane-based composite material (Filtek™ Silorane, 3 M-Espe) by comparing it with a methacrylate-based composite material (Ceram•X™, Dentsply DeTrey). A number of 72 patients (158 restorations) participated in the study. After 5 years, a total of 107 restorations (52 Filtek™ Silorane, 55 Ceram•X™) in 48 patients were evaluated. Only class II restorations were included. All the restorations were placed by the same dentist, and the restorations were scored by one experienced dentist/evaluator. Materials were applied following the manufacturer's instructions. The primary outcome was marginal adaptation. Secondary outcomes were: marginal discoloration, approximal contact, anatomic form, fracture, secondary caries, and hypersensitivity. After 5 years, no statistically significant differences between the two materials were found in marginal adaptation either occlusally (p = 0.96) or approximally (p = 0.62). No statistically significant differences were found between the two materials in terms of approximal contact, anatomic form, fractures, or discoloration. Secondary caries was found in two teeth (Filtek™ Silorane). One tooth showed hypersensitivity (Ceram•X™). Restorations of both materials were clinically acceptable after 5 years. This study did not find any advantage of the silorane-based composite over the methacrylate-based composite, which indicates that the low-shrinkage of Filtek™ Silorane may not be a determinant factor for clinical success in class II cavities. This paper is the first to evaluate the 5-year clinical performance of a low-shrinkage composite material.

  3. Mechanical characterization of glass fiber (woven roving/chopped strand mat E-glass fiber) reinforced polyester composites

    Science.gov (United States)

    Bhaskar, V. Vijaya; Srinivas, Kolla

    2017-07-01

    Polymer reinforced composites have been replacing most of the engineering material and their applications become more and more day by day. Polymer composites have been analyzing from past thirty five years for their betterment for adapting more applications. This paper aims at the mechanical properties of polyester reinforced with glass fiber composites. The glass fiber is reinforced with polyester in two forms viz Woven Rovings (WRG) and Chopped Strand Mat (CSMG) E-glass fibers. The composites are fabricated by hand lay-up technique and the composites are cut as per ASTM Standard sizes for corresponding tests like flexural, compression and impact tests, so that flexural strength, compression strength, impact strength and inter laminar shear stress(ILSS) of polymer matrix composites are analyzed. From the tests and further calculations, the polyester composites reinforced with Chopped Strand Mat glass fiber have shown better performance against flexural load, compression load and impact load than that of Woven Roving glass fiber.

  4. EFFECT OF PLACEMENT TECHNIQUES, FLOWABLE COMPOSITE , LINER AND FIBRE INSERTS ON MARGINAL MICROLEAKAGE OF CLASS II COMPOSITE RESTORATIONS

    Directory of Open Access Journals (Sweden)

    Anupriya

    2015-08-01

    Full Text Available AIM : T he aim of this study was to evaluate effect of placement techniques, flow able composite, and fiber inserts in marginal adaptation of class II composite restorations. MATERIALS AND METHODS : 120 class II box cavities were prepared on both mesial and distal surfaces of extracted human molars. The prepared teeth were randomly assigned to 6 groups : 1 bulk insertion . ( S ingle increment, 2 O blique incremental placement technique, 3 Centripetal incremental placement technique . 4 S plit horizontal incremental placement technique . 5 flow able composite as gingival increment 6 ribbond fiber insert in gingival increment . The preparations were restored with a total etch adhesive (Adper Single Bond, 3M ESPE and nano composite (Z350, 3M ESPE. Specimens were isola ted with nail varnish except for a 2 - mm - wide rim around the restoration and thermocycled (1,000 thermal cycles, 5°C/55°C; 30 - second dwell time. The specimens were immersed in a solution of 2% methylene blue dye for 24 hours. The teeth were sectioned longi tudinally, observed under stereomicroscope and evaluated for microleakage using an ordinal scale of 0 to 4. The microleakage scores obtained from gingival walls were analyzed with Kruskal - Wallis and Mann Whitney nonparametric tests. RESULTS: Among all plac ement techniques split incremental technique showed least microleakage scores . The group that used flowable composite liner did not show significant reduction in microleakage and group with fiber inserts showed significant decrease in microleakage scores. CONCLUSION : None of the techniques eliminated marginal microleakage in class II composite restorations . However, the split incremental technique and group with fiber inserts showed significantly lower microleakage at gingival margin when compared to other groups

  5. Microbial examination of anaerobic sludge adaptation to animal slurry.

    Science.gov (United States)

    Moset, V; Cerisuelo, A; Ferrer, P; Jimenez, A; Bertolini, E; Cambra-López, M

    2014-01-01

    The objective of this study was to evaluate changes in the microbial population of anaerobic sludge digesters during the adaptation to pig slurry (PS) using quantitative real-time polymerase chain reaction (qPCR) and qualitative scanning electron microscopy (SEM). Additionally, the relationship between microbial parameters and sludge physicochemical composition and methane yield was examined. Results showed that the addition of PS to an unadapted thermophilic anaerobic digester caused an increase in volatile fatty acids (VFA) concentration, a decrease in removal efficiency and CH4 yield. Additionally, increases in total bacteria and total archaea were observed using qPCR. Scanning electron micrographs provided a general overview of the sludge's cell morphology, morphological diversity and degree of organic matter degradation. A change in microbial morphotypes from homogeneous cell morphologies to a higher morphological diversity, similar to that observed in PS, was observed with the addition of PS by SEM. Therefore, the combination of qPCR and SEM allowed expanding the knowledge about the microbial adaptation to animal slurry in thermophilic anaerobic digesters.

  6. Polymer Nanocomposites with Cellulose Nanocrystals Featuring Adaptive Surface Groups.

    Science.gov (United States)

    Natterodt, Jens C; Sapkota, Janak; Foster, E Johan; Weder, Christoph

    2017-02-13

    Cellulose nanocrystals (CNCs) are mechanically rigid, toxicologically benign, fiber-like nanoparticles. They can easily be extracted from renewable biosources and have attracted significant interest as reinforcing fillers in polymers. We here report the modification of CNCs with the 2-ureido-4[1H]pyrimidinone (UPy) motif as an adaptive compatibilizer, which permits the dispersion of UPy-modified CNCs in nonpolar as well as polar media. In toluene, the UPy motifs appear to form intra-CNC dimers, so that the particles are somewhat hydrophobized and well-dispersible in this nonpolar solvent. By contrast, the UPy motifs dissociate in DMF and promote dispersibility through interactions with this polar solvent. We have exploited this adaptiveness and integrated UPy-modified CNCs into nonpolar and polar host polymers, which include different poly(ethylene)s, a polystyrene-block-polybutadiene-block-polystyrene elastomer and poly(ethylene oxide-co-epichlorohydrin). All nanocomposites display an increase of stiffness and strength in comparison to the neat polymer, and some compositions retain a high elongation at break, even at a filler content of 15% w/w.

  7. Haunted Bodies: Cell Switching, Getting Lost and Adaptive Geographies

    Directory of Open Access Journals (Sweden)

    Jane Grant

    2017-11-01

    Full Text Available This article proposes the ideas of stochastic resonance and noise as devices with which to think of the body or self as plural and porous. Boundaries and surfaces are proposed as indefinite; cell switching and narratives of the self are discussed in relation to external forces, via Arendt’s inter-subjectivity and La Celca’s colonization as infection. The sonic artwork Ghost, which uses models of spiking neurons to materialize endogenous and exogenous composition in relation to noise and sonic memory is presented as an exploration of the boundary or limit of the notion of self. This paper, which serves as a cogitatum (a force rather than cognitio (the result, articulates the human body as a complex and open system that steers towards chaos by adapting and accepting further complexity as, and within, constantly adaptive networks of creativity. We suggest that by focusing on the porosity of boundaries and the mechanisms that underlie their permeability, problems around identity and subjectivity might be seen in a new light.

  8. Investigating the Burden of Chronic Pain: An Inflammatory and Metabolic Composite

    Directory of Open Access Journals (Sweden)

    Kimberly T. Sibille

    2016-01-01

    Full Text Available Background. Chronic pain is associated with increased morbidity and mortality, predominated by cardiovascular disease and cancer. Investigating related risk factor measures may elucidate the biological burden of chronic pain. Objectives. We hypothesized that chronic pain severity would be positively associated with the risk factor composite. Methods. Data from 12,982 participants in the 6th Tromsø study were analyzed. Questionnaires included demographics, health behaviors, medical comorbidities, and chronic pain symptoms. The risk factor composite was comprised of body mass index, fibrinogen, C-reactive protein, and triglycerides. Chronic pain severity was characterized by frequency, intensity, time/duration, and total number of pain sites. Results. Individuals with chronic pain had a greater risk factor composite than individuals without chronic pain controlling for covariates and after excluding inflammation-related health conditions (p<0.001. A significant “dose-response” relationship was demonstrated with pain severity (p<0.001. In individuals with chronic pain, the risk factor composite varied by health behavior, exercise, lower levels and smoking, and higher levels. Discussion. The risk factor composite was higher in individuals with chronic pain, greater with increasing pain severity, and influenced by health behaviors. Conclusions. Identification of a biological composite sensitive to pain severity and adaptive/maladaptive behaviors would have significant clinical and research utility.

  9. Shape memory alloy wires turn composites into smart structures: I. Material requirements

    Science.gov (United States)

    Schrooten, Jan; Michaud, Veronique J.; Zheng, Yanjun; Balta-Neumann, J. Antonio; Manson, Jan-Anders E.

    2002-07-01

    Composites containing thin Shape Memory Alloy (SMA) wires show great potential as materials able to adapt their shape, thermal behavior or vibrational properties to external stimuli. The functional properties of SMA-composites are directly related to the constraining effect of the matrix on the reversible martensitic transformation of the embedded pre-strained SMA wires. The present work reports results of a concerted European effort towards a fundamental understanding of the manufacturing and design of SMA composites. This first part investigates the transformational behavior of constrained SMA wires and its translation into functional properties of SMA composites. Thermodynamic and thermomechanical experiments were performed on SMA wires. A model was developed to simulate the thermomechanical behavior of the wires. From the screening of potential wires it was concluded that NiTiCu, as well as R-phase NiTi appeared as best candidates. Requirements for the host composite materials were surveyed. A Kevlar-epoxy system was chosen. Finally, the quality of the SMA wire-resin interface was assessed by two different techniques. These indicated that a thin oxide layer seems to provide the best interfacial strength. A temperature window in which SMA composites can be safely used was also defined. The manufacturing and properties of the SMA composites will be discussed in Part II.

  10. The Effects of Weaning Methods on Gut Microbiota Composition and Horse Physiology

    Directory of Open Access Journals (Sweden)

    Núria Mach

    2017-07-01

    Full Text Available Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i the effect of two different weaning methods on the composition of gut microbiota across time and (ii how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P or an abrupt (A weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d. Different host phenotypes and gut microbiota composition were studied across 6 age strata (days −30, 0, 3, 5, 7, and 30 after weaning by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella, and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus, on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp. were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is

  11. The Effects of Weaning Methods on Gut Microbiota Composition and Horse Physiology.

    Science.gov (United States)

    Mach, Núria; Foury, Aline; Kittelmann, Sandra; Reigner, Fabrice; Moroldo, Marco; Ballester, Maria; Esquerré, Diane; Rivière, Julie; Sallé, Guillaume; Gérard, Philippe; Moisan, Marie-Pierre; Lansade, Léa

    2017-01-01

    Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i) the effect of two different weaning methods on the composition of gut microbiota across time and (ii) how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P) or an abrupt (A) weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d). Different host phenotypes and gut microbiota composition were studied across 6 age strata (days -30, 0, 3, 5, 7, and 30 after weaning) by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella , and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus , on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp.) were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is likely to

  12. Clinical Evaluation of Microhybrid Composite and Glass lonomer Restorative Material in Permanent Teeth.

    Science.gov (United States)

    Kharma, Khalil; Zogheib, Tatiana; Bhandi, Shilpa; Mehanna, Carina

    2018-02-01

    The aim of this study was to clinically compare glass ionomer cement (GIC) with microhybrid composite resin used in class I cavities on permanent teeth over a period of 9 months. A total of 40 teeth with class I cavities were divided into two groups (n = 20) and restored with GIC (EQUIA; GC) and microhybrid resin composite (Amelogen Plus; Ultradent). Restorations were evaluated at ×4.5 magnification using the United States Public Health Service (USPHS) criteria every 3 months. Statistical analysis was performed using the Fisher's exact test (a material handling, adaptation, and marginal staining. The results of this clinical study showed that GIC (EQUIA; GC) can be used for the restoration of permanent teeth and may be more appropriate for certain clinical situations than the resin composite material. EQUIA (GIC) is a viable alternative to resin composite in restoring class I cavities in permanent teeth.

  13. Disturbances catalyze the adaptation of forest ecosystems to changing climate conditions.

    Science.gov (United States)

    Thom, Dominik; Rammer, Werner; Seidl, Rupert

    2017-01-01

    The rates of anthropogenic climate change substantially exceed those at which forest ecosystems - dominated by immobile, long-lived organisms - are able to adapt. The resulting maladaptation of forests has potentially detrimental effects on ecosystem functioning. Furthermore, as many forest-dwelling species are highly dependent on the prevailing tree species, a delayed response of the latter to a changing climate can contribute to an extinction debt and mask climate-induced biodiversity loss. However, climate change will likely also intensify forest disturbances. Here, we tested the hypothesis that disturbances foster the reorganization of ecosystems and catalyze the adaptation of forest composition to climate change. Our specific objectives were (i) to quantify the rate of autonomous forest adaptation to climate change, (ii) examine the role of disturbance in the adaptation process, and (iii) investigate spatial differences in climate-induced species turnover in an unmanaged mountain forest landscape (Kalkalpen National Park, Austria). Simulations with a process-based forest landscape model were performed for 36 unique combinations of climate and disturbance scenarios over 1000 years. We found that climate change strongly favored European beech and oak species (currently prevailing in mid- to low-elevation areas), with novel species associations emerging on the landscape. Yet, it took between 357 and 706 years before the landscape attained a dynamic equilibrium with the climate system. Disturbances generally catalyzed adaptation and decreased the time needed to attain equilibrium by up to 211 years. However, while increasing disturbance frequency and severity accelerated adaptation, increasing disturbance size had the opposite effect. Spatial analyses suggest that particularly the lowest and highest elevation areas will be hotspots of future species change. We conclude that the growing maladaptation of forests to climate and the long lead times of autonomous

  14. Micro-CT evaluation of internal adaptation in resin fillings with different dentin adhesives

    Directory of Open Access Journals (Sweden)

    Seung-Hoon Han

    2014-02-01

    Full Text Available Objectives The purpose of present study was to evaluate the internal adaptation of composite restorations using different adhesive systems. Materials and Methods Typical class I cavities were prepared in 32 human third molars. The teeth were divided into the following four groups: 3-step etch-and-rinse, 2-step etch-and-rinse, 2-step self-etch and 1-step self-etch system were used. After the dentin adhesives were applied, composite resins were filled and light-cured in two layers. Then, silver nitrate solution was infiltrated, and all of the samples were scanned by micro-CT before and after thermo-mechanical load cycling. For each image, the length to which silver nitrate infiltrated, as a percentage of the whole pulpal floor length, was calculated (%SP. To evaluate the internal adaptation using conventional method, the samples were cut into 3 pieces by two sectioning at an interval of 1 mm in the middle of the cavity and they were dyed with Rhodamine-B. The cross sections of the specimens were examined by stereomicroscope. The lengths of the parts where actual leakage was shown were measured and calculated as a percentage of real leakage (%RP. The values for %SP and %RP were compared. Results After thermo-mechanical loading, all specimens showed significantly increased %SP compared to before thermo-mechanical loading and 1-step self-etch system had the highest %SP (p < 0.05. There was a tendency for %SP and %RP to show similar microleakage percentage depending on its sectioning. Conclusions After thermo-mechanical load cycling, there were differences in internal adaptation among the groups using different adhesive systems.

  15. Nature of changes in body composition indices in students during physical training using a set of athleticism.

    Directory of Open Access Journals (Sweden)

    Chernozub A.A.

    2011-06-01

    Full Text Available During investigations it was established that there are important changes in body composition parameters university students, who in the classroom with the general physical culture introduced by the training facilities with athleticism. The level indicators of body composition and dynamics are fully dependent on the employment structure, volume and intensity of physical exertion their focus. It is established that achieving the optimal performance of body composition may occur even with minimal training work. Planning sessions with physical cultures s light variation of volume and intensity of stress, achieves the required level of adaptation processes.

  16. Radiopacity of 28 Composite Resins for Teeth Restorations.

    Science.gov (United States)

    Raitz, Ricardo; Moruzzi, Patrizia Dubinskas; Vieira, Glauco; Fenyo-Pereira, Marlene

    2016-02-01

    Radiopacity is a fundamental requisite to check marginal adaptation of restorations. Our objective was to assess the radiopacity of 28 brands of light-cured composite resins and compare their radiopacity with that of enamel, dentin, and aluminum of equivalent thickness. Composite resin disks (0.2, 0.5, and 1 mm) were radiographed by the digital method, together with an aluminum penetrometer and a human tooth equivalent tooth section. The degree of radiopacity of each image was quantified using digital image processing. Wilcoxon nonparametric test was used for comparison of the mean thickness of each material. All of the materials tested had an equal or greater radiopacity than that of aluminum of equivalent thickness. Similar results for enamel were found with the exception of Durafill, which was less radiopaque than enamel (p composite resins comply with specification #27 of the American Dental Association. The radiopacity of Amelogen Plus, Aph, Brilhiante, Charisma, Concept Advanced, Evolux X, Exthet X, Inten S, Llis, Master Fill, Natural Look, Opallis, P60, Tetric, Tph, Z100, and Z250 was significantly higher than that of enamel (p composites, it is possible to observe the boundaries between restoration and tooth structure, thus allowing clinicians to establish the presence of microleakage or restoration gap. Suitable radiopacity is an essential requisite for good-quality esthetic restorative materials. We demonstrate that only some composites have the sufficient radiopacity to observe the boundaries between restoration and tooth structure, which is the main cause of restoration failure.

  17. Active materials for adaptive architectural envelopes based on plant adaptation principles

    Directory of Open Access Journals (Sweden)

    Marlen Lopez

    2015-06-01

    Full Text Available In this paper, the authors present research into adaptive architectural envelopes that adapt to environmental changes using active materials, as a result of application of biomimetic principles from plants to architecture. Buildings use large amounts of energy in order to maintain their internal comfort, because conventional buildings are designed to provide a static design solution. Most of the current solutions for facades are not designed for optimum adaptation to contextual issues and needs, while biological solutions to adaptation are often complex, multi-functional and highly responsive. We focus on plant adaptations to the environment, as, due to their immobility, they have developed special means of protection against weather changing conditions. Furthermore, recent developments in new technologies are allowing the possibility to transfer these plant adaptation strategies to technical implementation. These technologies include: multi-material 3D printing, advances in materials science and new capabilities in simulation software. Unlike traditional mechanical activation used for dynamic systems in kinetic facades, adaptive architectural envelopes require no complex electronics, sensors, or actuators. The paper proposes a research of the relationship that can be developed between active materials and environmental issues in order to propose innovative and low-tech design strategies to achieve living envelopes according to plant adaptation principles.  

  18. Adaptive protection scheme

    Directory of Open Access Journals (Sweden)

    R. Sitharthan

    2016-09-01

    Full Text Available This paper aims at modelling an electronically coupled distributed energy resource with an adaptive protection scheme. The electronically coupled distributed energy resource is a microgrid framework formed by coupling the renewable energy source electronically. Further, the proposed adaptive protection scheme provides a suitable protection to the microgrid for various fault conditions irrespective of the operating mode of the microgrid: namely, grid connected mode and islanded mode. The outstanding aspect of the developed adaptive protection scheme is that it monitors the microgrid and instantly updates relay fault current according to the variations that occur in the system. The proposed adaptive protection scheme also employs auto reclosures, through which the proposed adaptive protection scheme recovers faster from the fault and thereby increases the consistency of the microgrid. The effectiveness of the proposed adaptive protection is studied through the time domain simulations carried out in the PSCAD⧹EMTDC software environment.

  19. Inhabiting Adaptive Architecture

    Directory of Open Access Journals (Sweden)

    Holger Schnädelbach

    2017-12-01

    Full Text Available Adaptive Architecture concerns buildings that are specifically designed to adapt to their inhabitants and to their environments. Work in this space has a very long history, with a number of adaptive buildings emerging during the modernist period, such as Rietveld’s Schröder house, Gaudi’s Casa Batlló and Chareau's Maison de Verre. Such early work included manual adaptivity, even if that was motor-assisted. Today, buildings have started to combine this with varying degrees of automation and designed-for adaptivity is commonplace in office buildings and eco homes, where lighting, air conditioning, access and energy generation respond to and influence the behaviour of people, and the internal and external climate.

  20. Appraising Adaptive Management

    Directory of Open Access Journals (Sweden)

    Kai N. Lee

    1999-12-01

    Full Text Available Adaptive management is appraised as a policy implementation approach by examining its conceptual, technical, equity, and practical strengths and limitations. Three conclusions are drawn: (1 Adaptive management has been more influential, so far, as an idea than as a practical means of gaining insight into the behavior of ecosystems utilized and inhabited by humans. (2 Adaptive management should be used only after disputing parties have agreed to an agenda of questions to be answered using the adaptive approach; this is not how the approach has been used. (3 Efficient, effective social learning, of the kind facilitated by adaptive management, is likely to be of strategic importance in governing ecosystems as humanity searches for a sustainable economy.

  1. Adaptive user interfaces

    CERN Document Server

    1990-01-01

    This book describes techniques for designing and building adaptive user interfaces developed in the large AID project undertaken by the contributors.Key Features* Describes one of the few large-scale adaptive interface projects in the world* Outlines the principles of adaptivity in human-computer interaction

  2. The Compositional Rule of Inference and Zadeh’s Extension Principle for Non-normal Fuzzy Sets

    NARCIS (Netherlands)

    van den Broek, P.M.; Noppen, J.A.R.; Castillo, Oscar

    2007-01-01

    Defining the standard Boolean operations on fuzzy Booleans with the compositional rule of inference (CRI) or Zadeh's extension principle gives counter-intuitive results. We introduce and motivate a slight adaptation of the CRI, which only effects the results for non-normal fuzzy sets. It is shown

  3. Adaptive Education.

    Science.gov (United States)

    Anderson, Lorin W.

    1979-01-01

    Schools have devised several ways to adapt instruction to a wide variety of student abilities and needs. Judged by criteria for what adaptive education should be, most learning for mastery programs look good. (Author/JM)

  4. Thermal fatigue of refractory metal/graphite composites for fusion applications

    International Nuclear Information System (INIS)

    Smid, I; Nickel, H.; Kny, E.; Reheis, N.

    1995-01-01

    Reactor grade graphite and molybdenum (TZM) were brazed with different high temperature brazes. The resulting composite tiles had a size of 50 mm x 50 mm with a graphite thickness of 10 mm and a TZM thickness of 5 mm. The brazed composites have been tested in electron beam simulation for their thermal fatigue properties. The parameters of these tests were chosen to match NET design specifications for normal operation and 'slow' peak energy deposition. The resulting damages and microstructural changes on the graphites and the brazes are discussed. Additional information is supplied on X-ray diffraction data proving the presence of different phases in the brazes. Finally the influence of a hydrogen plasma on the adaptability of the investigated brazes in fusion devices is discussed. (author)

  5. A medicated polycarboxylate cement to prevent complications in composite resin therapy

    International Nuclear Information System (INIS)

    Okamoto, Y.; Shintani, H.; Yamaki, M.

    1990-01-01

    Preparative treatment is the preferred method to protect the dentin and pulp from complications in composite resin therapy. This study investigated the in vivo effects of the polycarboxylate cement containing zinc fluoride and tannic acid in composite resin restorations. Scanning electron micrographs established that the composite resin failed to contact the axial wall. The gaps varied from 10 to 60 microns. However, this polycarboxylate cement was shown to provide excellent adaptation to dentin when used as a base and its chemical adhesion allowed it to make close contact with the unetched dentin. The newly developed electron probe x-ray microanalyzer revealed that the in vivo penetration of fluoride and zinc occurred through the dentinal tubules. When this polycarboxylate cement was used, the orifices of dentinal tubules were partially occluded, possibly with the smear layer fixed by tannic acid. In addition, by releasing the components, this polycarboxylate cement adds acid resistance to dentin and increases the resistance of dentin collagen to proteolytic enzymes. As such this polycarboxylate cement offers advantages as a base to composite resin therapy

  6. Finite element reduction strategy for composite sandwich plates with viscoelastic layers

    Directory of Open Access Journals (Sweden)

    Adriana Amaro Diacenco

    2013-04-01

    Full Text Available Composite materials have been regarded as a convenient strategy in various types of engineering systems such as aeronautical and space structures, as well as architecture and light industry products due to their advantages over the traditional engineering materials, such as their high strength/stiffness relation characteristics and their anti-corrosion properties. This paper is devoted to the finite element modeling of composite laminated structures incorporating viscoelastic materials to the problem of vibration attenuation. However, the typically high dimension of large finite element models of composite structures incorporating viscoelastic materials makes the numerical processes sometimes unfeasible. Within this context, emphasis is placed on a general condensation strategy specially adapted for the case of viscoelastically damped structures, in which a constant (frequency- and temperature-independent reduction basis to be enriched by static residues associated to the applied loads and the viscoelastic forces is used. After presenting the theoretical foundations, the numerical applications of composite plates treated by viscoelastic materials are addressed, and the main features of the methodology are discussed.

  7. Finite element reduction strategy for composite sandwich plates with viscoelastic layers

    Directory of Open Access Journals (Sweden)

    Adriana Amaro Diacenco

    2012-01-01

    Full Text Available Composite materials have been regarded as a convenient strategy in various types of engineering systems such as aeronautical and space structures, as well as architecture and light industry products due to their advantages over the traditional engineering materials, such as their high strength/stiffness relation characteristics and their anti-corrosion properties. This paper is devoted to the finite element modeling of composite laminated structures incorporating viscoelastic materials to the problem of vibration attenuation. However, the typically high dimension of large finite element models of composite structures incorporating viscoelastic materials makes the numerical processes sometimes unfeasible. Within this context, emphasis is placed on a general condensation strategy specially adapted for the case of viscoelastically damped structures, in which a constant (frequency- and temperature-independent reduction basis to be enriched by static residues associated to the applied loads and the viscoelastic forces is used. After presenting the theoretical foundations, the numerical applications of composite plates treated by viscoelastic materials are addressed, and the main features of the methodology are discussed.

  8. Composite synchronization of three eccentric rotors driven by induction motors in a vibrating system

    Science.gov (United States)

    Kong, Xiangxi; Chen, Changzheng; Wen, Bangchun

    2018-03-01

    This paper addresses the problem of composite synchronization of three eccentric rotors (ERs) driven by induction motors in a vibrating system. The composite synchronous motion of three ERs is composed of the controlled synchronous motion of two ERs and the self-synchronous motion of the third ER. Combining an adaptive sliding mode control (ASMC) algorithm with a modified master-slave control structure, the controllers are designed to implement controlled synchronous motion of two ERs with zero phase difference. Based on Lyapunov stability theorem and Barbalat's lemma, the stability of the designed controllers is verified. On basis of controlled synchronization of two ERs, self-synchronization of the third ER is introduced to implement composite synchronous motion of three ERs. The feasibility of the proposed composite synchronization method is analyzed by numerical method. The effects of motor and structure parameters on composite synchronous motion are discussed. Experiments on a vibrating test bench driven by three ERs are operated to validate the effectiveness of the proposed composite synchronization method, including a comparison with self-synchronization method.

  9. Finite element analysis of Al 2024/Cu-Al-Ni shape memory alloy composites with defects/cracks

    Science.gov (United States)

    Kotresh, M.; Benal, M. M., Dr; Siddalinga Swamy, N. H., Dr

    2018-02-01

    In this work, a numerical approach to predict the stress field behaviour of defect/crack in shape memory alloy (SMA) particles reinforced composite known as the adaptive composite is presented. Simulation is based on the finite element method. The critical stress field approach was used to determine the stresses around defect/crack. Thereby stress amplification issue is being resolved. In this paper, the effect volume % of shape memory alloy and shape memory effect of reinforcement for as-cast and SME trained composites are examined and discussed. Shape memory effect known as training is achieved by pre-straining of reinforcement particles by equivalent changes in their expansion coefficients.

  10. Coupling internal cerebellar models enhances online adaptation and supports offline consolidation in sensorimotor tasks

    OpenAIRE

    Passot , Jean-Baptiste; Luque , Niceto R.; Arleo , Angelo

    2013-01-01

    International audience; The cerebellum is thought to mediate sensorimotor adaptation through the acquisition of internal models of the body-environment interaction. These representations can be of two types, identified as forward and inverse models. The first predicts the sensory consequences of actions, while the second provides the correct commands to achieve desired state transitions. In this paper, we propose a composite architecture consisting of multiple cerebellar internal models to ac...

  11. Novel Repair Concept for Composite Materials by Repetitive Geometrical Interlock Elements

    Directory of Open Access Journals (Sweden)

    David Zaremba

    2011-12-01

    Full Text Available Material adapted repair technologies for fiber-reinforced polymers with thermosetting matrix systems are currently characterized by requiring major efforts for repair preparation and accomplishment in all industrial areas of application. In order to allow for a uniform distribution of material and geometrical parameters over the repair zone, a novel composite interlock repair concept is introduced, which is based on a repair zone with undercuts prepared by water-jet technology. The presented numerical and experimental sensitivity analyses make a contribution to the systematic development of the interlock repair technology with respect to material and geometrical factors of influence. The results show the ability of the novel concept for a reproducible and automatable composite repair.

  12. A computational framework for modeling targets as complex adaptive systems

    Science.gov (United States)

    Santos, Eugene; Santos, Eunice E.; Korah, John; Murugappan, Vairavan; Subramanian, Suresh

    2017-05-01

    Modeling large military targets is a challenge as they can be complex systems encompassing myriad combinations of human, technological, and social elements that interact, leading to complex behaviors. Moreover, such targets have multiple components and structures, extending across multiple spatial and temporal scales, and are in a state of change, either in response to events in the environment or changes within the system. Complex adaptive system (CAS) theory can help in capturing the dynamism, interactions, and more importantly various emergent behaviors, displayed by the targets. However, a key stumbling block is incorporating information from various intelligence, surveillance and reconnaissance (ISR) sources, while dealing with the inherent uncertainty, incompleteness and time criticality of real world information. To overcome these challenges, we present a probabilistic reasoning network based framework called complex adaptive Bayesian Knowledge Base (caBKB). caBKB is a rigorous, overarching and axiomatic framework that models two key processes, namely information aggregation and information composition. While information aggregation deals with the union, merger and concatenation of information and takes into account issues such as source reliability and information inconsistencies, information composition focuses on combining information components where such components may have well defined operations. Since caBKBs can explicitly model the relationships between information pieces at various scales, it provides unique capabilities such as the ability to de-aggregate and de-compose information for detailed analysis. Using a scenario from the Network Centric Operations (NCO) domain, we will describe how our framework can be used for modeling targets with a focus on methodologies for quantifying NCO performance metrics.

  13. Building on the links between climate change adaptation and disaster risk reduction

    CSIR Research Space (South Africa)

    Vincent, K

    2017-09-01

    Full Text Available countries, genetically modified organisms (GMOs) have been embraced to address challenges of low productivity and related occurrences of food insecurity; but that adaptation to climate change may be seen as placing an increased risk on genetic diversity... and terrestrial ecosystems. This is because it can “out-compete” other varieties locally, reducing species composition and thus the gene pool; but also because forces such as wind dispersal and erosion mean that containing the effects of GMOs in one area...

  14. Adaptation to environmental temperature is a major determinant of molecular evolutionary rates in archaea.

    Science.gov (United States)

    Groussin, Mathieu; Gouy, Manolo

    2011-09-01

    Methods to infer the ancestral conditions of life are commonly based on geological and paleontological analyses. Recently, several studies used genome sequences to gain information about past ecological conditions taking advantage of the property that the G+C and amino acid contents of bacterial and archaeal ribosomal DNA genes and proteins, respectively, are strongly influenced by the environmental temperature. The adaptation to optimal growth temperature (OGT) since the Last Universal Common Ancestor (LUCA) over the universal tree of life was examined, and it was concluded that LUCA was likely to have been a mesophilic organism and that a parallel adaptation to high temperature occurred independently along the two lineages leading to the ancestors of Bacteria on one side and of Archaea and Eukarya on the other side. Here, we focus on Archaea to gain a precise view of the adaptation to OGT over time in this domain. It has been often proposed on the basis of indirect evidence that the last archaeal common ancestor was a hyperthermophilic organism. Moreover, many results showed the influence of environmental temperature on the evolutionary dynamics of archaeal genomes: Thermophilic organisms generally display lower evolutionary rates than mesophiles. However, to our knowledge, no study tried to explain the differences of evolutionary rates for the entire archaeal domain and to investigate the evolution of substitution rates over time. A comprehensive archaeal phylogeny and a non homogeneous model of the molecular evolutionary process allowed us to estimate ancestral base and amino acid compositions and OGTs at each internal node of the archaeal phylogenetic tree. The last archaeal common ancestor is predicted to have been hyperthermophilic and adaptations to cooler environments can be observed for extant mesophilic species. Furthermore, mesophilic species present both long branches and high variation of nucleotide and amino acid compositions since the last archaeal

  15. Molecular adaptation during adaptive radiation in the Hawaiian endemic genus Schiedea.

    Directory of Open Access Journals (Sweden)

    Maxim V Kapralov

    2006-12-01

    Full Text Available "Explosive" adaptive radiations on islands remain one of the most puzzling evolutionary phenomena. The rate of phenotypic and ecological adaptations is extremely fast during such events, suggesting that many genes may be under fairly strong selection. However, no evidence for adaptation at the level of protein coding genes was found, so it has been suggested that selection may work mainly on regulatory elements. Here we report the first evidence that positive selection does operate at the level of protein coding genes during rapid adaptive radiations. We studied molecular adaptation in Hawaiian endemic plant genus Schiedea (Caryophyllaceae, which includes closely related species with a striking range of morphological and ecological forms, varying from rainforest vines to woody shrubs growing in desert-like conditions on cliffs. Given the remarkable difference in photosynthetic performance between Schiedea species from different habitats, we focused on the "photosynthetic" Rubisco enzyme, the efficiency of which is known to be a limiting step in plant photosynthesis.We demonstrate that the chloroplast rbcL gene, encoding the large subunit of Rubisco enzyme, evolved under strong positive selection in Schiedea. Adaptive amino acid changes occurred in functionally important regions of Rubisco that interact with Rubisco activase, a chaperone which promotes and maintains the catalytic activity of Rubisco. Interestingly, positive selection acting on the rbcL might have caused favorable cytotypes to spread across several Schiedea species.We report the first evidence for adaptive changes at the DNA and protein sequence level that may have been associated with the evolution of photosynthetic performance and colonization of new habitats during a recent adaptive radiation in an island plant genus. This illustrates how small changes at the molecular level may change ecological species performance and helps us to understand the molecular bases of extremely

  16. Types of adaptation of the system of enterprise economic security to the impact of subjects of tax regulation

    Directory of Open Access Journals (Sweden)

    Pohorelov Yurii S.

    2014-01-01

    Full Text Available The article offers the authors’ approach to identification of types of adaptation of the system of enterprise economic security to negative influence of subjects of tax regulation. It determines composition of these subjects and, separately, regulation subjects that form fundamental grounds of the tax sphere and subjects of effective influence, which directly interact with entrepreneurial structures and realise tax regulation of their activity in practice. As regards direct adaptation of the system of enterprise economic security, the article offers to mark out its individual types with respect to the set goal, essence of changes in the system of economic security, degree of its manageability and nature of accumulated changes. Moreover, the article offers a list of catalysts and inhibitors of adaptation of the system of enterprise economic security to impact of subjects of tax regulation. It also marks out adaptation parameters of the system of enterprise economic security to the impact of subjects of tax regulation and provides their gradations.

  17. An adaptive signal-processing approach to online adaptive tutoring.

    Science.gov (United States)

    Bergeron, Bryan; Cline, Andrew

    2011-01-01

    Conventional intelligent or adaptive tutoring online systems rely on domain-specific models of learner behavior based on rules, deep domain knowledge, and other resource-intensive methods. We have developed and studied a domain-independent methodology of adaptive tutoring based on domain-independent signal-processing approaches that obviate the need for the construction of explicit expert and student models. A key advantage of our method over conventional approaches is a lower barrier to entry for educators who want to develop adaptive online learning materials.

  18. Long-term effective population sizes, temporal stability of genetic composition and potential for local adaptation in anadromous brown trout ( Salmo trutta ) populations

    DEFF Research Database (Denmark)

    Hansen, Michael Møller; Ruzzante, D.E.; Eg Nielsen, Einar

    2002-01-01

    temporal samples from the same populations than among samples from different populations. Estimates of N-e, using a likelihood-based implementation of the temporal method, revealed N-e greater than or equal to 500 in two of three populations for which we have historical data. A third population in a small...... (3 km) river showed Ne greater than or equal to 300. Assuming a stepping-stone model of gene flow we considered the relative roles of gene flow, random genetic drift and selection to assess the possibilities for local adaptation. The requirements for local adaptation were fulfilled, but only...... adaptations resulting from strong selection were expected to occur at the level of individual populations. Adaptations resulting from weak selection were more likely to occur on a regional basis, i.e. encompassing several populations. N-e appears to have declined recently in at least one of the studied...

  19. Uncertainty in adaptive capacity

    International Nuclear Information System (INIS)

    Neil Adger, W.; Vincent, K.

    2005-01-01

    The capacity to adapt is a critical element of the process of adaptation: it is the vector of resources that represent the asset base from which adaptation actions can be made. Adaptive capacity can in theory be identified and measured at various scales, from the individual to the nation. The assessment of uncertainty within such measures comes from the contested knowledge domain and theories surrounding the nature of the determinants of adaptive capacity and the human action of adaptation. While generic adaptive capacity at the national level, for example, is often postulated as being dependent on health, governance and political rights, and literacy, and economic well-being, the determinants of these variables at national levels are not widely understood. We outline the nature of this uncertainty for the major elements of adaptive capacity and illustrate these issues with the example of a social vulnerability index for countries in Africa. (authors)

  20. Assessment of vulnerability of forest ecosystems to climate change and adaptation planning in Nepal

    Science.gov (United States)

    Matin, M. A.; Chitale, V. S.

    2016-12-01

    Understanding ecosystem level vulnerability of forests and dependence of local communities on these ecosystems is a first step towards developing effective adaptation strategies. As forests are important components of livelihoods system for a large percentage of the population in the Himalayan region, they offer an important basis for creating and safeguarding more climate-resilient communities. Increased frequency, duration, and/or severity of drought and heat stress, changes in winter ecology, and pest and fire outbreaksunder climate change scenarios could fundamentally alter the composition, productivity and biogeography of forests affecting the potential ecosystem services offered and forest-based livelihoods. Hence, forest ecosystem vulnerability assessment to climate change and the development of a knowledgebase to identify and support relevant adaptation strategies is identified as an urgent need. Climate change vulnerability is measured as a function of exposure, sensitivity and the adaptive capacity of the system towards climate variability and extreme events. Effective adaptation to climate change depends on the availability of two important prerequisites: a) information on what, where, and how to adapt, and b) availability of resources to implement the adaptation measures. In the present study, we introduce the concept of two way multitier approach, which can support effective identification and implementation of adaptation measures in Nepal and the framework can be replicated in other countries in the HKH region. The assessment of overall vulnerability of forests comprises of two components: 1) understanding the relationship between exposure and sensitivity and positive feedback from adaptive capacity of forests; 2) quantifying the dependence of local communities on these ecosystems. We use climate datasets from Bioclim and biophysical products from MODIS, alongwith field datasets. We report that most of the forests along the high altitude areas and few

  1. Raters’ Perception and Expertise in Evaluating Second Language Compositions

    Directory of Open Access Journals (Sweden)

    Houman Bijani

    2010-11-01

    Full Text Available The consideration of rater training is very important in construct validation of a writing test because it is through training that raters are adapted to the use of students’ writing ability instead of their own criteria for assessing compositions (Charney, 1984. However, although training has been discussed in the literature of writing assessment, there is little research regarding raters’ perceptions and understandings of the training program. Although a few studies have looked at the differences between trained and untrained raters in writing assessment (Cumming, 1990; Huot, 1990, few studies have used a pre-and post-training design. The purpose of this study is to investigate the effectiveness of the training program on experienced and inexperienced raters with regard to a pre-and post- training design. Twelve EFL raters scored 45 pre-rated benchmark essay compositions by an authorized IELTS trainer. These essay compositions were scored before, during and after the training program. The results regarding the comparison across raters showed that inexperienced raters had wider range of inconsistency before training but they became more consistent than experienced raters after training.

  2. A data processing unit (DPU) for a satellite-borne charge composition experiment

    International Nuclear Information System (INIS)

    Koga, R.; Blake, J.B.; Chenette, D.L.; Fennell, J.F.; Imamoto, S.S.; Katz, N.; King, C.G.

    1985-01-01

    A data processing unit (DPU) for use with a charge composition experiment to be flown aboard the VIKING auroral research satellite is described. The function of this experiment is to measure the mass, charge state, energy, and pitch-angle distribution of ions in the earth's high-altitude magnetosphere in the energy range from 50 keV/q to 300 keV/q. In order to be compatible with the spacecraft telemetry limitations, raw sensor data are processed in the DPU using on-board composition analysis and the scalar compression. The design of this DPU is such that it can be readily adapted to a variety of space composition experiments. Special attention was given to the effect of the radiation environment on orbit since a microprocessor and a relatively large number of random access memories (RAMs) comprise a considerable portion of the DPU

  3. Adaptive capacity and human cognition: the process of individual adaptation to climate change

    Energy Technology Data Exchange (ETDEWEB)

    Grothmann, T. [Potsdam Institute for Climate Impact Research, Potsdam (Germany). Department of Global Change and Social Systems; Patt, A. [Boston University (United States). Department of Geography

    2005-10-01

    Adaptation has emerged as an important area of research and assessment among climate change scientists. Most scholarly work has identified resource constraints as being the most significant determinants of adaptation. However, empirical research on adaptation has so far mostly not addressed the importance of measurable and alterable psychological factors in determining adaptation. Drawing from the literature in psychology and behavioural economics, we develop a socio-cognitive Model of Private Proactive Adaptation to Climate Change (MPPACC). MPPACC separates out the psychological steps to taking action in response to perception, and allows one to see where the most important bottlenecks occur - including risk perception and perceived adaptive capacity, a factor largely neglected in previous climate change research. We then examine two case studies - one from urban Germany and one from rural Zimbabwe - to explore the validity of MPPACC to explaining adaptation. In the German study, we find that MPPACC provides better statistical power than traditional socio-economic models. In the Zimbabwean case study, we find a qualitative match between MPPACC and adaptive behaviour. Finally, we discuss the important implications of our findings both on vulnerability and adaptation assessments, and on efforts to promote adaptation through outside intervention. (author)

  4. Adaptation to new nutritional environments: larval performance, foraging decisions, and adult oviposition choices in Drosophila suzukii.

    Science.gov (United States)

    Silva-Soares, Nuno F; Nogueira-Alves, A; Beldade, P; Mirth, Christen Kerry

    2017-06-07

    Understanding how species adapt to new niches is a central issue in evolutionary ecology. Nutrition is vital for the survival of all organisms and impacts species fitness and distribution. While most Drosophila species exploit rotting plant parts, some species have diversified to use ripe fruit, allowing earlier colonization. The decomposition of plant material is facilitated by yeast colonization and proliferation. These yeasts serve as the main protein source for Drosophila larvae. This dynamic rotting process entails changes in the nutritional composition of the food and other properties, and animals feeding on material at different stages of decay are expected to have behavioural and nutritional adaptations. We compared larval performance, feeding behaviour and adult oviposition site choice between the ripe fruit colonizer and invasive pest Drosophila suzukii, and a closely-related rotting fruit colonizer, Drosophila biarmipes. Through the manipulation of protein:carbohydrate ratios in artificial diets, we found that D. suzukii larvae perform better at lower protein concentrations and consume less protein rich diets relative to D. biarmipes. For adult oviposition, these species differed in preference for substrate hardness, but not for the substrate nutritional composition. Our findings highlight that rather than being an exclusive specialist on ripe fruit, D. suzukii's adaptation to use ripening fruit allow it to colonize a wider range of food substrates than D. biarmipes, which is limited to soft foods with higher protein concentrations. Our results underscore the importance of nutritional performance and feeding behaviours in the colonization of new food niches.

  5. Detection of circuit-board components with an adaptive multiclass correlation filter

    Science.gov (United States)

    Diaz-Ramirez, Victor H.; Kober, Vitaly

    2008-08-01

    A new method for reliable detection of circuit-board components is proposed. The method is based on an adaptive multiclass composite correlation filter. The filter is designed with the help of an iterative algorithm using complex synthetic discriminant functions. The impulse response of the filter contains information needed to localize and classify geometrically distorted circuit-board components belonging to different classes. Computer simulation results obtained with the proposed method are provided and compared with those of known multiclass correlation based techniques in terms of performance criteria for recognition and classification of objects.

  6. Behavioural strategy: Adaptability context

    Directory of Open Access Journals (Sweden)

    Piórkowska Katarzyna

    2016-05-01

    Full Text Available The paper is embedded in the following fields: strategic management in terms of behavioural strategy concept, adaptability construct, and micro-foundations realm as well as organizational theory and psychology. Moreover, the paper concerns to some extent a multi-level approach in strategic management involving individual, team, and organizational level. The aim of the paper is to contribute to extend, on one hand, the ascertainment set in the field of behavioural strategy as behavioural strategy encompasses a mindboggling diversity of topics and methods and its conceptual unity has been hard to achieve (Powell, Lovallo, Fox 2011, p. 1371, and on the other hand, to order mixed approaches to adaptability especially to gain insights on micro-level adapting processes (individual adaptability and adaptive performance in terms of the multi-level approach. The method that has been used is literature studies and the interference is mostly deductive. The structure of the manuscript is four-fold. The first part involves the considerations in the field of adaptability and adaptive performance at the individual level. The issues of adaptability and adaptive performance at the team level have been presented in the second part. The third part encompasses the organizational adaptability assertions. Finally, the conclusion, limitations of the considerations highlighted as well as the future research directions have been emphasized. The overarching key finding is that the behavioural strategy concept may constitute the boundary spanner in exploring and explaining adaptability phenomenon at different levels of analysis.

  7. Adaptive noise cancellation

    International Nuclear Information System (INIS)

    Akram, N.

    1999-01-01

    In this report we describe the concept of adaptive noise canceling, an alternative method of estimating signals corrupted by additive noise of interference. The method uses 'primary' input containing the corrupted signal and a 'reference' input containing noise correlated in some unknown way with the primary noise, the reference input is adaptively filtered and subtracted from the primary input to obtain the signal estimate. Adaptive filtering before subtraction allows the treatment of inputs that are deterministic or stochastic, stationary or time variable. When the reference input is free of signal and certain other conditions are met then noise in the primary input can be essentially eliminated without signal distortion. It is further shown that the adaptive filter also acts as notch filter. Simulated results illustrate the usefulness of the adaptive noise canceling technique. (author)

  8. Adaptive signal processor

    Energy Technology Data Exchange (ETDEWEB)

    Walz, H.V.

    1980-07-01

    An experimental, general purpose adaptive signal processor system has been developed, utilizing a quantized (clipped) version of the Widrow-Hoff least-mean-square adaptive algorithm developed by Moschner. The system accommodates 64 adaptive weight channels with 8-bit resolution for each weight. Internal weight update arithmetic is performed with 16-bit resolution, and the system error signal is measured with 12-bit resolution. An adapt cycle of adjusting all 64 weight channels is accomplished in 8 ..mu..sec. Hardware of the signal processor utilizes primarily Schottky-TTL type integrated circuits. A prototype system with 24 weight channels has been constructed and tested. This report presents details of the system design and describes basic experiments performed with the prototype signal processor. Finally some system configurations and applications for this adaptive signal processor are discussed.

  9. Adaptive signal processor

    International Nuclear Information System (INIS)

    Walz, H.V.

    1980-07-01

    An experimental, general purpose adaptive signal processor system has been developed, utilizing a quantized (clipped) version of the Widrow-Hoff least-mean-square adaptive algorithm developed by Moschner. The system accommodates 64 adaptive weight channels with 8-bit resolution for each weight. Internal weight update arithmetic is performed with 16-bit resolution, and the system error signal is measured with 12-bit resolution. An adapt cycle of adjusting all 64 weight channels is accomplished in 8 μsec. Hardware of the signal processor utilizes primarily Schottky-TTL type integrated circuits. A prototype system with 24 weight channels has been constructed and tested. This report presents details of the system design and describes basic experiments performed with the prototype signal processor. Finally some system configurations and applications for this adaptive signal processor are discussed

  10. Ageing of fibre reinforced polymer composite selected as a bearing material for Rams of 540 MWe fuelling machine

    International Nuclear Information System (INIS)

    Limaye, P.K.; Soni, N.L.; Agrawal, R.G.

    2006-01-01

    Fibre-reinforced-polymer-composite material has been suggested as a bearing material to overcome tribological problems witnessed during the testing of Ram assembly of the 540 MWe fuelling machine at RTD. After successful trials at B-Ram the composite material has been adapted for B-RAM, C-Ram and RDB head at fuelling machines being tested at RTD, Hall 7 and at Tarapur. Laboratory evaluations were also carried out at Tribology Lab RTD to study effect of radiation on the composite. Paper deals with the various aspects of life prediction of this material in term of wear and radiation damage. (author)

  11. Adaptation in Living Systems

    Science.gov (United States)

    Tu, Yuhai; Rappel, Wouter-Jan

    2018-03-01

    Adaptation refers to the biological phenomenon where living systems change their internal states in response to changes in their environments in order to maintain certain key functions critical for their survival and fitness. Adaptation is one of the most ubiquitous and arguably one of the most fundamental properties of living systems. It occurs throughout all biological scales, from adaptation of populations of species over evolutionary time to adaptation of a single cell to different environmental stresses during its life span. In this article, we review some of the recent progress made in understanding molecular mechanisms of cellular-level adaptation. We take the minimalist (or the physicist) approach and study the simplest systems that exhibit generic adaptive behaviors, namely chemotaxis in bacterium cells (Escherichia coli) and eukaryotic cells (Dictyostelium). We focus on understanding the basic biochemical interaction networks that are responsible for adaptation dynamics. By combining theoretical modeling with quantitative experimentation, we demonstrate universal features in adaptation as well as important differences in different cellular systems. Future work in extending the modeling framework to study adaptation in more complex systems such as sensory neurons is also discussed.

  12. Dynamics of habitat selection in birds: adaptive response to nest predation depends on multiple factors.

    Science.gov (United States)

    Devries, J H; Clark, R G; Armstrong, L M

    2018-05-01

    According to theory, habitat selection by organisms should reflect underlying habitat-specific fitness consequences and, in birds, reproductive success has a strong impact on population growth in many species. Understanding processes affecting habitat selection also is critically important for guiding conservation initiatives. Northern pintails (Anas acuta) are migratory, temperate-nesting birds that breed in greatest concentrations in the prairies of North America and their population remains below conservation goals. Habitat loss and changing land use practices may have decoupled formerly reliable fitness cues with respect to nest habitat choices. We used data from 62 waterfowl nesting study sites across prairie Canada (1997-2009) to examine nest survival, a primary fitness metric, at multiple scales, in combination with estimates of habitat selection (i.e., nests versus random points), to test for evidence of adaptive habitat choices. We used the same habitat covariates in both analyses. Pintail nest survival varied with nest initiation date, nest habitat, pintail breeding pair density, landscape composition and annual moisture. Selection of nesting habitat reflected patterns in nest survival in some cases, indicating adaptive selection, but strength of habitat selection varied seasonally and depended on population density and landscape composition. Adaptive selection was most evident late in the breeding season, at low breeding densities and in cropland-dominated landscapes. Strikingly, at high breeding density, habitat choice appears to become maladaptive relative to nest predation. At larger spatial scales, the relative availability of habitats with low versus high nest survival, and changing land use practices, may limit the reproductive potential of pintails.

  13. Role of fatty acids in Bacillus environmental adaptation

    Directory of Open Access Journals (Sweden)

    Sara Esther Diomande

    2015-08-01

    Full Text Available The large bacterial genus genus Bacillus is widely distributed in the environment and is able to colonize highly diverse niches. Some Bacillus species harbour pathogenic characteristics. The fatty acid (FA composition is among the essential criteria used to define Bacillus species. Some elements of the FA pattern composition are common to Bacillus species, whereas others are specific and can be categorized in relation to the ecological niches of the species. Bacillus species are able to modify their FA patterns to adapt to a wide range of environmental changes, including changes in the growth medium, temperature, food processing conditions, and pH. Like many other Gram-positive bacteria, Bacillus strains display a well-defined FA synthesis II system that is equilibrated with a FA degradation pathway and regulated to efficiently respond to the needs of the cell. Like endogenous FAs, exogenous FAs may positively or negatively affect the survival of Bacillus vegetative cells and the spore germination ability in a given environment. Some of these exogenous FAs may provide a powerful strategy for preserving food against contamination by the Bacillus pathogenic strains responsible for foodborne illness.

  14. Normalised subband adaptive filtering with extended adaptiveness on degree of subband filters

    Science.gov (United States)

    Samuyelu, Bommu; Rajesh Kumar, Pullakura

    2017-12-01

    This paper proposes an adaptive normalised subband adaptive filtering (NSAF) to accomplish the betterment of NSAF performance. In the proposed NSAF, an extended adaptiveness is introduced from its variants in two ways. In the first way, the step-size is set adaptive, and in the second way, the selection of subbands is set adaptive. Hence, the proposed NSAF is termed here as variable step-size-based NSAF with selected subbands (VS-SNSAF). Experimental investigations are carried out to demonstrate the performance (in terms of convergence) of the VS-SNSAF against the conventional NSAF and its state-of-the-art adaptive variants. The results report the superior performance of VS-SNSAF over the traditional NSAF and its variants. It is also proved for its stability, robustness against noise and substantial computing complexity.

  15. Developing Large-Scale Bayesian Networks by Composition: Fault Diagnosis of Electrical Power Systems in Aircraft and Spacecraft

    Science.gov (United States)

    Mengshoel, Ole Jakob; Poll, Scott; Kurtoglu, Tolga

    2009-01-01

    In this paper, we investigate the use of Bayesian networks to construct large-scale diagnostic systems. In particular, we consider the development of large-scale Bayesian networks by composition. This compositional approach reflects how (often redundant) subsystems are architected to form systems such as electrical power systems. We develop high-level specifications, Bayesian networks, clique trees, and arithmetic circuits representing 24 different electrical power systems. The largest among these 24 Bayesian networks contains over 1,000 random variables. Another BN represents the real-world electrical power system ADAPT, which is representative of electrical power systems deployed in aerospace vehicles. In addition to demonstrating the scalability of the compositional approach, we briefly report on experimental results from the diagnostic competition DXC, where the ProADAPT team, using techniques discussed here, obtained the highest scores in both Tier 1 (among 9 international competitors) and Tier 2 (among 6 international competitors) of the industrial track. While we consider diagnosis of power systems specifically, we believe this work is relevant to other system health management problems, in particular in dependable systems such as aircraft and spacecraft. (See CASI ID 20100021910 for supplemental data disk.)

  16. Farming System Evolution and Adaptive Capacity: Insights for Adaptation Support

    Directory of Open Access Journals (Sweden)

    Jami L. Dixon

    2014-02-01

    Full Text Available Studies of climate impacts on agriculture and adaptation often provide current or future assessments, ignoring the historical contexts farming systems are situated within. We investigate how historical trends have influenced farming system adaptive capacity in Uganda using data from household surveys, semi-structured interviews, focus-group discussions and observations. By comparing two farming systems, we note three major findings: (1 similar trends in farming system evolution have had differential impacts on the diversity of farming systems; (2 trends have contributed to the erosion of informal social and cultural institutions and an increasing dependence on formal institutions; and (3 trade-offs between components of adaptive capacity are made at the farm-scale, thus influencing farming system adaptive capacity. To identify the actual impacts of future climate change and variability, it is important to recognize the dynamic nature of adaptation. In practice, areas identified for further adaptation support include: shift away from one-size-fits-all approach the identification and integration of appropriate modern farming method; a greater focus on building inclusive formal and informal institutions; and a more nuanced understanding regarding the roles and decision-making processes of influential, but external, actors. More research is needed to understand farm-scale trade-offs and the resulting impacts across spatial and temporal scales.

  17. Prediction of Spring Rate and Initial Failure Load due to Material Properties of Composite Leaf Spring

    International Nuclear Information System (INIS)

    Oh, Sung Ha; Choi, Bok Lok

    2014-01-01

    This paper presented analysis methods for adapting E-glass fiber/epoxy composite (GFRP) materials to an automotive leaf spring. It focused on the static behaviors of the leaf spring due to the material composition and its fiber orientation. The material properties of the GFRP composite were directly measured based on the ASTM standard test. A reverse implementation was performed to obtain the complete set of in-situ fiber and matrix properties from the ply test results. Next, the spring rates of the composite leaf spring were examined according to the variation of material parameters such as the fiber angles and resin contents of the composite material. Finally, progressive failure analysis was conducted to identify the initial failure load by means of an elastic stress analysis and specific damage criteria. As a result, it was found that damage first occurred along the edge of the leaf spring owing to the shear stresses

  18. SpotADAPT

    DEFF Research Database (Denmark)

    Kaulakiene, Dalia; Thomsen, Christian; Pedersen, Torben Bach

    2015-01-01

    by Amazon Web Services (AWS). The users aiming for the spot market are presented with many instance types placed in multiple datacenters in the world, and thus it is difficult to choose the optimal deployment. In this paper, we propose the framework SpotADAPT (Spot-Aware (re-)Deployment of Analytical...... of typical analytical workloads and real spot price traces. SpotADAPT's suggested deployments are comparable to the theoretically optimal ones, and in particular, it shows good cost benefits for the budget optimization -- on average SpotADAPT is at most 0.3% more expensive than the theoretically optimal...

  19. Design Intend Solving: Dynamic Composition Method for Innovative Design Based on Virtual Cloud Manufacturing Resource Generators

    Directory of Open Access Journals (Sweden)

    Yi-Cong Gao

    2013-01-01

    Full Text Available Recently, there has been growing interest in composition of cloud manufacturing resources (CMRs. Composition of CMRs is a feasible innovation to fulfill the user request while single cloud manufacturing resource cannot satisfy the functionality required by the user. In this paper, we propose a new case-based approach for the composition of CMRs. The basic idea of the present approach is to provide a computational framework for the composition of CMRs by imitating the common design method of reviewing past designs to obtain solution concepts for a new composite cloud manufacturing resource (CCMR. A notion of virtual cloud manufacturing resource generators (VCMRGs is introduced to conceptualize and represent underlying CCMRs contained in existing CCMRs. VCMRGs are derived from previous CCMRs and serve as new conceptual building blocks for the composition of CMRs. Feasible composite CMRs are generated by combining VCMRGs using some adaptation rules. The reuse of prior CCMRs is accomplished via VCMRGs within the framework of case-based reasoning. We demonstrate that the proposed approach yields lower execution time for fulfilling user request and shows good scalability.

  20. Eddy current modeling in linear and nonlinear multifilamentary composite materials

    Science.gov (United States)

    Menana, Hocine; Farhat, Mohamad; Hinaje, Melika; Berger, Kevin; Douine, Bruno; Lévêque, Jean

    2018-04-01

    In this work, a numerical model is developed for a rapid computation of eddy currents in composite materials, adaptable for both carbon fiber reinforced polymers (CFRPs) for NDT applications and multifilamentary high temperature superconductive (HTS) tapes for AC loss evaluation. The proposed model is based on an integro-differential formulation in terms of the electric vector potential in the frequency domain. The high anisotropy and the nonlinearity of the considered materials are easily handled in the frequency domain.