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Sample records for rapidly identify highly

  1. Rapid identifying high-influence nodes in complex networks

    Institute of Scientific and Technical Information of China (English)

    宋波; 蒋国平; 宋玉蓉; 夏玲玲

    2015-01-01

    A tiny fraction of infl uential individuals play a critical role in the dynamics on complex systems. Identifying the infl uential nodes in complex networks has theoretical and practical significance. Considering the uncertainties of network scale and topology, and the timeliness of dynamic behaviors in real networks, we propose a rapid identifying method (RIM) to find the fraction of high-infl uential nodes. Instead of ranking all nodes, our method only aims at ranking a small number of nodes in network. We set the high-infl uential nodes as initial spreaders, and evaluate the performance of RIM by the susceptible–infected–recovered (SIR) model. The simulations show that in different networks, RIM performs well on rapid identifying high-infl uential nodes, which is verified by typical ranking methods, such as degree, closeness, betweenness, and eigenvector centrality methods.

  2. Rapid identifying high-influence nodes in complex networks

    Science.gov (United States)

    Song, Bo; Jiang, Guo-Ping; Song, Yu-Rong; Xia, Ling-Ling

    2015-10-01

    A tiny fraction of influential individuals play a critical role in the dynamics on complex systems. Identifying the influential nodes in complex networks has theoretical and practical significance. Considering the uncertainties of network scale and topology, and the timeliness of dynamic behaviors in real networks, we propose a rapid identifying method (RIM) to find the fraction of high-influential nodes. Instead of ranking all nodes, our method only aims at ranking a small number of nodes in network. We set the high-influential nodes as initial spreaders, and evaluate the performance of RIM by the susceptible-infected-recovered (SIR) model. The simulations show that in different networks, RIM performs well on rapid identifying high-influential nodes, which is verified by typical ranking methods, such as degree, closeness, betweenness, and eigenvector centrality methods. Project supported by the National Natural Science Foundation of China (Grant Nos. 61374180 and 61373136), the Ministry of Education Research in the Humanities and Social Sciences Planning Fund Project, China (Grant No. 12YJAZH120), and the Six Projects Sponsoring Talent Summits of Jiangsu Province, China (Grant No. RLD201212).

  3. Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice

    Science.gov (United States)

    Tanger, Paul; Klassen, Stephen; Mojica, Julius P.; Lovell, John T.; Moyers, Brook T.; Baraoidan, Marietta; Naredo, Maria Elizabeth B.; McNally, Kenneth L.; Poland, Jesse; Bush, Daniel R.; Leung, Hei; Leach, Jan E.; McKay, John K.

    2017-01-01

    To ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. Here we demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor-intensive measures of flowering time, height, biomass, grain yield, and harvest index. Genetic mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution. PMID:28220807

  4. Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice.

    Science.gov (United States)

    Tanger, Paul; Klassen, Stephen; Mojica, Julius P; Lovell, John T; Moyers, Brook T; Baraoidan, Marietta; Naredo, Maria Elizabeth B; McNally, Kenneth L; Poland, Jesse; Bush, Daniel R; Leung, Hei; Leach, Jan E; McKay, John K

    2017-02-21

    To ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. Here we demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor-intensive measures of flowering time, height, biomass, grain yield, and harvest index. Genetic mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution.

  5. Treks'n Rapids: Identifying Motivational Factors for Adventure Sports

    Directory of Open Access Journals (Sweden)

    Kshitij Saxena

    2010-01-01

    Full Text Available Problem statement: Treks’n Rapids, a leading adventure sports and human resource enrichment company in India, wanted to identify main motivational factors of attraction towards adventure sports among youths of National Capital Region. Objective was to improve the effectiveness of integrated marketing communications strategy. Adventure sports are categorized into four classes: (1 mountain sports; (2 extreme sports like bungee jumping and free fall; (3 rafting and kayaking; (4 paragliding, sky diving and skiing. A total of fifteen motivational factors have been identified with the help of literature review and an exploratory study. These are: Thrill, Requires zeal/energy, Spells status, Builds confidence, Helps in personality development, Instills self-belief, Creates unique identity, Is a stress buster, Helps in goal-setting, Is challenging, Requires toughness, Builds sense of achievement, Is a unique experience, It is fun/adventure and Improved technology has reduced risk. Approach: A questionnaire was created and sent to over 500 people online. Through word of mouth people were encouraged to visit the website and respond to the questionnaire. Fifty-seven responses were obtained. These were analyzed using SPSS. Results: Only two factors were extracted. First all the 57 responses were analyzed as a whole to find out the main motivational factors. Next each of the four individual categories of adventure sports was separately analyzed and results were found to be highly consistent. Two composite variables that emerged are labeled as: (1 characteristics of the adventure sports encompassing: thrill, challenge, fun, toughness and zeal required; (2 characteristics of the self like: building confidence, personality development, sense of achievement, status, self-belief and help in goal setting. Resultant factors were used to discriminate respondents based on gender and spend. In both the cases more than 73% of original grouped cases were found to be

  6. Rapid and highly fieldable viral diagnostic

    Science.gov (United States)

    McKnight, Timothy E.

    2016-12-20

    The present invention relates to a rapid, highly fieldable, nearly reagentless diagnostic to identify active RNA viral replication in a live, infected cells, and more particularly in leukocytes and tissue samples (including biopsies and nasal swabs) using an array of a plurality of vertically-aligned nanostructures that impale the cells and introduce a DNA reporter construct that is expressed and amplified in the presence of active viral replication.

  7. Rapid and highly fieldable viral diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    McKnight, Timothy E.

    2016-12-20

    The present invention relates to a rapid, highly fieldable, nearly reagentless diagnostic to identify active RNA viral replication in a live, infected cells, and more particularly in leukocytes and tissue samples (including biopsies and nasal swabs) using an array of a plurality of vertically-aligned nanostructures that impale the cells and introduce a DNA reporter construct that is expressed and amplified in the presence of active viral replication.

  8. Identifying high-risk medication

    DEFF Research Database (Denmark)

    Sædder, Eva; Brock, Birgitte; Nielsen, Lars Peter

    2014-01-01

    salicylic acid, and beta-blockers; 30 drugs or drug classes caused 82 % of all serious MEs. The top ten drugs involved in fatal events accounted for 73 % of all drugs identified. CONCLUSION: Increasing focus on seven drugs/drug classes can potentially reduce hospitalizations, extended hospitalizations...

  9. Identifying high-redshift GRBs with RATIR

    CERN Document Server

    Littlejohns, O M; Cucchiara, A; Watson, A M; Kutyrev, A S; Lee, W H; Richer, M G; Klein, C R; Fox, O D; Prochaska, J X; Bloom, J S; Troja, E; Ramirez-Ruiz, E; de Diego, J A; Georgiev, L; González, J; Román-Zúñiga, C G; Gehrels, N; Moseley, H

    2013-01-01

    We present a template fitting algorithm for determining photometric redshifts, $z_{\\rm phot}$, of candidate high-redshift gamma-ray bursts (GRBs). Using afterglow photometry, obtained by the Reionization And Transients InfraRed (RATIR) camera, this algorithm accounts for the intrinsic GRB afterglow spectrum, host dust extinction and the effect of neutral hydrogen (local and cosmological) along the line of sight. We present the results obtained by this algorithm and RATIR photometry of GRB 130606A, finding $z_{\\rm phot} = 6.01_{-0.08}^{+0.16}$ for a model with negligible host dust extinction, consistent with spectroscopic measurements of the redshift of this GRB. Using simulated RATIR photometry, we find our algorithm provides precise measures of $z_{\\rm phot}$ in the ranges $4 4$. Further testing highlights the required caution in cases of highly dust extincted host galaxies. These tests also show that our algorithm minimizes false negatives thus allowing us to rapidly identify all potential high-redshift eve...

  10. Rapidly evolving microorganisms with high biofuel tolerance

    Science.gov (United States)

    Vyawahare, Saurabh; Zhang, Qiucen; Lang, Wendy; Austin, Robert

    2012-02-01

    Replacing non-renewable energy sources is one of the biggest and most exciting challenges of our generation. Algae and bacteria are poised to become major renewable biofuels if strains can be developed that provide a high,consistent and robust yield of oil. One major stumbling block towards this goal is the lack of tolerance to high concentrations of biofuels like isobutanol. Using traditional bioengineering techniques to remedy this face the hurdle of identifying the correct pathway or gene to modify. But the multiplicity of interactions inside a cell makes it very hard to determine what to modify a priori. Instead, we propose a technology that does not require prior knowledge of the genes or pathways to modify. In our approach that marries microfabrication and ecology, spatial heterogeneity is used as a knob to speed up evolution in the desired direction. Recently, we have successfully used this approach to demonstrate the rapid emergence of bacterial antibiotic resistance in as little as ten hours. Here, we describe our experimental results in developing new strains of micro-organisms with high oil tolerance. Besides biofuel production, our work is also relevant to oil spill clean-ups.

  11. High precision, rapid laser hole drilling

    Science.gov (United States)

    Chang, Jim J.; Friedman, Herbert W.; Comaskey, Brian J.

    2013-04-02

    A laser system produces a first laser beam for rapidly removing the bulk of material in an area to form a ragged hole. The laser system produces a second laser beam for accurately cleaning up the ragged hole so that the final hole has dimensions of high precision.

  12. Rapid Staining Method to Detect and Identify Downy Mildew (Peronospora belbahrii in Basil

    Directory of Open Access Journals (Sweden)

    Adolfina R. Koroch

    2013-07-01

    Full Text Available Premise of the study: Demand for fresh-market sweet basil continues to increase, but in 2009 a new pathogen emerged, threatening commercial field/greenhouse production and leading to high crop losses. This study describes a simple and effective staining method for rapid microscopic detection of basil downy mildew (Peronospora belbahrii from leaves of basil (Ocimum basilicum. Methods and Results: Fresh leaf sections infected with P. belbahrii were placed on a microscope slide, cleared with Visikol™, and stained with iodine solution followed by one drop of 70% sulfuric acid. Cell walls of the pathogen were stained with a distinct coloration, providing a high-contrast image between the pathogen and plant. Conclusions: This new staining method can be used successfully to identify downy mildew in basil, which then can significantly reduce its spread if identified early, coupled with mitigation strategies. This technique can facilitate the control of the disease, without expensive and specialized equipment.

  13. Identifying High Growth Firms in India

    DEFF Research Database (Denmark)

    Aggarwal, Aradhna; Sato, Takahiro

    growth and industry evolution, formulates testable hypotheses, and uses a novel methodology to identify it. The empirical analysis is based on the plant level panel data of 22 manufacturing industries in Indian manufacturing during the period 2000-01 to 2005-06. Our empirical results reveal that much...... in addressing this issue given the constantly changing population of HGFs. This study uses an alternative conceptual framework and proposes a concept of ‘High Impact Group of Firms’ (HIGF). It explains the HIGFs in the framework of a new stream of literature that focuses on business dynamics, productivity...... depends on the industry/sector specific characteristics....

  14. Rapid, computer vision-enabled murine screening system identifies neuropharmacological potential of two new mechanisms

    Directory of Open Access Journals (Sweden)

    Steven L Roberds

    2011-09-01

    Full Text Available The lack of predictive in vitro models for behavioral phenotypes impedes rapid advancement in neuropharmacology and psychopharmacology. In vivo behavioral assays are more predictive of activity in human disorders, but such assays are often highly resource-intensive. Here we describe the successful application of a computer vision-enabled system to identify potential neuropharmacological activity of two new mechanisms. The analytical system was trained using multiple drugs that are used clinically to treat depression, schizophrenia, anxiety, and other psychiatric or behavioral disorders. During blinded testing the PDE10 inhibitor TP-10 produced a signature of activity suggesting potential antipsychotic activity. This finding is consistent with TP-10’s activity in multiple rodent models that is similar to that of clinically used antipsychotic drugs. The CK1ε inhibitor PF-670462 produced a signature consistent with anxiolytic activity and, at the highest dose tested, behavioral effects similar to that of opiate analgesics. Neither TP-10 nor PF-670462 was included in the training set. Thus, computer vision-based behavioral analysis can facilitate drug discovery by identifying neuropharmacological effects of compounds acting through new mechanisms.

  15. The California Hotspots Project: identifying regions of rapid diversification of mammals.

    Science.gov (United States)

    Davis, Edward Byrd; Koo, Michelle S; Conroy, Chris; Patton, James L; Moritz, Craig

    2008-01-01

    The high rate of anthropogenic impact on natural systems mandates protection of the evolutionary processes that generate and sustain biological diversity. Environmental drivers of diversification include spatial heterogeneity of abiotic and biotic agents of divergent selection, features that suppress gene flow, and climatic or geological processes that open new niche space. To explore how well such proxies perform as surrogates for conservation planning, we need first to map areas with rapid diversification -'evolutionary hotspots'. Here we combine estimates of range size and divergence time to map spatial patterns of neo-endemism for mammals of California, a global biodiversity hotspot. Neo-endemism is explored at two scales: (i) endemic species, weighted by the inverse of range size and mtDNA sequence divergence from sisters; and (ii) as a surrogate for spatial patterns of phenotypic divergence, endemic subspecies, again using inverse-weighting of range size. The species-level analysis revealed foci of narrowly endemic, young taxa in the central Sierra Nevada, northern and central coast, and Tehachapi and Peninsular Ranges. The subspecies endemism-richness analysis supported the last four areas as hotspots for diversification, but also highlighted additional coastal areas (Monterey to north of San Francisco Bay) and the Inyo Valley to the east. We suggest these hotspots reflect the major processes shaping mammal neo-endemism: steep environmental gradients, biotic admixture areas, and areas with recent geological/climate change. Anthropogenic changes to both environment and land use will have direct impacts on regions of rapid divergence. However, despite widespread changes to land cover in California, the majority of the hotspots identified here occur in areas with relatively intact ecological landscapes. The geographical scope of conserving evolutionary process is beyond the scale of any single agency or nongovernmental organization. Choosing which land to

  16. Identifying hotspots and management of critical ecosystem services in rapidly urbanizing Yangtze River Delta Region, China.

    Science.gov (United States)

    Cai, Wenbo; Gibbs, David; Zhang, Lang; Ferrier, Graham; Cai, Yongli

    2017-04-15

    Rapid urbanization has altered many ecosystems, causing a decline in many ecosystem services, generating serious ecological crisis. To cope with these challenges, we presented a comprehensive framework comprising five core steps for identifying and managing hotspots of critical ecosystem services in a rapid urbanizing region. This framework was applied in the case study of the Yangtze River Delta (YRD) Region. The study showed that there was large spatial heterogeneity in the hotspots of ecosystem services in the region, hotspots of supporting services and regulating services aggregately distributing in the southwest mountainous areas while hotspots of provisioning services mainly in the northeast plain, and hotspots of cultural services widespread in the waterbodies and southwest mountainous areas. The regionalization of the critical ecosystem services was made through the hotspot analysis. This study provided valuable information for environmental planning and management in a rapid urbanizing region and helped improve China's ecological redlines policy at regional scale. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. SeqAnt: A web service to rapidly identify and annotate DNA sequence variations

    Directory of Open Access Journals (Sweden)

    Patel Viren

    2010-09-01

    Full Text Available Abstract Background The enormous throughput and low cost of second-generation sequencing platforms now allow research and clinical geneticists to routinely perform single experiments that identify tens of thousands to millions of variant sites. Existing methods to annotate variant sites using information from publicly available databases via web browsers are too slow to be useful for the large sequencing datasets being routinely generated by geneticists. Because sequence annotation of variant sites is required before functional characterization can proceed, the lack of a high-throughput pipeline to efficiently annotate variant sites can act as a significant bottleneck in genetics research. Results SeqAnt (Sequence Annotator is an open source web service and software package that rapidly annotates DNA sequence variants and identifies recessive or compound heterozygous loci in human, mouse, fly, and worm genome sequencing experiments. Variants are characterized with respect to their functional type, frequency, and evolutionary conservation. Annotated variants can be viewed on a web browser, downloaded in a tab-delimited text file, or directly uploaded in a BED format to the UCSC genome browser. To demonstrate the speed of SeqAnt, we annotated a series of publicly available datasets that ranged in size from 37 to 3,439,107 variant sites. The total time to completely annotate these data completely ranged from 0.17 seconds to 28 minutes 49.8 seconds. Conclusion SeqAnt is an open source web service and software package that overcomes a critical bottleneck facing research and clinical geneticists using second-generation sequencing platforms. SeqAnt will prove especially useful for those investigators who lack dedicated bioinformatics personnel or infrastructure in their laboratories.

  18. High pt identified particle production in ALICE

    CERN Document Server

    Christiansen, Peter

    2013-01-01

    The ALICE experiment is a dedicated heavy ion physics detector at the LHC with unique capabilities for studying identified particle production. In this proceeding preliminary results for RAA for pi and K+p (sum), are reported, based on measurements in pp at sqrt(s) = 2.76 TeV and Pb-Pb at sqrt(sNN) = 2.76 TeV. The results are compared to theoretical predictions and measurements at RHIC.

  19. Functional brain activation differences in stuttering identified with a rapid fMRI sequence

    Science.gov (United States)

    Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

    2011-01-01

    The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech motor and auditory brain activity in children who stutter closer to the age at which recovery from stuttering is documented. Rapid sequences may be preferred for individuals or populations who do not tolerate long scanning sessions. In this report, we document the application of a picture naming and phoneme monitoring task in three minute fMRI sequences with adults who stutter (AWS). If relevant brain differences are found in AWS with these approaches that conform to previous reports, then these approaches can be extended to younger populations. Pairwise contrasts of brain BOLD activity between AWS and normally fluent adults indicated the AWS showed higher BOLD activity in the right inferior frontal gyrus (IFG), right temporal lobe and sensorimotor cortices during picture naming and and higher activity in the right IFG during phoneme monitoring. The right lateralized pattern of BOLD activity together with higher activity in sensorimotor cortices is consistent with previous reports, which indicates rapid fMRI sequences can be considered for investigating stuttering in younger participants. PMID:22133409

  20. Identifying High Growth Firms in India

    DEFF Research Database (Denmark)

    Aggarwal, Aradhna; Sato, Takahiro

    Over the past two decades, considerable interest has grown in high growth firms (HGFs). However, the concept of HGFs still remains controversial. One of the most controversial issues is size and age of these firms. The present study argues that the current literature on HGFs may offer little help...

  1. Identifying the nature of high energy Astroparticles

    CERN Document Server

    Mora, Karen Salomé Caballero

    2016-01-01

    High energy Astroparticles include Cosmic Ray, gamma ray and neutrinos, all of them coming from the universe. The origin and production, acceleration and propagation mechanisms of ultrahigh-energy CR (up to $10^{20}$ eV) are still unknown. Knowledge on particle interactions taking place at those energies, useful for studying current theories on particle physics, can be obtained only from measurements of high energy astroparticles. In the present document some techniques on data analysis of mass composition of UHECR with the Pierre Auger Observatory are described. The relevance of the muon component of air showers produced by the primary CR, as well as some low energy simulations of that component, are explained.

  2. Identifying and preserving high-water mark data

    Science.gov (United States)

    Koenig, Todd A.; Bruce, Jennifer L.; O'Connor, Jim; McGee, Benton D.; Holmes, Jr., Robert R.; Hollins, Ryan; Forbes, Brandon T.; Kohn, Michael S.; Schellekens, Mathew; Martin, Zachary W.; Peppler, Marie C.

    2016-03-08

    High-water marks provide valuable data for understanding recent and historical flood events. The proper collection and recording of high-water mark data from perishable and preserved evidence informs flood assessments, research, and water resource management. Given the high cost of flooding in developed areas, experienced hydrographers, using the best available techniques, can contribute high-quality data toward efforts such as public education of flood risk, flood inundation mapping, flood frequency computations, indirect streamflow measurement, and hazard assessments.This manual presents guidance for skilled high-water mark identification, including marks left behind in natural and man-made environments by tranquil and rapid flowing water. This manual also presents pitfalls and challenges associated with various types of flood evidence that help hydrographers identify the best high-water marks and assess the uncertainty associated with a given mark. Proficient high-water mark data collection contributes to better understanding of the flooding process and reduces risk through greater ability to estimate flood probability.The U.S. Geological Survey, operating the Nation’s premier water data collection network, encourages readers of this manual to familiarize themselves with the art and science of high-water mark collection. The U.S. Geological survey maintains a national database at http://water.usgs.gov/floods/FEV/ that includes high-water mark information for many flood events, and local U.S. Geological Survey Water Science Centers can provide information to interested readers about participation in data collection and flood documentation efforts as volunteers or observers.

  3. Identifying and quantifying medication errors: evaluation of rapidly discontinued medication orders submitted to a computerized physician order entry system.

    Science.gov (United States)

    Koppel, Ross; Leonard, Charles E; Localio, A Russell; Cohen, Abigail; Auten, Ruthann; Strom, Brian L

    2008-01-01

    All methods of identifying medication prescribing errors are fraught with inaccuracies and systematic bias. A systematic, efficient, and inexpensive way of measuring and quantifying prescribing errors would be a useful step for reducing them. We ask if rapid discontinuations of prescription-orders--where physicians stop their orders within 2 hours--would be an expedient proxy for prescribing errors? To study this we analyzed CPOE-system medication orders entered and then discontinued within 2 hours. We investigated these phenomena in real time via interviews with corresponding ordering physicians. Each order was also independently reviewed by a clinical pharmacist or physicians. We found that of 114 rapidly discontinued orders by 75 physicians, two-thirds (35 of 53, PPV = 66; 95% CI = 53-77) of medication orders discontinued within 45 minutes were deemed inappropriate (overdose, underdose, etc.). Overall, 55% (63 of 114; 95% CI = 46-64%) of medication orders discontinued within 2 hours were deemed inappropriate. This measure offers a rapid, constant, inexpensive, and objective method to identify medication orders with a high probability of error. It may also serve as a screening and teaching mechanism for physicians-in-training.

  4. Rapid heating of matter using high power lasers

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Woosuk [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-04-08

    This slide presentation describes motivation (uniform and rapid heating of a target, opportunity to study warm dense matter, study of nuclear fusion reactions), rapid heating of matter with intense laser-driven ion beams, visualization of the expanding warm dense gold and diamond, and nuclear fusion experiments using high power lasers (direct heating of deuterium spheres (radius ~ 10nm) with an intense laser pulse.

  5. Usefulness of clinical data and rapid diagnostic tests to identify bacterial etiology in adult respiratory infections

    Directory of Open Access Journals (Sweden)

    Pilar Toledano-Sierra

    2015-01-01

    Full Text Available Respiratory tract infections are a common complaint and most of them, such as common cold and laryngitis, are viral in origin, so antibiotic use should be exceptional. However, there are other respiratory tract infections (sinusitis, pharyngitis, lower respiratory tract infections, and exacerbations of chronic obstructive pulmonary disease where a bacterial etiology is responsible for a non-negligible percentage, and antibiotics are often empirically indicated. The aim of the study is to identify the strength of the data obtained from the symptoms, physical examination and rapid diagnostic methods in respiratory infections in which antibiotic use is frequently proposed in order to improve diagnosis and influence the decision to prescribe these drugs. The review concludes that history, physical examination and rapid tests are useful to guide the need for antibiotic treatment in diseases such as acute sinusitis, acute pharyngitis, exacerbation of lower respiratory tract infection and chronic obstructive pulmonary disease. However, no isolated data is accurate enough by itself to confirm or rule out the need for antibiotics. Therefore, clinical prediction rules bring together history and physical examination, thereby improving the accuracy of the decision to indicate or not antibiotics.

  6. Differences between visual hemifields in identifying rapidly presented target stimuli: Letters and digits, faces, and shapes.

    Directory of Open Access Journals (Sweden)

    Dariusz eAsanowicz

    2013-07-01

    Full Text Available The right hemisphere has been shown to play a dominant role in processing of visuo-spatial information. Recently, this role has been studied in the two-stream rapid serial visual presentation task. In this task, two alphanumerical targets are embedded in left and right simultaneous streams of rapidly changing letters. The second target (T2 is identified better in the left than in the right visual field. This difference has been interpreted as advantage of the right hemisphere (RH. However, a disadvantage of the left hemisphere (LH could not be excluded so far. The LH, specialized for processing of verbal stimuli, might be overloaded due to constant input of letters from both visual fields. In the present study, this overload hypothesis was tested by reducing demands on verbal processing (Experiments 1, and by overloading the RH with nonverbal stimuli: faces (Experiment 2 and irregular shapes (Experiment 3. The left visual field advantage proved to be largely independent from the level of verbal load and from stimulus type. Therefore, although not entirely disproving the overload hypothesis, these results suggest as the most parsimonious explanation this asymmetry reflects a RH advantage, presumably in perceptual and attentional processing, rather than a LH disadvantage caused by verbal overload.

  7. Rapidity and pt dependence of identified-particle elliptic flow at RHIC

    Science.gov (United States)

    Sanders, S. J.; BRAHMS Collaboration

    2007-08-01

    Elliptic flow has been measured by the BRAHMS experiment as a function of transverse momentum and pseudorapidity for the Au+Au reaction at \\sqrt{s_{NN}} = 200 GeV. Identified-particle v2(η, pt) values were obtained with the two BRAHMS spectrometers at pseudorapidities ηap 0, 1 and 3.4. The results show that the differential v2(η, pt) values for a given particle type are essentially constant over the covered pseudorapidity range. It is suggested that the dominant cause of the observed fall-off of the integral v2 values going away from mid-rapidity is a corresponding softening of the particle spectra.

  8. Numerical analysis and experiment to identify origin of buckling in rapid cycling synchrotron core

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Y., E-mail: yuichi.morita@kek.jp [High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki (Japan); Kageyama, T. [High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba, Ibaraki (Japan); Akoshima, M. [The National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki (Japan); Torizuka, S.; Tsukamoto, M. [National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba, Ibaraki (Japan); Yamashita, S. [International Center for Elementary Particle Physics (ICEPP), University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo (Japan); Yoshikawa, N. [Institute of Industrial Science (IIS), University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo (Japan)

    2013-11-11

    The accelerating cavities used in the rapid cycling synchrotron (RCS) of the Japan Proton Accelerator Research Complex (J-PARC) are loaded with magnetic alloy (MA) cores. Over lengthly periods of RCS operation, significant reductions in the impedance of the cavities resulting from the buckling of the cores were observed. A series of thermal structural simulations and compressive strength tests showed that the buckling can be attributed to the low-viscosity epoxy resin impregnation of the MA core that causes the stiffening of the originally flexible MA–ribbon–wound core. Our results showed that thermal stress can be effectively reduced upon using a core that is not epoxy-impregnated. -- Highlights: • Study to identify the origin of buckling in the MA cores is presented. • Thermal stress simulations and compressive strength tests were carried out. • Results show that thermal stress is the origin of core buckling. • Thermal stress can be reduced by using cores without epoxy impregnation.

  9. Identifying high-redshift gamma-ray bursts with RATIR

    Energy Technology Data Exchange (ETDEWEB)

    Littlejohns, O. M.; Butler, N. R. [School of Earth and Space Exploration, Arizona State University, AZ 85287 (United States); Cucchiara, A. [Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Watson, A. M.; Lee, W. H.; Richer, M. G.; De Diego, J. A.; Georgiev, L.; González, J.; Román-Zúñiga, C. G. [Instituto de Astronomía, Universidad Nacional Autónoma de México, Apartado Postal 70-264, 04510 México, D. F. (Mexico); Kutyrev, A. S.; Troja, E.; Gehrels, N.; Moseley, H. [NASA, Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Klein, C. R.; Fox, O. D.; Bloom, J. S. [Astronomy Department, University of California, Berkeley, CA 94720-7450 (United States); Prochaska, J. X.; Ramirez-Ruiz, E. [Department of Astronomy and Astrophysics, UCO/Lick Observatory, University of California, 1156 High Street, Santa Cruz, CA 95064 (United States)

    2014-07-01

    We present a template-fitting algorithm for determining photometric redshifts, z {sub phot}, of candidate high-redshift gamma-ray bursts (GRBs). Using afterglow photometry, obtained by the Reionization and Transients InfraRed (RATIR) camera, this algorithm accounts for the intrinsic GRB afterglow spectral energy distribution, host dust extinction, and the effect of neutral hydrogen (local and cosmological) along the line of sight. We present the results obtained by this algorithm and the RATIR photometry of GRB 130606A, finding a range of best-fit solutions, 5.6 < z {sub phot} < 6.0, for models of several host dust extinction laws (none, the Milky Way, Large Magellanic Clouds, and Small Magellanic Clouds), consistent with spectroscopic measurements of the redshift of this GRB. Using simulated RATIR photometry, we find that our algorithm provides precise measures of z {sub phot} in the ranges of 4 < z {sub phot} ≲ 8 and 9 < z {sub phot} < 10 and can robustly determine when z {sub phot} > 4. Further testing highlights the required caution in cases of highly dust-extincted host galaxies. These tests also show that our algorithm does not erroneously find z {sub phot} < 4 when z {sub sim} > 4, thereby minimizing false negatives and allowing us to rapidly identify all potential high-redshift events.

  10. Rapidly detecting disorder in rhythmic biological signals: a spectral entropy measure to identify cardiac arrhythmias

    CERN Document Server

    Staniczenko, Phillip P A; Jones, Nick S

    2008-01-01

    We consider the use of a running measure of power spectrum disorder to distinguish between the normal sinus rhythm of the heart and two forms of cardiac arrhythmia: atrial fibrillation and atrial flutter. This is motivated by characteristic differences in the spectra of beats during the three rhythms. We plot patient data derived from 10-beat windows on a `disorder map' and identify rhythm-defining ranges in the level and variance of spectral entropy values. Employing the spectral entropy within an automatic arrhythmia detection algorithm enables the classification of periods of atrial fibrillation from the time series of patients' beats. When the algorithm is set to identify abnormal rhythms within 6s it agrees with 85.7% of the annotations of professional rhythm assessors; for a response time of 30s this becomes 89.5%, and with 60s it is 90.3%. The algorithm provides a rapid way to detect atrial fibrillation, demonstrating usable response times as low as six seconds. Measures of disorder in the frequency do...

  11. Ability of RapID Yeast Plus System to identify 304 clinically significant yeasts within 5 hours.

    OpenAIRE

    Kitch, T T; Jacobs, M R; McGinnis, M R; Appelbaum, P C

    1996-01-01

    The RapID Yeast Plus System (Innovative Diagnostic Systems, Norcross, Ga.) is a qualitative micromethod that uses conventional and chromogenic substrates for the identification of medically important yeasts. The ability of the RapID Yeast Plus system to accurately identify 304 clinical yeast isolates within 5 h was evaluated. The RapID Yeast Plus method correctly identified 286 (94.1%) of strains to the species level without the need for additional tests. A further 12 strains (3.9%) were clas...

  12. A Hidden Markov Movement Model for rapidly identifying behavioral states from animal tracks

    DEFF Research Database (Denmark)

    Whoriskey, Kim; Auger-Méthé, Marie; Albertsen, Christoffer Moesgaard

    2017-01-01

    1. Electronic telemetry is frequently used to document animal movement through time. Methods that can identify underlying behaviors driving specific movement patterns can help us understand how and why animals use available space, thereby aiding conservation and management efforts. For aquatic....... 2. We developed a new Hidden Markov Model (HMM) for identifying behavioral states from animal tracks with negligible error, which we called the Hidden Markov Movement Model (HMMM). We implemented as the basis for the HMMM the process equation of the DCRWS, but we used the method of maximum...... animal tracking data with significant measurement error, a Bayesian state-space model called the first-Difference Correlated Random Walk with Switching (DCRWS) has often been used for this purpose. However, for aquatic animals, highly accurate tracking data of animal movement are now becoming more common...

  13. The Rapid Emergence of High Level Gentamicin Resistance in Enterococci

    Directory of Open Access Journals (Sweden)

    Kevin R Forward

    1990-01-01

    Full Text Available The proportion of enterococci isolated from blood and urine cultures that were highly resistant to gentamicin and streptomycin were determined. No blood or urine isolates highly resistant to gentamicin were seen in 1983, whereas by 1986–87 25% of blood and 17% of urine isolates were highly resistant. The rapid emergence of gentamicin resistance has serious implications for patients with life threatening enterococcal disease.

  14. A rapid and robust method of identifying transformed Arabidopsis thaliana seedlings following floral dip transformation

    Directory of Open Access Journals (Sweden)

    Gray John C

    2006-11-01

    Full Text Available Abstract Background The floral dip method of transformation by immersion of inflorescences in a suspension of Agrobacterium is the method of choice for Arabidopsis transformation. The presence of a marker, usually antibiotic- or herbicide-resistance, allows identification of transformed seedlings from untransformed seedlings. Seedling selection is a lengthy process which does not always lead to easily identifiable transformants. Selection for kanamycin-, phosphinothricin- and hygromycin B-resistance commonly takes 7–10 d and high seedling density and fungal contamination may result in failure to recover transformants. Results A method for identifying transformed seedlings in as little as 3.25 d has been developed. Arabidopsis T1 seeds obtained after floral dip transformation are plated on 1% agar containing MS medium and kanamycin, phosphinothricin or hygromycin B, as appropriate. After a 2-d stratification period, seeds are subjected to a regime of 4–6 h light, 48 h dark and 24 h light (3.25 d. Kanamycin-resistant and phosphinothricin-resistant seedlings are easily distinguished from non-resistant seedlings by green expanded cotyledons whereas non-resistant seedlings have pale unexpanded cotyledons. Seedlings grown on hygromycin B differ from those grown on kanamycin and phosphinothricin as both resistant and non-resistant seedlings are green. However, hygromycin B-resistant seedlings are easily identified as they have long hypocotyls (0.8–1.0 cm whereas non-resistant seedlings have short hypocotyls (0.2–0.4 cm. Conclusion The method presented here is an improvement on current selection methods as it allows quicker identification of transformed seedlings: transformed seedlings are easily discernable from non-transformants in as little as 3.25 d in comparison to the 7–10 d required for selection using current protocols.

  15. Nocturnal Rapid Eye Movement Sleep Latency for Identifying Patients With Narcolepsy/Hypocretin Deficiency

    Science.gov (United States)

    Andlauer, Olivier; Moore, Hyatt; Jouhier, Laura; Drake, Christopher; Peppard, Paul E.; Han, Fang; Hong, Seung-Chul; Poli, Francesca; Plazzi, Giuseppe; O’Hara, Ruth; Haffen, Emmanuel; Roth, Thomas; Young, Terry; Mignot, Emmanuel

    2014-01-01

    IMPORTANCE Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically. OBJECTIVE To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency. DESIGN, SETTING, AND PARTICIPANTS Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels. MAIN OUTCOME AND MEASURES Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal

  16. Microelectromechanical high-density energy storage/rapid release system

    Science.gov (United States)

    Rodgers, M. Steven; Allen, James J.; Meeks, Kent D.; Jensen, Brian D.; Miller, Samuel L.

    1999-08-01

    One highly desirable characteristic of electrostatically driven microelectromechanical systems (MEMS) is that they consume very little power. The corresponding drawback is that the force they produce may be inadequate for many applications. It has previously been demonstrated that gear reduction units or microtransmissions can substantially increase the torque generated by microengines. Operating speed, however, is also reduced by the transmission gear ratio. Some applications require both high speed and high force. If this output is only required for a limited period of time, then energy could be stored in a mechanical system and rapidly released upon demand. We have designed, fabricated, and demonstrated a high-density energy storage/rapid release system that accomplishes this task. Built using a 5-level surface micromachining technology, the assembly closely resembles a medieval crossbow. Energy releases on the order of tens of nanojoules have already been demonstrated, and significantly higher energy systems are under development.

  17. Methods and systems for rapid prototyping of high density circuits

    Science.gov (United States)

    Palmer, Jeremy A.; Davis, Donald W.; Chavez, Bart D.; Gallegos, Phillip L.; Wicker, Ryan B.; Medina, Francisco R.

    2008-09-02

    A preferred embodiment provides, for example, a system and method of integrating fluid media dispensing technology such as direct-write (DW) technologies with rapid prototyping (RP) technologies such as stereolithography (SL) to provide increased micro-fabrication and micro-stereolithography. A preferred embodiment of the present invention also provides, for example, a system and method for Rapid Prototyping High Density Circuit (RPHDC) manufacturing of solderless connectors and pilot devices with terminal geometries that are compatible with DW mechanisms and reduce contact resistance where the electrical system is encapsulated within structural members and manual electrical connections are eliminated in favor of automated DW traces. A preferred embodiment further provides, for example, a method of rapid prototyping comprising: fabricating a part layer using stereolithography and depositing thermally curable media onto the part layer using a fluid dispensing apparatus.

  18. Transformed Recombinant Enrichment Profiling Rapidly Identifies HMW1 as an Intracellular Invasion Locus in Haemophilus influenza

    Science.gov (United States)

    Moleres, Javier; Sinha, Sunita; Fernández-Calvet, Ariadna; Porsch, Eric A.; St. Geme, Joseph W.; Nislow, Corey; Redfield, Rosemary J.; Garmendia, Junkal

    2016-01-01

    Many bacterial species actively take up and recombine homologous DNA into their genomes, called natural competence, a trait that offers a means to identify the genetic basis of naturally occurring phenotypic variation. Here, we describe “transformed recombinant enrichment profiling” (TREP), in which natural transformation is used to generate complex pools of recombinants, phenotypic selection is used to enrich for specific recombinants, and deep sequencing is used to survey for the genetic variation responsible. We applied TREP to investigate the genetic architecture of intracellular invasion by the human pathogen Haemophilus influenzae, a trait implicated in persistence during chronic infection. TREP identified the HMW1 adhesin as a crucial factor. Natural transformation of the hmw1 operon from a clinical isolate (86-028NP) into a laboratory isolate that lacks it (Rd KW20) resulted in ~1,000-fold increased invasion into airway epithelial cells. When a distinct recipient (Hi375, already possessing hmw1 and its paralog hmw2) was transformed by the same donor, allelic replacement of hmw2AHi375 by hmw1A86-028NP resulted in a ~100-fold increased intracellular invasion rate. The specific role of hmw1A86-028NP was confirmed by mutant and western blot analyses. Bacterial self-aggregation and adherence to airway cells were also increased in recombinants, suggesting that the high invasiveness induced by hmw1A86-028NP might be a consequence of these phenotypes. However, immunofluorescence results found that intracellular hmw1A86-028NP bacteria likely invaded as groups, instead of as individual bacterial cells, indicating an emergent invasion-specific consequence of hmw1A-mediated self-aggregation. PMID:27124727

  19. Use of Rapid Ascertainment Process for Institutional Deaths (RAPID) to identify pregnancy-related deaths in tertiary-care obstetric hospitals in three departments in Haiti.

    Science.gov (United States)

    Boyd, Andrew T; Hulland, Erin N; Grand'Pierre, Reynold; Nesi, Floris; Honoré, Patrice; Jean-Louis, Reginald; Handzel, Endang

    2017-05-16

    Accurate assessment of maternal deaths is difficult in countries lacking standardized data sources for their review. As a first step to investigate suspected maternal deaths, WHO suggests surveillance of "pregnancy-related deaths", defined as deaths of women while pregnant or within 42 days of termination of pregnancy, irrespective of cause. Rapid Ascertainment Process for Institutional Deaths (RAPID), a surveillance tool, retrospectively identifies pregnancy-related deaths occurring in health facilities that may be missed by routine surveillance to assess gaps in reporting these deaths. We used RAPID to review pregnancy-related deaths in six tertiary obstetric care facilities in three departments in Haiti. We reviewed registers and medical dossiers of deaths among women of reproductive age occurring in 2014 and 2015 from all wards, along with any additional available dossiers of deaths not appearing in registers, to capture pregnancy status, suspected cause of death, and timing of death in relation to the pregnancy. We used capture-recapture analyses to estimate the true number of in-hospital pregnancy-related deaths in these facilities. Among 373 deaths of women of reproductive age, we found 111 pregnancy-related deaths, 25.2% more than were reported through routine surveillance, and 22.5% of which were misclassified as non-pregnancy-related. Hemorrhage (27.0%) and hypertensive disorders (18.0%) were the most common categories of suspected causes of death, and deaths after termination of pregnancy were statistically significantly more common than deaths during pregnancy or delivery. Data were missing at multiple levels: 210 deaths had an undetermined pregnancy status, 48.7% of pregnancy-related deaths lacked specific information about timing of death in relation to the pregnancy, and capture-recapture analyses in three hospitals suggested that approximately one-quarter of pregnancy-related deaths were not captured by RAPID or routine surveillance. Across six

  20. Ability of RapID Yeast Plus System to identify 304 clinically significant yeasts within 5 hours.

    Science.gov (United States)

    Kitch, T T; Jacobs, M R; McGinnis, M R; Appelbaum, P C

    1996-05-01

    The RapID Yeast Plus System (Innovative Diagnostic Systems, Norcross, Ga.) is a qualitative micromethod that uses conventional and chromogenic substrates for the identification of medically important yeasts. The ability of the RapID Yeast Plus system to accurately identify 304 clinical yeast isolates within 5 h was evaluated. The RapID Yeast Plus method correctly identified 286 (94.1%) of strains to the species level without the need for additional tests. A further 12 strains (3.9%) were classified as correct to the genus level or to a low-probability identification with two or more possibilities. In these latter cases, additional tests were required to delineate the correct identification. Organisms in the latter group comprised Candida parapsilosis (n = 1), Candida tropicalis (n = 1), Candida ciferrii (n = 1), Candida guilliermondii (n = 2), Candida humicola (n = 1), Candida kefyr (n = 1), Cryptococcus neoformans (n = 1), and Rhodotorula rubra (n = 4). Six strains (2.0%) were misidentified or did not yield codes in the manufacturer's database. These included one Candida utilis (identified as Candida famata/Candida guilliermondii), one Trichosporon beigelii (identified as Cryptococcus neoformans), one Candida diddensiae (identified as Candida albicans), one Candida membranaefaciens (identified as Candida parapsilosis), one Candida norvegensis (identified as Candida zeylanoides), and one Candida catenulata (no code) isolate; the last four strains are not included in the firm's current database. The RapID Yeast Plus system yielded excellent results and may be recommended for use in the routine laboratory for accurate same-day identification of clinically significant yeasts.

  1. Lung cancer screening: identifying the high risk cohort

    OpenAIRE

    Marcus, Michael W.; Raji, Olaide Y; John K. Field

    2015-01-01

    Low dose computed tomography (LDCT) is a viable screening tool for early lung cancer detection and mortality reduction. In practice, the success of any lung cancer screening programme will depend on successful identification of individuals at high risk in order to maximise the benefit-harm ratio. Risk prediction models incorporating multiple risk factors have been recognised as a method of identifying individuals at high risk of developing lung cancer. Identification of individuals at high ri...

  2. The Rapidity Density Distributions and Longitudinal Expansion Dynamics of Identified Pions from the STAR Beam Energy Scan

    Science.gov (United States)

    Flores, Christopher E.

    2016-12-01

    The Beam Energy Scan (BES) at the Relativistic Heavy-Ion Collider was proposed to characterize the properties of the medium produced in heavy-ion interactions over a broad range of baryon chemical potential. The aptitude of the STAR detector for mid-rapidity measurements has previously been leveraged to measure identified particle yields and spectra to extract bulk properties for the BES energies for | y | ≤ 0.1. However, to extract information on expansion dynamics and full phase space particle production, it is necessary to study identified particle rapidity density distributions. We present the first rapidity density distributions of identified pions from Au+Au collisions at √{sNN} = 7.7 , 11.5, and 19.6 GeV from the BES program as measured by the STAR detector. We use these distributions to obtain the full phase space yields of the pions to provide additional information of the system's chemistry. Further, we report the width of the rapidity density distributions compared to the width expected from Landau hydrodynamics. Finally, we interpret the results as a function of collision energy and discuss them in the context of previous energy scans done at the AGS and SPS.

  3. Rapid variability at very high energies in Mrk 501

    CERN Document Server

    Chakraborty, Nachiketa; Kastendieck, Max Anton; Rieger, Frank; Romoli, Carlo; Wagner, Stefan J; Jacholkowska, Agnieszka; Taylor, Andrew

    2015-01-01

    A major flaring state of the BL Lac object Mrk 501 was observed by the High Energy Stereoscopic System (H.E.S.S.) in June, 2014. Flux levels higher than one Crab unit were recorded and rapid variability at very high energies ($\\sim$2-20 TeV) was revealed. The high statistics afforded by the flares allowed us to probe the presence of minutes timescale variability and study its statistical characteristics exclusively at TeV energies owing to the high energy threshold of approximately 2 TeV. Doubling times of a few minutes are estimated for fluxes greater than 2 TeV. Statistical tests on the light curves show interesting temporal structure in the variations including deviations from a normal flux distribution similar to those found in the PKS 2155-304 flare of July 2006, at nearly an order of magnitude higher threshold energy. Rapid variations at such high energies put strong constraints on the physical mechanisms in the blazar jet.

  4. Family and academic performance: identifying high school student profiles

    Directory of Open Access Journals (Sweden)

    Alicia Aleli Chaparro Caso López

    2016-01-01

    Full Text Available The objective of this study was to identify profiles of high school students, based on variables related to academic performance, socioeconomic status, cultural capital and family organization. A total of 21,724 high school students, from the five municipalities of the state of Baja California, took part. A K-means cluster analysis was performed to identify the profiles. The analyses identified two clearly-defined clusters: Cluster 1 grouped together students with high academic performance and who achieved higher scores for socioeconomic status, cultural capital and family involvement, whereas Cluster 2 brought together students with low academic achievement, and who also obtained lower scores for socioeconomic status and cultural capital, and had less family involvement. It is concluded that the family variables analyzed form student profiles that can be related to academic achievement.

  5. Identifying and Researching Market Opportunities for New High Technology Products.

    Science.gov (United States)

    Dunstan, Peter

    Using a product called the synchro-pulse welder as a case study example, this paper discusses the activities of CSIRO (Commonwealth Scientific and Industrial Research Organisation) in identifying and marketing new high-technology products. A general discussion of CSIRO's market research plans includes two goals to be attained within the next 5…

  6. Exome sequencing identifies ZNF644 mutations in high myopia.

    Directory of Open Access Journals (Sweden)

    Yi Shi

    2011-06-01

    Full Text Available Myopia is the most common ocular disorder worldwide, and high myopia in particular is one of the leading causes of blindness. Genetic factors play a critical role in the development of myopia, especially high myopia. Recently, the exome sequencing approach has been successfully used for the disease gene identification of Mendelian disorders. Here we show a successful application of exome sequencing to identify a gene for an autosomal dominant disorder, and we have identified a gene potentially responsible for high myopia in a monogenic form. We captured exomes of two affected individuals from a Han Chinese family with high myopia and performed sequencing analysis by a second-generation sequencer with a mean coverage of 30× and sufficient depth to call variants at ∼97% of each targeted exome. The shared genetic variants of these two affected individuals in the family being studied were filtered against the 1000 Genomes Project and the dbSNP131 database. A mutation A672G in zinc finger protein 644 isoform 1 (ZNF644 was identified as being related to the phenotype of this family. After we performed sequencing analysis of the exons in the ZNF644 gene in 300 sporadic cases of high myopia, we identified an additional five mutations (I587V, R680G, C699Y, 3'UTR+12 C>G, and 3'UTR+592 G>A in 11 different patients. All these mutations were absent in 600 normal controls. The ZNF644 gene was expressed in human retinal and retinal pigment epithelium (RPE. Given that ZNF644 is predicted to be a transcription factor that may regulate genes involved in eye development, mutation may cause the axial elongation of eyeball found in high myopia patients. Our results suggest that ZNF644 might be a causal gene for high myopia in a monogenic form.

  7. Ultrathin plasmonic nanogratings for rapid and highly-sensitive detection

    CERN Document Server

    Zeng, Beibei; Bartoli, Filbert J

    2014-01-01

    We developed a nanoplasmonic sensor platform employing the extraordinary optical properties of one-dimensional nanogratings patterned on 30nm-thick ultrathin Ag films. Excitation of Fano resonances in the ultrathin Ag nanogratings results in transmission spectra with high amplitude, large contrast, and narrow bandwidth, making them well-suited for rapid and highly-sensitive sensing applications. The ultrathin nanoplasmonic sensor chip was integrated with a polydimethylsiloxane (PDMS) microfluidic channel, and the measured refractive index resolution was found to be 1.46x10-6 refractive index units (RIU) with a high temporal resolution of 1 sec. This compares favorably with commercial prism-based surface plasmon resonance sensors, but is achieved using a more convenient collinear transmission geometry and a significantly smaller sensor footprint of 50x50um2. In addition, an order-of-magnitude improvement in the temporal and spatial resolutions was achieved relative to state-of-the-art nanoplasmonic sensors, fo...

  8. Rapid high-temperature synthesis of SAPO-34 nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Mahdi Dargahi; Hossein Kazemian; Mohammad Soltanieh; Sohrab Rohani; Morteza Hosseinpour

    2011-01-01

    Decreasing particle size results in larger increase of external surface area and shorter diffusion path,both reducing mass and heat transfer resistances in catalysis and sorption.A rapid high-temperature hydrothermal synthesis method was developed to synthesize uniform nanoparticles of SAPO-34 zeolite with high crystallinity.To investigate the effects of temperature and synthesis time on purity and crystallinity of the final products,the crystallization temperature was increased from 468 to 673 K while the synthesis time was decreased from 24h to 45 min.The products were characterized by XRD and SEM techniques.It was found that high temperature and short synthesis time reduce the particle size and change the morphology of the SAPO-34 final product.

  9. Research Area 7.4: Identifying a Path Towards Rapid Discrimination of Infection Disease Outbreaks

    Science.gov (United States)

    2014-07-15

    a sophisticated analysis identified the source, many countries acted proactively to remove cucumbers and tomatoes from store shelves, Russia issued...Eisenstein, M. (2012). Oxford Nanopore announcement sets sequencing sector abuzz. Nature Biotechnology , 30(4), 295–6. doi:10.1038/nbt0412-295... Biotechnology , 29(7). Grad, Y. H., Lipsitch, M., Feldgarden, M., Arachchi, H. M., Cerqueira, G. C., Fitzgerald, M., .. . Hanage, W. P. (2012). Genomic

  10. A rapid and specific derivatization procedure to identify acyl-glucuronides by mass spectrometry.

    Science.gov (United States)

    Vaz, Alfin D N; Wang, Wei Wei; Bessire, Andrew J; Sharma, Raman; Hagen, Anne E

    2010-07-30

    A simple procedure is described to identify acyl-glucuronides by coupled liquid chromatography/mass spectrometry after derivatization to a hydroxamic acid with hydroxylamine. The reaction specificity obviates the need for isolation of the acyl-glucuronide from an extract. Glucuronides derived from carbamic acids, and alkyl- and aromatic amines, are inert to the derivatization reaction conditions, making the hydroxamic acid derivative a fingerprint for acyl-glucuronides.

  11. Nectophotometer: an infrared motility monitor used to rapidly identify toxicity in effluents and receiving waters

    Science.gov (United States)

    Lo Pinto, Richard W.; Santelli, John

    2007-04-01

    A change in the motility pattern of fish and aquatic invertebrates when initially exposed to a toxin has long been used in tests designed to signal the presence of toxins in effluents and receiving waters. We have discovered that the level of motility change occurring within 2.5 hours of exposure to all concentrations of a test toxicant correlates well with mortality observed after three days exposure to the toxin, but that the first 30 minutes of exposure is a poor predictor of mortality. Defining this 'best to use exposure time' can increase the sensitivity of toxicity monitoring systems to a weak toxin, one that causes a motility change so minor that it may otherwise go unnoticed. Motility is monitored and automatically recorded using a Nectophotometer, an automated bio-monitor with computer interface that senses interruptions of infrared beams when organisms separately exposed to multiple concentrations of a toxin move through the beams. In our tests changes in the motility of Artemia salina within the first 2.5 hours of exposure predict 3 day mortality with an average accuracy of 89%. The Nectophotometer has promise for allowing rapid assessment of the toxicity to invertebrates and fish, and may also be used to assess airborne toxicity if motile insects respond in a similar manner.

  12. Towards identifying nurse educator competencies required for simulation-based learning: A systemised rapid review and synthesis

    DEFF Research Database (Denmark)

    Bøje, Rikke Buus; Topping, Annie; Rekola, Leena;

    2015-01-01

    Objectives: This paper presents the results of a systemised rapid reviewand synthesis of the literature undertaken to identify competencies required by nurse educators to facilitate simulation-based learning (SBL). Design: An international collaboration undertook a protocol-based search, retrieval...... and designing simulations, facilitating learning in “safe” environments, expert nursing knowledge based on credible clinical realism, reference to evidence-based knowledge and demonstration of professional values and identity. Conclusions: This review derived a preliminary competency framework. This needs...

  13. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2014-05-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  14. Rapid phenotyping of knockout mice to identify genetic determinants of bone strength

    Science.gov (United States)

    Freudenthal, Bernard; Logan, John; Croucher, Peter I

    2016-01-01

    The genetic determinants of osteoporosis remain poorly understood, and there is a large unmet need for new treatments in our ageing society. Thus, new approaches for gene discovery in skeletal disease are required to complement the current genome-wide association studies in human populations. The International Knockout Mouse Consortium (IKMC) and the International Mouse Phenotyping Consortium (IMPC) provide such an opportunity. The IKMC generates knockout mice representing each of the known protein-coding genes in C57BL/6 mice and, as part of the IMPC initiative, the Origins of Bone and Cartilage Disease project identifies mutants with significant outlier skeletal phenotypes. This initiative will add value to data from large human cohorts and provide a new understanding of bone and cartilage pathophysiology, ultimately leading to the identification of novel drug targets for the treatment of skeletal disease. PMID:27535945

  15. A multiway analysis for identifying high integrity bovine BACs

    OpenAIRE

    McEwan John C; Brauning Rudiger; McWilliam Sean; Barris Wesley; Ratnakumar Abhirami; Snelling Warren M; Dalrymple Brian P

    2009-01-01

    Abstract Background In large genomics projects involving many different types of analyses of bacterial artificial chromosomes (BACs), such as fingerprinting, end sequencing (BES) and full BAC sequencing there are many opportunities for the identities of BACs to become confused. However, by comparing the results from the different analyses, inconsistencies can be identified and a set of high integrity BACs preferred for future research can be defined. Results The location of each bovine BAC in...

  16. rep-PCR-Mediated Genomic Fingerprinting: A Rapid and Effective Method to Identify Clavibacter michiganensis.

    Science.gov (United States)

    Louws, F J; Bell, J; Medina-Mora, C M; Smart, C D; Opgenorth, D; Ishimaru, C A; Hausbeck, M K; de Bruijn, F J; Fulbright, D W

    1998-08-01

    ABSTRACT The genomic DNA fingerprinting technique known as repetitive-sequence-based polymerase chain reaction (rep-PCR) was evaluated as a tool to differentiate subspecies of Clavibacter michiganensis, with special emphasis on C. michiganensis subsp. michiganensis, the pathogen responsible for bacterial canker of tomato. DNA primers (REP, ERIC, and BOX), corresponding to conserved repetitive element motifs in the genomes of diverse bacterial species, were used to generate genomic fingerprints of C. michiganensis subsp. michiganensis, C. michiganensis subsp. sepedonicus, C. michiganensis subsp. nebraskensis, C. michiganensis subsp. tessellarius, and C. michiganensis subsp. insidiosum. The rep-PCR-generated patterns of DNA fragments observed after agarose gel electrophoresis support the current division of C. michiganensis into five subspecies. In addition, the rep-PCR fingerprints identified at least four types (A, B, C, and D) within C. michiganensis subsp. michiganensis based on limited DNA polymorphisms; the ability to differentiate individual strains may be of potential use in studies on the epidemiology and host-pathogen interactions of this organism. In addition, we have recovered from diseased tomato plants a relatively large number of naturally occurring avirulent C. michiganensis subsp. michiganensis strains with rep-PCR fingerprints identical to those of virulent C. michiganensis subsp. michiganensis strains.

  17. Transient elastography with the XL probe rapidly identifies patients with nonhepatic ascites

    Directory of Open Access Journals (Sweden)

    Mueller S

    2012-05-01

    significantly lower liver stiffness (<8 kPa as compared with the remaining patients with hepatic ascites (>30 kPa. Mean liver stiffness was 5.4 kPa ± 1.3 versus 66.2 ± 13.3 kPa.Conclusion: In conclusion, the presence of ascites and increased intra-abdominal pressure does not alter underlying liver stiffness as determined by transient elastography. We suggest that, using the XL probe, transient elastography can be used first-line to identify patients with nonhepatic ascites at an early stage.Keywords: ascites, liver stiffness, transient elastography, liver cirrhosis, noncirrhotic ascites, congestion, peritoneal carcinomatosis, intra-abdominal pressure, alcoholic liver disease

  18. Identifying the genes of unconventional high temperature superconductors.

    Science.gov (United States)

    Hu, Jiangping

    We elucidate a recently emergent framework in unifying the two families of high temperature (high [Formula: see text]) superconductors, cuprates and iron-based superconductors. The unification suggests that the latter is simply the counterpart of the former to realize robust extended s-wave pairing symmetries in a square lattice. The unification identifies that the key ingredients (gene) of high [Formula: see text] superconductors is a quasi two dimensional electronic environment in which the d-orbitals of cations that participate in strong in-plane couplings to the p-orbitals of anions are isolated near Fermi energy. With this gene, the superexchange magnetic interactions mediated by anions could maximize their contributions to superconductivity. Creating the gene requires special arrangements between local electronic structures and crystal lattice structures. The speciality explains why high [Formula: see text] superconductors are so rare. An explicit prediction is made to realize high [Formula: see text] superconductivity in Co/Ni-based materials with a quasi two dimensional hexagonal lattice structure formed by trigonal bipyramidal complexes.

  19. Rapid homogeneous endothelialization of high aspect ratio microvascular networks.

    Science.gov (United States)

    Naik, Nisarga; Hanjaya-Putra, Donny; Haller, Carolyn A; Allen, Mark G; Chaikof, Elliot L

    2015-08-01

    Microvascularization of an engineered tissue construct is necessary to ensure the nourishment and viability of the hosted cells. Microvascular constructs can be created by seeding the luminal surfaces of microfluidic channel arrays with endothelial cells. However, in a conventional flow-based system, the uniformity of endothelialization of such an engineered microvascular network is constrained by mass transfer of the cells through high length-to-diameter (L/D) aspect ratio microchannels. Moreover, given the inherent limitations of the initial seeding process to generate a uniform cell coating, the large surface-area-to-volume ratio of microfluidic systems demands long culture periods for the formation of confluent cellular microconduits. In this report, we describe the design of polydimethylsiloxane (PDMS) and poly(glycerol sebacate) (PGS) microvascular constructs with reentrant microchannels that facilitates rapid, spatially homogeneous endothelial cell seeding of a high L/D (2 cm/35 μm; > 550:1) aspect ratio microchannels. MEMS technology was employed for the fabrication of a monolithic, elastomeric, reentrant microvascular construct. Isotropic etching and PDMS micromolding yielded a near-cylindrical microvascular channel array. A 'stretch - seed - seal' operation was implemented for uniform incorporation of endothelial cells along the entire microvascular area of the construct yielding endothelialized microvascular networks in less than 24 h. The feasibility of this endothelialization strategy and the uniformity of cellularization were established using confocal microscope imaging.

  20. Probing charge correlations of quark gluon plasma by identified two-hadron rapidity correlations in ultra-relativistic AA collisions

    CERN Document Server

    Song, Jun; Liang, Zuo-tang

    2014-01-01

    We propose a new kind of two-particle correlation of identified hadrons in longitudinal rapidity space, called $G_{\\alpha\\beta}(y_{\\alpha},y_{\\beta})$, which can reflect clearly the charge correlations of hot quark system produced in AA collisions at LHC energies. It is derived from the basic scenario of quark combination mechanism of hadron production. Like the elliptic flow of identified hadrons at intermediate transverse momentum, this correlation is independent of the absolute hadronic yields but dependent only on the flavor compositions of hadrons, and thus exhibits interesting properties for different kinds of hadron species. We suggest the measurement of this observable in AA collisions at LHC to gain more insights into the charge correlation properties of produced hot quark matter.

  1. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity.

    Science.gov (United States)

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination.

  2. Seed oil polyphenols: rapid and sensitive extraction method and high resolution-mass spectrometry identification.

    Science.gov (United States)

    Koubaa, Mohamed; Mhemdi, Houcine; Vorobiev, Eugène

    2015-05-01

    Phenolic content is a primary parameter for vegetables oil quality evaluation, and directly involved in the prevention of oxidation and oil preservation. Several methods have been reported in the literature for polyphenols extraction from seed oil but the approaches commonly used remain manually handled. In this work, we propose a rapid and sensitive method for seed oil polyphenols extraction and identification. For this purpose, polyphenols were extracted from Opuntia stricta Haw seed oil, using high frequency agitation, separated, and then identified using a liquid chromatography-high resolution mass spectrometry method. Our results showed good sensitivity and reproducibility of the developed methods.

  3. Teacher Effectiveness in Identifying High-Risk Kindergarten Children.

    Science.gov (United States)

    Colarusso, Ronald P.; And Others

    1979-01-01

    Teacher effectiveness in identifying children "at risk" for learning problems was studied with five Head Start teachers. Results showed that, after training in classroom observation techniques, paraprofessional teachers are capable of identifying developmental delays in children. (PHR)

  4. Forward-rapidity azimuthal and radial flow of identified particles for s=200 GeV Au+Au collisions

    Science.gov (United States)

    Brahms Collaboration; Sanders, S. J.; BRAHMS Collaboration

    2009-11-01

    A strong azimuthal flow signature at RHIC suggests rapid system equilibration leading to an almost perfect fluid state. The longitudinal extent of the flow behavior depends on how this state is formed and can be studied by measuring the pseudorapidity and transverse momentum dependence of the second Fourier component (ν(p)) of the azimuthal angular distribution. We report on a measurement of identified-particle ν as a function of p(0.5-2.0 GeV/c), centrality (0-25%, 25-50%), and pseudorapidity (0⩽ηBRAHMS spectrometers are used for particle identification (π, K, p) and momentum determination and the BRAHMS global detectors are used to determine the corresponding reaction-plane angles. The results are discussed in terms of the pseudorapidity dependence of constituent quark scaling and in terms of models that develop the complete (azimuthal and radial) hydrodynamic aspects of the forward dynamics at RHIC.

  5. How can we identify the high-risk patient?

    Science.gov (United States)

    Sankar, Ashwin; Beattie, W Scott; Wijeysundera, Duminda N

    2015-08-01

    Accurate and early identification of high-risk surgical patients allows for targeted use of perioperative monitoring and interventions that may improve their outcomes. This review summarizes current evidence on how information from the preoperative, operative, and immediate postoperative periods can help identify such individuals. Simple risk indices, such as the Revised Cardiac Risk Index or American Society of Anesthesiologists Physical Status scale, and online calculators allow risk to be estimated with moderate accuracy using readily available preoperative clinical information. Both specific specialized tests (i.e., cardiopulmonary exercise testing and cardiac stress testing) and promising novel biomarkers (i.e., troponins and natriuretic peptides) can help refine these risk estimates before surgery. Estimates of perioperative risk can be further informed by information acquired during the operative and immediate postoperative periods, such as risk indices (i.e., surgical Apgar score), individual risk factors (i.e., intraoperative hypotension), or postoperative biomarkers (i.e., troponins and natriuretic peptides). Preoperative clinical risk indices and risk calculators estimate surgical risk with moderate accuracy. Although novel biomarkers, specialized preoperative testing, and immediate postoperative risk indices show promise as methods to refine these risk estimates, more research is needed on how best to integrate risk information from these different sources.

  6. Rapid Prototyping of High Performance Signal Processing Applications

    Science.gov (United States)

    Sane, Nimish

    Advances in embedded systems for digital signal processing (DSP) are enabling many scientific projects and commercial applications. At the same time, these applications are key to driving advances in many important kinds of computing platforms. In this region of high performance DSP, rapid prototyping is critical for faster time-to-market (e.g., in the wireless communications industry) or time-to-science (e.g., in radio astronomy). DSP system architectures have evolved from being based on application specific integrated circuits (ASICs) to incorporate reconfigurable off-the-shelf field programmable gate arrays (FPGAs), the latest multiprocessors such as graphics processing units (GPUs), or heterogeneous combinations of such devices. We, thus, have a vast design space to explore based on performance trade-offs, and expanded by the multitude of possibilities for target platforms. In order to allow systematic design space exploration, and develop scalable and portable prototypes, model based design tools are increasingly used in design and implementation of embedded systems. These tools allow scalable high-level representations, model based semantics for analysis and optimization, and portable implementations that can be verified at higher levels of abstractions and targeted toward multiple platforms for implementation. The designer can experiment using such tools at an early stage in the design cycle, and employ the latest hardware at later stages. In this thesis, we have focused on dataflow-based approaches for rapid DSP system prototyping. This thesis contributes to various aspects of dataflow-based design flows and tools as follows: 1. We have introduced the concept of topological patterns, which exploits commonly found repetitive patterns in DSP algorithms to allow scalable, concise, and parameterizable representations of large scale dataflow graphs in high-level languages. We have shown how an underlying design tool can systematically exploit a high

  7. Validation of a rapid type 1 diabetes autoantibody screening assay for community-based screening of organ donors to identify subjects at increased risk for the disease.

    Science.gov (United States)

    Wasserfall, C; Montgomery, E; Yu, L; Michels, A; Gianani, R; Pugliese, A; Nierras, C; Kaddis, J S; Schatz, D A; Bonifacio, E; Atkinson, M A

    2016-07-01

    The Network for Pancreatic Organ donors with Diabetes (nPOD) programme was developed in response to an unmet research need for human pancreatic tissue obtained from individuals with type 1 diabetes mellitus and people at increased risk [i.e. autoantibody (AAb)-positive] for the disease. This necessitated the establishment of a type 1 diabetes-specific AAb screening platform for organ procurement organizations (OPOs). Assay protocols for commercially available enzyme-linked immunosorbent assays (elisas) determining AAb against glutamic acid decarboxylase (GADA), insulinoma-associated protein-2 (IA-2A) and zinc transporter-8 (ZnT8A) were modified to identify AAb-positive donors within strict time requirements associated with organ donation programmes. These rapid elisas were evaluated by the international islet AAb standardization programme (IASP) and used by OPO laboratories as an adjunct to routine serological tests evaluating donors for organ transplantation. The rapid elisas performed well in three IASPs (2011, 2013, 2015) with 98-100% specificity for all three assays, including sensitivities of 64-82% (GADA), 60-64% (IA-2A) and 62-68% (ZnT8A). Since 2009, nPOD has screened 4442 organ donors by rapid elisa; 250 (5·6%) were identified as positive for one AAb and 14 (0.3%) for multiple AAb with 20 of these cases received by nPOD for follow-up studies (14 GADA+, two IA-2A(+) , four multiple AAb-positive). Rapid screening for type 1 diabetes-associated AAb in organ donors is feasible, allowing for identification of non-diabetic, high-risk individuals and procurement of valuable tissues for natural history studies of this disease. © 2016 British Society for Immunology.

  8. High throughput modular chambers for rapid evaluation of anesthetic sensitivity

    Directory of Open Access Journals (Sweden)

    Eckmann David M

    2006-11-01

    Full Text Available Abstract Background Anesthetic sensitivity is determined by the interaction of multiple genes. Hence, a dissection of genetic contributors would be aided by precise and high throughput behavioral screens. Traditionally, anesthetic phenotyping has addressed only induction of anesthesia, evaluated with dose-response curves, while ignoring potentially important data on emergence from anesthesia. Methods We designed and built a controlled environment apparatus to permit rapid phenotyping of twenty-four mice simultaneously. We used the loss of righting reflex to indicate anesthetic-induced unconsciousness. After fitting the data to a sigmoidal dose-response curve with variable slope, we calculated the MACLORR (EC50, the Hill coefficient, and the 95% confidence intervals bracketing these values. Upon termination of the anesthetic, Emergence timeRR was determined and expressed as the mean ± standard error for each inhaled anesthetic. Results In agreement with several previously published reports we find that the MACLORR of halothane, isoflurane, and sevoflurane in 8–12 week old C57BL/6J mice is 0.79% (95% confidence interval = 0.78 – 0.79%, 0.91% (95% confidence interval = 0.90 – 0.93%, and 1.96% (95% confidence interval = 1.94 – 1.97%, respectively. Hill coefficients for halothane, isoflurane, and sevoflurane are 24.7 (95% confidence interval = 19.8 – 29.7%, 19.2 (95% confidence interval = 14.0 – 24.3%, and 33.1 (95% confidence interval = 27.3 – 38.8%, respectively. After roughly 2.5 MACLORR • hr exposures, mice take 16.00 ± 1.07, 6.19 ± 0.32, and 2.15 ± 0.12 minutes to emerge from halothane, isoflurane, and sevoflurane, respectively. Conclusion This system enabled assessment of inhaled anesthetic responsiveness with a higher precision than that previously reported. It is broadly adaptable for delivering an inhaled therapeutic (or toxin to a population while monitoring its vital signs, motor reflexes, and providing precise control

  9. Rapid heating of matter using high power lasers

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Woosuk [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-11-05

    This report describes rapid heating technology with ion sources. LANL calculated the expected heating per atom and temperatures of the target materials, used alumium ion beams to heat gold and diamond, produced deuterium fusion plasmas and then measured the ion temperature at the time of the fusion reactions.

  10. Building a Rapid Learning Health Care System for Oncology: Why CancerLinQ Collects Identifiable Health Information to Achieve Its Vision.

    Science.gov (United States)

    Shah, Alaap; Stewart, Andrew K; Kolacevski, Andrej; Michels, Dina; Miller, Robert

    2016-03-01

    The ever-increasing volume of scientific discoveries, clinical knowledge, novel diagnostic tools, and treatment options juxtaposed with rising costs in health care challenge physicians to identify, prioritize, and use new information rapidly to deliver efficient and high-quality care to a growing and aging patient population. CancerLinQ, a rapid learning health care system in oncology, is an initiative of the American Society of Clinical Oncology and its Institute for Quality that addresses these challenges by collecting information from the electronic health records of large numbers of patients with cancer. CancerLinQ is first and foremost a quality measurement and reporting system through which oncologists can harness the depth and power of their patients' clinical records and other data to assess, monitor, and improve the care they deliver. However, in light of privacy and security concerns with regard to collection, use, and disclosure of patient information, this article addresses the need to collect protected health information as defined under the Health Insurance Portability and Accountability Act of 1996 to drive rapid learning through CancerLinQ.

  11. Identifying high-level components in combinational circuits

    Energy Technology Data Exchange (ETDEWEB)

    Doom, T.; White, J.; Wojcik, A. [Michigan State Univ., East Lansing, MI (United States). Dept. of Computer Science; Chisholm, G. [Argonne National Lab., IL (United States). Decision and Information Sciences Div.

    1998-07-01

    The problem of finding meaningful subcircuits in a logic layout appears in many contexts in computer-aided design. Existing techniques rely upon finding exact matchings of subcircuit structure within the layout. These syntactic techniques fail to identify functionally equivalent subcircuits that are differently implemented, optimized, or otherwise obfuscated. The authors present a mechanism for identifying functionally equivalent subcircuits that can overcome many of these limitations. Such semantic matching is particularly useful in the field of design recovery.

  12. A rapid method for identifying and characterizing structural impacts using distributed sensors: An application for automotive pedestrian protection

    Science.gov (United States)

    Kim, Andrew C.

    This research is motivated by recent activity to improve automotive safety, especially for pedestrians. In many parts of the world today, injuries and fatalities from road accidents are a significant problem. Safety features such as seat restraints and air bags provide considerable levels of protection for car occupants; however, no such protective measures currently exist for pedestrians. Drawing upon the success and effectiveness of occupant air bag systems, current research aims to develop similar devices for pedestrians. These active pedestrian protection systems deploy a safety feature such as an external air bag when a pedestrian is hit by a vehicle. Contact with the front bumper induces a body rotation that may result in a violent head collision. The deployable safety device provides a cushioning surface for the vulnerable pedestrian during impact. The challenge of such a system is an effective sensory unit that can rapidly and correctly discriminate pedestrian impacts from non-pedestrian ones. The fast kinematics of the automobile-pedestrian impact leaves a minimal amount of time for signal processing and computation. This research study focuses on a discrimination scheme that satisfies both the time and accuracy requirements for a proposed sensory system for pedestrian protection. A unique methodology was developed to identify structural impacts using dominant frequency features extracted from sensory data. Contact sensors mounted on the front bumper of an automobile measure the strain response from an impact event. The dominant frequencies obtained from these sensor signals are greatly influenced by the impact object's properties and can be used to discriminate between different objects. Extensive tests were conducted to gather sensor data and validate the proposed methodology and impact discrimination algorithm. Results of the impact tests indicate that the approach is sound, and the sensory system effectively identifies "pedestrian" impacts within a

  13. Identifying Children at High Risk for a Child Maltreatment Report

    Science.gov (United States)

    Dubowitz, Howard; Kim, Jeongeun; Black, Maureen M.; Weisbart, Cindy; Semiatin, Joshua; Magder, Laurence S.

    2011-01-01

    Objective: To help professionals identify factors that place families at risk for future child maltreatment, to facilitate necessary services and to potentially help prevent abuse and neglect. Method: The data are from a prospective, longitudinal study of 332 low-income families recruited from urban pediatric primary care clinics, followed for…

  14. Rapid Euler CFD for High-Performance Aircraft Design

    Science.gov (United States)

    Charlton, Eric F.

    2004-01-01

    The goal here was to present one approach to rapid CFD for S&C using an unstructured inviscid method, in order to eventually assess S&C properties as early in the design process as possible. Specific results are presented regarding time, accuracy (as compared to a baseline wind tunnel database) and simplicity for the user. For COMSAC, it s more important to talk about the "specifications" required by Advanced Design and S&C, as well as how the CFD results can be combined for envelope evaluation.

  15. Rapid analysis of phentolamine by high-performance liquid chromatography.

    Science.gov (United States)

    Webster, Gregory K; Lemmer, Robert R; Greenwald, Steven

    2003-02-01

    A rapid liquid chromatographic method is validated for the quantitative analysis of phentolamine. Phentolamine exists in three forms for this investigation: as a mesylate salt, hydrochloride salt, and free base. In solution, phentolamine dissociates from its salt and is chromatographed as free phentolamine. This validation confirms the analysis of each form, which is simply based upon molar mass differences encountered in weighing. As such, both the United States Pharmacopeia hydrochloride and mesylate standards are used throughout this validation to demonstrate this equivalency. The validation demonstrates that this method may be used to quantitate phentolamine, regardless of its salt form.

  16. Rapid, Machine-Learned Resource Allocation: Application to High-redshift GRB Follow-up

    CERN Document Server

    Morgan, Adam N; Richards, Joseph W; Broderick, Tamara; Butler, Nathaniel R; Bloom, Joshua S

    2011-01-01

    As the number of observed Gamma-Ray Bursts (GRBs) continues to grow, follow-up resources need to be used more efficiently in order to maximize science output from limited telescope time. As such, it is becoming increasingly important to rapidly identify bursts of interest as soon as possible after the event, before the afterglows fade beyond detectability. Studying the most distant (highest redshift) events, for instance, remains a primary goal for many in the field. Here we present our Random forest Automated Triage Estimator for GRB redshifts (RATE GRB-z) for rapid identification of high-redshift candidates using early-time metrics from the three telescopes onboard Swift. While the basic RATE methodology is generalizable to a number of resource allocation problems, here we demonstrate its utility for telescope-constrained follow-up efforts with the primary goal to identify and study high-z GRBs. For each new GRB, RATE GRB-z provides a recommendation - based on the available telescope time - of whether the e...

  17. Novel immune-modulator identified by a rapid, functional screen of the parapoxvirus ovis (Orf virus genome

    Directory of Open Access Journals (Sweden)

    McGuire Michael J

    2012-01-01

    Full Text Available Abstract Background The success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. We present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach. Results The genome of Parapoxvirus ovis (Orf virus was sequenced, annotated, and then used to PCR-amplify its open-reading-frames. Employing a cloning-independent protocol, a viral expression-library was rapidly built and arrayed into sub-library pools. These were directly delivered into mice as expressible cassettes and assayed for an immune-modulating activity associated with parapoxvirus infection. The product of the B2L gene, a homolog of vaccinia F13L, was identified as the factor eliciting immune cell accumulation at sites of skin inoculation. Administration of purified B2 protein also elicited immune cell accumulation activity, and additionally was found to serve as an adjuvant for antigen-specific responses. Co-delivery of the B2L gene with an influenza gene-vaccine significantly improved protection in mice. Furthermore, delivery of the B2L expression construct, without antigen, non-specifically reduced tumor growth in murine models of cancer. Conclusion A streamlined, functional approach to genome-wide screening of a biological activity in vivo is presented. Its application to screening in mice for an immune activity elicited by the pathogen genome of Parapoxvirus ovis yielded a novel immunomodulator. In this inverted discovery method, it was possible to identify the adjuvant responsible for a function of interest prior to a mechanistic study of the adjuvant. The non-specific immune activity of this modulator, B2, is similar to that associated with administration of inactivated particles to a host or to a live viral infection. Administration

  18. Rapid High-throughput Species Identification of Botanical Material Using Direct Analysis in Real Time High Resolution Mass Spectrometry.

    Science.gov (United States)

    Lesiak, Ashton D; Musah, Rabi A

    2016-10-02

    We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, and that these chemical fingerprints can be used for plant species identification. The mass spectral data can be acquired rapidly and in a high throughput manner without the need for sample extraction, derivatization or pH adjustment steps. The use of this technique bypasses challenges presented by more conventional techniques including lengthy chromatography analysis times and resource intensive methods. The high throughput capabilities of the direct analysis in real time-high resolution mass spectrometry protocol, coupled with multivariate statistical analysis processing of the data, provide not only class characterization of plants, but also yield species and varietal information. Here, the technique is demonstrated with two psychoactive plant products, Mitragyna speciosa (Kratom) and Datura (Jimsonweed), which were subjected to direct analysis in real time-high resolution mass spectrometry followed by statistical analysis processing of the mass spectral data. The application of these tools in tandem enabled the plant materials to be rapidly identified at the level of variety and species.

  19. Rapid High-throughput Species Identification of Botanical Material Using Direct Analysis in Real Time High Resolution Mass Spectrometry

    Science.gov (United States)

    Lesiak, Ashton D.; Musah, Rabi A.

    2016-01-01

    We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, and that these chemical fingerprints can be used for plant species identification. The mass spectral data can be acquired rapidly and in a high throughput manner without the need for sample extraction, derivatization or pH adjustment steps. The use of this technique bypasses challenges presented by more conventional techniques including lengthy chromatography analysis times and resource intensive methods. The high throughput capabilities of the direct analysis in real time-high resolution mass spectrometry protocol, coupled with multivariate statistical analysis processing of the data, provide not only class characterization of plants, but also yield species and varietal information. Here, the technique is demonstrated with two psychoactive plant products, Mitragyna speciosa (Kratom) and Datura (Jimsonweed), which were subjected to direct analysis in real time-high resolution mass spectrometry followed by statistical analysis processing of the mass spectral data. The application of these tools in tandem enabled the plant materials to be rapidly identified at the level of variety and species. PMID:27768072

  20. Identifying the genes of unconventional high temperature superconductors

    OpenAIRE

    Hu, Jiangping

    2016-01-01

    We elucidate a recently emergent framework in unifying the two families of high temperature (high \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{\\rm c}$$\\end{document} T c ) superconductors, cuprates and iron-based superconductors. The unification suggests that the latter is simply the counterpart of the forme...

  1. High-throughput screening and rapid inhibitor triage using an infectious chimeric Hepatitis C virus.

    Science.gov (United States)

    Wichroski, Michael J; Fang, Jie; Eggers, Betsy J; Rose, Ronald E; Mazzucco, Charles E; Pokornowski, Kevin A; Baldick, Carl J; Anthony, Monique N; Dowling, Craig J; Barber, Lauren E; Leet, John E; Beno, Brett R; Gerritz, Samuel W; Agler, Michele L; Cockett, Mark I; Tenney, Daniel J

    2012-01-01

    The recent development of a Hepatitis C virus (HCV) infectious virus cell culture model system has facilitated the development of whole-virus screening assays which can be used to interrogate the entire virus life cycle. Here, we describe the development of an HCV growth assay capable of identifying inhibitors against all stages of the virus life cycle with assay throughput suitable for rapid screening of large-scale chemical libraries. Novel features include, 1) the use of an efficiently-spreading, full-length, intergenotypic chimeric reporter virus with genotype 1 structural proteins, 2) a homogenous assay format compatible with miniaturization and automated liquid-handling, and 3) flexible assay end-points using either chemiluminescence (high-throughput screening) or Cellomics ArrayScan™ technology (high-content screening). The assay was validated using known HCV antivirals and through a large-scale, high-throughput screening campaign that identified novel and selective entry, replication and late-stage inhibitors. Selection and characterization of resistant viruses provided information regarding inhibitor target and mechanism. Leveraging results from this robust whole-virus assay represents a critical first step towards identifying inhibitors of novel targets to broaden the spectrum of antivirals for the treatment of HCV.

  2. Rapid-throughput skeletal phenotyping of 100 knockout mice identifies 9 new genes that determine bone strength.

    Directory of Open Access Journals (Sweden)

    J H Duncan Bassett

    Full Text Available Osteoporosis is a common polygenic disease and global healthcare priority but its genetic basis remains largely unknown. We report a high-throughput multi-parameter phenotype screen to identify functionally significant skeletal phenotypes in mice generated by the Wellcome Trust Sanger Institute Mouse Genetics Project and discover novel genes that may be involved in the pathogenesis of osteoporosis. The integrated use of primary phenotype data with quantitative x-ray microradiography, micro-computed tomography, statistical approaches and biomechanical testing in 100 unselected knockout mouse strains identified nine new genetic determinants of bone mass and strength. These nine new genes include five whose deletion results in low bone mass and four whose deletion results in high bone mass. None of the nine genes have been implicated previously in skeletal disorders and detailed analysis of the biomechanical consequences of their deletion revealed a novel functional classification of bone structure and strength. The organ-specific and disease-focused strategy described in this study can be applied to any biological system or tractable polygenic disease, thus providing a general basis to define gene function in a system-specific manner. Application of the approach to diseases affecting other physiological systems will help to realize the full potential of the International Mouse Phenotyping Consortium.

  3. High-Resolution Melt Analysis for Rapid Comparison of Bacterial Community Compositions

    DEFF Research Database (Denmark)

    Hjelmsø, Mathis Hjort; Hansen, Lars Hestbjerg; Bælum, Jacob

    2014-01-01

    and fertilization treatments. The HRM analysis identified a shift in the bacterial community composition in two of the treatments, both including the soil fumigant Basamid GR. These results were confirmed with both denaturing gradient gel electrophoresis (DGGE) analysis and 454-based 16S rRNA gene amplicon......In the study of bacterial community composition, 16S rRNA gene amplicon sequencing is today among the preferred methods of analysis. The cost of nucleotide sequence analysis, including requisite computational and bioinformatic steps, however, takes up a large part of many research budgets. High......-resolution melt (HRM) analysis is the study of the melt behavior of specific PCR products. Here we describe a novel high-throughput approach in which we used HRM analysis targeting the 16S rRNA gene to rapidly screen multiple complex samples for differences in bacterial community composition. We hypothesized...

  4. Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.

    Directory of Open Access Journals (Sweden)

    Wei Sun

    Full Text Available A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug, tacrolimus (an immunosuppressive agent and floxuridine (an antimetabolite were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.

  5. Identifying high ability students: a contribution from neuropsychological indicators

    OpenAIRE

    Dora Cortat Simonetti; Leandro S. Almeida; Zenita Guenther

    2010-01-01

    This paper presents some data on the convergence between psychometric intelligence measurements (IQ tests) and physiological signs of mental activity found in high ability adolescents. The research study focus on a small group of 15 subjects submitted to electric encephalograms, previously chosen from a larger group of 77 classmates on the basis of scores on the WISC-III IQ Test. The results suggest continuous predominance of Alpha waves for the gifted group (higher frequency percentile and h...

  6. Identifying patients at high risk of tuberculosis recurrence

    Directory of Open Access Journals (Sweden)

    Ruxana T Sadikot

    2016-01-01

    Full Text Available Several studies have been done in relation to recurrence of tuberculosis (TB following completion of treatment. However, recurrence of TB is still a major problem from a public health perspective in high-burden countries, where no special attention is being given to this issue. Disease recurrence is an important indicator of the efficacy of antituberculosis treatment. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 25%. This variability is not only a reflection of regional epidemiology of recurrence but differences in the definitions used by the TB control programs. In addition to treatment failure related to medication adherence, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include: malnutrition; human immunodeficiency virus; substance abuse including tobacco use; comorbidity such as diabetes, renal failure and systemic diseases, especially immunosuppressive states; and environmental exposure such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being discovered. Information on temporal and geographical trends of TB cases as well as genotyping might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and defining host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence.

  7. Identifying high ability students: a contribution from neuropsychological indicators

    Directory of Open Access Journals (Sweden)

    Dora Cortat Simonetti

    2010-06-01

    Full Text Available This paper presents some data on the convergence between psychometric intelligence measurements (IQ tests and physiological signs of mental activity found in high ability adolescents. The research study focus on a small group of 15 subjects submitted to electric encephalograms, previously chosen from a larger group of 77 classmates on the basis of scores on the WISC-III IQ Test. The results suggest continuous predominance of Alpha waves for the gifted group (higher frequency percentile and higher amplitude what was not observed in the group without any superior intellectual ability. Even taking into account methodological limitations, this study may contribute to the understanding of a relationship between the intellectual quotient (IQ and alpha waves frequency and amplitude, as observed during performance on cognitive tasks. Such results may suggest a possibility to complement psychometric measures with encephalic registers in giftedness research studies.

  8. Progress on high-performance rapid prototype aluminum mirrors

    Science.gov (United States)

    Woodard, Kenneth S.; Myrick, Bruce H.

    2017-05-01

    Near net shape parts can be produced using some very old processes (investment casting) and the relatively new direct metal laser sintering (DMLS) process. These processes have significant advantages for complex blank lightweighting and costs but are not inherently suited for producing high performance mirrors. The DMLS process can provide extremely complex lightweight structures but the high residual stresses left in the material results in unstable mirror figure retention. Although not to the extreme intricacy of DMLS, investment casting can also provide complex lightweight structures at considerably lower costs than DMLS and even conventional wrought mirror blanks but the less than 100% density for casting (and also DMLS) limits finishing quality. This paper will cover the progress that has been made to make both the DMLS and investment casting processes into viable near net shape blank options for high performance aluminum mirrors. Finish and figure results will be presented to show performance commensurate with existing conventional processes.

  9. Rapid Collapse of the Vavilov Ice Cap, Russian High Arctic.

    Science.gov (United States)

    Willis, M. J.; Zheng, W.; Durkin, W. J., IV; Pritchard, M. E.; Ramage, J. M.; Dowdeswell, J. A.; Benham, T. J.; Glazovsky, A.; Macheret, Y.; Porter, C. C.

    2016-12-01

    Cold based ice caps and glaciers are thought to respond slowly to environmental changes. As sea ice cover evolves in the Arctic, a feedback process alters air-temperatures and precipitation patterns across the region. During the last decades of the 20th century the land-terminating western margin of the Vavilov Ice Cap, on October Revolution Island of the Severnaya Zemlya Archipelago, advanced slowly westwards. The advance was driven by precipitation changes that occurred about half a millennia ago. InSAR shows that in 1996 the margin sustained ice speeds of around 20 m/yr. By 2000 the ice front had moved a short distance into the Kara Sea and had transitioned to a marine-terminating front, although an ice apron around the ice margin indicates the ice there was still frozen to the bed and there is no evidence of calving in satellite imagery. In 2013 ice motions near the terminus had accelerated to around 1 m/day. By late 2015 the main trunk of the newly activated outlet glacier attained speeds of 25 m/day and the inland portion of the ice cap thinned at rates of more than 0.3 m/day. The acceleration of the outlet glacier occurred due to its advance over weak, water-saturated marine sediments that provide little resistance to ice flow, and to the removal of lateral resistive stresses as the glacier advanced out into an open embayment. Longitudinal stretching at the front forces an increase in the surface slope upstream. Rapid rates of motion inland generate frictional melt at the bed, possibly aided by cryohydrological warming. Large areas of the interior of the Vavilov ice cap are now below the equilibrium line and the grounded portion of the ice cap is losing mass at a rate of 4.5 km3 w.e./year. The changes at the Vavilov are likely irrecoverable in a warming climate due to a reduction in the accumulation area of the ice cap. Increased precipitation drove the advance, which accelerated due to the presence of soft sediments. The acceleration lowered the elevation

  10. Rapid detection of functional gene polymorphisms of TLRs and IL-17 using high resolution melting analysis

    Science.gov (United States)

    Teräsjärvi, Johanna; Hakanen, Antti; Korppi, Matti; Nuolivirta, Kirsi; Gröndahl-Yli-Hannuksela, Kirsi; Mertsola, Jussi; Peltola, Ville; He, Qiushui

    2017-01-01

    Genetic variations in toll-like receptors (TLRs) and IL-17A have been widely connected to different diseases. Associations between susceptibility and resistance to different infections and single nucleotide polymorphisms (SNPs) in TLR1 to TLR4 and IL17A have been found. In this study, we aimed to develop a rapid and high throughput method to detect functional SNPs of above mentioned proteins. The following most studied and clinically important SNPs: TLR1 (rs5743618), TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790) and IL17 (rs2275913) were tested. High resolution melting analysis (HRMA) based on real-time PCR combined with melting analysis of a saturating double stranded-DNA binding dye was developed and used. The obtained results were compared to the “standard” sequencing method. A total of 113 DNA samples with known genotypes were included. The HRMA method correctly identified all genotypes of these five SNPs. Co-efficient values of variation of intra- and inter-run precision repeatability ranged from 0.04 to 0.23%. The determined limit of qualification for testing samples was from 0.5 to 8.0 ng/μl. The identical genotyping result was obtained from the same sample with these concentrations. Compared to “standard” sequencing methods HRMA is cost-effective, rapid and simple. All the five SNPs can be analyzed separately or in combination. PMID:28148965

  11. Rapidly expanding range of highly pathogenic avian influenza viruses

    Science.gov (United States)

    The recent introduction of highly pathogenic avian influenza virus (HPAIV) H5N8 into Europe and North America poses significant risks to poultry industries and wildlife populations and warrants continued and heightened vigilance. First discovered in South Korean poultry and wild birds in early 2014...

  12. Rapidly expanding range of highly pathogenic avian influenza viruses

    Science.gov (United States)

    Hall, Jeffrey S.; Dusek, Robert J.; Spackman, Erica

    2015-01-01

    The movement of highly pathogenic avian influenza (H5N8) virus across Eurasia and into North America and the virus’ propensity to reassort with co-circulating low pathogenicity viruses raise concerns among poultry producers, wildlife biologists, aviculturists, and public health personnel worldwide. Surveillance, modeling, and experimental research will provide the knowledge required for intelligent policy and management decisions.

  13. Peripheral blood mononuclear cell gene expression in healthy adults rapidly transported to high altitude

    Directory of Open Access Journals (Sweden)

    Herman NM

    2014-12-01

    Full Text Available Nicole M Herman,1 Diane E Grill,2 Paul J Anderson,1 Andrew D Miller,1 Jacob B Johnson,1 Kathy A O’Malley,1 Maile L Ceridon Richert,1 Bruce D Johnson1 1Department of Cardiovascular Diseases, 2Department of Biostatistics, Mayo Clinic Rochester, MN, USA Abstract: Although mechanisms of high altitude illness have been studied extensively, the processes behind the development of these conditions are still unclear. Few genome-wide studies on rapid exposure to high altitude have been performed. Each year, scientists and support workers are transferred by plane from McMurdo Station in Antarctica (sea level to the Amundsen-Scott South Pole Station at 2,835 meters. This uniform and rapid transfer to altitude provides a unique opportunity to study the effects of hypobaric hypoxia on gene expression that may help illustrate the body's adaptations to these conditions. We hypothesized that an extensive number of genes would change with rapid exposure to altitude and further expected that these genes would correspond to inflammatory pathways proposed as a mechanism in development of acute mountain sickness. Peripheral venous blood samples were drawn from 98 healthy subjects at sea level and again on day two at altitude. Microarray analysis was performed on these samples. In total, 1,118 probe sets with significant P-values and fold changes (90% upregulated were identified and entered into MetaCore™ software. Several pathways, including oxidative phosphorylation, cytoskeleton remodeling, and platelet aggregation, were significantly represented by the data set and all were upregulated. Many genes changed expression, and the vast majority of these increased. Increased metabolism in peripheral blood mononuclear cells suggests increased inflammatory activity. Keywords: peripheral blood mononuclear cells, microarray, gene expression, acute mountain sickness

  14. High flux inductors for the rapid heating of steel products

    Energy Technology Data Exchange (ETDEWEB)

    Pierret, R.; Griffay, G.; Galbrun, F. [Institut de Recherches de la Siderurgie Francaise (IRSID), 78 - Saint-Germain-en-Laye (France); Hellegouaec`h, J.; Prost, G.

    1995-03-01

    To reduce investment and operating costs of electroheating processes of long products by induction, we developed a new multilayed inductor with high flux density which represents a real technological step in regard of conventional technics: 4 MV/m{sup 2} instead of 1MW/m{sup 2}, efficiency of 85% instead of 55%, compacity and low costs of maintenance. The new technology can also be used with success in flat products plants. (authors). 10 figs., 1 tab.

  15. High and rapid alkali cation storage in ultramicroporous carbonaceous materials

    Science.gov (United States)

    Yun, Young Soo; Lee, Seulbee; Kim, Na Rae; Kang, Minjee; Leal, Cecilia; Park, Kyu-Young; Kang, Kisuk; Jin, Hyoung-Joon

    2016-05-01

    To achieve better supercapacitor performance, efforts have focused on increasing the specific surface area of electrode materials to obtain higher energy and power density. The control of pores in these materials is one of the most effective ways to increase the surface area. However, when the size of pores decreases to a sub-nanometer regime, it becomes difficult to apply the conventional parallel-plate capacitor model because the charge separation distance (d-value) of the electrical double layer has a similar length scale. In this study, ultramicroporous carbonaceous materials (UCMs) containing sub-nanometer-scale pores are fabricated using a simple in situ carbonization/activation of cellulose-based compounds containing potassium. The results show that alkali cations act as charge carriers in the ultramicropores (<0.7 nm), and these materials can deliver high capacitances of ∼300 F g-1 at 0.5 A g-1 and 130 F g-1, even at a high current rate of 65 A g-1 in an aqueous medium. In addition, the UCM-based symmetric supercapacitors are stable over 10,000 cycles and have a high energy and power densities of 8.4 Wh kg-1 and 15,000 W kg-1, respectively. This study provides a better understanding of the effects of ultramicropores in alkali cation storage.

  16. "Identifying the hospitalised patient in crisis"--a consensus conference on the afferent limb of rapid response systems

    DEFF Research Database (Denmark)

    DeVita, Michael A; Smith, Gary B; Adam, Sheila K

    2010-01-01

    Most reports of Rapid Response Systems (RRS) focus on the efferent, response component of the system, although evidence suggests that improved vital sign monitoring and recognition of a clinical crisis may have outcome benefits. There is no consensus regarding how best to detect patient deteriora......Most reports of Rapid Response Systems (RRS) focus on the efferent, response component of the system, although evidence suggests that improved vital sign monitoring and recognition of a clinical crisis may have outcome benefits. There is no consensus regarding how best to detect patient...

  17. A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity

    Science.gov (United States)

    Ymele-Leki, Patrick; Cao, Shugeng; Sharp, Jared; Lambert, Kathleen G.; McAdam, Alexander J.; Husson, Robert N.; Tamayo, Giselle; Clardy, Jon; Watnick, Paula I.

    2012-01-01

    Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis. This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples. PMID:22359585

  18. Rapid and high-throughput detection of highly pathogenic bacteria by Ibis PLEX-ID technology.

    Directory of Open Access Journals (Sweden)

    Daniela Jacob

    Full Text Available In this manuscript, we describe the identification of highly pathogenic bacteria using an assay coupling biothreat group-specific PCR with electrospray ionization mass spectrometry (PCR/ESI-MS run on an Ibis PLEX-ID high-throughput platform. The biothreat cluster assay identifies most of the potential bioterrorism-relevant microorganisms including Bacillus anthracis, Francisella tularensis, Yersinia pestis, Burkholderia mallei and pseudomallei, Brucella species, and Coxiella burnetii. DNA from 45 different reference materials with different formulations and different concentrations were chosen and sent to a service screening laboratory that uses the PCR/ESI-MS platform to provide a microbial identification service. The standard reference materials were produced out of a repository built up in the framework of the EU funded project "Establishment of Quality Assurances for Detection of Highly Pathogenic Bacteria of Potential Bioterrorism Risk" (EQADeBa. All samples were correctly identified at least to the genus level.

  19. Easy and Rapid Purification of Highly Active Nisin

    Directory of Open Access Journals (Sweden)

    André Abts

    2011-01-01

    Full Text Available Nisin is an antimicrobial peptide produced and secreted by several L. lactis strains and is specifically active against Gram-positive bacteria. In previous studies, nisin was purified via cation exchange chromatography at low pH employing a single-step elution using 1 M NaCl. Here, we describe an optimized purification protocol using a five-step NaCl elution to remove contaminants. The obtained nisin is devoid of impurities and shows high bactericidal activity against the nisin-sensitive L. lactis strain NZ9000. Purified nisin exhibits an IC50 of ~3 nM, which is a tenfold improvement as compared to nisin obtained via the one-step elution procedure.

  20. A RAPID THIN-LAYER CHROMATOGRAPHIC PROCEDURE TO IDENTIFY POOR AND EXTENSIVE OXIDATIVE DRUG METABOLIZERS IN MAN USING DEXTROMETHORPHAN

    NARCIS (Netherlands)

    DEZEEUW, RA; EIKEMA, D; FRANKE, JP; JONKMAN, JHG

    1992-01-01

    A rapid TLC method is presented to distinguish poor oxidative drug metabolizers from extensive oxidative drug metabolizers. Dextromethorphan (1) is used as test probe because it is safe, well characterized, generally available and easy to measure. The method is based on the extraction of 1 and its m

  1. A rapid seedling resistance assay identifies wild tomato lines that are resistant to Psuedomonas syringe pv. tomato race 1

    Science.gov (United States)

    Bacterial speck caused by Pseudomonas syringae has historically been controlled by the Pto/Prf gene cluster. Emerging strains like P. syringae pv. tomato race 1 overcome resistance conferred by Pto/Prf, and can cause serious crop loss under appropriate environmental conditions. We developed a rapid ...

  2. "Identifying the hospitalised patient in crisis"-A consensus conference on the afferent limb of Rapid Response Systems

    DEFF Research Database (Denmark)

    Devita, M.A.; Smith, G.B.; Adam, S.K.

    2010-01-01

    Background: Most reports of Rapid Response Systems (RRS) focus on the efferent, response component of the system, although evidence suggests that improved vital sign monitoring and recognition of a clinical crisis may have outcome benefits. There is no consensus regarding how best to detect patie...

  3. Rapid removal of bisphenol A on highly ordered mesoporous carbon

    Institute of Scientific and Technical Information of China (English)

    Qian Sui; Jun Huang; Yousong Liu; Xiaofeng Chang; Guangbin Ji; Shubo Deng; Tao Xie; Gang Yu

    2011-01-01

    Bisphenol A (BPA) is of global concern due to its disruption of endocrine systems and ubiquity in the aquatic environment. It is important, therefore, that efforts are made to remove it from the aqueous phase. A novel adsorbent, mesoporous carbon CMK-3,prepared from hexagonal SBA-15 mesoporous silica was studied for BPA removal from aqueous phase, and compared with conventional powdered activated carbon (PAC). Characterization of CMK-3 by transmission electron microscopy (TEM), X-ray diffraction, and nitrogen adsorption indicated that prepared CMK-3 had an ordered mesoporous structure with a high specific surface area of 920 m2/g and a pore-size of about 4.9 nm. The adsorption of BPA on CMK-3 followed a pseudo second-order kinetic model. The kinetic constant was 0.00049 g/(mg·min), much higher than the adsorption of BPA on PAC. The adsorption isotherm fitted slightly better with the Freundlich model than the Langmuir model, and adsorption capacity decreased as temperature increased from 10 to 40℃.No significant influence of pH on adsorption was observed at pH 3 to 9; however, adsorption capacity decreased dramatically from pH 9to 13.

  4. Rapid, high-accuracy detection of strabismus and amblyopia using the pediatric vision scanner.

    Science.gov (United States)

    Loudon, Sjoukje E; Rook, Caitlin A; Nassif, Deborah S; Piskun, Nadya V; Hunter, David G

    2011-07-07

    Purpose. The Pediatric Vision Scanner (PVS) detects strabismus by identifying ocular fixation in both eyes simultaneously. This study was undertaken to assess the ability of the PVS to identify patients with amblyopia or strabismus, particularly anisometropic amblyopia with no measurable strabismus. Methods. The PVS test, administered from 40 cm and requiring 2.5 seconds of attention, generated a binocularity score (BIN, 0%-100%). We tested 154 patients and 48 controls between the ages of 2 and 18 years. BIN scores of amblyopic children and controls were measured, and 21 children received sequential PVS measurements to detect any changes in BIN resulting from amblyopia treatment. Results. With the pass/refer threshold set at BIN 60%, sensitivity and specificity were 96% for the detection of amblyopia or strabismus. Assuming a 5% prevalence of amblyopia or strabismus, the inferred positive and negative predictive values of the PVS were 56% and 100%, respectively. Fixation accuracy was significantly reduced in amblyopic eyes. In anisometropic amblyopia patients treated successfully, the BIN improved to 100%. Conclusions. The PVS identified children with amblyopia or strabismus with high sensitivity and specificity, while successful treatment restored normal BIN scores in amblyopic patients without strabismus. The results support the hypothesis that the PVS detects strabismus and amblyopia directly. Future strategies for screening by nonspecialists may thus be based on diagnostic detection of amblyopia and strabismus rather than the estimation of risk factors, allowing for rapid, accurate identification of children with amblyopia early in life when it is most amenable to treatment.

  5. High strength microstructural forms developed in titanium alloys by rapid heat treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ivasishin, O.M. [Institute of Metal Physics, Kiev (Ukraine)

    2001-09-01

    It is shown that rapid heat treatment of alpha+beta and beta titanium alloys, which includes rapid heating of alloys with initial equiaxed microstructure into single-phase beta field is able to produce microstructural forms in which high strength can be well balanced with other mechanical properties. Main advantage of rapid heating approach comes from the possibility to extend the level of ''useful'' strength. Desirably high strength is provided by intragranular morphology and microchemistry while beta-grain refinement permits a reliability of such high strength conditions. (orig.)

  6. Highly Sensitive Marker Panel for Guidance in Lung Cancer Rapid Diagnostic Units

    Science.gov (United States)

    Blanco-Prieto, Sonia; De Chiara, Loretta; Rodríguez-Girondo, Mar; Vázquez-Iglesias, Lorena; Rodríguez-Berrocal, Francisco Javier; Fernández-Villar, Alberto; Botana-Rial, María Isabel; de la Cadena, María Páez

    2017-01-01

    While evidence for lung cancer screening implementation in Europe is awaited, Rapid Diagnostic Units have been established in many hospitals to accelerate the early diagnosis of lung cancer. We seek to develop an algorithm to detect lung cancer in a symptomatic population attending such unit, based on a sensitive serum marker panel. Serum concentrations of Epidermal Growth Factor, sCD26, Calprotectin, Matrix Metalloproteinases −1, −7, −9, CEA and CYFRA 21.1 were determined in 140 patients with respiratory symptoms (lung cancer and controls with/without benign pathology). Logistic Lasso regression was performed to derive a lung cancer prediction model, and the resulting algorithm was tested in a validation set. A classification rule based on EGF, sCD26, Calprotectin and CEA was established, able to reasonably discriminate lung cancer with 97% sensitivity and 43% specificity in the training set, and 91.7% sensitivity and 45.4% specificity in the validation set. Overall, the panel identified with high sensitivity stage I non-small cell lung cancer (94.7%) and 100% small-cell lung cancers. Our study provides a sensitive 4-marker classification algorithm for lung cancer detection to aid in the management of suspicious lung cancer patients in the context of Rapid Diagnostic Units. PMID:28117344

  7. Difficulties in differentiating Neisseria cinerea from Neisseria gonorrhoeae in rapid systems used for identifying pathogenic Neisseria species.

    OpenAIRE

    Boyce, J M; Mitchell, E B

    1985-01-01

    Neisseria cinerea and Neisseria gonorrhoeae may occur at the same body sites and may have similar colony morphologies. Ideally, systems used for rapid identification of N. gonorrhoeae should be able to differentiate N. cinerea from gonococci. We tested seven N. cinerea strains using the Gonochek II (Du Pont Diagnostics), Minitek (BBL Microbiology Systems), RapID-NH (Innovative Diagnostics, Inc.), RIM-N (American Microscan), and Phadebact (Pharmacia Diagnostics) systems. We found that the reac...

  8. Corifungin, a new drug lead against Naegleria, identified from a high-throughput screen.

    Science.gov (United States)

    Debnath, Anjan; Tunac, Josefino B; Galindo-Gómez, Silvia; Silva-Olivares, Angélica; Shibayama, Mineko; McKerrow, James H

    2012-11-01

    Primary amebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living ameba Naegleria fowleri. The drug of choice in treating PAM is the antifungal antibiotic amphotericin B, but its use is associated with severe adverse effects. Moreover, few patients treated with amphotericin B have survived PAM. Therefore, fast-acting and efficient drugs are urgently needed for the treatment of PAM. To facilitate drug screening for this pathogen, an automated, high-throughput screening methodology was developed and validated for the closely related species Naegleria gruberi. Five kinase inhibitors and an NF-kappaB inhibitor were hits identified in primary screens of three compound libraries. Most importantly for a preclinical drug discovery pipeline, we identified corifungin, a water-soluble polyene macrolide with a higher activity against Naegleria than that of amphotericin B. Transmission electron microscopy of N. fowleri trophozoites incubated with different concentrations of corifungin showed disruption of cytoplasmic and plasma membranes and alterations in mitochondria, followed by complete lysis of amebae. In vivo efficacy of corifungin in a mouse model of PAM was confirmed by an absence of detectable amebae in the brain and 100% survival of mice for 17 days postinfection for a single daily intraperitoneal dose of 9 mg/kg of body weight given for 10 days. The same dose of amphotericin B did not reduce ameba growth, and mouse survival was compromised. Based on these results, the U.S. FDA has approved orphan drug status for corifungin for the treatment of PAM.

  9. Genome-Wide Analysis in Three Fusarium Pathogens Identifies Rapidly Evolving Chromosomes and Genes Associated with Pathogenicity.

    Science.gov (United States)

    Sperschneider, Jana; Gardiner, Donald M; Thatcher, Louise F; Lyons, Rebecca; Singh, Karam B; Manners, John M; Taylor, Jennifer M

    2015-05-19

    Pathogens and hosts are in an ongoing arms race and genes involved in host-pathogen interactions are likely to undergo diversifying selection. Fusarium plant pathogens have evolved diverse infection strategies, but how they interact with their hosts in the biotrophic infection stage remains puzzling. To address this, we analyzed the genomes of three Fusarium plant pathogens for genes that are under diversifying selection. We found a two-speed genome structure both on the chromosome and gene group level. Diversifying selection acts strongly on the dispensable chromosomes in Fusarium oxysporum f. sp. lycopersici and on distinct core chromosome regions in Fusarium graminearum, all of which have associations with virulence. Members of two gene groups evolve rapidly, namely those that encode proteins with an N-terminal [SG]-P-C-[KR]-P sequence motif and proteins that are conserved predominantly in pathogens. Specifically, 29 F. graminearum genes are rapidly evolving, in planta induced and encode secreted proteins, strongly pointing toward effector function. In summary, diversifying selection in Fusarium is strongly reflected as genomic footprints and can be used to predict a small gene set likely to be involved in host-pathogen interactions for experimental verification. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. Rapid and High-throughout Identification of Recombinant Bacteria with Mass Spectrometry Assay

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Objective To construct a rapid and high-throughput assay for identifying recombinant bacteria based on mass spectrometry. Methods Matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) techniques were used to identify 12 recombinant proteins (10 of Yersinia pestis, 1 of Campylobacter jejuni and 1 of Helicobacter pylori). A classification model for the various phase of recombinant bacteria was established, optimized and validated, using MALDI-TOF MS-CIinProTools system. The differences in the peptide mass spectra were analyzed by using Biotyper and FIexAnalysis softwares. Results Models of GA, SNN, and QC were established. After optimizing the parameters, the GA recognition model showed good classification capabilities: RC=100%, mean CVA=98.7% (the CVA was 96.4% in phase 1, 100% in phase 2, 98.4% in phase 3, and 100% in phase 4, respectively) and PPV=95}. This model can be used to classify the bacteria and their recombinant, which only requires 3.7x103 cells for analysis. The total time needed is only 10 min from protein extraction to reporting the result for one sample. Furthermore, this assay can automatically detect and test 96 samples concurrently. A total of 48 specific peaks (9, 16, 9, and 14 for the four stages, respectively) was found in the various phase of recombinant bacteria. Conclusion MALDI-TOF MS can be used as a fast, accurate, and high-throughput method to identify recombinant bacteria, which provide a new ideas not only for recombinant bacteria but also for the identification of mutant strains and bioterrorism pathogens.

  11. A rapid and automated relocation method of an AFM probe for high-resolution imaging

    Science.gov (United States)

    Zhou, Peilin; Yu, Haibo; Shi, Jialin; Jiao, Niandong; Wang, Zhidong; Wang, Yuechao; Liu, Lianqing

    2016-09-01

    The atomic force microscope (AFM) is one of the most powerful tools for high-resolution imaging and high-precision positioning for nanomanipulation. The selection of the scanning area of the AFM depends on the use of the optical microscope. However, the resolution of an optical microscope is generally no larger than 200 nm owing to wavelength limitations of visible light. Taking into consideration the two determinants of relocation—relative angular rotation and positional offset between the AFM probe and nano target—it is therefore extremely challenging to precisely relocate the AFM probe to the initial scan/manipulation area for the same nano target after the AFM probe has been replaced, or after the sample has been moved. In this paper, we investigate a rapid automated relocation method for the nano target of an AFM using a coordinate transformation. The relocation process is both simple and rapid; moreover, multiple nano targets can be relocated by only identifying a pair of reference points. It possesses a centimeter-scale location range and nano-scale precision. The main advantages of this method are that it overcomes the limitations associated with the resolution of optical microscopes, and that it is label-free on the target areas, which means that it does not require the use of special artificial markers on the target sample areas. Relocation experiments using nanospheres, DNA, SWCNTs, and nano patterns amply demonstrate the practicality and efficiency of the proposed method, which provides technical support for mass nanomanipulation and detection based on AFM for multiple nano targets that are widely distributed in a large area.

  12. A rapid and automated relocation method of an AFM probe for high-resolution imaging.

    Science.gov (United States)

    Zhou, Peilin; Yu, Haibo; Shi, Jialin; Jiao, Niandong; Wang, Zhidong; Wang, Yuechao; Liu, Lianqing

    2016-09-30

    The atomic force microscope (AFM) is one of the most powerful tools for high-resolution imaging and high-precision positioning for nanomanipulation. The selection of the scanning area of the AFM depends on the use of the optical microscope. However, the resolution of an optical microscope is generally no larger than 200 nm owing to wavelength limitations of visible light. Taking into consideration the two determinants of relocation-relative angular rotation and positional offset between the AFM probe and nano target-it is therefore extremely challenging to precisely relocate the AFM probe to the initial scan/manipulation area for the same nano target after the AFM probe has been replaced, or after the sample has been moved. In this paper, we investigate a rapid automated relocation method for the nano target of an AFM using a coordinate transformation. The relocation process is both simple and rapid; moreover, multiple nano targets can be relocated by only identifying a pair of reference points. It possesses a centimeter-scale location range and nano-scale precision. The main advantages of this method are that it overcomes the limitations associated with the resolution of optical microscopes, and that it is label-free on the target areas, which means that it does not require the use of special artificial markers on the target sample areas. Relocation experiments using nanospheres, DNA, SWCNTs, and nano patterns amply demonstrate the practicality and efficiency of the proposed method, which provides technical support for mass nanomanipulation and detection based on AFM for multiple nano targets that are widely distributed in a large area.

  13. Rapid Detection and Identification of Infectious Pathogens Based on High-throughput Sequencing

    Institute of Scientific and Technical Information of China (English)

    Pei-Xiang Ni; Xin Ding; Yin-Xin Zhang; Xue Yao; Rui-Xue Sun; Peng Wang; Yan-Ping Gong

    2015-01-01

    Background:The dilemma of pathogens identification in patients with unidentified clinical symptoms such as fever of unknown origin exists,which not only poses a challenge to both the diagnostic and therapeutic process by itself,but also to expert physicians.Methods:In this report,we have attempted to increase the awareness of unidentified pathogens by developing a method to investigate hitherto unidentified infectious pathogens based on unbiased high-throughput sequencing.Results:Our observations show that this method supplements current diagnostic technology that predominantly relies on information derived five cases from the intensive care unit.This methodological approach detects viruses and corrects the incidence of false positive detection rates of pathogens in a much shorter period.Through our method is followed by polymerase chain reaction validation,we could identify infection with Epstein-Barr virus,and in another case,we could identify infection with Streptococcus viridians based on the culture,which was false positive.Conclusions:This technology is a promising approach to revolutionize rapid diagnosis of infectious pathogens and to guide therapy that might result in the improvement of personalized medicine.

  14. Rapid Detection and Identification of Infectious Pathogens Based on High-throughput Sequencing

    Directory of Open Access Journals (Sweden)

    Pei-Xiang Ni

    2015-01-01

    Full Text Available Background: The dilemma of pathogens identification in patients with unidentified clinical symptoms such as fever of unknown origin exists, which not only poses a challenge to both the diagnostic and therapeutic process by itself, but also to expert physicians. Methods: In this report, we have attempted to increase the awareness of unidentified pathogens by developing a method to investigate hitherto unidentified infectious pathogens based on unbiased high-throughput sequencing. Results: Our observations show that this method supplements current diagnostic technology that predominantly relies on information derived five cases from the intensive care unit. This methodological approach detects viruses and corrects the incidence of false positive detection rates of pathogens in a much shorter period. Through our method is followed by polymerase chain reaction validation, we could identify infection with Epstein-Barr virus, and in another case, we could identify infection with Streptococcus viridians based on the culture, which was false positive. Conclusions: This technology is a promising approach to revolutionize rapid diagnosis of infectious pathogens and to guide therapy that might result in the improvement of personalized medicine.

  15. Difficulties in differentiating Neisseria cinerea from Neisseria gonorrhoeae in rapid systems used for identifying pathogenic Neisseria species.

    Science.gov (United States)

    Boyce, J M; Mitchell, E B

    1985-11-01

    Neisseria cinerea and Neisseria gonorrhoeae may occur at the same body sites and may have similar colony morphologies. Ideally, systems used for rapid identification of N. gonorrhoeae should be able to differentiate N. cinerea from gonococci. We tested seven N. cinerea strains using the Gonochek II (Du Pont Diagnostics), Minitek (BBL Microbiology Systems), RapID-NH (Innovative Diagnostics, Inc.), RIM-N (American Microscan), and Phadebact (Pharmacia Diagnostics) systems. We found that the reactions produced by N. cinerea in Gonochek II, Minitek, and RapID-NH kits could be confused with the results produced by some strains of N. gonorrhoeae. The susceptibility of N. cinerea to colistin, its ability to grow on tryptic soy or Mueller-Hinton agar, and its inability to grow on modified Thayer-Martin medium help differentiate it from gonococci.

  16. Rapid approach to identify the presence of Arabica and Robusta species in coffee using 1H NMR spectroscopy.

    Science.gov (United States)

    Monakhova, Yulia B; Ruge, Winfried; Kuballa, Thomas; Ilse, Maren; Winkelmann, Ole; Diehl, Bernd; Thomas, Freddy; Lachenmeier, Dirk W

    2015-09-01

    NMR spectroscopy was used to verify the presence of Arabica and Robusta species in coffee. Lipophilic extracts of authentic roasted and green coffees showed the presence of established markers for Robusta (16-O-methylcafestol (16-OMC)) and for Arabica (kahweol). The integration of the 16-OMC signal (δ 3.165 ppm) was used to estimate the amount of Robusta in coffee blends with an approximate limit of detection of 1-3%. The method was successfully applied for the analysis of 77 commercial coffee samples (coffee pods, coffee capsules, and coffee beans). Furthermore, principal component analysis (PCA) was applied to the spectra of lipophilic and aqueous extracts of 20 monovarietal authentic samples. Clusters of the two species were observed. NMR spectroscopy can be used as a rapid prescreening tool to discriminate Arabica and Robusta coffee species before the confirmation applying the official method. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Improved protocol for rapid identification of certain spa types using high resolution melting curve analysis.

    Science.gov (United States)

    Mayerhofer, Benjamin; Stöger, Anna; Pietzka, Ariane T; Fernandez, Haizpea Lasa; Prewein, Bernhard; Sorschag, Sieglinde; Kunert, Renate; Allerberger, Franz; Ruppitsch, Werner

    2015-01-01

    Methicillin-resistant Staphylococcus aureus is one of the most significant pathogens associated with health care. For efficient surveillance, control and outbreak investigation, S. aureus typing is essential. A high resolution melting curve analysis was developed and evaluated for rapid identification of the most frequent spa types found in an Austrian hospital consortium covering 2,435 beds. Among 557 methicillin-resistant Staphylococcus aureus isolates 38 different spa types were identified by sequence analysis of the hypervariable region X of the protein A gene (spa). Identification of spa types through their characteristic high resolution melting curve profiles was considerably improved by double spiking with genomic DNA from spa type t030 and spa type t003 and allowed unambiguous and fast identification of the ten most frequent spa types t001 (58%), t003 (12%), t190 (9%), t041 (5%), t022 (2%), t032 (2%), t008 (2%), t002 (1%), t5712 (1%) and t2203 (1%), representing 93% of all isolates within this hospital consortium. The performance of the assay was evaluated by testing samples with unknown spa types from the daily routine and by testing three different high resolution melting curve analysis real-time PCR instruments. The ten most frequent spa types were identified from all samples and on all instruments with 100% specificity and 100% sensitivity. Compared to classical spa typing by sequence analysis, this gene scanning assay is faster, cheaper and can be performed in a single closed tube assay format. Therefore it is an optimal screening tool to detect the most frequent endemic spa types and to exclude non-endemic spa types within a hospital.

  18. A new delirium phenotype with rapid high amplitude onset and nearly as rapid reversal: Central Coast Australia Delirium Intervention Study

    Directory of Open Access Journals (Sweden)

    Regal PJ

    2015-02-01

    , and 45%/80% for the Delirium Index. General medicine and geriatric medicine groups had similar outcomes.Conclusion: This delirium phenotype selects for a rapid high amplitude critical decline in attention, executive function, IADL, and apathy that recovers almost as rapidly.Keywords: delirium, inattention, executive function, dementia

  19. Optical Whole-Genome Restriction Mapping as a Tool for Rapidly Distinguishing and Identifying Bacterial Contaminants in Clinical Samples

    Science.gov (United States)

    2015-08-01

    search results are obtained in approximately 0.5 – 1 hour. A list of identified organisms can be accessed by double-clicking the results icon . From...capacity, the relevant infrastructure requirements must be considered. A rudimentary form of this technology could be developed using electrostatic

  20. Blood pressure percentile charts to identify high or low blood pressure in children.

    Science.gov (United States)

    Banker, Ashish; Bell, Cynthia; Gupta-Malhotra, Monesha; Samuels, Joshua

    2016-07-19

    The goal was to develop familiar blood pressure (BP) charts representing BP percentile curves similar to CDC growth charts to improve screening of both high and low BP in children. Since height accounts for substantially more BP variability than age and is a more direct measure of body size and maturation in children, height-specific BP percentile curves were drawn separately for males and females. We used the 2004 Fourth Report data source and equations to calculate the BP threshold value for each gender and 5 cm height group. By slightly underestimating a child's BP percentile for high BP and slightly overestimating a child's BP percentile for low BP, these charts guarantee 100 % sensitivity in detecting abnormal BP. Sensitivity and specificity of the chart cut-offs were confirmed in a sample of 1254 healthy children from a school-based blood pressure screening program. The 1st, 5th, 25th, 50th, 75th, 90th, 95th, and 99th BP percentile curves are depicted in the chart for each corresponding gender and height from 85 to 190 cm, mimicking the ubiquitous CDC "growth charts". Shaded areas of the chart differentiate abnormal BP status categories: hypotension, normal BP, prehypertension, Stage 1 hypertension, and Stage 2 hypertension. Sensitivity was confirmed to be 100 % with specificity above 94 %. These simplified BP charts improve upon currently available BP screening reference with the following features: (a) tracking BP longitudinally in an individual child, (b) full physiological range of BP percentiles represented in percentile curve format for rapid identification both high and low BP, (c) easy to use with absolute height alone avoiding the additional step of determining height percentile, (d) incorporation of adult threshold for pre-hypertension to assist in accurate transition from adolescence into adulthood, (e) high sensitivity and specificity to ensure all children at risk are identified with very few false positives.

  1. Appraising bacterial strains for rapid BOD sensing--an empirical test to identify bacterial strains capable of reliably predicting real effluent BODs.

    Science.gov (United States)

    Webber, Judith B; Noonan, Mike; Pasco, Neil F; Hay, Joanne M

    2011-01-01

    The measured response of rapid biochemical oxygen demand (BOD) biosensors is often not identical to those measured using the conventional 5-day BOD assay. This paper highlights the efficacy of using both glucose-glutamic acid (GGA) and Organisation for Economic Cooperation and Development (OECD) BOD standards as a rapid screen for microorganisms most likely to reliably predict real effluent BODs when used in rapid BOD devices. Using these two synthetic BOD standards, a microorganism was identified that produced comparable BOD response profiles for two assays, the MICREDOX® assay and the conventional 5-day BOD(5) test. A factorial experimental design systematically evaluated the impact of four factors (microbial strain, growth media composition, media strength, and microbial growth phase) on the BOD response profiles using GGA and OECD synthetic standard substrates. An outlier was identified that showed an improved correlation between the MICREDOX® BOD (BOD(sens)) and BOD(5) assays for both the synthetic standards and for real wastewater samples. Microbial strain was the dominant factor influencing BOD(sens) values, with Arthrobacter globiformis single cultures clearly demonstrating superior rapid BOD(sens) response profiles for both synthetic and real waste samples. It was the only microorganism to approach the BOD(5) response for the OECD substrate (171 mg O(2)L(-1)), and also reported BOD values for real waste samples that were comparable to those produced by the BOD(5) test, including discriminating between filtered and unfiltered samples.

  2. An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure.

    Science.gov (United States)

    Roberts, Dean W; Lee, William M; Hinson, Jack A; Bai, Shasha; Swearingen, Christopher J; Stravitz, R Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M; Rule, Jody; Fontana, Robert J; Ganger, Daniel; Reddy, K Rajender; Liou, Iris; Fix, Oren; James, Laura P

    2017-04-01

    acetaminophen-associated acute liver injury in 3 of these cases. The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Rapidity and centrality dependence of particle production for identified hadrons in Cu + Cu collisions at √{sNN }=200 GeV

    Science.gov (United States)

    Arsene, I. C.; Bearden, I. G.; Beavis, D.; Bekele, S.; Besliu, C.; Budick, B.; Bøggild, H.; Chasman, C.; Christensen, C. H.; Christiansen, P.; Dalsgaard, H. H.; Debbe, R.; Gaardhøje, J. J.; Hagel, K.; Ito, H.; Jipa, A.; Johnson, E. B.; Jørgensen, C. E.; Karabowicz, R.; Katrynska, N.; Kim, E. J.; Larsen, T. M.; Lee, J. H.; Løvhøiden, G.; Majka, Z.; Murray, M. J.; Natowitz, J.; Nielsen, B. S.; Nygaard, C.; Pal, D.; Qviller, A.; Rami, F.; Ristea, C.; Ristea, O.; Röhrich, D.; Sanders, S. J.; Staszel, P.; Tveter, T. S.; Videbæk, F.; Wada, R.; Yang, H.; Yin, Z.; Zgura, I. S.; Brahms Collaboration

    2016-07-01

    The BRAHMS collaboration has measured transverse momentum spectra of pions, kaons, protons, and antiprotons at rapidities 0 and 3 for Cu+Cu collisions at √{sNN}=200 GeV. As the collisions become more central the collective radial flow increases while the temperature of kinetic freeze-out decreases. The temperature is lower and the radial flow weaker at forward rapidity. Pion and kaon yields with transverse momenta between 1.5 and 2.5 GeV /c are suppressed for central collisions relative to scaled p +p collisions. This suppression, which increases as the collisions become more central, is consistent with jet quenching models and is also present with comparable magnitude at forward rapidity. At such rapidities, initial state effects may also be present and persistence of the meson suppression to high rapidity may reflect a combination of jet quenching and nuclear shadowing. The ratio of protons to mesons increases as the collisions become more central and is largest at forward rapidities.

  4. Rapidity and centrality dependence of particle production for identified hadrons in Cu+Cu collisions at $\\sqrt{s_{NN}} = 200$ GeV

    CERN Document Server

    Arsene, I C; Beavis, D; Bekele, S; Besliu, C; Budick, B; Bøggild, H; Chasman, C; Christensen, C H; Christiansen, P; Dalsgaard, H H; Debbe, R; Gaardhøje, J J; Hagel, K; Ito, H; Jipa, A; Johnson, E B; Jørgensen, C E; Karabowicz, R; Katrynska, N; Kim, E J; Larsen, T M; Lee, J H; Løvhøiden, G; Majka, Z; Murray, M J; Natowitz, J; Nielsen, B S; Nygaard, C; Pal, D; Qviller, A; Rami, F; Ristea, C; Ristea, O; Rohrich, D; Sanders, S J; Stazel, P; Tveter, T S; Videbæk, F; Wada, R; Yang, H; Yin, Z; Zgura, I S

    2016-01-01

    The BRAHMS collaboration has measured transverse momentum spectra of pions, kaons, protons and antiprotons at rapidities 0 and 3 for Cu+Cu collisions at $\\sqrt{s_{NN}} = 200$ GeV. As the collisions become more central the collective radial flow increases while the temperature of kinetic freeze-out decreases. The temperature is lower and the radial flow weaker at forward rapidity. Pion and kaon yields with transverse momenta between 1.5 and 2.5 GeV/c are suppressed for central collisions relative to scaled $p+p$ collisions. This suppression, which increases as the collisions become more central is consistent with jet quenching models and is also present with comparable magnitude at forward rapidity. At such rapidities initial state effects may also be present and persistence of the meson suppression to high rapidity may reflect a combination of jet quenching and nuclear shadowing. The ratio of protons to mesons increases as the collisions become more central and is largest at forward rapidities.

  5. Identifying a Path Towards Rapid Discrimination of Infection Disease Outbreaks: Harnessing Next-Generation Sequencing Capabilities for Microbial Forensics

    Science.gov (United States)

    2014-07-15

    a sophisticated analysis identified the source, many countries acted proactively to remove cucumbers and tomatoes from store shelves, Russia issued...Eisenstein, M. (2012). Oxford Nanopore announcement sets sequencing sector abuzz. Nature Biotechnology , 30(4), 295–6. doi:10.1038/nbt0412-295... Biotechnology , 29(7). Grad, Y. H., Lipsitch, M., Feldgarden, M., Arachchi, H. M., Cerqueira, G. C., Fitzgerald, M., .. . Hanage, W. P. (2012). Genomic

  6. A simple and rapid flow cytometry-based assay to identify a competent embryo prior to embryo transfer

    OpenAIRE

    Pallinger, Eva; Bognar, Zoltan; Bodis, Jozsef; Csabai, Timea; Farkas, Nelli; Godony, Krisztina; Varnagy, Akos; Buzas, Edit; Szekeres-Bartho, Julia

    2017-01-01

    Multiple pregnancy is a risk for prematurity and preterm birth. The goal of assisted reproduction is to achieve a single pregnancy, by transferring a single embryo. This requires improved methods to identify the competent embryo. Here, we describe such a test, based on flow cytometric determination of the nucleic acid (PI+) containing extracellular vesicle (EV) count in day 5 embryo culture media. 88 women undergoing IVF were included in the study. More than 1 embryos were transferred to most...

  7. A simple and rapid flow cytometry-based assay to identify a competent embryo prior to embryo transfer

    Science.gov (United States)

    Pallinger, Eva; Bognar, Zoltan; Bodis, Jozsef; Csabai, Timea; Farkas, Nelli; Godony, Krisztina; Varnagy, Akos; Buzas, Edit; Szekeres-Bartho, Julia

    2017-01-01

    Multiple pregnancy is a risk for prematurity and preterm birth. The goal of assisted reproduction is to achieve a single pregnancy, by transferring a single embryo. This requires improved methods to identify the competent embryo. Here, we describe such a test, based on flow cytometric determination of the nucleic acid (PI+) containing extracellular vesicle (EV) count in day 5 embryo culture media. 88 women undergoing IVF were included in the study. More than 1 embryos were transferred to most patients. In 58 women, the transfer resulted in clinical pregnancy, whereas in 30 women in implantation failure. In 112 culture media of embryos from the “clinical pregnancy” group, the number of PI+ EVs was significantly lower than in those of 49 embryos, from the “implantation failure” group. In 14 women, transfer of a single embryo resulted in a singleton pregnancy, or, transfer of two embryos in twin pregnancy. The culture media of 19 out of the 20 “confirmed competent” embryos contained a lower level of PI+ EVs than the cut off level, suggesting that the competent embryo can indeed be identified by low PI+ EV counts. We developed a noninvasive, simple, inexpensive, quick test, which identifies the embryos that are most likely to implant. PMID:28057937

  8. Mapping with RAD (restriction-site associated DNA) markers to rapidly identify QTL for stem rust resistance in Lolium perenne.

    Science.gov (United States)

    Pfender, W F; Saha, M C; Johnson, E A; Slabaugh, M B

    2011-05-01

    A mapping population was created to detect quantitative trait loci (QTL) for resistance to stem rust caused by Puccinia graminis subsp. graminicola in Lolium perenne. A susceptible and a resistant plant were crossed to produce a pseudo-testcross population of 193 F(1) individuals. Markers were produced by the restriction-site associated DNA (RAD) process, which uses massively parallel and multiplexed sequencing of reduced-representation libraries. Additional simple sequence repeat (SSR) and sequence-tagged site (STS) markers were combined with the RAD markers to produce maps for the female (738 cM) and male (721 cM) parents. Stem rust phenotypes (number of pustules per plant) were determined in replicated greenhouse trials by inoculation with a field-collected, genetically heterogeneous population of urediniospores. The F(1) progeny displayed continuous distribution of phenotypes and transgressive segregation. We detected three resistance QTL. The most prominent QTL (qLpPg1) is located near 41 cM on linkage group (LG) 7 with a 2-LOD interval of 8 cM, and accounts for 30-38% of the stem rust phenotypic variance. QTL were detected also on LG1 (qLpPg2) and LG6 (qLpPg3), each accounting for approximately 10% of phenotypic variance. Alleles of loci closely linked to these QTL originated from the resistant parent for qLpPg1 and from both parents for qLpPg2 and qLpPg3. Observed quantitative nature of the resistance may be due to partial-resistance effects against all pathogen genotypes, or qualitative effects completely preventing infection by only some genotypes in the genetically mixed inoculum. RAD markers facilitated rapid construction of new genetic maps in this outcrossing species and will enable development of sequence-based markers linked to stem rust resistance in L. perenne.

  9. High Resolution Rapid Response observations of compact radio sources with the Ceduna Hobart Interferometer (CHI)

    CERN Document Server

    Blanchard, Jay M; Ojha, Roopesh; Kadler, Matthias; Dickey, John M; Edwards, Philip G

    2012-01-01

    Context. Frequent, simultaneous observations across the electromagnetic spectrum are essential to the study of a range of astrophysical phenomena including Active Galactic Nuclei. A key tool of such studies is the ability to observe an object when it flares i.e. exhibits a rapid and significant increase in its flux density. Aims. We describe the specific observational procedures and the calibration techniques that have been developed and tested to create a single baseline radio interferometer that can rapidly observe a flaring object. This is the only facility that is dedicated to rapid high resolution radio observations of an object south of -30 degrees declination. An immediate application is to provide rapid contemporaneous radio coverage of AGN flaring at {\\gamma}-ray frequencies detected by the Fermi Gamma-ray Space Telescope. Methods. A single baseline interferometer was formed with radio telescopes in Hobart, Tasmania and Ceduna, South Australia. A software correlator was set up at the University of Ta...

  10. Rapid solidification of M{sub 2} high-speed steel by laser melting

    Energy Technology Data Exchange (ETDEWEB)

    Benyounis, K.Y. [Department of Industrial Engineering, Faculty of Engineering, Garyounis University, P.O. Box 1308, Benghazi (Libyan Arab Jamahiriya)], E-mail: kybenyounis@yahoo.com; Fakron, O.M. [Department of Mechanical Engineering, Faculty of Engineering, Garyounis University, P.O. Box 130, Benghazi (Libyan Arab Jamahiriya); Abboud, J.H. [Department of Mechanical Engineering, Faculty of Engineering, Garyounis University, P.O. Box 130, Benghazi (Libyan Arab Jamahiriya)], E-mail: jhabboud@yahoo.com

    2009-03-15

    The effects of laser surface melting and rapid solidification on the microstructure of M2 high-speed steel (HSS) have been investigated. A solid state pulse Nd-YAG laser of wavelength 1.06 {mu}m, maximum power of 100 W, beam diameter {approx}1 mm, and pulse duration of 0.8 and 2.5 ms. Optical, scanning electron microscopy, and X-ray diffraction techniques were used to evaluate the microstructure and identify the phases. Results show that laser surface melting has led to a complete dissolution of the carbides and re-solidification of cellular/dendritic structure of a very fine scale surrounded by a continuous interdendritic (or intercellular) network of carbides eutectic. The phases appeared were mainly {delta} ferrite and M{sub 6}C and small amount of austenite {gamma}. Laser surface melting leads to a refinement of the microstructure and altering the morphology and the distribution of the phases. The microhardness of this material was not increased after laser melting.

  11. Rapid analysis of estrogen receptor heterogeneity by chromatofocusing with high-performance liquid chromatography.

    Science.gov (United States)

    Hutchens, T W; Wiehle, R D; Shahabi, N A; Wittliff, J L

    1983-08-26

    Chromatofocusing principles have been utilized to develop a high-performance liquid chromatographic technique for the rapid and routine analysis of steroid receptor heterogeneity. Two anion-exchange columns (SynChropak AX-300 and AX-500) were compared for analytical and preparative chromatofocusing of estrogen receptor components. As many as ten different [125I]iodoestradiol-labeled binding proteins were identified in cytosols prepared from mammary gland and uterus. Estrogen receptors were well separated from other cytosolic proteins and recovery of activity routinely exceeded 90%. Parallel analyses of these cytosols to determine receptor size and shape indicated that HPLC chromatofocusing can be used effectively to study receptor isoforms with Stokes radii ranging from 30 A to greater than 70 A. In contrast to isoelectric focusing, this technique is compatible with the inclusion of a commonly used receptor-stabilizing agent, sodium molybdate. Inclusion of molybdate during chromatofocusing of molybdate-stabilized receptor allowed the identification of two acidic receptor species not previously reported.

  12. High Nucleotide Polymorphism and Rapid Decay of Linkage Disequilibrium in Wild Populations of Caenorhabditis remanei

    Science.gov (United States)

    Cutter, Asher D.; Baird, Scott E.; Charlesworth, Deborah

    2006-01-01

    The common ancestor of the self-fertilizing nematodes Caenorhabditis elegans and C. briggsae must have reproduced by obligate outcrossing, like most species in this genus. However, we have only a limited understanding about how genetic variation is patterned in such male–female (gonochoristic) Caenorhabditis species. Here, we report results from surveying nucleotide variation of six nuclear loci in a broad geographic sample of wild isolates of the gonochoristic C. remanei. We find high levels of diversity in this species, with silent-site diversity averaging 4.7%, implying an effective population size close to 1 million. Additionally, the pattern of polymorphisms reveals little evidence for population structure or deviation from neutral expectations, suggesting that the sampled C. remanei populations approximate panmixis and demographic equilibrium. Combined with the observation that linkage disequilibrium between pairs of polymorphic sites decays rapidly with distance, this suggests that C. remanei will provide an excellent system for identifying the genetic targets of natural selection from deviant patterns of polymorphism and linkage disequilibrium. The patterns revealed in this obligately outcrossing species may provide a useful model of the evolutionary circumstances in C. elegans' gonochoristic progenitor. This will be especially important if self-fertilization evolved recently in C. elegans history, because most of the evolutionary time separating C. elegans from its known relatives would have occurred in a state of obligate outcrossing. PMID:16951062

  13. The role of rapid endoscopy for high-risk patients with acute nonvariceal upper gastrointestinal bleeding

    Science.gov (United States)

    Targownik, Laura E; Murthy, Sanjay; Keyvani, Leila; Leeson, Shauna

    2007-01-01

    BACKGROUND: Performance of endoscopy within 24 h is recommended for patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB). It is unknown whether performing endoscopy early within this 24 h window is beneficial for clinically high-risk patients. METHODS: A retrospective review was performed to identify patients presenting to two tertiary care centres with ANVUGIB and either systolic blood pressure lower than 100 mmHg or heart rate greater than 100 beats/min on presentation between 1999 and 2004. Patients receiving endoscopy within 6 h (rapid endoscopy [RE]) were compared with patients undergoing endoscopy between 6 h and 24 h (early endoscopy [EE]). The primary outcome measure was the development of any adverse bleeding outcome (rebleeding, surgery for control of bleeding, in-hospital mortality or readmission within 30 days for ANVUGIB). RESULTS: There were 169 patients who met the entry criteria (77 RE patients and 92 EE patients). There was no significant difference in the development of any adverse bleeding outcomes between RE and EE patients (25% RE versus 23% EE, difference between groups 2%, 95% CI −9% to 13%). Transfusion requirements and length of hospital stay also did not differ between the comparator groups. RE was not associated with fewer adverse outcomes, even after adjusting for confounders. CONCLUSION: For clinically high-risk ANVUGIB patients, performing endoscopy within 6 h of presentation is no more effective than performing endoscopy between 6 h and 24 h after presentation. The role of RE in high-risk ANVUGIB patients requires further delineation in a prospective fashion. PMID:17637943

  14. CRISPR/Cas9-Mediated Rapid Generation of Multiple Mouse Lines Identified Ccdc63 as Essential for Spermiogenesis

    Directory of Open Access Journals (Sweden)

    Samantha A. M. Young

    2015-10-01

    Full Text Available Spermatozoa are flagellated cells whose role in fertilization is dependent on their ability to move towards an oocyte. The structure of the sperm flagella is highly conserved across species, and much of what is known about this structure is derived from studies utilizing animal models. One group of proteins essential for the movement of the flagella are the dyneins. Using the advanced technology of CRISPR/Cas9 we have targeted three dynein group members; Dnaic1, Wdr63 and Ccdc63 in mice. All three of these genes are expressed strongly in the testis. We generated mice with amino acid substitutions in Dnaic1 to analyze two specific phosphorylation events at S124 and S127, and generated simple knockouts of Wdr63 and Ccdc63. We found that the targeted phosphorylation sites in Dnaic1 were not essential for male fertility. Similarly, Wdr63 was not essential for male fertility; however, Ccdc63 removal resulted in sterile male mice due to shortened flagella. This study demonstrates the versatility of the CRISPR/Cas9 system to generate animal models of a highly complex system by introducing point mutations and simple knockouts in a fast and efficient manner.

  15. Portland Identification and Early Referral: A Community-Based System for Identifying and Treating Youths at High Risk of Psychosis

    Science.gov (United States)

    McFarlane, William R.; Cook, William L.; Downing, Donna; Verdi, Mary B.; Woodberry, Kristen A.; Ruff, Anita

    2010-01-01

    Objective The Portland [Maine] Identification and Early Referral (PIER) Program was established in 2001 as a prevention system for identifying and treating youths at high risk of an initial psychotic episode. Methods During six years, 7,270 professionals from the educational, general medical, and mental health sectors were provided information on prodromal symptoms and means for rapid referral of at-risk youth, which resulted in referral of 780 youths who met eligibility criteria. Results After screening, 37% of the community referrals were found to be at high risk of psychosis, and another 20% had untreated psychosis, yielding an efficiency ratio of 57%. Prodromal cases identified were 46% of the expected incidence of psychosis in the catchment area. Community educational presentations were significantly associated with referrals six months later; half of referrals were from outside the mental health system. Conclusions Community-based identification is an efficient public health strategy, offering the opportunity for preventive intervention. PMID:20439374

  16. Developments in time-resolved high pressure x-ray diffraction using rapid compression and decompression

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jesse S.; Sinogeikin, Stanislav V.; Lin, Chuanlong; Rod, Eric; Bai, Ligang; Shen, Guoyin [High Pressure Collaborative Access Team, Geophysical Laboratory, Carnegie Institution of Washington, Argonne, Illinois 60439 (United States)

    2015-07-15

    Complementary advances in high pressure research apparatus and techniques make it possible to carry out time-resolved high pressure research using what would customarily be considered static high pressure apparatus. This work specifically explores time-resolved high pressure x-ray diffraction with rapid compression and/or decompression of a sample in a diamond anvil cell. Key aspects of the synchrotron beamline and ancillary equipment are presented, including source considerations, rapid (de)compression apparatus, high frequency imaging detectors, and software suitable for processing large volumes of data. A number of examples are presented, including fast equation of state measurements, compression rate dependent synthesis of metastable states in silicon and germanium, and ultrahigh compression rates using a piezoelectric driven diamond anvil cell.

  17. High-resolution Orbitrap™-based mass spectrometry for rapid detection of peanuts in nuts.

    Science.gov (United States)

    Monaci, Linda; De Angelis, Elisabetta; Bavaro, Simona L; Pilolli, Rosa

    2015-01-01

    Peanut represents one of the most harmful allergenic foods capable of triggering severe and sometimes lethal reactions in allergic consumers upon ingestion of even small amounts. Several proteins capable of inducing allergic reactions that have been recognised by patients' IgE antibodies have been identified from this nut source. Methods mainly based on ELISA assays have been developed in order to detect peanuts in several food commodities. In addition LC-MS/MS methods based on different mass analysers have also been devised for tracing peanut contamination in different foods achieving low limits of detection. The applicability of a benchtop high-resolution Exactive™ mass spectrometer has never been investigated for the rapid screening of peanut contamination in complex food matrices like mixtures of nuts. We report in this paper the design of suitable peanut markers and the development of an high-resolution Orbitrap™ mass spectrometer-based method for peanut detection in a mixture of nuts species. With this aim, different types of samples were prepared: (1) nuts-based powder made up of a mixture of hazelnuts, pistachios, almonds and walnuts; and (2) nuts powder fortified with peanuts. Different levels of fortifications were produced and the applicability of the method was tested. Finally, a subset of six peptides fulfilling specific analytical requirements was chosen to check the suitability of the method tailored to the detection of peanuts in nuts-based products, and two of them, peptides VYD and WLG, were selected as quantitative markers. The method proved to be a suitable screening tool to assess the presence of traces of peanuts in other tree nuts with a limit of detection as low as 4 µg of peanuts proteins or 26 µg of peanuts in 1 g of matrix.

  18. Rapid detection of malto-oligosaccharide-forming bacterial amylases by high performance anion-exchange chromatography

    DEFF Research Database (Denmark)

    Duedahl-Olesen, Lene; Larsen, K. L.; Zimmermann, W.

    2000-01-01

    High performance anion-exchange chromatography with pulsed amperometric detection was applied for the rapid analysis of malto-oligosaccharides formed by extracellular enzyme preparations from 49 starch-degrading bacterial strains isolated from soil and compost samples. Malto-oligosaccharide-formi...

  19. Rapid high temperature field test method for evaluation of geothermal calcite scale inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Asperger, R.G.

    1982-08-01

    A test method is described which allows the rapid field testing of calcite scale inhibitors in high- temperature geothermal brines. Five commercial formulations, chosen on the basis of laboratory screening tests, were tested in brines with low total dissolved solids at ca 500 F. Four were found to be effective; of these, 2 were found to be capable of removing recently deposited scale. One chemical was tested in the full-flow brine line for 6 wks. It was shown to stop a severe surface scaling problem at the well's control valve, thus proving the viability of the rapid test method. (12 refs.)

  20. Rapid transcriptional pulsing dynamics of high expressing retroviral transgenes in embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Mandy Y M Lo

    Full Text Available Single cell imaging studies suggest that transcription is not continuous and occurs as discrete pulses of gene activity. To study mechanisms by which retroviral transgenes can transcribe to high levels, we used the MS2 system to visualize transcriptional dynamics of high expressing proviral integration sites in embryonic stem (ES cells. We established two ES cell lines each bearing a single copy, self-inactivating retroviral vector with a strong ubiquitous human EF1α gene promoter directing expression of mRFP fused to an MS2-stem-loop array. Transfection of MS2-EGFP generated EGFP focal dots bound to the mRFP-MS2 stem loop mRNA. These transcription foci colocalized with the transgene integration site detected by immunoFISH. Live tracking of single cells for 20 minutes detected EGFP focal dots that displayed frequent and rapid fluctuations in transcription over periods as short as 25 seconds. Similarly rapid fluctuations were detected from focal doublet signals that colocalized with replicated proviral integration sites by immunoFISH, consistent with transcriptional pulses from sister chromatids. We concluded that retroviral transgenes experience rapid transcriptional pulses in clonal ES cell lines that exhibit high level expression. These events are directed by a constitutive housekeeping gene promoter and may provide precedence for rapid transcriptional pulsing at endogenous genes in mammalian stem cells.

  1. Rapid high-resolution characterization of functionally important monoclonal antibody N-glycans by capillary electrophoresis.

    Science.gov (United States)

    Szabo, Zoltan; Guttman, András; Bones, Jonathan; Karger, Barry L

    2011-07-01

    Characterization of the N-glycosylation present in the Fc region of therapeutic monoclonal antibodies requires rapid, high-resolution separation methods to guarantee product safety and efficacy during all stages of process development. Determination of fucosylated oligosaccharides is particularly important during clone selection, product characterization, and lot release as fucose has been shown to adversely affect the ability of mAbs to induce antibody dependent cellular cytotoxicity (ADCC). Here, we apply a general capillary electrophoresis optimization strategy to separate functionally relevant fucosylated and afucosylated glycans on mononclonal antibody products in the presence of several high mannose oligosaccharides. The N-glycans chosen represent those most commonly reported on CHO cell derived therapeutic antibodies. A rapid (processing for automated 96 well plate-based glycosylation analyses of two nonproprietary therapeutic monoclonal antibodies, demonstrating ruggedness and suitability for high-throughput process and product monitoring applications.

  2. A Clinical model to identify patients with high-risk coronary artery disease

    NARCIS (Netherlands)

    Y. Yang (Yelin); L. Chen (Li); Y. Yam (Yeung); S. Achenbach (Stephan); M. Al-Mallah (Mouaz); D.S. Berman (Daniel); M.J. Budoff (Matthew); F. Cademartiri (Filippo); T.Q. Callister (Tracy); H.-J. Chang (Hyuk-Jae); V.Y. Cheng (Victor); K. Chinnaiyan (Kavitha); R.C. Cury (Ricardo); A. Delago (Augustin); A. Dunning (Allison); G.M. Feuchtner (Gudrun); M. Hadamitzky (Martin); J. Hausleiter (Jörg); R.P. Karlsberg (Ronald); P.A. Kaufmann (Philipp); Y.-J. Kim (Yong-Jin); J. Leipsic (Jonathon); T.M. LaBounty (Troy); F.Y. Lin (Fay); E. Maffei (Erica); G.L. Raff (Gilbert); L.J. Shaw (Leslee); T.C. Villines (Todd); J.K. Min (James K.); B.J.W. Chow (Benjamin)

    2015-01-01

    textabstractObjectives This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). Background Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify th

  3. A Clinical model to identify patients with high-risk coronary artery disease

    NARCIS (Netherlands)

    Y. Yang (Yelin); L. Chen (Li); Y. Yam (Yeung); S. Achenbach (Stephan); M. Al-Mallah (Mouaz); D.S. Berman (Daniel); M.J. Budoff (Matthew); F. Cademartiri (Filippo); T.Q. Callister (Tracy); H.-J. Chang (Hyuk-Jae); V.Y. Cheng (Victor); K. Chinnaiyan (Kavitha); R.C. Cury (Ricardo); A. Delago (Augustin); A. Dunning (Allison); G.M. Feuchtner (Gudrun); M. Hadamitzky (Martin); J. Hausleiter (Jörg); R.P. Karlsberg (Ronald); P.A. Kaufmann (Philipp); Y.-J. Kim (Yong-Jin); J. Leipsic (Jonathon); T.M. LaBounty (Troy); F.Y. Lin (Fay); E. Maffei (Erica); G.L. Raff (Gilbert); L.J. Shaw (Leslee); T.C. Villines (Todd); J.K. Min (James K.); B.J.W. Chow (Benjamin)

    2015-01-01

    textabstractObjectives This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). Background Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify th

  4. Identified Moderate and High Temperature Geothermal Systems of the Western United States including AK and HI

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This layer contains the locations of identified moderate (90 - 150° C) and high (> 150° C) temperature geothermal systems and associated reservoir volumes,...

  5. Carotid Magnetic Resonance Imaging A Window to Study Atherosclerosis and Identify High-Risk Plaques

    National Research Council Canada - National Science Library

    Oikawa, Minako; Ota, Hideki; Takaya, Norihide; Miller, Zach; Hatsukami, Thomas S; Yuan, Chun

    2009-01-01

    ...: the so-called "vulnerable plaque". A reliable, in vivo, imaging method capable of identifying plaque characteristics associated with high-risk plaque will be immensely useful for evaluating plaque status and predicting future events...

  6. Structure and mechanical properties of high-temperature titanium alloys after rapid heat treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ivasishin, O.M. (Inst. for Metal Physics, Kiev (Ukraine)); Luetjering, G. (Technical Univ. Hamburg-Harburg, Hamburg (Germany))

    1993-08-30

    In this study a new approach to optimizing the mechanical properties of high-temperature titanium alloys was developed. It is based on using rapid heating of equiaxed structures into the [beta]-field to achieve a fine [beta] grain size (less than or equal to 100 [mu]m), transforming on subsequent cooling into a fully lamellar structure. This fine [beta] grain size is an order of magnitude smaller than the grain sizes achieved by conventional furnace [beta]-treatment. Structures and mechanical properties (tensile, fatigue and creep) of high temperature alloys after rapid and conventional furnace heat treatments were compared. The results are discussed in terms of structure-property relationships. (orig.)

  7. Rapid room temperature solubilization and depolymerization of polymeric lignin at high loadings

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jian; Dutta, Tanmoy; Parthasarathi, Ramakrishnan; Kim, Kwang Ho; Tolic, Nikola; Chu, Rosalie K.; Isern, Nancy G.; Cort, John R.; Simmons, Blake A.; Singh, Seema

    2016-10-03

    The relatively poor solubility of lignin in most pretreatment solvents remains one of the biggest challegnes in lignin valorization to improve overall biorefinery economics. In this work, rapid room temperature solubilization of lignin at high solid loadings (>30 wt%) can be easily achieved in a single step using ethylene glycol (EG). The solubilized lignin can be rapidly and quantitively recovered with the addtion of ethanol. The computational and nuclear magnetic resonance (NMR) spectroscopic studies confirm that strong hydrogen bond interactions between EG and the free hydroxyl groups present in lignin contribute to the lignin dissolution. In addition, hydrogen peroxide mediated depolymerization of dissolved lignin at low temperature (80 oC) was tested and the effect of EG molecules on depolymerization of ligin was also theoritically studied. The findings of this work provide mechanistic insights of hydrogen bond interactions in high lignin solubilization and valorization.

  8. Cost-effectiveness analysis of introduction of rapid, alternative methods to identify multidrug-resistant tuberculosis in middle-income countries.

    Science.gov (United States)

    Acuna-Villaorduna, Carlos; Vassall, Anna; Henostroza, German; Seas, Carlos; Guerra, Humberto; Vasquez, Lucy; Morcillo, Nora; Saravia, Juan; O'Brien, Richard; Perkins, Mark D; Cunningham, Jane; Llanos-Zavalaga, Luis; Gotuzzo, Eduardo

    2008-08-15

    Resistance to commonly used antituberculosis drugs is emerging worldwide. Conventional drug-susceptibility testing (DST) methods are slow and demanding. Alternative, rapid DST methods would permit the early detection of drug resistance and, in turn, arrest tuberculosis transmission. A cost-effectiveness analysis of 5 DST methods was performed in the context of a clinical trial that compared rapid with conventional DST methods. The methods under investigation were direct phage-replication assay (FASTPlaque-Response; Biotech), direct amplification and reverse hybridization of the rpoB gene (INNO-LiPA; Innogenetics), indirect colorimetric minimum inhibitory concentration assay (MTT; ICN Biomedicals), and direct proportion method on Löwenstein-Jensen medium. These were compared with the widely used indirect proportion method on Löwenstein-Jensen medium. All alternative DST methods were found to be cost-effective, compared with other health care interventions. DST methods also generate substantial cost savings in settings of high prevalence of multidrug-resistant tuberculosis. Excluding the effects of transmission, the direct proportion method on Löwenstein-Jensen medium was the most cost-effective alternative DST method for patient groups with prevalences of multidrug-resistant tuberculosis of 2%, 5%, 20%, and 50% (cost in US$2004, $94, $36, $8, and $2 per disability-adjusted life year, respectively). Alternative, rapid methods for DST are cost-effective and should be considered for use by national tuberculosis programs in middle-income countries.

  9. Rapid, automated, parallel quantitative immunoassays using highly integrated microfluidics and AlphaLISA

    Science.gov (United States)

    TakYu, Zeta; Guan, Huijiao; Ki Cheung, Mei; McHugh, Walker M.; Cornell, Timothy T.; Shanley, Thomas P.; Kurabayashi, Katsuo; Fu, Jianping

    2015-06-01

    Immunoassays represent one of the most popular analytical methods for detection and quantification of biomolecules. However, conventional immunoassays such as ELISA and flow cytometry, even though providing high sensitivity and specificity and multiplexing capability, can be labor-intensive and prone to human error, making them unsuitable for standardized clinical diagnoses. Using a commercialized no-wash, homogeneous immunoassay technology (‘AlphaLISA’) in conjunction with integrated microfluidics, herein we developed a microfluidic immunoassay chip capable of rapid, automated, parallel immunoassays of microliter quantities of samples. Operation of the microfluidic immunoassay chip entailed rapid mixing and conjugation of AlphaLISA components with target analytes before quantitative imaging for analyte detections in up to eight samples simultaneously. Aspects such as fluid handling and operation, surface passivation, imaging uniformity, and detection sensitivity of the microfluidic immunoassay chip using AlphaLISA were investigated. The microfluidic immunoassay chip could detect one target analyte simultaneously for up to eight samples in 45 min with a limit of detection down to 10 pg mL-1. The microfluidic immunoassay chip was further utilized for functional immunophenotyping to examine cytokine secretion from human immune cells stimulated ex vivo. Together, the microfluidic immunoassay chip provides a promising high-throughput, high-content platform for rapid, automated, parallel quantitative immunosensing applications.

  10. Ultra high performance liquid chromatography with tandem mass spectrometry for rapid separation and identification of main constituents in Chinese herbal formula Xuan Hu Suo San.

    Science.gov (United States)

    Tang, Huaqi; Zhang, Xinyue; Luo, Shilin; Shang, Fei; Chen, Jianping; Wang, Jinghong; Duan, Xiaojie; Gao, Xiaoyan; Sun, Yikun

    2017-02-15

    Xuan Hu Suo San (XHSS) is a traditional Chinese medicine that has been extensively applied in the treatment of osteoarthritis for many years, however, its chemical composition has not yet been elucidated. Thus, a rapid, efficient, and precise method based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied in both positive- and negative-ion modes to rapidly separate and identify the main chemical ingredients in XHSS for the first time. Finally, with the optimised separation and detection method, a total of 57 compounds were simultaneously separated within 13 min, among which 14 compounds were confirmed by comparing retention time and MS data with reference standards and others were tentatively identified by comparing with reference literatures. This rapid and sensitive approach is highly useful for the identification and characterisation of chemical constituents, and provides fundamental and extensive information supporting further metabolic and pharmacokinetic studies of XHSS.

  11. Identifying High School Physical Education Physical Activity Patterns after High School

    Science.gov (United States)

    Barney, David; Pleban, Francis T.; Wilkinson, Carol; Prusak, Keven A.

    2015-01-01

    National standards for physical education (PE) encompass five principles for the purpose of defining what high school students should recognize and be able to perform as a result of a quality PE program. The expectation is that youth will develop an active, healthy lifestyle into adulthood from activities and skills taught in PE. Researchers from…

  12. Imaging Gallium Nitride High Electron Mobility Transistors to Identify Point Defects

    Science.gov (United States)

    2014-03-01

    REPORT TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE IMAGING GALLIUM NITRIDE HIGH ELECTRON MOBILITY TRANSISTORS TO IDENTIFY...Identification of these trends will assist in the improvement of gallium nitride HEMT fabrication processes leading to the development of more...reliable devices. 14. SUBJECT TERMS Electron microscopy, Gallium Nitride (GaN), high electron mobility transistor (HEMT

  13. Identifying the Best Candidate for Radical Prostatectomy Among Patients with High-Risk Prostate Cancer

    NARCIS (Netherlands)

    Briganti, Alberto; Joniau, Steven; Gontero, Paolo; Abdollah, Firas; Passoni, Niccolo M.; Tombal, Bertrand; Marchioro, Giansilvio; Kneitz, Burkhard; Walz, Jochen; Frohneberg, Detlef; Bangma, Chris H.; Graefen, Markus; Tizzani, Alessandro; Frea, Bruno; Karnes, R. Jeffrey; Montorsi, Francesco; Van Poppel, Hein; Spahn, Martin

    2012-01-01

    Background: The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial. Objective: To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated. Design, setting, and participants: We evaluated

  14. Synthesis of a Novel Highly Oleophilic and Highly Hydrophobic Sponge for Rapid Oil Spill Cleanup.

    Science.gov (United States)

    Khosravi, Maryam; Azizian, Saeid

    2015-11-18

    A highly hydrophobic and highly oleophilic sponge was synthesized by simple vapor-phase deposition followed by polymerization of polypyrrole followed by modification with palmitic acid. The prepared sponge shows high absorption capacity in the field of separation and removal of different oil spills from water surface and was able to emulsify oil/water mixtures. The sponge can be compressed repeatedly without collapsing. Therefore, absorbed oils can be readily collected by simple mechanical squeezing of the sponge. The prepared hydrophobic sponge can collect oil from water in both static and turbulent conditions. The proposed method is simple and low cost for the manufacture of highly oleophilic and highly hydrophobic sponges, which can be successfully used for effective oil-spill cleanup and water filtration.

  15. Forward-rapidity azimuthal and radial flow of identified particles for $\\sqrt{s_{NN}}$ = 200 GeV Au+Au collisions

    CERN Document Server

    Sanders, S J

    2009-01-01

    A strong azimuthal flow signature at RHIC suggests rapid system equilibration leading to an almost perfect fluid state. The longitudinal extent of the flow behavior depends on how this state is formed and can be studied by measuring the pseudorapidity and transverse momentum dependence of the second Fourier component ($v_{2}(p_{T})$) of the azimuthal angular distribution. We report on a measurement of identified-particle $v_{2}$ as a function of $p_{T}$ (0.5-2.0 GeV/c), centrality (0-25%, 25-50%), and pseudorapidity ($0\\leq\\eta<3.2$) for $\\sqrt{s_{NN}} = 200 \\rm GeV$ Au+Au collisions. The BRAHMS spectrometers are used for particle identification ($\\pi$, K, p) and momentum determination and the BRAHMS global detectors are used to determine the corresponding reaction-plane angles. The results are discussed in terms of the rapidity dependence of constituent quark scaling and in terms of models that develop the complete (azimuthal and radial) hydrodynamic aspects of the forward dynamics at RHIC.

  16. A model to identify high crash road segments with the dynamic segmentation method.

    Science.gov (United States)

    Boroujerdian, Amin Mirza; Saffarzadeh, Mahmoud; Yousefi, Hassan; Ghassemian, Hassan

    2014-12-01

    Currently, high social and economic costs in addition to physical and mental consequences put road safety among most important issues. This paper aims at presenting a novel approach, capable of identifying the location as well as the length of high crash road segments. It focuses on the location of accidents occurred along the road and their effective regions. In other words, due to applicability and budget limitations in improving safety of road segments, it is not possible to recognize all high crash road segments. Therefore, it is of utmost importance to identify high crash road segments and their real length to be able to prioritize the safety improvement in roads. In this paper, after evaluating deficiencies of the current road segmentation models, different kinds of errors caused by these methods are addressed. One of the main deficiencies of these models is that they can not identify the length of high crash road segments. In this paper, identifying the length of high crash road segments (corresponding to the arrangement of accidents along the road) is achieved by converting accident data to the road response signal of through traffic with a dynamic model based on the wavelet theory. The significant advantage of the presented method is multi-scale segmentation. In other words, this model identifies high crash road segments with different lengths and also it can recognize small segments within long segments. Applying the presented model into a real case for identifying 10-20 percent of high crash road segment showed an improvement of 25-38 percent in relative to the existing methods.

  17. Rapid inactivation of Penicillium digitatum spores using high-density nonequilibrium atmospheric pressure plasma

    Science.gov (United States)

    Iseki, Sachiko; Ohta, Takayuki; Aomatsu, Akiyoshi; Ito, Masafumi; Kano, Hiroyuki; Higashijima, Yasuhiro; Hori, Masaru

    2010-04-01

    A promising, environmentally safe method for inactivating fungal spores of Penicillium digitatum, a difficult-to-inactivate food spoilage microorganism, was developed using a high-density nonequilibrium atmospheric pressure plasma (NEAPP). The NEAPP employing Ar gas had a high electron density on the order of 1015 cm-3. The spores were successfully and rapidly inactivated using the NEAPP, with a decimal reduction time in spores (D value) of 1.7 min. The contributions of ozone and UV radiation on the inactivation of the spores were evaluated and concluded to be not dominant, which was fundamentally different from the conventional sterilizations.

  18. Application of Rapid Prototyping Methods to High-Speed Wind Tunnel Testing

    Science.gov (United States)

    Springer, A. M.

    1998-01-01

    This study was undertaken in MSFC's 14-Inch Trisonic Wind Tunnel to determine if rapid prototyping methods could be used in the design and manufacturing of high speed wind tunnel models in direct testing applications, and if these methods would reduce model design/fabrication time and cost while providing models of high enough fidelity to provide adequate aerodynamic data, and of sufficient strength to survive the test environment. Rapid prototyping methods utilized to construct wind tunnel models in a wing-body-tail configuration were: fused deposition method using both ABS plastic and PEEK as building materials, stereolithography using the photopolymer SL-5170, selective laser sintering using glass reinforced nylon, and laminated object manufacturing using plastic reinforced with glass and 'paper'. This study revealed good agreement between the SLA model, the metal model with an FDM-ABS nose, an SLA nose, and the metal model for most operating conditions, while the FDM-ABS data diverged at higher loading conditions. Data from the initial SLS model showed poor agreement due to problems in post-processing, resulting in a different configuration. A second SLS model was tested and showed relatively good agreement. It can be concluded that rapid prototyping models show promise in preliminary aerodynamic development studies at subsonic, transonic, and supersonic speeds.

  19. A paper-based microbial fuel cell array for rapid and high-throughput screening of electricity-producing bacteria.

    Science.gov (United States)

    Choi, Gihoon; Hassett, Daniel J; Choi, Seokheun

    2015-06-21

    There is a large global effort to improve microbial fuel cell (MFC) techniques and advance their translational potential toward practical, real-world applications. Significant boosts in MFC performance can be achieved with the development of new techniques in synthetic biology that can regulate microbial metabolic pathways or control their gene expression. For these new directions, a high-throughput and rapid screening tool for microbial biopower production is needed. In this work, a 48-well, paper-based sensing platform was developed for the high-throughput and rapid characterization of the electricity-producing capability of microbes. 48 spatially distinct wells of a sensor array were prepared by patterning 48 hydrophilic reservoirs on paper with hydrophobic wax boundaries. This paper-based platform exploited the ability of paper to quickly wick fluid and promoted bacterial attachment to the anode pads, resulting in instant current generation upon loading of the bacterial inoculum. We validated the utility of our MFC array by studying how strategic genetic modifications impacted the electrochemical activity of various Pseudomonas aeruginosa mutant strains. Within just 20 minutes, we successfully determined the electricity generation capacity of eight isogenic mutants of P. aeruginosa. These efforts demonstrate that our MFC array displays highly comparable performance characteristics and identifies genes in P. aeruginosa that can trigger a higher power density.

  20. RAPID COMMUNICATION: High performance superconducting wire in high applied magnetic fields via nanoscale defect engineering

    Science.gov (United States)

    Wee, Sung Hun; Goyal, Amit; Zuev, Yuri L.; Cantoni, Claudia

    2008-09-01

    High temperature superconducting (HTS) wires capable of carrying large critical currents with low dissipation levels in high applied magnetic fields are needed for a wide range of applications. In particular, for electric power applications involving rotating machinery, such as large-scale motors and generators, a high critical current, Ic, and a high engineering critical current density, JE, in applied magnetic fields in the range of 3-5 Tesla (T) at 65 K are required. In addition, exceeding the minimum performance requirements needed for these applications results in a lower fabrication cost, which is regarded as crucial to realize or enable many large-scale bulk applications of HTS materials. Here we report the fabrication of short segments of a potential superconducting wire comprised of a 4 µm thick YBa2Cu3O7-δ (YBCO) layer on a biaxially textured substrate with a 50% higher Ic and JE than the highest values reported previously. The YBCO film contained columns of self-assembled nanodots of BaZrO3 (BZO) roughly oriented along the c-axis of YBCO. Although the YBCO film was grown at a high deposition rate, three-dimensional self-assembly of the insulating BZO nanodots still occurred. For all magnetic field orientations, minimum Ic and JE at 65 K, 3 T for the wire were 353 A cm-1 and 65.4 kA cm-2, respectively.

  1. Rapid molecular identification of Listeria species by use of real-time PCR and high-resolution melting analysis.

    Science.gov (United States)

    Jin, Dazhi; Luo, Yun; Zhang, Zheng; Fang, Weijia; Ye, Julian; Wu, Fang; Ding, Gangqiang

    2012-05-01

    Identification of Listeria species via a molecular method is critical for food safety and clinical diagnosis. In this study, an assay integrating real-time quantitative PCR (Q-PCR) with high-resolution melting (HRM) curve analysis was developed and assessed for rapid identification of six Listeria species. The ssrA gene, which encodes a transfer-messenger RNA (tmRNA) is conserved and common to all bacterial phyla, contains a variable domain in Listeria spp. Therefore, Q-PCR and a HRM profile were applied to characterize this gene. Fifty-three Listeria species and 45 non-Listeria species were detected using one primer set, with an accuracy of 100% in reference to conventional methods. There was a 93.3% correction rate to 30 artificially contaminated samples. Thus, Q-PCR with melting profiling analysis proved able to identify Listeria species accurately. Consequently, this study demonstrates that the assay we developed is a functional tool for rapidly identifying six Listeria species, and has the potential for discriminating novel species food safety and epidemiological research.

  2. Rapid in situ identification of bioactive compounds in plants by in vivo nanospray high-resolution mass spectrometry.

    Science.gov (United States)

    Chang, Qing; Peng, Yue'e; Dan, Conghui; Shuai, Qin; Hu, Shenghong

    2015-03-25

    A method for the rapid in situ identification of bioactive compounds in fresh plants has been developed using in vivo nanospray coupled to high-resolution mass spectrometry (HR-MS). Using a homemade in vivo nanospray ion source, the plant liquid was drawn out from a target region and ionized in situ. The ionized bioactive compounds were then identified using Q-Orbitrap HR-MS. The accurate mass measurements of these bioactive compounds were performed by full-scan or selected ion monitoring (SIM), and tandem mass spectrometry (MS/MS) was used in the structural elucidation. Without sample pretreatment, 12 bioactive compounds in 7 different plant species were identified, namely, isoalliin in onion; butylphthalide in celery; N-methylpelletierine, pelletierine, and pseudopelletierine in pomegranate; chlorogenic acid in crabapple; solamargine, solasonine, and solasodine in nightshade; aloin and aloe-emodin in aloe; and menthone in mint. This work demonstrates that in vivo nanospray HR-MS is a good method for rapid in situ identification of bioactive compounds in plants.

  3. Fluorescent QDs-polystyrene composite nanospheres for highly efficient and rapid protein antigen detection

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Changhua; Mao, Mao [Henan University, Key Laboratory for Special Functional Materials of the Ministry of Education (China); Yuan, Hang [Tsinghua University, Life Science Division, Graduate School at Shenzhen (China); Shen, Huaibin [Henan University, Key Laboratory for Special Functional Materials of the Ministry of Education (China); Wu, Feng; Ma, Lan, E-mail: malan@sz.tsinghua.edu.cn [Tsinghua University, Life Science Division, Graduate School at Shenzhen (China); Li, Lin Song, E-mail: lsli@henu.edu.cn [Henan University, Key Laboratory for Special Functional Materials of the Ministry of Education (China)

    2013-09-15

    In this paper, high-quality carboxyl-functionalized fluorescent (red, green, and blue emitting) nanospheres (46-103 nm) consisting of hydrophobic quantum dots (QDs) and polystyrene were prepared by a miniemulsion polymerization approach. This miniemulsion polymerization approach induced a homogeneous distribution and high aqueous-phase transport efficiency of fluorescent QDs in composite nanospheres, which proved the success of our encoding QDs strategy. The obtained fluorescent nanospheres exhibited high stability in aqueous solution under a wide range of pH, different salt concentrations, PBS buffer, and thermal treatment at 80 Degree-Sign C. Based on the red emitting composite nanosphere, we performed fluorescent lateral flow immunoassay (LFIA) strips for high-sensitivity and rapid alpha-fetal protein detection. The detection limit reached 0.1 ng/mL, which was 200 times higher than commercial colloidal gold-labeled LFIA strips, and it reached similar detection level in enzyme-linked immunosorbent assay kit.

  4. Fluorescent QDs-polystyrene composite nanospheres for highly efficient and rapid protein antigen detection

    Science.gov (United States)

    Zhou, Changhua; Mao, Mao; Yuan, Hang; Shen, Huaibin; Wu, Feng; Ma, Lan; Li, Lin Song

    2013-09-01

    In this paper, high-quality carboxyl-functionalized fluorescent (red, green, and blue emitting) nanospheres (46-103 nm) consisting of hydrophobic quantum dots (QDs) and polystyrene were prepared by a miniemulsion polymerization approach. This miniemulsion polymerization approach induced a homogeneous distribution and high aqueous-phase transport efficiency of fluorescent QDs in composite nanospheres, which proved the success of our encoding QDs strategy. The obtained fluorescent nanospheres exhibited high stability in aqueous solution under a wide range of pH, different salt concentrations, PBS buffer, and thermal treatment at 80 °C. Based on the red emitting composite nanosphere, we performed fluorescent lateral flow immunoassay (LFIA) strips for high-sensitivity and rapid alpha-fetal protein detection. The detection limit reached 0.1 ng/mL, which was 200 times higher than commercial colloidal gold-labeled LFIA strips, and it reached similar detection level in enzyme-linked immunosorbent assay kit.

  5. Rapidly-deposited polydopamine coating via high temperature and vigorous stirring: formation, characterization and biofunctional evaluation.

    Directory of Open Access Journals (Sweden)

    Ping Zhou

    Full Text Available Polydopamine (PDA coating provides a promising approach for immobilization of biomolecules onto almost all kinds of solid substrates. However, the deposition kinetics of PDA coating as a function of temperature and reaction method is not well elucidated. Since dopamine self-polymerization usually takes a long time, therefore, rapid-formation of PDA film becomes imperative for surface modification of biomaterials and medical devices. In the present study, a practical method for preparation of rapidly-deposited PDA coating was developed using a uniquely designed device, and the kinetics of dopamine self-polymerization was investigated by QCM sensor system. It was found that high temperature and vigorous stirring could dramatically speed up the formation of PDA film on QCM chip surface. Surface characterization, BSA binding study, cell viability assay and antibacterial test demonstrates that the polydopamine coating after polymerization for 30 min by our approach exhibits similar properties to those of 24 h counterpart. The method has a great potential for rapid-deposition of polydopamine films to modify biomaterial surfaces.

  6. Rapidly-deposited polydopamine coating via high temperature and vigorous stirring: formation, characterization and biofunctional evaluation.

    Science.gov (United States)

    Zhou, Ping; Deng, Yi; Lyu, Beier; Zhang, Ranran; Zhang, Hai; Ma, Hongwei; Lyu, Yalin; Wei, Shicheng

    2014-01-01

    Polydopamine (PDA) coating provides a promising approach for immobilization of biomolecules onto almost all kinds of solid substrates. However, the deposition kinetics of PDA coating as a function of temperature and reaction method is not well elucidated. Since dopamine self-polymerization usually takes a long time, therefore, rapid-formation of PDA film becomes imperative for surface modification of biomaterials and medical devices. In the present study, a practical method for preparation of rapidly-deposited PDA coating was developed using a uniquely designed device, and the kinetics of dopamine self-polymerization was investigated by QCM sensor system. It was found that high temperature and vigorous stirring could dramatically speed up the formation of PDA film on QCM chip surface. Surface characterization, BSA binding study, cell viability assay and antibacterial test demonstrates that the polydopamine coating after polymerization for 30 min by our approach exhibits similar properties to those of 24 h counterpart. The method has a great potential for rapid-deposition of polydopamine films to modify biomaterial surfaces.

  7. Rapidly-Deposited Polydopamine Coating via High Temperature and Vigorous Stirring: Formation, Characterization and Biofunctional Evaluation

    Science.gov (United States)

    Zhou, Ping; Deng, Yi; Lyu, Beier; Zhang, Ranran; Zhang, Hai; Ma, Hongwei; Lyu, Yalin; Wei, Shicheng

    2014-01-01

    Polydopamine (PDA) coating provides a promising approach for immobilization of biomolecules onto almost all kinds of solid substrates. However, the deposition kinetics of PDA coating as a function of temperature and reaction method is not well elucidated. Since dopamine self-polymerization usually takes a long time, therefore, rapid-formation of PDA film becomes imperative for surface modification of biomaterials and medical devices. In the present study, a practical method for preparation of rapidly-deposited PDA coating was developed using a uniquely designed device, and the kinetics of dopamine self-polymerization was investigated by QCM sensor system. It was found that high temperature and vigorous stirring could dramatically speed up the formation of PDA film on QCM chip surface. Surface characterization, BSA binding study, cell viability assay and antibacterial test demonstrates that the polydopamine coating after polymerization for 30 min by our approach exhibits similar properties to those of 24 h counterpart. The method has a great potential for rapid-deposition of polydopamine films to modify biomaterial surfaces. PMID:25415328

  8. High space-time resolution analysis of ice motion at a rapidly retreating tidewater glacier (Invited)

    Science.gov (United States)

    Oneel, S.; Joughin, I. R.; March, R. S.; Burgess, E. W.; Welty, E.; Pfeffer, W. T.; Larsen, C. F.

    2013-12-01

    Rapid changes to rates of sea level rise are forced in large part by tidewater glacier dynamics. Alaska's Columbia Glacier is an iconic example; in recent years, calving losses account for roughly 20% of the net mass loss from the entire Alaska region. In turn, the Alaska region accounts for ~20% of global new-water sea-level rise. To better understand the mechanics of rapid tidewater glacier mass loss, we present and analyze surface elevation and velocity data acquired at high time resolution since fall 2011. Strong seasonality in flow speed exists, with more than a doubling of near-terminus speed occurring between summer and winter. The imagery provides unprecedented spatial coverage, demonstrating spatial coherence in flow variability across most, but not all, tributaries. Preliminary calculations of ice flux also show strong seasonality, with variable year-to-year timing of peak discharge. Compared to previous estimates, the average flux in this most recent interval is reduced by ~30-40%. An additional overdeepening is located upstream from the present-day terminus, indicating another episode of increased flux is possible. However, total glacier volume has been reduced by ~50% during the retreat, and peak discharge from Columbia has likely already occurred. Our analysis suggests that, as the Columbia Glacier retreat comes to a conclusion, rates of mass loss from the Alaska region will decrease in the near-future, unless another tidewater glacier enters rapid retreat.

  9. A high-throughput method to examine protein-nucleotide interactions identifies targets of the bacterial transcriptional regulatory protein fur.

    Science.gov (United States)

    Yu, Chunxiao; Lopez, Carlos A; Hu, Han; Xia, Yu; Freedman, David S; Reddington, Alexander P; Daaboul, George G; Unlü, M Selim; Genco, Caroline Attardo

    2014-01-01

    The Ferric uptake regulatory protein (Fur) is a transcriptional regulatory protein that functions to control gene transcription in response to iron in a number of pathogenic bacteria. In this study, we applied a label-free, quantitative and high-throughput analysis method, Interferometric Reflectance Imaging Sensor (IRIS), to rapidly characterize Fur-DNA interactions in vitro with predicted Fur binding sequences in the genome of Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea. IRIS can easily be applied to examine multiple protein-protein, protein-nucleotide and nucleotide-nucleotide complexes simultaneously and demonstrated here that seventy percent of the predicted Fur boxes in promoter regions of iron-induced genes bound to Fur in vitro with a range of affinities as observed using this microarray screening technology. Combining binding data with mRNA expression levels in a gonococcal fur mutant strain allowed us to identify five new gonococcal genes under Fur-mediated direct regulation.

  10. High-density polymer microarrays: identifying synthetic polymers that control human embryonic stem cell growth.

    Science.gov (United States)

    Hansen, Anne; Mjoseng, Heidi K; Zhang, Rong; Kalloudis, Michail; Koutsos, Vasileios; de Sousa, Paul A; Bradley, Mark

    2014-06-01

    The fabrication of high-density polymer microarray is described, allowing the simultaneous and efficient evaluation of more than 7000 different polymers in a single-cellular-based screen. These high-density polymer arrays are applied in the search for synthetic substrates for hESCs culture. Up-scaling of the identified hit polymers enables long-term cellular cultivation and promoted successful stem-cell maintenance. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.

    Science.gov (United States)

    Lakshmi, Bhavana Sethu; Wang, Ruobing; Madhubala, Rentala

    2014-06-24

    Leishmaniasis is a neglected tropical disease caused by Leishmania species. It is a major health concern affecting 88 countries and threatening 350 million people globally. Unfortunately, there are no vaccines and there are limitations associated with the current therapeutic regimens for leishmaniasis. The emerging cases of drug-resistance further aggravate the situation, demanding rapid drug and vaccine development. The genome sequence of Leishmania, provides access to novel genes that hold potential as chemotherapeutic targets or vaccine candidates. In this study, we selected 19 antigenic genes from about 8000 common Leishmania genes based on the Leishmania major and Leishmania infantum genome information available in the pathogen databases. Potential vaccine candidates thus identified were screened using an in vitro high throughput immunological platform developed in the laboratory. Four candidate genes coding for tuzin, flagellar glycoprotein-like protein (FGP), phospholipase A1-like protein (PLA1) and potassium voltage-gated channel protein (K VOLT) showed a predominant protective Th1 response over disease exacerbating Th2. We report the immunogenic properties and protective efficacy of one of the four antigens, tuzin, as a DNA vaccine against Leishmania donovani challenge. Our results show that administration of tuzin DNA protected BALB/c mice against L. donovani challenge and that protective immunity was associated with higher levels of IFN-γ and IL-12 production in comparison to IL-4 and IL-10. Our study presents a simple approach to rapidly identify potential vaccine candidates using the exhaustive information stored in the genome and an in vitro high-throughput immunological platform.

  12. Products from the high temperature pyrolysis of RDF at slow and rapid heating rates

    OpenAIRE

    2015-01-01

    The high-temperature pyrolysis behaviour of a sample of refuse derived fuel (RDF) as a model of municipal solid waste (MSW) was investigated in a horizontal tubular reactor between 700 and 900 °C, at varying heating rates, and at an extended vapour residence time. Experiments were designed to evaluate the influence of process conditions on gas yields as well as gas and oil compositions. Pyrolysis of RDF at 800 °C and at rapid heating rate resulted in the gas yield with the highest CV of 24.8 ...

  13. High-throughput, temperature-controlled microchannel acoustophoresis device made with rapid prototyping

    DEFF Research Database (Denmark)

    Adams, Jonathan D; Ebbesen, Christian L.; Barnkob, Rune

    2012-01-01

    We report a temperature-controlled microfluidic acoustophoresis device capable of separating particles and transferring blood cells from undiluted whole human blood at a volume throughput greater than 1 L h−1. The device is fabricated from glass substrates and polymer sheets in microscope......-slide format using low-cost, rapid-prototyping techniques. This high-throughput acoustophoresis chip (HTAC) utilizes a temperature-stabilized, standing ultrasonic wave, which imposes differential acoustic radiation forces that can separate particles according to size, density and compressibility. The device...

  14. Rapid and highly informative diagnostic assay for H5N1 influenza viruses.

    Directory of Open Access Journals (Sweden)

    Nader Pourmand

    Full Text Available A highly discriminative and information-rich diagnostic assay for H5N1 avian influenza would meet immediate patient care needs and provide valuable information for public health interventions, e.g., tracking of new and more dangerous variants by geographic area as well as avian-to-human or human-to-human transmission. In the present study, we have designed a rapid assay based on multilocus nucleic acid sequencing that focuses on the biologically significant regions of the H5N1 hemagglutinin gene. This allows the prediction of viral strain, clade, receptor binding properties, low- or high-pathogenicity cleavage site and glycosylation status. H5 HA genes were selected from nine known high-pathogenicity avian influenza subtype H5N1 viruses, based on their diversity in biologically significant regions of hemagglutinin and/or their ability to cause infection in humans. We devised a consensus pre-programmed pyrosequencing strategy, which may be used as a faster, more accurate alternative to de novo sequencing. The available data suggest that the assay described here is a reliable, rapid, information-rich and cost-effective approach for definitive diagnosis of H5N1 avian influenza. Knowledge of the predicted functional sequences of the HA will enhance H5N1 avian influenza surveillance efforts.

  15. A Rapid, Multiplexed, High-Throughput Flow-Through Membrane Immunoassay: A Convenient Alternative to ELISA

    Directory of Open Access Journals (Sweden)

    Gonzalo J. Domingo

    2013-04-01

    Full Text Available This paper describes a rapid, high-throughput flow-through membrane immunoassay (FMIA platform. A nitrocellulose membrane was spotted in an array format with multiple capture and control reagents for each sample detection area, and assay steps were carried out by sequential aspiration of sample and reagents through each detection area using a 96-well vacuum manifold. The FMIA provides an alternate assay format with several advantages over ELISA. The high surface area of the membrane permits high label concentration using gold labels, and the small pores and vacuum control provide rapid diffusion to reduce total assay time to ~30 min. All reagents used in the FMIA are compatible with dry storage without refrigeration. The results appear as colored spots on the membrane that can be quantified using a flatbed scanner. We demonstrate the platform for detection of IgM specific to lipopolysaccharides (LPS derived from Salmonella Typhi. The FMIA format provides analytical results comparable to ELISA in less time, provides integrated assay controls, and allows compensation for specimen-to-specimen variability in background, which is a particular challenge for IgM assays.

  16. Applications of Luminex xMAP technology for rapid, high-throughput multiplexed nucleic acid detection.

    Science.gov (United States)

    Dunbar, Sherry A

    2006-01-01

    As we enter the post-genome sequencing era and begin to sift through the enormous amount of genetic information now available, the need for technologies that allow rapid, cost-effective, high-throughput detection of specific nucleic acid sequences becomes apparent. Multiplexing technologies, which allow for simultaneous detection of multiple nucleic acid sequences in a single reaction, can greatly reduce the time, cost and labor associated with single reaction detection technologies. The Luminex xMAP system is a multiplexed microsphere-based suspension array platform capable of analyzing and reporting up to 100 different reactions in a single reaction vessel. This technology provides a new platform for high-throughput nucleic acid detection and is being utilized with increasing frequency. Here we review specific applications of xMAP technology for nucleic acid detection in the areas of single nucleotide polymorphism (SNP) genotyping, genetic disease screening, gene expression profiling, HLA DNA typing and microbial detection. These studies demonstrate the speed, efficiency and utility of xMAP technology for simultaneous, rapid, sensitive and specific nucleic acid detection, and its capability to meet the current and future requirements of the molecular laboratory for high-throughput nucleic acid detection.

  17. Identifying High Potential Well Targets with 3D Seismic and Mineralogy

    Energy Technology Data Exchange (ETDEWEB)

    Mellors, R. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-10-30

    Seismic reflection the primary tool used in petroleum exploration and production, but use in geothermal exploration is less standard, in part due to cost but also due to the challenges in identifying the highly-permeable zones essential for economic hydrothermal systems [e.g. Louie et al., 2011; Majer, 2003]. Newer technology, such as wireless sensors and low-cost high performance computing, has helped reduce the cost and effort needed to conduct 3D surveys. The second difficulty, identifying permeable zones, has been less tractable so far. Here we report on the use of seismic attributes from a 3D seismic survey to identify and map permeable zones in a hydrothermal area.

  18. High pressure effect on structural transition of Fe cluster during rapid quenching processes

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Molecular dynamics simulations of 21,952 atoms have been performed to study local structure evolution and glass formation in iron melts rapidly cooled under high pressures.In the quenching processes,structural transition details have been analyzed by using the radial distribution function g(r) and bond pair analysis technique.It is shown that high pressure strengthens the order degree of the glass system and favors the glass formation.That means with the increase of pressures,a more compacted local structure with more ideal icosahedra can be obtained.The calculations of free volume of the system indicate that the decrease of the number of the defected ideal icosahedra under high pressure contributes to the glass formation of Fe.

  19. High power free space optical link for rapid energy and data transmission

    Science.gov (United States)

    Dhadwal, Harbans S.; Rastegar, Jahangir; Feng, Dake; Kwok, Philip

    2016-05-01

    Design and experimental data for a high power laser diode based free space point-to-point optical power/data link is presented. In time critical power up applications, such as providing power and guidance information to a munition shell just prior to deployment, energy of the order of 100 J needs to be transferred in under 10 s. Current inductive technology is slow and broadcasts a radio-frequency signal which is undesirable for stealth operation. Rapid energy transfer times require high irradiance levels at the surface of the photovoltaic cells, typically, exceeding 1000X suns. Through efficient thermal design of heat sinks, high optical to electrical power conversion efficiencies of 50%, which are usually attainable at low power levels of 1 W, are achievable at higher power levels.

  20. ION COMPOSITION ELUCIDATION (ICE): A HIGH RESOLUTION MASS SPECTROMETRIC TECHNIQUE FOR IDENTIFYING COMPOUNDS IN COMPLEX MIXTURES

    Science.gov (United States)

    When tentatively identifying compounds in complex mixtures using mass spectral libraries, multiple matches or no plausible matches due to a high level of chemical noise or interferences can occur. Worse yet, most analytes are not in the libraries. In each case, Ion Composition El...

  1. 49 CFR 192.905 - How does an operator identify a high consequence area?

    Science.gov (United States)

    2010-10-01

    ... SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Gas... 49 Transportation 3 2010-10-01 2010-10-01 false How does an operator identify a high consequence area? 192.905 Section 192.905 Transportation Other Regulations Relating to Transportation (Continued...

  2. Gender Fair Efficacy of Concept Mapping Tests in Identifying Students' Difficulties in High School Organic Chemistry

    Science.gov (United States)

    Gafoor, Kunnathodi Abdul; Shilna, V.

    2014-01-01

    In view of the perceived difficulty of organic chemistry unit for high schools students, this study examined the usefulness of concept mapping as a testing device to assess students' difficulty in the select areas. Since many tests used for identifying students misconceptions and difficulties in school subjects are observed to favour one or the…

  3. High-throughput genotoxicity assay identifies antioxidants as inducers of DNA damage response and cell death

    Science.gov (United States)

    Human ATAD5 is an excellent biomarker for identifying genotoxic compounds because ATADS protein levels increase post-transcriptionally following exposure to a variety of DNA damaging agents. Here we report a novel quantitative high-throughput ATAD5-Iuciferase assay that can moni...

  4. Rapid high-amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias.

    Science.gov (United States)

    O'Grady, G; Du, P; Paskaranandavadivel, N; Angeli, T R; Lammers, W J E P; Asirvatham, S J; Windsor, J A; Farrugia, G; Pullan, A J; Cheng, L K

    2012-07-01

    Gastric slow waves propagate aborally as rings of excitation. Circumferential propagation does not normally occur, except at the pacemaker region. We hypothesized that (i) the unexplained high-velocity, high-amplitude activity associated with the pacemaker region is a consequence of circumferential propagation; (ii) rapid, high-amplitude circumferential propagation emerges during gastric dysrhythmias; (iii) the driving network conductance might switch between interstitial cells of Cajal myenteric plexus (ICC-MP) and circular interstitial cells of Cajal intramuscular (ICC-IM) during circumferential propagation; and (iv) extracellular amplitudes and velocities are correlated. An experimental-theoretical study was performed. High-resolution gastric mapping was performed in pigs during normal activation, pacing, and dysrhythmia. Activation profiles, velocities, and amplitudes were quantified. ICC pathways were theoretically evaluated in a bidomain model. Extracellular potentials were modeled as a function of membrane potentials. High-velocity, high-amplitude activation was only recorded in the pacemaker region when circumferential conduction occurred. Circumferential propagation accompanied dysrhythmia in 8/8 experiments was faster than longitudinal propagation (8.9 vs 6.9 mm s(-1) ; P = 0.004) and of higher amplitude (739 vs 528 μV; P = 0.007). Simulations predicted that ICC-MP could be the driving network during longitudinal propagation, whereas during ectopic pacemaking, ICC-IM could outpace and activate ICC-MP in the circumferential axis. Experimental and modeling data demonstrated a linear relationship between velocities and amplitudes (P propagation. Rapid circumferential propagation also emerges during a range of gastric dysrhythmias, elevating extracellular amplitudes and organizing transverse wavefronts. One possible explanation for these findings is bidirectional coupling between ICC-MP and circular ICC-IM networks. © 2012 Blackwell Publishing Ltd.

  5. High risk and rapid appearance of multidrug resistance during tuberculosis treatment in Moldova.

    Science.gov (United States)

    Jenkins, Helen E; Crudu, Valeriu; Soltan, Viorel; Ciobanu, Ana; Domente, Liliana; Cohen, Ted

    2014-04-01

    Multidrug-resistant tuberculosis (MDR-TB) is a serious problem in the former Soviet Union and may appear during TB treatment. We aimed to estimate the prevalence of, timing of and factors associated with MDR-TB diagnosis during TB treatment in Moldova, which was part of the former Soviet Union. We analysed data on 3 754 confirmed non-MDR-TB cases (between January 1, 2007 and December 31, 2010) in the Moldovan TB surveillance database, where patients provided sputum specimens for drug-susceptibility testing, multiple times, during treatment. We estimated the percentage of individuals with confirmed baseline non-MDR-TB that were diagnosed with MDR-TB during treatment, documented the time at which MDR-TB was diagnosed, and used a failure-time model to identify factors associated with MDR-TB diagnosis. Between 7.2% and 9.2% of initially non-MDR-TB cases were diagnosed with MDR-TB during treatment. Half of these MDR-TB diagnoses occurred with 3 months of the initial diagnosis. An increased MDR-TB risk during treatment was associated with baseline resistance to first-line TB drugs (linear increase in risk per additional drug), previous incarceration and HIV co-infection. MDR can appear rapidly during TB treatment. Policy considerations should emphasise management during early treatment by increasing ambulatory TB treatment to prevent nosocomial transmission, and ensuring universal rapid diagnostics access to prevent acquisition and transmission of drug resistance.

  6. Field manual for identifying and preserving high-water mark data

    Science.gov (United States)

    Feaster, Toby D.; Koenig, Todd A.

    2017-09-26

    This field manual provides general guidance for identifying and collecting high-water marks and is meant to be used by field personnel as a quick reference. The field manual describes purposes for collecting and documenting high-water marks along with the most common types of high-water marks. The manual provides a list of suggested field equipment, describes rules of thumb and best practices for finding high-water marks, and describes the importance of evaluating each high-water mark and assigning a numeric uncertainty value as part of the flagging process. The manual also includes an appendix of photographs of a variety of high-water marks obtained from various U.S. Geological Survey field investigations along with general comments about the logic for the assigned uncertainty values.

  7. Highly sensitive multianalyte immunochromatographic test strip for rapid chemiluminescent detection of ractopamine and salbutamol

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Hongfei; Han, Jing; Yang, Shijia; Wang, Zhenxing; Wang, Lin; Fu, Zhifeng, E-mail: fuzf@swu.edu.cn

    2014-08-11

    Graphical abstract: A multianalyte immunochromatographic test strip was developed for the rapid detection of two β{sub 2}-agonists. Due to the application of chemiluminescent detection, this quantitative method shows much higher sensitivity. - Highlights: • An immunochromatographic test strip was developed for detection of multiple β{sub 2}-agonists. • The whole assay process can be completed within 20 min. • The proposed method shows much higher sensitivity due to the application of CL detection. • It is a portable analytical tool suitable for field analysis and rapid screening. - Abstract: A novel immunochromatographic assay (ICA) was proposed for rapid and multiple assay of β{sub 2}-agonists, by utilizing ractopamine (RAC) and salbutamol (SAL) as the models. Owing to the introduction of chemiluminescent (CL) approach, the proposed protocol shows much higher sensitivity. In this work, the described ICA was based on a competitive format, and horseradish peroxidase-tagged antibodies were used as highly sensitive CL probes. Quantitative analysis of β{sub 2}-agonists was achieved by recording the CL signals of the probes captured on the two test zones of the nitrocellulose membrane. Under the optimum conditions, RAC and SAL could be detected within the linear ranges of 0.50–40 and 0.10–50 ng mL{sup −1}, with the detection limits of 0.20 and 0.040 ng mL{sup −1} (S/N = 3), respectively. The whole process for multianalyte immunoassay of RAC and SAL can be completed within 20 min. Furthermore, the test strip was validated with spiked swine urine samples and the results showed that this method was reliable in measuring β{sub 2}-agonists in swine urine. This CL-based multianalyte test strip shows a series of advantages such as high sensitivity, ideal selectivity, simple manipulation, high assay efficiency and low cost. Thus, it opens up new pathway for rapid screening and field analysis, and shows a promising prospect in food safety.

  8. A new ultrasonic high-throughput instrument for rapid DNA release from microorganisms.

    Science.gov (United States)

    Hohnadel, Marisa; Felden, Luc; Fijuljanin, Demir; Jouette, Sébastien; Chollet, Renaud

    2014-04-01

    Rapid detection methods for microbiological contamination are requested by many industries that respond to public health concerns. The control laboratories are replacing traditional culturing methods with faster assays based on nucleic acid amplification technologies, such as real-time PCR. However, an optimal nucleic acid sample preparation method is critical for the sensitivity and specificity of such tools. A high-throughput automated external ultrasonic device was developed for rapid lysing of microorganisms. Based on Ct values obtained from real-time PCR, there was efficient DNA release from the 16 microorganisms tested, including Gram positive and negative bacteria, bacterial spores, yeasts and spores of molds. Linearity of the lysis method was also demonstrated for Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella enterica, Candida albicans and the spores of Aspergillus brasiliensis, with correlation coefficients (r(2)) between 0.90 and 0.98. After sonication, PCR analysis of the lysates revealed earlier Ct values (0.83 to 7.49) for S. aureus, P. aeruginosa and S. enterica compared to the bead-beating method of lysis. These results demonstrated more efficient DNA release from bacteria with the ultrasonication system. Nevertheless, for fungi, the Ct values were 0.94 to 1.61 later for sonication than for bead beating. This study demonstrates that 4min of sonication with this new automated high-throughput instrument allows for the efficient lysis of a large range of microorganisms.

  9. HIGH-RESOLUTION MONITORING OF CURRENT RAPID TRANSFORMATIONS ON GLACIAL AND PERIGLACIAL ENVIRONMENTS

    Directory of Open Access Journals (Sweden)

    L. Carturan

    2014-01-01

    Full Text Available Glacial and periglacial environments are highly sensitive to climatic changes. Processes of cryosphere degradation may strongly impact human activities and infrastructures, and need to be monitored for improved understanding and for mitigation/adaptation. Studying glacial and periglacial environments using traditional techniques may be difficult or not feasible, but new remote sensing techniques like terrestrial and aerial laser scanner opened new possibilities for cryospheric studies. This work presents an application of the terrestrial laser scanner (TLS for monitoring the current rapid changes occurring on the Montasio Occidentale glacier (Eastern Italian alps, which is representative of low-altitude, avalanche-fed and debris-cover glaciers. These glaciers are quite common in the Alps but their reaction to climate changes is still poorly known. The mass balance, surface velocity fields, debris cover dynamics and effects of meteorological extremes were investigated by repeat high-resolution TLS scanning from September 2010 to October 2012. The results were encouraging and shed light on the peculiar response of this glacier to climatic changes, on its current dynamics and on the feedback played by the debris cover, which is critical for its preservation. The rapid transformations in act, combined with the unstable ice mass, large amount of loose debris and channeled runoff during intense rainfalls, constitute a potential area for the formation of large debris flows, as shown by field evidences and documented by the recent literature.

  10. Construction of a high-performance magnetic enzyme nanosystem for rapid tryptic digestion

    Science.gov (United States)

    Cheng, Gong; Zheng, Si-Yang

    2014-01-01

    A magnetic enzyme nanosystem have been designed and constructed by a polydopamine (PDA)-modification strategy. The magnetic enzyme nanosystem has well defined core-shell structure and a relatively high saturation magnetization (Ms) value of 48.3 emu g−1. The magnetic enzyme system can realize rapid, efficient and reusable tryptic digestion of proteins by taking advantage of its magnetic core and biofunctional shell. Various standard proteins (e.g. cytochrome C (Cyt-C), myoglobin (MYO) and bovine serum albumin (BSA)) have been used to evaluate the effectiveness of the magnetic enzyme nanosystem. The results show that the magnetic enzyme nanosystem can digest the proteins in 30 minutes, and the results are comparable to conventional 12 hours in-solution digestion. Furthermore, the magnetic enzyme nanosystem is also effective in the digestion of low-concentration proteins, even at as low as 5 ng μL−1 substrate concentration. Importantly, the system can be reused several times, and has excellent stability for storage. Therefore, this work will be highly beneficial for the rapid digestion and identification of proteins in future proteomics. PMID:25374397

  11. Flow-Based Systems for Rapid and High-Precision Enzyme Kinetics Studies

    Directory of Open Access Journals (Sweden)

    Supaporn Kradtap Hartwell

    2012-01-01

    Full Text Available Enzyme kinetics studies normally focus on the initial rate of enzymatic reaction. However, the manual operation of steps of the conventional enzyme kinetics method has some drawbacks. Errors can result from the imprecise time control and time necessary for manual changing the reaction cuvettes into and out of the detector. By using the automatic flow-based analytical systems, enzyme kinetics studies can be carried out at real-time initial rate avoiding the potential errors inherent in manual operation. Flow-based systems have been developed to provide rapid, low-volume, and high-precision analyses that effectively replace the many tedious and high volume requirements of conventional wet chemistry analyses. This article presents various arrangements of flow-based techniques and their potential use in future enzyme kinetics applications.

  12. CGC/saturation approach for soft interactions at high energy: long range rapidity correlations

    Energy Technology Data Exchange (ETDEWEB)

    Gotsman, E.; Maor, U. [Tel Aviv University, Department of Particle Physics, School of Physics and Astronomy, Raymond and Beverly Sackler Faculty of Exact Science, Tel Aviv (Israel); Levin, E. [Tel Aviv University, Department of Particle Physics, School of Physics and Astronomy, Raymond and Beverly Sackler Faculty of Exact Science, Tel Aviv (Israel); Universidad Tecnica Federico Santa Maria and Centro Cientifico- Tecnologico de Valparaiso, Departemento de Fisica, Valparaiso (Chile)

    2015-11-15

    In this paper we continue our program to construct a model for high energy soft interactions that is based on the CGC/saturation approach. The main result of this paper is that we have discovered a mechanism that leads to large long range rapidity correlations and results in large values of the correlation function R(y{sub 1}, y{sub 2}) ≥ 1, which is independent of y{sub 1} and y{sub 2}. Such a behavior of the correlation function provides strong support for the idea that at high energies the system of partons that is produced is not only dense but also has strong attractive forces acting between the partons. (orig.)

  13. Rapid Growth of Ice Dendrite in Acoustically Levitated and Highly Undercooled Water

    Institute of Scientific and Technical Information of China (English)

    吕勇军; 解文军; 魏炳波

    2002-01-01

    Water drops with diameters ranging from 2.5 to 4 mm are highly undercooled by up to 24 K with the acousticlevitation technique. Compared to the case of water contained in a tube, acoustic levitation has efficientlyavoided the heterogeneous nucleation from container walls and consequently increased the undercooling level.However, the cavitation effect induced by ultrasound may prematurely catalyse nucleation, which hinders thefurther achievement of bulk undercooling. The growth velocity of ice dendrite determined experimentally inhighly undercooled water is characteristic of rapid dendritic growth, which reaches 0.17m/s at the undercoolingof 24 K. The Lipton-Kurz-Trivedi dendritic growth model is used to predict the kinetic characteristics of rapidgrowth of ice dendrite under high undercooling conditions, which shows good agreement with the experimentalresults.

  14. Identifying inhibitory effects of lignocellulosic by-products on growth of lactic acid producing micro-organisms using a rapid small-scale screening method.

    Science.gov (United States)

    van der Pol, Edwin C; Vaessen, Evelien; Weusthuis, Ruud A; Eggink, Gerrit

    2016-06-01

    Sugars obtained from pretreated lignocellulose are interesting as substrate for the production of lactic acid in fermentation processes. However, by-products formed during pretreatment of lignocellulose can inhibit microbial growth. In this study, a small-scale rapid screening method was used to identify inhibitory effects of single and combined by-products on growth of lactic acid producing micro-organisms. The small-scale screening was performed in 48-well plates using 5 bacterial species and 12 by-products. Large differences were observed in inhibitory effects of by-products between different species. Predictions can be made for growth behaviour of different micro-organisms on acid pretreated or alkaline pretreated bagasse substrates using data from the small-scale screening. Both individual and combined inhibition effects were shown to be important parameters to predict growth. Synergy between coumaric acid, formic acid and acetic acid is a key inhibitory parameter in alkaline pretreated lignocellulose, while furfural is a key inhibitor in acid pretreated lignocellulose.

  15. Pediatric Thoracoscopic Surgical Simulation Using a Rapid-Prototyped Chest Model and Motion Sensors Can Better Identify Skilled Surgeons Than a Conventional Box Trainer.

    Science.gov (United States)

    Takazawa, Shinya; Ishimaru, Tetsuya; Harada, Kanako; Deie, Kyoichi; Fujishiro, Jun; Sugita, Naohiko; Mitsuishi, Mamoru; Iwanaka, Tadashi

    2016-09-01

    We previously developed a pediatric thoracoscopic surgical simulator and showed its construct validity. In this study, the same skill assessment experiments were conducted in an additional 31 surgeons and the results of 53 surgeons in total were analyzed. A suture pad with force sensors was placed in a rapid-prototyped pediatric chest model of a 1-year-old patient. Participants completed the endoscopic intracorporeal suturing and knot-tying task, both in the pediatric chest model setup and in a box trainer setup. The task was evaluated using eight metrics: the 29-point checklist score, error score, number of manipulations, task completion time, force index, width of the pad's slit after suturing, and right and left tool paths. The 53 participants included skilled surgeons certified by the Endoscopic Surgical Skill Qualification (ESSQ) system (n = 8) and unskilled surgeons without the certification (n = 45). The skilled surgeons showed significantly better performance than the unskilled surgeons in six metrics in the pediatric chest model setup. In contrast, no significant differences between the two groups were observed in the box trainer setup. Upon comparison between the setups, the unskilled surgeons showed worse results in six metrics in the pediatric chest model than in the box trainer, whereas the skilled surgeons showed equivalent performance in both setups. Our pediatric thoracoscopic surgical simulator was superior to the conventional box trainer for identifying skilled surgeons. The skilled surgeons showed excellent performance even in the intricate pediatric chest model, providing quantified targets for young pediatric surgeons' training.

  16. Development of a simple and rapid method of precisely identifying the position of 10B atoms in tissue: an improvement in standard alpha autoradiography.

    Science.gov (United States)

    Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Masunaga, Shin-ichiro; Takamiya, Koichi; Maruhashi, Akira; Ono, Koji

    2014-03-01

    Boron neutron capture therapy (BNCT) can be utilized to selectively kill cancer cells using a boron compound that accumulates only in cancer cells and not in normal cells. Tumor-bearing animals treated by BNCT are routinely used to evaluate long-term antitumor effects of new boron compounds. Alpha-autoradiography is one of the methods employed in the evaluation of antitumor effects. However, a standard alpha-autoradiography cannot detect the microdistribution of (10)B because of the difficulty associated with the superposition of a tissue sample image and etched pits on a track detector with the etching process. In order to observe the microdistribution of (10)B, some special methods of alpha-autoradiography have been developed that make use of a special track detector, or the atomic force microscope combined with X-ray and UV light irradiation. In contrast, we propose, herein, a simple and rapid method of precisely identifying the position of (10)B using the imaging process and the shape of etched pits, such as their circularity, without the need to use special track detectors or a microscope. A brief description of this method and its verification test are presented in this article. We have established a method of detecting the microdistribution of (10)B with submicron deviation between the position of etched pits and the position of reaction in a tissue sample, for a given circularity of etched pits.

  17. Genetic isolation and morphological divergence mediated by high-energy rapids in two cichlid genera from the lower Congo rapids.

    Science.gov (United States)

    Markert, Jeffrey A; Schelly, Robert C; Stiassny, Melanie Lj

    2010-05-19

    It is hypothesized that one of the mechanisms promoting diversification in cichlid fishes in the African Great Lakes has been the well-documented pattern of philopatry along shoreline habitats leading to high levels of genetic isolation among populations. However lake habitats are not the only centers of cichlid biodiversity - certain African rivers also contain large numbers of narrowly endemic species. Patterns of isolation and divergence in these systems have tended to be overlooked and are not well understood. We examined genetic and morphological divergence among populations of two narrowly endemic cichlid species, Teleogramma depressum and Lamprologus tigripictilis, from a 100 km stretch of the lower Congo River using both nDNA microsatellites and mtDNA markers along with coordinate-based morphological techniques. In L. tigripictilis, the strongest genetic break was concordant with measurable phenotypic divergence but no morphological disjunction was detected for T. depressum despite significant differentiation at mtDNA and nDNA microsatellite markers. The genetic markers revealed patterns of philopatry and estimates of genetic isolation that are among the highest reported for any African cichlid species over a comparable geographic scale. We hypothesize that the high levels of philopatry observed are generated and maintained by the extreme hydrology of the lower Congo River.

  18. Genetic isolation and morphological divergence mediated by high-energy rapids in two cichlid genera from the lower Congo rapids

    Directory of Open Access Journals (Sweden)

    Stiassny Melanie LJ

    2010-05-01

    Full Text Available Abstract Background It is hypothesized that one of the mechanisms promoting diversification in cichlid fishes in the African Great Lakes has been the well-documented pattern of philopatry along shoreline habitats leading to high levels of genetic isolation among populations. However lake habitats are not the only centers of cichlid biodiversity - certain African rivers also contain large numbers of narrowly endemic species. Patterns of isolation and divergence in these systems have tended to be overlooked and are not well understood. Results We examined genetic and morphological divergence among populations of two narrowly endemic cichlid species, Teleogramma depressum and Lamprologus tigripictilis, from a 100 km stretch of the lower Congo River using both nDNA microsatellites and mtDNA markers along with coordinate-based morphological techniques. In L. tigripictilis, the strongest genetic break was concordant with measurable phenotypic divergence but no morphological disjunction was detected for T. depressum despite significant differentiation at mtDNA and nDNA microsatellite markers. Conclusions The genetic markers revealed patterns of philopatry and estimates of genetic isolation that are among the highest reported for any African cichlid species over a comparable geographic scale. We hypothesize that the high levels of philopatry observed are generated and maintained by the extreme hydrology of the lower Congo River.

  19. Augmenting Chinese hamster genome assembly by identifying regions of high confidence.

    Science.gov (United States)

    Vishwanathan, Nandita; Bandyopadhyay, Arpan A; Fu, Hsu-Yuan; Sharma, Mohit; Johnson, Kathryn C; Mudge, Joann; Ramaraj, Thiruvarangan; Onsongo, Getiria; Silverstein, Kevin A T; Jacob, Nitya M; Le, Huong; Karypis, George; Hu, Wei-Shou

    2016-09-01

    Chinese hamster Ovary (CHO) cell lines are the dominant industrial workhorses for therapeutic recombinant protein production. The availability of genome sequence of Chinese hamster and CHO cells will spur further genome and RNA sequencing of producing cell lines. However, the mammalian genomes assembled using shot-gun sequencing data still contain regions of uncertain quality due to assembly errors. Identifying high confidence regions in the assembled genome will facilitate its use for cell engineering and genome engineering. We assembled two independent drafts of Chinese hamster genome by de novo assembly from shotgun sequencing reads and by re-scaffolding and gap-filling the draft genome from NCBI for improved scaffold lengths and gap fractions. We then used the two independent assemblies to identify high confidence regions using two different approaches. First, the two independent assemblies were compared at the sequence level to identify their consensus regions as "high confidence regions" which accounts for at least 78 % of the assembled genome. Further, a genome wide comparison of the Chinese hamster scaffolds with mouse chromosomes revealed scaffolds with large blocks of collinearity, which were also compiled as high-quality scaffolds. Genome scale collinearity was complemented with EST based synteny which also revealed conserved gene order compared to mouse. As cell line sequencing becomes more commonly practiced, the approaches reported here are useful for assessing the quality of assembly and potentially facilitate the engineering of cell lines.

  20. Addressing model uncertainty through stochastic parameter perturbations within the High Resolution Rapid Refresh (HRRR) ensemble

    Science.gov (United States)

    Wolff, J.; Jankov, I.; Beck, J.; Carson, L.; Frimel, J.; Harrold, M.; Jiang, H.

    2016-12-01

    It is well known that global and regional numerical weather prediction ensemble systems are under-dispersive, producing unreliable and overconfident ensemble forecasts. Typical approaches to alleviate this problem include the use of multiple dynamic cores, multiple physics suite configurations, or a combination of the two. While these approaches may produce desirable results, they have practical and theoretical deficiencies and are more difficult and costly to maintain. An active area of research that promotes a more unified and sustainable system for addressing the deficiencies in ensemble modeling is the use of stochastic physics to represent model-related uncertainty. Stochastic approaches include Stochastic Parameter Perturbations (SPP), Stochastic Kinetic Energy Backscatter (SKEB), Stochastic Perturbation of Physics Tendencies (SPPT), or some combination of all three. The focus of this study is to assess the model performance within a convection-permitting ensemble at 3-km grid spacing across the Contiguous United States (CONUS) when using stochastic approaches. For this purpose, the test utilized a single physics suite configuration based on the operational High-Resolution Rapid Refresh (HRRR) model, with ensemble members produced by employing stochastic methods. Parameter perturbations were employed in the Rapid Update Cycle (RUC) land surface model and Mellor-Yamada-Nakanishi-Niino (MYNN) planetary boundary layer scheme. Results will be presented in terms of bias, error, spread, skill, accuracy, reliability, and sharpness using the Model Evaluation Tools (MET) verification package. Due to the high level of complexity of running a frequently updating (hourly), high spatial resolution (3 km), large domain (CONUS) ensemble system, extensive high performance computing (HPC) resources were needed to meet this objective. Supercomputing resources were provided through the National Center for Atmospheric Research (NCAR) Strategic Capability (NSC) project support

  1. High Resolution Melting Analysis for Rapid Mutation Screening in Gyrase and Topoisomerase IV Genes in Quinolone-Resistant Salmonella enterica

    Directory of Open Access Journals (Sweden)

    Soo Tein Ngoi

    2014-01-01

    Full Text Available The increased Salmonella resistance to quinolones and fluoroquinolones is a public health concern in the Southeast Asian region. The objective of this study is to develop a high resolution melt curve (HRM assay to rapidly screen for mutations in quinolone-resistant determining region (QRDR of gyrase and topoisomerase IV genes. DNA sequencing was performed on 62 Salmonella strains to identify mutations in the QRDR of gyrA, gyrB, parC, and parE genes. Mutations were detected in QRDR of gyrA (n=52; S83F, S83Y, S83I, D87G, D87Y, and D87N and parE (n=1; M438I. Salmonella strains with mutations within QRDR of gyrA are generally more resistant to nalidixic acid (MIC 16>256 μg/mL. Mutations were uncommon within the QRDR of gyrB, parC, and parE genes. In the HRM assay, mutants can be distinguished from the wild-type strains based on the transition of melt curves, which is more prominent when the profiles are displayed in difference plot. In conclusion, HRM analysis allows for rapid screening for mutations at the QRDRs of gyrase and topoisomerase IV genes in Salmonella. This assay markedly reduced the sequencing effort involved in mutational studies of quinolone-resistance genes.

  2. Rapid turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Weijun Zhu

    Full Text Available BACKGROUND: Despite prolonged treatment with highly active antiretroviral therapy (HAART, the infectious HIV-1 continues to replicate and resides latently in the resting memory CD4+ T lymphocytes, which blocks the eradication of HIV-1. The viral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated. Previous reports have largely focused on the dynamics of HIV-1 DNA from the samples collected with relatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes during the intervals in early treatment. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phase of HARRT treatment. Using optimized real time PCR, we observed significant changes in 2-LTR during the first 12-week of treatment, while total and integrated HIV-1 DNA remained stable. The doubling time and half-life of 2-LTR were not correlated with the baseline and the rate of changes in plasma viral load and various CD4+ T-cell populations. Longitudinal analyses on 2-LTR sequences and plasma lipopolysaccharide (LPS levels did not reveal any significant changes in the same treatment period. CONCLUSIONS/SIGNIFICANCE: Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patients during the early HAART treatment. The rapid changes indicate the rapid infusion and clearance of cells bearing 2-LTR in the peripheral blood. Those changes are not expected to be caused by the blocking of viral integration, as our study did not include the integrase inhibitor raltegravir. Our study helps better understand the dynamics of HIV-DNA and its potential role as a biomarker for the diseases and for the treatment efficacy of HAART.

  3. Rapid Thermal Annealing of Cathode-Garnet Interface toward High-Temperature Solid State Batteries.

    Science.gov (United States)

    Liu, Boyang; Fu, Kun; Gong, Yunhui; Yang, Chunpeng; Yao, Yonggang; Wang, Yanbin; Wang, Chengwei; Kuang, Yudi; Pastel, Glenn; Xie, Hua; Wachsman, Eric D; Hu, Liangbing

    2017-08-09

    High-temperature batteries require the battery components to be thermally stable and function properly at high temperatures. Conventional batteries have high-temperature safety issues such as thermal runaway, which are mainly attributed to the properties of liquid organic electrolytes such as low boiling points and high flammability. In this work, we demonstrate a truly all-solid-state high-temperature battery using a thermally stable garnet solid-state electrolyte, a lithium metal anode, and a V2O5 cathode, which can operate well at 100 °C. To address the high interfacial resistance between the solid electrolyte and cathode, a rapid thermal annealing method was developed to melt the cathode and form a continuous contact. The resulting interfacial resistance of the solid electrolyte and V2O5 cathode was significantly decreased from 2.5 × 10(4) to 71 Ω·cm(2) at room temperature and from 170 to 31 Ω·cm(2) at 100 °C. Additionally, the diffusion resistance in the V2O5 cathode significantly decreased as well. The demonstrated high-temperature solid-state full cell has an interfacial resistance of 45 Ω·cm(2) and 97% Coulombic efficiency cycling at 100 °C. This work provides a strategy to develop high-temperature all-solid-state batteries using garnet solid electrolytes and successfully addresses the high contact resistance between the V2O5 cathode and garnet solid electrolyte without compromising battery safety or performance.

  4. Rapid and high-throughput pan-Orthopoxvirus detection and identification using PCR and mass spectrometry.

    Science.gov (United States)

    Eshoo, Mark W; Whitehouse, Chris A; Nalca, Aysegul; Zoll, Scott; Ecker, Joseph A; Hall, Thomas A; Pennella, Thuy-Trang D; Duncan, David D; Desai, Anjali; Moradi, Emily K; Rudnick, Karl; Libby, Brian; Ranken, Raymond; Sampath, Rangarajan; Hofstadler, Steven A; Ecker, David J; Blyn, Lawrence B

    2009-07-22

    The genus Orthopoxvirus contains several species of related viruses, including the causative agent of smallpox (Variola virus). In addition to smallpox, several other members of the genus are capable of causing human infection, including monkeypox, cowpox, and other zoonotic rodent-borne poxviruses. Therefore, a single assay that can accurately identify all orthopoxviruses could provide a valuable tool for rapid broad orthopovirus identification. We have developed a pan-Orthopoxvirus assay for identification of all members of the genus based on four PCR reactions targeting Orthopoxvirus DNA and RNA helicase and polymerase genes. The amplicons are detected using electrospray ionization-mass spectrometry (PCR/ESI-MS) on the Ibis T5000 system. We demonstrate that the assay can detect and identify a diverse collection of orthopoxviruses, provide sub-species information and characterize viruses from the blood of rabbitpox infected rabbits. The assay is sensitive at the stochastic limit of PCR and detected virus in blood containing approximately six plaque-forming units per milliliter from a rabbitpox virus-infected rabbit.

  5. Rapid and high-throughput pan-Orthopoxvirus detection and identification using PCR and mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Mark W Eshoo

    Full Text Available The genus Orthopoxvirus contains several species of related viruses, including the causative agent of smallpox (Variola virus. In addition to smallpox, several other members of the genus are capable of causing human infection, including monkeypox, cowpox, and other zoonotic rodent-borne poxviruses. Therefore, a single assay that can accurately identify all orthopoxviruses could provide a valuable tool for rapid broad orthopovirus identification. We have developed a pan-Orthopoxvirus assay for identification of all members of the genus based on four PCR reactions targeting Orthopoxvirus DNA and RNA helicase and polymerase genes. The amplicons are detected using electrospray ionization-mass spectrometry (PCR/ESI-MS on the Ibis T5000 system. We demonstrate that the assay can detect and identify a diverse collection of orthopoxviruses, provide sub-species information and characterize viruses from the blood of rabbitpox infected rabbits. The assay is sensitive at the stochastic limit of PCR and detected virus in blood containing approximately six plaque-forming units per milliliter from a rabbitpox virus-infected rabbit.

  6. An In Vivo Platform for Rapid High-Throughput Antitubercular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Kevin Takaki

    2012-07-01

    Full Text Available Treatment of tuberculosis, like other infectious diseases, is increasingly hindered by the emergence of drug resistance. Drug discovery efforts would be facilitated by facile screening tools that incorporate the complexities of human disease. Mycobacterium marinum-infected zebrafish larvae recapitulate key aspects of tuberculosis pathogenesis and drug treatment. Here, we develop a model for rapid in vivo drug screening using fluorescence-based methods for serial quantitative assessment of drug efficacy and toxicity. We provide proof-of-concept that both traditional bacterial-targeting antitubercular drugs and newly identified host-targeting drugs would be discovered through the use of this model. We demonstrate the model’s utility for the identification of synergistic combinations of antibacterial drugs and demonstrate synergy between bacterial- and host-targeting compounds. Thus, the platform can be used to identify new antibacterial agents and entirely new classes of drugs that thwart infection by targeting host pathways. The methods developed here should be widely applicable to small-molecule screens for other infectious and noninfectious diseases.

  7. Big data in health care: using analytics to identify and manage high-risk and high-cost patients.

    Science.gov (United States)

    Bates, David W; Saria, Suchi; Ohno-Machado, Lucila; Shah, Anand; Escobar, Gabriel

    2014-07-01

    The US health care system is rapidly adopting electronic health records, which will dramatically increase the quantity of clinical data that are available electronically. Simultaneously, rapid progress has been made in clinical analytics--techniques for analyzing large quantities of data and gleaning new insights from that analysis--which is part of what is known as big data. As a result, there are unprecedented opportunities to use big data to reduce the costs of health care in the United States. We present six use cases--that is, key examples--where some of the clearest opportunities exist to reduce costs through the use of big data: high-cost patients, readmissions, triage, decompensation (when a patient's condition worsens), adverse events, and treatment optimization for diseases affecting multiple organ systems. We discuss the types of insights that are likely to emerge from clinical analytics, the types of data needed to obtain such insights, and the infrastructure--analytics, algorithms, registries, assessment scores, monitoring devices, and so forth--that organizations will need to perform the necessary analyses and to implement changes that will improve care while reducing costs. Our findings have policy implications for regulatory oversight, ways to address privacy concerns, and the support of research on analytics. Project HOPE—The People-to-People Health Foundation, Inc.

  8. A Clinical Drug Library Screen Identifies Tosufloxacin as Being Highly Active against Staphylococcus aureus Persisters

    Directory of Open Access Journals (Sweden)

    Hongxia Niu

    2015-07-01

    Full Text Available To identify effective compounds that are active against Staphylococcus aureus (S. aureus persisters, we screened a clinical drug library consisting of 1524 compounds and identified six drug candidates that had anti-persister activity: tosufloxacin, clinafloxacin, sarafloxacin, doxycycline, thiostrepton, and chlorosalicylanilide. Among them, tosufloxacin had the highest anti-persister activity, which could completely eradicate S. aureus persisters within 2 days in vitro. Clinafloxacin ranked the second with very few persisters surviving the drug exposure. Interestingly, we found that both tosufloxacin and trovafloxacin that had high activity against persisters contained at the N-1 position the 2,4-difluorophenyl group, which is absent in other less active quinolones and may be associated with the high anti-persister activity. Further studies are needed to evaluate tosufloxacin in animal models and to explain its unique activity against bacterial persisters. Our findings may have implications for improved treatment of persistent bacterial infections.

  9. Whole-exome sequencing identified mutational profiles of high-grade colon adenomas

    Science.gov (United States)

    Kim, Tae-Min; Rhee, Je-Keun; Park, Hyeon-Chun; Sung, Min Kim; Kim, Sung Soo; Hyeok, Chang An; Lee Hyung, Sug; Chung, Yeun-Jun

    2017-01-01

    Although gene-to-gene analyses identified genetic alterations such as APC, KRAS and TP53 mutations in colon adenomas, it is largely unknown whether there are any others in them. Mutational profiling of high-grade colon adenoma (HGCA) that just precedes colon carcinoma might identify not only novel adenoma-specific genes but also critical genes for its progression to carcinoma. For this, we performed whole-exome sequencing (WES) of 12 HGCAs and identified 11 non-hypermutated and one hypermutated (POLE-mutated) cases. We identified 22 genes including APC, KRAS, TP53, GNAS, NRAS, SMAD4, ARID2, and PIK3CA with non-silent mutations in the cancer Census Genes. Bi-allelic and mono-allelic APC alterations were found in nine and one HGCAs, respectively, while the other two harbored wild-type APC. Five HGCAs harbored either mono-allelic (four HGCAs) or bi-allelic (one HGCA) SMAD4 mutation or 18q loss that had been known as early carcinoma-specific changes. We identified MTOR, ACVR1B, GNAQ, ATM, CNOT1, EP300, ARID2, RET and MAP2K4 mutations for the first time in colon adenomas. Our WES data is largely matched with the earlier ‘adenoma-carcinoma model’ (APC, KRAS, NRAS and GNAS mutations), but there are newly identified SMAD4, MTOR, ACVR1B, GNAQ, ATM, CNOT1, EP300, ARID2, RET and MAP2K4 mutations in this study. Our findings provide resource for understanding colon premalignant lesions and for identifying genomic clues for differential diagnosis and therapy options for colon adenomas and carcinomas. PMID:28179590

  10. Identify high risk estrogen receptor-positive breast cancer patients for extended endocrine therapy.

    Science.gov (United States)

    Li, JunJie; Jiang, Yizhou; Liu, Yirong; Shao, Zhimin

    2017-02-01

    To demonstrate the patterns of breast cancer-specific mortality (BCSM) in estrogen receptor (ER)-positive diseases and to identify high-risk candidates for extended endocrine therapy. Using the Surveillance, Epidemiology and End Results database, we identified ER-positive patients diagnosed between 1990 and 2000 (cohort 1 [C1]) and between 2001 and 2005 (cohort 2 [C2]). The patterns of BCSM were calculated using Cox proportional hazard regression models. A risk classification model was developed, and X-tile software was used to divide patients with high BCSM rates into 3 risk groups. The annual BCSM rate of C2 was decreased by one-third and was maintained at 10-15 (per 1000 persons per year) from year 2 to year 10. Long-term mortality risks still persisted in C2, especially in patients with node-positive, grade 3 or T3 disease, who should be considered as "clinical-high-risk". These patients were further divided into 3 risk groups through our model: for C1, 42.2% were in the low-risk group, 38.9% in the medium-risk group, and 18.9% in the high-risk group; and for C2, 45.5% were in the low-risk group, 38.2% in the medium-risk group and 16.2% in the high-risk group (p risk group. ER-positive patients with node-positive, grade 3 or T3 diseases had sustained risks of death throughout the 10-year time frame, and our model is helpful to identify patients with high risk who are candidates for extended endocrine therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. HIGH NATURE VALUE GRASSLANDS FROM ARRHENATHERION ALLIANCE IDENTIFIED IN MUREŞ COUNTY

    OpenAIRE

    Silvia Oroian; Mihaela Samarghitan; MARIANA Hiritiu; SANDA Cosarca; CORNELIU Tanase

    2016-01-01

    Arrhenatherion alliance meadows are recognized to be among the best pastures in our country due to high productivity and good nutrition value. The research was conducted in several areas of Mures County. The studied grasslands were classified into two types of Natura 2000 habitats: 6510 Lowland hay meadows (Alopecurus pratensis, Sanguisorba officinalis) and 6520 Mountain hay meadows. The identified phytocoenosis belong to two plant associations: Arrhenatheretum elatioris Br.-Bl. Ex Scherrer 1...

  12. A BSL-4 High-Throughput Screen Identifies Sulfonamide Inhibitors of Nipah Virus

    OpenAIRE

    2014-01-01

    Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-...

  13. A high-throughput approach to identify compounds that impair envelope integrity in Escherichia coli

    DEFF Research Database (Denmark)

    Baker, Kristin Renee; Jana, Bimal; Franzyk, Henrik

    2016-01-01

    was to develop and validate an assay for identifying compounds that increase envelope permeability, thereby conferring antimicrobial susceptibility by weakening of the cell envelope barrier in Gram-negative bacteria. A high-throughput whole-cell screening platform was developed to measure Escherichia coli......- to 125-fold) the MICs of erythromycin, fusidic acid, novobiocin and rifampin and displayed synergy (fractional inhibitory concentration index, risk multidrug-resistant, CTX-M-15-producing...

  14. Preparation and Evaluation of Oxaliplatin Thermosensitive Liposomes with Rapid Release and High Stability.

    Directory of Open Access Journals (Sweden)

    Chunying Zeng

    Full Text Available Oxaliplatin (OXP was reported to show low anti-tumor activity when used alone and to display side effects; this low activity was attributed to high partitioning to erythrocytes and low accumulation in tumors. Thermosensitive liposomes (TSL were considered able to specifically deliver drugs to heated tumors and to resolve the OXP distribution problem. Regretfully, TSL encapsulating doxorubicin did not demonstrate significant improvement in progression-free survival. Drug release below 41°C and significant leakage were considered major reasons for the failure. The purpose of this study was to acquire OXP TSL with rapid release at the triggered temperature and high stability at body temperature and at storage temperatures. A small quantity of poloxamer 188 was introduced into the TSL formulation to stabilize the encapsulated drug. It was shown that the addition of poloxamer 188 had no influence on the TSL characteristics. More than 90% of OXP was released within 10 min at 42°C, and less than 15% was released within 60 min at temperatures below 39°C. TSL were stable at 37°C for 96 h and at 4°C for 6 months. The anti-tumor activity of TSL at the dose of 2.5 mg/kg was certified to be equal to those of OXP injection and non-thermosensitive liposomes (NTSL at the dose of 5 mg/kg, and significant improvement of tumor inhibition was observed in TSL compared with injection and NTSL at the same dose. It was also shown from the histological transmutation of tumors that TSL had stronger anti-tumor activity. Therefore, it could be concluded that TSL composed of a proper amount of poloxamer had rapid release and high stability, and OXP TSL would be anticipated to exert prominent anti-tumor activity in the clinic.

  15. A BSL-4 high-throughput screen identifies sulfonamide inhibitors of Nipah virus.

    Science.gov (United States)

    Tigabu, Bersabeh; Rasmussen, Lynn; White, E Lucile; Tower, Nichole; Saeed, Mohammad; Bukreyev, Alexander; Rockx, Barry; LeDuc, James W; Noah, James W

    2014-04-01

    Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC50 values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC50 values BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses.

  16. Accurate structure prediction of peptide–MHC complexes for identifying highly immunogenic antigens

    Energy Technology Data Exchange (ETDEWEB)

    Park, Min-Sun; Park, Sung Yong; Miller, Keith R.; Collins, Edward J.; Lee, Ha Youn

    2013-11-01

    Designing an optimal HIV-1 vaccine faces the challenge of identifying antigens that induce a broad immune capacity. One factor to control the breadth of T cell responses is the surface morphology of a peptide–MHC complex. Here, we present an in silico protocol for predicting peptide–MHC structure. A robust signature of a conformational transition was identified during all-atom molecular dynamics, which results in a model with high accuracy. A large test set was used in constructing our protocol and we went another step further using a blind test with a wild-type peptide and two highly immunogenic mutants, which predicted substantial conformational changes in both mutants. The center residues at position five of the analogs were configured to be accessible to solvent, forming a prominent surface, while the residue of the wild-type peptide was to point laterally toward the side of the binding cleft. We then experimentally determined the structures of the blind test set, using high resolution of X-ray crystallography, which verified predicted conformational changes. Our observation strongly supports a positive association of the surface morphology of a peptide–MHC complex to its immunogenicity. Our study offers the prospect of enhancing immunogenicity of vaccines by identifying MHC binding immunogens.

  17. High resolution melting analysis: a rapid and accurate method to detect CALR mutations.

    Directory of Open Access Journals (Sweden)

    Cristina Bilbao-Sieyro

    Full Text Available The recent discovery of CALR mutations in essential thrombocythemia (ET and primary myelofibrosis (PMF patients without JAK2/MPL mutations has emerged as a relevant finding for the molecular diagnosis of these myeloproliferative neoplasms (MPN. We tested the feasibility of high-resolution melting (HRM as a screening method for rapid detection of CALR mutations.CALR was studied in wild-type JAK2/MPL patients including 34 ET, 21 persistent thrombocytosis suggestive of MPN and 98 suspected secondary thrombocytosis. CALR mutation analysis was performed through HRM and Sanger sequencing. We compared clinical features of CALR-mutated versus 45 JAK2/MPL-mutated subjects in ET.Nineteen samples showed distinct HRM patterns from wild-type. Of them, 18 were mutations and one a polymorphism as confirmed by direct sequencing. CALR mutations were present in 44% of ET (15/34, 14% of persistent thrombocytosis suggestive of MPN (3/21 and none of the secondary thrombocytosis (0/98. Of the 18 mutants, 9 were 52 bp deletions, 8 were 5 bp insertions and other was a complex mutation with insertion/deletion. No mutations were found after sequencing analysis of 45 samples displaying wild-type HRM curves. HRM technique was reproducible, no false positive or negative were detected and the limit of detection was of 3%.This study establishes a sensitive, reliable and rapid HRM method to screen for the presence of CALR mutations.

  18. High Resolution Melting Analysis: A Rapid and Accurate Method to Detect CALR Mutations

    Science.gov (United States)

    Moreno, Melania; Torres, Laura; Santana-Lopez, Gonzalo; Rodriguez-Medina, Carlos; Perera, María; Bellosillo, Beatriz; de la Iglesia, Silvia; Molero, Teresa; Gomez-Casares, Maria Teresa

    2014-01-01

    Background The recent discovery of CALR mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients without JAK2/MPL mutations has emerged as a relevant finding for the molecular diagnosis of these myeloproliferative neoplasms (MPN). We tested the feasibility of high-resolution melting (HRM) as a screening method for rapid detection of CALR mutations. Methods CALR was studied in wild-type JAK2/MPL patients including 34 ET, 21 persistent thrombocytosis suggestive of MPN and 98 suspected secondary thrombocytosis. CALR mutation analysis was performed through HRM and Sanger sequencing. We compared clinical features of CALR-mutated versus 45 JAK2/MPL-mutated subjects in ET. Results Nineteen samples showed distinct HRM patterns from wild-type. Of them, 18 were mutations and one a polymorphism as confirmed by direct sequencing. CALR mutations were present in 44% of ET (15/34), 14% of persistent thrombocytosis suggestive of MPN (3/21) and none of the secondary thrombocytosis (0/98). Of the 18 mutants, 9 were 52 bp deletions, 8 were 5 bp insertions and other was a complex mutation with insertion/deletion. No mutations were found after sequencing analysis of 45 samples displaying wild-type HRM curves. HRM technique was reproducible, no false positive or negative were detected and the limit of detection was of 3%. Conclusions This study establishes a sensitive, reliable and rapid HRM method to screen for the presence of CALR mutations. PMID:25068507

  19. Rapid and high throughput detection of HBV YMDD mutants with fluorescence polarization

    Institute of Scientific and Technical Information of China (English)

    Yui-Jie Bai; Jin-Rong Zhao; Guan-Ting Lv; Wen-Hong Zhang; Yan Wang; Xiao-Jun Yan

    2003-01-01

    AIM: To develop a simple and rapid detection of HBV gene variants and prediction of lamivudine-resistance in patients.METHODS: Initially, plasmids harboring the wild-type or mutant HBV DNA fragments were used in a model system.The technique was then applied to clinical samples for an analysis of YMDD mutations. The sera were extracted from chronic hepatitis patients who had received lamivudine treatment for more than one year. P region gene of HBV was amplified by polymerase chain reaction. The excess primers and dNTPs in PCR products were removed by cleaning-up reagents. Template-directed dye-terminator incorporation reaction was performed and R110 or TAMRA labeled acyclo-terminator was added on the 3' end of TDIprimer specifically. Fluorescence polarization value was measured with Victor 2 multilabel counter and the genotypes of HBV were analyzed.RESULTS: The YMDD genotypes in recombined positive plasmid and 56 serum samples of HBV infected patients were analyzed by using our TDI-FP method and the specificity and sensitivity were confirmed by DNA sequencing. Five of 56 serum samples showed YVDD phenotype (9%), including 1 YMDD and YVDD mixed infection. Four of 56 showed YIDD phenotype (7.1%).CONCLUSION: This is a simple, rapid, low cost and high throughput assay to detect HBV polymerase gene variants and suitable for large-scale screening and prediction of the lamivudine-resistance in clinical samples.

  20. Production of Forward Rapidity Photons in High Energy Heavy Ion Collisions

    CERN Document Server

    Jalilian-Marian, J

    2005-01-01

    We consider production of prompt photons in high energy gold-gold and deuteron-gold collisions in the forward rapidity region of RHIC ($y \\sim 3.8$). In this kinematics, the projectile partons typically have large $x_{bj}$ while the target partons are mostly at very small $x_{bj}$ so that the primary partonic collisions involve valence quarks from the projectile and gluons from the target. We take the target nucleus to be a Color Glass Condensate while the projectile deuteron or nucleus is treated as a dilute system of partons. We show that the photon production cross section can be written as a convolution of a quark-nucleus scattering cross section, involving a quark anti-quark dipole, with the Leading Order quark-photon fragmentation function. We consider different models of the quark anti-quark dipole and show that measurement of photons in the forward rapidity region at RHIC can distinguish between different parameterizations of the dipole cross section as well as help clarify the role of parton coalesce...

  1. Three classes of glucocerebrosidase inhibitors identified by quantitative high-throughput screening are chaperone leads for Gaucher disease.

    Science.gov (United States)

    Zheng, Wei; Padia, Janak; Urban, Daniel J; Jadhav, Ajit; Goker-Alpan, Ozlem; Simeonov, Anton; Goldin, Ehud; Auld, Douglas; LaMarca, Mary E; Inglese, James; Austin, Christopher P; Sidransky, Ellen

    2007-08-01

    Gaucher disease is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene. Missense mutations result in reduced enzyme activity that may be due to misfolding, raising the possibility of small-molecule chaperone correction of the defect. Screening large compound libraries by quantitative high-throughput screening (qHTS) provides comprehensive information on the potency, efficacy, and structure-activity relationships (SAR) of active compounds directly from the primary screen, facilitating identification of leads for medicinal chemistry optimization. We used qHTS to rapidly identify three structural series of potent, selective, nonsugar glucocerebrosidase inhibitors. The three structural classes had excellent potencies and efficacies and, importantly, high selectivity against closely related hydrolases. Preliminary SAR data were used to select compounds with high activity in both enzyme and cell-based assays. Compounds from two of these structural series increased N370S mutant glucocerebrosidase activity by 40-90% in patient cell lines and enhanced lysosomal colocalization, indicating chaperone activity. These small molecules have potential as leads for chaperone therapy for Gaucher disease, and this paradigm promises to accelerate the development of leads for other rare genetic disorders.

  2. Identifying positive selection candidate loci for high-altitude adaptation in Andean populations

    Directory of Open Access Journals (Sweden)

    Bigham Abigail W

    2009-12-01

    Full Text Available Abstract High-altitude environments (>2,500 m provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach to understanding how life at high altitude has affected human metabolism is to survey genome-wide datasets for signatures of natural selection. In this work, we report on a study to identify selection-nominated candidate genes involved in adaptation to hypoxia in one highland group, Andeans from the South American Altiplano. We analysed dense microarray genotype data using four test statistics that detect departures from neutrality. Using a candidate gene, single nucleotide polymorphism-based approach, we identified genes exhibiting preliminary evidence of recent genetic adaptation in this population. These included genes that are part of the hypoxia-inducible transcription factor (HIF pathway, a biochemical pathway involved in oxygen homeostasis, as well as three other genomic regions previously not known to be associated with high-altitude phenotypes. In addition to identifying selection-nominated candidate genes, we also tested whether the HIF pathway shows evidence of natural selection. Our results indicate that the genes of this biochemical pathway as a group show no evidence of having evolved in response to hypoxia in Andeans. Results from particular HIF-targeted genes, however, suggest that genes in this pathway could play a role in Andean adaptation to high altitude, even if the pathway as a whole does not show higher relative rates of evolution. These data suggest a genetic role in high-altitude adaptation and provide a basis for genotype/phenotype association studies that are necessary to confirm the role of putative natural selection candidate genes and gene regions in adaptation to altitude.

  3. Rapidly solidified Fe-6.5%Si alloy powders for high frequency use (abstract)

    Science.gov (United States)

    Duk Choi, Seung; Jin Yang, Choong

    1996-04-01

    Fe-(3˜6.5%) Si alloy powders having a high magnetic induction (Bs) and a low core loss value for high frequency use were obtained by an extractive melt spinning as well as a centrifugal atomization technique. Sintered core rings made by the rapidly solidified Fe-6.5% Si powders exhibited the high frequency electromagnetic properties: saturated induction (B8) of 1.23 T, coercivity (Hc) of 9.5 A/m, relative permeability (μa) of 6321, and core loss (W10/50) of 1.27 W/kg from the rings of 1.1 mm thick. The saturated induction values were found to be almost identical to those of nonoriented Fe-3% Si steel sheet and 6.5% Si sheet prepared by the CVD technique. The high frequency core loss values were measured not to be changed much up to 10 kHz (W1/10k=55 W/kg) in applied ac frequency.

  4. Space-to-Space Power Beaming Enabling High Performance Rapid Geocentric Orbit Transfer

    Science.gov (United States)

    Dankanich, John W.; Vassallo, Corinne; Tadge, Megan

    2015-01-01

    The use of electric propulsion is more prevalent than ever, with industry pursuing all electric orbit transfers. Electric propulsion provides high mass utilization through efficient propellant transfer. However, the transfer times become detrimental as the delta V transitions from near-impulsive to low-thrust. Increasing power and therefore thrust has diminishing returns as the increasing mass of the power system limits the potential acceleration of the spacecraft. By using space-to-space power beaming, the power system can be decoupled from the spacecraft and allow significantly higher spacecraft alpha (W/kg) and therefore enable significantly higher accelerations while maintaining high performance. This project assesses the efficacy of space-to-space power beaming to enable rapid orbit transfer while maintaining high mass utilization. Concept assessment requires integrated techniques for low-thrust orbit transfer steering laws, efficient large-scale rectenna systems, and satellite constellation configuration optimization. This project includes the development of an integrated tool with implementation of IPOPT, Q-Law, and power-beaming models. The results highlight the viability of the concept, limits and paths to infusion, and comparison to state-of-the-art capabilities. The results indicate the viability of power beaming for what may be the only approach for achieving the desired transit times with high specific impulse.

  5. Ecological Niche Modeling Identifies Fine-Scale Areas at High Risk of Dengue Fever in the Pearl River Delta, China

    Directory of Open Access Journals (Sweden)

    Qiaoxuan Li

    2017-06-01

    Full Text Available Dengue fever (DF is one of the most common and rapidly spreading mosquito-borne viral diseases in tropical and subtropical regions. In recent years, this imported disease has posed a serious threat to public health in China, especially in the Pearl River Delta (PRD. Although the severity of DF outbreaks in the PRD is generally associated with known risk factors, fine scale assessments of areas at high risk for DF outbreaks are limited. We built five ecological niche models to identify such areas including a variety of climatic, environmental, and socioeconomic variables, as well as, in some models, extracted principal components. All the models we tested accurately identified the risk of DF, the area under the receiver operating characteristic curve (AUC were greater than 0.8, but the model using all original variables was the most accurate (AUC = 0.906. Socioeconomic variables had a greater impact on this model (total contribution 55.27% than climatic and environmental variables (total contribution 44.93%. We found the highest risk of DF outbreaks on the border of Guangzhou and Foshan (in the central PRD, and in northern Zhongshan (in the southern PRD. Our fine-scale results may help health agencies to focus epidemic monitoring tightly on the areas at highest risk of DF outbreaks.

  6. Area Efficient Rapid Signal Acquisition scheme for High Doppler DSSS Signals

    Directory of Open Access Journals (Sweden)

    D. Karunakar Reddy

    2013-04-01

    Full Text Available The Direct Sequence Spread Spectrum (DSSS communication system is widely used in ground to airmissile links due to its anti-jam and low Signal to Noise Ratio (SNR requirement advantages. The paperpresents the challenges in achieving fast signal acquisition in this scenario and brings out theimplementation challenges for achieving simultaneous Doppler estimation and phase delay of PseudoNoise (PN code. A new scheme for PN code phase delay estimation with correlation of differential signals,followed by precise Doppler estimation using Fast Fourier Transform (FFT is presented. The areaoptimized Field Programmable Gate Array (FPGA friendly architecture is utilized for rapid signalacquisition by combining both time and frequency domain approaches. The advanced design practices inFPGAs are used to achieve resource sharing and high clock speed of operation. The architecture issynthesized for Virtex-6 LX240T FPGA, resulting in 52% of area occupancy and 134 MHz of maximumallowed clock frequency value.

  7. Influence of rapid thermal vacuum annealing and high temperature treatment on the properties of PSG films

    Energy Technology Data Exchange (ETDEWEB)

    Beschkov, G [Georgi Nadjakov Institute of Solid State Physics, Bulgarian Academy of Science, 72 Tsarigradsko Chaussee, 1784 Sofia (Bulgaria); Bakardjieva, V; Alexieva, Z [Central Laboratory of Solar Energy and New Energy Sources, Bulgarian Academy of Science, 72 Tsarigradsko Chaussee, 1784 Sofia (Bulgaria)], E-mail: vlabakar@phys.bas.bg

    2008-05-01

    The effect is presented of rapid thermal annealing (RTA) in vacuum and thermal annealing in water vapor at 850 deg. C on the properties of phosphosilicate glass (PSG) films deposited in PECVD and {mu}PCVD reactors. The films were characterized by etch rates and XPS and AES analyses. The RTA was carried out at 800 - 1400 deg. C at annealing times varying from 15 to 180 sec. The RTA caused a significant decrease in the etch rate, which is indicative of structural changes. The XPS and AES analyses showed that the PECVD PSG films contain excess Si due to the lower oxidation activity of N{sub 2}O. The excess Si can be oxidized in water vapor at high temperatures. The excess Si leads to a decrease in the etching rate of the PECVD PSG layers as compared to that of the {mu}PCVD films.

  8. Influence of rapid thermal vacuum annealing and high temperature treatment on the properties of PSG films

    Science.gov (United States)

    Beschkov, G.; Bakardjieva, V.; Alexieva, Z.

    2008-05-01

    The effect is presented of rapid thermal annealing (RTA) in vacuum and thermal annealing in water vapor at 850 °C on the properties of phosphosilicate glass (PSG) films deposited in PECVD and μPCVD reactors. The films were characterized by etch rates and XPS and AES analyses. The RTA was carried out at 800 - 1400 °C at annealing times varying from 15 to 180 sec. The RTA caused a significant decrease in the etch rate, which is indicative of structural changes. The XPS and AES analyses showed that the PECVD PSG films contain excess Si due to the lower oxidation activity of N2O. The excess Si can be oxidized in water vapor at high temperatures. The excess Si leads to a decrease in the etching rate of the PECVD PSG layers as compared to that of the μPCVD films.

  9. Limits of rapid log P determination methods for highly lipophilic and flexible compounds.

    Science.gov (United States)

    Martel, Sophie; Begnaud, Frédéric; Schuler, William; Gillerat, Fabrice; Oberhauser, Nils; Nurisso, Alessandra; Carrupt, Pierre-Alain

    2016-04-01

    Lipophilicity is of crucial importance in many fields including pharmaceutical, environmental, cosmetic and food industries. Whereas different experimental strategies have been developed for rapid lipophilicity determination of new chemical entities, log P determination of highly lipophilic compounds is always challenging. In this study, three published chromatographic methods have been compared on a series of phenylalkanoic acids including the pro-perfume HaloscentD (HD-C12). Different log P values were obtained depending on the chromatographic method used for log P estimation. Molecular modelling suggested that log P variations may be due to the chromatographic conditions applied (isocratic or gradient mode, ratio methanol/water in the mobile phase), responsible of specific conformations of the molecule in solution. Thus, for flexible compounds, published methods have to be used with caution and considered as a good tool to estimate a log P range, depending on the molecular conformational state.

  10. A Rapid and Cost-Effective Laser Based Synthesis of High Purity Cadmium Selenide Quantum Dots.

    Science.gov (United States)

    Gondall, M A; Qahtan, Talal F; Dastageer, M A; Yamani, Z H; Anjum, D H

    2016-01-01

    A rapid and cost effective method is developed to synthesize high purity cadmium Selenide (CdSe) quantum dots in acetone medium using second harmonic of Nd:YAG nanosecond pulsed laser of 532 nm wavelength. The thermal agglomeration due the nanosecond pulse duration of the laser was successfully eliminated by using unfocussed laser beam and thereby providing a favorable conditions for the synthesis of quantum dots having the grain size of 3 nm. The morphological and optical characterizations like XRD, HRTEM, optical absorption of the synthesized CdSe quantum dots, reveal that the material possesses the similar characteristics of the one synthesized through cumbersome wet chemical methods. Relative to the CdSe bulk material, the synthesized CdSe quantum dots showed a blue shift in the measured band gap energy from near infrared spectral region to visible region, making this material very attractive for many solar energy harvesting applications like photo-catalysis and solar cells.

  11. Rapid production of organic fertilizer by dynamic high-temperature aerobic fermentation (DHAF) of food waste.

    Science.gov (United States)

    Jiang, Yang; Ju, Meiting; Li, Weizun; Ren, Qingbin; Liu, Le; Chen, Yu; Yang, Qian; Hou, Qidong; Liu, Yiliang

    2015-12-01

    Keep composting matrix in continuous collision and friction under a relatively high-temperature can significantly accelerate the progress of composting. A bioreactor was designed according to the novel process. Using this technology, organic fertilizer could be produced within 96h. The electric conductivity (EC) and pH value reached to a stable value of 2.35mS/cm and 7.7 after 96h of fermentation. The total carbon/total nitrogen (TC/TN) and dissolved carbon/dissolved nitrogen (DC/DN) ratio was decrease from 27.3 and 36.2 to 17.4 and 7.6 respectively. In contrast, it needed 24days to achieve the similar result in traditional static composting (TSC). Compost particles with different size were analyzed to explore the rapid degradation mechanism of food waste. The evidence of anaerobic fermentation was firstly discovered in aerobic composting.

  12. High-Frequency Oscillations in a Solar Active Region observed with the Rapid Dual Imager

    CERN Document Server

    Jess, D B; Mathioudakis, M; Bloomfield, D S; Keenan, F P

    2007-01-01

    High-cadence, synchronized, multiwavelength optical observations of a solar active region (NOAA 10794) are presented. The data were obtained with the Dunn Solar Telescope at the National Solar Observatory/Sacramento Peak using a newly developed camera system : the Rapid Dual Imager. Wavelet analysis is undertaken to search for intensity related oscillatory signatures, and periodicities ranging from 20 to 370 s are found with significance levels exceeding 95%. Observations in the H-alpha blue wing show more penumbral oscillatory phenomena when compared to simultaneous G-band observations. The H-alpha oscillations are interpreted as the signatures of plasma motions with a mean velocity of 20 km/s. The strong oscillatory power over H-alpha blue-wing and G-band penumbral bright grains is an indication of the Evershed flow with frequencies higher than previously reported.

  13. Rapid Hypoeutectic Growth Within a Highly Undercooled Liquid Under Containerless Condition

    Institute of Scientific and Technical Information of China (English)

    韩秀君; 姚文静; 魏炳波

    2002-01-01

    Rapid hypoeutectic growth from a highly undercooled liquid was accomplished by containerless processing Ni32%Sb hypoeutectic alloy in a 3m drop tube. The containerless state during the free fall of the droplet produces substantial undercooling up to 350K (0.24TL ). The growth mechanism is found to transform from primary α-Ni dendrite plus lamellar eutectic to lamellar eutectic and finally to anomalous eutectic if droplet undercooling exceeds the two thresholds of 112K and 242K, respectively. Based on the current eutectic and dendritic growth models, the eutectic coupled zone is calculated and used to explain the growth mechanism transition. Calculations also indicate that the growth of α-Ni primary dendrite was mainly controlled by solute diffusion.

  14. A High-affinity Activator of G551D-CFTR Chloride Channel Identified By High Throughput Screening

    Institute of Scientific and Technical Information of China (English)

    ZHAO Lu; HE Cheng-yan; LIU Yan-li; ZHOU Hong-lan; ZHOU Jin-song; SHANG De-jing; YANG Hong

    2004-01-01

    A stably transfected CHO cell line coexpressing G551D-CFTR and iodide-sensitive yellow fluorescent protein mutant EYFP-H148Q-I152L was successfully established and used as assay model to identify small-molecule activators of G551D-CFTR chloride channel from 100000 diverse combinatorial compounds by high throughput screening on a customized Beckman robotic system. A bicyclooctane compound was identified to activate G551D-CFTR chloride channel with high-affinity(Kd=1.8 μmol/L). The activity of the bicyclooctane compound is G551D-CFTR-specific, reversible and non-toxic. The G551D-CFTR activator may be useful as a tool to study the mutant G551D-CFTR chloride channel structure and transport properties and as a candidate drug to cure cystic fibrosis caused by G551D-CFTR mutation.

  15. Counter-Stereotypes and Feminism Promote Leadership Aspirations in Highly Identified Women.

    Science.gov (United States)

    Leicht, Carola; Gocłowska, Małgorzata A; Van Breen, Jolien A; de Lemus, Soledad; Randsley de Moura, Georgina

    2017-01-01

    Although women who highly identify with other women are more susceptible to stereotype threat effects, women's identification might associate with greater leadership aspirations contingent on (1) counter-stereotype salience and (2) feminist identification. When gender counter-stereotypes are salient, women's identification should associate with greater leadership aspiration regardless of feminism, while when gender stereotypes are salient, women's identification would predict greater leadership aspirations contingent on a high level of feminist identification. In our study US-based women (N = 208) attended to gender stereotypic (vs. counter-stereotypic) content. We measured identification with women and identification with feminism, and, following the manipulation, leadership aspirations in an imagined work scenario. The interaction between identification with women, identification with feminism, and attention to stereotypes (vs. counter-stereotypes) significantly predicted leadership aspirations. In the counter-stereotypic condition women's identification associated with greater leadership aspirations regardless of feminist identification. In the stereotypic condition women's identification predicted leadership aspirations only at high levels of feminist identification. We conclude that salient counter-stereotypes and a strong identification with feminism may help high women identifiers increase their leadership aspirations.

  16. Microstructure and Mechanical Properties of a Novel Rapidly Solidified, High-Temperature Al-Alloy

    Energy Technology Data Exchange (ETDEWEB)

    Overman, Nicole R.; Mathaudhu, Suveen; Choi, Jung-Pyung; Roosendaal, Timothy J.; Pitman, Stan G.

    2016-02-12

    Rapid solidification (RS) processing, as a production method, offers a variety of unique properties based on far-from-equilibrium microstructures obtained through rapid cooling rates. In this study, we seek to investigate the microstructures and properties of a novel Al-alloy specifically designed for high temperature mechanical stability. Synthesis of, AlFe11.4Si1.8V1.6Mn0.9 (wt. %), was performed by two approaches: rotating cup atomization (“shot”) and melt spinning (“flake”). These methods were chosen because of their ability to produce alloys with tailored microstructures due to their inherent differences in cooling rate. The as-solidified precursor materials were microstructurally characterized with electron microscopy. The results show that the higher cooling rate flake material exhibited the formation of nanocrystalline regions as well additional phase morphologies not seen in the shot material. Secondary dendritic branching in the flake material was on the order of 0.1-0.25µm whereas branching in the shot material was 0.5-1.0µm. Consolidated and extruded material from both precursor materials was mechanically evaluated at both ambient and high (300°C) temperature. The consolidated RS flake material is shown to exhibit higher strengths than the shot material. The ultimate tensile strength of the melt spun flake was reported as 544.2MPa at room temperature and 298.0MPa at 300°C. These results forecast the ability to design alloys and processing approaches with unique non-equilibrium microstructures with robust mechanical properties at elevated temperatures.

  17. A high-resolution chronology of rapid forest transitions following polynesian arrival in New Zealand.

    Science.gov (United States)

    McWethy, David B; Wilmshurst, Janet M; Whitlock, Cathy; Wood, Jamie R; McGlone, Matt S

    2014-01-01

    Human-caused forest transitions are documented worldwide, especially during periods when land use by dense agriculturally-based populations intensified. However, the rate at which prehistoric human activities led to permanent deforestation is poorly resolved. In the South Island, New Zealand, the arrival of Polynesians c. 750 years ago resulted in dramatic forest loss and conversion of nearly half of native forests to open vegetation. This transformation, termed the Initial Burning Period, is documented in pollen and charcoal records, but its speed has been poorly constrained. High-resolution chronologies developed with a series of AMS radiocarbon dates from two lake sediment cores suggest the shift from forest to shrubland occurred within decades rather than centuries at drier sites. We examine two sites representing extreme examples of the magnitude of human impacts: a drier site that was inherently more vulnerable to human-set fires and a wetter, less burnable site. The astonishing rate of deforestation at the hands of small transient populations resulted from the intrinsic vulnerability of the native flora to fire and from positive feedbacks in post-fire vegetation recovery that increased landscape flammability. Spatially targeting burning in highly-flammable seral vegetation in forests rarely experiencing fire was sufficient to create an alternate fire-prone stable state. The New Zealand example illustrates how seemingly stable forest ecosystems can experience rapid and permanent conversions. Forest loss in New Zealand is among the fastest ecological transitions documented in the Holocene; yet equally rapid transitions can be expected in present-day regions wherever positive feedbacks support alternate fire-inhibiting, fire-prone stable states.

  18. A high-resolution chronology of rapid forest transitions following polynesian arrival in New Zealand.

    Directory of Open Access Journals (Sweden)

    David B McWethy

    Full Text Available Human-caused forest transitions are documented worldwide, especially during periods when land use by dense agriculturally-based populations intensified. However, the rate at which prehistoric human activities led to permanent deforestation is poorly resolved. In the South Island, New Zealand, the arrival of Polynesians c. 750 years ago resulted in dramatic forest loss and conversion of nearly half of native forests to open vegetation. This transformation, termed the Initial Burning Period, is documented in pollen and charcoal records, but its speed has been poorly constrained. High-resolution chronologies developed with a series of AMS radiocarbon dates from two lake sediment cores suggest the shift from forest to shrubland occurred within decades rather than centuries at drier sites. We examine two sites representing extreme examples of the magnitude of human impacts: a drier site that was inherently more vulnerable to human-set fires and a wetter, less burnable site. The astonishing rate of deforestation at the hands of small transient populations resulted from the intrinsic vulnerability of the native flora to fire and from positive feedbacks in post-fire vegetation recovery that increased landscape flammability. Spatially targeting burning in highly-flammable seral vegetation in forests rarely experiencing fire was sufficient to create an alternate fire-prone stable state. The New Zealand example illustrates how seemingly stable forest ecosystems can experience rapid and permanent conversions. Forest loss in New Zealand is among the fastest ecological transitions documented in the Holocene; yet equally rapid transitions can be expected in present-day regions wherever positive feedbacks support alternate fire-inhibiting, fire-prone stable states.

  19. Clusters of Factors Identify A High Prevalence of Pregnancy Involvement Among US Adolescent Males.

    Science.gov (United States)

    Lau, May; Lin, Hua; Flores, Glenn

    2015-08-01

    The study purpose was to use recursive partitioning analysis (RPA) to identify factors that, when clustered, are associated with a high prevalence of pregnancy involvement among US adolescent males. The National Survey of Family Growth is a nationally representative survey of individuals 15-44 years old. RPA was done for the 2002 and 2006-2010 cycles to identify factors which, when combined, identify adolescent males with the highest prevalence of pregnancy involvement. Pregnancy-involvement prevalence among adolescent males was 6 %. Two clusters of adolescent males have the highest pregnancy-involvement prevalence, at 84-87 %. In RPA, the highest pregnancy-involvement prevalence (87 %) was seen in adolescent males who ever HIV tested, had >4 lifetime sexual partners, reported less than an almost certain chance of feeling less physical pleasure with condom use, had an educational attainment of 4 lifetime sexual partners, reported less than an almost certain chance of feeling less physical pleasure with condom use, had an educational attainment ≥11th grade, were >17 years old, and had their first contraceptive education ≥10th grade, had a pregnancy-involvement prevalence of 84 %. Pregnancy-prevention efforts among adolescent males who have been involved in a pregnancy may need to target risk factors identified in clusters with the highest pregnancy prevalence to prevent subsequent pregnancies in these adolescent males and improve their future outcomes.

  20. Keeping Minorities Happy: Hierarchy Maintenance and Whites' Decreased Support for Highly Identified White Politicians.

    Science.gov (United States)

    Jun, Sora; Lowery, Brian S; Guillory, Lucia

    2017-08-01

    We test the hypothesis that, to avoid provoking minorities, Whites will withhold their support for White political candidates who are highly identified with their race. In Study 1, we found that White Republicans were less supportive of White candidates the higher the perceived White identity of the candidate due to beliefs that such candidates would provoke racial minorities. In Study 2, we replicated this effect with a manipulation of candidates' White identity. Study 3 found that Whites reported less support for high-identity candidates when they were led to believe that the hierarchy was unstable rather than stable. Consistent with our hypothesis that those who have the most to lose are most likely to avoid provoking minorities, in Study 4, we found that Whites with high subjective socioeconomic status (SES) varied their support for provocative White candidates as a function of hierarchy stability, whereas those with low subjective SES did not.

  1. Monitoring deep twist drilling for a rapid manufacturing of light high-strength parts

    Science.gov (United States)

    López de Lacalle, L. N.; Fernández, A.; Olvera, D.; Lamikiz, A.; Olvera, D.; Rodríguez, C.; Elias, A.

    2011-10-01

    In this work the manufacturing of high strength and/or high functional components is presented, using a new technique based on considerably long twist drills, called Deep Twist Drilling (DTD). This technology opens a rapid and economical method to manufacture parts for structural applications. Components made with this technique can reach high mass reduction and better stress distribution in comparison with welding or bolted parts with the same weight. However the application of DTD must be optimized to improve the reliability of the process and to make it economically feasible. In order to reach it, previous optimization by process monitoring was performed in AISI 1045, stainless steels, Ti6Al4V and nodular cat iron GGG70(AISI A536, SAE-ASTM 100-70-03). These materials are commonly used for structural applications in several sectors. Monitoring opened the way to improve cutting conditions and allow the application of the DTD technique focusing on a new design concept. In the same way monitoring makes drilling process reliable enough to be systematically used in industrial applications by a controlled increase of the performance demanded from the tool. In this manner, not only the objective to produce high-strength and light pieces is achieved, but also a high repetitive process is reached. In this research work a case of study is presented. A monolithic satellite-type component, its mass were reduced from 25 to 4.5 kg. The structural behavior of the component was studied under FEM analysis and the results showed high strength to compression and shear forces. During the machining of this element there was a serious risk of drill breakage due to the depth of the holes and crossing points between them; however, the previous process optimization eliminated this drawback. As a matter of fact, this paper brings out a good example where manufacturing technology allows a better performance of mechanical components within the philosophy of "new processes drive to new

  2. Rapid and high-throughput construction of microbial cell-factories with regulatory noncoding RNAs.

    Science.gov (United States)

    Chaudhary, Amit Kumar; Na, Dokyun; Lee, Eun Yeol

    2015-11-01

    Due to global crises such as pollution and depletion of fossil fuels, sustainable technologies based on microbial cell-factories have been garnering great interest as an alternative to chemical factories. The development of microbial cell-factories is imperative in cutting down the overall manufacturing cost. Thus, diverse metabolic engineering strategies and engineering tools have been established to obtain a preferred genotype and phenotype displaying superior productivity. However, these tools are limited to only a handful of genes with permanent modification of a genome and significant labor costs, and this is one of the bottlenecks associated with biofactory construction. Therefore, a groundbreaking rapid and high-throughput engineering tool is needed for efficient construction of microbial cell-factories. During the last decade, copious small noncoding RNAs (ncRNAs) have been discovered in bacteria. These are involved in substantial regulatory roles like transcriptional and post-transcriptional gene regulation by modulating mRNA elongation, stability, or translational efficiency. Because of their vulnerability, ncRNAs can be used as another layer of conditional control over gene expression without modifying chromosomal sequences, and hence would be a promising high-throughput tool for metabolic engineering. Here, we review successful design principles and applications of ncRNAs for high-throughput metabolic engineering or physiological studies of diverse industrially important microorganisms.

  3. Rapid ester biosynthesis screening reveals a high activity alcohol-O-acyltransferase (AATase) from tomato fruit.

    Science.gov (United States)

    Lin, Jyun-Liang; Zhu, Jie; Wheeldon, Ian

    2016-05-01

    Ethyl and acetate esters are naturally produced in various yeasts, plants, and bacteria. The biosynthetic pathways that produce these esters share a common reaction step, the condensation of acetyl/acyl-CoA with an alcohol by alcohol-O-acetyl/acyltransferase (AATase). Recent metabolic engineering efforts exploit AATase activity to produce fatty acid ethyl esters as potential diesel fuel replacements as well as short- and medium-chain volatile esters as fragrance and flavor compounds. These efforts have been limited by the lack of a rapid screen to quantify ester biosynthesis. Enzyme engineering efforts have also been limited by the lack of a high throughput screen for AATase activity. Here, we developed a high throughput assay for AATase activity and used this assay to discover a high activity AATase from tomato fruit, Solanum lycopersicum (Atf-S.l). Atf1-S.l exhibited broad specificity towards acyl-CoAs with chain length from C4 to C10 and was specific towards 1-pentanol. The AATase screen also revealed new acyl-CoA substrate specificities for Atf1, Atf2, Eht1, and Eeb1 from Saccharomyces cerevisiae, and Atf-C.m from melon fruit, Cucumis melo, thus increasing the pool of characterized AATases that can be used in ester biosynthesis of ester-based fragrance and flavor compounds as well as fatty acid ethyl ester biofuels.

  4. Rapid startup and high rate nitrogen removal from anaerobic sludge digester liquor using a SNAP process.

    Science.gov (United States)

    Qiao, Sen; Nishiyama, Takashi; Fujii, Tatsuo; Bhatti, Zafar; Furukawa, Kenji

    2012-02-01

    In this study, a single-stage autotrophic nitrogen removal reactor, packed with a novel acrylic fiber biomass carrier material (Biofix), was applied for nitrogen removal from sludge digester liquor. For rapid start-up, conventional activated sludge was added to the reactor soon after the attachment of anammox biomass on the Biofix carriers, which allowed conventional activated sludge to form a protective layer of biofilm around the anammox biomass. The Nitrogen removal efficiency reached 75% within 1 week at a nitrogen loading rate of 0.46 kg-N/m(3)/day for synthetic wastewater treatment. By the end of the synthetic wastewater treatment period, the maximum nitrogen removal rate had increased to 0.92 kg-N/m(3)/day at a nitrogen loading rate of 1.0 kg-N/m(3)/day. High nitrogen removal rate was also achieved during the actual raw digester liquor treatment with the highest nitrogen removal rate being 0.83 kg-N/m(3)/day at a nitrogen loading rate of 0.93 kg-N/m(3)/day. The thick biofilm on Biofix carriers allowed anammox bacteria to survive under high DO concentration of 5-6 mg/l resulting in stable and high nitrogen removal performance. FISH and CLSM analysis demonstrated that anammox bacteria coexisted and surrounded by ammonium oxidizing bacteria.

  5. A Rapid Microwave-Assisted Thermolysis Route to Highly Crystalline Carbon Nitrides for Efficient Hydrogen Generation.

    Science.gov (United States)

    Guo, Yufei; Li, Jing; Yuan, Yupeng; Li, Lu; Zhang, Mingyi; Zhou, Chenyan; Lin, Zhiqun

    2016-11-14

    Highly crystalline graphitic carbon nitride (g-C3 N4 ) with decreased structural imperfections benefits from the suppression of electron-hole recombination, which enhances its hydrogen generation activity. However, producing such g-C3 N4 materials by conventional heating in an electric furnace has proven challenging. Herein, we report on the synthesis of high-quality g-C3 N4 with reduced structural defects by judiciously combining the implementation of melamine-cyanuric acid (MCA) supramolecular aggregates and microwave-assisted thermolysis. The g-C3 N4 material produced after optimizing the microwave reaction time can effectively generate H2 under visible-light irradiation. The highest H2 evolution rate achieved was 40.5 μmol h(-1) , which is two times higher than that of a g-C3 N4 sample prepared by thermal polycondensation of the same supramolecular aggregates in an electric furnace. The microwave-assisted thermolysis strategy is simple, rapid, and robust, thereby providing a promising route for the synthesis of high-efficiency g-C3 N4 photocatalysts. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Gentamicin rapidly inhibits mitochondrial metabolism in high-frequency cochlear outer hair cells.

    Directory of Open Access Journals (Sweden)

    Heather C Jensen-Smith

    Full Text Available Aminoglycosides (AG, including gentamicin (GM, are the most frequently used antibiotics in the world and are proposed to cause irreversible cochlear damage and hearing loss (HL in 1/4 of the patients receiving these life-saving drugs. Akin to the results of AG ototoxicity studies, high-frequency, basal turn outer hair cells (OHCs preferentially succumb to multiple HL pathologies while inner hair cells (IHCs are much more resilient. To determine if endogenous differences in IHC and OHC mitochondrial metabolism dictate differential sensitivities to AG-induced HL, IHC- and OHC-specific changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH fluorescence during acute (1 h GM treatment were compared. GM-mediated decreases in NADH fluorescence and succinate dehydrogenase activity were observed shortly after GM application. High-frequency basal turn OHCs were found to be metabolically biased to rapidly respond to alterations in their microenvironment including GM and elevated glucose exposures. These metabolic biases may predispose high-frequency OHCs to preferentially produce cell-damaging reactive oxygen species during traumatic challenge. Noise-induced and age-related HL pathologies share key characteristics with AG ototoxicity, including preferential OHC loss and reactive oxygen species production. Data from this report highlight the need to address the role of mitochondrial metabolism in regulating AG ototoxicity and the need to illuminate how fundamental differences in IHC and OHC metabolism may dictate differences in HC fate during multiple HL pathologies.

  7. High VEGF with Rapid Growth and Early Metastasis in a Mouse Osteosarcoma Model

    Directory of Open Access Journals (Sweden)

    Shang-You Yang

    2007-01-01

    Full Text Available A murine model of osteosarcoma was developed to investigate the association between the expression of VEGF and the progression of osteosarcoma. Two human osteosarcoma cell lines with distinct VEGF expressions were introduced into proximal tibiae of immuno-deficient SCID mice, either by direct injection through the cortical bone or surgical exposing and drilling on the tibial metaphysis to seed tumor cells. Bone tumors were obvious on microCT within 4 weeks following osteosarcoma cell inoculation through surgical delivery. In contrast, direct injection without drilling often resulted in periosteal tumors. Although neoplasms were developed regardless of VEGF levels, orthotopic tumors derived from high VEGF-expressing cells were detected 2 weeks earlier on CT images than the ones from VEGF negative cells. At sacrifice, high VEGF tumors were distinctively larger in size and more frequently invaded the adjacent bone tissue. Multiple metastatic lesions were found in all the lung tissues at 8 weeks from high VEGF group, whereas only 1 of 7 VEGF negative tumors exhibited pulmonary metastasis. Overall, this model developed with the surgical tumor cell delivery results in histological and radiographic features more consistent with primary osteosarcoma. Interestingly, VEGF expression correlates with the early establishment, rapid tumor growth, and the development of pulmonary metastasis.

  8. An integrated microfluidic device for rapid and high-sensitivity analysis of circulating tumor cells

    Science.gov (United States)

    Jiang, Jianing; Zhao, Hui; Shu, Weiliang; Tian, Jing; Huang, Yuqing; Song, Yongxin; Wang, Ruoyu; Li, Encheng; Slamon, Dennis; Hou, Dongmei; Du, Xiaohui; Zhang, Lichuan; Chen, Yan; Wang, Qi

    2017-01-01

    Recently there has been a more focus on the development of an efficient technique for detection of circulating tumor cells (CTCs), due to their significance in prognosis and therapy of metastatic cancer. However, it remains a challenge because of the low count of CTCs in the blood. Herein, a rapid and high-sensitivity approach for CTCs detection using an integrated microfluidic system, consisting of a deterministic lateral displacement (DLD) isolating structure, an automatic purifying device with CD45-labeled immunomagnetic beads and a capturing platform coated with rat-tail collagen was reported. We observed high capture rate of 90%, purity of about 50% and viability of more than 90% at the high throughput of 1 mL/min by capturing green fluorescent protein (GFP)-positive cells from blood. Further capturing of CTCs from metastatic cancers patients revealed a positive capture rate of 83.3%. Furthermore, our device was compared with CellSearch system via parallel analysis of 30 cancer patients, to find no significant difference between the capture efficiency of both methods. However, our device displayed advantage in terms of time, sample volume and cost for analysis. Thus, our integrated device with sterile environment and convenient use will be a promising platform for CTCs detection with potential clinical application. PMID:28198402

  9. High-throughput screening to identify selective inhibitors of microbial sulfate reduction (and beyond)

    Science.gov (United States)

    Carlson, H. K.; Coates, J. D.; Deutschbauer, A. M.

    2015-12-01

    The selective perturbation of complex microbial ecosystems to predictably influence outcomes in engineered and industrial environments remains a grand challenge for geomicrobiology. In some industrial ecosystems, such as oil reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which is toxic, explosive and corrosive. Current strategies to selectively inhibit sulfidogenesis are based on non-specific biocide treatments, bio-competitive exclusion by alternative electron acceptors or sulfate-analogs which are competitive inhibitors or futile/alternative substrates of the sulfate reduction pathway. Despite the economic cost of sulfidogenesis, there has been minimal exploration of the chemical space of possible inhibitory compounds, and very little work has quantitatively assessed the selectivity of putative souring treatments. We have developed a high-throughput screening strategy to target SRM, quantitatively ranked the selectivity and potency of hundreds of compounds and identified previously unrecognized SRM selective inhibitors and synergistic interactions between inhibitors. Once inhibitor selectivity is defined, high-throughput characterization of microbial community structure across compound gradients and identification of fitness determinants using isolate bar-coded transposon mutant libraries can give insights into the genetic mechanisms whereby compounds structure microbial communities. The high-throughput (HT) approach we present can be readily applied to target SRM in diverse environments and more broadly, could be used to identify and quantify the potency and selectivity of inhibitors of a variety of microbial metabolisms. Our findings and approach are relevant for engineering environmental ecosystems and also to understand the role of natural gradients in shaping microbial niche space.

  10. Exome sequencing identifies potential risk variants for Mendelian disorders at high prevalence in Qatar.

    Science.gov (United States)

    Rodriguez-Flores, Juan L; Fakhro, Khalid; Hackett, Neil R; Salit, Jacqueline; Fuller, Jennifer; Agosto-Perez, Francisco; Gharbiah, Maey; Malek, Joel A; Zirie, Mahmoud; Jayyousi, Amin; Badii, Ramin; Al-Nabet Al-Marri, Ajayeb; Chouchane, Lotfi; Stadler, Dora J; Mezey, Jason G; Crystal, Ronald G

    2014-01-01

    Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for Mendelian disorders. Here, we demonstrate the value of the reverse approach, where we use exome sequencing of a sample of unrelated individuals to analyze allele frequencies of known causal mutations for Mendelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Qatari population (Q1 Bedouin, Q2 Persian-South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. These include variants not present in 1000 Genomes and variants at high frequency when compared with 1000 Genomes populations. Several of these Mendelian variants were only segregating in one Qatari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Qataris. Premarital genetic screening in Qatar tests for only four out of the 37, such that this study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance. © 2013 WILEY PERIODICALS, INC.

  11. A clinical model to identify patients with high-risk coronary artery disease.

    Science.gov (United States)

    Yang, Yelin; Chen, Li; Yam, Yeung; Achenbach, Stephan; Al-Mallah, Mouaz; Berman, Daniel S; Budoff, Matthew J; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Cheng, Victor Y; Chinnaiyan, Kavitha; Cury, Ricardo; Delago, Augustin; Dunning, Allison; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Jörg; Karlsberg, Ronald P; Kaufmann, Philipp A; Kim, Yong-Jin; Leipsic, Jonathon; LaBounty, Troy; Lin, Fay; Maffei, Erica; Raff, Gilbert L; Shaw, Leslee J; Villines, Todd C; Min, James K; Chow, Benjamin J W

    2015-04-01

    This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify those patients with and without high-risk coronary anatomy. Retrospective analysis of a prospectively collected multinational coronary computed tomographic angiography (CTA) cohort was conducted. High-risk anatomy was defined as left main diameter stenosis ≥50%, 3-vessel disease with diameter stenosis ≥70%, or 2-vessel disease involving the proximal left anterior descending artery. Using a cohort of 27,125, patients with a history of CAD, cardiac transplantation, and congenital heart disease were excluded. The model was derived from 24,251 consecutive patients in the derivation cohort and an additional 7,333 nonoverlapping patients in the validation cohort. The risk score consisted of 9 variables: age, sex, diabetes, hypertension, current smoking, hyperlipidemia, family history of CAD, history of peripheral vascular disease, and chest pain symptoms. Patients were divided into 3 risk categories: low (≤7 points), intermediate (8 to 17 points) and high (≥18 points). The model was statistically robust with area under the curve of 0.76 (95% confidence interval [CI]: 0.75 to 0.78) in the derivation cohort and 0.71 (95% CI: 0.69 to 0.74) in the validation cohort. Patients who scored ≤7 points had a low negative likelihood ratio (risk CAD was 1% in patients with ≤7 points and 16.7% in those with ≥18 points. We propose a scoring system, based on clinical variables, that can be used to identify patients at high and low pre-test probability of having high-risk CAD. Identification of these populations may detect those who may benefit from a trial of medical therapy and those who may benefit most from an invasive strategy. Copyright © 2015 American College of Cardiology Foundation. Published by

  12. Molecular characterization of a novel luteovirus from peach identified by high-throughput sequencing.

    Science.gov (United States)

    Wu, L-P; Liu, H-W; Bateman, M; Liu, Z; Li, R

    2017-05-26

    Contigs with sequence homologies to cherry-associated luteovirus were identified by high-throughput sequencing analysis in two peach accessions. Complete genomic sequences of the two isolates of this virus were determined to be 5,819 and 5,814 nucleotides long, respectively. The genome of the new virus is typical of luteoviruses, containing eight open reading frames in a very similar arrangement. Its genomic sequence is 58-74% identical to those of other members of the genus Luteovirus. These sequences thus belong to a new virus, which we have named "peach-associated luteovirus".

  13. Towards the high spin–isospin frontier using isotopically-identified fission fragments

    Energy Technology Data Exchange (ETDEWEB)

    Navin, A., E-mail: navin@ganil.fr [GANIL, CEA/DSM–CNRS/IN2P3, Bd Henri Becquerel, BP 55027, F-14076 Caen Cedex 5 (France); Rejmund, M.; Schmitt, C. [GANIL, CEA/DSM–CNRS/IN2P3, Bd Henri Becquerel, BP 55027, F-14076 Caen Cedex 5 (France); Bhattacharyya, S. [Variable Energy Cyclotron Centre, 1/AF Bidhan Nagar, Kolkata 700064 (India); Lhersonneau, G.; Van Isacker, P. [GANIL, CEA/DSM–CNRS/IN2P3, Bd Henri Becquerel, BP 55027, F-14076 Caen Cedex 5 (France); Caamaño, M. [USC, Universidad de Santiago de Compostela, E-15706 Santiago de Compostela (Spain); Clément, E.; Delaune, O.; Farget, F.; France, G. de; Jacquot, B. [GANIL, CEA/DSM–CNRS/IN2P3, Bd Henri Becquerel, BP 55027, F-14076 Caen Cedex 5 (France)

    2014-01-20

    Measurements of prompt γ rays in coincidence with isotopically-identified fission fragments, produced in collisions of {sup 238}U on a {sup 9}Be target, at an energy around the Coulomb barrier are reported. This technique provides simultaneous access to the spectroscopy of many nuclei, extending to very neutron-rich isotopes and fairly high angular momenta. The structural evolution of the neutron-rich zirconium isotopes is discussed in the light of the present measurements in {sup 105,106}Zr and in the context of the interacting boson model with a global parameterization that includes triaxiality but no shape coexistence.

  14. Rapid response of soil fungal communities to low and high intensity fire

    Science.gov (United States)

    Smith, Jane E.; Cowan, Ariel D.; Reazin, Chris; Jumpponen, Ari

    2016-04-01

    burned soils within one growing season. Community results from both burn treatments suggest an increase in patchy spatial distribution of EMF. The importance of incorporating mixed fire effects in fuel management practices will help to provide EMF refugia for dry forest regeneration. Our studies highlight the strong and rapid fungal community responses to fires and differences among fires of different severities. We theorize that quick initiation of EMF recolonization is possible depending on the size of high burn patches, proximity of low and unburned soil, and survival of nearby hosts.

  15. Human Adenine Nucleotide Translocase (ANT) Modulators Identified by High-Throughput Screening of Transgenic Yeast.

    Science.gov (United States)

    Zhang, Yujian; Tian, Defeng; Matsuyama, Hironori; Hamazaki, Takashi; Shiratsuchi, Takayuki; Terada, Naohiro; Hook, Derek J; Walters, Michael A; Georg, Gunda I; Hawkinson, Jon E

    2016-04-01

    Transport of ADP and ATP across mitochondria is one of the primary points of regulation to maintain cellular energy homeostasis. This process is mainly mediated by adenine nucleotide translocase (ANT) located on the mitochondrial inner membrane. There are four human ANT isoforms, each having a unique tissue-specific expression pattern and biological function, highlighting their potential as drug targets for diverse clinical indications, including male contraception and cancer. In this study, we present a novel yeast-based high-throughput screening (HTS) strategy to identify compounds inhibiting the function of ANT. Yeast strains generated by deletion of endogenous proteins with ANT activity followed by insertion of individual human ANT isoforms are sensitive to cell-permeable ANT inhibitors, which reduce proliferation. Screening hits identified in the yeast proliferation assay were characterized in ADP/ATP exchange assays employing recombinant ANT isoforms expressed in isolated yeast mitochondria and Lactococcus lactis as well as by oxygen consumption rate in mammalian cells. Using this approach, closantel and CD437 were identified as broad-spectrum ANT inhibitors, whereas leelamine was found to be a modulator of ANT function. This yeast "knock-out/knock-in" screening strategy is applicable to a broad range of essential molecular targets that are required for yeast survival. © 2016 Society for Laboratory Automation and Screening.

  16. Validation of a Predictive Model to Identify Patients at High Risk for Hospital Readmission.

    Science.gov (United States)

    Spiva, LeeAnna; Hand, Marti; VanBrackle, Lewis; McVay, Frank

    2016-01-01

    Hospital readmission is an adverse patient outcome that is serious, common, and costly. For hospitals, identifying patients at risk for hospital readmission is a priority to reduce costs and improve care. The purposes were to validate a predictive algorithm to identify patients at a high risk for preventable hospital readmission within 30 days after discharge and determine if additional risk factors enhance readmission predictability. A retrospective study was conducted on a randomized sample of 598 patients discharged from a Southeast community hospital. Data were collected from the organization's database and manually abstracted from the electronic medical record using a structured tool. Two separate logistic regression models were fit for the probability of readmission within 30 days after discharge. The first model used the LACE index as the predictor variable, and the second model used the LACE index with additional risk factors. The two models were compared to determine if additional risk factors increased the model's predictive ability. The results indicate both models have reasonable prognostic capability. The LACE index with additional risk factors did little to improve prognostication, while adding to the model's complexity. Findings support the use of the LACE index as a practical tool to identify patients at risk for readmission.

  17. High Throughput Screening Identifies a Novel Compound Protecting Cardiomyocytes from Doxorubicin-Induced Damage

    Directory of Open Access Journals (Sweden)

    Szabolcs Gergely

    2015-01-01

    Full Text Available Antracyclines are effective antitumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors. Application of these drugs is limited by their cardiotoxic effect, which is determined by a lifetime cumulative dose. We set out to identify by high throughput screening cardioprotective compounds protecting cardiomyocytes from doxorubicin-induced injury. Ten thousand compounds of ChemBridge’s DIVERSet compound library were screened to identify compounds that can protect H9C2 rat cardiomyocytes against doxorubicin-induced cell death. The most effective compound proved protective in doxorubicin-treated primary rat cardiomyocytes and was further characterized to demonstrate that it significantly decreased doxorubicin-induced apoptotic and necrotic cell death and inhibited doxorubicin-induced activation of JNK MAP kinase without having considerable radical scavenging effect or interfering with the antitumor effect of doxorubicin. In fact the compound identified as 3-[2-(4-ethylphenyl-2-oxoethyl]-1,2-dimethyl-1H-3,1-benzimidazol-3-ium bromide was toxic to all tumor cell lines tested even without doxorubicine treatment. This benzimidazole compound may lead, through further optimalization, to the development of a drug candidate protecting the heart from doxorubicin-induced injury.

  18. The primary motor area for voluntary diaphragmatic motion identified by high field fMRI.

    Science.gov (United States)

    Nakayama, Takahiro; Fujii, Yukihiko; Suzuki, Kiyotaka; Kanazawa, Ichiro; Nakada, Tsutomu

    2004-06-01

    In order to identify the precise location of the primary motor area for the diaphragm with respect to the classical motor homunculus, functional magnetic resonance imaging (fMRI) experiments were performed utilizing independent component-cross correlation- sequential epoch (ICS) analysis on a high-field (3.0 Tesla) system. Activations which correlated with voluntary diaphragmatic motion mapped onto the area anterolateral to that for voluntary hand motion (internal control in ICS analysis). Multiple subject analysis yielded the primary motor cortex for the diaphragm to be (+/-48, -4, 47) in the Talairach and Tournoux coordinates. The results were highly consistent with the previously reported cortical area for the diaphragm determined by transcranial electrical/magnetic stimulation.

  19. Identifying fade mechanisms in high-power lithium-ion cells.

    Energy Technology Data Exchange (ETDEWEB)

    Abraham, D. P.; Knuth, J.; Dees, D. W.; Jansen, A. N.; Sammann, E.; Haasch, R.; Twesten, R. D.; MacLaren, S.; Chemical Engineering; Univ. of Illinois

    2004-01-01

    Hybrid electric vehicles (HEV) need long-lived high-power batteries as energy storage devices. Batteries based on lithium-ion technology can meet the high-power goals but have been unable to meet HEV calendar-life requirements. As part of the US Department of Energy's Advanced Technology Development (ATD) Program, diagnostic studies are being conducted on 18650-type lithium-ion cells that were subjected to accelerated aging tests at temperatures ranging from 40 to 70 C. This article summarizes data obtained by gas chromatography, liquid chromatography, electron microscopy, X-ray spectroscopy and electrochemical techniques, and identifies cell components that are responsible for the observed impedance rise and power fade.

  20. High Volume Throughput Computing: Identifying and Characterizing Throughput Oriented Workloads in Data Centers

    CERN Document Server

    Zhan, Jianfeng; Sun, Ninghui; Wang, Lei; Jia, Zhen; Luo, Chunjie

    2012-01-01

    For the first time, this paper systematically identifies three categories of throughput oriented workloads in data centers: services, data processing applications, and interactive real-time applications, whose targets are to increase the volume of throughput in terms of processed requests or data, or supported maximum number of simultaneous subscribers, respectively, and we coins a new term high volume throughput computing (in short HVC) to describe those workloads and data center systems designed for them. We characterize and compare HVC with other computing paradigms, e.g., high throughput computing, warehouse-scale computing, and cloud computing, in terms of levels, workloads, metrics, coupling degree, data scales, and number of jobs or service instances. We also preliminarily report our ongoing work on the metrics and benchmarks for HVC systems, which is the foundation of designing innovative data center systems for HVC workloads.

  1. Hypertrophic cardiomyopathy: Can the noninvasive diagnostic testing identify high risk patients?

    Institute of Scientific and Technical Information of China (English)

    Li; Zhang; Obinna; Mmagu; Liwen; Liu; Dayuan; Li; Yuxin; Fan; Adrian; Baranchuk; Peter; R; Kowey

    2014-01-01

    Hypertrophic cardiomyopathy(HCM) is the most common cause of sudden cardiac death(SCD) in the young, particularly among athletes. Identifying high risk individuals is very important for SCD prevention. The purpose of this review is to stress that noninvasive diagnostic testing is important for risk assessment. Extreme left ventricular hypertrophy and documented ventricular tachycardia and fibrillation increase the risk of SCD. Fragmented QRS and T wave inversion in multiple leads are more common in high risk patients. Cardiac magnetic resonance imaging provides complete visualization of the left ventricular chamber, allowing precise localization of the distribution of hypertrophy and measurement of wall thickness and cardiac mass. Moreover, with late gadolinium enhancement, patchy myocardial fibrosis within the area of hypertrophy can be detected, which is also helpful in risk stratification. Genetic testing is encouraged in all cases, especially in those with a family history of HCM and SCD.

  2. Microstructure and high temperature mechanical properties of laser rapidly formed Ti-6Al-4V alloy

    Institute of Scientific and Technical Information of China (English)

    XUE Lei; CHEN Jing; LIN Xin; LU Xiao-wei; WANG Wei; HUANG Wei-dong

    2006-01-01

    Several tensile samples were prepared using laser rapid forming (LRF) with Ti-6Al-4V alloy as powder material, and the samples were annealed. The microstructure and high temperature mechanical properties of laser formed Ti-6Al-4V alloy through annealing treatment were investigated. The short-term and long-term tensile tests at 350 ℃ were performed. The results show that the microstructure of LRF samples consists of the large columnar prior β grains which grow epitaxially from the substrate along the deposition direction. There are Widmanst-tten α laths in prior β grains, but α laths in annealed microstructure are coarser, and their aspect ratio is lower than that in as-deposited microstructure. In addition, the prior β grain boundary is also coarsened and broken off through the annealing treatment. The high temperature mechanical properties of the annealed LRF samples exceed those of casting alloy significantly, especially the stress-rupture lifetime reaches 661.7 h even while the test stress increases from initial value of 490 MPa to the final stress of 800 MPa gradually.

  3. Rapid and efficient cancer cell killing mediated by high-affinity death receptor homotrimerizing TRAIL variants.

    Science.gov (United States)

    Reis, C R; van der Sloot, A M; Natoni, A; Szegezdi, E; Setroikromo, R; Meijer, M; Sjollema, K; Stricher, F; Cool, R H; Samali, A; Serrano, L; Quax, W J

    2010-10-21

    The tumour necrosis factor family member TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in a variety of cancer cells through the activation of death receptors 4 (DR4) and 5 (DR5) and is considered a promising anticancer therapeutic agent. As apoptosis seems to occur primarily via only one of the two death receptors in many cancer cells, the introduction of DR selectivity is thought to create more potent TRAIL agonists with superior therapeutic properties. By use of a computer-aided structure-based design followed by rational combination of mutations, we obtained variants that signal exclusively via DR4. Besides an enhanced selectivity, these TRAIL-DR4 agonists show superior affinity to DR4, and a high apoptosis-inducing activity against several TRAIL-sensitive and -resistant cancer cell lines in vitro. Intriguingly, combined treatment of the DR4-selective variant and a DR5-selective TRAIL variant in cancer cell lines signalling by both death receptors leads to a significant increase in activity when compared with wild-type rhTRAIL or each single rhTRAIL variant. Our results suggest that TRAIL induced apoptosis via high-affinity and rapid-selective homotrimerization of each DR represent an important step towards an efficient cancer treatment.

  4. A high-precision chronology for the rapid extinction of New Zealand moa (Aves, Dinornithiformes)

    Science.gov (United States)

    Perry, George L. W.; Wheeler, Andrew B.; Wood, Jamie R.; Wilmshurst, Janet M.

    2014-12-01

    Megafaunal extinction followed the prehistoric human settlement of islands across the globe, but the exact duration and dynamics of the extinction processes are difficult to determine. The New Zealand moa (Aves, Dinornithiformes) are a prime example, where, despite an extensive fossil and archaeological record, debate continues about their extinction chronology and how extinction timings varied among regions and species. We apply probabilistic sightings methods to 111 high-quality radiocarbon dates (from a pool of 653 dates) on moa remains from natural and archaeological sites to provide a high-resolution spatio-temporal chronology of moa extinction. We interpret this alongside an estimated time for the onset of hunting pressure, obtained by applying the same methods to the most reliable proxies for initial human settlement of New Zealand: coprolites of and seeds gnawed by the commensal Pacific rat (Rattus exulans). By comparing local and national extinction times, we discriminate between the point at which hunting stopped (economic extinction) and the total extinction of moa (ca 150 and 200 years after settlement, respectively). Extinction occurred contemporaneously at sites separated by hundreds of kilometres. There was little difference between the extinction times of the smallest (20-50 kg) and largest (200+ kg) moa species. Our results demonstrate how rapidly megafauna were exterminated from even large, topographically- and ecologically-diverse islands such as New Zealand, and highlight the fragility of such ecosystems in the face of human impacts.

  5. A rapid relativistic distorted wave approach for calculating cross sections for ionization of highly charged ions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hong Lin; Sampson, D.H. (Pennsylvania State Univ., University Park, PA (USA). Dept. of Astronomy)

    1990-10-22

    The rapid relativistic distorted wave method of Zhang et al for excitation, which uses the atomic structure data of Sampson et al, has been extended to ionization. In this approach the same Dirac-Fock-Slater potential evaluated using a single mean configuration is used in calculating the orbitals of all electrons bound and free. Values for the cross sections Q for ionization of various ions have been calculated and generally good agreement is obtained with other recent relativistic calculations. When results are expressed in terms of the reduced ionization cross section Q{sub R}, which is proportional to I{sup 2}Q, they are close to the non-relativistic Coulomb-Born-Exchange values of Moores et al for hydrogenic ions except for high Z and/or high energies. This suggests that fits of the Q{sub R} to simple functions of the impact electron energy in threshold units with coefficients that are quite slowly varying functions of an effective Z can probably be made. This would be convenient for plasma modeling applications. 24 refs., 2 tabs.

  6. Rapid relativistic distorted-wave approach for calculating cross sections for ionization of highly charged ions

    Science.gov (United States)

    Zhang, Hong Lin; Sampson, Douglas H.

    1990-11-01

    The rapid relativistic distorted-wave method of Zhang, Sampson, and Mohanty [Phys. Rev. A 40, 616 (1989)] for excitation, which uses the atomic-structure data of Sampson et al. [Phys. Rev. A 40, 604 (1989)], has been extended to ionization. In this approach the same Dirac-Fock-Slater potential evaluated using a single mean configuration is used in calculating the orbitals of all electrons bound and free. Values for the cross sections Q for ionization of various ions have been calculated, and generally good agreement is obtained with other recent relativistic calculations. When results are expressed in terms of the reduced ionization cross section QR, which is proportional to I2Q, they are close to the nonrelativistic Coulomb-Born-exchange values of Moores, Golden, and Sampson [J. Phys. B 13, 385 (1980)] for hydrogenic ions except for high Z and/or high energies. This suggests that fits of the QR to simple functions of the impact electron energy in threshold units with coefficients that are quite slowly varying functions of an effective Z can probably be made. This would be convenient for plasma-modeling applications.

  7. Rapid, High-Resolution Forest Structure and Terrain Mapping over Large Areas using Single Photon Lidar.

    Science.gov (United States)

    Swatantran, Anu; Tang, Hao; Barrett, Terence; DeCola, Phil; Dubayah, Ralph

    2016-06-22

    Single photon lidar (SPL) is an innovative technology for rapid forest structure and terrain characterization over large areas. Here, we evaluate data from an SPL instrument - the High Resolution Quantum Lidar System (HRQLS) that was used to map the entirety of Garrett County in Maryland, USA (1700 km(2)). We develop novel approaches to filter solar noise to enable the derivation of forest canopy structure and ground elevation from SPL point clouds. SPL attributes are compared with field measurements and an existing leaf-off, low-point density discrete return lidar dataset as a means of validation. We find that canopy and ground characteristics from SPL are similar to discrete return lidar despite differences in wavelength and acquisition periods but the higher point density of the SPL data provides more structural detail. Our experience suggests that automated noise removal may be challenging, particularly over high albedo surfaces and rigorous instrument calibration is required to reduce ground measurement biases to accepted mapping standards. Nonetheless, its efficiency of data collection, and its ability to produce fine-scale, three-dimensional structure over large areas quickly strongly suggests that SPL should be considered as an efficient and potentially cost-effective alternative to existing lidar systems for large area mapping.

  8. Rapid, High-Resolution Forest Structure and Terrain Mapping over Large Areas using Single Photon Lidar

    Science.gov (United States)

    Swatantran, Anu; Tang, Hao; Barrett, Terence; Decola, Phil; Dubayah, Ralph

    2016-06-01

    Single photon lidar (SPL) is an innovative technology for rapid forest structure and terrain characterization over large areas. Here, we evaluate data from an SPL instrument - the High Resolution Quantum Lidar System (HRQLS) that was used to map the entirety of Garrett County in Maryland, USA (1700 km2). We develop novel approaches to filter solar noise to enable the derivation of forest canopy structure and ground elevation from SPL point clouds. SPL attributes are compared with field measurements and an existing leaf-off, low-point density discrete return lidar dataset as a means of validation. We find that canopy and ground characteristics from SPL are similar to discrete return lidar despite differences in wavelength and acquisition periods but the higher point density of the SPL data provides more structural detail. Our experience suggests that automated noise removal may be challenging, particularly over high albedo surfaces and rigorous instrument calibration is required to reduce ground measurement biases to accepted mapping standards. Nonetheless, its efficiency of data collection, and its ability to produce fine-scale, three-dimensional structure over large areas quickly strongly suggests that SPL should be considered as an efficient and potentially cost-effective alternative to existing lidar systems for large area mapping.

  9. The Formation of Rapidly Rotating Black Holes in High-mass X-Ray Binaries

    Science.gov (United States)

    Batta, Aldo; Ramirez-Ruiz, Enrico; Fryer, Chris

    2017-09-01

    High-mass X-ray binaries (HMXRBs), such as Cygnus X-1, host some of the most rapidly spinning black holes (BHs) known to date, reaching spin parameters a≳ 0.84. However, there are several effects that can severely limit the maximum BH spin parameter that could be obtained from direct collapse, such as tidal synchronization, magnetic core-envelope coupling, and mass loss. Here, we propose an alternative scenario where the BH is produced by a failed supernova (SN) explosion that is unable to unbind the stellar progenitor. A large amount of fallback material ensues, whose interaction with the secondary naturally increases its overall angular momentum content, and therefore the spin of the BH when accreted. Through SPH hydrodynamic simulations, we studied the unsuccessful explosion of an 8 {M}ȯ pre-SN star in a close binary with a 12 {M}ȯ companion with an orbital period of ≈1.2 days, finding that it is possible to obtain a BH with a high spin parameter a≳ 0.8 even when the expected spin parameter from direct collapse is a≲ 0.3. This scenario also naturally explains the atmospheric metal pollution observed in HMXRB stellar companions.

  10. Rapid high-throughput cloning and stable expression of antibodies in HEK293 cells.

    Science.gov (United States)

    Spidel, Jared L; Vaessen, Benjamin; Chan, Yin Yin; Grasso, Luigi; Kline, J Bradford

    2016-12-01

    Single-cell based amplification of immunoglobulin variable regions is a rapid and powerful technique for cloning antigen-specific monoclonal antibodies (mAbs) for purposes ranging from general laboratory reagents to therapeutic drugs. From the initial screening process involving small quantities of hundreds or thousands of mAbs through in vitro characterization and subsequent in vivo experiments requiring large quantities of only a few, having a robust system for generating mAbs from cloning through stable cell line generation is essential. A protocol was developed to decrease the time, cost, and effort required by traditional cloning and expression methods by eliminating bottlenecks in these processes. Removing the clonal selection steps from the cloning process using a highly efficient ligation-independent protocol and from the stable cell line process by utilizing bicistronic plasmids to generate stable semi-clonal cell pools facilitated an increased throughput of the entire process from plasmid assembly through transient transfections and selection of stable semi-clonal cell pools. Furthermore, the time required by a single individual to clone, express, and select stable cell pools in a high-throughput format was reduced from 4 to 6months to only 4 to 6weeks. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Rapid hybrid encoding for high-resolution whole-brain fluid-attenuated imaging.

    Science.gov (United States)

    Lee, Hoonjae; Sohn, Chul-Ho; Park, Jaeseok

    2013-12-01

    Single-slab three-dimensional (3D) turbo spin-echo (TSE) imaging combined with inversion recovery (IR), which employs short, spatially non-selective refocusing pulses and signal prescription based variable refocusing flip angles (VFA) to increase imaging efficiency, was recently introduced to produce fluid-attenuated brain images for lesion detection. Despite the advantages, the imaging efficiency in this approach still remains limited because a substantially long time of inversion is needed to selectively suppress the signal intensity of cerebrospinal fluid (CSF) while fully recovering that of brain tissues. The purpose of this work is to develop a novel, rapid hybrid encoding method for highly efficient whole-brain fluid-attenuated imaging. In each time of repetition, volumetric data are continuously encoded using the hybrid modular acquisition in a sequential fashion even during IR signal transition, wherein reversed fast imaging with steady-state free precession (PSIF) is employed to encode intermediate-to-high spatial frequency signals prior to CSF nulling, while VFA-TSE is used to collect low-to-intermediate spatial frequency signals afterwards. Gradient-induced spin de-phasing between a pair of neighboring radio-frequency (RF) pulses in both PSIF and TSE modules is kept identical to avoid the occurrence of multiple echoes in a single acquisition window. Additionally, a two-step, alternate RF phase-cycling scheme is employed in the low spatial frequency region to eliminate free induction decay induced edge artifacts. Numerical simulations of the Bloch equations were performed to evaluate signal evolution of brain tissues along the echo train while optimizing imaging parameters. In vivo studies demonstrate that the proposed technique produces high-resolution isotropic fluid-attenuated whole-brain images in a clinically acceptable imaging time with substantially high signal-to-noise ratio for white matter while retaining lesion conspicuity.

  12. [Predicting individual risk of high healthcare cost to identify complex chronic patients].

    Science.gov (United States)

    Coderch, Jordi; Sánchez-Pérez, Inma; Ibern, Pere; Carreras, Marc; Pérez-Berruezo, Xavier; Inoriza, José M

    2014-01-01

    To develop a predictive model for the risk of high consumption of healthcare resources, and assess the ability of the model to identify complex chronic patients. A cross-sectional study was performed within a healthcare management organization by using individual data from 2 consecutive years (88,795 people). The dependent variable consisted of healthcare costs above the 95th percentile (P95), including all services provided by the organization and pharmaceutical consumption outside of the institution. The predictive variables were age, sex, morbidity-based on clinical risk groups (CRG)-and selected data from previous utilization (use of hospitalization, use of high-cost drugs in ambulatory care, pharmaceutical expenditure). A univariate descriptive analysis was performed. We constructed a logistic regression model with a 95% confidence level and analyzed sensitivity, specificity, positive predictive values (PPV), and the area under the ROC curve (AUC). Individuals incurring costs >P95 accumulated 44% of total healthcare costs and were concentrated in ACRG3 (aggregated CRG level 3) categories related to multiple chronic diseases. All variables were statistically significant except for sex. The model had a sensitivity of 48.4% (CI: 46.9%-49.8%), specificity of 97.2% (CI: 97.0%-97.3%), PPV of 46.5% (CI: 45.0%-47.9%), and an AUC of 0.897 (CI: 0.892 to 0.902). High consumption of healthcare resources is associated with complex chronic morbidity. A model based on age, morbidity, and prior utilization is able to predict high-cost risk and identify a target population requiring proactive care. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  13. High-Throughput Chemical Screens Identify Disulfiram as an Inhibitor of Human Glioblastoma Stem Cells

    Science.gov (United States)

    Hothi, Parvinder; Martins, Timothy J.; Chen, LiPing; Deleyrolle, Loic; Yoon, Jae-Geun; Reynolds, Brent; Foltz, Greg

    2012-01-01

    Glioblastoma Multiforme (GBM) continues to have a poor patient prognosis despite optimal standard of care. Glioma stem cells (GSCs) have been implicated as the presumed cause of tumor recurrence and resistance to therapy. With this in mind, we screened a diverse chemical library of 2,000 compounds to identify therapeutic agents that inhibit GSC proliferation and therefore have the potential to extend patient survival. High-throughput screens (HTS) identified 78 compounds that repeatedly inhibited cellular proliferation, of which 47 are clinically approved for other indications and 31 are experimental drugs. Several compounds (such as digitoxin, deguelin, patulin and phenethyl caffeate) exhibited high cytotoxicity, with half maximal inhibitory concentrations (IC50) in the low nanomolar range. In particular, the FDA approved drug for the treatment of alcoholism, disulfiram (DSF), was significantly potent across multiple patient samples (IC50 of 31.1 nM). The activity of DSF was potentiated by copper (Cu), which markedly increased GSC death. DSF–Cu inhibited the chymotrypsin-like proteasomal activity in cultured GSCs, consistent with inactivation of the ubiquitin-proteasome pathway and the subsequent induction of tumor cell death. Given that DSF is a relatively non-toxic drug that can penetrate the blood-brain barrier, we suggest that DSF should be tested (as either a monotherapy or as an adjuvant) in pre-clinical models of human GBM. Data also support targeting of the ubiquitin-proteasome pathway as a therapeutic approach in the treatment of GBM. PMID:23165409

  14. High resolution modeling of agricultural nitrogen to identify private wells susceptible to nitrate contamination.

    Science.gov (United States)

    Hoppe, Brendalynn; White, Denis; Harding, Anna; Mueller-Warrant, George; Hope, Bruce; Main, Eric

    2014-12-01

    Given the lack of data on private wells, public health and water quality specialists must explore alternative datasets for understanding associated exposures and health risks. Characterizing agricultural nitrogen inputs would be valuable for identifying areas where well water safety may be compromised. This study incorporated existing methods for estimating nutrient loading at the county level with datasets derived from a state permitting program for confined animal feeding operations and agricultural enterprise budget worksheets to produce a high resolution agricultural nitrogen raster map. This map was combined with data on soil leachability and new well locations. An algorithm was developed to calculate nitrogen loading and leachability within 1,000 meters of each well. Wells with a nonzero nitrogen total linked to soils with high leachability were categorized and displayed on maps communicating well susceptibility across the state of Oregon. Results suggest that 4% of recently drilled wells may be susceptible to nitrate contamination, while areas identified for mitigation are too restrictive to include all susceptible wells. Predicted increases in population density and the steady addition of approximately 3,800 new wells annually may lead to a large number of residents, especially those in rural areas, experiencing long-term exposures to nitrate in drinking water.

  15. High expression of CD26 accurately identifies human bacteria-reactive MR1-restricted MAIT cells.

    Science.gov (United States)

    Sharma, Prabhat K; Wong, Emily B; Napier, Ruth J; Bishai, William R; Ndung'u, Thumbi; Kasprowicz, Victoria O; Lewinsohn, Deborah A; Lewinsohn, David M; Gold, Marielle C

    2015-07-01

    Mucosa-associated invariant T (MAIT) cells express the semi-invariant T-cell receptor TRAV1-2 and detect a range of bacteria and fungi through the MHC-like molecule MR1. However, knowledge of the function and phenotype of bacteria-reactive MR1-restricted TRAV1-2(+) MAIT cells from human blood is limited. We broadly characterized the function of MR1-restricted MAIT cells in response to bacteria-infected targets and defined a phenotypic panel to identify these cells in the circulation. We demonstrated that bacteria-reactive MR1-restricted T cells shared effector functions of cytolytic effector CD8(+) T cells. By analysing an extensive panel of phenotypic markers, we determined that CD26 and CD161 were most strongly associated with these T cells. Using FACS to sort phenotypically defined CD8(+) subsets we demonstrated that high expression of CD26 on CD8(+)  TRAV1-2(+) cells identified with high specificity and sensitivity, bacteria-reactive MR1-restricted T cells from human blood. CD161(hi) was also specific for but lacked sensitivity in identifying all bacteria-reactive MR1-restricted T cells, some of which were CD161(dim) . Using cell surface expression of CD8, TRAV1-2, and CD26(hi) in the absence of stimulation we confirm that bacteria-reactive T cells are lacking in the blood of individuals with active tuberculosis and are restored in the blood of individuals undergoing treatment for tuberculosis.

  16. Rapid 96-well plates DNA extraction and sequencing procedures to identify genome-wide transposon insertion sites in a difficult to lyse bacterium: Lactobacillus casei.

    Science.gov (United States)

    Scornec, Hélène; Tichit, Magali; Bouchier, Christiane; Pédron, Thierry; Cavin, Jean-François; Sansonetti, Philippe J; Licandro-Seraut, Hélène

    2014-11-01

    Random transposon mutagenesis followed by adequate screening methods is an unavoidable procedure to characterize genetics of bacterial adaptation to environmental changes. We have recently constructed a mutant library of Lactobacillus casei and we aimed to fully annotate it. However, we have observed that, for L. casei which is a difficult to lyse bacterium, methods used to identify the transposon insertion site in a few mutants (transposon rescue by restriction and recircularization or PCR-based methods) were not transposable for a larger number because they are too time-consuming and sometimes not reliable. Here, we describe a method for large-scale and reliable identification of transposon insertion sites in a L. casei mutant library of 9250 mutants. DNA extraction procedure based on silica membranes in 96-column format was optimized to obtain genomic DNA from a large number of mutants. Then reliable direct genomic sequencing was improved to fit the obtained genomic DNA extracts. Using this procedure, readable and identifiable sequences were obtained for 87% of the L. casei mutants. This method extends the applications of a library of this type, reduces the number of insertions needed to be screened, and allows selection of specific mutants from an arrayed and stored mutant library. This method is applicable to any already existing mutant library (obtained by transposon or insertional mutagenesis) and could be useful for other bacterial species, especially for highly lysis-resistant bacteria species such as lactic acid bacteria. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Surrogate models for identifying robust, high yield regions of parameter space for ICF implosion simulations

    Science.gov (United States)

    Humbird, Kelli; Peterson, J. Luc; Brandon, Scott; Field, John; Nora, Ryan; Spears, Brian

    2016-10-01

    Next-generation supercomputer architecture and in-transit data analysis have been used to create a large collection of 2-D ICF capsule implosion simulations. The database includes metrics for approximately 60,000 implosions, with x-ray images and detailed physics parameters available for over 20,000 simulations. To map and explore this large database, surrogate models for numerous quantities of interest are built using supervised machine learning algorithms. Response surfaces constructed using the predictive capabilities of the surrogates allow for continuous exploration of parameter space without requiring additional simulations. High performing regions of the input space are identified to guide the design of future experiments. In particular, a model for the yield built using a random forest regression algorithm has a cross validation score of 94.3% and is consistently conservative for high yield predictions. The model is used to search for robust volumes of parameter space where high yields are expected, even given variations in other input parameters. Surrogates for additional quantities of interest relevant to ignition are used to further characterize the high yield regions. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, Lawrence Livermore National Security, LLC. LLNL-ABS-697277.

  18. High throughput atmospheric pressure plasma-induced graft polymerization for identifying protein-resistant surfaces.

    Science.gov (United States)

    Gu, Minghao; Kilduff, James E; Belfort, Georges

    2012-02-01

    Three critical aspects of searching for and understanding how to find highly resistant surfaces to protein adhesion are addressed here with specific application to synthetic membrane filtration. They include the (i) discovery of a series of previously unreported monomers from a large library of monomers with high protein resistance and subsequent low fouling characteristics for membrane ultrafiltration of protein-containing fluids, (ii) development of a new approach to investigate protein-resistant mechanisms from structure-property relationships, and (iii) adaptation of a new surface modification method, called atmospheric pressure plasma-induced graft polymerization (APP), together with a high throughput platform (HTP), for low cost vacuum-free synthesis of anti-fouling membranes. Several new high-performing chemistries comprising two polyethylene glycol (PEG), two amines and one zwitterionic monomers were identified from a library (44 commercial monomers) of five different classes of monomers as strong protein-resistant monomers. Combining our analysis here, using the Hansen solubility parameters (HSP) approach, and data from the literature, we conclude that strong interactions with water (hydrogen bonding) and surface flexibility are necessary for producing the highest protein resistance. Superior protein-resistant surfaces and subsequent anti-fouling performance was obtained with the HTP-APP as compared with our earlier HTP-photo graft-induced polymerization (PGP).

  19. Hypercellularity Components of Glioblastoma Identified by High b-Value Diffusion-Weighted Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pramanik, Priyanka P. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Parmar, Hemant A. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Mammoser, Aaron G.; Junck, Larry R. [Department of Neurology, University of Michigan, Ann Arbor, Michigan (United States); Kim, Michelle M.; Tsien, Christina I.; Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue, E-mail: yuecao@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States)

    2015-07-15

    Purpose: Use of conventional magnetic resonance imaging (MRI) for target definition may expose glioblastomas (GB) to inadequate radiation dose coverage of the nonenhanced hypercellular subvolume. This study aimed to develop a technique to identify the hypercellular components of GB by using high b-value diffusion-weighted imaging (DWI) and to investigate its relationship with the prescribed 95% isodose volume (PDV) and progression-free survival (PFS). Methods and Materials: Twenty-one patients with GB underwent chemoradiation therapy post-resection and biopsy. Radiation therapy (RT) treatment planning was based upon conventional MRI. Pre-RT DWIs were acquired in 3 orthogonal directions with b-values of 0, 1000, and 3000 s/mm{sup 2}. Hypercellularity volume (HCV) was defined on the high b-value (3000 s/mm{sup 2}) DWI by a threshold method. Nonenhanced signified regions not covered by the Gd-enhanced gross tumor volume (GTV-Gd) on T1-weighted images. The PDV was used to evaluate spatial coverage of the HCV by the dose plan. Association between HCV and PFS or other clinical covariates were assessed using univariate proportional hazards regression models. Results: HCVs and nonenhanced HCVs varied from 0.58 to 67 cm{sup 3} (median: 9.8 cm{sup 3}) and 0.15 to 60 cm{sup 3} (median: 2.5 cm{sup 3}), respectively. Fourteen patients had incomplete dose coverage of the HCV, 6 of whom had >1 cm{sup 3} HCV missed by the 95% PDV (range: 1.01-25.4 cm{sup 3}). Of the 15 patients who progressed, 5 progressed earlier, within 6 months post-RT, and 10 patients afterward. Pre-RT HCVs within recurrent GTVs-Gd were 78% (range: 65%-89%) for the 5 earliest progressions but lower, 53% (range: 0%-85%), for the later progressions. HCV and nonenhanced HCV were significant negative prognostic indicators for PFS (P<.002 and P<.01, respectively). The hypercellularity subvolume not covered by the 95% PDV was a significant negative predictor for PFS (P<.05). Conclusions: High b-value DWI

  20. Rapid diagnostic test supply chain and consumption study in Cabo Delgado, Mozambique: estimating stock shortages and identifying drivers of stock-outs.

    Science.gov (United States)

    Hasselback, Leah; Crawford, Jessica; Chaluco, Timoteo; Rajagopal, Sharanya; Prosser, Wendy; Watson, Noel

    2014-08-02

    Malaria rapid diagnostic tests (RDTs) are particularly useful in low-resource settings where follow-through on traditional laboratory diagnosis is challenging or lacking. The availability of these tests depends on supply chain processes within the distribution system. In Mozambique, stock-outs of malaria RDTs are fairly common at health facilities. A longitudinal cross-sectional study was conducted to evaluate drivers of stock shortages in the Cabo Delgado province. Data were collected from purposively sampled health facilities, using monthly cross-sectional surveys between October 2011 and May 2012. Estimates of lost consumption (consumption not met due to stock-outs) served as the primary quantitative indicator of stock shortages. This is a better measure of the magnitude of stock-outs than binary indicators that only measure frequency of stock-outs at a given facility. Using a case study based methodology, distribution system characteristics were qualitatively analysed to examine causes of stock-outs at the provincial, district and health centre levels. 15 health facilities were surveyed over 120 time points. Stock-out patterns varied by data source; average monthly proportions of 59%, 17% and 17% of health centres reported a stock-out on stock cards, laboratory and pharmacy forms, respectively. Estimates of lost consumption percentage were significantly high; ranging from 0% to 149%; with a weighted average of 78%. Each ten-unit increase in monthly-observed consumption was associated with a nine-unit increase in lost consumption percentage indicating that higher rates of stock-outs occurred at higher levels of observed consumption. Causes of stock-outs included inaccurate tracking of lost consumption, insufficient sophistication in inventory management and replenishment, and poor process compliance by facility workers, all arguably stemming from inadequate attention to the design and implementation of the distribution system. Substantially high levels of RDT

  1. HIgh-Latitude Neutral Hydrogen Shells identified in GALFA-HI

    Science.gov (United States)

    Sallmen, Shauna; Taylor, Rebecca; Korpela, Eric J.; Goldston Peek, Joshua Eli; Babler, Brian

    2017-08-01

    Supernovae and stellar winds are important processes in the development and evolution of galaxies. Due to these effects in generations of stars, the interstellar medium (ISM) is turbulent, multiphase, and filled with complex interacting structures. HI (neutral hydrogen) shells are formed when hot, expanding bubbles sweep up shells of neutral material. These shells gradually cool, slow down, and mix with the surrounding interstellar material, but we still lack a complete, detailed picture of the physical state and evolution of gas in our Galaxy's ISM. Studies of numerous shells at different stages of evolution are needed, but biases in search techniques and limitations of data quality and coverage have hindered our efforts. The Galactic Arecibo L-band Feed Array (GALFA) 21-cm survey of the Arecibo sky provides have uniquely high angular resolution except within a few degrees of the Galactic plane. A visual search of these data can therefore identify new structures with small angular diameter at high Galactic latitudes, at all stages of evolution. We present the results of a partial search of these data, focusing on high Galactic latitudes. For each potential shell, the location, velocity, angular size, and velocity range were determined, as well as estimates of the shell wall completeness and persistence of shell completeness, shape, and location across its velocity range. To date, we have identified over 100 potential new shells, ranging in size from 0.1 to 4.5 degrees. Approximately 2/3 of these are smaller than 2 degrees in diameter, a size range that was significantly underrepresented in previous searches. The statistical properties of these newly found shells will be presented, along with details on selected examples.

  2. High-risk carotid plaques identified by CT-angiogram can predict acute myocardial infarction.

    Science.gov (United States)

    Mosleh, Wassim; Adib, Keenan; Natdanai, Punnanithinont; Carmona-Rubio, Andres; Karki, Roshan; Paily, Jacienta; Ahmed, Mohamed Abdel-Aal; Vakkalanka, Sujit; Madam, Narasa; Gudleski, Gregory D; Chung, Charles; Sharma, Umesh C

    2016-11-19

    Prior studies identified the incremental value of non-invasive imaging by CT-angiogram (CTA) to detect high-risk coronary atherosclerotic plaques. Due to their superficial locations, larger calibers and motion-free imaging, the carotid arteries provide the best anatomic access for the non-invasive characterization of atherosclerotic plaques. We aim to assess the ability of predicting obstructive coronary artery disease (CAD) or acute myocardial infarction (MI) based on high-risk carotid plaque features identified by CTA. We retrospectively examined carotid CTAs of 492 patients that presented with acute stroke to characterize the atherosclerotic plaques of the carotid arteries and examined development of acute MI and obstructive CAD within 12-months. Carotid lesions were defined in terms of calcifications (large or speckled), presence of low-attenuation plaques, positive remodeling, and presence of napkin ring sign. Adjusted relative risks were calculated for each plaque features. Patients with speckled (<3 mm) calcifications and/or larger calcifications on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year compared to patients without (adjusted RR of 7.51, 95%CI 1.26-73.42, P = 0.001). Patients with low-attenuation plaques on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year than patients without (adjusted RR of 2.73, 95%CI 1.19-8.50, P = 0.021). Presence of carotid calcifications and low-attenuation plaques also portended higher sensitivity (100 and 79.17%, respectively) for the development of acute MI. Presence of carotid calcifications and low-attenuation plaques can predict the risk of developing acute MI and/or obstructive CAD within 12-months. Given their high sensitivity, their absence can reliably exclude 12-month events.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Rapid screening mitochondrial DNA mutation by using denaturing high-performance liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    Man-Ran Liu; Kai-Feng Pan; Zhen-Fu Li; Yi Wang; Da-Jun Deng; Lian Zhang; You-Yong Lu

    2002-01-01

    AIM: To optimize conditions of DHPLC and analyze theeffectiveness of various DNA polymerases on DHPLCresolution, and evaluate the sensitivity of DHPLC in themutation screening of mitochondrial DNA (mtDNA).METHODS: Two fragments of 16s gene of mitochondrial DNA(one of them F2 is a mutant fragment) and an A3243Gmutated fragment were used to analyze the UV detectionlimit and determine the minimum percentage of mutant PCRproducts for DHPLC and evaluate effects of DNApolymerases on resolution of DHPLC. Under the optimalconditions, we analyzed the mtDNA mutations from muscletissues of mitochondrial encephalomyopathy with lacticacidosis and stroke-like episodes (NELAS) and screenedblindly for variances in D-loop region of mtDNA from humangastric tumor specimen.RESULTS: Ten A3243G variants were detected in 12 cases ofMELAS, no alterations were detected in controls and theseresults were consistent with the results obtained by analysisof RFLP with Apel. We also identified 26 D-loop variances in46 cases of human gastric cancer tissues and 38 alterationsin 13 gastric cancer cell lines. The mutation of mtDNA at 80 ngPCFI products containing a minimum of 5 % mutant sequencescould be detected by using DHPLC with UV detector.Moreover, Ampli-Taq Gold polymerase was equally as good asthe proofreading DNA polymerase (e. g., Pfu) in eliminatingthe false positive produced by Taq DNA polymerases.CONCLUSION: DHPLC is a powerful, rapid and sensitivemutation screening method for mtDNA. Proofreading DNApolymerase is more suitable for DHPLC analysis than Taqpolymerase.

  5. A homogeneous, high-throughput assay for phosphatidylinositol 5-phosphate 4-kinase with a novel, rapid substrate preparation.

    Directory of Open Access Journals (Sweden)

    Mindy I Davis

    Full Text Available Phosphoinositide kinases regulate diverse cellular functions and are important targets for therapeutic development for diseases, such as diabetes and cancer. Preparation of the lipid substrate is crucial for the development of a robust and miniaturizable lipid kinase assay. Enzymatic assays for phosphoinositide kinases often use lipid substrates prepared from lyophilized lipid preparations by sonication, which result in variability in the liposome size from preparation to preparation. Herein, we report a homogeneous 1536-well luciferase-coupled bioluminescence assay for PI5P4Kα. The substrate preparation is novel and allows the rapid production of a DMSO-containing substrate solution without the need for lengthy liposome preparation protocols, thus enabling the scale-up of this traditionally difficult type of assay. The Z'-factor value was greater than 0.7 for the PI5P4Kα assay, indicating its suitability for high-throughput screening applications. Tyrphostin AG-82 had been identified as an inhibitor of PI5P4Kα by assessing the degree of phospho transfer of γ-(32P-ATP to PI5P; its inhibitory activity against PI5P4Kα was confirmed in the present miniaturized assay. From a pilot screen of a library of bioactive compounds, another tyrphostin, I-OMe tyrphostin AG-538 (I-OMe-AG-538, was identified as an ATP-competitive inhibitor of PI5P4Kα with an IC(50 of 1 µM, affirming the suitability of the assay for inhibitor discovery campaigns. This homogeneous assay may apply to other lipid kinases and should help in the identification of leads for this class of enzymes by enabling high-throughput screening efforts.

  6. A Pilot Study Investigating the Potential of High-Intensity Focused Ultrasound to Treat Tumours Rapidly

    Science.gov (United States)

    Cranston, Jonathan M.; Rivens, Ian; ter Haar, Gail; Kennedy, James

    2007-05-01

    The aim of this project was to investigate the possibility of rapid tumour destruction by a novel method of treating the periphery of a tumour and inducing ischemia by impeding the blood supply. Ex vivo experiments were initially carried out in bovine liver to determine the optimum conditions for focal depth, gantry transducer speed circle diameter and intensity of the ultrasound beam. In vivo experiments were then performed in PGV rat livers implanted with a HSN fibrosarcoma cell line. The tumours were treated by novel technique of creating an annular lesion around the perimeter of the tumour. Macroscopic and microscopic examination of the lesion at post mortem was performed. In addition histological examination of the untreated tumour which was within the annular circle of treatment was examined. This showed evidence of karyolytic nuclei a week after treatment suggesting death by infarction within this area. There was also some evidence of endothelial damage in the blood vessels with fragmented nuclei visible in the lumen. The work presented here adds to our understanding of how high intensity focused ultrasound may be used to treat tumours in as faster and more efficient way. Further work in this area will facilitate the design of future therapeutic interventions in the medical and veterinary world.

  7. Rapid separation of polysaccharides using a novel spiral coil column by high-speed countercurrent chromatography.

    Science.gov (United States)

    Li, Weili; Wu, Tao

    2016-04-01

    The separation of polysaccharides is time consuming. We developed and optimized a type-J counter-current chromatography system with a novel tri-rotor spiral coil column for the rapid separation of polysaccharides. The optimal composition of an aqueous PEG1000/K2 HPO4 /KH2 PO4 system was found to be 14:16:14 w/w/w where the lower phase was the mobile phase. Optimal performance was achieved at a column rotational speed, temperature, and flow rate of 1200 rpm, 45°C, and 3.0 mL/min, respectively. The mobile phase was pumped from the inner terminal in a ''head-to-tail'' elution mode. Polysaccharide LCP-1 (10.7 mg) was successfully obtained in high purity in one step from 50.0 mg of a crude polysaccharide extracted from the lychee fruit (Litchi chinensis) within 100 min. LCP-1 possess a number-average molecular weight and weight-average molecular weight of 1.05 × 10(5) and 1.59 × 10(5) kDa, respectively. The monosaccharide composition consists of the molar ratio of glucose, galactose, and arabinose of 1.3:3.5:1.

  8. I Zw 18 as morphological paradigm for rapidly assembling high-z galaxies

    CERN Document Server

    Papaderos, Polychronis

    2011-01-01

    IZw18, ever since regarded as the prototypical blue compact dwarf (BCD) galaxy, is, quite ironically, the most atypical BCD known. This is because its large exponential low-surface brightness envelope is not due to an old stellar host but entirely due to extended nebular emission (ne) (Papaderos et al. 2002; P02). We study IZw18 and IZw18C down to an unprecedently faint surface brightness level using HST ACS data. We argue that the properties of IZw18C can be consistently accounted for by propagating star formation over the past ~100 Myr, in combination with stellar diffusion and the associated radial stellar mass filtering effect (P02). As for IZw18, we find that ne extends out to ~16 stellar scale lengths and provides at least 1/3 of the total optical emission. The case of IZw18 suggests caution in studies of distant galaxies in dominant stages of their evolution, rapidly assembling their stellar mass at high specific star formation rates (SSFRs). It calls attention to the fact that ne is not necessarily co...

  9. Rapid RNA-ligand interaction analysis through high-information content conformational and stability landscapes

    Energy Technology Data Exchange (ETDEWEB)

    Baird, Nathan J. [National Inst. of Health (NIH), Bethesda, MD (United States); Inglese, James [National Inst. of Health (NIH), Bethesda, MD (United States); Ferré-D’Amaré, Adrian R. [National Inst. of Health (NIH), Bethesda, MD (United States)

    2015-12-07

    The structure and biological properties of RNAs are a function of changing cellular conditions, but comprehensive, simultaneous investigation of the effect of multiple interacting environmental variables is not easily achieved. We have developed an efficient, high-throughput method to characterize RNA structure and thermodynamic stability as a function of multiplexed solution conditions using Förster resonance energy transfer (FRET). In a single FRET experiment using conventional quantitative PCR instrumentation, 19,400 conditions of MgCl2, ligand and temperature are analysed to generate detailed empirical conformational and stability landscapes of the cyclic diguanylate (c-di-GMP) riboswitch. This method allows rapid comparison of RNA structure modulation by cognate and non-cognate ligands. Landscape analysis reveals that kanamycin B stabilizes a non-native, idiosyncratic conformation of the riboswitch that inhibits c-di-GMP binding. Our research demonstrates that allosteric control of folding, rather than direct competition with cognate effectors, is a viable approach for pharmacologically targeting riboswitches and other structured RNA molecules.

  10. Microfluidic immunosensor for rapid and highly-sensitive salivary cortisol quantification.

    Science.gov (United States)

    Pinto, V; Sousa, P; Catarino, S O; Correia-Neves, M; Minas, G

    2017-04-15

    This paper presents a novel poly(dimethylsiloxane) (PDMS) microfluidic immunosensor that integrates a complementary metal-oxide-semiconductor (CMOS) optical detection system for a rapid and highly-sensitive quantification of salivary cortisol. The simple and non-invasive method of saliva sampling provides an interesting alternative to the blood, allowing a fast sampling at short intervals, relevant for many clinical diagnostic applications. The developed approach is based on the covalent immobilization of a coating antibody (Ab), a polyclonal anti-IgG, onto a treated PDMS surface. The coating Ab binds the capture Ab, an IgG specific for cortisol, allowing its correct orientation. Horseradish peroxidase (HRP)-labelled cortisol is added to compete with the cortisol in the sample, for the capture Ab binding sites. The HRP-labelled cortisol, bonded to the capture Ab, is measured through the HRP enzyme and the tetramethylbenzidine (TMB) substrate reaction. The cortisol quantification is performed by colorimetric detection of HRP-labelled cortisol, through optical absorption at 450nm, using a CMOS silicon photodiode as the photodetector. Under the developed optimized conditions presented here, e.g., microfluidic channels geometry, immobilization method and immunoassay conditions, the immunosensor shows a linear range of detection between 0.01-20ng/mL, a limit of detection (LOD) of 18pg/mL and an analysis time of 35min, featuring a great potential for point-of-care applications requiring continuous monitoring of the salivary cortisol levels during a circadian cycle.

  11. Human respiration at rest in rapid compression and at high pressures and gas densities

    Science.gov (United States)

    Gelfand, R.; Lambertsen, C. J.; Strauss, R.; Clark, J. M.; Puglia, C. D.

    1983-01-01

    The ventilation (V), end-tidal PCO2 (PACO2), and CO2 elimination rate were determined in men at rest breathing CO2-free gas over the pressure range 1-50 ATA and the gas density range 0.4-25 g/l, during slow and rapid compressions, at stable elevated ambient pressures and during slow decompressions. Progressive increase in pulmonary gas flow resistance due to elevation of ambient pressure and inspired gas density to the He-O2 equivalent of 5000 feet of seawater was found to produce a complex pattern of change in PACO2. It was found that as both ambient pressure and pulmonary gas flow resistance were progressively raised, PACO2 at first increased, went through a maximum, and then declined towards values near the 1 ATA level. It is concluded that this pattern of PACO2 change results from the interaction on ventilation of the increase in pulmonary resistance due to the elevation of gas density with the increase in respiratory drive postulated as due to generalized central nervous system excitation associated with exposure to high hydrostatic pressure. It is suggested that a similar interaction exists between increased gas flow resistance and the increase in respiratory drive related to nitrogen partial pressure and the resulting narcosis.

  12. Highly sensitive label-free dual sensor array for rapid detection of wound bacteria.

    Science.gov (United States)

    Sheybani, Roya; Shukla, Anita

    2017-06-15

    Wound infections are a critical healthcare concern worldwide. Rapid and effective antibiotic treatments that can mitigate infection severity and prevent the spread of antibiotic resistance are contingent upon timely infection detection. In this work, dual electrochemical pH and cell-attachment sensor arrays were developed for the real-time spatial and temporal monitoring of potential wound infections. Biocompatible polymeric device coatings were integrated to stabilize the sensors and promote bacteria attachment while preventing non-specific cell and protein fouling. High sensitivity (bacteria concentration of 10(2) colony forming units (CFU)/mL and -88.1±6.3mV/pH over a pH range of 1-13) and stability over 14 days were achieved without the addition of biological recognition elements. The dual sensor array was demonstrated to successfully monitor the growth of both gram-positive (Staphylococcus aureus and Streptococcus pyogenes) and gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli) over time through lag and log growth phases and following antibiotic administration and in simulated shallow wounds conditions. The versatile fabrication methods utilized in sensor development, superior sensitivity, prolonged stability, and lack of non-specific sensor fouling may enable long-term in situ sensor array operation in low resource settings. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Synthesis of Pt3Ni Microspheres with High Performance for Rapid Degradation of Organic Dyes

    Science.gov (United States)

    Wang, Min; Yang, Yushi; Long, Jia; Mao, Zhou; Qiu, Tong; Wu, Qingzhi; Chen, Xiaohui

    2015-05-01

    In this study, Pt3Ni microspheres consisted of nanoparticles were synthesized without addition of surfactants via the solvothermal route. The obtained sample was characterized by X-ray diffraction (XRD), inductively coupled plasma-atomic emission spectrometer (ICP-AES), X-ray photoelectron spectroscopy (XPS), and field-emission scanning electron microscopy (FESEM). Furthermore, the catalytic performance of as-synthesized Pt3Ni microspheres was evaluated on the degradation of different organic dyes (methylene blue, methyl orange, Congo red, and rhodamine B). The results show that different dyes were rapidly decomposed by Pt3Ni microspheres in different pathways. Among different dyes, the formation and further degradation of the intermediates was observed during the degradation of methylene blue and methyl orange, suggesting the indirect degradation process of these dyes. This study provides not only a promising catalyst for the removal of organic contaminants for environment remediation, but also new insights for Pt3Ni alloy as a high-performance catalyst in organic synthesis.

  14. Rapid and high resolution capillary supercritical fluid chromatography (SFC) and SFC/MS of trichothecene mycotoxins.

    Science.gov (United States)

    Smith, R D; Udseth, H R; Wright, B W

    1985-05-01

    The potential application of capillary column supercritical fluid chromatography (SFC) and SFC/mass spectrometry (SFC/MS) for the separation and analysis of mycotoxins of the trichothecene group was examined. Trichothecenes present significant analytical problems for both gas and liquid chromatography with a major difficulty for the latter being the lack of sufficiently sensitive and selective detectors. Supercritical carbon dioxide mobile phases at temperatures up to 100 degrees C were used with deactivated fused silica columns coated with crosslinked stationary phases. Separations were obtained under pressure ramped conditions using long (15 m) 50-micron i.d. columns for several trichothecenes (diacetoxyscirpenol, deoxynivalenol, and T-2 toxin) and related higher molecular weight macrocyclic (roridin and verrucarin) trichothecenes. In addition, new rapid pressure programming techniques with short (less than 2m) 25- to 50-micron i.d. capillary columns were used to obtain fast separations in as little as 1 min. SFC/MS with ammonia chemical ionization provided high selectivity and sensitive detection (with approximately 1-pg detection limits) for trichothecene mixtures. The extension to complex sample matrices is discussed and the application of selective MS/MS detection is demonstrated.

  15. Synthesis of Pt3Ni microspheres with high performance for rapid degradation of organic dyes.

    Science.gov (United States)

    Wang, Min; Yang, Yushi; Long, Jia; Mao, Zhou; Qiu, Tong; Wu, Qingzhi; Chen, Xiaohui

    2015-12-01

    In this study, Pt3Ni microspheres consisted of nanoparticles were synthesized without addition of surfactants via the solvothermal route. The obtained sample was characterized by X-ray diffraction (XRD), inductively coupled plasma-atomic emission spectrometer (ICP-AES), X-ray photoelectron spectroscopy (XPS), and field-emission scanning electron microscopy (FESEM). Furthermore, the catalytic performance of as-synthesized Pt3Ni microspheres was evaluated on the degradation of different organic dyes (methylene blue, methyl orange, Congo red, and rhodamine B). The results show that different dyes were rapidly decomposed by Pt3Ni microspheres in different pathways. Among different dyes, the formation and further degradation of the intermediates was observed during the degradation of methylene blue and methyl orange, suggesting the indirect degradation process of these dyes. This study provides not only a promising catalyst for the removal of organic contaminants for environment remediation, but also new insights for Pt3Ni alloy as a high-performance catalyst in organic synthesis.

  16. Rapid telomere motions in live human cells analyzed by highly time-resolved microscopy

    Directory of Open Access Journals (Sweden)

    Wang Xueying

    2008-10-01

    Full Text Available Abstract Background Telomeres cap chromosome ends and protect the genome. We studied individual telomeres in live human cancer cells. In capturing telomere motions using quantitative imaging to acquire complete high-resolution three-dimensional datasets every second for 200 seconds, telomere dynamics were systematically analyzed. Results The motility of individual telomeres within the same cancer cell nucleus was widely heterogeneous. One class of internal heterochromatic regions of chromosomes analyzed moved more uniformly and showed less motion and heterogeneity than telomeres. The single telomere analyses in cancer cells revealed that shorter telomeres showed more motion, and the more rapid telomere motions were energy dependent. Experimentally increasing bulk telomere length dampened telomere motion. In contrast, telomere uncapping, but not a DNA damaging agent, methyl methanesulfonate, significantly increased telomere motion. Conclusion New methods for seconds-scale, four-dimensional, live cell microscopic imaging and data analysis, allowing systematic tracking of individual telomeres in live cells, have defined a previously undescribed form of telomere behavior in human cells, in which the degree of telomere motion was dependent upon telomere length and functionality.

  17. Colorimetry and SERS dual-mode detection of telomerase activity: combining rapid screening with high sensitivity.

    Science.gov (United States)

    Zong, Shenfei; Wang, Zhuyuan; Chen, Hui; Hu, Guohua; Liu, Min; Chen, Peng; Cui, Yiping

    2014-01-01

    As an important biomarker and therapeutic target, telomerase has attracted considerable attention concerning its detection and monitoring. Here, we present a colorimetry and surface enhanced Raman scattering (SERS) dual-mode telomerase activity detection method, which has several distinctive advantages. First, colorimetric functionality allows rapid preliminary discrimination of telomerase activity by the naked eye. Second, the employment of SERS technique results in greatly improved detection sensitivity. Third, the combination of colorimetry and SERS into one detection system can ensure highly efficacious and sensitive screening of numerous samples. Besides, the avoidance of polymerase chain reaction (PCR) procedures further guarantees fine reliability and simplicity. Generally, the presented method is realized by an "elongate and capture" procedure. To be specific, gold nanoparticles modified with Raman molecules and telomeric repeat complementary oligonucleotide are employed as the colorimetric-SERS bifunctional reporting nanotag, while magnetic nanoparticles functionalized with telomerase substrate oligonucleotide are used as the capturing substrate. Telomerase can synthesize and elongate telomeric repeats onto the capturing substrate. The elongated telomeric repeats subsequently facilitate capturing of the reporting nanotag via hybridization between telomeric repeat and its complementary strand. The captured nanotags can cause a significant difference in the color and SERS intensity of the magnetically separated sediments. Thus both the color and SERS can be used as indicators of the telomerase activity. With fast screening ability and outstanding sensitivity, we anticipate that this method would greatly promote practical application of telomerase-based early-stage cancer diagnosis.

  18. Rapid shape determination of tissue transglutaminase using high-throughput computing.

    Science.gov (United States)

    Lammie, Donna; Osborne, James; Aeschlimann, Daniel; Wess, Timothy J

    2007-09-01

    Small-angle X-ray scattering can be used to determine the molecular shape of macromolecules in solution which are otherwise refractory to conventional high-resolution studies. DAMMIN and GASBOR are applications that utilize ab initio methods to build models of proteins using simulated annealing; both DAMMIN and GASBOR have to be run numerous times on the same input data to generate the most likely protein shape. Condor is a specialized workload-management system for PC computation-intensive tasks. Using Condor, DAMMIN and GASBOR can be run a number of times simultaneously on the same input data, allowing the shape of proteins to be determined in a fraction of the time it would have taken to have run DAMMIN and GASBOR sequentially. The main advantage of this approach is that it allows quicker data processing; therefore, results are obtained promptly and without undue delay. Tissue transglutaminase is a multidomain enzyme that catalyses the formation of isopeptide bonds between polypeptide chains. This reaction requires the enzyme to undergo a series of conformational changes that are not well understood in order to allow the sequential interaction with the two substrate proteins and their subsequent release when cross-linked. Condor was applied to determine the solution shape of tissue transglutaminase in a rapid fashion. Eventually, the next step will be to move towards online analysis at synchrotron sources by developing a graphical user interface that will enable remote access, allowing users to submit jobs to Condor whilst at synchrotrons.

  19. Rapid RNA-ligand interaction analysis through high-information content conformational and stability landscapes

    Science.gov (United States)

    Baird, Nathan J.; Inglese, James; Ferré-D'Amaré, Adrian R.

    2015-12-01

    The structure and biological properties of RNAs are a function of changing cellular conditions, but comprehensive, simultaneous investigation of the effect of multiple interacting environmental variables is not easily achieved. We have developed an efficient, high-throughput method to characterize RNA structure and thermodynamic stability as a function of multiplexed solution conditions using Förster resonance energy transfer (FRET). In a single FRET experiment using conventional quantitative PCR instrumentation, 19,400 conditions of MgCl2, ligand and temperature are analysed to generate detailed empirical conformational and stability landscapes of the cyclic diguanylate (c-di-GMP) riboswitch. The method allows rapid comparison of RNA structure modulation by cognate and non-cognate ligands. Landscape analysis reveals that kanamycin B stabilizes a non-native, idiosyncratic conformation of the riboswitch that inhibits c-di-GMP binding. This demonstrates that allosteric control of folding, rather than direct competition with cognate effectors, is a viable approach for pharmacologically targeting riboswitches and other structured RNA molecules.

  20. Rapid sympatry explains greater color pattern divergence in high latitude birds.

    Science.gov (United States)

    Martin, Paul R; Montgomerie, Robert; Lougheed, Stephen C

    2010-02-01

    Latitudinal variation in patterns of evolution has fascinated biologists for over a century, but our understanding of latitudinal differences in evolutionary processes-such as selection and drift-remains limited. Here, we test for, and find, accelerated evolution of color patterns in bird taxa that breed at higher latitudes compared with those breeding in the tropics, analyzing data from seven diverse avian families. Most important, we show that the extent of overlap of species' breeding ranges (degree of sympatry) explains the elevated rate of color pattern evolution at higher latitudes. We suggest that the dynamic shifts in breeding ranges that accompanied climatic changes during the last 3 million years (Milankovitch Oscillations) resulted in more rapid and more frequent secondary contact at high latitudes. We argue that sympatry among diverging clades causes greater divergence of color traits in birds at higher latitudes through sexual, social, or ecological character displacement that accelerate rates of evolution, and through the selective elimination of weakly differentiated lineages that hybridize and fuse in sympatry (differential fusion).

  1. Rapid fabrication of a poly(dimethylsiloxane) microfluidic capillary gel electrophoresis system utilizing high precision machining.

    Science.gov (United States)

    Zhao, Dong S; Roy, Binayak; McCormick, Matthew T; Kuhr, Werner G; Brazill, Sara A

    2003-05-01

    In this work, we demonstrate a rapid protocol to address one of the major barriers that exists in the fabrication of chip devices, creating the micron-sized structures in the substrate material. This approach makes it possible to design, produce, and fabricate a microfluidic system with channel features >10 microm in poly(dimethylsiloxane)(PDMS) in under 8 hours utilizing instrumentation common to most machine shops. The procedure involves the creation of a master template with negative features, using high precision machining. This master is then employed to create an acrylic mold that is used in the final fabrication step to cast channel structures into the PDMS substrate. The performance of the microfluidic system prepared using this fabrication procedure is evaluated by constructing a miniaturized capillary gel electrophoresis (micro-CGE) system for the analysis of DNA fragments. Agarose is utilized as the sieving medium in the micro-CGE device and is shown to give reproducible (RSD (n= 34) approximately 5.0%) results for about 34 individual separations without replenishing the gel. To demonstrate the functionality of the micro-CGE device, a DNA restriction ladder (spanning 26-700 base pairs) and DNA fragments generated by PCR are separated and detected with laser-induced fluorescence (LIF). The microchip is shown to achieve a separation efficiency of 2.53 x 10(5) plates m(-1).

  2. Microstructure simulation of rapidly solidified ASP30 high-speed steel particles by gas atomization

    Science.gov (United States)

    Ma, Jie; Wang, Bo; Yang, Zhi-liang; Wu, Guang-xin; Zhang, Jie-yu; Zhao, Shun-li

    2016-03-01

    In this study, the microstructure evolution of rapidly solidified ASP30 high-speed steel particles was predicted using a simulation method based on the cellular automaton-finite element (CAFE) model. The dendritic growth kinetics, in view of the characteristics of ASP30 steel, were calculated and combined with macro heat transfer calculations by user-defined functions (UDFs) to simulate the microstructure of gas-atomized particles. The relationship among particle diameter, undercooling, and the convection heat transfer coefficient was also investigated to provide cooling conditions for simulations. The simulated results indicated that a columnar grain microstructure was observed in small particles, whereas an equiaxed microstructure was observed in large particles. In addition, the morphologies and microstructures of gas-atomized ASP30 steel particles were also investigated experimentally using scanning electron microscopy (SEM). The experimental results showed that four major types of microstructures were formed: dendritic, equiaxed, mixed, and multi-droplet microstructures. The simulated results and the available experimental data are in good agreement.

  3. A Class of High-affinity Bicyclooctane G551D-CFTR Activators Identified by High Throughput Screening

    Institute of Scientific and Technical Information of China (English)

    HE Cheng-yan; ZHAO Lu; LIU Yan-li; XU Li-na; SHANG De-jing; YANG Hong

    2004-01-01

    The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmembrane conductance regulator(CFTR) is one of the five most frequent cystic fibrosis(CF) mutations associated with a severe CF phenotype. To explore the feasibility of pharmacological correction of disrupted activation of CFTR chloride channel caused by G551D mutation, we developed a halide-sensitive fluorescence miniassay for G551D-CFTR in Fisher rat thyroid(FRT) epithelial cells for the discovery of novel activators of G551D-CFTR. A class of bicyclooctane small molecule compounds that efficiently stimulate G551D-CFTR chloride channel activity was identified by high throughput screening via the FRT cell-based assay. This class of compounds selectively activates G551D-CFTR with a high affinity, whereas little effect of the compounds on wildtype CFTR can be seen. The discovery of a class of bicyclooctane G551D-CFTR activators will permit the analysis of structure-activity relationship of the compounds to identify ideal leads for in vivo therapeutic studies.

  4. Potential High-Temperature Shape-Memory Alloys Identified in the Ti(Ni,Pt) System

    Science.gov (United States)

    Noebe, Ronald D.; Biles, Tiffany A.; Garg, Anita; Nathal, Michael V.

    2004-01-01

    "Shape memory" is a unique property of certain alloys that, when deformed (within certain strain limits) at low temperatures, will remember and recover to their original predeformed shape upon heating. It occurs when an alloy is deformed in the low-temperature martensitic phase and is then heated above its transformation temperature back to an austenitic state. As the material passes through this solid-state phase transformation on heating, it also recovers its original shape. This behavior is widely exploited, near room temperature, in commercially available NiTi alloys for connectors, couplings, valves, actuators, stents, and other medical and dental devices. In addition, there are limitless applications in the aerospace, automotive, chemical processing, and many other industries for materials that exhibit this type of shape-memory behavior at higher temperatures. But for high temperatures, there are currently no commercial shape-memory alloys. Although there are significant challenges to the development of high-temperature shape-memory alloys, at the NASA Glenn Research Center we have identified a series of alloy compositions in the Ti-Ni-Pt system that show great promise as potential high-temperature shape-memory materials.

  5. Evaluation of approaches for identifying population informative markers from high density SNP Chips

    Directory of Open Access Journals (Sweden)

    McKay Stephanie D

    2011-05-01

    Full Text Available Abstract Background Genetic markers can be used to identify and verify the origin of individuals. Motivation for the inference of ancestry ranges from conservation genetics to forensic analysis. High density assays featuring Single Nucleotide Polymorphism (SNP markers can be exploited to create a reduced panel containing the most informative markers for these purposes. The objectives of this study were to evaluate methods of marker selection and determine the minimum number of markers from the BovineSNP50 BeadChip required to verify the origin of individuals in European cattle breeds. Delta, Wright's FST, Weir & Cockerham's FST and PCA methods for population differentiation were compared. The level of informativeness of each SNP was estimated from the breed specific allele frequencies. Individual assignment analysis was performed using the ranked informative markers. Stringency levels were applied by log-likelihood ratio to assess the confidence of the assignment test. Results A 95% assignment success rate for the 384 individually genotyped animals was achieved with ST (60 to 140 SNPs depending on the chosen degree of confidence. Certain breeds required fewer markers ( 95% assignment success. The power of assignment success, and therefore the number of SNP markers required, is dependent on the levels of genetic heterogeneity and pool of samples considered. Conclusions While all SNP selection methods produced marker panels capable of breed identification, the power of assignment varied markedly among analysis methods. Thus, with effective exploration of available high density genetic markers, a diagnostic panel of highly informative markers can be produced.

  6. Application of (13)C flux analysis to identify high-productivity CHO metabolic phenotypes.

    Science.gov (United States)

    Templeton, Neil; Smith, Kevin D; McAtee-Pereira, Allison G; Dorai, Haimanti; Betenbaugh, Michael J; Lang, Steven E; Young, Jamey D

    2017-01-23

    Industrial bioprocesses place high demands on the energy metabolism of host cells to meet biosynthetic requirements for maximal protein expression. Identifying metabolic phenotypes that promote high expression is therefore a major goal of the biotech industry. We conducted a series of (13)C flux analysis studies to examine the metabolic response to IgG expression during early stationary phase of CHO cell cultures grown in 3L fed-batch bioreactors. We examined eight clones expressing four different IgGs and compared with three non-expressing host-cell controls. Some clones were genetically manipulated to be apoptosis-resistant by expressing Bcl-2Δ, which correlated with increased IgG production and elevated glucose metabolism. The metabolic phenotypes of the non-expressing, IgG-expressing, and Bcl-2Δ/IgG-expressing clones were fully segregated by hierarchical clustering analysis. Lactate consumption and citric acid cycle fluxes were most strongly associated with specific IgG productivity. These studies indicate that enhanced oxidative metabolism is a characteristic of high-producing CHO cell lines.

  7. Mining environmental high-throughput sequence data sets to identify divergent amplicon clusters for phylogenetic reconstruction and morphotype visualization.

    Science.gov (United States)

    Gimmler, Anna; Stoeck, Thorsten

    2015-08-01

    Environmental high-throughput sequencing (envHTS) is a very powerful tool, which in protistan ecology is predominantly used for the exploration of diversity and its geographic and local patterns. We here used a pyrosequenced V4-SSU rDNA data set from a solar saltern pond as test case to exploit such massive protistan amplicon data sets beyond this descriptive purpose. Therefore, we combined a Swarm-based blastn network including 11 579 ciliate V4 amplicons to identify divergent amplicon clusters with targeted polymerase chain reaction (PCR) primer design for full-length small subunit of the ribosomal DNA retrieval and probe design for fluorescence in situ hybridization (FISH). This powerful strategy allows to benefit from envHTS data sets to (i) reveal the phylogenetic position of the taxon behind divergent amplicons; (ii) improve phylogenetic resolution and evolutionary history of specific taxon groups; (iii) solidly assess an amplicons (species') degree of similarity to its closest described relative; (iv) visualize the morphotype behind a divergent amplicons cluster; (v) rapidly FISH screen many environmental samples for geographic/habitat distribution and abundances of the respective organism and (vi) to monitor the success of enrichment strategies in live samples for cultivation and isolation of the respective organisms.

  8. A high-throughput method to examine protein-nucleotide interactions identifies targets of the bacterial transcriptional regulatory protein fur.

    Directory of Open Access Journals (Sweden)

    Chunxiao Yu

    Full Text Available The Ferric uptake regulatory protein (Fur is a transcriptional regulatory protein that functions to control gene transcription in response to iron in a number of pathogenic bacteria. In this study, we applied a label-free, quantitative and high-throughput analysis method, Interferometric Reflectance Imaging Sensor (IRIS, to rapidly characterize Fur-DNA interactions in vitro with predicted Fur binding sequences in the genome of Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea. IRIS can easily be applied to examine multiple protein-protein, protein-nucleotide and nucleotide-nucleotide complexes simultaneously and demonstrated here that seventy percent of the predicted Fur boxes in promoter regions of iron-induced genes bound to Fur in vitro with a range of affinities as observed using this microarray screening technology. Combining binding data with mRNA expression levels in a gonococcal fur mutant strain allowed us to identify five new gonococcal genes under Fur-mediated direct regulation.

  9. Nosocomial infections in brazilian pediatric patients: using a decision tree to identify high mortality groups

    Directory of Open Access Journals (Sweden)

    Julia M.M. Lopes

    Full Text Available Nosocomial infections (NI are frequent events with potentially lethal outcomes. We identified predictive factors for mortality related to NI and developed an algorithm for predicting that risk in order to improve hospital epidemiology and healthcare quality programs. We made a prospective cohort NI surveillance of all acute-care patients according to the National Nosocomial Infections Surveillance System guidelines since 1992, applying the Centers for Disease Control and Prevention 1988 definitions adapted to a Brazilian pediatric hospital. Thirty-eight deaths considered to be related to NI were analyzed as the outcome variable for 754 patients with NI, whose survival time was taken into consideration. The predictive factors for mortality related to NI (p < 0.05 in the Cox regression model were: invasive procedures and use of two or more antibiotics. The mean survival time was significantly shorter (p < 0.05 with the Kaplan-Meier method for patients who suffered invasive procedures and for those who received two or more antibiotics. Applying a tree-structured survival analysis (TSSA, two groups with high mortality rates were identified: one group with time from admission to the first NI less than 11 days, received two or more antibiotics and suffered invasive procedures; the other group had the first NI between 12 and 22 days after admission and was subjected to invasive procedures. The possible modifiable factors to prevent mortality involve invasive devices and antibiotics. The TSSA approach is helpful to identify combinations of predictors and to guide protective actions to be taken in continuous-quality-improvement programs.

  10. Nosocomial infections in brazilian pediatric patients: using a decision tree to identify high mortality groups

    Directory of Open Access Journals (Sweden)

    Julia M.M. Lopes

    2009-04-01

    Full Text Available Nosocomial infections (NI are frequent events with potentially lethal outcomes. We identified predictive factors for mortality related to NI and developed an algorithm for predicting that risk in order to improve hospital epidemiology and healthcare quality programs. We made a prospective cohort NI surveillance of all acute-care patients according to the National Nosocomial Infections Surveillance System guidelines since 1992, applying the Centers for Disease Control and Prevention 1988 definitions adapted to a Brazilian pediatric hospital. Thirty-eight deaths considered to be related to NI were analyzed as the outcome variable for 754 patients with NI, whose survival time was taken into consideration. The predictive factors for mortality related to NI (p < 0.05 in the Cox regression model were: invasive procedures and use of two or more antibiotics. The mean survival time was significantly shorter (p < 0.05 with the Kaplan-Meier method for patients who suffered invasive procedures and for those who received two or more antibiotics. Applying a tree-structured survival analysis (TSSA, two groups with high mortality rates were identified: one group with time from admission to the first NI less than 11 days, received two or more antibiotics and suffered invasive procedures; the other group had the first NI between 12 and 22 days after admission and was subjected to invasive procedures. The possible modifiable factors to prevent mortality involve invasive devices and antibiotics. The TSSA approach is helpful to identify combinations of predictors and to guide protective actions to be taken in continuous-quality-improvement programs.

  11. High Incidence of Mammalian Orthoreovirus Identified by Environmental Surveillance in Taiwan.

    Directory of Open Access Journals (Sweden)

    Matthew C Y Lim

    Full Text Available Wild poliovirus (WPV persists in diverse locales worldwide, spreading outward from endemic areas. In response to the international threat of WPV transmission and changes in the national vaccination policy, we established an environmental surveillance system to monitor the circulation of wild and vaccine-related poliovirus in Taiwan. From July 2012 to December 2013, we collected sewage specimens every month from 10 sewage treatment plants located throughout Taiwan. The specimens were concentrated by the two-phase separation method and then inoculated into L20B, RD, and A549 cells for virus isolation. Viral isolates were identified and serotyped by immunofluorescence assay or molecular analysis. A total of 300 sewage samples were collected, and the results showed 163 samples (54.3% were positive for virus, and 268 isolates were identified. Among these, 75 samples (25% were positive for enterovirus (EV, but no poliovirus was found. In addition, 92 isolates were identified as enteroviruses and the most common serotypes were coxsackievirus B4, coxsackievirus B3, and coxsackievirus B2. Interestingly, 102 (34% and 82 (27.3% specimens were positive for mammalian orthoreovirus (MRV and adenovirus, respectively. This study confirmed that sewage surveillance can be a useful additional modality for monitoring the possible presence of wild-type or vaccine-derived poliovirus in wastewater, and can indicate the current types of viruses circulating in the population. Furthermore, since MRV was found in children with acute necrotizing encephalopathy and meningitis, the high incidence of MRV detected by environmental surveillance warrants further investigation.

  12. Transmission and selection of macrolide resistant Mycoplasma genitalium infections detected by rapid high resolution melt analysis.

    Directory of Open Access Journals (Sweden)

    Jimmy Twin

    Full Text Available BACKGROUND: Mycoplasma genitalium (MG causes urethritis, cervicitis and pelvic inflammatory disease. The MG treatment failure rate using 1 g azithromycin at an Australian Sexual Health clinic in 2007-9 was 31% (95%CI 23-40%. We developed a rapid high resolution melt analysis (HRMA assay targeting resistance mutations in the MG 23S rRNA gene, and validated it against DNA sequencing by examining pre- and post-treatment archived samples from MG-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Available MG-positive pre-treatment (n = 82 and post-treatment samples from individuals with clinical treatment failure (n = 20 were screened for 23S rRNA gene mutations. Sixteen (20% pre-treatment samples possessed resistance mutations (A2058G, A2059G, A2059C, which were significantly more common in patients with symptomatic azithromycin-treatment failure (12/26; 44% than in those clinically cured (4/56; 7%, p<0.001. All 20 patients experiencing azithromycin-failure had detectable mutations in their post-treatment samples. In 9 of these cases, the same mutational types were present in both pre- and post-treatment samples indicating transmitted resistance, whilst in 11 of these cases (55%, mutations were absent in pre-treatment samples indicating likely selection of resistant isolates have occurred. HRMA was able to detect all mutational changes determined in this study by DNA sequencing. An additional HRMA assay incorporating an unlabelled probe was also developed to detect type 4 single-nucleotide polymorphisms found in other populations, with a slightly lower sensitivity of 90%. CONCLUSIONS/SIGNIFICANCE: Treatment failure is associated with the detection of macrolide resistance mutations, which appear to be almost equally due to selection of resistant isolates following exposure to 1 g azithromycin and pre-existing transmitted resistance. The application of a rapid molecular assay to detect resistance at the time of initial detection of infection allows

  13. Metagenomics and single-cell genomics reveal high abundance of comammox Nitrospira in a rapid gravity sand filter treating groundwater

    DEFF Research Database (Denmark)

    Palomo, Alejandro; Fowler, Jane; Gülay, Arda;

    , the ecological relevance of comammox remains unknown. In this study, we analyzed the microbial communities from various locations within a groundwater-fed rapid sand filter (RSF), where Nitrospira were at very high relative abundances. Through metagenomics, a highly abundant composite multi-genome of Nitrospira...

  14. A PCR-high-resolution melt assay for rapid differentiation of nontypeable Haemophilus influenzae and Haemophilus haemolyticus.

    Science.gov (United States)

    Pickering, Janessa; Binks, Michael J; Beissbarth, Jemima; Hare, Kim M; Kirkham, Lea-Ann S; Smith-Vaughan, Heidi

    2014-02-01

    We have developed a PCR-high-resolution melt (PCR-HRM) assay to discriminate nontypeable Haemophilus influenzae (NTHi) colonies from Haemophilus haemolyticus. This method is rapid and robust, with 96% sensitivity and 92% specificity compared to the hpd#3 assay. PCR-HRM is ideal for high-throughput screening for NTHi surveillance and clinical trials.

  15. Automated neural network classifiers for identifying micrometastases in peripheral blood via high-throughput microscopy

    Science.gov (United States)

    Agustin, Ramses M.; Azimi, Behrad; Price, Jeffrey H.

    2007-02-01

    Tissue-specific biomarkers have been studied to identify micrometastases in bone marrow and/or peripheral blood. Many studies, however, have shown conflicting results for sensitivity and specificity of detection, forestalling translation of these findings into routine clinical use for prognosis or diagnosis. Genetic instability and heterogeneity of cancers may make using an absolute set of differential expression markers difficult, if not impossible, for accurate detection of rare cancer cells via a simple blood test. The literature is rich with examples of pathologists using morphology to identify cancer in tissue sections. We hypothesize that morphological features based on fluorescent staining of common subcellular compartments, in particular, the nucleus, may be useful for detection and classification. Highthroughput/ high-content image cytometry and computer-automated classification can aid pathologists to find suspicious cells, independent of biomarkers. Feature data are collected from an in vitro spiked model of breast cancer in the circulation; prestaining with CellTracker Orange creates a gold standard for assessing cancer origin. A neural network classifier is designed using seven nuclear morphology features thought a priori to be important for classification. With adequate training data, sensitive and specific detection may be achieved. Neural networks may be robustly trained to assist pathologists in detecting a wide variety of cancers.

  16. Identifying and quantifying heterogeneity in high content analysis: application of heterogeneity indices to drug discovery.

    Directory of Open Access Journals (Sweden)

    Albert H Gough

    Full Text Available One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology.

  17. Identifying the 'inorganic gene' for high-temperature piezoelectric perovskites through statistical learning.

    Science.gov (United States)

    Balachandran, Prasanna V; Broderick, Scott R; Rajan, Krishna

    2011-08-01

    This paper develops a statistical learning approach to identify potentially new high-temperature ferroelectric piezoelectric perovskite compounds. Unlike most computational studies on crystal chemistry, where the starting point is some form of electronic structure calculation, we use a data-driven approach to initiate our search. This is accomplished by identifying patterns of behaviour between discrete scalar descriptors associated with crystal and electronic structure and the reported Curie temperature (TC) of known compounds; extracting design rules that govern critical structure-property relationships; and discovering in a quantitative fashion the exact role of these materials descriptors. Our approach applies linear manifold methods for data dimensionality reduction to discover the dominant descriptors governing structure-property correlations (the 'genes') and Shannon entropy metrics coupled to recursive partitioning methods to quantitatively assess the specific combination of descriptors that govern the link between crystal chemistry and TC (their 'sequencing'). We use this information to develop predictive models that can suggest new structure/chemistries and/or properties. In this manner, BiTmO3-PbTiO3 and BiLuO3-PbTiO3 are predicted to have a TC of 730(°)C and 705(°)C, respectively. A quantitative structure-property relationship model similar to those used in biology and drug discovery not only predicts our new chemistries but also validates published reports.

  18. Accuracy of the high-throughput amplicon sequencing to identify species within the genus Aspergillus.

    Science.gov (United States)

    Lee, Seungeun; Yamamoto, Naomichi

    2015-12-01

    This study characterized the accuracy of high-throughput amplicon sequencing to identify species within the genus Aspergillus. To this end, we sequenced the internal transcribed spacer 1 (ITS1), β-tubulin (BenA), and calmodulin (CaM) gene encoding sequences as DNA markers from eight reference Aspergillus strains with known identities using 300-bp sequencing on the Illumina MiSeq platform, and compared them with the BLASTn outputs. The identifications with the sequences longer than 250 bp were accurate at the section rank, with some ambiguities observed at the species rank due to mostly cross detection of sibling species. Additionally, in silico analysis was performed to predict the identification accuracy for all species in the genus Aspergillus, where 107, 210, and 187 species were predicted to be identifiable down to the species rank based on ITS1, BenA, and CaM, respectively. Finally, air filter samples were analysed to quantify the relative abundances of Aspergillus species in outdoor air. The results were reproducible across biological duplicates both at the species and section ranks, but not strongly correlated between ITS1 and BenA, suggesting the Aspergillus detection can be taxonomically biased depending on the selection of the DNA markers and/or primers.

  19. Using high frequency consumption data to identify demand response potential for solar energy integration

    Science.gov (United States)

    Jin, L.; Borgeson, S.; Fredman, D.; Hans, L.; Spurlock, A.; Todd, A.

    2015-12-01

    California's renewable portfolio standard (2012) requires the state to get 33% of its electricity from renewable sources by 2020. Increased share of variable renewable sources such as solar and wind in the California electricity system may require more grid flexibility to insure reliable power services. Such grid flexibility can be potentially provided by changes in end use electricity consumptions in response to grid conditions (demand-response). In the solar case, residential consumption in the late afternoon can be used as reserve capacity to balance the drop in solar generation. This study presents our initial attempt to identify, from a behavior perspective, residential demand response potentials in relation to solar ramp events using a data-driven approach. Based on hourly residential energy consumption data, we derive representative daily load shapes focusing on discretionary consumption with an innovative clustering analysis technique. We aggregate the representative load shapes into behavior groups in terms of the timing and rhythm of energy use in the context of solar ramp events. Households of different behavior groups that are active during hours with high solar ramp rates are identified for capturing demand response potential. Insights into the nature and predictability of response to demand-response programs are provided.

  20. A p53 drug response signature identifies prognostic genes in high-risk neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Eveline Barbieri

    Full Text Available Chemotherapy induces apoptosis and tumor regression primarily through activation of p53-mediated transcription. Neuroblastoma is a p53 wild type malignancy at diagnosis and repression of p53 signaling plays an important role in its pathogenesis. Recently developed small molecule inhibitors of the MDM2-p53 interaction are able to overcome this repression and potently activate p53 dependent apoptosis in malignancies with intact p53 downstream signaling. We used the small molecule MDM2 inhibitor, Nutlin-3a, to determine the p53 drug response signature in neuroblastoma cells. In addition to p53 mediated apoptotic signatures, GSEA and pathway analysis identified a set of p53-repressed genes that were reciprocally over-expressed in neuroblastoma patients with the worst overall outcome in multiple clinical cohorts. Multifactorial regression analysis identified a subset of four genes (CHAF1A, RRM2, MCM3, and MCM6 whose expression together strongly predicted overall and event-free survival (p<0.0001. The expression of these four genes was then validated by quantitative PCR in a large independent clinical cohort. Our findings further support the concept that oncogene-driven transcriptional networks opposing p53 activation are essential for the aggressive behavior and poor response to therapy of high-risk neuroblastoma.

  1. High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor

    Science.gov (United States)

    Zhang, Le; Yang, Zhaoying; Granieri, Letizia; Pasculescu, Adrian; Datti, Alessandro; Asa, Sylvia L.; Xu, Zheli; Ezzat, Shereen

    2016-01-01

    We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer. PMID:26942566

  2. High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor.

    Science.gov (United States)

    Zhang, Le; Yang, Zhaoying; Granieri, Letizia; Pasculescu, Adrian; Datti, Alessandro; Asa, Sylvia L; Xu, Zheli; Ezzat, Shereen

    2016-04-12

    We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer.

  3. Identifying firing mammalian neurons in networks with high-resolution multi-transistor array (MTA)

    Science.gov (United States)

    Lambacher, A.; Vitzthum, V.; Zeitler, R.; Eickenscheidt, M.; Eversmann, B.; Thewes, R.; Fromherz, P.

    2011-01-01

    The electrical activity of a network of mammalian neurons is mapped with a Multi-Transistor Array (MTA) fabricated with extended CMOS technology. The spatial resolution is 7.4 μm on an area of 1 mm2 at a sampling frequency of 6 kHz for a complete readout of 16,384 sensor transistors. Action potentials give rise to extracellular voltages with amplitudes in a range of 500 μV. On the basis of the high resolution in space and time, correlation algorithms are used to identify single action potentials with amplitudes as low as about 200μV, and to assign the signals to the activity of individual neurons even in a dense network.

  4. Rapid and High Seed Germination and Large Soil Seed Bank of Senecio aquaticus in Managed Grassland

    Directory of Open Access Journals (Sweden)

    Matthias Suter

    2012-01-01

    Full Text Available Senecio aquaticus, regionally a Red List species in Europe, has become increasingly abundant in agricultural grassland of medium to high management intensity in Switzerland, Southern Germany, and Austria in recent years, where it is a threat for animal and human health due to its toxicity. In this study, we investigated the seed ecology of S. aquaticus to help protection of the species in relic populations while improving its control when abundant in managed grassland. Germination percentages of fresh ripe seeds of S. aquaticus were on average 68% in 2008, but only 45% in 2010, indicating yearly variation. Germination was generally fast: ten days after the onset of the tests, often more than 45% of all seeds had germinated. When covered with a soil layer of 5 mm, germination was only 16% compared to 63% in full light. Seeds buried in the soil for one and two years showed a germination of 78%, significantly higher than that of fresh ripe seeds, thus suggesting a stimulating effect of cold-wet stratification on germination and long seed survival in the soil. In grasslands with established populations of S. aquaticus, the number of germinable seeds of the species ranged from 361 to 1875 m-2 in topsoil (0–10 cm with an average of 1139 m-2. The large seed bank and the rapid and high germination of S. aquaticus suggest that allowing seed formation is important for its preservation in relic populations. With respect to agricultural grassland, strategies to control the species should initially target hindering seed production and dispersal.

  5. Climatology of rapid geomagnetic variations at high latitudes over two solar cycles

    Directory of Open Access Journals (Sweden)

    A. Viljanen

    2011-10-01

    Full Text Available We investigate the characteristics of rapid geomagnetic variations at high latitudes based on the occurrence of large time derivatives of the horizontal magnetic field (dH/dt exceeding 1 nT s−1. Analysis of IMAGE magnetometer data from North Europe in 1983–2010, covering more than two solar cycles, confirms and specifies several previous findings. We show that dH/dt activity is high around the midnight and early morning hours, and nearly vanishes at noon and early afternoon. This happens during all seasons, although the midnight maximum is nearly invisible during summer. As indicated by modelled ionospheric equivalent currents, large dH/dt values occur predominantly during westward ionospheric electrojets. Before and around midnight, dH/dt tends to be north-south oriented, whereas in the morning hours, its direction is more west-east directed. dH/dt tends to be more strictly north-south oriented during winter than other seasons. The seasonal occurrence of large dH/dt values is similar to the variation of the maximum amplitude of westward equivalent currents. The yearly fraction of east-west directed large dH/dt vectors at the Kilpisjärvi station (MLAT 65.88 varies from 31 to 47 % without any clear correlation with the general geomagnetic activity nor with the yearly averages of solar wind parameters.

  6. Parasitic slow extraction of extremely weak beam from a high-intensity proton rapid cycling synchrotron

    Science.gov (United States)

    Zou, Ye; Tang, Jingyu; Yang, Zheng; Jing, Hantao

    2014-02-01

    This paper proposes a novel method to extract extremely weak beam from a high-intensity proton rapid cycling synchrotron (RCS) in the parasitic mode, while maintaining the normal fast extraction. The usual slow extraction method from a synchrotron by employing third-order resonance cannot be applied in a high-intensity RCS due to a very short flat-top at the extraction energy and the strict control on beam loss. The proposed parasitic slow extraction method moves the beam to scrape a scattering foil prior to the fast beam extraction by employing either a local orbit bump or momentum deviation or their combination, so that the halo part of the beam will be scattered. A part of the scattered particles will be extracted from the RCS and guided to the experimental area. The slow extraction process can last about a few milliseconds before the beam is extracted by the fast extraction system. The method has been applied to the RCS of China Spallation Neutron Source. With 1.6 GeV in the extraction energy, 62.5 μA in the average current and 25 Hz in the repetition rate for the RCS, the proton intensity by the slow extraction method can be up to 2×104 protons per cycle or 5×105 protons per second. The extracted beam has also a good time structure of approximately uniform in a spill which is required for many applications such as detector tests. Detailed studies including the scattering effect in the foil, the local orbit bump by the bump magnets and dispersive orbit bump by modifying the RF pattern, the multi-particle simulations by ORBIT and TURTLE codes, and some technical features for the extraction magnets are presented.

  7. Computational model explains high activity and rapid cycling of Rho GTPases within protein complexes.

    Directory of Open Access Journals (Sweden)

    Andrew B Goryachev

    2006-12-01

    Full Text Available Formation of multiprotein complexes on cellular membranes is critically dependent on the cyclic activation of small GTPases. FRAP-based analyses demonstrate that within protein complexes, some small GTPases cycle nearly three orders of magnitude faster than they would spontaneously cycle in vitro. At the same time, experiments report concomitant excess of the activated, GTP-bound form of GTPases over their inactive form. Intuitively, high activity and rapid turnover are contradictory requirements. How the cells manage to maximize both remains poorly understood. Here, using GTPases of the Rab and Rho families as a prototype, we introduce a computational model of the GTPase cycle. We quantitatively investigate several plausible layouts of the cycling control module that consist of GEFs, GAPs, and GTPase effectors. We explain the existing experimental data and predict how the cycling of GTPases is controlled by the regulatory proteins in vivo. Our model explains distinct and separable roles that the activating GEFs and deactivating GAPs play in the GTPase cycling control. While the activity of GTPase is mainly defined by GEF, the turnover rate is a sole function of GAP. Maximization of the GTPase activity and turnover rate places conflicting requirements on the concentration of GAP. Therefore, to achieve a high activity and turnover rate at once, cells must carefully maintain concentrations of GEFs and GAPs within the optimal range. The values of these optimal concentrations indicate that efficient cycling can be achieved only within dense protein complexes typically assembled on the membrane surfaces. We show that the concentration requirement for GEF can be dramatically reduced by a GEF-activating GTPase effector that can also significantly boost the cycling efficiency. Interestingly, we find that the cycling regimes are only weakly dependent on the concentration of GTPase itself.

  8. Net ecosystem exchange of CO2 with rapidly changing high Arctic landscapes.

    Science.gov (United States)

    Emmerton, Craig A; St Louis, Vincent L; Humphreys, Elyn R; Gamon, John A; Barker, Joel D; Pastorello, Gilberto Z

    2016-03-01

    High Arctic landscapes are expansive and changing rapidly. However, our understanding of their functional responses and potential to mitigate or enhance anthropogenic climate change is limited by few measurements. We collected eddy covariance measurements to quantify the net ecosystem exchange (NEE) of CO2 with polar semidesert and meadow wetland landscapes at the highest latitude location measured to date (82°N). We coupled these rare data with ground and satellite vegetation production measurements (Normalized Difference Vegetation Index; NDVI) to evaluate the effectiveness of upscaling local to regional NEE. During the growing season, the dry polar semidesert landscape was a near-zero sink of atmospheric CO2 (NEE: -0.3 ± 13.5 g C m(-2) ). A nearby meadow wetland accumulated over 300 times more carbon (NEE: -79.3 ± 20.0 g C m(-2) ) than the polar semidesert landscape, and was similar to meadow wetland NEE at much more southerly latitudes. Polar semidesert NEE was most influenced by moisture, with wetter surface soils resulting in greater soil respiration and CO2 emissions. At the meadow wetland, soil heating enhanced plant growth, which in turn increased CO2 uptake. Our upscaling assessment found that polar semidesert NDVI measured on-site was low (mean: 0.120-0.157) and similar to satellite measurements (mean: 0.155-0.163). However, weak plant growth resulted in poor satellite NDVI-NEE relationships and created challenges for remotely detecting changes in the cycling of carbon on the polar semidesert landscape. The meadow wetland appeared more suitable to assess plant production and NEE via remote sensing; however, high Arctic wetland extent is constrained by topography to small areas that may be difficult to resolve with large satellite pixels. We predict that until summer precipitation and humidity increases enough to offset poor soil moisture retention, climate-related changes to productivity on polar semideserts may be restricted.

  9. The hourly updated US High-Resolution Rapid Refresh (HRRR) storm-scale forecast model

    Science.gov (United States)

    Alexander, Curtis; Dowell, David; Benjamin, Stan; Weygandt, Stephen; Olson, Joseph; Kenyon, Jaymes; Grell, Georg; Smirnova, Tanya; Ladwig, Terra; Brown, John; James, Eric; Hu, Ming

    2016-04-01

    The 3-km convective-allowing High-Resolution Rapid Refresh (HRRR) is a US NOAA hourly updating weather forecast model that use a specially configured version of the Advanced Research WRF (ARW) model and assimilate many novel and most conventional observation types on an hourly basis using Gridpoint Statistical Interpolation (GSI). Included in this assimilation is a procedure for initializing ongoing precipitation systems from observed radar reflectivity data (and proxy reflectivity from lightning and satellite data), a cloud analysis to initialize stable layer clouds from METAR and satellite observations, and special techniques to enhance retention of surface observation information. The HRRR is run hourly out to 15 forecast hours over a domain covering the entire conterminous United States using initial and boundary conditions from the hourly-cycled 13km Rapid Refresh (RAP, using similar physics and data assimilation) covering North America and a significant part of the Northern Hemisphere. The HRRR is continually developed and refined at NOAA's Earth System Research Laboratory, and an initial version was implemented into the operational NOAA/NCEP production suite in September 2014. Ongoing experimental RAP and HRRR model development throughout 2014 and 2015 has culminated in a set of data assimilation and model enhancements that will be incorporated into the first simultaneous upgrade of both the operational RAP and HRRR that is scheduled for spring 2016 at NCEP. This presentation will discuss the operational RAP and HRRR changes contained in this upgrade. The RAP domain is being expanded to encompass the NAM domain and the forecast lengths of both the RAP and HRRR are being extended. RAP and HRRR assimilation enhancements have focused on (1) extending surface data assimilation to include mesonet observations and improved use of all surface observations through better background estimates of 2-m temperature and dewpoint including projection of 2-m temperature

  10. Yeast-Based High-Throughput Screens to Identify Novel Compounds Active against Brugia malayi.

    Directory of Open Access Journals (Sweden)

    Elizabeth Bilsland

    2016-01-01

    Full Text Available Lymphatic filariasis is caused by the parasitic worms Wuchereria bancrofti, Brugia malayi or B. timori, which are transmitted via the bites from infected mosquitoes. Once in the human body, the parasites develop into adult worms in the lymphatic vessels, causing severe damage and swelling of the affected tissues. According to the World Health Organization, over 1.2 billion people in 58 countries are at risk of contracting lymphatic filariasis. Very few drugs are available to treat patients infected with these parasites, and these have low efficacy against the adult stages of the worms, which can live for 7-15 years in the human body. The requirement for annual treatment increases the risk of drug-resistant worms emerging, making it imperative to develop new drugs against these devastating diseases.We have developed a yeast-based, high-throughput screening system whereby essential yeast genes are replaced with their filarial or human counterparts. These strains are labeled with different fluorescent proteins to allow the simultaneous monitoring of strains with parasite or human genes in competition, and hence the identification of compounds that inhibit the parasite target without affecting its human ortholog. We constructed yeast strains expressing eight different Brugia malayi drug targets (as well as seven of their human counterparts, and performed medium-throughput drug screens for compounds that specifically inhibit the parasite enzymes. Using the Malaria Box collection (400 compounds, we identified nine filarial specific inhibitors and confirmed the antifilarial activity of five of these using in vitro assays against Brugia pahangi.We were able to functionally complement yeast deletions with eight different Brugia malayi enzymes that represent potential drug targets. We demonstrated that our yeast-based screening platform is efficient in identifying compounds that can discriminate between human and filarial enzymes. Hence, we are confident

  11. Exploiting jet binning to identify the initial state of high-mass resonances

    CERN Document Server

    Ebert, Markus A; Moult, Ian; Stewart, Iain W; Tackmann, Frank J; Tackmann, Kerstin; Zeune, Lisa

    2016-01-01

    If a new high-mass resonance is discovered at the Large Hadron Collider, model-independent techniques to identify the production mechanism will be crucial to understand its nature and effective couplings to Standard Model particles. We present a powerful and model-independent method to infer the initial state in the production of any high-mass color-singlet system by using a tight veto on accompanying hadronic jets to divide the data into two mutually exclusive event samples (jet bins). For a resonance of several hundred GeV, the jet binning cut needed to discriminate quark and gluon initial states is in the experimentally accessible range of several tens of GeV. It also yields comparable cross sections for both bins, making this method viable already with the small event samples available shortly after a discovery. Theoretically, the method is made feasible by utilizing an effective field theory setup to compute the jet cut dependence precisely and model-independently and to systematically control all source...

  12. Exploiting jet binning to identify the initial state of high-mass resonances

    Science.gov (United States)

    Ebert, Markus A.; Liebler, Stefan; Moult, Ian; Stewart, Iain W.; Tackmann, Frank J.; Tackmann, Kerstin; Zeune, Lisa

    2016-09-01

    If a new high-mass resonance is discovered at the Large Hadron Collider, model-independent techniques to identify the production mechanism will be crucial to understand its nature and effective couplings to Standard Model particles. We present a powerful and model-independent method to infer the initial state in the production of any high-mass color-singlet system by using a tight veto on accompanying hadronic jets to divide the data into two mutually exclusive event samples (jet bins). For a resonance of several hundred GeV, the jet binning cut needed to discriminate quark and gluon initial states is in the experimentally accessible range of several tens of GeV. It also yields comparable cross sections for both bins, making this method viable already with the small event samples available shortly after a discovery. Theoretically, the method is made feasible by utilizing an effective field theory setup to compute the jet cut dependence precisely and model independently and to systematically control all sources of theoretical uncertainties in the jet binning, as well as their correlations. We use a 750 GeV scalar resonance as an example to demonstrate the viability of our method.

  13. Identifying galaxy candidates in WSRT HI imaging of ultra-compact high velocity clouds

    CERN Document Server

    Adams, Elizabeth A K; Cannon, John M; Giovanelli, Riccardo; Haynes, Martha P

    2016-01-01

    Ultra-compact high velocity clouds (UCHVCs) were identified in the ALFALFA HI survey as potential gas-bearing dark matter halos. Here we present higher resolution neutral hydrogen (HI) observations of twelve UCHVCS with the Westerbork Synthesis Radio Telescope (WSRT). The UCHVCs were selected based on a combination of size, isolation, large recessional velocity and high column density as the best candidate dark matter halos. The WSRT data were tapered to image the UCHVCs at 210" (comparable to Arecibo) and 105" angular resolution. In a comparison of the single-dish to interferometer data, we find that the line flux recovered in the WSRT observations is comparable to that from the single-dish ALFALFA data. In addition, any structure seen in the ALFALFA data is reproduced in the WSRT maps at the same angular resolution. At 210'" resolution all the sources are generally compact with a smooth HI morphology, as expected from their identification as UCHVCs. At the higher angular resolution, a majority of the source...

  14. Duplex high-throughput flow cytometry screen identifies two novel formylpeptide receptor family probes.

    Science.gov (United States)

    Young, Susan M; Bologa, Cristian M; Fara, Dan; Bryant, Bj K; Strouse, Juan Jacob; Arterburn, Jeffrey B; Ye, Richard D; Oprea, Tudor I; Prossnitz, Eric R; Sklar, Larry A; Edwards, Bruce S

    2009-03-01

    Of recent, clinical interest have been two related human G-protein coupled receptors: formylpeptide receptor (FPR), linked to antibacterial inflammation and malignant glioma cell metastasis; and FPR like-1 (FPRL1), linked to chronic inflammation in systemic amyloidosis, Alzheimer's disease, and prion diseases. In association with the National Institutes of Health (NIH) Molecular Library Screening Network, we implemented a flow-cytometry-based high-throughput screening (HTS) approach for identifying selective small molecule FPR and FPRL1 ligands. The screening assay measured the ability of test compounds to competitively displace a high-affinity, fluorescein- labeled peptide ligand from FPR, FPRL1, or both. U937 cells expressing FPR and rat basophil leukemia (RBL) cells expressing FPRL1 were tested together in a "duplex" format. The U937 cells were color coded with red-fluorescent dye allowing their distinction during analysis. Compounds, cells, and fluorescent ligand were sequentially combined (no wash) in 15 microl assay volumes in 384-well plates. Throughput averaged approximately 11 min per plate to analyze approximately 4,000 cells ( approximately 2,000/receptor) in a 2 microl aspirate from each well. In primary single concentration HTS of 24,304 NIH Small Molecule Repository compounds, 253 resulted in inhibition >30% (181 for FPR, 72 for FPRL1) of which 40 had selective binding inhibition constants (K(i)) probes.

  15. Exploiting jet binning to identify the initial state of high-mass resonances

    Energy Technology Data Exchange (ETDEWEB)

    Ebert, Markus A.; Liebler, Stefan; Tackmann, Frank J.; Tackmann, Kerstin [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Moult, Ian; Stewart, Iain W. [Massachusetts Institute of Technology, Cambridge, MA (United States). Center for Theoretical Physics; Zeune, Lisa [NIKHEF, Amsterdam (Netherlands). Theory Group

    2016-05-15

    If a new high-mass resonance is discovered at the Large Hadron Collider, model-independent techniques to identify the production mechanism will be crucial to understand its nature and effective couplings to Standard Model particles. We present a powerful and model-independent method to infer the initial state in the production of any high-mass color-singlet system by using a tight veto on accompanying hadronic jets to divide the data into two mutually exclusive event samples (jet bins). For a resonance of several hundred GeV, the jet binning cut needed to discriminate quark and gluon initial states is in the experimentally accessible range of several tens of GeV. It also yields comparable cross sections for both bins, making this method viable already with the small event samples available shortly after a discovery. Theoretically, the method is made feasible by utilizing an effective field theory setup to compute the jet cut dependence precisely and model-independently and to systematically control all sources of theoretical uncertainties in the jet binning, as well as their correlations. We use a 750 GeV scalar resonance as an example to demonstrate the viability of our method.

  16. Novel high-molecular weight fucosylated milk oligosaccharides identified in dairy streams.

    Directory of Open Access Journals (Sweden)

    Raj Mehra

    Full Text Available Oligosaccharides are the third largest component in human milk. This abundance is remarkable because oligosaccharides are not digestible by the newborn, and yet they have been conserved and amplified during evolution. In addition to encouraging the growth of a protective microbiota dominated by bifidobacteria, oligosaccharides have anti-infective activity, preventing pathogens from binding to intestinal cells. Although it would be advantageous adding these valuable molecules to infant milk formula, the technologies to reproduce the variety and complexity of human milk oligosaccharides by enzymatic/organic synthesis are not yet mature. Consequently, there is an enormous interest in alternative sources of these valuable oligosaccharides. Recent research has demonstrated that bovine milk and whey permeate also contain oligosaccharides. Thus, a thorough characterization of oligosaccharides in bovine dairy streams is an important step towards fully assessing their specific functionalities. In this study, bovine milk oligosaccharides (BMOs were concentrated by membrane filtration from a readily available dairy stream called "mother liquor", and analyzed by high accuracy MALDI FT-ICR mass spectrometry. The combination of HPLC and accurate mass spectrometry allowed the identification of ideal processing conditions leading to the production of Kg amount of BMO enriched powders. Among the BMOs identified, 18 have high-molecular weight and corresponded in size to the most abundant oligosaccharides present in human milk. Notably 6 oligosaccharides contained fucose, a sugar monomer that is highly abundant in human milk, but is rarely observed in bovine milk. This work shows that dairy streams represent a potential source of complex milk oligosaccharides for commercial development of unique dairy ingredients in functional foods that reproduce the benefits of human milk.

  17. Remote Sensing as a Landscape Epidemiologic Tool to Identify Villages at High Risk for Malaria Transmission

    Science.gov (United States)

    Beck, Louisa R.; Rodriquez, Mario H.; Dister, Sheri W.; Rodriquez, Americo D.; Rejmankova, Eliska; Ulloa, Armando; Meza, Rosa A.; Roberts, Donald R.; Paris, Jack F.; Spanner, Michael A.; hide

    1994-01-01

    A landscape approach using remote sensing and Geographic Information System (GIS) technologies was developed to discriminate between villages at high and low risk for malaria transmission, as defined by adult Anopheles albimanus abundance. Satellite data for an area in southern Chiapas, Mexico were digitally processed to generate a map of landscape elements. The GIS processes were used to determine the proportion of mapped landscape elements surrounding 40 villages where An. albimanus data had been collected. The relationships between vector abundance and landscape element proportions were investigated using stepwise discriminant analysis and stepwise linear regression. Both analyses indicated that the most important landscape elements in terms of explaining vector abundance were transitional swamp and unmanaged pasture. Discriminant functions generated for these two elements were able to correctly distinguish between villages with high ind low vector abundance, with an overall accuracy of 90%. Regression results found both transitional swamp and unmanaged pasture proportions to be predictive of vector abundance during the mid-to-late wet season. This approach, which integrates remotely sensed data and GIS capabilities to identify villages with high vector-human contact risk, provides a promising tool for malaria surveillance programs that depend on labor-intensive field techniques. This is particularly relevant in areas where the lack of accurate surveillance capabilities may result in no malaria control action when, in fact, directed action is necessary. In general, this landscape approach could be applied to other vector-borne diseases in areas where: 1. the landscape elements critical to vector survival are known and 2. these elements can be detected at remote sensing scales.

  18. Convergent polishing: a simple, rapid, full aperture polishing process of high quality optical flats & spheres.

    Science.gov (United States)

    Suratwala, Tayyab; Steele, Rusty; Feit, Michael; Dylla-Spears, Rebecca; Desjardin, Richard; Mason, Dan; Wong, Lana; Geraghty, Paul; Miller, Phil; Shen, Nan

    2014-12-01

    Convergent Polishing is a novel polishing system and method for finishing flat and spherical glass optics in which a workpiece, independent of its initial shape (i.e., surface figure), will converge to final surface figure with excellent surface quality under a fixed, unchanging set of polishing parameters in a single polishing iteration. In contrast, conventional full aperture polishing methods require multiple, often long, iterative cycles involving polishing, metrology and process changes to achieve the desired surface figure. The Convergent Polishing process is based on the concept of workpiece-lap height mismatch resulting in pressure differential that decreases with removal and results in the workpiece converging to the shape of the lap. The successful implementation of the Convergent Polishing process is a result of the combination of a number of technologies to remove all sources of non-uniform spatial material removal (except for workpiece-lap mismatch) for surface figure convergence and to reduce the number of rogue particles in the system for low scratch densities and low roughness. The Convergent Polishing process has been demonstrated for the fabrication of both flats and spheres of various shapes, sizes, and aspect ratios on various glass materials. The practical impact is that high quality optical components can be fabricated more rapidly, more repeatedly, with less metrology, and with less labor, resulting in lower unit costs. In this study, the Convergent Polishing protocol is specifically described for fabricating 26.5 cm square fused silica flats from a fine ground surface to a polished ~λ/2 surface figure after polishing 4 hr per surface on a 81 cm diameter polisher.

  19. Survival of rapidly fluctuating natural low winter temperatures by High Arctic soil invertebrates.

    Science.gov (United States)

    Convey, Peter; Abbandonato, Holly; Bergan, Frode; Beumer, Larissa Teresa; Biersma, Elisabeth Machteld; Bråthen, Vegard Sandøy; D'Imperio, Ludovica; Jensen, Christina Kjellerup; Nilsen, Solveig; Paquin, Karolina; Stenkewitz, Ute; Svoen, Mildrid Elvik; Winkler, Judith; Müller, Eike; Coulson, Stephen James

    2015-12-01

    The extreme polar environment creates challenges for its resident invertebrate communities and the stress tolerance of some of these animals has been examined over many years. However, although it is well appreciated that standard air temperature records often fail to describe accurately conditions experienced at microhabitat level, few studies have explicitly set out to link field conditions experienced by natural multispecies communities with the more detailed laboratory ecophysiological studies of a small number of 'representative' species. This is particularly the case during winter, when snow cover may insulate terrestrial habitats from extreme air temperature fluctuations. Further, climate projections suggest large changes in precipitation will occur in the polar regions, with the greatest changes expected during the winter period and, hence, implications for the insulation of overwintering microhabitats. To assess survival of natural High Arctic soil invertebrate communities contained in soil and vegetation cores to natural winter temperature variations, the overwintering temperatures they experienced were manipulated by deploying cores in locations with varying snow accumulation: No Snow, Shallow Snow (30 cm) and Deep Snow (120 cm). Air temperatures during the winter period fluctuated frequently between +3 and -24 °C, and the No Snow soil temperatures reflected this variation closely, with the extreme minimum being slightly lower. Under 30 cm of snow, soil temperatures varied less and did not decrease below -12 °C. Those under deep snow were even more stable and did not decline below -2 °C. Despite these striking differences in winter thermal regimes, there were no clear differences in survival of the invertebrate fauna between treatments, including oribatid, prostigmatid and mesostigmatid mites, Araneae, Collembola, Nematocera larvae or Coleoptera. This indicates widespread tolerance, previously undocumented for the Araneae, Nematocera or Coleoptera, of

  20. [Rapid determination of propranolol enantiomers in rat plasma by column-switching-high performance liquid chromatography].

    Science.gov (United States)

    Wu, Xiaoyu; Wang, Rong; Xie, Hua; Wang, Jianfeng; Jia, Zhengping; Zhang, Qiang; Wang, Xianhua

    2011-12-01

    A high performance liquid chromatographic (HPLC) method with column-switching was developed and validated for rapid determination of two propranolol enantiomers in rat plasma. The column of restricted-access media was used as a pre-treatment column and a Chiralcel OD-RH was used as analytical column. The plasma samples were injected directly into the pretreatment column to remove plasma protein and endogenous constituents as well as to retent the propranolol enantiomers in the column using the mobile phase of borate buffer (pH 8.5)-methanol (95:5, v/v) at the flow rate of 1.0 mL/min. Then the propranolol enantiomers were transferred to the Chiralcel OD-RH column using the mobile phase of isopropanol-ethanol-0.2 mmol/L borate buffer (pH 8.5) (30: 30: 40, v/v/v) at a flow rate of 0.8 mL/min by column-switching technology. The column-switching time was 3.0 min, the used wavelength was 293 nm and the column temperature was set at 25 degrees C. The calibration curve showed excellent linear relationship (r = 0.999 5) in the concentration range from 25 mg/L to 500 mg/L for propranolol enantiomers in plasma. The intra-day and inter-day assay precisions and accuracies were well and the relative standard deviations (RSDs) were less than 5%. The average recoveries (n = 6) of the two enantiomers at 3 spiked levels were from 97.89% to 101.56%. All the values of the method validation were within the generally accepted criteria for biological sample analysis. The results show that the method is convenient, quick, sensitive and accurate. The method was successfully applied in the determination of propranolol enantiomers in rat blood pharmacokinetics study.

  1. NIR-Triggered Rapid Shape Memory PAM-GO-Gelatin Hydrogels with High Mechanical Strength.

    Science.gov (United States)

    Huang, Jiahe; Zhao, Lei; Wang, Tao; Sun, Weixiang; Tong, Zhen

    2016-05-18

    Shape memory hydrogels containing over 76 wt % of water were synthesized in a one-pot method, and interpenetrating double network was formed by physically cross-linked gelatin network and chemically cross-linked polyacrylamide (PAM) network with graphene oxide (GO). The temporary shape was quickly fixed by cooling in ice water for 30 s after deformation at 80 °C for 10 s. Shape recovery started in 10 s under near-infrared (NIR) irradiation and almost completed within 60 s depending on the curling angle. A small amount of GO in the hydrogels (≤1.5 mg/mL) played a key role in NIR energy absorption and transformation into thermal energy. The hydrogel without GO showed no response to the NIR irradiation and cannot recover to its permanent shape by NIR irradiation. Temperature sweep was conducted in the cycle of 20 °C → 80 °C → 20 °C, and the structure change in the hydrogels with temperature was investigated according to the storage modulus G' and tangent of the loss angle tan δ as a function of the hydrogel composition. The shape-memory capability was confirmed as the contribution from the triple-helix cross-linking network of gelatin. High mechanical toughness (strength > 400 kPa and broken strain > 500%) was achieved by the double-network with the sacrificial gelatin network and GO bridging to dissipate deformation energy. The optimized composition of the hydrogel was found to be a key point to realize stable temporary shape and rapid recovery to the permanent shape controlled by NIR irradiation with reasonable strength. The facile preparation and noncontact gentle stimulus of the present hydrogel hold great potential to be used in soft actuator materials.

  2. Rapid Hydrogen and Oxygen Atom Transfer by a High-Valent Nickel-Oxygen Species.

    Science.gov (United States)

    Corona, Teresa; Draksharapu, Apparao; Padamati, Sandeep K; Gamba, Ilaria; Martin-Diaconescu, Vlad; Acuña-Parés, Ferran; Browne, Wesley R; Company, Anna

    2016-10-05

    Terminal high-valent metal-oxygen species are key reaction intermediates in the catalytic cycle of both enzymes (e.g., oxygenases) and synthetic oxidation catalysts. While tremendous efforts have been directed toward the characterization of the biologically relevant terminal manganese-oxygen and iron-oxygen species, the corresponding analogues based on late-transition metals such as cobalt, nickel or copper are relatively scarce. This scarcity is in part related to the "Oxo Wall" concept, which predicts that late transition metals cannot support a terminal oxido ligand in a tetragonal environment. Here, the nickel(II) complex (1) of the tetradentate macrocyclic ligand bearing a 2,6-pyridinedicarboxamidate unit is shown to be an effective catalyst in the chlorination and oxidation of C-H bonds with sodium hypochlorite as terminal oxidant in the presence of acetic acid (AcOH). Insight into the active species responsible for the observed reactivity was gained through the study of the reaction of 1 with ClO(-) at low temperature by UV-vis absorption, resonance Raman, EPR, ESI-MS, and XAS analyses. DFT calculations aided the assignment of the trapped chromophoric species (3) as a nickel-hypochlorite species. Despite the fact that the formal oxidation state of the nickel in 3 is +4, experimental and computational analysis indicate that 3 is best formulated as a Ni(III) complex with one unpaired electron delocalized in the ligands surrounding the metal center. Most remarkably, 3 reacts rapidly with a range of substrates including those with strong aliphatic C-H bonds, indicating the direct involvement of 3 in the oxidation/chlorination reactions observed in the 1/ClO(-)/AcOH catalytic system.

  3. Simple Test of Manual Dexterity Can Help to Identify Persons at High Risk for Neurodegenerative Diseases in the Community.

    Science.gov (United States)

    Darweesh, Sirwan K L; Wolters, Frank J; Hofman, Albert; Stricker, Bruno H; Koudstaal, Peter J; Ikram, M Arfan

    2017-01-01

    Early identification of individuals at high risk of developing neurodegenerative diseases is essential for timely preventive intervention. However, simple methods that can be used for risk assessment in general practice are lacking. Within the population-based Rotterdam Study, we used the Purdue Pegboard Test (PPT) to assess manual dexterity in 4,856 persons (median age 70 years, 58% women) free of parkinsonism and dementia between 2000 and 2004. We followed these persons until January 1, 2012 for the onset of neurodegenerative diseases (defined as first diagnosis of parkinsonism or dementia). We determined the association of PPT scores with incident neurodegenerative disease, adjusting for age, sex, study cohort, level of education, smoking, preferred hand, parental history, memory complaints, and Mini-Mental State Examination. Furthermore, we determined the incremental predictive value of PPT, expressed as change in risk classification and discrimination. During follow-up (median 9.2 years), 277 participants were diagnosed with a neurodegenerative disease (227 with dementia and 50 with parkinsonism). Lower PPT scores were associated with higher risk of incident neurodegenerative diseases (hazard ratio [HR] = 1.28, 95% confidence interval [CI]: 1.18-1.41) and improved discrimination of incident neurodegenerative diseases. We also observed significant associations of PPT scores separately with incident dementia (HR = 1.25; 95% CI: 1.14-1.39]) and incident parkinsonism (HR = 1.41; 95% CI: 1.19-1.67). A rapid, nonlaboratory test of manual dexterity may help to identify persons at high risk for neurodegenerative diseases. This highlights the importance of motor function in the preclinical phase of both dementia and parkinsonism and may aid in selecting individuals for refined screening and neuroprotective trials. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e

  4. Quantitative high-throughput screening identifies 8-hydroxyquinolines as cell-active histone demethylase inhibitors.

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    Oliver N F King

    Full Text Available BACKGROUND: Small molecule modulators of epigenetic processes are currently sought as basic probes for biochemical mechanisms, and as starting points for development of therapeutic agents. N(ε-Methylation of lysine residues on histone tails is one of a number of post-translational modifications that together enable transcriptional regulation. Histone lysine demethylases antagonize the action of histone methyltransferases in a site- and methylation state-specific manner. N(ε-Methyllysine demethylases that use 2-oxoglutarate as co-factor are associated with diverse human diseases, including cancer, inflammation and X-linked mental retardation; they are proposed as targets for the therapeutic modulation of transcription. There are few reports on the identification of templates that are amenable to development as potent inhibitors in vivo and large diverse collections have yet to be exploited for the discovery of demethylase inhibitors. PRINCIPAL FINDINGS: High-throughput screening of a ∼236,000-member collection of diverse molecules arrayed as dilution series was used to identify inhibitors of the JMJD2 (KDM4 family of 2-oxoglutarate-dependent histone demethylases. Initial screening hits were prioritized by a combination of cheminformatics, counterscreening using a coupled assay enzyme, and orthogonal confirmatory detection of inhibition by mass spectrometric assays. Follow-up studies were carried out on one of the series identified, 8-hydroxyquinolines, which were shown by crystallographic analyses to inhibit by binding to the active site Fe(II and to modulate demethylation at the H3K9 locus in a cell-based assay. CONCLUSIONS: These studies demonstrate that diverse compound screening can yield novel inhibitors of 2OG dependent histone demethylases and provide starting points for the development of potent and selective agents to interrogate epigenetic regulation.

  5. Grapevine powdery mildew resistance and susceptibility loci identified on a high-resolution SNP map.

    Science.gov (United States)

    Barba, Paola; Cadle-Davidson, Lance; Harriman, James; Glaubitz, Jeffrey C; Brooks, Siraprapa; Hyma, Katie; Reisch, Bruce

    2014-01-01

    Improved efficacy and durability of powdery mildew resistance can be enhanced via knowledge of the genetics of resistance and susceptibility coupled with the development of high-resolution maps to facilitate the stacking of multiple resistance genes and other desirable traits. We studied the inheritance of powdery mildew (Erysiphe necator) resistance and susceptibility of wild Vitis rupestris B38 and cultivated V. vinifera 'Chardonnay', finding evidence for quantitative variation. Molecular markers were identified using genotyping-by-sequencing, resulting in 16,833 single nucleotide polymorphisms (SNPs) based on alignment to the V. vinifera 'PN40024' reference genome sequence. With an average density of 36 SNPs/Mbp and uniform coverage of the genome, this 17K set was used to identify 11 SNPs on chromosome 7 associated with a resistance locus from V. rupestris B38 and ten SNPs on chromosome 9 associated with a locus for susceptibility from 'Chardonnay' using single marker association and linkage disequilibrium analysis. Linkage maps for V. rupestris B38 (1,146 SNPs) and 'Chardonnay' (1,215 SNPs) were constructed and used to corroborate the 'Chardonnay' locus named Sen1 (Susceptibility to Erysiphe necator 1), providing the first insight into the genetics of susceptibility to powdery mildew from V. vinifera. The identification of markers associated with a susceptibility locus in a V. vinifera background can be used for negative selection among breeding progenies. This work improves our understanding of the nature of powdery mildew resistance in V. rupestris B38 and 'Chardonnay', while applying next-generation sequencing tools to advance grapevine genomics and breeding.

  6. A prognostic tool to identify adolescents at high risk of becoming daily smokers

    Directory of Open Access Journals (Sweden)

    Paradis Gilles

    2011-08-01

    Full Text Available Abstract Background The American Academy of Pediatrics advocates that pediatricians should be involved in tobacco counseling and has developed guidelines for counseling. We present a prognostic tool for use by health care practitioners in both clinical and non-clinical settings, to identify adolescents at risk of becoming daily smokers. Methods Data were drawn from the Nicotine Dependence in Teens (NDIT Study, a prospective investigation of 1293 adolescents, initially aged 12-13 years, recruited in 10 secondary schools in Montreal, Canada in 1999. Questionnaires were administered every three months for five years. The prognostic tool was developed using estimated coefficients from multivariable logistic models. Model overfitting was corrected using bootstrap cross-validation. Goodness-of-fit and predictive ability of the models were assessed by R2, the c-statistic, and the Hosmer-Lemeshow test. Results The 1-year and 2-year probability of initiating daily smoking was a joint function of seven individual characteristics: age; ever smoked; ever felt like you needed a cigarette; parent(s smoke; sibling(s smoke; friend(s smoke; and ever drank alcohol. The models were characterized by reasonably good fit and predictive ability. They were transformed into user-friendly tables such that the risk of daily smoking can be easily computed by summing points for responses to each item. The prognostic tool is also available on-line at http://episerve.chumontreal.qc.ca/calculation_risk/daily-risk/daily_smokingadd.php. Conclusions The prognostic tool to identify youth at high risk of daily smoking may eventually be an important component of a comprehensive tobacco control system.

  7. Analyzing treatment aggressiveness and identifying high-risk patients in diabetic foot ulcer return to care.

    Science.gov (United States)

    Remington, Austin C; Hernandez-Boussard, Tina; Warstadt, Nicholus M; Finnegan, Micaela A; Shaffer, Robyn; Kwong, Jereen Z; Curtin, Catherine

    2016-07-01

    Rates of diabetes and its associated comorbidities have been increasing in the United States, with diabetic foot ulcer treatment representing a large cost to the patient and healthcare system. These ulcers often result in multiple hospital admissions. This study examined readmissions following inpatient care for a diabetic foot ulcer and identified modifiable factors associated with all-cause 30-day readmissions to the inpatient or emergency department (ED) setting. We hypothesized that patients undergoing aggressive treatment would have lower 30-day readmission rates. We identified patient discharge records containing International Classification of Disease ninth revision codes for both diabetes mellitus and distal foot ulcer in the State Inpatient and Emergency Department databases from the Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project in Florida and New York, 2011-2012. All-cause 30-day return to care visits (ED or inpatient) were analyzed. Patient demographics and treatment characteristics were evaluated using univariate and multivariable regression models. The cohort included 25,911 discharges, having a mean age of 63 and an average of 3.8 comorbidities. The overall rate of return to care was 30%, and 21% of subjects underwent a toe or midfoot amputation during their index stay. The most common diagnosis codes upon readmission were diabetes mellitus (19%) and infection (13%). Patients with a toe or midfoot amputation procedure were less likely to be readmitted within 30 days (odds ratio: 0.78; 95% confidence interval: 0.73, 0.84). Presence of comorbidities, black and Hispanic ethnicities, and Medicare and Medicaid payer status were also associated with higher odds of readmission following initial hospitalization (p < 0.05). The study suggests that there are many factors that affect readmission rates for diabetic foot ulcer patients. Understanding patients at high-risk for readmission can improve counseling and

  8. NSC23925, identified in a high-throughput cell-based screen, reverses multidrug resistance.

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    Zhenfeng Duan

    Full Text Available BACKGROUND: Multidrug resistance (MDR is a major factor which contributes to the failure of cancer chemotherapy, and numerous efforts have been attempted to overcome MDR. To date, none of these attempts have yielded a tolerable and effective therapy to reverse MDR; thus, identification of new agents would be useful both clinically and scientifically. METHODOLOGY/PRINCIPAL FINDINGS: To identify small molecule compounds that can reverse chemoresistance, we developed a 96-well plate high-throughput cell-based screening assay in a paclitaxel resistant ovarian cancer cell line. Coincubating cells with a sublethal concentration of paclitaxel in combination with each of 2,000 small molecule compounds from the National Cancer Institute Diversity Set Library, we identified a previously uncharacterized molecule, NSC23925, that inhibits Pgp1 and reverses MDR1 (Pgp1 but does not inhibit MRP or BCRP-mediated MDR. The cytotoxic activity of NSC23925 was further evaluated using a panel of cancer cell lines expressing Pgp1, MRP, and BCRP. We found that at a concentration of >10 microM NSC23925 moderately inhibits the proliferation of both sensitive and resistant cell lines with almost equal activity, but its inhibitory effect was not altered by co-incubation with the Pgp1 inhibitor, verapamil, suggesting that NSC23925 itself is not a substrate of Pgp1. Additionally, NSC23925 increases the intracellular accumulation of Pgp1 substrates: calcein AM, Rhodamine-123, paclitaxel, mitoxantrone, and doxorubicin. Interestingly, we further observed that, although NSC23925 directly inhibits the function of Pgp1 in a dose-dependent manner without altering the total expression level of Pgp1, NSC23925 actually stimulates ATPase activity of Pgp, a phenomenon seen in other Pgp inhibitors. CONCLUSIONS/SIGNIFICANCE: The ability of NSC23925 to restore sensitivity to the cytotoxic effects of chemotherapy or to prevent resistance could significantly benefit cancer patients.

  9. Rapid, non-invasive imaging of alphaviral brain infection: Reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals

    OpenAIRE

    Patterson, Michael; Poussard, Allison; Taylor, Katherine; Seregin, Alexey; Smith, Jeanon; Peng, Bi-Hung; Walker, Aida; Linde, Jenna; Smith, Jennifer; Salazar, Milagros; Paessler, Slobodan

    2011-01-01

    Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume’s 3Rs (replacement, reduction, refinement) described by Russel and Burch. In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomp...

  10. Rapid screening of ascorbic acid, glycoalkaloids, and phenolics in potato using high-performance liquid chromatography.

    Science.gov (United States)

    Shakya, Roshani; Navarre, Duroy A

    2006-07-26

    Evaluation of phenolic metabolism in potato tubers (Solanum tuberosum) would be facilitated by faster analytical methods. A high-throughput HPLC method was developed for the qualitative and quantitative determination in potato of numerous phenolic compounds, the sum of the glycoalkaloids chaconine and solanine, plus ascorbic acid. Following a fast extraction, HPLC run times of 12 min were achieved with the use of a monolithic RP C18 column. UV and MS analyses were used to characterize the phenolic complement in extracts from two white-fleshed varieties. Over 30 compounds were identified, some of which are thought to possess either nutritional value or are involved in plant disease resistance. This method is expected to be useful for germplasm mining and for varietal development programs in which large numbers of lines are generated.

  11. Rapid detection and non-subjective characterisation of infectious bronchitis virus isolates using high-resolution melt curve analysis and a mathematical model.

    Science.gov (United States)

    Hewson, Kylie; Noormohammadi, Amir H; Devlin, Joanne M; Mardani, Karim; Ignjatovic, Jagoda

    2009-01-01

    Infectious bronchitis virus (IBV) is a coronavirus that causes upper respiratory, renal and/or reproductive diseases with high morbidity in poultry. Classification of IBV is important for implementation of vaccination strategies to control the disease in commercial poultry. Currently, the lengthy process of sequence analysis of the IBV S1 gene is considered the gold standard for IBV strain identification, with a high nucleotide identity (e.g. > or =95%) indicating related strains. However, this gene has a high propensity to mutate and/or undergo recombination, and alone it may not be reliable for strain identification. A real-time polymerase chain reaction (RT-PCR) combined with high-resolution melt (HRM) curve analysis was developed based on the 3'UTR of IBV for rapid detection and classification of IBV from commercial poultry. HRM curves generated from 230 to 435-bp PCR products of several IBV strains were subjected to further analysis using a mathematical model also developed during this study. It was shown that a combination of HRM curve analysis and the mathematical model could reliably group 189 out of 190 comparisons of pairs of IBV strains in accordance with their 3'UTR and S1 gene identities. The newly developed RT-PCR/HRM curve analysis model could detect and rapidly identify novel and vaccine-related IBV strains, as confirmed by S1 gene and 3'UTR nucleotide sequences. This model is a rapid, reliable, accurate and non-subjective system for detection of IBVs in poultry flocks.

  12. Arbovirus detection in insect vectors by rapid, high-throughput pyrosequencing.

    Directory of Open Access Journals (Sweden)

    Kimberly A Bishop-Lilly

    Full Text Available BACKGROUND: Despite the global threat caused by arthropod-borne viruses, there is not an efficient method for screening vector populations to detect novel viral sequences. Current viral detection and surveillance methods based on culture can be costly and time consuming and are predicated on prior knowledge of the etiologic agent, as they rely on specific oligonucleotide primers or antibodies. Therefore, these techniques may be unsuitable for situations when the causative agent of an outbreak is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we explored the use of high-throughput pyrosequencing for surveillance of arthropod-borne RNA viruses. Dengue virus, a member of the positive strand RNA Flavivirus family that is transmitted by several members of the Aedes genus of mosquitoes, was used as a model. Aedes aegypti mosquitoes experimentally infected with dengue virus type 1 (DENV-1 were pooled with noninfected mosquitoes to simulate samples derived from ongoing arbovirus surveillance programs. Using random-primed methods, total RNA was reverse-transcribed and resulting cDNA subjected to 454 pyrosequencing. CONCLUSIONS/SIGNIFICANCE: In two types of samples, one with 5 adult mosquitoes infected with DENV-1- and the other with 1 DENV-1 infected mosquito and 4 noninfected mosquitoes, we identified DENV-1 DNA sequences. DENV-1 sequences were not detected in an uninfected control pool of 5 adult mosquitoes. We calculated the proportion of the Ae. aegypti metagenome contributed by each infecting Dengue virus genome (p(IP, which ranged from 2.75×10(-8 to 1.08×10(-7. DENV-1 RNA was sufficiently concentrated in the mosquito that its detection was feasible using current high-throughput sequencing instrumentation. We also identified some of the components of the mosquito microflora on the basis of the sequence of expressed RNA. This included members of the bacterial genera Pirellula and Asaia, various fungi, and a potentially uncharacterized

  13. Identifying Children at Risk of High Myopia Using Population Centile Curves of Refraction.

    Science.gov (United States)

    Chen, Yanxian; Zhang, Jian; Morgan, Ian G; He, Mingguang

    2016-01-01

    To construct reference centile curves of refraction based on population-based data as an age-specific severity scale to evaluate their efficacy as a tool for identifying children at risk of developing high myopia in a longitudinal study. Data of 4218 children aged 5-15 years from the Guangzhou Refractive Error Study in Children (RESC) study, and 354 first-born twins from the Guangzhou Twin Eye Study (GTES) with annual visit were included in the analysis. Reference centile curves for refraction were constructed using a quantile regression model based on the cycloplegic refraction data from the RESC. The risk of developing high myopia (spherical equivalent ≤ -6 diopters [D]) was evaluated as a diagnostic test using the twin follow-up data. The centile curves suggested that the 3rd, 5th, and 10th percentile decreased from -0.25 D, 0.00 D and 0.25 D in 5 year-olds to -6.00 D, -5.65D and -4.63 D in 15 year-olds in the population-based data from RESC. In the GTES cohort, the 5th centile showed the most effective diagnostic value with a sensitivity of 92.9%, a specificity of 97.9% and a positive predictive value (PPV) of 65.0% in predicting high myopia onset (≤-6.00D) before the age of 15 years. The PPV was highest (87.5%) in 3rd centile but with only 50.0% sensitivity. The Mathew's correlation coefficient of 5th centile in predicting myopia of -6.0D/-5.0D/-4.0D by age of 15 was 0.77/0.51/0.30 respectively. Reference centile curves provide an age-specific estimation on a severity scale of refractive error in school-aged children. Children located under lower percentiles at young age were more likely to have high myopia at 15 years or probably in adulthood.

  14. High throughput sequencing in mice: a platform comparison identifies a preponderance of cryptic SNPs

    Directory of Open Access Journals (Sweden)

    Darakjian Priscila

    2009-08-01

    Full Text Available Abstract Background Allelic variation is the cornerstone of genetically determined differences in gene expression, gene product structure, physiology, and behavior. However, allelic variation, particularly cryptic (unknown or not annotated variation, is problematic for follow up analyses. Polymorphisms result in a high incidence of false positive and false negative results in hybridization based analyses and hinder the identification of the true variation underlying genetically determined differences in physiology and behavior. Given the proliferation of mouse genetic models (e.g., knockout models, selectively bred lines, heterogeneous stocks derived from standard inbred strains and wild mice and the wealth of gene expression microarray and phenotypic studies using genetic models, the impact of naturally-occurring polymorphisms on these data is critical. With the advent of next-generation, high-throughput sequencing, we are now in a position to determine to what extent polymorphisms are currently cryptic in such models and their impact on downstream analyses. Results We sequenced the two most commonly used inbred mouse strains, DBA/2J and C57BL/6J, across a region of chromosome 1 (171.6 – 174.6 megabases using two next generation high-throughput sequencing platforms: Applied Biosystems (SOLiD and Illumina (Genome Analyzer. Using the same templates on both platforms, we compared realignments and single nucleotide polymorphism (SNP detection with an 80 fold average read depth across platforms and samples. While public datasets currently annotate 4,527 SNPs between the two strains in this interval, thorough high-throughput sequencing identified a total of 11,824 SNPs in the interval, including 7,663 new SNPs. Furthermore, we confirmed 40 missense SNPs and discovered 36 new missense SNPs. Conclusion Comparisons utilizing even two of the best characterized mouse genetic models, DBA/2J and C57BL/6J, indicate that more than half of naturally

  15. A computational method to help identify and measure metal lines in high resolution QSO spectra

    Institute of Scientific and Technical Information of China (English)

    Xi-Heng Shi; David Tytler; Jin-Liang Hou; David Kirkman; Jeffery Lee; Benjamin Ou

    2011-01-01

    A computational code is developed to help identify metal absorption lines in high resolution QSO spectra,especially in the Lyα forest.The input to the code includes a list of line central wavelengths,column densities and Doppler widths.The code then searches for candidate metal absorption systems and assesses the probability that each system could be real.The framework of the strategy we employ is described in detail and we discuss how to estimate the errors in line profile fitting that are essential to identification.A series of artificial spectra is constructed to calibrate the performance of the code.Due to the effects of blending and noise on Voigt profile fitting,the completeness of the identification depends on the column density of absorbers.For intermediate and strong artificial metal absorbers,more than 90% could be confirmed by the code.The results of applying the code to the real spectra of QSOs HS0757+5218 and Q0100+1300 are also presented.

  16. HIGH NATURE VALUE GRASSLANDS FROM ARRHENATHERION ALLIANCE IDENTIFIED IN MUREŞ COUNTY

    Directory of Open Access Journals (Sweden)

    Silvia Oroian

    2016-11-01

    Full Text Available Arrhenatherion alliance meadows are recognized to be among the best pastures in our country due to high productivity and good nutrition value. The research was conducted in several areas of Mures County. The studied grasslands were classified into two types of Natura 2000 habitats: 6510 Lowland hay meadows (Alopecurus pratensis, Sanguisorba officinalis and 6520 Mountain hay meadows. The identified phytocoenosis belong to two plant associations: Arrhenatheretum elatioris Br.-Bl. Ex Scherrer 1925 and Poo Trisetetum flavescentis (Knapp 1951 Oberd. 1957. The analysis of data collected in the field reveals that the current state of conservation of the two types of habitat is good and very good. Habitats in a good and very good state of preservation is distinguish by a great floristic composition: approx. 100-150 cormophyte species with good and very good forage value. As habitats are more susceptible to the management applied and any changes to land use can affect habitat quality (eg abandoning  mowing and turning the land into pasture, the ecological functions of this habitat will be satisfied as long as they are mowed after Poaceae species matured.

  17. Efficacy of the Kyoto Classification of Gastritis in Identifying Patients at High Risk for Gastric Cancer.

    Science.gov (United States)

    Sugimoto, Mitsushige; Ban, Hiromitsu; Ichikawa, Hitomi; Sahara, Shu; Otsuka, Taketo; Inatomi, Osamu; Bamba, Shigeki; Furuta, Takahisa; Andoh, Akira

    2017-01-01

    Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, pgastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all pgastritis classification may thus be useful for detecting these patients.

  18. Identified particle yield associated with a high-$p_T$ trigger particle at the LHC

    CERN Document Server

    Veldhoen, Misha; van Leeuwen, Marco

    Identified particle production ratios are important observables, used to constrain models of particle production in heavy-ion collisions. Measurements of the inclusive particle ratio in central heavy-ion collisions showed an increase of the baryon-to-meson ratio compared to proton-proton collisions at intermediate pT, the so-called baryon anomaly. One possible explanation of the baryon anomaly is that partons from the thermalized deconfined QCD matter hadronize in a different way compared to hadrons produced in a vacuum jet. In this work we extend on previous measurements by measuring particle ratios in the yield associated with a high-pT trigger particle. These measurements can potentially further constrain the models of particle production since they are sensitive to the difference between particles from a jet and particles that are produced in the bulk. We start by developing a particle identification method that uses both the specific energy loss of a particle and the time of flight. From there, we presen...

  19. Multicomponent statistical analysis to identify flow and transport processes in a highly-complex environment

    Science.gov (United States)

    Moeck, Christian; Radny, Dirk; Borer, Paul; Rothardt, Judith; Auckenthaler, Adrian; Berg, Michael; Schirmer, Mario

    2016-11-01

    A combined approach of multivariate statistical analysis, namely factor analysis (FA) and hierarchical cluster analysis (HCA), interpretation of geochemical processes, stable water isotope data and organic micropollutants enabling to assess spatial patterns of water types was performed for a study area in Switzerland, where drinking water production is close to different potential input pathways for contamination. To avoid drinking water contamination, artificial groundwater recharge with surface water into an aquifer is used to create a hydraulic barrier between potential intake pathways for contamination and drinking water extraction wells. Inter-aquifer mixing in the subsurface is identified, where a high amount of artificial infiltrated surface water is mixed with a lesser amount of water originating from the regional flow pathway in the vicinity of drinking water extraction wells. The spatial distribution of different water types can be estimated and a conceptual system understanding is developed. Results of the multivariate statistical analysis are comparable with gained information from isotopic data and organic micropollutants analyses. The integrated approach using different kinds of observations can be easily transferred to a variety of hydrological settings to synthesise and evaluate large hydrochemical datasets. The combination of additional data with different information content is conceivable and enabled effective interpretation of hydrological processes. Using the applied approach leads to more sound conceptual system understanding acting as the very basis to develop improved water resources management practices in a sustainable way.

  20. Comparison of rapid MMP-8 and interleukin-6 point-of-care tests to identify intra-amniotic inflammation/infection and impending preterm delivery in patients with preterm labor and intact membranes().

    Science.gov (United States)

    Chaemsaithong, Piya; Romero, Roberto; Docheva, Nikolina; Chaiyasit, Noppadol; Bhatti, Gaurav; Pacora, Percy; Hassan, Sonia S; Yeo, Lami; Erez, Offer

    2017-03-01

    Among patients presenting with preterm labor and intact membranes, those with intra-amniotic inflammation have adverse obstetrical and neonatal outcomes. The diagnosis of intra-amniotic inflammation can easily be made by detecting an elevated concentration of the cytokine interleukin (IL)-6 or the enzyme neutrophil collagenase, also known as matrix metalloproteinase (MMP)-8. The diagnostic performances of MMP-8 and IL-6 enzyme-linked immunosorbent assay tests are similar. Recently, a rapid test has become available for point-of-care determination of either MMP-8 or IL-6. The objectives of this study were to compare the diagnostic indices and predictive values between the rapid MMP-8 and IL-6 tests for the identification of intra-amniotic inflammation in patients with preterm labor and intact membranes. We performed a retrospective cohort study including 124 women with singleton pregnancies who presented with symptoms of preterm labor and underwent transabdominal amniocentesis for the evaluation of microbial invasion of the amniotic cavity (MIAC). MIAC was defined according to amniotic fluid culture results (aerobic and anaerobic bacteria as well as genital Mycoplasmas). Amniotic fluid white blood cell (WBC) counts were determined using a hemocytometer chamber. An elevated amniotic fluid MMP-8 concentration was assessed using Yoon's MMP-8 Check(®) (cutoff: 10 ng/mL). An elevated amniotic fluid IL-6 concentration was scored when there was a positive result for the lateral flow-based immunoassay (cutoff: ≥745 pg/mL and ≥1000 pg/mL). In order to objectively compare rapid MMP-8 and rapid IL-6 tests to identify intra-amniotic inflammation, an amniotic fluid WBC count of ≥50 cells/mm(3) was used to define intra-amniotic inflammation. (1) The rapid tests had the same sensitivity for the detection of intra-amniotic inflammation [85.7% (18/21) for all]; (2) the specificity of the rapid MMP-8 test was higher than that of the rapid IL-6 test (cutoff: 745

  1. Elevated intrabolus pressure identifies obstructive processes when integrated relaxation pressure is normal on esophageal high-resolution manometry.

    Science.gov (United States)

    Quader, Farhan; Reddy, Chanakyaram; Patel, Amit; Gyawali, C Prakash

    2017-07-01

    Elevated integrated relaxation pressure (IRP) on esophageal high-resolution manometry (HRM) identifies obstructive processes at the esophagogastric junction (EGJ). Our aim was to determine whether intrabolus pressure (IBP) can identify structural EGJ processes when IRP is normal. In this observational cohort study, adult patients with dysphagia and undergoing HRM were evaluated for endoscopic evidence of structural EGJ processes (strictures, rings, hiatus hernia) in the setting of normal IRP. HRM metrics [IRP, distal contractile integral (DCI), distal latency (DL), IBP, and EGJ contractile integral (EGJ-CI)] were compared among 74 patients with structural EGJ findings (62.8 ± 1.6 yr, 67.6% women), 27 patients with normal EGD (52.9 ± 3.2 yr, 70.3% women), and 21 healthy controls (27.6 ± 0.6 yr, 52.4% women). Findings were validated in 85 consecutive symptomatic patients to address clinical utility. In the primary cohort, mean IBP (18.4 ± 0.9 mmHg) was higher with structural EGJ findings compared with dysphagia with normal EGD (13.5 ± 1.1 mmHg, P = 0.002) and healthy controls (10.9 ± 0.9 mmHg, P 0.05 for each comparison). During multiple rapid swallows, IBP remained higher in the structural findings group compared with controls (P = 0.02). Similar analysis of the prospective validation cohort confirmed IBP elevation in structural EGJ processes, but correlation with dysphagia could not be demonstrated. We conclude that elevated IBP predicts the presence of structural EGJ processes even when IRP is normal, but correlation with dysphagia is suboptimal.NEW & NOTEWORTHY Integrated relaxation pressure (IRP) above the upper limit of normal defines esophageal outflow obstruction using high-resolution manometry. In patients with normal IRP, elevated intrabolus pressure (IBP) can be a surrogate marker for a structural restrictive or obstructive process at the esophagogastric junction (EGJ). This has the potential to augment the clinical value of

  2. Highly differentiated ZW sex microchromosomes in the Australian Varanus species evolved through rapid amplification of repetitive sequences.

    Directory of Open Access Journals (Sweden)

    Kazumi Matsubara

    Full Text Available Transitions between sex determination systems have occurred in many lineages of squamates and it follows that novel sex chromosomes will also have arisen multiple times. The formation of sex chromosomes may be reinforced by inhibition of recombination and the accumulation of repetitive DNA sequences. The karyotypes of monitor lizards are known to be highly conserved yet the sex chromosomes in this family have not been fully investigated. Here, we compare male and female karyotypes of three Australian monitor lizards, Varanus acanthurus, V. gouldii and V. rosenbergi, from two different clades. V. acanthurus belongs to the acanthurus clade and the other two belong to the gouldii clade. We applied C-banding and comparative genomic hybridization to reveal that these species have ZZ/ZW sex micro-chromosomes in which the W chromosome is highly differentiated from the Z chromosome. In combination with previous reports, all six Varanus species in which sex chromosomes have been identified have ZZ/ZW sex chromosomes, spanning several clades on the varanid phylogeny, making it likely that the ZZ/ZW sex chromosome is ancestral for this family. However, repetitive sequences of these ZW chromosome pairs differed among species. In particular, an (AATn microsatellite repeat motif mapped by fluorescence in situ hybridization on part of W chromosome in V. acanthurus only, whereas a (CGGn motif mapped onto the W chromosomes of V. gouldii and V. rosenbergi. Furthermore, the W chromosome probe for V. acanthurus produced hybridization signals only on the centromeric regions of W chromosomes of the other two species. These results suggest that the W chromosome sequences were not conserved between gouldii and acanthurus clades and that these repetitive sequences have been amplified rapidly and independently on the W chromosome of the two clades after their divergence.

  3. Identifying High-Risk Alcohol Users in First-Year College Students: Attitude, Intention, and Facebook.

    Science.gov (United States)

    Pumper, Megan A; Moreno, Megan A

    2013-07-29

    It is challenging to identify older adolescents at risk for alcohol dependence. This study investigated first-year college students who scored as dependent alcohol users (DAU), and examined their alcohol use and Facebook displays. This longitudinal study recruited college students at two universities to complete a phone interview prior to college (Time 1) and one year later (Time 2). Interviews assessed lifetime and current alcohol use, and attitude (scale of 0=very negative to 6=very positive) and intention (scale of 0=not at all likely to 5=very likely) toward alcohol use. The alcohol use disorders identification test (AUDIT) was administered at Time 2. Facebook profiles were evaluated for the presence of references to alcohol use and intoxication/problematic drinking (I/PD) prior to and throughout the participants first year at the university. Analyses included Chi-squared tests and Wilcoxon sign rank tests. Of 315 participants in the study, a total of 21 (6.7%) of participants met criteria as a DAU at Time 2. DAUs were 54.5% female, 86.4% Caucasian, and 73.7% from University A. At Time 1 all DAUs reported lifetime alcohol use and 91.1% were current drinkers. At Time 2, 95.7% were current drinkers. At Time 1, DAU's mean attitude toward alcohol was 4.0 (SD=1.0) and mean intention was 4.0 (SD=1.4); by Time 2 attitude was 4.6 (SD=0.9), p=0.02, and intention was 4.9 (SD=0.3). At Time 1, 39.1% of DAUs displayed alcohol references on Facebook but only one referenced I/PD. By Time 2, 20 DAU profile owners (90.4%) displayed some reference to alcohol and 52.2% referenced I/PD. Findings suggest areas in which dependence could be identified early, specifically attitude towards alcohol and assessment of Facebook profiles for references to alcohol. These findings have the potential to guide future intervention efforts for this high-risk population.

  4. Rapid and Highly Sensitive Non-Competitive Immunoassay for Specific Detection of Nodularin

    Directory of Open Access Journals (Sweden)

    Sultana Akter

    2017-09-01

    Full Text Available Nodularin (NOD is a cyclic penta-peptide hepatotoxin mainly produced by Nodularia spumigena, reported from the brackish water bodies of various parts of the world. It can accumulate in the food chain and, for safety reasons, levels of NOD not only in water bodies but also in food matrices are of interest. Here, we report on a non-competitive immunoassay for the specific detection of NOD. A phage display technique was utilized to interrogate a synthetic antibody phage library for binders recognizing NOD bound to an anti-ADDA (3-Amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4(E,6(E-dienoic acid monoclonal antibody (Mab. One of the obtained immunocomplex binders, designated SA32C11, showed very high specificity towards nodularin-R (NOD-R over to the tested 10 different microcystins (microcystin-LR, -dmLR, -RR, -dmRR, -YR, -LY, -LF, -LW, -LA, -WR. It was expressed in Escherichia coli as a single chain antibody fragment (scFv fusion protein and used to establish a time-resolved fluorometry-based assay in combination with the anti-ADDA Mab. The detection limit (blank + 3SD of the immunoassay, with a total assay time of 1 h 10 min, is 0.03 µg/L of NOD-R. This represents the most sensitive immunoassay method for the specific detection of NOD reported so far. The assay was tested for its performance to detect NOD using spiked (0.1 to 3 µg/L of NOD-R water samples including brackish sea and coastal water and the recovery ranged from 79 to 127%. Furthermore, a panel of environmental samples, including water from different sources, fish and other marine tissue specimens, were analyzed for NOD using the assay. The assay has potential as a rapid screening tool for the analysis of a large number of water samples for the presence of NOD. It can also find applications in the analysis of the bioaccumulation of NOD in marine organisms and in the food chain.

  5. Rapid identification of mycolic acid patterns of mycobacteria by high-performance liquid chromatography using pattern recognition software and a Mycobacterium library.

    Science.gov (United States)

    Glickman, S E; Kilburn, J O; Butler, W R; Ramos, L S

    1994-01-01

    Current methods for identifying mycobacteria by high-performance liquid chromatography (HPLC) require a visual assessment of the generated chromatographic data, which often involves time-consuming hand calculations and the use of flow charts. Our laboratory has developed a personal computer-based file containing patterns of mycolic acids detected in 45 species of Mycobacterium, including both slowly and rapidly growing species, as well as Tsukamurella paurometabolum and members of the genera Corynebacterium, Nocardia, Rhodococcus, and Gordona. The library was designed to be used in conjunction with a commercially available pattern recognition software package, Pirouette (Infometrix, Seattle, Wash.). Pirouette uses the K-nearest neighbor algorithm, a similarity-based classification method, to categorize unknown samples on the basis of their multivariate proximities to samples of a preassigned category. Multivariate proximity is calculated from peak height data, while peak heights are named by retention time matching. The system was tested for accuracy by using 24 species of Mycobacterium. Of the 1,333 strains evaluated, > or = 97% were correctly identified. Identification of M. tuberculosis (n = 649) was 99.85% accurate, and identification of the M. avium complex (n = 211) was > or = 98% accurate; > or = 95% of strains of both double-cluster and single-cluster M. gordonae (n = 47) were correctly identified. This system provides a rapid, highly reliable assessment of HPLC-generated chromatographic data for the identification of mycobacteria. PMID:8195387

  6. Rapid die manufacturing - high pressure casting of low volume non ferrous metals components

    CSIR Research Space (South Africa)

    Pereira, MFV

    2006-11-01

    Full Text Available Pressure Casting of Low Volume Non Ferrous Metals Components Date: 2 November 2006 Slide 2 © CSIR 2006 www.csir.co.za Introduction to RPT • Rapid Prototyping Techniques (RPT) generally used for non functional prototypes • RPT...

  7. Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene.

    Directory of Open Access Journals (Sweden)

    Amélie Bonnefond

    Full Text Available BACKGROUND: Maturity-onset of the young (MODY is a clinically heterogeneous form of diabetes characterized by an autosomal-dominant mode of inheritance, an onset before the age of 25 years, and a primary defect in the pancreatic beta-cell function. Approximately 30% of MODY families remain genetically unexplained (MODY-X. Here, we aimed to use whole-exome sequencing (WES in a four-generation MODY-X family to identify a new susceptibility gene for MODY. METHODOLOGY: WES (Agilent-SureSelect capture/Illumina-GAIIx sequencing was performed in three affected and one non-affected relatives in the MODY-X family. We then performed a high-throughput multiplex genotyping (Illumina-GoldenGate assay of the putative causal mutations in the whole family and in 406 controls. A linkage analysis was also carried out. PRINCIPAL FINDINGS: By focusing on variants of interest (i.e. gains of stop codon, frameshift, non-synonymous and splice-site variants not reported in dbSNP130 present in the three affected relatives and not present in the control, we found 69 mutations. However, as WES was not uniform between samples, a total of 324 mutations had to be assessed in the whole family and in controls. Only one mutation (p.Glu227Lys in KCNJ11 co-segregated with diabetes in the family (with a LOD-score of 3.68. No KCNJ11 mutation was found in 25 other MODY-X unrelated subjects. CONCLUSIONS/SIGNIFICANCE: Beyond neonatal diabetes mellitus (NDM, KCNJ11 is also a MODY gene ('MODY13', confirming the wide spectrum of diabetes related phenotypes due to mutations in NDM genes (i.e. KCNJ11, ABCC8 and INS. Therefore, the molecular diagnosis of MODY should include KCNJ11 as affected carriers can be ideally treated with oral sulfonylureas.

  8. A high throughput genetic screen identifies new early meiotic recombination functions in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Arnaud De Muyt

    2009-09-01

    Full Text Available Meiotic recombination is initiated by the formation of numerous DNA double-strand breaks (DSBs catalysed by the widely conserved Spo11 protein. In Saccharomyces cerevisiae, Spo11 requires nine other proteins for meiotic DSB formation; however, unlike Spo11, few of these are conserved across kingdoms. In order to investigate this recombination step in higher eukaryotes, we took advantage of a high-throughput meiotic mutant screen carried out in the model plant Arabidopsis thaliana. A collection of 55,000 mutant lines was screened, and spo11-like mutations, characterised by a drastic decrease in chiasma formation at metaphase I associated with an absence of synapsis at prophase, were selected. This screen led to the identification of two populations of mutants classified according to their recombination defects: mutants that repair meiotic DSBs using the sister chromatid such as Atdmc1 or mutants that are unable to make DSBs like Atspo11-1. We found that in Arabidopsis thaliana at least four proteins are necessary for driving meiotic DSB repair via the homologous chromosomes. These include the previously characterised DMC1 and the Hop1-related ASY1 proteins, but also the meiotic specific cyclin SDS as well as the Hop2 Arabidopsis homologue AHP2. Analysing the mutants defective in DSB formation, we identified the previously characterised AtSPO11-1, AtSPO11-2, and AtPRD1 as well as two new genes, AtPRD2 and AtPRD3. Our data thus increase the number of proteins necessary for DSB formation in Arabidopsis thaliana to five. Unlike SPO11 and (to a minor extent PRD1, these two new proteins are poorly conserved among species, suggesting that the DSB formation mechanism, but not its regulation, is conserved among eukaryotes.

  9. High occurrence of jellyfish predation by black-browed and Campbell albatross identified by DNA metabarcoding.

    Science.gov (United States)

    McInnes, Julie C; Alderman, Rachael; Lea, Mary-Anne; Raymond, Ben; Deagle, Bruce E; Phillips, Richard A; Stanworth, Andrew; Thompson, David R; Catry, Paulo; Weimerskirch, Henri; Suazo, Cristián G; Gras, Michaël; Jarman, Simon N

    2017-07-22

    Gelatinous zooplankton are a large component of the animal biomass in all marine environments, but are considered to be uncommon in the diet of most marine top predators. However, the diets of key predator groups like seabirds have conventionally been assessed from stomach content analyses, which cannot detect most gelatinous prey. As marine top predators are used to identify changes in the overall species composition of marine ecosystems, such biases in dietary assessment may impact our detection of important ecosystem regime shifts. We investigated albatross diet using DNA metabarcoding of scats to assess the prevalence of gelatinous zooplankton consumption by two albatross species, one of which is used as an indicator species for ecosystem monitoring. Black-browed and Campbell albatross scats were collected from eight breeding colonies covering the circumpolar range of these birds over two consecutive breeding seasons. Fish was the main dietary item at most sites; however, cnidarian DNA, primarily from scyphozoan jellyfish, was present in 42% of samples overall and up to 80% of samples at some sites. Jellyfish was detected during all breeding stages and consumed by adults and chicks. Trawl fishery catches of jellyfish near the Falkland Islands indicate a similar frequency of jellyfish occurrence in albatross diets in years of high and low jellyfish availability, suggesting jellyfish consumption may be selective rather than opportunistic. Warmer oceans and overfishing of finfish are predicted to favour jellyfish population increases, and we demonstrate here that dietary DNA metabarcoding enables measurements of the contribution of gelatinous zooplankton to the diet of marine predators. © 2017 John Wiley & Sons Ltd.

  10. Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease.

    Science.gov (United States)

    Stepniak, Dariusz; Spaenij-Dekking, Liesbeth; Mitea, Cristina; Moester, Martine; de Ru, Arnoud; Baak-Pablo, Renee; van Veelen, Peter; Edens, Luppo; Koning, Frits

    2006-10-01

    Celiac disease is a T cell-driven intolerance to wheat gluten. The gluten-derived T cell epitopes are proline-rich and thereby highly resistant to proteolytic degradation within the gastrointestinal tract. Oral supplementation with prolyl oligopeptidases has therefore been proposed as a potential therapeutic approach. The enzymes studied, however, have limitations as they are irreversibly inactivated by pepsin and acidic pH, both present in the stomach. As a consequence, these enzymes will fail to degrade gluten before it reaches the small intestine, the site where gluten induces inflammatory T cell responses that lead to celiac disease. We have now determined the usefulness of a newly identified prolyl endoprotease from Aspergillus niger for this purpose. Gluten and its peptic/tryptic digest were treated with prolyl endoprotease, and the destruction of the T cell epitopes was tested using mass spectrometry, T cell proliferation assays, ELISA, reverse-phase HPLC, SDS-PAGE, and Western blotting. We observed that the A. niger prolyl endoprotease works optimally at 4-5 pH, remains stable at 2 pH, and is completely resistant to digestion with pepsin. Moreover, the A. niger-derived enzyme efficiently degraded all tested T cell stimulatory peptides as well as intact gluten molecules. On average, the endoprotease from A. niger degraded gluten peptides 60 times faster than a prolyl oligopeptidase. Together these results indicate that the enzyme from A. niger efficiently degrades gluten proteins. Future studies are required to determine if the prolyl endoprotease can be used as an oral supplement to reduce gluten intake in patients.

  11. Identifying modular flows on multilayer networks reveals highly overlapping organization in social systems

    CERN Document Server

    De Domenico, Manlio; Arenas, Alex; Rosvall, Martin

    2014-01-01

    Unveiling the community structure of networks is a powerful methodology to comprehend interconnected systems across the social and natural sciences. To identify different types of functional modules in interaction data aggregated in a single network layer, researchers have developed many powerful methods. For example, flow-based methods have proven useful for identifying modular dynamics in weighted and directed networks that capture constraints on flow in the systems they represent. However, many networked systems consist of agents or components that exhibit multiple layers of interactions. Inevitably, representing this intricate network of networks as a single aggregated network leads to information loss and may obscure the actual organization. Here we propose a method based on compression of network flows that can identify modular flows in non-aggregated multilayer networks. Our numerical experiments on synthetic networks show that the method can accurately identify modules that cannot be identified in agg...

  12. Rapid high-yield expression of full-size IgG antibodies in plants coinfected with noncompeting viral vectors

    OpenAIRE

    Giritch, Anatoli; Marillonnet, Sylvestre; Engler, Carola; van Eldik, Gerben; Botterman, Johan; Klimyuk, Victor; Gleba, Yuri

    2006-01-01

    Plant viral vectors allow expression of heterologous proteins at high yields, but so far, they have been unable to express heterooligomeric proteins efficiently. We describe here a rapid and indefinitely scalable process for high-level expression of functional full-size mAbs of the IgG class in plants. The process relies on synchronous coinfection and coreplication of two viral vectors, each expressing a separate antibody chain. The two vectors are derived from two different plant viruses tha...

  13. Massively parallel digital high resolution melt for rapid and absolutely quantitative sequence profiling

    Science.gov (United States)

    Velez, Daniel Ortiz; Mack, Hannah; Jupe, Julietta; Hawker, Sinead; Kulkarni, Ninad; Hedayatnia, Behnam; Zhang, Yang; Lawrence, Shelley; Fraley, Stephanie I.

    2017-02-01

    In clinical diagnostics and pathogen detection, profiling of complex samples for low-level genotypes represents a significant challenge. Advances in speed, sensitivity, and extent of multiplexing of molecular pathogen detection assays are needed to improve patient care. We report the development of an integrated platform enabling the identification of bacterial pathogen DNA sequences in complex samples in less than four hours. The system incorporates a microfluidic chip and instrumentation to accomplish universal PCR amplification, High Resolution Melting (HRM), and machine learning within 20,000 picoliter scale reactions, simultaneously. Clinically relevant concentrations of bacterial DNA molecules are separated by digitization across 20,000 reactions and amplified with universal primers targeting the bacterial 16S gene. Amplification is followed by HRM sequence fingerprinting in all reactions, simultaneously. The resulting bacteria-specific melt curves are identified by Support Vector Machine learning, and individual pathogen loads are quantified. The platform reduces reaction volumes by 99.995% and achieves a greater than 200-fold increase in dynamic range of detection compared to traditional PCR HRM approaches. Type I and II error rates are reduced by 99% and 100% respectively, compared to intercalating dye-based digital PCR (dPCR) methods. This technology could impact a number of quantitative profiling applications, especially infectious disease diagnostics.

  14. A high-resolution optical measurement system for rapid acquisition of radiation flux density maps

    Science.gov (United States)

    Thelen, Martin; Raeder, Christian; Willsch, Christian; Dibowski, Gerd

    2017-06-01

    To identify the power and flux density of concentrated solar radiation the Institute of Solar Research at the German Aerospace Center (DLR - Deutsches Zentrum für Luft-und Raumfahrt e. V.) has used the camera-based measurement system FATMES (Flux and Temperature Measurement System) since 1995. The disadvantages of low resolution, difficult handling and poor computing power required a revision of the existing measurement system. The measurement system FMAS (Flux Mapping Acquisition system) is equipped with state-of-the-art-hardware, is compatible with computers off-the-shelf and is programmed in LabView. The expenditure of time for an image evaluation is reduced by the factor 60 compared to FATMES. The new measurement system is no longer associated with the facilities Solar Furnace and High Flux Solar Simulator at the DLR in Cologne but is also applicable as a mobile system. The data and the algorithms are transparent throughout the complete process. The measurement accuracy of FMAS is determined to at most ±3 % until now. The error of measurement of FATMES is at least 2 % higher according to the conducted comparison tests.

  15. Massively parallel digital high resolution melt for rapid and absolutely quantitative sequence profiling

    Science.gov (United States)

    Velez, Daniel Ortiz; Mack, Hannah; Jupe, Julietta; Hawker, Sinead; Kulkarni, Ninad; Hedayatnia, Behnam; Zhang, Yang; Lawrence, Shelley; Fraley, Stephanie I.

    2017-01-01

    In clinical diagnostics and pathogen detection, profiling of complex samples for low-level genotypes represents a significant challenge. Advances in speed, sensitivity, and extent of multiplexing of molecular pathogen detection assays are needed to improve patient care. We report the development of an integrated platform enabling the identification of bacterial pathogen DNA sequences in complex samples in less than four hours. The system incorporates a microfluidic chip and instrumentation to accomplish universal PCR amplification, High Resolution Melting (HRM), and machine learning within 20,000 picoliter scale reactions, simultaneously. Clinically relevant concentrations of bacterial DNA molecules are separated by digitization across 20,000 reactions and amplified with universal primers targeting the bacterial 16S gene. Amplification is followed by HRM sequence fingerprinting in all reactions, simultaneously. The resulting bacteria-specific melt curves are identified by Support Vector Machine learning, and individual pathogen loads are quantified. The platform reduces reaction volumes by 99.995% and achieves a greater than 200-fold increase in dynamic range of detection compared to traditional PCR HRM approaches. Type I and II error rates are reduced by 99% and 100% respectively, compared to intercalating dye-based digital PCR (dPCR) methods. This technology could impact a number of quantitative profiling applications, especially infectious disease diagnostics. PMID:28176860

  16. Massively parallel digital high resolution melt for rapid and absolutely quantitative sequence profiling.

    Science.gov (United States)

    Velez, Daniel Ortiz; Mack, Hannah; Jupe, Julietta; Hawker, Sinead; Kulkarni, Ninad; Hedayatnia, Behnam; Zhang, Yang; Lawrence, Shelley; Fraley, Stephanie I

    2017-02-08

    In clinical diagnostics and pathogen detection, profiling of complex samples for low-level genotypes represents a significant challenge. Advances in speed, sensitivity, and extent of multiplexing of molecular pathogen detection assays are needed to improve patient care. We report the development of an integrated platform enabling the identification of bacterial pathogen DNA sequences in complex samples in less than four hours. The system incorporates a microfluidic chip and instrumentation to accomplish universal PCR amplification, High Resolution Melting (HRM), and machine learning within 20,000 picoliter scale reactions, simultaneously. Clinically relevant concentrations of bacterial DNA molecules are separated by digitization across 20,000 reactions and amplified with universal primers targeting the bacterial 16S gene. Amplification is followed by HRM sequence fingerprinting in all reactions, simultaneously. The resulting bacteria-specific melt curves are identified by Support Vector Machine learning, and individual pathogen loads are quantified. The platform reduces reaction volumes by 99.995% and achieves a greater than 200-fold increase in dynamic range of detection compared to traditional PCR HRM approaches. Type I and II error rates are reduced by 99% and 100% respectively, compared to intercalating dye-based digital PCR (dPCR) methods. This technology could impact a number of quantitative profiling applications, especially infectious disease diagnostics.

  17. High-resolution isotope measurements resolve rapid ecohydrological dynamics at the soil-plant interface.

    Science.gov (United States)

    Volkmann, Till H M; Haberer, Kristine; Gessler, Arthur; Weiler, Markus

    2016-05-01

    Plants rely primarily on rainfall infiltrating their root zones - a supply that is inherently variable, and fluctuations are predicted to increase on most of the Earth's surface. Yet, interrelationships between water availability and plant use on short timescales are difficult to quantify and remain poorly understood. To overcome previous methodological limitations, we coupled high-resolution in situ observations of stable isotopes in soil and transpiration water. We applied the approach along with Bayesian mixing modeling to track the fate of (2) H-labeled rain pulses following drought through soil and plants of deciduous tree ecosystems. We resolve how rainwater infiltrates the root zones in a nonequilibrium process and show that tree species differ in their ability to quickly acquire the newly available source. Sessile oak (Quercus petraea) adjusted root uptake to vertical water availability patterns under drought, but readjustment toward the rewetted topsoil was delayed. By contrast, European beech (Fagus sylvatica) readily utilized water from all soil depths independent of water depletion, enabling faster uptake of rainwater. Our results demonstrate that species-specific plasticity and responses to water supply fluctuations on short timescales can now be identified and must be considered to predict vegetation functional dynamics and water cycling under current and future climatic conditions.

  18. Rapid microbiology - raising awareness.

    Science.gov (United States)

    Bailie, Jonathan

    2016-01-01

    A 'high-level overview' of some of the emerging rapid microbiology technologies designed to help healthcare engineering and infection control teams working in hospitals and other healthcare facilities more rapidly identify potentially hazardous levels of waterborne microorganisms in their water systems, enabling them to take prompt remedial action, and a look at the some of the 'pros and cons' of such testing techniques, was given by Nalco technical director, Howard Barnes, the vice-chair of the Legionella Control Association (LCA), at a recent LCA open day. HEJ editor, Jonathan Bailie, reports.

  19. Array Manipulation And Matrix-Tree Method To Identify High Concentration Regions HCRs

    Directory of Open Access Journals (Sweden)

    Rachana Arora

    2015-08-01

    Full Text Available Abstract-Sequence Alignment and Analysis is one of the most important applications of bioinformatics. It involves alignment a pair or more sequences with each other and identify a common pattern that would ultimately lead to conclusions of homology or dissimilarity. A number of algorithms that make use of dynamic programming to perform alignment between sequences are available. One of their main disadvantages is that they involve complicated computations and backtracking methods that are difficult to implement. This paper describes a much simpler method to identify common regions in 2 sequences and align them based on the density of common sequences identified.

  20. Rapid high-silica magma generation in basalt-dominated rift settings

    Science.gov (United States)

    Berg, Sylvia E.; Troll, Valentin R.; Burchardt, Steffi; Deegan, Frances M.; Riishuus, Morten S.; Whitehouse, Martin J.; Harris, Chris; Freda, Carmela; Ellis, Ben S.; Krumbholz, Michael; Gústafsson, Ludvik E.

    2015-04-01

    The processes that drive large-scale silicic magmatism in basalt-dominated provinces have been widely debated for decades, with Iceland being at the centre of this discussion [1-5]. Iceland hosts large accumulations of silicic rocks in a largely basaltic oceanic setting that is considered by some workers to resemble the situation documented for the Hadean [6-7]. We have investigated the time scales and processes of silicic volcanism in the largest complete pulse of Neogene rift-related silicic magmatism preserved in Iceland (>450 km3), which is a potential analogue of initial continent nucleation in early Earth. Borgarfjörður Eystri in NE-Iceland hosts silicic rocks in excess of 20 vol.%, which exceeds the ≤12 vol% usual for Iceland [3,8]. New SIMS zircon ages document that the dominantly explosive silicic pulse was generated within a ≤2 Myr window (13.5 ± 0.2 to 12.2 ± 03 Ma), and sub-mantle zircon δ18O values (1.2 to 4.5 ± 0.2‰, n=337) indicate ≤33% assimilation of low-δ18O hydrothermally-altered crust (δ18O=0‰), with intense crustal melting at 12.5 Ma, followed by rapid termination of silicic magma production once crustal fertility declined [9]. This silicic outburst was likely caused by extensive rift flank volcanism due to a rift relocation and a flare of the Iceland plume [4,10] that triggered large-scale crustal melting and generated mixed-origin silicic melts. High-silica melt production from a basaltic parent was replicated in a set of new partial melting experiments of regional hydrated basalts, conducted at 800-900°C and 150 MPa, that produced silicic melt pockets up to 77 wt.% SiO2. Moreover, Ti-in-zircon thermometry from Borgarfjörður Eystri give a zircon crystallisation temperature ~713°C (Ti range from 2.4 to 22.1 ppm, average=7.7 ppm, n=142), which is lower than recorded elsewhere in Iceland [11], but closely overlaps with the zircon crystallisation temperatures documented for Hadean zircon populations [11-13], hinting at

  1. High undercooling and rapid dendritic growth of Cu-Sb alloy in drop tube

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Droplets of Cu-20%Sb hypoeutectic alloy has been rapidly solidified in drop tube within the containerless condition. With the decrease of droplet diameter, undercooling increases and the microstructures of primary copper dendrite refines. Undercooling up to 207 K (0.17 TL) is obtained in experiment. Theoretic analysis indicated that, because of the broad temperature range of solidification, the rapid growth of primary copper dendrite is controlled by the solutal diffusion. Judging from the calculation of T0 curve in the phase diagram, it is shown that the critical undercooling of segregationless solidification is (T0 = 474 K. At the maximum undercooling of 207 K, the growth velocity of primary copper phase exceeds to 37 mm/s, and the distinct solute trapping occurs.

  2. Development of a highly visual, simple, and rapid test for the discovery of novel insulin mimetics in living vertebrates.

    Science.gov (United States)

    Lee, Jinho; Jung, Da-Woon; Kim, Woong-Hee; Um, Jung-In; Yim, Soon-Ho; Oh, Won Keun; Williams, Darren R

    2013-08-16

    Diabetes mellitus is a global epidemic with major impacts on human health and society. Drug discovery for diabetes can be facilitated by the development of a rapid, vertebrate-based screen for identifying new insulin mimetic compounds. Our study describes the first development of a zebrafish-based system based on direct monitoring of glucose flux and validated for identifying novel anti-diabetic drugs. Our system utilizes a fluorescent-tagged glucose probe in an experimentally convenient 96-well plate format. To validate our new system, we identified compounds that can induce glucose uptake via activity-guided fractionation of the inner shell from the Japanese Chestnut (Castanea crenata). The best performing compound, UP3.2, was identified as fraxidin and validated as a novel insulin mimetic using a mammalian adipocyte system. Additional screening using sets of saponin- and triazine-based compounds was undertaken to further validate this assay, which led to the discovery of triazine PP-II-A03 as a novel insulin mimetic. Moreover, we demonstrate that our zebrafish-based system allows concomitant toxicological analysis of anti-diabetic drug candidates. Thus, we have developed a rapid and inexpensive vertebrate model that can enhance diabetes drug discovery by preselecting hits from chemical library screens, before testing in relatively expensive rodent assays.

  3. NLO vertex for a forward jet plus a rapidity gap at high energies

    Science.gov (United States)

    Hentschinski, Martin; Madrigal Martínez, José Daniel; Murdaca, Beatrice; Vera, Agustín Sabio

    2015-04-01

    We present the calculation of the forward jet vertex associated to a rapidity gap (coupling of a hard pomeron to the jet) in the BFKL formalism at next-to-leading order (NLO). Real emission contributions are computed via Lipatov's effective action. The NLO jet vertex turns out to be finite within collinear factorization and allows, together with the NLO non-forward gluon Green's function, to perform NLO studies of jet production in diffractive events (e.g. Mueller-Tang dijets).

  4. NLO Vertex for a Forward Jet plus a Rapidity Gap at High Energies

    CERN Document Server

    Hentschinski, Martin; Murdaca, Beatrice; Vera, Agustín Sabio

    2015-01-01

    We present the calculation of the forward jet vertex associated to a rapidity gap (coupling of a hard pomeron to the jet) in the BFKL formalism at next-to-leading order (NLO). Real emission contributions are computed via Lipatov's effective action. The NLO jet vertex turns out to be finite within collinear factorization and allows, together with the NLO non-forward gluon Green's function, to perform NLO studies of jet production in diffractive events (e.g. Mueller-Tang dijets).

  5. Rapid and highly variable warming of lake surface waters around the globe

    Science.gov (United States)

    O'Reilly, Catherine; Sharma, Sapna; Gray, Derek; Hampton, Stephanie; Read, Jordan S.; Rowley, Rex J.; Schneider, Philipp; Lenters, John D.; McIntyre, Peter B.; Kraemer, Benjamin M.; Weyhenmeyer, Gesa A.; Straile, Dietmar; Dong, Bo; Adrian, Rita; Allan, Mathew G.; Anneville, Orlane; Arvola, Lauri; Austin, Jay; Bailey, John L.; Baron, Jill S.; Brookes, Justin D; de Eyto, Elvira; Dokulil, Martin T.; Hamilton, David P.; Havens, Karl; Hetherington, Amy L.; Higgins, Scott N.; Hook, Simon; Izmest'eva, Lyubov R.; Jöhnk, Klaus D.; Kangur, Külli; Kasprzak, Peter; Kumagai, Michio; Kuusisto, Esko; Leshkevich, George; Livingstone, David M.; MacIntyre, Sally; May, Linda; Melack, John M.; Mueller-Navara, Doerthe C.; Naumenko, Mikhail; Noges, Peeter; Noges, Tiina; North, Ryan P.; Plisnier, Pierre-Denis; Rigosi, Anna; Rimmer, Alon; Rogora, Michela; Rudstam, Lars G.; Rusak, James A.; Salmaso, Nico; Samal, Nihar R.; Schindler, Daniel E.; Schladow, Geoffrey; Schmid, Martin; Schmidt, Silke R.; Silow, Eugene A.; Soylu, M. Evren; Teubner, Katrin; Verburg, Piet; Voutilainen, Ari; Watkinson, Andrew; Williamson, Craig E.; Zhang, Guoqing

    2015-01-01

    In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors—from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade−1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade−1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes.

  6. Rapid ABO genotyping by high-speed droplet allele-specific PCR using crude samples.

    Science.gov (United States)

    Taira, Chiaki; Matsuda, Kazuyuki; Takeichi, Naoya; Furukawa, Satomi; Sugano, Mitsutoshi; Uehara, Takeshi; Okumura, Nobuo; Honda, Takayuki

    2017-03-13

    ABO genotyping has common tools for personal identification of forensic and transplantation field. We developed a new method based on a droplet allele-specific PCR (droplet-AS-PCR) that enabled rapid PCR amplification. We attempted rapid ABO genotyping using crude DNA isolated from dried blood and buccal cells. We designed allele-specific primers for three SNPs (at nucleotides 261, 526, and 803) in exons 6 and 7 of the ABO gene. We pretreated dried blood and buccal cells with proteinase K, and obtained crude DNAs without DNA purification. Droplet-AS-PCR allowed specific amplification of the SNPs at the three loci using crude DNA, with results similar to those for DNA extracted from fresh peripheral blood. The sensitivity of the methods was 5%-10%. The genotyping of extracted DNA and crude DNA were completed within 8 and 9 minutes, respectively. The genotypes determined by the droplet-AS-PCR method were always consistent with those obtained by direct sequencing. The droplet-AS-PCR method enabled rapid and specific amplification of three SNPs of the ABO gene from crude DNA treated with proteinase K. ABO genotyping by the droplet-AS-PCR has the potential to be applied to various fields including a forensic medicine and transplantation medical care. © 2017 Wiley Periodicals, Inc.

  7. The phenotypic patterns of essential hypertension are the key to identifying "high blood pressure" genes.

    Science.gov (United States)

    Korner, P I

    2010-01-01

    hypertension provide targets for identifying high BP genes. Reading the genome from the phenotype will require new approaches, such as those used in developmental genetics. In addition, transgenic technology may help verify hypotheses and examine whether an observed effect is through single or multiple mechanisms. To obtain answers will require substantial collaborative efforts between physiologists and geneticists.

  8. Novel Dielectric Coagulometer Identifies Hypercoagulability in Patients with a High CHADS2 Score without Atrial Fibrillation.

    Directory of Open Access Journals (Sweden)

    Yuki Hasegawa

    Full Text Available Recent reports showed that the CHADS2 score predicted the risk of strokes in patients without atrial fibrillation (AF. Although the hypercoagulability may contribute to the thrombogenesis, it has not been fully investigated due to a lack of a sensitive evaluation modality. Recently a novel dielectric blood coagulometry (DBCM was invented for evaluating the coagulability by measuring the temporal change in whole blood dielectric permittivity.We evaluated the utility of the DBCM for identifying the coagulability.For fundamental experiments, 133 citrated blood samples were drawn from subjects with or without heparin administration. A DBCM analysis was performed to find the adequate coagulation index, and to delineate its measurement range by adding recombinant human tissue factor (TF or heparin. Then the coagulability was assessed by DBCM and conventional coagulation assays in 84 subjects without AF, who were divided into 3 groups by their CHADS2 score. Another 17 patients who received warfarin were also assessed by DBCM to evaluate the effect of anticoagulants.We calculated the derivative of the dielectric permittivity change after recalcification, and extracted the end of acceleration time (EAT as a novel index. The EAT showed a dose-dependent shortening with the addition of serial dilutions of TF (×10-2 to ×10-4, and a dose-dependent prolongation with the addition of heparin (0.05 to 0.15 U/ml. The EAT was significantly shorter in the higher CHADS2 score group (19.8 ± 4.8, 18.6 ± 3.1, and 16.3 ± 2.7 min in the CHADS2 = 0, 1, and ≥2 groups, respectively, p = 0.0065 by ANOVA. Patients receiving warfarin had a significantly more prolonged EAT than those without warfarin (18.6±4.2 vs. 25.8±7.3 min, p <0.001. DBCM detected the whole blood coagulability with a high sensitivity. Subjects with higher CHADS2 scores exhibited hypercoagulability without AF.

  9. A rapid typing method for Listeria monocytogenes based on high-throughput multilocus sequence typing (Hi-MLST).

    Science.gov (United States)

    Takahashi, Hajime; Iwakawa, Ai; Ohshima, Chihiro; Kyoui, Daisuke; Kumano, Shiori; Kuda, Takashi; Kimura, Bon

    2017-02-21

    Listeria monocytogenes infects humans via food products, causing listeriosis. Consequently, food companies pay meticulous attention to the risk of contamination of their products by this bacterium. While fragment analysis methods such as pulsed-field gel electrophoresis (PFGE) are used to trace the sources of contamination for this bacterium, some drawbacks have been identified, namely the complexity of the methods and the difficulty of making data comparisons. As an alternative, multilocus sequence typing (MLST) is now seeing widespread use; however, owing to its cost, time, and labor requirements, its diffusion into the food industry has been slow. Thus, in the present study, a High-throughput MLST (Hi-MLST) method, which can rapidly, simply, and cheaply perform MLST analyses using a next-generation sequencer (NGS) that can analyze a large volume of base sequences at once was developed. Firstly, a multiplex PCR method designed to amplify seven genes for use in MLST was developed. The discriminatory potential of the developed method was confirmed in silico, and was verified that it has the same discriminatory potential as conventional methods. Next, MLST analysis using multiplex PCR and NGS was performed for 48 strains of L. monocytogenes. The sequences obtained from this analysis have sufficiently reliable quality for all of the genes from of all the strains. Thus, this method could classify the 48 strains into 39 sequence types (ST) with a Diversity index (DI) of 0.989. In summary, using the Hi-MLST method developed in the present study, which combined multiplex PCR and NGS, cut the costs to 1/6th and the time to 1/20th that of conventional MLST methods.

  10. A reference substance free diagnostic fragment ion-based approach for rapid identification of non-target components in Pudilan Xiaoyan oral liquid by high resolution mass spectrometry.

    Science.gov (United States)

    Dai, Chen; Wang, Chong; Zhang, Chunhua; Wang, Guoxiang; Wang, Jin; Chen, Jun; Guo, Bin; Yang, Tianshu; Cai, Bo

    2016-05-30

    Rapid and reliable identification of non-target components in herbal preparations remains a primary challenge, especially when corresponding reference substances are inaccessible. In this work, an efficient post-experiment data processing methodology, named reference substance free diagnostic fragment ion (RSFDFI), was developed based on ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC/LTQ-Orbitrap). The first step of this approach was to cluster the components that share common fragment ions into several groups. After querying the database using a predicted chemical formula, the component with the fewest primary hits was preferentially deduced based on its MS/MS spectrum. Once the structure was characterized, its common fragment ions could be used as the prior structural information to select the possible candidates that would facilitate the subsequent identification for each group. Taking Pudilan Xiaoyan oral liquid (PDL) as a model herbal preparation, which has been extensively used for the treatment of epidemic parotitis and children with hand-foot-mouth diseases, this strategy enables a nearly eight-fold narrowing of the database hits, with fifty-two components, including lignans, flavonoids, alkaloids and steroids, being rapidly identified. In conclusion, our work clearly demonstrates that integrating RSFDFI with high-resolution mass spectrometry is a powerful methodology for rapid identification of non-target components from herbal prescriptions and may open new avenues for chemical analysis in other complex mixtures.

  11. Rapid, high-accuracy detection of strabismus and amblyopia using the pediatric vision scanner

    NARCIS (Netherlands)

    S.E. Loudon (Sjoukje); C.A. Rook (Caitlin); D.S. Nassif (Deborah); N.V. Piskun (Nadya); D.G. Hunter (David)

    2011-01-01

    textabstractPurpose. The Pediatric Vision Scanner (PVS) detects strabismus by identifying ocular fixation in both eyes simultaneously. This study was undertaken to assess the ability of the PVS to identify patients with amblyopia or strabismus, particularly anisometropic amblyopia with no measurable

  12. A Comparative Study of Two Groups of Sex Offenders Identified as High and Low Risk on the Static-99

    Science.gov (United States)

    Coxe, Ray; Holmes, William

    2009-01-01

    The purpose of this study was to identify possible differences between high- and low-risk sex offenders. The subjects included 285 sex offenders on probation. They were evaluated with the Static-99, Abel Assessment, Raven's, and MMPI-2. A criminal history review identified the number of prior offenses and the age/sex category in the index offense.…

  13. The Development of Deaf and Hard of Hearing Children Identified Early through the High-Risk Registry.

    Science.gov (United States)

    Apuzzo, Mah-rya L.; Yoshinaga-Itano, Christine

    1998-01-01

    This study examined developmental characteristics of 82 deaf and hard-of-hearing children identified through the high-risk registry in Colorado either before or after 6 months of age. Children identified early and receiving intervention two to three months after identification had significantly higher levels of receptive and expressive language,…

  14. Detection of previously undiagnosed cases of COPD in a high-risk population identified in general practice

    DEFF Research Database (Denmark)

    Løkke, Anders; Ulrik, Charlotte Suppli; Dahl, Ronald;

    2012-01-01

    Background and Aim: Under-diagnosis of COPD is a widespread problem. This study aimed to identify previously undiagnosed cases of COPD in a high-risk population identified through general practice. Methods: Participating GPs (n = 241) recruited subjects with no previous diagnosis of lung disease,...

  15. Rapid eye movements during sleep in mice: High trait-like stability qualifies rapid eye movement density for characterization of phenotypic variation in sleep patterns of rodents

    Directory of Open Access Journals (Sweden)

    Fulda Stephany

    2011-11-01

    Full Text Available Abstract Background In humans, rapid eye movements (REM density during REM sleep plays a prominent role in psychiatric diseases. Especially in depression, an increased REM density is a vulnerability marker for depression. In clinical practice and research measurement of REM density is highly standardized. In basic animal research, almost no tools are available to obtain and systematically evaluate eye movement data, although, this would create increased comparability between human and animal sleep studies. Methods We obtained standardized electroencephalographic (EEG, electromyographic (EMG and electrooculographic (EOG signals from freely behaving mice. EOG electrodes were bilaterally and chronically implanted with placement of the electrodes directly between the musculus rectus superior and musculus rectus lateralis. After recovery, EEG, EMG and EOG signals were obtained for four days. Subsequent to the implantation process, we developed and validated an Eye Movement scoring in Mice Algorithm (EMMA to detect REM as singularities of the EOG signal, based on wavelet methodology. Results The distribution of wakefulness, non-REM (NREM sleep and rapid eye movement (REM sleep was typical of nocturnal rodents with small amounts of wakefulness and large amounts of NREM sleep during the light period and reversed proportions during the dark period. REM sleep was distributed correspondingly. REM density was significantly higher during REM sleep than NREM sleep. REM bursts were detected more often at the end of the dark period than the beginning of the light period. During REM sleep REM density showed an ultradian course, and during NREM sleep REM density peaked at the beginning of the dark period. Concerning individual eye movements, REM duration was longer and amplitude was lower during REM sleep than NREM sleep. The majority of single REM and REM bursts were associated with micro-arousals during NREM sleep, but not during REM sleep. Conclusions Sleep

  16. Case finding for patients at risk of readmission to hospital: development of algorithm to identify high risk patients

    National Research Council Canada - National Science Library

    John Billings; Jennifer Dixon; Tod Mijanovich; David Wennberg

    2006-01-01

    Objective To develop a method of identifying patients at high risk of readmission to hospital in the next 12 months for practical use by primary care trusts and general practices in the NHS in England...

  17. A rapid and high-throughput quantum dots bioassay for monitoring of perfluorooctane sulfonate in environmental water samples

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jiong; Wan Yanjian; Li Yuanyuan; Zhang Qiongfang; Xu Shunqing [Minister of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430030 (China); Zhu Huijun [Cranfield Health, Cranfield University, Kempston, Bedfordshire, MK43 0AL (United Kingdom); Shu Baihua, E-mail: shubaihua@hotmail.com [Minister of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430030 (China)

    2011-05-15

    Currently HPLC/MS is the state of the art tool for environmental/drinking water perfluorooctane sulfonate (PFOS) monitoring. PFOS can bind to peroxisomal proliferator-activated receptor-alpha (PPAR{alpha}), which forms heterodimers with retinoid X receptors (RXRs) and binds to PPAR response elements. In this bioassay free PFOS in water samples competes with immobilized PFOS in ELISA plates for a given amount of PPAR{alpha}-RXR{alpha}. It can be determined indirectly by immobilizing PPAR{alpha}-RXR{alpha}-PFOS complex to another plate coated with PPAR{alpha} antibody and subsequent measuring the level of PPAR{alpha}-RXR{alpha} by using biotin-modified PPAR{alpha}-RXR{alpha} probes-quantum dots-streptavidin detection system. The rapid and high-throughput bioassay demonstrated a detection limit of 2.5 ng L{sup -1} with linear range between 2.5 ng L{sup -1} and 75 ng L{sup -1}. Detection results of environmental water samples were highly consistent between the bioassay and HPLC/MS. - We developed a rapid and high-throughput bioassay for monitoring of PFOS in environmental water samples. - Highlights: > We developed a rapid and high-throughput bioassay for monitoring of PFOS in water. > We detected the PFOS concentration of water samples by two methods. > The bioassay is effective for evaluating PFOS contamination level.

  18. Establishment of a simple and rapid identification method for Listeria spp. by using high-resolution melting analysis, and its application in food industry.

    Science.gov (United States)

    Ohshima, Chihiro; Takahashi, Hajime; Phraephaisarn, Chirapiphat; Vesaratchavest, Mongkol; Keeratipibul, Suwimon; Kuda, Takashi; Kimura, Bon

    2014-01-01

    Listeria monocytogenes is the causative bacteria of listeriosis, which has a higher mortality rate than that of other causes of food poisoning. Listeria spp., of which L. monocytogenes is a member, have been isolated from food and manufacturing environments. Several methods have been published for identifying Listeria spp.; however, many of the methods cannot identify newly categorized Listeria spp. Additionally, they are often not suitable for the food industry, owing to their complexity, cost, or time consumption. Recently, high-resolution melting analysis (HRMA), which exploits DNA-sequence differences, has received attention as a simple and quick genomic typing method. In the present study, a new method for the simple, rapid, and low-cost identification of Listeria spp. has been presented using the genes rarA and ldh as targets for HRMA. DNA sequences of 9 Listeria species were first compared, and polymorphisms were identified for each species for primer design. Species specificity of each HRM curve pattern was estimated using type strains of all the species. Among the 9 species, 7 were identified by HRMA using rarA gene, including 3 new species. The remaining 2 species were identified by HRMA of ldh gene. The newly developed HRMA method was then used to assess Listeria isolates from the food industry, and the method efficiency was compared to that of identification by 16S rDNA sequence analysis. The 2 methods were in coherence for 92.6% of the samples, demonstrating the high accuracy of HRMA. The time required for identifying Listeria spp. was substantially low, and the process was considerably simplified, providing a useful and precise method for processing multiple samples per day. Our newly developed method for identifying Listeria spp. is highly valuable; its use is not limited to the food industry, and it can be used for the isolates from the natural environment.

  19. Models for Very Rapid High-Energy -Ray Variability in Blazars

    Indian Academy of Sciences (India)

    G. E. Romero; M. M. Reynoso

    2014-09-01

    We present a family of models for rapid -ray variability in blazars based on a two-component jet. Fast variability occurs when relativistic electron–positron pairs interact with small-scale perturbations in the inner jet. These perturbations are produced by Kelvin–Helmholtz instabilities. We fit the minute-scale strong variability displayed by the blazar PKS 2155−304 and present synthetic light-curves of the kind that might be observed with forthcoming instruments such as the Cherenkov telescope array.

  20. Hypertension and hydronephrosis: rapid resolution of high blood pressure following relief of bilateral ureteric obstruction.

    Science.gov (United States)

    Chalisey, Anil; Karim, Mahzuz

    2013-03-01

    Hypertension secondary to hydronephrosis is not commonly reported in the medical literature. Tubuloglomerular feedback and the renin-angiotensin-aldosterone axis are thought to mediate this process. We describe a patient presenting with acute kidney injury and bilateral hydronephrosis secondary to pelvic malignancy in which peripheral venous renin and aldosterone were elevated. Her blood pressure improved rapidly following insertion of bilateral nephrostomies. The speed of resolution of hypertension following relief of obstruction suggests that humorally mediated vasoconstriction can play an important role in the mechanism by which hydronephrosis causes hypertension. We also discuss other causes of renal parenchymal compression that may lead to the development of hypertension.

  1. Identifying and Remediating High Water Production Problems in Basin-Centered Formations

    Energy Technology Data Exchange (ETDEWEB)

    R.L. Billingsley

    2005-12-01

    Through geochemical analyses of produced waters, petrophysics, and reservoir simulation we developed concepts and approaches for mitigating unwanted water production in tight gas reservoirs and for increasing recovery of gas resources presently considered noncommercial. Only new completion research (outside the scope of this study) will validate our hypothesis. The first task was assembling and interpreting a robust regional database of historical produced-water analyses to address the production of excessive water in basin-centered tight gas fields in the Greater Green (GGRB ) and Wind River basins (WRB), Wyoming. The database is supplemented with a sampling program in currently active areas. Interpretation of the regional water chemistry data indicates most produced waters reflect their original depositional environments and helps identify local anomalies related to basement faulting. After the assembly and evaluation phases of this project, we generated a working model of tight formation reservoir development, based on the regional nature and occurrence of the formation waters. Through an integrative approach to numerous existing reservoir concepts, we synthesized a generalized development scheme organized around reservoir confining stress cycles. This single overarching scheme accommodates a spectrum of outcomes from the GGRB and Wind River basins. Burial and tectonic processes destroy much of the depositional intergranular fabric of the reservoir, generate gas, and create a rock volume marked by extremely low permeabilities to gas and fluids. Stress release associated with uplift regenerates reservoir permeability through the development of a penetrative grain bounding natural fracture fabric. Reservoir mineral composition, magnitude of the stress cycle and local tectonics govern the degree, scale and exact mechanism of permeability development. We applied the reservoir working model to an area of perceived anomalous water production. Detailed water analyses

  2. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

    NARCIS (Netherlands)

    Eyre, Steve; Bowes, John; Diogo, Dorothee; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I.; Padyukov, Leonid; Toes, Rene E. M.; Huizinga, Tom W. J.; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I. W.; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E.; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S.; Deloukas, Panos; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Arlsetig, Lisbeth; Martin, Javier; Rantapaa-Dahlqvist, Solbritt; Plenge, Robert M.; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K.; Worthington, Jane

    2012-01-01

    Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data

  3. Identified particle yield associated with a high-pT trigger particle at the LHC

    NARCIS (Netherlands)

    Veldhoen, M.

    2016-01-01

    Identified particle production ratios are important observables, used to constrain models of particle production in heavy-ion collisions. Measurements of the inclusive particle ratio in central heavy-ion collisions showed an increase of the baryon-to-meson ratio compared to proton-proton collisions

  4. Identifying Modular Flows on Multilayer Networks Reveals Highly Overlapping Organization in Interconnected Systems

    Science.gov (United States)

    De Domenico, Manlio; Lancichinetti, Andrea; Arenas, Alex; Rosvall, Martin

    2015-01-01

    To comprehend interconnected systems across the social and natural sciences, researchers have developed many powerful methods to identify functional modules. For example, with interaction data aggregated into a single network layer, flow-based methods have proven useful for identifying modular dynamics in weighted and directed networks that capture constraints on flow processes. However, many interconnected systems consist of agents or components that exhibit multiple layers of interactions, possibly from several different processes. Inevitably, representing this intricate network of networks as a single aggregated network leads to information loss and may obscure the actual organization. Here, we propose a method based on a compression of network flows that can identify modular flows both within and across layers in nonaggregated multilayer networks. Our numerical experiments on synthetic multilayer networks, with some layers originating from the same interaction process, show that the analysis fails in aggregated networks or when treating the layers separately, whereas the multilayer method can accurately identify modules across layers that originate from the same interaction process. We capitalize on our findings and reveal the community structure of two multilayer collaboration networks with topics as layers: scientists affiliated with the Pierre Auger Observatory and scientists publishing works on networks on the arXiv. Compared to conventional aggregated methods, the multilayer method uncovers connected topics and reveals smaller modules with more overlap that better capture the actual organization.

  5. High-throughput respirometric assay identifies predictive toxicophore of mitochondrial injury

    Energy Technology Data Exchange (ETDEWEB)

    Wills, Lauren P. [MitoHealth Inc., Charleston, SC 29403 (United States); Beeson, Gyda C.; Trager, Richard E.; Lindsey, Christopher C. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Beeson, Craig C. [MitoHealth Inc., Charleston, SC 29403 (United States); Peterson, Yuri K. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Schnellmann, Rick G., E-mail: schnell@musc.edu [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Ralph H. Johnson VA Medical Center, Charleston, SC 29401 (United States)

    2013-10-15

    Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unidentified mitochondrial toxicants. We used a respirometric assay to screen 1760 compounds (5 μM) from the LOPAC and ChemBridge DIVERSet libraries. Thirty-one of the assayed compounds decreased uncoupled respiration, a stress test for mitochondrial dysfunction, prior to a decrease in cell viability and reduced the oxygen consumption rate in isolated mitochondria. The mitochondrial toxicants were grouped by chemical similarity and two clusters containing four compounds each were identified. Cheminformatic analysis of one of the clusters identified previously uncharacterized mitochondrial toxicants from the ChemBridge DIVERSet. This approach will enable the identification of mitochondrial toxicants and advance the prediction of mitochondrial toxicity for both drug discovery and risk assessment. - Highlights: • Respirometric assay conducted in RPTC to create mitochondrial toxicant database. • Chemically similar mitochondrial toxicants aligned as mitochondrial toxicophores • Mitochondrial toxicophore identifies five novel mitochondrial toxicants.

  6. The Baby TALK Model: An Innovative Approach to Identifying High-Risk Children and Families

    Science.gov (United States)

    Villalpando, Aimee Hilado; Leow, Christine; Hornstein, John

    2012-01-01

    This research report examines the Baby TALK model, an innovative early childhood intervention approach used to identify, recruit, and serve young children who are at-risk for developmental delays, mental health needs, and/or school failure, and their families. The report begins with a description of the model. This description is followed by an…

  7. Rapid fabrication and packaging of AlGaN/GaN high-temperature ultraviolet photodetectors using direct wire bonding

    Science.gov (United States)

    So, Hongyun; Senesky, Debbie G.

    2016-07-01

    Cost-effective fabrication and rapid packaging of AlGaN/GaN ultraviolet (UV) photodetectors was demonstrated using direct wire bonding between aluminum wires and a GaN surface. The fabricated photodetectors showed stable dark current levels through the highly conductive 2D electron gas (2DEG), which was electrically connected to aluminum bonding wires. At room temperature, the current passing through the 2DEG rapidly increased upon exposure to UV light because of the generated electrons excited in the AlGaN/GaN layers. In addition, the devices showed consistent and reliable operation at high temperatures up to 100 °C with mechanically stable bonding wires (pull strength of 3-5.2 gram-force), supporting the use of direct wire bonding techniques to fabricate simple AlGaN/GaN sensors for UV detection within harsh environments, such as downhole and space exploration applications.

  8. Teaching Rapid and Slow Learners in High Schools: The Status of Adaptations in Junior, Senior, and Regular High Schools Enrolling More than 300 Pupils. Bulletin, 1954, No. 5

    Science.gov (United States)

    Jewett, Arno; Hull, J. Dan; Brown, Kenneth E.; Cummings, Howard H.; Johnson, Philip G.; Laxson, Mary; Ludington, John R.; Mallory, Berenice; Segel, David

    1954-01-01

    This bulletin represents a cooperative effort of nine secondary school specialists in the Office of Education to picture the provisions used in large high schools to adapt teaching methods in different subjects for pupils who are not average. It is recognized that a pupil may be a rapid learner in one subject and a slow learner in another. Each of…

  9. Causative factors of high intensity areas identified by MRI in the pontine base

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masaki; Takahashi, Akira [Nagoya Univ. (Japan). Faculty of Medicine; Arahata, Yutaka; Motegi, Yoshimasa

    1994-08-01

    High intensity areas in the pontine base were found more frequently in patients of group A who had multiple supratentorial high intensity areas smaller than 15 mm in size and of group B whose vertebral arteries were asymmetric on MR angiography, as compared to those who had none of the above findings of MRI and MR angiography. The high intensity areas of group A were often found bilaterally in the upper pons and those of group B were present unilaterally in the lower pons. Pontine high intensity areas were found frequently on the same side as the smaller vertebral artery in group B. Periventricular hyperintensity was more severe in group A than than in group B. These results suggest that high intensity lesions in the pontine base may conform with the following conditions: (1) multiple small high intensity areas in the supratentorium due to diffuse arteriosclerosis, and (2) asymmetry of the vertebral arteries inducing hemodynamic disorders. (author).

  10. Rapid multiplex high resolution melting method to analyze inflammatory related SNPs in preterm birth

    Directory of Open Access Journals (Sweden)

    Pereyra Silvana

    2012-01-01

    Full Text Available Abstract Background Complex traits like cancer, diabetes, obesity or schizophrenia arise from an intricate interaction between genetic and environmental factors. Complex disorders often cluster in families without a clear-cut pattern of inheritance. Genomic wide association studies focus on the detection of tens or hundreds individual markers contributing to complex diseases. In order to test if a subset of single nucleotide polymorphisms (SNPs from candidate genes are associated to a condition of interest in a particular individual or group of people, new techniques are needed. High-resolution melting (HRM analysis is a new method in which polymerase chain reaction (PCR and mutations scanning are carried out simultaneously in a closed tube, making the procedure fast, inexpensive and easy. Preterm birth (PTB is considered a complex disease, where genetic and environmental factors interact to carry out the delivery of a newborn before 37 weeks of gestation. It is accepted that inflammation plays an important role in pregnancy and PTB. Methods Here, we used real time-PCR followed by HRM analysis to simultaneously identify several gene variations involved in inflammatory pathways on preterm labor. SNPs from TLR4, IL6, IL1 beta and IL12RB genes were analyzed in a case-control study. The results were confirmed either by sequencing or by PCR followed by restriction fragment length polymorphism. Results We were able to simultaneously recognize the variations of four genes with similar accuracy than other methods. In order to obtain non-overlapping melting temperatures, the key step in this strategy was primer design. Genotypic frequencies found for each SNP are in concordance with those previously described in similar populations. None of the studied SNPs were associated with PTB. Conclusions Several gene variations related to the same inflammatory pathway were screened through a new flexible, fast and non expensive method with the purpose of analyzing

  11. Sex Differences in Children with Autism Spectrum Disorder Identified within a High-Risk Infant Cohort

    Science.gov (United States)

    Zwaigenbaum, Lonnie; Bryson, Susan E.; Szatmari, Peter; Brian, Jessica; Smith, Isabel M.; Roberts, Wendy; Vaillancourt, Tracy; Roncadin, Caroline

    2012-01-01

    Sex differences were examined in 3-year-olds with autism spectrum disorders (ASD) ascertained from a high-risk cohort, and high- and low-risk comparison groups. Participants included 319 high-risk siblings and 129 low-risk controls. Eighty-five siblings were diagnosed with ASD, including 57 of 176 boys (32.4%) and 28 of 143 girls (19.6%), implying…

  12. Rapid Emergence of Highly Pathogenic Avian Influenza Subtypes from a Subtype H5N1 Hemagglutinin Variant.

    Science.gov (United States)

    de Vries, Erik; Guo, Hongbo; Dai, Meiling; Rottier, Peter J M; van Kuppeveld, Frank J M; de Haan, Cornelis A M

    2015-05-01

    In 2014, novel highly pathogenic avian influenza A H5N2, H5N5, H5N6, and H5N8 viruses caused outbreaks in Asia, Europe, and North America. The H5 genes of these viruses form a monophyletic group that evolved from a clade 2.3.4 H5N1 variant. This rapid emergence of new H5Nx combinations is unprecedented in the H5N1 evolutionary history.

  13. Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes.

    Science.gov (United States)

    Fu, Glenn K; Wang, Jonathan T; Yang, Junming; Au-Young, Janice; Stuve, Laura L

    2004-07-01

    The rapid amplification of cDNA ends (RACE) procedure is a widely used PCR-based method to clone the cDNA ends of mRNA transcripts. Current RACE methods often produce a high background of nonspecific PCR products, which can exclude the identification of the target cDNA of interest. We describe here an improved RACE procedure using circular cDNA templates and demonstrate the successful extension cloning of 4406 cDNAs.

  14. Expert Opinion to Identify High-Risk Entry Routes of Canine Rabies into Papua New Guinea.

    Science.gov (United States)

    Brookes, V J; Ward, M P

    2017-03-01

    The proximity of Papua New Guinea (PNG) to canine rabies-endemic countries in South-East Asia presents a risk of incursion of this disease into PNG and the rest of the Oceanic region. The objective of this study was to identify the highest risk routes for entry of dogs - associated with movement of people - into PNG from canine rabies-endemic countries. A structured, in-country expert-elicitation workshop was used, and 20 entry routes were identified. The highest risk routes were three land routes from Papua, Indonesia (hunters, traditional border crossers and unregulated, unchecked 'shopper-crossers') and two sea routes (fishing and logging). These results will be used to direct more detailed risk assessments to develop surveillance strategies and incursion response plans.

  15. Identifying Students' Misconceptions about Nuclear Chemistry: A Study of Turkish High School Students

    Science.gov (United States)

    Nakiboglu, Canan; Tekin, Berna Bulbul

    2006-01-01

    This study represents the first attempt to elucidate and detail the types of misconceptions high school students hold relating to basic concepts and topics of nuclear chemistry. A diagnostic multiple-choice test was administered to 157 tenth-grade students (15-16 years old) and the data were analyzed. The results show that high school students…

  16. Using High Throughput Screens to Identify Lead Compounds for Alzheimer’s Disease Therapeutics

    Science.gov (United States)

    2008-11-01

    26  Figure 2.3. Selection rules to identify compounds hits in the AB-GFP fusion assay...example, γ secretase is critical for Notch signaling in embryological development, so completely inhibiting this secretase may have undesirable side...concentrations of AB (68). However, the 12 13 FDA recently ruled that the data from the Phase III clinical trial were inconclusive and problematic

  17. Genetic mapping identifies novel highly protective antigens for an apicomplexan parasite.

    Directory of Open Access Journals (Sweden)

    Damer P Blake

    Full Text Available Apicomplexan parasites are responsible for a myriad of diseases in humans and livestock; yet despite intensive effort, development of effective sub-unit vaccines remains a long-term goal. Antigenic complexity and our inability to identify protective antigens from the pool that induce response are serious challenges in the development of new vaccines. Using a combination of parasite genetics and selective barriers with population-based genetic fingerprinting, we have identified that immunity against the most important apicomplexan parasite of livestock (Eimeria spp. was targeted against a few discrete regions of the genome. Herein we report the identification of six genomic regions and, within two of those loci, the identification of true protective antigens that confer immunity as sub-unit vaccines. The first of these is an Eimeria maxima homologue of apical membrane antigen-1 (AMA-1 and the second is a previously uncharacterised gene that we have termed 'immune mapped protein-1' (IMP-1. Significantly, homologues of the AMA-1 antigen are protective with a range of apicomplexan parasites including Plasmodium spp., which suggest that there may be some characteristic(s of protective antigens shared across this diverse group of parasites. Interestingly, homologues of the IMP-1 antigen, which is protective against E. maxima infection, can be identified in Toxoplasma gondii and Neospora caninum. Overall, this study documents the discovery of novel protective antigens using a population-based genetic mapping approach allied with a protection-based screen of candidate genes. The identification of AMA-1 and IMP-1 represents a substantial step towards development of an effective anti-eimerian sub-unit vaccine and raises the possibility of identification of novel antigens for other apicomplexan parasites. Moreover, validation of the parasite genetics approach to identify effective antigens supports its adoption in other parasite systems where legitimate

  18. High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

    OpenAIRE

    Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I.; Padyukov, Leonid; Toes, Rene E. M.; Huizinga, Tom W J; Wijmenga, Cisca

    2012-01-01

    Summary Using the Immunochip custom single nucleotide polymorphism (SNP) array, designed for dense genotyping of 186 genome wide association study (GWAS) confirmed loci we analysed 11,475 rheumatoid arthritis cases of European ancestry and 15,870 controls for 129,464 markers. The data were combined in meta-analysis with GWAS data from additional independent cases (n=2,363) and controls (n=17,872). We identified fourteen novel loci; nine were associated with rheumatoid arthritis overall and 5 ...

  19. Beta-Blockers for Exams Identify Students at High Risk of Psychiatric Morbidity

    DEFF Research Database (Denmark)

    Butt, Jawad H; Dalsgaard, Søren; Torp-Pedersen, Christian

    2017-01-01

    OBJECTIVES: Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students at...... (HR, 2.67 [95% CI, 1.04-6.82] p = 0.04). CONCLUSION: In healthy students, use of beta-blockers during the exam period was associated with an increased risk of psychiatric outcomes and might identify psychologically vulnerable students who need special attention.......OBJECTIVES: Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students...... at risk of later psychiatric events. METHODS: Using Danish nationwide administrative registries, we studied healthy students aged 14-30 years (1996-2012) with a first-time claimed prescription for a beta-blocker during the exam period (May-June); students who were prescribed a beta-blocker for medical...

  20. High Speed and Rapid State Switching ESI- TOF- MS Technology and Its Applications

    Institute of Scientific and Technical Information of China (English)

    Shi- da Shen; Bruce Andrien; Craig Whitehouse; Staffan Renlund; Henrik Wadensten; Jun-lin Mao

    2001-01-01

    @@ Due to new emerging fast separation technology and the great demand of high sample throughput in discovery, large number of samples now needed to be analyzed by mass spectrometer with high conformation accuracy.

  1. All-high-Tc superconductor rapid-single-flux-quantum circuit operating at ˜30 K

    Science.gov (United States)

    Shokhor, S.; Nadgorny, B.; Gurvitch, M.; Semenov, V.; Polyakov, Yu.; Likharev, K.; Hou, S. Y.; Phillips, Julia M.

    1995-11-01

    We have implemented a simple circuit of the rapid single-flux-quantum (RSFQ) logic family using a single-layer YBa2Cu3O7-x thin-film structure with 14 in-plane Josephson junctions formed by direct electron beam writing. The circuit includes two dc/SFQ converters, two Josephson transmission lines, a complete RS SFQ flip-flop, and an SFQ/dc converter (readout SQUID). Low-frequency testing has shown that the dc-current-biased circuit operates correctly and reliably at T˜30 K, a few degrees below the effective critical temperature of the junctions. Prospects for a further increase of the operation temperature and implementation of more complex RSFQ circuits are discussed in brief.

  2. High performance liquid chromatography method for rapid and accurate determination of homocysteine in plasma and serum

    DEFF Research Database (Denmark)

    Vester, Birte; Rasmussen, K

    1991-01-01

    Determination of homocysteine in plasma or serum for evaluation of cobalamin and folate deficiency is becoming an important diagnostic procedure. Accurate, rapid and low cost methods for measuring homocysteine are therefore required. We have improved an HPLC method and made it suitable for clinical...... application. The more important changes are the addition of an internal standard, mercaptopropionylglycine, and the use of a plasma/serum based calibration material. The method consists of the following steps: reduction of the sample with tri-n-butylphosphine, precipitation of proteins, derivatisation...... with ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate, and HPLC separation followed by fluorescence detection. The linearity of the assays is established and the coefficient of variation is 3.0%. Stability studies show that blood samples must be cooled or centrifuged immediately after venipuncture...

  3. Highly sensitive and rapid bacteria detection using molecular beacon-Au nanoparticles hybrid nanoprobes.

    Science.gov (United States)

    Cao, Jing; Feng, Chao; Liu, Yan; Wang, Shouyu; Liu, Fei

    2014-07-15

    Since many diseases are caused by pathogenic bacterial infections, accurate and rapid detection of pathogenic bacteria is in urgent need to timely apply appropriate treatments and to reduce economic costs. To end this, we designed molecular beacon-Au nanoparticle hybrid nanoprobes to improve the bacterial detection efficiency and sensitivity. Here, we show that the designed molecular beacon modified Au nanoparticles could specifically recognize synthetic DNAs targets and can readily detect targets in clinical samples. Moreover, the hybrid nanoprobes can recognize Escherichia coli within an hour at a concentration of 10(2) cfu/ml, which is 1000-folds sensitive than using molecular beacon directly. Our results show that the molecular beacon-Au nanoparticle hybrid nanoprobes have great potential in medical and biological applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Rapid and Highly Sensitive Detection of Lead Ions in Drinking Water Based on a Strip Immunosensor

    Directory of Open Access Journals (Sweden)

    Chuanlai Xu

    2013-03-01

    Full Text Available In this study, we have first developed a rapid and sensitive strip immunosensor based on two heterogeneously-sized gold nanoparticles (Au NPs probes for the detection of trace lead ions in drinking water. The sensitivity was 4-fold higher than that of the conventional LFA under the optimized conditions. The visual limit of detection (LOD of the amplified method for qualitative detection lead ions was 2 ng/mL and the LOD for semi-quantitative detection could go down to 0.19 ng/mL using a scanning reader. The method suffered from no interference from other metal ions and could be used to detect trace lead ions in drinking water without sample enrichment. The recovery of the test samples ranged from 96% to 103%. As the detection method could be accomplished within 15 min, this method could be used as a potential tool for preliminary monitoring of lead contamination in drinking water.

  5. Rapid microplate, green method for high-throughput evaluation of vinegar acidity using thermal infrared enthalpimetry.

    Science.gov (United States)

    Tischer, Bruna; Oliveira, Alessandra Stangherlin; Ferreira, Daniele de Freitas; Menezes, Cristiano Ragagnin; Duarte, Fábio Andrei; Wagner, Roger; Barin, Juliano Smanioto

    2017-01-15

    Infrared thermal imaging was combined with disposable microplates to perform enthalpimetric analysis using an infrared camera to monitor temperature without contact. The proposed thermal infrared enthalpimetry (TIE) method was used to determine the total, fixed and volatile acidities of vinegars. Sample preparation and analysis were performed in the same vessel, avoiding excessive sample handling and reducing energy expenditure by more than ten times. The results agreed with those of the conventional method for different kinds of vinegars, with values of 1.7%, and 2.3% for repeatability and intermediate precision, respectively. A linear calibration curve was obtained from 0.040 to 1.30molL(-1). The proposed method provided rapid results (within 10s) for four samples simultaneously, a sample throughput of up to 480 samples per hour. In addition, the method complies with at least eight of twelve recommendations for green analytical chemistry, making TIE a promising tool for routine vinegar analysis.

  6. High-speed rapid single-flux-quantum (RSFQ) Batcher-banyan switching core

    Science.gov (United States)

    Zinoviev, Dmitry Y.

    1996-11-01

    We have carried out a paper feasibility study of the implementation of most common packet switching cores (crossbar, Batcher-banyan, time-division shared bus, and token ring) using the superconductor rapid single flux quantum (RSFQ) digital technology. According to our estimates, the best performance-to-complexity ratio may be obtained for the Batcher-banyan network. For example, a 128 by 128 switching core with self-routing (but without address translation, contention resolution, and broadcast features), consisting of about 180,000 Josephson junctions with the internal clock frequency of 60 GHz could handle a workload of 7.5 Tbps. This core could fit on a single 1 cm by 1 cm chip and dissipate as low as 45 mW. The estimated parameters are achievable using a simple 1.5-micrometer niobium- trilayer technology.

  7. Rapid growth of primary dendrite in highly undercooled copper-antimany alloy

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The droplets of Cu-11wt.%Sb hypoeutectic alloy have been rapidly solidified during containerless processing in a 3 m drop tube. The undercooling and cooling rates are estimated, and both play a dominant role in the dendritic growth of primary Cu phase. Undercoolings up to 200 K (0.16TL, where TL is the liquidus temperature) have been obtained in the experiment. With the increase of undercooling, the microstructural evolution of primary Cu phase proceeds from remelted dendrites to the equiaxed grains. A coarse dendritic grain microstructure can form in the undercooling range of 61~102 K and at cooling rates of 1.35×102~2.66×103 K/s. The segregationless solidification of Cu-11wt.%Sb hypoeutectic alloy occurs when undercooling is more than 176 K. The growth of primary Cu phase is mainly controlled by solute diffusion.

  8. Rapid range shifts of species associated with high levels of climate warming.

    Science.gov (United States)

    Chen, I-Ching; Hill, Jane K; Ohlemüller, Ralf; Roy, David B; Thomas, Chris D

    2011-08-19

    The distributions of many terrestrial organisms are currently shifting in latitude or elevation in response to changing climate. Using a meta-analysis, we estimated that the distributions of species have recently shifted to higher elevations at a median rate of 11.0 meters per decade, and to higher latitudes at a median rate of 16.9 kilometers per decade. These rates are approximately two and three times faster than previously reported. The distances moved by species are greatest in studies showing the highest levels of warming, with average latitudinal shifts being generally sufficient to track temperature changes. However, individual species vary greatly in their rates of change, suggesting that the range shift of each species depends on multiple internal species traits and external drivers of change. Rapid average shifts derive from a wide diversity of responses by individual species.

  9. Rapid and highly sensitive detection of lead ions in drinking water based on a strip immunosensor.

    Science.gov (United States)

    Kuang, Hua; Xing, Changrui; Hao, Changlong; Liu, Liqiang; Wang, Libing; Xu, Chuanlai

    2013-03-28

    In this study, we have first developed a rapid and sensitive strip immunosensor based on two heterogeneously-sized gold nanoparticles (Au NPs) probes for the detection of trace lead ions in drinking water. The sensitivity was 4-fold higher than that of the conventional LFA under the optimized conditions. The visual limit of detection (LOD) of the amplified method for qualitative detection lead ions was 2 ng/mL and the LOD for semi-quantitative detection could go down to 0.19 ng/mL using a scanning reader. The method suffered from no interference from other metal ions and could be used to detect trace lead ions in drinking water without sample enrichment. The recovery of the test samples ranged from 96% to 103%. As the detection method could be accomplished within 15 min, this method could be used as a potential tool for preliminary monitoring of lead contamination in drinking water.

  10. Ultra high performance liquid chromatography with mass spectrometry for the rapid analysis and global characterization of multiple constituents from Zibu Piyin Recipe.

    Science.gov (United States)

    Dong, Peipei; Zhang, Lin; Zhan, Libin; Liu, Yanqiu

    2016-02-01

    Zibu Piyin Recipe is a traditional Chinese medicine that has been used for the clinical treatment of memory loss in China. However, the chemical components have not been thoroughly studied so far. To quickly identify the chemical components and understand the chemical profiles related to cognition improvement activity, ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry has been applied. The analysis was performed on an Agilent 1290 ultra-high performance liquid chromatography system with a Poroshell 120 EC-C18 column (3.0 × 150 mm, 2.7 μm) using gradient elution. Using the optimized method, 155 chemical components in Zibu Piyin Recipe were tentatively identified. Among them, 112 components in negative ion mode, 73 constituents in positive ion mode, and 30 compounds in both modes could be detected. The major components were identified from Red Ginseng, Dan shen Root, White Paeony Root, liquorice root, Radix Polygalae, Tangerine Red Epicarp, Grassleaf Sweetflag Rhizome, Indian Buead, and lotus seed. These results suggest that the established rapid and robust method will be useful for identifying multiple constituents of traditional Chinese medicine prescriptions. This method could provide helpful chemical information for further in vivo pharmacological mechanism research of Zibu Piyin Recipe and new drug development for cognition improvement.

  11. Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia

    NARCIS (Netherlands)

    Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J H; Wardenaar, René; Volders, Haukeline H; Klip, Harry G; Hollema, Harry; Jansen, Ritsert C; Schuuring, Ed; Wisman, G Bea A; van der Zee, Ate G J

    2012-01-01

    Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve curr

  12. Identifying suitable substrates for high-quality graphene-based heterostructures

    Science.gov (United States)

    Banszerus, L.; Janssen, H.; Otto, M.; Epping, A.; Taniguchi, T.; Watanabe, K.; Beschoten, B.; Neumaier, D.; Stampfer, C.

    2017-06-01

    We report on a scanning confocal Raman spectroscopy study investigating the strain-uniformity and the overall strain and doping of high-quality chemical vapour deposited (CVD) graphene-based heterostuctures on a large number of different substrate materials, including hexagonal boron nitride (hBN), transition metal dichalcogenides, silicon, different oxides and nitrides, as well as polymers. By applying a hBN-assisted, contamination free, dry transfer process for CVD graphene, high-quality heterostructures with low doping densities and low strain variations are assembled. The Raman spectra of these pristine heterostructures are sensitive to substrate-induced doping and strain variations and are thus used to probe the suitability of the substrate material for potential high-quality graphene devices. We find that the flatness of the substrate material is a key figure for gaining, or preserving high-quality graphene.

  13. Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia

    NARCIS (Netherlands)

    Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J H; Wardenaar, René; Volders, Haukeline H; Klip, Harry G; Hollema, Harry; Jansen, Ritsert C; Schuuring, Ed; Wisman, G Bea A; van der Zee, Ate G J

    2012-01-01

    Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve curr

  14. Beta-Blockers for Exams Identify Students at High Risk of Psychiatric Morbidity.

    Science.gov (United States)

    Butt, Jawad H; Dalsgaard, Søren; Torp-Pedersen, Christian; Køber, Lars; Gislason, Gunnar H; Kruuse, Christina; Fosbøl, Emil L

    2017-04-01

    Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students at risk of later psychiatric events. Using Danish nationwide administrative registries, we studied healthy students aged 14-30 years (1996-2012) with a first-time claimed prescription for a beta-blocker during the exam period (May-June); students who were prescribed a beta-blocker for medical reasons were excluded. We matched these students on age, sex, and time of year to healthy and study active controls with no use of beta-blockers. Risk of incident use of antidepressants, incident use of other psychotropic medications, and suicide attempts was examined by cumulative incidence curves for unadjusted associations and multivariable cause-specific Cox proportional hazard analyses for adjusted hazard ratios (HRs). We identified 12,147 healthy students with exam-related beta-blocker use and 12,147 matched healthy students with no current or prior use of beta-blockers (median age, 19 years; 80.3% women). Among all healthy students, 0.14% had a first-time prescription for a beta-blocker during the exam period with the highest proportion among students aged 19 years (0.39%). Eighty-one percent of the students filled only that single prescription for a beta-blocker during follow-up. During follow-up, 2225 (18.3%) beta-blocker users and 1400 (11.5%) nonbeta-blocker users were prescribed an antidepressant (p risk of antidepressant use (adjusted HRs, 1.68 [95% confidence intervals (CIs), 1.57-1.79], p risk of psychiatric outcomes and might identify psychologically vulnerable students who need special attention.

  15. Rapid screening for drugs of abuse in biological fluids by ultra high performance liquid chromatography/Orbitrap mass spectrometry.

    Science.gov (United States)

    Jagerdeo, Eshwar; Schaff, Jason E

    2016-08-01

    We present a UPLC(®)-High Resolution Mass Spectrometric method to simultaneously screen for nineteen benzodiazepines, twelve opiates, cocaine and three metabolites, and three "Z-drug" hypnotic sedatives in both blood and urine specimens. Sample processing consists of a high-speed, high-temperature enzymatic hydrolysis for urine samples followed by a rapid supported liquid extraction (SLE). The combination of ultra-high resolution chromatography with high resolution mass spectrometry allows all 38 analytes to be uniquely detected with a ten minute analytical run. Limits of detection for all target analytes are 3ng/mL or better, with only 0.3mL of specimen used for analysis. The combination of low sample volume with fast processing and analysis makes this method a suitable replacement for immunoassay screening of the targeted drug classes, while providing far superior specificity and better limits of detection than can routinely be obtained by immunoassay.

  16. High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

    Science.gov (United States)

    Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I.; Padyukov, Leonid; Toes, Rene E.M.; Huizinga, Tom W.J.; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I.W.; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

    2012-01-01

    Summary Using the Immunochip custom single nucleotide polymorphism (SNP) array, designed for dense genotyping of 186 genome wide association study (GWAS) confirmed loci we analysed 11,475 rheumatoid arthritis cases of European ancestry and 15,870 controls for 129,464 markers. The data were combined in meta-analysis with GWAS data from additional independent cases (n=2,363) and controls (n=17,872). We identified fourteen novel loci; nine were associated with rheumatoid arthritis overall and 5 specifically in anti-citrillunated peptide antibody positive disease, bringing the number of confirmed European ancestry rheumatoid arthritis loci to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at six loci and association to low frequency variants (minor allele frequency <0.05) at 4 loci. Bioinformatic analysis of the data generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations. PMID:23143596

  17. Engaging Communities in Identifying Local Strategies for Expanding Integrated Employment During and After High School.

    Science.gov (United States)

    Carter, Erik W; Blustein, Carly L; Bumble, Jennifer L; Harvey, Sarah; Henderson, Lynnette M; McMillan, Elise D

    2016-09-01

    Amidst decades of attention directed toward improving employment outcomes for people with intellectual and developmental disabilities (IDD), few efforts have been made to engage communities in identifying local solutions for expanding integrated employment opportunities. We examined the implementation and outcomes of "community conversation" events held in 6 geographically and economically diverse locales. Each event used an asset-based dialogue approach called the World Café ( Brown & Isaacs, 2005 ) to solicit ideas from a broad cross-section of community members on improving integrated employment that reflect local priorities and possibilities. Six key themes encapsulated the 1,556 strategies generated by the almost 400 attendees. Although considerable consistency was found among the categories of strategies raised across events, the manner in which those individual strategies would be implemented locally reflected the unique accent of each community. Attendees also viewed these events as promising and productive pathways for identifying next steps for their community. We offer recommendations for community-level intervention efforts and suggest directions for future research.

  18. Identifying and assessing highly hazardous drugs within quality risk management programs.

    Science.gov (United States)

    Sussman, Robert G; Schatz, Anthony R; Kimmel, Tracy A; Ader, Allan; Naumann, Bruce D; Weideman, Patricia A

    2016-08-01

    Historically, pharmaceutical industry regulatory guidelines have assigned certain active pharmaceutical ingredients (APIs) to various categories of concern, such as "cytotoxic", "hormones", and "steroids". These categories have been used to identify APIs requiring segregation or dedication in order to prevent cross-contamination and protect the quality and safety of drug products. Since these terms were never defined by regulatory authorities, and many novel pharmacological mechanisms challenge these categories, there is a recognized need to modify the historical use of these terms. The application of a risk-based approach using a health-based limit, such as an acceptable daily exposure (ADE), is more appropriate for the development of a Quality Risk Management Program (QRMP) than the use of categories of concern. The toxicological and pharmacological characteristics of these categories are discussed to help identify and prioritize compounds requiring special attention. Controlling airborne concentrations and the contamination of product contact surfaces in accordance with values derived from quantitative risk assessments can prevent adverse effects in workers and patients, regardless of specific categorical designations to which these APIs have been assigned. The authors acknowledge the movement away from placing compounds into categories and, while not yet universal, the importance of basing QRMPs on compound-specific ADEs and risk assessments. Based on the results of a risk assessment, segregation and dedication may also be required for some compounds to prevent cross contamination during manufacture of APIs. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Clinical significance of pontine high signals identified on magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masaki; Takahashi, Akira (Nagoya Univ. (Japan). Faculty of Medicine); Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro

    1993-07-01

    Spin-echo magnetic resonance imaging (MRI) was evaluated to 530 cases in order to investigate the clinical significance of pontine high signals. The subjects comprised 109 cases of pontine infarction with high signal on T[sub 2]-weighted image and low signal on T[sub 1]-weighted image (PI group), 145 of pontine high signal with high signal on T[sub 2]-weighted image but normal signal on T[sub 1]-weighted image (PH group) and 276 of age-matched control without abnormality either on T[sub 1] or T[sub 2]-weighted images (AC group). Subjective complaints such as vertigo-dizziness were more frequent in the PH group than in the PI group. In both PI and groups, periventricular hyperintensity as well as subcortical high signals in the supratentorium were more severe than in the AC group. These degrees were higher in the PI group than in the PH group. In conclusion, PH as well as PI may result from diffuse arteriosclerosis and PH is considered to be an early finding of pontine ischemia. (author).

  20. Rapid determination of trace semicarbazide in flour products by high-performance liquid chromatography based on a nucleophilic substitution reaction.

    Science.gov (United States)

    Wei, Tianfu; Li, Gongke; Zhang, Zhuomin

    2017-05-01

    Semicarbazide, a toxic food contaminant, widely exists in food products and it originates from the thermal degradation of a food additive of azodicarbonamide or a metabolite of nitrofurazone abused in meat specimens. Many previous methods for semicarbazide determination usually required expensive instruments, difficult-to-prepare monoclonal antibodies, and a long operation time. In this study, a high-performance liquid chromatography method was developed for the rapid determination of trace semicarbazide coupling with a nucleophilic substitution reaction firstly using 4-nitrobenzoyl chloride as derivatization reagent. The derivatization reaction was mild at room temperature for 1 min in neutral solution. Then, semicarbazide derivative was separated and quantified by high-performance liquid chromatography with ultraviolet detection under optimal separation conditions at λmax = 261 nm. The proposed method offered the detection limit of 1.8 μg/L and was successfully applied for the rapid determination of trace semicarbazide in flour products. Semicarbazide in positive real samples could be actually found and quantified in the range of 0.47-7.53 mg/kg. The recoveries were 76.6-119% with relative standard deviations of 0.5-9.1% (n = 3). This developed method was rapid, reliable, and convenient for the determination of trace semicarbazide in food. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Rapid and noncontact photoacoustic tomography imaging system using an interferometer with high-speed phase modulation technique

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jun [School of Physics and Telecom Engineering, South China Normal University, Guangzhou 510006 (China); Tang, Zhilie; Wu, Yongbo [School of Physics and Telecom Engineering, South China Normal University, Guangzhou 510006 (China); GuangDong Province Key Laboratory of Quantum Engineering and Quantum Materials, South China Normal University, IMOT, Guangzhou 510006 (China); Wang, Yi [School of Control Engineering, Northeastern University at Qinhuangdao, Qinhuangdao 066004 (China)

    2015-04-15

    We designed, fabricated, and tested a rapid and noncontact photoacoustic tomography (PAT) imaging system using a low-coherence interferometer with high-speed phase modulation technique. Such a rapid and noncontact probing system can greatly decrease the time of imaging. The proposed PAT imaging system is experimentally verified by capturing images of a simulated tissue sample and the blood vessels within the ear flap of a mouse (pinna) in vivo. The axial and lateral resolutions of the system are evaluated at 45 and ∼15 μm, respectively. The imaging depth of the system is 1 mm in a special phantom. Our results show that the proposed system opens a promising way to realize noncontact, real-time PAT.

  2. Combining infobuttons and semantic web rules for identifying patterns and delivering highly-personalized education materials.

    Science.gov (United States)

    Hulse, Nathan C; Long, Jie; Tao, Cui

    2013-01-01

    Infobuttons have been established to be an effective resource for addressing information needs at the point of care, as evidenced by recent research and their inclusion in government-based electronic health record incentive programs in the United States. Yet their utility has been limited to wide success for only a specific set of domains (lab data, medication orders, and problem lists) and only for discrete, singular concepts that are already documented in the electronic medical record. In this manuscript, we present an effort to broaden their utility by connecting a semantic web-based phenotyping engine with an infobutton framework in order to identify and address broader issues in patient data, derived from multiple data sources. We have tested these patterns by defining and testing semantic definitions of pre-diabetes and metabolic syndrome. We intend to carry forward relevant information to the infobutton framework to present timely, relevant education resources to patients and providers.

  3. High-throughput sequencing enhanced phage display identifies peptides that bind mycobacteria

    CSIR Research Space (South Africa)

    Ngubane, NAC

    2013-11-01

    Full Text Available tuberculosis. Chest 95: 1193–1197. 7. Davis JL, Huang L, Worodria W, Masur H, Cattamanchi A, et al. (2011) Nucleic acid amplification tests for diagnosis of smear-negative TB in a high HIV-prevalence setting: a prospective cohort study. PLoS One 6: e16321. 8...

  4. A Rapid Screening Assay Identifies Monotherapy with Interferon-ß and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus.

    Directory of Open Access Journals (Sweden)

    Stephen D S McCarthy

    2016-01-01

    Full Text Available To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD. While a number of candidate drugs have shown limited efficacy in vitro and/or in non-human primate studies, differences in experimental methodologies make it difficult to compare their therapeutic effectiveness. Using an in vitro model of Ebola Zaire replication with transcription-competent virus like particles (trVLPs, requiring only level 2 biosafety containment, we compared the activities of the type I interferons (IFNs IFN-α and IFN-ß, a panel of viral polymerase inhibitors (lamivudine (3TC, zidovudine (AZT tenofovir (TFV, favipiravir (FPV, the active metabolite of brincidofovir, cidofovir (CDF, and the estrogen receptor modulator, toremifene (TOR, in inhibiting viral replication in dose-response and time course studies. We also tested 28 two- and 56 three-drug combinations against Ebola replication. IFN-α and IFN-ß inhibited viral replication 24 hours post-infection (IC50 0.038μM and 0.016μM, respectively. 3TC, AZT and TFV inhibited Ebola replication when used alone (50-62% or in combination (87%. They exhibited lower IC50 (0.98-6.2μM compared with FPV (36.8μM, when administered 24 hours post-infection. Unexpectedly, CDF had a narrow therapeutic window (6.25-25μM. When dosed >50μM, CDF treatment enhanced viral infection. IFN-ß exhibited strong synergy with 3TC (97.3% inhibition or in triple combination with 3TC and AZT (95.8% inhibition. This study demonstrates that IFNs and viral polymerase inhibitors may have utility in EVD. We identified several 2 and 3 drug combinations with strong anti-Ebola activity, confirmed in studies using fully infectious ZEBOV, providing a rationale for testing combination therapies in animal models of lethal Ebola challenge. These studies open up new possibilities for novel therapeutic options, in particular combination therapies, which could prevent and treat Ebola infection and potentially reduce drug

  5. The habits of highly effective phages: population dynamics as a framework for identifying therapeutic phages

    Directory of Open Access Journals (Sweden)

    James J Bull

    2014-11-01

    Full Text Available The use of bacteriophages as antibacterial agents is being actively researched on a global scale. Typically, the phages used are isolated from the wild by plating on the bacteria of interest, and a far larger set of candidate phages is often available than can be used in any application. When an excess of phages is available, how should the best phages be identified? Here we consider phage-bacterial population dynamics as a basis for evaluating and predicting phage success. A central question is whether the innate dynamical properties of phages are the determinants of success, or instead, whether extrinsic, indirect effects can be responsible. We address the dynamical perspective, motivated in part by the absence of dynamics in previously suggested principles of phage therapy. Current mathematical models of bacterial-phage dynamics do not capture the realities of in vivo dynamics, nor is this likely to change, but they do give insight to qualitative properties that may be generalizable. In particular, phage adsorption rate may be critical to treatment success, so understanding the effects of the in vivo environment on host availability may allow prediction of useful phages prior to in vivo experimentation. Principles for predicting efficacy may be derived by developing a greater understanding of the in vivo system, or such principles could be determined empirically by comparing phages with known differences in their dynamic properties. The comparative approach promises to be a powerful method of discovering the key to phage success. We offer five recommendations for future study: (i compare phages differing in treatment efficacy to identify the phage properties associated with success, (ii assay dynamics in vivo, (iii understand mechanisms of bacterial escape from phages, (iv test phages in model infections that are relevant to the intended clinical applications, and (v develop new classes of models for phage growth in spatially heterogeneous

  6. Rapid, high-temperature, field test method for evaluation of geothermal calcium carbonate scale inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Asperger, R.G.

    1986-09-01

    A new test method is described that allows the rapid field testing of calcium carbonate scale inhibitors at 500/sup 0/F (260/sup 0/C). The method evolved from use of a full-flow test loop on a well with a mass flow rate of about 1 x 10/sup 6/ lbm/hr (126 kg/s). It is a simple, effective way to evaluate the effectiveness of inhibitors under field conditions. Five commercial formulations were chosen for field evaluation on the basis of nonflowing, laboratory screening tests at 500/sup 0/F (260/sup 0/C). Four of these formulations from different suppliers controlled calcium carbonate scale deposition as measured by the test method. Two of these could dislodge recently deposited scale that had not age-hardened. Performance-profile diagrams, which were measured for these four effective inhibitors, show the concentration interrelationship between brine calcium and inhibitor concentrations at which the formulations will and will not stop scale formation in the test apparatus. With these diagrams, one formulation was chosen for testing on the full-flow brine line. The composition was tested for 6 weeks and showed a dramatic decrease in the scaling occurring at the flow-control valve. This scaling was about to force a shutdown of a major, long-term flow test being done for reservoir economic evaluations. The inhibitor stopped the scaling, and the test was performed without interruption.

  7. High Performance Microreactor for Rapid Fluid Mixing and Redox Reaction of Ascorbic Acid

    CERN Document Server

    Fang, Wei-Feng

    2008-01-01

    A novel micro device with a mechanism of split and recombination (SNR) for rapid fluidic mixing and reaction, named a SNR micro-reactor, was designed, fabricated and systematically analyzed. This SNR micro-reactor possessing an in-plane dividing structure requires only simple fabrication. We investigated this reactor and compared it numerically and experimentally with a slanted-groove micromixer (SGM). From the numerical results the mixing indices and mixing patterns demonstrated that the mixing ability of the SNR micro-reactor was much superior to that of the SGM. From a mixing test with phenolphthalein and sodium hydroxide solutions, the mixing lengths of the SNR micro-reactor were less than 4 mm for a Reynolds number over a wide range (Re = 0.1 - 10). From a comparison of mixing lengths, the results revealed also that the SNR micro-reactor surpassed the SGM in mixing performance by more than 200 %. As a reaction length is a suitable test of the performance of a reactor, we introduced a redox reaction betwe...

  8. Rapid growth of nickel dendrite in highly undercooled Ni-Mo alloys

    Institute of Scientific and Technical Information of China (English)

    姚文静; 魏炳波

    2003-01-01

    Ni-39.3%Mo, Ni-45%Mo hypoeutectic alloys and Ni-47.7%Mo eutectic alloy have been rapidly solidified with different droplet sizes by containerless processing in a drop tube. For Ni-39.3%Mo hypoeutectic alloy, which corresponds to the maximum solid solubility of nickel phase, the solidification microstructure is characterized by nickel dendrite plus (Ni+NiMo) eutectic structure. The undercooling of this alloy up to 182 K has been realized in the experiments. With an increase in undercooling, the dendritic microstructure is refined. The microstructural evolution of primary Ni phase in Ni-45%Mo hypoeutectic alloy evolves from remelted dendrite to equiaxed grains, whereas Ni-47.7%Mo eutectic alloy exhibits a structural transition from lamellar eutectic to anomalous eutectic. Theoretical analyses indicate that, for Ni-39.3%Mo, Ni-45%Mo and Ni-47.7%Mo alloys, the nickel phase shows a transition from solutal-diffusion-controlled growth to thermal-diffusion-controlled growth at undercoolings of 66.6, 81.9 and 85.0 K. The critical transition temperature decreases with a reduction in the nickel content.

  9. Rapid generation of single-tumor spheroids for high-throughput cell function and toxicity analysis.

    Science.gov (United States)

    Ivascu, Andrea; Kubbies, Manfred

    2006-12-01

    Spheroids are widely used in biology because they provide an in vitro 3-dimensional (3D) model to study proliferation, cell death, differentiation, and metabolism of cells in tumors and the response of tumors to radiotherapy and chemotherapy. The methods of generating spheroids are limited by size heterogeneity, long cultivation time, or mechanical accessibility for higher throughput fashion. The authors present a rapid method to generate single spheroids in suspension culture in individual wells. A defined number of cells ranging from 1000 to 20,000 were seeded into wells of poly-HEMA-coated, 96-well, round-or conical-bottom plates in standard medium and centrifuged for 10 min at 1000 g. This procedure generates single spheroids in each well within a 24-h culture time with homogeneous sizes, morphologies, and stratification of proliferating cells in the rim and dying cells in the core region. Because a large number of tumor cell lines form only loose aggregates when cultured in 3D, the authors also performed a screen for medium additives to achieve a switch from aggregate to spheroid morphology. Small quantities of the basement membrane extract Matrigel, added to the culture medium prior to centrifugation, most effectively induced compact spheroid formation. The compact spheroid morphology is evident as early as 24 h after centrifugation in a true suspension culture. Twenty tumor cell lines of different lineages have been used to successfully generate compact, single spheroids with homogenous size in 96-well plates and are easily accessible for subsequent functional analysis.

  10. [The rapid analysis of polychlorinated quaterphenyls in blood using different diameter capillary column with the high-resolution gas chromatograph high-resolution mass spectrometer].

    Science.gov (United States)

    Yasutake, Daisuke; Ashizuka, Yuki; Hori, Tsuguhide; Kurokawa, Youichi; Kajiwara, Jumboku; Hirata, Teruaki; Ishiguro, Yasuhisa; Iida, Takao; Uchi, Hiroshi; Furue, Masutaka

    2011-04-01

    The polychlorinated quaterphenyl (PCQ) concentrations in blood are important discriminative parameters in yusho patient. In this study, a rapid analytical method for PCQ using different diameter capillary column (rapid-Rtx65TG) with high-resolution gas chromatograph high-resolution mass spectrometer (HRGC/HRMS) instead of the gas chromatograph electron capture detector (ECD/GC) was developed. Using different diameter capillary columns, the analysis time of the HRGC/HRMS was drastically shortened, and the detection sensitivity was improved. In the rapid-Rtx65TG column, a small-bore capillary column (length 1m, I.D. 0.1mm) was connected with the inlet side of the GC, and behind that column, a large-bore capillary column (length 15mm, I.D. 0.53mm) for octadecachloroquaterphenyl (ODCQ) analysis was connected. In the HRGC/HRMS measurement of ODCQ by the rapid-Rtx65TG column, the minimum limit of detection for the apparatus was 0.4 pg, and the minimum limit of determination for the blood was 0.008 ppb. On ECD/GC in the conventional method and HRGC/HRMS in this study, the PCQ concentration in blood including yusho patients and yusho suspected persons was almost equivalent.

  11. Rapid identification of bovine mastitis pathogens by high-resolution melt analysis of 16S rDNA sequences.

    Science.gov (United States)

    Ajitkumar, Praseeda; Barkema, Herman W; De Buck, Jeroen

    2012-03-23

    Accurate identification of mastitis pathogens is often compromised when using conventional culture-based methods. Here, we report a novel, rapid assay tested for speciation of bacterial mastitis pathogens using high-resolution melt analysis (HRMA) of 16S rDNA sequences. Real-time PCR amplification of 16S rRNA gene fragment, spanning the variable region V5 and V6 was performed with a resulting amplicon of 290bp. First, a library was generated of melt curves of 9 common pathogens that are implicated in bovine mastitis. Six of the isolates, Escherichia coli, Streptococcus agalactiae, Klebsiella pneumoniae, Streptococcus uberis, Staphylococcus aureus and Mycoplasma bovis, were type strains while the other 3, Arcanobacterium pyogenes, Corynebacterium bovis and Streptococcus dysgalactiae, were bovine mastitis field isolates. Four of the type strains, E. coli, S. agalactiae, K. pneumoniae and S. aureus, were found to be of human origin, while the other 3 type strains were isolated from bovine infections. Secondly, the melt curves and corresponding amplicon sequences of A. pyogenes, E. coli, S. agalactiae, S. dysgalactiae, K. pneumoniae, S. uberis and S. aureus were compared with 10 bovine mastitis field isolates of each pathogen. Based on the distinct differences in melt curves and sequences between human and bovine isolates of E. coli and K. pneumoniae, it was deemed necessary to select a set of bovine strains for these pathogens to be used as reference strains in the HRMA. Next, the HRMA was validated by three interpreters analyzing the differential clustering pattern of melt curves of 60 bacterial cultures obtained from mastitis milk samples. The three test interpreters were blinded to the culture and sequencing results of the isolates. Overall accuracy of the validation assay was 95% as there was difficulty in identifying the streptococci due to heterogeneity observed in the PCR amplicons of S. uberis. The present study revealed that broad-range real-time PCR with

  12. Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Dubbels, R.; Klenke, E.; Schnakenberg, E.; Ehlers, C.; Schloot, W. [Univ. of Bremen, Center of Human Genetics and Genetic Counselling, Bremen (Germany); Reiter, R.J. [The Univ. of Texas Health Science Center at San Antonio, Dept. of Cellular and Structural Biology, San Antonio, Texas (United States); Goebel, A.; Schiware, H.W. [Gemeinschaftslabor Dr. Schiwara et al., Breman (Germany)

    1995-01-01

    Melatonin, the chief hormone of the pineal gland in vertebrates, is widely distributed in the animal kingdom. Among many functions, melatonin synchronizes circadian and circannual rhythms, stimulates immune function, may increase life span, inhibits growth of cancer cells in vitro and cancer progression and promotion in vivo, and was recently shown to be a potent hydroxyl radical scavenger and antioxidant. Hydroxyl radicals are highly toxic by-products of oxygen metabolism that damage cellular DNA and other macromolecules. Herein we report that melatonin, in varying concentrations, is also found in a variety of plants. Melatonin concentrations, measured in nine different plants by radioimmunoassay, ranged from 0 to 862 pg melatonin/mg protein. The presence of melatonin was verified by gas chromatography/mass spectrometry. Our findings suggest that the consumption of plant materials that contain high levels of melatonin could alter blood melatonin levels of the indole as well as provide protection of macromolecules against oxidative damage. (au) 30 refs.

  13. High-index immersion lithography: preventing lens photocontamination and identifying optical behavior of LuAG

    Science.gov (United States)

    Liberman, V.; Rothschild, M.; Palmacci, S. T.; Bristol, R.; Byers, J.; Turro, N. J.; Lei, X.; O'Connor, N.; Zimmerman, P. A.

    2008-03-01

    A potential extension of water-based 193-nm immersion lithography involves transition to a higher refractive index organic immersion fluid coupled with a higher index last lens element. While considerable progress has been made in improving the photo-durability of the immersion fluid itself, photo-induced contamination of the last lens element caused by laser exposure in the presence of such organic fluids remains a major concern. In this work, we study remediation strategies for such contamination, which would be compatible with conventional lithographic production environments. In general, surface photocontamination layers were found to be highly graphitic in nature, where the first monolayer is strongly bound to the substrate. We have attempted to develop a surface passivation treatment for altering the monolayer chemistry and preventing large-scale contamination, but found such treatments to be unstable under laser irradiation. On the other hand, using hydrogen peroxide as a in-situ cleaning solution has been shown to be extremely effective. We also present first laser-based durability results of LuAG, which is a leading candidate material for high index last element to be used with high index fluids.

  14. Identifying undetected cases of chronic kidney disease in Mexico. Targeting high-risk populations.

    Science.gov (United States)

    García-García, Guillermo; Gutiérrez-Padilla, Alfonso J; Chávez-Iñiguez, Jonathan; Pérez-Gómez, Héctor R; Mendoza-García, Martha; González-De la Peña, Ma Del Mar; Tonelli, Marcello

    2013-11-01

    Chronic kidney disease (CKD) is a major public health problem in Mexico. Current guidelines recommend routine CKD testing in patients at increased risk for CKD. We undertook this study to examine the diagnostic yield of targeted screening (case-finding) for CKD in high-risk populations in rural and urban communities in Jalisco, Mexico. In a cross-sectional study, we did laboratory tests searching for CKD and its risk factors and compared the characteristics of participants with those reported by the National Health and Nutrition Survey 2006 (NHNS). Individuals who were aware that they had CKD and those 126 mg/dl (56.1 vs. 14.4%, p = 0.0001) were more prevalent among the participants; self-reported hypertension (41.9 vs. 7.3%, p = 0.0001), systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg (52.5 vs. 43.2%, p = 0.0001), and obesity (42.8. vs. 29.3%, p = 0.0001) were also more frequent among participants. There were 19.7% with proteinuria; CKD was more prevalent among the high risk participants in our study (31.3 vs. 8.0%, p = 0.0001) than in the general population. CKD was detected frequently in high-risk Mexican populations. Trials of case-finding and intervention are feasible and warranted in Mexico. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  15. High-Throughput Screening Methodology to Identify Alpha-Synuclein Aggregation Inhibitors.

    Science.gov (United States)

    Pujols, Jordi; Peña-Díaz, Samuel; Conde-Giménez, María; Pinheiro, Francisca; Navarro, Susanna; Sancho, Javier; Ventura, Salvador

    2017-03-02

    An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinson's disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. Thus, compounds that inhibit α-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of α-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of α-syn is exceedingly slow and highly irreproducible, therefore precluding fast high throughput anti-aggregation drug screening. Here, we present a simple and easy-to-implement in-plate method for screening large chemical libraries in the search for α-syn aggregation modulators. It allows us to monitor aggregation kinetics with high reproducibility, while being faster and requiring lower protein amounts than conventional aggregation assays. We illustrate how the approach enables the identification of strong aggregation inhibitors in a library of more than 14,000 compounds.

  16. HIGH YIELD AND RAPID SYNTHESES METHODS FOR PRODUCING METALLO-ORGANIC SALTS

    DEFF Research Database (Denmark)

    2005-01-01

    A new method for preparing salts of metal cations and organic acids, especially divalent salts of alkaline earth metal ions from group II of the periodic system and carboxylic acids. The method comprising the use of a high temperature (about 90° or more) and, optionally. high pressure, in order t...... to obtain a higher yield, purity and faster reaction speed than obtained with known synthesis methods. In particular, the present invention relates to the production of strontium salts of carboxylic acids. Novel strontium salts are also provided by the present method.......A new method for preparing salts of metal cations and organic acids, especially divalent salts of alkaline earth metal ions from group II of the periodic system and carboxylic acids. The method comprising the use of a high temperature (about 90° or more) and, optionally. high pressure, in order...

  17. Integrated techniques to identify groundwater vulnerability to pollution in a highly industrialized terrain, Tamilnadu, India.

    Science.gov (United States)

    Srinivasamoorthy, Krishnaraj; Vijayaraghavan, K; Vasanthavigar, Murugesan; Rajivgandhi, R; Sarma, V S

    2011-11-01

    Investigation has been made to identify groundwater vulnerability to pollution by using geoelectric and hydrochemical investigations in an important industrial town Mettur located in Tamilnadu state of India. Schlumberger vertical electric soundings were carried out in 23 locations and groundwater samples collected from bore wells in the same locations. The resistivity value with groundwater in areas influenced by sewages from industries, domestic and agricultural practices in the central and southern part of the study area. The calculated specific conductance was noted higher than EC in central and southern part of the study area with low resistivity indicating the contaminated nature of groundwater. Concentrations of Ca, Na, Mg and K along with Cl, HCO(3), SO(4) and NO(3) were higher in certain locations when compared with WHO and ISI standards. The facies concept demarcated four groups based on the nature of groundwater contamination. The trace elements Fe and Pb were higher in locations confined to industrial zones and Zn and Cu were within the prescribed limit in all the samples.

  18. Development of CAPS markers to identify Indian tea (Camellia sinensis) clones with high catechin content.

    Science.gov (United States)

    Elangbam, M; Misra, A K

    2016-06-10

    Tea leaves are rich in plant secondary phenolics, especially flavonoids. Catechins are considered to be the most valuable flavonoids, and the catechin content in tea is an important trait for determining its quality. We have developed cleaved amplified polymorphic sequence (CAPS)-based markers for evaluating total catechin content that target two important secondary metabolite pathway genes, PAL (phenylalanine ammonia-lyase) and CHS (chalcone synthase). Catechin content levels in the tea samples tested ranged from 9 to 33 mg/mg. The CAPS technique identified clones with the homozygous profile PRc1, which has relatively lower catechin content than clones with the heterozygous profile PRc2. A significant difference (t = 16.85) in the level of catechin content was also detected between heterozygotes and homozygotes in the tea seed stock TS379. We found a polynomial relationship between the marker developed for CHS2 and catechin content in these tea samples with R2 = 0.9788. Moreover, PAL has less of a relationship with catechin content. Therefore, we recommend tea clones with heterozygous CAPS profiles for the gene CHS2+RcaI for the further improvement in these clones.

  19. Rapid and highly efficient construction of TALE-based transcriptional regulators and nucleases for genome modification

    KAUST Repository

    Li, Lixin

    2012-01-22

    Transcription activator-like effectors (TALEs) can be used as DNA-targeting modules by engineering their repeat domains to dictate user-selected sequence specificity. TALEs have been shown to function as site-specific transcriptional activators in a variety of cell types and organisms. TALE nucleases (TALENs), generated by fusing the FokI cleavage domain to TALE, have been used to create genomic double-strand breaks. The identity of the TALE repeat variable di-residues, their number, and their order dictate the DNA sequence specificity. Because TALE repeats are nearly identical, their assembly by cloning or even by synthesis is challenging and time consuming. Here, we report the development and use of a rapid and straightforward approach for the construction of designer TALE (dTALE) activators and nucleases with user-selected DNA target specificity. Using our plasmid set of 100 repeat modules, researchers can assemble repeat domains for any 14-nucleotide target sequence in one sequential restriction-ligation cloning step and in only 24 h. We generated several custom dTALEs and dTALENs with new target sequence specificities and validated their function by transient expression in tobacco leaves and in vitro DNA cleavage assays, respectively. Moreover, we developed a web tool, called idTALE, to facilitate the design of dTALENs and the identification of their genomic targets and potential off-targets in the genomes of several model species. Our dTALE repeat assembly approach along with the web tool idTALE will expedite genome-engineering applications in a variety of cell types and organisms including plants. © 2012 Springer Science+Business Media B.V.

  20. Rapid high-throughput genotyping of HBV DNA using a modified hybridization-extension technique.

    Science.gov (United States)

    Bao, Han; Zhao, Wenliang; Ruan, Banjun; Wang, Qing; Zhao, Jinrong; Lei, Xiaoying; Wang, Weihua; Liu, Yonglan; Sun, Jianbing; Xiang, An; Guo, Yanhai; Yan, Zhen

    2013-11-07

    China has the highest incidence of hepatitis B virus (HBV) infection worldwide. HBV genotypes have variable impacts on disease pathogenesis and drug tolerance. We have developed a technically simple and accurate method for HBV genotyping that will be applicable to pre-treatment diagnosis and individualized treatment. Multiple sequence alignments of HBV genomes from GenBank were used to design primers and probes for genotyping of HBV A through H. The hybridization was carried out on nitrocellulose (NC) membranes with probes fixed in an array format, which was followed by hybrid amplification by an extension step with DNA polymerase to reinforce the double-stranded DNA hybrids on the NC membrane and subsequent visualization using an avidin-biotin system. Genotyping results were confirmed by DNA sequencing and bioinformatics analysis using the National Center for Biotechnology Information genotyping database, and compared with results from the line probe assay. The data show that multiple sequence alignment defined a 630 bp region in the HBV PreS and S regions that was suitable for genotyping. All genotyping significant single nucleotides in the region were defined. Two-hundred-and-ninety-one HBV-positive serum samples from Northwest Chinese patients were genotyped, and the genotyping rate from the new modified hybridization-extension method was 100% compared with direct sequencing. Compared with line probe assay, the newly developed method is superior, featuring reduced reaction time, lower risk of contamination, and increased accuracy for detecting single nucleotide mutation. In conclusion, a novel hybridization-extension method for HBV genotyping was established, which represents a new tool for accurate and rapid SNP detection that will benefit clinical testing.

  1. Rapidity dependence of multiplicity fluctuations and correlations in high-energy nucleus–nucleus interactions

    Indian Academy of Sciences (India)

    Dipak Ghosh; Argha Deb; Swarnapratim Bhattacharyya; Utpal Datta

    2011-08-01

    The multiplicity fluctuations of the produced pions were studied using scaled variance method in 16O–AgBr interactions at 2.1 AGeV, 24Mg–AgBr interactions at 4.5 AGeV, 12C–AgBr interactions at 4.5 AGeV, 16O–AgBr interactions at 60 AGeV and 32S–AgBr interactions at 200 AGeV at two different binning conditions. In the first binning condition, the rapidity interval was varied in steps of one centring about the central rapidity until it reached 14. In the second case, the rapidity interval was increased in steps of 1.6 up to 14.4. Multiplicity distributions and their scaled variances were presented as a function of the dependence on the rapidity width for both the binning conditions. Multiplicity fluctuations were found to increase with the increase of rapidity interval and later found to saturate at larger rapidity window for all the interactions and in both the binning conditions. Multiplicity fluctuations were found to increase with the energy of the projectile beam. The values of the scaled variances were found to be greater than one in all the cases in both the binning conditions indicating the presence of correlation during the multiparticle production process in high-energy nucleus–nucleus interactions. Experimental results were compared with the results obtained from the Monte Carlo simulated events for all the interactions. The Monte Carlo simulated data showed very small values of scaled variance suggesting very small fluctuations for the simulated events. Experimental results obtained from 16O–AgBr interactions at 60 AGeV and 32S–AgBr interactions at 200 AGeV were compared with the events generated by Lund Monte Carlo code (FRITIOF model). FRITIOF model failed to explain the multiplicity fluctuations of pions emitted from 16O–AgBr interactions at 60 AGeV for both the binning conditions. However, the experimental data agreed well with the FRITIOF model for 32S–AgBr interactions at 200 AGeV.

  2. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.

    Science.gov (United States)

    Lim, Weng Khong; Ong, Choon Kiat; Tan, Jing; Thike, Aye Aye; Ng, Cedric Chuan Young; Rajasegaran, Vikneswari; Myint, Swe Swe; Nagarajan, Sanjanaa; Nasir, Nur Diyana Md; McPherson, John R; Cutcutache, Ioana; Poore, Gregory; Tay, Su Ting; Ooi, Wei Siong; Tan, Veronique Kiak Mien; Hartman, Mikael; Ong, Kong Wee; Tan, Benita K T; Rozen, Steven G; Tan, Puay Hoon; Tan, Patrick; Teh, Bin Tean

    2014-08-01

    Fibroadenomas are the most common breast tumors in women under 30 (refs. 1,2). Exome sequencing of eight fibroadenomas with matching whole-blood samples revealed recurrent somatic mutations solely in MED12, which encodes a Mediator complex subunit. Targeted sequencing of an additional 90 fibroadenomas confirmed highly frequent MED12 exon 2 mutations (58/98, 59%) that are probably somatic, with 71% of mutations occurring in codon 44. Using laser capture microdissection, we show that MED12 fibroadenoma mutations are present in stromal but not epithelial mammary cells. Expression profiling of MED12-mutated and wild-type fibroadenomas revealed that MED12 mutations are associated with dysregulated estrogen signaling and extracellular matrix organization. The fibroadenoma MED12 mutation spectrum is nearly identical to that of previously reported MED12 lesions in uterine leiomyoma but not those of other tumors. Benign tumors of the breast and uterus, both of which are key target tissues of estrogen, may thus share a common genetic basis underpinned by highly frequent and specific MED12 mutations.

  3. 3D metal-organic framework as highly efficient biosensing platform for ultrasensitive and rapid detection of bisphenol A.

    Science.gov (United States)

    Wang, Xue; Lu, Xianbo; Wu, Lidong; Chen, Jiping

    2015-03-15

    As is well known, bisphenol A (BPA), usually exists in daily plastic products, is one of the most important endocrine disrupting chemicals. In this work, copper-centered metal-organic framework (Cu-MOF) was synthesized, which was characterized by SEM, TEM, XRD, FTIR and electrochemical method. The resultant Cu-MOF was explored as a robust electrochemical biosensing platform by choosing tyrosinase (Tyr) as a model enzyme for ultrasensitive and rapid detection of BPA. The Cu-MOF provided a 3D structure with a large specific surface area, which was beneficial for enzyme and BPA absorption, and thus improved the sensitivity of the biosensor. Furthermore, Cu-MOF as a novel sorbent could increase the available BPA concentration to react with tyrosinase through π-π stacking interactions between BPA and Cu-MOF. The Tyr biosensor exhibited a high sensitivity of 0.2242A M(-1) for BPA, a wide linear range from 5.0×10(-8) to 3.0×10-6moll(-1), and a low detection limit of 13nmoll(-1). The response time for detection of BPA is less than 11s. The proposed method was successfully applied to rapid and selective detection of BPA in plastic products with satisfactory results. The recoveries are in the range of 94.0-101.6% for practical applications. With those remarkable advantages, MOFs-based 3D structures show great prospect as robust biosensing platform for ultrasensitive and rapid detection of BPA.

  4. Rapid high resolution genotyping of Francisella tularensis by whole genome sequence comparison of annotated genes ("MLST+".

    Directory of Open Access Journals (Sweden)

    Markus H Antwerpen

    Full Text Available The zoonotic disease tularemia is caused by the bacterium Francisella tularensis. This pathogen is considered as a category A select agent with potential to be misused in bioterrorism. Molecular typing based on DNA-sequence like canSNP-typing or MLVA has become the accepted standard for this organism. Due to the organism's highly clonal nature, the current typing methods have reached their limit of discrimination for classifying closely related subpopulations within the subspecies F. tularensis ssp. holarctica. We introduce a new gene-by-gene approach, MLST+, based on whole genome data of 15 sequenced F. tularensis ssp. holarctica strains and apply this approach to investigate an epidemic of lethal tularemia among non-human primates in two animal facilities in Germany. Due to the high resolution of MLST+ we are able to demonstrate that three independent clones of this highly infectious pathogen were responsible for these spatially and temporally restricted outbreaks.

  5. High-Ti, bright-CL rims in volcanic quartz: a result of very rapid growth

    Science.gov (United States)

    Pamukcu, Ayla S.; Ghiorso, Mark S.; Gualda, Guilherme A. R.

    2016-12-01

    Volcanic quartz commonly contains Ti-enriched zones and CO2-enriched melt inclusions, and crystallization temperatures and pressures derived from Ti-in-quartz geothermobarometry and H2O-CO2 glass geobarometry applied to these compositions are typically high. Consequently, these features are generally interpreted to represent high temperatures and/or pressures. Yet, growth rate estimates from some high-Ti/bright-CL quartz rims suggest they grew at rates orders of magnitude faster than did cores and interiors of the crystals. This observation is notable in light of studies that suggest that fast crystal growth rates can produce a boundary layer in the melt surrounding a growing crystal that is enriched in components that diffuse comparatively slowly in the melt. In these circumstances, the composition of zones or melt inclusions formed from such a boundary layer melt will not accurately represent that of the far-field melt, and temperatures and pressures estimated from these compositions will be anomalous. We use a numerical model based on the coupled growth-diffusion equation of Lasaga (1982) to assess the effect of growth rate on the production of high-Ti/bright-CL zones and high-CO2 melt inclusions in quartz in rhyolitic melts. Simulations span a wide range of growth rates (10-7 to 10-13 m/s) and timescales (1 minute-1 year), and results suggest that quartz growth at 10-10 m/s or faster can produce a boundary layer enriched in these components. This suggests that appropriate application of Ti-in-quartz and H2O-CO2 glass geothermobarometry is contingent upon the verification that the compositions used are not those of boundary layer melts. Applying our model to the Bishop Tuff, which contains quartz displaying high-Ti/bright-CL rims and high-CO2 rim-hosted melt inclusions, we find that growth rates of 10-7 to 10-9 m/s can produce the observed enrichments in these components over the timescales estimated for the growth of the rims (days-weeks); these growth rates

  6. Identifying Unidentified Fermi-LAT Objects (UFOs) at High-Latitude

    Science.gov (United States)

    Cheung, Chi Teddy

    2009-09-01

    We propose a Chandra study of 8 high Galactic latitude gamma-ray sources in the Fermi-LAT bright source list. These sources are currently unidentified, i.e., they are not clearly associated with established classes of gamma-ray emitters like blazars and pulsars. The proposed observations will determine the basic properties (fluxes, positions, hardness ratio/spectra) of all X-ray sources down to a 0.3-10 keV flux limit of 1.5e-14 erg/cm2/s within the Fermi-LAT localization circles. This will enable further follow-up at other wavelengths, with the ultimate goal to reveal the nature of these enigmatic gamma-ray sources.

  7. High-throughput screening identifies small molecules that enhance the pharmacological effects of oligonucleotides

    Science.gov (United States)

    Yang, B.; Ming, X.; Cao, C.; Laing, B.; Yuan, A.; Porter, M. A.; Hull-Ryde, E. A.; Maddry, J.; Suto, M.; Janzen, W. P.; Juliano, R. L.

    2015-01-01

    The therapeutic use of antisense and siRNA oligonucleotides has been constrained by the limited ability of these membrane-impermeable molecules to reach their intracellular sites of action. We sought to address this problem using small organic molecules to enhance the effects of oligonucleotides by modulating their intracellular trafficking and release from endosomes. A high-throughput screen of multiple small molecule libraries yielded several hits that markedly potentiated the actions of splice switching oligonucleotides in cell culture. These compounds also enhanced the effects of antisense and siRNA oligonucleotides. The hit compounds preferentially caused release of fluorescent oligonucleotides from late endosomes rather than other intracellular compartments. Studies in a transgenic mouse model indicated that these compounds could enhance the in vivo effects of a splice-switching oligonucleotide without causing significant toxicity. These observations suggest that selected small molecule enhancers may eventually be of value in oligonucleotide-based therapeutics. PMID:25662226

  8. A High-Resolution Aeromagnetic Survey to Identify Buried Faults at Dixie Valley, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Richard Paul; Grauch, V. J. S.; Blackwell, David D.

    2002-09-01

    Preliminary results from a high-resolution aeromagnetic survey (200m line spacing) acquired in Dixie Valley early in 2002 provide confirmation of intra-basin faulting based on subtle surface indications. In addition the data allow identification of the locations and trends of many faults that have not been recognized at the surface, and provide a picture of intrabasin faulting patterns not possible using other techniques. The data reveal a suite of northeasterly-trending curving and branching faults that surround a relatively coherent block in the area of Humboldt Salt Marsh, the deepest part of the basin. The producing reservoir occurs at the north end of this coherent block, where rampart faults from the northwest side of the valley merge with anthithetic faults from the central and southeast parts of the valley.

  9. Exploring High-Dimensional Data Space: Identifying Optimal Process Conditions in Photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Suh, C.; Biagioni, D.; Glynn, S.; Scharf, J.; Contreras, M. A.; Noufi, R.; Jones, W. B.

    2011-01-01

    We demonstrate how advanced exploratory data analysis coupled to data-mining techniques can be used to scrutinize the high-dimensional data space of photovoltaics in the context of thin films of Al-doped ZnO (AZO), which are essential materials as a transparent conducting oxide (TCO) layer in CuIn{sub x}Ga{sub 1-x}Se{sub 2} (CIGS) solar cells. AZO data space, wherein each sample is synthesized from a different process history and assessed with various characterizations, is transformed, reorganized, and visualized in order to extract optimal process conditions. The data-analysis methods used include parallel coordinates, diffusion maps, and hierarchical agglomerative clustering algorithms combined with diffusion map embedding.

  10. Exploring High-Dimensional Data Space: Identifying Optimal Process Conditions in Photovoltaics: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Suh, C.; Glynn, S.; Scharf, J.; Contreras, M. A.; Noufi, R.; Jones, W. B.; Biagioni, D.

    2011-07-01

    We demonstrate how advanced exploratory data analysis coupled to data-mining techniques can be used to scrutinize the high-dimensional data space of photovoltaics in the context of thin films of Al-doped ZnO (AZO), which are essential materials as a transparent conducting oxide (TCO) layer in CuInxGa1-xSe2 (CIGS) solar cells. AZO data space, wherein each sample is synthesized from a different process history and assessed with various characterizations, is transformed, reorganized, and visualized in order to extract optimal process conditions. The data-analysis methods used include parallel coordinates, diffusion maps, and hierarchical agglomerative clustering algorithms combined with diffusion map embedding.

  11. Identifying Sources of Volatile Organic Compounds and Aldehydes in a High Performance Building

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz, Anna C.; Russell, Marion; Lee, Wen-Yee; Apte, Michael; Maddalena, Randy

    2010-09-20

    The developers of the Paharpur Business Center (PBC) and Software Technology Incubator Park in New Delhi, India offer an environmentally sustainable building with a strong emphasis on energy conservation, waste minimization and superior indoor air quality (IAQ). To achieve the IAQ goal, the building utilizes a series of air cleaning technologies for treating the air entering the building. These technologies include an initial water wash followed by ultraviolet light treatment and biolfiltration using a greenhouse located on the roof and numerous plants distributed throughout the building. Even with the extensive treatment of makeup air and room air in the PBC, a recent study found that the concentrations of common volatile organic compounds and aldehydes appear to rise incrementally as the air passes through the building from the supply to the exhaust. This finding highlights the need to consider the minimization of chemical sources in buildings in combination with the use of advanced air cleaning technologies when seeking to achieve superior IAQ. The goal of this project was to identify potential source materials for indoor chemicals in the PBC. Samples of building materials, including wood paneling (polished and unpolished), drywall, and plastic from a hydroponic drum that was part of the air cleaning system, were collected from the building for testing. All materials were collected from the PBC building and shipped to the Lawrence Berkeley National Laboratory (LBNL) for testing. The materials were pre-conditioned for two different time periods before measuring material and chemical specific emission factors for a range of VOCs and Aldehydes. Of the six materials tested, we found that the highest emitter of formaldehyde was new plywood paneling. Although polish and paint contribute to some VOC emissions, the main influence of the polish was in altering the capacity of the surface to accumulate formaldehyde. Neither the new nor aged polish contributed

  12. The Role of Rapid Endoscopy for High-Risk Patients with Acute Nonvariceal Upper Gastrointestinal Bleeding

    Directory of Open Access Journals (Sweden)

    Laura E Targownik

    2007-01-01

    Full Text Available BACKGROUND: Performance of endoscopy within 24 h is recommended for patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB. It is unknown whether performing endoscopy early within this 24 h window is beneficial for clinically high-risk patients.

  13. Rapid hydrogen and oxygen atom transfer by a high-valent nickel-oxygen species

    NARCIS (Netherlands)

    Corona, Teresa; Draksharapu, Apparao; Padamati, Sandeep K; Gamba, Ilaria; Martin-Diaconescu, Vlad; Acuña-Parés, Ferran; Browne, Wesley R; Company, Anna

    2016-01-01

    Terminal high-valent metal-oxygen species are key reaction intermediates in the catalytic cycle of both enzymes (e.g., oxygenases) and synthetic oxidation catalysts. While tremendous efforts have been directed towards the characterization of the biologically relevant terminal manganese-oxygen and

  14. Rat adipose tissue rapidly accumulates and slowly releases an orally-administered high vitamin D dose

    NARCIS (Netherlands)

    Brouwer, DAJ; van Beek, J; Ferwerda, H; Brugman, AM; van der Klis, FRM; Muskiet, FAJ

    1998-01-01

    We investigated the effect of oral high-dose cholecalciferol on plasma and adipose tissue cholecalciferol and its subsequent release, and on plasma 25-hydroxyvitamin D (25(OH)D). Female Wistar rats (n 126) received 37.5 mu g cholecalciferol/d for 14 d and were subsequently studied for a further 88 d

  15. Residual gas entering high density hydrogen plasma: rarefaction due to rapid heating

    NARCIS (Netherlands)

    N. den Harder,; D.C. Schram,; W. J. Goedheer,; de Blank, H. J.; M. C. M. van de Sanden,; van Rooij, G. J.

    2015-01-01

    The interaction of background molecular hydrogen with magnetized (0.4 T) high density (1–5 × 10 20  m −3 ) low temperature (∼3 eV) hydrogen plasma was inferred from the Fulcher band emission in the linear plasma generator Pilot-PSI. In the plasma center,

  16. Algorithm Development and Application of High Order Numerical Methods for Shocked and Rapid Changing Solutions

    Science.gov (United States)

    2007-12-06

    high order well-balanced schemes to a class of hyperbolic systems with source terms, Boletin de la Sociedad Espanola de Matematica Aplicada, v34 (2006...schemes to a class of hyperbolic systems with source terms, Boletin de la Sociedad Espanola de Matematica Aplicada, v34 (2006), pp.69-80. 39. Y. Xu and C.-W

  17. A simple and rapid method for high-resolution visualization of single-ion tracks

    Directory of Open Access Journals (Sweden)

    Masaaki Omichi

    2014-11-01

    Full Text Available Prompt determination of spatial points of single-ion tracks plays a key role in high-energy particle induced-cancer therapy and gene/plant mutations. In this study, a simple method for the high-resolution visualization of single-ion tracks without etching was developed through the use of polyacrylic acid (PAA-N, N’-methylene bisacrylamide (MBAAm blend films. One of the steps of the proposed method includes exposure of the irradiated films to water vapor for several minutes. Water vapor was found to promote the cross-linking reaction of PAA and MBAAm to form a bulky cross-linked structure; the ion-track scars were detectable at a nanometer scale by atomic force microscopy. This study demonstrated that each scar is easily distinguishable, and the amount of generated radicals of the ion tracks can be estimated by measuring the height of the scars, even in highly dense ion tracks. This method is suitable for the visualization of the penumbra region in a single-ion track with a high spatial resolution of 50 nm, which is sufficiently small to confirm that a single ion hits a cell nucleus with a size ranging between 5 and 20 μm.

  18. A simple and rapid method for high-resolution visualization of single-ion tracks

    Energy Technology Data Exchange (ETDEWEB)

    Omichi, Masaaki [Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Osaka 565-0871 (Japan); Center for Collaborative Research, Anan National College of Technology, Anan, Tokushima 774-0017 (Japan); Choi, Wookjin; Sakamaki, Daisuke; Seki, Shu, E-mail: seki@chem.eng.osaka-u.ac.jp [Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Osaka 565-0871 (Japan); Tsukuda, Satoshi [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Miyagi 980-8577 (Japan); Sugimoto, Masaki [Japan Atomic Energy Agency, Takasaki Advanced Radiation Research Institute, Gunma, Gunma 370-1292 (Japan)

    2014-11-15

    Prompt determination of spatial points of single-ion tracks plays a key role in high-energy particle induced-cancer therapy and gene/plant mutations. In this study, a simple method for the high-resolution visualization of single-ion tracks without etching was developed through the use of polyacrylic acid (PAA)-N, N’-methylene bisacrylamide (MBAAm) blend films. One of the steps of the proposed method includes exposure of the irradiated films to water vapor for several minutes. Water vapor was found to promote the cross-linking reaction of PAA and MBAAm to form a bulky cross-linked structure; the ion-track scars were detectable at a nanometer scale by atomic force microscopy. This study demonstrated that each scar is easily distinguishable, and the amount of generated radicals of the ion tracks can be estimated by measuring the height of the scars, even in highly dense ion tracks. This method is suitable for the visualization of the penumbra region in a single-ion track with a high spatial resolution of 50 nm, which is sufficiently small to confirm that a single ion hits a cell nucleus with a size ranging between 5 and 20 μm.

  19. Rapid hydrogen and oxygen atom transfer by a high-valent nickel-oxygen species

    NARCIS (Netherlands)

    Corona, Teresa; Draksharapu, Apparao; Padamati, Sandeep K; Gamba, Ilaria; Martin-Diaconescu, Vlad; Acuña-Parés, Ferran; Browne, Wesley R; Company, Anna

    2016-01-01

    Terminal high-valent metal-oxygen species are key reaction intermediates in the catalytic cycle of both enzymes (e.g., oxygenases) and synthetic oxidation catalysts. While tremendous efforts have been directed towards the characterization of the biologically relevant terminal manganese-oxygen and ir

  20. Rapid detection and differentiation of Clonorchis sinensis and Opisthorchis viverrini using real-time PCR and high resolution melting analysis.

    Science.gov (United States)

    Cai, Xian-Quan; Yu, Hai-Qiong; Li, Rong; Yue, Qiao-Yun; Liu, Guo-Hua; Bai, Jian-Shan; Deng, Yan; Qiu, De-Yi; Zhu, Xing-Quan

    2014-01-01

    Clonorchis sinensis and Opisthorchis viverrini are both important fish-borne pathogens, causing serious public health problem in Asia. The present study developed an assay integrating real-time PCR and high resolution melting (HRM) analysis for the specific detection and rapid identification of C. sinensis and O. viverrini. Primers targeting COX1 gene were highly specific for these liver flukes, as evidenced by the negative amplification of closely related trematodes. Assays using genomic DNA extracted from the two flukes yielded specific amplification and their identity was confirmed by sequencing, having the accuracy of 100% in reference to conventional methods. The assay was proved to be highly sensitive with a detection limit below 1 pg of purified genomic DNA, 5 EPG, or 1 metacercaria of C. sinensis. Moreover, C. sinensis and O. viverrini were able to be differentiated by their HRM profiles. The method can reduce labor of microscopic examination and the contamination of agarose electrophoresis. Moreover, it can differentiate these two flukes which are difficult to be distinguished using other methods. The established method provides an alternative tool for rapid, simple, and duplex detection of C. sinensis and O. viverrini.

  1. Rapid Detection and Differentiation of Clonorchis sinensis and Opisthorchis viverrini Using Real-Time PCR and High Resolution Melting Analysis

    Directory of Open Access Journals (Sweden)

    Xian-Quan Cai

    2014-01-01

    Full Text Available Clonorchis sinensis and Opisthorchis viverrini are both important fish-borne pathogens, causing serious public health problem in Asia. The present study developed an assay integrating real-time PCR and high resolution melting (HRM analysis for the specific detection and rapid identification of C. sinensis and O. viverrini. Primers targeting COX1 gene were highly specific for these liver flukes, as evidenced by the negative amplification of closely related trematodes. Assays using genomic DNA extracted from the two flukes yielded specific amplification and their identity was confirmed by sequencing, having the accuracy of 100% in reference to conventional methods. The assay was proved to be highly sensitive with a detection limit below 1 pg of purified genomic DNA, 5 EPG, or 1 metacercaria of C. sinensis. Moreover, C. sinensis and O. viverrini were able to be differentiated by their HRM profiles. The method can reduce labor of microscopic examination and the contamination of agarose electrophoresis. Moreover, it can differentiate these two flukes which are difficult to be distinguished using other methods. The established method provides an alternative tool for rapid, simple, and duplex detection of C. sinensis and O. viverrini.

  2. Optimized holographic femtosecond laser patterning method towards rapid integration of high-quality functional devices in microchannels

    Science.gov (United States)

    Zhang, Chenchu; Hu, Yanlei; Du, Wenqiang; Wu, Peichao; Rao, Shenglong; Cai, Ze; Lao, Zhaoxin; Xu, Bing; Ni, Jincheng; Li, Jiawen; Zhao, Gang; Wu, Dong; Chu, Jiaru; Sugioka, Koji

    2016-09-01

    Rapid integration of high-quality functional devices in microchannels is in highly demand for miniature lab-on-a-chip applications. This paper demonstrates the embellishment of existing microfluidic devices with integrated micropatterns via femtosecond laser MRAF-based holographic patterning (MHP) microfabrication, which proves two-photon polymerization (TPP) based on spatial light modulator (SLM) to be a rapid and powerful technology for chip functionalization. Optimized mixed region amplitude freedom (MRAF) algorithm has been used to generate high-quality shaped focus field. Base on the optimized parameters, a single-exposure approach is developed to fabricate 200 × 200 μm microstructure arrays in less than 240 ms. Moreover, microtraps, QR code and letters are integrated into a microdevice by the advanced method for particles capture and device identification. These results indicate that such a holographic laser embellishment of microfluidic devices is simple, flexible and easy to access, which has great potential in lab-on-a-chip applications of biological culture, chemical analyses and optofluidic devices.

  3. Inner ear tissue preservation by rapid freezing: improving fixation by high-pressure freezing and hybrid methods.

    Science.gov (United States)

    Bullen, A; Taylor, R R; Kachar, B; Moores, C; Fleck, R A; Forge, A

    2014-09-01

    In the preservation of tissues in as 'close to life' state as possible, rapid freeze fixation has many benefits over conventional chemical fixation. One technique by which rapid freeze-fixation can be achieved, high pressure freezing (HPF), has been shown to enable ice crystal artefact-free freezing and tissue preservation to greater depths (more than 40 μm) than other quick-freezing methods. Despite increasingly becoming routine in electron microscopy, the use of HPF for the fixation of inner ear tissue has been limited. Assessment of the quality of preservation showed routine HPF techniques were suitable for preparation of inner ear tissues in a variety of species. Good preservation throughout the depth of sensory epithelia was achievable. Comparison to chemically fixed tissue indicated that fresh frozen preparations exhibited overall superior structural preservation of cells. However, HPF fixation caused characteristic artefacts in stereocilia that suggested poor quality freezing of the actin bundles. The hybrid technique of pre-fixation and high pressure freezing was shown to produce cellular preservation throughout the tissue, similar to that seen in HPF alone. Pre-fixation HPF produced consistent high quality preservation of stereociliary actin bundles. Optimising the preparation of samples with minimal artefact formation allows analysis of the links between ultrastructure and function in inner ear tissues. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  4. M2KMIX: Identifying the Type of High Rate Flooding Attacks using a Mixture of Expert Systems

    Directory of Open Access Journals (Sweden)

    Arun Raj Kumar P.

    2012-02-01

    Full Text Available High rate flooding attacks such as SYN flood, UDP flood, and HTTP flood have been posing a perilous threat to Web servers, DNS servers, Mail servers, VoIP servers, etc. These high rate flooding attacks deplete the limited capacity of the server resources. Hence, there is a need for the protection of these critical resources from high rate flooding attacks. Existing detection techniques used in Firewalls, IPS, IDS, etc., fail to identify the illegitimate traffic due to its self-similarity nature of legitimate traffic and suffer from low detection accuracy and high false alarms. Also, very few in the literature have focused on identifying the type of attack. This paper focuses on the identification of type of high rate flooding attack with High detection accuracy and fewer false alarms. The attack type identification is achieved by training the classifiers with different feature subsets. Therefore, each trained classifier is an expert in different feature space. High detection accuracy is achieved by creating a mixture of expert classifiers and the ensemble output decisions are identified by our proposed Preferential Agreement (PA rule. Our proposed classification algorithm, M2KMix (mixture of two Multi Layer Perceptron and one K-Nearest Neighbor models differs from the existing solutions in feature selection, error cost reduction, and attack type identification. M2KMix was trained and tested with our own SSE Lab 2011 dataset and CAIDA dataset. Detection accuracy and False Alarms are the two metrics used to analyze the performance of the proposed M2KMix algorithm with the existing output combination methods such as mean, maximum, minimum, and product. From the simulation results, it is evident that M2KMix algorithm achieves high detection accuracy (97.8% with fewer false alarms than the existing output combination methods. M2KMix identifies three types of flooding attacks, viz., the SYN Flood, UDP flood, and HTTP Flood, effectively with detection

  5. Using very high resolution satellite images to identify coastal zone dynamics at North Western Black Sea

    Science.gov (United States)

    Florin Zoran, Liviu; Ionescu Golovanov, Carmen; Zoran, Maria

    2010-05-01

    The availability of updated information about the extension and characteristics of land cover is a crucial issue in the perspective of a correct landscape planning and management of marine coastal zones. Satellite remote sensing data can provide accurate information about land coverage at different scales and the recent availability of very high resolution images definitely improved the precision of coastal zone spatio-temporal changes. The Romanian North Western coastal and shelf zones of the Black Sea and Danube delta are a mosaic of complex, interacting ecosystems, rich natural resources and socio-economic activity. Dramatic changes in the Black Sea's ecosystem and resources are due to natural and anthropogenic causes (increase in the nutrient and pollutant load of rivers input, industrial and municipal wastewater pollution along the coast, and dumping on the open sea). A scientific management system for protection, conservation and restoration must be based on reliable information on bio-geophysical and geomorphologic processes, coastal erosion, sedimentation dynamics, mapping of macrophyte fields, water quality, and climatic change effects. Use of satellite images is of great help for coastal zone monitoring and environmental impact assessment. Synergetic use of in situ measurements with multisensors satellite data could provide a complex assessment of spatio-temporal changes. In this study was developed a method for extracting coastal zone features information as well as landcover dynamics from IKONOS, very high resolution images for North-Western Black Sea marine coastal zone. The main objective was obtaining reliable data about the spatio-temporal coastal zone changes in two study areas located in Constanta urban area and Danube Delta area. We used an object-oriented approach based on preliminary segmentation and classification of the resulting object. First of all, segmentation parameters were tested and selected comparing segmented polygons with

  6. Rapid determination of Papaver somniferum alkaloids in process streams using monolithic column high-performance liquid chromatography with chemiluminescence detection

    Energy Technology Data Exchange (ETDEWEB)

    Costin, Jason W. [School of Life and Environmental Sciences, Deakin University, Geelong, Victoria 3217 (Australia); Lewis, Simon W. [Department of Applied Chemistry, Curtin University of Technology, Perth, WA 6845 (Australia); Purcell, Stuart D. [GlaxoSmithKline, Port Fairy, Victoria 3284 (Australia); Waddell, Lucy R. [GlaxoSmithKline, Port Fairy, Victoria 3284 (Australia); Francis, Paul S. [School of Life and Environmental Sciences, Deakin University, Geelong, Victoria 3217 (Australia); Barnett, Neil W. [School of Life and Environmental Sciences, Deakin University, Geelong, Victoria 3217 (Australia)]. E-mail: barnie@deakin.edu.au

    2007-07-30

    We have combined high-performance liquid chromatography (HPLC) separations using a monolithic column with acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence detection in a rapid and highly sensitive method to monitor the process of extracting opiate alkaloids from Papaver somniferum. Due to the high flow rates allowed with the monolithic column and the inherent selectivity of the chemiluminescence reactions, the four predominant alkaloids - morphine, codeine, oripavine and thebaine - were determined in less than 2 min. The results obtained with numerous process samples compared favourable with those of the standard HPLC methodology. Limits of detection were 1 x 10{sup -10} M, 5 x 10{sup -10} M, 5 x 10{sup -10} M and 1 x 10{sup -9} M, for morphine, codeine, oripavine and thebaine, respectively.

  7. High-latitude E and F region coupling signature: A case study results from rapid-run ionosonde

    Science.gov (United States)

    Shalimov, S.; Kozlovsky, A.

    2015-04-01

    Rapid-run ionosonde installed in the high-latitude Sodankylä Geophysical Observatory enables us to observe for the first time extraordinary details of E-F region coupling process in high-latitude ionosphere during geomagnetically quiet period. We present an example on 15 August 2009 when a dense, patchy sporadic E layer was detected. Associated with this unstable sporadic E layer, exhibiting in addition an unusual enhancement with a vertical extent of about 10 km, the highly structured F layer plasma was observed with apparent plasma depletions. We examine this event taking into account the presence of mesoscale traveling ionospheric disturbances which can initiate coupling between these two regions and compare the data with current theories.

  8. Using geographical information systems mapping to identify areas presenting high risk for traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Colantonio Angela

    2011-11-01

    Full Text Available Abstract Background The aim of this study is to show how geographical information systems (GIS can be used to track and compare hospitalization rates for traumatic brain injury (TBI over time and across a large geographical area using population based data. Results & Discussion Data on TBI hospitalizations, and geographic and demographic variables, came from the Ontario Trauma Registry Minimum Data Set for the fiscal years 1993-1994 and 2001-2002. Various visualization techniques, exploratory data analysis and spatial analysis were employed to map and analyze these data. Both the raw and standardized rates by age/gender of the geographical unit were studied. Data analyses revealed persistent high rates of hospitalization for TBI resulting from any injury mechanism between two time periods in specific geographic locations. Conclusions This study shows how geographic information systems can be successfully used to investigate hospitalizaton rates for traumatic brain injury using a range of tools and techniques; findings can be used for local planning of both injury prevention and post discharge services, including rehabilitation.

  9. High content analysis at single cell level identifies different cellular responses dependent on nanomaterial concentrations.

    Science.gov (United States)

    Manshian, Bella B; Munck, Sebastian; Agostinis, Patrizia; Himmelreich, Uwe; Soenen, Stefaan J

    2015-09-08

    A mechanistic understanding of nanomaterial (NM) interaction with biological environments is pivotal for the safe transition from basic science to applied nanomedicine. NM exposure results in varying levels of internalized NM in different neighboring cells, due to variances in cell size, cell cycle phase and NM agglomeration. Using high-content analysis, we investigated the cytotoxic effects of fluorescent quantum dots on cultured cells, where all effects were correlated with the concentration of NMs at the single cell level. Upon binning the single cell data into different categories related to NM concentration, this study demonstrates, for the first time, that quantum dots activate both cytoprotective and cytotoxic mechanisms, resulting in a zero net result on the overall cell population, yet with significant effects in cells with higher cellular NM levels. Our results suggest that future NM cytotoxicity studies should correlate NM toxicity with cellular NM numbers on the single cell level, as conflicting mechanisms in particular cell subpopulations are commonly overlooked using classical toxicological methods.

  10. Identifying Contributing Harmonics in the Gravitational Wave Spectrum of Highly Eccentric EMRIs

    Science.gov (United States)

    Kaiser, Andrew; Stone, Jordan; Ahrens, Sloan; Kennefick, Daniel

    2016-03-01

    In the study of gravitational waves emitted from extreme mass ratio inspirals highly eccentric orbits are problematic because of the large number of harmonics, and thus the lengthy computation times that were thought to be inherent to it. The issue however, is made simpler because the spectrum is not that broad and is fairly localized. The true complexity lies in finding the peaks of the largest contributors to accurately describe the complete spectrum, since for any given multipole of the spectrum the position of the peak in the emission is difficult to predict. This project uses two methods of finding the peak harmonic of a given spectrum. The first method uses a skipping algorithm to systematically jump over harmonics with insignificant contributions to the total waveform. Because this method is still not completely efficient, a second method uses a Newtonian order approximation given by Peters and Matthews to give an estimate of the frequency of the actual waveform peak, and then fills in around this harmonics to give the spectrum. The two methods are complementary since the skipping algorithm can be used when the Newtonian estimation fails to find the peak immediately.

  11. Applying high-resolution melting (HRM) technology to identify five commonly used Artemisia species

    Science.gov (United States)

    Song, Ming; Li, Jingjian; Xiong, Chao; Liu, Hexia; Liang, Junsong

    2016-01-01

    Many members of the genus Artemisia are important for medicinal purposes with multiple pharmacological properties. Often, these herbal plants sold on the markets are in processed forms so it is difficult to authenticate. Routine testing and identification of these herbal materials should be performed to ensure that the raw materials used in pharmaceutical products are suitable for their intended use. In this study, five commonly used Artemisia species included Artemisia argyi, Artemisia annua, Artemisia lavandulaefolia, Artemisia indica, and Artemisia atrovirens were analyzed using high resolution melting (HRM) analysis based on the internal transcribed spacer 2 (ITS2) sequences. The melting profiles of the ITS2 amplicons of the five closely related herbal species are clearly separated so that they can be differentiated by HRM method. The method was further applied to authenticate commercial products in powdered. HRM curves of all the commercial samples tested are similar to the botanical species as labeled. These congeneric medicinal products were also clearly separated using the neighbor-joining (NJ) tree. Therefore, HRM method could provide an efficient and reliable authentication system to distinguish these commonly used Artemisia herbal products on the markets and offer a technical reference for medicines quality control in the drug supply chain. PMID:27698485

  12. High content analysis at single cell level identifies different cellular responses dependent on nanomaterial concentrations

    Science.gov (United States)

    Manshian, Bella B.; Munck, Sebastian; Agostinis, Patrizia; Himmelreich, Uwe; Soenen, Stefaan J.

    2015-09-01

    A mechanistic understanding of nanomaterial (NM) interaction with biological environments is pivotal for the safe transition from basic science to applied nanomedicine. NM exposure results in varying levels of internalized NM in different neighboring cells, due to variances in cell size, cell cycle phase and NM agglomeration. Using high-content analysis, we investigated the cytotoxic effects of fluorescent quantum dots on cultured cells, where all effects were correlated with the concentration of NMs at the single cell level. Upon binning the single cell data into different categories related to NM concentration, this study demonstrates, for the first time, that quantum dots activate both cytoprotective and cytotoxic mechanisms, resulting in a zero net result on the overall cell population, yet with significant effects in cells with higher cellular NM levels. Our results suggest that future NM cytotoxicity studies should correlate NM toxicity with cellular NM numbers on the single cell level, as conflicting mechanisms in particular cell subpopulations are commonly overlooked using classical toxicological methods.

  13. Using the CPTAC Assay Portal to identify and implement highly characterized targeted proteomics assays

    Science.gov (United States)

    Whiteaker, Jeffrey R; Halusa, Goran N; Hoofnagle, Andrew N; Sharma, Vagisha; MacLean, Brendan; Yan, Ping; Wrobel, John A; Kennedy, Jacob; Mani, DR; Zimmerman, Lisa J; Meyer, Matthew R.; Mesri, Mehdi; Abbatiello, Susan E; Boja, Emily; Carr, Steven A.; Chan, Daniel W.; Chen, Xian; Chen, Jing; Davies, Sherri R; Ellis, Matthew J. C.; Fenyö, David; Hiltke, Tara; Ketchum, Karen A.; Kinsinger, Chris; Kuhn, Eric; Liebler, Daniel C.; Lin, De; Liu, Tao; Loss, Michael; MacCoss, Michael J; Qian, Wei-Jun; Rivers, Robert; Rodland, Karin D.; Ruggles, Kelly V; Scott, Mitchell G; Smith, Richard D.; Thomas, Stefani; Townsend, R. Reid; Whiteley, Gordon; Wu, Chaochao; Zhang, Hui; Zhang, Zhen; Rodriguez, Henry; Paulovich, Amanda G

    2016-01-01

    Summary The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI) has launched an Assay Portal (http://assays.cancer.gov) to serve as an open-source repository of well-characterized targeted proteomic assays. The portal is designed to curate and disseminate highly characterized, targeted mass spectrometry (MS)-based assays by providing detailed assay performance characterization data, standard operating procedures, and access to reagents. Assay content is accessed via the portal through queries to find assays targeting proteins associated with specific cellular pathways, protein complexes, or specific chromosomal regions. The position of the peptide analytes for which there are available assays are mapped relative to other features of interest in the protein, such as sequence domains, isoforms, single nucleotide polymorphisms, and post-translational modifications. The overarching goals are to enable robust quantification of all human proteins and to standardize the quantification of targeted MS-based assays to ultimately enable harmonization of results over time and across laboratories. PMID:26867747

  14. Identifying highly connected counties compensates for resource limitations when evaluating national spread of an invasive pathogen.

    Science.gov (United States)

    Sutrave, Sweta; Scoglio, Caterina; Isard, Scott A; Hutchinson, J M Shawn; Garrett, Karen A

    2012-01-01

    Surveying invasive species can be highly resource intensive, yet near-real-time evaluations of invasion progress are important resources for management planning. In the case of the soybean rust invasion of the United States, a linked monitoring, prediction, and communication network saved U.S. soybean growers approximately $200 M/yr. Modeling of future movement of the pathogen (Phakopsora pachyrhizi) was based on data about current disease locations from an extensive network of sentinel plots. We developed a dynamic network model for U.S. soybean rust epidemics, with counties as nodes and link weights a function of host hectarage and wind speed and direction. We used the network model to compare four strategies for selecting an optimal subset of sentinel plots, listed here in order of increasing performance: random selection, zonal selection (based on more heavily weighting regions nearer the south, where the pathogen overwinters), frequency-based selection (based on how frequently the county had been infected in the past), and frequency-based selection weighted by the node strength of the sentinel plot in the network model. When dynamic network properties such as node strength are characterized for invasive species, this information can be used to reduce the resources necessary to survey and predict invasion progress.

  15. Identifying highly connected counties compensates for resource limitations when evaluating national spread of an invasive pathogen.

    Directory of Open Access Journals (Sweden)

    Sweta Sutrave

    Full Text Available Surveying invasive species can be highly resource intensive, yet near-real-time evaluations of invasion progress are important resources for management planning. In the case of the soybean rust invasion of the United States, a linked monitoring, prediction, and communication network saved U.S. soybean growers approximately $200 M/yr. Modeling of future movement of the pathogen (Phakopsora pachyrhizi was based on data about current disease locations from an extensive network of sentinel plots. We developed a dynamic network model for U.S. soybean rust epidemics, with counties as nodes and link weights a function of host hectarage and wind speed and direction. We used the network model to compare four strategies for selecting an optimal subset of sentinel plots, listed here in order of increasing performance: random selection, zonal selection (based on more heavily weighting regions nearer the south, where the pathogen overwinters, frequency-based selection (based on how frequently the county had been infected in the past, and frequency-based selection weighted by the node strength of the sentinel plot in the network model. When dynamic network properties such as node strength are characterized for invasive species, this information can be used to reduce the resources necessary to survey and predict invasion progress.

  16. Cry me a river: identifying the behavioral consequences of extremely high-stakes interpersonal deception.

    Science.gov (United States)

    Ten Brinke, Leanne; Porter, Stephen

    2012-12-01

    Deception evolved as a fundamental aspect of human social interaction. Numerous studies have examined behavioral cues to deception, but most have involved inconsequential lies and unmotivated liars in a laboratory context. We conducted the most comprehensive study to date of the behavioral consequences of extremely high-stakes, real-life deception--relative to comparable real-life sincere displays--via 3 communication channels: speech, body language, and emotional facial expressions. Televised footage of a large international sample of individuals (N = 78) emotionally pleading to the public for the return of a missing relative was meticulously coded frame-by-frame (30 frames/s for a total of 74,731 frames). About half of the pleaders eventually were convicted of killing the missing person on the basis of overwhelming evidence. Failed attempts to simulate sadness and leakage of happiness revealed deceptive pleaders' covert emotions. Liars used fewer words but more tentative words than truth-tellers, likely relating to increased cognitive load and psychological distancing. Further, each of these cues explained unique variance in predicting pleader sincerity.

  17. Using the CPTAC Assay Portal to identify and implement highly characterized targeted proteomics assays

    Energy Technology Data Exchange (ETDEWEB)

    Whiteaker, Jeffrey R.; Halusa, Goran; Hoofnagle, Andrew N.; Sharma, Vagisha; MacLean, Brendan; Yan, Ping; Wrobel, John; Kennedy, Jacob; Mani, DR; Zimmerman, Lisa J.; Meyer, Matthew R.; Mesri, Mehdi; Boja, Emily; Carr, Steven A.; Chan, Daniel W.; Chen, Xian; Chen, Jing; Davies, Sherri; Ellis, Matthew; Fenyo, David; Hiltket, Tara; Ketchum, Karen; Kinsinger, Christopher; Kuhn, Eric; Liebler, Daniel; Liu, Tao; Loss, Michael; MacCoss, Michael; Qian, Weijun; Rivers, Robert; Rodland, Karin D.; Ruggles, Kelly; Scott, Mitchell; Smith, Richard D.; Thomas, Stefani N.; Townsend, Reid; Whiteley, Gordon; Wu, Chaochao; Zhang, Hui; Zhang, Zhen; Rodriguez, Henry; Paulovich, Amanda G.

    2016-02-12

    The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI) has launched an Assay Portal (http://assays.cancer.gov) to serve as an open-source repository of well-characterized targeted proteomic assays. The portal is designed to curate and disseminate highly characterized, targeted mass spectrometry (MS)-based assays by providing detailed assay performance characterization data, standard operating procedures, and access to reagents. Assay content is accessed via the portal through queries to find assays targeting proteins associated with specific cellular pathways, protein complexes, or specific chromosomal regions. The position of the peptide analytes for which there are available assays are mapped relative to other features of interest in the protein, such as sequence domains, isoforms, single nucleotide polymorphisms, and post-translational modifications. The overarching goals are to enable robust quantification of all human proteins and to standardize the quantification of