Complementing in vitro screening assays with in silico ...

Science.gov (United States)

High-throughput in vitro assays offer a rapid, cost-efficient means to screen thousands of chemicals across hundreds of pathway-based toxicity endpoints. However, one main concern involved with the use of in vitro assays is the erroneous omission of chemicals that are inactive under assay conditions but that can generate active metabolites under in vivo conditions. To address this potential issue, a case study will be presented to demonstrate the use of in silico tools to identify inactive parents with the ability to generate active metabolites. This case study used the results from an orthogonal assay designed to improve confidence in the identification of active chemicals tested across eighteen estrogen receptor (ER)-related in vitro assays by accounting for technological limitations inherent within each individual assay. From the 1,812 chemicals tested within the orthogonal assay, 1,398 were considered inactive. These inactive chemicals were analyzed using Chemaxon Metabolizer software to predict the first and second generation metabolites. From the nearly 1,400 inactive chemicals, over 2,200 first-generation (i.e., primary) metabolites and over 5,500 second-generation (i.e., secondary) metabolites were predicted. Nearly 70% of primary metabolites were immediately detoxified or converted to other metabolites, while over 70% of secondary metabolites remained stable. Among these predicted metabolites, those that are most likely to be produced and remain

In vitro screening for population variability in toxicity of pesticide-containing mixtures

Science.gov (United States)

Abdo, Nour; Wetmore, Barbara A.; Chappell, Grace A.; Shea, Damian; Wright, Fred A.; Rusyna, Ivan

2016-01-01

Population-based human in vitro models offer exceptional opportunities for evaluating the potential hazard and mode of action of chemicals, as well as variability in responses to toxic insults among individuals. This study was designed to test the hypothesis that comparative population genomics with efficient in vitro experimental design can be used for evaluation of the potential for hazard, mode of action, and the extent of population variability in responses to chemical mixtures. We selected 146 lymphoblast cell lines from 4 ancestrally and geographically diverse human populations based on the availability of genome sequence and basal RNA-seq data. Cells were exposed to two pesticide mixtures – an environmental surface water sample comprised primarily of organochlorine pesticides and a laboratory-prepared mixture of 36 currently used pesticides – in concentration response and evaluated for cytotoxicity. On average, the two mixtures exhibited a similar range of in vitro cytotoxicity and showed considerable inter-individual variability across screened cell lines. However, when in vitroto-in vivo extrapolation (IVIVE) coupled with reverse dosimetry was employed to convert the in vitro cytotoxic concentrations to oral equivalent doses and compared to the upper bound of predicted human exposure, we found that a nominally more cytotoxic chlorinated pesticide mixture is expected to have greater margin of safety (more than 5 orders of magnitude) as compared to the current use pesticide mixture (less than 2 orders of magnitude) due primarily to differences in exposure predictions. Multivariate genome-wide association mapping revealed an association between the toxicity of current use pesticide mixture and a polymorphism in rs1947825 in C17orf54. We conclude that a combination of in vitro human population-based cytotoxicity screening followed by dosimetric adjustment and comparative population genomics analyses enables quantitative evaluation of human health hazard

In vitro and in vivo screening of azole fungicides for antiandrogenic effects

DEFF Research Database (Denmark)

Taxvig, Camilla; Vinggaard, Anne; Hass, Ulla

signs of feminization of the male offspring were investigated. Tebuconazole caused an increase in testicular 17alfa-hydroxyprogesterone and progesterone levels, and a decrease in testosterone levels in male fetuses. Epoxiconazole had no effect on any of the mesured hormonelevels. Furthermore...... and antiandrogenic effects both in vitro and in vivo. Two other azole fungicides, tebuconazole and epoxiconazole, have now been investigated for antiandrogenic effects in vitro and in vivo as well. The fungicides were screened in two well-established cell assays, including testing for agonistic and antagonistic...... effects on AR in transfected CHO cells, using an AR reporter gene assay. The compounds were also analyzed for effects on steroidogenesis in H295R cells, a human adrenocorticocarcinoma cell line, used to detect effects on steroid production. In vitro tebuconazole and epoxiconazole proved to be antagonists...

In Vitro Screening of Environmental Chemicals for Targeted Testing Prioritization: The ToxCast Project

OpenAIRE

Judson, Richard S.; Houck, Keith A.; Kavlock, Robert J.; Knudsen, Thomas B.; Martin, Matthew T.; Mortensen, Holly M.; Reif, David M.; Rotroff, Daniel M.; Shah, Imran; Richard, Ann M.; Dix, David J.

2009-01-01

Background Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use, and the thousands of environmental chemicals lacking toxicity data. The U.S. Environmental Protection Agency?s ToxCast program aims to address these concerns by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. Objectives This project aims to evaluate the use of in vitro assays for understanding the ty...

DNA binding properties of the small cascade subunit Csa5.

Directory of Open Access Journals (Sweden)

Michael Daume

Full Text Available CRISPR-Cas systems provide immunity against viral attacks in archaeal and bacterial cells. Type I systems employ a Cas protein complex termed Cascade, which utilizes small CRISPR RNAs to detect and degrade the exogenic DNA. A small sequence motif, the PAM, marks the foreign substrates. Previously, a recombinant type I-A Cascade complex from the archaeon Thermoproteus tenax was shown to target and degrade DNA in vitro, dependent on a native PAM sequence. Here, we present the biochemical analysis of the small subunit, Csa5, of this Cascade complex. T. tenax Csa5 preferentially bound ssDNA and mutants that showed decreased ssDNA-binding and reduced Cascade-mediated DNA cleavage were identified. Csa5 oligomerization prevented DNA binding. Specific recognition of the PAM sequence was not observed. Phylogenetic analyses identified Csa5 as a universal member of type I-A systems and revealed three distinct groups. A potential role of Csa5 in R-loop stabilization is discussed.

A new in vitro screening system for anticancer drugs for the treatment of non-small cell lung cancer

International Nuclear Information System (INIS)

Hanauske, U.; Hanauske, A.R.; Clark, G.M.; Tsen, D.; Buchok, J.; Hoff, D.D. von

1989-01-01

We have evaluated a semiautomated radiometric assay (BACTEC 460 system) for screening of activity of anticancer drugs against human non-small cell lung cancer cell lines. Cells from seven cell lines were exposed to standard antineoplastic agents at four different concentrations using a 1-h incubation. Alpha 2-interferon was tested using a continuous incubation. In vitro drug activity was analyzed as a function of the clinically achievable serum concentration. Our results indicate that two cell lines (CALU-3, SK-MES-1) exhibit in vitro drug sensitivity patterns closest to those observed in clinical studies. These two cell lines might therefore be most useful for screening new anticancer compounds for activity against non-small cell lung cancer. The radiometric assay is a semiautomated system which has advantages over other, more time-consuming screening systems

IN VITRO SCREENING OF LOCALLY ISOLATED LACTOBACILLUS SPECIES FOR PROBIOTIC PROPERTIES

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M. ASHRAF, M. ARSHAD, M. SIDDIQUE AND G. MUHAMMAD1

2009-10-01

Full Text Available The present study was conducted to determine the probiotic properties of locally isolated lactobacilli in-vitro conditions. For this purpose, intestinal contents (n=20 were collected from crop, gizzard, ileum and caecum of adult healthy chicks and conventional yogurt samples (n=20 were procured from the local market for the isolation of lactobacilli. These samples were mixed homogeneously in sterilized phosphate buffer saline (PBS separately. Samples from both sources were inoculated on deMan Rogosa and Sharpe (MRS agar. L. acidophilus 3, L. rhamnosus and L. salivarius were isolated from intestinal contents, while L. delbrucekii ssp bulgaricus and L. paracasei ssp paracasei 1 were isolated from yogurt samples. These lactobacilli were identified through standard API-50 CHL system and then screened for resistance against bile salt, acidic pH, gastric transit and ability to inhibit pathogens as well as survival under different storage temperatures. Tolerance level was found variable (P<0.05 among all the tested species of lactobacillus. All the tested species, except L. delbrucekii and L. paracasei, showed good survival (P<0.05. All lactobacilli inhibited the growth of E. coli and Staphylococcus aureus, except L. delbrucekii that showed significantly (P<0.05 low antimicrobial effect. The results showed that L. acidophilus 3, L. rhamnosus and L. salivarius fulfilled the criteria of in-vitro screening for probiotic properties.

A mix-and-read drop-based in vitro two-hybrid method for screening high-affinity peptide binders

Science.gov (United States)

Cui, Naiwen; Zhang, Huidan; Schneider, Nils; Tao, Ye; Asahara, Haruichi; Sun, Zhiyi; Cai, Yamei; Koehler, Stephan A.; de Greef, Tom F. A.; Abbaspourrad, Alireza; Weitz, David A.; Chong, Shaorong

2016-01-01

Drop-based microfluidics have recently become a novel tool by providing a stable linkage between phenotype and genotype for high throughput screening. However, use of drop-based microfluidics for screening high-affinity peptide binders has not been demonstrated due to the lack of a sensitive functional assay that can detect single DNA molecules in drops. To address this sensitivity issue, we introduced in vitro two-hybrid system (IVT2H) into microfluidic drops and developed a streamlined mix-and-read drop-IVT2H method to screen a random DNA library. Drop-IVT2H was based on the correlation between the binding affinity of two interacting protein domains and transcriptional activation of a fluorescent reporter. A DNA library encoding potential peptide binders was encapsulated with IVT2H such that single DNA molecules were distributed in individual drops. We validated drop-IVT2H by screening a three-random-residue library derived from a high-affinity MDM2 inhibitor PMI. The current drop-IVT2H platform is ideally suited for affinity screening of small-to-medium-sized libraries (103–106). It can obtain hits within a single day while consuming minimal amounts of reagents. Drop-IVT2H simplifies and accelerates the drop-based microfluidics workflow for screening random DNA libraries, and represents a novel alternative method for protein engineering and in vitro directed protein evolution. PMID:26940078

Complementing in vitro screening assays with in silico molecular chemistry tools to examine potential in vivo metabolite-mediated effects

Science.gov (United States)

High-throughput in vitro assays offer a rapid, cost-efficient means to screen thousands of chemicals across hundreds of pathway-based toxicity endpoints. However, one main concern involved with the use of in vitro assays is the erroneous omission of chemicals that are inactive un...

Calibration of screen-type X-ray films for electron beams

International Nuclear Information System (INIS)

Kobayashi, T.; Sato, Y.; Yoshida, K.; Tateyama, N.; Komori, Y.; Nakabayashi, T.; Oyamada, M.; Nishimura, J.

2002-01-01

In order to extract the maximum performance of the screen-type X-ray film for the detection of cascade showers in emulsion chambers, we examined the effect of the thickness of the phosphor screen by irradiation with 200 MeV electron beams. The observed data is in agreement with our analytical prediction of the radiative transfer of photons in a phosphor screen. If we use a combination of the specially prepared screen, HR16B, with a phosphor layer of 400 μm and a green-sensitive X-ray film, HA30, the detection threshold energy of cascade showers can be considerably lowered down to 140 GeV. (author)

Calibration of screen-type X-ray films for electron beams

CERN Document Server

Kobayashi, T; Yoshida, K; Tateyama, N; Komori, Y; Nakabayashi, T; Oyamada, M; Nishimura, J

2002-01-01

In order to extract the maximum performance of the screen-type X-ray film for the detection of cascade showers in emulsion chambers, we examined the effect of the thickness of the phosphor screen by irradiation with 200 MeV electron beams. The observed data is in agreement with our analytical prediction of the radiative transfer of photons in a phosphor screen. If we use a combination of the specially prepared screen, HR16B, with a phosphor layer of 400 mu m and a green-sensitive X-ray film, HA30, the detection threshold energy of cascade showers can be considerably lowered down to 140 GeV. (author)

Occurrence and in vitro bioactivity of estrogen, androgen, and glucocorticoid compounds in a nationwide screen of United States stream waters

Science.gov (United States)

In vitro bioassays are sensitive, effect-based tools used to quantitatively screen for chemicals with nuclear receptor activity in environmental samples. We measured in vitro estrogen (ER), androgen (AR), and glucocorticoid receptor (GR) activity, along with a suite of chemical a...

Screening of wheat endophytes as biological control agents against Fusarium head blight using two different in vitro tests.

Science.gov (United States)

Comby, Morgane; Gacoin, Marie; Robineau, Mathilde; Rabenoelina, Fanja; Ptas, Sébastien; Dupont, Joëlle; Profizi, Camille; Baillieul, Fabienne

2017-09-01

In order to find biological control agents (BCAs) for the management of Fusarium head blight (FHB), a major disease on wheat crops worldwide, 86 microorganisms isolated from inner tissues of wheat plants were discriminated for their ability to inhibit the growth of Fusarium graminearum and Fusarium culmorum by in vitro dual culture assays. A group of 22 strains appeared very effective to inhibit F. graminearum (inhibition of 30-51%) and they were also globally effective in controlling F. culmorum (inhibition of 15-53%). Further evaluation of a subselection of strains by screening on detached spikelets in vitro confirmed three species, namely Phoma glomerata, Aureobasidium proteae and Sarocladium kiliense, that have not yet been reported for their efficacy against Fusarium spp., indicating that looking for BCAs toward FHB among wheat endophytes proved to be promising. The efficacy of some strains turned out different between both in vitro screening approaches, raising the importance of finding the most appropriate screening approach for the search of BCAs. This study pointed out the interest of the test on detached wheat spikelets that provided information about a potential pathogenicity, the growth capacity and efficacy of the endophyte strains on the targeted plant, before testing them on whole plants. Copyright © 2017 Elsevier GmbH. All rights reserved.

In vitro screening of snake venom against multidrug-resistant tuberculosis

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Sujay Kumar Bhunia

2015-12-01

Full Text Available The re-emergence of multidrug-resistant tuberculosis (MDR-TB has brought to light the importance of screening effective novel drugs. In the present study, in vitro activities of different snake (Naja naja, Bungarus fasciatus, Daboia russelli russelli, Naja kaouthia venoms have been investigated against clinical isolate of MDR-TB strains. The treatment with all the venoms inhibited the mycobacterial growth for at least a week in common and two of them (Naja naja and Naja kaouthia showed significantly longer inhibition up to two weeks against the MDR-TB strain with single dose and a repetition of those two venoms exhibited inhibition up to more than four weeks.

Stem Cuttings as a Quick In Vitro Screening Method of Sodium Chloride Tolerance in Potato (Solanum) Genotypes

International Nuclear Information System (INIS)

Elhag, A. Z.; Mix-Wagnar, G.; Elbassam, N.; Horst, W.

2008-01-01

This study was conducted to find how far in vitro explants stem cuttings technique could be suitable for quick screening of NaCl tolerance solanum genotypes and to identify some aspects of their NaCl tolerance. Fifteen solanum genotypes were tested on four NaCl concentrations both in vitro and in vivo, two-node stem cuttings of in vitro produced explants were grown on Murashige and Skoog (MS) salts supplemented with four NaCl concentrations (0,40,80 and 120 mM) for six weeks in vitro. The other part of the in vitro grown explants were transplanted in Kick- Brauck- Manns pots containing sandy loam soil supplemented also with four NaCl concentration (0, 0.1, 0.2 and 0.3 NaCl, w/w) and grown further either for eight weeks or till harvest in a green house. Both experiments were in a completely randomized design with four replicates. The main stem length, shoot dry matter and tuber yield as well as mineral element (Na''+, K + , Ca''2''+ and Cl''-) were measured. The growth of all genotypes was affected by increasing of NaCl. There was a close correlation between growth response (length of explant main stem) in vitro and shoot dry matter and tuber yield in vivo (r=0.81** for dry matter and 0.72** for tuber yield. Na''+ and Cl''- concentrations in shoots wee inversely correlated with the vegetative growth (r=-0.73** for both in vitro and r=-0.89** and r=-0.88** in vivo, respectively). The genotypes showed varied ability to reduce the transport of Na''+ and Cl''- to the shoots, where by NaCl tolerant genotypes showed lower content of both elements than the sensitive ones. K''+ and Ca''2''+ concentrations were decreased with increasing NaCl concentration. The responses for mineral element (Na''+ and Cl - ) accumulation or restriction of explants in vitro and intact plants in vivo were also closely correlated (r=0.79** and 0.71**, respectively) especially at the medium NaCl concentrations (80 mM and 0.2% NaCl). The similar response of the explant and the intact plant

Quarkonium suppression: Gluonic dissociation vs. colour screening

Indian Academy of Sciences (India)

mechanism comes into play for the initial conditions taken from the self screened parton cascade model in these studies. Keywords. Quark gluon plasma; J ψ; suppression; dissociation; colour screening. PACS No. 12.38.M. 1. Introduction. The last two decades have seen hectic activity towards identifying unique signatures ...

Defect production in simulated cascades: Cascade quenching and short-term annealing

International Nuclear Information System (INIS)

Heinisch, H.L.

1983-01-01

Defect production in displacement cascades in copper has been modeled using the MARLOWE code to generate cascades and the stochastic annealing code ALSOME to simulate cascade quenching and short-term annealing of isolated cascades. Quenching is accomplished by using exaggerated values for defect mobilities and for critical reaction distances in ALSOME for a very short time. The quenched cascades are then short-term annealed with normal parameter values. The quenching parameter values were empirically determined by comparison with results of resistivity measurements. Throughout the collisional, quenching and short-term annealing phases of cascade development, the high energy cascades continue to behave as a collection of independent lower energy lobes. For recoils above about 30 keV the total number of defects and the numbers of free defects scale with the damage energy. As the energy decreases from 30 keV, defect production varies with the changing nature of the cascade configuration, resulting in more defects per unit damage energy. The simulated annealing of a low fluence of interacting cascades revealed an interstitial shielding effect on depleted zones during Stage I recovery. (orig.)

A non-conventional isotope separation cascade without any mixing: net cascade

International Nuclear Information System (INIS)

Zeng Shi; Jiang Dongjun; Ying Zhengen

2012-01-01

A component has different concentrations in the incoming flows at a confluent point in all existing isotope separations cascades for multi-component isotope separation and mixing is inevitable, which results in deterioration of separation performance of the separation cascade. However, realization of no-mixing at a confluent point is impossible with a conventional cascade. A non-conventional isotope separation cascade, net cascade, is found to be able to realize no mixings for all components at confluent points, and its concept is further developed here. No-mixing is fulfilled by requiring symmetrical separation of two specified key components at every stage, and the procedure of realizing no-mixing is presented in detail. Some properties of net cascade are investigated preliminarily, and the results demonstrated the no-mixing property is indeed realized. Net cascade is the only separation cascade that so far possesses the no-mixing property. (authors)

Screening and Selection of High Carotenoid Producing in Vitro Tomato Cell Culture Lines for [13C]-Carotenoid Production

OpenAIRE

Engelmann, Nancy J.; Campbell, Jessica K.; Rogers, Randy B.; Rupassara, S. Indumathie; Garlick, Peter J.; Lila, Mary Ann; Erdman, John W.

2010-01-01

Isotopically labeled tomato carotenoids, phytoene, phytofluene, and lycopene, are needed for mammalian bioavailability and metabolism research but are currently commercially unavailable. The goals of this work were to establish and screen multiple in vitro tomato cell lines for carotenoid production, test the best producers with or without the bleaching herbicides, norflurazon and 2-(4-chlorophenyl-thio)-triethylamine (CPTA), and to use the greatest carotenoid accumulator for in vitro 13C-lab...

An in vitro model for screening estrogen activity of environmental samples after metabolism

Energy Technology Data Exchange (ETDEWEB)

Chahbane, N.; Schramm, K.W. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Oekologische Chemie; Kettrup, A. [Technische Univ. Muenchen, Freising (Germany). Lehrstuhl fuer Oekologische Chemie

2004-09-15

For a few years, yeast estrogen assay (YES) was accepted as a reliable and economic model for screening of environmental estrogens. Though the chemicals directly act with estrogen receptor (ER) can be filtered out by this model, there are still chemicals act with ER only after metabolism and some chemicals eliminate their estrogen activities after metabolism. That is to say, their metabolites exert or have stronger estrogen activities than themselves, which can be called bio-activation. In this case, for the lack of the metabolism enzyme system as human and other animals, only the assay with recombinant yeast cells is insufficient. So, it is necessary to combine the YES with metabolism procedure to evaluate the estrogen activities of these chemicals. The most common method used currently for in vitro metabolic activation in mutagenicity testing and also be applied to the estrogen screening field is S-9 mixture. Also, there is an attempt to develop a chemical model for cytochrome P450 as a bio-mimetic metabolic activation system. All these methods can be used as in vitro models for metabolism. Compare with these models, using whole H4II E cells for metabolism is an alternative and with superiorities. It has the excellence of short experiment period as all other in vitro models, but is much more close to the real surroundings as in vivo. Furthermore, the activity of 7-ethoxyresorufin-O-deethylase (EROD) can be easily measured during the whole incubation period for us to discuss the metabolic activities in a quantitative foundation, not only in qualitative. Methoxychlor is one of the chemicals with bio-activation ability. When directly used in the YES, it shows weak estrogen activity. But a main metabolite of methoxychlor, 2,2-bis (p-hydroxyphenyl) - 1,1,1-trichloroethane (HPTE) is a known estrogen mimic. For the long time using methoxychlor as a pesticide and its clear background, it is an ideal chemical to establish this in vitro system.

In vitro application of integrated selection index for screening drought tolerant genotypes in common wheat

Directory of Open Access Journals (Sweden)

Ezatollah FARSHADFAR

2016-10-01

Full Text Available This experiment was conducted on 20 wheat genotypes during 2010-2011 growing season at the Razi University, Kermanshah, Iran. A completely randomized design with six replications was used for callus induction and a 20 × 2 factorial experiment with three replications was used for response of genotypes to in vitro drought stress. ANOVA exhibited highly significant differences among the genotypes for callus growth rate, relative fresh mass growth, relative growth rate, callus water content, percent of callus chlorosis and proline content under stress condition (15 % PEG. PCA showed that the integrated selection index was correlated with callus growth index, relative fresh mass growth, relative growth rate and proline content indicating that these screening techniques can be useful for selecting drought tolerant genotypes. Screening drought tolerant genotypes and in vitro indicators of drought tolerance using mean rank, standard deviation of ranks and biplot analysis, discriminated genotypes 2, 18 and 10 as the most drought tolerant. Therefore they are recommended to be used as parents for genetic analysis, gene mapping and improvement of drought tolerance.

Alginate based 3D hydrogels as an in vitro co-culture model platform for the toxicity screening of new chemical entities

International Nuclear Information System (INIS)

Lan, Shih-Feng; Starly, Binil

2011-01-01

Prediction of human response to potential therapeutic drugs is through conventional methods of in vitro cell culture assays and expensive in vivo animal testing. Alternatives to animal testing require sophisticated in vitro model systems that must replicate in vivo like function for reliable testing applications. Advancements in biomaterials have enabled the development of three-dimensional (3D) cell encapsulated hydrogels as in vitro drug screening tissue model systems. In this study, we have developed an in vitro platform to enable high density 3D culture of liver cells combined with a monolayer growth of target breast cancer cell line (MCF-7) in a static environment as a representative example of screening drug compounds for hepatotoxicity and drug efficacy. Alginate hydrogels encapsulated with serial cell densities of HepG2 cells (10 5 -10 8 cells/ml) are supported by a porous poly-carbonate disc platform and co-cultured with MCF-7 cells within standard cell culture plates during a 3 day study period. The clearance rates of drug transformation by HepG2 cells are measured using a coumarin based pro-drug. The platform was used to test for HepG2 cytotoxicity 50% (CT 50 ) using commercially available drugs which further correlated well with published in vivo LD 50 values. The developed test platform allowed us to evaluate drug dose concentrations to predict hepatotoxicity and its effect on the target cells. The in vitro 3D co-culture platform provides a scalable and flexible approach to test multiple-cell types in a hybrid setting within standard cell culture plates which may open up novel 3D in vitro culture techniques to screen new chemical entity compounds. - Graphical abstract: Display Omitted Highlights: → A porous support disc design to support the culture of desired cells in 3D hydrogels. → Demonstrated the co-culture of two cell types within standard cell-culture plates. → A scalable, low cost approach to toxicity screening involving multiple cell

Newborn Congenital Cytomegalovirus Screening Based on Clinical Manifestations and Evaluation of DNA-based Assays for In Vitro Diagnostics.

Science.gov (United States)

Fujii, Tomoyuki; Oka, Akira; Morioka, Ichiro; Moriuchi, Hiroyuki; Koyano, Shin; Yamada, Hideto; Saito, Shigeru; Sameshima, Hiroshi; Nagamatsu, Takeshi; Tsuchida, Shinya; Inoue, Naoki

2017-10-01

To establish a strategy for congenital cytomegalovirus (cCMV) screening and to establish confirmatory assays approved as in vitro diagnostics by the regulatory authorities, we evaluated the clinical risks and performance of diagnostic assays developed by commercial companies, since cCMV infection has significant clinical consequences. Newborns with clinical manifestations considered to be consequences of cCMV infection (n = 575) were screened for the presence of cytomegalovirus (CMV) DNA in urine specimens collected onto filter paper placed in their diapers using the polymerase chain reaction-based assay reported previously. Liquid urine specimens were obtained from all of 20 CMV-positive newborns and 107 of the CMV-negative newborns identified in the screening. We used these 127 specimens, as well as 12 from cCMV cases identified in a previous study and 41 from healthy newborns, to compare the performance of 2 commercial assays and 1 in-house assay. The risk-based screening allowed the identification of cCMV cases at least 10-fold more efficiently than our previous universal screening, although there appears to be a limit to the identification of asymptomatically infected newborns. Although CMV-specific IgM during pregnancy was found frequently in mothers of cCMV newborns, CMV-IgM alone is not an effective diagnostic marker. The urine-filter-based assay and the 3 diagnostic assays yielded identical results. Although risk-based and universal newborn screening strategies for cCMV infection each have their respective advantages and disadvantages, urine-filter-based assay followed by confirmatory in vitro diagnostics assays is able to identify cCMV cases efficiently.

Defect production in simulated cascades: cascade quenching and short-term annealing

International Nuclear Information System (INIS)

Heinisch, H.L.

1982-01-01

Defect production in high energy displacement cascades has been modeled using the computer code MARLOWE to generate the cascades and the stochastic computer code ALSOME to simulate the cascade quenching and short-term annealing of isolated cascades. The quenching is accomplished by using ALSOME with exaggerated values for defect mobilities and critical reaction distanes for recombination and clustering, which are in effect until the number of defect pairs is equal to the value determined from resistivity experiments at 4K. Then normal mobilities and reaction distances are used during short-term annealing to a point representative of Stage III recovery. Effects of cascade interactions at low fluences are also being investigated. The quenching parameter values were empirically determined for 30 keV cascades. The results agree well with experimental information throughout the range from 1 keV to 100 keV. Even after quenching and short-term annealing the high energy cascades behave as a collection of lower energy subcascades and lobes. Cascades generated in a crystal having thermal displacements were found to be in better agreement with experiments after quenching and annealing than those generated in a non-thermal crystal

Preimplantation genetic screening.

Science.gov (United States)

Harper, Joyce C

2018-03-01

Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.

Occurrence and in vitro bioactivity of estrogen, androgen, and glucocorticoid compounds in a nationwide screen of United States stream waters

Data.gov (United States)

U.S. Environmental Protection Agency — In vitro bioactivity concentrations and chemical concentrations of estrogens, androgens, and glucocorticoids from a nationwide screen of United States stream water...

IspE inhibitors identified by a combination of in silico and in vitro high-throughput screening.

Directory of Open Access Journals (Sweden)

Naomi Tidten-Luksch

Full Text Available CDP-ME kinase (IspE contributes to the non-mevalonate or deoxy-xylulose phosphate (DOXP pathway for isoprenoid precursor biosynthesis found in many species of bacteria and apicomplexan parasites. IspE has been shown to be essential by genetic methods and since it is absent from humans it constitutes a promising target for antimicrobial drug development. Using in silico screening directed against the substrate binding site and in vitro high-throughput screening directed against both, the substrate and co-factor binding sites, non-substrate-like IspE inhibitors have been discovered and structure-activity relationships were derived. The best inhibitors in each series have high ligand efficiencies and favourable physico-chemical properties rendering them promising starting points for drug discovery. Putative binding modes of the ligands were suggested which are consistent with established structure-activity relationships. The applied screening methods were complementary in discovering hit compounds, and a comparison of both approaches highlights their strengths and weaknesses. It is noteworthy that compounds identified by virtual screening methods provided the controls for the biochemical screens.

Neuronal models for evaluation of proliferation in vitro using high content screening

International Nuclear Information System (INIS)

Mundy, William R.; Radio, Nicholas M.; Freudenrich, Theresa M.

2010-01-01

In vitro test methods can provide a rapid approach for the screening of large numbers of chemicals for their potential to produce toxicity (hazard identification). In order to identify potential developmental neurotoxicants, a battery of in vitro tests for neurodevelopmental processes such as cell proliferation, differentiation, growth, and synaptogenesis has been proposed. The development of in vitro approaches for toxicity testing will require choosing a model system that is appropriate to the endpoint of concern. This study compared several cell lines as models for neuronal proliferation. The sensitivities of neuronal cell lines derived from three species (PC12, rat; N1E-115, mouse; SH-SY5Y, human) to chemicals known to affect cell proliferation were assessed using a high content screening system. After optimizing conditions for cell growth in 96-well plates, proliferation was measured as the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into replicating DNA during S phase. BrdU-labeled cells were detected by immunocytochemistry and cell counts were obtained using automated image acquisition and analysis. The three cell lines showed approximately 30-40% of the population in S phase after a 4 h pulse of BrdU. Exposure to the DNA polymerase inhibitor aphidicolin for 20 h prior to the 4 h pulse of BrdU significantly decreased proliferation in all three cell lines. The sensitivities of the cell lines were compared by exposure to eight chemicals known to affect proliferation (positive controls) and determination of the concentration inhibiting proliferation by 50% of control (I 50 ). PC12 cells were the most sensitive to chemicals; 6 out of 8 chemicals (aphidicolin, cadmium, cytosine arabinoside, dexamethasone, 5-fluorouracil, and methylmercury) inhibited proliferation at the concentrations tested. SH-SY5Y cells were somewhat less sensitive to chemical effects, with five out of eight chemicals inhibiting proliferation; dexamethasone had no effect, and cadmium

Escherichia coli Uropathogenesis In Vitro

DEFF Research Database (Denmark)

Andersen, Thomas E; Khandige, Surabhi; Madelung, Michelle

2012-01-01

-stage infection events have not been replicated in vitro. We have established an in vitro model of human bladder cell infection by the use of a flow chamber (FC)-based culture system, which allows investigation of steps subsequent to initial invasion. Short-term bacterial colonization on the FC-BEC layer led...... to rods that could invade other BECs. Hence, under growth conditions established to resemble those present in vivo, the elements of the proposed uropathogenic cascade were inducible in a human BEC model system. Here, we describe the model and show how these characteristics are reproduced in vitro....

In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors.

Science.gov (United States)

Park, Jae B

2017-12-13

p38 Mitogen-activated protein kinase (p38 MAPK) is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR) spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; -20 to -39) and several analogues with ΔE; -34 to -39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; -34 to -39) and in silico scores (Avg. score; -27.5 to -29.3). Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; -27.5 to -29.3) were found to inhibit p38 MAPK by 27-31% ( p silico score (Avg. score; -29.2) inhibited p38 MAPK (IC 50 = 9.9 μM) a little better than its methyl ester with best in silico score (Avg. score; -29.3). To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22-73% ( p silico and in vitro assay approach may be a useful and efficient solution as a functional screening approach in searching new lead compounds for targeted molecules.

Discovery of Dual ETA/ETB Receptor Antagonists from Traditional Chinese Herbs through in Silico and in Vitro Screening

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Xing Wang

2016-03-01

Full Text Available Endothelin-1 receptors (ETAR and ETBR act as a pivotal regulator in the biological effects of ET-1 and represent a potential drug target for the treatment of multiple cardiovascular diseases. The purpose of the study is to discover dual ETA/ETB receptor antagonists from traditional Chinese herbs. Ligand- and structure-based virtual screening was performed to screen an in-house database of traditional Chinese herbs, followed by a series of in vitro bioassay evaluation. Aristolochic acid A (AAA was first confirmed to be a dual ETA/ETB receptor antagonist based intracellular calcium influx assay and impedance-based assay. Dose-response curves showed that AAA can block both ETAR and ETBR with IC50 of 7.91 and 7.40 μM, respectively. Target specificity and cytotoxicity bioassay proved that AAA is a selective dual ETA/ETB receptor antagonist and has no significant cytotoxicity on HEK293/ETAR and HEK293/ETBR cells within 24 h. It is a feasible and effective approach to discover bioactive compounds from traditional Chinese herbs using in silico screening combined with in vitro bioassay evaluation. The structural characteristic of AAA for its activity was especially interpreted, which could provide valuable reference for the further structural modification of AAA.

Development of assay platforms for in vitro screening of Treg modulating potential of pharmacological compounds

DEFF Research Database (Denmark)

Pedersen, Anders Elm; Holmstrøm, Kim; Jørgensen, Flemming

2015-01-01

that investigates Treg modulation by current drugs. For such research as well as for novel cell based therapies based on Treg infusions, rapid in vitro assays as well as functional assays based on inhibitory capacity of Tregs are required. Here, we report on such assays using highly pure fluorescence-activated cell...... and TNF-α. In conclusion, these assays have the potential for use in pharmacological screening and discovery in relation to drug development in immunology....

Generation of peanut drought tolerant plants by pingyangmycin-mediated in vitro mutagenesis and hydroxyproline-resistance screening.

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Jiongming Sui

Full Text Available In order to enlarge the potential resources of drought-tolerant peanuts, we conducted in vitro mutagenesis with Pingyangmycin (PYM as the mutagen as well as directed screening on a medium supplemented with Hydroxyproline (HYP. After being extracted from mature seeds (cv. Huayu 20, the embryonic leaflets were cultured on somatic embryogenesis-induction medium with 4 mg/L PYM and the generated embryos were successively transferred to a germination medium with 4 and then 8 mmol/L HYP to screen HYP-tolerant plantlets. After that, these plantlets were grafted and transplanted to the experimental field. In the next generation, all seeds were sown in the field, and phenotype variation and trait segregation can be observed in most of the offspring (M2 generation. The M3 generation individuals were subjected to drought stress at the seedling stages. The activities of SOD and POD were substantially increased in eight offspring of 11 HYP-tolerant, regenerated plants than in their mutagenic parents. To determine the correlation between mutant phenotypes and genomic modification, we carried out a comparison of the DNA polymorphisms between the mutagenic parents and 13 M3 generation individuals from different HYP-tolerant, regenerated plants with SSR primers. Results showed that most mutants and parent plants had signs of polymorphisms. Under drought stress, some M3 generation individuals of 10 original HYP-tolerant, regenerated plants produced more pods than the mutagenic parent; twenty individuals among them produced >60 g pods/plant. M4-generation seeds were tested for quality characteristics by Near Infrared Spectroscopy (NIS and nine individuals with higher protein content (>30% and 21 individuals with higher oil content (>58% were screened. We concluded that the use of PYM-based in vitro mutagenesis in combination with directed screening with HYP is effective for the creation of potential drought-tolerant mutants of peanut.

Electroluminescent TCC, C3dg and fB/Bb epitope assays for profiling complement cascade activation in vitro using an activated complement serum calibration standard.

Science.gov (United States)

van Vuuren, B Jansen; Bergseth, G; Mollnes, T E; Shaw, A M

2014-01-15

Electroluminescent assays for epitopes on the complement components C3dg, terminal complement complex (TCC) and factor B/Bb (fB/Bb) have been developed with capture and detection antibodies to produce detection limits C3dg=91±9ng/mL, TCC=3±0.1ng/mL and fB=55.7±0.1ng/mL. The assay performance was assessed against a series of zymosan and heat aggregated IgG (HAIgG) in vitro activations of complement using a calibrated activated complement serum (ACS) as calibration standard. The ACS standard was stable within 20% accuracy over a 6-month period with freeze-thaw cycles as required. Differential activation of the complement cascade was observed for TCC showing a pseudo-first order formation half-life of 3.5h after activation with zymosan. The C3dg activation fragment indicates a 10% total activation for both activation agents. The kinetic-epitope analysis for fB indicates that the capture epitope is on the fB/Bb protein fragment which can then become covered by the formation of C3bBb or C3bBbP complexes during the time course of the cascade. Copyright © 2013 Elsevier B.V. All rights reserved.

Modeling of cascade and sub-cascade formation at high pka energies in irradiated fusion structural materials

International Nuclear Information System (INIS)

Ryazanov, A.; Metelkin, E.V.; Semenov, E.A.

2007-01-01

Full text of publication follows: A new theoretical model is developed for the investigations of cascade and sub-cascade formation in fusion structural materials under fast neutron irradiation at high primary knock atom (PKA) energies. Under 14 MeV neutron irradiation especially of light fusion structural materials such as Be, C, SiC materials PKA will have the energies up to 1 MeV. At such high energies it is very difficult to use the Monte Carlo or molecular dynamic simulations. The developed model is based on the analytical consideration of elastic collisions between displaced moving atoms into atomic cascades produced by a PKAs with the some kinetic energy obtained from fast neutrons. The Tomas-Fermy interaction potential is used for the describing of elastic collisions between moving atoms. The suggested model takes into account also the electronic losses for moving atoms between elastic collisions. The self consistent criterion for sub-cascade formation is suggested here which is based on the comparison of mean distance between two consequent PKA collisions and size of sub-cascade produced by PKA. The analytical relations for the most important characteristics of cascades and sub-cascade are determined including the average number of sub-cascades per one PKA in the dependence on PKA energy, the distance between sub-cascades and the average cascade and sub-cascade sizes as a function of PKA energy. The developed model allows determining the total numbers, distribution functions of cascades and sub-cascades in dependence on their sizes and generation rate of cascades and sub-cascades for different fusion neutron energy spectra. Based on the developed model the numerical calculations for main characteristics of cascades and sub-cascades in different fusion structural materials are performed using the neutron flux and PKA energy spectra for fusion reactors: ITER and DEMO. The main characteristics for cascade and sub-cascade formation are calculated here for the

Atom-atom collision cascades localization

International Nuclear Information System (INIS)

Kirsanov, V.V.

1980-01-01

The presence of an impurity and thermal vibration influence on the atom-atom collision cascade development is analysed by the computer simulation method (the modificated dynamic model). It is discovered that the relatively low energetic cascades are localized with the temperature increase of an irradiated crystal. On the basis of the given effect the mechanism of splitting of the high energetic cascades into subcascades is proposed. It accounts for two factors: the primary knocked atom energy and the irradiated crystal temperature. Introduction of an impurity also localizes the cascades independently from the impurity atom mass. The cascades localization leads to intensification of the process of annealing in the cascades and reduction of the post-cascade vacancy cluster sizes. (author)

The immature electrophysiological phenotype of iPSC-CMs still hampers in vitro drug screening: Special focus on IK1.

Science.gov (United States)

Goversen, Birgit; van der Heyden, Marcel A G; van Veen, Toon A B; de Boer, Teun P

2018-03-01

Preclinical drug screens are not based on human physiology, possibly complicating predictions on cardiotoxicity. Drug screening can be humanised with in vitro assays using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, in contrast to adult ventricular cardiomyocytes, iPSC-CMs beat spontaneously due to presence of the pacemaking current I f and reduced densities of the hyperpolarising current I K1 . In adult cardiomyocytes, I K1 finalises repolarisation by stabilising the resting membrane potential while also maintaining excitability. The reduced I K1 density contributes to proarrhythmic traits in iPSC-CMs, which leads to an electrophysiological phenotype that might bias drug responses. The proarrhythmic traits can be suppressed by increasing I K1 in a balanced manner. We systematically evaluated all studies that report strategies to mature iPSC-CMs and found that only few studies report I K1 current densities. Furthermore, these studies did not succeed in establishing sufficient I K1 levels as they either added too little or too much I K1 . We conclude that reduced densities of I K1 remain a major flaw in iPSC-CMs, which hampers their use for in vitro drug screening. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Mechanisms of cascade collapse

International Nuclear Information System (INIS)

Diaz de la Rubia, T.; Smalinskas, K.; Averback, R.S.; Robertson, I.M.; Hseih, H.; Benedek, R.

1988-12-01

The spontaneous collapse of energetic displacement cascades in metals into vacancy dislocation loops has been investigated by molecular dynamics (MD) computer simulation and transmission electron microscopy (TEM). Simulations of 5 keV recoil events in Cu and Ni provide the following scenario of cascade collapse: atoms are ejected from the central region of the cascade by replacement collision sequences; the central region subsequently melts; vacancies are driven to the center of the cascade during resolidification where they may collapse into loops. Whether or not collapse occurs depends critically on the melting temperature of the metal and the energy density and total energy in the cascade. Results of TEM are presented in support of this mechanism. 14 refs., 4 figs., 1 tab

Learning optimal embedded cascades.

Science.gov (United States)

Saberian, Mohammad Javad; Vasconcelos, Nuno

2012-10-01

The problem of automatic and optimal design of embedded object detector cascades is considered. Two main challenges are identified: optimization of the cascade configuration and optimization of individual cascade stages, so as to achieve the best tradeoff between classification accuracy and speed, under a detection rate constraint. Two novel boosting algorithms are proposed to address these problems. The first, RCBoost, formulates boosting as a constrained optimization problem which is solved with a barrier penalty method. The constraint is the target detection rate, which is met at all iterations of the boosting process. This enables the design of embedded cascades of known configuration without extensive cross validation or heuristics. The second, ECBoost, searches over cascade configurations to achieve the optimal tradeoff between classification risk and speed. The two algorithms are combined into an overall boosting procedure, RCECBoost, which optimizes both the cascade configuration and its stages under a detection rate constraint, in a fully automated manner. Extensive experiments in face, car, pedestrian, and panda detection show that the resulting detectors achieve an accuracy versus speed tradeoff superior to those of previous methods.

In vivo RNAi screen reveals neddylation genes as novel regulators of Hedgehog signaling.

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Juan Du

Full Text Available Hedgehog (Hh signaling is highly conserved in all metazoan animals and plays critical roles in many developmental processes. Dysregulation of the Hh signaling cascade has been implicated in many diseases, including cancer. Although key components of the Hh pathway have been identified, significant gaps remain in our understanding of the regulation of individual Hh signaling molecules. Here, we report the identification of novel regulators of the Hh pathway, obtained from an in vivo RNA interference (RNAi screen in Drosophila. By selectively targeting critical genes functioning in post-translational modification systems utilizing ubiquitin (Ub and Ub-like proteins, we identify two novel genes (dUba3 and dUbc12 that negatively regulate Hh signaling activity. We provide in vivo and in vitro evidence illustrating that dUba3 and dUbc12 are essential components of the neddylation pathway; they function in an enzyme cascade to conjugate the ubiquitin-like NEDD8 modifier to Cullin proteins. Neddylation activates the Cullin-containing ubiquitin ligase complex, which in turn promotes the degradation of Cubitus interruptus (Ci, the downstream transcription factor of the Hh pathway. Our study reveals a conserved molecular mechanism of the neddylation pathway in Drosophila and sheds light on the complex post-translational regulations in Hh signaling.

Modeling of cascade and sub-cascade formation at high PKA energies in irradiated fusion structural materials

International Nuclear Information System (INIS)

Ryazanov, A.I.; Metelkin, E.V.; Semenov, E.V.

2009-01-01

A new theoretical model is developed for the investigations of cascade and sub-cascade formation in fusion structural materials under fast neutron irradiation at high primary knock-on atom energies. Light fusion structural materials: such as Be, C and SiC under 14 MeV neutron irradiation in fusion reactor will have the primary knock-on atoms with the energies up to 1 MeV. It is very difficult to use at such high energies the Monte-Carlo or molecular dynamic simulations [H.L. Heinisch, B.N. Singh, Philos. Mag. A67 (1993) 407; H.L. Heinisch, B.N. Singh, J. Nucl. Mater. 251 (1997) 77]. The developed model is based on the analytical consideration of elastic collisions between displaced moving atoms produced by primary knock-on atoms with some kinetic energies obtained from fast neutrons and crystal lattice atoms. The Thomas-Fermi interaction potential is used here for the description of these elastic atomic collisions. The suggested model takes into account also the electronic losses for moving atoms between elastic collisions. The self-consistent criterion for sub-cascade formation is suggested here which is based on the comparison of mean distance of primary knock-on atoms between consequent collisions of them with the target atoms and a size of sub-cascade produced by moving secondary knock-on atoms produced in such collisions. The analytical relations for the most important characteristics of cascades and sub-cascades are determined including the average number of sub-cascades per one primary knock-on atom in the dependence on its energy, the distance between sub-cascades and the average cascade and sub-cascade sizes. The developed model allows determining the total numbers, distribution functions of cascades and sub-cascades in dependence on their sizes and generation rate of cascades and sub-cascades for the different fusion neutron energy spectra. On the basis of this developed model the numerical calculations for main characteristics of cascades and sub-cascades

In Silico Screening and In Vitro Activity Measurement of Javamide Analogues as Potential p38 MAPK Inhibitors

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Jae B. Park

2017-12-01

Full Text Available p38 Mitogen-activated protein kinase (p38 MAPK is a protein kinase critically involved in the progress of inflammation/stress-associated diseases. Our data suggested that javamide analogues may contain strong anti-inflammation activities, but there is little information about their effects on p38 MAPK. Therefore, in this paper, the effects of thirty javamide analogues on p38 MAPK were investigated using in silico screening and in vitro p38 MAPK assay methods. The javamide analogues were synthesized and their chemical structures were confirmed using nuclear magnetic resonance (NMR spectroscopic methods. Then, the javamide analogues were screened using an in silico modeling program. The screened analogues demonstrated a wide range of binding energy (ΔE; −20 to −39 and several analogues with ΔE; −34 to −39 showed strong binding affinity to p38 MAPK. In vitro p38 MAPK assay, the kinase was significantly inhibited by the analogues with great binding energy (ΔE; −34 to −39 and in silico scores (Avg. score; −27.5 to −29.3. Furthermore, the comparative analysis of both assays showed a positive correlation between the in silico scores and p38 MAPK inhibition. In fact, the javamide analogues with top five in silico scores (Avg. score; −27.5 to −29.3 were found to inhibit p38 MAPK by 27–31% (p < 0.05 better than those with less scores (ΔE < −27.0. Especially, javamide-II-O-ethyl ester with relatively high in silico score (Avg. score; −29.2 inhibited p38 MAPK (IC50 = 9.9 μM a little better than its methyl ester with best in silico score (Avg. score; −29.3. To support the ability to inhibit p38 MAPK, the treatment of javamide-II-ethyl and -methyl esters could suppress the production of IL-8 and MCP-1 protein significantly by 22–73% (p < 0.05 in the differentiated THP-1 cells, and the inhibition was slightly stronger by the ethyl ester than the methyl ester. Altogether, this study suggests that javamide-II-O-ethyl ester may

Cascade annealing: an overview

International Nuclear Information System (INIS)

Doran, D.G.; Schiffgens, J.O.

1976-04-01

Concepts and an overview of radiation displacement damage modeling and annealing kinetics are presented. Short-term annealing methodology is described and results of annealing simulations performed on damage cascades generated using the Marlowe and Cascade programs are included. Observations concerning the inconsistencies and inadequacies of current methods are presented along with simulation of high energy cascades and simulation of longer-term annealing

In vitro screening of environmental chemicals for targeted testing prioritization: the ToxCast project.

Science.gov (United States)

Judson, Richard S; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Mortensen, Holly M; Reif, David M; Rotroff, Daniel M; Shah, Imran; Richard, Ann M; Dix, David J

2010-04-01

Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use, and the thousands of environmental chemicals lacking toxicity data. The U.S. Environmental Protection Agency's ToxCast program aims to address these concerns by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. This project aims to evaluate the use of in vitro assays for understanding the types of molecular and pathway perturbations caused by environmental chemicals and to build initial prioritization models of in vivo toxicity. We tested 309 mostly pesticide active chemicals in 467 assays across nine technologies, including high-throughput cell-free assays and cell-based assays, in multiple human primary cells and cell lines plus rat primary hepatocytes. Both individual and composite scores for effects on genes and pathways were analyzed. Chemicals displayed a broad spectrum of activity at the molecular and pathway levels. We saw many expected interactions, including endocrine and xenobiotic metabolism enzyme activity. Chemicals ranged in promiscuity across pathways, from no activity to affecting dozens of pathways. We found a statistically significant inverse association between the number of pathways perturbed by a chemical at low in vitro concentrations and the lowest in vivo dose at which a chemical causes toxicity. We also found associations between a small set of in vitro assays and rodent liver lesion formation. This approach promises to provide meaningful data on the thousands of untested environmental chemicals and to guide targeted testing of environmental contaminants.

Integrated Broadband Quantum Cascade Laser

Science.gov (United States)

Mansour, Kamjou (Inventor); Soibel, Alexander (Inventor)

2016-01-01

A broadband, integrated quantum cascade laser is disclosed, comprising ridge waveguide quantum cascade lasers formed by applying standard semiconductor process techniques to a monolithic structure of alternating layers of claddings and active region layers. The resulting ridge waveguide quantum cascade lasers may be individually controlled by independent voltage potentials, resulting in control of the overall spectrum of the integrated quantum cascade laser source. Other embodiments are described and claimed.

Identification of potential glutaminyl cyclase inhibitors from lead-like libraries by in silico and in vitro fragment-based screening.

Science.gov (United States)

Szaszkó, Mária; Hajdú, István; Flachner, Beáta; Dobi, Krisztina; Magyar, Csaba; Simon, István; Lőrincz, Zsolt; Kapui, Zoltán; Pázmány, Tamás; Cseh, Sándor; Dormán, György

2017-02-01

A glutaminyl cyclase (QC) fragment library was in silico selected by disconnection of the structure of known QC inhibitors and by lead-like 2D virtual screening of the same set. The resulting fragment library (204 compounds) was acquired from commercial suppliers and pre-screened by differential scanning fluorimetry followed by functional in vitro assays. In this way, 10 fragment hits were identified ([Formula: see text]5 % hit rate, best inhibitory activity: 16 [Formula: see text]). The in vitro hits were then docked to the active site of QC, and the best scoring compounds were analyzed for binding interactions. Two fragments bound to different regions in a complementary manner, and thus, linking those fragments offered a rational strategy to generate novel QC inhibitors. Based on the structure of the virtual linked fragment, a 77-membered QC target focused library was selected from vendor databases and docked to the active site of QC. A PubChem search confirmed that the best scoring analogues are novel, potential QC inhibitors.

An improved single cell ultrahigh throughput screening method based on in vitro compartmentalization.

Directory of Open Access Journals (Sweden)

Fuqiang Ma

Full Text Available High-throughput screening is a key technique in discovery and engineering of enzymes. In vitro compartmentalization based fluorescence-activated cell sorting (IVC-FACS has recently emerged as a powerful tool for ultrahigh-throughput screening of biocatalysts. However, the accuracy of current IVC-FACS assays is severely limited by the wide polydispersity of micro-reactors generated by homogenizing. Here, an improved protocol based on membrane-extrusion technique was reported to generate the micro-reactors in a more uniform manner. This crucial improvement enables ultrahigh-throughput screening of enzymatic activity at a speed of >10⁸ clones/day with an accuracy that could discriminate as low as two-fold differences in enzymatic activity inside the micro-reactors, which is higher than similar IVC-FACS systems ever have reported. The enzymatic reaction in the micro-reactors has very similar kinetic behavior compared to the bulk reaction system and shows wide dynamic range. By using the modified IVC-FACS, E. coli cells with esterase activity could be enriched 330-fold from large excesses of background cells through a single round of sorting. The utility of this new IVC-FACS system was further illustrated by the directed evolution of thermophilic esterase AFEST. The catalytic activity of the very efficient esterase was further improved by ∼2-fold, resulting in several improved mutants with k(cat/K(M values approaching the diffusion-limited efficiency of ∼10⁸ M⁻¹s⁻¹.

Conjugation of cascades

International Nuclear Information System (INIS)

San Martin, Jesus; Rodriguez-Perez, Daniel

2009-01-01

Presented in this work are some results relative to sequences found in the logistic equation bifurcation diagram, which is the unimodal quadratic map prototype. All of the different saddle-node bifurcation cascades, associated with every last appearance p-periodic orbit (p=3,4,5,...), can also be generated from the very Feigenbaum cascade. In this way it is evidenced the relationship between both cascades. The orbits of every saddle-node bifurcation cascade, mentioned above, are located in different chaotic bands, and this determines a sequence of orbits converging to every band-merging Misiurewicz point. In turn, these accumulation points form a sequence whose accumulation point is the Myrberg-Feigenbaum point. It is also proven that the first appearance orbits in the n-chaotic band converge to the same point as the last appearance orbits of the (n + 1)-chaotic band. The symbolic sequences of band-merging Misiurewicz points are computed for any window.

Improvement of the green fluorescent protein reporter system in Leishmania spp. for the in vitro and in vivo screening of antileishmanial drugs.

Science.gov (United States)

Pulido, Sergio A; Muñoz, Diana L; Restrepo, Adriana M; Mesa, Carol V; Alzate, Juan F; Vélez, Iván D; Robledo, Sara M

2012-04-01

Development of new therapeutic approaches for leishmaniasis treatment requires new high throughput screening methodologies for the antileishmanial activity of the new compounds both in vitro and in vivo. Reporter genes as the GFP have become one of the most promissory and widely used tools for drug screening in several models, since it offers live imaging, high sensibility, specificity and flexibility; additionally, the use of GFP as a reporter gene in screening assays eliminates all the drawbacks presented in conventional assays and also those technical problems found using other reporter genes. The utility of the GFP as a reporter gene in drug screening assays with Leishmania parasites depends on the homogeneity and stability of the GFP transfected strains. Stable expression of the GFP in the Old World Leishmania species has been demonstrated using integration vectors; however, no reports exist yet about the success of this methodology in the New World species. Here we report the generation of New World Leishmania strains expressing the GFP protein from an integration vector, which replaces one copy of the 18S RNA in the chromosome with the GFP coding sequence by homologous recombination. We also prove that the expression of the integrated GFP is stable and homogeneous in the transfected parasites after months in culture without selective pressure or during its use in hamster infection assays. The fluorescent strains are useful for in vitro, ex vivo and in vivo drug screening assays since no considerable variations in virulence or infectivity where seen attributable to the genetic manipulation during both in vitro and in vivo infection experiments. The platform described here for drug testing assays based on the use of stable fluorescent Leishmania strains coupled to flow cytometry and fluorescent microscopy is more sensitive, more specific and faster than conventional assays used normally for the evaluation of compounds with potential antileishmanial activity

Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity

Energy Technology Data Exchange (ETDEWEB)

Sirenko, Oksana, E-mail: oksana.sirenko@moldev.com [Molecular Devices LLC, Sunnyvale, CA 94089 (United States); Cromwell, Evan F., E-mail: evan.cromwell@moldev.com [Molecular Devices LLC, Sunnyvale, CA 94089 (United States); Crittenden, Carole [Molecular Devices LLC, Sunnyvale, CA 94089 (United States); Wignall, Jessica A. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Wright, Fred A. [Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599 (United States); Rusyn, Ivan [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)

2013-12-15

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes show promise for screening during early drug development. Here, we tested a hypothesis that in vitro assessment of multiple cardiomyocyte physiological parameters enables predictive and mechanistically-interpretable evaluation of cardiotoxicity in a high-throughput format. Human iPSC-derived cardiomyocytes were exposed for 30 min or 24 h to 131 drugs, positive (107) and negative (24) for in vivo cardiotoxicity, in up to 6 concentrations (3 nM to 30 uM) in 384-well plates. Fast kinetic imaging was used to monitor changes in cardiomyocyte function using intracellular Ca{sup 2+} flux readouts synchronous with beating, and cell viability. A number of physiological parameters of cardiomyocyte beating, such as beat rate, peak shape (amplitude, width, raise, decay, etc.) and regularity were collected using automated data analysis. Concentration–response profiles were evaluated using logistic modeling to derive a benchmark concentration (BMC) point-of-departure value, based on one standard deviation departure from the estimated baseline in vehicle (0.3% dimethyl sulfoxide)-treated cells. BMC values were used for cardiotoxicity classification and ranking of compounds. Beat rate and several peak shape parameters were found to be good predictors, while cell viability had poor classification accuracy. In addition, we applied the Toxicological Prioritization Index (ToxPi) approach to integrate and display data across many collected parameters, to derive “cardiosafety” ranking of tested compounds. Multi-parameter screening of beating profiles allows for cardiotoxicity risk assessment and identification of specific patterns defining mechanism-specific effects. These data and analysis methods may be used widely for compound screening and early safety evaluation in drug development. - Highlights: • Induced pluripotent stem cell-derived cardiomyocytes are promising in vitro models. • We tested if evaluation

Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity

International Nuclear Information System (INIS)

Sirenko, Oksana; Cromwell, Evan F.; Crittenden, Carole; Wignall, Jessica A.; Wright, Fred A.; Rusyn, Ivan

2013-01-01

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes show promise for screening during early drug development. Here, we tested a hypothesis that in vitro assessment of multiple cardiomyocyte physiological parameters enables predictive and mechanistically-interpretable evaluation of cardiotoxicity in a high-throughput format. Human iPSC-derived cardiomyocytes were exposed for 30 min or 24 h to 131 drugs, positive (107) and negative (24) for in vivo cardiotoxicity, in up to 6 concentrations (3 nM to 30 uM) in 384-well plates. Fast kinetic imaging was used to monitor changes in cardiomyocyte function using intracellular Ca 2+ flux readouts synchronous with beating, and cell viability. A number of physiological parameters of cardiomyocyte beating, such as beat rate, peak shape (amplitude, width, raise, decay, etc.) and regularity were collected using automated data analysis. Concentration–response profiles were evaluated using logistic modeling to derive a benchmark concentration (BMC) point-of-departure value, based on one standard deviation departure from the estimated baseline in vehicle (0.3% dimethyl sulfoxide)-treated cells. BMC values were used for cardiotoxicity classification and ranking of compounds. Beat rate and several peak shape parameters were found to be good predictors, while cell viability had poor classification accuracy. In addition, we applied the Toxicological Prioritization Index (ToxPi) approach to integrate and display data across many collected parameters, to derive “cardiosafety” ranking of tested compounds. Multi-parameter screening of beating profiles allows for cardiotoxicity risk assessment and identification of specific patterns defining mechanism-specific effects. These data and analysis methods may be used widely for compound screening and early safety evaluation in drug development. - Highlights: • Induced pluripotent stem cell-derived cardiomyocytes are promising in vitro models. • We tested if evaluation of

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

Directory of Open Access Journals (Sweden)

Amanda J. Watson

2016-05-01

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

Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum.

Science.gov (United States)

Avery, Vicky M; Bashyam, Sridevi; Burrows, Jeremy N; Duffy, Sandra; Papadatos, George; Puthukkuti, Shyni; Sambandan, Yuvaraj; Singh, Shivendra; Spangenberg, Thomas; Waterson, David; Willis, Paul

2014-05-27

In view of the need to continuously feed the pipeline with new anti-malarial agents adapted to differentiated and more stringent target product profiles (e.g., new modes of action, transmission-blocking activity or long-duration chemo-protection), a chemical library consisting of more than 250,000 compounds has been evaluated in a blood-stage Plasmodium falciparum growth inhibition assay and further assessed for chemical diversity and novelty. The selection cascade used for the triaging of hits from the chemical library started with a robust three-step in vitro assay followed by an in silico analysis of the resulting confirmed hits. Upon reaching the predefined requirements for selectivity and potency, the set of hits was subjected to computational analysis to assess chemical properties and diversity. Furthermore, known marketed anti-malarial drugs were co-clustered acting as 'signposts' in the chemical space defined by the hits. Then, in cerebro evaluation of the chemical structures was performed to identify scaffolds that currently are or have been the focus of anti-malarial medicinal chemistry programmes. Next, prioritization according to relaxed physicochemical parameters took place, along with the search for structural analogues. Ultimately, synthesis of novel chemotypes with desired properties was performed and the resulting compounds were subsequently retested in a P. falciparum growth inhibition assay. This screening campaign led to a 1.25% primary hit rate, which decreased to 0.77% upon confirmatory repeat screening. With the predefined potency (EC₅₀  10) criteria, 178 compounds progressed to the next steps where chemical diversity, physicochemical properties and novelty assessment were taken into account. This resulted in the selection of 15 distinct chemical series. A selection cascade was applied to prioritize hits resulting from the screening of a medium-sized chemical library against blood-stage P. falciparum. Emphasis was placed on chemical

Energy cascades in Canada

Energy Technology Data Exchange (ETDEWEB)

Hayden, A. C.; Brown, T. D.

1979-03-15

Combining energy uses in a cascade can result in significant overall reductions in fuel requirements. The simplest applications for a cascade are in the recovery of waste heat from existing processes using special boilers or turbines. Specific applications of more-complex energy cascades for Canada are discussed. A combined-cycle plant at a chemical refinery in Ontario is world leader in energy efficiency. Total-energy systems for commercial buildings, such as one installed in a school in Western Canada, offer attractive energy and operating cost benefits. A cogeneration plant proposed for the National Capital Region, generating electricity as well as steam for district heating, allows the use of a low-grade fossil fuel (coal), greatly improves energy-transformation efficiency, and also utilizes an effectively renewable resource (municipal garbage). Despite the widespread availability of equipment and technology of energy cascades, the sale of steam and electricity across plant boundaries presents a barrier. More widespread use of cascades will require increased cooperation among industry, electric utilities and the various levels of government if Canada is to realize the high levels of energy efficiency potential available.

Cascade reactor: introduction

International Nuclear Information System (INIS)

Pitts, J.H.

1985-01-01

Cascade is a concept for an ultrasafe, highly efficient, easily built reactor to convert inertial-confinement fusion energy into electrical power. The Cascade design includes a rotating double-cone-shaped chamber in which a moving, 1-m-thick ceramic granular blanket is held against the reactor wall by centrifugal action. The granular material absorbs energy from the fusion reactions. Accomplishments this year associated with Cascade included improvements to simplify chamber design and lower activation. The authors switched from a steel chamber wall to one made from silicon-carbide (SiC) panels held in compression by SiC-fiber/Al-composite tendons that gird the chamber both circumferentially and axially. The authors studies a number of heat-exchanger designs and selected a gravity-flow cascade design with a vacuum on the primary side. This design allows granules leaving the chamber to be transported to the heat exchangers using their own peripheral speed. The granules transfer their thermal energy and return to the chamber gravitationally: no vacuum locks or conveyors are needed

Cascade quantum teleportation

Institute of Scientific and Technical Information of China (English)

ZHOU Nan-run; GONG Li-hua; LIU Ye

2006-01-01

In this letter a cascade quantum teleportation scheme is proposed. The proposed scheme needs less local quantum operations than those of quantum multi-teleportation. A quantum teleportation scheme based on entanglement swapping is presented and compared with the cascade quantum teleportation scheme. Those two schemes can effectively teleport quantum information and extend the distance of quantum communication.

An Arabidopsis kinase cascade influences auxin-responsive cell expansion.

Science.gov (United States)

Enders, Tara A; Frick, Elizabeth M; Strader, Lucia C

2017-10-01

Mitogen-activated protein kinase (MPK) cascades are conserved mechanisms of signal transduction across eukaryotes. Despite the importance of MPK proteins in signaling events, specific roles for many Arabidopsis MPK proteins remain unknown. Multiple studies have suggested roles for MPK signaling in a variety of auxin-related processes. To identify MPK proteins with roles in auxin response, we screened mpk insertional alleles and identified mpk1-1 as a mutant that displays hypersensitivity in auxin-responsive cell expansion assays. Further, mutants defective in the upstream MAP kinase kinase MKK3 also display hypersensitivity in auxin-responsive cell expansion assays, suggesting that this MPK cascade affects auxin-influenced cell expansion. We found that MPK1 interacts with and phosphorylates ROP BINDING PROTEIN KINASE 1 (RBK1), a protein kinase that interacts with members of the Rho-like GTPases from Plants (ROP) small GTPase family. Similar to mpk1-1 and mkk3-1 mutants, rbk1 insertional mutants display auxin hypersensitivity, consistent with a possible role for RBK1 downstream of MPK1 in influencing auxin-responsive cell expansion. We found that RBK1 directly phosphorylates ROP4 and ROP6, supporting the possibility that RBK1 effects on auxin-responsive cell expansion are mediated through phosphorylation-dependent modulation of ROP activity. Our data suggest a MKK3 • MPK1 • RBK1 phosphorylation cascade that may provide a dynamic module for altering cell expansion. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Cascade theory in isotopic separation processes; Theorie des cascades en separation isotopique

Energy Technology Data Exchange (ETDEWEB)

Agostini, J P

1994-06-01

Three main areas are developed within the scope of this work: - the first one is devoted to fundamentals: separative power, value function, ideal cascade and square cascade. Applications to two main cases are carried out, namely: Study of binary isotopic mix, Study of processes with a small enrichment coefficient. - The second one is devoted to cascade coupling -high-flux coupling (more widely used and better known) as well as low-flux coupling are presented and compared to one another. - The third one is an outlook on problems linked to cascade transients. Those problem are somewhat intricate and their interest lies mainly into two areas: economics where the start-up time may have a large influence on the interests paid during the construction and start-up period, military productions where the start-up time has a direct bearing on the production schedule. (author). 50 figs. 3 annexes. 12 refs. 6 tabs.

Effective screening strategy using ensembled pharmacophore models combined with cascade docking: application to p53-MDM2 interaction inhibitors.

Science.gov (United States)

Xue, Xin; Wei, Jin-Lian; Xu, Li-Li; Xi, Mei-Yang; Xu, Xiao-Li; Liu, Fang; Guo, Xiao-Ke; Wang, Lei; Zhang, Xiao-Jin; Zhang, Ming-Ye; Lu, Meng-Chen; Sun, Hao-Peng; You, Qi-Dong

2013-10-28

Protein-protein interactions (PPIs) play a crucial role in cellular function and form the backbone of almost all biochemical processes. In recent years, protein-protein interaction inhibitors (PPIIs) have represented a treasure trove of potential new drug targets. Unfortunately, there are few successful drugs of PPIIs on the market. Structure-based pharmacophore (SBP) combined with docking has been demonstrated as a useful Virtual Screening (VS) strategy in drug development projects. However, the combination of target complexity and poor binding affinity prediction has thwarted the application of this strategy in the discovery of PPIIs. Here we report an effective VS strategy on p53-MDM2 PPI. First, we built a SBP model based on p53-MDM2 complex cocrystal structures. The model was then simplified by using a Receptor-Ligand complex-based pharmacophore model considering the critical binding features between MDM2 and its small molecular inhibitors. Cascade docking was subsequently applied to improve the hit rate. Based on this strategy, we performed VS on NCI and SPECS databases and successfully discovered 6 novel compounds from 15 hits with the best, compound 1 (NSC 5359), K(i) = 180 ± 50 nM. These compounds can serve as lead compounds for further optimization.

In vitro screening of durum wheat against water-stress mediated through polyethylene glycol

Directory of Open Access Journals (Sweden)

Nadia Sandra Kacem

2017-06-01

Full Text Available Three durum wheat (Triticum durum Desf. genotypes with three levels of drought tolerance were screened in order to evaluate their response to water stress at callus induction and plant regeneration levels. Significant differences were observed among the genotypes, and polyethylene glycol (PEG levels used, and their interactions were however, significant for all the studied characters. Increase in PEG concentration increased the time required for callus initiation and reduced the number of calli frequency of embryogenic structures and number of plants regenerated, showing the adverse effect of PEG on the somatic embryogenesis developmental., under in vitro conditions tested, and Djenah Khetifa was the most tolerant genotype, followed by Oued Zenati and Waha. This pattern was per their drought tolerance behavior under field conditions. Principal component analysis (PCA showed that 95.56% of the total variation was explained by the first two principal components. Biplot analysis allowed the stress-tolerant genotype to be distinguished from the two less tolerant genotypes. Time required for callus initiation was strongly negatively correlated with all other studied traits. These traits can be recommended as suitable selection criteria for screening drought-tolerant genotypes. The selected cells and plants will provide a tool for determining the mechanisms involved in tolerance to water stress.

Cascading costs: an economic nitrogen cycle.

Science.gov (United States)

Moomaw, William R; Birch, Melissa B L

2005-09-01

The chemical nitrogen cycle is becoming better characterized in terms of fluxes and reservoirs on a variety of scales. Galloway has demonstrated that reactive nitrogen can cascade through multiple ecosystems causing environmental damage at each stage before being denitrified to N(2). We propose to construct a parallel economic nitrogen cascade (ENC) in which economic impacts of nitrogen fluxes can be estimated by the costs associated with each stage of the chemical cascade. Using economic data for the benefits of damage avoided and costs of mitigation in the Chesapeake Bay basin, we have constructed an economic nitrogen cascade for the region. Since a single ton of nitrogen can cascade through the system, the costs also cascade. Therefore evaluating the benefits of mitigating a ton of reactive nitrogen released needs to consider the damage avoided in all of the ecosystems through which that ton would cascade. The analysis reveals that it is most cost effective to remove a ton of nitrogen coming from combustion since it has the greatest impact on human health and creates cascading damage through the atmospheric, terrestrial, aquatic and coastal ecosystems. We will discuss the implications of this analysis for determining the most cost effective policy option for achieving environmental quality goals.

Contingency Analysis of Cascading Line Outage Events

Energy Technology Data Exchange (ETDEWEB)

Thomas L Baldwin; Magdy S Tawfik; Miles McQueen

2011-03-01

As the US power systems continue to increase in size and complexity, including the growth of smart grids, larger blackouts due to cascading outages become more likely. Grid congestion is often associated with a cascading collapse leading to a major blackout. Such a collapse is characterized by a self-sustaining sequence of line outages followed by a topology breakup of the network. This paper addresses the implementation and testing of a process for N-k contingency analysis and sequential cascading outage simulation in order to identify potential cascading modes. A modeling approach described in this paper offers a unique capability to identify initiating events that may lead to cascading outages. It predicts the development of cascading events by identifying and visualizing potential cascading tiers. The proposed approach was implemented using a 328-bus simplified SERC power system network. The results of the study indicate that initiating events and possible cascading chains may be identified, ranked and visualized. This approach may be used to improve the reliability of a transmission grid and reduce its vulnerability to cascading outages.

Monte Carlo Investigation of Phosphor Screens for X-ray Imaging

International Nuclear Information System (INIS)

Lim, Chang Hwy; Cheong, Min Ho; Cho, Min Kook; Shon, Choel Soon; Kim, Ho Kyung

2006-01-01

In order to detect X rays with pixel detectors, there are two technical methods; a direct detection using photoconductive material that permits the conversion of the incident X rays into the signal charges, and an indirect detection using scintillation material that converts the incident X rays into the optical photons. Therefore, two-dimensional (2D) photosensitive pixel array is necessary for the indirect-detection scheme. Terbium-doped gadolinium oxysulfide (Gd 2 O 2 S:Tb) phosphor screen is the most popular X-ray converter, and often employed to the digital radiographic system owing to its well-known technology and easy handling in size, thickness, and flexibility. Furthermore, the cost is effective. In cascaded imaging chains of the indirect-detection system, the phosphor screen is served as the first stage. Since the image signal-to-noise ratio (SNR) is irreversible through the cascaded system, the phosphor screen is largely responsible for the eventual image quality. For the various radiation qualities suggested by IEC (International Electrotechnical Commission, Report 1267), we have investigated important physical quantities of Gd 2 O 2 S:Tb screen with a wide range of coverages (34 . 135 mg/cm 2 ) by using Monte Carlo calculations. The results will be useful for the optimal design of digital X-ray imaging systems

Screening and selection of high carotenoid producing in vitro tomato cell culture lines for [13C]-carotenoid production.

Science.gov (United States)

Engelmann, Nancy J; Campbell, Jessica K; Rogers, Randy B; Rupassara, S Indumathie; Garlick, Peter J; Lila, Mary Ann; Erdman, John W

2010-09-22

Isotopically labeled tomato carotenoids, phytoene, phytofluene, and lycopene, are needed for mammalian bioavailability and metabolism research but are currently commercially unavailable. The goals of this work were to establish and screen multiple in vitro tomato cell lines for carotenoid production, test the best producers with or without the bleaching herbicides, norflurazon and 2-(4-chlorophenyl-thio)triethylamine (CPTA), and to use the greatest carotenoid accumulator for in vitro 13C-labeling. Different Solanum lycopersicum allelic variants for high lycopene and varying herbicide treatments were compared for carotenoid accumulation in callus and suspension culture, and cell suspension cultures of the hp-1 line were chosen for isotopic labeling. When grown with [U]-13C-glucose and treated with CPTA, hp-1 suspensions yielded highly enriched 13C-lycopene with 45% of lycopene in the M+40 form and 88% in the M+35 to M+40 isotopomer range. To the authors' knowledge this is the first report of highly enriched 13C-carotenoid production from in vitro plant cell culture.

Simulation of concentration spikes in cascades

International Nuclear Information System (INIS)

Wood, H.G.

2006-01-01

Research has been conducted to investigate the maximum possible enrichment that might be temporarily achieved in a facility that is producing enriched uranium for fuel for nuclear power reactors. The purpose is to provide information to evaluate if uranium enrichment facilities are producing 235 U enriched within declared limits appropriate for power reactors or if the facilities are actually producing more highly enriched uranium. The correlation between feed rate and separation factor in a gas centrifuge cascade shows that as flow decreases, the separation factor increases, thereby, creating small amounts of higher enriched uranium than would be found under optimum design operating conditions. The research uses a number of cascade enrichment programs to model the phenomenon and determine the maximum enrichment possible during the time transient of a gas centrifuge cascade. During cascade start-up, the flow through the centrifuges begins at lower than centrifuge design stage flow rates. Steady-state cascade models have been used to study the maximum 235 U concentrations that would be predicted in the cascade. These calculations should produce an upper bound of product concentrations expected during the transient phase of start-up. Due to the fact that there are different ways in which to start a cascade, several methods are used to determine the maximum enrichment during the time transient. Model cascades were created for gas centrifuges with several product to .feed assay separation factors. With this information, the models were defined and the equilibrium programs were used to determine the maximum enrichment level during the time transient. The calculations predict in a cascade with separation factor 1.254 designed to produce enriched uranium for the purpose of supplying reactor fuel, it would not be unreasonable to see some 235 U in the range of 12-15%. Higher assays produced during the start-up period might lead inspectors to believe the cascade is being

In vitro screening of potato genotypes for osmotic stress tolerance

Directory of Open Access Journals (Sweden)

Gelmesa Dandena

2017-02-01

genotypes. Most of the genotypes collected from Ethiopia were found to be susceptible to osmotic stress, except one farmers’ cultivar (Dadafa and two improved varieties (Zemen and Belete. Field evaluation of the tested materials under drought conditions would confirm the capacity of osmotic stress tolerant genotypes to perform well under drought-prone conditions and the potential interest of in vitro evaluation as a pre-screening component in potato breeding programs.

Stability of cascade search

Energy Technology Data Exchange (ETDEWEB)

Fomenko, Tatiana N [M. V. Lomonosov Moscow State University, Faculty of Computational Mathematics and Cybernetics, Moscow (Russian Federation)

2010-10-22

We find sufficient conditions on a searching multi-cascade for a modification of the set of limit points of the cascade that satisfy an assessing inequality for the distance from each of these points to the initial point to be small, provided that the modifications of the initial point and the initial set-valued functionals or maps used to construct the multi-cascade are small. Using this result, we prove the stability (in the above sense) of the cascade search for the set of common pre-images of a closed subspace under the action of n set-valued maps, n{>=}1 (in particular, for the set of common roots of these maps and for the set of their coincidences). For n=2 we obtain generalizations of some results of A. V. Arutyunov; the very statement of the problem comes from a recent paper of his devoted to the study of the stability of the subset of coincidences of a Lipschitz map and a covering map.

Genetic algorithm based separation cascade optimization

International Nuclear Information System (INIS)

Mahendra, A.K.; Sanyal, A.; Gouthaman, G.; Bera, T.K.

2008-01-01

The conventional separation cascade design procedure does not give an optimum design because of squaring-off, variation of flow rates and separation factor of the element with respect to stage location. Multi-component isotope separation further complicates the design procedure. Cascade design can be stated as a constrained multi-objective optimization. Cascade's expectation from the separating element is multi-objective i.e. overall separation factor, cut, optimum feed and separative power. Decision maker may aspire for more comprehensive multi-objective goals where optimization of cascade is coupled with the exploration of separating element optimization vector space. In real life there are many issues which make it important to understand the decision maker's perception of cost-quality-speed trade-off and consistency of preferences. Genetic algorithm (GA) is one such evolutionary technique that can be used for cascade design optimization. This paper addresses various issues involved in the GA based multi-objective optimization of the separation cascade. Reference point based optimization methodology with GA based Pareto optimality concept for separation cascade was found pragmatic and promising. This method should be explored, tested, examined and further developed for binary as well as multi-component separations. (author)

Ion-implantation dense cascade data

International Nuclear Information System (INIS)

Winterbon, K.B.

1983-04-01

A tabulation is given of data useful in estimating various aspects of ion-implantation cascades in the nuclear stopping regime, particularly with respect to nonlinearity of the cascade at high energy densities. The tabulation is restricted to self-ion implantation. Besides power-cross-section cascade dimensions, various material properties are included. Scaling of derived quantities with input data is noted, so one is not limited to the values assumed by the author

Hadron cascades produced by electromagnetic cascades

International Nuclear Information System (INIS)

Nelson, W.R.; Jenkins, T.M.; Ranft, J.

1986-12-01

A method for calculating high energy hadron cascades induced by multi-GeV electron and photon beams is described. Using the EGS4 computer program, high energy photons in the EM shower are allowed to interact hadronically according to the vector meson dominance (VMD) model, facilitated by a Monte Carlo version of the dual multistring fragmentation model which is used in the hadron cascade code FLUKA. The results of this calculation compare very favorably with experimental data on hadron production in photon-proton collisions and on the hadron production by electron beams on targets (i.e., yields in secondary particle beam lines). Electron beam induced hadron star density contours are also presented and are compared with those produced by proton beams. This FLUKA-EGS4 coupling technique could find use in the design of secondary beams, in the determination high energy hadron source terms for shielding purposes, and in the estimation of induced radioactivity in targets, collimators and beam dumps

In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.

Science.gov (United States)

Ozcelikkale, Altug; Moon, Hye-Ran; Linnes, Michael; Han, Bumsoo

2017-09-01

Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high-throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Cascade Organic Solar Cells

KAUST Repository

Schlenker, Cody W.

2011-09-27

We demonstrate planar organic solar cells consisting of a series of complementary donor materials with cascading exciton energies, incorporated in the following structure: glass/indium-tin-oxide/donor cascade/C 60/bathocuproine/Al. Using a tetracene layer grown in a descending energy cascade on 5,6-diphenyl-tetracene and capped with 5,6,11,12-tetraphenyl- tetracene, where the accessibility of the π-system in each material is expected to influence the rate of parasitic carrier leakage and charge recombination at the donor/acceptor interface, we observe an increase in open circuit voltage (Voc) of approximately 40% (corresponding to a change of +200 mV) compared to that of a single tetracene donor. Little change is observed in other parameters such as fill factor and short circuit current density (FF = 0.50 ± 0.02 and Jsc = 2.55 ± 0.23 mA/cm2) compared to those of the control tetracene-C60 solar cells (FF = 0.54 ± 0.02 and Jsc = 2.86 ± 0.23 mA/cm2). We demonstrate that this cascade architecture is effective in reducing losses due to polaron pair recombination at donor-acceptor interfaces, while enhancing spectral coverage, resulting in a substantial increase in the power conversion efficiency for cascade organic photovoltaic cells compared to tetracene and pentacene based devices with a single donor layer. © 2011 American Chemical Society.

Cascade Organic Solar Cells

KAUST Repository

Schlenker, Cody W.; Barlier, Vincent S.; Chin, Stephanie W.; Whited, Matthew T.; McAnally, R. Eric; Forrest, Stephen R.; Thompson, Mark E.

2011-01-01

We demonstrate planar organic solar cells consisting of a series of complementary donor materials with cascading exciton energies, incorporated in the following structure: glass/indium-tin-oxide/donor cascade/C 60/bathocuproine/Al. Using a tetracene layer grown in a descending energy cascade on 5,6-diphenyl-tetracene and capped with 5,6,11,12-tetraphenyl- tetracene, where the accessibility of the π-system in each material is expected to influence the rate of parasitic carrier leakage and charge recombination at the donor/acceptor interface, we observe an increase in open circuit voltage (Voc) of approximately 40% (corresponding to a change of +200 mV) compared to that of a single tetracene donor. Little change is observed in other parameters such as fill factor and short circuit current density (FF = 0.50 ± 0.02 and Jsc = 2.55 ± 0.23 mA/cm2) compared to those of the control tetracene-C60 solar cells (FF = 0.54 ± 0.02 and Jsc = 2.86 ± 0.23 mA/cm2). We demonstrate that this cascade architecture is effective in reducing losses due to polaron pair recombination at donor-acceptor interfaces, while enhancing spectral coverage, resulting in a substantial increase in the power conversion efficiency for cascade organic photovoltaic cells compared to tetracene and pentacene based devices with a single donor layer. © 2011 American Chemical Society.

Photochemical binding of photoallergens to human serum albumin: a simple in vitro method for screening potential photoallergens

International Nuclear Information System (INIS)

Barratt, M.D.; Brown, K.R.

1985-01-01

A simple procedure employing UV spectroscopy is described for testing the ability of chemicals to form covalent conjugates with proteins after irradiation with the appropriate wavelength of light. A range of known photoallergens of widely differing structure has been tested using this procedure; results of these experiments, together with evidence from the scientific literature, provide a correlation between compounds known to be photoallergens and their ability to form covalent conjugates with proteins on irradiation with the appropriate wavelength of light. The method is proposed as an in vitro screening procedure for potential photoallergens. (Auth.)

In vitro antioxidant activity and phytochemical screening of Garhwal Himalaya medicinal plants

Directory of Open Access Journals (Sweden)

Subhash Chandra

2016-08-01

Full Text Available Bistorta macrophylla, B.vaccinifolia and Persicaria polystachya are used for the treatment and prevention of many ailments including tuberculosis, inflammation, pyretic, fever, flue, lungs disorders, diarrhea, vomiting, arthritis, gout, kidney stones or hyperacidity and hypertension. This study was aimed to evaluate the possible in vitro antioxidant activity and phytochemical screening of B. macrophylla, B.vaccinifolia and P. polystachya. The results of antioxidant activity study of B. macrophylla showed maximum activity in the methanolic extracts at different concentration of 20, 40, 60, 80 and 100 µg/ml. The percent inhibition of writhing response by the extract was 36.18%, 44.72%, 59.21%. 67.08% and 83.39% respectively. In the present work a potent anti-oxidant activity of methanolic extract of the whole plants of B. macrophylla were demonstrated, validating the ethno pharmacological claims. These experimental findings would further establish the scientific basis of the traditional uses of the plant in the management of different conditions as well as control of different disease.

Cascaded Bragg scattering in fiber optics.

Science.gov (United States)

Xu, Y Q; Erkintalo, M; Genty, G; Murdoch, S G

2013-01-15

We report on a theoretical and experimental study of cascaded Bragg scattering in fiber optics. We show that the usual energy-momentum conservation of Bragg scattering can be considerably relaxed via cascade-induced phase-matching. Experimentally we demonstrate frequency translation over six- and 11-fold cascades, in excellent agreement with derived phase-matching conditions.

Cascade redox flow battery systems

Science.gov (United States)

Horne, Craig R.; Kinoshita, Kim; Hickey, Darren B.; Sha, Jay E.; Bose, Deepak

2014-07-22

A reduction/oxidation ("redox") flow battery system includes a series of electrochemical cells arranged in a cascade, whereby liquid electrolyte reacts in a first electrochemical cell (or group of cells) before being directed into a second cell (or group of cells) where it reacts before being directed to subsequent cells. The cascade includes 2 to n stages, each stage having one or more electrochemical cells. During a charge reaction, electrolyte entering a first stage will have a lower state-of-charge than electrolyte entering the nth stage. In some embodiments, cell components and/or characteristics may be configured based on a state-of-charge of electrolytes expected at each cascade stage. Such engineered cascades provide redox flow battery systems with higher energy efficiency over a broader range of current density than prior art arrangements.

Study of the radiation around a high energy accelerator. Production and scattering of cascade neutrons; Etude du rayonnement autour d'un accelerateur de haute energie. Production et diffusion des neutrons de cascade

Energy Technology Data Exchange (ETDEWEB)

Tardy-Joubert, P [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1966-03-01

The cascade induced in protective screens by a 3 GeV proton beam has been studied using activation detectors; the results have been compared with the cosmic neutron spectrum in the atmosphere. A study of the secondary neutron spectrum has made, it possible to obtain the distribution of the dose and to determine the maximum permissible fluxes expressed in terms of the energy, taking into account all the daughter products present. The dose calculated has been checked experimentally. The proportion of cascade neutrons has been studied using the idea of an imaginary source. The parameters which have to be introduced into the general equations to take into account scattering in the the air have been determined. (author) [French] La cascade induite dans les ecrans de protection par un faisceau de protons de 3 GeV a ete etudiee au moyen de detecteurs a activation et la comparaison a ete faite avec le spectre des neutrons cosmiques dans l'atmosphere. L'etude du spectre des neutrons secondaires a permis de preciser la distribution de la dose et de determiner les flux maximaux admissibles qui sont exprimes en fonction de l'energie, en tenant compte de l'ensemble des descendants presents. La dose calculee a ete verifiee experimentalement. La propagation des neutrons de cascade a ete etudiee en introduisant la notion de source fictive. Les parametres a introduire dans les equations generales pour rendre compte de la diffusion dans l'air ont ete determines. (auteur)

Cascade of links in complex networks

Energy Technology Data Exchange (ETDEWEB)

Feng, Yeqian; Sun, Bihui [Department of Management Science, School of Government, Beijing Normal University, 100875 Beijing (China); Zeng, An, E-mail: anzeng@bnu.edu.cn [School of Systems Science, Beijing Normal University, 100875 Beijing (China)

2017-01-30

Cascading failure is an important process which has been widely used to model catastrophic events such as blackouts and financial crisis in real systems. However, so far most of the studies in the literature focus on the cascading process on nodes, leaving the possibility of link cascade overlooked. In many real cases, the catastrophic events are actually formed by the successive disappearance of links. Examples exist in the financial systems where the firms and banks (i.e. nodes) still exist but many financial trades (i.e. links) are gone during the crisis, and the air transportation systems where the airports (i.e. nodes) are still functional but many airlines (i.e. links) stop operating during bad weather. In this letter, we develop a link cascade model in complex networks. With this model, we find that both artificial and real networks tend to collapse even if a few links are initially attacked. However, the link cascading process can be effectively terminated by setting a few strong nodes in the network which do not respond to any link reduction. Finally, a simulated annealing algorithm is used to optimize the location of these strong nodes, which significantly improves the robustness of the networks against the link cascade. - Highlights: • We propose a link cascade model in complex networks. • Both artificial and real networks tend to collapse even if a few links are initially attacked. • The link cascading process can be effectively terminated by setting a few strong nodes. • A simulated annealing algorithm is used to optimize the location of these strong nodes.

Cascade of links in complex networks

International Nuclear Information System (INIS)

Feng, Yeqian; Sun, Bihui; Zeng, An

2017-01-01

Cascading failure is an important process which has been widely used to model catastrophic events such as blackouts and financial crisis in real systems. However, so far most of the studies in the literature focus on the cascading process on nodes, leaving the possibility of link cascade overlooked. In many real cases, the catastrophic events are actually formed by the successive disappearance of links. Examples exist in the financial systems where the firms and banks (i.e. nodes) still exist but many financial trades (i.e. links) are gone during the crisis, and the air transportation systems where the airports (i.e. nodes) are still functional but many airlines (i.e. links) stop operating during bad weather. In this letter, we develop a link cascade model in complex networks. With this model, we find that both artificial and real networks tend to collapse even if a few links are initially attacked. However, the link cascading process can be effectively terminated by setting a few strong nodes in the network which do not respond to any link reduction. Finally, a simulated annealing algorithm is used to optimize the location of these strong nodes, which significantly improves the robustness of the networks against the link cascade. - Highlights: • We propose a link cascade model in complex networks. • Both artificial and real networks tend to collapse even if a few links are initially attacked. • The link cascading process can be effectively terminated by setting a few strong nodes. • A simulated annealing algorithm is used to optimize the location of these strong nodes.

The comparison of extraction of energy in two-cascade and one-cascade targets

Energy Technology Data Exchange (ETDEWEB)

Dolgoleva, G. V., E-mail: dolgg@list.ru [National Research Tomsk State University, 36, Lenin Ave., 634050, Tomsk (Russian Federation); Ponomarev, I. V., E-mail: wingof17@mail.ru [Moscow State University, Department of Mechanics and Mathematics, 1, Vorobyovy Gory, Moscow,119961 (Russian Federation)

2016-01-15

The paper is devoted to numerical designing of cylindrical microtargets on the basis of shock-free compression. When designing microtargets for the controlled thermonuclear fusion, the core tasks are to select geometry and make-up of layers, and the law of energy embedding as well, which allow receiving of “burning” of deuterium- tritium mix, that is, the existence of thermonuclear reactions of working area. Yet, the energy yield as a result of thermonuclear reactions has to be more than the embedded energy (the coefficient of amplification is more than a unit). So, an important issue is the value of the embedded energy. The purpose of the present paper is to study the extraction of energy by working DT area in one-cascade and two-cascade targets. A bigger extraction of energy will contribute to a better burning of DT mix and a bigger energy yield as a result of thermonuclear reactions. The comparison of analytical results to numerical calculations is carried out. The received results show advantages of a two-cascade target compared to a one-cascade one.

Occurrence and in vitro bioactivity of estrogen, androgen, and glucocorticoid compounds in a nationwide screen of United States stream waters

Science.gov (United States)

Conley, Justin M.; Evans, Nicola; Cardon, Mary C.; Rosenblum, Laura; Iwanowicz, Luke; Hartig, Phillip C.; Schenck, Kathleen M.; Bradley, Paul M.; Wilson, Vickie S.

2017-01-01

In vitro bioassays are sensitive, effect-based tools used to quantitatively screen for chemicals with nuclear receptor activity in environmental samples. We measured in vitro estrogen (ER), androgen (AR), and glucocorticoid receptor (GR) activity, along with a broad suite of chemical analytes, in streamwater from 35 well-characterized sites (3 reference and 32 impacted) across 24 states and Puerto Rico. ER agonism was the most frequently detected with nearly all sites (34/35) displaying activity (range, 0.054–116 ng E2Eq L–1). There was a strong linear relationship (r2 = 0.917) between in vitro ER activity and concentrations of steroidal estrogens after correcting for the in vitro potency of each compound. AR agonism was detected in 5/35 samples (range, 1.6–4.8 ng DHTEq L–1) but concentrations of androgenic compounds were largely unable to account for the in vitro activity. Similarly, GR agonism was detected in 9/35 samples (range, 6.0–43 ng DexEq L–1); however, none of the recognized GR-active compounds on the target-chemical analyte list were detected. The utility of in vitro assays in water quality monitoring was evident from both the quantitative agreement between ER activity and estrogen concentrations, as well as the detection of AR and GR activity for which there were limited or no corresponding target-chemical detections to explain the bioactivity. Incorporation of in vitro bioassays as complements to chemical analyses in standard water quality monitoring efforts would allow for more complete assessment of the chemical mixtures present in many surface waters.

Experimental study of flow through compressor Cascade

Directory of Open Access Journals (Sweden)

Satyam Panchal

2017-09-01

Full Text Available The objective of this research work is to study the behaviour of flow at the inlet, within the blade passage and at the exit of a compressor cascade. For this purpose, a cascade with six numbers of aerofoil blades was designed and constructed. The cascade was fitted on the cascade test tunnel. Out of six blades two were instrumented for measuring the pressure distribution on the pressure and suction surface. The blades had a parabolic camber line, with a maximum camber position at 40% of the chord from the leading edge of the blade. The profile of the blade was C4, height of the blade was 160 mm, chord length was 80 mm, camber angle was 45° and stagger angle was 30°. Similarly, the length of the cascade was 300 mm, span was 160 mm, pitch was 60 mm, the actual chord of the cascade was 80 mm, the axial chord of the cascade was 70 mm, the stagger angle of the cascade was 30° and the pitch-chord ratio was 0.75. The data was taken and analyzed at −500% of the axial chord before the cascade, −25% of the axial chord before the leading edge, 25%, 50%, 75% and 150% of the axial chord from the leading edge of the blade. The readings were taken from the cascade wall to the mid span position along the pitch wise direction. The angle of incidence was also changed during the experiment and varied from i=−50°, −30°, −10° to 5°.

Accurate and noninvasive embryos screening during in vitro fertilization (IVF) assisted by Raman analysis of embryos culture medium Accurate and noninvasive embryos screening during IVF

Science.gov (United States)

Shen, A. G.; Peng, J.; Zhao, Q. H.; Su, L.; Wang, X. H.; Hu, J. M.; Yang, J.

2012-04-01

In combination with morphological evaluation tests, we employ Raman spectroscopy to select higher potential reproductive embryos during in vitro fertilization (IVF) based on chemical composition of embryos culture medium. In this study, 57 Raman spectra are acquired from both higher and lower quality embryos culture medium (ECM) from 10 patients which have been preliminarily confirmed by clinical assay. Data are fit by using a linear combination model of least squares method in which 12 basis spectra represent the chemical features of ECM. The final fitting coefficients provide insight into the chemical compositions of culture medium samples and are subsequently used as criterion to evaluate the quality of embryos. The relative fitting coefficients ratios of sodium pyruvate/albumin and phenylalanine/albumin seem act as key roles in the embryo screening, attaining 85.7% accuracy in comparison with clinical pregnancy. The good results demonstrate that Raman spectroscopy therefore is an important candidate for an accurate and noninvasive screening of higher quality embryos, which potentially decrease the time-consuming clinical trials during IVF.

Design, synthesis, and validation of an in vitro platform peptide-whole cell screening assay using MTT reagent

Directory of Open Access Journals (Sweden)

Sahar Ahmed

2017-05-01

Full Text Available An in vitro platform to perform peptide screening against different cancer cell lines was designed. The strategy for this screening relied on the design and detection of high-affinity cancer-targeting peptides based on the sequences of NGR and P160. Evaluation of the best binding peptides was performed via incubation of the peptide array-bounded cells with MTT reagent, which is reduced to purple formazan in living cells and further quantified using an Elispot and Kodak imager. For proof of concept, a peptide library (132 spots, and 66 different peptides was designed, synthesized, and screened against different cancer cell lines. The current strategy assists in the identification of positive and negative peptides as well as the relative binding between positive ones. Better binding peptide sequences of the NGR motif were demonstrated to show up to a 2.6-fold increase in CD13+ cell lines with insignificant binding to CD13− ones. Comparable results were observed for P160 peptide sequences, to which different peptides had increased binding, with an up to 3-fold increase relative to the native P160 peptide. Based on our results, new peptide sequences for cancer targeting were identified, and the developed strategy was applied to two different peptide libraries.

A comparison of methods for cascade prediction

OpenAIRE

Guo, Ruocheng; Shakarian, Paulo

2016-01-01

Information cascades exist in a wide variety of platforms on Internet. A very important real-world problem is to identify which information cascades can go viral. A system addressing this problem can be used in a variety of applications including public health, marketing and counter-terrorism. As a cascade can be considered as compound of the social network and the time series. However, in related literature where methods for solving the cascade prediction problem were proposed, the experimen...

Computer simulation of displacement cascades in copper

International Nuclear Information System (INIS)

Heinisch, H.L.

1983-06-01

More than 500 displacement cascades in copper have been generated with the computer simulation code MARLOWE over an energy range pertinent to both fission and fusion neutron spectra. Three-dimensional graphical depictions of selected cascades, as well as quantitative analysis of cascade shapes and sizes and defect densities, illustrate cascade behavior as a function of energy. With increasing energy, the transition from production of single compact damage regions to widely spaced multiple damage regions is clearly demonstrated

Piperazine derivatives inhibit PrP/PrP(res) propagation in vitro and in vivo.

Science.gov (United States)

Leidel, Fabienne; Eiden, Martin; Geissen, Markus; Hirschberger, Thomas; Tavan, Paul; Giese, Armin; Kretzschmar, Hans A; Schätzl, Hermann; Groschup, Martin H

2014-02-28

Prion diseases are fatal neurodegenerative disorders, which are not curable and no effective treatment exists so far. The major neuropathological change in diseased brains is the conversion of the normal cellular form of the prion protein PrPc(C) into a disease-associated isoform PrP(Sc). PrP(Sc) accumulates into multimeres and fibrillar aggregates, which leads to the formation of amyloid plaques. Increasing evidence indicates a fundamental role of PrP(Sc) species and its aggregation in the pathogenesis of prion diseases, which initiates the pathological cascade and leads to neurodegeneration accompanied by spongiform changes. In search of compounds that have the potential to interfere with PrP(Sc) formation and propagation, we used a cell based assay for the screening of potential aggregation inhibitors. The assay deals with a permanently prion infected cell line that was adapted for a high-throughput screening of a compound library composed of 10,000 compounds (DIVERset 2, ChemBridge). We could detect six different classes of highly potent inhibitors of PrP(Sc) propagation in vitro and identified piperazine derivatives as a new inhibitory lead structure, which increased incubation time of scrapie infected mice. Copyright © 2014 Elsevier Inc. All rights reserved.

Cascade Error Projection Learning Algorithm

Science.gov (United States)

Duong, T. A.; Stubberud, A. R.; Daud, T.

1995-01-01

A detailed mathematical analysis is presented for a new learning algorithm termed cascade error projection (CEP) and a general learning frame work. This frame work can be used to obtain the cascade correlation learning algorithm by choosing a particular set of parameters.

Ultrarelativistic cascades and strangeness production

International Nuclear Information System (INIS)

Kahana, D.E.; Kahana, S.H.

1998-02-01

A two phase cascade, LUCIFER II, developed for the treatment of ultra high energy Ion-Ion collisions is applied to the production of strangeness at SPS energies. This simulation is able to simultaneously describe both hard processes such as Drell-Yan and slower, soft processes such as the production of light mesons by separating the dynamics into two steps, a fast cascade involving only the nucleons in the original colliding relativistic ions followed, after an appropriate delay, by a normal multiscattering of the resulting excited baryons and mesons produced virtually in the first step. No energy loss can take place in the short time interval over which the first cascade takes place. The chief result is a reconciliation of the important Drell-Yan measurements with the apparent success of standard cascades to describe the nucleon stopping and meson production in heavy ion experiments at the CERN SPS

Quartz-Containing Ceramic Dusts: In vitro screening of the cytotoxic, genotoxic and pro-inflammatory potential of 5 factory samples

Energy Technology Data Exchange (ETDEWEB)

Ziemann, C; Creutzenberg, O [Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover (Germany); Jackson, P [CERAM Research Ltd., Stoke-on-Trent (United Kingdom); Brown, R [TOXSERVICES, Stretton (United Kingdom); Attik, G; Rihn, B H, E-mail: christina.ziemann@item.fraunhofer.d [Nancy-University, Faculte de Pharmacie, Nancy (France)

2009-02-01

Inhalation of some respirable crystalline silica (MMAD < approx. 4 mum) leads to inflammatory and malignant diseases. Comprehensive physicochemical/biological data and suitable in vitro/in vivo methods may distinguish between more or less harmful quartz-varieties. Within the European Collective Research Project SILICERAM an in vitro screening battery was established to evaluate cytotoxicity (LDH-release, MTT-assay), genotoxicity (Comet-assay) and pro-inflammatory potential (PGE{sub 2}-liberation, TNF-a mRNA expression) of 5 respirable quartz-containing dusts from ceramic plants: brickwork (BR: 7.8% quartz), tableware granulate/cast (TG/TC: 5.8%/3.1%), tiles (TI: 8.1%), refractory (RF: 3.7%). DQ12 (87% a-quartz) and Al{sub 2}O{sub 3} were used as particulate positive and negative controls, respectively. Primary rat alveolar macrophages and the macrophage cell line NR8383 served as model systems. Aluminium lactate was used as inhibitor of biologically active silica, enabling differentiation of silica- and non-specific toxicity. At 200mug/cm{sup 2} (2h) the dusts did not alter significantly LDH-release (except TC), whereas the MTT-assay demonstrated the mainly quartz-independent rank order: DQ12>RF>TG>Ti>BR>TC>Al{sub 2}O{sub 3}. DNA-damage was maximal for BR and TI followed by DQ12>TG>TC>RF>Al{sub 2}O{sub 3}. All dusts induced PGE{sub 2}-liberation (DQ12>BR>TC>TG>Ti>RF>Al{sub 2}O{sub 3}) at 50mug/cm{sup 2} (4h), but TNF-a mRNA (10mug/cm{sup 2}, 24h) was only increased by DQ12, TG (quartz-dependently), and TC. In conclusion, these in vitro tests were an adequate approach to screen the toxic potential of quartz-containing ceramic dusts, but the quartz-content was too low to differentiate the various quartz-varieties.

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA

DEFF Research Database (Denmark)

Greenaway, Christina; Pareek, Manish; Chakra, Claire Nour Abou

2018-01-01

Background: Migrants account for a large and growing proportion of tuberculosis (TB) cases in lowincidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achi...... by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit....... to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living...... eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited...

Inferring network structure from cascades

Science.gov (United States)

Ghonge, Sushrut; Vural, Dervis Can

2017-07-01

Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.

Abnormal cascading failure spreading on complex networks

International Nuclear Information System (INIS)

Wang, Jianwei; Sun, Enhui; Xu, Bo; Li, Peng; Ni, Chengzhang

2016-01-01

Applying the mechanism of the preferential selection of the flow destination, we develop a new method to quantify the initial load on an edge, of which the flow is transported along the path with the shortest edge weight between two nodes. Considering the node weight, we propose a cascading model on the edge and investigate cascading dynamics induced by the removal of the edge with the largest load. We perform simulated attacks on four types of constructed networks and two actual networks and observe an interesting and counterintuitive phenomenon of the cascading spreading, i.e., gradually improving the capacity of nodes does not lead to the monotonous increase in the robustness of these networks against cascading failures. The non monotonous behavior of cascading dynamics is well explained by the analysis on a simple graph. We additionally study the effect of the parameter of the node weight on cascading dynamics and evaluate the network robustness by a new metric.

Gas separation performance of tapered cascade with membrane

International Nuclear Information System (INIS)

Ohno, Masayoshi; Morisue, Tetsuo; Ozaki, Osamu; Miyauchi, Terukatsu.

1978-01-01

Membrane gas separation cascades are analyzed at steady state. The method of calculating the flow rate and concentration profiles in the cascade are examined, using formulas expressing the various membrane separation cell characteristics. The method adopted is applicable to relatively high concentrations and separation factors. Considerations are further given on the steady state performance of four theoretical forms of cascade: (a) with common value of cut for all stages, (b) with symmetric separation cells, (c) with no mixing at the junction at each stage, and (d) ideal cascade. The analysis showed that, with membrane cells, the ideal cascade would have a pressure ratio varying from stage to stage. The symmetric separation cascade would provide a separation performance lower than the ideal cascade on account of the mixing at the junctions of streams possessing different concentrations, whereas the cut and separation factor of the no-mixing cascade requiring minimum membrane area exhibits zig-zag curves when plotted against stage number. Both these circumstances contribute to the lower separation performance obtained with these two forms as compared with the ideal cascade, and results in larger total membrane area; but these semi-ideal forms retain the advantage of easy practical treatment with their pressure ratio common to all stages. (auth.)

Initial in vitro screening approach to investigate the potential health and environmental hazards of Envirox™ – a nanoparticulate cerium oxide diesel fuel additive

Directory of Open Access Journals (Sweden)

Whittingham Andrew

2007-12-01

Full Text Available Abstract Nanotechnology is the new industrial revolution of the 21st Century as the various processes lead to radical improvements in medicine, manufacturing, energy production, land remediation, information technology and many other everyday products and applications. With this revolution however, there are undoubted concerns for health, safety and the environment which arise from the unique nature of materials and processes at the nanometre scale. The in vitro assays used in the screening strategy are all validated, internationally accepted protocols and provide a useful indication of potential toxicity of a chemical as a result of effects on various toxicological endpoints such as local site of contact (dermal irritation, general cytotoxicity and mutagenicity. The initial in vitro screening strategy described in this paper to investigate the potential health implications, if any, which may arise following exposure to one specific application of nanoparticulate cerium oxide used as a diesel fuel borne catalyst, reflects a precautionary approach and the results will inform judgement on how best to proceed to ensure safe use.

Ultrarelativistic cascades and strangeness production

Energy Technology Data Exchange (ETDEWEB)

Kahana, D.E. [State Univ. of New York, Stony Brook, NY (United States). Dept. of Physics; Kahana, S.H. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.

1998-08-24

A two-phase cascade code, LUCIFER II, developed for the treatment of ultra high energy-ion-ion collisions is applied to the production of strangeness at SPS energies {radical}(s)=17-20. This simulation is able to simultaneously describe both hard processes such as Drell-Yan and slower, soft processes such as the production of light mesons by separating the dynamics into two steps, a fast cascade involving only the nucleons in the original colliding relativistic ions followed, after an appropriate delay, by a normal multiscattering of the resulting excited baryons and mesons produced virtually in the first step. No energy loss can take place in the short time interval over which the first cascade takes place. The chief result is a reconciliation of the important Drell-Yan measurements with the apparent success of standard cascades to describe the nucleon stopping and meson production in heavy-ion experiments at the CERN SPS. (orig.) 26 refs.

Ultrarelativistic cascades and strangeness production

International Nuclear Information System (INIS)

Kahana, D.E.; Kahana, S.H.

1998-01-01

A two-phase cascade code, LUCIFER II, developed for the treatment of ultra high energy-ion-ion collisions is applied to the production of strangeness at SPS energies √(s)=17-20. This simulation is able to simultaneously describe both hard processes such as Drell-Yan and slower, soft processes such as the production of light mesons by separating the dynamics into two steps, a fast cascade involving only the nucleons in the original colliding relativistic ions followed, after an appropriate delay, by a normal multiscattering of the resulting excited baryons and mesons produced virtually in the first step. No energy loss can take place in the short time interval over which the first cascade takes place. The chief result is a reconciliation of the important Drell-Yan measurements with the apparent success of standard cascades to describe the nucleon stopping and meson production in heavy-ion experiments at the CERN SPS. (orig.)

MAPK cascades in guard cell signal transduction

Directory of Open Access Journals (Sweden)

Yuree eLee

2016-02-01

Full Text Available Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions.

Defect accumulation under cascade damage conditions

DEFF Research Database (Denmark)

Trinkaus, H.; Singh, B.N.; Woo, C.H.

1994-01-01

in terms of this reaction kinetics taking into account cluster production, dissociation, migration and annihilation at extended sinks. Microstructural features which are characteristic of cascade damage and cannot be explained in terms of the conventional single defect reaction kinetics are emphasized......There is now ample evidence from both experimental and computer simulation studies that in displacement cascades not only intense recombination takes place but also efficient clustering of both self-interstitial atoms (SIAs) and vacancies. The size distributions of the two types of defects produced...... reactions kinetics associated with the specific features of cascade damage is described, with emphasis on asymmetries between SIA and vacancy type defects concerning their production, stability, mobility and interactions with other defects. Defect accumulation under cascade damage conditions is discussed...

In vitro screening of the endocrine disrupting potency of brominated flame retardants and their metabolites

Energy Technology Data Exchange (ETDEWEB)

Hamers, T.; Kamstra, J.H. [Inst. for Environmental Studies (IVM), Amsterdam (Netherlands); Sonneveld, E. [BioDetection Systems (BDS), Amsterdam (Netherlands); Murk, A.J. [Wageningen Univ., Toxicology Group, Wageningen (Netherlands); Zegers, B.N.; Boon, J.P. [Royal Netherlands Inst. for Sea Research (NIOZ), Den Burg (Netherlands); Brouwer, A. [Umea Univ., Umea (Sweden)

2004-09-15

Substantial evidence is recently becoming available that brominated flame retardants (BFRs) are potential endocrine disruptors. The toxicological profile of BFRs, however, is too incomplete and insufficient to perform human and ecological risk assessment. To fill these gaps, the EU funded research program FIRE was started in December 2002. This program aims at the identification and toxicological characterization of the most potent and environmentally relevant BFRs and their possible risk for human and wildlife health. As part of a hazard identification approach, twenty seven BFRs have been selected within the framework of FIRE for pre-screening their endocrinedisrupting potencies. Selection of test compounds was based on a maximal variation in physicochemical characteristics of BFRs within the test set, allowing the establishment of quantitative structure-activity relationships (QSARs). In addition, environmental relevance (e.g. high production volumes and persistence) and availability for testing were used as selection criteria. BFRs were tested in seven different in vitro bioassays for their potency to interfere via estrogenic, thyroidal, androgenic, progestagenic, and Ah-receptor mediated pathways. Metabolisation rates of BFRs were determined using phenobarbital-induced rat liver microsomes. Finally, the endocrine disrupting potency of the metabolites was determined in the same in vitro bio-assays and compared to the potency of the parent compounds.

Survival of Flavobacterium psychrophilum in rainbow trout ( Oncorhynchus mykiss ) serum in vitro

DEFF Research Database (Denmark)

Wiklund, T.; Dalsgaard, Inger

2002-01-01

Virulent and non-virulent strains of Flavobacterium psychrophilum of different serotypes were examined for survival and growth in non-immune and immune rainbow trout serum, in vitro. A majority of the examined strains consumed complement of non-immune serum, but the complement cascade was not able...

Interpreting in vitro developmental toxicity test battery results: The consideration of toxicokinetics

NARCIS (Netherlands)

Bosgra, S.; Westerhout, J.

2015-01-01

In the EU collaborative project ChemScreen an alternative, in vitro assay-based test strategy was developed to screen compounds for reproductive toxicity. A toxicokinetic modeling approach was used to allow quantitative comparison between effective concentrations in the in vitro test battery and

Cascade Error Projection: An Efficient Hardware Learning Algorithm

Science.gov (United States)

Duong, T. A.

1995-01-01

A new learning algorithm termed cascade error projection (CEP) is presented. CEP is an adaption of a constructive architecture from cascade correlation and the dynamical stepsize of A/D conversion from the cascade back propagation algorithm.

Salicylic and jasmonic acid pathways are necessary for defence against Dickeya solani as revealed by a novel method for Blackleg disease screening of in vitro grown potato.

Science.gov (United States)

Burra, D D; Mühlenbock, P; Andreasson, E

2015-09-01

Potato is major crop ensuring food security in Europe, and blackleg disease is increasingly causing losses in yield and during storage. Recently, one blackleg pathogen, Dickeya solani has been shown to be spreading in Northern Europe that causes aggressive disease development. Currently, identification of tolerant commercial potato varieties has been unsuccessful; this is confounded by the complicated etiology of the disease and a strong environmental influence on disease development. There is currently a lack of efficient testing systems. Here, we describe a system for quantification of blackleg symptoms on shoots of sterile in vitro potato plants, which saves time and space compared to greenhouse and existing field assays. We found no evidence for differences in infection between the described in vitro-based screening method and existing greenhouse assays. This system facilitates efficient screening of blackleg disease response of potato plants independent of other microorganisms and variable environmental conditions. We therefore used the in vitro screening method to increase understanding of plant mechanisms involved in blackleg disease development by analysing disease response of hormone- related (salicylic and jasmonic acid) transgenic potato plants. We show that both jasmonic (JA) and salicylic (SA) acid pathways regulate tolerance to blackleg disease in potato, a result unlike previous findings in Arabidopsis defence response to necrotrophic bacteria. We confirm this by showing induction of a SA marker, pathogenesis-related protein 1 (StPR1), and a JA marker, lipoxygenase (StLOX), in Dickeya solani infected in vitro potato plants. We also observed that tubers of transgenic potato plants were more susceptible to soft rot compared to wild type, suggesting a role for SA and JA pathways in general tolerance to Dickeya. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

The Identification of Genes Important in Pseudomonas syringae pv. phaseolicola Plant Colonisation Using In Vitro Screening of Transposon Libraries.

Directory of Open Access Journals (Sweden)

Bharani Manoharan

Full Text Available The bacterial plant pathogen Pseudomonas syringae pv. phaseolicola (Pph colonises the surface of common bean plants before moving into the interior of plant tissue, via wounds and stomata. In the intercellular spaces the pathogen proliferates in the apoplastic fluid and forms microcolonies (biofilms around plant cells. If the pathogen can suppress the plant's natural resistance response, it will cause halo blight disease. The process of resistance suppression is fairly well understood, but the mechanisms used by the pathogen in colonisation are less clear. We hypothesised that we could apply in vitro genetic screens to look for changes in motility, colony formation, and adhesion, which are proxies for infection, microcolony formation and cell adhesion. We made transposon (Tn mutant libraries of Pph strains 1448A and 1302A and found 106/1920 mutants exhibited alterations in colony morphology, motility and biofilm formation. Identification of the insertion point of the Tn identified within the genome highlighted, as expected, a number of altered motility mutants bearing mutations in genes encoding various parts of the flagellum. Genes involved in nutrient biosynthesis, membrane associated proteins, and a number of conserved hypothetical protein (CHP genes were also identified. A mutation of one CHP gene caused a positive increase in in planta bacterial growth. This rapid and inexpensive screening method allows the discovery of genes important for in vitro traits that can be correlated to roles in the plant interaction.

Noise propagation in two-step series MAPK cascade.

Directory of Open Access Journals (Sweden)

Venkata Dhananjaneyulu

Full Text Available Series MAPK enzymatic cascades, ubiquitously found in signaling networks, act as signal amplifiers and play a key role in processing information during signal transduction in cells. In activated cascades, cell-to-cell variability or noise is bound to occur and thereby strongly affects the cellular response. Commonly used linearization method (LM applied to Langevin type stochastic model of the MAPK cascade fails to accurately predict intrinsic noise propagation in the cascade. We prove this by using extensive stochastic simulations for various ranges of biochemical parameters. This failure is due to the fact that the LM ignores the nonlinear effects on the noise. However, LM provides a good estimate of the extrinsic noise propagation. We show that the correct estimate of intrinsic noise propagation in signaling networks that contain at least one enzymatic step can be obtained only through stochastic simulations. Noise propagation in the cascade depends on the underlying biochemical parameters which are often unavailable. Based on a combination of global sensitivity analysis (GSA and stochastic simulations, we developed a systematic methodology to characterize noise propagation in the cascade. GSA predicts that noise propagation in MAPK cascade is sensitive to the total number of upstream enzyme molecules and the total number of molecules of the two substrates involved in the cascade. We argue that the general systematic approach proposed and demonstrated on MAPK cascade must accompany noise propagation studies in biological networks.

Phytochemical screening, anti-oxidant activity and in vitro anticancer potential of ethanolic and water leaves extracts of Annona muricata (Graviola).

Science.gov (United States)

Gavamukulya, Yahaya; Abou-Elella, Faten; Wamunyokoli, Fred; AEl-Shemy, Hany

2014-09-01

To determine the phytochemical composition, antioxidant and anticancer activities of ethanolic and water leaves extracts of Annona muricata (A. muricata) from the Eastern Uganda. Phytochemical screening was conducted using standard qualitative methods and a Chi-square goodness of fit test was used to assign the relative abundance of the different phytochemicals. The antioxidant activity was determined using the 2, 2-diphenyl-2-picrylhydrazyl and reducing power methods whereas the in vitro anticancer activity was determined using three different cell lines. Phytochemical screening of the extracts revealed that they were rich in secondary class metabolite compounds such as alkaloids, saponins, terpenoids, flavonoids, coumarins and lactones, anthraquinones, tannins, cardiac glycosides, phenols and phytosterols. Total phenolics in the water extract were (683.69±0.09) μg/mL gallic acid equivalents (GAE) while it was (372.92±0.15) μg/mL GAE in the ethanolic extract. The reducing power was 216.41 μg/mL in the water extract and 470.51 μg/mL GAE in the ethanolic extract. In vitro antioxidant activity IC50 was 2.0456 mg/mL and 0.9077 mg/mL for ethanolic and water leaves extracts of A. muricata respectively. The ethanolic leaves extract was found to be selectively cytotoxic in vitro to tumor cell lines (EACC, MDA and SKBR3) with IC50 values of 335.85 μg/mL, 248.77 μg/mL, 202.33 μg/mL respectively, while it had no cytotoxic effect on normal spleen cells. The data also showed that water leaves extract of A. muricata had no anticancer effect at all tested concentrations. The results showed that A. muricata was a promising new antioxidant and anticancer agent. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

A Workflow to Investigate Exposure and Pharmacokinetic Influences on High-Throughput in Vitro Chemical Screening Based on Adverse Outcome Pathways

Science.gov (United States)

Phillips, Martin B.; Leonard, Jeremy A.; Grulke, Christopher M.; Chang, Daniel T.; Edwards, Stephen W.; Brooks, Raina; Goldsmith, Michael-Rock; El-Masri, Hisham; Tan, Yu-Mei

2015-01-01

Background Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires incorporation of knowledge on exposure, along with absorption, distribution, metabolism, and excretion (ADME) properties of chemicals. Objectives We developed a conceptual workflow to examine exposure and ADME properties in relation to an MIE. The utility of this workflow was evaluated using a previously established AOP, acetylcholinesterase (AChE) inhibition. Methods Thirty chemicals found to inhibit human AChE in the ToxCast™ assay were examined with respect to their exposure, absorption potential, and ability to cross the blood–brain barrier (BBB). Structures of active chemicals were compared against structures of 1,029 inactive chemicals to detect possible parent compounds that might have active metabolites. Results Application of the workflow screened 10 “low-priority” chemicals of 30 active chemicals. Fifty-two of the 1,029 inactive chemicals exhibited a similarity threshold of ≥ 75% with their nearest active neighbors. Of these 52 compounds, 30 were excluded due to poor absorption or distribution. The remaining 22 compounds may inhibit AChE in vivo either directly or as a result of metabolic activation. Conclusions The incorporation of exposure and ADME properties into the conceptual workflow eliminated 10 “low-priority” chemicals that may otherwise have undergone additional, resource-consuming analyses. Our workflow also increased confidence in interpretation of in vitro results by identifying possible “false negatives.” Citation Phillips MB, Leonard JA, Grulke CM, Chang DT, Edwards SW, Brooks R, Goldsmith MR, El-Masri H, Tan YM. 2016. A workflow to investigate exposure and pharmacokinetic influences on high-throughput in vitro chemical screening based on adverse outcome pathways. Environ

Assessment on tracking error performance of Cascade P/PI, NPID and N-Cascade controller for precise positioning of xy table ballscrew drive system

International Nuclear Information System (INIS)

Abdullah, L; Jamaludin, Z; Rafan, N A; Jamaludin, J; Chiew, T H

2013-01-01

At present, positioning plants in machine tools are looking for high degree of accuracy and robustness attributes for the purpose of compensating various disturbance forces. The objective of this paper is to assess the tracking performance of Cascade P/PI, Nonlinear PID (NPID) and Nonlinear cascade (N-Cascade) controller with the existence of disturbance forces in the form of cutting forces. Cutting force characteristics at different cutting parameters; such as spindle speed rotations is analysed using Fast Fourier Transform. The tracking performance of a Nonlinear cascade controller in presence of these cutting forces is compared with NPID controller and Cascade P/PI controller. Robustness of these controllers in compensating different cutting characteristics is compared based on reduction in the amplitudes of cutting force harmonics using Fast Fourier Transform. It is found that the N-cascade controller performs better than both NPID controller and Cascade P/PI controller. The average percentage error reduction between N-cascade controller and Cascade P/PI controller is about 65% whereas the average percentage error reduction between cascade controller and NPID controller is about 82% at spindle speed of 3000 rpm spindle speed rotation. The finalized design of N-cascade controller could be utilized further for machining application such as milling process. The implementation of N-cascade in machine tools applications will increase the quality of the end product and the productivity in industry by saving the machining time. It is suggested that the range of the spindle speed could be made wider to accommodate the needs for high speed machining

Time structure of cascade showers

International Nuclear Information System (INIS)

Nakatsuka, Takao

1984-01-01

Interesting results have been reported on the time structure of the electromagnetic components of air showers which have been obtained by using recent fast electronic circuit technology. However, these analyses and explanations seem not very persuasive. One of the reasons is that there is not satisfactory theoretical calculation yet to explain the delay of electromagnetic components in cascade processes which are the object of direct observation. Therefore, Monte Carlo calculation was attempted for examining the relationship between the altitude at which high energy γ-ray is generated up in the air and the time structure of cascade showers at the level of observation. The investigation of a dominant factor over the delay of electromagnetic components indicated that the delay due to the multiple scattering of electrons was essential. The author used the analytical solution found by himself of C. N. Yang's equation for the study on the delay due to multiple scattering. The results were as follows: The average delay time and the spread of distribution of electromagnetic cascades were approximately in linear relationship with the mass of a material having passed in a thin uniform medium; the rise time of arrival time distribution for electromagnetic cascade showers was very steep under the condition that they were generated up in the air and observed on the ground; the subpeaks delayed by tens of ns in arrival time may sometimes appear due to the perturbation in electromagnetic cascade processes. (Wakatsuki, Y.)

A multipumping flow system for in vitro screening of peroxynitrite scavengers.

Science.gov (United States)

Ribeiro, Marta F T; Dias, Ana C B; Santos, João L M; Fernandes, Eduarda; Lima, José L F C; Zagatto, Elias A G

2007-09-01

Peroxynitrite anion is a reactive nitrogen species formed in vivo by the rapid, controlled diffusion reaction between nitric oxide and superoxide radicals. By reacting with several biological molecules, peroxynitrite may cause important cellular and tissue deleterious effects, which have been associated with many diseases. In this work, an automated flow-based procedure for the in vitro generation of peroxynitrite and subsequent screening of the scavenging activity of selected compounds is developed. This procedure involves a multipumping flow system (MPFS) and exploits the ability of compounds such as lipoic acid, dihydrolipoic acid, cysteine, reduced glutathione, oxidized glutathione, sulindac, and sulindac sulfone to inhibit the chemiluminescent reaction of luminol with peroxynitrite under physiological simulated conditions. Peroxynitrite was generated in the MPFS by the online reaction of acidified hydrogen peroxide with nitrite, followed by a subsequent stabilization by merging with a sodium hydroxide solution to rapidly quench the developing reaction. The pulsed flow and the timed synchronized insertion of sample and reagent solutions provided by the MPFS ensure the establishment of the reaction zone only inside the flow cell, thus allowing maximum chemiluminescence emission detection. The results obtained for the assayed compounds show that, with the exception of oxidized glutathione, all are highly potent scavengers of peroxynitrite at the studied concentrations.

Formalism of continual integrals for cascade processes with particle fusion

International Nuclear Information System (INIS)

Gedalin, Eh.V.

1987-01-01

Formalism of continuous integrals for description of cascade processes, in which besides cascade particle reproduction, their synthesis and coalescence take place, is used. Account of cascade particle coalescence leads to the fact that the development of some cascade branches cannot be independent and main equations of the cascade process become functional instead of integral. The method of continuous intagrals permits to construct in the closed form producing functionals for the cascade process and to obtain the rules of their calculation using diagrams. Analytical expressions in the form of continuous integrals for producing functionals describing cascade development are obtained

Morphologic abnormalities in 2-year-old children born after in vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic screening: follow-up of a randomized controlled trial

NARCIS (Netherlands)

Beukers, Fenny; van der Heide, Maaike; Middelburg, Karin J.; Cobben, Jan Maarten; Mastenbroek, Sebastiaan; Breur, Rinske; van der Lee, Johanna H.; Hadders-Algra, Mijna; Bos, Arend F.; Kok, Joke H.; Houtzager, Bregje A.; Repping, Sjoerd; Twisk, Moniek; van der Veen, Fulco; Haadsma, Maaike; Heineman, Maas Jan; van Hoften, Jacorina; Jongbloed-Pereboom, Marjolein; Keating, Paul; Seggers, Jorien

2013-01-01

To evaluate the effect of preimplantation genetic screening (PGS) on morphologic outcome in children. Follow-up of a randomized controlled trial (RCT). University hospital. Two-year-old children born to mothers who participated in an RCT on the efficacy of PGS: 50 children born after in vitro

Cascade theory in isotopic separation processes

International Nuclear Information System (INIS)

Agostini, J.P.

1994-06-01

Three main areas are developed within the scope of this work: - the first one is devoted to fundamentals: separative power, value function, ideal cascade and square cascade. Applications to two main cases are carried out, namely: Study of binary isotopic mix, Study of processes with a small enrichment coefficient. - The second one is devoted to cascade coupling -high-flux coupling (more widely used and better known) as well as low-flux coupling are presented and compared to one another. - The third one is an outlook on problems linked to cascade transients. Those problem are somewhat intricate and their interest lies mainly into two areas: economics where the start-up time may have a large influence on the interests paid during the construction and start-up period, military productions where the start-up time has a direct bearing on the production schedule. (author). 50 figs. 3 annexes. 12 refs. 6 tabs

21 CFR 866.2420 - Oxidase screening test for gonorrhea.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Oxidase screening test for gonorrhea. 866.2420... screening test for gonorrhea. (a) Identification. An oxidase screening test for gonorrhea is an in vitro... of gonorrhea. (b) Classification. Class III (premarket approval) (transitional device). (c) Date PMA...

Ion-irradiation studies of cascade damage in metals

International Nuclear Information System (INIS)

Averback, R.S.

1982-03-01

Ion-irradiation studies of the fundamental aspects of cascade damage in metals are reviewed. The emphasis of these studies has been the determination of the primary state of damage (i.e. the arrangement of atoms in the cascade region prior to thermal migration of defects). Progress has been made towards understanding the damage function (i.e. the number of Frenkel pairs produced as a function of primary recoil atom energy), the spatial configuration of vacancies and interstitials in the cascade and the cascade-induced mixing of atoms. It is concluded for these studies that the agitation of the lattice in the vicinity of energetic displacement cascades stimulates the defect motion and that such thermal spike motion induces recombination and clustering of Frenkel defects. 9 figures

iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Takayuki Kondo

2017-11-01

Full Text Available In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD. Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ, a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development.

In vitro screening of azole fungicides for antiandrogenic effects – comparison with in vivo effects

DEFF Research Database (Denmark)

testosterone and progesterone production. Epoxiconazole showed now effect. Furthermore tebuconazole increased the AGD in female pups and resulted in an increased number of nipples in male pups at PND 13, a tendency that was also seen for epoxiconazole, though it was not significant. In conclusion the results...... in H295R cells, a cell line, which produces a wide range of steroid hormones in measurable quantities, including testosterone, progesterone and estradiol, a property that makes it suitable as a screening assay to detect effects on steroidogenesis. In the in vitro tebuconazole and epoxiconazole showed...... antiandrogenic effects, and in the H295R cell assay, tebuconazole and epoxiconazole were like prochloraz able to inhibit testosterone and estradiol levels and increase progesterone levels. For the in vivo testing, a study was conducted testing the developmental effects on offspring after prenatal exposure...

Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

International Nuclear Information System (INIS)

Morton, M.J.; Armstrong, D.; Abi Gerges, N.; Bridgland-Taylor, M.; Pollard, C.E.; Bowes, J.; Valentin, J.-P.

2014-01-01

Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility

Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

Energy Technology Data Exchange (ETDEWEB)

Morton, M.J., E-mail: michael.morton@astrazeneca.com [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Armstrong, D.; Abi Gerges, N. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Bridgland-Taylor, M. [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Pollard, C.E.; Bowes, J.; Valentin, J.-P. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom)

2014-09-01

Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility.

Cascading failure in the wireless sensor scale-free networks

Science.gov (United States)

Liu, Hao-Ran; Dong, Ming-Ru; Yin, Rong-Rong; Han, Li

2015-05-01

In the practical wireless sensor networks (WSNs), the cascading failure caused by a failure node has serious impact on the network performance. In this paper, we deeply research the cascading failure of scale-free topology in WSNs. Firstly, a cascading failure model for scale-free topology in WSNs is studied. Through analyzing the influence of the node load on cascading failure, the critical load triggering large-scale cascading failure is obtained. Then based on the critical load, a control method for cascading failure is presented. In addition, the simulation experiments are performed to validate the effectiveness of the control method. The results show that the control method can effectively prevent cascading failure. Project supported by the Natural Science Foundation of Hebei Province, China (Grant No. F2014203239), the Autonomous Research Fund of Young Teacher in Yanshan University (Grant No. 14LGB017) and Yanshan University Doctoral Foundation, China (Grant No. B867).

Corneal tissue ablation using 6.1 μm quantum cascade laser

Science.gov (United States)

Huang, Yong; Kang, Jin U.

2012-03-01

High absorption property of tissues in the IR range (λ> 2 μm) results in effective tissue ablation, especially near 3 μm. In the mid-infrared range, wavelengths of 6.1 μm and 6.45 μm fall into the absorption bands of the amide protein groups Amide-I and Amide-II, respectively. They also coincide with the deformation mode of water, which has an absorption peak at 6.1 μm. This coincidence makes 6.1 μm laser a better ablation tool that has promising effectiveness and minimum collateral damages than 3 μm lasers. In this work, we performed bovine corneal ablation test in-vitro using high-power 6.1μm quantum cascade laser (QCL) operated at pulse mode. Quantum cascade laser has the advantages of low cost, compact size and tunable wavelength, which makes it great alternative Mid-IR light source to conventional tunable free-electron lasers (FEL) for medical applications. Preliminary results show that effective corneal stroma craters were achieved with much less collateral damage in corneal tissue that contains less water. Future study will focus on optimizing the control parameters of QCL to attain neat and precise ablation of corneal tissue and development of high peak power QCL.

Accurate and noninvasive embryos screening during in vitro fertilization (IVF) assisted by Raman analysis of embryos culture medium

International Nuclear Information System (INIS)

Shen, A G; Peng, J; Su, L; Wang, X H; Hu, J M; Zhao, Q H; Yang, J

2012-01-01

In combination with morphological evaluation tests, we employ Raman spectroscopy to select higher potential reproductive embryos during in vitro fertilization (IVF) based on chemical composition of embryos culture medium. In this study, 57 Raman spectra are acquired from both higher and lower quality embryos culture medium (ECM) from 10 patients which have been preliminarily confirmed by clinical assay. Data are fit by using a linear combination model of least squares method in which 12 basis spectra represent the chemical features of ECM. The final fitting coefficients provide insight into the chemical compositions of culture medium samples and are subsequently used as criterion to evaluate the quality of embryos. The relative fitting coefficients ratios of sodium pyruvate/albumin and phenylalanine/albumin seem act as key roles in the embryo screening, attaining 85.7% accuracy in comparison with clinical pregnancy. The good results demonstrate that Raman spectroscopy therefore is an important candidate for an accurate and noninvasive screening of higher quality embryos, which potentially decrease the time-consuming clinical trials during IVF

Energy and carbon balances of wood cascade chains

Energy Technology Data Exchange (ETDEWEB)

Sathre, Roger; Gustavsson, Leif [Ecotechnology, Mid Sweden University, SE-831 25 OEstersund (Sweden)

2006-07-15

In this study we analyze the energy and carbon balances of various cascade chains for recovered wood lumber. Post-recovery options include reuse as lumber, reprocessing as particleboard, pulping to form paper products, and burning for energy recovery. We compare energy and carbon balances of chains of cascaded products to the balances of products obtained from virgin wood fiber or from non-wood material. We describe and quantify several mechanisms through which cascading can affect the energy and carbon balances: direct cascade effects due to different properties and logistics of virgin and recovered materials, substitution effects due to the reduced demand for non-wood materials when wood is cascaded, and land use effects due to alternative possible land uses when less timber harvest is needed because of wood cascading. In some analyses we assume the forest is a limiting resource, and in others we include a fixed amount of forest land from which biomass can be harvested for use as material or biofuel. Energy and carbon balances take into account manufacturing processes, recovery and transportation energy, material recovery losses, and forest processes. We find that land use effects have the greatest impact on energy and carbon balances, followed by substitution effects, while direct cascade effects are relatively minor. (author)

Cascaded impedance networks for NPC inverter

DEFF Research Database (Denmark)

Li, Ding; Gao, Feng; Loh, Poh Chiang

2010-01-01

they are subject to the renewable sources. To date, three distinct types of impedance networks can be summarized for implementing a hybrid source impedance network, which can in principle be combined and cascaded before connected to a NPC inverter by proposed two ways. The resulting cascaded impedance network NPC...

Development in Assay Methods for in Vitro Antimalarial Drug Efficacy Testing: A Systematic Review

Directory of Open Access Journals (Sweden)

Shweta Sinha

2017-10-01

Full Text Available The emergence and spread of drug resistance are the major challenges in malaria eradication mission. Besides various strategies laid down by World Health Organization, such as vector management, source reduction, early case detection, prompt treatment, and development of new diagnostics and vaccines, nevertheless the need for new and efficacious drugs against malaria has become a critical priority on the global malaria research agenda. At several screening stages, millions of compounds are screened (1,000–2,000,000 compounds per screening campaign, before pre-clinical trials to select optimum lead. Carrying out in vitro screening of antimalarials is very difficult as different assay methods are subject to numerous sources of variability across different laboratories around the globe. Despite this, in vitro screening is an essential part of antimalarial drug development as it enables to resource various confounding factors such as host immune response and drug–drug interaction. Therefore, in this article, we try to illustrate the basic necessity behind in vitro study and how new methods are developed and subsequently adopted for high-throughput antimalarial drug screening and its application in achieving the next level of in vitro screening based on the current approaches (such as stem cells.

Learning Cascading

CERN Document Server

Covert, Michael

2015-01-01

This book is intended for software developers, system architects and analysts, big data project managers, and data scientists who wish to deploy big data solutions using the Cascading framework. You must have a basic understanding of the big data paradigm and should be familiar with Java development techniques.

Information cascade on networks

Science.gov (United States)

Hisakado, Masato; Mori, Shintaro

2016-05-01

In this paper, we discuss a voting model by considering three different kinds of networks: a random graph, the Barabási-Albert (BA) model, and a fitness model. A voting model represents the way in which public perceptions are conveyed to voters. Our voting model is constructed by using two types of voters-herders and independents-and two candidates. Independents conduct voting based on their fundamental values; on the other hand, herders base their voting on the number of previous votes. Hence, herders vote for the majority candidates and obtain information relating to previous votes from their networks. We discuss the difference between the phases on which the networks depend. Two kinds of phase transitions, an information cascade transition and a super-normal transition, were identified. The first of these is a transition between a state in which most voters make the correct choices and a state in which most of them are wrong. The second is a transition of convergence speed. The information cascade transition prevails when herder effects are stronger than the super-normal transition. In the BA and fitness models, the critical point of the information cascade transition is the same as that of the random network model. However, the critical point of the super-normal transition disappears when these two models are used. In conclusion, the influence of networks is shown to only affect the convergence speed and not the information cascade transition. We are therefore able to conclude that the influence of hubs on voters' perceptions is limited.

Computation of inverse magnetic cascades

International Nuclear Information System (INIS)

Montgomery, D.

1981-10-01

Inverse cascades of magnetic quantities for turbulent incompressible magnetohydrodynamics are reviewed, for two and three dimensions. The theory is extended to the Strauss equations, a description intermediate between two and three dimensions appropriate to tokamak magnetofluids. Consideration of the absolute equilibrium Gibbs ensemble for the system leads to a prediction of an inverse cascade of magnetic helicity, which may manifest itself as a major disruption. An agenda for computational investigation of this conjecture is proposed

Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis.

Directory of Open Access Journals (Sweden)

Britta Stadelmann

2016-03-01

Full Text Available The metacestode (larval stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE, a very severe and in many cases incurable disease. To date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. Benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. Thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some patients. We here describe a newly developed screening cascade for the evaluation of the in vitro efficacy of new compounds that includes assessment of parasiticidal activity. The Malaria Box from Medicines for Malaria Venture (MMV, comprised of 400 commercially available chemicals that show in vitro activity against Plasmodium falciparum, was repurposed. Primary screening was carried out at 10 μM by employing the previously described PGI assay, and resulted in the identification of 24 compounds that caused physical damage in metacestodes. Seven out of these 24 drugs were also active at 1 μM. Dose-response assays revealed that only 2 compounds, namely MMV665807 and MMV665794, exhibited an EC50 value below 5 μM. Assessments using human foreskin fibroblasts and Reuber rat hepatoma cells showed that the salicylanilide MMV665807 was less toxic for these two mammalian cell lines than for metacestodes. The parasiticidal activity of MMV665807 was then confirmed using isolated germinal layer cell cultures as well as metacestode vesicles by employing viability assays, and its effect on metacestodes was morphologically evaluated by electron microscopy. However, both oral and intraperitoneal application of MMV665807 to mice experimentally infected with E. multilocularis metacestodes did not result in any reduction of the parasite load.

Directed Evolution of Proteins through In Vitro Protein Synthesis in Liposomes

Directory of Open Access Journals (Sweden)

Takehiro Nishikawa

2012-01-01

Full Text Available Directed evolution of proteins is a technique used to modify protein functions through “Darwinian selection.” In vitro compartmentalization (IVC is an in vitro gene screening system for directed evolution of proteins. IVC establishes the link between genetic information (genotype and the protein translated from the information (phenotype, which is essential for all directed evolution methods, by encapsulating both in a nonliving microcompartment. Herein, we introduce a new liposome-based IVC system consisting of a liposome, the protein synthesis using recombinant elements (PURE system and a fluorescence-activated cell sorter (FACS used as a microcompartment, in vitro protein synthesis system, and high-throughput screen, respectively. Liposome-based IVC is characterized by in vitro protein synthesis from a single copy of a gene in a cell-sized unilamellar liposome and quantitative functional evaluation of the synthesized proteins. Examples of liposome-based IVC for screening proteins such as GFP and β-glucuronidase are described. We discuss the future directions for this method and its applications.

Antitumor Activity of Tenacissoside H on Esophageal Cancer through Arresting Cell Cycle and Regulating PI3K/Akt-NF-κB Transduction Cascade

Directory of Open Access Journals (Sweden)

Yong-sen Jia

2015-01-01

Full Text Available Objective. The purpose of the study was to elucidate the molecular mechanism of tenacissoside H (TDH inhibiting esophageal carcinoma infiltration and proliferation. Methods. In vitro, EC9706 cells were treated with TDH. Cells proliferation and cell cycle were assayed. PI3K and NF-κB mRNAs expression were determined by real time PCR. In vivo, model of nude mice with tumor was established. Mice were treated with TDH. Inhibition ratio of tumor volume was calculated. PCNA expression was examined. Protein expression in PI3K/Akt-NF-κB signaling pathway was determined. Results. In vitro, TDH significantly inhibited cells proliferation in a time-and-dose-dependent manner. TDH arrested the cell cycle in S phase and significantly inhibited PI3K and NF-κB mRNA expression, compared with blank controlled group (P<0.05. In vivo, TDH strongly inhibits tumor growth and volume. PCNA expression was significantly decreased after treatment of TDH. TDH downregulated proteins expression in PI3K/Akt-NF-κB transduction cascade (P<0.05. Conclusion. TDH inhibited esophageal carcinoma infiltration and proliferation both in vitro and in vivo. The anticancer activity has relation to arresting the cell cycle at the S phase, inhibited the PCNA expression of transplanted tumors in nude mice, and regulated the protein expression in the PI3K/Akt-NF-κB transduction cascade.

Non-spill control squared cascade

International Nuclear Information System (INIS)

Kai, Tsunetoshi; Inoue, Yoshiya; Oya, Akio; Suemori, Nobuo.

1974-01-01

Object: To reduce a mixed loss thus enhancing separating efficiency by the provision of a simple arrangement wherein a reflux portion in a conventional spill control squared cascade is replaced by a special stage including centrifugal separators. Structure: Steps in the form of a square cascade, in which a plurality of centrifugal separators are connected by pipe lines, are accumulated in multistage fashion to form a squared cascade. Between the adjoining steps is disposed a special stage including a centrifugal separator which receives both lean flow from the upper step and rich flow from the lower step. The centrifugal separator in the special stage has its rich side connected to the upper step and its lean side connected to the lower step. Special stages are each disposed at the upper side of the uppermost step and at the lower side of the lowermost step. (Kamimura, M.)

Population-Based in Vitro Hazard and Concentration–Response Assessment of Chemicals: The 1000 Genomes High-Throughput Screening Study

Science.gov (United States)

Abdo, Nour; Xia, Menghang; Brown, Chad C.; Kosyk, Oksana; Huang, Ruili; Sakamuru, Srilatha; Zhou, Yi-Hui; Jack, John R.; Gallins, Paul; Xia, Kai; Li, Yun; Chiu, Weihsueh A.; Motsinger-Reif, Alison A.; Austin, Christopher P.; Tice, Raymond R.

2015-01-01

Background: Understanding of human variation in toxicity to environmental chemicals remains limited, so human health risk assessments still largely rely on a generic 10-fold factor (10½ each for toxicokinetics and toxicodynamics) to account for sensitive individuals or subpopulations. Objectives: We tested a hypothesis that population-wide in vitro cytotoxicity screening can rapidly inform both the magnitude of and molecular causes for interindividual toxicodynamic variability. Methods: We used 1,086 lymphoblastoid cell lines from the 1000 Genomes Project, representing nine populations from five continents, to assess variation in cytotoxic response to 179 chemicals. Analysis included assessments of population variation and heritability, and genome-wide association mapping, with attention to phenotypic relevance to human exposures. Results: For about half the tested compounds, cytotoxic response in the 1% most “sensitive” individual occurred at concentrations within a factor of 10½ (i.e., approximately 3) of that in the median individual; however, for some compounds, this factor was > 10. Genetic mapping suggested important roles for variation in membrane and transmembrane genes, with a number of chemicals showing association with SNP rs13120371 in the solute carrier SLC7A11, previously implicated in chemoresistance. Conclusions: This experimental approach fills critical gaps unaddressed by recent large-scale toxicity testing programs, providing quantitative, experimentally based estimates of human toxicodynamic variability, and also testable hypotheses about mechanisms contributing to interindividual variation. Citation: Abdo N, Xia M, Brown CC, Kosyk O, Huang R, Sakamuru S, Zhou YH, Jack JR, Gallins P, Xia K, Li Y, Chiu WA, Motsinger-Reif AA, Austin CP, Tice RR, Rusyn I, Wright FA. 2015. Population-based in vitro hazard and concentration–response assessment of chemicals: the 1000 Genomes high-throughput screening study. Environ Health Perspect 123:458�

Dynamics robustness of cascading systems.

Directory of Open Access Journals (Sweden)

Jonathan T Young

2017-03-01

Full Text Available A most important property of biochemical systems is robustness. Static robustness, e.g., homeostasis, is the insensitivity of a state against perturbations, whereas dynamics robustness, e.g., homeorhesis, is the insensitivity of a dynamic process. In contrast to the extensively studied static robustness, dynamics robustness, i.e., how a system creates an invariant temporal profile against perturbations, is little explored despite transient dynamics being crucial for cellular fates and are reported to be robust experimentally. For example, the duration of a stimulus elicits different phenotypic responses, and signaling networks process and encode temporal information. Hence, robustness in time courses will be necessary for functional biochemical networks. Based on dynamical systems theory, we uncovered a general mechanism to achieve dynamics robustness. Using a three-stage linear signaling cascade as an example, we found that the temporal profiles and response duration post-stimulus is robust to perturbations against certain parameters. Then analyzing the linearized model, we elucidated the criteria of when signaling cascades will display dynamics robustness. We found that changes in the upstream modules are masked in the cascade, and that the response duration is mainly controlled by the rate-limiting module and organization of the cascade's kinetics. Specifically, we found two necessary conditions for dynamics robustness in signaling cascades: 1 Constraint on the rate-limiting process: The phosphatase activity in the perturbed module is not the slowest. 2 Constraints on the initial conditions: The kinase activity needs to be fast enough such that each module is saturated even with fast phosphatase activity and upstream changes are attenuated. We discussed the relevance of such robustness to several biological examples and the validity of the above conditions therein. Given the applicability of dynamics robustness to a variety of systems, it

Molecular dynamics simulation of displacement cascades in iron-alpha; Cascades de deplacements atomiques dans le FER-alpha simulation par dynamique moleculaire

Energy Technology Data Exchange (ETDEWEB)

Vascon, R

1997-12-31

Radiation damage by neutrons or ions in bcc iron has been investigated by molecular dynamics simulations using an embedded atom type many-body potential (EAM). Displacement cascades with energies of 1 to 30 keV were generated in the microcanonical system where the number of atoms (up to 1.5 million) is chosen high enough to compensate the fact that the dissipation of energy is not taken into account in our model. The defect number at the end of cascade lifetime was found to be 60 percent of the NRT standard value. This tendency is in good agreement with experimental data. However, compared with other simulations in iron, we found significant differences in the defect production and distribution. The comparison with results obtained form simulations of cascades in other metals, leads on the one hand to a higher value of the defect number in bcc iron than in fcc metals like copper or nickel, and on the other hand to a ratio, between the number of replacements and the number of defects, lower in iron ( 100). We observed the transient melting of the core of the cascade during simulations. We showed that a higher value of the initial iron crystal temperature, as the mass difference between the components of an artificial binary alloy Fe-X(X=Al,Sb,Au,U) both produce a `cascade effect`: a decrease of the number of defects and an increase of the number of replacements. We also showed up the quasi-channeling of some atoms in high energy cascades. They are at the origin of sub-cascades formation; as a result they induce an opposite effect to the `cascade effect`. (author). 286 refs.

Cascade fuzzy control for gas engine driven heat pump

International Nuclear Information System (INIS)

Li Shuze; Zhang Wugao; Zhang Rongrong; Lv Dexu; Huang Zhen

2005-01-01

In addition to absorption chillers, today's gas cooling technology includes gas engine driven heat pump systems (GEHP) in a range of capacities and temperature capacities suitable for most commercial air conditioning and refrigeration applications. Much is expected from GEHPs as a product that would help satisfy the air conditioning system demand from medium and small sized buildings, restrict electric power demand peaks in summer and save energy in general. This article describes a kind of control strategy for a GEHP, a cascade fuzzy control. GEHPs have large and varying time constants and their dynamic modeling cannot be easily achieved. A cascade control strategy is effective for systems that have large time constants and disturbances, and a fuzzy control strategy is fit for a system that lacks an accurate model. This cascade fuzzy control structure brings together the best merits of fuzzy control and cascade control structures. The performance of the cascade fuzzy control is compared to that of a cascade PI (proportional and integral) control strategy, and it is shown by example that the cascade fuzzy control strategy gives a better performance, reduced reaction time and smaller overshoot temperature

A cryogenic distillation column cascade for a fusion reactor

International Nuclear Information System (INIS)

Kinoshita, M.

1984-01-01

A cryogenic distillation column cascade composed of only two columns is proposed. Compared with the Tritium Systems Test Assembly (TSTA) cascade, the tritium inventory is about 1.5 times more and the packed height of the highest column increases by about 40%. However, the number of the columns is halved with the separation performance unchanged. The number of the instruments needed and the number of the process parameters to be monitored are also reduced. Unlike in the case of the TSTA cascade, the performance of the proposed cascade is not subject to the flow rate of the neutral beam injector recycle stream. The high performance can be maintained even if the protium percentage in the raw fuel input increases significantly (e.g., from 1 to 3%), just by adjusting the flow rates of the top, bottom, and side streams. Because of this great flexibility, it is worthwhile to build and study the proposed cascade as a possible alternative to the TSTA cascade

Risk-based high-throughput chemical screening and prioritization using exposure models and in vitro bioactivity assays

International Nuclear Information System (INIS)

Shin, Hyeong-Moo; Ernstoff, Alexi; Csiszar, Susan A.

2015-01-01

We present a risk-based high-throughput screening (HTS) method to identify chemicals for potential health concerns or for which additional information is needed. The method is applied to 180 organic chemicals as a case study. We first obtain information on how the chemical is used and identify relevant use scenarios (e.g., dermal application, indoor emissions). For each chemical and use scenario, exposure models are then used to calculate a chemical intake fraction, or a product intake fraction, accounting for chemical properties and the exposed population. We then combine these intake fractions with use scenario-specific estimates of chemical quantity to calculate daily intake rates (iR; mg/kg/day). These intake rates are compared to oral equivalent doses (OED; mg/kg/day), calculated from a suite of ToxCast in vitro bioactivity assays using in vitro-to-in vivo extrapolation and reverse dosimetry. Bioactivity quotients (BQs) are calculated as iR/OED to obtain estimates of potential impact associated with each relevant use scenario. Of the 180 chemicals considered, 38 had maximum iRs exceeding minimum OEDs (i.e., BQs > 1). For most of these compounds, exposures are associated with direct intake, food/oral contact, or dermal exposure. The method provides high-throughput estimates of exposure and important input for decision makers to identify chemicals of concern for further evaluation with additional information or more refined models

Identification by virtual screening and in vitro testing of human DOPA decarboxylase inhibitors.

Directory of Open Access Journals (Sweden)

Frederick Daidone

Full Text Available Dopa decarboxylase (DDC, a pyridoxal 5'-phosphate (PLP enzyme responsible for the biosynthesis of dopamine and serotonin, is involved in Parkinson's disease (PD. PD is a neurodegenerative disease mainly due to a progressive loss of dopamine-producing cells in the midbrain. Co-administration of L-Dopa with peripheral DDC inhibitors (carbidopa or benserazide is the most effective symptomatic treatment for PD. Although carbidopa and trihydroxybenzylhydrazine (the in vivo hydrolysis product of benserazide are both powerful irreversible DDC inhibitors, they are not selective because they irreversibly bind to free PLP and PLP-enzymes, thus inducing diverse side effects. Therefore, the main goals of this study were (a to use virtual screening to identify potential human DDC inhibitors and (b to evaluate the reliability of our virtual-screening (VS protocol by experimentally testing the "in vitro" activity of selected molecules. Starting from the crystal structure of the DDC-carbidopa complex, a new VS protocol, integrating pharmacophore searches and molecular docking, was developed. Analysis of 15 selected compounds, obtained by filtering the public ZINC database, yielded two molecules that bind to the active site of human DDC and behave as competitive inhibitors with K(i values ≥10 µM. By performing in silico similarity search on the latter compounds followed by a substructure search using the core of the most active compound we identified several competitive inhibitors of human DDC with K(i values in the low micromolar range, unable to bind free PLP, and predicted to not cross the blood-brain barrier. The most potent inhibitor with a K(i value of 500 nM represents a new lead compound, targeting human DDC, that may be the basis for lead optimization in the development of new DDC inhibitors. To our knowledge, a similar approach has not been reported yet in the field of DDC inhibitors discovery.

MOLECULAR DYNAMICS SIMULATIONS OF DISPLACEMENT CASCADES IN MOLYBDENUM

International Nuclear Information System (INIS)

Smith, Richard Whiting

2003-01-01

Molecular dynamics calculations have been employed to simulate displacement cascades in neutron irradiated Mo. A total of 90 simulations were conducted for PKA energies between 1 and 40 keV and temperatures from 298 to 923K. The results suggest very little effect of temperature on final defect count and configuration, but do display a temperature effect on peak defect generation prior to cascade collapse. Cascade efficiency, relative to the NRT model, is computed to lie between 1/4 and 1/3 in agreement with simulations performed on previous systems. There is a tendency for both interstitials and vacancies to cluster together following cascade collapse producing vacancy rich regions surrounded by interstitials. Although coming to rest in close proximity, the point defects comprising the clusters generally do not lie within the nearest neighbor positions of one another, except for the formation of dumbbell di-interstitials. Cascades produced at higher PKA energies (20 or 40 keV) exhibit the formation of subcascades

Stochastic background of atmospheric cascades

International Nuclear Information System (INIS)

Wilk, G.; Wlodarczyk, Z.

1993-01-01

Fluctuations in the atmospheric cascades developing during the propagation of very high energy cosmic rays through the atmosphere are investigated using stochastic branching model of pure birth process with immigration. In particular, we show that the multiplicity distributions of secondaries emerging from gamma families are much narrower than those resulting from hadronic families. We argue that the strong intermittent like behaviour found recently in atmospheric families results from the fluctuations in the cascades themselves and are insensitive to the details of elementary interactions

Volcano geodesy in the Cascade arc, USA

Science.gov (United States)

Poland, Michael; Lisowski, Michael; Dzurisin, Daniel; Kramer, Rebecca; McLay, Megan; Pauk, Benjamin

2017-01-01

Experience during historical time throughout the Cascade arc and the lack of deep-seated deformation prior to the two most recent eruptions of Mount St. Helens might lead one to infer that Cascade volcanoes are generally quiescent and, specifically, show no signs of geodetic change until they are about to erupt. Several decades of geodetic data, however, tell a different story. Ground- and space-based deformation studies have identified surface displacements at five of the 13 major Cascade arc volcanoes that lie in the USA (Mount Baker, Mount St. Helens, South Sister, Medicine Lake, and Lassen volcanic center). No deformation has been detected at five volcanoes (Mount Rainier, Mount Hood, Newberry Volcano, Crater Lake, and Mount Shasta), and there are not sufficient data at the remaining three (Glacier Peak, Mount Adams, and Mount Jefferson) for a rigorous assessment. In addition, gravity change has been measured at two of the three locations where surveys have been repeated (Mount St. Helens and Mount Baker show changes, while South Sister does not). Broad deformation patterns associated with heavily forested and ice-clad Cascade volcanoes are generally characterized by low displacement rates, in the range of millimeters to a few centimeters per year, and are overprinted by larger tectonic motions of several centimeters per year. Continuous GPS is therefore the best means of tracking temporal changes in deformation of Cascade volcanoes and also for characterizing tectonic signals so that they may be distinguished from volcanic sources. Better spatial resolution of volcano deformation can be obtained through the use of campaign GPS, semipermanent GPS, and interferometric synthetic aperture radar observations, which leverage the accumulation of displacements over time to improve signal to noise. Deformation source mechanisms in the Cascades are diverse and include magma accumulation and withdrawal, post-emplacement cooling of recent volcanic deposits, magmatic

Volcano geodesy in the Cascade arc, USA

Science.gov (United States)

Poland, Michael P.; Lisowski, Michael; Dzurisin, Daniel; Kramer, Rebecca; McLay, Megan; Pauk, Ben

2017-08-01

Experience during historical time throughout the Cascade arc and the lack of deep-seated deformation prior to the two most recent eruptions of Mount St. Helens might lead one to infer that Cascade volcanoes are generally quiescent and, specifically, show no signs of geodetic change until they are about to erupt. Several decades of geodetic data, however, tell a different story. Ground- and space-based deformation studies have identified surface displacements at five of the 13 major Cascade arc volcanoes that lie in the USA (Mount Baker, Mount St. Helens, South Sister, Medicine Lake, and Lassen volcanic center). No deformation has been detected at five volcanoes (Mount Rainier, Mount Hood, Newberry Volcano, Crater Lake, and Mount Shasta), and there are not sufficient data at the remaining three (Glacier Peak, Mount Adams, and Mount Jefferson) for a rigorous assessment. In addition, gravity change has been measured at two of the three locations where surveys have been repeated (Mount St. Helens and Mount Baker show changes, while South Sister does not). Broad deformation patterns associated with heavily forested and ice-clad Cascade volcanoes are generally characterized by low displacement rates, in the range of millimeters to a few centimeters per year, and are overprinted by larger tectonic motions of several centimeters per year. Continuous GPS is therefore the best means of tracking temporal changes in deformation of Cascade volcanoes and also for characterizing tectonic signals so that they may be distinguished from volcanic sources. Better spatial resolution of volcano deformation can be obtained through the use of campaign GPS, semipermanent GPS, and interferometric synthetic aperture radar observations, which leverage the accumulation of displacements over time to improve signal to noise. Deformation source mechanisms in the Cascades are diverse and include magma accumulation and withdrawal, post-emplacement cooling of recent volcanic deposits, magmatic

Geothermal segmentation of the Cascade Range in the USA

Science.gov (United States)

Guffanti, Marianne; Muffler, L.J.; Mariner, R.H.; Sherrod, D.R.; Smith, James G.; Blackwell, D.D.; Weaver, C.S.

1990-01-01

Characteristics of the crustal thermal regime of the Quaternary Cascades vary systematically along the range. Spatially congruent changes in volcanic vent distribution, volcanic extrusion rate, hydrothermal discharge rate, and regional conductive heat flow define 5 geothermal segments. These segments are, from north to south: (1) the Washington Cascades north of Mount Rainier, (2) the Cascades from Mount Rainier to Mount Hood, (3) the Oregon Cascades from south of Mount Hood to the California border, (4) northernmost California, including Mount Shasta and Medicine Lake volcano, and (5) the Lassen region of northern California. This segmentation indicates that geothermal resource potential is not uniform in the Cascade Range. Potential varies from high in parts of Oregon to low in Washington north of Mount Rainier.

Photoreactivity of biologically active compounds. VII. Interaction of antimalarial drugs with melanin in vitro as part of phototoxicity screening.

Science.gov (United States)

Kristensen, S; Orsteen, A L; Sande, S A; Tønnesen, H H

1994-10-01

The drugs commonly used in the treatment of malaria are photochemically unstable. Several of these compounds accumulate in melanin-rich tissues and cause toxic reactions which may be light induced. As part of the screening of the photochemical properties and phototoxic capabilities of antimalarials, the in vitro interaction of eight antimalarials with melanin was studied. The dissociation constant for the drug-melanin complex and the relative number of binding sites on melanin were estimated for six of the drugs using a curve-fitting program. The reaction rate for the formation of the melanin-drug complex was determined, and the complexes were further characterized by zeta potential measurements.

Cascade processes in kaonic and muonic atoms

International Nuclear Information System (INIS)

Faifman, M.P.; Men'shikov, L.I.

2003-01-01

Cascade processes in exotic (kaonic and muonic) hydrogen/deuterium have been studied with the quantum-classical Monte Carlo code (QCMC) developed for 'ab initio' - calculations. It has been shown that the majority of kaonic hydrogen atoms during cascade are accelerated to high energies E ∼ 100 eV, which leads to a much lower value for the calculated yields Y of x-rays than predicted by the 'standard cascade model'. The modified QCMC scheme has been applied to the study of the cascade in μp and μd muonic atoms. A comparison of the calculated yields for K-series x-rays with experimental data directly indicates that the molecular structure of the hydrogen target and new types of non-radiative transitions are essential for the light muonic atoms, while they are negligible for heavy (kaonic) atoms. These processes have been considered and estimates of their probabilities are presented. (author)

Rescuing Ecosystems from Extinction Cascades

Science.gov (United States)

Sahasrabudhe, Sagar; Motter, Adilson

2010-03-01

Food web perturbations stemming from climate change, overexploitation, invasive species, and natural disasters often cause an initial loss of species that results in a cascade of secondary extinctions. Using a predictive modeling framework, here we will present a systematic network-based approach to reduce the number of secondary extinctions. We will show that the extinction of one species can often be compensated by the concurrent removal of a second specific species, which is a counter-intuitive effect not previously tested in complex food webs. These compensatory perturbations frequently involve long-range interactions that are not a priori evident from local predator-prey relationships. Strikingly, in numerous cases even the early removal of a species that would eventually be extinct by the cascade is found to significantly reduce the number of cascading extinctions. Other nondestructive interventions based on partial removals and growth suppression and/or mortality increase are shown to sometimes prevent all secondary extinctions.

A simple model of global cascades on random networks

Science.gov (United States)

Watts, Duncan J.

2002-04-01

The origin of large but rare cascades that are triggered by small initial shocks is a phenomenon that manifests itself as diversely as cultural fads, collective action, the diffusion of norms and innovations, and cascading failures in infrastructure and organizational networks. This paper presents a possible explanation of this phenomenon in terms of a sparse, random network of interacting agents whose decisions are determined by the actions of their neighbors according to a simple threshold rule. Two regimes are identified in which the network is susceptible to very large cascadesherein called global cascadesthat occur very rarely. When cascade propagation is limited by the connectivity of the network, a power law distribution of cascade sizes is observed, analogous to the cluster size distribution in standard percolation theory and avalanches in self-organized criticality. But when the network is highly connected, cascade propagation is limited instead by the local stability of the nodes themselves, and the size distribution of cascades is bimodal, implying a more extreme kind of instability that is correspondingly harder to anticipate. In the first regime, where the distribution of network neighbors is highly skewed, it is found that the most connected nodes are far more likely than average nodes to trigger cascades, but not in the second regime. Finally, it is shown that heterogeneity plays an ambiguous role in determining a system's stability: increasingly heterogeneous thresholds make the system more vulnerable to global cascades; but an increasingly heterogeneous degree distribution makes it less vulnerable.

Basic characteristics of a low uranium enrichment cascade by centrifugation, (2)

International Nuclear Information System (INIS)

Kai, Tsunetoshi

1975-01-01

The theory for a cascade of centrifuges described in the preceding report of the same general title is further developed. First, equations describing the distributions of the flow and the mole concentration are derived from the material balance relations for a square cascade. Corresponding equations are next obtained to cover a squared-off cascade consisting of a series of square cascades. A computer program is outlined which makes it possible to obtain the shape of the most efficient squared-off cascade. The efficiency of the current form of squared-off centrifuge cascade with reflux pipes is found to be lower than obtainable with gaseous diffusion. The efficiency can be improved by the adoption of a tapered squared-off cascade with centrifuges provided with eccentric cuts to take the place of reflux pipes. The dynamic characteristics are also discussed. Analysis of the start-up behavior reveals that the equilibrium time of the centrifuge cascade is much shorter than for a coresponding gaseous diffusion cascade, and that the mole concentration of the product rapidly rises to attain steady state condition. It is also found that even when the feed flow rate fluctuates, the mole concentration of the product is relatively stable. The effect of a centrifuge failure in the cascade is examined. The optimum mole concentration for the waste effluent discarded from the cascade is calculated from the viewpoint of cost. (auth.)

In Vitro Screening of Cytotoxic, Antimicrobial and Antioxidant ...

African Journals Online (AJOL)

Purpose: To evaluate the in vitro cytotoxic, antioxidant and antimicrobial activities of Clinacanthus nutans extracts and semi-fractions. Method: The plant was subjected to cold solvent extraction to produce petroleum ether, ethyl acetate and methanol crude extracts, followed by isolation using bioassay-guided fractionation.

Molecular dynamics studies of displacement cascades

International Nuclear Information System (INIS)

Averback, R.S.; Hsieh, Horngming; Diaz de la Rubia, T.

1990-02-01

Molecular-dynamics simulations of cascades in Cu and Ni with primary-knock-on energies up to 5 keV and lattice temperatures in the range 0 K--700 K are described. Interatomic forces were represented by either the Gibson II (Cu) or Johnson-Erginsoy (Ni) potentials in most of this work, although some simulations using ''Embedded Atom Method'' potentials, e.g., for threshold events in Ni 3 Al, are also presented. The results indicate that the primary state of damage produced by displacement cascades is controlled by two phenomena, replacement collision sequences during the collisional phase of the cascade and local melting during the thermal spike. As expected, the collisional phase is rather similar in Cu and Ni, however, the thermal spike is of longer duration and has a more pronounced influence in Cu than Ni. When the ambient temperature of the lattice is increased, the melt zones are observed to both increase in size and cool more slowly. This has the effect of reducing defect production and enhancing atomic mixing and disordering. The implications of these results for defect production, cascade collapse, atomic disordering will be discussed. 34 refs., 7 figs., 2 tabs

Forecasting Social Unrest Using Activity Cascades.

Science.gov (United States)

Cadena, Jose; Korkmaz, Gizem; Kuhlman, Chris J; Marathe, Achla; Ramakrishnan, Naren; Vullikanti, Anil

2015-01-01

Social unrest is endemic in many societies, and recent news has drawn attention to happenings in Latin America, the Middle East, and Eastern Europe. Civilian populations mobilize, sometimes spontaneously and sometimes in an organized manner, to raise awareness of key issues or to demand changes in governing or other organizational structures. It is of key interest to social scientists and policy makers to forecast civil unrest using indicators observed on media such as Twitter, news, and blogs. We present an event forecasting model using a notion of activity cascades in Twitter (proposed by Gonzalez-Bailon et al., 2011) to predict the occurrence of protests in three countries of Latin America: Brazil, Mexico, and Venezuela. The basic assumption is that the emergence of a suitably detected activity cascade is a precursor or a surrogate to a real protest event that will happen "on the ground." Our model supports the theoretical characterization of large cascades using spectral properties and uses properties of detected cascades to forecast events. Experimental results on many datasets, including the recent June 2013 protests in Brazil, demonstrate the effectiveness of our approach.

Forecasting Social Unrest Using Activity Cascades.

Directory of Open Access Journals (Sweden)

Jose Cadena

Full Text Available Social unrest is endemic in many societies, and recent news has drawn attention to happenings in Latin America, the Middle East, and Eastern Europe. Civilian populations mobilize, sometimes spontaneously and sometimes in an organized manner, to raise awareness of key issues or to demand changes in governing or other organizational structures. It is of key interest to social scientists and policy makers to forecast civil unrest using indicators observed on media such as Twitter, news, and blogs. We present an event forecasting model using a notion of activity cascades in Twitter (proposed by Gonzalez-Bailon et al., 2011 to predict the occurrence of protests in three countries of Latin America: Brazil, Mexico, and Venezuela. The basic assumption is that the emergence of a suitably detected activity cascade is a precursor or a surrogate to a real protest event that will happen "on the ground." Our model supports the theoretical characterization of large cascades using spectral properties and uses properties of detected cascades to forecast events. Experimental results on many datasets, including the recent June 2013 protests in Brazil, demonstrate the effectiveness of our approach.

Simulated annealing of displacement cascades in FCC metals. 1. Beeler cascades

International Nuclear Information System (INIS)

Doran, D.G.; Burnett, R.A.

1974-09-01

An important source of damage to structural materials in fast reactors is the displacement of atoms from normal lattice sites. A high energy neutron may impart sufficient energy to an atom to initiate a displacement cascade consisting of a localized high density of hundreds of interstitials and vacancies. These defects subsequently interact to form clusters and to reduce their density by mutual annihilation. This short term annealing of an isolated cascade has been simulated at high and low temperatures using a correlated random walk model. The cascade representations used were developed by Beeler and the point defect properties were based on the model of γ-iron by Johnson. Low temperature anneals, characterized by no vacancy migration and a 104 site annihilation region (AR), resulted in 49 defect pairs at 20 keV and 11 pairs at 5 keV. High temperature anneals, characterized by both interstitial and vacancy migration and a 32 site AR, resulted in 68 pairs at 20 keV and 18 pairs at 5 keV when no cluster dissociation was permitted; most of the vacancies were in immobile clusters. These high temperature values dropped to 40 and 14 upon dissolution of the vacancy clusters. Parameter studies showed that, at a given temperature, the large AR resulted in about one-half as many defects as the small AR. Cluster size distributions and examples of spatial configurations are included. (U.S.)

Quantum Cascade Lasers Modulation and Applications

Science.gov (United States)

Luzhansky, Edward

The mid-wave IR (MWIR) spectral band, extending from 3 to 5 microns, is considered to be a low loss atmospheric window. There are several spectral sub-bands with relatively low atmospheric attenuation in this region making it popular for various commercial and military applications. Relatively low thermal and solar background emissions, effective penetration through the natural and anthropogenic obscurants and eye safety add to the long list of advantages of MWIR wavelengths. Quantum Cascade Lasers are compact semiconductor devices capable of operating in MWIR spectrum. They are based on inter-subband transitions in a multiple-quantum-well (QW) hetero-structure, designed by means of band-structure engineering. The inter-subband nature of the optical transition has several key advantages. First, the emission wavelength is primarily a function of the QW thickness. This characteristic allows choosing well-understood and reliable semiconductors for the generation of light in a wavelength range of interest. Second, a cascade process in which tens of photons are generated per injected electron. This cascading process is behind the intrinsic high-power capabilities of QCLs. This dissertation is focused on modulation properties of Quantum Cascade Lasers. Both amplitude and phase/frequency modulations were studied including modulation bandwidth, modulation efficiency and chirp linearity. Research was consisted of the two major parts. In the first part we describe the theory of frequency modulation (FM) response of Distributed Feedback Quantum Cascade Lasers (DFB QCL). It includes cascading effect on the QCL's maximum modulation frequency. The "gain levering" effect for the maximum FM response of the two section QCLs was studied as well. In the second part of research we concentrated on the Pulse Position Amplitude Modulation of a single section QCL. The low complexity, low size, weight and power Mid-Wavelength Infra-Red optical communications transceiver concept is

Bursting behaviours in cascaded stimulated Brillouin scattering

International Nuclear Information System (INIS)

Liu Zhan-Jun; He Xian-Tu; Zheng Chun-Yang; Wang Yu-Gang

2012-01-01

Stimulated Brillouin scattering is studied by numerically solving the Vlasov—Maxwell system. A cascade of stimulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma. It is found that a stimulated Brillouin scattering cascade can reduce the scattering and increase the transmission of light, as well as introduce a bursting behaviour in the evolution of the laser-plasma interaction. The bursting time in the reflectivity is found to be less than half the ion acoustic period. The ion temperature can affect the stimulated Brillouin scattering cascade, which can repeat several times at low ion temperatures and can be completely eliminated at high ion temperatures. For stimulated Brillouin scattering saturation, higher-harmonic generation and wave—wave interaction of the excited ion acoustic waves can restrict the amplitude of the latter. In addition, stimulated Brillouin scattering cascade can restrict the amplitude of the scattered light. (physics of gases, plasmas, and electric discharges)

Cascades on a stochastic pulse-coupled network

Science.gov (United States)

Wray, C. M.; Bishop, S. R.

2014-09-01

While much recent research has focused on understanding isolated cascades of networks, less attention has been given to dynamical processes on networks exhibiting repeated cascades of opposing influence. An example of this is the dynamic behaviour of financial markets where cascades of buying and selling can occur, even over short timescales. To model these phenomena, a stochastic pulse-coupled oscillator network with upper and lower thresholds is described and analysed. Numerical confirmation of asynchronous and synchronous regimes of the system is presented, along with analytical identification of the fixed point state vector of the asynchronous mean field system. A lower bound for the finite system mean field critical value of network coupling probability is found that separates the asynchronous and synchronous regimes. For the low-dimensional mean field system, a closed-form equation is found for cascade size, in terms of the network coupling probability. Finally, a description of how this model can be applied to interacting agents in a financial market is provided.

Framework for cascade size calculations on random networks

Science.gov (United States)

Burkholz, Rebekka; Schweitzer, Frank

2018-04-01

We present a framework to calculate the cascade size evolution for a large class of cascade models on random network ensembles in the limit of infinite network size. Our method is exact and applies to network ensembles with almost arbitrary degree distribution, degree-degree correlations, and, in case of threshold models, for arbitrary threshold distribution. With our approach, we shift the perspective from the known branching process approximations to the iterative update of suitable probability distributions. Such distributions are key to capture cascade dynamics that involve possibly continuous quantities and that depend on the cascade history, e.g., if load is accumulated over time. As a proof of concept, we provide two examples: (a) Constant load models that cover many of the analytically tractable casacade models, and, as a highlight, (b) a fiber bundle model that was not tractable by branching process approximations before. Our derivations cover the whole cascade dynamics, not only their steady state. This allows us to include interventions in time or further model complexity in the analysis.

Measurement and Analysis of in vitro Actin Polymerization

Science.gov (United States)

Doolittle, Lynda K.; Rosen, Michael K.; Padrick, Shae B.

2014-01-01

Summary The polymerization of actin underlies force generation in numerous cellular processes. While actin polymerization can occur spontaneously, cells maintain control over this important process by preventing actin filament nucleation and then allowing stimulated polymerization and elongation by several regulated factors. Actin polymerization, regulated nucleation and controlled elongation activities can be reconstituted in vitro, and used to probe the signaling cascades cells use to control when and where actin polymerization occurs. Introducing a pyrene fluorophore allows detection of filament formation by an increase in pyrene fluorescence. This method has been used for many years and continues to be broadly used, owing to its simplicity and flexibility. Here we describe how to perform and analyze these in vitro actin polymerization assays, with an emphasis on extracting useful descriptive parameters from kinetic data. PMID:23868594

Towards the development of lipid multilayer microarrays for dose dependent in vitro delivery and screening

Science.gov (United States)

Kusi-Appiah, Aubrey Emmanuel

Screening for effects of small molecules on cells grown in culture is a well-established method for drug discovery and testing, and faster throughput at lower cost is needed especially for lipophilic materials. Small-molecule arrays present a promising approach. However, it has been a challenge to use them to obtain quantitative surface based dose-response curves in vitro, especially for lipophilic compounds. This thesis first introduces a simple novel method of surface-mediated delivery of drugs to cells from a microarray of phospholipid multilayers (layers thicker than a bilayer) encapsulating small molecules. The capability of controlling the dosage of the lipophilic molecules delivered to cells using the lipid multilayer microarray assay is further demonstrated using the nanointaglio printing method. This control enabled the variation of the volumes of surface supported lipid micro- and nanostructure arrays fabricated with nanointaglio. The volumes of the lipophilic drug-containing nanostructures were determined using a fluorescence microscope calibrated by atomic-force microscopy. The surface supported lipid volume information was used to obtain EC-50 values for the response of HeLa cells to treatment with three FDA-approved lipophilic anticancer drugs, docetaxel, imiquimod and triethylenemelamine, which were found to be significantly different from neat lipid controls. Features with sub-cellular lateral dimensions were found to be necessary to obtain normal cell adhesion with HeLa cells. Comparison of the microarray data to dose-response curves for the same drugs delivered liposomally from solution revealed quantitative differences in the efficacy values, which may be explained in terms of cell-adhesion playing a more important role in the surface-based assay. Finally, solution encapsulation was done for a library of hydrophilic silicon nanocrystals in order to set a solution standard for comparison with future surface supported delivery of the library. The

20180311 - High Throughput Transcriptomics: From screening to pathways (SOT 2018)

Science.gov (United States)

The EPA ToxCast effort has screened thousands of chemicals across hundreds of high-throughput in vitro screening assays. The project is now leveraging high-throughput transcriptomic (HTTr) technologies to substantially expand its coverage of biological pathways. The first HTTr sc...

In Silico Screening, Synthesis and In Vitro Evaluation of Some Quinazolinone and Pyridine Derivatives as Dihydrofolate Reductase Inhibitors for Anticancer Activity

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A. G. Nerkar

2009-01-01

Full Text Available Dihydrofolate reductase (DHFR is the important target for anticancer drugs belonging to the class of antimetabolites as the enzyme plays important role in the de novo purine synthesis. We here report the in silico screening to obtain best fit molecules as DHFR inhibitors, synthesis of some ʻbest fitʼ quinazolinone from 2-phenyl-3-(substituted-benzilidine-amino quinazolinones (Quinazolinone Shiff's bases QSB1-5 and pyridine-4-carbohydrazide Shiff's bases (ISB1-5 derivatives and their in vitro anticancer assay. Synthesis of the molecules was performed using microwave assisted synthesis. The structures of these molecules were elucidated by IR and 1H-NMR. These compounds were then subjected for in vitro anticancer evaluation against five human cancer cell-lines for anticancer cyto-toxicity assay. Methotrexate (MTX was used as standard for this evaluation to give a comparable inhibition of the cell proliferation by DHFR inhibition. Placlitaxel, adriamycin and 5-fluoro-uracil were also used as standard to give a comparable activity of these compounds with other mechanism of anticancer activity. ISB3 (4-(N, N-dimethyl-amino-phenyl Schiff''s base derivative of pyridine carbohydrazide showed equipotent activity with the standards used in in vitro anticancer assay as per the NCI (National Cancer Institute guidelines.

Increasing sensitivity of MOS dosemeters in cascade connection

International Nuclear Information System (INIS)

Vychytil, F.; Cechak, T.; Gerndt, J.; Petr, I.

1978-01-01

The possibilities of increasing the sensitivity of MOS transistors in their cascade connection were studied theoretically and experimentally. The measurements confirmed the presumption that the instability of cascade-connected MOS transistors increased with the square of the number of transistors in the system. This allows systems to be formed with different sensitivity to ionizing radiation by encasing 10 to 10 4 transistors connected in cascade, which is technologically feasible. The procedure is also acceptable from the point of view of cost. (Z.M.)

Evaluation of refrigerating and air-conditioning technologies in heat cascading systems under the carbon dioxide emissions constraint: the proposal of the energy cascade balance table

International Nuclear Information System (INIS)

Shimazaki, Yoichi

2003-01-01

The aim of this study was to evaluate the refrigerating and air-conditioning technologies in cases of introducing both heat cascading systems and thermal recycling systems in industries located around urban areas. It is necessary to introduce heat cascading systems in the industrial sector in Japan to reduce carbon dioxide emissions. The concept of heat cascading is the multi-stage use of thermal energy by temperature level. This paper introduces three energy policies for introducing the heat cascading systems. The author develops an energy cascade model based on linear programming so as to minimize the total system costs with carbon taxes. Five cases are investigated. Carbon dioxide emission constraints result in the enhancement of heat cascading, where high temperature heat is supplied for process heating while low temperature heat is shifted to refrigeration. It was found that increasing the amount of garbage combustion waste heat could reduce electric power for the turbo compression refrigerator by promoting waste heat driven ammonia absorption refrigerator. In addition, this study proposes an energy cascade balance table with respect to the temperature level

On the trajectories of CRL...LR...R orbits, their period-doubling cascades and saddle-node bifurcation cascades

International Nuclear Information System (INIS)

Cerrada, Lucia; San Martin, Jesus

2011-01-01

In this Letter, it is shown that from a two region partition of the phase space of a one-dimensional dynamical system, a p-region partition can be obtained for the CRL...LR...R orbits. That is, permutations associated with symbolic sequences are obtained. As a consequence, the trajectory in phase space is directly deduced from permutation. From this permutation other permutations associated with period-doubling and saddle-node bifurcation cascades are derived, as well as other composite permutations. - Research highlights: → Symbolic sequences are the usual topological approach to dynamical systems. → Permutations bear more physical information than symbolic sequences. → Period-doubling cascade permutations associated with original sequences are obtained. → Saddle-node cascade permutations associated with original sequences are obtained. → Composite permutations are derived.

Prevalence, specificity and determinants of lipid-interacting PDZ domains from an in-cell screen and in vitro binding experiments.

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Ylva Ivarsson

Full Text Available BACKGROUND: PDZ domains are highly abundant protein-protein interaction modules involved in the wiring of protein networks. Emerging evidence indicates that some PDZ domains also interact with phosphoinositides (PtdInsPs, important regulators of cell polarization and signaling. Yet our knowledge on the prevalence, specificity, affinity, and molecular determinants of PDZ-PtdInsPs interactions and on their impact on PDZ-protein interactions is very limited. METHODOLOGY/PRINCIPAL FINDINGS: We screened the human proteome for PtdInsPs interacting PDZ domains by a combination of in vivo cell-localization studies and in vitro dot blot and Surface Plasmon Resonance (SPR experiments using synthetic lipids and recombinant proteins. We found that PtdInsPs interactions contribute to the cellular distribution of some PDZ domains, intriguingly also in nuclear organelles, and that a significant subgroup of PDZ domains interacts with PtdInsPs with affinities in the low-to-mid micromolar range. In vitro specificity for the head group is low, but with a trend of higher affinities for more phosphorylated PtdInsPs species. Other membrane lipids can assist PtdInsPs-interactions. PtdInsPs-interacting PDZ domains have generally high pI values and contain characteristic clusters of basic residues, hallmarks that may be used to predict additional PtdInsPs interacting PDZ domains. In tripartite binding experiments we established that peptide binding can either compete or cooperate with PtdInsPs binding depending on the combination of ligands. CONCLUSIONS/SIGNIFICANCE: Our screen substantially expands the set of PtdInsPs interacting PDZ domains, and shows that a full understanding of the biology of PDZ proteins will require a comprehensive insight into the intricate relationships between PDZ domains and their peptide and lipid ligands.

Development of a New Cascade Voltage-Doubler for Voltage Multiplication

OpenAIRE

Toudeshki, Arash; Mariun, Norman; Hizam, Hashim; Abdul Wahab, Noor Izzri

2014-01-01

For more than eight decades, cascade voltage-doubler circuits are used as a method to produce DC output voltage higher than the input voltage. In this paper, the topological developments of cascade voltage-doublers are reviewed. A new circuit configuration for cascade voltage-doubler is presented. This circuit can produce a higher value of the DC output voltage and better output quality compared to the conventional cascade voltage-doubler circuits, with the same number of stages.

A Novel Concept for Three-Phase Cascaded Multilevel Inverter Topologies

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Md Mubashwar Hasan

2018-01-01

Full Text Available One of the key challenges in multilevel inverters (MLIs design is to reduce the number of components used in the implementation while maximising the number of output voltage levels. This paper proposes a new concept that facilitates a device count reduction technique of existing cascaded MLIs. Moreover, the proposed concept can be utilised to extend existing single phase cascaded MLI topologies to three-phase structure without tripling the number of semiconductor components and input dc-supplies as per the current practice. The new generalized concept involves two stages; namely, cascaded stage and phase generator stage. The phase generator stage is a combination of a conventional three-phase two level inverter and three bi-directional switches while the cascaded stage can employ any existing cascaded topology. A laboratory prototype model is built and extensive experimental analyses are conducted to validate the feasibility of the proposed cascaded MLI concept.

Molecular dynamics simulation of displacement cascades in iron-alpha

International Nuclear Information System (INIS)

Vascon, R.

1997-01-01

Radiation damage by neutrons or ions in bcc iron has been investigated by molecular dynamics simulations using an embedded atom type many-body potential (EAM). Displacement cascades with energies of 1 to 30 keV were generated in the microcanonical system where the number of atoms (up to 1.5 million) is chosen high enough to compensate the fact that the dissipation of energy is not taken into account in our model. The defect number at the end of cascade lifetime was found to be 60 percent of the NRT standard value. This tendency is in good agreement with experimental data. However, compared with other simulations in iron, we found significant differences in the defect production and distribution. The comparison with results obtained form simulations of cascades in other metals, leads on the one hand to a higher value of the defect number in bcc iron than in fcc metals like copper or nickel, and on the other hand to a ratio, between the number of replacements and the number of defects, lower in iron ( 100). We observed the transient melting of the core of the cascade during simulations. We showed that a higher value of the initial iron crystal temperature, as the mass difference between the components of an artificial binary alloy Fe-X(X=Al,Sb,Au,U) both produce a 'cascade effect': a decrease of the number of defects and an increase of the number of replacements. We also showed up the quasi-channeling of some atoms in high energy cascades. They are at the origin of sub-cascades formation; as a result they induce an opposite effect to the 'cascade effect'. (author)

Design concept of Hydro cascade control system

International Nuclear Information System (INIS)

Fustik, Vangel; Kiteva, Nevenka

2006-01-01

In this paper a design concept of the comple hydro cascade scheme is presented with the design parameters of the main technical features. The cascade control system architecture is designed considering up-to-date communication and information technology. The control algorithm is based on Pond Level Control and Economic Load Allocation concepts.

On calculating of squared-off cascades for multicomponent isotope separation

International Nuclear Information System (INIS)

Potapov, D.V.; Soulaberidze, G.A.; Chuzhinov, V.A.; Filipppov, I.G.

1996-01-01

Calculation on a cascade of specified configuration (specified number of stages and flows in the enriching and stripping sections of the cascade) is performed with two approaches. The first one, which is advisable to use for for calculation of so-called 'long' cascades (for example, squared-off cascades of distillation columns), is based on either analytical transitions enabling the problem to be reduced to to the algebraic transcendental equations, or based on the direct integration of the equations describing the cascade separation process, with the subsequent iteration on the boundary conditions and the balance equations. This approach also involves the orthogonal-collocation technique consisting in the approximation of the differential equations solution by an Lagrangian polynomial interpolation

Sample Selection for Training Cascade Detectors.

Science.gov (United States)

Vállez, Noelia; Deniz, Oscar; Bueno, Gloria

2015-01-01

Automatic detection systems usually require large and representative training datasets in order to obtain good detection and false positive rates. Training datasets are such that the positive set has few samples and/or the negative set should represent anything except the object of interest. In this respect, the negative set typically contains orders of magnitude more images than the positive set. However, imbalanced training databases lead to biased classifiers. In this paper, we focus our attention on a negative sample selection method to properly balance the training data for cascade detectors. The method is based on the selection of the most informative false positive samples generated in one stage to feed the next stage. The results show that the proposed cascade detector with sample selection obtains on average better partial AUC and smaller standard deviation than the other compared cascade detectors.

The temporal development of collision cascades in the binary collision approximation

International Nuclear Information System (INIS)

Robinson, M.T.

1989-07-01

A modified binary collision approximation (BCA) was developed to allow explicit evaluation of the times at which projectiles in a collision cascade reach significant points in their trajectories, without altering the ''event-driven'' character of the model. The modified BCA was used to study the temporal development of cascades in copper and gold, initiated by primary atoms of up to 10 keV initial kinetic energy. Cascades generated with time-ordered collisions show fewer ''distant'' Frenkel pairs than do cascades generated with velocity-ordered collisions. In the former, the slower projectiles tend to move in less-damaged crystal than they do in the latter. The effect is larger in Au than in Cu and increases with primary energy. As an approach to cascade nonlinearities, cascades were generated in which stopped cascade atoms were allowed to be redisplaced in later encounters. There were many more redisplacements in time-ordered cascades than in velocity-ordered ones. Because of the additional stopping introduced by the redisplacement events, the cascades in which they were allowed had fewer defects than occurred otherwise. This effect also was larger in Au than in Cu and larger at high energies although most of the redisplacement encounters involved only low-energy particles. 13 refs., 5 figs., 4 tabs

All passive architecture for high efficiency cascaded Raman conversion

Science.gov (United States)

Balaswamy, V.; Arun, S.; Chayran, G.; Supradeepa, V. R.

2018-02-01

Cascaded Raman fiber lasers have offered a convenient method to obtain scalable, high-power sources at various wavelength regions inaccessible with rare-earth doped fiber lasers. A limitation previously was the reduced efficiency of these lasers. Recently, new architectures have been proposed to enhance efficiency, but this came at the cost of enhanced complexity, requiring an additional low-power, cascaded Raman laser. In this work, we overcome this with a new, all-passive architecture for high-efficiency cascaded Raman conversion. We demonstrate our architecture with a fifth-order cascaded Raman converter from 1117nm to 1480nm with output power of ~64W and efficiency of 60%.

Minimum Entropy-Based Cascade Control for Governing Hydroelectric Turbines

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Mifeng Ren

2014-06-01

Full Text Available In this paper, an improved cascade control strategy is presented for hydroturbine speed governors. Different from traditional proportional-integral-derivative (PID control and model predictive control (MPC strategies, the performance index of the outer controller is constructed by integrating the entropy and mean value of the tracking error with the constraints on control energy. The inner controller is implemented by a proportional controller. Compared with the conventional PID-P and MPC-P cascade control methods, the proposed cascade control strategy can effectively decrease fluctuations of hydro-turbine speed under non-Gaussian disturbance conditions in practical hydropower plants. Simulation results show the advantages of the proposed cascade control method.

Quantitative high-throughput screen identifies inhibitors of the Schistosoma mansoni redox cascade.

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Anton Simeonov

2008-01-01

Full Text Available Schistosomiasis is a tropical disease associated with high morbidity and mortality, currently affecting over 200 million people worldwide. Praziquantel is the only drug used to treat the disease, and with its increased use the probability of developing drug resistance has grown significantly. The Schistosoma parasites can survive for up to decades in the human host due in part to a unique set of antioxidant enzymes that continuously degrade the reactive oxygen species produced by the host's innate immune response. Two principal components of this defense system have been recently identified in S. mansoni as thioredoxin/glutathione reductase (TGR and peroxiredoxin (Prx and as such these enzymes present attractive new targets for anti-schistosomiasis drug development. Inhibition of TGR/Prx activity was screened in a dual-enzyme format with reducing equivalents being transferred from NADPH to glutathione via a TGR-catalyzed reaction and then to hydrogen peroxide via a Prx-catalyzed step. A fully automated quantitative high-throughput (qHTS experiment was performed against a collection of 71,028 compounds tested as 7- to 15-point concentration series at 5 microL reaction volume in 1536-well plate format. In order to generate a robust data set and to minimize the effect of compound autofluorescence, apparent reaction rates derived from a kinetic read were utilized instead of end-point measurements. Actives identified from the screen, along with previously untested analogues, were subjected to confirmatory experiments using the screening assay and subsequently against the individual targets in secondary assays. Several novel active series were identified which inhibited TGR at a range of potencies, with IC(50s ranging from micromolar to the assay response limit ( approximately 25 nM. This is, to our knowledge, the first report of a large-scale HTS to identify lead compounds for a helminthic disease, and provides a paradigm that can be used to jump

Long term simulation of point defect cluster size distributions from atomic displacement cascades in Fe70Cr20Ni10

International Nuclear Information System (INIS)

Souidi, A.; Hou, M.; Becquart, C.S.; Domain, C.; De Backer, A.

2015-01-01

We have used an Object Kinetic Monte Carlo (OKMC) model to simulate the long term evolution of the primary damage in Fe 70 Cr 20 Ni 10 alloys. The mean number of Frenkel pairs created by different Primary Knocked on Atoms (PKA) was estimated by Molecular Dynamics using a ternary EAM potential developed in the framework of the PERFORM-60 European project. This number was then used to obtain the vacancy–interstitial recombination distance required in the calculation of displacement cascades in the Binary Collision Approximation (BCA) with code MARLOWE (Robinson, 1989). The BCA cascades have been generated in the 10–100 keV range with the MARLOWE code and two different screened Coulomb potentials, namely, the Molière approximation to the Thomas–Fermi potential and the so-called “Universal” potential by Ziegler, Biersack and Littmark (ZBL). These cascades have been used as input to the OKMC code LAKIMOCA (Domain et al., 2004), with a set of parameters for describing the mobility of point defect clusters based on ab initio calculations and experimental data. The cluster size distributions have been estimated for irradiation doses of 0.1 and 1 dpa, and a dose rate of 10 −7 dpa/s at 600 K. We demonstrate that, like in the case of BCC iron, cluster size distributions in the long term are independent of the cascade energy and that the recursive cascade model suggested for BCC iron in Souidi et al. (2011) also applies to FCC Fe 70 Cr 20 Ni 10. The results also show that the influence of the BCA potential is sizeable but the qualitative correspondence in the predicted long term evolution is excellent

Space-time evolution of electron cascades in diamond

International Nuclear Information System (INIS)

Ziaja, Beata; Szoeke, Abraham; Spoel, David van der; Hajdu, Janos

2002-01-01

The impact of a primary electron initiates a cascade of secondary electrons in solids, and these cascades play a significant role in the dynamics of ionization. Here we describe model calculations to follow the spatiotemporal evolution of secondary electron cascades in diamond. The band structure of the insulator has been explicitly incorporated into the calculations as it affects ionizations from the valence band. A Monte Carlo model was constructed to describe the path of electrons following the impact of a single electron of energy E∼250 eV. This energy is similar to the energy of an Auger electron from carbon. Two limiting cases were considered: the case in which electrons transmit energy to the lattice, and the case where no such energy transfer is permitted. The results show the evolution of the secondary electron cascades in terms of the number of electrons liberated, the spatial distribution of these electrons, and the energy distribution among the electrons as a function of time. The predicted ionization rates (∼5-13 electrons in 100 fs) lie within the limits given by experiments and phenomenological models. Calculation of the local electron density and the corresponding Debye length shows that the latter is systematically larger than the radius of the electron cloud, and it increases exponentially with the radial size of the cascade. This means that the long-range Coulomb field is not shielded within this cloud, and the electron gas generated does not represent a plasma in a single impact cascade triggered by an electron of E∼250 eV energy. This is important as it justifies the independent-electron approximation used in the model. At 1 fs, the (average) spatial distribution of secondary electrons is anisotropic with the electron cloud elongated in the direction of the primary impact. The maximal radius of the cascade is about 50 A at this time. At 10 fs the cascade has a maximal radius of ∼70 A, and is already dominated by low-energy electrons

Energy cascading in the beat-wave accelerator

International Nuclear Information System (INIS)

McKinstrie, C.J.; Batha, S.H.

1987-01-01

A review is given of energy cascading in the beat-wave accelerator. The properties of the electromagnetic cascade and the corresponding plasma-wave evolution are well understood within the framework of an approximate analytic model. Based on this model, idealized laser-plasma coupling efficiencies of the order of 10% do not seem unreasonable. 28 refs

Simulation of short-term annealing of displacement cascades in FCC metals

International Nuclear Information System (INIS)

Heinisch, H.L.; Doran, D.G.; Schwartz, D.M.

1980-01-01

Computer models have been developed for the simulation of high energy displacement cascades. The objective is the generation of defect production functions for use in correlation analysis of radiation effects in fusion reactor materials. In particular, the stochastic cascade annealing simulation code SCAS has been developed and used to model the short-term annealing behavior of simulated cascades in FCC metals. The code is fast enough to make annealing of high energy cascades practical. Sets of cascades from 5 keV to 100 keV in copper were generated by the binary collision code MARLOWE

The hepatitis C cascade of care: identifying priorities to improve clinical outcomes.

Science.gov (United States)

Linas, Benjamin P; Barter, Devra M; Leff, Jared A; Assoumou, Sabrina A; Salomon, Joshua A; Weinstein, Milton C; Kim, Arthur Y; Schackman, Bruce R

2014-01-01

As highly effective hepatitis C virus (HCV) therapies emerge, data are needed to inform the development of interventions to improve HCV treatment rates. We used simulation modeling to estimate the impact of loss to follow-up on HCV treatment outcomes and to identify intervention strategies likely to provide good value for the resources invested in them. We used a Monte Carlo state-transition model to simulate a hypothetical cohort of chronically HCV-infected individuals recently screened positive for serum HCV antibody. We simulated four hypothetical intervention strategies (linkage to care; treatment initiation; integrated case management; peer navigator) to improve HCV treatment rates, varying efficacies and costs, and identified strategies that would most likely result in the best value for the resources required for implementation. Sustained virologic responses (SVRs), life expectancy, quality-adjusted life expectancy (QALE), costs from health system and program implementation perspectives, and incremental cost-effectiveness ratios (ICERs). We estimate that imperfect follow-up reduces the real-world effectiveness of HCV therapies by approximately 75%. In the base case, a modestly effective hypothetical peer navigator program maximized the number of SVRs and QALE, with an ICER compared to the next best intervention of $48,700/quality-adjusted life year. Hypothetical interventions that simultaneously addressed multiple points along the cascade provided better outcomes and more value for money than less costly interventions targeting single steps. The 5-year program cost of the hypothetical peer navigator intervention was $14.5 million per 10,000 newly diagnosed individuals. We estimate that imperfect follow-up during the HCV cascade of care greatly reduces the real-world effectiveness of HCV therapy. Our mathematical model shows that modestly effective interventions to improve follow-up would likely be cost-effective. Priority should be given to developing and

The hepatitis C cascade of care: identifying priorities to improve clinical outcomes.

Directory of Open Access Journals (Sweden)

Benjamin P Linas

Full Text Available As highly effective hepatitis C virus (HCV therapies emerge, data are needed to inform the development of interventions to improve HCV treatment rates. We used simulation modeling to estimate the impact of loss to follow-up on HCV treatment outcomes and to identify intervention strategies likely to provide good value for the resources invested in them.We used a Monte Carlo state-transition model to simulate a hypothetical cohort of chronically HCV-infected individuals recently screened positive for serum HCV antibody. We simulated four hypothetical intervention strategies (linkage to care; treatment initiation; integrated case management; peer navigator to improve HCV treatment rates, varying efficacies and costs, and identified strategies that would most likely result in the best value for the resources required for implementation.Sustained virologic responses (SVRs, life expectancy, quality-adjusted life expectancy (QALE, costs from health system and program implementation perspectives, and incremental cost-effectiveness ratios (ICERs.We estimate that imperfect follow-up reduces the real-world effectiveness of HCV therapies by approximately 75%. In the base case, a modestly effective hypothetical peer navigator program maximized the number of SVRs and QALE, with an ICER compared to the next best intervention of $48,700/quality-adjusted life year. Hypothetical interventions that simultaneously addressed multiple points along the cascade provided better outcomes and more value for money than less costly interventions targeting single steps. The 5-year program cost of the hypothetical peer navigator intervention was $14.5 million per 10,000 newly diagnosed individuals.We estimate that imperfect follow-up during the HCV cascade of care greatly reduces the real-world effectiveness of HCV therapy. Our mathematical model shows that modestly effective interventions to improve follow-up would likely be cost-effective. Priority should be given to

One pot synthesis of GDP-mannose by a multi-enzyme cascade for enzymatic assembly of lipid-linked oligosaccharides.

Science.gov (United States)

Rexer, Thomas F T; Schildbach, Anna; Klapproth, Jan; Schierhorn, Angelika; Mahour, Reza; Pietzsch, Markus; Rapp, Erdmann; Reichl, Udo

2018-01-01

Glycosylation of proteins is a key function of the biosynthetic-secretory pathway in the endoplasmic reticulum (ER) and Golgi apparatus. Glycosylated proteins play a crucial role in cell trafficking and signaling, cell-cell adhesion, blood-group antigenicity, and immune response. In addition, the glycosylation of proteins is an important parameter in the optimization of many glycoprotein-based drugs such as monoclonal antibodies. In vitro glycoengineering of proteins requires glycosyltransferases as well as expensive nucleotide sugars. Here, we present a designed pathway consisting of five enzymes, glucokinase (Glk), phosphomannomutase (ManB), mannose-1-phosphate-guanyltransferase (ManC), inorganic pyrophosphatase (PmPpA), and 1-domain polyphosphate kinase 2 (1D-Ppk2) expressed in E. coli for the cell-free production and regeneration of GDP-mannose from mannose and polyphosphate with catalytic amounts of GDP and ADP. It was shown that GDP-mannose is produced at various conditions, that is pH 7-8, temperature 25-35°C and co-factor concentrations of 5-20 mM MgCl 2 . The maximum reaction rate of GDP-mannose achieved was 2.7 μM/min at 30°C and 10 mM MgCl 2 producing 566 nmol GDP-mannose after a reaction time of 240 min. With respect to the initial GDP concentration (0.8 mM) this is equivalent to a yield of 71%. Additionally, the cascade was coupled to purified, transmembrane-deleted Alg1 (ALG1ΔTM), the first mannosyltransferase in the ER-associated lipid-linked oligosaccharide (LLO) assembly. Thereby, in a one-pot reaction, phytanyl-PP-(GlcNAc) 2 -Man 1 was produced with efficient nucleotide sugar regeneration for the first time. Phytanyl-PP-(GlcNAc) 2 -Man 1 can serve as a substrate for the synthesis of LLO for the cell-free in vitro glycosylation of proteins. A high-performance anion exchange chromatography method with UV and conductivity detection (HPAEC-UV/CD) assay was optimized and validated to determine the enzyme kinetics. The established

One pot synthesis of GDP‐mannose by a multi‐enzyme cascade for enzymatic assembly of lipid‐linked oligosaccharides

Science.gov (United States)

Schildbach, Anna; Klapproth, Jan; Schierhorn, Angelika; Mahour, Reza; Pietzsch, Markus; Rapp, Erdmann; Reichl, Udo

2017-01-01

Abstract Glycosylation of proteins is a key function of the biosynthetic‐secretory pathway in the endoplasmic reticulum (ER) and Golgi apparatus. Glycosylated proteins play a crucial role in cell trafficking and signaling, cell‐cell adhesion, blood‐group antigenicity, and immune response. In addition, the glycosylation of proteins is an important parameter in the optimization of many glycoprotein‐based drugs such as monoclonal antibodies. In vitro glycoengineering of proteins requires glycosyltransferases as well as expensive nucleotide sugars. Here, we present a designed pathway consisting of five enzymes, glucokinase (Glk), phosphomannomutase (ManB), mannose‐1‐phosphate‐guanyltransferase (ManC), inorganic pyrophosphatase (PmPpA), and 1‐domain polyphosphate kinase 2 (1D‐Ppk2) expressed in E. coli for the cell‐free production and regeneration of GDP‐mannose from mannose and polyphosphate with catalytic amounts of GDP and ADP. It was shown that GDP‐mannose is produced at various conditions, that is pH 7–8, temperature 25–35°C and co‐factor concentrations of 5–20 mM MgCl2. The maximum reaction rate of GDP‐mannose achieved was 2.7 μM/min at 30°C and 10 mM MgCl2 producing 566 nmol GDP‐mannose after a reaction time of 240 min. With respect to the initial GDP concentration (0.8 mM) this is equivalent to a yield of 71%. Additionally, the cascade was coupled to purified, transmembrane‐deleted Alg1 (ALG1ΔTM), the first mannosyltransferase in the ER‐associated lipid‐linked oligosaccharide (LLO) assembly. Thereby, in a one‐pot reaction, phytanyl‐PP‐(GlcNAc)2‐Man1 was produced with efficient nucleotide sugar regeneration for the first time. Phytanyl‐PP‐(GlcNAc)2‐Man1 can serve as a substrate for the synthesis of LLO for the cell‐free in vitro glycosylation of proteins. A high‐performance anion exchange chromatography method with UV and conductivity detection (HPAEC‐UV/CD) assay was optimized and

Optimization of the cascade with gas centrifuges for uranium enrichment

International Nuclear Information System (INIS)

Ozaki, N.; Harada, I.

1976-01-01

Computer programs to optimize the step and tapered-step cascades with gas centrifuges are developed. The 'Complex Method', one of the direct search method, is employed to find the optimum of the nonlinear function of several variables within a constrained region. The separation characteristics of the optimized step and tapered-step cascades are discussed in comparison with that of the ideal cascade. The local optima of the cascade profile, the convergence of the object function, and the stopping criterion for the optimization trial are also discussed. (author)

Centrifugal separator cascade connected in zigzag manner

International Nuclear Information System (INIS)

Kai, Tsunetoshi; Inoue, Yoshiya; Oya, Akio; Nagakura, Masaaki.

1974-01-01

Object: To effectively accommodate centrifugal separators of the entire cascade within the available space in a plant by freely selecting perpendicular direction of connection of the centrifugal separator. Structure: Centrifugal separators are connected in zigzag fashion by using a single header for each stage so that in a rectangular shape the entire cascade is arranged. (Kamimura, M.)

A period-doubling cascade precedes chaos for planar maps.

Science.gov (United States)

Sander, Evelyn; Yorke, James A

2013-09-01

A period-doubling cascade is often seen in numerical studies of those smooth (one-parameter families of) maps for which as the parameter is varied, the map transitions from one without chaos to one with chaos. Our emphasis in this paper is on establishing the existence of such a cascade for many maps with phase space dimension 2. We use continuation methods to show the following: under certain general assumptions, if at one parameter there are only finitely many periodic orbits, and at another parameter value there is chaos, then between those two parameter values there must be a cascade. We investigate only families that are generic in the sense that all periodic orbit bifurcations are generic. Our method of proof in showing there is one cascade is to show there must be infinitely many cascades. We discuss in detail two-dimensional families like those which arise as a time-2π maps for the Duffing equation and the forced damped pendulum equation.

A defect in the inflammation-primed macrophage-activation cascade in osteopetrotic rats.

Science.gov (United States)

Yamamoto, N; Lindsay, D D; Naraparaju, V R; Ireland, R A; Popoff, S N

1994-05-15

Macrophages were activated by administration of lysophosphatidylcholine (lyso-Pc) or dodecylglycerol (DDG) to wild-type rats but not in osteopetrotic (op) mutant rats. In vitro treatment of wild-type rat peritoneal cells with lyso-Pc or DDG efficiently activated macrophages whereas treatment of op mutant rat peritoneal cells with lyso-Pc or DDG did not activate macrophages. The inflammation-primed macrophage activation cascade in rats requires participation of B lymphocytes and vitamin D binding protein (DBP). Lyso-Pc-inducible beta-galactosidase of wild-type rat B lymphocytes can convert DBP to the macrophage-activating factor (MAF), whereas B lymphocytes of the op mutant rats were shown to be deficient in lyso-Pc-inducible beta-galactosidase. DBP is conserved among mammalian species. Treatment of human DBP (Gc1 protein) with commercial glycosidases yields an extremely high titrated MAF as assayed on mouse and rat macrophages. Because the enzymatically generated MAF (GcMAF) bypasses the role of lymphocytes in macrophage activation, the op mutant rat macrophages were efficiently activated by administration of a small quantity (100 pg/rat) of GcMAF. Likewise, in vitro treatment of op rat peritoneal cells with as little as 40 pg GcMAF/ml activated macrophages.

Sample Selection for Training Cascade Detectors.

Directory of Open Access Journals (Sweden)

Noelia Vállez

Full Text Available Automatic detection systems usually require large and representative training datasets in order to obtain good detection and false positive rates. Training datasets are such that the positive set has few samples and/or the negative set should represent anything except the object of interest. In this respect, the negative set typically contains orders of magnitude more images than the positive set. However, imbalanced training databases lead to biased classifiers. In this paper, we focus our attention on a negative sample selection method to properly balance the training data for cascade detectors. The method is based on the selection of the most informative false positive samples generated in one stage to feed the next stage. The results show that the proposed cascade detector with sample selection obtains on average better partial AUC and smaller standard deviation than the other compared cascade detectors.

Multilevel Inverter by Cascading Industrial VSI

DEFF Research Database (Denmark)

Teodorescu, Remus; Blaabjerg, Frede; Pedersen, John Kim

2002-01-01

In this paper the modularity concept applied to medium-voltage adjustable speed drives is addressed. First, the single-phase cascaded voltage-source inverter that uses series connection of IGBT H-bridge modules with isolated dc-buses is presented. Next, a novel three-phase cascaded voltage......-source inverter that uses three IGBT triphase inverter modules along with an output transformer to obtain a 3 p.u. multilevel output voltage is introduced. The system yields in high-quality multistep voltage with up to 4 levels and low dv/dt, balanced operation of the inverter modules, each supplying a third...... of the motor rated kVA. The concept of using cascaded inverters is further extended to a new modular motor-modular inverter system where the motor winding connections are reconnected into several three-phase groups, either six-lead or 12-lead connection according to the voltage level, each powered...

Particle fluxes in atomic collision cascades

International Nuclear Information System (INIS)

Sckerl, B.W.; Sigmund, P.; Vicanek, M.

1996-01-01

The flux of recoil atoms in atomic collision cascades induced by an ion beam or another source of energetic particles in a material is known to approach isotropy at kinetic energies far below the beam energy. A variety of irradiation effects can be explained satisfactorily on the basis of an isotropic particle flux, but significant deviations from this simple behavior are known to exist. While numerous examples have been studied by numerical simulation of cascade processes, the systematics is, by and large, unknown. The present study aims at general scaling properties and estimates of the magnitude of moderate deviations from isotropy and their spatial dependence for a wide range of beam and material parameters. Anisotropies introduced by crystal structure are ignored. Although it is well established that cascade anisotropy is related to the momentum of beam particles, previous attempts to quantify this relation have failed. We have found that there are two leading correction terms to the isotropic particle flux, a well-known term centered around the beam direction as a symmetry axis and a new term proportional to the gradient of the deposited-energy density. As a general rule the two contributions are either both significant or both negligible. Specific situations in which the gradient term dominates are, however, of considerable interest in applications. The parameters which characterize the anisotropy of collision cascades also determine the deposition of momentum, but the connection is less straightforward than asserted hitherto. General principles are first illustrated on the specific case of elastic-collision cascades under self-bombardment which contains the essentials. Thereafter several generalizations are made, including atomic binding forces and inelasticity as well as allowance for multicomponent materials. Application areas in mixing and sputtering are outlined. (au) 58 refs

Cascading Generative Adversarial Networks for Targeted

KAUST Repository

Hamdi, Abdullah

2018-01-01

Abundance of labelled data played a crucial role in the recent developments in computer vision, but that faces problems like scalability and transferability to the wild. One alternative approach is to utilize the data without labels, i.e. unsupervised learning, in learning valuable information and put it in use to tackle vision problems. Generative Adversarial Networks (GANs) have gained momentum for their ability to model image distributions in unsupervised manner. They learn to emulate the training set and that enables sampling from that domain and using the knowledge learned for useful applications. Several methods proposed enhancing GANs, including regularizing the loss with some feature matching. We seek to push GANs beyond the data in the training and try to explore unseen territory in the image manifold. We first propose a new regularizer for GAN based on K-Nearest Neighbor (K-NN) selective feature matching to a target set Y in high-level feature space, during the adversarial training of GAN on the base set X, and we call this novel model K-GAN. We show that minimizing the added term follows from cross-entropy minimization between the distributions of GAN and set Y. Then, we introduce a cascaded framework for GANs that try to address the task of imagining a new distribution that combines the base set X and target set Y by cascading sampling GANs with translation GANs, and we dub the cascade of such GANs as the Imaginative Adversarial Network (IAN). Several cascades are trained on a collected dataset Zoo-Faces and generated innovative samples are shown, including from K-GAN cascade. We conduct an objective and subjective evaluation for different IAN setups in the addressed task of generating innovative samples and we show the effect of regularizing GAN on different scores. We conclude with some useful applications for these IANs, like multi-domain manifold traversing.

Cascading Generative Adversarial Networks for Targeted

KAUST Repository

Hamdi, Abdullah

2018-04-09

Abundance of labelled data played a crucial role in the recent developments in computer vision, but that faces problems like scalability and transferability to the wild. One alternative approach is to utilize the data without labels, i.e. unsupervised learning, in learning valuable information and put it in use to tackle vision problems. Generative Adversarial Networks (GANs) have gained momentum for their ability to model image distributions in unsupervised manner. They learn to emulate the training set and that enables sampling from that domain and using the knowledge learned for useful applications. Several methods proposed enhancing GANs, including regularizing the loss with some feature matching. We seek to push GANs beyond the data in the training and try to explore unseen territory in the image manifold. We first propose a new regularizer for GAN based on K-Nearest Neighbor (K-NN) selective feature matching to a target set Y in high-level feature space, during the adversarial training of GAN on the base set X, and we call this novel model K-GAN. We show that minimizing the added term follows from cross-entropy minimization between the distributions of GAN and set Y. Then, we introduce a cascaded framework for GANs that try to address the task of imagining a new distribution that combines the base set X and target set Y by cascading sampling GANs with translation GANs, and we dub the cascade of such GANs as the Imaginative Adversarial Network (IAN). Several cascades are trained on a collected dataset Zoo-Faces and generated innovative samples are shown, including from K-GAN cascade. We conduct an objective and subjective evaluation for different IAN setups in the addressed task of generating innovative samples and we show the effect of regularizing GAN on different scores. We conclude with some useful applications for these IANs, like multi-domain manifold traversing.

A RabGAP regulates life-cycle duration via trimeric G-protein cascades in Dictyostelium discoideum.

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Hidekazu Kuwayama

Full Text Available BACKGROUND: The life-cycle of cellular slime molds comprises chronobiologically regulated processes. During the growth phase, the amoeboid cells proliferate at a definite rate. Upon starvation, they synthesize cAMP as both first and second messengers in signalling pathways and form aggregates, migrating slugs, and fruiting bodies, consisting of spores and stalk cells, within 24 h. In Dictyostelium discoideum, because most growth-specific events cease during development, proliferative and heterochronic mutations are not considered to be interrelated and no genetic factor governing the entire life-cycle duration has ever been identified. METHODOLOGY/PRINCIPAL FINDINGS: Using yeast 2-hybrid library screening, we isolated a Dictyostelium discoideum RabGAP, Dd Rbg-3, as a candidate molecule by which the Dictyostelium Gα2 subunit directs its effects. Rab GTPase-activating protein, RabGAP, acts as a negative regulator of Rab small GTPases, which orchestrate the intracellular membrane trafficking involved in cell proliferation. Deletion mutants of Dd rbg-3 exhibited an increased growth rate and a shortened developmental period, while an overexpression mutant demonstrated the opposite effects. We also show that Dd Rbg-3 interacts with 2 Gα subunits in an activity-dependent manner in vitro. Furthermore, both human and Caenorhabditis elegans rbg-3 homologs complemented the Dd rbg-3-deletion phenotype in D. discoideum, indicating that similar pathways may be generally conserved in multicellular organisms. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that Dd Rbg-3 acts as a key element regulating the duration of D. discoideum life-span potentially via trimeric G-protein cascades.

Displacement cascades and defect annealing in tungsten, Part II: Object kinetic Monte Carlo simulation of tungsten cascade aging

Energy Technology Data Exchange (ETDEWEB)

Nandipati, Giridhar, E-mail: giridhar.nandipati@pnnl.gov [Pacific Northwest National Laboratory, Richland, WA (United States); Setyawan, Wahyu; Heinisch, Howard L. [Pacific Northwest National Laboratory, Richland, WA (United States); Roche, Kenneth J. [Pacific Northwest National Laboratory, Richland, WA (United States); Department of Physics, University of Washington, Seattle, WA 98195 (United States); Kurtz, Richard J. [Pacific Northwest National Laboratory, Richland, WA (United States); Wirth, Brian D. [University of Tennessee, Knoxville, TN (United States)

2015-07-15

The results of object kinetic Monte Carlo (OKMC) simulations of the annealing of primary cascade damage in bulk tungsten using a comprehensive database of cascades obtained from molecular dynamics (Setyawan et al.) are described as a function of primary knock-on atom (PKA) energy at temperatures of 300, 1025 and 2050 K. An increase in SIA clustering coupled with a decrease in vacancy clustering with increasing temperature, in addition to the disparate mobilities of SIAs versus vacancies, causes an interesting effect of temperature on cascade annealing. The annealing efficiency (the ratio of the number of defects after and before annealing) exhibits an inverse U-shape curve as a function of temperature. The capabilities of the newly developed OKMC code KSOME (kinetic simulations of microstructure evolution) used to carry out these simulations are described.

Displacement cascades and defect annealing in tungsten, Part II: Object kinetic Monte Carlo Simulation of Tungsten Cascade Aging

Energy Technology Data Exchange (ETDEWEB)

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.; Roche, Kenneth J.; Kurtz, Richard J.; Wirth, Brian D.

2015-07-01

The results of object kinetic Monte Carlo (OKMC) simulations of the annealing of primary cascade damage in bulk tungsten using a comprehensive database of cascades obtained from molecular dynamics (Setyawan et al.) are described as a function of primary knock-on atom (PKA) energy at temperatures of 300, 1025 and 2050 K. An increase in SIA clustering coupled with a decrease in vacancy clustering with increasing temperature, in addition to the disparate mobilities of SIAs versus vacancies, causes an interesting effect of temperature on cascade annealing. The annealing efficiency (the ratio of the number of defects after and before annealing) exhibits an inverse U-shape curve as a function of temperature. The capabilities of the newly developed OKMC code KSOME (kinetic simulations of microstructure evolution) used to carry out these simulations are described.

Sign epistasis caused by hierarchy within signalling cascades.

Science.gov (United States)

Nghe, Philippe; Kogenaru, Manjunatha; Tans, Sander J

2018-04-13

Sign epistasis is a central evolutionary constraint, but its causal factors remain difficult to predict. Here we use the notion of parameterised optima to explain epistasis within a signalling cascade, and test these predictions in Escherichia coli. We show that sign epistasis arises from the benefit of tuning phenotypic parameters of cascade genes with respect to each other, rather than from their complex and incompletely known genetic bases. Specifically, sign epistasis requires only that the optimal phenotypic parameters of one gene depend on the phenotypic parameters of another, independent of other details, such as activating or repressing nature, position within the cascade, intra-genic pleiotropy or genotype. Mutational effects change sign more readily in downstream genes, indicating that optimising downstream genes is more constrained. The findings show that sign epistasis results from the inherent upstream-downstream hierarchy between signalling cascade genes, and can be addressed without exhaustive genotypic mapping.

Phytochemical screening and in vitro bioactivities of the extracts of aerial part of Boerhavia diffusa Linn.

Science.gov (United States)

Apu, Apurba Sarker; Liza, Mahmuda Sultana; Jamaluddin, A T M; Howlader, Md Amran; Saha, Repon Kumer; Rizwan, Farhana; Nasrin, Nishat

2012-09-01

To investigate the bioactivities of crude n-hexane, ethyl acetate and methanol extracts of aerial part of Boerhavia diffusa Linn. (B. diffusa) and its phytochemical analysis. The identification of phytoconstituents and assay of antioxidant, thrombolytic, cytotoxic, antimicrobial activities were conducted using specific standard in vitro procedures. The results showed that the plant extracts were a rich source of phytoconstituents. Methanol extract showed higher antioxidant, thrombolytic activity and less cytotoxic activity than those of n-hexane and ethyl acetate extracts of B. diffusa. Among the bioactivities, antioxidant activity was the most notable compared to the positive control and thus could be a potential rich source of natural antioxidant. In case of antimicrobial screening, crude extracts of the plant showed remarkable antibacterial activity against tested microorganisms. All the extracts showed significant inhibitory activity against Candida albicuns, at a concentration of 1000 µg/disc. The present findings suggest that, the plant widely available in Bangladesh, could be a prominent source of medicinally important natural compounds.

A thermal modelling of displacement cascades in uranium dioxide

Energy Technology Data Exchange (ETDEWEB)

Martin, G., E-mail: guillaume.martin@cea.fr [CEA – DEN/DEC/SESC/LLCC, Bât. 352, 13108 Saint-Paul-Lez-Durance Cedex (France); Garcia, P.; Sabathier, C. [CEA – DEN/DEC/SESC/LLCC, Bât. 352, 13108 Saint-Paul-Lez-Durance Cedex (France); Devynck, F.; Krack, M. [Laboratory for Reactor Physics and Systems Behaviour, Paul Scherrer Institute, CH-5232 Villigen PSI (Switzerland); Maillard, S. [CEA – DEN/DEC/SESC/LLCC, Bât. 352, 13108 Saint-Paul-Lez-Durance Cedex (France)

2014-05-01

The space and time dependent temperature distribution was studied in uranium dioxide during displacement cascades simulated by classical molecular dynamics (MD). The energy for each simulated radiation event ranged between 0.2 keV and 20 keV in cells at initial temperatures of 700 K or 1400 K. Spheres into which atomic velocities were rescaled (thermal spikes) have also been simulated by MD to simulate the thermal excitation induced by displacement cascades. Equipartition of energy was shown to occur in displacement cascades, half of the kinetic energy of the primary knock-on atom being converted after a few tenths of picoseconds into potential energy. The kinetic and potential parts of the system energy are however subjected to little variations during dedicated thermal spike simulations. This is probably due to the velocity rescaling process, which impacts a large number of atoms in this case and would drive the system away from a dynamical equilibrium. This result makes questionable MD simulations of thermal spikes carried out up to now (early 2014). The thermal history of cascades was compared to the heat equation solution of a punctual thermal excitation in UO{sub 2}. The maximum volume brought to a temperature above the melting temperature during the simulated cascade events is well reproduced by this simple model. This volume eventually constitutes a relevant estimate of the volume affected by a displacement cascade in UO{sub 2}. This definition of the cascade volume could also make sense in other materials, like iron.

Staged anticonvulsant screening for chronic epilepsy.

Science.gov (United States)

Berdichevsky, Yevgeny; Saponjian, Yero; Park, Kyung-Il; Roach, Bonnie; Pouliot, Wendy; Lu, Kimberly; Swiercz, Waldemar; Dudek, F Edward; Staley, Kevin J

2016-12-01

Current anticonvulsant screening programs are based on seizures evoked in normal animals. One-third of epileptic patients do not respond to the anticonvulsants discovered with these models. We evaluated a tiered program based on chronic epilepsy and spontaneous seizures, with compounds advancing from high-throughput in vitro models to low-throughput in vivo models. Epileptogenesis in organotypic hippocampal slice cultures was quantified by lactate production and lactate dehydrogenase release into culture media as rapid assays for seizure-like activity and cell death, respectively. Compounds that reduced these biochemical measures were retested with in vitro electrophysiological confirmation (i.e., second stage). The third stage involved crossover testing in the kainate model of chronic epilepsy, with blinded analysis of spontaneous seizures after continuous electrographic recordings. We screened 407 compound-concentration combinations. The cyclooxygenase inhibitor, celecoxib, had no effect on seizures evoked in normal brain tissue but demonstrated robust antiseizure activity in all tested models of chronic epilepsy. The use of organotypic hippocampal cultures, where epileptogenesis occurs on a compressed time scale, and where seizure-like activity and seizure-induced cell death can be easily quantified with biomarker assays, allowed us to circumvent the throughput limitations of in vivo chronic epilepsy models. Ability to rapidly screen compounds in a chronic model of epilepsy allowed us to find an anticonvulsant that would be missed by screening in acute models.

Pre-participation screening of asymptomatic athletes : "Don't do stupid stuff".

Science.gov (United States)

Mosterd, A

2018-03-01

Catastrophic events, be it traffic accidents, natural disasters or homicides, always lead to scrutiny. Could we have seen the event coming and could it have been prevented? In the case of a sudden cardiac arrest of a seemingly healthy athlete the public outcry is not any different. Despite an intrinsic appeal for screening to prevent similar events, there is no evidence that justifies routine cardiovascular pre-participation screening of athletes. On balance, cardiovascular screening in athletes will most likely do more harm than good. Fatal exercise-related cardiac arrests do not occur very often. The true diagnostic yield of the pre-participation evaluation is not known and once a cardiac condition has been identified, the most appropriate intervention is often unclear. It follows that pre-participation screening of large groups of athletes without known cardiac disease will inevitably result in many false positive findings, while at the same time providing a false sense of security to those screened negative. Except for compelling reasons (e. g. cascade screening, research settings, professional athletes), physicians should not engage in routine examination of asymptomatic athletes to prevent cardiac events.

Criticality safety study of shutdown diffusion cascade coolers

International Nuclear Information System (INIS)

Paschal, L.S.; Basoglu, B.; Bentley, C.L.; Dunn, M.E.

1996-01-01

Gaseous diffusion plants use cascade coolers in the production of highly enriched uranium (HEU) to remove heat from the enriched stream of UF 6 . The cascade coolers operate like shell and tube heat exchangers with the UF 6 on the shell side and Freon on the tube side. Recirculating cooling water (RCW) in condensers is used to cool the Freon. A criticality safety analysis was previously performed for cascade coolers during normal operation. The purpose of this paper is to evaluate several different hypothetical accidents regarding RCW ingress into the cooler to determine whether criticality safety concerns exist

Positional information generated by spatially distributed signaling cascades.

Directory of Open Access Journals (Sweden)

Javier Muñoz-García

2009-03-01

Full Text Available The temporal and stationary behavior of protein modification cascades has been extensively studied, yet little is known about the spatial aspects of signal propagation. We have previously shown that the spatial separation of opposing enzymes, such as a kinase and a phosphatase, creates signaling activity gradients. Here we show under what conditions signals stall in the space or robustly propagate through spatially distributed signaling cascades. Robust signal propagation results in activity gradients with long plateaus, which abruptly decay at successive spatial locations. We derive an approximate analytical solution that relates the maximal amplitude and propagation length of each activation profile with the cascade level, protein diffusivity, and the ratio of the opposing enzyme activities. The control of the spatial signal propagation appears to be very different from the control of transient temporal responses for spatially homogenous cascades. For spatially distributed cascades where activating and deactivating enzymes operate far from saturation, the ratio of the opposing enzyme activities is shown to be a key parameter controlling signal propagation. The signaling gradients characteristic for robust signal propagation exemplify a pattern formation mechanism that generates precise spatial guidance for multiple cellular processes and conveys information about the cell size to the nucleus.

Phytochemical screening and antimalarial activity of some plants traditionally used in Indonesia

Directory of Open Access Journals (Sweden)

Syamsudin Abdillah

2015-06-01

Full Text Available Objective: To evaluate ethanolic extracts of phytochemical screening, in vitro and in vivo antiplasmodial activities of 15 plants used as antimalarial in Sei Kepayang, North Sumatra. Methods: Extraction was done through maceration with 70% ethanol and screened against chemical content, in vitro test anti-plasmodium against Plasmodium falciparum 3D7 strain and in vivo test in mice infected Plasmodium berghei. Results: The results showed that the plant extract contained a group of saponins, flavonoids, alkaloids, quinone, sterols, triterpene, tannins and cumarine. However, extract of Momordica charantia, Carica papaya, Garcinia atroviridis, Alstonia scholaris, Smallanthus sonchifolia and Cassia siamea had strong anti-plasmodium activity both in vitro and in vivo. Conclusions: In vitro and in vivo antiplasmodial activities of 15 plants are used as antimalarial in Sei Kepayang, North Sumatra. All the plants have in vitro and in vivo anti-plasmodium activity except Orthosiphon stamineus and Luffa cylindrica (ED50 > 1 000 mg/kg body weight and IC50 > 100 μg/mL, respectively.

The flow analysis of supercavitating cascade by linear theory

Energy Technology Data Exchange (ETDEWEB)

Park, E.T. [Sung Kyun Kwan Univ., Seoul (Korea, Republic of); Hwang, Y. [Seoul National Univ., Seoul (Korea, Republic of)

1996-06-01

In order to reduce damages due to cavitation effects and to improve performance of fluid machinery, supercavitation around the cascade and the hydraulic characteristics of supercavitating cascade must be analyzed accurately. And the study on the effects of cavitation on fluid machinery and analysis on the performances of supercavitating hydrofoil through various elements governing flow field are critically important. In this study comparison of experiment results with the computed results of linear theory using singularity method was obtainable. Specially singularity points like sources and vortexes on hydrofoil and freestreamline were distributed to analyze two dimensional flow field of supercavitating cascade, and governing equations of flow field were derived and hydraulic characteristics of cascade were calculated by numerical analysis of the governing equations. 7 refs., 6 figs.

Computer simulation of high energy displacement cascades

International Nuclear Information System (INIS)

Heinisch, H.L.

1990-01-01

A methodology developed for modeling many aspects of high energy displacement cascades with molecular level computer simulations is reviewed. The initial damage state is modeled in the binary collision approximation (using the MARLOWE computer code), and the subsequent disposition of the defects within a cascade is modeled with a Monte Carlo annealing simulation (the ALSOME code). There are few adjustable parameters, and none are set to physically unreasonable values. The basic configurations of the simulated high energy cascades in copper, i.e., the number, size and shape of damage regions, compare well with observations, as do the measured numbers of residual defects and the fractions of freely migrating defects. The success of these simulations is somewhat remarkable, given the relatively simple models of defects and their interactions that are employed. The reason for this success is that the behavior of the defects is very strongly influenced by their initial spatial distributions, which the binary collision approximation adequately models. The MARLOWE/ALSOME system, with input from molecular dynamics and experiments, provides a framework for investigating the influence of high energy cascades on microstructure evolution. (author)

Influence of non-binary effects on intranuclear cascade method

International Nuclear Information System (INIS)

Gomes, E.H.C.

1985-01-01

The importance of non binary process effects in the intranuclear cascade method is analysed. It is shown that, in the higher density steps, the non binary collisions lead to baryon density distribution and rapidity differents from the one obtained using the usual intranuclear cascade method (limited to purely binary collisions). The validity of the applications of binary intranuclear cascade method to the simulation of the thermal equilibrium, nuclear transparency and particle production, is discussed. (M.C.K.) [pt

A virtual component method in numerical computation of cascades for isotope separation

International Nuclear Information System (INIS)

Zeng Shi; Cheng Lu

2014-01-01

The analysis, optimization, design and operation of cascades for isotope separation involve computations of cascades. In analytical analysis of cascades, using virtual components is a very useful analysis method. For complicated cases of cascades, numerical analysis has to be employed. However, bound up to the conventional idea that the concentration of a virtual component should be vanishingly small, virtual component is not yet applied to numerical computations. Here a method of introducing the method of using virtual components to numerical computations is elucidated, and its application to a few types of cascades is explained and tested by means of numerical experiments. The results show that the concentration of a virtual component is not restrained at all by the 'vanishingly small' idea. For the same requirements on cascades, the cascades obtained do not depend on the concentrations of virtual components. (authors)

Tunable signal processing in synthetic MAP kinase cascades.

Science.gov (United States)

O'Shaughnessy, Ellen C; Palani, Santhosh; Collins, James J; Sarkar, Casim A

2011-01-07

The flexibility of MAPK cascade responses enables regulation of a vast array of cell fate decisions, but elucidating the mechanisms underlying this plasticity is difficult in endogenous signaling networks. We constructed insulated mammalian MAPK cascades in yeast to explore how intrinsic and extrinsic perturbations affect the flexibility of these synthetic signaling modules. Contrary to biphasic dependence on scaffold concentration, we observe monotonic decreases in signal strength as scaffold concentration increases. We find that augmenting the concentration of sequential kinases can enhance ultrasensitivity and lower the activation threshold. Further, integrating negative regulation and concentration variation can decouple ultrasensitivity and threshold from the strength of the response. Computational analyses show that cascading can generate ultrasensitivity and that natural cascades with different kinase concentrations are innately biased toward their distinct activation profiles. This work demonstrates that tunable signal processing is inherent to minimal MAPK modules and elucidates principles for rational design of synthetic signaling systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Quality control methodology for high-throughput protein-protein interaction screening.

Science.gov (United States)

Vazquez, Alexei; Rual, Jean-François; Venkatesan, Kavitha

2011-01-01

Protein-protein interactions are key to many aspects of the cell, including its cytoskeletal structure, the signaling processes in which it is involved, or its metabolism. Failure to form protein complexes or signaling cascades may sometimes translate into pathologic conditions such as cancer or neurodegenerative diseases. The set of all protein interactions between the proteins encoded by an organism constitutes its protein interaction network, representing a scaffold for biological function. Knowing the protein interaction network of an organism, combined with other sources of biological information, can unravel fundamental biological circuits and may help better understand the molecular basics of human diseases. The protein interaction network of an organism can be mapped by combining data obtained from both low-throughput screens, i.e., "one gene at a time" experiments and high-throughput screens, i.e., screens designed to interrogate large sets of proteins at once. In either case, quality controls are required to deal with the inherent imperfect nature of experimental assays. In this chapter, we discuss experimental and statistical methodologies to quantify error rates in high-throughput protein-protein interactions screens.

Chemometrics Optimized Extraction Procedures, Phytosynergistic Blending and in vitro Screening of Natural Enzyme Inhibitors Amongst Leaves of Tulsi, Banyan and Jamun.

Science.gov (United States)

De, Baishakhi; Bhandari, Koushik; Singla, Rajeev K; Katakam, Prakash; Samanta, Tanmoy; Kushwaha, Dilip Kumar; Gundamaraju, Rohit; Mitra, Analava

2015-10-01

Tulsi, Banyan, and Jamun are popular Indian medicinal plants with notable hypoglycemic potentials. Now the work reports chemo-profiling of the three species with in-vitro screening approach for natural enzyme inhibitors (NEIs) against enzymes pathogenic for type 2 diabetes. Further along with the chemometrics optimized extraction process technology, phyto-synergistic studies of the composite polyherbal blends have also been reported. Chemometrically optimized extraction procedures, ratios of polyherbal composites to achieve phyto-synergistic actions, and in-vitro screening of NEIs amongst leaves of Tulsi, Banyan, and Jamun. The extraction process parameters of the leaves of three plant species (Ficus benghalensis, Syzigium cumini and Ocimum sanctum) were optimized by rotatable central composite design of chemometrics so as to get maximal yield of bio-actives. Phyto-blends of three species were prepared so as to achieve synergistic antidiabetic and antioxidant potentials and the ratios were optimized by chemometrics. Next, for in vitro screening of natural enzyme inhibitors the individual leaf extracts as well as composite blends were subjected to assay procedures to see their inhibitory potentials against the enzymes pathogenic in type 2 diabetes. The antioxidant potentials were also estimated by DPPH radical scavenging, ABTS, FRAP and Dot Blot assay. Considering response surface methodology studies and from the solutions obtained using desirability function, it was found that hydro-ethanolic or methanolic solvent ratio of 52.46 ± 1.6 and at a temperature of 20.17 ± 0.6 gave an optimum yield of polyphenols with minimal chlorophyll leaching. The species also showed the presence of glycosides, alkaloids, and saponins. Composites in the ratios of 1:1:1 and 1:1:2 gave synergistic effects in terms of polyphenol yield and anti-oxidant potentials. All composites (1:1:1, 1:2:1, 2:1:1, 1:1:2) showed synergistic anti-oxidant actions. Inhibitory activities against the

High throughput ADME screening: practical considerations, impact on the portfolio and enabler of in silico ADME models.

Science.gov (United States)

Hop, Cornelis E C A; Cole, Mark J; Davidson, Ralph E; Duignan, David B; Federico, James; Janiszewski, John S; Jenkins, Kelly; Krueger, Suzanne; Lebowitz, Rebecca; Liston, Theodore E; Mitchell, Walter; Snyder, Mark; Steyn, Stefan J; Soglia, John R; Taylor, Christine; Troutman, Matt D; Umland, John; West, Michael; Whalen, Kevin M; Zelesky, Veronica; Zhao, Sabrina X

2008-11-01

Evaluation and optimization of drug metabolism and pharmacokinetic data plays an important role in drug discovery and development and several reliable in vitro ADME models are available. Recently higher throughput in vitro ADME screening facilities have been established in order to be able to evaluate an appreciable fraction of synthesized compounds. The ADME screening process can be dissected in five distinct steps: (1) plate management of compounds in need of in vitro ADME data, (2) optimization of the MS/MS method for the compounds, (3) in vitro ADME experiments and sample clean up, (4) collection and reduction of the raw LC-MS/MS data and (5) archival of the processed ADME data. All steps will be described in detail and the value of the data on drug discovery projects will be discussed as well. Finally, in vitro ADME screening can generate large quantities of data obtained under identical conditions to allow building of reliable in silico models.

Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

International Nuclear Information System (INIS)

Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei; Ouyang, Zhengxiao; Wu, Chuanlong; Liu, Guangwang; Fan, Qiming; Tang, Tingting; Qin, An; Dai, Kerong

2014-01-01

Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases

Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

Energy Technology Data Exchange (ETDEWEB)

Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Ouyang, Zhengxiao [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha (China); Wu, Chuanlong [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Guangwang [Department of Orthopaedic Surgery, The Central Hospital of Xuzhou, Affiliated Hospital of Medical Collage of Southeast University, Xuzhou (China); Fan, Qiming; Tang, Tingting [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Qin, An, E-mail: dr.qinan@gmail.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Dai, Kerong, E-mail: krdai@163.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

2014-01-10

Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.

Cascade ICF power reactor

International Nuclear Information System (INIS)

Hogan, W.J.; Pitts, J.H.

1986-01-01

The double-cone-shaped Cascade reaction chamber rotates at 50 rpm to keep a blanket of ceramic granules in place against the wall as they slide from the poles to the exit slots at the equator. The 1 m-thick blanket consists of layers of carbon, beryllium oxide, and lithium aluminate granules about 1 mm in diameter. The x rays and debris are stopped in the carbon granules; the neutrons are multiplied and moderated in the BeO and breed tritium in the LiAlO 2 . The chamber wall is made up of SiO tiles held in compression by a network of composite SiC/Al tendons. Cascade operates at a 5 Hz pulse rate with 300 MJ in each pulse. The temperature in the blanket reaches 1600 K on the inner surface and 1350 K at the outer edge. The granules are automatically thrown into three separate vacuum heat exchangers where they give up their energy to high pressure helium. The helium is used in a Brayton cycle to obtain a thermal-to-electric conversion efficiency of 55%. Studies have been done on neutron activation, debris recovery, vaporization and recondensation of blanket material, tritium control and recovery, fire safety, and cost. These studies indicate that Cascade appears to be a promising ICF reactor candidate from all standpoints. At the 1000 MWe size, electricity could be made for about the same cost as in a future fission reactor

Bioactive screening and in vitro antioxidant assessment of Nauclea latifolia leaf decoction

Science.gov (United States)

Iheagwam, Franklyn Nonso; Nsedu, Emmanuel Israel; Kayode, Kazeem Oyindamola; Emiloju, Opeyemi Christianah; Ogunlana, Olubanke Olujoke; Chinedu, Shalom Nwodo

2018-04-01

The phytochemical constituents and antioxidant properties of Nauclea latifolia leaf decoction were investigated. Dried leaves were extracted in ethanol. Qualitative and quantitative phytochemical analysis was determined spectrometrically. The antioxidant activities were examined in vitro using 2,2-diphenyl-1-picrylhydrazyl radical, total antioxidant capacity and ferric reducing antioxidant power assays. Phytochemical screening confirmed the presence of flavonoids, alkaloids, anthocyanins, betacyanins, phenols, saponins, terpenoids, cardiac glycosides and quinones. The total lycopene, β-carotene, phenolics, flavonoid and alkaloid content were found to be 0.038 ± 0.01 mg CAE/g, 0.120 ± 0.04 mg CAE/g, 58.08 ± 0.58 mg GAE/g, 10.75 ± 0.17 mg RE/g and 0.32 ± 0.08% respectively. N. latifolia ethanol leaf extract demonstrated effective antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl with an IC50 of 2.58 ± 0.08 mg/mL compared to 0.86 ± 0.02 mg/mL and < 0.01 ± 0.01 mg/mL for butylated hydroxytoluene and ascorbic acid respectively. Total antioxidant capacity and ferric reducing antioxidant power of the extract were 73.81 ± 2.27 and 1314.45 ± 197.64 mg AAE/g respectively. Excellent positive correlations between the phenolic content and antioxidant activities of the extract were observed. The leaf of N. latifolia is of therapeutic value and may be exploited for its rich antioxidant components.

Performance of the flow cytometric E-screen assay in screening estrogenicity of pure compounds and environmental samples

Energy Technology Data Exchange (ETDEWEB)

Vanparys, Caroline, E-mail: caroline.vanparys@ua.ac.be [Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Antwerp (Belgium); Depiereux, Sophie; Nadzialek, Stephanie [Research Unit in Organismal Biology (URBO), University of Namur (FUNDP), Namur (Belgium); Robbens, Johan; Blust, Ronny [Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Antwerp (Belgium); Kestemont, Patrick [Research Unit in Organismal Biology (URBO), University of Namur (FUNDP), Namur (Belgium); De Coen, Wim [Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Antwerp (Belgium); European Chemicals Agency (ECHA), Helsinki (Finland)

2010-09-15

In vitro estrogenicity screens are believed to provide a first prioritization step in hazard characterization of endocrine disrupting chemicals. When applied to complex environmental matrices or mixture samples, they have been indicated valuable in estimating the overall estrogen-mimicking load. In this study, the performance of an adapted format of the classical E-screen or MCF-7 cell proliferation assay was profoundly evaluated to rank pure compounds as well as influents and effluents of sewage treatment plants (STPs) according to estrogenic activity. In this adapted format, flow cytometric cell cycle analysis was used to allow evaluation of the MCF-7 cell proliferative effects after only 24 h of exposure. With an average EC{sub 50} value of 2 pM and CV of 22%, this assay appears as a sensitive and reproducible system for evaluation of estrogenic activity. Moreover, estrogenic responses of 17 pure compounds corresponded well, qualitatively and quantitatively, with other in vitro and in vivo estrogenicity screens, such as the classical E-screen (R{sup 2} = 0.98), the estrogen receptor (ER) binding (R{sup 2} = 0.84) and the ER transcription activation assay (R{sup 2} = 0.87). To evaluate the applicability of this assay for complex samples, influents and effluents of 10 STPs covering different treatment processes, were compared and ranked according to estrogenic removal efficiencies. Activated sludge treatment with phosphorus and nitrogen removal appeared most effective in eliminating estrogenic activity, followed by activated sludge, lagoon and filter bed. This is well in agreement with previous findings based on chemical analysis or biological activity screens. Moreover, ER blocking experiments indicated that cell proliferative responses were mainly ER mediated, illustrating that the complexity of the end point, cell proliferation, compared to other ER screens, does not hamper the interpretation of the results. Therefore, this study, among other E-screen studies

Performance of the flow cytometric E-screen assay in screening estrogenicity of pure compounds and environmental samples

International Nuclear Information System (INIS)

Vanparys, Caroline; Depiereux, Sophie; Nadzialek, Stephanie; Robbens, Johan; Blust, Ronny; Kestemont, Patrick; De Coen, Wim

2010-01-01

In vitro estrogenicity screens are believed to provide a first prioritization step in hazard characterization of endocrine disrupting chemicals. When applied to complex environmental matrices or mixture samples, they have been indicated valuable in estimating the overall estrogen-mimicking load. In this study, the performance of an adapted format of the classical E-screen or MCF-7 cell proliferation assay was profoundly evaluated to rank pure compounds as well as influents and effluents of sewage treatment plants (STPs) according to estrogenic activity. In this adapted format, flow cytometric cell cycle analysis was used to allow evaluation of the MCF-7 cell proliferative effects after only 24 h of exposure. With an average EC 50 value of 2 pM and CV of 22%, this assay appears as a sensitive and reproducible system for evaluation of estrogenic activity. Moreover, estrogenic responses of 17 pure compounds corresponded well, qualitatively and quantitatively, with other in vitro and in vivo estrogenicity screens, such as the classical E-screen (R 2 = 0.98), the estrogen receptor (ER) binding (R 2 = 0.84) and the ER transcription activation assay (R 2 = 0.87). To evaluate the applicability of this assay for complex samples, influents and effluents of 10 STPs covering different treatment processes, were compared and ranked according to estrogenic removal efficiencies. Activated sludge treatment with phosphorus and nitrogen removal appeared most effective in eliminating estrogenic activity, followed by activated sludge, lagoon and filter bed. This is well in agreement with previous findings based on chemical analysis or biological activity screens. Moreover, ER blocking experiments indicated that cell proliferative responses were mainly ER mediated, illustrating that the complexity of the end point, cell proliferation, compared to other ER screens, does not hamper the interpretation of the results. Therefore, this study, among other E-screen studies, supports the use of

A cascading failure model for analyzing railway accident causation

Science.gov (United States)

Liu, Jin-Tao; Li, Ke-Ping

2018-01-01

In this paper, a new cascading failure model is proposed for quantitatively analyzing the railway accident causation. In the model, the loads of nodes are redistributed according to the strength of the causal relationships between the nodes. By analyzing the actual situation of the existing prevention measures, a critical threshold of the load parameter in the model is obtained. To verify the effectiveness of the proposed cascading model, simulation experiments of a train collision accident are performed. The results show that the cascading failure model can describe the cascading process of the railway accident more accurately than the previous models, and can quantitatively analyze the sensitivities and the influence of the causes. In conclusion, this model can assist us to reveal the latent rules of accident causation to reduce the occurrence of railway accidents.

Cascade Structure of Digital Predistorter for Power Amplifier Linearization

Directory of Open Access Journals (Sweden)

E. B. Solovyeva

2015-12-01

Full Text Available In this paper, a cascade structure of nonlinear digital predistorter (DPD synthesized by the direct learning adaptive algorithm is represented. DPD is used for linearization of power amplifier (PA characteristic, namely for compensation of PA nonlinear distortion. Blocks of the cascade DPD are described by different models: the functional link artificial neural network (FLANN, the polynomial perceptron network (PPN and the radially pruned Volterra model (RPVM. At synthesis of the cascade DPD there is possibility to overcome the ill conditionality problem due to reducing the dimension of DPD nonlinear operator approximation. Results of compensating nonlinear distortion in Wiener–Hammerstein model of PA at the GSM–signal with four carriers are shown. The highest accuracy of PA linearization is produced by the cascade DPD containing PPN and RPVM.

Increase of transient lower esophageal sphincter relaxation associated with cascade stomach

Science.gov (United States)

Kawada, Akiyo; Kusano, Motoyasu; Hosaka, Hiroko; Kuribayashi, Shiko; Shimoyama, Yasuyuki; Kawamura, Osamu; Akiyama, Junichi; Yamada, Masanobu; Akuzawa, Masako

2017-01-01

We previously reported that cascade stomach was associated with reflux symptoms and esophagitis. Delayed gastric emptying has been believed to initiate transient lower esophageal sphincter relaxation (TLESR). We hypothesized that cascade stomach may be associated with frequent TLESR with delayed gastric emptying. Eleven subjects with cascade stomach and 11 subjects without cascade stomach were enrolled. Postprandial gastroesophageal manometry and gastric emptying using a continuous 13C breath system were measured simultaneously after a liquid test meal. TLESR events were counted in early period (0–60 min), late period (60–120 min), and total monitoring period. Three parameters of gastric emptying were calculated: the half emptying time, lag time, and gastric emptying coefficient. The median frequency of TLESR events in the cascade stomach and non-cascade stomach groups was 6.0 (median), 4.6 (interquartile range) vs 5.0, 3.0 in the early period, 5.0, 3.2 vs 3.0, 1.8 in the late period, and 10.0, 6.2 vs 8.0, 5.0 in the total monitoring period. TLESR events were significantly more frequent in the cascade stomach group during the late and total monitoring periods. In contrast, gastric emptying parameters showed no significant differences between the two groups. We concluded that TLESR events were significantly more frequent in persons with cascade stomach without delayed gastric emptying. PMID:28584403

Cyquant cell proliferation assay as a fluorescence-based method for in vitro screening of antimalarial activity.

Science.gov (United States)

Sriwilaijaroen, Nongluk; Kelly, Jane Xu; Riscoe, Michael; Wilairat, Prapon

2004-12-01

The appearance of drug resistant parasites and the absence of an effective vaccine have resulted in the need for new effective antimalarial drugs. Consequently, a convenient method for in vitro screening of large numbers of antimalarial drug candidates has become apparent. The CyQUANT cell proliferation assay is a highly sensitive fluorescence-based method for quantitation of cell number by measuring the strong fluorescence produced when green GR dye binds to nucleic acids. We have applied the CyQUANT assay method to evaluate the growth of Plasmodium falciparum D6 strain in culture. The GR-nucleic acid fluorescence linearly correlated with percent parasitemia at both 0.75 or 1 percent hematocrit with the same correlation coefficient of r2 = 0.99. The sensitivity of P. falciparum D6 strain to chloroquine and to 3,6-bis-omega-diethylaminoamyloxyxanthone, a novel antimalarial, determined by the CyQUANT assay were comparable to those obtained by the traditional [3H]-ethanolamine assay: IC50 value of chloroquine was 54 nM and 51 nM by the CyQUANT and [3H]-ethanolamine assay, respectively; IC50 value for 3,6-bis-omega-diethylaminoamyloxyxanthone was 254 nM and 223 nM by the CyQUANT and [3H]-ethanolamine assay, respectively. This procedure requires no radioisotope, uses simple equipment, and is an easy and convenient procedure, with no washing and harvesting steps. Moreover, all procedures can be set up continuously and thus, the CyQUANT assay is suitable in automatic high through-put drug screening of antimalarial drugs.

On peculiarities of the cascade γ decay of heavy nuclei

International Nuclear Information System (INIS)

Boneva, S.T.; Khitrov, V.A.; Popov, Yu.P.; Sukhovoj, A.M.; Vasil'eva, E.V.; Yazvitskij, Yu.S.

1987-01-01

Comparison of measured and calculated by statistical theory sums of two-quanta cascade intensities in compound-nuclei 163 ≤ A ≤ 183 points to the dependence of cascade intensity on the structure of initial and intermediate levels. The dependence of two-quanta cascade intensity sum on reduced neutron widths of compound states of even-even nuclei-targets of rare earth regions is detected. In 175 Yb and 179 Hf nuclei a considerable increase in the intensity of two-quanta cascades at the energy of their intermediate level in the range of the calculated position of one-quasiparticle states of the Saxon-Woods deformed potential is observed

Designing the Cascade inertial confinement fusion reactor

International Nuclear Information System (INIS)

Pitts, J.H.

1987-01-01

The primary goal in designing inertial confinement fusion (ICF) reactors is to produce electrical power as inexpensively as possible, with minimum activation and without compromising safety. This paper discusses a method for designing the Cascade rotating ceramic-granule-blanket reactor (Pitts, 1985) and its associated power plant (Pitts and Maya, 1985). Although focus is on the cascade reactor, the design method and issues presented are applicable to most other ICF reactors

Hadronic cascade processes

International Nuclear Information System (INIS)

Ilgenfritz, E.M.; Kripfganz, J.; Moehring, H.J.

1977-01-01

The analytical treatment of hadronic decay cascades within the framework of the statistical bootstrap model is demonstrated on the basis of a simple variant. Selected problems for a more comprehensive formulation of the model such as angular momentum conservation, quantum statistical effects, and the immediate applicability to particle production processes at high energies are discussed in detail

INCAS: an analytical model to describe displacement cascades

Energy Technology Data Exchange (ETDEWEB)

Jumel, Stephanie E-mail: stephanie.jumel@edf.fr; Claude Van-Duysen, Jean E-mail: jean-claude.van-duysen@edf.fr

2004-07-01

REVE (REactor for Virtual Experiments) is an international project aimed at developing tools to simulate neutron irradiation effects in Light Water Reactor materials (Fe, Ni or Zr-based alloys). One of the important steps of the project is to characterise the displacement cascades induced by neutrons. Accordingly, the Department of Material Studies of Electricite de France developed an analytical model based on the binary collision approximation. This model, called INCAS (INtegration of CAScades), was devised to be applied on pure elements; however, it can also be used on diluted alloys (reactor pressure vessel steels, etc.) or alloys composed of atoms with close atomic numbers (stainless steels, etc.). INCAS describes displacement cascades by taking into account the nuclear collisions and electronic interactions undergone by the moving atoms. In particular, it enables to determine the mean number of sub-cascades induced by a PKA (depending on its energy) as well as the mean energy dissipated in each of them. The experimental validation of INCAS requires a large effort and could not be carried out in the framework of the study. However, it was verified that INCAS results are in conformity with those obtained from other approaches. As a first application, INCAS was applied to determine the sub-cascade spectrum induced in iron by the neutron spectrum corresponding to the central channel of the High Flux Irradiation Reactor of Oak Ridge National Laboratory.

INCAS: an analytical model to describe displacement cascades

Science.gov (United States)

Jumel, Stéphanie; Claude Van-Duysen, Jean

2004-07-01

REVE (REactor for Virtual Experiments) is an international project aimed at developing tools to simulate neutron irradiation effects in Light Water Reactor materials (Fe, Ni or Zr-based alloys). One of the important steps of the project is to characterise the displacement cascades induced by neutrons. Accordingly, the Department of Material Studies of Electricité de France developed an analytical model based on the binary collision approximation. This model, called INCAS (INtegration of CAScades), was devised to be applied on pure elements; however, it can also be used on diluted alloys (reactor pressure vessel steels, etc.) or alloys composed of atoms with close atomic numbers (stainless steels, etc.). INCAS describes displacement cascades by taking into account the nuclear collisions and electronic interactions undergone by the moving atoms. In particular, it enables to determine the mean number of sub-cascades induced by a PKA (depending on its energy) as well as the mean energy dissipated in each of them. The experimental validation of INCAS requires a large effort and could not be carried out in the framework of the study. However, it was verified that INCAS results are in conformity with those obtained from other approaches. As a first application, INCAS was applied to determine the sub-cascade spectrum induced in iron by the neutron spectrum corresponding to the central channel of the High Flux Irradiation Reactor of Oak Ridge National Laboratory.

INCAS: an analytical model to describe displacement cascades

International Nuclear Information System (INIS)

Jumel, Stephanie; Claude Van-Duysen, Jean

2004-01-01

REVE (REactor for Virtual Experiments) is an international project aimed at developing tools to simulate neutron irradiation effects in Light Water Reactor materials (Fe, Ni or Zr-based alloys). One of the important steps of the project is to characterise the displacement cascades induced by neutrons. Accordingly, the Department of Material Studies of Electricite de France developed an analytical model based on the binary collision approximation. This model, called INCAS (INtegration of CAScades), was devised to be applied on pure elements; however, it can also be used on diluted alloys (reactor pressure vessel steels, etc.) or alloys composed of atoms with close atomic numbers (stainless steels, etc.). INCAS describes displacement cascades by taking into account the nuclear collisions and electronic interactions undergone by the moving atoms. In particular, it enables to determine the mean number of sub-cascades induced by a PKA (depending on its energy) as well as the mean energy dissipated in each of them. The experimental validation of INCAS requires a large effort and could not be carried out in the framework of the study. However, it was verified that INCAS results are in conformity with those obtained from other approaches. As a first application, INCAS was applied to determine the sub-cascade spectrum induced in iron by the neutron spectrum corresponding to the central channel of the High Flux Irradiation Reactor of Oak Ridge National Laboratory

Cascades and Dissipative Anomalies in Compressible Fluid Turbulence

Directory of Open Access Journals (Sweden)

Gregory L. Eyink

2018-02-01

Full Text Available We investigate dissipative anomalies in a turbulent fluid governed by the compressible Navier-Stokes equation. We follow an exact approach pioneered by Onsager, which we explain as a nonperturbative application of the principle of renormalization-group invariance. In the limit of high Reynolds and Péclet numbers, the flow realizations are found to be described as distributional or “coarse-grained” solutions of the compressible Euler equations, with standard conservation laws broken by turbulent anomalies. The anomalous dissipation of kinetic energy is shown to be due not only to local cascade but also to a distinct mechanism called pressure-work defect. Irreversible heating in stationary, planar shocks with an ideal-gas equation of state exemplifies the second mechanism. Entropy conservation anomalies are also found to occur via two mechanisms: an anomalous input of negative entropy (negentropy by pressure work and a cascade of negentropy to small scales. We derive “4/5th-law”-type expressions for the anomalies, which allow us to characterize the singularities (structure-function scaling exponents required to sustain the cascades. We compare our approach with alternative theories and empirical evidence. It is argued that the “Big Power Law in the Sky” observed in electron density scintillations in the interstellar medium is a manifestation of a forward negentropy cascade or an inverse cascade of usual thermodynamic entropy.

Cascades and Dissipative Anomalies in Compressible Fluid Turbulence

Science.gov (United States)

Eyink, Gregory L.; Drivas, Theodore D.

2018-02-01

We investigate dissipative anomalies in a turbulent fluid governed by the compressible Navier-Stokes equation. We follow an exact approach pioneered by Onsager, which we explain as a nonperturbative application of the principle of renormalization-group invariance. In the limit of high Reynolds and Péclet numbers, the flow realizations are found to be described as distributional or "coarse-grained" solutions of the compressible Euler equations, with standard conservation laws broken by turbulent anomalies. The anomalous dissipation of kinetic energy is shown to be due not only to local cascade but also to a distinct mechanism called pressure-work defect. Irreversible heating in stationary, planar shocks with an ideal-gas equation of state exemplifies the second mechanism. Entropy conservation anomalies are also found to occur via two mechanisms: an anomalous input of negative entropy (negentropy) by pressure work and a cascade of negentropy to small scales. We derive "4 /5 th-law"-type expressions for the anomalies, which allow us to characterize the singularities (structure-function scaling exponents) required to sustain the cascades. We compare our approach with alternative theories and empirical evidence. It is argued that the "Big Power Law in the Sky" observed in electron density scintillations in the interstellar medium is a manifestation of a forward negentropy cascade or an inverse cascade of usual thermodynamic entropy.

Gradients in Catostomid assemblages along a reservoir cascade

Science.gov (United States)

Miranda, Leandro E.; Keretz, Kevin R.; Gilliland, Chelsea R.

2017-01-01

Serial impoundment of major rivers leads to alterations of natural flow dynamics and disrupts longitudinal connectivity. Catostomid fishes (suckers, family Catostomidae) are typically found in riverine or backwater habitats yet are able to persist in impounded river systems. To the detriment of conservation, there is limited information about distribution of catostomid fishes in impounded rivers. We examined the longitudinal distribution of catostomid fishes over 23 reservoirs of the Tennessee River reservoir cascade, encompassing approximately 1600 km. Our goal was to develop a basin-scale perspective to guide conservation efforts. Catostomid species composition and assemblage structure changed longitudinally along the reservoir cascade. Catostomid species biodiversity was greatest in reservoirs lower in the cascade. Assemblage composition shifted from dominance by spotted sucker Minytrema melanops and buffalos Ictiobus spp. in the lower reservoirs to carpsuckers Carpiodes spp. midway through the cascade and redhorses Moxostoma spp. in the upper reservoirs. Most species did not extend the length of the cascade, and some species were rare, found in low numbers and in few reservoirs. The observed gradients in catostomid assemblages suggest the need for basin-scale conservation measures focusing on three broad areas: (1) conservation and management of the up-lake riverine reaches of the lower reservoirs, (2) maintenance of the access to quality habitat in tributaries to the upper reservoirs and (3) reintroductions into currently unoccupied habitat within species' historic distributions

Cascade reactor: granule fabrication processes

International Nuclear Information System (INIS)

Erlandson, O.D.; Winkler, E.O.; Maya, I.; Pitts, J.H.

1985-01-01

A key feature of Cascade is the granular blanket. Of the many blanket material options open to Cascade, fabrication of Li 2 O granules was felt to offer the greatest challenge. The authors explored available methods for initial Li 2 O granule fabrication. They identified three cost-effective processes for fabricating Li 2 O granules: the VSM drop-melt furnace process, which is based on melting and spheroidizing irregularly shaped Li 2 O feed granules; the LiOH process, which spheroidizes liquefied LiOH and uses GA Technologies' sphere-forming procedures; and the Li 2 CO 3 sol-gel process, used for making spherical fuel particles for the high-temperature gas-cooled reactor (HTGR). Each process is described below

Genetic counseling and cascade genetic testing in Lynch syndrome.

Science.gov (United States)

Hampel, Heather

2016-07-01

Lynch syndrome is the most common cause of inherited colorectal and endometrial cancers. Individuals with Lynch syndrome have a 10-80 % lifetime risk for colorectal cancer and a 15-60 % lifetime risk for endometrial cancer. Both cancers are preventable through chemoprevention, intensive cancer surveillance, and risk-reducing surgery options. Efforts to identify as many individuals with Lynch syndrome as possible will prevent cancers and save lives. This includes the traditional cancer genetic counseling model whereby individuals with and without cancer are evaluated for a possible Lynch syndrome diagnosis based on their personal and family history of colon polyps and cancers. It also includes universal tumor screening for Lynch syndrome whereby all individuals with colorectal or endometrial cancer are screened for tumor features of Lynch syndrome at the time of diagnosis. Those with tumors suspicious for Lynch syndrome are referred for cancer genetic counseling regardless of their family history of cancer. This two approaches must be maximized to attain high patient reach. Finally, and perhaps most importantly, cascade testing among the at-risk relatives of those diagnosed with Lynch syndrome is critically important to maximize the diagnosis of individuals with Lynch syndrome. In fact, the cost-effectiveness of universal tumor screening for Lynch syndrome relies entirely on counseling and testing as many at-risk individuals as possible since young unaffected individuals stand to benefit the most from an early diagnosis of Lynch syndrome. This approach must be optimized to achieve high family reach. It will take a concerted effort from patients, clinicians and public health officials to improve current approaches to the diagnosis of Lynch syndrome and the prevention and treatment of Lynch syndrome-associated cancer but these lessons can be applied to other conditions as the ultimate example of personalized medicine.

In vitro systems in pneumocystis research

DEFF Research Database (Denmark)

Dei-Cas, E; Cailliez, J C; Lundgren, Bettina

1996-01-01

as well as elimination of host cell debris from parasite extracts. In other investigations, such as transmission, infectivity, life cycle, biochemical, in vitro culture or drug-screening studies, viable and infectious Pneumocystis organisms are urgently required. However, there is no generally accepted...

In vitro evaluation of medicinal, antioxidant activities and phytochemical screening of iphiona grantioides and pluchea arguta subsp

International Nuclear Information System (INIS)

Naveed, S.; Ibrar, M.

2016-01-01

The crude ethanolic extracts (EE) derived from different parts of Iphiona grantioides (flower, leaf, stem and root) and Pluchea arguta subsp glabra Qaiser (leaf, stem and root) were screened In vitro for possible antioxidant, antibacterial, antifungal activities and phytochemical profile. Results for phytochemical screening revealed the presence of various important primary and secondary metabolites including carbohydrates, protein, essential oils, tannins, flavonoids, saponins, glycosides, phytosterol, tri-terphenoids and volatile oil in the ethanolic extracts (EE) of different parts of I. grantioides and P. arguta. Significant antibacterial activity was observed for flower and leaf (EE) of I. grantioides against Klebsiela pneumonia and Escherichia coli, while moderate antibacterial activity was showed by extracts from other parts of this plant. Similarly P. arguta leaf (EE) showed significant inhibitory activity against Escherichia coli, Pseudomonas aeroginosa and Micrococcus luteus than its stem and roots extract. The crude ethanolic extract of all parts of I. grantioides and P. arguta proved a rich source of fungicidal potential. Both the plants proved to have antioxidant potential by exhibiting DPPH radical scavenging activity. So it may be concluded from the present investigations that I. grantioides and P. arguta, both have a wide range of antibacterial, antifungal and antioxidant properties and can be utilized for the development of antimicrobial drugs for human beings, animals and as safe pesticides in agricultural practices as well as could be an important source of natural radical scavengers. (author)

A simple method for potential flow simulation of cascades

Indian Academy of Sciences (India)

vortex panel method to simulate potential flow in cascades is presented. The cascade ... The fluid loading on the blades, such as the normal force and pitching moment, may ... of such discrete infinite array singularities along the blade surface.

In silico study of in vitro GPCR assays by QSAR modeling

Science.gov (United States)

The U.S. EPA is screening thousands of chemicals of environmental interest in hundreds of in vitro high-throughput screening (HTS) assays (the ToxCast program). One goal is to prioritize chemicals for more detailed analyses based on activity in molecular initiating events (MIE) o...

DECREASING OF WATER TROPHY IN CASCADE SYSTEMS, ON EXAMPLE OF THE SOŁA RIVER DAM CASCADE (SOUTHERN POLAND

Directory of Open Access Journals (Sweden)

Ewa Jachniak

2014-10-01

Full Text Available In this thesis the subject of water self-purification in cascade systems of water reservoirs was engaged. The results of hydrobiological research of three dam reservoirs (Tresna, Porąbka and Czaniec, creating the Soła river dam cascade were presented. The trophic status of these reservoirs was defined on the grounds of the concentration of chlorophyll a, biomass of phytoplankton and occurrence of indicating species of planktonic algae. The results of research indicated on decreasing of water trophy in the layout from the highest into the lowest reservoir of the cascade. The average concentrations of chlorophyll a amounted appropriately 19,99 μg·dm-3, 8,74 μg·dm-3 and 4,29 μg·dm-3, instead the average biomass of phytoplankton amounted appropriately 4,1 mg·dm-3, 3,4 mg·dm-3 and 0,1 mg·dm-3. The observed species of algae confirmed occurrence of differences between reservoirs. In Tresna reservoir more species of phytoplankton indicating for eutrophy were thrived, instead in Porąbka and Czaniec reservoirs the species occurring in oligomesotrophic water thrived. Water self-purification in the Soła river dam cascade expressed decreasing of their fertility is important for water management of the region, because the Czaniec reservoir fulfill a function of water-supply reservoir.

Cascades for hydrogen isotope separation using metal hydrides

International Nuclear Information System (INIS)

Hill, F.B.; Grzetic, V.

1982-01-01

Designs are presented for continuous countercurrent hydrogen isotope separation cascades based on the use of metal hydrides. The cascades are made up of pressure swing adsorption (PSA) or temperature swing adsorption (TSA) stages. The designs were evolved from consideration of previously conducted studies of the separation performance of four types of PSA and TSA processes

Cascades for hydrogen isotope separation using metal hydrides

Energy Technology Data Exchange (ETDEWEB)

Hill, F B; Grzetic, V [Brookhaven National Lab., Upton, NY (USA)

1983-02-01

Designs are presented for continuous countercurrent hydrogen isotope separation cascades based on the use of metal hydrides. The cascades are made up of pressure swing adsorption (PSA) or temperature swing adsorption (TSA) stages. The designs were evolved from consideration of previously conducted studies of the separation performance of four types of PSA and TSA processes.

A cascaded online uninterruptible power supply using reduced semiconductor

DEFF Research Database (Denmark)

Zhang, Lei; Loh, Poh Chiang; Gao, Feng

2011-01-01

A cascaded online uninterruptible power supply (UPS) is proposed here that uses 25% lesser semiconductor, as compared to its traditional H-bridge cascaded precedence. Unlike other component-saving configurations where compromises are unavoidable, almost no performance degradations and constraints...

Intermittent Flow Regimes in a Transonic Fan Airfoil Cascade

Directory of Open Access Journals (Sweden)

J. Lepicovsky

2004-01-01

velocity.To date, this flow behavior has only been observed in a linear transonic cascade. Further research is necessary to confirm this phenomenon occurs in actual transonic fans and is not the by-product of an endwall restricted linear cascade.

Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

DEFF Research Database (Denmark)

Hansen, Suzanne L.; Sterjev, Zoran; Werngreen, Marie

2012-01-01

The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been...... screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline...

Peroxisome Proliferator-Activated Receptor-γ Ligands: Potential Pharmacological Agents for Targeting the Angiogenesis Signaling Cascade in Cancer

Directory of Open Access Journals (Sweden)

Costas Giaginis

2008-01-01

Full Text Available Peroxisome proliferator-activated receptor-γ (PPAR-γ has currently been considered as molecular target for the treatment of human metabolic disorders. Experimental data from in vitro cultures, animal models, and clinical trials have shown that PPAR-γ ligand activation regulates differentiation and induces cell growth arrest and apoptosis in a variety of cancer types. Tumor angiogenesis constitutes a multifaceted process implicated in complex downstream signaling pathways that triggers tumor growth, invasion, and metastasis. In this aspect, accumulating in vitro and in vivo studies have provided extensive evidence that PPAR-γ ligands can function as modulators of the angiogenic signaling cascade. In the current review, the crucial role of PPAR-γ ligands and the underlying mechanisms participating in tumor angiogenesis are summarized. Targeting PPAR-γ may prove to be a potential therapeutic strategy in combined treatments with conventional chemotherapy; however, special attention should be taken as there is also substantial evidence to support that PPAR-γ ligands can enhance angiogenic phenotype in tumoral cells.

Performance of a novel keratinocyte-based reporter cell line to screen skin sensitizers in vitro

International Nuclear Information System (INIS)

Emter, Roger; Ellis, Graham; Natsch, Andreas

2010-01-01

In vitro tests are needed to replace animal tests to screen for the skin sensitization potential of chemicals. Skin sensitizers are electrophilic molecules and the Nrf2-electrophile-sensing pathway comprising the repressor protein Keap1, the transcription factor Nrf2 and the antioxidant response element (ARE) is emerging as a toxicity pathway induced by skin sensitizers. Previously, we screened a large set of chemicals in the reporter cell line AREc32, which contains an eight-fold repeat of the rat GSTA2 ARE-sequence upstream of a luciferase reporter gene in the human breast cancer cell line MCF7. This approach was now further developed to bring it closer to the conditions in the human skin and to propose a fully standardized assay. To this end, a luciferase reporter gene under control of a single copy of the ARE-element of the human AKR1C2 gene was stably inserted into HaCaT keratinocytes. A standard operating procedure was developed whereby chemicals are routinely tested at 12 concentrations in triplicate for significant induction of gene activity. We report results from this novel assay on (i) a list of reference chemicals published by ECVAM, (ii) the ICCVAM list of chemicals for validation of alternative endpoints in the LLNA and (iii) on a more general list of 67 chemicals derived from the ICCVAM database. For comparison, peptide reactivity data are presented for the same chemicals. The results indicate a good predictive value of this approach for hazard identification. Its technical simplicity, the high-throughput format and the good predictivity may make this assay a candidate for rapid validation to meet the tight deadline to replace animal tests for skin sensitization by 2013 set by the European authorities.

Assessment of pyrrolizidine alkaloid-induced toxicity in an in vitro screening model.

Science.gov (United States)

Li, Yan Hong; Kan, Winnie Lai Ting; Li, Na; Lin, Ge

2013-11-25

Pyrrolizidine alkaloids (PAs) are a group of heterocyclic phytotoxins present in a wide range of plants. The consumption of PA-containing medicinal herbs or PA-contaminated foodstuffs has long been reported to cause human hepatotoxicity. However, the degrees of hepatotoxicity of different PAs are unknown, which makes it difficult to determine a universal threshold of toxic dose of individual PAs for safe regulation of PA-containing natural products. The aim of the present study is to develop a simple and convenient in vitro model to assess the hepatotoxicity of different PAs. Six common cytotoxicity assays were used to evaluate the hepatotoxicity of different PAs in human hepatocellular carcinoma HepG2 cells. The combination of MTT and bromodeoxyuridine incorporation (BrdU) assays demonstrated to be a suitable method to evaluate the toxic potencies of various PAs in HepG2 cells, and the results indicated that otonecine-type PA (clivorine: IC₂₀=0.013 ± 0.004 mM (MTT), 0.066 ± 0.031 mM (BrdU)) exhibited significantly higher cytotoxic and anti-proliferative effects than retronecine-type PA (retrorsine: IC₂₀=0.27 ± 0.07 mM (MTT), 0.19 ± 0.03 mM (BrdU)). While as expected, the known less toxic platyphylline-type PA (platyphylline: IC₂₀=0.85 ± 0.11 mM (MTT), 1.01 ± 0.40 mM (BrdU)) exhibited significantly less toxicity. The different cytotoxic and anti-proliferative potencies of various PAs in the same retronecine-type could also be discriminated by using the combined MTT and BrdU assays. In addition, the developed assays were further utilized to test alkaloid extract of Gynura segetum, a senecionine and seneciphylline-containing herb, the overall cytotoxicity of two PAs in the extract was comparable to that of these two PAs tested individually. Using the developed in vitro model, the cytotoxicity of different PAs and the extract of a PA-containing herb were investigated in parallel in one system, and their different hepatotoxic potencies were determined

Collision cascades in HTSC [high temperature superconductors] as possible pinning centres

International Nuclear Information System (INIS)

Kirsanov, V.V.; Musin, N.N.; Roskin, D.G.; Shamarina, E.I.

1993-01-01

Computer simulation was used to study the development of collision cascades in monocrystals of YBa 2 Cu 3 O 7 , YBa 2 Cu 3 O 6.5 and YBa 2 Cu 3 O 6 which were produced by primary knock-on atoms (PKAs) during fast particle irradiation. Oxygen deficit was found to have an effect on the development of cascades in these phases, with a lowering of oxygen deficit decreasing cascade sizes. The type of PKA was observed to influence the geometry of a cascade. When heavy PKAs form a cascade, the oxygen sublattice is practically undisturbed, with very little disorder; while with oxygen ions as the PKA, the main displacements fall within the oxygen subsystem. In addition, the angular dependences of the displacement threshold energy for yttrium and barium ions are given. (Author)

In vitro mutagenesis and production of agronomically useful potato variants

International Nuclear Information System (INIS)

Das, A.; Gosal, S.S.; Sidhu, J.S.; Dhaliwal, H.S.

2001-01-01

In vitro grown shoot cultures of two Indian potato varieties 'Kufri jyoti' and 'Kufri Chandramukhi' were subjected to gamma irradiation at 20 and 40 Gy. The irradiated shoot cultures were subcultured to yield a generation of plantlets. After 4-6 weeks of incubation, these shoots were transferred onto MS medium supplemented with benzylaminopurine, BAP (10mg/1) and sucrose (8% w/v) and incubated at 20 deg. C. The M 1 V 3 plants were screened in vitro for late blight resistance by detached leaf method. The resistant plants were screened in M 1 V 4 generation by artificial inoculation of sporangial inoculum on the pot sown plants. Chlorophyll persistence is a simple screening method for heat tolerance. Chlorophyll persistence of different plantlets showed that the percentage of injury was less in the case of plants, which had been obtained from irradiated material. In the case of control plants, there was one hundred-percent damage to the plants. The mutation frequency was calculated for characters like late blight resistance and heat tolerance (in vitro microtuberisation and chlorophyll persistence). The gamma ray dose of 40 Gy was observed to produce a higher mutation frequency

3D Printing of Tissue Engineered Constructs for in vitro Modeling of Disease Progression and Drug Screening

Science.gov (United States)

Vanderburgh, Joseph; Sterling, Julie A.

2016-01-01

2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D versus 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design (CAD) file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs (TECs) that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs. PMID:27169894

Interband cascade light emitting devices based on type-II quantum wells

International Nuclear Information System (INIS)

Yang, Rui Q.; Lin, C.H.; Murry, S.J.

1997-01-01

The authors discuss physical processes in the newly developed type-II interband cascade light emitting devices, and review their recent progress in the demonstration of the first type-II interband cascade lasers and the observation of interband cascade electroluminescence up to room temperature in a broad mid-infrared wavelength region (extended to 9 μm)

Cascade Processes in Muonic Hydrogen Atoms

International Nuclear Information System (INIS)

Faifman, M. P.; Men'Shikov, L. I.

2001-01-01

The QCMC scheme created earlier for cascade calculations in heavy hadronic atoms of hydrogen isotopes has been modified and applied to the study of cascade processes in the μp muonic hydrogen atoms. The distribution of μp atoms over kinetic energies has been obtained and the yields of K-series X-rays per one stopped muon have been calculated.Comparison with experimental data indicated directly that for muonic and pionic atoms new types of non-radiative transitions are essential, while they are negligible for heavy (kaonic, antiprotonic, etc.) atoms. These processes have been considered and their probabilities have been estimated.

Numerical routine for magnetic heat pump cascading

DEFF Research Database (Denmark)

Filonenko, Konstantin; Lei, Tian; Engelbrecht, Kurt

Heat pumps use low-temperature heat absorbed from the energy source to create temperature gradient (TG) across the energy sink. Magnetic heat pumps (MHP) can perform this function through operating active magnetic regeneration (AMR) cycle. For building heating, TGs of up to a few K might...... and 3 K. Changing the number of MHPs, we optimized input parameters to achieve maximum heating powers. We have found that both maximum heating power and COP decrease together with number of heat pumps, but the TGs and the temperature span can be largely increased. References [1] M. Tahavori et al., “A...... be necessary, which is hardly achievable with a single MHP and such techniques as cascading are required. Series and parallel cascading increase the AMR span and heating power, respectively, but do not change TG. Therefore, the intermediate type of cascading was proposed with individual MHPs separately...

Cascade enzymatic reactions for efficient carbon sequestration.

Science.gov (United States)

Xia, Shunxiang; Zhao, Xueyan; Frigo-Vaz, Benjamin; Zheng, Wenyun; Kim, Jungbae; Wang, Ping

2015-04-01

Thermochemical processes developed for carbon capture and storage (CCS) offer high carbon capture capacities, but are generally hampered by low energy efficiency. Reversible cascade enzyme reactions are examined in this work for energy-efficient carbon sequestration. By integrating the reactions of two key enzymes of RTCA cycle, isocitrate dehydrogenase and aconitase, we demonstrate that intensified carbon capture can be realized through such cascade enzymatic reactions. Experiments show that enhanced thermodynamic driving force for carbon conversion can be attained via pH control under ambient conditions, and that the cascade reactions have the potential to capture 0.5 mol carbon at pH 6 for each mole of substrate applied. Overall it manifests that the carbon capture capacity of biocatalytic reactions, in addition to be energy efficient, can also be ultimately intensified to approach those realized with chemical absorbents such as MEA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Microengineering methods for cell-based microarrays and high-throughput drug-screening applications

International Nuclear Information System (INIS)

Xu Feng; Wu Jinhui; Wang Shuqi; Gurkan, Umut Atakan; Demirci, Utkan; Durmus, Naside Gozde

2011-01-01

Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

Microengineering methods for cell-based microarrays and high-throughput drug-screening applications

Energy Technology Data Exchange (ETDEWEB)

Xu Feng; Wu Jinhui; Wang Shuqi; Gurkan, Umut Atakan; Demirci, Utkan [Department of Medicine, Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Durmus, Naside Gozde, E-mail: udemirci@rics.bwh.harvard.edu [School of Engineering and Division of Biology and Medicine, Brown University, Providence, RI (United States)

2011-09-15

Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

Rapid Screening of In-Vitro Regenerated Plantlets of Four Nigerian ...

African Journals Online (AJOL)

Prof. Ogunji

Tissue culture technique provides a rapid means of studying plant-pathogen interaction in a controlled ... Keywords: cowpea, in-vitro regeneration, hormones, Fusarium wilt, protocols. .... solanacearum and evaluation of tomato in Nepal.

Hybrid Modulation Scheme for Cascaded H-Bridge Inverter Cells ...

African Journals Online (AJOL)

This work proposes a switching technique for cascaded H-Bridge (CHB) cells. Single carrier Sinusoidal PWM (SCSPWM) scheme is employed in the generation of the gating signals. A sequential switching and base PWM circulation schemes are presented for this fundamental cascaded multilevel inverter topology.

Cascade in muonic and pionic atoms with Z = 1

International Nuclear Information System (INIS)

Markushin, V.E.

1999-01-01

Recent theoretical and experimental studies of the exotic atoms with Z = 1 are reviewed. An interplay between the atomic internal and external degrees of freedom is essential for a good description of the atomic cascade. The perspective of ab initio cascade calculations is outlined

Climate Change and Baleen Whale Trophic Cascades in Greenland

Science.gov (United States)

2009-09-30

DISTRIBUTION STATEMENT A: Approved for public release; distribution is unlimited. Climate Change and Baleen Whale Trophic Cascades in Greenland...SUBTITLE Climate Change And Baleen Whale Trophic Cascades In Greenland 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss.

Science.gov (United States)

Murugappan, Gayathree; Ohno, Mika S; Lathi, Ruth B

2015-05-01

To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL). Decision analytic model comparing costs and clinical outcomes. Academic recurrent pregnancy loss programs. Women with unexplained RPL. IVF/PGS with 24-chromosome screening and expectant management. Cost per live birth. The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300 per live birth compared with $418 per live birth with expectant management. In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A multivariate approach to heavy flavour tagging with cascade training

International Nuclear Information System (INIS)

Bastos, J; Liu, Y

2007-01-01

This paper compares the performance of artificial neural networks and boosted decision trees, with and without cascade training, for tagging b-jets in a collider experiment. It is shown, using a Monte Carlo simulation of WH→lνq q-bar events, that for a b-tagging efficiency of 50%, the light jet rejection power given by boosted decision trees without cascade training is about 55% higher than that given by artificial neural networks. The cascade training technique can improve the performance of boosted decision trees and artificial neural networks at this b-tagging efficiency level by about 35% and 80% respectively. We conclude that the cascade trained boosted decision trees method is the most promising technique for tagging heavy flavours at collider experiments

Study on computer-aided simulation procedure for multicomponent separating cascade

International Nuclear Information System (INIS)

Kinoshita, Masahiro

1982-11-01

The present report reviews the author's study on the computer-aided simulation procedure for a multicomponent separating cascade. As a conclusion, two very powerful simulation procedures have been developed for cascades composed of separating elements whose separation factors are very large. They are applicable in cases where interstage flow rates are input variables for the calculation and stage separation factors are given either as constants or as functions of compositions of the up and down streams. As an application of the new procedure, a computer-aided simulation study has been performed for hydrogen isotope separating cascades by porous membrane method. A cascade system configuration is developed and pertinent design specifications are determined in an example case of the feed conditions and separation requirements. (author)

Annealing simulation of cascade damage using MARLOWE-DAIQUIRI codes

International Nuclear Information System (INIS)

Muroga, Takeo

1984-01-01

The localization effect of the defects generated by the cascade damage on the properties of solids was studied by using a computer code. The code is based on the two-body collision approximation method and the Monte Carlo method. The MARLOWE and DAIQUIRI codes were partly improved to fit the present calculation of the annealing of cascade damage. The purpose of this study is to investigate the behavior of defects under the simulated reactive and irradiation condition. Calculation was made for alpha iron (BCC), and the threshold energy was set at 40 eV. The temperature dependence of annealing and the growth of a cluster were studied. The overlapping effect of cascade was studied. At first, the extreme case of overlapping was studied, then the practical cases were estimated by interpolation. The state of overlapping of cascade corresponded to the irradiation speed. The interaction between cascade and dislocations was studied, and the calculation of the annealing of primary knock-out atoms (PKA) in alpha iron was performed. At low temperature, the effect of dislocations was large, but the growth of vacancy was not seen. At high temperature, the effect of dislocations was small. The evaluation of the simulation of various ion irradiation and the growth efficiency of defects were performed. (Kato, T.)

Substrate-driven chemotactic assembly in an enzyme cascade

Science.gov (United States)

Zhao, Xi; Palacci, Henri; Yadav, Vinita; Spiering, Michelle M.; Gilson, Michael K.; Butler, Peter J.; Hess, Henry; Benkovic, Stephen J.; Sen, Ayusman

2018-03-01

Enzymatic catalysis is essential to cell survival. In many instances, enzymes that participate in reaction cascades have been shown to assemble into metabolons in response to the presence of the substrate for the first enzyme. However, what triggers metabolon formation has remained an open question. Through a combination of theory and experiments, we show that enzymes in a cascade can assemble via chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to study the coordinated movement of the first four enzymes of the glycolysis cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase. We show that each enzyme independently follows its own specific substrate gradient, which in turn is produced by the preceding enzymatic reaction. Furthermore, we find that the chemotactic assembly of enzymes occurs even under cytosolic crowding conditions.

The relationship between collisional phase defect distribution and cascade collapse efficiency

International Nuclear Information System (INIS)

Morishita, K.; Heinisch, H.L.; Ishino, S.; Sekimura, N.

1994-01-01

Defect distributions after the collisional phase of cascade damage processes were calculated using the computer simulation code MARLOWE, which is based on the binary collision approximation. The densities of vacant sites were evaluated in defect-dense regions at the end of the collisional phase in simulated ion irradiations of several pure metals (Au, Ag, Cu, Ni, Fe, Mo and W). The vacancy density distributions were compared to the measured cascade collapse efficiencies obtained from low-dose ion irradiations of thin foils reported in the literature to identify the minimum or ''critical'' values of the vacancy densities during the collisional phase corresponding to cascade collapse. The critical densities are generally independent of the cascade energy in the same metal. The relationships between physical properties of the target elements and the critical densities are discussed within the framework of the cascade thermal spike model. ((orig.))

Cascade statistics in the binary collision approximation and in full molecular dynamics

International Nuclear Information System (INIS)

Hou, M.; Pan, Z.Y.

1995-01-01

The Binary Collision Approximation (BCA) and Molecular Dynamics (MD) are used to simulate low energy atomic collision cascades in solids. Results are compared and discussed on the example of copper and gold self irradiation. For MD, long range N-body potentials are built, similar to those deduced from the second moment semi-empirical tight binding model. The pair interaction contribution is splined to a Moliere screened Coulomb potential at small separation distances. The BCA calculations are performed with the MARLOWE program, using the same Moliere potential as for MD, and modelling the N-body contribution by a binding of the atoms to their equilibrium lattice sites. The scattering integrals are estimated by means of a 4 points Gauss-Mehler quadrature. In MD, the NVT equations of motion are integrated with a constant time step of 2 fs. For the NVE cascade simulations, the Newton equations of motion are solved with a dynamically adjusted time step, kept lower than 2 fs. The influence of the time step on the simulated trajectories is discussed. The mean number of moving atoms with total energy above threshold values ranging from 1 to 100 eV is estimated as a function of time over 300 fs both with MARLOWE and by MD. This estimate is repeated for external primary energies ranging from 250 eV to 1 keV. In the case of copper, the BCA results are found to be in remarkable agreement with MD over about 200 fs cascade development, provided the size of the crystallite used in MD is sufficiently large in order to account for the early mechanical response of the close environment. This agreement between the two methods is found to be the best when the binding energy of the target atoms as modelled in the BCA is adjusted to a value close to the cohesive energy. In the case of gold, the agreement between BCA and MD is reasonable and the results suggest the need of an accurate modelling of linear collision sequences in the BCA. (orig.)

Signaling Cascades: Consequences of Varying Substrate and Phosphatase Levels

DEFF Research Database (Denmark)

Feliu, Elisenda; Knudsen, Michael; Wiuf, Carsten Henrik

2012-01-01

We study signaling cascades with an arbitrary number of layers of one-site phosphorylation cycles. Such cascades are abundant in nature and integrated parts of many pathways. Based on the Michaelis-Menten model of enzyme kinetics and the law of mass-action, we derive explicit analytic expressions...

High energy evolution of soft gluon cascades

International Nuclear Information System (INIS)

Shuvaev, A.; Wallon, S.

2006-01-01

In this paper we derive an evolution equation for the gluon density in soft gluon cascades emitted from any colored source, in the leading logarithmic approximation of perturbative QCD. We show that this equation has the same form as the BFKL equation in the forward case. An explicit expression for the total cascade wavefunction involving an arbitrary number of soft gluons is obtained. Renormalization of the colored source wavefunction turns out to be responsible for the reggeization of the source. (orig.)

High energy evolution of soft gluon cascades

Energy Technology Data Exchange (ETDEWEB)

Shuvaev, A. [St. Petersburg Nuclear Physics Institute, Gatchina, St. Petersburg district (Russian Federation); Wallon, S. [Universite Paris XI, Laboratoire de Physique Theorique, Orsay Cedex (France)

2006-04-15

In this paper we derive an evolution equation for the gluon density in soft gluon cascades emitted from any colored source, in the leading logarithmic approximation of perturbative QCD. We show that this equation has the same form as the BFKL equation in the forward case. An explicit expression for the total cascade wavefunction involving an arbitrary number of soft gluons is obtained. Renormalization of the colored source wavefunction turns out to be responsible for the reggeization of the source. (orig.)

Synthesis of d‐ and l‐Phenylalanine Derivatives by Phenylalanine Ammonia Lyases: A Multienzymatic Cascade Process†

Science.gov (United States)

Parmeggiani, Fabio; Lovelock, Sarah L.; Weise, Nicholas J.; Ahmed, Syed T.

2015-01-01

Abstract The synthesis of substituted d‐phenylalanines in high yield and excellent optical purity, starting from inexpensive cinnamic acids, has been achieved with a novel one‐pot approach by coupling phenylalanine ammonia lyase (PAL) amination with a chemoenzymatic deracemization (based on stereoselective oxidation and nonselective reduction). A simple high‐throughput solid‐phase screening method has also been developed to identify PALs with higher rates of formation of non‐natural d‐phenylalanines. The best variants were exploited in the chemoenzymatic cascade, thus increasing the yield and ee value of the d‐configured product. Furthermore, the system was extended to the preparation of those l‐phenylalanines which are obtained with a low ee value using PAL amination. PMID:27478261

Synthesis of d- and l-Phenylalanine Derivatives by Phenylalanine Ammonia Lyases: A Multienzymatic Cascade Process**

Science.gov (United States)

Parmeggiani, Fabio; Lovelock, Sarah L; Weise, Nicholas J; Ahmed, Syed T; Turner, Nicholas J

2015-01-01

The synthesis of substituted d-phenylalanines in high yield and excellent optical purity, starting from inexpensive cinnamic acids, has been achieved with a novel one-pot approach by coupling phenylalanine ammonia lyase (PAL) amination with a chemoenzymatic deracemization (based on stereoselective oxidation and nonselective reduction). A simple high-throughput solid-phase screening method has also been developed to identify PALs with higher rates of formation of non-natural d-phenylalanines. The best variants were exploited in the chemoenzymatic cascade, thus increasing the yield and ee value of the d-configured product. Furthermore, the system was extended to the preparation of those l-phenylalanines which are obtained with a low ee value using PAL amination. PMID:25728350

Modeling techniques for quantum cascade lasers

Energy Technology Data Exchange (ETDEWEB)

Jirauschek, Christian [Institute for Nanoelectronics, Technische Universität München, D-80333 Munich (Germany); Kubis, Tillmann [Network for Computational Nanotechnology, Purdue University, 207 S Martin Jischke Drive, West Lafayette, Indiana 47907 (United States)

2014-03-15

Quantum cascade lasers are unipolar semiconductor lasers covering a wide range of the infrared and terahertz spectrum. Lasing action is achieved by using optical intersubband transitions between quantized states in specifically designed multiple-quantum-well heterostructures. A systematic improvement of quantum cascade lasers with respect to operating temperature, efficiency, and spectral range requires detailed modeling of the underlying physical processes in these structures. Moreover, the quantum cascade laser constitutes a versatile model device for the development and improvement of simulation techniques in nano- and optoelectronics. This review provides a comprehensive survey and discussion of the modeling techniques used for the simulation of quantum cascade lasers. The main focus is on the modeling of carrier transport in the nanostructured gain medium, while the simulation of the optical cavity is covered at a more basic level. Specifically, the transfer matrix and finite difference methods for solving the one-dimensional Schrödinger equation and Schrödinger-Poisson system are discussed, providing the quantized states in the multiple-quantum-well active region. The modeling of the optical cavity is covered with a focus on basic waveguide resonator structures. Furthermore, various carrier transport simulation methods are discussed, ranging from basic empirical approaches to advanced self-consistent techniques. The methods include empirical rate equation and related Maxwell-Bloch equation approaches, self-consistent rate equation and ensemble Monte Carlo methods, as well as quantum transport approaches, in particular the density matrix and non-equilibrium Green's function formalism. The derived scattering rates and self-energies are generally valid for n-type devices based on one-dimensional quantum confinement, such as quantum well structures.

Modeling techniques for quantum cascade lasers

Science.gov (United States)

Jirauschek, Christian; Kubis, Tillmann

2014-03-01

Quantum cascade lasers are unipolar semiconductor lasers covering a wide range of the infrared and terahertz spectrum. Lasing action is achieved by using optical intersubband transitions between quantized states in specifically designed multiple-quantum-well heterostructures. A systematic improvement of quantum cascade lasers with respect to operating temperature, efficiency, and spectral range requires detailed modeling of the underlying physical processes in these structures. Moreover, the quantum cascade laser constitutes a versatile model device for the development and improvement of simulation techniques in nano- and optoelectronics. This review provides a comprehensive survey and discussion of the modeling techniques used for the simulation of quantum cascade lasers. The main focus is on the modeling of carrier transport in the nanostructured gain medium, while the simulation of the optical cavity is covered at a more basic level. Specifically, the transfer matrix and finite difference methods for solving the one-dimensional Schrödinger equation and Schrödinger-Poisson system are discussed, providing the quantized states in the multiple-quantum-well active region. The modeling of the optical cavity is covered with a focus on basic waveguide resonator structures. Furthermore, various carrier transport simulation methods are discussed, ranging from basic empirical approaches to advanced self-consistent techniques. The methods include empirical rate equation and related Maxwell-Bloch equation approaches, self-consistent rate equation and ensemble Monte Carlo methods, as well as quantum transport approaches, in particular the density matrix and non-equilibrium Green's function formalism. The derived scattering rates and self-energies are generally valid for n-type devices based on one-dimensional quantum confinement, such as quantum well structures.

Bearing-Only Formation Control for Cascade Multirobots

Directory of Open Access Journals (Sweden)

Qing Han

2016-01-01

Full Text Available A new formation control method is proposed, which is used to queue multirobots in a single-direction cascade structure. In the cascade formation, each robot is a follower for the previous robot and a leader for the next robot, and the robots in the middle act as both leader and follower. The follower robot can only observe the bearing information of the leader robot. The observability of the cascade leader-follower formation is studied, which shows that the bearing-only observation meets the observability conditions required for the nonlinear system. Based on the bearing-only observations, the unscented Kalman filter (UKF is employed for the state estimation of the leader and the follower robots at all levels, which enables the real-time movement control of the follower robots via the input-output feedback control. Simulation results demonstrate that the proposed approach can efficiently control the formation of multirobots as desired.

The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers

International Nuclear Information System (INIS)

Azam, Philippe; Peiffer, Jean-Luc; Chamousset, Delphine; Tissier, Marie-Helene; Bonnet, Pierre-Antoine; Vian, Laurence; Fabre, Isabelle; Ourlin, Jean-Claude

2006-01-01

Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Only MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers

Cascade laser applications: trends and challenges

Science.gov (United States)

d'Humières, B.; Margoto, Éric; Fazilleau, Yves

2016-03-01

When analyses need rapid measurements, cost effective monitoring and miniaturization, tunable semiconductor lasers can be very good sources. Indeed, applications like on-field environmental gas analysis or in-line industrial process control are becoming available thanks to the advantage of tunable semiconductor lasers. Advances in cascade lasers (CL) are revolutionizing Mid-IR spectroscopy with two alternatives: interband cascade lasers (ICL) in the 3-6μm spectrum and quantum cascade lasers (QCL), with more power from 3 to 300μm. The market is getting mature with strong players for driving applications like industry, environment, life science or transports. CL are not the only Mid-IR laser source. In fact, a strong competition is now taking place with other technologies like: OPO, VCSEL, Solid State lasers, Gas, SC Infrared or fiber lasers. In other words, CL have to conquer a share of the Mid-IR application market. Our study is a market analysis of CL technologies and their applications. It shows that improvements of components performance, along with the progress of infrared laser spectroscopy will drive the CL market growth. We compare CL technologies with other Mid-IR sources and estimate their share in each application market.

Noise properties and cascadability of SOA-EA regenerators

DEFF Research Database (Denmark)

Öhman, Filip; Bischoff, Svend; Tromborg, Bjarne

2002-01-01

We suggest and analyse a new device containing concatenated pairs of semiconductor optical amplifiers (SOAs) and electroabsorption modulators (EAs). The device has regenerative properties and improves the cascadability of optical fibre links.......We suggest and analyse a new device containing concatenated pairs of semiconductor optical amplifiers (SOAs) and electroabsorption modulators (EAs). The device has regenerative properties and improves the cascadability of optical fibre links....

Computer codes for simulating atomic-displacement cascades in solids subject to irradiation

International Nuclear Information System (INIS)

Asaoka, Takumi; Taji, Yukichi; Tsutsui, Tsuneo; Nakagawa, Masayuki; Nishida, Takahiko

1979-03-01

In order to study atomic displacement cascades originating from primary knock-on atoms in solids subject to incident radiation, the simulation code CASCADE/CLUSTER is adapted for use on FACOM/230-75 computer system. In addition, the code is modified so as to plot the defect patterns in crystalline solids. As other simulation code of the cascade process, MARLOWE is also available for use on the FACOM system. To deal with the thermal annealing of point defects produced in the cascade process, the code DAIQUIRI developed originally for body-centered cubic crystals is modified to be applicable also for face-centered cubic lattices. By combining CASCADE/CLUSTER and DAIQUIRI, we then prepared a computer code system CASCSRB to deal with heavy irradiation or saturation damage state of solids at normal temperature. Furthermore, a code system for the simulation of heavy irradiations CASCMARL is available, in which MARLOWE code is substituted for CASCADE in the CASCSRB system. (author)

Status and understanding of groundwater quality in the Cascade Range and Modoc Plateau study unit, 2010: California GAMA Priority Basin Project

Science.gov (United States)

Fram, Miranda S.; Shelton, Jennifer L.

2015-01-01

Groundwater quality in the Cascade Range and Modoc Plateau study unit was investigated as part of the California State Water Resources Control Board’s Groundwater Ambient Monitoring and Assessment (GAMA) Program Priority Basin Project. The study was designed to provide a statistically unbiased assessment of untreated groundwater quality in the primary aquifer system. The depth of the primary aquifer system for the Cascade Range and Modoc Plateau study unit was delineated by the depths of the screened or open intervals of wells in the State of California’s database of public-supply wells. Two types of assessments were made: a status assessment that described the current quality of the groundwater resource, and an understanding assessment that made evaluations of relations between groundwater quality and potential explanatory factors representing characteristics of the primary aquifer system. The assessments characterize the quality of untreated groundwater, not the quality of treated drinking water delivered to consumers by water distributors.

LIMIT SOLUTIONS OF EQUATIONS OF A DC HIGH-VOLTAGE CASCADE GENERATOR

Directory of Open Access Journals (Sweden)

V. O. Brzhezitsky

2015-04-01

Full Text Available In the paper the issue of calculating the high voltage cascade mode oscillator with a nonlinear load using the analytical method under different conditions of selection values of its components is presented. The peculiarity of the method of the study is that during multivariate calculations output parameters load generator remain unchanged. For high-voltage cascade direct current power found conditions under which can be significantly reduced high capacity capacitors cascade generator. The calculations show that acceptable for practical applications of high-voltage characteristics of cascade generators can be achieved with substantial reduction of the volume of their constituents, and thus substantial decline in their value.

Electrical conductivity and charge carrier screening in weakly non-ideal argon plasmas

International Nuclear Information System (INIS)

Guenther, K.; Lang, S.; Radtke, R.

1983-01-01

A pulsed argon discharge as a stable source of weakly non-ideal plasmas is described in connection with the diagnostic necessities for conductivity measurements. The parameters overlap the range for stationary arcs and allow comparison with measurements in cascade arcs. The measured conductivities are explained using the binary collision model considering collisions with neutrals, excited atoms, and ions. A relation between the screening parameter and non-ideality is proposed which should be valid for all elements. (author)

Electrical conductivity and charge carrier screening in weakly non-ideal argon plasmas

Energy Technology Data Exchange (ETDEWEB)

Guenther, K; Lang, S; Radtke, R [Akademie der Wissenschaften der DDR, Jena. Zentralinstitut fuer Elektronenphysik

1983-07-14

A pulsed argon discharge as a stable source of weakly non-ideal plasmas is described in connection with the diagnostic necessities for conductivity measurements. The parameters overlap the range for stationary arcs and allow comparison with measurements in cascade arcs. The measured conductivities are explained using the binary collision model considering collisions with neutrals, excited atoms, and ions. A relation between the screening parameter and non-ideality is proposed which should be valid for all elements.

Interferometric modulation of quantum cascade interactions

Science.gov (United States)

Cusumano, Stefano; Mari, Andrea; Giovannetti, Vittorio

2018-05-01

We consider many-body quantum systems dissipatively coupled by a cascade network, i.e., a setup in which interactions are mediated by unidirectional environmental modes propagating through a linear optical interferometer. In particular we are interested in the possibility of inducing different effective interactions by properly engineering an external dissipative network of beam splitters and phase shifters. In this work we first derive the general structure of the master equation for a symmetric class of translation-invariant cascade networks. Then we show how, by tuning the parameters of the interferometer, one can exploit interference effects to tailor a large variety of many-body interactions.

In-Vitro Antibacterial Activities And Preliminary Phytochemical ...

African Journals Online (AJOL)

Studies on the in-vitro antibacterial activities and phytochemical screening of the aqueous and ethanolic extracts of Zingiber officinale (ginger) against some clinical bacterial isolates (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa) obtained from ear and urine samples were carried out using ...

Cascade multiplicity inside deuteron in Π d high energy collisions

International Nuclear Information System (INIS)

Kisielewska, D.

1983-01-01

Multiplicity distribution of double scattering events is analysed using the additive quark model including the cascading effect. The mean multiplicity of particles produced in the process of cascading estimated for Π d experiments at 100, 205 and 360 GeV/c is equal to 1.15 ± .31. This value does not depend on the momentum of the incident pion. Some indications are found that the probability of cascading depends on multiplicity of the collision with the first nucleon and is smaller for low multiplicities. (author)

Is cascade reinforcement likely when sympatric and allopatric populations exchange migrants?

Science.gov (United States)

Yukilevich, Roman; Aoki, Fumio

2016-04-01

When partially reproductively isolated species come back into secondary contact, these taxa may diverge in mating preferences and sexual cues to avoid maladaptive hybridization, a process known as reinforcement. This phenomenon often leads to reproductive character displacement (RCD) between sympatric and allopatric populations of reinforcing species that differ in their exposure to hybridization. Recent discussions have reinvigorated the idea that RCD may give rise to additional speciation between conspecific sympatric and allopatric populations, dubbing the concept "cascade reinforcement." Despite some empirical studies supporting cascade reinforcement, we still know very little about the conditions for its evolution. In the present article, we address this question by developing an individual-based population genetic model that explicitly simulates cascade reinforcement when one of the hybridizing species is split into sympatric and allopatric populations. Our results show that when sympatric and allopatric populations reside in the same environment and only differ in their exposure to maladaptive hybridization, migration between them generally inhibits the evolution of cascade by spreading the reinforcement alleles from sympatry into allopatry and erasing RCD. Under these conditions, cascade reinforcement only evolved when migration rate between sympatric and allopatric populations was very low. This indicates that stabilizing sexual selection in allopatry is generally ineffective in preventing the spread of reinforcement alleles. Only when sympatric and allopatric populations experienced divergent ecological selection did cascade reinforcement evolve in the presence of substantial migration. These predictions clarify the conditions for cascade reinforcement and facilitate our understanding of existing cases in nature.

Effect of collision cascades on dislocations in tungsten: A molecular dynamics study

Energy Technology Data Exchange (ETDEWEB)

Fu, B.Q., E-mail: bqfu@scu.edu.cn [Key Laboratory for Radiation Physics and Technology, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610065 (China); Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Fitzgerald, S.P. [Department of Applied Mathematics, University of Leeds, Leeds LS2 9JT (United Kingdom); Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Hou, Q.; Wang, J.; Li, M. [Key Laboratory for Radiation Physics and Technology, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610065 (China)

2017-02-15

Highlights: • A cascde near a dislocation promotes climb motion. • Kinks induced by cascade facilitate the dipoles motion toward the cascade. • Shearing of dipole is dependent on PKA energy, position, direction, and dipole width. - Abstract: Tungsten (W) is the prime candidate material for the divertor and other plasma-facing components in DEMO. The point defects (i.e. vacancies and self-interstitials) produced in collision cascades caused by incident neutrons aggregate into dislocation loops (and voids), which strongly affect the mechanical properties. The point defects also interact with existing microstructural features, and understanding these processes is crucial for modelling the long term microstructural evolution of the material under fusion conditions. In this work, we performed molecular dynamics simulations of cascades interacting with initially straight edge dislocation dipoles. It was found that the residual vacancy number usually exceeds the residual interstitial number for cascades interacting with vacancy type dipoles, but for interstitial type dipoles these are close. We observed that a cascade near a dislocation promotes climb, i.e. it facilitates the movement of point defects along the climb direction. We also observed that the dislocations move easily along the glide direction, and that kinks are formed near the centre of the cascade, which then facilitate the movement of the dipoles. Some dipoles are sheared off by the cascade, and this is dependent on PKA energy, position, direction, and the width of dipole.

Parton-hadron cascade approach at SPS and RHIC

Energy Technology Data Exchange (ETDEWEB)

Nara, Yasushi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

1998-07-01

A parton-hadron cascade model which is the extension of hadronic cascade model incorporating hard partonic scattering based on HIJING is presented to describe the space-time evolution of parton/hadron system produced by ultra-relativistic nuclear collisions. Hadron yield, baryon stopping and transverse momentum distribution are calculated and compared with HIJING and VNI. Baryon density, energy density and temperature for RHIC are calculated within this model. (author)

Efficient collective influence maximization in cascading processes with first-order transitions

Science.gov (United States)

Pei, Sen; Teng, Xian; Shaman, Jeffrey; Morone, Flaviano; Makse, Hernán A.

2017-01-01

In many social and biological networks, the collective dynamics of the entire system can be shaped by a small set of influential units through a global cascading process, manifested by an abrupt first-order transition in dynamical behaviors. Despite its importance in applications, efficient identification of multiple influential spreaders in cascading processes still remains a challenging task for large-scale networks. Here we address this issue by exploring the collective influence in general threshold models of cascading process. Our analysis reveals that the importance of spreaders is fixed by the subcritical paths along which cascades propagate: the number of subcritical paths attached to each spreader determines its contribution to global cascades. The concept of subcritical path allows us to introduce a scalable algorithm for massively large-scale networks. Results in both synthetic random graphs and real networks show that the proposed method can achieve larger collective influence given the same number of seeds compared with other scalable heuristic approaches. PMID:28349988

Cascading Dynamics of Heterogenous Scale-Free Networks with Recovery Mechanism

Directory of Open Access Journals (Sweden)

Shudong Li

2013-01-01

Full Text Available In network security, how to use efficient response methods against cascading failures of complex networks is very important. In this paper, concerned with the highest-load attack (HL and random attack (RA on one edge, we define five kinds of weighting strategies to assign the external resources for recovering the edges from cascading failures in heterogeneous scale-free (SF networks. The influence of external resources, the tolerance parameter, and the different weighting strategies on SF networks against cascading failures is investigated carefully. We find that, under HL attack, the fourth kind of weighting method can more effectively improve the integral robustness of SF networks, simultaneously control the spreading velocity, and control the outburst of cascading failures in SF networks than other methods. Moreover, the third method is optimal if we only knew the local structure of SF networks and the uniform assignment is the worst. The simulations of the real-world autonomous system in, Internet have also supported our findings. The results are useful for using efficient response strategy against the emergent accidents and controlling the cascading failures in the real-world networks.

Critical assessment and ramifications of a purported marine trophic cascade

Science.gov (United States)

Grubbs, R. Dean; Carlson, John K; Romine, Jason G.; Curtis, Tobey H; McElroy, W. David; McCandless, Camilla T; Cotton, Charles F; Musick, John A.

2016-01-01

When identifying potential trophic cascades, it is important to clearly establish the trophic linkages between predators and prey with respect to temporal abundance, demographics, distribution, and diet. In the northwest Atlantic Ocean, the depletion of large coastal sharks was thought to trigger a trophic cascade whereby predation release resulted in increased cownose ray abundance, which then caused increased predation on and subsequent collapse of commercial bivalve stocks. These claims were used to justify the development of a predator-control fishery for cownose rays, the “Save the Bay, Eat a Ray” fishery, to reduce predation on commercial bivalves. A reexamination of data suggests declines in large coastal sharks did not coincide with purported rapid increases in cownose ray abundance. Likewise, the increase in cownose ray abundance did not coincide with declines in commercial bivalves. The lack of temporal correlations coupled with published diet data suggest the purported trophic cascade is lacking the empirical linkages required of a trophic cascade. Furthermore, the life history parameters of cownose rays suggest they have low reproductive potential and their populations are incapable of rapid increases. Hypothesized trophic cascades should be closely scrutinized as spurious conclusions may negatively influence conservation and management decisions.

A Discrete Dynamical System Approach to Pathway Activation Profiles of Signaling Cascades.

Science.gov (United States)

Catozzi, S; Sepulchre, J-A

2017-08-01

In living organisms, cascades of covalent modification cycles are one of the major intracellular signaling mechanisms, allowing to transduce physical or chemical stimuli of the external world into variations of activated biochemical species within the cell. In this paper, we develop a novel method to study the stimulus-response of signaling cascades and overall the concept of pathway activation profile which is, for a given stimulus, the sequence of activated proteins at each tier of the cascade. Our approach is based on a correspondence that we establish between the stationary states of a cascade and pieces of orbits of a 2D discrete dynamical system. The study of its possible phase portraits in function of the biochemical parameters, and in particular of the contraction/expansion properties around the fixed points of this discrete map, as well as their bifurcations, yields a classification of the cascade tiers into three main types, whose biological impact within a signaling network is examined. In particular, our approach enables to discuss quantitatively the notion of cascade amplification/attenuation from this new perspective. The method allows also to study the interplay between forward and "retroactive" signaling, i.e., the upstream influence of an inhibiting drug bound to the last tier of the cascade.

Interrelation of structure and operational states in cascading failure of overloading lines in power grids

Science.gov (United States)

Xue, Fei; Bompard, Ettore; Huang, Tao; Jiang, Lin; Lu, Shaofeng; Zhu, Huaiying

2017-09-01

As the modern power system is expected to develop to a more intelligent and efficient version, i.e. the smart grid, or to be the central backbone of energy internet for free energy interactions, security concerns related to cascading failures have been raised with consideration of catastrophic results. The researches of topological analysis based on complex networks have made great contributions in revealing structural vulnerabilities of power grids including cascading failure analysis. However, existing literature with inappropriate assumptions in modeling still cannot distinguish the effects between the structure and operational state to give meaningful guidance for system operation. This paper is to reveal the interrelation between network structure and operational states in cascading failure and give quantitative evaluation by integrating both perspectives. For structure analysis, cascading paths will be identified by extended betweenness and quantitatively described by cascading drop and cascading gradient. Furthermore, the operational state for cascading paths will be described by loading level. Then, the risk of cascading failure along a specific cascading path can be quantitatively evaluated considering these two factors. The maximum cascading gradient of all possible cascading paths can be used as an overall metric to evaluate the entire power grid for its features related to cascading failure. The proposed method is tested and verified on IEEE30-bus system and IEEE118-bus system, simulation evidences presented in this paper suggests that the proposed model can identify the structural causes for cascading failure and is promising to give meaningful guidance for the protection of system operation in the future.

Node vulnerability of water distribution networks under cascading failures

International Nuclear Information System (INIS)

Shuang, Qing; Zhang, Mingyuan; Yuan, Yongbo

2014-01-01

Water distribution networks (WDNs) are important in modern lifeline system. Its stability and reliability are critical for guaranteeing high living quality and continuous operation of urban functions. The aim of this paper is to evaluate the nodal vulnerability of WDNs under cascading failures. Vulnerability is defined to analyze the effects of the consequent failures. A cascading failure is a step-by-step process which is quantitatively investigated by numerical simulation with intentional attack. Monitored pressures in different nodes and flows in different pipes have been used to estimate the network topological structure and the consequences of nodal failure. Based on the connectivity loss of topological structure, the nodal vulnerability has been evaluated. A load variation function is established to record the nodal failure reason and describe the relative differences between the load and the capacity. The proposed method is validated by an illustrative example. The results revealed that the network vulnerability should be evaluated with the consideration of hydraulic analysis and network topology. In the case study, 70.59% of the node failures trigger the cascading failures with different failure processes. It is shown that the cascading failures result in severe consequences in WDNs. - Highlights: • The aim of this paper is to evaluate the nodal vulnerability of water distribution networks under cascading failures. • Monitored pressures and flows have been used to estimate the network topological structure and the consequences of nodal failure. • Based on the connectivity loss of topological structure, the nodal vulnerability has been evaluated. • A load variation function is established to record the failure reason and describe the relative differences between load and capacity. • The results show that 70.59% of the node failures trigger the cascading failures with different failure processes

Placement of Synchronized Measurements for Power System Observability during Cascaded Outages

Science.gov (United States)

Thirugnanasambandam, Venkatesh; Jain, Trapti

2017-11-01

Cascaded outages often result in power system islanding followed by a blackout and therefore considered as a severe disturbance. Maintaining the observability of each island may help in taking proper control actions to preserve the stability of individual islands thus, averting system collapse. With this intent, a strategy for placement of synchronized measurements, which can be obtained from phasor measurement units (PMU), has been proposed in this paper to keep the system observable during cascaded outages also. Since, all the cascaded failures may not lead to islanding situations, therefore, failures leading to islanding as well as non-islanding situations have been considered. A topology based algorithm has been developed to identify the islanding/non-islanding condition created by a particular cascaded event. Additional contingencies such as single line loss and single PMU failure have also been considered after the occurrence of cascaded events. The proposed method is further extended to incorporate the measurement redundancy, which is desirable for a reliable state estimation. The proposed scheme is tested on IEEE 14-bus, IEEE 30-bus and a practical Indian 246-bus networks. The numerical results ensure the observability of the power system under system intact as well as during cascaded islanding and non-islanding disturbances.

Use of external metabolizing systems when testing for endocrine disruption in the T-screen assay

International Nuclear Information System (INIS)

Taxvig, Camilla; Olesen, Pelle Thonning; Nellemann, Christine

2011-01-01

Although, it is well-established that information on the metabolism of a substance is important in the evaluation of its toxic potential, there is limited experience with incorporating metabolic aspects into in vitro tests for endocrine disrupters. The aim of the current study was a) to study different in vitro systems for biotransformation of ten known endocrine disrupting chemicals (EDs): five azole fungicides, three parabens and 2 phthalates, b) to determine possible changes in the ability of the EDs to bind and activate the thyroid receptor (TR) in the in vitro T-screen assay after biotransformation and c) to investigate the endogenous metabolic capacity of the GH3 cells, the cell line used in the T-screen assay, which is a proliferation assay used for the in vitro detection of agonistic and antagonistic properties of compounds at the level of the TR. The two in vitro metabolizing systems tested the human liver S9 mix and the PCB-induced rat microsomes gave an almost complete metabolic transformation of the tested parabens and phthalates. No marked difference the effects in the T-screen assay was observed between the parent compounds and the effects of the tested metabolic extracts. The GH3 cells themselves significantly metabolized the two tested phthalates dimethyl phthalate (DMP) and diethyl phthalate (DEP). Overall the results and qualitative data from the current study show that an in vitro metabolizing system using liver S9 or microsomes could be a convenient method for the incorporation of metabolic and toxicokinetic aspects into in vitro testing for endocrine disrupting effects.

Atomistic simulations of displacement cascades in Y2O3 single crystal

International Nuclear Information System (INIS)

Dholakia, Manan; Chandra, Sharat; Valsakumar, M.C.; Mathi Jaya, S.

2014-01-01

Graphical abstract: (a) The averaged distortion index and the Y–O bond length of the Y 2 O 3 octahedra as a function of the simulation time for 5 keV PKA. (b) Shows the nearest neighbourhood of one of the Y ions as a function of simulation time, showing the destruction and the recovery of the YO 6 octahedron during the cascade corresponding to 5 keV Y PKA. - Highlights: • Qualitative difference in displacement cascades exists for Y and O PKA. • Nearest neighbour correlation between Y and O ions exists even at cascade peak. • Cascade core in Y 2 O 3 does not undergo melting. • Topological connectivity of YO 6 polyhedra plays important role in stability of Y 2 O 3 . - Abstract: We study the characteristics of displacement cascades in single crystal Y 2 O 3 using classical molecular dynamics. There are two possible ways to generate the cascades in yttria, using either the Y or the O atoms as the primary knock-on (PKA) atom. It is shown that there is a qualitative difference in the characteristics of the cascades obtained in these two cases. Even though the crystal is seen to be in a highly disordered state in the cascade volume, as seen from the plots of radial distribution function, the correlation between the Y and O atoms is not completely lost. This facilitates a quick recovery of the system during the annealing phase. Topological connectivity of the YO 6 polyhedral units plays an important role in imparting stability to the Y 2 O 3 crystal. These characteristics of the cascades can help explain the stability of the yttria nanoparticles when they are dispersed in oxide dispersion strengthened steels

Cascade Chaotic System With Applications.

Science.gov (United States)

Zhou, Yicong; Hua, Zhongyun; Pun, Chi-Man; Chen, C L Philip

2015-09-01

Chaotic maps are widely used in different applications. Motivated by the cascade structure in electronic circuits, this paper introduces a general chaotic framework called the cascade chaotic system (CCS). Using two 1-D chaotic maps as seed maps, CCS is able to generate a huge number of new chaotic maps. Examples and evaluations show the CCS's robustness. Compared with corresponding seed maps, newly generated chaotic maps are more unpredictable and have better chaotic performance, more parameters, and complex chaotic properties. To investigate applications of CCS, we introduce a pseudo-random number generator (PRNG) and a data encryption system using a chaotic map generated by CCS. Simulation and analysis demonstrate that the proposed PRNG has high quality of randomness and that the data encryption system is able to protect different types of data with a high-security level.

Bankruptcy cascades in interbank markets.

Directory of Open Access Journals (Sweden)

Gabriele Tedeschi

Full Text Available We study a credit network and, in particular, an interbank system with an agent-based model. To understand the relationship between business cycles and cascades of bankruptcies, we model a three-sector economy with goods, credit and interbank market. In the interbank market, the participating banks share the risk of bad debits, which may potentially spread a bank's liquidity problems through the network of banks. Our agent-based model sheds light on the correlation between bankruptcy cascades and the endogenous economic cycle of booms and recessions. It also demonstrates the serious trade-off between, on the one hand, reducing risks of individual banks by sharing them and, on the other hand, creating systemic risks through credit-related interlinkages of banks. As a result of our study, the dynamics underlying the meltdown of financial markets in 2008 becomes much better understandable.

A high-throughput inhibition screening of major human cytochrome P450 enzymes using an in vitro cocktail and liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Qin, Chong-Zhen; Ren, Xian; Tan, Zhi-Rong; Chen, Yao; Yin, Ji-Ye; Yu, Jing; Qu, Jian; Zhou, Hong-Hao; Liu, Zhao-Qian

2014-02-01

A sensitive and high-throughput inhibition screening liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of five probe metabolites (7-hydroxycoumarin, CYP2A6; 4-hydroxytolbutamide, CYP2C9; 4'-hydroxymephenytoin, CYP2C19; α-hydroxymetoprolol, CYP2D6; and 1-hydroxymidazolam, CYP3A4) for in vitro cytochrome P450 activity determination in human liver microsome and recombinant. All the metabolites and the internal standard, tramadol, were separated on a Waters 2695 series liquid chromatograph with a Phenomenex Luna C18 column (150 × 2.0 mm, 5 µm). Quality control samples and a positive control CYP inhibitor were included in the method. The IC50 values determined for typical CYP inhibitors were reproducible and in agreement with the literature. The method was selective and showed good accuracy (99.13-103.37%), and inter-day (RSD high-quality and -throughput cocktail provides suitable information in drug discovery and screening for new drug entities. Copyright © 2013 John Wiley & Sons, Ltd.

Investigation of cascade effect failure for tungsten armour

International Nuclear Information System (INIS)

Makhankov, A.; Barabash, V.; Berkhov, N.; Divavin, V.; Giniatullin, R.; Grigoriev, S.; Ibbott, C.; Komarov, V.; Labusov, A.; Mazul, I.; McDonald, J.; Tanchuk, V.; Youchison, D.

2001-01-01

The glancing angle of incident power on the target of a tokamak divertor results in doubled and highly peaked heat flux onto adjacent downstream tile in the case of lost of tile event (LOTE). As a result downstream tile has higher probability to fail resulting in triple loads to the next downstream tile and so on (cascade effect). This paper devoted to analytical and experimental investigation of the cascade effect failure for the flat tile option of tungsten armoured plasma facing components. Armour geometry resistant to the cascade effect failure was selected on the base of thermal and stress analyses. Experimental investigation of the LOTE has been performed also. Small size W/Cu mock-up withstood not only LOTE simulation load, but also survived afterwards for 1500 cycles at 26-28 MW/m 2 without damage in joint

Process Evaluation Tools for Enzymatic Cascades Welcome Message

DEFF Research Database (Denmark)

Abu, Rohana

improvement and implementation. Hence, the goal of this thesis is to evaluate the process concepts in enzymatic cascades in a systematic manner, using tools such as thermodynamic and kinetic analysis. Three relevant case studies have been used to exemplify the approach. In the first case study, thermodynamic......Biocatalysis is attracting significant attention from both academic and industrial scientists due to the excellent capability of enzyme to catalyse selective reactions. Recently, much interest has been shown in the application of enzymatic cascades as a useful tool in organic synthesis......, the kinetics can be controlled in a highly efficient way to achieve a sufficiently favourable conversion to a given target product. This is exemplified in the second case study, in the kinetic modelling of the formation of 2-ketoglutarate from glucoronate, the second case study. This cascade consists of 4...

Some characteristics of the development of high energy electromagnetic cascades in the atmosphere

International Nuclear Information System (INIS)

Jablonski, Z.; Tomaszewski, A.; Wrotniak, J.A.

1977-01-01

Results of the calculations of some characteristics of electromagnetic cascades induced by cosmic radiation are showed. The cascade parameters are influenced by effect of threshold energy of gamma quanta registration in emulsion chambers. Ratio of integral gamma quanta energies in cascade to initial particle energy and mean energy weighted radius as a function of primary interaction hight, as well as total energy and number of gamma quanta in the cascade are calculated. (S.B.)

Malignant transformation in vitro: criteria, biological markers, and application in environmental screening of carcinogens

International Nuclear Information System (INIS)

Borek, C.

1979-01-01

Biological markers which distinguish malignantly transformed fibroblasts from their normal counterpart include pleomorphic morphology, lowered requirement for nutritional factors, loss of density inhibition of growth, complex topography as discernible by scanning electron microscopy, loss in surface proteins, incomplete glycosylation of membrane glycolylipids and glycoproteins, increased production of specific proteases, decreased organization of the cytoskeleton, and acquisition of neoantigens. Several of these markers are not consistently found in transformed epithelial cells and therefore cannot serve to distinguish unequivocally neoplastic epithelial cells from the normal counterparts. The only criteria associated with the transformed nature of both fibroblasts and epithelial cells are the ability of the cells to proliferate in semisolid medium and to induce tumors in appropriate hosts. In vitro systems represent a powerful tool for screening the mutagenic/oncogenic potential of physical, chemical, and environmental agents. Fibroblasts rather than epithelial cells are preferred for this purpose at the present time because of the clear-cut phenotypic differences between the normal and the transformed cells. These systems have been useful in establishing that malignant transformation can be induced by doses as low as 1 rad of X rays or 0.1 rad of neutrons, and that fractionation at low dose levelsleads to enhanced transformation. They have been useful in identifying a large number of hazardous chemicals and in evaluating the relationship between the mutagenic and carcinogenic potential of radiation and chemicals

Cascade Apartments: Deep Energy Multifamily Retrofit

Energy Technology Data Exchange (ETDEWEB)

Gordon, A. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mattheis, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kunkle, R. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Howard, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Lubliner, M. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2014-02-01

In December of 2009-10, King County Housing Authority (KCHA) implemented energy retrofit improvements in the Cascade multifamily community, located in Kent, Washington (marine climate.)This research effort involved significant coordination from stakeholders KCHA, WA State Department of Commerce, utility Puget Sound Energy, and Cascade tenants. This report focuses on the following three primary BA research questions : 1. What are the modeled energy savings using DOE low income weatherization approved TREAT software? 2. How did the modeled energy savings compare with measured energy savings from aggregate utility billing analysis? 3. What is the Savings to Investment Ratio (SIR) of the retrofit package after considering utility window incentives and KCHA capitol improvement funding.

In vitro methods for hazard assessment of industrial chemicals – opportunities and challenges

Directory of Open Access Journals (Sweden)

Chin Lin eWong

2015-05-01

Full Text Available Allergic contact dermatitis (ACD is a delayed-type hypersensitivity immune reaction mediated by T-lymphocytes as a result of repeated exposure of an allergen primarily on skin. ACD accounts for up to 95% of occupational skin diseases (OSDs, with epoxy resins implicated as one of the most common causes of ACD. Efficient high-throughput in vitro screening for accurate identification of compounds and materials that may pose hazardous risks in the workplace is crucial. At present, the murine local lymph node assay (LLNA is the ‘method of choice’ for predicting the sensitizing potency of contact allergens. As the 3Rs principles of reduction, refinement and replacement in animal testing has gained political and economic momentum, several in vitro screening methods have been developed for identifying potential contact allergens. To date, these latter methods have been utilized primarily to assess the skin sensitizing potential of the chemical components of cosmetic products with scant research attention as to the applicability of these methods to industrial chemicals, particularly epoxy resins. Herein we review the currently utilized in vitro methods and identify the knowledge gaps with regard to assessing the generalizability of in vitro screening methods for assessing the skin sensitizing potential of industrial chemicals.

Molecular dynamics simulation of cascade damage in gold

International Nuclear Information System (INIS)

Alonso, E.; Caturla, M.J.; Tang, M.; Huang, H.; Diaz de la Rubia, T.

1997-01-01

High-energy cascades have been simulated in gold using molecular dynamics with a modified embedded atom method potential. The results show that both vacancy and interstitial clusters form with high probability as a result of intracascade processes. The formation of clusters has been interpreted in terms of the high pressures generated in the core of the cascade during the early stages. The authors provide evidence that correlation between interstitial and vacancy clustering exists

Prenatal screening for chromosomal abnormalities in IVF patients that opted for preimplantation genetic screening/diagnosis (PGS/D): a need for revised algorithms in the era of personalized medicine.

Science.gov (United States)

Takyi, Afua; Santolaya-Forgas, Joaquin

2017-06-01

Obstetricians offer prenatal screening for most common chromosomal abnormalities to all pregnant women including those that had in vitro fertilization (IVF) and preimplantation genetic screening/diagnosis (PGS/D). We propose that free fetal DNA in maternal circulation together with the second trimester maternal serum alfa feto protein (MSAFP) and ultrasound imaging is the best prenatal screening test for chromosomal abnormalities and congenital anomalies in IVF-PGD/S patients because risk estimations from all other prenatal screening algorithms for chromosomal abnormalities depend heavily on maternal age which is irrelevant in PGS/D patients.

Participant intimacy: A cluster analysis of the intranuclear cascade

International Nuclear Information System (INIS)

Cugnon, J.; Knoll, J.; Randrup, J.

1981-01-01

The intranuclear cascade for relativistic nuclear collisions is analyzed in terms of clusters consisting of groups of nucleons which are dynamically linked to each other by violent interactions. The formation cross sections for the different cluster types as well as their intrinsic dynamics are studied and compared with the predictions of the linear cascade model ( rows-on-rows ). (orig.)

Damped trophic cascades driven by fishing in model marine ecosystems

DEFF Research Database (Denmark)

Andersen, Ken Haste; Pedersen, Martin

2010-01-01

The largest perturbation on upper trophic levels of many marine ecosystems stems from fishing. The reaction of the ecosystem goes beyond the trophic levels directly targeted by the fishery. This reaction has been described either as a change in slope of the overall size spectrum or as a trophic...... cascade triggered by the removal of top predators. Here we use a novel size- and trait-based model to explore how marine ecosystems might react to perturbations from different types of fishing pressure. The model explicitly resolves the whole life history of fish, from larvae to adults. The results show...... that fishing does not change the overall slope of the size spectrum, but depletes the largest individuals and induces trophic cascades. A trophic cascade can propagate both up and down in trophic levels driven by a combination of changes in predation mortality and food limitation. The cascade is damped...

Cascaded FSO-VLC Communication System

KAUST Repository

Gupta, Akash; Sharma, Nikhil; Garg, Parul; Alouini, Mohamed-Slim

2017-01-01

The proposed cascaded free space optics (FSO)-visible light communication (VLC) system consists of multiple VLC access points which caters the end users connected via a decode and forward (DF) relay to the FSO backhaul link. The FSO link is assumed

A multi-infrastructure gateway for virtual drug screening

NARCIS (Netherlands)

Jaghoori, Mohammad Mahdi; van Altena, Allard J.; Bleijlevens, Boris; Ramezani, Sara; Font, Juan Luis; Olabarriaga, Silvia D.

2015-01-01

In computer-aided drug design, software tools are used to narrow down possible drug candidates, thereby reducing the amount of expensive in vitro research, by a process called virtual screening. This process includes large computations that require advanced computing infrastructure; however, using

Deterministic Role of Collision Cascade Density in Radiation Defect Dynamics in Si

Science.gov (United States)

Wallace, J. B.; Aji, L. B. Bayu; Shao, L.; Kucheyev, S. O.

2018-05-01

The formation of stable radiation damage in solids often proceeds via complex dynamic annealing (DA) processes, involving point defect migration and interaction. The dependence of DA on irradiation conditions remains poorly understood even for Si. Here, we use a pulsed ion beam method to study defect interaction dynamics in Si bombarded in the temperature range from ˜-30 ° C to 210 °C with ions in a wide range of masses, from Ne to Xe, creating collision cascades with different densities. We demonstrate that the complexity of the influence of irradiation conditions on defect dynamics can be reduced to a deterministic effect of a single parameter, the average cascade density, calculated by taking into account the fractal nature of collision cascades. For each ion species, the DA rate exhibits two well-defined Arrhenius regions where different DA mechanisms dominate. These two regions intersect at a critical temperature, which depends linearly on the cascade density. The low-temperature DA regime is characterized by an activation energy of ˜0.1 eV , independent of the cascade density. The high-temperature regime, however, exhibits a change in the dominant DA process for cascade densities above ˜0.04 at.%, evidenced by an increase in the activation energy. These results clearly demonstrate a crucial role of the collision cascade density and can be used to predict radiation defect dynamics in Si.

Spider foraging strategy affects trophic cascades under natural and drought conditions.

Science.gov (United States)

Liu, Shengjie; Chen, Jin; Gan, Wenjin; Schaefer, Douglas; Gan, Jianmin; Yang, Xiaodong

2015-07-23

Spiders can cause trophic cascades affecting litter decomposition rates. However, it remains unclear how spiders with different foraging strategies influence faunal communities, or present cascading effects on decomposition. Furthermore, increased dry periods predicted in future climates will likely have important consequences for trophic interactions in detritus-based food webs. We investigated independent and interactive effects of spider predation and drought on litter decomposition in a tropical forest floor. We manipulated densities of dominant spiders with actively hunting or sit-and-wait foraging strategies in microcosms which mimicked the tropical-forest floor. We found a positive trophic cascade on litter decomposition was triggered by actively hunting spiders under ambient rainfall, but sit-and-wait spiders did not cause this. The drought treatment reversed the effect of actively hunting spiders on litter decomposition. Under drought conditions, we observed negative trophic cascade effects on litter decomposition in all three spider treatments. Thus, reduced rainfall can alter predator-induced indirect effects on lower trophic levels and ecosystem processes, and is an example of how such changes may alter trophic cascades in detritus-based webs of tropical forests.

An ant colony based resilience approach to cascading failures in cluster supply network

Science.gov (United States)

Wang, Yingcong; Xiao, Renbin

2016-11-01

Cluster supply chain network is a typical complex network and easily suffers cascading failures under disruption events, which is caused by the under-load of enterprises. Improving network resilience can increase the ability of recovery from cascading failures. Social resilience is found in ant colony and comes from ant's spatial fidelity zones (SFZ). Starting from the under-load failures, this paper proposes a resilience method to cascading failures in cluster supply chain network by leveraging on social resilience of ant colony. First, the mapping between ant colony SFZ and cluster supply chain network SFZ is presented. Second, a new cascading model for cluster supply chain network is constructed based on under-load failures. Then, the SFZ-based resilience method and index to cascading failures are developed according to ant colony's social resilience. Finally, a numerical simulation and a case study are used to verify the validity of the cascading model and the resilience method. Experimental results show that, the cluster supply chain network becomes resilient to cascading failures under the SFZ-based resilience method, and the cluster supply chain network resilience can be enhanced by improving the ability of enterprises to recover and adjust.

Repositioning FDA Drugs as Potential Cruzain Inhibitors from Trypanosoma cruzi: Virtual Screening, In Vitro and In Vivo Studies

Directory of Open Access Journals (Sweden)

Isidro Palos

2017-06-01

Full Text Available Chagas disease (CD is a neglected disease caused by the parasite Trypanosoma cruzi, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn as cruzain (Cz inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies. 3180 FDA drugs were virtually screened using a structure-based approach. From a first molecular docking analysis, a set of 33 compounds with the best binding energies were selected. Subsequent consensus affinity binding, ligand amino acid contact clustering analysis, and ranked position were used to choose four known pharmacological compounds to be tested in vitro. Mouse blood samples infected with trypomastigotes from INC-5 and NINOA strains were used to test the trypanocidal effect of four selected compounds. Among these drugs, one fibrate antilipemic (etofyllin clofibrate and three β-lactam antibiotics (piperacillin, cefoperazone, and flucloxacillin showed better trypanocidal effects (LC50 range 15.8–26.1 μg/mL in comparison with benznidazole and nifurtimox (LC50 range 33.1–46.7 μg/mL. A short-term in vivo evaluation of these compounds showed a reduction of parasitemia in infected mice (range 90–60% at 6 h, but this was low compared to benznidazole (50%. This work suggests that four known FDA drugs could be used to design and obtain new trypanocidal agents.

Method and apparatus for rapid adjustment of process gas inventory in gaseous diffusion cascades

International Nuclear Information System (INIS)

Dyer, R.H.; Fowler, A.H.; Vanstrum, P.R.

1977-01-01

The invention relates to an improved method and system for making relatively large and rapid adjustments in the process gas inventory of an electrically powered gaseous diffusion cascade in order to accommodate scheduled changes in the electrical power available for cascade operation. In the preferred form of the invention, the cascade is readied for a decrease in electrical input by simultaneously withdrawing substreams of the cascade B stream into respective process-gas-freezing and storage zones while decreasing the datum-pressure inputs to the positioning systems for the cascade control valves in proportion to the weight of process gas so removed. Consequently, the control valve positions are substantially unchanged by the reduction in invention, and there is minimal disturbance of the cascade isotopic gradient. The cascade is readied for restoration of the power cut by simultaneously evaporating the solids in the freezing zones to regenerate the process gas substreams and introducing them to the cascade A stream while increasing the aforementioned datum pressure inputs in proportion to the weight of process gas so returned. In the preferred form of the system for accomplishing these operations, heat exchangers are provided for freezing, storing, and evaporating the various substreams. Preferably, the heat exchangers are connected to use existing cascade auxiliary systems as a heat sink. A common control is employed to adjust and coordinate the necessary process gas transfers and datum pressure adjustments

Mathematical modeling of filling of gas centrifuge cascade for nickel isotope separation by various feed flow rate

Science.gov (United States)

Ushakov, Anton; Orlov, Alexey; Sovach, Victor P.

2018-03-01

This article presents the results of research filling of gas centrifuge cascade for separation of the multicomponent isotope mixture with process gas by various feed flow rate. It has been used mathematical model of the nonstationary hydraulic and separation processes occurring in the gas centrifuge cascade. The research object is definition of the regularity transient of nickel isotopes into cascade during filling of the cascade. It is shown that isotope concentrations into cascade stages after its filling depend on variable parameters and are not equal to its concentration on initial isotope mixture (or feed flow of cascade). This assumption is used earlier any researchers for modeling such nonstationary process as set of steady-state concentration of isotopes into cascade. Article shows physical laws of isotope distribution into cascade stage after its filling. It's shown that varying each parameters of cascade (feed flow rate, feed stage number or cascade stage number) it is possible to change isotope concentration on output cascade flows (light or heavy fraction) for reduction of duration of further process to set of steady-state concentration of isotopes into cascade.

τ polarization in SUSY cascade decays

International Nuclear Information System (INIS)

Choi, S.Y.; Hagiwara, K.; Kim, Y.G.

2006-12-01

τ leptons emitted in cascade decays of supersymmetric particles are polarized. The polarization may be exploited to determine spin and mixing properties of the neutralinos and stau particles involved. (orig.)

Search for neutrino-induced cascade events in the icecube detector

Energy Technology Data Exchange (ETDEWEB)

Panknin, Sebastian

2011-09-15

This thesis presents results of a search for a diffuse flux of high energetic neutrinos from extra-terrestrial origin. Such a flux is predicted by several models of sources of cosmic ray particles. In a neutrino detector, such as IceCube, there are mainly two signatures available for detection of neutrinos: The track-like light signal of a neutrino induced muon and the spherical light pattern of a neutrino induced particle shower, called cascades in this context. The search is based on the measurement of neutrino induced cascades within the IceCube neutrino detector. The data were taken in 2008/2009 with a total uptime of 367 days. At that time the detector was still under construction and had just reached half of its final size. A search for a neutrino flux using cascades is sensitive to all neutrino flavors. A cascade develops within few meters, in contrast to the muon track of several kilometers length. Therefore a good energy reconstruction is possible. With such a reconstruction the astrophysical neutrino flux can be statistically distinguished from the background of atmospheric neutrinos. In the simulation of cascades so far it was not included, that in hadronic cascades muons are produced. This can influence the shape of the cascade, to a less spherical one. Therefore the effect was parameterized in this thesis and included in the simulation. Further cuts on the event topology and reconstructed energy were developed, in order to reduce the background of atmospheric muons and atmospheric neutrinos. Four events from the measured data pass these cuts. Taking the high systematic uncertainties into account, this result is in agreement with the expected background of 0.72{+-}0.28{+-}{sup 1.54}{sub 0.49} events. For an assumed flavor ratio of {nu}{sub e}:{nu}{sub {mu}}:{nu}{sub {tau}}=1:1:1 the upper limit for the all flavor neutrino flux is 9.5.10{sup -8}E{sup -2} GeVs{sup -1}sr{sup -1}cm{sup -2}.

Search for neutrino-induced cascade events in the icecube detector

International Nuclear Information System (INIS)

Panknin, Sebastian

2011-01-01

This thesis presents results of a search for a diffuse flux of high energetic neutrinos from extra-terrestrial origin. Such a flux is predicted by several models of sources of cosmic ray particles. In a neutrino detector, such as IceCube, there are mainly two signatures available for detection of neutrinos: The track-like light signal of a neutrino induced muon and the spherical light pattern of a neutrino induced particle shower, called cascades in this context. The search is based on the measurement of neutrino induced cascades within the IceCube neutrino detector. The data were taken in 2008/2009 with a total uptime of 367 days. At that time the detector was still under construction and had just reached half of its final size. A search for a neutrino flux using cascades is sensitive to all neutrino flavors. A cascade develops within few meters, in contrast to the muon track of several kilometers length. Therefore a good energy reconstruction is possible. With such a reconstruction the astrophysical neutrino flux can be statistically distinguished from the background of atmospheric neutrinos. In the simulation of cascades so far it was not included, that in hadronic cascades muons are produced. This can influence the shape of the cascade, to a less spherical one. Therefore the effect was parameterized in this thesis and included in the simulation. Further cuts on the event topology and reconstructed energy were developed, in order to reduce the background of atmospheric muons and atmospheric neutrinos. Four events from the measured data pass these cuts. Taking the high systematic uncertainties into account, this result is in agreement with the expected background of 0.72±0.28± 1.54 0.49 events. For an assumed flavor ratio of ν e :ν μ :ν τ =1:1:1 the upper limit for the all flavor neutrino flux is 9.5.10 -8 E -2 GeVs -1 sr -1 cm -2 .

Exciton management in organic photovoltaic multidonor energy cascades.

Science.gov (United States)

Griffith, Olga L; Forrest, Stephen R

2014-05-14

Multilayer donor regions in organic photovoltaics show improved power conversion efficiency when arranged in decreasing exciton energy order from the anode to the acceptor interface. These so-called "energy cascades" drive exciton transfer from the anode to the dissociating interface while reducing exciton quenching and allowing improved overlap with the solar spectrum. Here we investigate the relative importance of exciton transfer and blocking in a donor cascade employing diphenyltetracene (D1), rubrene (D2), and tetraphenyldibenzoperiflanthene (D3) whose optical gaps monotonically decrease from D1 to D3. In this structure, D1 blocks excitons from quenching at the anode, D2 accepts transfer of excitons from D1 and blocks excitons at the interface between D2 and D3, and D3 contributes the most to the photocurrent due to its strong absorption at visible wavelengths, while also determining the open circuit voltage. We observe singlet exciton Förster transfer from D1 to D2 to D3 consistent with cascade operation. The power conversion efficiency of the optimized cascade OPV with a C60 acceptor layer is 7.1 ± 0.4%, which is significantly higher than bilayer devices made with only the individual donors. We develop a quantitative model to identify the dominant exciton processes that govern the photocurrent generation in multilayer organic structures.

Technical Update: Preimplantation Genetic Diagnosis and Screening.

Science.gov (United States)

Dahdouh, Elias M; Balayla, Jacques; Audibert, François; Wilson, R Douglas; Audibert, François; Brock, Jo-Ann; Campagnolo, Carla; Carroll, June; Chong, Karen; Gagnon, Alain; Johnson, Jo-Ann; MacDonald, William; Okun, Nanette; Pastuck, Melanie; Vallée-Pouliot, Karine

2015-05-01

To update and review the techniques and indications of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Discussion about the genetic and technical aspects of preimplantation reproductive techniques, particularly those using new cytogenetic technologies and embryo-stage biopsy. Clinical outcomes of reproductive techniques following the use of PGD and PGS are included. This update does not discuss in detail the adverse outcomes that have been recorded in association with assisted reproductive technologies. Published literature was retrieved through searches of The Cochrane Library and Medline in April 2014 using appropriate controlled vocabulary (aneuploidy, blastocyst/physiology, genetic diseases, preimplantation diagnosis/methods, fertilization in vitro) and key words (e.g., preimplantation genetic diagnosis, preimplantation genetic screening, comprehensive chromosome screening, aCGH, SNP microarray, qPCR, and embryo selection). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies published from 1990 to April 2014. There were no language restrictions. Searches were updated on a regular basis and incorporated in the update to January 2015. Additional publications were identified from the bibliographies of retrieved articles. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. (Table 1) BENEFITS, HARMS, AND COSTS: This update will educate readers about new preimplantation genetic concepts, directions, and technologies. The major harms and costs identified are those of assisted reproductive

The effects of self-interstitial clusters on cascade defect evolution beyond the primary damage state

Energy Technology Data Exchange (ETDEWEB)

Heinisch, H.L. [Pacific Northwest National Lab., Richland, WA (United States)

1997-04-01

The intracascade evolution of the defect distributions of cascades in copper is investigated using stochastic annealing simulations applied to cascades generated with molecular dynamics (MD). The temperature and energy dependencies of annihilation, clustering and free defect production are determined for individual cascades. The annealing simulation results illustrate the strong influence on intracascade evolution of the defect configuration existing in the primary damage state. Another factor significantly affecting the evolution of the defect distribution is the rapid one-dimensional diffusion of small, glissile interstitial loops produced directly in cascades. This phenomenon introduces a cascade energy dependence of defect evolution that is apparent only beyond the primary damage state, amplifying the need for further study of the annealing phase of cascade evolution and for performing many more MD cascade simulations at higher energies.

The effects of self-interstitial clusters on cascade defect evolution beyond the primary damage state

International Nuclear Information System (INIS)

Heinisch, H.L.

1997-01-01

The intracascade evolution of the defect distributions of cascades in copper is investigated using stochastic annealing simulations applied to cascades generated with molecular dynamics (MD). The temperature and energy dependencies of annihilation, clustering and free defect production are determined for individual cascades. The annealing simulation results illustrate the strong influence on intracascade evolution of the defect configuration existing in the primary damage state. Another factor significantly affecting the evolution of the defect distribution is the rapid one-dimensional diffusion of small, glissile interstitial loops produced directly in cascades. This phenomenon introduces a cascade energy dependence of defect evolution that is apparent only beyond the primary damage state, amplifying the need for further study of the annealing phase of cascade evolution and for performing many more MD cascade simulations at higher energies

Use Deflected Trailing Edge to Improve the Aerodynamic Performance and Develop Low Solidity LPT Cascade

Science.gov (United States)

Chao, Li; Peigang, Yan; Xiangfeng, Wang; Wanjin, Han; Qingchao, Wang

2017-08-01

This paper investigates the feasibility of improving the aerodynamic performance of low pressure turbine (LPT) blade cascades and developing low solidity LPT blade cascades through deflected trailing edge. A deflected trailing edge improved aerodynamic performance of both LPT blade cascades and low solidity LPT blade cascades. For standard solidity LPT cascades, deflecting the trailing edge can decrease the energy loss coefficient by 20.61 % for a Reynolds number (Re) of 25,000 and freestream turbulence intensities (FSTI) of 1 %. For a low solidity LPT cascade, aerodynamic performance was also improved by deflecting the trailing edge. Solidity of the LPT cascade can be reduced by 12.5 % for blades with a deflected trailing edge without a drop in efficiency. Here, the flow control mechanism surrounding a deflected trailing edge was also revealed.

Phytochemical characteristics and in vitro antibacterial activity of ...

African Journals Online (AJOL)

The aqueous and ethanol stem bark-extracts of Caesalpinia pulcherrima (Pride of Barbados) were screened for phyto-constituents and in vitro antimicrobial activity on clinical isolates of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis, Salmonella typhi and Klebsiella pneumoniae using ...

TfR Binding Peptide Screened by Phage Display Technology ...

African Journals Online (AJOL)

Purpose: To screen an hTfR affinity peptide and investigate its activity in vitro. Methods: hTfR ... Keywords: Peptide, hTfR, Transferrin receptor, Phage display technology, Enhanced green ..... mediated uptake of peptides that bind the human.

Cascading off the West Greenland Shelf: A numerical perspective

Science.gov (United States)

Marson, Juliana M.; Myers, Paul G.; Hu, Xianmin; Petrie, Brian; Azetsu-Scott, Kumiko; Lee, Craig M.

2017-07-01

Cascading of dense water from the shelf to deeper layers of the adjacent ocean basin has been observed in several locations around the world. The West Greenland Shelf (WGS), however, is a region where this process has never been documented. In this study, we use a numerical model with a 1/4° resolution to determine (i) if cascading could happen from the WGS; (ii) where and when it could take place; (iii) the forcings that induce or halt this process; and (iv) the path of the dense plume. Results show cascading happening off the WGS at Davis Strait. Dense waters form there due to brine rejection and slide down the slope during spring. Once the dense plume leaves the shelf, it gradually mixes with waters of similar density and moves northward into Baffin Bay. Our simulation showed events happening between 2003-2006 and during 2014; but no plume was observed in the simulation between 2007 and 2013. We suggest that the reason why cascading was halted in this period is related to: the increased freshwater transport from the Arctic Ocean through Fram Strait; the additional sea ice melting in the region; and the reduced presence of Irminger Water at Davis Strait during fall/early winter. Although observations at Davis Strait show that our simulation usually overestimates the seasonal range of temperature and salinity, they agree with the overall variability captured by the model. This suggests that cascades have the potential to develop on the WGS, albeit less dense than the ones estimated by the simulation.

In vitro models to evaluate the permeability of poorly soluble drug entities: Challenges and perspectives

DEFF Research Database (Denmark)

Buckley, S. T.; Fischer, S. M.; Fricker, G.

2012-01-01

The application of in vitro models in drug permeability studies represents a useful screening tool for assessing the biopharmaceutical appropriateness of new chemical entities (NCEs). Of note, there remains an ever-increasing number of NCEs which exhibit poor aqueous solubility. However, in their......The application of in vitro models in drug permeability studies represents a useful screening tool for assessing the biopharmaceutical appropriateness of new chemical entities (NCEs). Of note, there remains an ever-increasing number of NCEs which exhibit poor aqueous solubility. However...

The 17/5 spectrum of the Kelvin-wave cascade

OpenAIRE

Kozik, Evgeny; Svistunov, Boris

2010-01-01

Direct numeric simulation of the Biot-Savart equation readily resolves the 17/5 spectrum of the Kelvin-wave cascade from the 11/3 spectrum of the non-local (in the wavenumber space) cascade scenario by L'vov and Nazarenko. This result is a clear-cut visualisation of the unphysical nature of the 11/3 solution, which was established earlier on the grounds of symmetry.

Design of ideal cascades of gas centrifuges with variable separation factors

International Nuclear Information System (INIS)

Olander, D.R.

1976-01-01

A method of designing ideal cascades in which the separation factor varies with stage number is presented and applied to centrifuges as separating units. The centrifuge is characterized by a performance function, which gives the separative power, optimized with respect to all internal variables, as a function of cut and throughput. For centrifuges with certain types of performance functions, variable-α ideal cascades can provide a product at a lower cost than the conventional ideal cascade in which the separation factor is independent of stage number

Terahertz quantum cascade laser as local oscillator in a heterodyne receiver.

Science.gov (United States)

Hübers, Heinz-Wilhelm; Pavlov, S; Semenov, A; Köhler, R; Mahler, L; Tredicucci, A; Beere, H; Ritchie, D; Linfield, E

2005-07-25

Terahertz quantum cascade lasers have been investigated with respect to their performance as a local oscillator in a heterodyne receiver. The beam profile has been measured and transformed in to a close to Gaussian profile resulting in a good matching between the field patterns of the quantum cascade laser and the antenna of a superconducting hot electron bolometric mixer. Noise temperature measurements with the hot electron bolometer and a 2.5 THz quantum cascade laser yielded the same result as with a gas laser as local oscillator.

A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library.

Science.gov (United States)

Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G; Zhang, Ying

2016-01-01

Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi

Modeling defect production in high energy collision cascades

International Nuclear Information System (INIS)

Heinisch, H.L.; Singh, B.N.

1993-01-01

A multi-model approach roach (MMA) to simulating defect production processes at the atomic scale is described that incorporates molecular dynamics (MD), binary collision approximation (BCA) calculations and stochastic annealing simulations. The central hypothesis of the MMA is that the simple, fast computer codes capable of simulating large numbers of high energy cascades (e.g., BCA codes) can be made to yield the correct defect configurations when their parameters are calibrated using the results of the more physically realistic MD simulations. The calibration procedure is investigated using results of MD simulations of 25 keV cascades in copper. The configurations of point defects are extracted from the MD cascade simulations at the end of the collisional phase, similar to the information obtained with a binary collision model. The MD collisional phase defect configurations are used as input to the ALSOME annealing simulation code, and values of the ALSOME quenching parameters are determined that yield the best fit to the post-quenching defect configurations of the MD simulations

Photoproduction of the Cascade Baryons at GlueX

Science.gov (United States)

Ernst, Ashley; GlueX Collaboration

2017-09-01

Multi-strange baryons play an important role in understanding the strong interaction and despite their importance, little is known about such hyperons. Almost all knowledge of the Cascades today stems from Kaon-nucleon interactions in bubble chamber experiments performed in the 1960s and 1970s, of which only the octet and decuplet ground states, Ξ (1320) and Ξ (1530) respectively, are well established. This research uses the GlueX experiment at Jefferson Laboratory to map out the spectrum of doubly-strange Cascade resonances, as well as to measure the spin-parity for each of the detected resonances. The first physics run for GlueX has recently been completed and a clear signature of the Ξ (1320) is observed. The systematics of the Cascade spectrum will be presented motivated by prior discoveries in the N* program. This work was supported by the U.S. Department of Energy Grant DE-FG02-92ER40735 and National Science Foundation Grant 1449440.

A New In Vivo Screening Paradigm to Accelerate Antimalarial Drug Discovery

Science.gov (United States)

Jiménez-Díaz, María Belén; Viera, Sara; Ibáñez, Javier; Mulet, Teresa; Magán-Marchal, Noemí; Garuti, Helen; Gómez, Vanessa; Cortés-Gil, Lorena; Martínez, Antonio; Ferrer, Santiago; Fraile, María Teresa; Calderón, Félix; Fernández, Esther; Shultz, Leonard D.; Leroy, Didier; Wilson, David M.; García-Bustos, José Francisco; Gamo, Francisco Javier; Angulo-Barturen, Iñigo

2013-01-01

The emergence of resistance to available antimalarials requires the urgent development of new medicines. The recent disclosure of several thousand compounds active in vitro against the erythrocyte stage of Plasmodium falciparum has been a major breakthrough, though converting these hits into new medicines challenges current strategies. A new in vivo screening concept was evaluated as a strategy to increase the speed and efficiency of drug discovery projects in malaria. The new in vivo screening concept was developed based on human disease parameters, i.e. parasitemia in the peripheral blood of patients on hospital admission and parasite reduction ratio (PRR), which were allometrically down-scaled into P. berghei-infected mice. Mice with an initial parasitemia (P0) of 1.5% were treated orally for two consecutive days and parasitemia measured 24 h after the second dose. The assay was optimized for detection of compounds able to stop parasite replication (PRR = 1) or induce parasite clearance (PRR >1) with statistical power >99% using only two mice per experimental group. In the P. berghei in vivo screening assay, the PRR of a set of eleven antimalarials with different mechanisms of action correlated with human-equivalent data. Subsequently, 590 compounds from the Tres Cantos Antimalarial Set with activity in vitro against P. falciparum were tested at 50 mg/kg (orally) in an assay format that allowed the evaluation of hundreds of compounds per month. The rate of compounds with detectable efficacy was 11.2% and about one third of active compounds showed in vivo efficacy comparable with the most potent antimalarials used clinically. High-throughput, high-content in vivo screening could rapidly select new compounds, dramatically speeding up the discovery of new antimalarial medicines. A global multilateral collaborative project aimed at screening the significant chemical diversity within the antimalarial in vitro hits described in the literature is a feasible task

A new in vivo screening paradigm to accelerate antimalarial drug discovery.

Directory of Open Access Journals (Sweden)

María Belén Jiménez-Díaz

Full Text Available The emergence of resistance to available antimalarials requires the urgent development of new medicines. The recent disclosure of several thousand compounds active in vitro against the erythrocyte stage of Plasmodium falciparum has been a major breakthrough, though converting these hits into new medicines challenges current strategies. A new in vivo screening concept was evaluated as a strategy to increase the speed and efficiency of drug discovery projects in malaria. The new in vivo screening concept was developed based on human disease parameters, i.e. parasitemia in the peripheral blood of patients on hospital admission and parasite reduction ratio (PRR, which were allometrically down-scaled into P. berghei-infected mice. Mice with an initial parasitemia (P0 of 1.5% were treated orally for two consecutive days and parasitemia measured 24 h after the second dose. The assay was optimized for detection of compounds able to stop parasite replication (PRR = 1 or induce parasite clearance (PRR >1 with statistical power >99% using only two mice per experimental group. In the P. berghei in vivo screening assay, the PRR of a set of eleven antimalarials with different mechanisms of action correlated with human-equivalent data. Subsequently, 590 compounds from the Tres Cantos Antimalarial Set with activity in vitro against P. falciparum were tested at 50 mg/kg (orally in an assay format that allowed the evaluation of hundreds of compounds per month. The rate of compounds with detectable efficacy was 11.2% and about one third of active compounds showed in vivo efficacy comparable with the most potent antimalarials used clinically. High-throughput, high-content in vivo screening could rapidly select new compounds, dramatically speeding up the discovery of new antimalarial medicines. A global multilateral collaborative project aimed at screening the significant chemical diversity within the antimalarial in vitro hits described in the literature is a

Analysis of static characteristic roots and propagation of disturbance of adjustable centrifuge cascade

International Nuclear Information System (INIS)

Li Weijie; Wu Zhongdi; Nong Guowei; Zeng Shi

2014-01-01

The hydraulic characteristic roots of a centrifuge cascade represent an important property of the cascade performance. Regulators and centrifuges are the key components that have a significant influence on the cascade hydraulic performance. The method used in diffusion cascades was adopted to obtain the static characteristic roots by solving the small disturbance equation for an adjustable centrifuge cascade in which all stages have the same fluid parameters. As the light stream flowrate of a centrifuge is irrelevant to the pressure at the outlet of the light flow, and the heavy stream flows at the speed of sound, there are only 2 static characteristic roots in the centrifuge cascade: the first root Z_1 is the main characteristic root and the second one Z_2 comes into play only when there exists a feed. The value of the main characteristic root is influenced by the amplification factor of the regulators, the fluid resistance in the main feed pipe and other factors. When Z_1 is smaller than 1, it increases with the fluid resistance. A large enough amplification factor has little impact on Z_1. The same distribution of the relative changes of the light fraction along the cascade is obtained by an analytical and a numerical method. (authors)

Optimization Control of Bidirectional Cascaded DC-AC Converter Systems

DEFF Research Database (Denmark)

Tian, Yanjun

in bidirectional cascaded converter. This research work analyses the control strategies based on the topology of dual active bridges converter cascaded with a three phase inverter. It firstly proposed a dc link voltage and active power coordinative control method for this cascaded topology, and it can reduce dc....... The connections of the renewable energy sources to the power system are mostly through the power electronic converters. Moreover, for high controllability and flexibility, power electronic devices are gradually acting as the interface between different networks in power systems, promoting conventional power...... the bidirectional power flow in the distribution level of power systems. Therefore direct contact of converters introduces significant uncertainties to power system, especially for the stability and reliability. This dissertation studies the optimization control of the two stages directly connected converters...

Cascade Controller Including Back-stepping for Hydraulic-Mechanical Systems

DEFF Research Database (Denmark)

Choux, Martin; Hovland, Geir; Blanke, Mogens

2012-01-01

Development of a cascade controller structure including adaptive backstepping for a nonlinear hydraulic-mechanical system is considered in this paper where a dynamic friction (LuGre) model is included to obtain the necessary accuracy. The paper compares the performance of two variants of an adapt......Development of a cascade controller structure including adaptive backstepping for a nonlinear hydraulic-mechanical system is considered in this paper where a dynamic friction (LuGre) model is included to obtain the necessary accuracy. The paper compares the performance of two variants...... of an adaptive backstepping tracking controller with earlier results. The new control architecture is analysed and enhanced tracking performance is demonstrated when including the extended friction model. The complexity of the backstepping procedure is significantly reduced due to the cascade structure. Hence...

Cascaded Photoenhancement: Implications for Photonic Chemical and Biological Sensors

Science.gov (United States)

Fuller, Kirk A.; Smith, David D.

2006-01-01

Our analysis shows that coupling of gold nanoparticles to microspheres will evoke a cascading effect from the respective photoenhancement mechanisms. We refer to this amplification process as cascaded photoenhancement, and the resulting cavity amplification of surface-enhanced Raman scattering (SERS) and fluorescence as CASERS and CAF, respectively. Calculations, based on modal analysis of scattering and absorption by compound spheres, presented herein indicate that the absorption cross sections of metal nanoparticles immobilized onto dielectric microspheres can be greatly enhanced by cavity resonances in the microspheres without significant degradation of the resonators. Gain factors associated with CSP of 10(exp 3) - 10(exp 4) are predicted for realistic experimental conditions using homogenous microspheres. Cascaded surface photoenhancement thus has the potential of dramatically increasing the sensitivities of fluorescence and vibrational spectroscopies.

Correlation Scales of the Turbulent Cascade at 1 au

Science.gov (United States)

Smith, Charles W.; Vasquez, Bernard J.; Coburn, Jesse T.; Forman, Miriam A.; Stawarz, Julia E.

2018-05-01

We examine correlation functions of the mixed, third-order expressions that, when ensemble-averaged, describe the cascade of energy in the inertial range of magnetohydrodynamic turbulence. Unlike the correlation function of primitive variables such as the magnetic field, solar wind velocity, temperature, and density, the third-order expressions decorrelate at a scale that is approximately 20% of the lag. This suggests the nonlinear dynamics decorrelate in less than one wavelength. Therefore, each scale can behave differently from one wavelength to the next. In the same manner, different scales within the inertial range can behave independently at any given time or location. With such a cascade that can be strongly patchy and highly variable, it is often possible to obtain negative cascade rates for short periods of time, as reported earlier for individual samples of data.

Total output operation chart optimization of cascade reservoirs and its application

International Nuclear Information System (INIS)

Jiang, Zhiqiang; Ji, Changming; Sun, Ping; Wang, Liping; Zhang, Yanke

2014-01-01

Highlights: • We propose a new double nested model for cascade reservoirs operation optimization. • We use two methods to extract the output distribution ratio. • The adopted two methods perform better than the widely used methods at present. • Stepwise regression method performs better than mean value method on the whole. - Abstract: With the rapid development of cascade hydropower stations in recent decades, the cascade system composed of multiple reservoirs needs unified operation and management. However, the output distribution problem has not yet been solved reasonably when the total output of cascade system obtained, which makes the full utilization of hydropower resources in cascade reservoirs very difficult. Discriminant criterion method is a traditional and common method to solve the output distribution problem at present, but some shortcomings cannot be ignored in the practical application. In response to the above concern, this paper proposes a new total output operation chart optimization model and a new optimal output distribution model, the two models constitute to a double nested model with the goal of maximizing power generation. This paper takes the cascade reservoirs of Li Xianjiang River in China as an instance to obtain the optimal total output operation chart by the proposed double nested model and the 43 years historical runoff data, progressive searching method and progressive optimality algorithm are used in solving the model. In order to take the obtained total output operation chart into practical operation, mean value method and stepwise regression method are adopted to extract the output distribution ratios on the basis of the optimal simulation intermediate data. By comparing with discriminant criterion method and conventional method, the combined utilization of total output operation chart and output distribution ratios presents better performance in terms of power generation and assurance rate, which proves it is an effective

In vitro differentiation of mouse embryonic stem cells into functional ...

African Journals Online (AJOL)

Jane

2011-08-22

Aug 22, 2011 ... hepatocyte transplantation therapy and toxicity screening in drug discovery. Key words: Embryonic stem cells, hepatic-like cells, in vitro differentiation, sodium butyrate, ... from embryonic stem (ES) cell or induced pluripotent.

In vitro cytotoxic screening of selected Saudi medicinal plants.

Science.gov (United States)

Almehdar, Hussein; Abdallah, Hossam M; Osman, Abdel-Moneim M; Abdel-Sattar, Essam A

2012-04-01

Many natural products from plants have been identified to exert anticancer activity. It might be expected to be a challenge to look at the Saudi plants in order to discover new sources for new molecules which may have anticancer activity. The methanolic extracts of forty species of plants traditionally used in Saudi Arabia for the treatment of a variety of diseases were tested in vitro for their potential anticancer activity on different human cancer cell lines. The cytotoxic activity of the methanolic extracts of the tested plants were determined using three human cancer cell lines, namely, breast cancer (MCF7), hepatocellular carcinoma (HEPG2), and cervix cancer (HELA) cells. In addition, human normal melanocyte (HFB4) was used as normal nonmalignant cells. Sulforhodamine B colorimetric assay was used to evaluate the in vitro cytotoxic activity of the different extracts. The growth inhibition of 50% (IC(50)) for each extract was calculated from the optical density of treated and untreated cells. Doxorubicin, a broad-spectrum anticancer drug, was used as the positive control. Nine plant extracts were chosen for further fractionation based on their activity and availability. Interesting cytotoxic activity was observed for Hypoestes forskaolii, Withania somnifera, Solanum glabratum, Adenium obesum, Pistacia vera oleoresin, Caralluma quadrangula, Eulophia petersii, Phragmanthera austroarabica, and Asparagus officinalis. Other extracts showed poor activity.

Major disruptions, inverse cascades, and the Strauss equations

International Nuclear Information System (INIS)

Montgomery, D.

1982-01-01

Current-carrying plasmas in a strong dc magnetic field are subject to violent disruptions above certain thresholds. At present difficult to verify, explanations are typically sought in terms of tearing modes. An alternative explanation is in terms of inverse magnetic helicity cascades, generated from a variety of possible sources of small-scale MHD turbulence. Strongly anisotropic MHD plasmas may be described by the Strauss equations. Indications of turbulent inverse cascade behavior for the Strauss equations are sought, in parallel with earlier examples from MHD and fluid mechanics

Synthesis of Marine Polycyclic Polyethers via Endo-Selective Epoxide-Opening Cascades

Directory of Open Access Journals (Sweden)

Timothy F. Jamison

2010-03-01

Full Text Available The proposed biosynthetic pathways to ladder polyethers of polyketide origin and oxasqualenoids of terpenoid origin share a dramatic epoxide-opening cascade as a key step. Polycyclic structures generated in these biosynthetic pathways display biological effects ranging from potentially therapeutic properties to extreme lethality. Much of the structural complexity of ladder polyether and oxasqualenoid natural products can be traced to these hypothesized cascades. In this review we summarize how such epoxide-opening cascade reactions have been used in the synthesis of ladder polyethers and oxasqualenoid natural products.

Universal resilience patterns in cascading load model: More capacity is not always better

Science.gov (United States)

Wang, Jianwei; Wang, Xue; Cai, Lin; Ni, Chengzhang; Xie, Wei; Xu, Bo

We study the problem of universal resilience patterns in complex networks against cascading failures. We revise the classical betweenness method and overcome its limitation of quantifying the load in cascading model. Considering that the generated load by all nodes should be equal to the transported one by all edges in the whole network, we propose a new method to quantify the load on an edge and construct a simple cascading model. By attacking the edge with the highest load, we show that, if the flow between two nodes is transported along the shortest paths between them, then the resilience of some networks against cascading failures inversely decreases with the enhancement of the capacity of every edge, i.e. the more capacity is not always better. We also observe the abnormal fluctuation of the additional load that exceeds the capacity of each edge. By a simple graph, we analyze the propagation of cascading failures step by step, and give a reasonable explanation of the abnormal fluctuation of cascading dynamics.

Dirhodium(II Carbenes : The Chiral Product Cascade

Directory of Open Access Journals (Sweden)

Gregory H. P. Roos

2000-12-01

Full Text Available The last decade has witnessed enormous growth in the spectrum of highly efficient asymmetric synthetic transformations. One prominent example of this progress is the application of dirhodium (II carbenes generated from diazo- precursors. Innovative construction of ‘designer’ catalysts has played a integral role in extending the breadth of the synthetic cascade of non-racemic products now available through the range of cyclopropanation, C-X insertion, aromatic cycloaddition-rearrangement, and ylide-based reaction types. This review deals briefly with an overview of the important catalytic systems and maintains as its primary focus the cascade of diverse optically enriched products that flow from their applications.

Cascade: a high-efficiency ICF power reactor

International Nuclear Information System (INIS)

Pitts, J.H.

1985-01-01

Cascade attains a net power-plant efficiency of 49% and its cost is competitive with high-temperature gas-cooled reactor, pressurized-water reactor, and coal-fired power plants. The Cascade reactor and blanket are made of ceramic materials and activation is 6 times less than that of the MARS Tandem Mirror Reactor operating at comparable power. Hands-on maintenance of the heat exchangers is possible one day after shutdown. Essentially all tritium is recovered in the vacuum system, with the remainder recovered from the helium power conversion loop. Tritium leakage external to the vacuum system and power conversion loop is only 0.03 Ci/d

Transgenic Mouse Models Transferred into the Test Tube: New Perspectives for Developmental Toxicity Testing In Vitro?

Science.gov (United States)

Kugler, Josephine; Luch, Andreas; Oelgeschläger, Michael

2016-10-01

Despite our increasing understanding of molecular mechanisms controlling embryogenesis, the identification and characterization of teratogenic substances still heavily relies on animal testing. Embryonic development depends on cell-autonomous and non-autonomous processes including spatiotemporally regulated extracellular signaling activities. These have been elucidated in transgenic mouse models harboring easily detectable reporter genes under the control of evolutionarily conserved signaling cascades. We propose combining these transgenic mouse models and cells derived thereof with existing alternative toxicological testing strategies. This would enable the plausibility of in vitro data to be verified in light of in vivo data and, ultimately, facilitate regulatory acceptance of in vitro test methods. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hazard assessment of exhaust emissions - The next generation of fast and reliable tools for in vitro screening

Science.gov (United States)

Rothen-Rutishauser, B.

2017-12-01

Hazard assessment of exhaust emissions - The next generation of fast and reliable tools for in vitro screening Barbara Rothen-Rutishauser Adolphe Merkle Institute, University of Fribourg, Switzerland; barbara.rothen@unifr.ch Pollution by vehicles is a major problem for the environment due to the various components in the exhaust gasses that are emitted into the atmosphere. A large number of epidemiological studies demonstrate the profound impact of vehicle emissions upon human health [1-3]. Such studies however, are unable to attribute a given subset of emissions to a certain adverse effect, which renders decision making difficult. Standardized protocols for exhaust toxicity assessment are lacking and it relies in many aspects on epidemiological and in vivo studies (animals), which are very time and cost-intensive and suffer from considerable ethical issues. An overview about the current state of research and clinical aspects in the field, as well as about the development of sophisticated in vitro approaches mimicking the inhalation of airborne particles / exhaust for the toxicological testing of engine emissions will be provided. Data will be presented that show that the combination of an air-liquid exposure system and 3D lung-cell culture model offers an adequate tool for fast and reliable investigations of complete exhaust toxicity as well as the effects of particulate fraction [4,5]. This approach yields important results for novel and improved emission technologies in the early stages of product development. [1] Donaldson et al. Part Fibre Toxicol 2005, 2: 10. [2] Ghio et al. J Toxicol Environ Health B Crit Rev 2012, 15: 1-21. [3] Peters et al. Res Rep Health Eff Inst 2009, 5-77. [4] Bisig et al. Emiss Control Sci Technol 2015, 1: 237-246. [5] Steiner et al. Atmos Environ 2013, 81: 380-388.

Phytochemical and in vitro screening of some Ficus and Morus spp. for hypolipidaemic and antioxidant activities and in vivo assessment of Ficus mysorensis (Roth).

Science.gov (United States)

Awad, Nagwa E; Seida, Ahmed A; Hamed, Manal A; Mahmoud, Ahlam H; Elbatanony, Marwa M

2012-01-01

Phytochemical screening of air-dried leaves and fruit juice of certain Ficus and Morus spp. have been studied. In an in vitro study, the ethanol and hexane extracts of the investigated plants were evaluated against hyperlipidaemia by estimating the rate limiting enzyme of cholesterol biothenysis; β-hydroxy-β-methylglutaryl coenzyme A reductase (HMG-CoA reductase). The antioxidant activity was evaluated by reduction of DPPH(-) free radical. Extra phytochemical screening of Ficus extracts was undertaken, which recorded potent hypolipidaemic and antioxidant activities. The more pronounced extract, Ficus mysorensis (hexane extract), was evaluated in vivo by estimation of the lipid profile and certain antioxidant parameters in hypercholesterolemic rats. The hexane fraction was chromatographed and six isolated compounds were identified. Furthermore, its saponifiable fraction was identified by a MS/MS technique. In conclusion, F. mysorensis recorded hypolipidaemic and antioxidant effects. Detailed studies of the isolated compounds must be undertaken for an evaluation against hypercholesterolemia and free radical elevation.

In vitro and in vivo suppository studies with perturbed angular correlation and external scintigraphy

International Nuclear Information System (INIS)

Jay, M.; Beihn, R.M.; Snyder, G.A.; McClanahan, J.S.; Digenis, G.A.; Caldwell, L.; Mlodozeniec, A.

1983-01-01

Recently, there has been an increased interest in the rectal delivery of drugs as an alternative to parenteral administration. Because of their complexity, little is known about the release behavior of drugs from suppositories in vivo, and the universal applicability of most in vitro tests developed to date awaits broad acceptance. A novel technique has recently been utilized for the measurement of both in vitro and in vivo dissolution profiles of solid oral dosage forms. This technique, known as perturbed angular correlation (PAC), utilizes the property of cascading decay exhibited by indium-111. The authors now wish to report on the application of this technique for in vitro studies measuring the dissolution of an [ 111 In]salicylate coprecipitate incorporated in a suppository base. The PAC technique was also used in combination with external scintigraphic techniques for the in vivo measurement of the deformation and liquefaction of a suppository containing 111 In in humans in a totally non-invasive manner. (Auth.)

In vitro and in vivo suppository studies with perturbed angular correlation and external scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Jay, M.; Beihn, R.M.; Snyder, G.A.; McClanahan, J.S.; Digenis, G.A. (Kentucky Univ., Lexington (USA). College of Pharmacy and Medicine); Caldwell, L.; Mlodozeniec, A. (INTER Research Corporation, Lawrence, KS (USA). Merck, Sharp and Dohme Research Laboratories)

1983-04-01

Recently, there has been an increased interest in the rectal delivery of drugs as an alternative to parenteral administration. Because of their complexity, little is known about the release behavior of drugs from suppositories in vivo, and the universal applicability of most in vitro tests developed to date awaits broad acceptance. A novel technique has recently been utilized for the measurement of both in vitro and in vivo dissolution profiles of solid oral dosage forms. This technique, known as perturbed angular correlation (PAC), utilizes the property of cascading decay exhibited by indium-111. The authors now wish to report on the application of this technique for in vitro studies measuring the dissolution of an (/sup 111/In)salicylate coprecipitate incorporated in a suppository base. The PAC technique was also used in combination with external scintigraphic techniques for the in vivo measurement of the deformation and liquefaction of a suppository containing /sup 111/In in humans in a totally non-invasive manner.

Pluripotent stem cells: An in vitro model for nanotoxicity assessments.

Science.gov (United States)

Handral, Harish K; Tong, Huei Jinn; Islam, Intekhab; Sriram, Gopu; Rosa, Vinicus; Cao, Tong

2016-10-01

The advent of technology has led to an established range of engineered nanoparticles that are used in diverse applications, such as cell-cell interactions, cell-material interactions, medical therapies and the target modulation of cellular processes. The exponential increase in the utilization of nanomaterials and the growing number of associated criticisms has highlighted the potential risks of nanomaterials to human health and the ecosystem. The existing in vivo and in vitro platforms show limitations, with fluctuations being observed in the results of toxicity assessments. Pluripotent stem cells (PSCs) are viable source of cells that are capable of developing into specialized cells of the human body. PSCs can be efficiently used to screen new biomaterials/drugs and are potential candidates for studying impairments of biophysical morphology at both the cellular and tissue levels during interactions with nanomaterials and for diagnosing toxicity. Three-dimensional in vitro models obtained using PSC-derived cells would provide a realistic, patient-specific platform for toxicity assessments and in drug screening applications. The current review focuses on PSCs as an alternative in vitro platform for assessing the hazardous effects of nanomaterials on health systems and highlights the importance of PSC-derived in vitro platforms. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Screening of drugs inhibiting in vitro oligomerization of Cu/Zn-superoxide dismutase with a mutation causing amyotrophic lateral sclerosis

Directory of Open Access Journals (Sweden)

Itsuki Anzai

2016-08-01

Full Text Available Dominant mutations in Cu/Zn-superoxide dismutase (SOD1 gene have been shown to cause a familial form of amyotrophic lateral sclerosis (SOD1-ALS. A major pathological hallmark of this disease is abnormal accumulation of mutant SOD1 oligomers in the affected spinal motor neurons. While no effective therapeutics for SOD1-ALS is currently available, SOD1 oligomerization will be a good target for developing cures of this disease. Recently, we have reproduced the formation of SOD1 oligomers abnormally cross-linked via disulfide bonds in a test tube. Using our in vitro model of SOD1 oligomerization, therefore, we screened 640 FDA-approved drugs for inhibiting the oligomerization of SOD1 proteins, and three effective classes of chemical compounds were identified. Those hit compounds will provide valuable information on the chemical structures for developing a novel drug candidate suppressing the abnormal oligomerization of mutant SOD1 and possibly curing the disease.

A molecular dynamics study of high-energy displacement cascades in α-zirconium

International Nuclear Information System (INIS)

Wooding, S.J.; Howe, L.M.; Gao, F.; Calder, A.F.; Bacon, D.J.

1998-01-01

The damage produced in α-zirconium at 100 K by displacement cascades with energy, E p , up to 20 keV has been investigated by molecular dynamics using a many-body interatomic potential. The results are compared with similar data for cascades of energy up to 10 keV in α-titanium. The production efficiency of Frenkel pairs falls to about 25% of the NRT value as E p rises above 10 keV in zirconium, and to about 30% at 10 keV in titanium. The power-law dependence of the number of Frenkel pairs, N F , on E p found previously is obeyed, i.e., N F = A(E p ) m . Interstitial and vacancy clusters with sizes of the same order are created in the cascade process, and clusters containing up to 25 interstitials and 30 vacancies were formed in zirconium by 20 keV cascades. Two thirds of the SIAs are produced in clusters in zirconium at high cascade energy. Most interstitial clusters have dislocation character with perfect Burgers vectors of the form 1/3(11 2 - 0), but a few metastable clusters are formed and are persistent over the timescale of MD simulations. Collapse of the 30-vacancy cluster to a faulted loop on the prism plane was found to occur over a period of more than 100 ps. Annealing over this timescale has a stronger effect on the number and clustering of defects in cascades that are dispersed over a large region of crystal than in cascades that form a compact region of damage. (author)

In vitro screening of soil bacteria for inhibiting phytopathogenic fungi ...

African Journals Online (AJOL)

At present, the greatest interest resides with the development and application of specific biocontrol agent for the control of diseases on plant and this form the focus of this work. Several soil bacteria were evaluated in vitro for their effectiveness on the basis of their ability to suppress fungi in plate inhibition assays. 51 strains ...

Evolution of the vertebrate phototransduction cascade activation steps.

Science.gov (United States)

Lamb, Trevor D; Hunt, David M

2017-11-01

We examine the molecular phylogeny of the proteins underlying the activation steps of vertebrate phototransduction, for both agnathan and jawed vertebrate taxa. We expand the number of taxa analysed and we update the alignment and tree building methodology from a previous analysis. For each of the four primary components (the G-protein transducin alpha subunit, Gα T , the cyclic GMP phosphodiesterase, PDE6, and the alpha and beta subunits of the cGMP-gated ion channel, CNGC), the phylogenies appear consistent with expansion from an ancestral proto-vertebrate cascade during two rounds of whole-genome duplication followed by divergence of the agnathan and jawed vertebrate lineages. In each case, we consider possible scenarios for the underlying gene duplications and losses, and we apply relevant constraints to the tree construction. From tests of the topology of the resulting trees, we obtain a scenario for the expansion of each component during 2R that accurately fits the observations. Similar analysis of the visual opsins indicates that the only expansion to have occurred during 2R was the formation of Rh1 and Rh2. Finally, we propose a hypothetical scenario for the conversion of an ancestral chordate cascade into the proto-vertebrate phototransduction cascade, prior to whole-genome duplication. Together, our models provide a plausible account for the origin and expansion of the vertebrate phototransduction cascade. Copyright © 2017 Elsevier Inc. All rights reserved.

On the optimity of separation cascade for a binary and a multi-component case

International Nuclear Information System (INIS)

Song, T.M.; Zeng, S.

2006-01-01

The optimity discussed in this article means minimum total interstage flow which is studied for two cases, a binary and a multi-component case, using direct numerical optimizations for countercurrent symmetric cascades with the concentrations of the target component specified in the .feed flow, the product and waste withdrawals In binary separation, the ideal cascade in which there are no mixing losses and whose stages are working under symmetric separation is the optimum cascade that has the minimum total flow However when the separation factor is large, there may not exist an ideal cascade for certain prescribed external parameters. Cascades are optimized numerically to minimize mixing losses and total flows, respectively The results are compared for the minimum mixing losses and the minimum total flow, and analyzed with theoretically derived formulas. For the multi-component case, satisfying the non-mixing condition is impossible. There is a counterpart of the binary ideal cascade named MARC which matches the abundance ratio at mixing points. An optimization example for a four-cornponent mixture separation cascade is analyzed with the first and the last components as the targets, respectively. The results show that MARC is not the optimum cascade for the separation of one certain isotope. The separation power of each stage in the optimized cascades is calculated using several different definitions, and the rationality of these definitions is discussed. The Q-iteration method is used to calculate the concentration distribution in both the binary and the multi-component cases. Ns-2 stage cuts out of the Ns stages of the cascade are the optimization variables in the optimization process and a combination of the simulated annealing and the Hooke-Jeeves method is applied as the optimization technique to find the minimum. (authors)

Screening of Lactobacillus plantarum isolated from fermented idli ...

African Journals Online (AJOL)

Probiotics are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host. The objective of this study was to screen eight potential probiotic Lactobacillus plantarum strains from fermented idli batter using in vitro assays such as bile tolerance, acid tolerance, transit ...

Cascading Corruption News

DEFF Research Database (Denmark)

Damgaard, Mads

2018-01-01

Through a content analysis of 8,800 news items and six months of front pages in three Brazilian newspapers, all dealing with corruption and political transgression, this article documents the remarkable skew of media attention to corruption scandals. The bias is examined as an information...... phenomenon, arising from systemic and commercial factors of Brazil’s news media: An information cascade of news on corruption formed, destabilizing the governing coalition and legitimizing the impeachment process of Dilma Rousseff. As this process gained momentum, questions of accountability were disregarded...

Efficient cascade multiple heterojunction organic solar cells with inverted structure

Science.gov (United States)

Guo, Tingting; Li, Mingtao; Qiao, Zhenfang; Yu, Leiming; Zhao, Jianhong; Feng, Nianjun; Shi, Peiguang; Wang, Xiaoyan; Pu, Xiaoyun; Wang, Hai

2018-05-01

In this work, we demonstrate an efficient cascade multiple heterojunction organic solar cell with inverted structure. By using two donor materials, poly(3-hexylthiosphene) (P3HT) and titanyl phthalocyanine (TiOPc), as well as two acceptor materials, [6,6]-phenyl C61 butyric acid methyl ester (PCBM) and C60, the cascade multiple heterojunctions of P3HT:PCBM/TiOPc:C60/C60 have been constructed. Applying the optimized inverted configuration of FTO/Zinc Tin Oxide (ZTO)/C60 (30 nm)/TiOPc:C60 (1:1.5, 25 nm)/P3HT:PCBM (1:0.8, 100 nm)/MoO3 (4 nm)/Ag, the considerably enhanced open circuit voltage (VOC) and short circuit current (JSC) can be harvested together, and the power conversion efficiency (PCE) is three times higher than that of the control cell with conventional structure. The significant improvements of the inverted cell are mostly due to the broadened spectral absorption and high efficient multi-interface exciton dissociation in the cascade multiple heterojunctions, indicating that the optimized cascade heterojunctions match the inverted structure well.

ON THE POLAR CAP CASCADE PAIR MULTIPLICITY OF YOUNG PULSARS

Energy Technology Data Exchange (ETDEWEB)

Timokhin, A. N.; Harding, A. K., E-mail: andrey.timokhin@nasa.gov [Astrophysics Science Division, NASA/Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

2015-09-10

We study the efficiency of pair production in polar caps of young pulsars under a variety of conditions to estimate the maximum possible multiplicity of pair plasma in pulsar magnetospheres. We develop a semi-analytic model for calculation of cascade multiplicity which allows efficient exploration of the parameter space and corroborate it with direct numerical simulations. Pair creation processes are considered separately from particle acceleration in order to assess different factors affecting cascade efficiency, with acceleration of primary particles described by recent self-consistent non-stationary model of pair cascades. We argue that the most efficient cascades operate in the curvature radiation/synchrotron regime, the maximum multiplicity of pair plasma in pulsar magnetospheres is ∼few × 10{sup 5}. The multiplicity of pair plasma in magnetospheres of young energetic pulsars weakly depends on the strength of the magnetic field and the radius of curvature of magnetic field lines and has a stronger dependence on pulsar inclination angle. This result questions assumptions about very high pair plasma multiplicity in theories of pulsar wind nebulae.

Successful treatment of homozygous familial hypercholesterolemia using cascade filtration plasmapheresis.

Science.gov (United States)

Kardaş, Fatih; Cetin, Aysun; Solmaz, Musa; Büyükoğlan, Rüksan; Kaynar, Leylagül; Kendirci, Mustafa; Eser, Bülent; Unal, Ali

2012-12-01

The aim of this study was to report the efficacy of low-density lipoprotein cholesterol (LDL-C) apheresisusing a cascade filtration system in pediatric patients with homozygous familial hypercholesterolemia (FH), and toclarify the associated adverse effects and difficulties. LDL-C apheresis using a cascade filtration system was performed in 3 pediatric patientswith homozygous FH; in total, 120 apheresis sessions were performed. Cascade filtration therapy significantly reduced the mean LDL-C values from 418 ± 62 mg/dL to 145 ± 43 mg/dL (p= 0.011). We observed an acute mean reduction in the plasma level of total cholesterol (57.9%), LDL-C (70.8%),and high-density lipoprotein cholesterol (HDL-C) (40.7%). Treatments were well tolerated. The most frequent clinicaladverse effects were hypotension in 3 sessions (2.5%), chills (1.7%) in 2 sessions, and nausea/vomiting in 3 sessions(2.5%). Our experience using the cascade filtration system with 3 patients included good clinical outcomes andlaboratory findings, safe usage, and minor adverse effects and technical problems. None declared.

Modeling cascading failures with the crisis of trust in social networks

Science.gov (United States)

Yi, Chengqi; Bao, Yuanyuan; Jiang, Jingchi; Xue, Yibo

2015-10-01

In social networks, some friends often post or disseminate malicious information, such as advertising messages, informal overseas purchasing messages, illegal messages, or rumors. Too much malicious information may cause a feeling of intense annoyance. When the feeling exceeds a certain threshold, it will lead social network users to distrust these friends, which we call the crisis of trust. The crisis of trust in social networks has already become a universal concern and an urgent unsolved problem. As a result of the crisis of trust, users will cut off their relationships with some of their untrustworthy friends. Once a few of these relationships are made unavailable, it is likely that other friends will decline trust, and a large portion of the social network will be influenced. The phenomenon in which the unavailability of a few relationships will trigger the failure of successive relationships is known as cascading failure dynamics. To our best knowledge, no one has formally proposed cascading failures dynamics with the crisis of trust in social networks. In this paper, we address this potential issue, quantify the trust between two users based on user similarity, and model the minimum tolerance with a nonlinear equation. Furthermore, we construct the processes of cascading failures dynamics by considering the unique features of social networks. Based on real social network datasets (Sina Weibo, Facebook and Twitter), we adopt two attack strategies (the highest trust attack (HT) and the lowest trust attack (LT)) to evaluate the proposed dynamics and to further analyze the changes of the topology, connectivity, cascading time and cascade effect under the above attacks. We numerically find that the sparse and inhomogeneous network structure in our cascading model can better improve the robustness of social networks than the dense and homogeneous structure. However, the network structure that seems like ripples is more vulnerable than the other two network

Non-peptidic cruzain inhibitors with trypanocidal activity discovered by virtual screening and in vitro assay.

Directory of Open Access Journals (Sweden)

Helton J Wiggers

Full Text Available A multi-step cascade strategy using integrated ligand- and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected compounds, 12 non-covalent binding cruzain inhibitors with affinity values (K i in the low micromolar range (3-60 µM acting through a competitive inhibition mechanism were identified. This mechanism has been confirmed by determining the binding mode of the cruzain inhibitor Nequimed176 through X-ray crystallographic studies. Cruzain, a validated therapeutic target for new chemotherapy for Chagas disease, also shares high similarity with the mammalian homolog cathepsin L. Because increased activity of cathepsin L is related to invasive properties and has been linked to metastatic cancer cells, cruzain inhibitors from the same library were assayed against it. Affinity values were in a similar range (4-80 µM, yielding poor selectivity towards cruzain but raising the possibility of investigating such inhibitors for their effect on cell proliferation. In order to select the most promising enzyme inhibitors retaining trypanocidal activity for structure-activity relationship (SAR studies, the most potent cruzain inhibitors were assayed against T. cruzi-infected cells. Two compounds were found to have trypanocidal activity. Using compound Nequimed42 as precursor, an SAR was established in which the 2-acetamidothiophene-3-carboxamide group was identified as essential for enzyme and parasite inhibition activities. The IC50 value for compound Nequimed42 acting against the trypomastigote form of the Tulahuen lacZ strain was found to be 10.6±0.1 µM, tenfold lower than that obtained for benznidazole, which was taken as positive control. In addition, by employing the strategy of molecular simplification, a smaller compound derived from Nequimed42 with a ligand efficiency (LE of 0.33 kcal mol(-1 atom(-1

Non-peptidic cruzain inhibitors with trypanocidal activity discovered by virtual screening and in vitro assay.

Science.gov (United States)

Wiggers, Helton J; Rocha, Josmar R; Fernandes, William B; Sesti-Costa, Renata; Carneiro, Zumira A; Cheleski, Juliana; da Silva, Albérico B F; Juliano, Luiz; Cezari, Maria H S; Silva, João S; McKerrow, James H; Montanari, Carlos A

2013-01-01

A multi-step cascade strategy using integrated ligand- and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected compounds, 12 non-covalent binding cruzain inhibitors with affinity values (K i) in the low micromolar range (3-60 µM) acting through a competitive inhibition mechanism were identified. This mechanism has been confirmed by determining the binding mode of the cruzain inhibitor Nequimed176 through X-ray crystallographic studies. Cruzain, a validated therapeutic target for new chemotherapy for Chagas disease, also shares high similarity with the mammalian homolog cathepsin L. Because increased activity of cathepsin L is related to invasive properties and has been linked to metastatic cancer cells, cruzain inhibitors from the same library were assayed against it. Affinity values were in a similar range (4-80 µM), yielding poor selectivity towards cruzain but raising the possibility of investigating such inhibitors for their effect on cell proliferation. In order to select the most promising enzyme inhibitors retaining trypanocidal activity for structure-activity relationship (SAR) studies, the most potent cruzain inhibitors were assayed against T. cruzi-infected cells. Two compounds were found to have trypanocidal activity. Using compound Nequimed42 as precursor, an SAR was established in which the 2-acetamidothiophene-3-carboxamide group was identified as essential for enzyme and parasite inhibition activities. The IC50 value for compound Nequimed42 acting against the trypomastigote form of the Tulahuen lacZ strain was found to be 10.6±0.1 µM, tenfold lower than that obtained for benznidazole, which was taken as positive control. In addition, by employing the strategy of molecular simplification, a smaller compound derived from Nequimed42 with a ligand efficiency (LE) of 0.33 kcal mol(-1) atom(-1) (compound

Energy Cascade Analysis: from Subscale Eddies to Mean Flow

Science.gov (United States)

Cheikh, Mohamad Ibrahim; Wonnell, Louis; Chen, James

2017-11-01

Understanding the energy transfer between eddies and mean flow can provide insights into the energy cascade process. Much work has been done to investigate the energy cascade at the level of the smallest eddies using different numerical techniques derived from the Navier-Stokes equations. These methodologies, however, prove to be computationally inefficient when producing energy spectra for a wide range of length scales. In this regard, Morphing Continuum Theory (MCT) resolves the length-scales issues by assuming the fluid continuum to be composed of inner structures that play the role of subscale eddies. The current study show- cases the capabilities of MCT in capturing the dynamics of energy cascade at the level of subscale eddies, through a supersonic turbulent flow of Mach 2.93 over an 8× compression ramp. Analysis of the results using statistical averaging procedure shows the existence of a statistical coupling of the internal and translational kinetic energy fluctuations with the corresponding rotational kinetic energy of the subscale eddies, indicating a multiscale transfer of energy. The results show that MCT gives a new characterization of the energy cascade within compressible turbulence without the use of excessive computational resources. This material is based upon work supported by the Air Force Office of Scientific Research under Award Number FA9550-17-1-0154.

Experimental investigation on a high subsonic compressor cascade flow

Directory of Open Access Journals (Sweden)

Zhang Haideng

2015-08-01

Full Text Available With the aim of deepening the understanding of high-speed compressor cascade flow, this paper reports an experimental study on NACA-65 K48 compressor cascade with high subsonic inlet flow. With the increase of passage pressurizing ability, endwall boundary layer behavior is deteriorated, and the transition zone is extended from suction surface to the endwall as the adverse pressure gradient increases. Cross flow from endwall to midspan, mixing of corner boundary layer and the main stream, and reversal flow on the suction surface are caused by corner separation vortex structures. Passage vortex is the main corner separation vortex. During its movement downstream, the size grows bigger while the rotating direction changes, forming a limiting circle. With higher incidence, corner separation is further deteriorated, leading to higher flow loss. Meanwhile, corner separation structure, flow mixing characteristics and flow loss distribution vary a lot with the change of incidence. Compared with low aspect-ratio model, corner separation of high aspect-ratio model moves away from the endwall and is more sufficiently developed downstream the cascade. Results obtained present details of high-speed compressor cascade flow, which is rare in the relating research fields and is beneficial to mechanism analysis, aerodynamic optimization and flow control design.

Biochemical and biophysical characterization of cell-free synthesized Rift Valley fever virus nucleoprotein capsids enables in vitro screening to identify novel antivirals.

Science.gov (United States)

Broce, Sean; Hensley, Lisa; Sato, Tomoharu; Lehrer-Graiwer, Joshua; Essrich, Christian; Edwards, Katie J; Pajda, Jacqueline; Davis, Christopher J; Bhadresh, Rami; Hurt, Clarence R; Freeman, Beverly; Lingappa, Vishwanath R; Kelleher, Colm A; Karpuj, Marcela V

2016-05-14

Viral capsid assembly involves the oligomerization of the capsid nucleoprotein (NP), which is an essential step in viral replication and may represent a potential antiviral target. An in vitro transcription-translation reaction using a wheat germ (WG) extract in combination with a sandwich ELISA assay has recently been used to identify small molecules with antiviral activity against the rabies virus. Here, we examined the application of this system to viruses with capsids with a different structure, such as the Rift Valley fever virus (RVFV), the etiological agent of a severe emerging infectious disease. The biochemical and immunological characterization of the in vitro-generated RVFV NP assembly products enabled the distinction between intermediately and highly ordered capsid structures. This distinction was used to establish a screening method for the identification of potential antiviral drugs for RVFV countermeasures. These results indicated that this unique analytical system, which combines nucleoprotein oligomerization with the specific immune recognition of a highly ordered capsid structure, can be extended to various viral families and used both to study the early stages of NP assembly and to assist in the identification of potential antiviral drugs in a cost-efficient manner. Reviewed by Jeffry Skolnick and Noah Isakov. For the full reviews please go to the Reviewers' comments section.

Disaster Mythology and Availability Cascades

Directory of Open Access Journals (Sweden)

Lisa Grow Sun

2013-04-01

Full Text Available Sociological research conducted in the aftermath of natural disasters has uncovered a number of “disaster myths” – widely shared misconceptions about typical post-disaster human behavior. This paper discusses the possibility that perpetuation of disaster mythology reflects an “availability cascade,” defined in prior scholarship as a “self-reinforcing process of collective belief formation by which an expressed perception triggers a chain reaction that gives the perception increasing plausibility through its rising availability in public discourse.” (Kuran and Sunstein 1999. Framing the spread of disaster mythology as an availability cascade suggests that certain tools may be useful in halting the myths’ continued perpetuation. These tools include changing the legal and social incentives of so-called “availability entrepreneurs” – those principally responsible for beginning and perpetuating the cascade, as well as insulating decision-makers from political pressures generated by the availability cascade. This paper evaluates the potential effectiveness of these and other solutions for countering disaster mythology. Las investigaciones sociológicas realizadas tras los desastres naturales han hecho evidentes una serie de “mitos del desastre”, conceptos erróneos ampliamente compartidos sobre el comportamiento humano típico tras un desastre. Este artículo analiza la posibilidad de que la perpetuación de los mitos del desastre refleje una “cascada de disponibilidad”, definida en estudios anteriores como un “proceso de auto-refuerzo de la formación de una creencia colectiva, a través del que una percepción expresada produce una reacción en cadena que hace que la percepción sea cada vez más verosímil, a través de una mayor presencia en el discurso público” (Kuran y Sunstein 1999. Enmarcar la propagación de los mitos del desastre como una cascada de disponibilidad sugiere que ciertas herramientas pueden ser

Kinetics of Grinding of Secondary Serpentine Raw Material at Cascade Operating Mode

Directory of Open Access Journals (Sweden)

Marek Matik

2004-12-01

Full Text Available The paper deals with the grinding of secondary serpentine material from the Dobšiná´s heap in a ball ceramic mill. The raw material was pre-sieved to prepare fraction of +250 –1,000 µm that was fed to the mill. During batch experiment an amount of oversize on the screen with a mesh size of 200 µm was observed as a function of time. Two speed modes were tested. Firstly, it was the mode designed by mill producer implicit from the structure of milling stand equipped by electromotor, friction gear onto driving shaft with given diameter. The speed of this original alignment attains 40 rmp. Secondly, it was cascade speed mode according to the Haase´s equation, namely 53 rmp, achieved by enlargement of driving shaft diameter. As to winning of required final product 90 % –200 µm, increased speed resulted in the shortening of grinding time from 17.5 to15.7 hour.

Time development of cascades by the binary collision approximation code

International Nuclear Information System (INIS)

Fukumura, A.; Ishino, S.; Sekimura, N.

1991-01-01

To link a molecular dynamic calculation to binary collision approximation codes to explore high energy cascade damage, time between consecutive collisions is introduced into the binary collision MARLOWE code. Calculated results for gold by the modified code show formation of sub-cascades and their spatial and time overlapping, which can affect formation of defect clusters. (orig.)

Fabrication of a novel cascade high-pressure electro-osmotic pump.

Science.gov (United States)

Zhang, Feifang; Wang, Rong; Han, Tingting; Yang, Bingcheng; Liang, Xinmiao

2011-07-07

A novel cascade electro-osmotic pump (EOP) has been fabricated by alternately connecting a cation monolithic column and anion monolithic column in series. In this manner, the change of electric polarity between each stage of the cascade EOP is easily achieved and the pressure output of the EOP could be greatly enhanced without increase of the applied voltage.

Cascadability of Silicon Microring Resonators for40-Gbit/s OOK and DPSK Optical Signals

DEFF Research Database (Denmark)

Ozolins, Oskars; An, Yi; Lali-Dastjerdi, Zohreh

2012-01-01

The cascadability of a single silicon micro-ring resonator for CSRZ-OOK and CSRZ-DPSK signals is experimentally demonstrated at 40 Gbit/s for the first time. Error-free performance is obtained for both modulation formats after 5 cascaded resonators.......The cascadability of a single silicon micro-ring resonator for CSRZ-OOK and CSRZ-DPSK signals is experimentally demonstrated at 40 Gbit/s for the first time. Error-free performance is obtained for both modulation formats after 5 cascaded resonators....

Towards a continuous glucose monitoring system using tunable quantum cascade lasers

Science.gov (United States)

Haase, Katharina; Müller, Niklas; Petrich, Wolfgang

2018-02-01

We present a reagent-free approach for long-term continuous glucose monitoring (cgm) of liquid samples using midinfrared absorption spectroscopy. This method could constitute an alternative to enzymatic glucose sensors in order to manage the widespread disease of Diabetes. In order to acquire spectra of the liquid specimen, we use a spectrally tunable external-cavity (EC-) quantum cascade laser (QCL) as radiation source in combination with a fiber-based in vitro sensor setup. Hereby we achieve a glucose sensitivity in pure glucose solutions of 3 mg/dL (RMSEP). Furthermore, the spectral tunability of the EC-QCL enables us to discriminate glucose from other molecules. We exemplify this by detecting glucose among other saccharides with an accuracy of 8 mg/dL (within other monosaccharides, RMSEVC) and 14 mg/dL (within other mono- and disaccharides, RMSECV). Moreover, we demonstrate a characterization of the significance of each wavenumber for an accurate prediction of glucose among other saccharides using an evolutionary algorithm. We show, that by picking 10 distinct wavenumbers we can achieve comparable accuracies to the use of a complete spectrum.

Development of a novel cascading TPV and TE power generation system

International Nuclear Information System (INIS)

Qiu, K.; Hayden, A.C.S.

2012-01-01

Highlights: ► A novel cascading thermophotovoltaic (TPV) and thermoelectric (TE) power generation system is proposed and developed. ► The used heat stream is taken from the TPV and applied to the input of a TE converter in the system. ► A prototype was built and tested where GaSb TPV cells and PbSnTe-based TE converter were used. ► The TPV cells generate 123.5 We whereas the TE converter generates 306.2 We in the prototype. ► It is shown the cascading power generation is feasible in fuel-fired furnaces and can be applied to micro-CHP. -- Abstract: Thermophotovoltaic (TPV) cells can convert infrared radiation into electricity. They open up possibilities for silent and stand-alone power production in fuel-fired heating equipment. Similarly, thermoelectric (TE) devices convert thermal energy directly into electricity with no moving parts. However, TE devices have relatively low efficiency for electric power generation. In this study, the concept of cascading TPV and TE power generation was developed where the used heat stream is taken from the TPV and applied to the input of a TE converter. A prototype cascading TPV and TE generation system was built and tested. GaSb TPV cells and an integrated semiconductor TE converter were used in the cascading power system. The electric output characteristics of the TPV cells and the TE converter have been investigated in the power generation system at various operating conditions. Experimental results show that the cascading power generation is feasible and has the potential for certain applications.

Linewidth and tuning characteristics of terahertz quantum cascade lasers.

Science.gov (United States)

Barkan, A; Tittel, F K; Mittleman, D M; Dengler, R; Siegel, P H; Scalari, G; Ajili, L; Faist, J; Beere, H E; Linfield, E H; Davies, A G; Ritchie, D A

2004-03-15

We have measured the spectral linewidths of three continuous-wave quantum cascade lasers operating at terahertz frequencies by heterodyning the free-running quantum cascade laser with two far-infrared gas lasers. Beat notes are detected with a GaAs diode mixer and a microwave spectrum analyzer, permitting very precise frequency measurements and giving instantaneous linewidths of less than -30 kHz. Characteristics are also reported for frequency tuning as the injection current is varied.

Three-Dimensional Flow Field Measurements in a Transonic Turbine Cascade

Science.gov (United States)

Giel, P. W.; Thurman, D. R.; Lopez, I.; Boyle, R. J.; VanFossen, G. J.; Jett, T. A.; Camperchioli, W. P.; La, H.

1996-01-01

Three-dimensional flow field measurements are presented for a large scale transonic turbine blade cascade. Flow field total pressures and pitch and yaw flow angles were measured at an inlet Reynolds number of 1.0 x 10(exp 6) and at an isentropic exit Mach number of 1.3 in a low turbulence environment. Flow field data was obtained on five pitchwise/spanwise measurement planes, two upstream and three downstream of the cascade, each covering three blade pitches. Three-hole boundary layer probes and five-hole pitch/yaw probes were used to obtain data at over 1200 locations in each of the measurement planes. Blade and endwall static pressures were also measured at an inlet Reynolds number of 0.5 x 10(exp 6) and at an isentropic exit Mach number of 1.0. Tests were conducted in a linear cascade at the NASA Lewis Transonic Turbine Blade Cascade Facility. The test article was a turbine rotor with 136 deg of turning and an axial chord of 12.7 cm. The flow field in the cascade is highly three-dimensional as a result of thick boundary layers at the test section inlet and because of the high degree of flow turning. The large scale allowed for very detailed measurements of both flow field and surface phenomena. The intent of the work is to provide benchmark quality data for CFD code and model verification.

Effects of temperature in binary-collision simulations of high-energy displacement cascades

International Nuclear Information System (INIS)

Heinisch, H.L.

1981-10-01

Several hundred cascades ranging from 1 to 500 keV were generated using the binary collision code MARLOWE for primary knock-on atoms (PKAs) with randomly chosen directions in both a non-thermal copper lattice and one having atomic displacements representative of room temperature. To simulate the recombination occurring during localized quenching of the highly excited cascade region, an effective spontaneous recombination radius was applied to reduce the number of defect pairs to be consistent with values extracted from resistivity measurements at 4 0 K. At room temperature fewer widely separated pairs are produced, thus the recombination radius is smaller, however, the recombination radii were found to be independent of energy over the entire energy range investigated for both the cold and room temperature cases. The sizes and other features of the point defect distributions were determined as a function of energy. Differences between cold and room temperature cascade dimensions are small. The room temperature cascades tend to have a greater number of distinct damage regions per cascade, with about the same frequency of widely separated subcascades

A data-driven weighting scheme for multivariate phenotypic endpoints recapitulates zebrafish developmental cascades

Energy Technology Data Exchange (ETDEWEB)

Zhang, Guozhu, E-mail: gzhang6@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Roell, Kyle R., E-mail: krroell@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Truong, Lisa, E-mail: lisa.truong@oregonstate.edu [Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR (United States); Tanguay, Robert L., E-mail: robert.tanguay@oregonstate.edu [Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR (United States); Reif, David M., E-mail: dmreif@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC (United States)

2017-01-01

Zebrafish have become a key alternative model for studying health effects of environmental stressors, partly due to their genetic similarity to humans, fast generation time, and the efficiency of generating high-dimensional systematic data. Studies aiming to characterize adverse health effects in zebrafish typically include several phenotypic measurements (endpoints). While there is a solid biomedical basis for capturing a comprehensive set of endpoints, making summary judgments regarding health effects requires thoughtful integration across endpoints. Here, we introduce a Bayesian method to quantify the informativeness of 17 distinct zebrafish endpoints as a data-driven weighting scheme for a multi-endpoint summary measure, called weighted Aggregate Entropy (wAggE). We implement wAggE using high-throughput screening (HTS) data from zebrafish exposed to five concentrations of all 1060 ToxCast chemicals. Our results show that our empirical weighting scheme provides better performance in terms of the Receiver Operating Characteristic (ROC) curve for identifying significant morphological effects and improves robustness over traditional curve-fitting approaches. From a biological perspective, our results suggest that developmental cascade effects triggered by chemical exposure can be recapitulated by analyzing the relationships among endpoints. Thus, wAggE offers a powerful approach for analysis of multivariate phenotypes that can reveal underlying etiological processes. - Highlights: • Introduced a data-driven weighting scheme for multiple phenotypic endpoints. • Weighted Aggregate Entropy (wAggE) implies differential importance of endpoints. • Endpoint relationships reveal developmental cascade effects triggered by exposure. • wAggE is generalizable to multi-endpoint data of different shapes and scales.

Frozen waterfall (or ice cascade) growth and decay: a thermodynamic approach

Science.gov (United States)

Gauthier, Francis; Montagnat, Maurine; Weiss, Jérôme; Allard, Michel; Hétu, Bernard

2013-04-01

The ice volume evolution of an ice cascade was studied using a thermodynamic model. The model was developed from meteorological data collected in the vicinity of the waterfall and validated from ice volume measurements estimated from terrestrial LiDAR images. The ice cascade forms over a 45 m high rockwall located in northern Gaspésie, Québec, Canada. Two stages of formation were identified. During the first stage, the growth is mainly controlled by air convection around the flowing and freefalling water. The ice cascade growth rate increases with the decreasing air temperature below 0°C and when the water flow reaches its lowest level. During the second stage, the ice cascade covers the entire rockwall surface, water flow is isolated from the outside environment and ice volume increases asymptotically. Heat is evacuated from the water flow through the ice cover by conduction. The growth is mainly controlled by the radiation energy balance but more specifically by the longwave radiation emitted at the ice surface during the night. In spring, melting of the ice cascade is clearly dependant on the sensible heat carried by the increasing water flow and the diffuse solar radiation received at the ice surface during the day.

Hybrid Cascading Outage Analysis of Extreme Events with Optimized Corrective Actions

Energy Technology Data Exchange (ETDEWEB)

Vallem, Mallikarjuna R.; Vyakaranam, Bharat GNVSR; Holzer, Jesse T.; Samaan, Nader A.; Makarov, Yuri V.; Diao, Ruisheng; Huang, Qiuhua; Ke, Xinda

2017-10-19

Power system are vulnerable to extreme contingencies (like an outage of a major generating substation) that can cause significant generation and load loss and can lead to further cascading outages of other transmission facilities and generators in the system. Some cascading outages are seen within minutes following a major contingency, which may not be captured exclusively using the dynamic simulation of the power system. The utilities plan for contingencies either based on dynamic or steady state analysis separately which may not accurately capture the impact of one process on the other. We address this gap in cascading outage analysis by developing Dynamic Contingency Analysis Tool (DCAT) that can analyze hybrid dynamic and steady state behavior of the power system, including protection system models in dynamic simulations, and simulating corrective actions in post-transient steady state conditions. One of the important implemented steady state processes is to mimic operator corrective actions to mitigate aggravated states caused by dynamic cascading. This paper presents an Optimal Power Flow (OPF) based formulation for selecting corrective actions that utility operators can take during major contingency and thus automate the hybrid dynamic-steady state cascading outage process. The improved DCAT framework with OPF based corrective actions is demonstrated on IEEE 300 bus test system.

Cascade system using both trough system and dish system for power generation

International Nuclear Information System (INIS)

Zhang, Cheng; Zhang, Yanping; Arauzo, Inmaculada; Gao, Wei; Zou, Chongzhe

2017-01-01

Highlights: • A novel solar cascade system using both trough and dish collectors is proposed. • Heat rejected by the Stirling engines is collected by the condensed water. • The directions to increase the efficiency improvement has been pointed out • Influence of flow type of heating/cooling fluids of Stirling engines is considered. - Abstract: This paper represents a novel solar thermal cascade system using both trough and dish systems for power generation. An effective structure using the condensed fluid of Rankine cycle to cool the Stirling engines to use the heat released by Stirling engines was proposed. The cascade system model with different fluid circuits was developed. The models of some important components of the system, such as dish collector, trough collector and Stirling engine array, are presented with detail explanation in this paper. Corresponding stand-alone systems were also developed for comparison. Simulations were conducted with the models to find out efficiency difference between cascade system and corresponding stand-alone systems. The directions to increase the efficiency difference were also considered. Results show that the cascade system can achieve a higher efficiency with a high solar irradiance (>550 W/m"2). The flow type of fluids between heating and cooling Stirling engine array is also required to concern on designing a cascade system with Stirling engine array.

Cascade of circulations in fluid turbulence.

Science.gov (United States)

Eyink, Gregory L

2006-12-01

Kelvin's theorem on conservation of circulations is an essential ingredient of Taylor's theory of turbulent energy dissipation by the process of vortex-line stretching. In previous work, we have proposed a nonlinear mechanism for the breakdown of Kelvin's theorem in ideal turbulence at infinite Reynolds number. We develop here a detailed physical theory of this cascade of circulations. Our analysis is based upon an effective equation for large-scale coarse-grained velocity, which contains a turbulent-induced vortex force that can violate Kelvin's theorem. We show that singularities of sufficient strength, which are observed to exist in turbulent flow, can lead to nonvanishing dissipation of circulation for an arbitrarily small coarse-graining length in the effective equations. This result is an analog for circulation of Onsager's theorem on energy dissipation for singular Euler solutions. The physical mechanism of the breakdown of Kelvin's theorem is diffusion of lines of large-scale vorticity out of the advected loop. This phenomenon can be viewed as a classical analog of the Josephson-Anderson phase-slip phenomenon in superfluids due to quantized vortex lines. We show that the circulation cascade is local in scale and use this locality to develop concrete expressions for the turbulent vortex force by a multiscale gradient expansion. We discuss implications for Taylor's theory of turbulent dissipation and we point out some related cascade phenomena, in particular for magnetic flux in magnetohydrodynamic turbulence.

Phytochemicals Screening and In Vitro Antibacterial Activity of Elaeis guineensis Leaves Extracts Against Human Pathogenic Bacteria

International Nuclear Information System (INIS)

Noorshilawati Abdul Aziz; Umi Nadhirah Halim; Nur Suraya Abdullah

2015-01-01

Chloroform and methanol extracts of Elaeis guineensis leaves were investigated for in vitro antibacterial activity against the human pathogenic bacteria Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Four different concentrations of both extracts consists of 50, 100, 200 and 300 mg/ ml were prepared for antibacterial activity using disc diffusion method. The results revealed that chloroform and methonal extract showed high toxicity against all bacterial strain tested. However, both extracts is more effective and exhibit better inhibiting activity against gram positive bacteria, S. aureus compared to gram negative bacteria (E. coli and P. aeruginosa). Methanol extract of Elaeis guineensis leaves shows greater inhibition zone compared to chloroform extract as phyto chemical screening revealed that this extracts contain terpenoids, tannins and saponin. The highest antibacterial activity was exhibited by 300 mg/ ml methanolic extracts against S. aureus which inhibited 10.67 ± 0.33 mm of the diameter zone. Followed by 200 mg/ ml methanolic extracts and 300 mg/ ml chloroform extracts against S. aureus which inhibited 9.17 ± 0.17 mm and 8.33 ± 1.67 mm respectively. This result revealed the potentials of Elaeis guineensis as antibacterial agent in combating infections from human pathogenic bacteria. However, further studies, including identification and purification of the active compounds, will need to be pursued. (author)

Cascading Corruption News

DEFF Research Database (Denmark)

Damgaard, Mads

2018-01-01

Through a content analysis of 8,800 news items and six months of front pages in three Brazilian newspapers, all dealing with corruption and political transgression, this article documents the remarkable skew of media attention to corruption scandals. The bias is examined as an information...... phenomenon, arising from systemic and commercial factors of Brazil’s news media: An information cascade of news on corruption formed, destabilizing the governing coalition and legitimizing the impeachment process of Dilma Rousseff. As this process gained momentum, questions of accountability were disregarded...... by the media, with harmful effects on democracy....

An evolutionary cascade model for sauropod dinosaur gigantism--overview, update and tests.

Directory of Open Access Journals (Sweden)

P Martin Sander

Full Text Available Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM. This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades ("Reproduction", "Feeding", "Head and neck", "Avian-style lung", and "Metabolism". Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait "Very high body mass". Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size.

An evolutionary cascade model for sauropod dinosaur gigantism--overview, update and tests.

Science.gov (United States)

Sander, P Martin

2013-01-01

Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM). This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades ("Reproduction", "Feeding", "Head and neck", "Avian-style lung", and "Metabolism"). Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait "Very high body mass". Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits) were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size.

Failure cascade in interdependent network with traffic loads

International Nuclear Information System (INIS)

Hong, Sheng; Wang, Baoqing; Wang, Jianghui; Zhao, Tingdi; Ma, Xiaomin

2015-01-01

Complex networks have been widely studied recent years, but most researches focus on the single, non-interacting networks. With the development of modern systems, many infrastructure networks are coupled together and therefore should be modeled as interdependent networks. For interdependent networks, failure of nodes in one network may lead to failure of dependent nodes in the other networks. This may happen recursively and lead to a failure cascade. In the real world, different networks carry different traffic loads. Overload and load redistribution may lead to more nodes’ failure. Considering the dependency between the interdependent networks and the traffic load, a small fraction of fault nodes may lead to complete fragmentation of a system. Based on the robust analysis of interdependent networks, we propose a costless defense strategy to suppress the failure cascade. Our findings highlight the need to consider the load and coupling preference when designing robust interdependent networks. And it is necessary to take actions in the early stage of the failure cascade to decrease the losses caused by the large-scale breakdown of infrastructure networks. (paper)

A cascaded three-phase symmetrical multistage voltage multiplier

International Nuclear Information System (INIS)

Iqbal, Shahid; Singh, G K; Besar, R; Muhammad, G

2006-01-01

A cascaded three-phase symmetrical multistage Cockcroft-Walton voltage multiplier (CW-VM) is proposed in this report. It consists of three single-phase symmetrical voltage multipliers, which are connected in series at their smoothing columns like string of batteries and are driven by three-phase ac power source. The smoothing column of each voltage multiplier is charged twice every cycle independently by respective oscillating columns and discharged in series through load. The charging discharging process completes six times a cycle and therefore the output voltage ripple's frequency is of sixth order of the drive signal frequency. Thus the proposed approach eliminates the first five harmonic components of load generated voltage ripples and sixth harmonic is the major ripple component. The proposed cascaded three-phase symmetrical voltage multiplier has less than half the voltage ripple, and three times larger output voltage and output power than the conventional single-phase symmetrical CW-VM. Experimental and simulation results of the laboratory prototype are given to show the feasibility of proposed cascaded three-phase symmetrical CW-VM

Cascade-based attacks on complex networks

Science.gov (United States)

Motter, Adilson E.; Lai, Ying-Cheng

2002-12-01

We live in a modern world supported by large, complex networks. Examples range from financial markets to communication and transportation systems. In many realistic situations the flow of physical quantities in the network, as characterized by the loads on nodes, is important. We show that for such networks where loads can redistribute among the nodes, intentional attacks can lead to a cascade of overload failures, which can in turn cause the entire or a substantial part of the network to collapse. This is relevant for real-world networks that possess a highly heterogeneous distribution of loads, such as the Internet and power grids. We demonstrate that the heterogeneity of these networks makes them particularly vulnerable to attacks in that a large-scale cascade may be triggered by disabling a single key node. This brings obvious concerns on the security of such systems.

Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations.

Directory of Open Access Journals (Sweden)

Edgar Altszyler

Full Text Available Ultrasensitive response motifs, capable of converting graded stimuli into binary responses, are well-conserved in signal transduction networks. Although it has been shown that a cascade arrangement of multiple ultrasensitive modules can enhance the system's ultrasensitivity, how a given combination of layers affects a cascade's ultrasensitivity remains an open question for the general case. Here, we introduce a methodology that allows us to determine the presence of sequestration effects and to quantify the relative contribution of each module to the overall cascade's ultrasensitivity. The proposed analysis framework provides a natural link between global and local ultrasensitivity descriptors and it is particularly well-suited to characterize and understand mathematical models used to study real biological systems. As a case study, we have considered three mathematical models introduced by O'Shaughnessy et al. to study a tunable synthetic MAPK cascade, and we show how our methodology can help modelers better understand alternative models.

Astrophysical Gyrokinetics: Kinetic and Fluid Turbulent Cascades In Magentized Weakly Collisional Plasmas

Energy Technology Data Exchange (ETDEWEB)

Schekochihin, A. A.; Cowley, S. C.; Dorland, W.; Hammett, G. W.; Howes, G. G.; Quataert, E.; Tatsuno, T.

2009-04-23

This paper presents a theoretical framework for understanding plasma turbulence in astrophysical plasmas. It is motivated by observations of electromagnetic and density fluctuations in the solar wind, interstellar medium and galaxy clusters, as well as by models of particle heating in accretion disks. All of these plasmas and many others have turbulentmotions at weakly collisional and collisionless scales. The paper focuses on turbulence in a strong mean magnetic field. The key assumptions are that the turbulent fluctuations are small compared to the mean field, spatially anisotropic with respect to it and that their frequency is low compared to the ion cyclotron frequency. The turbulence is assumed to be forced at some system-specific outer scale. The energy injected at this scale has to be dissipated into heat, which ultimately cannot be accomplished without collisions. A kinetic cascade develops that brings the energy to collisional scales both in space and velocity. The nature of the kinetic cascade in various scale ranges depends on the physics of plasma fluctuations that exist there. There are four special scales that separate physically distinct regimes: the electron and ion gyroscales, the mean free path and the electron diffusion scale. In each of the scale ranges separated by these scales, the fully kinetic problem is systematically reduced to a more physically transparent and computationally tractable system of equations, which are derived in a rigorous way. In the "inertial range" above the ion gyroscale, the kinetic cascade separates into two parts: a cascade of Alfvenic fluctuations and a passive cascade of density and magnetic-fieldstrength fluctuations. The former are governed by the Reduced Magnetohydrodynamic (RMHD) equations at both the collisional and collisionless scales; the latter obey a linear kinetic equation along the (moving) field lines associated with the Alfvenic component (in the collisional limit, these compressive fluctuations

Astrophysical Gyrokinetics: Kinetic and Fluid Turbulent Cascades In Magnetized Weakly Collisional Plasmas

International Nuclear Information System (INIS)

Schekochihin, A.A.; Cowley, S.C.; Dorland, W.; Hammett, G.W.; Howes, G.G.; Quataert, E.; Tatsuno, T.

2009-01-01

This paper presents a theoretical framework for understanding plasma turbulence in astrophysical plasmas. It is motivated by observations of electromagnetic and density fluctuations in the solar wind, interstellar medium and galaxy clusters, as well as by models of particle heating in accretion disks. All of these plasmas and many others have turbulent motions at weakly collisional and collisionless scales. The paper focuses on turbulence in a strong mean magnetic field. The key assumptions are that the turbulent fluctuations are small compared to the mean field, spatially anisotropic with respect to it and that their frequency is low compared to the ion cyclotron frequency. The turbulence is assumed to be forced at some system-specific outer scale. The energy injected at this scale has to be dissipated into heat, which ultimately cannot be accomplished without collisions. A kinetic cascade develops that brings the energy to collisional scales both in space and velocity. The nature of the kinetic cascade in various scale ranges depends on the physics of plasma fluctuations that exist there. There are four special scales that separate physically distinct regimes: the electron and ion gyroscales, the mean free path and the electron diffusion scale. In each of the scale ranges separated by these scales, the fully kinetic problem is systematically reduced to a more physically transparent and computationally tractable system of equations, which are derived in a rigorous way. In the 'inertial range' above the ion gyroscale, the kinetic cascade separates into two parts: a cascade of Alfvenic fluctuations and a passive cascade of density and magnetic-field strength fluctuations. The former are governed by the Reduced Magnetohydrodynamic (RMHD) equations at both the collisional and collisionless scales; the latter obey a linear kinetic equation along the (moving) field lines associated with the Alfvenic component (in the collisional limit, these compressive fluctuations

Effect of inelastic energy losses on development of atom-atom collision cascades

International Nuclear Information System (INIS)

Marinyuk, V.V.; Remizovich, V.S.

2001-01-01

The problem of influence of inelastic energy losses (ionization braking) of particles on the development of atom-atom collision cascades in infinite medium was studied theoretically. Main attention was paid to study of angular and energy distributions of primary ions and cascade atoms in the presence of braking. Analytical calculations were made in the assumption that single scattering of particles occurs by solid balls law, while the value of electron braking ability of a medium is determined by the Lindhard formula. It is shown that account of braking (directly when solving the Boltzmann transport equation) changes in principle the previously obtained angular and energy spectra of ions and cascade atoms. Moreover, it is the braking that is the determining factor responsible for anisotropy of angular distributions of low-energy primary ions and cascade atoms [ru

Gene regulation by MAP kinase cascades

DEFF Research Database (Denmark)

Fiil, Berthe Katrine; Petersen, Klaus; Petersen, Morten

2009-01-01

Mitogen-activated protein kinase (MAPK) cascades are signaling modules that transduce extracellular stimuli to a range of cellular responses. Research in yeast and metazoans has shown that MAPK-mediated phosphorylation directly or indirectly regulates the activity of transcription factors. Plant ...

Molecular dynamics studies on the structural effects of displacement cascades in UO2 matrix

International Nuclear Information System (INIS)

Brutzel, L. Van; Rarivomanantsoa, M.; Ghaleb, D.

2004-01-01

A set of molecular dynamics simulations have been carried out in order to study, at the atomic scale, the ballistic damages undergo by the UO 2 matrix. The morphologies of the displacement cascades simulations initiated by an uranium atoms with a Primary Knout on Atom (PKA) energy ranges from 1 keV to 20 keV are analysed. In agreement with all the experimental results no amorphization has been found even at small scales. For the cascade initiated with a PKA energy of 20 keV several sub-cascade branches appear in many directions from the cascade core. It seems that these sub-cascades arise from a quasi channeling of uranium atoms in specific direction over long distances. However, in average the atoms are displaced no more than 2 to 3 crystallographic sites. The evolution of the Frenkel pairs with the initial energy of the PKA exhibits a power law behavior with an exponent close to 0.9 showing a discrepancy with the linear NRT law. No significant clustering of local defects such as vacancies and interstitials have been found, nevertheless vacancies are preferentially created near the core of the cascade whereas the atoms in interstitial positions are mainly located at the periphery of the sub-cascade branches. (authors)

Successful Treatment Of Homozygous Familial Hypercholesterolemia Using Cascade Filtration Plasmapheresis

Directory of Open Access Journals (Sweden)

Fatih Kardas

2012-12-01

Full Text Available OBJECTIVE: The aim of our study is to discuss the efficacy of low-density lipoprotein-cholesterol (LDL-C apheresis procedure using the cascade filtration system for pediatric patients with homozygous familial hypercholesterolemia (FH, and to clarify the adverse effects and difficulties. METHODS: LDL apheresis using the cascade filtration system was performed in 3 pediatric patients with homozygous FH. In total, 120 apheresis sessions were performed for all patients. RESULTS: Cascade filtration therapy significantly reduced the mean LDL-C values from 418 ± 62 mg/dl to 145 ± 43 mg/dl (p<0.05. We determined an acute mean reduction in the plasma levels of total cholesterol (57.9%, LDL cholesterol (70.8%, and high-density lipoprotein (HDL cholesterol (40.7%. Treatments were well tolerated. The most frequent clinical adverse effects were hypotension in 3 sessions (2.5%, chills/feeling cold (1.7% in 2 sessions, and nausea and vomiting in 3 sessions (2.5%. CONCLUSION: Our experience with three patients using the cascade filtration system were, good clinical outcomes, laboratory findings, safety of usage, minor adverse effects and technical problems.

Search for Magnetically Broadened Cascade Emission from Blazars with VERITAS

Energy Technology Data Exchange (ETDEWEB)

Archambault, S.; Griffin, S. [Physics Department, McGill University, Montreal, QC H3A 2T8 (Canada); Archer, A.; Bugaev, V. [Department of Physics, Washington University, St. Louis, MO 63130 (United States); Benbow, W.; Cerruti, M. [Fred Lawrence Whipple Observatory, Harvard-Smithsonian Center for Astrophysics, Amado, AZ 85645 (United States); Buchovecky, M. [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095 (United States); Connolly, M. P. [School of Physics, National University of Ireland Galway, University Road, Galway (Ireland); Cui, W.; Finley, J. P. [Department of Physics and Astronomy, Purdue University, West Lafayette, IN 47907 (United States); Falcone, A. [Department of Astronomy and Astrophysics, 525 Davey Lab, Pennsylvania State University, University Park, PA 16802 (United States); Alonso, M. Fernández [Instituto de Astronomía y Física del Espacio (IAFE, CONICET-UBA), CC 67—Suc. 28, (C1428ZAA) Ciudad Autónoma de Buenos Aires (Argentina); Fleischhack, H.; Hütten, M. [DESY, Platanenallee 6, D-15738 Zeuthen (Germany); Fortson, L. [School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455 (United States); Furniss, A. [Department of Physics, California State University—East Bay, Hayward, CA 94542 (United States); Hervet, O.; Johnson, C. A. [Santa Cruz Institute for Particle Physics and Department of Physics, University of California, Santa Cruz, CA 95064 (United States); Holder, J. [Department of Physics and Astronomy and the Bartol Research Institute, University of Delaware, Newark, DE 19716 (United States); Humensky, T. B., E-mail: elisa.pueschel@ucd.ie, E-mail: weisgarber@physics.wisc.edu [Physics Department, Columbia University, New York, NY 10027 (United States); and others

2017-02-01

We present a search for magnetically broadened gamma-ray emission around active galactic nuclei (AGNs), using VERITAS observations of seven hard-spectrum blazars. A cascade process occurs when multi-TeV gamma-rays from an AGN interact with extragalactic background light (EBL) photons to produce electron–positron pairs, which then interact with cosmic microwave background photons via inverse-Compton scattering to produce gamma-rays. Due to the deflection of the electron–positron pairs, a non-zero intergalactic magnetic field (IGMF) would potentially produce detectable effects on the angular distribution of the cascade emission. In particular, an angular broadening compared to the unscattered emission could occur. Through non-detection of angularly broadened emission from 1ES 1218+304, the source with the largest predicted cascade fraction, we exclude a range of IGMF strengths around 10{sup −14} G at the 95% confidence level. The extent of the exclusion range varies with the assumptions made about the intrinsic spectrum of 1ES 1218+304 and the EBL model used in the simulation of the cascade process. All of the sources are used to set limits on the flux due to extended emission.

MD simulation of atomic displacement cascades in Fe-10 at.%Cr binary alloy

International Nuclear Information System (INIS)

Tikhonchev, M.; Svetukhin, V.; Kadochkin, A.; Gaganidze, E.

2009-01-01

Molecular dynamics simulation of atomic displacement cascades up to 20 keV has been performed in Fe-10 at.%Cr binary alloy at a temperature of 600 K. The N-body interatomic potentials of Finnis-Sinclair type were used. According to the obtained results the dependence of 'surviving' defects amount is well approximated by power function that coincides with other researchers' results. Obtained cascade efficiency for damage energy in the range from 10 to 20 keV is ∼0.2 NRT that is slightly higher than for pure α-Fe. In post-cascade area Cr fraction in interstitials is in range 2-5% that is essentially lower than Cr content in the base alloy. The results on size and amount of vacancy and interstitial clusters generated in displacement cascades are obtained. For energies of 2 keV and higher the defect cluster average size increases and it is well approximated by a linear dependence on cascade energy both for interstitials and vacancies.

MD simulation of atomic displacement cascades in Fe-10 at.%Cr binary alloy

Energy Technology Data Exchange (ETDEWEB)

Tikhonchev, M., E-mail: tikhonchev@sv.ulsu.r [Ulyanovsk State University, Leo Tolstoy Str., 42, Ulyanovsk 432970 (Russian Federation); Joint Stock Company, ' State Scientific Center Research Institute of Atomic Reactors' , 433510 Dimitrovgrad-10 (Russian Federation); Svetukhin, V.; Kadochkin, A. [Ulyanovsk State University, Leo Tolstoy Str., 42, Ulyanovsk 432970 (Russian Federation); Gaganidze, E. [Forschungszentrum Karlsruhe, IMF II, 3640, D-76021 Karlsruhe (Germany)

2009-12-15

Molecular dynamics simulation of atomic displacement cascades up to 20 keV has been performed in Fe-10 at.%Cr binary alloy at a temperature of 600 K. The N-body interatomic potentials of Finnis-Sinclair type were used. According to the obtained results the dependence of 'surviving' defects amount is well approximated by power function that coincides with other researchers' results. Obtained cascade efficiency for damage energy in the range from 10 to 20 keV is approx0.2 NRT that is slightly higher than for pure alpha-Fe. In post-cascade area Cr fraction in interstitials is in range 2-5% that is essentially lower than Cr content in the base alloy. The results on size and amount of vacancy and interstitial clusters generated in displacement cascades are obtained. For energies of 2 keV and higher the defect cluster average size increases and it is well approximated by a linear dependence on cascade energy both for interstitials and vacancies.

76 FR 9613 - USEC Inc. (American Centrifuge Lead Cascade Facility and American Centrifuge Plant); Order...

Science.gov (United States)

2011-02-18

... NUCLEAR REGULATORY COMMISSION [EA-11-013] USEC Inc. (American Centrifuge Lead Cascade Facility and American Centrifuge Plant); Order Approving Direct Transfer of Licenses and Conforming Amendment I USEC... Centrifuge Lead Cascade Facility (Lead Cascade) and American Centrifuge Plant (ACP), respectively, which...

Effects of in-cascade defect clustering on near-term defect evolution

Energy Technology Data Exchange (ETDEWEB)

Heinisch, H.L. [Pacific Northwest National Lab., Richland, WA (United States)

1997-08-01

The effects of in-cascade defect clustering on the nature of the subsequent defect population are being studied using stochastic annealing simulations applied to cascades generated in molecular dynamics (MD) simulations. The results of the simulations illustrates the strong influence of the defect configuration existing in the primary damage state on subsequent defect evolution. The large differences in mobility and stability of vacancy and interstitial defects and the rapid one-dimensional diffusion of small, glissile interstitial loops produced directly in cascades have been shown to be significant factors affecting the evolution of the defect distribution. In recent work, the effects of initial cluster sizes appear to be extremely important.

In vitro Inhibition of Mycobacterium smegmatis and Mycobacterium ...

African Journals Online (AJOL)

Some Nigerian plants used in traditional medicine to treat tuberculosis and/or some of its symptoms were screened for in vitro activity against Mycobacterium smegmatis and a clinical isolate of Mycobacterium tuberculosis. Only 3 of the 6 crude methanolic extracts of the 6 plant species exhibited inhibitory activities against ...

An Evolutionary Cascade Model for Sauropod Dinosaur Gigantism - Overview, Update and Tests

Science.gov (United States)

Sander, P. Martin

2013-01-01

Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM). This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades (“Reproduction”, “Feeding”, “Head and neck”, “Avian-style lung”, and “Metabolism”). Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait “Very high body mass”. Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits) were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size. PMID:24205267

Evaluation of Power Generation Efficiency of Cascade Hydropower Plants: A Case Study

Directory of Open Access Journals (Sweden)

Jiahua Wei

2013-02-01

Full Text Available Effective utilization of scarce water resources has presented a significant challenge to respond to the needs created by rapid economic growth in China. In this study, the efficiency of the joint operation of the Three Gorges and Gezhouba cascade hydropower plants in terms of power generation was evaluated on the basis of a precise simulation-optimization technique. The joint operation conditions of the Three Gorges and Gezhouba hydropower plants between 2004 and 2010 were utilized in this research in order to investigate the major factors that could affect power output of the cascade complex. The results showed that the current power output of the Three Gorges and Gezhouba cascade complex had already reached around 90% of the maximum theoretical value. Compared to other influencing factors evaluated in this study, the accuracy of hydrological forecasts and flood control levels can have significant impact on the power generating efficiency, whereas the navigation has a minor influence. This research provides a solid quantitative-based methodology to assess the operation efficiency of cascade hydropower plants, and more importantly, proposes potential methods that could improve the operation efficiency of cascade hydropower plants.

PARAMETRIC STUDY OF ENERGY, EXERGY AND THERMOECONOMIC ANALYSES ON VAPOR-COMPRESSION SYSTEM CASCADED WITH LIBR/WATER AND NH3/WATER ABSORBTION CASCADE REFRIGERATION CYCLE

Directory of Open Access Journals (Sweden)

ahmet selim dalkilic

2017-03-01

Full Text Available Energy savings on cooling systems can be performed by using novel refrigeration cycles. For this aim, vapour compression-vapour absorption cascade refrigeration systems can be considered as substitute to single-stage vapour compression refrigeration systems. Renewable energy sources of geothermal and solar heat, waste heat of processes have been used by these cycles to provide cooling and they also require less electrical energy than vapour compression cycles having alternative refrigerants. In this study, a vapour compression (VC and vapour absorption (VA cascade systems are analysed with the second law analysis for varied cooling capacities. While lithium bromide-water and NH3/H2O are the working fluids in VA part, various refrigerants are used in VC section. The refrigerants of R134a and R600a, R410A and R407C are tested as drop in alternatives for R12 and R22, respectively. The effects of alteration in cooling capacity, superheating and sub cooling in VC part, temperature in the generator and absorber, and degree of overlap in cascade condenser in VA part on the coefficient of system performance are studied. Validation of the results have been performed by the values given in the literature. Improvement in COP of VC, VA and cascade system are obtained separately. According to the analyses, cascade systems’ COP values increase with increasing the temperatures of generator and evaporator and they also increase with decreasing the condenser and absorber temperatures. Moreover, the generator has the highest exergy destruction rates, second and third one were the condenser and absorber, respectively. Electricity consumption and payback period are also determined considering the various parameters of the study.

Neutron cross sections for defect production by high-energy displacement cascades in copper

International Nuclear Information System (INIS)

Heinisch, H.L.; Mann, F.M.

1983-08-01

Defect production cross sections for copper have been devised, based on computer simulations of displacement cascades. One thousand cascades ranging in energy from 200 eV to 200 keV were generated with the MARLOWE computer code. The cascades were subjected to a semi-empirical cascade quenching procedure and to short-term annealing with the ALSOME computer code. Functions were fitted to the numbers of defects produced as a function of primary knock-on atom (PKA) damage energy for the following defect types: 1) the total number of point defects after quenching and after short-term annealing, 2) the numbers of free interstitials and free vacancies after shortterm annealing, and 3) the numbers and sizes of vacancy and interstitial clusters after shortterm annealing. In addition, a function describing the number of distinct damage regions (lobes) per cascade was fitted to results of a graphical analysis of the cascade configurations. The defect production functions have been folded into PKA spectra using the NJOY nuclear data processing code system with ENDF/B-V nuclear data to yield neutron cross sections for defect production in copper. The free vacancy cross section displays much less variation with neutron energy than the cross sections for damage energy or total point defects

Closed Loop Fuzzy Logic Controlled PV Based Cascaded Boost Five-Level Inverter System

Science.gov (United States)

Revana, Guruswamy; Kota, Venkata Reddy

2018-04-01

Recent developments in intelligent control methods and power electronics have produced PV based DC to AC converters related to AC drives. Cascaded boost converter and inverter find their way in interconnecting PV and Induction Motor. This paper deals with digital simulation and implementation of closed loop controlled five-level inverter based Photo-Voltaic (PV) system. The objective of this work is to reduce the harmonics using Multi Level Inverter based system. The DC output from the PV panel is boosted using cascaded-boost-converters. The DC output of these cascaded boost converters is applied to the bridges of the cascaded inverter. The AC output voltage is obtained by the series cascading of the output voltage of the two inverters. The investigations are done with Induction motor load. Cascaded boost-converter is proposed in the present work to produce the required DC Voltage at the input of the bridge inverter. A simple FLC is applied to CBFLIIM system. The FLC is proposed to reduce the steady state error. The simulation results are compared with the hardware results. The results of the comparison are made to show the improvement in dynamic response in terms of settling time and steady state error. Design procedure and control strategy are presented in detail.

Neutron cross sections for defect production by high energy displacement cascades in copper

International Nuclear Information System (INIS)

Heinisch, H.L.; Mann, F.M.

1984-01-01

Defect production cross sections for copper have been devised, based on computer simulations of displacement cascades. One thousand cascades ranging in energy from 200 eV to 200 keV were generated with the MARLOWE computer code. The cascades were subjected to a semi-empirical cascade quenching procedure and to short-term annealing with the ALSOME computer code. Functions were fitted to the numbers of defects produced as a function of primary knock-on atom (PKA) damage energy for the following defect types: 1) the total number of point defects after quenching and after short-term annealing, 2) the numbers of free interstitials and free vacancies after short-term annealing, and 3) the numbers and sizes of vacancy and interstitial clusters after short-term annealing. In addition, a function describing the number of distinct damage regions (lobes) per cascade was fitted to results of a graphical analysis of the cascade configurations. The defect production functions have been folded into PKA spectra using the NJOY nuclear data processing code system with ENDF/B-V nuclear data to yield neutron cross sections for defect production in copper. The free vacancy cross section displays much less variation with neutron energy than the cross sections for damage energy or total point defects. (orig.)

Multiplicity distributions in QCD cascades

International Nuclear Information System (INIS)

Gustafson, G.

1992-03-01

Multiplicity distributions for hadrons and for jets are studied in QCD parton cascades. The colour dipole formalism is used and earlier results in the double log approximation are generalized to include terms which are suppressed by colour factors or factors of ln s. The result is a set of coupled differential equations, together with appropriate boundary conditions

Staged anticonvulsant screening for chronic epilepsy

OpenAIRE

Berdichevsky, Yevgeny; Saponjian, Yero; Park, Kyung‐Il; Roach, Bonnie; Pouliot, Wendy; Lu, Kimberly; Swiercz, Waldemar; Dudek, F. Edward; Staley, Kevin J.

2016-01-01

Abstract Objective: Current anticonvulsant screening programs are based on seizures evoked in normal animals. One‐third of epileptic patients do not respond to the anticonvulsants discovered with these models. We evaluated a tiered program based on chronic epilepsy and spontaneous seizures, with compounds advancing from high‐throughput in vitro models to low‐throughput in vivo models. Methods: Epileptogenesis in organotypic hippocampal slice cultures was quantified by lactate production and l...

Impedance interactions in bidirectional cascaded converter

DEFF Research Database (Denmark)

Tian, Yanjun; Loh, Poh Chiang; Chen, Zhe

2016-01-01

A cascaded converter is built by connecting one elementary converter to another. Output impedance of one converter will therefore interact with input impedance of the other converter. This interaction will change when power flow reverses. To compare this difference, an investigation is performed...

75 FR 70300 - USEC, Inc.; American Centrifuge Lead Cascade Facility; American Centrifuge Plant; Notice of...

Science.gov (United States)

2010-11-17

... Centrifuge Lead Cascade Facility; American Centrifuge Plant; Notice of Receipt of a License Transfer... SNM-2011, for the American Centrifuge Lead Cascade Facility and the American Centrifuge Plant... USEC Inc., (the Licensee), for its American Centrifuge Lead Cascade Facility (LCF) and American...

In vitro gastrointestinal digestion increases the translocation of polystyrene nanoparticles in an in vitro intestinal co-culture model.

Science.gov (United States)

Walczak, Agata P; Kramer, Evelien; Hendriksen, Peter J M; Helsdingen, Richard; van der Zande, Meike; Rietjens, Ivonne M C M; Bouwmeester, Hans

2015-01-01

The conditions of the gastrointestinal tract may change the physicochemical properties of nanoparticles (NPs) and therewith the bioavailability of orally taken NPs. Therefore, we assessed the impact of in vitro gastrointestinal digestion on the protein corona of polystyrene NPs (PS-NPs) and their subsequent translocation across an in vitro intestinal barrier. A co-culture of intestinal Caco-2 and HT29-MTX cells was exposed to 50 nm PS-NPs of different charges (positive and negative) in two forms: pristine and digested in an in vitro gastrointestinal digestion model. In vitro digestion significantly increased the translocation of all, except the "neutral", PS-NPs. Upon in vitro digestion, translocation was 4-fold higher for positively charged NPs and 80- and 1.7-fold higher for two types of negatively charged NPs. Digestion significantly reduced the amount of protein in the corona of three out of four types of NPs. This reduction of proteins was 4.8-fold for "neutral", 3.5-fold for positively charged and 1.8-fold for one type of negatively charged PS-NPs. In vitro digestion also affected the composition of the protein corona of PS-NPs by decreasing the presence of higher molecular weight proteins and shifting the protein content of the corona to low molecular weight proteins. These findings are the first to report that in vitro gastrointestinal digestion significantly affects the protein corona and significantly increases the in vitro translocation of differently charged PS-NPs. These findings stress the importance of including the in vitro digestion in future in vitro intestinal translocation screening studies for risk assessment of orally taken NPs.

Volatile emissions from Cascade cinder cone eruptions: Implications for future hazard assessments in the Central and Southern Cascades

Science.gov (United States)

Walsh, L. K.; Wallace, P. J.; Cashman, K. V.

2012-12-01

An abundance of hazardous effects including ash fall out, basaltic lava flows and poisonous volcanic gas have been documented at active volcanic centers (e.g. Auckland Volcanic Field, New Zealand; Bebbington and Cronin 2011) and have been inferred using tools such as geologic mapping and geochemical analyses for prehistoric eruptions (e.g. Cerro Negro, Nicaragua; Hill et al. 1995; McKnight and Williams 1997). The Cascades volcanic history is also dominated by prehistoric eruptions; however the associated hazards have yet to be studied in-depth. Short recurrence rates of cinder cone volcanism (1x10-5 to 5x10-4 events/yr; Smid et al. 2009) likely intensify the probability of human experience with cinder cone hazards. Hence, it is important to understand the effects that cinder cone volcanism can have on communities near the Cascades. In this study, we estimate volatile fluxes of prehistoric Cascade cinder cone eruptions by analyzing olivine-hosted melt inclusions and rapidly quenched tephra matrix glass. The melt inclusions provide pre-eruptive volatile concentrations whereas tephra groundmass glass provides post-eruptive volatile concentrations. By comparing initial and final concentrations we can determine the amounts of sulfur, chlorine and fluorine released into the atmosphere. We have analyzed S, Cl and F concentrations in melt inclusions from cinder cones in the Central Oregon Cascades (Collier Cone, Yapoah Crater, Four-in-One Fissure, Garrison Butte) and in Northern California near Mt. Lassen (Cinder Cone, Basalt of Old Railroad Grade, Basalt of Highway 44). Analyses of volatiles in melt inclusions and matrix glasses were done using the Cameca SX100 electron microprobe at the University of Oregon. Melt inclusions and matrix glass were run under 15kV, 50nA, and 10μm-beam conditions. For F analyses, a use of an LTAP crystal and relatively long counting times (160 sec. on peak) resulted in good analytical precision. Preliminary results for melt inclusions from

Diode pumped cascade Er:Y2O3 laser

International Nuclear Information System (INIS)

Sanamyan, T

2015-01-01

A cascade, diode-pumped, continuous wave (CW), dual-wavelength operation in a 0.5% Er 3+ :Y 2 O 3 cryogenic ceramic laser is demonstrated for the first time. The laser operates on cascaded Er ( 4 I 11/2   →   4 I 13/2   →   4 I 15/2 ) transitions and can deliver 24 and 13 W at 1.6 and 2.7 μm, respectively. The overall efficiency with respect to the absorbed ∼980 nm power was 62%. This is, to our best knowledge, the first demonstration of an efficient, high power, cascade, erbium laser achieved in bulk solid-state lasers. The analysis of the output power, the laser’s wavelengths and slope efficiency for each individual laser transition are presented for pure CW operation mode. Also presented are the temporal behaviors of each laser line as a function of pump pulse duration in the quasi-CW regime. (letter)

Controle qualite de l'eau de baignade de la Cascade de Man en ...

African Journals Online (AJOL)

La cascade Ypou du mont Tonkoui appelée couramment « cascade de Man » est un joyau naturel qui attire de nombreux touristes. Elle est très fréquentée pour sa beauté mais aussi pour la baignade. En amont de cette cascade, le paysage se compose de champs de café et selon la période, de maïs et de manioc. Il nous ...

High-yield continuous production of nicotinic acid via nitrile hydratase–amidase cascade reactions using cascade CSMRs

Czech Academy of Sciences Publication Activity Database

Cantarella, L.; Gallifuoco, A.; Malandra, A.; Martínková, Ludmila; Spera, A.; Cantarella, M.

2011-01-01

Roč. 48, 4-5 (2011), 345-350 ISSN 0141-0229 R&D Projects: GA MŠk OC09046 Institutional research plan: CEZ:AV0Z50200510 Keywords : Nitrile hydratase-amidase cascade system * 3-Cyanopyridine bioconversion * Nicotinic acid Subject RIV: EE - Microbiology, Virology Impact factor: 2.367, year: 2011

Cascade Error Projection: A New Learning Algorithm

Science.gov (United States)

Duong, T. A.; Stubberud, A. R.; Daud, T.; Thakoor, A. P.

1995-01-01

A new neural network architecture and a hardware implementable learning algorithm is proposed. The algorithm, called cascade error projection (CEP), handles lack of precision and circuit noise better than existing algorithms.

Inhibitors of MyD88-dependent proinflammatory cytokine production identified utilizing a novel RNA interference screening approach.

Directory of Open Access Journals (Sweden)

John S Cho

2009-09-01

Full Text Available The events required to initiate host defenses against invading pathogens involve complex signaling cascades comprised of numerous adaptor molecules, kinases, and transcriptional elements, ultimately leading to the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha. How these signaling cascades are regulated, and the proteins and regulatory elements participating are still poorly understood.We report here the development a completely random short-hairpin RNA (shRNA library coupled with a novel forward genetic screening strategy to identify inhibitors of Toll-like receptor (TLR dependent proinflammatory responses. We developed a murine macrophage reporter cell line stably transfected with a construct expressing diphtheria toxin-A (DT-A under the control of the TNF-alpha-promoter. Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide (LPS resulted in DT-A induced cell death, which could be prevented by the addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA (shRNA library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression. Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3-dependent TNF-alpha production.Thus, we describe the generation of novel tools to facilitate large-scale forward genetic screens in mammalian cells and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent proinflammatory responses.

Analysis on Invulnerability of Wireless Sensor Network towards Cascading Failures Based on Coupled Map Lattice

Directory of Open Access Journals (Sweden)

Xiuwen Fu

2018-01-01

Full Text Available Previous research of wireless sensor networks (WSNs invulnerability mainly focuses on the static topology, while ignoring the cascading process of the network caused by the dynamic changes of load. Therefore, given the realistic features of WSNs, in this paper we research the invulnerability of WSNs with respect to cascading failures based on the coupled map lattice (CML. The invulnerability and the cascading process of four types of network topologies (i.e., random network, small-world network, homogenous scale-free network, and heterogeneous scale-free network under various attack schemes (i.e., random attack, max-degree attack, and max-status attack are investigated, respectively. The simulation results demonstrate that the rise of interference R and coupling coefficient ε will increase the risks of cascading failures. Cascading threshold values Rc and εc exist, where cascading failures will spread to the entire network when R>Rc or ε>εc. When facing a random attack or max-status attack, the network with higher heterogeneity tends to have a stronger invulnerability towards cascading failures. Conversely, when facing a max-degree attack, the network with higher uniformity tends to have a better performance. Besides that, we have also proved that the spreading speed of cascading failures is inversely proportional to the average path length of the network and the increase of average degree k can improve the network invulnerability.

Cascade plant control by timer method

International Nuclear Information System (INIS)

Kiguchi, Takashi; Inoue, Kotaro; Kawai, Toshio; Senoo, Makoto.

1970-01-01

The present invention relates to a method of controlling uranium flow rate through a cascaded centrifuge plant for the purpose of enriching uranium 235. Such a cascade includes multiple gas separation stage each of which consists of a plurality of centrifuges. The product gas usually includes a large amount of He gas, and a cold trap is used to eliminate the He from UF 6 . The cold trap is operated periodically in such a way that the mixed gas of He and UF 6 is cooled to solidify only UF 6 and then warmed to obtain UF 6 by gasification. In order to operate the plant continuously, parallel multiple cold traps are operated alternatively. The operating conditions in such a complex cascade system are difficult to alter by conventional control methods. The present invention provides a rapid method of controlling the system when a certain percentage of the centrifuges in one stage malfunction. The control system consists of timers which are provided one for each cold trap to control the operational period of the trap. For example, if 20% of the centrifuges in a particular stage malfunction, the timer period of the cold traps attached to the normally operating centrifuge within the stage is maintained, and the period of all the other centrifuges are changed to 10/8 times that of the initial value. In this way the flow volume through all centrifuges except that in the particular stage is reduced to 80% of the initial value and the operation of the system can be continued with reduced efficiency. (Masui, R.)

In vitro and biomechanical screening of polyethylene glycol and poly(trimethylene carbonate) block copolymers for annulus fibrosus repair.

Science.gov (United States)

Long, Rose G; Rotman, Stijn G; Hom, Warren W; Assael, Dylan J; Illien-Jünger, Svenja; Grijpma, Dirk W; Iatridis, James C

2018-02-01

Herniated intervertebral discs (IVDs) are a common cause of back and neck pain. There is an unmet clinical need to seal annulus fibrosus (AF) defects, as discectomy surgeries address acute pain but are complicated by reherniation and recurrent pain. Copolymers of polyethylene glycol with trimethylene carbonate (TMC) and hexamethylene diisocyanate (HDI) end-groups were formulated as AF sealants as the HDI form covalent bonds with native AF tissue. TMC adhesives were evaluated and optimized using the design criteria: stable size, strong adherence to AF tissue, high cytocompatibility, restoration of IVD biomechanics to intact levels following in situ repair, and low extrusion risk. TMC adhesives had high adhesion strength as assessed with a pushout test (150 kPa), and low degradation rates over 3 weeks in vitro. Both TMC adhesives had shear moduli (220 and 490 kPa) similar to, but somewhat higher than, AF tissue. The adhesive with three TMC moieties per branch (TMC3) was selected for additional in situ testing because it best matched AF shear properties. TMC3 restored torsional stiffness, torsional hysteresis area and axial range of motion to intact states. However, in a failure test of compressive deformation under fixed 5 ° flexion, some herniation risk was observed with failure strength of 5.9 MPa compared with 13.5 MPa for intact samples; TMC3 herniated under cyclic organ culture testing. These TMC adhesives performed well during in vitro and in situ testing, but additional optimization to enhance failure strength is required to further this material to advanced screening tests, such as long-term degradation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Numerical integration of electromagnetic cascade equations, discussion of results for air, copper, iron, and lead

International Nuclear Information System (INIS)

Adler, A.; Fuchs, B.; Thielheim, K.O.

1977-01-01

The longitudinal development of electromagnetic cascades in air, copper, iron, and lead is studied on the basis of results derived recently by numerical integration of the cascade equations applying rather accurate expressions for the cross-sections involved with the interactions of high energy electrons, positrons, and photons in electromagnetic cascades. Special attention is given to scaling properties of transition curves. It is demonstrated that a good scaling may be achieved by means of the depth of maximum cascade development. (author)

Research perspectives for pre-screening alternatives to animal experimentation

International Nuclear Information System (INIS)

Walum, Erik; Hedander, Jan; Garberg, Per

2005-01-01

The MEIC study revealed a high predictivity of in vitro cytotoxicity data for human acute systemic toxicity. The idea, put forward by several authors, that compounds that show high cytotoxicity should not need further testing for confirmation but could be assumed toxic also in vivo provides a convenient concept for the selection of the most relevant compounds for further studies in large sets of chemicals, as in the REACH program. The automated techniques applied in high throughput screening (HTS) by the pharmaceutical and biotech industries to select hits in extensive compound collections represent an opportunity to significantly increase the capacity of cytotoxicity testing. Furthermore, it has been suggested that a combination of cytotoxicity data and some basic biokinetic information would greatly improve the accuracy in the extrapolation from in vitro to in vivo and thus make it possible to identify additional toxic compounds that might have escaped in the initial screen. Such information, which can be obtained in a medium throughput screening mode (MTS), includes biotransformation, absorption and some aspects of distribution. The measurement of the net flux of a compound over a cellular barrier, as the one formed in culture by human Caco-2 cells, gives useful, but limited, information on both gut absorption and blood-brain barrier penetration. The test procedures discussed here, as well as other supplementary in vitro tests, cannot always easily be described in terms of animal-based test replacements. In those instances, the necessary test validation cannot be carried out using animal reference data, and prediction models may have to be adapted to new ideas. Consequently, concepts of prospective validation to supplement the now well-established retrospective validation have to be developed

Dynamic behavior and control of product enrichment in a centrifuge cascade

International Nuclear Information System (INIS)

Okamoto, Tsuyoshi; Suzuki, Atsuyuki; Nishimura, Hideo.

1989-05-01

It was agreed as a conclusion of the HEXAPARTITE project that a limited frequency unannounced access (LFUA) inspection should be carried out in a centrifuge type enrichment plant as a basic safeguards approach. It might be adopted at a large scale, future commercial enrichment plant, too. Application of the LFUA approach to such a plant, however, should be fully investigated because the plant will have not only a larger capability of enriching uranium 235 but also a more sensitive information to be protected from the commercial and non-proliferation viewpoint. As a part of a design study on the safeguards approach for a model commercial plant, a study of process simulation of the plant has been carried out. This report describes a result of the study. When a commercial uranium enrichment plant is constructed, a nuisance problem arises; What kind of products should be produced from the plant in order to match a wide range of nuclear fuel enrichment requirements for light-water power reactors. In this report, a reasonable solution to such a problem is investigated. At first, a transient analysis of start-up for a model centrifuge cascade is made by using the dynamic equations, which were so developed as to be able to accurately compute interstage flow rates and enrichment in a transient state. Then it is investigated how wide in its acceptable range the product enrichment can be controlled by regulating cascade characteristic parameters such as cascade cut, recycle flow rate and cascade feed flow rate, and as a result an information about the optimal regulating mode is brought out. As a result of this study, it has become clear that the specific requirements of a customer are almost fulfilled with only one type of unit cascade system if 10 % loss of cascade efficiency is allowed in the plant operation. (author)

Method of fault diagnosis in nozzle cascades for U-235 enrichment

International Nuclear Information System (INIS)

Schuette, R.; Steinhaus, H.

1978-09-01

In a separation nozzle cascade for enrichment of the light uranium isotope U-235 some 450 stages are connected in series. For optimum separation performance of such a plant the design values of the nozzle inlet pressure, of the UF 6 concentration of the UF 6 -cut and the cut of the light additional gas must be matched in all separation stages. Also the feed stream, the product stream, and the tails stream have to be controlled according to the cascade design values. Since it is not possible to measure the cuts directly, these values are calculated on the basis of the material flow balances of the cascade using the pressure values and the UF 6 concentration measurements in each stage, these data being supplemented by concentration measurements in the light and heavy fractions of selected stages. This approach requires the use of a digital computer for processing some 1500 readings to calculate the 2500 plant parameters defining the plant state. This study describes a method of diagnosing the major faults to be expected in a separation nozzle cascade. It is based on the fact that the fault profiles are characterized sufficiently well by maximum values and values to identify the cause of a fault and localize the point where it occurs by means of simple relations between these six values and of their relative positions. The performance of the method has been tested in experiments in the ten-stage pilot plant. For use in commercial separation nozzle cascades the range of performance and the special mode of implementation can be derived from the characteristics of the plant components (separation nozzles, compressors, control valves). The methodological approach in this fault diagnosis also provides the basis for computer aided control procedures to raise a separation cascade from any steady plant condition to its set point operation. (orig./HP) 891 HP [de

Dynamic behavior and control of product enrichment in a centrifuge cascade

International Nuclear Information System (INIS)

Okamoto, Tsuyoshi; Suzuki, Atsuyuki; Nishimura, Hideo.

1988-02-01

It was agreed as a conclusion of the HEXAPARTITE project that a limited frequency unannounced access (LFUA) inspection should be carried out in a centrifuge type enrichment plant as a basic safeguards approach. It might be adopted at a large scale, future commercial enrichment plant, too. Application of the LFUA approach to such a plant, however, should be fully investigated because the plant will have not only a larger capability of enriching uranium 235 but also a more sensitive information to be protected from the commercial and nonproliferation viewpoint. As a part of a design study on the safeguards approach for a model commercial plant, a study of process simulation of the plant has been carried out. This report describes a result of the study. When a commercial uranium enrichment plant is constructed, a nuisance problem arises; What kind of products should be produced from the plant in order to match a wide range of nuclear fuel enrichment requirements for light-water power reactors. In this report, a reasonable solution to such a problem is investigated. At first, a transient analysis of start-up for a model centrifuge cascade is made by using the dynamic equations, which were so developed as to be able to accurately compute interstage flow rates and enrichment in a transient state. Then it is investigated how wide in its acceptable range the product enrichment can be controlled by regulating cascade characteristic parameters such as cascade cut, recycle flow rate and cascade feed flow rate, and as a result an information about the optimal regulating mode is brought out. As a result of this study, it has become clear that the specific requirements of a customer are almost fulfilled with only one type of unit cascade system if 10 % loss of cascade efficiency is allowed in the plant operation. (author)

Novel High Power Type-I Quantum Well Cascade Diode Lasers

Science.gov (United States)

2017-08-30

Novel High Power Type-I Quantum Well Cascade Diode Lasers The views, opinions and/or findings contained in this report are those of the author(s...SECURITY CLASSIFICATION OF: 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND SUBTITLE 13. SUPPLEMENTARY NOTES 12. DISTRIBUTION AVAILIBILITY STATEMENT 6... High Power Type-I Quantum Well Cascade Diode Lasers Report Term: 0-Other Email: leon.shterengas@stonybrook.edu Distribution Statement: 1-Approved

Cardiac magnetic resonance imaging after ventricular tachyarrhythmias increases diagnostic precision and reduces the need for family screening for inherited cardiac disease

DEFF Research Database (Denmark)

Marstrand, Peter; Axelsson, Anna; Thune, Jens Jakob

2016-01-01

-CAG) (81%), exercise stress test (47%), late potentials (54%), electrophysiological study (44%), pharmacological provocation (44%), and/or myocardial biopsy (16%). Family screening was indicated for 53 probands (67%) prior to CMR. After full workup, only 43 cases (54%) warranted evaluation of relatives (19......AIMS: Guidelines recommend evaluation of family members of sudden cardiac death victims. However, initiation of cascade screening in families with uncertain diagnoses is not cost-effective and may cause unnecessary concern. For these reasons, we set out to assess to what extent cardiac magnetic...... resonance imaging (CMR) would increase the diagnostic precision and thereby possibly change the indication for family screening in patients with ventricular tachyarrhythmias. METHODS AND RESULTS: We retrospectively collected data from 79 patients hospitalized with aborted cardiac arrest (resuscitated from...

Unified model of secondary electron cascades in diamond

International Nuclear Information System (INIS)

Ziaja, Beata; London, Richard A.; Hajdu, Janos

2005-01-01

In this article we present a detailed and unified theoretical treatment of secondary electron cascades that follow the absorption of x-ray photons. A Monte Carlo model has been constructed that treats in detail the evolution of electron cascades induced by photoelectrons and by Auger electrons following inner shell ionizations. Detailed calculations are presented for cascades initiated by electron energies between 0.1 and 10 keV. The present article expands our earlier work [B. Ziaja, D. van der Spoel, A. Szoeke, and J. Hajdu, Phys. Rev. B 64, 214104 (2001), Phys. Rev. B 66, 024116 (2002)] by extending the primary energy range, by improving the treatment of secondary electrons, especially at low electron energies, by including ionization by holes, and by taking into account their coupling to the crystal lattice. The calculations describe the three-dimensional evolution of the electron cloud, and monitor the equivalent instantaneous temperature of the free electron gas as the system cools. The dissipation of the impact energy proceeds predominantly through the production of secondary electrons whose energies are comparable to the binding energies of the valence (40-50 eV) and of the core electrons (300 eV). The electron cloud generated by a 10 keV electron is strongly anisotropic in the early phases of the cascade (t≤1 fs). At later times, the sample is dominated by low energy electrons, and these are scattered more isotropically by atoms in the sample. Our results for the total number of secondary electrons agree with available experimental data, and show that the emission of secondary electrons approaches saturation within about 100 fs following the primary impact

Bayesian models trained with HTS data for predicting β-haematin inhibition and in vitro antimalarial activity.

Science.gov (United States)

Wicht, Kathryn J; Combrinck, Jill M; Smith, Peter J; Egan, Timothy J

2015-08-15

A large quantity of high throughput screening (HTS) data for antimalarial activity has become available in recent years. This includes both phenotypic and target-based activity. Realising the maximum value of these data remains a challenge. In this respect, methods that allow such data to be used for virtual screening maximise efficiency and reduce costs. In this study both in vitro antimalarial activity and inhibitory data for β-haematin formation, largely obtained from publically available sources, has been used to develop Bayesian models for inhibitors of β-haematin formation and in vitro antimalarial activity. These models were used to screen two in silico compound libraries. In the first, the 1510 U.S. Food and Drug Administration approved drugs available on PubChem were ranked from highest to lowest Bayesian score based on a training set of β-haematin inhibiting compounds active against Plasmodium falciparum that did not include any of the clinical antimalarials or close analogues. The six known clinical antimalarials that inhibit β-haematin formation were ranked in the top 2.1% of compounds. Furthermore, the in vitro antimalarial hit-rate for this prioritised set of compounds was found to be 81% in the case of the subset where activity data are available in PubChem. In the second, a library of about 5000 commercially available compounds (Aldrich(CPR)) was virtually screened for ability to inhibit β-haematin formation and then for in vitro antimalarial activity. A selection of 34 compounds was purchased and tested, of which 24 were predicted to be β-haematin inhibitors. The hit rate for inhibition of β-haematin formation was found to be 25% and a third of these were active against P. falciparum, corresponding to enrichments estimated at about 25- and 140-fold relative to random screening, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Magnetic field sensor based on cascaded microfiber coupler with magnetic fluid

Energy Technology Data Exchange (ETDEWEB)

Mao, Lianmin; Su, Delong; Wang, Zhaofang [College of Science, University of Shanghai for Science and Technology, Shanghai 200093 (China); Pu, Shengli, E-mail: shlpu@usst.edu.cn [College of Science, University of Shanghai for Science and Technology, Shanghai 200093 (China); Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai 200093 (China); Zeng, Xianglong [The Key Lab of Specialty Fiber Optics and Optical Access Network, Shanghai University, Shanghai 200072 (China); Lahoubi, Mahieddine [Laboratory L.P.S., Department of Physics, Faculty of Sciences, Badji-Mokhtar Annaba University, Annaba 23000 (Algeria)

2016-09-07

A kind of magnetic field sensor based on cascaded microfiber coupler with magnetic fluid is proposed and experimentally demonstrated. The magnetic fluid is utilized as the cladding of the fused regions of the cascaded microfiber coupler. As the interference valley wavelength of the sensing structure is sensitive to the ambient variation, considering the magnetic-field-dependent refractive index of magnetic fluid, the proposed structure is employed for magnetic field sensing. The effective coupling length for each coupling region of the as-fabricated cascaded microfiber coupler is 6031 μm. The achieved sensitivity is 125 pm/Oe, which is about three times larger than that of the previously similar structure based on the single microfiber coupler. Experimental results indicate that the sensing sensitivity can be easily improved by increasing the effective coupling length or cascading more microfiber couplers. The proposed magnetic field sensor is attractive due to its low cost, immunity to electromagnetic interference, as well as high sensitivity, which also has the potentials in other tunable all-fiber photonic devices, such as filter.

Mid and long-term optimize scheduling of cascade hydro-power stations based on modified GA-POA method

Directory of Open Access Journals (Sweden)

J. Li

2018-06-01

Full Text Available In this paper, to explore the efficiency and rationality of the cascade combined generation, a cascade combined optimal model with the maximum generating capacity is established, and solving the model by the modified GA-POA method. It provides a useful reference for the joint development of cascade hydro-power stations in large river basins. The typical annual runoff data are selected to calculate the difference between the calculated results under different representative years. The results show that the cascade operation of cascaded hydro-power stations can significantly increase the overall power generation of cascade and ease the flood risk caused by concentration of flood season.

Digital redesign of anti-wind-up controller for cascaded analog system.

Science.gov (United States)

Chen, Y S; Tsai, J S H; Shieh, L S; Moussighi, M M

2003-01-01

The cascaded conventional anti-wind-up (CAW) design method for integral controller is discussed. Then, the prediction-based digital redesign methodology is utilized to find the new pulse amplitude modulated (PAM) digital controller for effective digital control of the analog plant with input saturation constraint. The desired digital controller is determined from existing or pre-designed CAW analog controller. The proposed method provides a novel methodology for indirect digital design of a continuous-time unity output-feedback system with a cascaded analog controller as in the case of PID controllers for industrial control processes with the presence of actuator saturations. It enables us to implement an existing or pre-designed cascaded CAW analog controller via a digital controller effectively.

[Impacts of hydroelectric cascade exploitation on river ecosystem and landscape: a review].

Science.gov (United States)

Yang, Kun; Deng, Xi; Li, Xue-Ling; Wen, Ping

2011-05-01

Hydroelectric cascade exploitation, one of the major ways for exploiting water resources and developing hydropower, not only satisfies the needs of various national economic sectors, but also promotes the socio-economic sustainable development of river basin. unavoidable anthropogenic impacts on the entire basin ecosystem. Based on the process of hydroelectric cascade exploitation and the ecological characteristics of river basins, this paper reviewed the major impacts of hydroelectric cascade exploitation on dam-area ecosystems, river reservoirs micro-climate, riparian ecosystems, river aquatic ecosystems, wetlands, and river landscapes. Some prospects for future research were offered, e.g., strengthening the research of chain reactions and cumulative effects of ecological factors affected by hydroelectric cascade exploitation, intensifying the study of positive and negative ecological effects under the dam networks and their joint operations, and improving the research of successional development and stability of basin ecosystems at different temporal and spatial scales.

Special Issue ;Sediment cascades in cold climate geosystems;

Science.gov (United States)

Morche, David; Krautblatter, Michael; Beylich, Achim A.

2017-06-01

This Editorial introduces the Special Issue on sediment cascades in cold climate geosystems that evolved from the eighth I.A.G./A.I.G. SEDIBUD (Sediment Budgets in Cold Environments; http://www.geomorph.org/sedibud-working-group/) workshop. The workshop was held from 1st to 4th September 2014 at the Environmental Research Station ;Schneefernerhaus; (http://www.schneefernerhaus.de/en/home.html) located at Mt. Zugspitze, the highest peak of Germany, (2962 m asl). Paper and poster presentations focused on observations, measurements and modeling of geomorphological processes in sediment cascades in cold climate geosystems. This resulting Special Issue brings together ten selected contributions from arctic and alpine environments.

Pathogen and biological contamination management in plant tissue culture: phytopathogens, vitro pathogens, and vitro pests.

Science.gov (United States)

Cassells, Alan C

2012-01-01

The ability to establish and grow plant cell, organ, and tissue cultures has been widely exploited for basic and applied research, and for the commercial production of plants (micro-propagation). Regardless of whether the application is for research or commerce, it is essential that the cultures be established in vitro free of biological contamination and be maintained as aseptic cultures during manipulation, growth, and storage. The risks from microbial contamination are spurious experimental results due to the effects of latent contaminants or losses of valuable experimental or commercial cultures. Much of the emphasis in culture contamination management historically focussed on the elimination of phytopathogens and the maintenance of cultures free from laboratory contamination by environmental bacteria, fungi (collectively referred to as "vitro pathogens", i.e. pathogens or environmental micro-organisms which cause culture losses), and micro-arthropods ("vitro pests"). Microbial contamination of plant tissue cultures is due to the high nutrient availability in the almost universally used Murashige and Skoog (Physiol Plant 15:473-497, 1962) basal medium or variants of it. In recent years, it has been shown that many plants, especially perennials, are at least locally endophytically colonized intercellularly by bacteria. The latter, and intracellular pathogenic bacteria and viruses/viroids, may pass latently into culture and be spread horizontally and vertically in cultures. Growth of some potentially cultivable endophytes may be suppressed by the high salt and sugar content of the Murashige and Skoog basal medium and suboptimal temperatures for their growth in plant tissue growth rooms. The management of contamination in tissue culture involves three stages: disease screening (syn. disease indexing) of the stock plants with disease and endophyte elimination where detected; establishment and pathogen and contaminant screening of established initial cultures

High performance 5.6μm quantum cascade lasers

Science.gov (United States)

Suttinger, M.; Go, R.; Figueiredo, P.; Todi, A.; Shu, Hong; Lyakh, A.

2017-02-01

5.6 μm quantum cascade lasers based on Al 0.78 In 0.22 As/In 0.69 Ga 0.31 As active region composition with measured pulsed room temperature wall plug efficiency of 28.3% are reported. Injection efficiency for the upper laser level of 75% was measured for the new design by testing devices with variable cavity length. Threshold current density of 1.7kA/cm2 and slope efficiency of 4.9W/A were measured for uncoated 3.15mm × 9μm lasers. Threshold current density and slope efficiency dependence on temperature in the range from 288K to 348K for the new structure can be described by characteristic temperatures T0 140K and T1 710K, respectively. Experimental data for inverse slope efficiency dependence on cavity length for 15-stage quantum cascade lasers with the same design are also presented. When combined with the 40-stage device data, the new data allowed for separate evaluation of the losses originating from the active region and from the cladding layers of the laser structure. Specifically, the active region losses for the studied design were found to be 0.77 cm-1, while cladding region losses - 0.33 cm-1. The data demonstrate that active region losses in mid wave infrared quantum cascade lasers largely define total waveguide losses and that their reduction should be one of the main priorities in the quantum cascade laser design.

Investigation of the Shear Flow Effect and Tip Clearance on a Low Speed Axial Flow Compressor Cascade

Directory of Open Access Journals (Sweden)

Mahesh Varpe

2013-01-01

Full Text Available This paper explores the effect of inlet shear flow on the tip leakage flow in an axial flow compressor cascade. A flow with a high shear rate is generated in the test section of an open circuit cascade wind tunnel by using a combination of screens with a prescribed solidity. It is observed that a stable shear flow of shear rate 1.33 is possible and has a gradual decay rate until 15 times the height of the shear flow generator downstream. The computational results obtained agree well with the available experimental data on the baseline configuration. The detailed numerical analysis shows that the tip clearance improves the blade loading near the tip through the promotion of favorable incidence by the tip leakage flow. The tip clearance shifts the centre of pressure on the blade surface towards the tip. It, however, has no effect on the distribution of end wall loss and deviation angle along the span up to 60% from the hub. In the presence of a shear inflow, the end wall effects are considerable. On the other hand, with a shear inflow, the effects of tip leakage flow are observed to be partly suppressed. The shear flow reduces the tip leakage losses substantially in terms of kinetic energy associated with it.

High-Throughput Screening to Identify Regulators of Meiosis-Specific Gene Expression in Saccharomyces cerevisiae.

Science.gov (United States)

Kassir, Yona

2017-01-01

Meiosis and gamete formation are processes that are essential for sexual reproduction in all eukaryotic organisms. Multiple intracellular and extracellular signals feed into pathways that converge on transcription factors that induce the expression of meiosis-specific genes. Once triggered the meiosis-specific gene expression program proceeds in a cascade that drives progress through the events of meiosis and gamete formation. Meiosis-specific gene expression is tightly controlled by a balance of positive and negative regulatory factors that respond to a plethora of signaling pathways. The budding yeast Saccharomyces cerevisiae has proven to be an outstanding model for the dissection of gametogenesis owing to the sophisticated genetic manipulations that can be performed with the cells. It is possible to use a variety selection and screening methods to identify genes and their functions. High-throughput screening technology has been developed to allow an array of all viable yeast gene deletion mutants to be screened for phenotypes and for regulators of gene expression. This chapter describes a protocol that has been used to screen a library of homozygous diploid yeast deletion strains to identify regulators of the meiosis-specific IME1 gene.

Identification of anthranilamide derivatives as potential factor Xa inhibitors: drug design, synthesis and biological evaluation.

Science.gov (United States)

Xing, Junhao; Yang, Lingyun; Li, Hui; Li, Qing; Zhao, Leilei; Wang, Xinning; Zhang, Yuan; Zhou, Muxing; Zhou, Jinpei; Zhang, Huibin

2015-05-05

The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against fXa. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 μM). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 × PT value of 8.7 μM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Single phase cascaded H5 inverter with leakage current elimination for transformerless photovoltaic system

DEFF Research Database (Denmark)

Guo, Xiaoqiang; Jia, X.; Lu, Z.

2016-01-01

Leakage current reduction is one of the important issues for the transformelress PV systems. In this paper, the transformerless single-phase cascaded H-bridge PV inverter is investigated. The common mode model for the cascaded H4 inverter is analyzed. And the reason why the conventional cascade H4...... inverter fails to reduce the leakage current is clarified. In order to solve the problem, a new cascaded H5 inverter is proposed to solve the leakage current issue. Finally, the experimental results are presented to verify the effectiveness of the proposed topology with the leakage current reduction...... for the single-phase transformerless PV systems....

Phosphorylation of paxillin via the ERK mitogen-activated protein kinase cascade in EL4 thymoma cells.

Science.gov (United States)

Ku, H; Meier, K E

2000-04-14

Intracellular signals can regulate cell adhesion via several mechanisms in a process referred to as "inside-out" signaling. In phorbol ester-sensitive EL4 thymoma cells, phorbol-12-myristate 13-acetate (PMA) induces activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases and promotes cell adhesion. In this study, clonal EL4 cell lines with varying abilities to activate ERKs in response to PMA were used to examine signaling events occurring downstream of ERK activation. Paxillin, a multifunctional docking protein involved in cell adhesion, was phosphorylated on serine/threonine residues in response to PMA treatment. This response was correlated with the extent and time course of ERK activation. PMA-induced phosphorylation of paxillin was inhibited by compounds that block the ERK activation pathway in EL4 cells, primary murine thymocytes, and primary murine splenocytes. Paxillin was phosphorylated in vitro by purified active ERK2. Two-dimensional electrophoresis revealed that PMA treatment generated a complex pattern of phosphorylated paxillin species in intact cells, some of which were generated by ERK-mediated phosphorylation in vitro. An ERK pathway inhibitor interfered with PMA-induced adhesion of sensitive EL4 cells to substrate. These findings describe a novel inside-out signaling pathway by which the ERK cascade may regulate events involved in adhesion.

Invariant mass distributions in cascade decays

CERN Document Server

Miller, D J; Raklev, A R

2006-01-01

We derive analytical expressions for the shape of the invariant mass distributions of massless Standard Model endproducts in cascade decays involving massive New Physics (NP) particles, D -> Cc -> Bbc -> Aabc, where the final NP particle A in the cascade is unobserved and where two of the particles a, b, c may be indistinguishable. Knowledge of these expressions can improve the determination of NP parameters at the LHC. The shape formulas are composite, but contain nothing more complicated than logarithms of simple expressions. We study the effects of cuts, final state radiation and detector effects on the distributions through Monte Carlo simulations, using a supersymmetric model as an example. We also consider how one can deal with the width of NP particles and with combinatorics from the misidentification of final state particles. The possible mismeasurements of NP masses through `feet' in the distributions are discussed. Finally, we demonstrate how the effects of different spin configurations can be inclu...

Invariant mass distributions in cascade decays

International Nuclear Information System (INIS)

Miller, David J.; Osland, Per; Raklev, Are R.

2006-01-01

We derive analytical expressions for the shape of the invariant mass distributions of massless Standard Model endproducts in cascade decays involving massive New Physics (NP) particles, D→Cc→Bbc→Aabc, where the final NP particle A in the cascade is unobserved and where two of the particles a, b, c may be indistinguishable. Knowledge of these expressions can improve the determination of NP parameters at the LHC. The shape formulas are composite, but contain nothing more complicated than logarithms of simple expressions. We study the effects of cuts, final state radiation and detector effects on the distributions through Monte Carlo simulations, using a supersymmetric model as an example. We also consider how one can deal with the width of NP particles and with combinatorics from the misidentification of final state particles. The possible mismeasurements of NP masses through 'feet' in the distributions are discussed. Finally, we demonstrate how the effects of different spin configurations can be included in the distributions

Common and uncommon pathogenic cascades in lysosomal storage diseases.

Science.gov (United States)

Vitner, Einat B; Platt, Frances M; Futerman, Anthony H

2010-07-02

Lysosomal storage diseases (LSDs), of which about 50 are known, are caused by the defective activity of lysosomal proteins, resulting in accumulation of unmetabolized substrates. As a result, a variety of pathogenic cascades are activated such as altered calcium homeostasis, oxidative stress, inflammation, altered lipid trafficking, autophagy, endoplasmic reticulum stress, and autoimmune responses. Some of these pathways are common to many LSDs, whereas others are only altered in a subset of LSDs. We now review how these cascades impact upon LSD pathology and suggest how intervention in the pathways may lead to novel therapeutic approaches.

The CCFM Monte Carlo generator CASCADE Version 2.2.03

International Nuclear Information System (INIS)

Jung, H.; Baranov, S.; Deak, M.; Grebenyuk, A.; Hentschinski, M.; Knutsson, A.; Kraemer, M.; Hautmann, F.; Kutak, K.; Lipatov, A.; Zotov, N.

2010-01-01

Cascade is a full hadron level Monte Carlo event generator for ep, γp and p anti p and pp processes, which uses the CCFM evolution equation for the initial state cascade in a backward evolution approach supplemented with off-shell matrix elements for the hard scattering. A detailed program description is given, with emphasis on parameters the user wants to change and common block variables which completely specify the generated events. (orig.)

The CCFM Monte Carlo Generator CASCADE version 2.2.0

Energy Technology Data Exchange (ETDEWEB)

Jung, H. [DESY, Hamburg (Germany); Antwerp Univ. (Belgium); Baranov, S. [Lebedev Physics Inst. (Russian Federation); Deak, M. [Madrid Univ. (ES). Inst. de Fisica Teorica UAM/CSIC] (and others)

2010-08-15

CASCADE is a full hadron level Monte Carlo event generator for ep, {gamma}p and p anti p and pp processes, which uses the CCFM evolution equation for the initial state cascade in a backward evolution approach supplemented with off - shell matrix elements for the hard scattering. A detailed program description is given, with emphasis on parameters the user wants to change and common block variables which completely specify the generated events. (orig.)

Acceptability and feasibility of an e-mental health intervention for parents of childhood cancer survivors: "Cascade".

Science.gov (United States)

Wakefield, Claire E; Sansom-Daly, Ursula M; McGill, Brittany C; Ellis, Sarah J; Doolan, Emma L; Robertson, Eden G; Mathur, Sanaa; Cohn, Richard J

2016-06-01

The aim of this study was to evaluate the feasibility and acceptability of "Cascade": an online, group-based, cognitive behavioral therapy intervention, delivered "live" by a psychologist, to assist parents of children who have completed cancer treatment. Forty-seven parents were randomized to Cascade (n = 25) or a 6-month waitlist (n = 22). Parents completed questionnaires at baseline, 1-2 weeks and 6 months post-intervention. Thirty parents completed full evaluations of the Cascade program (n = 21 randomized to Cascade, n = 9 completed Cascade post-waitlist). Ninety-six percent of Cascade participants completed the intervention (n = 24/25). Eighty percent of parents completed every questionnaire (mean completion time 25 min (SD = 12)). Cascade was described as at least "somewhat" helpful by all parents. None rated Cascade as "very/quite" burdensome. Parents reported that the "online format was easy to use" (n = 28, 93.3 %), "I learnt new skills" (n = 28, 93.3 %), and "I enjoyed talking to others" (n = 29, 96.7 %). Peer-to-peer benefits were highlighted by good group cohesion scores. Cascade is highly acceptable and feasible. Its online delivery mechanism may address inequities in post-treatment support for parents, a particularly acute concern for rural/remote families. Future research needs to establish the efficacy of the intervention. ACTRN12613000270718, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12613000270718.

Exploiting PubChem for Virtual Screening.

Science.gov (United States)

Xie, Xiang-Qun

2010-12-01

IMPORTANCE OF THE FIELD: PubChem is a public molecular information repository, a scientific showcase of the NIH Roadmap Initiative. The PubChem database holds over 27 million records of unique chemical structures of compounds (CID) derived from nearly 70 million substance depositions (SID), and contains more than 449,000 bioassay records with over thousands of in vitro biochemical and cell-based screening bioassays established, with targeting more than 7000 proteins and genes linking to over 1.8 million of substances. AREAS COVERED IN THIS REVIEW: This review builds on recent PubChem-related computational chemistry research reported by other authors while providing readers with an overview of the PubChem database, focusing on its increasing role in cheminformatics, virtual screening and toxicity prediction modeling. WHAT THE READER WILL GAIN: These publicly available datasets in PubChem provide great opportunities for scientists to perform cheminformatics and virtual screening research for computer-aided drug design. However, the high volume and complexity of the datasets, in particular the bioassay-associated false positives/negatives and highly imbalanced datasets in PubChem, also creates major challenges. Several approaches regarding the modeling of PubChem datasets and development of virtual screening models for bioactivity and toxicity predictions are also reviewed. TAKE HOME MESSAGE: Novel data-mining cheminformatics tools and virtual screening algorithms are being developed and used to retrieve, annotate and analyze the large-scale and highly complex PubChem biological screening data for drug design.

Mechanisms of defect production and atomic mixing in high energy displacement cascades: A molecular dynamics study

International Nuclear Information System (INIS)

Diaz de la Rubia, T.; Guinan, M.W.

1991-01-01

We have performed molecular dynamics computer simulation studies of displacement cascades in Cu at low temperature. For 25 keV recoils we observe the splitting of a cascade into subcascades and show that cascades in Cu may lead to the formation of vacancy and interstitial dislocation loops. We discuss a new mechanism of defect production based on the observation of interstitial prismatic dislocation loop punching from cascades at 10 K. We also show that below the subcascade threshold, atomic mixing in the cascade is recoil-energy dependent and obtain a mixing efficiency that scales as the square root of the primary recoil energy. 44 refs., 12 figs

Using In Vitro High-Throughput Screening Data for Predicting ...

Science.gov (United States)

Today there are more than 80,000 chemicals in commerce and the environment. The potential human health risks are unknown for the vast majority of these chemicals as they lack human health risk assessments, toxicity reference values and risk screening values. We aim to use computational toxicology and quantitative high throughput screening (qHTS) technologies to fill these data gaps, and begin to prioritize these chemicals for additional assessment. By coupling qHTS data with adverse outcome pathways (AOPs) we can use ontologies to make predictions about potential hazards and to identify those assays which are sufficient to infer these same hazards. Once those assays are identified, we can use bootstrap natural spline-based metaregression to integrate the evidence across multiple replicates or assays (if a combination of assays are together necessary to be sufficient). In this pilot, we demonstrate how we were able to identify that benzo[k]fluoranthene (B[k]F) may induce DNA damage and steatosis using qHTS data and two separate AOPs. We also demonstrate how bootstrap natural spline-based metaregression can be used to integrate the data across multiple assay replicates to generate a concentration-response curve. We used this analysis to calculate an internal point of departure of 0.751µM and risk-specific concentrations of 0.378µM for both 1:1,000 and 1:10,000 additive risk for B[k]F induced DNA damage based on the p53 assay. Based on the available evidence, we