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Sample records for top-down proteomic approach

  1. A Routine 'Top-Down' Approach to Analysis of the Human Serum Proteome.

    Science.gov (United States)

    D'Silva, Arlene M; Hyett, Jon A; Coorssen, Jens R

    2017-06-06

    Serum provides a rich source of potential biomarker proteoforms. One of the major obstacles in analysing serum proteomes is detecting lower abundance proteins owing to the presence of hyper-abundant species (e.g., serum albumin and immunoglobulins). Although depletion methods have been used to address this, these can lead to the concomitant removal of non-targeted protein species, and thus raise issues of specificity, reproducibility, and the capacity for meaningful quantitative analyses. Altering the native stoichiometry of the proteome components may thus yield a more complex series of issues than dealing directly with the inherent complexity of the sample. Hence, here we targeted method refinements so as to ensure optimum resolution of serum proteomes via a top down two-dimensional gel electrophoresis (2DE) approach that enables the routine assessment of proteoforms and is fully compatible with subsequent mass spectrometric analyses. Testing included various fractionation and non-fractionation approaches. The data show that resolving 500 µg protein on 17 cm 3-10 non-linear immobilised pH gradient strips in the first dimension followed by second dimension resolution on 7-20% gradient gels with a combination of lithium dodecyl sulfate (LDS) and sodium dodecyl sulfate (SDS) detergents markedly improves the resolution and detection of proteoforms in serum. In addition, well established third dimension electrophoretic separations in combination with deep imaging further contributed to the best available resolution, detection, and thus quantitative top-down analysis of serum proteomes.

  2. Top Down proteomics: Facts and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Catherman, Adam D.; Skinner, Owen S.; Kelleher, Neil L., E-mail: n-kelleher@northwestern.edu

    2014-03-21

    Highlights: • Top Down versus Bottom Up proteomics analysis. • Separations methods for Top Down proteomics. • Developments in mass spectrometry instrumentation and fragmentation. • Native mass spectrometry. - Abstract: The rise of the “Top Down” method in the field of mass spectrometry-based proteomics has ushered in a new age of promise and challenge for the characterization and identification of proteins. Injecting intact proteins into the mass spectrometer allows for better characterization of post-translational modifications and avoids several of the serious “inference” problems associated with peptide-based proteomics. However, successful implementation of a Top Down approach to endogenous or other biologically relevant samples often requires the use of one or more forms of separation prior to mass spectrometric analysis, which have only begun to mature for whole protein MS. Recent advances in instrumentation have been used in conjunction with new ion fragmentation using photons and electrons that allow for better (and often complete) protein characterization on cases simply not tractable even just a few years ago. Finally, the use of native electrospray mass spectrometry has shown great promise for the identification and characterization of whole protein complexes in the 100 kDa to 1 MDa regime, with prospects for complete compositional analysis for endogenous protein assemblies a viable goal over the coming few years.

  3. Top Down proteomics: Facts and perspectives

    International Nuclear Information System (INIS)

    Catherman, Adam D.; Skinner, Owen S.; Kelleher, Neil L.

    2014-01-01

    Highlights: • Top Down versus Bottom Up proteomics analysis. • Separations methods for Top Down proteomics. • Developments in mass spectrometry instrumentation and fragmentation. • Native mass spectrometry. - Abstract: The rise of the “Top Down” method in the field of mass spectrometry-based proteomics has ushered in a new age of promise and challenge for the characterization and identification of proteins. Injecting intact proteins into the mass spectrometer allows for better characterization of post-translational modifications and avoids several of the serious “inference” problems associated with peptide-based proteomics. However, successful implementation of a Top Down approach to endogenous or other biologically relevant samples often requires the use of one or more forms of separation prior to mass spectrometric analysis, which have only begun to mature for whole protein MS. Recent advances in instrumentation have been used in conjunction with new ion fragmentation using photons and electrons that allow for better (and often complete) protein characterization on cases simply not tractable even just a few years ago. Finally, the use of native electrospray mass spectrometry has shown great promise for the identification and characterization of whole protein complexes in the 100 kDa to 1 MDa regime, with prospects for complete compositional analysis for endogenous protein assemblies a viable goal over the coming few years

  4. Understanding microelectronics a top-down approach

    CERN Document Server

    Maloberti, Franco

    2011-01-01

    The microelectronics evolution has given rise to many modern benefits but has also changed design methods and attitudes to learning. Technology advancements shifted focus from simple circuits to complex systems with major attention to high-level descriptions. The design methods moved from a bottom-up to a top-down approach. For today's students, the most beneficial approach to learning is this top-down method that demonstrates a global view of electronics before going into specifics. Franco Maloberti uses this approach to explain the fundamentals of electronics, such as processing functions,

  5. An integrated top-down and bottom-up proteomic approach to characterize the antigen-binding fragment of antibodies.

    Science.gov (United States)

    Dekker, Lennard; Wu, Si; Vanduijn, Martijn; Tolić, Nikolai; Stingl, Christoph; Zhao, Rui; Luider, Theo; Paša-Tolić, Ljiljana

    2014-05-01

    We have previously shown that different individuals exposed to the same antigen produce antibodies with identical mutations in their complementarity determining regions (CDR), suggesting that CDR tryptic peptides can serve as biomarkers for disease diagnosis and prognosis. Complete Fabs derived from disease specific antibodies have even higher potential; they could potentially be used for disease treatment and are required to identify the antigens toward which the antibodies are directed. However, complete Fab sequence characterization via LC-MS analysis of tryptic peptides (i.e. bottom-up) has proven to be impractical for mixtures of antibodies. To tackle this challenge, we have developed an integrated bottom-up and top-down MS approach, employing 2D chromatography coupled with Fourier transform mass spectrometry (FTMS), and applied this approach for full characterization of the variable parts of two pharmaceutical monoclonal antibodies with sensitivity comparable to the bottom-up standard. These efforts represent an essential step toward the identification of disease specific antibodies in patient samples with potentially significant clinical impact. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Populating the Landscape: a top down approach

    CERN Document Server

    Hawking, Stephen William; Hertog, Thomas

    2006-01-01

    We put forward a framework for cosmology that combines the string landscape with no boundary initial conditions. In this framework, amplitudes for alternative histories for the universe are calculated with final boundary conditions only. This leads to a top down approach to cosmology, in which the histories of the universe depend on the precise question asked. We study the observational consequences of no boundary initial conditions on the landscape, and outline a scheme to test the theory. This is illustrated in a simple model landscape that admits several alternative inflationary histories for the universe. Only a few of the possible vacua in the landscape will be populated. We also discuss in what respect the top down approach differs from other approaches to cosmology in the string landscape, like eternal inflation.

  7. Computer networking a top-down approach

    CERN Document Server

    Kurose, James

    2017-01-01

    Unique among computer networking texts, the Seventh Edition of the popular Computer Networking: A Top Down Approach builds on the author’s long tradition of teaching this complex subject through a layered approach in a “top-down manner.” The text works its way from the application layer down toward the physical layer, motivating readers by exposing them to important concepts early in their study of networking. Focusing on the Internet and the fundamentally important issues of networking, this text provides an excellent foundation for readers interested in computer science and electrical engineering, without requiring extensive knowledge of programming or mathematics. The Seventh Edition has been updated to reflect the most important and exciting recent advances in networking.

  8. Informed-Proteomics: open-source software package for top-down proteomics

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jungkap; Piehowski, Paul D.; Wilkins, Christopher; Zhou, Mowei; Mendoza, Joshua; Fujimoto, Grant M.; Gibbons, Bryson C.; Shaw, Jared B.; Shen, Yufeng; Shukla, Anil K.; Moore, Ronald J.; Liu, Tao; Petyuk, Vladislav A.; Tolić, Nikola; Paša-Tolić, Ljiljana; Smith, Richard D.; Payne, Samuel H.; Kim, Sangtae

    2017-08-07

    Top-down proteomics involves the analysis of intact proteins. This approach is very attractive as it allows for analyzing proteins in their endogenous form without proteolysis, preserving valuable information about post-translation modifications, isoforms, proteolytic processing or their combinations collectively called proteoforms. Moreover, the quality of the top-down LC-MS/MS datasets is rapidly increasing due to advances in the liquid chromatography and mass spectrometry instrumentation and sample processing protocols. However, the top-down mass spectra are substantially more complex compare to the more conventional bottom-up data. To take full advantage of the increasing quality of the top-down LC-MS/MS datasets there is an urgent need to develop algorithms and software tools for confident proteoform identification and quantification. In this study we present a new open source software suite for top-down proteomics analysis consisting of an LC-MS feature finding algorithm, a database search algorithm, and an interactive results viewer. The presented tool along with several other popular tools were evaluated using human-in-mouse xenograft luminal and basal breast tumor samples that are known to have significant differences in protein abundance based on bottom-up analysis.

  9. Venom Proteomics of Indonesian King Cobra, Ophiophagus hannah: Integrating Top-Down and Bottom-Up Approaches.

    Science.gov (United States)

    Petras, Daniel; Heiss, Paul; Süssmuth, Roderich D; Calvete, Juan J

    2015-06-05

    We report on the first application of top-down mass spectrometry in snake venomics. De novo sequence tags generated by, and ProSight Lite supported analysis of, combined collisional based dissotiations (CID and HCD) recorded in a hybrid LTQ Orbitrap instrument in data-dependent mode identified a number of proteins from different toxin families, namely, 11 three-finger toxins (7-7.9 kDa), a Kunitz-type inhibitor (6.3 kDa), ohanin (11.9 kDa), a novel phospholipase A2 molecule (13.8 kDa), and the cysteine-rich secretory protein (CRISP) ophanin (25 kDa) from Indonesian king cobra venom. Complementary bottom-up MS/MS analyses contributed to the completion of a locus-resolved venom phenotypic map for Ophiophagus hannah, the world's longest venomous snake and a species of medical concern across its wide distribution range in forests from India to Southeast Asia. Its venom composition, comprising 32-35 proteins/peptides from 10 protein families, is dominated by α-neurotoxins and convincingly explains the main neurotoxic effects of human envenoming caused by king cobra bite. The integration of efficient chromatographic separation of the venom's components and locus-resolved toxin identification through top-down and bottom-up MS/MS-based species-specific database searching and de novo sequencing holds promise that the future will be bright for the field of venom research.

  10. Top-down proteomics for the analysis of proteolytic events - Methods, applications and perspectives.

    Science.gov (United States)

    Tholey, Andreas; Becker, Alexander

    2017-11-01

    Mass spectrometry based proteomics is an indispensable tool for almost all research areas relevant for the understanding of proteolytic processing, ranging from the identification of substrates, products and cleavage sites up to the analysis of structural features influencing protease activity. The majority of methods for these studies are based on bottom-up proteomics performing analysis at peptide level. As this approach is characterized by a number of pitfalls, e.g. loss of molecular information, there is an ongoing effort to establish top-down proteomics, performing separation and MS analysis both at intact protein level. We briefly introduce major approaches of bottom-up proteomics used in the field of protease research and highlight the shortcomings of these methods. We then discuss the present state-of-the-art of top-down proteomics. Together with the discussion of known challenges we show the potential of this approach and present a number of successful applications of top-down proteomics in protease research. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Top-Down Approach for the Social Capital Development

    OpenAIRE

    Shah, Syed Akhter Hussain; Shah, Tari shah; Ahmed, Eatzaz

    2011-01-01

    This study provides the compatibility of top-down approach of the collectivist society with the algebraic representation of social capital matrix [22], which establishes algebraic based model having capability of interpreting the state intervention in building social capital. The study also suggests a policy framework for the developing economic strategies and effective planing at government level regarding social capital development in perspective of top-down approach.

  12. Top-down approach to biological therapy of Crohn's disease.

    Science.gov (United States)

    Hirschmann, Simon; Neurath, Markus F

    2017-03-01

    Crohn's disease (CD) is a chronic, immune-mediated condition with a potentially disabling and destructive course. Despite growing data on when to use a therapeutic 'top-down' strategy, clinical management of this complex disorder is still challenging. Currently, the discussion of 'top-down' strategy in CD mostly includes biological therapy alone or in combination. Areas covered: This article is based on a review of existing literature regarding the use of biological therapy in a 'top-down' approach for the treatment of Crohn's disease. The authors reviewed all the major databases including MEDLINE as well as DDW and ECCO abstracts, respectively. Expert opinion: A 'top-down' therapeutic approach in Crohn's disease is strongly supported by existing data in patients with several risk factors for a severe course of disease. Moreover, there is an increasing amount of published data recommending a more individualised therapeutic strategy to identify candidates for 'top-down' treatment, based on enhanced diagnostics using biomarkers. Emerging therapeutic approaches besides existing therapy concepts using biologicals may possibly redefine the 'top-down' therapeutic strategy for Crohn's disease in the future.

  13. Intact cell MALDI-TOF mass spectrometry on single bovine oocyte and follicular cells combined with top-down proteomics: A novel approach to characterise markers of oocyte maturation.

    Science.gov (United States)

    Labas, Valérie; Teixeira-Gomes, Ana-Paula; Bouguereau, Laura; Gargaros, Audrey; Spina, Lucie; Marestaing, Aurélie; Uzbekova, Svetlana

    2018-03-20

    Intact cell MALDI-TOF mass spectrometry (ICM-MS) was adapted to bovine follicular cells from individual ovarian follicles to obtain the protein/peptide signatures (top-down workflow using high resolution MS/MS (TD HR-MS) was performed on the protein extracts from oocytes, CC and GC. The TD HR-MS proteomic approach allowed for: (1) identification of 386 peptide/proteoforms encoded by 194 genes; and (2) characterisation of proteolysis products likely resulting from the action of kallikreins and caspases. In total, 136 peaks observed by ICM-MS were annotated by TD HR-MS (ProteomeXchange PXD004892). Among these, 16 markers of maturation were identified, including IGF2 binding protein 3 and hemoglobin B in the oocyte, thymosins beta-4 and beta-10, histone H2B and ubiquitin in CC. The combination of ICM-MS and TD HR-MS proved to be a suitable strategy to identify non-invasive markers of oocyte quality using limited biological samples. Intact cell MALDI-TOF mass spectrometry on single oocytes and their surrounding cumulus cells, coupled to an optimised top-down HR-MS proteomic approach on ovarian follicular cells, was used to identify specific markers of oocyte meiotic maturation represented by whole low molecular weight proteins or products of degradation by specific proteases. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The Ups and Downs of Repeated Cleavage and Internal Fragment Production in Top-Down Proteomics

    Science.gov (United States)

    Lyon, Yana A.; Riggs, Dylan; Fornelli, Luca; Compton, Philip D.; Julian, Ryan R.

    2018-01-01

    Analysis of whole proteins by mass spectrometry, or top-down proteomics, has several advantages over methods relying on proteolysis. For example, proteoforms can be unambiguously identified and examined. However, from a gas-phase ion-chemistry perspective, proteins are enormous molecules that present novel challenges relative to peptide analysis. Herein, the statistics of cleaving the peptide backbone multiple times are examined to evaluate the inherent propensity for generating internal versus terminal ions. The raw statistics reveal an inherent bias favoring production of terminal ions, which holds true regardless of protein size. Importantly, even if the full suite of internal ions is generated by statistical dissociation, terminal ions are predicted to account for at least 50% of the total ion current, regardless of protein size, if there are three backbone dissociations or fewer. Top-down analysis should therefore be a viable approach for examining proteins of significant size. Comparison of the purely statistical analysis with actual top-down data derived from ultraviolet photodissociation (UVPD) and higher-energy collisional dissociation (HCD) reveals that terminal ions account for much of the total ion current in both experiments. Terminal ion production is more favored in UVPD relative to HCD, which is likely due to differences in the mechanisms controlling fragmentation. Importantly, internal ions are not found to dominate from either the theoretical or experimental point of view. [Figure not available: see fulltext.

  15. Populating the landscape: A top-down approach

    International Nuclear Information System (INIS)

    Hawking, S.W.; Hertog, Thomas

    2006-01-01

    We put forward a framework for cosmology that combines the string landscape with no boundary initial conditions. In this framework, amplitudes for alternative histories for the universe are calculated with final boundary conditions only. This leads to a top-down approach to cosmology, in which the histories of the universe depend on the precise question asked. We study the observational consequences of no boundary initial conditions on the landscape, and outline a scheme to test the theory. This is illustrated in a simple model landscape that admits several alternative inflationary histories for the universe. Only a few of the possible vacua in the landscape will be populated. We also discuss in what respect the top-down approach differs from other approaches to cosmology in the string landscape, like eternal inflation

  16. 'Top-down' BACT analysis - Recommended approach and recent determinations

    International Nuclear Information System (INIS)

    Cochran, J.R.; Fagan, M.E.

    1991-01-01

    New EPA requirements for 'top-down' best available control technology (BACT) analyses have resulted in determinations that require more stringent control technologies. Accordingly, these permit decisions include nitrogen oxide (NO x ), sulfur dioxide, and particulate emission limits significantly lower than applicable New Source Performance Standards. However, with careful consideration of acceptable site-specific impacts, obtaining a reasonable BACT determination is still possible. This paper presents a step-by-step approach for conducting a top-down BACT analysis, and summarizes important considerations that will lead to a more effective BACT analysis. In addition, recent permit decisions regarding NO x emission rate and control technology requirements for combined cycle combustion turbine and coal fueled power plants are summarized and examined to ascertain the basis for decisions. Guidance from this paper will help applicants in preparing an accurate and comprehensive BACT analysis for their proposed projects

  17. Deep imaging: how much of the proteome does current top-down technology already resolve?

    Directory of Open Access Journals (Sweden)

    Elise P Wright

    Full Text Available Effective proteome analyses are based on interplay between resolution and detection. It had been claimed that resolution was the main factor limiting the use of two-dimensional gel electrophoresis. Improved protein detection now indicates that this is unlikely to be the case. Using a highly refined protocol, the rat brain proteome was extracted, resolved, and detected. In order to overcome the stain saturation threshold, high abundance protein species were excised from the gel following standard imaging. Gels were then imaged again using longer exposure times, enabling detection of lower abundance, less intensely stained protein species. This resulted in a significant enhancement in the detection of resolved proteins, and a slightly modified digestion protocol enabled effective identification by standard mass spectrometric methods. The data indicate that the resolution required for comprehensive proteome analyses is already available, can assess multiple samples in parallel, and preserve critical information concerning post-translational modifications. Further optimization of staining and detection methods promises additional improvements to this economical, widely accessible and effective top-down approach to proteome analysis.

  18. Factors That Modulate Neurogenesis: A Top-Down Approach.

    Science.gov (United States)

    LaDage, Lara D

    2016-08-24

    Although hippocampal neurogenesis in the adult brain has been conserved across the vertebrate lineage, laboratory studies have primarily examined this phenomenon in rodent models. This approach has been successful in elucidating important factors and mechanisms that can modulate rates of hippocampal neurogenesis, including hormones, environmental complexity, learning and memory, motor stimulation, and stress. However, recent studies have found that neurobiological research on neurogenesis in rodents may not easily translate to, or explain, neurogenesis patterns in nonrodent systems, particularly in species examined in the field. This review examines some of the evolutionary and ecological variables that may also modulate neurogenesis patterns. This 'top-down' and more naturalistic approach, which incorporates ecology and natural history, particularly of nonmodel species, may allow for a more comprehensive understanding of the functional significance of neurogenesis. © 2016 S. Karger AG, Basel.

  19. Top Down Proteomics Reveals Mature Proteoforms Expressed in Subcellular Fractions of the Echinococcus granulosus Preadult Stage.

    Science.gov (United States)

    Lorenzatto, Karina R; Kim, Kyunggon; Ntai, Ioanna; Paludo, Gabriela P; Camargo de Lima, Jeferson; Thomas, Paul M; Kelleher, Neil L; Ferreira, Henrique B

    2015-11-06

    Echinococcus granulosus is the causative agent of cystic hydatid disease, a neglected zoonosis responsible for high morbidity and mortality. Several molecular mechanisms underlying parasite biology remain poorly understood. Here, E. granulosus subcellular fractions were analyzed by top down and bottom up proteomics for protein identification and characterization of co-translational and post-translational modifications (CTMs and PTMs, respectively). Nuclear and cytosolic extracts of E. granulosus protoscoleces were fractionated by 10% GELFrEE and proteins under 30 kDa were analyzed by LC-MS/MS. By top down analysis, 186 proteins and 207 proteoforms were identified, of which 122 and 52 proteoforms were exclusively detected in nuclear and cytosolic fractions, respectively. CTMs were evident as 71% of the proteoforms had methionine excised and 47% were N-terminal acetylated. In addition, in silico internal acetylation prediction coupled with top down MS allowed the characterization of 9 proteins differentially acetylated, including histones. Bottom up analysis increased the overall number of identified proteins in nuclear and cytosolic fractions to 154 and 112, respectively. Overall, our results provided the first description of the low mass proteome of E. granulosus subcellular fractions and highlighted proteoforms with CTMs and PTMS whose characterization may lead to another level of understanding about molecular mechanisms controlling parasitic flatworm biology.

  20. Comprehensive Analysis of Low-Molecular-Weight Human Plasma Proteome Using Top-Down Mass Spectrometry.

    Science.gov (United States)

    Cheon, Dong Huey; Nam, Eun Ji; Park, Kyu Hyung; Woo, Se Joon; Lee, Hye Jin; Kim, Hee Cheol; Yang, Eun Gyeong; Lee, Cheolju; Lee, Ji Eun

    2016-01-04

    While human plasma serves as a great source for disease diagnosis, low-molecular-weight (LMW) proteome (mass spectrometry to analyze the LMW proteoforms present in four types of human plasma samples pooled from three healthy controls (HCs) without immunoaffinity depletion and with depletion of the top two, six, and seven high-abundance proteins. The LMW proteoforms were first fractionated based on molecular weight using gel-eluted liquid fraction entrapment electrophoresis (GELFrEE). Then, the GELFrEE fractions containing up to 30 kDa were subjected to nanocapillary-LC-MS/MS, and the high-resolution MS and MS/MS data were processed using ProSightPC 3.0. As a result, a total of 442 LMW proteins and cleaved products, including those with post-translational modifications and single amino acid variations, were identified. From additional comparative analysis of plasma samples without immunoaffinity depletion between HCs and colorectal cancer (CRC) patients via top-down approach, tens of LMW proteoforms, including platelet factor 4, were found to show >1.5-fold changes between the plasma samples of HCs and CRC patients, and six of the LMW proteins were verified by Western blot analysis.

  1. Top-Down Proteomics and Direct Surface Sampling of Neonatal Dried Blood Spots: Diagnosis of Unknown Hemoglobin Variants

    Science.gov (United States)

    Edwards, Rebecca L.; Griffiths, Paul; Bunch, Josephine; Cooper, Helen J.

    2012-11-01

    We have previously shown that liquid microjunction surface sampling of dried blood spots coupled with high resolution top-down mass spectrometry may be used for screening of common hemoglobin variants HbS, HbC, and HbD. In order to test the robustness of the approach, we have applied the approach to unknown hemoglobin variants. Six neonatal dried blood spot samples that had been identified as variants, but which could not be diagnosed by current screening methods, were analyzed by direct surface sampling top-down mass spectrometry. Both collision-induced dissociation and electron transfer dissociation mass spectrometry were employed. Four of the samples were identified as β-chain variants: two were heterozygous Hb D-Iran, one was heterozygous Hb Headington, and one was heterozygous Hb J-Baltimore. The fifth sample was identified as the α-chain variant heterozygous Hb Phnom Penh. Analysis of the sixth sample suggested that it did not in fact contain a variant. Adoption of the approach in the clinic would require speed in both data collection and interpretation. To address that issue, we have compared manual data analysis with freely available data analysis software (ProsightPTM). The results demonstrate the power of top-down proteomics for hemoglobin variant analysis in newborn samples.

  2. Quantitative Analysis of Human Salivary Gland-Derived Intact Proteome Using Top-Down Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Si; Brown, Joseph N.; Tolic, Nikola; Meng, Da; Liu, Xiaowen; Zhang, Haizhen; Zhao, Rui; Moore, Ronald J.; Pevzner, Pavel A.; Smith, Richard D.; Pasa-Tolic, Ljiljana

    2014-05-31

    There are several notable challenges inherent to fully characterizing the entirety of the human saliva proteome using bottom-up approaches, including polymorphic isoforms, post-translational modifications, unique splice variants, deletions, and truncations. To address these challenges, we have developed a top-down based liquid chromatography-mass spectrometry (LC-MS) approach, which cataloged 20 major human salivary proteins with a total of 83 proteoforms, containing a broad range of post-translational modifications. Among these proteins, several previously reported disease biomarker proteins were identified at the intact protein level, such as beta-2 microglobulin (B2M). In addition, intact glycosylated proteoforms of several saliva proteins were also characterized, including intact N-glycosylated protein prolactin inducible protein (PIP) and O-glycosylated acidic protein rich protein (aPRP). These characterized proteoforms constitute an intact saliva proteoform database, which was used for quantitative comparison of intact salivary proteoforms among six healthy individuals. Human parotid (PS) and submandibular/sublingual gland (SMSL) secretion samples (2 μg of protein each) from six healthy individuals were compared using RPLC coupled with the 12T FTICR mass spectrometer. Significantly different protein and PTM patterns were resolved with high reproducibility between PS and SMSL glands. The results from this study provide further insight into the potential mechanisms of PTM pathways in oral glandular secretion, expanding our knowledge of this complex yet easily accessible fluid. Intact protein LC-MS approach presented herein can potentially be applied for rapid and accurate identification of biomarkers from only a few microliters of human glandular saliva.

  3. Transferring Codified Knowledge: Socio-Technical versus Top-Down Approaches

    Science.gov (United States)

    Guzman, Gustavo; Trivelato, Luiz F.

    2008-01-01

    Purpose: This paper aims to analyse and evaluate the transfer process of codified knowledge (CK) performed under two different approaches: the "socio-technical" and the "top-down". It is argued that the socio-technical approach supports the transfer of CK better than the top-down approach. Design/methodology/approach: Case study methodology was…

  4. Establishing a campylobacter-free pig population through a top-down approach

    NARCIS (Netherlands)

    Weijtens, M.J.B.M.; Urlings, H.A.P.; Plas, J. van der

    2000-01-01

    Fattening pigs are often infected with campylobacter. To eliminate campylobacter from the pig population, a top-down approach, involving the breeding and reproduction farms, seems appropriate. In order to investigate the effectiveness of a top-down approach, sows' faeces from the following farms

  5. Combined Mass Spectrometry Imaging and Top-down Microproteomics Reveals Evidence of a Hidden Proteome in Ovarian Cancer.

    Science.gov (United States)

    Delcourt, Vivian; Franck, Julien; Leblanc, Eric; Narducci, Fabrice; Robin, Yves-Marie; Gimeno, Jean-Pascal; Quanico, Jusal; Wisztorski, Maxence; Kobeissy, Firas; Jacques, Jean-François; Roucou, Xavier; Salzet, Michel; Fournier, Isabelle

    2017-07-01

    Recently, it was demonstrated that proteins can be translated from alternative open reading frames (altORFs), increasing the size of the actual proteome. Top-down mass spectrometry-based proteomics allows the identification of intact proteins containing post-translational modifications (PTMs) as well as truncated forms translated from reference ORFs or altORFs. Top-down tissue microproteomics was applied on benign, tumor and necrotic-fibrotic regions of serous ovarian cancer biopsies, identifying proteins exhibiting region-specific cellular localization and PTMs. The regions of interest (ROIs) were determined by MALDI mass spectrometry imaging and spatial segmentation. Analysis with a customized protein sequence database containing reference and alternative proteins (altprots) identified 15 altprots, including alternative G protein nucleolar 1 (AltGNL1) found in the tumor, and translated from an altORF nested within the GNL1 canonical coding sequence. Co-expression of GNL1 and altGNL1 was validated by transfection in HEK293 and HeLa cells with an expression plasmid containing a GNL1-FLAG (V5) construct. Western blot and immunofluorescence experiments confirmed constitutive co-expression of altGNL1-V5 with GNL1-FLAG. Taken together, our approach provides means to evaluate protein changes in the case of serous ovarian cancer, allowing the detection of potential markers that have never been considered. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  6. A New Approach to Programming Language Education for Beginners with Top-Down Learning

    Directory of Open Access Journals (Sweden)

    Daisuke Saito

    2013-12-01

    Full Text Available There are two basic approaches in learning new programming language: a bottom-up approach and a top-down approach. It has been said that if a learner has already acquired one language, the top-down approach is more efficient to learn another while, for a person who has absolutely no knowledge of any programming languages; the bottom-up approach is preferable. The major problem of the bottom-up approach is that it requires longer period to acquire the language. For quicker learning, this paper applies a top-down approach for a beginners who has not yet acquired any programming languages.

  7. Stability of Polymer Ultrathin Films (Top-Down Approach.

    Science.gov (United States)

    Bal, Jayanta Kumar; Beuvier, Thomas; Unni, Aparna Beena; Chavez Panduro, Elvia Anabela; Vignaud, Guillaume; Delorme, Nicolas; Chebil, Mohamed Souheib; Grohens, Yves; Gibaud, Alain

    2015-08-25

    In polymer physics, the dewetting of spin-coated polystyrene ultrathin films on silicon remains mysterious. By adopting a simple top-down method based on good solvent rinsing, we are able to prepare flat polystyrene films with a controlled thickness ranging from 1.3 to 7.0 nm. Their stability was scrutinized after a classical annealing procedure above the glass transition temperature. Films were found to be stable on oxide-free silicon irrespective of film thickness, while they were unstable (2.9 nm) on 2 nm oxide-covered silicon substrates. The Lifshitz-van der Waals intermolecular theory that predicts the domains of stability as a function of the film thickness and of the substrate nature is now fully reconciled with our experimental observations. We surmise that this reconciliation is due to the good solvent rinsing procedure that removes the residual stress and/or the density variation of the polystyrene films inhibiting thermodynamically the dewetting on oxide-free silicon.

  8. High-resolution ultrahigh-pressure long column reversed-phase liquid chromatography for top-down proteomics

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Yufeng; Tolic, Nikola; Piehowski, Paul D.; Shukla, Anil K.; Kim, Sangtae; Zhao, Rui; Qu, Yi; Robinson, E. W.; Smith, Richard D.; Pasa-Tolic, Ljiljana

    2017-05-01

    We report development of an approach providing high-resolution RPLC of proteins and its utility for mass spectrometry-based top-down proteomics. A chromatographic peak capacity of ~450 was achieved for proteins and large polypeptides having MWs up to 43 kDa in the context of proteomics applications. RPLC column lengths from 20 to 200 cm, particle sizes from 1.5 to 5 m, bonding alkyl chains from C1 to C2, C4, C8, and C18, and particle surface structures that spanned porous, superficially porous (porous shell, core-shell), and nonporous were investigated at pressures up to14K psi. Column length was found as the most important factor for >20 kDa proteins in gradient RPLC, and shortening column length degraded RPLC resolution and sensitivity regardless of the size and surface structure of the packing particles used. The alkyl chains bonded to the silica particle surface significantly affected the RPLC recovery and efficiency, and short alkyl C1-C4 phases provided higher sensitivity and resolution than C8 and C18 phases. Long gradient separations (e.g., >10 hours) with long columns (e.g., 100 cm) were particularly effective in conjunction with use of high accuracy mass spectrometers (e.g., the Orbitrap Elite) for top-down proteomics with improved proteoform coverage by allowing multiple HCD, CID, and ETD dissociation modes. It was also found that HCD produced small fragments useful for proteoform identification, while low energy CID and ETD often complemented HCD by providing large fragments.

  9. Towards a routine application of Top-Down approaches for label-free discovery workflows.

    Science.gov (United States)

    Schmit, Pierre-Olivier; Vialaret, Jerome; Wessels, Hans J C T; van Gool, Alain J; Lehmann, Sylvain; Gabelle, Audrey; Wood, Jason; Bern, Marshall; Paape, Rainer; Suckau, Detlev; Kruppa, Gary; Hirtz, Christophe

    2018-03-20

    Thanks to proteomics investigations, our vision of the role of different protein isoforms in the pathophysiology of diseases has largely evolved. The idea that protein biomarkers like tau, amyloid peptides, ApoE, cystatin, or neurogranin are represented in body fluids as single species is obviously over-simplified, as most proteins are present in different isoforms and subjected to numerous processing and post-translational modifications. Measuring the intact mass of proteins by MS has the advantage to provide information on the presence and relative amount of the different proteoforms. Such Top-Down approaches typically require a high degree of sample pre-fractionation to allow the MS system to deliver optimal performance in terms of dynamic range, mass accuracy and resolution. In clinical studies, however, the requirements for pre-analytical robustness and sample size large enough for statistical power restrict the routine use of a high degree of sample pre-fractionation. In this study, we have investigated the capacities of current-generation Ultra-High Resolution Q-Tof systems to deal with high complexity intact protein samples and have evaluated the approach on a cohort of patients suffering from neurodegenerative disease. Statistical analysis has shown that several proteoforms can be used to distinguish Alzheimer disease patients from patients suffering from other neurodegenerative disease. Top-down approaches have an extremely high biological relevance, especially when it comes to biomarker discovery, but the necessary pre-fractionation constraints are not easily compatible with the robustness requirements and the size of clinical sample cohorts. We have demonstrated that intact protein profiling studies could be run on UHR-Q-ToF with limited pre-fractionation. The proteoforms that have been identified as candidate biomarkers in the-proof-of concept study are derived from proteins known to play a role in the pathophysiology process of Alzheimer disease

  10. Top-down proteomics reveals a unique protein S-thiolation switch in Salmonella Typimurium in response to infection-like conditions

    Energy Technology Data Exchange (ETDEWEB)

    Ansong, Charles; Wu, Si; Meng, Da; Liu, Xiaowen; Brewer, Heather M.; Kaiser, Brooke LD; Nakayasu, Ernesto S.; Cort, John R.; Pevzner, Pavel A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.; Pasa-Tolic, Ljiljana

    2013-06-18

    Characterization of the mature protein complement in cells is crucial for a better understanding of cellular processes on a systems-wide scale. Bottom-up proteomic approaches often lead to loss of critical information about an endogenous protein’s actual state due to post translational modifications (PTMs) and other processes. Top-down approaches that involve analysis of the intact protein can address this concern but present significant analytical challenges related to the separation quality needed, measurement sensitivity, and speed that result in low throughput and limited coverage. Here we used single-dimension ultra high pressure liquid chromatography mass spectrometry to investigate the comprehensive ‘intact’ proteome of the Gram negative bacterial pathogen Salmonella Typhimurium. Top-down proteomics analysis revealed 563 unique proteins including 1665 proteoforms generated by PTMs, representing the largest microbial top-down dataset reported to date. Our analysis not only confirmed several previously recognized aspects of Salmonella biology and bacterial PTMs in general, but also revealed several novel biological insights. Of particular interest was differential utilization of the protein S-thiolation forms S-glutathionylation and S-cysteinylation in response to infection-like conditions versus basal conditions, which was corroborated by changes in corresponding biosynthetic pathways. This differential utilization highlights underlying metabolic mechanisms that modulate changes in cellular signaling, and represents to our knowledge the first report of S-cysteinylation in Gram negative bacteria. The demonstrated utility of our simple proteome-wide intact protein level measurement strategy for gaining biological insight should promote broader adoption and applications of top-down proteomics approaches.

  11. Comparison between bottom-up and top-down approaches in the estimation of measurement uncertainty.

    Science.gov (United States)

    Lee, Jun Hyung; Choi, Jee-Hye; Youn, Jae Saeng; Cha, Young Joo; Song, Woonheung; Park, Ae Ja

    2015-06-01

    Measurement uncertainty is a metrological concept to quantify the variability of measurement results. There are two approaches to estimate measurement uncertainty. In this study, we sought to provide practical and detailed examples of the two approaches and compare the bottom-up and top-down approaches to estimating measurement uncertainty. We estimated measurement uncertainty of the concentration of glucose according to CLSI EP29-A guideline. Two different approaches were used. First, we performed a bottom-up approach. We identified the sources of uncertainty and made an uncertainty budget and assessed the measurement functions. We determined the uncertainties of each element and combined them. Second, we performed a top-down approach using internal quality control (IQC) data for 6 months. Then, we estimated and corrected systematic bias using certified reference material of glucose (NIST SRM 965b). The expanded uncertainties at the low glucose concentration (5.57 mmol/L) by the bottom-up approach and top-down approaches were ±0.18 mmol/L and ±0.17 mmol/L, respectively (all k=2). Those at the high glucose concentration (12.77 mmol/L) by the bottom-up and top-down approaches were ±0.34 mmol/L and ±0.36 mmol/L, respectively (all k=2). We presented practical and detailed examples for estimating measurement uncertainty by the two approaches. The uncertainties by the bottom-up approach were quite similar to those by the top-down approach. Thus, we demonstrated that the two approaches were approximately equivalent and interchangeable and concluded that clinical laboratories could determine measurement uncertainty by the simpler top-down approach.

  12. Top-down approach to unified supergravity models

    International Nuclear Information System (INIS)

    Hempfling, R.

    1994-03-01

    We introduce a new approach for studying unified supergravity models. In this approach all the parameters of the grand unified theory (GUT) are fixed by imposing the corresponding number of low energy observables. This determines the remaining particle spectrum whose dependence on the low energy observables can now be investigated. We also include some SUSY threshold corrections that have previously been neglected. In particular the SUSY threshold corrections to the fermion masses can have a significant impact on the Yukawa coupling unification. (orig.)

  13. A Top-Down Approach to Construct Execution Views of a Large Software-Intensive System

    NARCIS (Netherlands)

    Callo Arias, T.B.; America, P.H.M.; Avgeriou, P.

    2011-01-01

    This paper presents a top-down approach to construct execution views of a large and complex software intensive system. Execution viewsdescribe what the software does at runtime and how it does it. The presented approach represents a reverse architecting solution that follows a set of pre-defined

  14. A top-down approach to fabrication of high quality vertical heterostructure nanowire arrays

    NARCIS (Netherlands)

    Wang, Hua; Sun, Minghua; Ding, K.; Hill, M.T.; Ning, C.Z.

    2011-01-01

    We demonstrate a novel top-down approach for fabricating nanowires with unprecedented complexity and optical quality by taking advantage of a nanoscale self-masking effect. We realized vertical arrays of nanowires of 20-40 nm in diameter with 16 segments of complex longitudinal InGaAsP/InP

  15. Comparing Top-Down with Bottom-Up Approaches: Teaching Data Modeling

    Science.gov (United States)

    Kung, Hsiang-Jui; Kung, LeeAnn; Gardiner, Adrian

    2013-01-01

    Conceptual database design is a difficult task for novice database designers, such as students, and is also therefore particularly challenging for database educators to teach. In the teaching of database design, two general approaches are frequently emphasized: top-down and bottom-up. In this paper, we present an empirical comparison of students'…

  16. Bottom-up and Top-down: An alternate classification of LD authoring approaches

    NARCIS (Netherlands)

    Sodhi, Tim; Miao, Yongwu; Brouns, Francis; Koper, Rob

    2007-01-01

    Sodhi, T., Miao, Y., Brouns, F., & Koper, E. J. R. (2007). Bottom-up and Top-down: An alternate classification of LD authoring approaches. Paper presented at the TENCompetence Open Workshop on Current research on IMS Learning Design and Lifelong Competence Development Infrastructures. June, 21-22,

  17. A top-down approach to fabrication of high quality vertical heterostructure nanowire arrays.

    Science.gov (United States)

    Wang, Hua; Sun, Minghua; Ding, Kang; Hill, Martin T; Ning, Cun-Zheng

    2011-04-13

    We demonstrate a novel top-down approach for fabricating nanowires with unprecedented complexity and optical quality by taking advantage of a nanoscale self-masking effect. We realized vertical arrays of nanowires of 20-40 nm in diameter with 16 segments of complex longitudinal InGaAsP/InP structures. The unprecedented high quality of etched wires is evidenced by the narrowest photoluminescence linewidth ever produced in similar wavelengths, indistinguishable from that of the corresponding wafer. This top-down, mask-free, large scale approach is compatible with the established device fabrication processes and could serve as an important alternative to the bottom-up approach, significantly expanding ranges and varieties of applications of nanowire technology.

  18. Approaches in studying the pharmacology of Chinese Medicine formulas: bottom-up, top-down-and meeting in the middle.

    Science.gov (United States)

    Huang, Tao; Zhong, Linda L D; Lin, Chen-Yuan; Zhao, Ling; Ning, Zi-Wan; Hu, Dong-Dong; Zhang, Man; Tian, Ke; Cheng, Chung-Wah; Bian, Zhao-Xiang

    2018-01-01

    Investigating the pharmacology is key to the modernization of Chinese Medicine (CM) formulas. However, identifying which are the active compound(s) of CM formulas, which biological entities they target, and through which signaling pathway(s) they act to modify disease symptoms, are still difficult tasks for researchers, even when equipped with an arsenal of advanced modern technologies. Multiple approaches, including network pharmacology, pharmaco-genomics, -proteomics, and -metabolomics, have been developed to study the pharmacology of CM formulas. They fall into two general categories in terms of how they tackle a problem: bottom-up and top-down. In this article, we compared these two different approaches in several dimensions by using the case of MaZiRenWan (MZRW, also known as Hemp Seed Pill), a CM herbal formula for functional constipation. Multiple hypotheses are easy to be proposed in the bottom-up approach (e.g. network pharmacology); but these hypotheses are usually false positives and hard to be tested. In contrast, it is hard to suggest hypotheses in the top-down approach (e.g. pharmacometabolomics); however, once a hypothesis is proposed, it is much easier to be tested. Merging of these two approaches could results in a powerful approach, which could be the new paradigm for the pharmacological study of CM formulas.

  19. Sustainability and Uncertainty: Bottom-Up and Top-Down Approaches

    Directory of Open Access Journals (Sweden)

    K. Klint Jensen

    2010-04-01

    Full Text Available The widely used concept of sustainability is seldom precisely defined, and its clarification involves making up one’s mind about a range of difficult questions. One line of research (bottom-up takes sustaining a system over time as its starting point and then infers prescriptions from this requirement. Another line (top-down takes an economical interpretation of the Brundtland Commission’s suggestion that the present generation’s needsatisfaction should not compromise the need-satisfaction of future generations as its starting point. It then measures sustainability at the level of society and infers prescriptions from this requirement. These two approaches may conflict, and in this conflict the top-down approach has the upper hand, ethically speaking. However, the implicit goal in the top-down approach of justice between generations needs to be refined in several dimensions. But even given a clarified ethical goal, disagreements can arise. At present we do not know what substitutions will be possible in the future. This uncertainty clearly affects the prescriptions that follow from the measure of sustainability. Consequently, decisions about how to make future agriculture sustainable are decisions under uncertainty. There might be different judgments on likelihoods; but even given some set of probabilities, there might be disagreement on the right level of precaution in face of the uncertainty.

  20. Comprehensive analysis of tropomyosin isoforms in skeletal muscles by top-down proteomics.

    Science.gov (United States)

    Jin, Yutong; Peng, Ying; Lin, Ziqing; Chen, Yi-Chen; Wei, Liming; Hacker, Timothy A; Larsson, Lars; Ge, Ying

    2016-04-01

    Mammalian skeletal muscles are heterogeneous in nature and are capable of performing various functions. Tropomyosin (Tpm) is a major component of the thin filament in skeletal muscles and plays an important role in controlling muscle contraction and relaxation. Tpm is known to consist of multiple isoforms resulting from different encoding genes and alternative splicing, along with post-translational modifications. However, a systematic characterization of Tpm isoforms in skeletal muscles is still lacking. Therefore, we employed top-down mass spectrometry (MS) to identify and characterize Tpm isoforms present in different skeletal muscles from multiple species, including swine, rat, and human. Our study revealed that Tpm1.1 and Tpm2.2 are the two major Tpm isoforms in swine and rat skeletal muscles, whereas Tpm1.1, Tpm2.2, and Tpm3.12 are present in human skeletal muscles. Tandem MS was utilized to identify the sequences of the major Tpm isoforms. Furthermore, quantitative analysis revealed muscle-type specific differences in the abundance of un-modified and modified Tpm isoforms in rat and human skeletal muscles. This study represents the first systematic investigation of Tpm isoforms in skeletal muscles, which not only demonstrates the capabilities of top-down MS for the comprehensive characterization of skeletal myofilament proteins but also provides the basis for further studies on these Tpm isoforms in muscle-related diseases.

  1. Top-down approach for the direct characterization of low molecular weight heparins using LC-FT-MS.

    Science.gov (United States)

    Li, Lingyun; Zhang, Fuming; Zaia, Joseph; Linhardt, Robert J

    2012-10-16

    Low molecular heparins (LMWHs) are structurally complex, heterogeneous, polydisperse, and highly negatively charged mixtures of polysaccharides. The direct characterization of LMWH is a major challenge for currently available analytical technologies. Electrospray ionization (ESI) liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for the characterization complex biological samples in the fields of proteomics, metabolomics, and glycomics. LC-MS has been applied to the analysis of heparin oligosaccharides, separated by size exclusion, reversed phase ion-pairing chromatography, and chip-based amide hydrophilic interaction chromatography (HILIC). However, there have been limited applications of ESI-LC-MS for the direct characterization of intact LMWHs (top-down analysis) due to their structural complexity, low ionization efficiency, and sulfate loss. Here we present a simple and reliable HILIC-Fourier transform (FT)-ESI-MS platform to characterize and compare two currently marketed LMWH products using the top-down approach requiring no special sample preparation steps. This HILIC system relies on cross-linked diol rather than amide chemistry, affording highly resolved chromatographic separations using a relatively high percentage of acetonitrile in the mobile phase, resulting in stable and high efficiency ionization. Bioinformatics software (GlycReSoft 1.0) was used to automatically assign structures within 5-ppm mass accuracy.

  2. Gauging the ungauged basin: a top-down approach in a large semiarid watershed in China

    Directory of Open Access Journals (Sweden)

    F. K. Barthold

    2008-06-01

    Full Text Available A major research challenge in ungauged basins is to quickly assess the dominant hydrological processes of watersheds. In this paper we present a top-down approach from first field reconnaissance to perceptual model development, model conceptualization, evaluation, rejection and eventually, to a more substantial field campaign to build upon the initial modeling. This approach led us from an initial state where very little was known about catchment behavior towards a more complete view of catchment hydrological processes, including the preliminary identification of water sources and an assessment of the effectiveness of our sampling design.

  3. Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics.

    Science.gov (United States)

    Melani, Rafael D; Skinner, Owen S; Fornelli, Luca; Domont, Gilberto B; Compton, Philip D; Kelleher, Neil L

    2016-07-01

    Characterizing whole proteins by top-down proteomics avoids a step of inference encountered in the dominant bottom-up methodology when peptides are assembled computationally into proteins for identification. The direct interrogation of whole proteins and protein complexes from the venom of Ophiophagus hannah (king cobra) provides a sharply clarified view of toxin sequence variation, transit peptide cleavage sites and post-translational modifications (PTMs) likely critical for venom lethality. A tube-gel format for electrophoresis (called GELFrEE) and solution isoelectric focusing were used for protein fractionation prior to LC-MS/MS analysis resulting in 131 protein identifications (18 more than bottom-up) and a total of 184 proteoforms characterized from 14 protein toxin families. Operating both GELFrEE and mass spectrometry to preserve non-covalent interactions generated detailed information about two of the largest venom glycoprotein complexes: the homodimeric l-amino acid oxidase (∼130 kDa) and the multichain toxin cobra venom factor (∼147 kDa). The l-amino acid oxidase complex exhibited two clusters of multiproteoform complexes corresponding to the presence of 5 or 6 N-glycans moieties, each consistent with a distribution of N-acetyl hexosamines. Employing top-down proteomics in both native and denaturing modes provides unprecedented characterization of venom proteoforms and their complexes. A precise molecular inventory of venom proteins will propel the study of snake toxin variation and the targeted development of new antivenoms or other biotherapeutics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Evaluations of carbon fluxes estimated by top-down and bottom-up approaches

    Science.gov (United States)

    Murakami, K.; Sasai, T.; Kato, S.; Hiraki, K.; Maksyutov, S. S.; Yokota, T.; Nasahara, K.; Matsunaga, T.

    2013-12-01

    There are two types of estimating carbon fluxes using satellite observation data, and these are referred to as top-down and bottom-up approaches. Many uncertainties are however still remain in these carbon flux estimations, because the true values of carbon flux are still unclear and estimations vary according to the type of the model (e.g. a transport model, a process based model) and input data. The CO2 fluxes in these approaches are estimated by using different satellite data such as the distribution of CO2 concentration in the top-down approach and the land cover information (e.g. leaf area, surface temperature) in the bottom-up approach. The satellite-based CO2 flux estimations with reduced uncertainty can be used efficiently for identifications of large emission area and carbon stocks of forest area. In this study, we evaluated the carbon flux estimates from two approaches by comparing with each other. The Greenhouse gases Observing SATellite (GOSAT) has been observing atmospheric CO2 concentrations since 2009. GOSAT L4A data product is the monthly CO2 flux estimations for 64 sub-continental regions and is estimated by using GOSAT FTS SWIR L2 XCO2 data and atmospheric tracer transport model. We used GOSAT L4A CO2 flux as top-down approach estimations and net ecosystem productions (NEP) estimated by the diagnostic type biosphere model BEAMS as bottom-up approach estimations. BEAMS NEP is only natural land CO2 flux, so we used GOSAT L4A CO2 flux after subtraction of anthropogenic CO2 emissions and oceanic CO2 flux. We compared with two approach in temperate north-east Asia region. This region is covered by grassland and crop land (about 60 %), forest (about 20 %) and bare ground (about 20 %). The temporal variation for one year period was indicated similar trends between two approaches. Furthermore we show the comparison of CO2 flux estimations in other sub-continental regions.

  5. Different top-down approaches to estimate measurement uncertainty of whole blood tacrolimus mass concentration values.

    Science.gov (United States)

    Rigo-Bonnin, Raül; Blanco-Font, Aurora; Canalias, Francesca

    2018-05-08

    Values of mass concentration of tacrolimus in whole blood are commonly used by the clinicians for monitoring the status of a transplant patient and for checking whether the administered dose of tacrolimus is effective. So, clinical laboratories must provide results as accurately as possible. Measurement uncertainty can allow ensuring reliability of these results. The aim of this study was to estimate measurement uncertainty of whole blood mass concentration tacrolimus values obtained by UHPLC-MS/MS using two top-down approaches: the single laboratory validation approach and the proficiency testing approach. For the single laboratory validation approach, we estimated the uncertainties associated to the intermediate imprecision (using long-term internal quality control data) and the bias (utilizing a certified reference material). Next, we combined them together with the uncertainties related to the calibrators-assigned values to obtain a combined uncertainty for, finally, to calculate the expanded uncertainty. For the proficiency testing approach, the uncertainty was estimated in a similar way that the single laboratory validation approach but considering data from internal and external quality control schemes to estimate the uncertainty related to the bias. The estimated expanded uncertainty for single laboratory validation, proficiency testing using internal and external quality control schemes were 11.8%, 13.2%, and 13.0%, respectively. After performing the two top-down approaches, we observed that their uncertainty results were quite similar. This fact would confirm that either two approaches could be used to estimate the measurement uncertainty of whole blood mass concentration tacrolimus values in clinical laboratories. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  6. Supervisor localization a top-down approach to distributed control of discrete-event systems

    CERN Document Server

    Cai, Kai

    2016-01-01

    This monograph presents a systematic top-down approach to distributed control synthesis of discrete-event systems (DES). The approach is called supervisor localization; its essence is the allocation of external supervisory control action to individual component agents as their internal control strategies. The procedure is: first synthesize a monolithic supervisor, to achieve globally optimal and nonblocking controlled behavior, then decompose the monolithic supervisor into local controllers, one for each agent. The collective behavior of the resulting local controllers is identical to that achieved by the monolithic supervisor. The basic localization theory is first presented in the Ramadge–Wonham language-based supervisory control framework, then demonstrated with distributed control examples of multi-robot formations, manufacturing systems, and distributed algorithms. An architectural approach is adopted to apply localization to large-scale DES; this yields a heterarchical localization procedure, which is...

  7. Top-down approach from satellite to terrestrial rover application for environmental monitoring of landfills.

    Science.gov (United States)

    Manzo, C; Mei, A; Zampetti, E; Bassani, C; Paciucci, L; Manetti, P

    2017-04-15

    This paper describes a methodology to perform chemical analyses in landfill areas by integrating multisource geomatic data. We used a top-down approach to identify Environmental Point of Interest (EPI) based on very high-resolution satellite data (Pleiades and WorldView 2) and on in situ thermal and photogrammetric surveys. Change detection techniques and geostatistical analysis supported the chemical survey, undertaken using an accumulation chamber and an RIIA, an unmanned ground vehicle developed by CNR IIA, equipped with a multiparameter sensor platform for environmental monitoring. Such an approach improves site characterization, identifying the key environmental points of interest where it is necessary to perform detailed chemical analyses. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. A top-down approach to crystal engineering of a racemic Δ2-isoxazoline.

    Science.gov (United States)

    Lombardo, Giuseppe M; Rescifina, Antonio; Chiacchio, Ugo; Bacchi, Alessia; Punzo, Francesco

    2014-02-01

    The crystal structure of racemic dimethyl (4RS,5RS)-3-(4-nitrophenyl)-4,5-dihydroisoxazole-4,5-dicarboxylate, C13H12N2O7, has been determined by single-crystal X-ray diffraction. By analysing the degree of growth of the morphologically important crystal faces, a ranking of the most relevant non-covalent interactions determining the crystal structure can be inferred. The morphological information is considered with an approach opposite to the conventional one: instead of searching inside the structure for the potential key interactions and using them to calculate the crystal habit, the observed crystal morphology is used to define the preferential lines of growth of the crystal, and then this information is interpreted by means of density functional theory (DFT) calculations. Comparison with the X-ray structure confirms the validity of the strategy, thus suggesting this top-down approach to be a useful tool for crystal engineering.

  9. Manipulation of strain state in silicon nanoribbons by top-down approach

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Zhiqiang; Zhang, Miao; Xue, Zhongying; Sun, Gaodi; Guo, Qinglei; Chen, Da; Di, Zengfeng, E-mail: zfdi@mail.sim.ac.cn; Wang, Xi [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Huang, Gaoshan; Mei, Yongfeng [Department of Materials Science, Fudan University, Shanghai 200433 (China); Chu, Paul K. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong (China)

    2015-04-27

    Tensile strain is often utilized to enhance the electron mobility and luminescent characteristics of semiconductors. A top-down approach in conjunction with roll-up technology is adopted to produce high tensile strain in Si nanoribbons by patterning and releasing of the bridge-like structures. The tensile strain can be altered between uniaxial state and biaxial state by adjusting the dimensions of the patterns and can be varied controllably up to 3.2% and 0.9% for the uniaxial- and biaxial-strained Si nanoribbons, respectively. Three-dimensional finite element analysis is performed to investigate the mechanism of strain generation during patterning and releasing of the structure. Since the process mainly depends on the geometrical factors, the technique can be readily extended to other types of mechanical, electrical, and optical membranes.

  10. A top-down approach for the prediction of hardness and toughness of hierarchical materials

    International Nuclear Information System (INIS)

    Carpinteri, Alberto; Paggi, Marco

    2009-01-01

    Many natural and man-made materials exhibit structure over more than one length scale. In this paper, we deal with hierarchical grained composite materials that have recently been designed to achieve superior hardness and toughness as compared to their traditional counterparts. Their nested structure, where meso-grains are recursively composed of smaller and smaller micro-grains at the different scales with a fractal-like topology, is herein studied from a hierarchical perspective. Considering a top-down approach, i.e. from the largest to the smallest scale, we propose a recursive micromechanical model coupled with a generalized fractal mixture rule for the prediction of hardness and toughness of a grained material with n hierarchical levels. A relationship between hardness and toughness is also derived and the analytical predictions are compared with experimental data.

  11. Top-down approach in protein RDC data analysis: de novo estimation of the alignment tensor

    International Nuclear Information System (INIS)

    Chen Kang; Tjandra, Nico

    2007-01-01

    In solution NMR spectroscopy the residual dipolar coupling (RDC) is invaluable in improving both the precision and accuracy of NMR structures during their structural refinement. The RDC also provides a potential to determine protein structure de novo. These procedures are only effective when an accurate estimate of the alignment tensor has already been made. Here we present a top-down approach, starting from the secondary structure elements and finishing at the residue level, for RDC data analysis in order to obtain a better estimate of the alignment tensor. Using only the RDCs from N-H bonds of residues in α-helices and CA-CO bonds in β-strands, we are able to determine the offset and the approximate amplitude of the RDC modulation-curve for each secondary structure element, which are subsequently used as targets for global minimization. The alignment order parameters and the orientation of the major principal axis of individual helix or strand, with respect to the alignment frame, can be determined in each of the eight quadrants of a sphere. The following minimization against RDC of all residues within the helix or strand segment can be carried out with fixed alignment order parameters to improve the accuracy of the orientation. For a helical protein Bax, the three components A xx , A yy and A zz , of the alignment order can be determined with this method in average to within 2.3% deviation from the values calculated with the available atomic coordinates. Similarly for β-sheet protein Ubiquitin they agree in average to within 8.5%. The larger discrepancy in β-strand parameters comes from both the diversity of the β-sheet structure and the lower precision of CA-CO RDCs. This top-down approach is a robust method for alignment tensor estimation and also holds a promise for providing a protein topological fold using limited sets of RDCs

  12. Characterization of the Vibrio cholerae extracellular matrix: a top-down solid-state NMR approach.

    Science.gov (United States)

    Reichhardt, Courtney; Fong, Jiunn C N; Yildiz, Fitnat; Cegelski, Lynette

    2015-01-01

    Bacterial biofilms are communities of bacterial cells surrounded by a self-secreted extracellular matrix. Biofilm formation by Vibrio cholerae, the human pathogen responsible for cholera, contributes to its environmental survival and infectivity. Important genetic and molecular requirements have been identified for V. cholerae biofilm formation, yet a compositional accounting of these parts in the intact biofilm or extracellular matrix has not been described. As insoluble and non-crystalline assemblies, determinations of biofilm composition pose a challenge to conventional biochemical and biophysical analyses. The V. cholerae extracellular matrix composition is particularly complex with several proteins, complex polysaccharides, and other biomolecules having been identified as matrix parts. We developed a new top-down solid-state NMR approach to spectroscopically assign and quantify the carbon pools of the intact V. cholerae extracellular matrix using ¹³C CPMAS and ¹³C{(¹⁵N}, ¹⁵N{³¹P}, and ¹³C{³¹P}REDOR. General sugar, lipid, and amino acid pools were first profiled and then further annotated and quantified as specific carbon types, including carbonyls, amides, glycyl carbons, and anomerics. In addition, ¹⁵N profiling revealed a large amine pool relative to amide contributions, reflecting the prevalence of molecular modifications with free amine groups. Our top-down approach could be implemented immediately to examine the extracellular matrix from mutant strains that might alter polysaccharide production or lipid release beyond the cell surface; or to monitor changes that may accompany environmental variations and stressors such as altered nutrient composition, oxidative stress or antibiotics. More generally, our analysis has demonstrated that solid-state NMR is a valuable tool to characterize complex biofilm systems. Copyright © 2014. Published by Elsevier B.V.

  13. Metabolic Network Discovery by Top-Down and Bottom-Up Approaches and Paths for Reconciliation

    Energy Technology Data Exchange (ETDEWEB)

    Çakır, Tunahan, E-mail: tcakir@gyte.edu.tr [Computational Systems Biology Group, Department of Bioengineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey); Khatibipour, Mohammad Jafar [Computational Systems Biology Group, Department of Bioengineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey); Department of Chemical Engineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey)

    2014-12-03

    The primary focus in the network-centric analysis of cellular metabolism by systems biology approaches is to identify the active metabolic network for the condition of interest. Two major approaches are available for the discovery of the condition-specific metabolic networks. One approach starts from genome-scale metabolic networks, which cover all possible reactions known to occur in the related organism in a condition-independent manner, and applies methods such as the optimization-based Flux-Balance Analysis to elucidate the active network. The other approach starts from the condition-specific metabolome data, and processes the data with statistical or optimization-based methods to extract information content of the data such that the active network is inferred. These approaches, termed bottom-up and top-down, respectively, are currently employed independently. However, considering that both approaches have the same goal, they can both benefit from each other paving the way for the novel integrative analysis methods of metabolome data- and flux-analysis approaches in the post-genomic era. This study reviews the strengths of constraint-based analysis and network inference methods reported in the metabolic systems biology field; then elaborates on the potential paths to reconcile the two approaches to shed better light on how the metabolism functions.

  14. Metabolic Network Discovery by Top-Down and Bottom-Up Approaches and Paths for Reconciliation

    International Nuclear Information System (INIS)

    Çakır, Tunahan; Khatibipour, Mohammad Jafar

    2014-01-01

    The primary focus in the network-centric analysis of cellular metabolism by systems biology approaches is to identify the active metabolic network for the condition of interest. Two major approaches are available for the discovery of the condition-specific metabolic networks. One approach starts from genome-scale metabolic networks, which cover all possible reactions known to occur in the related organism in a condition-independent manner, and applies methods such as the optimization-based Flux-Balance Analysis to elucidate the active network. The other approach starts from the condition-specific metabolome data, and processes the data with statistical or optimization-based methods to extract information content of the data such that the active network is inferred. These approaches, termed bottom-up and top-down, respectively, are currently employed independently. However, considering that both approaches have the same goal, they can both benefit from each other paving the way for the novel integrative analysis methods of metabolome data- and flux-analysis approaches in the post-genomic era. This study reviews the strengths of constraint-based analysis and network inference methods reported in the metabolic systems biology field; then elaborates on the potential paths to reconcile the two approaches to shed better light on how the metabolism functions.

  15. Top-down proteomics with mass spectrometry imaging: a pilot study towards discovery of biomarkers for neurodevelopmental disorders.

    Directory of Open Access Journals (Sweden)

    Hui Ye

    Full Text Available In the developing mammalian brain, inhibition of NMDA receptor can induce widespread neuroapoptosis, inhibit neurogenesis and cause impairment of learning and memory. Although some mechanistic insights into adverse neurological actions of these NMDA receptor antagonists exist, our understanding of the full spectrum of developmental events affected by early exposure to these chemical agents in the brain is still limited. Here we attempt to gain insights into the impact of pharmacologically induced excitatory/inhibitory imbalance in infancy on the brain proteome using mass spectrometric imaging (MSI. Our goal was to study changes in protein expression in postnatal day 10 (P10 rat brains following neonatal exposure to the NMDA receptor antagonist dizocilpine (MK801. Analysis of rat brains exposed to vehicle or MK801 and comparison of their MALDI MS images revealed differential relative abundances of several proteins. We then identified these markers such as ubiquitin, purkinje cell protein 4 (PEP-19, cytochrome c oxidase subunits and calmodulin, by a combination of reversed-phase (RP HPLC fractionation and top-down tandem MS platform. More in-depth large scale study along with validation experiments will be carried out in the future. Overall, our findings indicate that a brief neonatal exposure to a compound that alters excitatory/inhibitory balance in the brain has a long term effect on protein expression patterns during subsequent development, highlighting the utility of MALDI-MSI as a discovery tool for potential biomarkers.

  16. Critical appraisal of the top-down approach for vesicoureteral reflux.

    Science.gov (United States)

    Abdelhalim, Ahmed; Khoury, Antoine E

    2017-06-01

    Vesicoureteral reflux (VUR) has been linked to recurrent urinary tract infections (UTIs), renal scarring, hypertension, renal insufficiency and end-stage kidney disease. Different imaging strategies have been proposed to approach children presenting with UTI to sort out patients with significant VUR while minimizing patient morbidity, radiation exposure and financial burden. None of these imaging strategies is universally accepted. The"top-down approach" (TDA) aims at restricting the number of voiding cystourethrograms (VCUGs) and its associated morbidity while identifying patients with clinically-significant reflux. In this approach, children presenting with febrile UTIs are acutely investigated with dimercapto-succinic acid (DMSA) renal scans to identify patients with renal parenchymal inflammation. Those with evidence of renal affection are offered VCUG and late DMSA scan to identify VUR and permanent renal scarring, respectively. Although TDA could identify clinically-significant VUR with high sensitivity, it is not without limitations. The approach segregates patients based on the presence of DMSA cortical lesions omitting the morbidity and the economic burden of UTI. Additionally, some of DMSA lesions are attributed to congenital dysplasia and unrelated to UTI. Ionizing radiation exposure, financial costs, limited availability of DMSA scans in the acute setting, variability in interpreting the results and low yield of actionable findings on DMSA scans are some other limitations. In this review, we tried to address the drawbacks of the TDA and reinforce the value of patient-centered approach for VUR.

  17. Critical appraisal of the top-down approach for vesicoureteral reflux

    Directory of Open Access Journals (Sweden)

    Ahmed Abdelhalim

    2017-06-01

    Full Text Available Vesicoureteral reflux (VUR has been linked to recurrent urinary tract infections (UTIs, renal scarring, hypertension, renal insufficiency and end-stage kidney disease. Different imaging strategies have been proposed to approach children presenting with UTI to sort out patients with significant VUR while minimizing patient morbidity, radiation exposure and financial burden. None of these imaging strategies is universally accepted. The “top-down approach” (TDA aims at restricting the number of voiding cystourethrograms (VCUGs and its associated morbidity while identifying patients with clinically-significant reflux. In this approach, children presenting with febrile UTIs are acutely investigated with dimercapto-succinic acid (DMSA renal scans to identify patients with renal parenchymal inflammation. Those with evidence of renal affection are offered VCUG and late DMSA scan to identify VUR and permanent renal scarring, respectively. Although TDA could identify clinically-significant VUR with high sensitivity, it is not without limitations. The approach segregates patients based on the presence of DMSA cortical lesions omitting the morbidity and the economic burden of UTI. Additionally, some of DMSA lesions are attributed to congenital dysplasia and unrelated to UTI. Ionizing radiation exposure, financial costs, limited availability of DMSA scans in the acute setting, variability in interpreting the results and low yield of actionable findings on DMSA scans are some other limitations. In this review, we tried to address the drawbacks of the TDA and reinforce the value of patient-centered approach for VUR.

  18. A mass graph-based approach for the identification of modified proteoforms using top-down tandem mass spectra.

    Science.gov (United States)

    Kou, Qiang; Wu, Si; Tolic, Nikola; Paša-Tolic, Ljiljana; Liu, Yunlong; Liu, Xiaowen

    2017-05-01

    Although proteomics has rapidly developed in the past decade, researchers are still in the early stage of exploring the world of complex proteoforms, which are protein products with various primary structure alterations resulting from gene mutations, alternative splicing, post-translational modifications, and other biological processes. Proteoform identification is essential to mapping proteoforms to their biological functions as well as discovering novel proteoforms and new protein functions. Top-down mass spectrometry is the method of choice for identifying complex proteoforms because it provides a 'bird's eye view' of intact proteoforms. The combinatorial explosion of various alterations on a protein may result in billions of possible proteoforms, making proteoform identification a challenging computational problem. We propose a new data structure, called the mass graph, for efficient representation of proteoforms and design mass graph alignment algorithms. We developed TopMG, a mass graph-based software tool for proteoform identification by top-down mass spectrometry. Experiments on top-down mass spectrometry datasets showed that TopMG outperformed existing methods in identifying complex proteoforms. http://proteomics.informatics.iupui.edu/software/topmg/. xwliu@iupui.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  19. Assessing a Top-Down Modeling Approach for Seasonal Scale Snow Sensitivity

    Science.gov (United States)

    Luce, C. H.; Lute, A.

    2017-12-01

    Mechanistic snow models are commonly applied to assess changes to snowpacks in a warming climate. Such assessments involve a number of assumptions about details of weather at daily to sub-seasonal time scales. Models of season-scale behavior can provide contrast for evaluating behavior at time scales more in concordance with climate warming projections. Such top-down models, however, involve a degree of empiricism, with attendant caveats about the potential of a changing climate to affect calibrated relationships. We estimated the sensitivity of snowpacks from 497 Snowpack Telemetry (SNOTEL) stations in the western U.S. based on differences in climate between stations (spatial analog). We examined the sensitivity of April 1 snow water equivalent (SWE) and mean snow residence time (SRT) to variations in Nov-Mar precipitation and average Nov-Mar temperature using multivariate local-fit regressions. We tested the modeling approach using a leave-one-out cross-validation as well as targeted two-fold non-random cross-validations contrasting, for example, warm vs. cold years, dry vs. wet years, and north vs. south stations. Nash-Sutcliffe Efficiency (NSE) values for the validations were strong for April 1 SWE, ranging from 0.71 to 0.90, and still reasonable, but weaker, for SRT, in the range of 0.64 to 0.81. From these ranges, we exclude validations where the training data do not represent the range of target data. A likely reason for differences in validation between the two metrics is that the SWE model reflects the influence of conservation of mass while using temperature as an indicator of the season-scale energy balance; in contrast, SRT depends more strongly on the energy balance aspects of the problem. Model forms with lower numbers of parameters generally validated better than more complex model forms, with the caveat that pseudoreplication could encourage selection of more complex models when validation contrasts were weak. Overall, the split sample validations

  20. A combined bottom-up/top-down approach to prepare a sterile injectable nanosuspension.

    Science.gov (United States)

    Hu, Xi; Chen, Xi; Zhang, Ling; Lin, Xia; Zhang, Yu; Tang, Xing; Wang, Yanjiao

    2014-09-10

    To prepare a uniform nanosuspension of strongly hydrophobic riboflavin laurate (RFL) allowing sterile filtration, physical modification (bottom-up) was combined with high-pressure homogenization (top-down) method. Unlike other bottom-up approaches, physical modification with surfactants (TPGS and PL-100) by lyophilization controlled crystallization and compensated for the poor wettability of RFL. On one hand, crystal growth and aggregation during freezing was restricted by a stabilizer-layer adsorbed on the drug surface by hydrophobic interaction. On the other hand, subsequent crystallization of drug in the sublimation process was limited to the interstitial spaces between solvent crystals. After lyophilization, modified drug with a smaller particle size and better wettability was obtained. When adding surfactant solution, water molecules passed between the hydrophilic groups of surface active molecules and activated the polymer chains allowing them to stretch into water. The coarse suspension was crushed into a nanosuspension (MP=162 nm) by high-pressure homogenization. For long term stability, lyophilization was applied again to solidify the nanosuspension (sorbitol as cryoprotectant). A slight crystal growth to about 600 nm was obtained to allow slow release for a sustained effect after muscular administration. Moreover, no paw-licking responses and very slight muscular inflammation demonstrated the excellent biocompatibility of this long-acting RFL injection. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Spongy Gels by a Top-Down Approach from Polymer Fibrous Sponges.

    Science.gov (United States)

    Jiang, Shaohua; Duan, Gaigai; Kuhn, Ute; Mörl, Michaela; Altstädt, Volker; Yarin, Alexander L; Greiner, Andreas

    2017-03-13

    Ultralight cellular sponges offer a unique set of properties. We show here that solvent uptake by these sponges results in new gel-like materials, which we term spongy gels. The appearance of the spongy gels is very similar to classic organogels. Usually, organogels are formed by a bottom-up process. In contrast, the spongy gels are formed by a top-down approach that offers numerous advantages for the design of their properties, reproducibility, and stability. The sponges themselves represent the scaffold of a gel that could be filled with a solvent, and thereby form a mechanically stable gel-like material. The spongy gels are independent of a time-consuming or otherwise demanding in situ scaffold formation. As solvent evaporation from gels is a concern for various applications, we also studied solvent evaporation of wetting and non-wetting liquids dispersed in the sponge. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  2. Integrating the bottom-up and top-down approach to energy economy modelling. The case of Denmark

    DEFF Research Database (Denmark)

    Klinge Jacobsen, Henrik

    1998-01-01

    This paper presents results from an integration project covering Danish models based on bottom-up and top-down approaches to energy]economy modelling. The purpose of the project was to identify theoretical and methodological problems for integrating existing models for Denmark and to implement...... an integration of the models. The integration was established through a number of links between energy bottom-up modules and a macroeconomic model. In this integrated model it is possible to analyse both top-down instruments, such as taxes along with bottom-up instruments, such as regulation of technology...

  3. Top-down and bottom-up approaches for cost estimating new reactor designs

    International Nuclear Information System (INIS)

    Berbey, P.; Gautier, G.M.; Duflo, D.; Rouyer, J.L.

    2007-01-01

    For several years, Generation-4 designs will be 'pre-conceptual' for the less mature concepts and 'preliminary' for the more mature concepts. In this situation, appropriate data for some of the plant systems may be lacking to develop a bottom-up cost estimate. Therefore, a more global approach, the Top-Down Approach (TDA), is needed to help the designers and decision makers in comparing design options. It utilizes more or less simple models for cost estimating the different parts of a design. TDA cost estimating effort applies to a whole functional element whose cost is approached by similar estimations coming from existing data, ratios and models, for a given range of variation of parameters. Modeling is used when direct analogy is not possible. There are two types of models, global and specific ones. Global models are applied to cost modules related to Code Of Account. Exponential formulae such as Ci = Ai + (Bi x Pi n ) are used when there are cost data for comparable modules in nuclear or other industries. Specific cost models are developed for major specific components of the plant: - process equipment such as reactor vessel, steam generators or large heat exchangers. - buildings, with formulae estimating the construction cost from base cost of m3 of building volume. - systems, when unit costs, cost ratios and models are used, depending on the level of detail of the design. Bottom Up Approach (BUA), which is based on unit prices coming from similar equipment or from manufacturer consulting, is very valuable and gives better cost estimations than TDA when it can be applied, that is at a rather late stage of the design. Both approaches are complementary when some parts of the design are detailed enough to be estimated by BUA, and when BUA results are used to check TDA results and to improve TDA models. This methodology is applied to the HTR (High Temperature Reactor) concept and to an advanced PWR design

  4. Rehabilitation of gait after stroke: a review towards a top-down approach

    Science.gov (United States)

    2011-01-01

    This document provides a review of the techniques and therapies used in gait rehabilitation after stroke. It also examines the possible benefits of including assistive robotic devices and brain-computer interfaces in this field, according to a top-down approach, in which rehabilitation is driven by neural plasticity. The methods reviewed comprise classical gait rehabilitation techniques (neurophysiological and motor learning approaches), functional electrical stimulation (FES), robotic devices, and brain-computer interfaces (BCI). From the analysis of these approaches, we can draw the following conclusions. Regarding classical rehabilitation techniques, there is insufficient evidence to state that a particular approach is more effective in promoting gait recovery than other. Combination of different rehabilitation strategies seems to be more effective than over-ground gait training alone. Robotic devices need further research to show their suitability for walking training and their effects on over-ground gait. The use of FES combined with different walking retraining strategies has shown to result in improvements in hemiplegic gait. Reports on non-invasive BCIs for stroke recovery are limited to the rehabilitation of upper limbs; however, some works suggest that there might be a common mechanism which influences upper and lower limb recovery simultaneously, independently of the limb chosen for the rehabilitation therapy. Functional near infrared spectroscopy (fNIRS) enables researchers to detect signals from specific regions of the cortex during performance of motor activities for the development of future BCIs. Future research would make possible to analyze the impact of rehabilitation on brain plasticity, in order to adapt treatment resources to meet the needs of each patient and to optimize the recovery process. PMID:22165907

  5. Pharmacy-based statewide naloxone distribution: A novel "top-down, bottom-up" approach.

    Science.gov (United States)

    Morton, Kate J; Harrand, Brianna; Floyd, Carly Cloud; Schaefer, Craig; Acosta, Julie; Logan, Bridget Claire; Clark, Karen

    To highlight New Mexico's multifaceted approach to widespread pharmacy naloxone distribution and to share the interventions as a tool for improving pharmacy-based naloxone practices in other states. New Mexico had the second highest drug overdose death rate in 2014 of which 53% were related to prescription opioids. Opioid overdose death is preventable through the use of naloxone, a safe and effective medication that reverses the effects of prescription opioids and heroin. Pharmacists can play an important role in providing naloxone to individuals who use prescription opioids. Not applicable. Not applicable. A multifaceted approach was utilized in New Mexico from the top down with legislative passage of provisions for a statewide standing order and New Mexico Department of Health support for pharmacy-based naloxone delivery. A bottom up approach was also initiated with the development and implementation of a training program for pharmacists and pharmacy technicians. Naloxone Medicaid claims were used to illustrate statewide distribution and utilization of the pharmacist statewide standing order for naloxone. Percent of pharmacies dispensing naloxone in each county were calculated. Trained pharmacy staff completed a program evaluation form. Questions about quality of instruction and ability of trainer to meet stated objectives were rated on a Likert scale. There were 808 naloxone Medicaid claims from 100 outpatient pharmacies during the first half of 2016, a 9-fold increase over 2014. The "A Dose of R x eality" training program evaluation indicated that participants felt the training was free from bias and met all stated objectives (4 out of 4 on Likert scale). A multi-pronged approach coupling state and community collaboration was successful in overcoming barriers and challenges associated with pharmacy naloxone distribution and ensured its success as an effective avenue for naloxone acquisition in urban and rural communities. Copyright © 2017 American Pharmacists

  6. Rehabilitation of gait after stroke: a review towards a top-down approach

    Directory of Open Access Journals (Sweden)

    Belda-Lois Juan-Manuel

    2011-12-01

    Full Text Available Abstract This document provides a review of the techniques and therapies used in gait rehabilitation after stroke. It also examines the possible benefits of including assistive robotic devices and brain-computer interfaces in this field, according to a top-down approach, in which rehabilitation is driven by neural plasticity. The methods reviewed comprise classical gait rehabilitation techniques (neurophysiological and motor learning approaches, functional electrical stimulation (FES, robotic devices, and brain-computer interfaces (BCI. From the analysis of these approaches, we can draw the following conclusions. Regarding classical rehabilitation techniques, there is insufficient evidence to state that a particular approach is more effective in promoting gait recovery than other. Combination of different rehabilitation strategies seems to be more effective than over-ground gait training alone. Robotic devices need further research to show their suitability for walking training and their effects on over-ground gait. The use of FES combined with different walking retraining strategies has shown to result in improvements in hemiplegic gait. Reports on non-invasive BCIs for stroke recovery are limited to the rehabilitation of upper limbs; however, some works suggest that there might be a common mechanism which influences upper and lower limb recovery simultaneously, independently of the limb chosen for the rehabilitation therapy. Functional near infrared spectroscopy (fNIRS enables researchers to detect signals from specific regions of the cortex during performance of motor activities for the development of future BCIs. Future research would make possible to analyze the impact of rehabilitation on brain plasticity, in order to adapt treatment resources to meet the needs of each patient and to optimize the recovery process.

  7. Sodium-cutting: a new top-down approach to cut open nanostructures on nonplanar surfaces on a large scale.

    Science.gov (United States)

    Chen, Wei; Deng, Da

    2014-11-11

    We report a new, low-cost and simple top-down approach, "sodium-cutting", to cut and open nanostructures deposited on a nonplanar surface on a large scale. The feasibility of sodium-cutting was demonstrated with the successfully cutting open of ∼100% carbon nanospheres into nanobowls on a large scale from Sn@C nanospheres for the first time.

  8. Changing physician perspectives on complementary and alternative medicine: the need for a top-down approach

    Directory of Open Access Journals (Sweden)

    MacKinnon TS

    2017-09-01

    Full Text Available Thomas S MacKinnon,1 Norbert F Banhidy,1 Daniel R Tuite21School of Medicine, Imperial College London, London, 2Faculty of Medicine, Brighton and Sussex Medical School, Brighton, UKWe read with great interest the article by Patel et al1 discussing the changing perspectives towards complementary and alternative medicine (CAM, and an impetus for additional physician knowledge of the strengths and drawbacks of CAM. These findings are indeed relevant in the UK, with an estimated 41.1% one-year prevalence of CAM use, responsible for an annual out-of-pocket expenditure of £1.6 billion.2 We agree that improved training and education in medical school and residencies – which can be thought of as a “bottom-up” approach – are fundamental in preparing the health care system for improved integration of CAM. However, we also suggest that “top-down” changes are required to optimize patient care.Authors' reply Sejal J Patel,1 Kathi J Kemper,2 Joseph P Kitzmiller31College of Public Health, The Ohio State University, 2Center for Integrative Health and Wellness, The Ohio State Wexner University Medical Center, 3Department of Biological Chemistry and Pharmacology, College of Medicine, The Ohio State University, Columbus, OH, USAWe agree the letter is worthy of publication but have a little to add: a top-down approach (as suggested and described by the authors of the letter certainly complements the bottom-up approach (described in our article.1View the original paper by Patel et al.

  9. Efficacy of top-down approaches to post-conflict social coexistence ...

    African Journals Online (AJOL)

    This paper provides an assessment of the work done by the Organ on National Healing, Reconciliation and Integration (ONHRI) in post- 2008 Zimbabwe. ONHRI was employed by the Zimbabwean government (precisely as Government of National Unity) to ensure national healing and integration. The efficacy of top-down ...

  10. Biodiversity mediates top-down control in eelgrass ecosystems: a global comparative-experimental approach.

    Science.gov (United States)

    Duffy, J Emmett; Reynolds, Pamela L; Boström, Christoffer; Coyer, James A; Cusson, Mathieu; Donadi, Serena; Douglass, James G; Eklöf, Johan S; Engelen, Aschwin H; Eriksson, Britas Klemens; Fredriksen, Stein; Gamfeldt, Lars; Gustafsson, Camilla; Hoarau, Galice; Hori, Masakazu; Hovel, Kevin; Iken, Katrin; Lefcheck, Jonathan S; Moksnes, Per-Olav; Nakaoka, Masahiro; O'Connor, Mary I; Olsen, Jeanine L; Richardson, J Paul; Ruesink, Jennifer L; Sotka, Erik E; Thormar, Jonas; Whalen, Matthew A; Stachowicz, John J

    2015-07-01

    Nutrient pollution and reduced grazing each can stimulate algal blooms as shown by numerous experiments. But because experiments rarely incorporate natural variation in environmental factors and biodiversity, conditions determining the relative strength of bottom-up and top-down forcing remain unresolved. We factorially added nutrients and reduced grazing at 15 sites across the range of the marine foundation species eelgrass (Zostera marina) to quantify how top-down and bottom-up control interact with natural gradients in biodiversity and environmental forcing. Experiments confirmed modest top-down control of algae, whereas fertilisation had no general effect. Unexpectedly, grazer and algal biomass were better predicted by cross-site variation in grazer and eelgrass diversity than by global environmental gradients. Moreover, these large-scale patterns corresponded strikingly with prior small-scale experiments. Our results link global and local evidence that biodiversity and top-down control strongly influence functioning of threatened seagrass ecosystems, and suggest that biodiversity is comparably important to global change stressors. © 2015 John Wiley & Sons Ltd/CNRS.

  11. MOD/R : A knowledge assisted approach towards top-down only CMOS VLSI design

    NARCIS (Netherlands)

    Spaanenburg, L.; Beunder, M.; Beune, F.A.; Gerez, Sabih H.; Holstein, B.; Luchtmeyer, R.C.C.; Smit, Jaap; van der Werf, A.; Willems, H.

    1985-01-01

    MOD/R models all views on the design space in relations. This is achieved by eliminating the package constraints, as are apparent in PCB oriented hardware description languages. Assisted by knowledge engineering it allows for a top-down, mostly hierarchical decomposition, virtually eliminating the

  12. A top-down approach for fabricating free-standing bio-carbon supercapacitor electrodes with a hierarchical structure

    OpenAIRE

    Yingzhi Li; Qinghua Zhang; Junxian Zhang; Lei Jin; Xin Zhao; Ting Xu

    2015-01-01

    Biomass has delicate hierarchical structures, which inspired us to develop a cost-effective route to prepare electrode materials with rational nanostructures for use in high-performance storage devices. Here, we demonstrate a novel top-down approach for fabricating bio-carbon materials with stable structures and excellent diffusion pathways; this approach is based on carbonization with controlled chemical activation. The developed free-standing bio-carbon electrode exhibits a high specific ca...

  13. Validity of the top-down approach of inverse dynamics analysis in fast and large rotational trunk movements.

    Science.gov (United States)

    Iino, Yoichi; Kojima, Takeji

    2012-08-01

    This study investigated the validity of the top-down approach of inverse dynamics analysis in fast and large rotational movements of the trunk about three orthogonal axes of the pelvis for nine male collegiate students. The maximum angles of the upper trunk relative to the pelvis were approximately 47°, 49°, 32°, and 55° for lateral bending, flexion, extension, and axial rotation, respectively, with maximum angular velocities of 209°/s, 201°/s, 145°/s, and 288°/s, respectively. The pelvic moments about the axes during the movements were determined using the top-down and bottom-up approaches of inverse dynamics and compared between the two approaches. Three body segment inertial parameter sets were estimated using anthropometric data sets (Ae et al., Biomechanism 11, 1992; De Leva, J Biomech, 1996; Dumas et al., J Biomech, 2007). The root-mean-square errors of the moments and the absolute errors of the peaks of the moments were generally smaller than 10 N·m. The results suggest that the pelvic moment in motions involving fast and large trunk movements can be determined with a certain level of validity using the top-down approach in which the trunk is modeled as two or three rigid-link segments.

  14. Supervisor Localization: A Top-Down Approach to Distributed Control of Discrete-Event Systems

    International Nuclear Information System (INIS)

    Cai, K.; Wonham, W. M.

    2009-01-01

    A purely distributed control paradigm is proposed for discrete-event systems (DES). In contrast to control by one or more external supervisors, distributed control aims to design built-in strategies for individual agents. First a distributed optimal nonblocking control problem is formulated. To solve it, a top-down localization procedure is developed which systematically decomposes an external supervisor into local controllers while preserving optimality and nonblockingness. An efficient localization algorithm is provided to carry out the computation, and an automated guided vehicles (AGV) example presented for illustration. Finally, the 'easiest' and 'hardest' boundary cases of localization are discussed.

  15. Top-down approach for nanophase reconstruction in bulk heterojunction solar cells.

    Science.gov (United States)

    Kong, Jaemin; Hwang, In-Wook; Lee, Kwanghee

    2014-09-01

    "Top-Down" nanophase reconstruction via a post-additive soaking process is first presented with various BHJ binary composites. By simply rinsing as-cast BHJ films with a solvent mixture containing a few traces of a nanophase-control reagent such as 1,8-diiodooctane, oversized fullerene-rich clusters (>100 nm in dia-meter) in the BHJ film are instataneously disassembled and entirely reorganized into finely intermixed donor/acceptor nanophases (ca. 10 nm) with a 3D compositional homogeneity, without surface segregation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. A top-down approach for fabricating three-dimensional closed hollow nanostructures with permeable thin metal walls.

    Science.gov (United States)

    Barrios, Carlos Angulo; Canalejas-Tejero, Víctor

    2017-01-01

    We report on a top-down method for the controlled fabrication of three-dimensional (3D), closed, thin-shelled, hollow nanostructures (nanocages) on planar supports. The presented approach is based on conventional microelectronic fabrication processes and exploits the permeability of thin metal films to hollow-out polymer-filled metal nanocages through an oxygen-plasma process. The technique is used for fabricating arrays of cylindrical nanocages made of thin Al shells on silicon substrates. This hollow metal configuration features optical resonance as revealed by spectral reflectance measurements and numerical simulations. The fabricated nanocages were demonstrated as a refractometric sensor with a measured bulk sensitivity of 327 nm/refractive index unit (RIU). The pattern design flexibility and controllability offered by top-down nanofabrication techniques opens the door to the possibility of massive integration of these hollow 3D nano-objects on a chip for applications such as nanocontainers, nanoreactors, nanofluidics, nano-biosensors and photonic devices.

  17. Automatic Polyp Detection via A Novel Unified Bottom-up and Top-down Saliency Approach.

    Science.gov (United States)

    Yuan, Yixuan; Li, Dengwang; Meng, Max Q-H

    2017-07-31

    In this paper, we propose a novel automatic computer-aided method to detect polyps for colonoscopy videos. To find the perceptually and semantically meaningful salient polyp regions, we first segment images into multilevel superpixels. Each level corresponds to different sizes of superpixels. Rather than adopting hand-designed features to describe these superpixels in images, we employ sparse autoencoder (SAE) to learn discriminative features in an unsupervised way. Then a novel unified bottom-up and top-down saliency method is proposed to detect polyps. In the first stage, we propose a weak bottom-up (WBU) saliency map by fusing the contrast based saliency and object-center based saliency together. The contrast based saliency map highlights image parts that show different appearances compared with surrounding areas while the object-center based saliency map emphasizes the center of the salient object. In the second stage, a strong classifier with Multiple Kernel Boosting (MKB) is learned to calculate the strong top-down (STD) saliency map based on samples directly from the obtained multi-level WBU saliency maps. We finally integrate these two stage saliency maps from all levels together to highlight polyps. Experiment results achieve 0.818 recall for saliency calculation, validating the effectiveness of our method. Extensive experiments on public polyp datasets demonstrate that the proposed saliency algorithm performs favorably against state-of-the-art saliency methods to detect polyps.

  18. Comparison of the top-down and bottom-up approach to fabricate nanowire-based Silicon/Germanium heterostructures

    International Nuclear Information System (INIS)

    Wolfsteller, A.; Geyer, N.; Nguyen-Duc, T.-K.; Das Kanungo, P.; Zakharov, N.D.; Reiche, M.; Erfurth, W.; Blumtritt, H.; Werner, P.; Goesele, U.

    2010-01-01

    Silicon nanowires (NWs) and vertical nanowire-based Si/Ge heterostructures are expected to be building blocks for future devices, e.g. field-effect transistors or thermoelectric elements. In principle two approaches can be applied to synthesise these NWs: the 'bottom-up' and the 'top-down' approach. The most common method for the former is the vapour-liquid-solid (VLS) mechanism which can also be applied to grow NWs by molecular beam epitaxy (MBE). Although MBE allows a precise growth control under highly reproducible conditions, the general nature of the growth process via a eutectic droplet prevents the synthesis of heterostructures with sharp interfaces and high Ge concentrations. We compare the VLS NW growth with two different top-down methods: The first is a combination of colloidal lithography and metal-assisted wet chemical etching, which is an inexpensive and fast method and results in large arrays of homogenous Si NWs with adjustable diameters down to 50 nm. The second top-down method combines the growth of Si/Ge superlattices by MBE with electron beam lithography and reactive ion etching. Again, large and homogeneous arrays of NWs were created, this time with a diameter of 40 nm and the Si/Ge superlattice inside.

  19. Controlled synthesis of organic single-crystalline nanowires via the synergy approach of the bottom-up/top-down processes.

    Science.gov (United States)

    Zhuo, Ming-Peng; Zhang, Ye-Xin; Li, Zhi-Zhou; Shi, Ying-Li; Wang, Xue-Dong; Liao, Liang-Sheng

    2018-03-15

    The controlled fabrication of organic single-crystalline nanowires (OSCNWs) with a uniform diameter in the nanoscale via the bottom-up approach, which is just based on weak intermolecular interaction, is a great challenge. Herein, we utilize the synergy approach of the bottom-up and the top-down processes to fabricate OSCNWs with diameters of 120 ± 10 nm through stepwise evolution processes. Specifically, the evolution processes vary from the self-assembled organic micro-rods with a quadrangular pyramid-like end-structure bounded with {111}s and {11-1}s crystal planes to the "top-down" synthesized organic micro-rods with the flat cross-sectional {002}s plane, to the organic micro-tubes with a wall thickness of ∼115 nm, and finally to the organic nanowires. Notably, the anisotropic etching process caused by the protic solvent molecules (such as ethanol) is crucial for the evolution of the morphology throughout the whole top-down process. Therefore, our demonstration opens a new avenue for the controlled-fabrication of organic nanowires, and also contributes to the development of nanowire-based organic optoelectronics such as organic nanowire lasers.

  20. An integrated native mass spectrometry and top-down proteomics method that connects sequence to structure and function of macromolecular complexes

    Science.gov (United States)

    Li, Huilin; Nguyen, Hong Hanh; Ogorzalek Loo, Rachel R.; Campuzano, Iain D. G.; Loo, Joseph A.

    2018-02-01

    Mass spectrometry (MS) has become a crucial technique for the analysis of protein complexes. Native MS has traditionally examined protein subunit arrangements, while proteomics MS has focused on sequence identification. These two techniques are usually performed separately without taking advantage of the synergies between them. Here we describe the development of an integrated native MS and top-down proteomics method using Fourier-transform ion cyclotron resonance (FTICR) to analyse macromolecular protein complexes in a single experiment. We address previous concerns of employing FTICR MS to measure large macromolecular complexes by demonstrating the detection of complexes up to 1.8 MDa, and we demonstrate the efficacy of this technique for direct acquirement of sequence to higher-order structural information with several large complexes. We then summarize the unique functionalities of different activation/dissociation techniques. The platform expands the ability of MS to integrate proteomics and structural biology to provide insights into protein structure, function and regulation.

  1. A top-down bottom-up modeling approach to climate change policy analysis

    International Nuclear Information System (INIS)

    Tuladhar, Sugandha D.; Yuan, Mei; Bernstein, Paul; Montgomery, W. David; Smith, Anne

    2009-01-01

    This paper analyzes macroeconomic impacts of U.S. climate change policies for three different emissions pathways using a top-down bottom-up integrated model. The integrated model couples a technology-rich, bottom-up model of the U.S. electricity sector with a fully dynamic, forward-looking general equilibrium model of the U.S. economy. Our model provides a unique and consistent modeling framework for climate change analysis. Because of the model's detail and flexibility, we use it to examine additional scenarios to analyze many of the major uncertainties surrounding the implementation and impact of climate change policies - the role of command-and-control measures, loss in flexibility mechanisms such as banking, limits on low-emitting technology, and availability of offsets. The results consistently demonstrate that those policies that combine market-oriented abatement incentives with full flexibility are the most cost-effective. (author)

  2. Mesoporous ZSM-5 Zeolites in Acid Catalysis: Top-Down vs. Bottom-Up Approach

    Directory of Open Access Journals (Sweden)

    Pit Losch

    2017-07-01

    Full Text Available A top-down desilication of Al-rich ZSM-5 zeolites and a bottom-up mesopores creating method were evaluated in this study. Three liquid–solid and one gas–solid heterogeneously-catalysed reactions were chosen to establish relationships between zeolites textural properties and their catalytic behavior in acid-catalysed model reactions that are influenced by shape selectivity: Diels-Alder cyclization between isoprene and methylacrylate, Methanol-to-Olefins (MTO reaction, chlorination of iodobenzene with trichloroisocyanuric acid (TCCA, and Friedel-Crafts acylation of anisole by carboxylic acids with differing sizes. It is found amongst others that no optimal mesoporosity for all the different reactions can be easily obtained, but depending on the chosen application, a specific treatment has to be set to achieve high activity/selectivity and stability.

  3. The Ideological Divide Concerning Climate Change Opinion: Integrating Top-Down and Bottom-Up Approaches

    Directory of Open Access Journals (Sweden)

    Jennifer eJacquet

    2014-12-01

    Full Text Available The United States wields disproportionate global influence in terms of carbon dioxide emissions and international climate policy. This renders it an especially important context in which to examine the interplay among social, psychological, and political factors in shaping attitudes and behaviors about climate change. In this article, we review the emerging literature addressing the liberal-conservative divide in the U.S. with respect to thought, communication, and action concerning climate change. Because of its theoretical and practical significance, we focus on the motivational basis for skepticism and inaction on the part of some, including top-down institutional forces, such as corporate strategy, and bottom-up psychological factors, such as ego, group, and system justification. Although more research is needed to elucidate fully the social, cognitive, and motivational bases of environmental attitudes and behavior, a great deal has been learned in just a few years by focusing on specific ideological factors in addition to general psychological principles.

  4. Hemispheric lateralization in top-down attention during spatial relation processing: a Granger causal model approach.

    Science.gov (United States)

    Falasca, N W; D'Ascenzo, S; Di Domenico, A; Onofrj, M; Tommasi, L; Laeng, B; Franciotti, R

    2015-04-01

    Magnetoencephalography was recorded during a matching-to-sample plus cueing paradigm, in which participants judged the occurrence of changes in either categorical (CAT) or coordinate (COO) spatial relations. Previously, parietal and frontal lobes were identified as key areas in processing spatial relations and it was shown that each hemisphere was differently involved and modulated by the scope of the attention window (e.g. a large and small cue). In this study, Granger analysis highlighted the patterns of causality among involved brain areas--the direction of information transfer ran from the frontal to the visual cortex in the right hemisphere, whereas it ran in the opposite direction in the left side. Thus, the right frontal area seems to exert top-down influence, supporting the idea that, in this task, top-down signals are selectively related to the right side. Additionally, for CAT change preceded by a small cue, the right frontal gyrus was not involved in the information transfer, indicating a selective specialization of the left hemisphere for this condition. The present findings strengthen the conclusion of the presence of a remarkable hemispheric specialization for spatial relation processing and illustrate the complex interactions between the lateralized parts of the neural network. Moreover, they illustrate how focusing attention over large or small regions of the visual field engages these lateralized networks differently, particularly in the frontal regions of each hemisphere, consistent with the theory that spatial relation judgements require a fronto-parietal network in the left hemisphere for categorical relations and on the right hemisphere for coordinate spatial processing. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Modeling eye movements in visual agnosia with a saliency map approach: bottom-up guidance or top-down strategy?

    Science.gov (United States)

    Foulsham, Tom; Barton, Jason J S; Kingstone, Alan; Dewhurst, Richard; Underwood, Geoffrey

    2011-08-01

    Two recent papers (Foulsham, Barton, Kingstone, Dewhurst, & Underwood, 2009; Mannan, Kennard, & Husain, 2009) report that neuropsychological patients with a profound object recognition problem (visual agnosic subjects) show differences from healthy observers in the way their eye movements are controlled when looking at images. The interpretation of these papers is that eye movements can be modeled as the selection of points on a saliency map, and that agnosic subjects show an increased reliance on visual saliency, i.e., brightness and contrast in low-level stimulus features. Here we review this approach and present new data from our own experiments with an agnosic patient that quantifies the relationship between saliency and fixation location. In addition, we consider whether the perceptual difficulties of individual patients might be modeled by selectively weighting the different features involved in a saliency map. Our data indicate that saliency is not always a good predictor of fixation in agnosia: even for our agnosic subject, as for normal observers, the saliency-fixation relationship varied as a function of the task. This means that top-down processes still have a significant effect on the earliest stages of scanning in the setting of visual agnosia, indicating severe limitations for the saliency map model. Top-down, active strategies-which are the hallmark of our human visual system-play a vital role in eye movement control, whether we know what we are looking at or not. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. A top-down approach for fabricating three-dimensional closed hollow nanostructures with permeable thin metal walls

    Directory of Open Access Journals (Sweden)

    Carlos Angulo Barrios

    2017-06-01

    Full Text Available We report on a top-down method for the controlled fabrication of three-dimensional (3D, closed, thin-shelled, hollow nanostructures (nanocages on planar supports. The presented approach is based on conventional microelectronic fabrication processes and exploits the permeability of thin metal films to hollow-out polymer-filled metal nanocages through an oxygen-plasma process. The technique is used for fabricating arrays of cylindrical nanocages made of thin Al shells on silicon substrates. This hollow metal configuration features optical resonance as revealed by spectral reflectance measurements and numerical simulations. The fabricated nanocages were demonstrated as a refractometric sensor with a measured bulk sensitivity of 327 nm/refractive index unit (RIU. The pattern design flexibility and controllability offered by top-down nanofabrication techniques opens the door to the possibility of massive integration of these hollow 3D nano-objects on a chip for applications such as nanocontainers, nanoreactors, nanofluidics, nano-biosensors and photonic devices.

  7. A multi-protease, multi-dissociation, bottom-up-to-top-down proteomic view of the Loxosceles intermedia venom

    Science.gov (United States)

    Trevisan-Silva, Dilza; Bednaski, Aline V.; Fischer, Juliana S.G.; Veiga, Silvio S.; Bandeira, Nuno; Guthals, Adrian; Marchini, Fabricio K.; Leprevost, Felipe V.; Barbosa, Valmir C.; Senff-Ribeiro, Andrea; Carvalho, Paulo C.

    2017-01-01

    Venoms are a rich source for the discovery of molecules with biotechnological applications, but their analysis is challenging even for state-of-the-art proteomics. Here we report on a large-scale proteomic assessment of the venom of Loxosceles intermedia, the so-called brown spider. Venom was extracted from 200 spiders and fractioned into two aliquots relative to a 10 kDa cutoff mass. Each of these was further fractioned and digested with trypsin (4 h), trypsin (18 h), pepsin (18 h), and chymotrypsin (18 h), then analyzed by MudPIT on an LTQ-Orbitrap XL ETD mass spectrometer fragmenting precursors by CID, HCD, and ETD. Aliquots of undigested samples were also analyzed. Our experimental design allowed us to apply spectral networks, thus enabling us to obtain meta-contig assemblies, and consequently de novo sequencing of practically complete proteins, culminating in a deep proteome assessment of the venom. Data are available via ProteomeXchange, with identifier PXD005523. PMID:28696408

  8. A top-down approach in control engineering third-level teaching: The case of hydrogen-generation

    Science.gov (United States)

    Setiawan, Eko; Habibi, M. Afnan; Fall, Cheikh; Hodaka, Ichijo

    2017-09-01

    This paper presents a top-down approach in control engineering third-level teaching. The paper shows the control engineering solution for the issue of practical implementation in order to motivate students. The proposed strategy only focuses on one technique of control engineering to lead student correctly. The proposed teaching steps are 1) defining the problem, 2) listing of acquired knowledge or required skill, 3) selecting of one control engineering technique, 4) arrangement the order of teaching: problem introduction, implementation of control engineering technique, explanation of system block diagram, model derivation, controller design, and 5) enrichment knowledge by the other control techniques. The approach presented highlights hardware implementation and the use of software simulation as a self-learning tool for students.

  9. Phase structuring in metal alloys: Ultrasound-assisted top-down approach to engineering of nanostructured catalytic materials.

    Science.gov (United States)

    Cherepanov, Pavel V; Andreeva, Daria V

    2017-03-01

    High intensity ultrasound (HIUS) is a novel and efficient tool for top-down nanostructuring of multi-phase metal systems. Ultrasound-assisted structuring of the phase in metal alloys relies on two main mechanisms including interfacial red/ox reactions and temperature driven solid state phase transformations which affect surface composition and morphology of metals. Physical and chemical properties of sonication medium strongly affects the structuring pathways as well as morphology and composition of catalysts. HIUS can serve as a simple, fast, and effective approach for the tuning of structure and surface properties of metal particles, opening the new perspectives in design of robust and efficient catalysts. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Costs of CO2 abatement in Egypt using both bottom-up and top-down approaches

    International Nuclear Information System (INIS)

    El Mahgary, Y.; Ibrahim, A.-F.; Shama, M.A.-F.

    1994-01-01

    Within the frame of UNEP's project on the Methodologies of Determining the Costs of Abatement of GHG emissions, a case study on Egypt was undertaken by the Technical Research Centre of Finland (VTT) in cooperation with the Egyptian Environment Affairs Authority (EEAA), together with an expert team from different Egyptian organizations. Both bottom-up and top-down approaches were used. Several measures/technologies, including energy conservation, fuel switching, use of renewable energy and material replacement, were considered to decrease CO 2 emissions. It was found that most of the measures were cost-effective, as a considerable potential for energy conservation exists in Egypt. The impact of energy conservation measures on the economy of the country was found to be positive using a macroeconomic model. (author)

  11. Chassis organism from Corynebacterium glutamicum--a top-down approach to identify and delete irrelevant gene clusters.

    Science.gov (United States)

    Unthan, Simon; Baumgart, Meike; Radek, Andreas; Herbst, Marius; Siebert, Daniel; Brühl, Natalie; Bartsch, Anna; Bott, Michael; Wiechert, Wolfgang; Marin, Kay; Hans, Stephan; Krämer, Reinhard; Seibold, Gerd; Frunzke, Julia; Kalinowski, Jörn; Rückert, Christian; Wendisch, Volker F; Noack, Stephan

    2015-02-01

    For synthetic biology applications, a robust structural basis is required, which can be constructed either from scratch or in a top-down approach starting from any existing organism. In this study, we initiated the top-down construction of a chassis organism from Corynebacterium glutamicum ATCC 13032, aiming for the relevant gene set to maintain its fast growth on defined medium. We evaluated each native gene for its essentiality considering expression levels, phylogenetic conservation, and knockout data. Based on this classification, we determined 41 gene clusters ranging from 3.7 to 49.7 kbp as target sites for deletion. 36 deletions were successful and 10 genome-reduced strains showed impaired growth rates, indicating that genes were hit, which are relevant to maintain biological fitness at wild-type level. In contrast, 26 deleted clusters were found to include exclusively irrelevant genes for growth on defined medium. A combinatory deletion of all irrelevant gene clusters would, in a prophage-free strain, decrease the size of the native genome by about 722 kbp (22%) to 2561 kbp. Finally, five combinatory deletions of irrelevant gene clusters were investigated. The study introduces the novel concept of relevant genes and demonstrates general strategies to construct a chassis suitable for biotechnological application. © 2014 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial-NoDerivs Licence, which permits use and distribution in any medium, provided the original work is properly cited, the use is non- commercial and no modifications or adaptations are made.

  12. A top-down approach to construct execution views of a large software-intensive system

    NARCIS (Netherlands)

    Callo Arias, Trosky B.; America, Pierre; Avgeriou, Paris

    This paper presents an approach to construct execution views, which are views that describe what the software of a software-intensive system does at runtime and how it does it. The approach represents an architecture reconstruction solution based on a metamodel, a set of viewpoints, and a dynamic

  13. Top-Down and Bottom-Up Approach for Model-Based Testing of Product Lines

    Directory of Open Access Journals (Sweden)

    Stephan Weißleder

    2013-03-01

    Full Text Available Systems tend to become more and more complex. This has a direct impact on system engineering processes. Two of the most important phases in these processes are requirements engineering and quality assurance. Two significant complexity drivers located in these phases are the growing number of product variants that have to be integrated into the requirements engineering and the ever growing effort for manual test design. There are modeling techniques to deal with both complexity drivers like, e.g., feature modeling and model-based test design. Their combination, however, has been seldom the focus of investigation. In this paper, we present two approaches to combine feature modeling and model-based testing as an efficient quality assurance technique for product lines. We present the corresponding difficulties and approaches to overcome them. All explanations are supported by an example of an online shop product line.

  14. Bottom-up photonic crystal approach with top-down defect and heterostructure fine-tuning.

    Science.gov (United States)

    Ding, Tao; Song, Kai; Clays, Koen; Tung, Chen-Ho

    2010-03-16

    We combine the most efficient (chemical) approach toward three-dimensional photonic crystals with the most convenient (physical) technique for creating non-close-packed crystalline structures. Self-assembly of colloidal particles in artificial opals is followed by a carefully tuned plasma etching treatment. By covering the resulting top layer of more open structure with original dense opal, embedded defect layers and heterostructures can be conveniently designed for advanced photonic band gap and band edge engineering.

  15. MinGenome: An In Silico Top-Down Approach for the Synthesis of Minimized Genomes.

    Science.gov (United States)

    Wang, Lin; Maranas, Costas D

    2018-02-16

    Genome minimized strains offer advantages as production chassis by reducing transcriptional cost, eliminating competing functions and limiting unwanted regulatory interactions. Existing approaches for identifying stretches of DNA to remove are largely ad hoc based on information on presumably dispensable regions through experimentally determined nonessential genes and comparative genomics. Here we introduce a versatile genome reduction algorithm MinGenome that implements a mixed-integer linear programming (MILP) algorithm to identify in size descending order all dispensable contiguous sequences without affecting the organism's growth or other desirable traits. Known essential genes or genes that cause significant fitness or performance loss can be flagged and their deletion can be prohibited. MinGenome also preserves needed transcription factors and promoter regions ensuring that retained genes will be properly transcribed while also avoiding the simultaneous deletion of synthetic lethal pairs. The potential benefit of removing even larger contiguous stretches of DNA if only one or two essential genes (to be reinserted elsewhere) are within the deleted sequence is explored. We applied the algorithm to design a minimized E. coli strain and found that we were able to recapitulate the long deletions identified in previous experimental studies and discover alternative combinations of deletions that have not yet been explored in vivo.

  16. Beyond Defining the Smart City. Meeting Top-Down and Bottom-Up Approaches in the Middle

    Directory of Open Access Journals (Sweden)

    Jonas Breuer

    2014-05-01

    Full Text Available This paper aims to better frame the discussion and the various, divergent operationalisations and interpretations of the Smart City concept. We start by explicating top-down approaches to the Smart City, followed by what purely bottom-up initiatives can look like. We provide a clear overview of stakeholders’ different viewpoints on the city of tomorrow. Particularly the consequences and potential impacts of these differing interpretations and approaches should be of specific interest to researchers, policy makers, city administrations, private actors and anyone involved and concerned with life in cities. Therefore the goal of this article is not so much answering the question of what the Smart City is, but rather what the concept can mean for different stakeholders as well as the consequences of their interpretation. We do this by assembling an eclectic overview, bringing together definitions, examples and operationalisations from academia, policy and industry as well as identifying major trends and approaches to realizing the Smart City. We add to the debate by proposing a different approach that starts from the collective, collaboration and context when researching Smart City initiatives.

  17. A top-down approach for fabricating free-standing bio-carbon supercapacitor electrodes with a hierarchical structure.

    Science.gov (United States)

    Li, Yingzhi; Zhang, Qinghua; Zhang, Junxian; Jin, Lei; Zhao, Xin; Xu, Ting

    2015-09-23

    Biomass has delicate hierarchical structures, which inspired us to develop a cost-effective route to prepare electrode materials with rational nanostructures for use in high-performance storage devices. Here, we demonstrate a novel top-down approach for fabricating bio-carbon materials with stable structures and excellent diffusion pathways; this approach is based on carbonization with controlled chemical activation. The developed free-standing bio-carbon electrode exhibits a high specific capacitance of 204 F g(-1) at 1 A g(-1); good rate capability, as indicated by the residual initial capacitance of 85.5% at 10 A g(-1); and a long cycle life. These performance characteristics are attributed to the outstanding hierarchical structures of the electrode material. Appropriate carbonization conditions enable the bio-carbon materials to inherit the inherent hierarchical texture of the original biomass, thereby facilitating effective channels for fast ion transfer. The macropores and mesopores that result from chemical activation significantly increase the specific surface area and also play the role of temporary ion-buffering reservoirs, further shortening the ionic diffusion distance.

  18. Cost-of-illness studies based on massive data: a prevalence-based, top-down regression approach.

    Science.gov (United States)

    Stollenwerk, Björn; Welchowski, Thomas; Vogl, Matthias; Stock, Stephanie

    2016-04-01

    Despite the increasing availability of routine data, no analysis method has yet been presented for cost-of-illness (COI) studies based on massive data. We aim, first, to present such a method and, second, to assess the relevance of the associated gain in numerical efficiency. We propose a prevalence-based, top-down regression approach consisting of five steps: aggregating the data; fitting a generalized additive model (GAM); predicting costs via the fitted GAM; comparing predicted costs between prevalent and non-prevalent subjects; and quantifying the stochastic uncertainty via error propagation. To demonstrate the method, it was applied to aggregated data in the context of chronic lung disease to German sickness funds data (from 1999), covering over 7.3 million insured. To assess the gain in numerical efficiency, the computational time of the innovative approach has been compared with corresponding GAMs applied to simulated individual-level data. Furthermore, the probability of model failure was modeled via logistic regression. Applying the innovative method was reasonably fast (19 min). In contrast, regarding patient-level data, computational time increased disproportionately by sample size. Furthermore, using patient-level data was accompanied by a substantial risk of model failure (about 80 % for 6 million subjects). The gain in computational efficiency of the innovative COI method seems to be of practical relevance. Furthermore, it may yield more precise cost estimates.

  19. Pioneering In Situ Recrystallization during Bead Milling: A Top-down Approach to Prepare Zeolite A Nanocrystals.

    Science.gov (United States)

    Anand, Chokkalingam; Yamaguchi, Yudai; Liu, Zhendong; Ibe, Sayoko; Elangovan, Shanmugam P; Ishii, Toshihiro; Ishikawa, Tsuyoshi; Endo, Akira; Okubo, Tatsuya; Wakihara, Toru

    2016-07-05

    Top-down approach has been viewed as an efficient and straightforward method to prepare nanosized zeolites. Yet, the mechanical breaking of zeolite causes amorphization, which usually requires a post-milling recrystallization to obtain fully crystalline nanoparticles. Herein we present a facile methodology to prepare zeolite nanocrystals, where milling and recrystallization can be performed in situ. A milling apparatus specially designed to work under conditions of high alkalinity and temperature enables the in situ recrystallization during milling. Taking zeolite A as an example, we demonstrate its size reduction from ~3 μm to 66 nm in 30 min, which is quite faster than previous methods reported. Three functions, viz., miniaturization, amorphization and recrystallization were found to take effect concurrently during this one-pot process. The dynamic balance between these three functions was achieved by adjusting the milling period and temperature, which lead to the tuning of zeolite A particle size. Particle size and crystallinity of the zeolite A nanocrystals were confirmed by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and water adsorption-desorption. This work presents a pioneering advancement in this field of nanosized zeolites, and will facilitate the mass production as well as boost the wide applications of nanosized zeolites.

  20. 2D FT-ICR MS of Calmodulin: A Top-Down and Bottom-Up Approach.

    Science.gov (United States)

    Floris, Federico; van Agthoven, Maria; Chiron, Lionel; Soulby, Andrew J; Wootton, Christopher A; Lam, Yuko P Y; Barrow, Mark P; Delsuc, Marc-André; O'Connor, Peter B

    2016-09-01

    Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry (2D FT-ICR MS) allows data-independent fragmentation of all ions in a sample and correlation of fragment ions to their precursors through the modulation of precursor ion cyclotron radii prior to fragmentation. Previous results show that implementation of 2D FT-ICR MS with infrared multi-photon dissociation (IRMPD) and electron capture dissociation (ECD) has turned this method into a useful analytical tool. In this work, IRMPD tandem mass spectrometry of calmodulin (CaM) has been performed both in one-dimensional and two-dimensional FT-ICR MS using a top-down and bottom-up approach. 2D IRMPD FT-ICR MS is used to achieve extensive inter-residue bond cleavage and assignment for CaM, using its unique features for fragment identification in a less time- and sample-consuming experiment than doing the same thing using sequential MS/MS experiments. Graphical Abstract ᅟ.

  1. A top-down system engineering approach as an alternative to the tradiotinal over-the-bench methodology for the design of a building

    NARCIS (Netherlands)

    Bluyssen, P.M.; Oostra, M.A.R.; Böhms, H.M.

    2010-01-01

    The traditional over-the-bench methodology for the design of a building is resulting in failure costs, failures at delivery and severe problems. An interactive top-down approach is required, both for the communication process necessary to facilitate the design, construction, maintenance and

  2. Top-down approach is possible strategy for predicting breakthrough fUTIs and renal scars in infants.

    Science.gov (United States)

    Kawai, Shina; Kanai, Takahiro; Hyuga, Taiju; Nakamura, Shigeru; Aoyagi, Jun; Ito, Takane; Saito, Takashi; Odaka, Jun; Furukawa, Rieko; Aihara, Toshinori; Nakai, Hideo

    2017-07-01

    Acute-phase technetium-99 m dimercaptosuccinic acid (DMSA) scintigraphy is recommended for initial imaging in children with febrile urinary tract infection (fUTI). Recently, the importance of identifying patients at risk of recurrent fUTI (r-fUTI) has been emphasized. To clarify the effectiveness of DMSA scintigraphy for predicting r-fUTI in infants, we investigated the relationship between defects on DMSA scintigraphy and r-fUTI. Seventy-nine consecutive infants (male: female, 60:19) with fUTI were enrolled in this study. DMSA scintigraphy was performed in the acute phase, and patients with defect underwent voiding cystourethrography and chronic-phase (6 months later) DMSA scintigraphy. Patients were followed on continuous antibiotic prophylaxis (CAP). Defects on acute-phase DMSA scintigraphy were observed in 32 children (40.5%) of 79. The mean follow-up observation period was 17.0 ± 10.1 months. Four patients had r-fUTI (5%). Two of them had defects on DMSA scintigraphy in both the acute phase and chronic phase, and had bilateral vesicoureteral reflux (VUR) grade IV. Two others had r-fUTI without defects on DMSA and did not have VUR. Twelve patients had defect on chronic-phase DMSA scintigraphy and four of them had no VUR. The top-down approach is a possible method for predicting r-fUTI in infants and does not miss clinically significant VUR. Also, given that the prevalence of r-fUTI was 5% regardless of the presence of defects on acute-phase DMSA, then, in conjunction with genital hygiene and CAP, acute-phase DMSA might be unnecessary if chronic-phase DMSA is performed for all patients to detect renal scar. © 2017 Japan Pediatric Society.

  3. River food webs: an integrative approach to bottom-up flow webs, top-down impact webs, and trophic position.

    Science.gov (United States)

    Benke, Arthur C

    2018-03-31

    The majority of food web studies are based on connectivity, top-down impacts, bottom-up flows, or trophic position (TP), and ecologists have argued for decades which is best. Rarely have any two been considered simultaneously. The present study uses a procedure that integrates the last three approaches based on taxon-specific secondary production and gut analyses. Ingestion flows are quantified to create a flow web and the same data are used to quantify TP for all taxa. An individual predator's impacts also are estimated using the ratio of its ingestion (I) of each prey to prey production (P) to create an I/P web. This procedure was applied to 41 invertebrate taxa inhabiting submerged woody habitat in a southeastern U.S. river. A complex flow web starting with five basal food resources had 462 flows >1 mg·m -2 ·yr -1 , providing far more information than a connectivity web. Total flows from basal resources to primary consumers/omnivores were dominated by allochthonous amorphous detritus and ranged from 1 to >50,000 mg·m -2 ·yr -1 . Most predator-prey flows were much lower (1,000  mg·m -2 ·yr -1 . The I/P web showed that 83% of individual predator impacts were weak (90%). Quantitative estimates of TP ranged from 2 to 3.7, contrasting sharply with seven integer-based trophic levels based on longest feeding chain. Traditional omnivores (TP = 2.4-2.9) played an important role by consuming more prey and exerting higher impacts on primary consumers than strict predators (TP ≥ 3). This study illustrates how simultaneous quantification of flow pathways, predator impacts, and TP together provide an integrated characterization of natural food webs. © 2018 by the Ecological Society of America.

  4. Modifications of the acidic soluble salivary proteome in human children from birth to the age of 48months investigated by a top-down HPLC-ESI-MS platform.

    Science.gov (United States)

    Manconi, B; Cabras, T; Pisano, E; Sanna, M T; Olianas, A; Fanos, V; Faa, G; Nemolato, S; Iavarone, F; Castagnola, M; Messana, I

    2013-10-08

    During the first year of life the infant oral environment undergoes dramatic changes. To investigate how the salivary proteome of human children evolves during infant development we have analyzed whole saliva of 88 children aged between 0 and 48months by a top-down platform based on RP-HPLC-ESI-MS. Children were divided according to their age into five groups (A, 0-6months, N=17; B, 7-12months, N=14; C, 13-24months, N=32; D, 25-36months, N=16; E, 37-48months, N=9). The proteins and peptides analyzed were histatins (histatin-1, histatin-3 1/24), acidic proline-rich proteins, statherin, P-B peptide, and salivary cystatins. Protein and peptide quantification based on the area of the RP-HPLC-ESI-MS extracted ion current peak evidenced that: (i) concentrations of the major salivary proteins/peptides showed a minimum in the 0-6-month-old group and increased with age; (ii) the level of histatin-1 reached a maximum in the 7-12-month-old group, a minimum in the 13-24-month-aged babies and it increased again in the 25-36-month-old group; (iii) S-type cystatins were almost undetectable in the 0-6-month-old group; (iv) P-B peptide concentration greatly increased with age; (v) histatin-3 1/24 and statherin concentrations did not show any age-related variation. The top-down proteomic approach undertaken in this work reveals that the salivary proteome of human children from birth to 48months of age shows important quantitative modifications. The concentrations of the major salivary proteins, with the exception of statherin and histatin-3 1/24, showed a minimum in the 0-6-month-old group when the expression in salivary glands is probably not fully activated. Concentrations of the salivary proteins slowly increased with age, with different trends. Only histatin-1 showed the highest concentration in the 7-12-month-old group, followed by a decrease in the 13-24-month-aged children. This particular trend could be related to the phenomenon of eruption of primary dentition. This study

  5. Hierarchical structure and modules in the Escherichia coli transcriptional regulatory network revealed by a new top-down approach

    Directory of Open Access Journals (Sweden)

    Buer Jan

    2004-12-01

    Full Text Available Abstract Background Cellular functions are coordinately carried out by groups of genes forming functional modules. Identifying such modules in the transcriptional regulatory network (TRN of organisms is important for understanding the structure and function of these fundamental cellular networks and essential for the emerging modular biology. So far, the global connectivity structure of TRN has not been well studied and consequently not applied for the identification of functional modules. Moreover, network motifs such as feed forward loop are recently proposed to be basic building blocks of TRN. However, their relationship to functional modules is not clear. Results In this work we proposed a top-down approach to identify modules in the TRN of E. coli. By studying the global connectivity structure of the regulatory network, we first revealed a five-layer hierarchical structure in which all the regulatory relationships are downward. Based on this regulatory hierarchy, we developed a new method to decompose the regulatory network into functional modules and to identify global regulators governing multiple modules. As a result, 10 global regulators and 39 modules were identified and shown to have well defined functions. We then investigated the distribution and composition of the two basic network motifs (feed forward loop and bi-fan motif in the hierarchical structure of TRN. We found that most of these network motifs include global regulators, indicating that these motifs are not basic building blocks of modules since modules should not contain global regulators. Conclusion The transcriptional regulatory network of E. coli possesses a multi-layer hierarchical modular structure without feedback regulation at transcription level. This hierarchical structure builds the basis for a new and simple decomposition method which is suitable for the identification of functional modules and global regulators in the transcriptional regulatory network of E

  6. A top-down approach of surface carbonyl sulfide exchange by a Mediterranean oak forest ecosystem in southern France

    Science.gov (United States)

    Belviso, Sauveur; Reiter, Ilja Marco; Loubet, Benjamin; Gros, Valérie; Lathière, Juliette; Montagne, David; Delmotte, Marc; Ramonet, Michel; Kalogridis, Cerise; Lebegue, Benjamin; Bonnaire, Nicolas; Kazan, Victor; Gauquelin, Thierry; Fernandez, Catherine; Genty, Bernard

    2016-12-01

    The role that soil, foliage, and atmospheric dynamics have on surface carbonyl sulfide (OCS) exchange in a Mediterranean forest ecosystem in southern France (the Oak Observatory at the Observatoire de Haute Provence, O3HP) was investigated in June of 2012 and 2013 with essentially a top-down approach. Atmospheric data suggest that the site is appropriate for estimating gross primary production (GPP) directly from eddy covariance measurements of OCS fluxes, but it is less adequate for scaling net ecosystem exchange (NEE) to GPP from observations of vertical gradients of OCS relative to CO2 during the daytime. Firstly, OCS and carbon dioxide (CO2) diurnal variations and vertical gradients show no net exchange of OCS at night when the carbon fluxes are dominated by ecosystem respiration. This contrasts with other oak woodland ecosystems of a Mediterranean climate, where nocturnal uptake of OCS by soil and/or vegetation has been observed. Since temperature, water, and organic carbon content of soil at the O3HP should favor the uptake of OCS, the lack of nocturnal net uptake would indicate that its gross consumption in soil is compensated for by emission processes that remain to be characterized. Secondly, the uptake of OCS during the photosynthetic period was characterized in two different ways. We measured ozone (O3) deposition velocities and estimated the partitioning of O3 deposition between stomatal and non-stomatal pathways before the start of a joint survey of OCS and O3 surface concentrations. We observed an increasing trend in the relative importance of the stomatal pathway during the morning hours and synchronous steep drops of mixing ratios of OCS (amplitude in the range of 60-100 ppt) and O3 (amplitude in the range of 15-30 ppb) after sunrise and before the break up of the nocturnal boundary layer. The uptake of OCS by plants was also characterized from vertical profiles. However, the time window for calculation of the ecosystem relative uptake (ERU) of OCS

  7. Top-down Approach for the Direct Synthesis, Patterning, and Operation of Artificial Micromuscles on Flexible Substrates.

    Science.gov (United States)

    Maziz, Ali; Plesse, Cédric; Soyer, Caroline; Cattan, Eric; Vidal, Frédéric

    2016-01-27

    Recent progress in the field of microsystems on flexible substrates raises the need for alternatives to the stiffness of classical actuation technologies. This paper reports a top-down process to microfabricate soft conducting polymer actuators on substrates on which they ultimately operate. The bending microactuators were fabricated by sequentially stacking layers using a layer polymerization by layer polymerization of conducting polymer electrodes and a solid polymer electrolyte. Standalone microbeams thinner than 10 μm were fabricated on SU-8 substrates associated with a bottom gold electrical contact. The operation of microactuators was demonstrated in air and at low voltage (±4 V).

  8. Bottom-up and Top-down Approaches to Explore Sodium Dodecyl Sulfate and Soluplus on the Crystallization Inhibition and Dissolution of Felodipine Extrudates.

    Science.gov (United States)

    Chen, Jiali; Chen, Yuqi; Huang, Wencong; Wang, Hanning; Du, Yang; Xiong, Subin

    2018-05-05

    The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and/or SDS were prepared by hot melt extrusion (HME), and characterized by PLM, DSC and FT-IR. Results indicated that Soluplus inhibited FLDP crystallization and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS(1:2:0.15∼0.3 and 1:3:0.2∼0.4) extrudates. Internal SDS (5%-10%) decreased Tgs of FLDP-Soluplus-SDS ternary ASDs without presenting molecular interactions with FLDP or Soluplus. The enhanced dissolution rate of binary or ternary Soluplus-rich ASDs in the non-sink condition of 0.05%SDS was achieved. Bottom-up approach indicated that Soluplus was a much stronger crystal inhibitor to the supersaturated FLDP in solutions than SDS. Top-down approach demonstrated that SDS enhanced the dissolution of Soluplus-rich ASDs via wettability and complexation with Soluplus to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. In conclusion, top-down approach is a promising strategy to explore the mechanisms of ASDs' dissolution, and small amount of SDS enhances the dissolution rate of polymer-rich ASDs in the non-sink condition. Copyright © 2018. Published by Elsevier Inc.

  9. Using Top-down and Bottom-up Costing Approaches in LMICs: The Case for Using Both to Assess the Incremental Costs of New Technologies at Scale.

    Science.gov (United States)

    Cunnama, Lucy; Sinanovic, Edina; Ramma, Lebogang; Foster, Nicola; Berrie, Leigh; Stevens, Wendy; Molapo, Sebaka; Marokane, Puleng; McCarthy, Kerrigan; Churchyard, Gavin; Vassall, Anna

    2016-02-01

    Estimating the incremental costs of scaling-up novel technologies in low-income and middle-income countries is a methodologically challenging and substantial empirical undertaking, in the absence of routine cost data collection. We demonstrate a best practice pragmatic approach to estimate the incremental costs of new technologies in low-income and middle-income countries, using the example of costing the scale-up of Xpert Mycobacterium tuberculosis (MTB)/resistance to riframpicin (RIF) in South Africa. We estimate costs, by applying two distinct approaches of bottom-up and top-down costing, together with an assessment of processes and capacity. The unit costs measured using the different methods of bottom-up and top-down costing, respectively, are $US16.9 and $US33.5 for Xpert MTB/RIF, and $US6.3 and $US8.5 for microscopy. The incremental cost of Xpert MTB/RIF is estimated to be between $US14.7 and $US17.7. While the average cost of Xpert MTB/RIF was higher than previous studies using standard methods, the incremental cost of Xpert MTB/RIF was found to be lower. Costs estimates are highly dependent on the method used, so an approach, which clearly identifies resource-use data collected from a bottom-up or top-down perspective, together with capacity measurement, is recommended as a pragmatic approach to capture true incremental cost where routine cost data are scarce. © 2016 The Authors. Health Economics published by John Wiley & Sons Ltd.

  10. Improved Understanding of Microbial Iron and Sulfate Reduction Through a Combination of Bottom-up and Top-down Functional Proteomics Assays

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, Ruth [Cornell Univ., Ithaca, NY (United States)

    2016-02-28

    Our overall goal was to improve the understanding of microbial iron and sulfate reduction by evaluating a diverse iron and sulfate reducing organisms utilizing a multi-omics approach combining “top-down” and “bottom-up” omics methodologies. We initiated one of the first combined comparative genomics, shotgun proteomics, RTqPCR, and heterologous expression studies in pursuit of our project objectives. Within the first year of this project, we created a new bioinformatics tool for ortholog identification (“SPOCS”). SPOCS is described in our publication, Curtis et al., 2013. Using this tool we were able to identify conserved orthologous groups across diverse iron and sulfate reducing microorganisms from Firmicutes, gamma-proteobacteria and delta-proteobacteria. For six iron and sulfate reducers we also performed shotgun proteomics (“bottom-up” proteomics including accurate mass and time (AMT) tag and iTRAQ approaches). Cultures include Gram (-) and Gram (+) microbes. Gram (-) were: Geobacter sulfureducens (grown on iron citrate and fumarate), Geobacter bemidjiensis (grown on iron citrate and fumarate), Shewanella oneidiensis (grown on iron citrate and fumarate) and Anaeromyxobacter dehalogenans (grown on iron citrate and fumarate). Although all cultures grew on insoluble iron, the iron precipitates interfered with protein extraction and analysis; which remains a major challenge for researchers in disparate study systems. Among the Gram (-) organisms studied, Anaeromyxobacter dehalogenans remains the most poorly characterized. Yet, it is arguably the most versatile organisms we studied. In this work we have used comparative proteomics to hypothesize which two of the dozens of predicted c-type cytochromes within Anaeromyxobacter dehalogenans may be directly involved in soluble iron reduction. Unfortunately, heterologous expression of these Anaeromyxobacter dehalogenans ctype cytochromes led to poor protein production and/or formation of inclusion bodies

  11. Consideration on the health risk reduction related to attainment of the new particulate matter standards in Poland: A top-down policy risk assessment approach.

    Science.gov (United States)

    Kobza, Joanna; Pastuszka, Józef S; Gulis, Gabriel

    2016-01-01

    Policies can influence health of a population in various ways. Numerous epidemiological studies supported by toxicological investigations demonstrate a positive association between ambient concentrations of airborne particulate matter and increased adverse cardio-respiratory events, including morbidity and mortality. The aim of this paper was to present the concept of the top-down health policy risk assessment approach model developed to estimate the expected health risk reduction associated with policy aiming at attaining the new particulate matter ≤ 10 μm in diameter (PM10) standards in Poland. The top-down approach guides the analysis of causal chains from the policy to health outcomes. In this case study we tried to estimate the predicted health effects of the policy change over the past 20 years. Since Polish annual standard for PM10 changed from 50 μg/m³ in 1990 to 40 μg/m³ in 2010, we calculated the relative risk associated with decreasing PM10 in diameter to 10 μg/m3 in the annual level of PM10 for 6 adverse health effects. The relative risk slightly decreased for almost all adverse health effects, which means that the relative decrease in the incidence of health effects from the baseline incidence should range from about 0.5-0.6% for heart disease admissions to > 1% for respiratory admissions. The obtained results indicate that implementation of the new ambient air standards could influence improvement of the health status of Polish population. A top-down policy health risk assessment model can be one of the main tools in this process, providing harmonized guidance how to seek evidence-based information, which could serve policy-makers. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  12. Top-Down and Bottom-Up Approaches in Engineering 1 T Phase Molybdenum Disulfide (MoS2 ): Towards Highly Catalytically Active Materials.

    Science.gov (United States)

    Chua, Chun Kiang; Loo, Adeline Huiling; Pumera, Martin

    2016-09-26

    The metallic 1 T phase of MoS2 has been widely identified to be responsible for the improved performances of MoS2 in applications including hydrogen evolution reactions and electrochemical supercapacitors. To this aim, various synthetic methods have been reported to obtain 1 T phase-rich MoS2 . Here, the aim is to evaluate the efficiencies of the bottom-up (hydrothermal reaction) and top-down (chemical exfoliation) approaches in producing 1 T phase MoS2 . It is established in this study that the 1 T phase MoS2 produced through the bottom-up approach contains a high proportion of 1 T phase and demonstrates excellent electrochemical and electrical properties. Its performance in the hydrogen evolution reaction and electrochemical supercapacitors also surpassed that of 1 T phase MoS2 produced through a top-down approach. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Making a commercial carbon fiber cloth having comparable capacitances to carbon nanotubes and graphene in supercapacitors through a "top-down" approach.

    Science.gov (United States)

    Zhang, Tianchang; Kim, Christine H J; Cheng, Yingwen; Ma, Yanwen; Zhang, Hongbo; Liu, Jie

    2015-02-21

    A "top-down" and scalable approach for processing carbon fiber cloth (CFC) into flexible and all-carbon electrodes with remarkable areal capacity and cyclic stability was developed. CFC is commercially available in large quantities but its use as an electrode material in supercapacitors is not satisfactory. The approach demonstrated in this work is based on the sequential treatment of CFC with KOH activation and high temperature annealing that can effectively improve its specific surface area to a remarkable 2780 m(2) g(-1) while at the same time achieving a good electrical conductivity of 320 S m(-1) without sacrificing its intrinsic mechanical strength and flexibility. The processed CFC can be directly used as an electrode for supercapacitors without any binders, conductive additives and current collectors while avoiding elaborate electrode processing steps to deliver a specific capacitance of ∼0.5 F cm(-2) and ∼197 F g(-1) with remarkable rate performance and excellent cyclic stability. The properties of these processed CFCs are comparable or better than graphene and carbon nanotube based electrodes. We further demonstrate symmetric solid-state supercapacitors based on these processed CFCs with very good flexibility. This "top-down" and scalable approach can be readily applied to other types of commercially available carbon materials and therefore can have a substantial significance for high performance supercapacitor devices.

  14. Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: impact of a "Top-Down" approach to intestinal fibrosis in mice.

    Science.gov (United States)

    Johnson, Laura A; Luke, Amy; Sauder, Kay; Moons, David S; Horowitz, Jeffrey C; Higgins, Peter D R

    2012-03-01

    The natural history of Crohn's disease follows a path of progression from an inflammatory to a fibrostenosing disease, with most patients requiring surgical resection of fibrotic strictures. Potent antiinflammatory therapies reduce inflammation but do not appear to alter the natural history of intestinal fibrosis. The aim of this study was to determine the relationship between intestinal inflammation and fibrogenesis and the impact of a very early "top-down" interventional approach on fibrosis in vivo. In this study we removed the inflammatory stimulus from the Salmonella typhimurium mouse model of intestinal fibrosis by eradicating the S. typhimurium infection with levofloxacin at sequential timepoints during the infection. We evaluated the effect of this elimination of the inflammatory stimulus on the natural history of inflammation and fibrosis as determined by gross pathology, histopathology, mRNA expression, and protein expression. Fibrogenesis is preceded by inflammation. Delayed eradication of the inflammatory stimulus by antibiotic treatment represses inflammation without preventing fibrosis. Early intervention significantly ameliorates but does not completely prevent subsequent fibrosis. This study demonstrates that intestinal fibrosis develops despite removal of an inflammatory stimulus and elimination of inflammation. Early intervention ameliorates but does not abolish subsequent fibrosis, suggesting that fibrosis, once initiated, is self-propagating, suggesting that a very early top-down interventional approach may have the most impact on fibrostenosing disease. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  15. Scalable Top-Down Approach Tailored by Interferometric Lithography to Achieve Large-Area Single-Mode GaN Nanowire Laser Arrays on Sapphire Substrate.

    Science.gov (United States)

    Behzadirad, Mahmoud; Nami, Mohsen; Wostbrock, Neal; Zamani Kouhpanji, Mohammad Reza; Feezell, Daniel F; Brueck, Steven R J; Busani, Tito

    2018-03-27

    GaN nanowires are promising for optical and optoelectronic applications because of their waveguiding properties and large optical band gap. However, developing a precise, scalable, and cost-effective fabrication method with a high degree of controllability to obtain high-aspect-ratio nanowires with high optical properties and minimum crystal defects remains a challenge. Here, we present a scalable two-step top-down approach using interferometric lithography, for which parameters can be controlled precisely to achieve highly ordered arrays of nanowires with excellent quality and desired aspect ratios. The wet-etch mechanism is investigated, and the etch rates of m-planes {11̅00} (sidewalls) were measured to be 2.5 to 70 nm/h depending on the Si doping concentration. Using this method, uniform nanowire arrays were achieved over a large area (>10 5 μm 2 ) with an spect ratio as large as 50, a radius as small as 17 nm, and atomic-scale sidewall roughness (top-down approach using interferometric lithography and is promising for fabrication of III-nitride-based nanophotonic devices (radial/axial) on the original substrate.

  16. Evolutionary Steps in the Emergence of Life Deduced from the Bottom-Up Approach and GADV Hypothesis (Top-Down Approach).

    Science.gov (United States)

    Ikehara, Kenji

    2016-01-26

    It is no doubt quite difficult to solve the riddle of the origin of life. So, firstly, I would like to point out the kinds of obstacles there are in solving this riddle and how we should tackle these difficult problems, reviewing the studies that have been conducted so far. After that, I will propose that the consecutive evolutionary steps in a timeline can be rationally deduced by using a common event as a juncture, which is obtained by two counter-directional approaches: one is the bottom-up approach through which many researchers have studied the origin of life, and the other is the top-down approach, through which I established the [GADV]-protein world hypothesis or GADV hypothesis on the origin of life starting from a study on the formation of entirely new genes in extant microorganisms. Last, I will describe the probable evolutionary process from the formation of Earth to the emergence of life, which was deduced by using a common event-the establishment of the first genetic code encoding [GADV]-amino acids-as a juncture for the results obtained from the two approaches.

  17. Evolutionary Steps in the Emergence of Life Deduced from the Bottom-Up Approach and GADV Hypothesis (Top-Down Approach

    Directory of Open Access Journals (Sweden)

    Kenji Ikehara

    2016-01-01

    Full Text Available It is no doubt quite difficult to solve the riddle of the origin of life. So, firstly, I would like to point out the kinds of obstacles there are in solving this riddle and how we should tackle these difficult problems, reviewing the studies that have been conducted so far. After that, I will propose that the consecutive evolutionary steps in a timeline can be rationally deduced by using a common event as a juncture, which is obtained by two counter-directional approaches: one is the bottom-up approach through which many researchers have studied the origin of life, and the other is the top-down approach, through which I established the [GADV]-protein world hypothesis or GADV hypothesis on the origin of life starting from a study on the formation of entirely new genes in extant microorganisms. Last, I will describe the probable evolutionary process from the formation of Earth to the emergence of life, which was deduced by using a common event—the establishment of the first genetic code encoding [GADV]-amino acids—as a juncture for the results obtained from the two approaches.

  18. Middle-Out Approaches to Reform of University Teaching and Learning: Champions striding between the top-down and bottom-up approaches

    Directory of Open Access Journals (Sweden)

    Rick Cummings

    2005-03-01

    Full Text Available In recent years, Australian universities have been driven by a diversity of external forces, including funding cuts, massification of higher education, and changing student demographics, to reform their relationship with students and improve teaching and learning, particularly for those studying off-campus or part-time. Many universities have responded to these forces either through formal strategic plans developed top-down by executive staff or through organic developments arising from staff in a bottom-up approach. By contrast, much of Murdoch University’s response has been led by a small number of staff who have middle management responsibilities and who have championed the reform of key university functions, largely in spite of current policy or accepted practice. This paper argues that the ‘middle-out’ strategy has both a basis in change management theory and practice, and a number of strengths, including low risk, low cost, and high sustainability. Three linked examples of middle-out change management in teaching and learning at Murdoch University are described and the outcomes analyzed to demonstrate the benefits and pitfalls of this approach.

  19. Idihom industrialization of high-order methods a top-down approach : results of a collaborative research project funded by the European Union, 2010-2014

    CERN Document Server

    Hirsch, Charles; Bassi, Francesco; Johnston, Craig; Hillewaert, Koen

    2015-01-01

    The book describes the main findings of the EU-funded project IDIHOM (Industrialization of High-Order Methods – A Top-Down Approach). The goal of this project was the improvement, utilization and demonstration of innovative higher-order simulation capabilities for large-scale aerodynamic application challenges in the aircraft industry. The IDIHOM consortium consisted of 21 organizations, including aircraft manufacturers, software vendors, as well as the major European research establishments and several universities, all of them with proven expertise in the field of computational fluid dynamics. After a general introduction to the project, the book reports on new approaches for curved boundary-grid generation, high-order solution methods and visualization techniques. It summarizes the achievements, weaknesses and perspectives of the new simulation capabilities developed by the project partners for various industrial applications, and includes internal- and external-aerodynamic as well as multidisciplinary t...

  20. The synthesis of bottom-up and top-down approaches to climate policy modeling: Electric power technology detail in a social accounting framework

    International Nuclear Information System (INIS)

    Sue Wing, Ian

    2008-01-01

    ''Hybrid'' climate policy simulations have sought to bridge the gap between ''bottom-up'' engineering and ''top-down'' macroeconomic models by integrating the former's energy technology detail into the latter's macroeconomic framework. Construction of hybrid models is complicated by the need to numerically calibrate them to multiple, incommensurate sources of economic and engineering data. I develop a solution to this problem following Howitt's [Howitt, R.E., 1995. Positive Mathematical Programming, American Journal of Agricultural Economics 77: 329-342] positive mathematical programming approach. Using data for the U.S., I illustrate how the inputs to the electricity sector in a social accounting matrix may be allocated among discrete types of generation so as to be consistent with both technologies' input shares from engineering cost estimates, and the zero profit and market clearance conditions of the sector's macroeconomic production structure. (author)

  1. Object detection approach using generative sparse, hierarchical networks with top-down and lateral connections for combining texture/color detection and shape/contour detection

    Science.gov (United States)

    Paiton, Dylan M.; Kenyon, Garrett T.; Brumby, Steven P.; Schultz, Peter F.; George, John S.

    2015-07-28

    An approach to detecting objects in an image dataset may combine texture/color detection, shape/contour detection, and/or motion detection using sparse, generative, hierarchical models with lateral and top-down connections. A first independent representation of objects in an image dataset may be produced using a color/texture detection algorithm. A second independent representation of objects in the image dataset may be produced using a shape/contour detection algorithm. A third independent representation of objects in the image dataset may be produced using a motion detection algorithm. The first, second, and third independent representations may then be combined into a single coherent output using a combinatorial algorithm.

  2. Object detection approach using generative sparse, hierarchical networks with top-down and lateral connections for combining texture/color detection and shape/contour detection

    Energy Technology Data Exchange (ETDEWEB)

    Paiton, Dylan M.; Kenyon, Garrett T.; Brumby, Steven P.; Schultz, Peter F.; George, John S.

    2016-10-25

    An approach to detecting objects in an image dataset may combine texture/color detection, shape/contour detection, and/or motion detection using sparse, generative, hierarchical models with lateral and top-down connections. A first independent representation of objects in an image dataset may be produced using a color/texture detection algorithm. A second independent representation of objects in the image dataset may be produced using a shape/contour detection algorithm. A third independent representation of objects in the image dataset may be produced using a motion detection algorithm. The first, second, and third independent representations may then be combined into a single coherent output using a combinatorial algorithm.

  3. From War to Tolerance? Bottom-up and Top-down Approaches to (Rebuilding Interethnic Ties in the Areas of the Former Yugoslavia

    Directory of Open Access Journals (Sweden)

    Boris Banovac

    2014-01-01

    Full Text Available In recent history the Balkans passed through periods of conflict and violence typical of many post-imperial nation-states that are unable to establish lateral links with their neighbors without or outside the central (imperial connection. In a way, these states imitated historical path of imperial conquests. In this regard, ethnic conflicts that escalated into wars of the former Yugoslavia can be taken as examples of an erratic transformation of post-imperial into modern nation-states that are eager to build up democracy at home and develop peaceful coexistence with others in international environment. Nevertheless, not all multiethnic areas were caught up in violence (e.g. instances of “peace enclaves” in multiethnic areas in Croatia, Bosnia and Heregovina and in Kosovo. Through such examples, which will be illustrated with results of empirical research, we recognize potentials for building tolerance from below. On the other hand, in most other places peace was a follow up of post-conflict processes. In these cases, local potentials of ethnic tolerance were rather weak. The paper provides some examples illustrating regional differences in this regard within Croatia. Actually, the whole process of normalization of ethnic relations in peaceful terms is far from being linear and is hardly going smoothly. Some parts of national elites foster distance and antagonism against the ”others”. On the other hand, especially following EU accession of Croatia, nationalistic rhetoric significantly receded on the level of the official politics. The question is then whether the impact of policies in institutional sphere, both national and international, i.e. top-down approach, is decisive in shaping inter-ethnic relations. The conclusion is that the institutional, top-down arrangements of peace and tolerance cannot be sustainable without concomitant bottom-up processes on micro level, which theoretically corresponds to a “conformant policy” against

  4. Linking top-down and bottom-up approaches for assessing the vulnerability of a 100 % renewable energy system in Northern-Italy

    Science.gov (United States)

    Borga, Marco; Francois, Baptiste; Hingray, Benoit; Zoccatelli, Davide; Creutin, Jean-Dominique; brown, Casey

    2016-04-01

    Due to their variable and un-controllable features, integration of Variable Renewable Energies (e.g. solar-power, wind-power and hydropower, denoted as VRE) into the electricity network implies higher production variability and increased risk of not meeting demand. Two approaches are commonly used for assessing this risk and especially its evolution in a global change context (i.e. climate and societal changes); top-down and bottom-up approaches. The general idea of a top-down approach is to drive analysis of global change or of some key aspects of global change on their systems (e.g., the effects of the COP 21, of the deployment of Smart Grids, or of climate change) with chains of loosely linked simulation models within a predictive framework. The bottom-up approach aims to improve understanding of the dependencies between the vulnerability of regional systems and large-scale phenomenon from knowledge gained through detailed exploration of the response to change of the system of interest, which may reveal vulnerability thresholds, tipping points as well as potential opportunities. Brown et al. (2012) defined an analytical framework to merge these two approaches. The objective is to build, a set of Climate Response Functions (CRFs) putting in perspective i) indicators of desired states ("success") and undesired states ("failure") of a system as defined in collaboration with stakeholders 2) exhaustive exploration of the effects of uncertain forcings and imperfect system understanding on the response of the system itself to a plausible set of possible changes, implemented a with multi-dimensionally consistent "stress test" algorithm, and 3) a set "ex post" hydroclimatic and socioeconomic scenarios that provide insight into the differential effectiveness of alternative policies and serve as entry points for the provision of climate information to inform policy evaluation and choice. We adapted this approach for analyzing a 100 % renewable energy system within a region

  5. MALDI-ISD Mass Spectrometry Analysis of Hemoglobin Variants: a Top-Down Approach to the Characterization of Hemoglobinopathies

    Science.gov (United States)

    Théberge, Roger; Dikler, Sergei; Heckendorf, Christian; Chui, David H. K.; Costello, Catherine E.; McComb, Mark E.

    2015-08-01

    Hemoglobinopathies are the most common inherited disorders in humans and are thus the target of screening programs worldwide. Over the past decade, mass spectrometry (MS) has gained a more important role as a clinical means to diagnose variants, and a number of approaches have been proposed for characterization. Here we investigate the use of matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF MS) with sequencing using in-source decay (MALDI-ISD) for the characterization of Hb variants. We explored the effect of matrix selection using super DHB or 1,5-diaminonaphthalene on ISD fragment ion yield and distribution. MALDI-ISD MS of whole blood using super DHB simultaneously provided molecular weights for the alpha and beta chains, as well as extensive fragmentation in the form of sequence defining c-, (z + 2)-, and y-ion series. We observed sequence coverage on the first 70 amino acids positions from the N- and C-termini of the alpha and beta chains in a single experiment. An abundant beta chain N-terminal fragment ion corresponding to βc34 was determined to be a diagnostic marker ion for Hb S (β6 Glu→Val, sickle cell), Hb C (β6 Glu→Lys), and potentially for Hb E (β26 Glu→Lys). The MALDI-ISD analysis of Hb S and HbSC yielded mass shifts corresponding to the variants, demonstrating the potential for high-throughput screening. Characterization of an alpha chain variant, Hb Westmead (α122 His→Gln), generated fragments that established the location of the variant. This study is the first clinical application of MALDI-ISD MS for the determination and characterization of hemoglobin variants.

  6. A comparison of top-down and bottom-up approaches to benthic habitat mapping to inform offshore wind energy development

    Science.gov (United States)

    LaFrance, Monique; King, John W.; Oakley, Bryan A.; Pratt, Sheldon

    2014-07-01

    Recent interest in offshore renewable energy within the United States has amplified the need for marine spatial planning to direct management strategies and address competing user demands. To assist this effort in Rhode Island, benthic habitat classification maps were developed for two sites in offshore waters being considered for wind turbine installation. Maps characterizing and representing the distribution and extent of benthic habitats are valuable tools for improving understanding of ecosystem patterns and processes, and promoting scientifically-sound management decisions. This project presented the opportunity to conduct a comparison of the methodologies and resulting map outputs of two classification approaches, “top-down” and “bottom-up” in the two study areas. This comparison was undertaken to improve understanding of mapping methodologies and their applicability, including the bottom-up approach in offshore environments where data density tends to be lower, as well as to provide case studies for scientists and managers to consider for their own areas of interest. Such case studies can offer guidance for future work for assessing methodologies and translating them to other areas. The traditional top-down mapping approach identifies biological community patterns based on communities occurring within geologically defined habitat map units, under the concept that geologic environments contain distinct biological assemblages. Alternatively, the bottom-up approach aims to establish habitat map units centered on biological similarity and then uses statistics to identify relationships with associated environmental parameters and determine habitat boundaries. When applied to the two study areas, both mapping approaches produced habitat classes with distinct macrofaunal assemblages and each established statistically strong and significant biotic-abiotic relationships with geologic features, sediment characteristics, water depth, and/or habitat

  7. An expanded framework to define and measure shared decision-making in dialogue: A 'top-down' and 'bottom-up' approach.

    Science.gov (United States)

    Callon, Wynne; Beach, Mary Catherine; Links, Anne R; Wasserman, Carly; Boss, Emily F

    2018-03-11

    We aimed to develop a comprehensive, descriptive framework to measure shared decision making (SDM) in clinical encounters. We combined a top-down (theoretical) approach with a bottom-up approach based on audio-recorded dialogue to identify all communication processes related to decision making. We coded 55 pediatric otolaryngology visits using the framework and report interrater reliability. We identified 14 clinician behaviors and 5 patient behaviors that have not been previously described, and developed a new SDM framework that is descriptive (what does happen) rather than normative (what should happen). Through the bottom-up approach we identified three broad domains not present in other SDM frameworks: socioemotional support, understandability of clinician dialogue, and recommendation-giving. We also specify the ways in which decision-making roles are assumed implicitly rather than discussed explicitly. Interrater reliability was >75% for 92% of the coded behaviors. This SDM framework allows for a more expansive understanding and analysis of how decision making takes place in clinical encounters, including new domains and behaviors not present in existing measures. We hope that this new framework will bring attention to a broader conception of SDM and allow researchers to further explore the new domains and behaviors identified. Copyright © 2018. Published by Elsevier B.V.

  8. Entanglement entropy in top-down models

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Peter A.R.; Taylor, Marika [Mathematical Sciences and STAG Research Centre, University of Southampton,Highfield, Southampton, SO17 1BJ (United Kingdom)

    2016-08-26

    We explore holographic entanglement entropy in ten-dimensional supergravity solutions. It has been proposed that entanglement entropy can be computed in such top-down models using minimal surfaces which asymptotically wrap the compact part of the geometry. We show explicitly in a wide range of examples that the holographic entanglement entropy thus computed agrees with the entanglement entropy computed using the Ryu-Takayanagi formula from the lower-dimensional Einstein metric obtained from reduction over the compact space. Our examples include not only consistent truncations but also cases in which no consistent truncation exists and Kaluza-Klein holography is used to identify the lower-dimensional Einstein metric. We then give a general proof, based on the Lewkowycz-Maldacena approach, of the top-down entanglement entropy formula.

  9. Entanglement entropy in top-down models

    International Nuclear Information System (INIS)

    Jones, Peter A.R.; Taylor, Marika

    2016-01-01

    We explore holographic entanglement entropy in ten-dimensional supergravity solutions. It has been proposed that entanglement entropy can be computed in such top-down models using minimal surfaces which asymptotically wrap the compact part of the geometry. We show explicitly in a wide range of examples that the holographic entanglement entropy thus computed agrees with the entanglement entropy computed using the Ryu-Takayanagi formula from the lower-dimensional Einstein metric obtained from reduction over the compact space. Our examples include not only consistent truncations but also cases in which no consistent truncation exists and Kaluza-Klein holography is used to identify the lower-dimensional Einstein metric. We then give a general proof, based on the Lewkowycz-Maldacena approach, of the top-down entanglement entropy formula.

  10. Ultra rapidly dissolving repaglinide nanosized crystals prepared via bottom-up and top-down approach: influence of food on pharmacokinetics behavior.

    Science.gov (United States)

    Gadadare, Rahul; Mandpe, Leenata; Pokharkar, Varsha

    2015-08-01

    The present work was undertaken with the objectives of improving the dissolution velocity, related oral bioavailability, and minimizing the fasted/fed state variability of repaglinide, a poorly water-soluble anti-diabetic active by exploring the principles of nanotechnology. Nanocrystal formulations were prepared by both top-down and bottom-up approaches. These approaches were compared in light of their ability to provide the formulation stability in terms of particle size. Soluplus® was used as a stabilizer and Kolliphor™ E-TPGS was used as an oral absorption enhancer. In vitro dissolution profiles were investigated in distilled water, fasted and fed state simulated gastric fluid, and compared with the pure repaglinide. In vivo pharmacokinetics was performed in both the fasted and fed state using Wistar rats. Oral hypoglycemic activity was also assessed in streptozotocin-induced diabetic rats. Nanocrystals TD-A and TD-B showed 19.86 and 25.67-fold increase in saturation solubility, respectively, when compared with pure repaglinide. Almost 10 (TD-A) and 15 (TD-B)-fold enhancement in the oral bioavailability of nanocrystals was observed regardless of the fasted/fed state compared to pure repaglinide. Nanocrystal formulations also demonstrated significant (p < 0.001) hypoglycemic activity with faster onset (less than 30 min) and prolonged duration (up to 8 h) compared to pure repaglinide (after 60 min; up to 4 h, respectively).

  11. Explaining the Decrease in Deaths from Cardiovascular Disease in Poland. The Top-Down Risk Assessment Approach, from Policy to Health Impact.

    Science.gov (United States)

    Kobza, Joanna; Geremek, Mariusz

    2016-04-13

    The purpose of this paper was to assess the relations between policy and health outcome The CVD mortality rate in Poland over the past two decades has decreased by about 40%. It was the highest decrease among Central and Eastern European countries and also exceptional on a global scale. Key determinants which can account for these phenomena include CVD-related life style factors, better environmental indicators, and better access to medical technologies and to pharmacological treatment. Health policy played a vital role. The study was based on an extensive literature review, documentation analysis and questionnaire survey research. The top-down risk assessment approach model was implemented, which followed the logical pathway between the policy, health determinants, risk factors and health outcome. Several national public health programs have been implemented since the beginning of the 1990s. The National Health Fund has constantly increased the expenditures on cardiology treatment. The number of invasive cardiology units has increased, as has the number of coronarography and angioplasty procedures in the same period. The significant mortality decrease can indicate to policy makers that it is necessary to prioritize policies to manage effective, innovative medical interventions. Topdown policy risk assessment is a useful methodological tool to present the full chain of interactions.

  12. A metagenomics-based approach to the top-down effect on the detritivore food web: a salamanders influence on fungal communities within a deciduous forest.

    Science.gov (United States)

    Walker, Donald M; Lawrence, Brandy R; Esterline, Dakota; Graham, Sean P; Edelbrock, Michael A; Wooten, Jessica A

    2014-11-01

    The flow of energy within an ecosystem can be considered either top-down, where predators influence consumers, or bottom-up, where producers influence consumers. Plethodon cinereus (Red-backed Salamander) is a terrestrial keystone predator who feeds on invertebrates within the ecosystem. We investigated the impact of the removal of P. cinereus on the detritivore food web in an upland deciduous forest in northwest Ohio, U.S.A. A total of eight aluminum enclosures, each containing a single P. cinereus under a small log, were constructed in the deciduous forest. On Day 1 of the experiment, four salamanders were evicted from four of the eight enclosures. Organic matter and soil were collected from the center of each enclosure at Day 1 and Day 21. From each sample, DNA was extracted, fungal-specific amplification performed, and 454 pyrosequencing was used to sequence the nuclear ribosomal internal transcribed spacer (ITS2) region and partial ribosomal large subunit (LSU). Changes in overall fungal community composition or species diversity were not statistically significant between treatments. Statistically significant shifts in the most abundant taxonomic groups of fungi were documented in presence but not absence enclosures. We concluded that P. cinereus does not affect the overall composition or diversity of fungal communities, but does have an impact on specific groups of fungi. This study used a metagenomics-based approach to investigate a missing link among a keystone predator, P. cinereus, invertebrates, and fungal communities, all of which are critical in the detritivore food web.

  13. An efficient top-down approach for the fabrication of large-aspect-ratio g-C3N4 nanosheets with enhanced photocatalytic activities.

    Science.gov (United States)

    Tong, Jincheng; Zhang, Li; Li, Fei; Li, Mingming; Cao, Shaokui

    2015-09-28

    Graphitic carbon nitride (g-C3N4) nanosheets with large aspect ratios were fabricated from bulk g-C3N4 through an efficient top-down approach of moderate disintegration-exfoliation using diluted H2SO4 as an "efficient knife". By prior disintegration in a diluted H2SO4 solution, the exfoliation of bulk g-C3N4 was effectively accelerated. The as-prepared g-C3N4 nanosheets possess a two-dimensional (2D) thin-layer structure with seven-atom thickness, a large lateral size of about 1 μm, and a high specific surface area of 80 m(2) g(-1). Compared with the bulk precursor, the g-C3N4 nanosheets showed much higher efficiency of photogenerated charge transfer and separation, and consequently exhibited enhanced photocatalytic activity toward hydrogen evolution and pollutant decomposition under both full-sunlight and visible-light irradiation.

  14. Top-Down Chemoenzymatic Approach to Synthesizing Diverse High-Mannose N-Glycans and Related Neoglycoproteins for Carbohydrate Microarray Analysis.

    Science.gov (United States)

    Toonstra, Christian; Wu, Lisa; Li, Chao; Wang, Denong; Wang, Lai-Xi

    2018-05-22

    High-mannose-type N-glycans are an important component of neutralizing epitopes on HIV-1 envelope glycoprotein gp120. They also serve as signals for protein folding, trafficking, and degradation in protein quality control. A number of lectins and antibodies recognize high-mannose-type N-glycans, and glycan array technology has provided an avenue to probe these oligomannose-specific proteins. We describe in this paper a top-down chemoenzymatic approach to synthesize a library of high-mannose N-glycans and related neoglycoproteins for glycan microarray analysis. The method involves the sequential enzymatic trimming of two readily available natural N-glycans, the Man 9 GlcNAc 2 Asn prepared from soybean flour and the sialoglycopeptide (SGP) isolated from chicken egg yolks, coupled with chromatographic separation to obtain a collection of a full range of natural high-mannose N-glycans. The Asn-linked N-glycans were conjugated to bovine serum albumin (BSA) to provide neoglycoproteins containing the oligomannose moieties. The glycoepitopes displayed were characterized using an array of glycan-binding proteins, including the broadly virus-neutralizing agents, glycan-specific antibody 2G12, Galanthus nivalis lectin (GNA), and Narcissus pseudonarcissus lectin (NPA).

  15. Climatic and physiographic controls on catchment-scale nitrate loss at different spatial scales: insights from a top-down model development approach

    Science.gov (United States)

    Shafii, Mahyar; Basu, Nandita; Schiff, Sherry; Van Cappellen, Philippe

    2017-04-01

    Dramatic increase in nitrogen circulating in the biosphere due to anthropogenic activities has resulted in impairment of water quality in groundwater and surface water causing eutrophication in coastal regions. Understanding the fate and transport of nitrogen from landscape to coastal areas requires exploring the drivers of nitrogen processes in both time and space, as well as the identification of appropriate flow pathways. Conceptual models can be used as diagnostic tools to provide insights into such controls. However, diagnostic evaluation of coupled hydrological-biogeochemical models is challenging. This research proposes a top-down methodology utilizing hydrochemical signatures to develop conceptual models for simulating the integrated streamflow and nitrate responses while taking into account dominant controls on nitrate variability (e.g., climate, soil water content, etc.). Our main objective is to seek appropriate model complexity that sufficiently reproduces multiple hydrological and nitrate signatures. Having developed a suitable conceptual model for a given watershed, we employ it in sensitivity studies to demonstrate the dominant process controls that contribute to the nitrate response at scales of interest. We apply the proposed approach to nitrate simulation in a range of small to large sub-watersheds in the Grand River Watershed (GRW) located in Ontario. Such multi-basin modeling experiment will enable us to address process scaling and investigate the consequences of lumping processes in terms of models' predictive capability. The proposed methodology can be applied to the development of large-scale models that can help decision-making associated with nutrients management at regional scale.

  16. Approach to characterization of the higher order structure of disulfide-containing proteins using hydrogen/deuterium exchange and top-down mass spectrometry.

    Science.gov (United States)

    Wang, Guanbo; Kaltashov, Igor A

    2014-08-05

    Top-down hydrogen/deuterium exchange (HDX) with mass spectrometric (MS) detection has recently matured to become a potent biophysical tool capable of providing valuable information on higher order structure and conformational dynamics of proteins at an unprecedented level of structural detail. However, the scope of the proteins amenable to the analysis by top-down HDX MS still remains limited, with the protein size and the presence of disulfide bonds being the two most important limiting factors. While the limitations imposed by the physical size of the proteins gradually become more relaxed as the sensitivity, resolution and dynamic range of modern MS instrumentation continue to improve at an ever accelerating pace, the presence of the disulfide linkages remains a much less forgiving limitation even for the proteins of relatively modest size. To circumvent this problem, we introduce an online chemical reduction step following completion and quenching of the HDX reactions and prior to the top-down MS measurements of deuterium occupancy of individual backbone amides. Application of the new methodology to the top-down HDX MS characterization of a small (99 residue long) disulfide-containing protein β2-microglobulin allowed the backbone amide protection to be probed with nearly a single-residue resolution across the entire sequence. The high-resolution backbone protection pattern deduced from the top-down HDX MS measurements carried out under native conditions is in excellent agreement with the crystal structure of the protein and high-resolution NMR data, suggesting that introduction of the chemical reduction step to the top-down routine does not trigger hydrogen scrambling either during the electrospray ionization process or in the gas phase prior to the protein ion dissociation.

  17. Top-down cellular pyramids

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A Y; Rosenfeld, A

    1983-10-01

    A cellular pyramid is an exponentially tapering stack of arrays of processors (cells), where each cell is connected to its neighbors (siblings) on its own level, to a parent on the level above, and to its children on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case. 23 references.

  18. Structural transformations of mechanically induced top-down approach BaFe{sub 12}O{sub 19} nanoparticles synthesized from high crystallinity bulk materials

    Energy Technology Data Exchange (ETDEWEB)

    Low, Zhi Huang [Institute of Advanced Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan (Malaysia); Chen, Soo Kien [Institute of Advanced Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan (Malaysia); Department of Physics, Faculty of Science, University Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan (Malaysia); Ismail, Ismayadi, E-mail: kayzen@gmail.com [Institute of Advanced Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan (Malaysia); Tan, Kim Song [Advanced Imaging Centre, Malaysian Rubber Board, RRIM Sungai Buloh, 47000 Selangor (Malaysia); Liew, J.Y.C. [Department of Physics, Faculty of Science, University Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan (Malaysia)

    2017-05-01

    In this work, a top-down approach was applied to high crystallinity BaFe{sub 12}O{sub 19} bulks, breaking them into smaller nanoparticles by mechanochemical route. The effects of milling time, reaction mechanisms and structural information were investigated. Interestingly, three distinct stages of the mechanochemical mechanism were observed. The XRD results indicated that the BaFe{sub 12}O{sub 19} phase existed even though the mechanical energy had induced the formation of an amorphous phase in the material. The average crystallite size decreased during the first stage and the intermediate stage, and increased during the final stage of the mechanical alloying. A Rietveld refinement analysis suggested the deformation of a mechanically-triggered polyhedral in the magnetoplumbite structure. FESEM micrographs indicated that fragmentation predominated during the first and intermediate stages, until a steady equilibrium state was achieved at in the final stage, where a narrow particle size distribution was observed. HRTEM micrographs suggested the formation of a non-uniform nanostructure shell surrounding the ordered core materials at the edge-interface region. The thickness of the amorphous surface layer extended up to 12 nm during the first and intermediate stages, and diminished to approximately 3 nm after 20 h milling. VSM results showed a mixture of ferromagnetic, superparamagnetic, and paramagnetic behaviours. However, different magnetic behaviours predominated at different milling time, which strongly related to the defects, distorted polyhedra, and non-equilibrium amorphous layers of the material. - Highlights: • Nanoparticles of BaFe{sub 12}O{sub 19} are successfully prepared. • Morphological and structural properties rely on mechanochemical mechanism. • Three stages of mechanochemical mechanism was observed. • Core shell structures (3–12 nm) was found during by extending the milling time. • Magnetic properties were strongly related with the

  19. Structural transformations of mechanically induced top-down approach BaFe12O19 nanoparticles synthesized from high crystallinity bulk materials

    International Nuclear Information System (INIS)

    Low, Zhi Huang; Chen, Soo Kien; Ismail, Ismayadi; Tan, Kim Song; Liew, J.Y.C.

    2017-01-01

    In this work, a top-down approach was applied to high crystallinity BaFe 12 O 19 bulks, breaking them into smaller nanoparticles by mechanochemical route. The effects of milling time, reaction mechanisms and structural information were investigated. Interestingly, three distinct stages of the mechanochemical mechanism were observed. The XRD results indicated that the BaFe 12 O 19 phase existed even though the mechanical energy had induced the formation of an amorphous phase in the material. The average crystallite size decreased during the first stage and the intermediate stage, and increased during the final stage of the mechanical alloying. A Rietveld refinement analysis suggested the deformation of a mechanically-triggered polyhedral in the magnetoplumbite structure. FESEM micrographs indicated that fragmentation predominated during the first and intermediate stages, until a steady equilibrium state was achieved at in the final stage, where a narrow particle size distribution was observed. HRTEM micrographs suggested the formation of a non-uniform nanostructure shell surrounding the ordered core materials at the edge-interface region. The thickness of the amorphous surface layer extended up to 12 nm during the first and intermediate stages, and diminished to approximately 3 nm after 20 h milling. VSM results showed a mixture of ferromagnetic, superparamagnetic, and paramagnetic behaviours. However, different magnetic behaviours predominated at different milling time, which strongly related to the defects, distorted polyhedra, and non-equilibrium amorphous layers of the material. - Highlights: • Nanoparticles of BaFe 12 O 19 are successfully prepared. • Morphological and structural properties rely on mechanochemical mechanism. • Three stages of mechanochemical mechanism was observed. • Core shell structures (3–12 nm) was found during by extending the milling time. • Magnetic properties were strongly related with the mechanically induced defects.

  20. Tailored dendritic core-multishell nanocarriers for efficient dermal drug delivery: A systematic top-down approach from synthesis to preclinical testing.

    Science.gov (United States)

    Hönzke, Stefan; Gerecke, Christian; Elpelt, Anja; Zhang, Nan; Unbehauen, Michael; Kral, Vivian; Fleige, Emanuel; Paulus, Florian; Haag, Rainer; Schäfer-Korting, Monika; Kleuser, Burkhard; Hedtrich, Sarah

    2016-11-28

    Drug loaded dendritic core-multishell (CMS) nanocarriers are of especial interest for the treatment of skin diseases, owing to their striking dermal delivery efficiencies following topical applications. CMS nanocarriers are composed of a polyglycerol core, connected by amide-bonds to an inner alkyl shell and an outer methoxy poly(ethylene glycol) shell. Since topically applied nanocarriers are subjected to biodegradation, the application of conventional amide-based CMS nanocarriers (10-A-18-350) has been limited by the potential production of toxic polyglycerol amines. To circumvent this issue, three tailored ester-based CMS nanocarriers (10-E-12-350, 10-E-15-350, 10-E-18-350) of varying inner alkyl chain length were synthesized and comprehensively characterized in terms of particle size, drug loading, biodegradation and dermal drug delivery efficiency. Dexamethasone (DXM), a potent drug widely used for the treatment of inflammatory skin diseases, was chosen as a therapeutically relevant test compound for the present study. Ester- and amide-based CMS nanocarriers delivered DXM more efficiently into human skin than a commercially available DXM cream. Subsequent in vitro and in vivo toxicity studies identified CMS (10-E-15-350) as the most biocompatible carrier system. The anti-inflammatory potency of DXM-loaded CMS (10-E-15-350) nanocarriers was assessed in TNFα supplemented skin models, where a significant reduction of the pro-inflammatory cytokine IL-8 was seen, with markedly greater efficacy than commercial DXM cream. In summary, we report the rational design and characterization of tailored, biodegradable, ester-based CMS nanocarriers, and their subsequent stepwise screening for biocompatibility, dermal delivery efficiency and therapeutic efficacy in a top-down approach yielding the best carrier system for topical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The synthesis of bottom-up and top-down approaches to climate policy modeling: Electric power technologies and the cost of limiting US CO2 emissions

    International Nuclear Information System (INIS)

    Wing, Ian Sue

    2006-01-01

    In the US, the bulk of CO 2 abatement induced by carbon taxes comes from electric power. This paper incorporates technology detail into the electricity sector of a computable general equilibrium model of the US economy to characterize electric power's technological margins of adjustment to carbon taxes and to elucidate their general equilibrium effects. Compared to the top-down production function representation of the electricity sector, the technology-rich hybrid specification produces less abatement at a higher welfare cost, suggesting that bottom-up models do not necessarily generate lower costs of abatement than top-down models. This result is shown to be sensitive to the elasticity with which technologies' generating capacities adjust to relative prices

  2. 'Targeted top down' approach for the investigation of UTI: A 10-year follow-up study in a cohort of 1000 children.

    Science.gov (United States)

    Broadis, E; Kronfli, R; Flett, M E; Cascio, S; O'Toole, S J

    2016-02-01

    symptoms underwent a DMSA scan, which showed scarring in three (6%). Only 12% of children have a significant radiological abnormality picked up on investigation following a UTI. The present investigation approach differed from the NICE guidelines, where imaging is based on patient age and characteristics of the UTI. All children had a renal US, while DMSA scans were reserved for those children UTI. This promptly identified those with pelvi-ureteric junction obstruction and those with PUV, who all presented >6 months of age with a single UTI and, therefore, based on the NICE guidelines would not have undergone a renal US. Of the children who re-presented with further UTIs, a significant number were found to have dysfunctional voiding. As this link is well reported, it may be appropriate to screen for this in older children at initial presentation. Only three patients, who had a US at presentation, were subsequently found to have scarring on DMSA. After 10 years of follow-up, this could represent a false negative rate of 0.3% for the screening programme. None of the girls were found to have VUR or needed any surgical intervention, which suggested that early identification of the scarring might not have altered management. Few patients required surgical intervention, all of whom were identified early. No patient who re-presented required intervention. This would suggest that the present protocol is effective at picking up abnormalities that require surgical management. This study suggested that after a childhood UTI, the liberal use of renal ultrasound and a focused 'top down' approach to investigation is likely to identify the vast majority of children who require intervention. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  3. Exploring the underlying structure of mental disorders: cross-diagnostic differences and similarities from a network perspective using both a top-down and a bottom-up approach.

    Science.gov (United States)

    Wigman, J T W; van Os, J; Borsboom, D; Wardenaar, K J; Epskamp, S; Klippel, A; Viechtbauer, W; Myin-Germeys, I; Wichers, M

    2015-08-01

    It has been suggested that the structure of psychopathology is best described as a complex network of components that interact in dynamic ways. The goal of the present paper was to examine the concept of psychopathology from a network perspective, combining complementary top-down and bottom-up approaches using momentary assessment techniques. A pooled Experience Sampling Method (ESM) dataset of three groups (individuals with a diagnosis of depression, psychotic disorder or no diagnosis) was used (pooled N = 599). The top-down approach explored the network structure of mental states across different diagnostic categories. For this purpose, networks of five momentary mental states ('cheerful', 'content', 'down', 'insecure' and 'suspicious') were compared between the three groups. The complementary bottom-up approach used principal component analysis to explore whether empirically derived network structures yield meaningful higher order clusters. Individuals with a clinical diagnosis had more strongly connected moment-to-moment network structures, especially the depressed group. This group also showed more interconnections specifically between positive and negative mental states than the psychotic group. In the bottom-up approach, all possible connections between mental states were clustered into seven main components that together captured the main characteristics of the network dynamics. Our combination of (i) comparing network structure of mental states across three diagnostically different groups and (ii) searching for trans-diagnostic network components across all pooled individuals showed that these two approaches yield different, complementary perspectives in the field of psychopathology. The network paradigm therefore may be useful to map transdiagnostic processes.

  4. Top-Down Budgeting—An Instrument to Strengthen Budget Management

    OpenAIRE

    Gösta Ljungman

    2009-01-01

    This paper examines the rationale for a top-down approach to budget preparation and approval, and discusses some factors that have to be considered when reorienting the budget process along these lines. The paper argues that the sequence in which budgetary decisions are taken matters, and that a strong top-down approach strengthens fiscal discipline and improves policy prioritization and coordination. Top-down budgeting also alters the division of roles and responsibilities between the centra...

  5. Piezoresistive effect in top-down fabricated silicon nanowires

    DEFF Research Database (Denmark)

    Reck, Kasper; Richter, Jacob; Hansen, Ole

    2008-01-01

    We have designed and fabricated silicon test chips to investigate the piezoresistive properties of both crystalline and polycrystalline nanowires using a top-down approach, in order to comply with conventional fabrication techniques. The test chip consists of 5 silicon nanowires and a reference...

  6. Combining Top-down and Bottom-up Accountability: Evidence from a Bribery Experiment.

    OpenAIRE

    Danila Serra

    2008-01-01

    Monitoring corruption typically relies on top-down interventions aimed at increasing the probability of external controls and the severity of punishment. An alternative approach to fighting corruption is to induce bottom-up pressure for reform. Recent studies have shown that both top-down and bottom-up mechanisms are rarely able to keep service providers accountable. This paper investigates the effectiveness of an accountability system that combines bottom-up monitoring and top-down auditing ...

  7. Salivary Cystatins: Exploring New Post-Translational Modifications and Polymorphisms by Top-Down High-Resolution Mass Spectrometry.

    Science.gov (United States)

    Manconi, Barbara; Liori, Barbara; Cabras, Tiziana; Vincenzoni, Federica; Iavarone, Federica; Castagnola, Massimo; Messana, Irene; Olianas, Alessandra

    2017-11-03

    Cystatins are a complex family of cysteine peptidase inhibitors. In the present study, various proteoforms of cystatin A, cystatin B, cystatin S, cystatin SN, and cystatin SA were detected in the acid-soluble fraction of human saliva and characterized by a top-down HPLC-ESI-MS approach. Proteoforms of cystatin D were also detected and characterized by an integrated top-down and bottom-up strategy. The proteoforms derive from coding sequence polymorphisms and post-translational modifications, in particular, phosphorylation, N-terminal processing, and oxidation. This study increases the current knowledge of salivary cystatin proteoforms and provides the basis to evaluate possible qualitative/quantitative variations of these proteoforms in different pathological states and reveal new potential salivary biomarkers of disease. Data are available via ProteomeXchange with identifier PXD007170.

  8. Proteomics - new analytical approaches

    International Nuclear Information System (INIS)

    Hancock, W.S.

    2001-01-01

    Full text: Recent developments in the sequencing of the human genome have indicated that the number of coding gene sequences may be as few as 30,000. It is clear, however, that the complexity of the human species is dependent on the much greater diversity of the corresponding protein complement. Estimates of the diversity (discrete protein species) of the human proteome range from 200,000 to 300,000 at the lower end to 2,000,000 to 3,000,000 at the high end. In addition, proteomics (the study of the protein complement to the genome) has been subdivided into two main approaches. Global proteomics refers to a high throughput examination of the full protein set present in a cell under a given environmental condition. Focused proteomics refers to a more detailed study of a restricted set of proteins that are related to a specified biochemical pathway or subcellular structure. While many of the advances in proteomics will be based on the sequencing of the human genome, de novo characterization of protein microheterogeneity (glycosylation, phosphorylation and sulfation as well as the incorporation of lipid components) will be required in disease studies. To characterize these modifications it is necessary to digest the protein mixture with an enzyme to produce the corresponding mixture of peptides. In a process analogous to sequencing of the genome, shot-gun sequencing of the proteome is based on the characterization of the key fragments produced by such a digest. Thus, a glycopeptide and hence a specific glycosylation motif will be identified by a unique mass and then a diagnostic MS/MS spectrum. Mass spectrometry will be the preferred detector in these applications because of the unparalleled information content provided by one or more dimensions of mass measurement. In addition, highly efficient separation processes are an absolute requirement for advanced proteomic studies. For example, a combination of the orthogonal approaches, HPLC and HPCE, can be very powerful

  9. Top-down modulation, emotion, and hallucination

    NARCIS (Netherlands)

    Aleman, A; Kahn, RS

    2002-01-01

    We argue that the pivotal role assigned by Northoff to the principle of top-down modulation in catatonia might successfully be applied to other symptoms of schizophrenia, for example, hallucinations. Second, we propose that Northoffs account would benefit from a more comprehensive analysis of the

  10. Proteomic approach to nanotoxicity.

    Science.gov (United States)

    Matysiak, Magdalena; Kapka-Skrzypczak, Lucyna; Brzóska, Kamil; Gutleb, Arno C; Kruszewski, Marcin

    2016-03-30

    In recent years a large number of engineered nanomaterials (NMs) have been developed with promising technical benefits for consumers and medical appliances. In addition to already known potentially advantageous biological properties (antibiotic, antifungal and antiviral activity) of NMs, many new medical applications of NMs are foreseen, such as drug carriers, contrast agents, radiopharmaceuticals and many others. However, there is increasing concern about potential environmental and health effects due to NMs exposure. An increasing body of evidence suggests that NMs may trigger undesirable hazardous interactions with biological systems with potential to generate harmful effects. In this review we summarized a current state of knowledge on the proteomics approaches to nanotoxicity, including protein corona formation, in vitro and in vivo effects of exposure to NMs on proteome of different classes of organisms, from bacteria and plants to mammals. The effects of NMs on the proteome of environmentally relevant organisms are also described. Despite the benefit that development of nanotechnology may bring to the society, there are still major gaps of knowledge on the influence of nanomaterials on human health and the environment. Thus, it seems necessary to conduct further interdisciplinary research to fill the knowledge gaps in NM toxicity, using more holistic approaches than offered by conventional biological techniques. “OMICS” techniques will certainly help researchers in this field. In this paper we summarized the current stage of knowledge of the effects of nanoparticles on the proteome of different organisms, including those commonly used as an environmentally relevant indicator organisms.

  11. Bridging the Gap between the Nanometer-Scale Bottom-Up and Micrometer-Scale Top-Down Approaches for Site-Defined InP/InAs Nanowires.

    Science.gov (United States)

    Zhang, Guoqiang; Rainville, Christophe; Salmon, Adrian; Takiguchi, Masato; Tateno, Kouta; Gotoh, Hideki

    2015-11-24

    This work presents a method that bridges the gap between the nanometer-scale bottom-up and micrometer-scale top-down approaches for site-defined nanostructures, which has long been a significant challenge for applications that require low-cost and high-throughput manufacturing processes. We realized the bridging by controlling the seed indium nanoparticle position through a self-assembly process. Site-defined InP nanowires were then grown from the indium-nanoparticle array in the vapor-liquid-solid mode through a "seed and grow" process. The nanometer-scale indium particles do not always occupy the same locations within the micrometer-scale open window of an InP exposed substrate due to the scale difference. We developed a technique for aligning the nanometer-scale indium particles on the same side of the micrometer-scale window by structuring the surface of a misoriented InP (111)B substrate. Finally, we demonstrated that the developed method can be used to grow a uniform InP/InAs axial-heterostructure nanowire array. The ability to form a heterostructure nanowire array with this method makes it possible to tune the emission wavelength over a wide range by employing the quantum confinement effect and thus expand the application of this technology to optoelectronic devices. Successfully pairing a controllable bottom-up growth technique with a top-down substrate preparation technique greatly improves the potential for the mass-production and widespread adoption of this technology.

  12. Electrochemistry-assisted top-down characterization of disulfide-containing proteins.

    Science.gov (United States)

    Zhang, Yun; Cui, Weidong; Zhang, Hao; Dewald, Howard D; Chen, Hao

    2012-04-17

    Covalent disulfide bond linkage in a protein represents an important challenge for mass spectrometry (MS)-based top-down protein structure analysis as it reduces the backbone cleavage efficiency for MS/MS dissociation. This study presents a strategy for solving this critical issue via integrating electrochemistry (EC) online with a top-down MS approach. In this approach, proteins undergo electrolytic reduction in an electrochemical cell to break disulfide bonds and then undergo online ionization into gaseous ions for analysis by electron-capture dissociation (ECD) and collision-induced dissociation (CID). The electrochemical reduction of proteins allows one to remove disulfide bond constraints and also leads to increased charge numbers of the resulting protein ions. As a result, sequence coverage was significantly enhanced, as exemplified by β-lactoglobulin A (24 vs 75 backbone cleavages before and after electrolytic reduction, respectively) and lysozyme (5 vs 66 backbone cleavages before and after electrolytic reduction, respectively). This methodology is fast and does not need chemical reductants, which would have an important impact in high-throughput proteomics research.

  13. Bottom-up vs. top-down effects on terrestrial insect herbivores: a meta-analysis.

    Science.gov (United States)

    Vidal, Mayra C; Murphy, Shannon M

    2018-01-01

    Primary consumers are under strong selection from resource ('bottom-up') and consumer ('top-down') controls, but the relative importance of these selective forces is unknown. We performed a meta-analysis to compare the strength of top-down and bottom-up forces on consumer fitness, considering multiple predictors that can modulate these effects: diet breadth, feeding guild, habitat/environment, type of bottom-up effects, type of top-down effects and how consumer fitness effects are measured. We focused our analyses on the most diverse group of primary consumers, herbivorous insects, and found that in general top-down forces were stronger than bottom-up forces. Notably, chewing, sucking and gall-making herbivores were more affected by top-down than bottom-up forces, top-down forces were stronger than bottom-up in both natural and controlled (cultivated) environments, and parasitoids and predators had equally strong top-down effects on insect herbivores. Future studies should broaden the scope of focal consumers, particularly in understudied terrestrial systems, guilds, taxonomic groups and top-down controls (e.g. pathogens), and test for more complex indirect community interactions. Our results demonstrate the surprising strength of forces exerted by natural enemies on herbivorous insects, and thus the necessity of using a tri-trophic approach when studying insect-plant interactions. © 2017 John Wiley & Sons Ltd/CNRS.

  14. The protection pyramid approach : A contribution to the protection of internally displaced persons by combining bottom up coping mechanisms and top down protection strategies into a partnership approach to protection

    NARCIS (Netherlands)

    Janssen, Laura

    2017-01-01

    In het huidige debat over de bescherming van Intern Ontheemde Mensen (IDPs) spelen twee groepen actoren een rol. Enerzijds de ontheemden zelf (Bottom Up actoren genoemd), anderzijds de Staat, niet-Statelijke actoren en andere hulpverleners (Top Down actoren). Van oudsher wordt er meer aandacht

  15. Top-down, bottom-up, and around the jungle gym: a social exchange and networks approach to engaging afterschool programs in implementing evidence-based practices.

    Science.gov (United States)

    Smith, Emilie Phillips; Wise, Eileen; Rosen, Howard; Rosen, Alison; Childs, Sharon; McManus, Margaret

    2014-06-01

    This paper uses concepts from social networks and social exchange theories to describe the implementation of evidence-based practices in afterschool programs. The members of the LEGACY Together Afterschool Project team have been involved in conducting collaborative research to migrate a behavioral strategy that has been documented to reduce disruptive behaviors in classroom settings to a new setting-that of afterschool programs. We adapted the Paxis Institute's version of the Good Behavior Game to afterschool settings which differ from in-school settings, including more fluid attendance, multiple age groupings, diverse activities that may take place simultaneously, and differences in staff training and experience (Barrish et al. in J Appl Behav Anal 2(2):119-124, 1969; Embry et al. in The Pax Good Behavior Game. Hazelden, Center City, 2003; Hynes et al. in J Child Serv 4(3):4-20, 2009; Kellam et al. in Drug Alcohol Depend 95:S5-S28, 2008; Tingstrom et al. in Behav Modif 30(2):225-253, 2006). This paper presents the experiences of the three adult groups involved in the implementation process who give first-person accounts of implementation: (1) university-based scientist-practitioners, (2) community partners who trained and provided technical assistance/coaching, and (3) an afterschool program administrator. We introduce here the AIMS model used to frame the implementation process conceptualized by this town-gown collaborative team. AIMS builds upon previous work in implementation science using four phases in which the three collaborators have overlapping roles: approach/engagement, implementation, monitoring, and sustainability. Within all four phases principles of Social Exchange Theory and Social Network Theory are highlighted.

  16. A top-down / bottom-up approach for multi-actors and multi-criteria assessment of mining projects for sustainable development. Application on Arlit Uranium mines (Niger)

    International Nuclear Information System (INIS)

    Chamaret, A.

    2007-06-01

    This thesis aims to appraise the relevance of using an hybrid top-down / bottom-up approach to evaluate mining projects in the perspective of sustainable development. With the advent of corporate social responsibility and sustainable development concepts, new social expectations have appeared towards companies that go beyond a sole requirement of profit earning capacity. If companies do not answer to these expectations, they risk to lose their social legitimacy. Traditionally associated with social, environmental, economical and political impacts and risks, mining activity is particularly concerned by these new issues. Whereas mineral resources needs have never been so high, mining companies are now expected to limit their negative effects and to take into account their different audiences' expectations in order to define, together, the terms of their social license to operate. Considering the diversity of issues, scales, actors and contexts, the challenge is real and necessitates tools to better understand issues and to structure dialogues. Based on the Uranium mines of Arlit (Niger) case study, this work shows that associating participatory approaches to structuration tools and literature propositions, appears as an efficient formula to better organize issues diversity and to build a structured dialogue between mining companies and their stakeholders. First Part aims to present the theoretical, institutional and sectorial contexts of the thesis. Second Part exposes work and results of the evaluation carried out in Niger. And, Third Part, shows the conclusions that can be derived from this work and presents a proposal for an evaluation framework, potentially applicable to other mining sites. (author)

  17. Integrating top-down and bottom-up approaches to design a cost-effective and equitable programme of measures for adaptation of a river basin to global change

    Science.gov (United States)

    Girard, Corentin; Rinaudo, Jean-Daniel; Pulido-Velazquez, Manuel

    2016-04-01

    Adaptation to the multiple facets of global change challenges the conventional means of sustainably planning and managing water resources at the river basin scale. Numerous demand or supply management options are available, from which adaptation measures need to be selected in a context of high uncertainty of future conditions. Given the interdependency of water users, agreements need to be found at the local level to implement the most effective adaptation measures. Therefore, this work develops an approach combining economics and water resources engineering to select a cost-effective programme of adaptation measures in the context of climate change uncertainty, and to define an equitable allocation of the cost of the adaptation plan between the stakeholders involved. A framework is developed to integrate inputs from the two main approaches commonly used to plan for adaptation. The first, referred to as "top-down", consists of a modelling chain going from global greenhouse gases emission scenarios to local hydrological models used to assess the impact of climate change on water resources. Conversely, the second approach, called "bottom-up", starts from assessing vulnerability at the local level to then identify adaptation measures used to face an uncertain future. The methodological framework presented in this contribution relies on a combination of these two approaches to support the selection of adaptation measures at the local level. Outcomes from these two approaches are integrated to select a cost-effective combination of adaptation measures through a least-cost optimization model developed at the river basin scale. The performances of a programme of measures are assessed under different climate projections to identify cost-effective and least-regret adaptation measures. The issue of allocating the cost of the adaptation plan is considered through two complementary perspectives. The outcome of a negotiation process between the stakeholders is modelled through

  18. Top-Down Enterprise Application Integration with Reference Models

    Directory of Open Access Journals (Sweden)

    Willem-Jan van den Heuvel

    2000-11-01

    Full Text Available For Enterprise Resource Planning (ERP systems such as SAP R/3 or IBM SanFrancisco, the tailoring of reference models for customizing the ERP systems to specific organizational contexts is an established approach. In this paper, we present a methodology that uses such reference models as a starting point for a top-down integration of enterprise applications. The re-engineered models of legacy systems are individually linked via cross-mapping specifications to the forward-engineered reference model's specification. The actual linking of reference and legacy models is done with a methodology for connecting (new business objects with (old legacy systems.

  19. A top-down / bottom-up approach for multi-actors and multi-criteria assessment of mining projects for sustainable development. Application on Arlit Uranium mines (Niger); Une demarche Top-Down / Bottom-Up pour l'evaluation en termes multicriteres et multi-acteurs des projets miniers dans l'optique du developpement durable. Application sur les mines d'Uranium d'Arlit (Niger)

    Energy Technology Data Exchange (ETDEWEB)

    Chamaret, A

    2007-06-15

    This thesis aims to appraise the relevance of using an hybrid top-down / bottom-up approach to evaluate mining projects in the perspective of sustainable development. With the advent of corporate social responsibility and sustainable development concepts, new social expectations have appeared towards companies that go beyond a sole requirement of profit earning capacity. If companies do not answer to these expectations, they risk to lose their social legitimacy. Traditionally associated with social, environmental, economical and political impacts and risks, mining activity is particularly concerned by these new issues. Whereas mineral resources needs have never been so high, mining companies are now expected to limit their negative effects and to take into account their different audiences' expectations in order to define, together, the terms of their social license to operate. Considering the diversity of issues, scales, actors and contexts, the challenge is real and necessitates tools to better understand issues and to structure dialogues. Based on the Uranium mines of Arlit (Niger) case study, this work shows that associating participatory approaches to structuration tools and literature propositions, appears as an efficient formula to better organize issues diversity and to build a structured dialogue between mining companies and their stakeholders. First Part aims to present the theoretical, institutional and sectorial contexts of the thesis. Second Part exposes work and results of the evaluation carried out in Niger. And, Third Part, shows the conclusions that can be derived from this work and presents a proposal for an evaluation framework, potentially applicable to other mining sites. (author)

  20. Developing Multi-Level Institutions from Top-Down Ancestors

    Directory of Open Access Journals (Sweden)

    Martha Dowsley

    2007-11-01

    Full Text Available The academic literature contains numerous examples of the failures of both top-down and bottom-up common pool resource management frameworks. Many authors agree that management regimes instead need to utilize a multi-level governance approach to meet diverse objectives in management. However, many currently operating systems do not have that history. This paper explores the conversion of ancestral top-down regimes to complex systems involving multiple scales, levels and objectives through the management of the polar bear (Ursus maritimus in its five range countries. The less successful polar bear management systems continue to struggle with the challenges of developing institutions with the capacity to learn and change, addressing multiple objectives while recognizing the conservation backbone to management, and matching the institutional scale with biophysical, economic and social scales. The comparatively successful institutions incorporate these features, but reveal on-going problems with vertical links that are partially dealt with through the creation of links to other groups.

  1. Top-Down Influence in Young Children's Linguistic Ambiguity Resolution

    Science.gov (United States)

    Rabagliati, Hugh; Pylkkanen, Liina; Marcus, Gary F.

    2013-01-01

    Language is rife with ambiguity. Do children and adults meet this challenge in similar ways? Recent work suggests that while adults resolve syntactic ambiguities by integrating a variety of cues, children are less sensitive to top-down evidence. We test whether this top-down insensitivity is specific to syntax or a general feature of children's…

  2. Piezoresistance of top-down suspended Si nanowires

    International Nuclear Information System (INIS)

    Koumela, A; Mercier, D; Dupre, C; Jourdan, G; Marcoux, C; Ollier, E; Duraffourg, L; Purcell, S T

    2011-01-01

    Measurements of the gauge factor of suspended, top-down silicon nanowires are presented. The nanowires are fabricated with a CMOS compatible process and with doping concentrations ranging from 2 x 10 20 down to 5 x 10 17 cm -3 . The extracted gauge factors are compared with results on identical non-suspended nanowires and with state-of-the-art results. An increase of the gauge factor after suspension is demonstrated. For the low doped nanowires a value of 235 is measured. Particular attention was paid throughout the experiments to distinguishing real resistance change due to strain modulation from resistance fluctuations due to charge trapping. Furthermore, a numerical model correlating surface charge density with the gauge factor is presented. Comparison of the simulations with experimental measurements shows the validity of this approach. These results contribute to a deeper understanding of the piezoresistive effect in Si nanowires.

  3. A top-down / bottom-up approach for multi-actors and multi-criteria assessment of mining projects for sustainable development. Application on Arlit Uranium mines (Niger); Une demarche Top-Down / Bottom-Up pour l'evaluation en termes multicriteres et multi-acteurs des projets miniers dans l'optique du developpement durable. Application sur les mines d'Uranium d'Arlit (Niger)

    Energy Technology Data Exchange (ETDEWEB)

    Chamaret, A

    2007-06-15

    This thesis aims to appraise the relevance of using an hybrid top-down / bottom-up approach to evaluate mining projects in the perspective of sustainable development. With the advent of corporate social responsibility and sustainable development concepts, new social expectations have appeared towards companies that go beyond a sole requirement of profit earning capacity. If companies do not answer to these expectations, they risk to lose their social legitimacy. Traditionally associated with social, environmental, economical and political impacts and risks, mining activity is particularly concerned by these new issues. Whereas mineral resources needs have never been so high, mining companies are now expected to limit their negative effects and to take into account their different audiences' expectations in order to define, together, the terms of their social license to operate. Considering the diversity of issues, scales, actors and contexts, the challenge is real and necessitates tools to better understand issues and to structure dialogues. Based on the Uranium mines of Arlit (Niger) case study, this work shows that associating participatory approaches to structuration tools and literature propositions, appears as an efficient formula to better organize issues diversity and to build a structured dialogue between mining companies and their stakeholders. First Part aims to present the theoretical, institutional and sectorial contexts of the thesis. Second Part exposes work and results of the evaluation carried out in Niger. And, Third Part, shows the conclusions that can be derived from this work and presents a proposal for an evaluation framework, potentially applicable to other mining sites. (author)

  4. Application of Tandem Two-Dimensional Mass Spectrometry for Top-Down Deep Sequencing of Calmodulin.

    Science.gov (United States)

    Floris, Federico; Chiron, Lionel; Lynch, Alice M; Barrow, Mark P; Delsuc, Marc-André; O'Connor, Peter B

    2018-06-04

    Two-dimensional mass spectrometry (2DMS) involves simultaneous acquisition of the fragmentation patterns of all the analytes in a mixture by correlating their precursor and fragment ions by modulating precursor ions systematically through a fragmentation zone. Tandem two-dimensional mass spectrometry (MS/2DMS) unites the ultra-high accuracy of Fourier transform ion cyclotron resonance (FT-ICR) MS/MS and the simultaneous data-independent fragmentation of 2DMS to achieve extensive inter-residue fragmentation of entire proteins. 2DMS was recently developed for top-down proteomics (TDP), and applied to the analysis of calmodulin (CaM), reporting a cleavage coverage of about ~23% using infrared multiphoton dissociation (IRMPD) as fragmentation technique. The goal of this work is to expand the utility of top-down protein analysis using MS/2DMS in order to extend the cleavage coverage in top-down proteomics further into the interior regions of the protein. In this case, using MS/2DMS, the cleavage coverage of CaM increased from ~23% to ~42%. Graphical Abstract Two-dimensional mass spectrometry, when applied to primary fragment ions from the source, allows deep-sequencing of the protein calmodulin.

  5. The top-down reflooding model in the Cathare code

    International Nuclear Information System (INIS)

    Bartak, J.; Bestion, D.; Haapalehto, T.

    1993-01-01

    A top-down reflooding model was developed for the French best-estimate thermalhydraulic code CATHARE. The paper presents the current state of development of this model. Based on a literature survey and on compatibility considerations with respect to the existing CATHARE bottom reflooding package, a falling film top-down reflooding model was developed and implemented into CATHARE version 1.3E. Following a brief review of previous work, the paper describes the most important features of the model. The model was validated with the WINFRITH single tube top-down reflooding experiment and with the REWET - II simultaneous bottom and top-down reflooding experiment in rod bundle geometry. The results demonstrate the ability of the new package to describe the falling film rewetting phenomena and the main parametric trends both in a simple analytical experimental setup and in a much more complex rod bundle reflooding experiment. (authors). 9 figs., 28 refs

  6. Top-Down Beta Enhances Bottom-Up Gamma.

    Science.gov (United States)

    Richter, Craig G; Thompson, William H; Bosman, Conrado A; Fries, Pascal

    2017-07-12

    Several recent studies have demonstrated that the bottom-up signaling of a visual stimulus is subserved by interareal gamma-band synchronization, whereas top-down influences are mediated by alpha-beta band synchronization. These processes may implement top-down control of stimulus processing if top-down and bottom-up mediating rhythms are coupled via cross-frequency interaction. To test this possibility, we investigated Granger-causal influences among awake macaque primary visual area V1, higher visual area V4, and parietal control area 7a during attentional task performance. Top-down 7a-to-V1 beta-band influences enhanced visually driven V1-to-V4 gamma-band influences. This enhancement was spatially specific and largest when beta-band activity preceded gamma-band activity by ∼0.1 s, suggesting a causal effect of top-down processes on bottom-up processes. We propose that this cross-frequency interaction mechanistically subserves the attentional control of stimulus selection. SIGNIFICANCE STATEMENT Contemporary research indicates that the alpha-beta frequency band underlies top-down control, whereas the gamma-band mediates bottom-up stimulus processing. This arrangement inspires an attractive hypothesis, which posits that top-down beta-band influences directly modulate bottom-up gamma band influences via cross-frequency interaction. We evaluate this hypothesis determining that beta-band top-down influences from parietal area 7a to visual area V1 are correlated with bottom-up gamma frequency influences from V1 to area V4, in a spatially specific manner, and that this correlation is maximal when top-down activity precedes bottom-up activity. These results show that for top-down processes such as spatial attention, elevated top-down beta-band influences directly enhance feedforward stimulus-induced gamma-band processing, leading to enhancement of the selected stimulus. Copyright © 2017 Richter, Thompson et al.

  7. Top-down and middle-down approach by fraction collection enrichment using off-line capillary electrophoresis - mass spectrometry coupling: Application to monoclonal antibody Fc/2 charge variants.

    Science.gov (United States)

    Biacchi, Michael; Said, Nassur; Beck, Alain; Leize-Wagner, Emmanuelle; François, Yannis-Nicolas

    2017-05-19

    The characterization of complex protein mixtures represents one of the biggest challenge in many research fields such as biological or biopharmaceutical sciences. Out of all categories, monoclonal antibodies (mAbs) and related products drawn the most interest due to their strong therapeutic potency and specificity. Because of their intrinsic complexity due to a large number of micro-heterogeneities, there is a crucial need for analytical methods to provide comprehensive in-depth characterization of these proteins. In this work, we developed a methodology using CE-UV/MALDI-MS to perform top-down or middle-down characterization after fraction collection enrichment applied to intact protein and mAbs samples. The performance of the method was evaluated with the rapid separation of three intact protein mixture. Good robustness of CZE separation and quality of MALDI-MS spectra and MALDI-ISD spectra of each protein confirms the usefulness of sample enrichment to obtain adequate quantity of deposed protein for top-down analysis and the proof of principle of the method. In a second step, the method was applied to the middle-down characterization of Fc/2 cetuximab variants. Identification of around 9% sequence coverage of Fc/2 cetuximab fragments allows to conclude on the feasibility of the strategy for middle-down characterization of Fc/2 cetuximab variants using CE-UV/MALDI-MS. Moreover, MALDI-ISD fragmentation of Fc/2 cetuximab variants confirm separation phenomenon based on the formation of Fc/2 dimers with and without C-terminal truncation. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Integrated Assessment of Energy Policies: A Decomposition of Top-Down and Bottom-Up

    Energy Technology Data Exchange (ETDEWEB)

    Boehringer, Christoph (Univ. of Oldenburg (Germany)); Rutherford, Thomas F. (ETH Zuerich (Switzerland))

    2008-01-15

    The formulation of market equilibrium problems as mixed complementarity problems (MCP) permits integration of bottom-up programming models of the energy system into top-down general equilibrium models of the overall economy. Yet, in practise the MCP approach loses analytical tractability of income effects, when the energy system includes upper and lowrbounds on many decision variables . We therefore advocate the use of complementarity methods to solve only the top-down economic equilibrium model and employ quadratic programming to solve the underlying bottom-up energy supply model. A simple iterative procedure reconciles the equilibrium prices and quantities between both models.

  9. Top-down and bottom-up definitions of human failure events in human reliability analysis

    International Nuclear Information System (INIS)

    Boring, Ronald Laurids

    2014-01-01

    In the probabilistic risk assessments (PRAs) used in the nuclear industry, human failure events (HFEs) are determined as a subset of hardware failures, namely those hardware failures that could be triggered by human action or inaction. This approach is top-down, starting with hardware faults and deducing human contributions to those faults. Elsewhere, more traditionally human factors driven approaches would tend to look at opportunities for human errors first in a task analysis and then identify which of those errors is risk significant. The intersection of top-down and bottom-up approaches to defining HFEs has not been carefully studied. Ideally, both approaches should arrive at the same set of HFEs. This question is crucial, however, as human reliability analysis (HRA) methods are generalized to new domains like oil and gas. The HFEs used in nuclear PRAs tend to be top-down - defined as a subset of the PRA - whereas the HFEs used in petroleum quantitative risk assessments (QRAs) often tend to be bottom-up - derived from a task analysis conducted by human factors experts. The marriage of these approaches is necessary in order to ensure that HRA methods developed for top-down HFEs are also sufficient for bottom-up applications.

  10. A top-down perspective on dopamine, motivation and memory.

    Science.gov (United States)

    Phillips, Anthony G; Vacca, Giada; Ahn, Soyon

    2008-08-01

    Dopamine (DA) activity, in the form of increased neural firing or enhanced release of transmitter from nerve terminals and varicosities, is linked to a number of important psychological processes including: movement; hedonic reactions to positive reward; provision of an error detection signal during the acquisition of new learning; response to novel stimuli; provision of reinforcement signals essential for acquisition of new action patterns; and incentive motivation. This review focuses primarily on our research linking dynamic changes in DA efflux on the timescale of minutes, with incentive motivation, as revealed by brain dialysis experiments in behaving animals. Recent experiments on sensory-specific satiety and successive positive and negative contrast are discussed along with the distinction between preparatory behaviors that precede contact with biologically significant stimuli and subsequent consummatory behaviors. The relationship between DA efflux in the medial prefrontal cortex (mPFC) and foraging for food based on working memory is also discussed in support of the conjecture that DA may serve as a link between motivation and memory functions. Evidence in support of 'top-down' regulation of dopaminergic activity in the mesocorticolimbic DA pathways is reviewed briefly to introduce a mechanism by which activation of ascending DA projections in this manner might optimize dopaminergic modulation of executive function within regions such as the mPFC. Collectively, these processes could ensure coordination between cognitive processes that assess current opportunities and the motivational systems that select and engage patterns of approach behavior that bring organisms into contact with the essentials for survival.

  11. Impact of top-down control during mental fatigue

    NARCIS (Netherlands)

    Lorist, Monicque M.

    2008-01-01

    The influence of mental fatigue, as induced by time on task, on top-down control involved in planning goal-directed behavior and conflict resolution was examined, using an S1-S2 paradigm. S2 stimuli consisted of compatible and incompatible stimuli, placing dissimilar demands on automatic and

  12. Flipped Top-Down is Systematic Bottom-Up

    NARCIS (Netherlands)

    Zaytsev, V.; Sturm, A.; Clark, T.

    2016-01-01

    The paper presents an experience report in course design for a versatile group of computer science students where their needs were surfaced and met by the combination of strict top-down exposure to course material and the flipped classroom model of lecturing.

  13. The generation of myricetin-nicotinamide nanococrystals by top down and bottom up technologies.

    Science.gov (United States)

    Liu, Mingyu; Hong, Chao; Li, Guowen; Ma, Ping; Xie, Yan

    2016-09-30

    Myricetin-nicotinamide (MYR-NIC) nanococrystal preparation methods were developed and optimized using both top down and bottom up approaches. The grinding (top down) method successfully achieved nanococrystals, but there were some micrometer range particles and aggregation. The key consideration of the grinding technology was to control the milling time to determine a balance between the particle size and distribution. In contrast, a modified bottom up approach based on a solution method in conjunction with sonochemistry resulted in a uniform MYR-NIC nanococrystal that was confirmed by powder x-ray diffraction, scanning electron microscopy, dynamic light scattering, and differential scanning calorimeter, and the particle dissolution rate and amount were significantly greater than that of MYR-NIC cocrystal. Notably, this was a simple method without the addition of any non-solvent. We anticipate our findings will provide some guidance for future nanococrystal preparation as well as its application in both chemical and pharmaceutical area.

  14. A balance of bottom-up and top-down in linking climate policies

    Science.gov (United States)

    Green, Jessica F.; Sterner, Thomas; Wagner, Gernot

    2014-12-01

    Top-down climate negotiations embodied by the Kyoto Protocol have all but stalled, chiefly because of disagreements over targets and objections to financial transfers. To avoid those problems, many have shifted their focus to linkage of bottom-up climate policies such as regional carbon markets. This approach is appealing, but we identify four obstacles to successful linkage: different levels of ambition; competing domestic policy objectives; objections to financial transfers; and the difficulty of close regulatory coordination. Even with a more decentralized approach, overcoming the 'global warming gridlock' of the intergovernmental negotiations will require close international coordination. We demonstrate how a balance of bottom-up and top-down elements can create a path toward an effective global climate architecture.

  15. Proteomic approaches in research of cyanobacterial photosynthesis.

    Science.gov (United States)

    Battchikova, Natalia; Angeleri, Martina; Aro, Eva-Mari

    2015-10-01

    Oxygenic photosynthesis in cyanobacteria, algae, and plants is carried out by a fabulous pigment-protein machinery that is amazingly complicated in structure and function. Many different approaches have been undertaken to characterize the most important aspects of photosynthesis, and proteomics has become the essential component in this research. Here we describe various methods which have been used in proteomic research of cyanobacteria, and demonstrate how proteomics is implemented into on-going studies of photosynthesis in cyanobacterial cells.

  16. The Interplay of Top-Down and Bottom-Up

    DEFF Research Database (Denmark)

    Winkler, Till; Brown, Carol V.; Ozturk, Pinar

    2014-01-01

    The exchange of patient health information across different organizations involved in healthcare delivery has potential benefits for a wide range of stakeholders. However, many governments in Europe and in the U.S. have, despite both top-down and bottom-up initiatives, experienced major barriers...... in achieving sustainable models for implementing health information exchange (HIE) throughout their healthcare systems. In the case of the U.S., three years after stimulus funding allocated as part of the 2009 HITECH Act, the extent to which government funding will be needed to sustain health information...... organizations (HIOs) that facilitate HIE across regional stakeholders remains an unanswered question. This research investigates the impacts of top-down and bottom-up initiatives on the evolutionary paths of HIOs in two contingent states in the U.S. (New Jersey and New York) which had different starting...

  17. Identification of ultramodified proteins using top-down spectra

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaowen; Hengel, Shawna M.; Wu, Si; Tolic, Nikola; Pasa-Tolic, Ljiljana; Pevzner, Pavel A.

    2013-04-10

    Post-translational modifications (PTMs) play an important role in various biological processes through changing protein structure and function. Some ultramodified proteins (like histones) have multiple PTMs forming PTM patterns that define the functionality of a protein. While bottom-up mass spectrometry (MS) has been successful in identifying individual PTMs within short peptides, it is unable to identify PTM patterns spread along entire proteins in a coordinated fashion. In contrast, top-down MS analyzes intact proteins and reveals PTM patterns along the entire proteins. However, while recent advances in instrumentation have made top-down MS accessible to many laboratories, most computational tools for top-down MS focus on proteins with few PTMs and are unable to identify complex PTM patterns. We propose a new algorithm, MS-Align-E, that identifies both expected and unexpected PTMs in ultramodified proteins. We demonstrate that MS-Align-E identifies many protein forms of histone H4 and benchmark it against the currently accepted software tools.

  18. Identification of Ultramodified Proteins Using Top-Down Mass Spectra

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaowen; Hengel, Shawna M.; Wu, Si; Tolic, Nikola; Pasa-Tolic, Ljiljana; Pevzner, Pavel A.

    2013-11-05

    Post-translational modifications (PTMs) play an important role in various biological processes through changing protein structure and function. Some ultramodified proteins (like histones) have multiple PTMs forming PTM patterns that define the functionality of a protein. While bottom-up mass spectrometry (MS) has been successful in identifying individual PTMs within short peptides, it is unable to identify PTM patterns spread along entire proteins in a coordinated fashion. In contrast, top-down MS analyzes intact proteins and reveals PTM patterns along the entire proteins. However, while recent advances in instrumentation have made top-down MS accessible to many laboratories, most computational tools for top-down MS focus on proteins with few PTMs and are unable to identify complex PTM patterns. We propose a new algorithm, MS-Align-E, that identifies both expected and unexpected PTMs in ultramodified proteins. We demonstrate that MS-Align-E identifies many protein forms of histone H4 and benchmark it against the currently accepted software tools.

  19. Enhanced stimulated emission in ZnO thin films using microdisk top-down structuring

    Energy Technology Data Exchange (ETDEWEB)

    Nomenyo, K.; Kostcheev, S.; Lérondel, G. [Laboratoire de Nanotechnologie et d' Instrumentation Optique, Institut Charles Delaunay, CNRS UMR 6281, Université de Technologie de Troyes, 12 rue Marie Curie, CS 42060, 10004 Troyes Cedex (France); Gadallah, A.-S. [Laboratoire de Nanotechnologie et d' Instrumentation Optique, Institut Charles Delaunay, CNRS UMR 6281, Université de Technologie de Troyes, 12 rue Marie Curie, CS 42060, 10004 Troyes Cedex (France); Department of Laser Sciences and Interactions, National Institute of Laser Enhanced Sciences, Cairo University, Giza (Egypt); Rogers, D. J. [Nanovation, 8, route de Chevreuse, 78117 Châteaufort (France)

    2014-05-05

    Microdisks were fabricated in zinc oxide (ZnO) thin films using a top-down approach combining electron beam lithography and reactive ion etching. These microdisk structured thin films exhibit a stimulated surface emission between 3 and 7 times higher than that from a reference film depending on the excitation power density. Emission peak narrowing, reduction in lasing threshold and blue-shifting of the emission wavelength were observed along with enhancement in the emitted intensity. Results indicate that this enhancement is due to an increase in the internal quantum efficiency combined with an amplification of the stimulated emission. An analysis in terms of waveguiding is presented in order to explain these effects. These results demonstrate that very significant gains in emission can be obtained through conventional microstructuration without the need for more onerous top-down nanostructuration techniques.

  20. Identification of hemoglobin variants by top-down mass spectrometry using selected diagnostic product ions.

    Science.gov (United States)

    Coelho Graça, Didia; Hartmer, Ralf; Jabs, Wolfgang; Beris, Photis; Clerici, Lorella; Stoermer, Carsten; Samii, Kaveh; Hochstrasser, Denis; Tsybin, Yury O; Scherl, Alexander; Lescuyer, Pierre

    2015-04-01

    Hemoglobin disorder diagnosis is a complex procedure combining several analytical steps. Due to the lack of specificity of the currently used protein analysis methods, the identification of uncommon hemoglobin variants (proteoforms) can become a hard task to accomplish. The aim of this work was to develop a mass spectrometry-based approach to quickly identify mutated protein sequences within globin chain variants. To reach this goal, a top-down electron transfer dissociation mass spectrometry method was developed for hemoglobin β chain analysis. A diagnostic product ion list was established with a color code strategy allowing to quickly and specifically localize a mutation in the hemoglobin β chain sequence. The method was applied to the analysis of rare hemoglobin β chain variants and an (A)γ-β fusion protein. The results showed that the developed data analysis process allows fast and reliable interpretation of top-down electron transfer dissociation mass spectra by nonexpert users in the clinical area.

  1. A Top Down Strategy to Enhance Information Technologies into Israeli Higher Education

    Directory of Open Access Journals (Sweden)

    Sarah Guri-Rosenblit

    2002-01-01

    Full Text Available This article examines the integration of the new information technologies (IT into Israeli higher education, and most particularly its research universities through a top-down strategy, initiated by the Israeli Council for Higher Education since the end of 1999. This top-down strategy has created a systemic change that will affect the many layers of university activities rather than in a random, sporadic manner undertaken by enthusiastic individuals. This article discusses the built-in contradictions and dilemmas in the process of adapting distance teaching methods by conventional universities in Israel (as well as in other higher education systems. It examines the merits of a top-down strategy aimed to implement the IT through a macro-level, systemic approach, and analyses the differential uses of the IT in Israeli higher education institutions, relating to variables of: access-outreach; teaching-learning processes; study materials production; data and information retrieval; administrative functions; the creation of researchers' communities; inter-institutional collaboration; and associated costs. The article concludes with some suggestions for effective implementation of the IT in different types of higher education institutions in a comprehensive and systematic manner, that will take into account their academic ethos and organizational infrastructure, and cater to the unique needs and characteristics of their relevant constituencies.

  2. Propulsion integration of hypersonic air-breathing vehicles utilizing a top-down design methodology

    Science.gov (United States)

    Kirkpatrick, Brad Kenneth

    In recent years, a focus of aerospace engineering design has been the development of advanced design methodologies and frameworks to account for increasingly complex and integrated vehicles. Techniques such as parametric modeling, global vehicle analyses, and interdisciplinary data sharing have been employed in an attempt to improve the design process. The purpose of this study is to introduce a new approach to integrated vehicle design known as the top-down design methodology. In the top-down design methodology, the main idea is to relate design changes on the vehicle system and sub-system level to a set of over-arching performance and customer requirements. Rather than focusing on the performance of an individual system, the system is analyzed in terms of the net effect it has on the overall vehicle and other vehicle systems. This detailed level of analysis can only be accomplished through the use of high fidelity computational tools such as Computational Fluid Dynamics (CFD) or Finite Element Analysis (FEA). The utility of the top-down design methodology is investigated through its application to the conceptual and preliminary design of a long-range hypersonic air-breathing vehicle for a hypothetical next generation hypersonic vehicle (NHRV) program. System-level design is demonstrated through the development of the nozzle section of the propulsion system. From this demonstration of the methodology, conclusions are made about the benefits, drawbacks, and cost of using the methodology.

  3. Top-Down Hydrogen-Deuterium Exchange Analysis of Protein Structures Using Ultraviolet Photodissociation.

    Science.gov (United States)

    Brodie, Nicholas I; Huguet, Romain; Zhang, Terry; Viner, Rosa; Zabrouskov, Vlad; Pan, Jingxi; Petrotchenko, Evgeniy V; Borchers, Christoph H

    2018-03-06

    Top-down hydrogen-deuterium exchange (HDX) analysis using electron capture or transfer dissociation Fourier transform mass spectrometry (FTMS) is a powerful method for the analysis of secondary structure of proteins in solution. The resolution of the method is a function of the degree of fragmentation of backbone bonds in the proteins. While fragmentation is usually extensive near the N- and C-termini, electron capture (ECD) or electron transfer dissociation (ETD) fragmentation methods sometimes lack good coverage of certain regions of the protein, most often in the middle of the sequence. Ultraviolet photodissociation (UVPD) is a recently developed fast-fragmentation technique, which provides extensive backbone fragmentation that can be complementary in sequence coverage to the aforementioned electron-based fragmentation techniques. Here, we explore the application of electrospray ionization (ESI)-UVPD FTMS on an Orbitrap Fusion Lumos Tribrid mass spectrometer to top-down HDX analysis of proteins. We have incorporated UVPD-specific fragment-ion types and fragment-ion mixtures into our isotopic envelope fitting software (HDX Match) for the top-down HDX analysis. We have shown that UVPD data is complementary to ETD, thus improving the overall resolution when used as a combined approach.

  4. Combinatorial modification of human histone H4 quantitated by two-dimensional liquid chromatography coupled with top down mass spectrometry.

    Science.gov (United States)

    Pesavento, James J; Bullock, Courtney R; LeDuc, Richard D; Mizzen, Craig A; Kelleher, Neil L

    2008-05-30

    Quantitative proteomics has focused heavily on correlating protein abundances, ratios, and dynamics by developing methods that are protein expression-centric (e.g. isotope coded affinity tag, isobaric tag for relative and absolute quantification, etc.). These methods effectively detect changes in protein abundance but fail to provide a comprehensive perspective of the diversity of proteins such as histones, which are regulated by post-translational modifications. Here, we report the characterization of modified forms of HeLa cell histone H4 with a dynamic range >10(4) using a strictly Top Down mass spectrometric approach coupled with two dimensions of liquid chromatography. This enhanced dynamic range enabled the precise characterization and quantitation of 42 forms uniquely modified by combinations of methylation and acetylation, including those with trimethylated Lys-20, monomethylated Arg-3, and the novel dimethylated Arg-3 (each <1% of all H4 forms). Quantitative analyses revealed distinct trends in acetylation site occupancy depending on Lys-20 methylation state. Because both modifications are dynamically regulated through the cell cycle, we simultaneously investigated acetylation and methylation kinetics through three cell cycle phases and used these data to statistically assess the robustness of our quantitative analysis. This work represents the most comprehensive analysis of histone H4 forms present in human cells reported to date.

  5. Effect of Astringent Stimuli on Salivary Protein Interactions Elucidated by Complementary Proteomics Approaches.

    Science.gov (United States)

    Delius, Judith; Médard, Guillaume; Kuster, Bernhard; Hofmann, Thomas

    2017-03-15

    The interaction of astringent substances with salivary proteins, which results in protein precipitation, is considered a key event in the molecular mechanism underlying the oral sensation of puckering astringency. As the chemical nature of orally active astringents is diverse and the knowledge of their interactions with salivary proteins rather fragmentary, human whole saliva samples were incubated with suprathreshold and isointensity solutions of the astringent polyphenol (-)-epigallocatechin gallate, the multivalent metal salt iron(III) sulfate, the amino-functionalized polysaccharide chitosan, and the basic protein lysozyme. After separation of the precipitated proteins, the proteins affected by the astringents were identified and relatively quantified for the first time by complementary bottom-up and top-down mass spectrometry-based proteomics approaches. Major salivary target proteins, which may be involved in astringency perception, are reported here for each astringent stimulus.

  6. Integrating Top-down and Bottom-up Cybersecurity Guidance using XML.

    Science.gov (United States)

    Lubell, Joshua

    2016-08-01

    This paper describes a markup-based approach for synthesizing disparate information sources and discusses a software implementation of the approach. The implementation makes it easier for people to use two complementary, but differently structured, guidance specifications together: the (top-down) Cybersecurity Framework and the (bottom-up) National Institute of Standards and Technology Special Publication 800-53 security control catalog. An example scenario demonstrates how the software implementation can help a security professional select the appropriate safeguards for restricting unauthorized access to an Industrial Control System. The implementation and example show the benefits of this approach and suggest its potential application to disciplines other than cybersecurity.

  7. Integrating Top-down and Bottom-up Cybersecurity Guidance using XML

    Science.gov (United States)

    Lubell, Joshua

    2016-01-01

    This paper describes a markup-based approach for synthesizing disparate information sources and discusses a software implementation of the approach. The implementation makes it easier for people to use two complementary, but differently structured, guidance specifications together: the (top-down) Cybersecurity Framework and the (bottom-up) National Institute of Standards and Technology Special Publication 800-53 security control catalog. An example scenario demonstrates how the software implementation can help a security professional select the appropriate safeguards for restricting unauthorized access to an Industrial Control System. The implementation and example show the benefits of this approach and suggest its potential application to disciplines other than cybersecurity. PMID:27795810

  8. Top down arsenic uncertainty measurement in water and sediments from Guarapiranga dam (Brazil)

    Science.gov (United States)

    Faustino, M. G.; Lange, C. N.; Monteiro, L. R.; Furusawa, H. A.; Marques, J. R.; Stellato, T. B.; Soares, S. M. V.; da Silva, T. B. S. C.; da Silva, D. B.; Cotrim, M. E. B.; Pires, M. A. F.

    2018-03-01

    Total arsenic measurements assessment regarding legal threshold demands more than average and standard deviation approach. In this way, analytical measurement uncertainty evaluation was conducted in order to comply with legal requirements and to allow the balance of arsenic in both water and sediment compartments. A top-down approach for measurement uncertainties was applied to evaluate arsenic concentrations in water and sediments from Guarapiranga dam (São Paulo, Brazil). Laboratory quality control and arsenic interlaboratory tests data were used in this approach to estimate the uncertainties associated with the methodology.

  9. Top-down contextual knowledge guides visual attention in infancy.

    Science.gov (United States)

    Tummeltshammer, Kristen; Amso, Dima

    2017-10-26

    The visual context in which an object or face resides can provide useful top-down information for guiding attention orienting, object recognition, and visual search. Although infants have demonstrated sensitivity to covariation in spatial arrays, it is presently unclear whether they can use rapidly acquired contextual knowledge to guide attention during visual search. In this eye-tracking experiment, 6- and 10-month-old infants searched for a target face hidden among colorful distracter shapes. Targets appeared in Old or New visual contexts, depending on whether the visual search arrays (defined by the spatial configuration, shape and color of component items in the search display) were repeated or newly generated throughout the experiment. Targets in Old contexts appeared in the same location within the same configuration, such that context covaried with target location. Both 6- and 10-month-olds successfully distinguished between Old and New contexts, exhibiting faster search times, fewer looks at distracters, and more anticipation of targets when contexts repeated. This initial demonstration of contextual cueing effects in infants indicates that they can use top-down information to facilitate orienting during memory-guided visual search. © 2017 John Wiley & Sons Ltd.

  10. Top-Down Control of Diesel-Degrading Prokaryotic Communities.

    Science.gov (United States)

    Sauret, Caroline; Böttjer, Daniela; Talarmin, Agathe; Guigue, Catherine; Conan, Pascal; Pujo-Pay, Mireille; Ghiglione, Jean-François

    2015-08-01

    Biostimulation through the addition of inorganic nutrients has been the most widely practiced bioremediation strategy in oil-polluted marine waters. However, little attention has so far been paid to the microbial food web and the impact of top-down control that directly or indirectly influences the success of the bioremediation. We designed a mesocosm experiment using pre-filtered (diesel fuel. Prokaryotes, HNF and VLP abundances showed a predator-prey succession, with a co-development of HNF and VLP. In the polluted system, we observed a stronger impact of viral lysis on prokaryotic abundances than in the control. Analysis of the diversity revealed that a bloom of Vibrio sp. occurred in the polluted mesocosm. That bloom was rapidly followed by a less abundant and more even community of predation-resistant bacteria, including known hydrocarbon degraders such as Oleispira spp. and Methylophaga spp. and opportunistic bacteria such as Percisivirga spp., Roseobacter spp. and Phaeobacter spp. The shift in prokaryotic dominance in response to viral lysis provided clear evidence of the 'killing the winner' model. Nevertheless, despite clear effects on prokaryotic abundance, activity and diversity, the diesel degradation was not impacted by top-down control. The present study investigates for the first time the functioning of a complex microbial network (including VLP) using a nutrient-based biostimulation strategy and highlights some key processes useful for tailoring bioremediation.

  11. Afterimages are biased by top-down information.

    Science.gov (United States)

    Utz, Sandra; Carbon, Claus-Christian

    2015-01-01

    The afterimage illusion refers to a complementary colored image continuing to appear in the observer's vision after the exposure to the original image has ceased. It is assumed to be a phenomenon of the primary visual pathway, caused by overstimulation of photoreceptors of the retina. The aim of the present study was to investigate the nature of afterimage perceptions; mainly whether it is a mere physical, that is, low-level effect or whether it can be modulated by top-down processes, that is, high-level processes. Participants were first exposed to five either strongly female or male faces (Experiment 1), objects highly associated with female or male gender (Experiment 2) or female versus male names (Experiment 3), followed by a negativated image of a gender-neutral face which had to be fixated for 20s to elicit an afterimage. Participants had to rate their afterimages according to sexual dimorphism, showing that the afterimage of the gender-neutral face was perceived as significantly more female in the female priming condition compared with the male priming condition, independently of the priming quality (faces, objects, and names). Our results documented, in addition to previously presumed bottom-up mechanisms, a prominent influence of top-down processing on the perception of afterimages via priming mechanisms (female primes led to more female afterimage perception). © The Author(s) 2015.

  12. Top-down instead of bottom-up estimates of uncertainty in INAA results?

    International Nuclear Information System (INIS)

    Bode, P.; De Nadai Fernandes, E.A.

    2005-01-01

    The initial publication of the ISO Guide to the Expression of Uncertainty in Measurement (GUM) and many related documents has resulted in a worldwide awareness of the importance of a realistic estimate of the value reported after the +/- sign. The evaluation of uncertainty in measurement, as introduced by the GUM, is derived from the principles applied in physical measurements. Many testing laboratories have already experienced large problems in applying these principles in e.g. (bio)chemical measurements, resulting in time-consuming evaluations and costly additional experiments. Other, more pragmatic and less costly approaches have been proposed to obtain a realistic estimate of the range in which the true value of the measurement may be found with a certain degree of probability. One of these approaches, the 'top-down method', is based on the standard deviation in the results of intercomparison data. This approach is much easier for tests for which it is either difficult to establish a full measurement equation, or if e.g. matrix-matching reference materials are absent. It has been demonstrated that the GUM 'bottom-up' approach of evaluating uncertainty in measurement can easily be applied in instrumental neutron activation analysis (INAA) as all significant sources of uncertainty can be evaluated. INAA is therefore a valuable technique to test the validity of the top-down approach. In this contribution, examples of the top-down evaluation of uncertainty in INAA derived from participation in intercomparison rounds and proficiency testing schemes will be presented. The results will be compared with the bottom-up evaluation of uncertainty, and ease of applicability, validity and usefullness of both approaches will be discussed.

  13. Conflict-Triggered Top-Down Control: Default Mode, Last Resort, or No Such Thing?

    Science.gov (United States)

    Bugg, Julie M.

    2014-01-01

    The conflict monitoring account posits that globally high levels of conflict trigger engagement of top-down control; however, recent findings point to the mercurial nature of top-down control in high conflict contexts. The current study examined the potential moderating effect of associative learning on conflict-triggered top-down control…

  14. Experience with a top-down versus bottom-up nuclear engineering educational paradigm

    International Nuclear Information System (INIS)

    Harms, A.A.

    1991-01-01

    Nuclear engineering courses are generally taught from a top-down pedagogical perspective; i.e., one begins with a body of knowledge drawn from advanced nuclear science, engineering, and experience and from this distills a selected part to match the intellectual capacity of the class. This pedagogical approach has evidently been most effect at the graduate level of instruction as evidenced by the ready entry of masters and doctoral students into the professions. A schematic depiction of this approach is suggested and is extended to the undergraduate level of nuclear engineering education

  15. Proteomic and metabolomic approaches to biomarker discovery

    CERN Document Server

    Issaq, Haleem J

    2013-01-01

    Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

  16. Top-Down Historical Phonology of Rote-Meto

    Directory of Open Access Journals (Sweden)

    Owen Edwards

    2018-05-01

    Full Text Available This paper examines the historical phonology of the Rote-Meto languages through a top-down perspective. It describes the sound changes which have taken place between Proto-Malayo-Polynesian and the present-day languages. This reveals a number of shared innovations between Meto and the languages of west Rote, as well as changes shared by the other languages of Rote. Thus, a West Rote-Meto subgroup is identified, as well as a Nuclear Rote subgroup. Within Austronesian, there are phonological innovations shared between Rote-Meto and a number of languages of Timor and surrounding islands. This provides evidence for a Timor-Wetar-Babar subgroup, though this group does not include all languages of Timor.

  17. Combining bottom-up and top-down

    International Nuclear Information System (INIS)

    Boehringer, Christoph; Rutherford, Thomas F.

    2008-01-01

    We motivate the formulation of market equilibrium as a mixed complementarity problem which explicitly represents weak inequalities and complementarity between decision variables and equilibrium conditions. The complementarity format permits an energy-economy model to combine technological detail of a bottom-up energy system with a second-best characterization of the over-all economy. Our primary objective is pedagogic. We first lay out the complementarity features of economic equilibrium and demonstrate how we can integrate bottom-up activity analysis into a top-down representation of the broader economy. We then provide a stylized numerical example of an integrated model - within both static and dynamic settings. Finally, we present illustrative applications to three themes figuring prominently on the energy policy agenda of many industrialized countries: nuclear phase-out, green quotas, and environmental tax reforms

  18. Combining bottom-up and top-down

    Energy Technology Data Exchange (ETDEWEB)

    Boehringer, Christoph [Department of Economics, University of Oldenburg, Oldenburg (Germany); Centre for European Economic Research (ZEW), Mannheim (Germany); Rutherford, Thomas F. [Ann Arbor, Michigan (United States)

    2008-03-15

    We motivate the formulation of market equilibrium as a mixed complementarity problem which explicitly represents weak inequalities and complementarity between decision variables and equilibrium conditions. The complementarity format permits an energy-economy model to combine technological detail of a bottom-up energy system with a second-best characterization of the over-all economy. Our primary objective is pedagogic. We first lay out the complementarity features of economic equilibrium and demonstrate how we can integrate bottom-up activity analysis into a top-down representation of the broader economy. We then provide a stylized numerical example of an integrated model - within both static and dynamic settings. Finally, we present illustrative applications to three themes figuring prominently on the energy policy agenda of many industrialized countries: nuclear phase-out, green quotas, and environmental tax reforms. (author)

  19. What to measure next to improve decision making? On top-down task driven feature saliency

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Karadogan, Seliz; Marchegiani, Letizia

    2011-01-01

    Top-down attention is modeled as decision making based on incomplete information. We consider decisions made in a sequential measurement situation where initially only an incomplete input feature vector is available, however, where we are given the possibility to acquire additional input values...... among the missing features. The procecure thus poses the question what to do next? We take an information theoretical approach implemented for generality in a generative mixture model. The framework allows us reduce the decision about what to measure next in a classification problem to the estimation...

  20. Data on endogenous bovine ovarian follicular cells peptides and small proteins obtained through Top-down High Resolution Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Valérie Labas

    2017-08-01

    Full Text Available The endogenous peptides and small proteins extracted from bovine ovarian follicular cells (oocytes, cumulus and granulosa cells were identified by Top-down High Resolution Mass Spectrometry (TD-HR-MS/MS in order to annotate peptido- and proteoforms detected using qualitative and quantitative profiling method based on ICM-MS (Intact Cell Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. The description and analysis of these Top-down MS data in the context of oocyte quality biomarkers research are available in the original research article of Labas et al. (2017 http://dx.doi.org/10.1016/j.jprot.2017.03.027 [1]. Raw data derived from this peptidomic/proteomic analysis have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository (dataset identifier PXD004892. Here, we described the inventory of all identified peptido- and proteoforms including their biochemical and structural features, and functional annotation of correspondent proteins. This peptide/protein inventory revealed that TD-HR-MS/MS was appropriate method for both global and targeted proteomic analysis of ovarian tissues, and it can be further employed as a reference for other studies on follicular cells including single oocytes.

  1. Integrating cell biology and proteomic approaches in plants.

    Science.gov (United States)

    Takáč, Tomáš; Šamajová, Olga; Šamaj, Jozef

    2017-10-03

    Significant improvements of protein extraction, separation, mass spectrometry and bioinformatics nurtured advancements of proteomics during the past years. The usefulness of proteomics in the investigation of biological problems can be enhanced by integration with other experimental methods from cell biology, genetics, biochemistry, pharmacology, molecular biology and other omics approaches including transcriptomics and metabolomics. This review aims to summarize current trends integrating cell biology and proteomics in plant science. Cell biology approaches are most frequently used in proteomic studies investigating subcellular and developmental proteomes, however, they were also employed in proteomic studies exploring abiotic and biotic stress responses, vesicular transport, cytoskeleton and protein posttranslational modifications. They are used either for detailed cellular or ultrastructural characterization of the object subjected to proteomic study, validation of proteomic results or to expand proteomic data. In this respect, a broad spectrum of methods is employed to support proteomic studies including ultrastructural electron microscopy studies, histochemical staining, immunochemical localization, in vivo imaging of fluorescently tagged proteins and visualization of protein-protein interactions. Thus, cell biological observations on fixed or living cell compartments, cells, tissues and organs are feasible, and in some cases fundamental for the validation and complementation of proteomic data. Validation of proteomic data by independent experimental methods requires development of new complementary approaches. Benefits of cell biology methods and techniques are not sufficiently highlighted in current proteomic studies. This encouraged us to review most popular cell biology methods used in proteomic studies and to evaluate their relevance and potential for proteomic data validation and enrichment of purely proteomic analyses. We also provide examples of

  2. Rapid evolution leads to differential population dynamics and top-down control in resurrected Daphnia populations.

    Science.gov (United States)

    Goitom, Eyerusalem; Kilsdonk, Laurens J; Brans, Kristien; Jansen, Mieke; Lemmens, Pieter; De Meester, Luc

    2018-01-01

    There is growing evidence of rapid genetic adaptation of natural populations to environmental change, opening the perspective that evolutionary trait change may subsequently impact ecological processes such as population dynamics, community composition, and ecosystem functioning. To study such eco-evolutionary feedbacks in natural populations, however, requires samples across time. Here, we capitalize on a resurrection ecology study that documented rapid and adaptive evolution in a natural population of the water flea Daphnia magna in response to strong changes in predation pressure by fish, and carry out a follow-up mesocosm experiment to test whether the observed genetic changes influence population dynamics and top-down control of phytoplankton. We inoculated populations of the water flea D. magna derived from three time periods of the same natural population known to have genetically adapted to changes in predation pressure in replicate mesocosms and monitored both Daphnia population densities and phytoplankton biomass in the presence and absence of fish. Our results revealed differences in population dynamics and top-down control of algae between mesocosms harboring populations from the time period before, during, and after a peak in fish predation pressure caused by human fish stocking. The differences, however, deviated from our a priori expectations. An S-map approach on time series revealed that the interactions between adults and juveniles strongly impacted the dynamics of populations and their top-down control on algae in the mesocosms, and that the strength of these interactions was modulated by rapid evolution as it occurred in nature. Our study provides an example of an evolutionary response that fundamentally alters the processes structuring population dynamics and impacts ecosystem features.

  3. Reconciling Top-Down and Bottom-Up Estimates of Oil and Gas Methane Emissions in the Barnett Shale

    Science.gov (United States)

    Hamburg, S.

    2015-12-01

    Top-down approaches that use aircraft, tower, or satellite-based measurements of well-mixed air to quantify regional methane emissions have typically estimated higher emissions from the natural gas supply chain when compared to bottom-up inventories. A coordinated research campaign in October 2013 used simultaneous top-down and bottom-up approaches to quantify total and fossil methane emissions in the Barnett Shale region of Texas. Research teams have published individual results including aircraft mass-balance estimates of regional emissions and a bottom-up, 25-county region spatially-resolved inventory. This work synthesizes data from the campaign to directly compare top-down and bottom-up estimates. A new analytical approach uses statistical estimators to integrate facility emission rate distributions from unbiased and targeted high emission site datasets, which more rigorously incorporates the fat-tail of skewed distributions to estimate regional emissions of well pads, compressor stations, and processing plants. The updated spatially-resolved inventory was used to estimate total and fossil methane emissions from spatial domains that match seven individual aircraft mass balance flights. Source apportionment of top-down emissions between fossil and biogenic methane was corroborated with two independent analyses of methane and ethane ratios. Reconciling top-down and bottom-up estimates of fossil methane emissions leads to more accurate assessment of natural gas supply chain emission rates and the relative contribution of high emission sites. These results increase our confidence in our understanding of the climate impacts of natural gas relative to more carbon-intensive fossil fuels and the potential effectiveness of mitigation strategies.

  4. A GENERALIZED NON-LINEAR METHOD FOR DISTORTION CORRECTION AND TOP-DOWN VIEW CONVERSION OF FISH EYE IMAGES

    Directory of Open Access Journals (Sweden)

    Vivek Singh Bawa

    2017-06-01

    Full Text Available Advanced driver assistance systems (ADAS have been developed to automate and modify vehicles for safety and better driving experience. Among all computer vision modules in ADAS, 360-degree surround view generation of immediate surroundings of the vehicle is very important, due to application in on-road traffic assistance, parking assistance etc. This paper presents a novel algorithm for fast and computationally efficient transformation of input fisheye images into required top down view. This paper also presents a generalized framework for generating top down view of images captured by cameras with fish-eye lenses mounted on vehicles, irrespective of pitch or tilt angle. The proposed approach comprises of two major steps, viz. correcting the fish-eye lens images to rectilinear images, and generating top-view perspective of the corrected images. The images captured by the fish-eye lens possess barrel distortion, for which a nonlinear and non-iterative method is used. Thereafter, homography is used to obtain top-down view of corrected images. This paper also targets to develop surroundings of the vehicle for wider distortion less field of view and camera perspective independent top down view, with minimum computation cost which is essential due to limited computation power on vehicles.

  5. Top-down models in biology: explanation and control of complex living systems above the molecular level.

    Science.gov (United States)

    Pezzulo, Giovanni; Levin, Michael

    2016-11-01

    It is widely assumed in developmental biology and bioengineering that optimal understanding and control of complex living systems follows from models of molecular events. The success of reductionism has overshadowed attempts at top-down models and control policies in biological systems. However, other fields, including physics, engineering and neuroscience, have successfully used the explanations and models at higher levels of organization, including least-action principles in physics and control-theoretic models in computational neuroscience. Exploiting the dynamic regulation of pattern formation in embryogenesis and regeneration requires new approaches to understand how cells cooperate towards large-scale anatomical goal states. Here, we argue that top-down models of pattern homeostasis serve as proof of principle for extending the current paradigm beyond emergence and molecule-level rules. We define top-down control in a biological context, discuss the examples of how cognitive neuroscience and physics exploit these strategies, and illustrate areas in which they may offer significant advantages as complements to the mainstream paradigm. By targeting system controls at multiple levels of organization and demystifying goal-directed (cybernetic) processes, top-down strategies represent a roadmap for using the deep insights of other fields for transformative advances in regenerative medicine and systems bioengineering. © 2016 The Author(s).

  6. Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents.

    Science.gov (United States)

    Tan, Zhibing; Robinson, Heath L; Yin, Dong-Min; Liu, Yu; Liu, Fang; Wang, Hongsheng; Lin, Thiri W; Xing, Guanglin; Gan, Lin; Xiong, Wen-Cheng; Mei, Lin

    2018-04-18

    Top-down attention is crucial for meaningful behaviors and impaired in various mental disorders. However, its underpinning regulatory mechanisms are poorly understood. We demonstrate that the hippocampal-prefrontal synchrony associates with levels of top-down attention. Both attention and synchrony are reduced in mutant mice of ErbB4, a receptor of neuregulin-1. We used chemical genetic and optogenetic approaches to inactivate ErbB4 kinase and ErbB4+ interneurons, respectively, both of which reduce gamma-aminobutyric acid (GABA) activity. Such inhibitions in the hippocampus impair both hippocampal-prefrontal synchrony and top-down attention, whereas those in the prefrontal cortex alter attention, but not synchrony. These observations identify a role of ErbB4-dependent GABA activity in the hippocampus in synchronizing the hippocampal-prefrontal pathway and demonstrate that acute, dynamic ErbB4 signaling is required to command top-down attention. Because both neuregulin-1 and ErbB4 are susceptibility genes of schizophrenia and major depression, our study contributes to a better understanding of these disorders. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. An integrated top-down and bottom-up strategy for characterization protein isoforms and modifications

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Si; Tolic, Nikola; Tian, Zhixin; Robinson, Errol W.; Pasa-Tolic, Ljiljana

    2011-04-15

    Bottom-up and top-down strategies are two commonly used methods for mass spectrometry (MS) based protein identification; each method has its own advantages and disadvantages. In this chapter, we describe an integrated top-down and bottom-up approach facilitated by concurrent liquid chromatography-mass spectrometry (LC-MS) analysis and fraction collection for comprehensive high-throughput intact protein profiling. The approach employs a high resolution reversed phase (RP) LC separation coupled with LC eluent fraction collection and concurrent on-line MS with a high field (12 Tesla) Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer. Protein elusion profiles and tentative modified protein identification are made using detected intact protein mass in conjunction with bottom-up protein identifications from the enzymatic digestion and analysis of corresponding LC fractions. Specific proteins of biological interest are incorporated into a target ion list for subsequent off-line gas-phase fragmentation that uses an aliquot of the original collected LC fraction, an aliquot of which was also used for bottom-up analysis.

  8. Implementing collaborative improvement - top-down, bottom-up or both?

    DEFF Research Database (Denmark)

    Kaltoft, Rasmus; Boer, Harry; Caniato, Federico

    2007-01-01

    , the study identifies three different implementation approaches. The bottom-up learning-by-doing approach starts at a practical level, with simple improvement activities, and aims at gradually developing a wide range of CoI knowledge, skills and initiatives. The top-down directive approach starts...... with aligning the partners' CoI objectives and an assessment of their collaboration and CoI maturity in order to provide a common platform before actually starting improvement activities. The laissez-faire approach builds on shared goals/vision, meetings on equal terms and joint work, in a non-directive and non......-facilitated way, though. The article demonstrates how and why the different approaches have different effects on the development of collaborative improvement....

  9. Proteomics-grade de novo sequencing approach

    DEFF Research Database (Denmark)

    Savitski, Mikhail M; Nielsen, Michael L; Kjeldsen, Frank

    2005-01-01

    The conventional approach in modern proteomics to identify proteins from limited information provided by molecular and fragment masses of their enzymatic degradation products carries an inherent risk of both false positive and false negative identifications. For reliable identification of even kn...

  10. Development Policy in Thailand: From Top-down to Grass Roots.

    Science.gov (United States)

    Kelly, Matthew; Yutthaphonphinit, Phattaraphon; Seubsman, Sam-Ang; Sleigh, Adrian

    2012-11-01

    Top-down industrial development strategies initially dominated the developing world after the second World War but were eventually found to produce inequitable economic growth. For a decade or more, governments and international development agencies have embraced the idea of participatory grass roots development as a potential solution. Here we review Thailand's experience with development strategies and we examine the current focus on participatory approaches. Thai government planning agencies have adopted "people centred development" and a "sufficiency economy", particularly emphasised since the disruptions caused by the 1997 Asian financial crisis. They aim to address the inequitable sharing of the benefits of decades of rapid growth that was particularly unfair for the rural poor. Thai policies aim to decentralise power to the local level, allowing civil society and Non-Governmental Organisations (NGOs) more of a voice in national decision making and promoting sustainable farming practices aimed at enriching rural communities. An example of this change in Thai government policy is the Community Worker Accreditation Scheme which is aiming to develop human resources at the local level by training community based leaders and supporting networks of community organisations. This enables autonomous local development projects led by trained and accredited individuals and groups. The political tensions notable in Thailand at present are part of this modern transition driven by conflicting models of top-down (industrial) development and the bottom-up (participatory) development ideals described above. Once resolved, Thailand will have few obstacles to moving to a new economic level.

  11. Conflict-Triggered Top-Down Control: Default Mode, Last Resort, or No Such Thing?

    Science.gov (United States)

    Bugg, Julie M.

    2014-01-01

    The conflict monitoring account posits that globally high levels of conflict trigger engagement of top-down control; however, recent findings point to the mercurial nature of top-down control in high conflict contexts. The current study examined the potential moderating effect of associative learning on conflict-triggered top-down control engagement by testing the Associations as Antagonists to Top-Down Control (AATC) hypothesis. In 4 experiments, list-wide proportion congruence was manipulated, and conflict-triggered top-down control engagement was examined by comparing interference for 50% congruent items across mostly congruent (low conflict) and mostly incongruent (high conflict) lists. Despite the fact that global levels of conflict were varied identically across experiments, evidence of conflict-triggered top-down control engagement was selective to those experiments in which responses could not be predicted on the majority of trials via simple associative learning, consistent with the AATC hypothesis. In a fifth experiment, older adults showed no evidence of top-down control engagement under conditions in which young adults did, a finding that refined the interpretation of the patterns observed in the prior experiments. Collectively, these findings suggest that top-down control engagement in high conflict contexts is neither the default mode nor an unused (or non-existent) strategy. Top-down control is best characterized as a last resort that is engaged when reliance on one’s environment, and in particular associative responding, is unproductive for achieving task goals. PMID:24274385

  12. Selective Area Sublimation: A Simple Top-down Route for GaN-Based Nanowire Fabrication.

    Science.gov (United States)

    Damilano, B; Vézian, S; Brault, J; Alloing, B; Massies, J

    2016-03-09

    Post-growth in situ partial SiNx masking of GaN-based epitaxial layers grown in a molecular beam epitaxy reactor is used to get GaN selective area sublimation (SAS) by high temperature annealing. Using this top-down approach, nanowires (NWs) with nanometer scale diameter are obtained from GaN and InxGa1-xN/GaN quantum well epitaxial structures. After GaN regrowth on InxGa1-xN/GaN NWs resulting from SAS, InxGa1-xN quantum disks (QDisks) with nanometer sizes in the three dimensions are formed. Low temperature microphotoluminescence experiments demonstrate QDisk multilines photon emission around 3 eV with individual line widths of 1-2 meV.

  13. Spatial inter-comparison of Top-down emission inventories in European urban areas

    Science.gov (United States)

    Trombetti, Marco; Thunis, Philippe; Bessagnet, Bertrand; Clappier, Alain; Couvidat, Florian; Guevara, Marc; Kuenen, Jeroen; López-Aparicio, Susana

    2018-01-01

    This paper presents an inter-comparison of the main Top-down emission inventories currently used for air quality modelling studies at the European level. The comparison is developed for eleven European cities and compares the distribution of emissions of NOx, SO2, VOC and PPM2.5 from the road transport, residential combustion and industry sectors. The analysis shows that substantial differences in terms of total emissions, sectorial emission shares and spatial distribution exist between the datasets. The possible reasons in terms of downscaling approaches and choice of spatial proxies are analysed and recommendations are provided for each inventory in order to work towards the harmonisation of spatial downscaling and proxy calibration, in particular for policy purposes. The proposed methodology may be useful for the development of consistent and harmonised European-wide inventories with the aim of reducing the uncertainties in air quality modelling activities.

  14. The changing Chinese SEA indicator guidelines: Top-down or bottom-up?

    International Nuclear Information System (INIS)

    Gao, Jingjing; Christensen, Per; Kørnøv, Lone

    2014-01-01

    In the last decades, China has introduced a set of indicators to guide the Strategic Environmental Assessment (SEA) practice. The most recent indicator system proposed in 2009 is based on sector-specific guidelines and it found its justification in past negative experiences with more general guidelines (from 2003), which were mostly inspired by, or copied from, international experiences. Based on interviews with practitioners, researchers and administrators, we map and analyse the change in the national guidelines. This analysis is based on a description of the indicators that makes it possible to discern different aggregation levels of indicators and then trace the changes occurring under two sets of guidelines. The analysis also reveals the reasons and rationales behind the changes found in the guidelines. This analysis is inspired by implementation theory and a description of some of the more general trends in the development of SEA and other environmental policies in a recent Chinese context. Beside a more top-down, intentional approach specifying indicators for different sectors based on Chinese experiences from the preceding years, another significant change, following the new guidelines, is a more bottom-up approach which gives more discretion to practitioners. This entails a call for practitioners to make decisions on indicators, which involves an interpretation of the ones present in sector guidance. Highlights: • Focusing on the new Chinese national SEA guidelines proposed in 2009 • Mapping and analysing the most recent change in the indicator system • Revealing the reasons and rationales behind the changes found in the new guidelines • A top-down intention specifying indicators for different sectors • A bottom-up effect in giving discretion and interpretation of using indicators

  15. The changing Chinese SEA indicator guidelines: Top-down or bottom-up?

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Jingjing, E-mail: Jingjing@plan.aau.dk; Christensen, Per; Kørnøv, Lone

    2014-01-15

    In the last decades, China has introduced a set of indicators to guide the Strategic Environmental Assessment (SEA) practice. The most recent indicator system proposed in 2009 is based on sector-specific guidelines and it found its justification in past negative experiences with more general guidelines (from 2003), which were mostly inspired by, or copied from, international experiences. Based on interviews with practitioners, researchers and administrators, we map and analyse the change in the national guidelines. This analysis is based on a description of the indicators that makes it possible to discern different aggregation levels of indicators and then trace the changes occurring under two sets of guidelines. The analysis also reveals the reasons and rationales behind the changes found in the guidelines. This analysis is inspired by implementation theory and a description of some of the more general trends in the development of SEA and other environmental policies in a recent Chinese context. Beside a more top-down, intentional approach specifying indicators for different sectors based on Chinese experiences from the preceding years, another significant change, following the new guidelines, is a more bottom-up approach which gives more discretion to practitioners. This entails a call for practitioners to make decisions on indicators, which involves an interpretation of the ones present in sector guidance. Highlights: • Focusing on the new Chinese national SEA guidelines proposed in 2009 • Mapping and analysing the most recent change in the indicator system • Revealing the reasons and rationales behind the changes found in the new guidelines • A top-down intention specifying indicators for different sectors • A bottom-up effect in giving discretion and interpretation of using indicators.

  16. Clinical veterinary proteomics: Techniques and approaches to decipher the animal plasma proteome.

    Science.gov (United States)

    Ghodasara, P; Sadowski, P; Satake, N; Kopp, S; Mills, P C

    2017-12-01

    Over the last two decades, technological advancements in the field of proteomics have advanced our understanding of the complex biological systems of living organisms. Techniques based on mass spectrometry (MS) have emerged as powerful tools to contextualise existing genomic information and to create quantitative protein profiles from plasma, tissues or cell lines of various species. Proteomic approaches have been used increasingly in veterinary science to investigate biological processes responsible for growth, reproduction and pathological events. However, the adoption of proteomic approaches by veterinary investigators lags behind that of researchers in the human medical field. Furthermore, in contrast to human proteomics studies, interpretation of veterinary proteomic data is difficult due to the limited protein databases available for many animal species. This review article examines the current use of advanced proteomics techniques for evaluation of animal health and welfare and covers the current status of clinical veterinary proteomics research, including successful protein identification and data interpretation studies. It includes a description of an emerging tool, sequential window acquisition of all theoretical fragment ion mass spectra (SWATH-MS), available on selected mass spectrometry instruments. This newly developed data acquisition technique combines advantages of discovery and targeted proteomics approaches, and thus has the potential to advance the veterinary proteomics field by enhancing identification and reproducibility of proteomics data. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Depression-biased reverse plasticity rule is required for stable learning at top-down connections.

    Directory of Open Access Journals (Sweden)

    Kendra S Burbank

    Full Text Available Top-down synapses are ubiquitous throughout neocortex and play a central role in cognition, yet little is known about their development and specificity. During sensory experience, lower neocortical areas are activated before higher ones, causing top-down synapses to experience a preponderance of post-synaptic activity preceding pre-synaptic activity. This timing pattern is the opposite of that experienced by bottom-up synapses, which suggests that different versions of spike-timing dependent synaptic plasticity (STDP rules may be required at top-down synapses. We consider a two-layer neural network model and investigate which STDP rules can lead to a distribution of top-down synaptic weights that is stable, diverse and avoids strong loops. We introduce a temporally reversed rule (rSTDP where top-down synapses are potentiated if post-synaptic activity precedes pre-synaptic activity. Combining analytical work and integrate-and-fire simulations, we show that only depression-biased rSTDP (and not classical STDP produces stable and diverse top-down weights. The conclusions did not change upon addition of homeostatic mechanisms, multiplicative STDP rules or weak external input to the top neurons. Our prediction for rSTDP at top-down synapses, which are distally located, is supported by recent neurophysiological evidence showing the existence of temporally reversed STDP in synapses that are distal to the post-synaptic cell body.

  18. Depression-Biased Reverse Plasticity Rule Is Required for Stable Learning at Top-Down Connections

    Science.gov (United States)

    Burbank, Kendra S.; Kreiman, Gabriel

    2012-01-01

    Top-down synapses are ubiquitous throughout neocortex and play a central role in cognition, yet little is known about their development and specificity. During sensory experience, lower neocortical areas are activated before higher ones, causing top-down synapses to experience a preponderance of post-synaptic activity preceding pre-synaptic activity. This timing pattern is the opposite of that experienced by bottom-up synapses, which suggests that different versions of spike-timing dependent synaptic plasticity (STDP) rules may be required at top-down synapses. We consider a two-layer neural network model and investigate which STDP rules can lead to a distribution of top-down synaptic weights that is stable, diverse and avoids strong loops. We introduce a temporally reversed rule (rSTDP) where top-down synapses are potentiated if post-synaptic activity precedes pre-synaptic activity. Combining analytical work and integrate-and-fire simulations, we show that only depression-biased rSTDP (and not classical STDP) produces stable and diverse top-down weights. The conclusions did not change upon addition of homeostatic mechanisms, multiplicative STDP rules or weak external input to the top neurons. Our prediction for rSTDP at top-down synapses, which are distally located, is supported by recent neurophysiological evidence showing the existence of temporally reversed STDP in synapses that are distal to the post-synaptic cell body. PMID:22396630

  19. Anterior Cingulate Cortex Input to the Claustrum Is Required for Top-Down Action Control

    Directory of Open Access Journals (Sweden)

    Michael G. White

    2018-01-01

    Full Text Available Summary: Cognitive abilities, such as volitional attention, operate under top-down, executive frontal cortical control of hierarchically lower structures. The circuit mechanisms underlying this process are unresolved. The claustrum possesses interconnectivity with many cortical areas and, thus, is hypothesized to orchestrate the cortical mantle for top-down control. Whether the claustrum receives top-down input and how this input may be processed by the claustrum have yet to be formally tested, however. We reveal that a rich anterior cingulate cortex (ACC input to the claustrum encodes a preparatory top-down information signal on a five-choice response assay that is necessary for optimal task performance. We further show that ACC input monosynaptically targets claustrum inhibitory interneurons and spiny glutamatergic projection neurons, the latter of which amplify ACC input in a manner that is powerfully constrained by claustrum inhibitory microcircuitry. These results demonstrate ACC input to the claustrum is critical for top-down control guiding action. : White et al. show that anterior cingulate cortex (ACC input to the claustrum encodes a top-down preparatory signal on a 5-choice response assay that is critical for task performance. Claustrum microcircuitry amplifies top-down ACC input in a frequency-dependent manner for eventual propagation to the cortex for cognitive control of action. Keywords: 5CSRTT, optogenetics, fiber photometry, microcircuit, attention, bottom-up, sensory cortices, motor cortices

  20. Mapping practices of project management – merging top-down and bottom-up perspectives

    DEFF Research Database (Denmark)

    Thuesen, Christian

    2015-01-01

    This paper presents a new methodology for studying different accounts of project management practices based on network mapping and analysis. Drawing upon network mapping and visualization as an analytical strategy top-down and bottom-up accounts of project management practice are analysed...... and compared. The analysis initially reveals a substantial difference between the top-down and bottom-up accounts of practice. Furthermore it identifies a soft side of project management that is central in the bottom-up account but absent from the top-down. Finally, the study shows that network mapping...

  1. Task-related modulation of anterior theta and posterior alpha EEG reflects top-down preparation

    Directory of Open Access Journals (Sweden)

    Park Hae-Jeong

    2010-06-01

    Full Text Available Abstract Background Prestimulus EEG alpha activity in humans has been considered to reflect ongoing top-down preparation for the performance of subsequent tasks. Since theta oscillations may be related to poststimulus top-down processing, we investigated whether prestimulus EEG theta activity also reflects top-down cognitive preparation for a stimulus. Results We recorded EEG data from 15 healthy controls performing a color and shape discrimination task, and used the wavelet transformation to investigate the time course and power of oscillatory activity in the signals. We observed a relationship between both anterior theta and posterior alpha power in the prestimulus period and the type of subsequent task. Conclusions Since task-differences were reflected in both theta and alpha activities prior to stimulus onset, both prestimulus theta (particularly around the anterior region and prestimulus alpha (particularly around the posterior region activities may reflect prestimulus top-down preparation for the performance of subsequent tasks.

  2. What does distractibility in ADHD reveal about mechanisms for top-down attentional control?

    OpenAIRE

    Friedman-Hill, Stacia R.; Wagman, Meryl R.; Gex, Saskia E.; Pine, Daniel S.; Leibenluft, Ellen; Ungerleider, Leslie G.

    2010-01-01

    In this study, we attempted to clarify whether distractibility in ADHD might arise from increased sensory-driven interference or from inefficient top-down control. We employed an attentional filtering paradigm in which discrimination difficulty and distractor salience (amount of image “graying”) were parametrically manipulated. Increased discrimination difficulty should add to the load of top-down processes, whereas increased distractor salience should produce stronger sensory interference. W...

  3. Top-down knowledge modulates onset capture in a feedforward manner.

    Science.gov (United States)

    Becker, Stefanie I; Lewis, Amanda J; Axtens, Jenna E

    2017-04-01

    How do we select behaviourally important information from cluttered visual environments? Previous research has shown that both top-down, goal-driven factors and bottom-up, stimulus-driven factors determine which stimuli are selected. However, it is still debated when top-down processes modulate visual selection. According to a feedforward account, top-down processes modulate visual processing even before the appearance of any stimuli, whereas others claim that top-down processes modulate visual selection only at a late stage, via feedback processing. In line with such a dual stage account, some studies found that eye movements to an irrelevant onset distractor are not modulated by its similarity to the target stimulus, especially when eye movements are launched early (within 150-ms post stimulus onset). However, in these studies the target transiently changed colour due to a colour after-effect that occurred during premasking, and the time course analyses were incomplete. The present study tested the feedforward account against the dual stage account in two eye tracking experiments, with and without colour after-effects (Exp. 1), as well when the target colour varied randomly and observers were informed of the target colour with a word cue (Exp. 2). The results showed that top-down processes modulated the earliest eye movements to the onset distractors (feedforward account of top-down modulation.

  4. Top-down (Prior Knowledge) and Bottom-up (Perceptual Modality) Influences on Spontaneous Interpersonal Synchronization.

    Science.gov (United States)

    Gipson, Christina L; Gorman, Jamie C; Hessler, Eric E

    2016-04-01

    Coordination with others is such a fundamental part of human activity that it can happen unintentionally. This unintentional coordination can manifest as synchronization and is observed in physical and human systems alike. We investigated the role of top-down influences (prior knowledge of the perceptual modality their partner is using) and bottom-up factors (perceptual modality combination) on spontaneous interpersonal synchronization. We examine this phenomena with respect to two different theoretical perspectives that differently emphasize top-down and bottom-up factors in interpersonal synchronization: joint-action/shared cognition theories and ecological-interactive theories. In an empirical study twelve dyads performed a finger oscillation task while attending to each other's movements through either visual, auditory, or visual and auditory perceptual modalities. Half of the participants were given prior knowledge of their partner's perceptual capabilities for coordinating across these different perceptual modality combinations. We found that the effect of top-down influence depends on the perceptual modality combination between two individuals. When people used the same perceptual modalities, top-down influence resulted in less synchronization and when people used different perceptual modalities, top-down influence resulted in more synchronization. Furthermore, persistence in the change in behavior as a result of having perceptual information about each other ('social memory') was stronger when this top-down influence was present.

  5. Top-down workforce demand extrapolation based on an EC energy road-map scenario

    International Nuclear Information System (INIS)

    Roelofs, F.; Von Estorff, U.

    2014-01-01

    The EHRO-N team of JRC-IET provides the EC with essential data related to supply and demand for nuclear experts based on bottom-up information from the nuclear industry. The current paper deals with an alternative approach to derive figures for the demand side information of the nuclear workforce. Complementary to the bottom-up approach, a top-down modelling approach extrapolation of an EC Energy road-map nuclear energy demand scenario is followed here in addition to the survey information. In this top-down modelling approach, the number of nuclear power plants that are in operation and under construction is derived as a function of time from 2010 up to 2050 assuming that the current reactor park will be replaced by generic third generation reactors of 1400 MWe or 1000 MWe. Depending on the size of new build reactors, the analysis shows the number of new reactors required to fulfil the demand for nuclear energy. Based on workforce models for operation and construction of nuclear power plants, the model allows an extrapolation of these respective work-forces. Using the nuclear skills pyramid, the total workforce employed at a plant is broken down in a nuclear (experts), nuclearized, and nuclear aware workforce. With retirement profiles for nuclear power plants derived from the bottom-up EHRO-N survey, the replacement of the current workforce is taken into account. The peak of the new workforce (partly replacing the retiring workforce and additionally keeping up with the growing total workforce demand) for nuclear experts and nuclearized employees is to be expected at the end of the considered period (2050). However, the peak workforce for nuclear aware employees is to be expected around 2020. When comparing to historical data for the nuclear capacity being installed at the same time in Europe, it is clear that the expected future capacity to be installed at the same time in Europe is significantly lower (factor of 2) than in the early 1980's. However, it should

  6. A Generalizable Top-Down Nanostructuring Method of Bulk Oxides: Sequential Oxygen-Nitrogen Exchange Reaction.

    Science.gov (United States)

    Lee, Lanlee; Kang, Byungwuk; Han, Suyoung; Kim, Hee-Eun; Lee, Moo Dong; Bang, Jin Ho

    2018-05-27

    A thermal reaction route that induces grain fracture instead of grain growth is devised and developed as a top-down approach to prepare nanostructured oxides from bulk solids. This novel synthesis approach, referred to as the sequential oxygen-nitrogen exchange (SONE) reaction, exploits the reversible anion exchange between oxygen and nitrogen in oxides that is driven by a simple two-step thermal treatment in ammonia and air. Internal stress developed by significant structural rearrangement via the formation of (oxy)nitride and the creation of oxygen vacancies and their subsequent combination into nanopores transforms bulk solid oxides into nanostructured oxides. The SONE reaction can be applicable to most transition metal oxides, and when utilized in a lithium-ion battery, the produced nanostructured materials are superior to their bulk counterparts and even comparable to those produced by conventional bottom-up approaches. Given its simplicity and scalability, this synthesis method could open a new avenue to the development of high-performance nanostructured electrode materials that can meet the industrial demand of cost-effectiveness for mass production. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Top-down Estimates of Greenhouse Gas Intensities and Emissions for Individual Oil Sands Facilities in Alberta Canada

    Science.gov (United States)

    Liggio, J.; Li, S. M.; Staebler, R. M.; Hayden, K. L.; Mittermeier, R. L.; McLaren, R.; Baray, S.; Darlington, A.; Worthy, D.; O'Brien, J.

    2017-12-01

    The oil sands (OS) region of Alberta contributes approximately 10% to Canada's overall anthropogenic greenhouse gas (GHG) emissions. Such emissions have traditionally been estimated through "bottom-up" methods which seek to account for all individual sources of GHGs within a given facility. However, it is recognized that bottom-up approaches for complex industrial facilities can be subject to uncertainties associated with incomplete or inaccurate emission factor and/or activity data. In order to quantify air pollutant emissions from oil sands activities an aircraft-based measurement campaign was performed in the summer of 2013. The aircraft measurements could also be used to quantify GHG emissions for comparison to the bottom up emissions estimates. Utilizing specific flight patterns, together with an emissions estimation algorithm and measurements of CO2 and methane, a "top-down" estimate of GHG intensities for several large surface mining operations was obtained. The results demonstrate that there is a wide variation in emissions intensities (≈80 - 220 kg CO2/barrel oil) across OS facilities, which in some cases agree with calculated intensities, and in other cases are larger than that estimated using industry reported GHG emission and oil production data. When translated to annual GHG emissions, the "top-down" approach results in a CO2 emission of approximately 41 Mega Tonnes (MT) CO2/year for the 4 OS facilities investigated, in contrast to the ≈26 MT CO2/year reported by industry. The results presented here highlight the importance of using "top-down" approaches as a complimentary method in evaluating GHG emissions from large industrial sources.

  8. Dynamic formulation of a top-down and bottom-up merging energy policy model

    International Nuclear Information System (INIS)

    Frei, Christoph W.; Haldi, P.-A.; Sarlos, G.Gerard

    2003-01-01

    The impact of energy policy measures is not restricted to the energy system and should therefore be analysed within an economy-wide framework, while keeping the essential details of the energy sector. The aim of this paper is to present new developments in the field of the consistent evaluation of indicators for the sustainability assessment of energy policy measures. Starting from the static concept of Boehringer (Energy Econ. 20 (1998) 233), this paper shows how the complementarity format can be used in computable general equilibrium (CGE) modelling for a dynamic formulation of bottom-up and top-down approach merging models. While a hybrid approach increases the credibility of CGE models in energy policy analysis by replacing the energy sector generic functional forms with a bottom-up activity analysis based on specific technologies, the endogenous formulation of investment decisions makes an explicit description of evolving specific capital stocks and technology mixes possible. Both features are essential when assessing effects of policy measures that may be affected by structural change--which is typically the case in the long-term assessment of energy policy measures

  9. Auditory top-down control and affective theory of mind in schizophrenia with and without hallucinations.

    Science.gov (United States)

    Rominger, Christian; Bleier, Angelika; Fitz, Werner; Marksteiner, Josef; Fink, Andreas; Papousek, Ilona; Weiss, Elisabeth M

    2016-07-01

    Social cognitive impairments may represent a core feature of schizophrenia and above all are a strong predictor of positive psychotic symptoms. Previous studies could show that reduced inhibitory top-down control contributes to deficits in theory of mind abilities and is involved in the genesis of hallucinations. The current study aimed to investigate the relationship between auditory inhibition, affective theory of mind and the experience of hallucinations in patients with schizophrenia. In the present study, 20 in-patients with schizophrenia and 20 healthy controls completed a social cognition task (the Reading the Mind in the Eyes Test) and an inhibitory top-down Dichotic Listening Test. Schizophrenia patients with greater severity of hallucinations showed impaired affective theory of mind as well as impaired inhibitory top-down control. More dysfunctional top-down inhibition was associated with poorer affective theory of mind performance, and seemed to mediate the association between impairment to affective theory of mind and severity of hallucinations. The findings support the idea of impaired theory of mind as a trait marker of schizophrenia. In addition, dysfunctional top-down inhibition may give rise to hallucinations and may further impair affective theory of mind skills in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Face processing pattern under top-down perception: a functional MRI study

    Science.gov (United States)

    Li, Jun; Liang, Jimin; Tian, Jie; Liu, Jiangang; Zhao, Jizheng; Zhang, Hui; Shi, Guangming

    2009-02-01

    Although top-down perceptual process plays an important role in face processing, its neural substrate is still puzzling because the top-down stream is extracted difficultly from the activation pattern associated with contamination caused by bottom-up face perception input. In the present study, a novel paradigm of instructing participants to detect faces from pure noise images is employed, which could efficiently eliminate the interference of bottom-up face perception in topdown face processing. Analyzing the map of functional connectivity with right FFA analyzed by conventional Pearson's correlation, a possible face processing pattern induced by top-down perception can be obtained. Apart from the brain areas of bilateral fusiform gyrus (FG), left inferior occipital gyrus (IOG) and left superior temporal sulcus (STS), which are consistent with a core system in the distributed cortical network for face perception, activation induced by top-down face processing is also found in these regions that include the anterior cingulate gyrus (ACC), right oribitofrontal cortex (OFC), left precuneus, right parahippocampal cortex, left dorsolateral prefrontal cortex (DLPFC), right frontal pole, bilateral premotor cortex, left inferior parietal cortex and bilateral thalamus. The results indicate that making-decision, attention, episodic memory retrieving and contextual associative processing network cooperate with general face processing regions to process face information under top-down perception.

  11. A fusion of top-down and bottom-up modeling techniques to constrain regional scale carbon budgets

    Science.gov (United States)

    Goeckede, M.; Turner, D. P.; Michalak, A. M.; Vickers, D.; Law, B. E.

    2009-12-01

    The effort to constrain regional scale carbon budgets benefits from assimilating as many high quality data sources as possible in order to reduce uncertainties. Two of the most common approaches used in this field, bottom-up and top-down techniques, both have their strengths and weaknesses, and partly build on very different sources of information to train, drive, and validate the models. Within the context of the ORCA2 project, we follow both bottom-up and top-down modeling strategies with the ultimate objective of reconciling their surface flux estimates. The ORCA2 top-down component builds on a coupled WRF-STILT transport module that resolves the footprint function of a CO2 concentration measurement in high temporal and spatial resolution. Datasets involved in the current setup comprise GDAS meteorology, remote sensing products, VULCAN fossil fuel inventories, boundary conditions from CarbonTracker, and high-accuracy time series of atmospheric CO2 concentrations. Surface fluxes of CO2 are normally provided through a simple diagnostic model which is optimized against atmospheric observations. For the present study, we replaced the simple model with fluxes generated by an advanced bottom-up process model, Biome-BGC, which uses state-of-the-art algorithms to resolve plant-physiological processes, and 'grow' a biosphere based on biogeochemical conditions and climate history. This approach provides a more realistic description of biomass and nutrient pools than is the case for the simple model. The process model ingests various remote sensing data sources as well as high-resolution reanalysis meteorology, and can be trained against biometric inventories and eddy-covariance data. Linking the bottom-up flux fields to the atmospheric CO2 concentrations through the transport module allows evaluating the spatial representativeness of the BGC flux fields, and in that way assimilates more of the available information than either of the individual modeling techniques alone

  12. Temperature regulation of marine heterotrophic prokaryotes increases latitudinally as a breach between bottom-up and top-down controls

    KAUST Repository

    Moran, Xose Anxelu G.

    2017-04-19

    Planktonic heterotrophic prokaryotes make up the largest living biomass and process most organic matter in the ocean. Determining when and where the biomass and activity of heterotrophic prokaryotes are controlled by resource availability (bottom-up), predation and viral lysis (top-down) or temperature will help in future carbon cycling predictions. We conducted an extensive survey across subtropical and tropical waters of the Atlantic, Indian and Pacific Oceans during the Malaspina 2010 Global Circumnavigation Expedition and assessed indices for these three types of controls at 109 stations (mostly from the surface to 4000 m depth). Temperature control was approached by the apparent activation energy in eV (ranging from 0.46 to 3.41), bottom-up control by the slope of the log-log relationship between biomass and production rate (ranging from -0.12 to 1.09) and top-down control by an index that considers the relative abundances of heterotrophic nanoflagellates and viruses (ranging from 0.82 to 4.83). We conclude that temperature becomes dominant (i.e. activation energy >1.5 eV) within a narrow window of intermediate values of bottom-up (0.3-0.6) and top-down 0.8-1.2) controls. A pervasive latitudinal pattern of decreasing temperature regulation towards the Equator, regardless of the oceanic basin, suggests that the impact of global warming on marine microbes and their biogeochemical function will be more intense at higher latitudes. Our analysis predicts that 1°C ocean warming will result in increased biomass of heterotrophic prokaryoplankton only in waters with <26°C of mean annual surface temperature. This article is protected by copyright. All rights reserved.

  13. Does Top-Down Feedback Modulate the Encoding of Orthographic Representations During Visual-Word Recognition?

    Science.gov (United States)

    Perea, Manuel; Marcet, Ana; Vergara-Martínez, Marta

    2016-09-01

    In masked priming lexical decision experiments, there is a matched-case identity advantage for nonwords, but not for words (e.g., ERTAR-ERTAR words when top-down feedback is minimized. We employed a task that taps prelexical orthographic processes: the masked prime same-different task. For "same" trials, results showed faster response times for targets when preceded by a briefly presented matched-case identity prime than when preceded by a mismatched-case identity prime. Importantly, this advantage was similar in magnitude for nonwords and words. This finding constrains the interplay of bottom-up versus top-down mechanisms in models of visual-word identification.

  14. ''Top-down'' versus ''side-on'' viewing of the inductively coupled plasma

    International Nuclear Information System (INIS)

    Faires, L.M.; Bieniewski, T.M.; Apel, C.T.; Niemczyk, T.M.

    1985-01-01

    The inductively coupled plasma is viewed by a ''top-down'' optical configuration, and the analytical performance is compared to conventional ''side-on'' viewing in terms of sensitivity, detection limits, linear dynamical range, self-reversal effects, and multielement performance. This comparison is made for a selection of eleven atom and ion lines of eight elements. The results of this study indicate distinct advantages in ''top-down'' viewing including improved sensitivity, lower detection limits, better signal-to-background ratios, and better compromise viewing position for multielement analysis. An exception to these advantages is increased self-absorption effects observed for the alkali elements

  15. Profiling Changes in Histone Post-translational Modifications by Top-Down Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Mowei; Wu, Si; Stenoien, David L.; Zhang, Zhaorui; Connolly, Lanelle; Freitag, Michael; Pasa-Tolic, Ljiljana

    2016-11-11

    Top-down mass spectrometry is a valuable tool for charactering post-translational modifications on histones for understanding of gene control and expression. In this protocol, we describe a top-down workflow using liquid chromatography coupled to mass spectrometry for fast global profiling of changes in histone proteoforms between a wild-type and a mutant of a fungal species. The proteoforms exhibiting different abundances can be subjected to further targeted studies by other mass spectrometric or biochemical assays. This method can be generally adapted for preliminary screening for changes in histone modifications between samples such as wild-type vs. mutant, and control vs. disease.

  16. Segregating Top-Down Selective Attention from Response Inhibition in a Spatial Cueing Go/NoGo Task: An ERP and Source Localization Study.

    Science.gov (United States)

    Hong, Xiangfei; Wang, Yao; Sun, Junfeng; Li, Chunbo; Tong, Shanbao

    2017-08-29

    Successfully inhibiting a prepotent response tendency requires the attentional detection of signals which cue response cancellation. Although neuroimaging studies have identified important roles of stimulus-driven processing in the attentional detection, the effects of top-down control were scarcely investigated. In this study, scalp EEG was recorded from thirty-two participants during a modified Go/NoGo task, in which a spatial-cueing approach was implemented to manipulate top-down selective attention. We observed classical event-related potential components, including N2 and P3, in the attended condition of response inhibition. While in the ignored condition of response inhibition, a smaller P3 was observed and N2 was absent. The correlation between P3 and CNV during the foreperiod suggested an inhibitory role of P3 in both conditions. Furthermore, source analysis suggested that P3 generation was mainly localized to the midcingulate cortex, and the attended condition showed increased activation relative to the ignored condition in several regions, including inferior frontal gyrus, middle frontal gyrus, precentral gyrus, insula and uncus, suggesting that these regions were involved in top-down attentional control rather than inhibitory processing. Taken together, by segregating electrophysiological correlates of top-down selective attention from those of response inhibition, our findings provide new insights in understanding the neural mechanisms of response inhibition.

  17. Top-down or bottom-up: Contrasting perspectives on psychiatric diagnoses

    Directory of Open Access Journals (Sweden)

    Willem MA Verhoeven

    2008-09-01

    Full Text Available Willem MA Verhoeven1,2, Siegfried Tuinier1, Ineke van der Burgt31Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands; 2Department of Psychiatry, Erasmus University Medical Centre, Rotterdam, The Netherlands; 3Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The NetherlandsAbstract: Clinical psychiatry is confronted with the expanding knowledge of medical genetics. Most of the research into the genetic underpinnings of major mental disorders as described in the categorical taxonomies, however, did reveal linkage with a variety of chromosomes. This heterogeneity of results is most probably due to the assumption that the nosological categories as used in these studies are disease entities with clear boundaries. If the reverse way of looking, the so-called bottom-up approach, is applied, it becomes clear that genetic abnormalities are in most cases not associated with a single psychiatric disorder but with a certain probability to develop a variety of aspecific psychiatric symptoms. The adequacy of the categorical taxonomy, the so-called top-down approach, seems to be inversely related to the amount of empirical etiological data. This is illustrated by four rather prevalent genetic syndromes, fragile X syndrome, Prader-Willi syndrome, 22q11 deletion syndrome, and Noonan syndrome, as well as by some cases with rare chromosomal abnormalities. From these examples, it becomes clear that psychotic symptoms as well as mood, anxiety, and autistic features can be found in a great variety of different genetic syndromes. A psychiatric phenotype exists, but comprises, apart from the chance to present several psychiatric symptoms, all elements from developmental, neurocognitive, and physical characteristics.Keywords: genetic disorders, psychiatric symptoms, phenotype, mental disorders

  18. A Top Down Strategy To Enhance Information Technologies into Israeli Higher Education.

    Science.gov (United States)

    Guri-Rosenblit, Sara

    2002-01-01

    The integration of information technologies (IT) into Israeli higher education through a top-down strategy has created systemic change. The use of IT in Israeli universities varies in terms of access-outreach, teaching-learning processes, study materials production, data and information retrieval, administrative functions, the creation of…

  19. Top-down design and verification methodology for analog mixed-signal integrated circuits

    NARCIS (Netherlands)

    Beviz, P.

    2016-01-01

    The current report contains the introduction of a novel Top-Down Design and Verification methodology for AMS integrated circuits. With the introduction of new design and verification flow, more reliable and efficient development of AMS ICs is possible. The assignment incorporated the research on the

  20. Functional dissociations in top-down control dependent neural repetition priming.

    NARCIS (Netherlands)

    Klaver, P.; Schnaidt, M.; Fell, J.; Ruhlmann, J.; Elger, C.E.; Fernandez, G.S.E.

    2007-01-01

    Little is known about the neural mechanisms underlying top-down control of repetition priming. Here, we use functional brain imaging to investigate these mechanisms. Study and repetition tasks used a natural/man-made forced choice task. In the study phase subjects were required to respond to either

  1. Bottom-up and top-down emotion generation: implications for emotion regulation

    Science.gov (United States)

    Misra, Supriya; Prasad, Aditya K.; Pereira, Sean C.; Gross, James J.

    2012-01-01

    Emotion regulation plays a crucial role in adaptive functioning and mounting evidence suggests that some emotion regulation strategies are often more effective than others. However, little attention has been paid to the different ways emotions can be generated: from the ‘bottom-up’ (in response to inherently emotional perceptual properties of the stimulus) or ‘top-down’ (in response to cognitive evaluations). Based on a process priming principle, we hypothesized that mode of emotion generation would interact with subsequent emotion regulation. Specifically, we predicted that top-down emotions would be more successfully regulated by a top-down regulation strategy than bottom-up emotions. To test this hypothesis, we induced bottom-up and top-down emotions, and asked participants to decrease the negative impact of these emotions using cognitive reappraisal. We observed the predicted interaction between generation and regulation in two measures of emotional responding. As measured by self-reported affect, cognitive reappraisal was more successful on top-down generated emotions than bottom-up generated emotions. Neurally, reappraisal of bottom-up generated emotions resulted in a paradoxical increase of amygdala activity. This interaction between mode of emotion generation and subsequent regulation should be taken into account when comparing of the efficacy of different types of emotion regulation, as well as when reappraisal is used to treat different types of clinical disorders. PMID:21296865

  2. Phenomenology without conscious access is a form of consciousness without top-down attention

    OpenAIRE

    Koch, Christof; Tsuchiya, Naotsugu

    2007-01-01

    We agree with Block's basic hypothesis postulating the existence of phenomenal consciousness without cognitive access. We explain such states in terms of consciousness without top-down, endogenous attention and speculate that their correlates may be a coalition of neurons that are consigned to the back of cortex, without access to working memory and planning in frontal cortex.

  3. Decoding of top-down cognitive processing for SSVEP-controlled BMI

    Science.gov (United States)

    Min, Byoung-Kyong; Dähne, Sven; Ahn, Min-Hee; Noh, Yung-Kyun; Müller, Klaus-Robert

    2016-11-01

    We present a fast and accurate non-invasive brain-machine interface (BMI) based on demodulating steady-state visual evoked potentials (SSVEPs) in electroencephalography (EEG). Our study reports an SSVEP-BMI that, for the first time, decodes primarily based on top-down and not bottom-up visual information processing. The experimental setup presents a grid-shaped flickering line array that the participants observe while intentionally attending to a subset of flickering lines representing the shape of a letter. While the flickering pixels stimulate the participant’s visual cortex uniformly with equal probability, the participant’s intention groups the strokes and thus perceives a ‘letter Gestalt’. We observed decoding accuracy of 35.81% (up to 65.83%) with a regularized linear discriminant analysis; on average 2.05-fold, and up to 3.77-fold greater than chance levels in multi-class classification. Compared to the EEG signals, an electrooculogram (EOG) did not significantly contribute to decoding accuracies. Further analysis reveals that the top-down SSVEP paradigm shows the most focalised activation pattern around occipital visual areas; Granger causality analysis consistently revealed prefrontal top-down control over early visual processing. Taken together, the present paradigm provides the first neurophysiological evidence for the top-down SSVEP BMI paradigm, which potentially enables multi-class intentional control of EEG-BMIs without using gaze-shifting.

  4. Top-down control of visual perception: attention in natural vision.

    Science.gov (United States)

    Rolls, Edmund T

    2008-01-01

    Top-down perceptual influences can bias (or pre-empt) perception. In natural scenes, the receptive fields of neurons in the inferior temporal visual cortex (IT) shrink to become close to the size of objects. This facilitates the read-out of information from the ventral visual system, because the information is primarily about the object at the fovea. Top-down attentional influences are much less evident in natural scenes than when objects are shown against blank backgrounds, though are still present. It is suggested that the reduced receptive-field size in natural scenes, and the effects of top-down attention contribute to change blindness. The receptive fields of IT neurons in complex scenes, though including the fovea, are frequently asymmetric around the fovea, and it is proposed that this is the solution the IT uses to represent multiple objects and their relative spatial positions in a scene. Networks that implement probabilistic decision-making are described, and it is suggested that, when in perceptual systems they take decisions (or 'test hypotheses'), they influence lower-level networks to bias visual perception. Finally, it is shown that similar processes extend to systems involved in the processing of emotion-provoking sensory stimuli, in that word-level cognitive states provide top-down biasing that reaches as far down as the orbitofrontal cortex, where, at the first stage of affective representations, olfactory, taste, flavour, and touch processing is biased (or pre-empted) in humans.

  5. Top-Down Cognitive and Linguistic Influences on the Suppression of Spontaneous Otoacoustic Emissions

    Directory of Open Access Journals (Sweden)

    Viorica Marian

    2018-06-01

    Full Text Available Auditory sensation is often thought of as a bottom-up process, yet the brain exerts top-down control to affect how and what we hear. We report the discovery that the magnitude of top-down influence varies across individuals as a result of differences in linguistic background and executive function. Participants were 32 normal-hearing individuals (23 female varying in language background (11 English monolinguals, 10 Korean-English late bilinguals, and 11 Korean-English early bilinguals, as well as cognitive abilities (working memory, cognitive control. To assess efferent control over inner ear function, participants were presented with speech-sounds (e.g., /ba/, /pa/ in one ear while spontaneous otoacoustic emissions (SOAEs were measured in the contralateral ear. SOAEs are associated with the amplification of sound in the cochlea, and can be used as an index of top-down efferent activity. Individuals with bilingual experience and those with better cognitive control experienced larger reductions in the amplitude of SOAEs in response to speech stimuli, likely as a result of greater efferent suppression of amplification in the cochlea. This suppression may aid in the critical task of speech perception by minimizing the disruptive effects of noise. In contrast, individuals with better working memory exert less control over the cochlea, possibly due to a greater capacity to process complex stimuli at later stages. These findings demonstrate that even peripheral mechanics of auditory perception are shaped by top-down cognitive and linguistic influences.

  6. Early Top-Down Influences on Bistable Perception Revealed by Event-Related Potentials

    Science.gov (United States)

    Pitts, Michael A.; Gavin, William J.; Nerger, Janice L.

    2008-01-01

    A longstanding debate exists in the literature concerning bottom-up vs. top-down influences on bistable perception. Recently, a technique has been developed to measure early changes in brain activity (via ERPs) related to perceptual reversals (Kornmeier & Bach, 2004). An ERP component, the reversal negativity (RN) has been identified, and is…

  7. Top-down cascades in lakes and oceans: Different perspectives but same story?

    KAUST Repository

    Hessen, Dag Olav; Kaartvedt, Stein

    2014-01-01

    While top-down cascades from fish to phytoplankton have been a core topic in limnology for the past four decades, it has attracted far less interest in marine ecology. This is partly for historical reasons, since lake studies have been motivated

  8. Introducing Electronic Textbooks as Daily-Use Technology in Schools: A Top-Down Adoption Process

    Science.gov (United States)

    Chiu, Thomas K. F.

    2017-01-01

    This study took frequency of use and the adoption process into account to define the participants and external variables of the research model. School electronic textbooks are a daily-use technology and they are adopted in a compulsory, top-down way. Their introduction can evoke feelings of anxiety among teachers because of a possible increase in…

  9. Dietary self-control influences top-down guidance of attention to food cues

    NARCIS (Netherlands)

    Higgs, S.; Dolmans, D.; Humphreys, G.W.; Rutters, F.

    2015-01-01

    Motivational objects attract attention due to their rewarding properties, but less is known about the role that top-down cognitive processes play in the attention paid to motivationally relevant objects and how this is affected by relevant behavioural traits. Here we assess how thinking about food

  10. The distributed neural system for top-down letter processing: an fMRI study

    Science.gov (United States)

    Liu, Jiangang; Feng, Lu; Li, Ling; Tian, Jie

    2011-03-01

    This fMRI study used Psychophysiological interaction (PPI) to investigate top-down letter processing with an illusory letter detection task. After an initial training that became increasingly difficult, participant was instructed to detect a letter from pure noise images where there was actually no letter. Such experimental paradigm allowed for isolating top-down components of letter processing and minimizing the influence of bottom-up perceptual input. A distributed cortical network of top-down letter processing was identified by analyzing the functional connectivity patterns of letter-preferential area (LA) within the left fusiform gyrus. Such network extends from the visual cortex to high level cognitive cortexes, including the left middle frontal gyrus, left medial frontal gyrus, left superior parietal gyrus, bilateral precuneus, and left inferior occipital gyrus. These findings suggest that top-down letter processing contains not only regions for processing of letter phonology and appearance, but also those involved in internal information generation and maintenance, and attention and memory processing.

  11. VLSI top-down design based on the separation of hierarchies

    NARCIS (Netherlands)

    Spaanenburg, L.; Broekema, A.; Leenstra, J.; Huys, C.

    1986-01-01

    Despite the presence of structure, interactions between the three views on VLSI design still lead to lengthy iterations. By separating the hierarchies for the respective views, the interactions are reduced. This separated hierarchy allows top-down design with functional abstractions as exemplified

  12. When seeing depends on knowing: adults with Autism Spectrum Conditions show diminished top-down processes in the visual perception of degraded faces but not degraded objects.

    Science.gov (United States)

    Loth, Eva; Gómez, Juan Carlos; Happé, Francesca

    2010-04-01

    Behavioural, neuroimaging and neurophysiological approaches emphasise the active and constructive nature of visual perception, determined not solely by the environmental input, but modulated top-down by prior knowledge. For example, degraded images, which at first appear as meaningless 'blobs', can easily be recognized as, say, a face, after having seen the same image un-degraded. This conscious perception of the fragmented stimuli relies on top-down priming influences from systems involved in attention and mental imagery on the processing of stimulus attributes, and feature-binding [Dolan, R. J., Fink, G. R., Rolls, E., Booth, M., Holmes, A., Frackowiak, R. S. J., et al. (1997). How the brain learns to see objects and faces in an impoverished context. Nature, 389, 596-599]. In Autism Spectrum Conditions (ASC), face processing abnormalities are well-established, but top-down anomalies in various domains have also been shown. Thus, we tested two alternative hypotheses: (i) that people with ASC show overall reduced top-down modulation in visual perception, or (ii) that top-down anomalies affect specifically the perception of faces. Participants were presented with sets of three consecutive images: degraded images (of faces or objects), corresponding or non-corresponding grey-scale photographs, and the same degraded images again. In a passive viewing sequence we compared gaze times (an index of focal attention) on faces/objects vs. background before and after viewers had seen the undegraded photographs. In an active viewing sequence, we compared how many faces/objects were identified pre- and post-exposure. Behavioural and gaze tracking data showed significantly reduced effects of prior knowledge on the conscious perception of degraded faces, but not objects in the ASC group. Implications for future work on the underlying mechanisms, at the cognitive and neurofunctional levels, are discussed. (c) 2009 Elsevier Ltd. All rights reserved.

  13. Top-down Fabrication and Enhanced Active Area Electronic Characteristics of Amorphous Oxide Nanoribbons for Flexible Electronics.

    Science.gov (United States)

    Jang, Hyun-June; Joong Lee, Ki; Jo, Kwang-Won; Katz, Howard E; Cho, Won-Ju; Shin, Yong-Beom

    2017-07-18

    Inorganic amorphous oxide semiconductor (AOS) materials such as amorphous InGaZnO (a-IGZO) possess mechanical flexibility and outstanding electrical properties, and have generated great interest for use in flexible and transparent electronic devices. In the past, however, AOS devices required higher activation energies, and hence higher processing temperatures, than organic ones to neutralize defects. It is well known that one-dimensional nanowires tend to have better carrier mobility and mechanical strength along with fewer defects than the corresponding two-dimensional films, but until now it has been difficult, costly, and impractical to fabricate such nanowires in proper alignments by either "bottom-up" growth techniques or by "top-down" e-beam lithography. Here we show a top-down, cost-effective, and scalable approach for the fabrication of parallel, laterally oriented AOS nanoribbons based on lift-off and nano-imprinting. High mobility (132 cm 2 /Vs), electrical stability, and transparency are obtained in a-IGZO nanoribbons, compared to the planar films of the same a-IGZO semiconductor.

  14. Profiling of Histone Post-Translational Modifications in Mouse Brain with High-Resolution Top-Down Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Mowei; Paša-Tolić, Ljiljana; Stenoien, David L.

    2016-12-21

    Histones play central roles in most chromosomal functions and both their basic biology and roles in disease have been the subject of intense study. Since multiple PTMs along the entire protein sequence are potential regulators of histones, a top-down approach, where intact proteins are analyzed, is ultimately required for complete characterization of proteoforms. However, significant challenges remain for top-down histone analysis primarily because of deficiencies in separation/resolving power and effective identification algorithms. Here, we used state of the art mass spectrometry and a bioinformatics workflow for targeted data analysis and visualization. The workflow uses ProMex for intact mass deconvolution, MSPathFinder as search engine, and LcMsSpectator as a data visualization tool. ProMex sums across retention time to maximize sensitivity and accuracy for low abundance species in MS1deconvolution. MSPathFinder searches the MS2 data against protein sequence databases with user-defined modifications. LcMsSpectator presents the results from ProMex and MSPathFinder in a format that allows quick manual evaluation of critical attributes for high-confidence identifications. When complemented with the open-modification tool TopPIC, this workflow enabled identification of novel histone PTMs including tyrosine bromination on histone H4 and H2A, H3 glutathionylation, and mapping of conventional PTMs along the entire protein for many histone subunits.

  15. Grain size engineering of bcc refractory metals: Top-down and bottom-up-Application to tungsten

    International Nuclear Information System (INIS)

    Kecskes, L.J.; Cho, K.C.; Dowding, R.J.; Schuster, B.E.; Valiev, R.Z.; Wei, Q.

    2007-01-01

    We have used two general methodologies for the production of ultrafine grained (UFG) and nanocrystalline (NC) tungsten (W) metal samples: top-down and bottom-up. In the first, Equal channel angular extrusion (ECAE), coupled with warm rolling has been used to fabricate UFG W, and high pressure torsion (HPT) was used to fabricate NC W. We demonstrate an abrupt shift in the deformation mechanism, particularly under dynamic compressive loading, in UFG and NC W. This novel deformation mechanism, a dramatic transition from a uniform deformation mode to that of localized shearing, is shared by other UFG and NC body-centerd cubic (BCC) metals. We have also conducted a series of bottom-up experiments to consolidate powdered UFG W precursors into solid bodies. The bottom-up approach relies on rapid, high-temperature consolidation, specifically designed for UFG and NC W powders. The mechanical property results from the top-down UFG and NC W were used as minimum property benchmarks to guide and design the experimental protocols and parameters for use in the bottom-up procedures. Preliminary results, showing rapid grain growth during the consolidation cycle, did not achieve full density in the W samples. Further development of high-purity W nanopowders and appropriate grain-growth inhibitors (e.g., Zener pinning) will be required to successfully produce bulk-sized UFG and NC W samples

  16. Proteomic approaches in brain research and neuropharmacology.

    Science.gov (United States)

    Vercauteren, Freya G G; Bergeron, John J M; Vandesande, Frans; Arckens, Lut; Quirion, Rémi

    2004-10-01

    Numerous applications of genomic technologies have enabled the assembly of unprecedented inventories of genes, expressed in cells under specific physiological and pathophysiological conditions. Complementing the valuable information generated through functional genomics with the integrative knowledge of protein expression and function should enable the development of more efficient diagnostic tools and therapeutic agents. Proteomic analyses are particularly suitable to elucidate posttranslational modifications, expression levels and protein-protein interactions of thousands of proteins at a time. In this review, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) investigations of brain tissues in neurodegenerative diseases such as Alzheimer's disease, Down syndrome and schizophrenia, and the construction of 2D-PAGE proteome maps of the brain are discussed. The role of the Human Proteome Organization (HUPO) as an international coordinating organization for proteomic efforts, as well as challenges for proteomic technologies and data analysis are also addressed. It is expected that the use of proteomic strategies will have significant impact in neuropharmacology over the coming decade.

  17. The Role of Top-down Attention in the Cocktail Party: Revisiting Cherry's Experiment after Sixty Years

    DEFF Research Database (Denmark)

    Marchegiani, Letizia; Karadogan, Seliz; Andersen, Taja

    2011-01-01

    We investigate the role of top-down task drive attention in the cocktail party problem. In a recently proposed computational model of top-down attention it is possible to simulate the cocktail party problem and make predictions about sensitivity to confounders under different levels of attention....... Based on such simulations we expect that under strong top-down attention pattern recognition is improved as the model can compensate for noise and confounders. We next investigate the role of temporal and spectral overlaps and speech intelligibility in humans, and how the presence of a task influences...... computational top-down attention model....

  18. Non-destructive Inspection of Top-Down Construction Joints of Column in SRC Structure using Ultrasonic Method

    International Nuclear Information System (INIS)

    Park, Seok Kyun; Baek, Un Chan; Lee, Han Bum; Kim, Myoung Mo

    2000-01-01

    The joint treatment of concrete is one of the technical problems in top down construction method. Joints created with the top down construction result in serious weakness from the aspects of both structural and water-barrier function. Ultrasonic method was used for the inspection of top down construction joints of a various column in SRC structure in this study. The advantages and limitations of this method for non-destructive inspection in top down construction joints are investigated. As a result, it has been verified that the semi-direct measurement method is more effective than the other methods for detecting the voids of construction joints using ultrasonic method

  19. Government conservation policies on Mexican coastal areas: is "top-down" management working?

    Directory of Open Access Journals (Sweden)

    Héctor Nava

    2011-12-01

    . Current conditions are the result of "top-down" conservation strategies in Zihuatanejo, as Federal and Municipal authorities do not coordinate, disregard local community in coral reef management, and ignore the intimate relationship between the coastal and marine realms. This work confirms the importance of conservation strategies with a holistic approach, considering both terrestrial and marine ecosystems in coastal areas; and that these initiatives should include local coastal communities in management and decision-taking processes done by government authorities. Rev. Biol. Trop. 59 (4: 1487-1501. Epub 2011 December 01.

  20. Relative importance of plant-mediated bottom-up and top-down forces on herbivore abundance on Brassica oleracea

    NARCIS (Netherlands)

    Kos, M.; Broekgaarden, C.; Kabouw, P.; Oude Lenferink, K.; Poelman, E.H.; Vet, L.E.M.; Dicke, M.; Loon, van J.J.A.

    2011-01-01

    1. Arthropod communities are structured by complex interactions between bottom-up (resource-based) and top-down (natural enemy-based) forces. Their relative importance in shaping arthropod communities, however, continues to be under debate. Bottom-up and top-down forces can be affected by

  1. Semi top-down method combined with earth-bank, an effective method for basement construction.

    Science.gov (United States)

    Tuan, B. Q.; Tam, Ng M.

    2018-04-01

    Choosing an appropriate method of deep excavation not only plays a decisive role in technical success, but also in economics of the construction project. Presently, we mainly base on to key methods: “Bottom-up” and “Top-down” construction method. Right now, this paper presents an another method of construction that is “Semi Top-down method combining with earth-bank” in order to take the advantages and limit the weakness of the above methods. The Bottom-up method was improved by using the earth-bank to stabilize retaining walls instead of the bracing steel struts. The Top-down method was improved by using the open cut method for the half of the earthwork quantities.

  2. Mechanisms of knowledge flows in bottom-up and top-down cluster initiatives

    Directory of Open Access Journals (Sweden)

    Wojciech Dyba

    2016-01-01

    Full Text Available Knowledge flows are widely believed to be a phenomenon of clusters, and inducing them is one of the chief objectives in establishing and promoting cluster initiatives (CI. However, not many studies discuss how these flows and their effects may differ depending on the mode of CI creation and on the role of public authorities in this process. The main aim of this article is to compare mechanisms of knowledge flows in bottom-up and top-down cluster initiatives. The results of an empirical research involving two case studies in western Poland, obtained through the use of Social Network Analysis (SNA, allowed stating that in bottom-up cluster initiatives firms which were innovation leaders played a prime role in disseminating technological and business knowledge, while in the top-down initiatives the most important were representatives of universities and research centres as well as formal coordinators of cooperation. Policy implications stemming from these results were identified.

  3. Learning affects top down and bottom up modulation of eye movements in decision making

    DEFF Research Database (Denmark)

    Orquin, Jacob Lund; Bagger, Martin; Mueller Loose, Simone

    2013-01-01

    Repeated decision making is subject to changes over time such as decreases in decision time and information use and increases in decision accuracy. We show that a traditional strategy selection view of decision making cannot account for these temporal dynamics without relaxing main assumptions...... about what defines a decision strategy. As an alternative view we suggest that temporal dynamics in decision making are driven by attentional and perceptual processes and that this view has been expressed in the information reduction hypothesis. We test the information reduction hypothesis by integrating...... it in a broader framework of top down and bottom up processes and derive the predictions that repeated decisions increase top down control of attention capture which in turn leads to a reduction in bottom up attention capture. To test our hypotheses we conducted a repeated discrete choice experiment with three...

  4. Top down and bottom up selection drives variations in frequency and form of a visual signal

    OpenAIRE

    Yeh, Chien-Wei; Blamires, Sean J.; Liao, Chen-Pan; Tso, I.-Min

    2015-01-01

    The frequency and form of visual signals can be shaped by selection from predators, prey or both. When a signal simultaneously attracts predators and prey, selection may favour a strategy that minimizes risks while attracting prey. Accordingly, varying the frequency and form of the silken decorations added to their web may be a way that Argiope spiders minimize predation while attracting prey. Nonetheless, the role of extraneous factors renders the influences of top down and bottom up selecti...

  5. Dissociable effects of top-down and bottom-up attention during episodic encoding

    Science.gov (United States)

    Uncapher, Melina R.; Hutchinson, J. Benjamin; Wagner, Anthony D.

    2011-01-01

    It is well established that the formation of memories for life’s experiences—episodic memory—is influenced by how we attend to those experiences, yet the neural mechanisms by which attention shapes episodic encoding are still unclear. We investigated how top-down and bottom-up attention contribute to memory encoding of visual objects in humans by manipulating both types of attention during functional magnetic resonance imaging (fMRI) of episodic memory formation. We show that dorsal parietal cortex—specifically, intraparietal sulcus (IPS)—was engaged during top-down attention and was also recruited during the successful formation of episodic memories. By contrast, bottom-up attention engaged ventral parietal cortex—specifically, temporoparietal junction (TPJ)—and was also more active during encoding failure. Functional connectivity analyses revealed further dissociations in how top-down and bottom-up attention influenced encoding: while both IPS and TPJ influenced activity in perceptual cortices thought to represent the information being encoded (fusiform/lateral occipital cortex), they each exerted opposite effects on memory encoding. Specifically, during a preparatory period preceding stimulus presentation, a stronger drive from IPS was associated with a higher likelihood that the subsequently attended stimulus would be encoded. By contrast, during stimulus processing, stronger connectivity with TPJ was associated with a lower likelihood the stimulus would be successfully encoded. These findings suggest that during encoding of visual objects into episodic memory, top-down and bottom-up attention can have opposite influences on perceptual areas that subserve visual object representation, suggesting that one manner in which attention modulates memory is by altering the perceptual processing of to-be-encoded stimuli. PMID:21880922

  6. Top-Down Influences on Local Networks: Basic Theory with Experimental Implications

    Directory of Open Access Journals (Sweden)

    Ramesh eSrinivasan

    2013-04-01

    Full Text Available The response of a population of sensory neurons to an external stimulus depends not only on the receptive field properties of the neurons, but also the level of arousal and attention or goal-oriented cognitive biases that guide information processing. These top-down effects on the sensory neurons bias the output of the neurons and affect behavioral outcomes such as stimulus detection, discrimination, and response time. In any physiological study, neural dynamics are observed in a specific brain state; the background state partly determines neuronal excitability. Experimental studies in humans and animal models have also demonstrated that slow oscillations (typically in the alpha or theta bands modulate the fast oscillations (gamma band associated with local networks of neurons. Cross-frequency interaction is of interest as a mechanism for top-down or bottom-up interactions between systems at different spatial scales. We develop a generic model of top-down influences on local networks appropriate for comparison with EEG. EEG provides excellent temporal resolution to investigate neuronal oscillations but is space-averaged on the cm scale. Thus, appropriate EEG models are developed in terms of population synaptic activity. We used the Wilson-Cowan population model to investigate fast (gamma band oscillations generated by a local network of excitatory and inhibitory neurons. We modified the Wilson-Cowan equations to make them more physiologically realistic by explicitly incorporating background state variables into the model. We found that the population response is strongly influenced by the background state. We apply the model to reproduce the modulation of gamma rhythms by theta rhythms as has been observed in animal models and human ECoG and EEG studies. The concept of a dynamic background state presented here using the Wilson-Cowan model can be readily applied to incorporate top-down modulation in more detailed models of specific sensory

  7. Experimental evidence for enhanced top-down control of freshwater macrophytes with nutrient enrichment.

    Science.gov (United States)

    Bakker, Elisabeth S; Nolet, Bart A

    2014-11-01

    The abundance of primary producers is controlled by bottom-up and top-down forces. Despite the fact that there is consensus that the abundance of freshwater macrophytes is strongly influenced by the availability of resources for plant growth, the importance of top-down control by vertebrate consumers is debated, because field studies yield contrasting results. We hypothesized that these bottom-up and top-down forces may interact, and that consumer impact on macrophyte abundance depends on the nutrient status of the water body. To test this hypothesis, experimental ponds with submerged vegetation containing a mixture of species were subjected to a fertilization treatment and we introduced consumers (mallard ducks, for 8 days) on half of the ponds in a full factorial design. Over the whole 66-day experiment fertilized ponds became dominated by Elodea nuttallii and ponds without extra nutrients by Chara globularis. Nutrient addition significantly increased plant N and P concentrations. There was a strong interactive effect of duck presence and pond nutrient status: macrophyte biomass was reduced (by 50%) after the presence of the ducks on fertilized ponds, but not in the unfertilized ponds. We conclude that nutrient availability interacts with top-down control of submerged vegetation. This may be explained by higher plant palatability at higher nutrient levels, either by a higher plant nutrient concentration or by a shift towards dominance of more palatable plant species, resulting in higher consumer pressure. Including nutrient availability may offer a framework to explain part of the contrasting field observations of consumer control of macrophyte abundance.

  8. Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex.

    Science.gov (United States)

    Raz, Aeyal; Grady, Sean M; Krause, Bryan M; Uhlrich, Daniel J; Manning, Karen A; Banks, Matthew I

    2014-01-01

    The mechanism of loss of consciousness (LOC) under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up "core" thalamo-cortical (TC) vs. top-down cortico-cortical (CC) and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural basis of consciousness.

  9. Warming increases the top-down effects and metabolism of a subtidal herbivore

    Directory of Open Access Journals (Sweden)

    Lindsey A. Carr

    2013-07-01

    Full Text Available Ecological theory and experiments indicate that warming can increase the relative strength of top-down effects via alterations to metabolic rates in several different systems, thereby resulting in decreased plant biomass at higher temperatures. However, the general influence of increased environmental temperature on top-down effects is not well understood in systems where organisms experience relatively large variation in temperature. Rapid ocean temperature changes are pervasive throughout the Galápagos Islands due to upwelling and downwelling of internal waves, ENSO events and seasonality. We measured the effect of large, but not uncommon, water temperature variation on the metabolism and grazing rate of a common subtidal herbivore and on photosynthesis of their algal prey in the Galápagos Islands in July 2012. We found that green urchin consumption and metabolism were greater at the higher temperature treatment (28°C, resulting in significantly less algal biomass. Our result that warming increased green urchin metabolic rates, even in a highly dynamic system, provides further support for a mechanistic link between environmental temperature and feeding rates. And further, our findings suggest individual response to temperature results in changes in top-down effects. And if this response is maintained over longer-time scales of days to weeks, this could translate to alterations of larger-scale ecological patterns, such as primary producer community composition and structure.

  10. A top-down design methodology and its implementation for VCSEL-based optical links design

    Science.gov (United States)

    Li, Jiguang; Cao, Mingcui; Cai, Zilong

    2005-01-01

    In order to find the optimal design for a given specification of an optical communication link, an integrated simulation of electronic, optoelectronic, and optical components of a complete system is required. It is very important to be able to simulate at both system level and detailed model level. This kind of model is feasible due to the high potential of Verilog-AMS language. In this paper, we propose an effective top-down design methodology and employ it in the development of a complete VCSEL-based optical links simulation. The principle of top-down methodology is that the development would proceed from the system to device level. To design a hierarchical model for VCSEL based optical links, the design framework is organized in three levels of hierarchy. The models are developed, and implemented in Verilog-AMS. Therefore, the model parameters are fitted to measured data. A sample transient simulation demonstrates the functioning of our implementation. Suggestions for future directions in top-down methodology used for optoelectronic systems technology are also presented.

  11. The Primary Visual Cortex Is Differentially Modulated by Stimulus-Driven and Top-Down Attention

    Science.gov (United States)

    Bekisz, Marek; Bogdan, Wojciech; Ghazaryan, Anaida; Waleszczyk, Wioletta J.; Kublik, Ewa; Wróbel, Andrzej

    2016-01-01

    Selective attention can be focused either volitionally, by top-down signals derived from task demands, or automatically, by bottom-up signals from salient stimuli. Because the brain mechanisms that underlie these two attention processes are poorly understood, we recorded local field potentials (LFPs) from primary visual cortical areas of cats as they performed stimulus-driven and anticipatory discrimination tasks. Consistent with our previous observations, in both tasks, we found enhanced beta activity, which we have postulated may serve as an attention carrier. We characterized the functional organization of task-related beta activity by (i) cortical responses (EPs) evoked by electrical stimulation of the optic chiasm and (ii) intracortical LFP correlations. During the anticipatory task, peripheral stimulation that was preceded by high-amplitude beta oscillations evoked large-amplitude EPs compared with EPs that followed low-amplitude beta. In contrast, during the stimulus-driven task, cortical EPs preceded by high-amplitude beta oscillations were, on average, smaller than those preceded by low-amplitude beta. Analysis of the correlations between the different recording sites revealed that beta activation maps were heterogeneous during the bottom-up task and homogeneous for the top-down task. We conclude that bottom-up attention activates cortical visual areas in a mosaic-like pattern, whereas top-down attentional modulation results in spatially homogeneous excitation. PMID:26730705

  12. Top-down influences of written text on perceived clarity of degraded speech.

    Science.gov (United States)

    Sohoglu, Ediz; Peelle, Jonathan E; Carlyon, Robert P; Davis, Matthew H

    2014-02-01

    An unresolved question is how the reported clarity of degraded speech is enhanced when listeners have prior knowledge of speech content. One account of this phenomenon proposes top-down modulation of early acoustic processing by higher-level linguistic knowledge. Alternative, strictly bottom-up accounts argue that acoustic information and higher-level knowledge are combined at a late decision stage without modulating early acoustic processing. Here we tested top-down and bottom-up accounts using written text to manipulate listeners' knowledge of speech content. The effect of written text on the reported clarity of noise-vocoded speech was most pronounced when text was presented before (rather than after) speech (Experiment 1). Fine-grained manipulation of the onset asynchrony between text and speech revealed that this effect declined when text was presented more than 120 ms after speech onset (Experiment 2). Finally, the influence of written text was found to arise from phonological (rather than lexical) correspondence between text and speech (Experiment 3). These results suggest that prior knowledge effects are time-limited by the duration of auditory echoic memory for degraded speech, consistent with top-down modulation of early acoustic processing by linguistic knowledge. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  13. How to inhibit a distractor location? Statistical learning versus active, top-down suppression.

    Science.gov (United States)

    Wang, Benchi; Theeuwes, Jan

    2018-05-01

    Recently, Wang and Theeuwes (Journal of Experimental Psychology: Human Perception and Performance, 44(1), 13-17, 2018a) demonstrated the role of lingering selection biases in an additional singleton search task in which the distractor singleton appeared much more often in one location than in all other locations. For this location, there was less capture and selection efficiency was reduced. It was argued that statistical learning induces plasticity within the spatial priority map such that particular locations that are high likely to contain a distractor are suppressed relative to all other locations. The current study replicated these findings regarding statistical learning (Experiment 1) and investigated whether similar effects can be obtained by cueing the distractor location in a top-down way on a trial-by-trial basis. The results show that top-down cueing of the distractor location with long (1,500 ms; Experiment 2) and short stimulus-onset symmetries (SOAs) (600 ms; Experiment 3) does not result in suppression: The amount of capture nor the efficiency of selection was affected by the cue. If anything, we found an attentional benefit (instead of the suppression) for the short SOA. We argue that through statistical learning, weights within the attentional priority map are changed such that one location containing a salient distractor is suppressed relative to all other locations. Our cueing experiments show that this effect cannot be accomplished by active, top-down suppression. Consequences for recent theories of distractor suppression are discussed.

  14. 3D virtual human rapid modeling method based on top-down modeling mechanism

    Directory of Open Access Journals (Sweden)

    LI Taotao

    2017-01-01

    Full Text Available Aiming to satisfy the vast custom-made character demand of 3D virtual human and the rapid modeling in the field of 3D virtual reality, a new virtual human top-down rapid modeling method is put for-ward in this paper based on the systematic analysis of the current situation and shortage of the virtual hu-man modeling technology. After the top-level realization of virtual human hierarchical structure frame de-sign, modular expression of the virtual human and parameter design for each module is achieved gradu-al-level downwards. While the relationship of connectors and mapping restraints among different modules is established, the definition of the size and texture parameter is also completed. Standardized process is meanwhile produced to support and adapt the virtual human top-down rapid modeling practice operation. Finally, the modeling application, which takes a Chinese captain character as an example, is carried out to validate the virtual human rapid modeling method based on top-down modeling mechanism. The result demonstrates high modelling efficiency and provides one new concept for 3D virtual human geometric mod-eling and texture modeling.

  15. Top-down attention affects sequential regularity representation in the human visual system.

    Science.gov (United States)

    Kimura, Motohiro; Widmann, Andreas; Schröger, Erich

    2010-08-01

    Recent neuroscience studies using visual mismatch negativity (visual MMN), an event-related brain potential (ERP) index of memory-mismatch processes in the visual sensory system, have shown that although sequential regularities embedded in successive visual stimuli can be automatically represented in the visual sensory system, an existence of sequential regularity itself does not guarantee that the sequential regularity will be automatically represented. In the present study, we investigated the effects of top-down attention on sequential regularity representation in the visual sensory system. Our results showed that a sequential regularity (SSSSD) embedded in a modified oddball sequence where infrequent deviant (D) and frequent standard stimuli (S) differing in luminance were regularly presented (SSSSDSSSSDSSSSD...) was represented in the visual sensory system only when participants attended the sequential regularity in luminance, but not when participants ignored the stimuli or simply attended the dimension of luminance per se. This suggests that top-down attention affects sequential regularity representation in the visual sensory system and that top-down attention is a prerequisite for particular sequential regularities to be represented. Copyright 2010 Elsevier B.V. All rights reserved.

  16. Top-down control of arousal and sleep: Fundamentals and clinical implications.

    Science.gov (United States)

    Krone, Lukas; Frase, Lukas; Piosczyk, Hannah; Selhausen, Peter; Zittel, Sulamith; Jahn, Friederike; Kuhn, Marion; Feige, Bernd; Mainberger, Florian; Klöppel, Stefan; Riemann, Dieter; Spiegelhalder, Kai; Baglioni, Chiara; Sterr, Annette; Nissen, Christoph

    2017-02-01

    Mammalian sleep emerges from attenuated activity in the ascending reticular arousal system (ARAS), the main arousal network of the brain. This system originates in the brainstem and activates the thalamus and cortex during wakefulness via a well-characterized 'bottom-up' pathway. Recent studies propose that a less investigated cortico-thalamic 'top-down' pathway also regulates sleep. The present work integrates the current evidence on sleep regulation with a focus on the 'top-down' pathway and explores the potential to translate this information into clinically relevant interventions. Specifically, we elaborate the concept that arousal and sleep continuity in humans can be modulated by non-invasive brain stimulation (NIBS) techniques that increase or decrease cortical excitability. Based on preclinical studies, the modulatory effects of the stimulation are thought to extend to subcortical arousal networks. Further exploration of the 'top-down' regulation of sleep and its modulation through non-invasive brain stimulation techniques may contribute to the development of novel treatments for clinical conditions of disrupted arousal and sleep, which are among the major health problems worldwide. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Interactive effects of trait and state affect on top-down control of attention.

    Science.gov (United States)

    Hur, Juyoen; Miller, Gregory A; McDavitt, Jenika R B; Spielberg, Jeffrey M; Crocker, Laura D; Infantolino, Zachary P; Towers, David N; Warren, Stacie L; Heller, Wendy

    2015-08-01

    Few studies have investigated how attentional control is affected by transient affective states while taking individual differences in affective traits into consideration. In this study, participants completed a color-word Stroop task immediately after undergoing a positive, neutral or negative affective context manipulation (ACM). Behavioral performance was unaffected by any ACM considered in isolation. For individuals high in trait negative affect (NA), performance was impaired by the negative but not the positive or neutral ACM. Neuroimaging results indicate that activity in primarily top-down control regions of the brain (inferior frontal gyrus and dorsal anterior cingulate cortex) was suppressed in the presence of emotional arousal (both negative and positive ACMs). This effect appears to have been exacerbated or offset by co-occurring activity in other top-down control regions (parietal) and emotion processing regions (orbitofrontal cortex, amygdala and nucleus accumbens) as a function of the valence of state affect (positive or negative) and trait affect (trait NA or trait PA). Neuroimaging results are consistent with behavioral findings. In combination, they indicate both additive and interactive influences of trait and state affect on top-down control of attention. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Energetic conditions promoting top-down control of prey by predators.

    Directory of Open Access Journals (Sweden)

    Kristin N Marshall

    Full Text Available Humans remove large amounts of biomass from natural ecosystems, and large bodied high trophic level animals are especially sensitive and vulnerable to exploitation. The effects of removing top-predators on food webs are often difficult to predict because of limited information on species interaction strengths. Here we used a three species predator-prey model to explore relationships between energetic properties of trophodynamic linkages and interaction strengths to provide heuristic rules that indicate observable energetic conditions that are most likely to lead to stable and strong top-down control of prey by predator species. We found that strong top-down interaction strengths resulted from low levels of energy flow from prey to predators. Strong interactions are more stable when they are a consequence of low per capita predation and when predators are subsidized by recruitment. Diet composition also affects stability, but the relationship depends on the form of the functional response. Our results imply that for generalist satiating predators, strong top-down control on prey is most likely for prey items that occupy a small portion of the diet and when density dependent recruitment is moderately high.

  19. Sleep deprivation selectively disrupts top-down adaptation to cognitive conflict in the Stroop test.

    Science.gov (United States)

    Gevers, Wim; Deliens, Gaetane; Hoffmann, Sophie; Notebaert, Wim; Peigneux, Philippe

    2015-12-01

    Sleep deprivation is known to exert detrimental effects on various cognitive domains, including attention, vigilance and working memory. Seemingly at odds with these findings, prior studies repeatedly failed to evidence an impact of prior sleep deprivation on cognitive interference in the Stroop test, a hallmark paradigm in the study of cognitive control abilities. The present study investigated further the effect of sleep deprivation on cognitive control using an adapted version of the Stroop test that allows to segregate top-down (attentional reconfiguration on incongruent items) and bottom-up (facilitated processing after repetitions in responses and/or features of stimuli) components of performance. Participants underwent a regular night of sleep or a night of total sleep deprivation before cognitive testing. Results disclosed that sleep deprivation selectively impairs top-down adaptation mechanisms: cognitive control no longer increased upon detection of response conflict at the preceding trial. In parallel, bottom-up abilities were found unaffected by sleep deprivation: beneficial effects of stimulus and response repetitions persisted. Changes in vigilance states due to sleep deprivation selectively impact on cognitive control in the Stroop test by affecting top-down, but not bottom-up, mechanisms that guide adaptive behaviours. © 2015 European Sleep Research Society.

  20. Top-down cascades in lakes and oceans: Different perspectives but same story?

    KAUST Repository

    Hessen, Dag Olav

    2014-05-16

    While top-down cascades from fish to phytoplankton have been a core topic in limnology for the past four decades, it has attracted far less interest in marine ecology. This is partly for historical reasons, since lake studies have been motivated by the ability to regulate algal blooms induced by cultural eutrophication, while marine studies have been more oriented towards fish yield and thus bottom-up processes. Also freshwaters are closed ecosystems with lower diversity and complexity, making models and predictions on trophic levels and interactions comparatively simpler. Here, we compare some key properties of freshwater and marine top-down cascades and argue that despite some striking differences, the large number of freshwater studies may pose valuable insights also for marine systems. Moreover, we argue that there is an urgent need for more focus on top-down cascades in marine systems that address how top predators or fishing may propagate through the food web and impact autotrophic biomass, production, C-sequestration and thus ultimately the global carbon cycle and climate. © 2014 The Author. Published by Oxford University Press. All rights reserved.

  1. Crustal inheritance and arc magmatism: Magnetotelluric constraints from the Washington Cascades on top-down control

    Science.gov (United States)

    Bedrosian, P.; Peacock, J.; Bowles-martinez, E.; Schultz, A.; Hill, G.

    2017-12-01

    Worldwide, arc volcanism occurs along relatively narrow magmatic arcs, the locations of which are considered to mark the onset of dehydration reactions within the subducting slab. This `bottom-up' approach, in which the location of arc volcanism reflects where fluids and melt are generated, explains first-order differences in trench-to-arc distance and is consistent with known variations in the thermal structure and geometry of subducting slabs. At a finer scale, arc segmentation, magmatic gaps, and anomalous forearc and backarc magmatism are also frequently interpreted in terms of variations in slab geometry, composition, or thermal structure.The role of inherited crustal structure in controlling faulting and deformation is well documented; less well examined is the role of crustal structure in controlling magmatism. While the source distribution of melt and subduction fluids is critical to determining the location of arc magmatism, we argue that crustal structure provides `top-down' control on patterns or seismicity and deformation as well as the channeling and ascent of arc magmas. We present evidence within the Washington Cascades based upon correlation between a new three-dimensional resistivity model, potential-field data, seismicity, and Quaternary volcanism. We image a mid-Tertiary batholith, intruded within an Eocene crustal suture zone, and extending throughout much of the crustal column. This and neighboring plutons are interpreted to channel crustal fluids and melt along their margins within steeply dipping zones of marine to transitional metasedimentary rock. Mount St. Helens is interpreted to be fed by fluids and melt generated further east at greater slab depths, migrating laterally (underplating?) beneath the Spirit Lake batholith, and ascending through metasedimentary rocks within the brittle crust. At a regional scale, we argue that this concealed suture zone controls present-day deformation and seismicity as well as the distribution of forearc

  2. Top-down and bottom-up lipidomic analysis of rabbit lipoproteins under different metabolic conditions using flow field-flow fractionation, nanoflow liquid chromatography and mass spectrometry.

    Science.gov (United States)

    Byeon, Seul Kee; Kim, Jin Yong; Lee, Ju Yong; Chung, Bong Chul; Seo, Hong Seog; Moon, Myeong Hee

    2015-07-31

    This study demonstrated the performances of top-down and bottom-up approaches in lipidomic analysis of lipoproteins from rabbits raised under different metabolic conditions: healthy controls, carrageenan-induced inflammation, dehydration, high cholesterol (HC) diet, and highest cholesterol diet with inflammation (HCI). In the bottom-up approach, the high density lipoproteins (HDL) and the low density lipoproteins (LDL) were size-sorted and collected on a semi-preparative scale using a multiplexed hollow fiber flow field-flow fractionation (MxHF5), followed by nanoflow liquid chromatography-ESI-MS/MS (nLC-ESI-MS/MS) analysis of the lipids extracted from each lipoprotein fraction. In the top-down method, size-fractionated lipoproteins were directly infused to MS for quantitative analysis of targeted lipids using chip-type asymmetrical flow field-flow fractionation-electrospray ionization-tandem mass spectrometry (cAF4-ESI-MS/MS) in selected reaction monitoring (SRM) mode. The comprehensive bottom-up analysis yielded 122 and 104 lipids from HDL and LDL, respectively. Rabbits within the HC and HCI groups had lipid patterns that contrasted most substantially from those of controls, suggesting that HC diet significantly alters the lipid composition of lipoproteins. Among the identified lipids, 20 lipid species that exhibited large differences (>10-fold) were selected as targets for the top-down quantitative analysis in order to compare the results with those from the bottom-up method. Statistical comparison of the results from the two methods revealed that the results were not significantly different for most of the selected species, except for those species with only small differences in concentration between groups. The current study demonstrated that top-down lipid analysis using cAF4-ESI-MS/MS is a powerful high-speed analytical platform for targeted lipidomic analysis that does not require the extraction of lipids from blood samples. Copyright © 2015 Elsevier B

  3. Top-down or bottom-up? Assessing crevassing directions on surging glaciers and developments for physically testing glacier crevassing models.

    Science.gov (United States)

    Rea, B.; Evans, D. J. A.; Benn, D. I.; Brennan, A. J.

    2012-04-01

    Networks of crevasse squeeze ridges (CSRs) preserved on the forelands of many surging glaciers attest to extensive full-depth crevassing. Full-depth connections have been inferred from turbid water up-welling in crevasses and the formation of concertina eskers however, it has not been clearly established if the crevasses formed from the top-down or the bottom-up. A Linear Elastic Fracture Mechanics (LEFM) approach is used to determine the likely propagation direction for Mode I crevasses on seven surging glaciers. Results indicate that, the high extensional surface strain rates are insufficient to promote top-down full-depth crevasses but have sufficient magnitude to penetrate to depths of 4-12 m, explaining the extensive surface breakup accompanying glacier surges. Top-down, full-depth crevassing is only possible when water depth approaches 97% of the crevasse depth. However, the provision of sufficient meltwater is problematic due to the aforementioned extensive shallow surface crevassing. Full-depth, bottom-up crevassing can occur provided basal water pressures are in excess of 80-90% of flotation which is the default for surging and on occasion water pressures may even become artesian. Therefore CSRs, found across many surging glacier forelands and ice margins most likely result from the infilling of basal crevasses formed, for the most part, by bottom-up hydrofracturing. Despite the importance of crevassing for meltwater routing and calving dynamics physically testing numerical crevassing models remains problematic due to technological limitations, changing stress regimes and difficulties associated with working in crevasse zones on glaciers. Mapping of CSR spacing and matching to surface crevasse patterns can facilitate quantitative comparison between the LEFM model and observed basal crevasses provided ice dynamics are known. However, assessing full-depth top-down crevasse propagation is much harder to monitor in the field and no geomorphological record is

  4. Encouraging top-down attention in visual search:A developmental perspective.

    Science.gov (United States)

    Lookadoo, Regan; Yang, Yingying; Merrill, Edward C

    2017-10-01

    Four experiments are reported in which 60 younger children (7-8 years old), 60 older children (10-11 years old), and 60 young adults (18-25 years old) performed a conjunctive visual search task (15 per group in each experiment). The number of distractors of each feature type was unbalanced across displays to evaluate participants' ability to restrict search to the smaller subset of features. The use of top-down attention processes to restrict search was encouraged by providing external aids for identifying and maintaining attention on the smaller set. In Experiment 1, no external assistance was provided. In Experiment 2, precues and instructions were provided to focus attention on that subset. In Experiment 3, trials in which the smaller subset was represented by the same feature were presented in alternating blocks to eliminate the need to switch attention between features from trial to trial. In Experiment 4, consecutive blocks of the same subset features were presented in the first or second half of the experiment, providing additional consistency. All groups benefited from external support of top-down attention, although the pattern of improvement varied across experiments. The younger children benefited most from precues and instruction, using the subset search strategy when instructed. Furthermore, younger children benefited from blocking trials only when blocks of the same features did not alternate. Older participants benefited from the blocking of trials in both Experiments 3 and 4, but not from precues and instructions. Hence, our results revealed both malleability and limits of children's top-down control of attention.

  5. Top-down attention based on object representation and incremental memory for knowledge building and inference.

    Science.gov (United States)

    Kim, Bumhwi; Ban, Sang-Woo; Lee, Minho

    2013-10-01

    Humans can efficiently perceive arbitrary visual objects based on an incremental learning mechanism with selective attention. This paper proposes a new task specific top-down attention model to locate a target object based on its form and color representation along with a bottom-up saliency based on relativity of primitive visual features and some memory modules. In the proposed model top-down bias signals corresponding to the target form and color features are generated, which draw the preferential attention to the desired object by the proposed selective attention model in concomitance with the bottom-up saliency process. The object form and color representation and memory modules have an incremental learning mechanism together with a proper object feature representation scheme. The proposed model includes a Growing Fuzzy Topology Adaptive Resonance Theory (GFTART) network which plays two important roles in object color and form biased attention; one is to incrementally learn and memorize color and form features of various objects, and the other is to generate a top-down bias signal to localize a target object by focusing on the candidate local areas. Moreover, the GFTART network can be utilized for knowledge inference which enables the perception of new unknown objects on the basis of the object form and color features stored in the memory during training. Experimental results show that the proposed model is successful in focusing on the specified target objects, in addition to the incremental representation and memorization of various objects in natural scenes. In addition, the proposed model properly infers new unknown objects based on the form and color features of previously trained objects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Top-down modulation on perceptual decision with balanced inhibition through feedforward and feedback inhibitory neurons.

    Directory of Open Access Journals (Sweden)

    Cheng-Te Wang

    Full Text Available Recent physiological studies have shown that neurons in various regions of the central nervous systems continuously receive noisy excitatory and inhibitory synaptic inputs in a balanced and covaried fashion. While this balanced synaptic input (BSI is typically described in terms of maintaining the stability of neural circuits, a number of experimental and theoretical studies have suggested that BSI plays a proactive role in brain functions such as top-down modulation for executive control. Two issues have remained unclear in this picture. First, given the noisy nature of neuronal activities in neural circuits, how do the modulatory effects change if the top-down control implements BSI with different ratios between inhibition and excitation? Second, how is a top-down BSI realized via only excitatory long-range projections in the neocortex? To address the first issue, we systematically tested how the inhibition/excitation ratio affects the accuracy and reaction times of a spiking neural circuit model of perceptual decision. We defined an energy function to characterize the network dynamics, and found that different ratios modulate the energy function of the circuit differently and form two distinct functional modes. To address the second issue, we tested BSI with long-distance projection to inhibitory neurons that are either feedforward or feedback, depending on whether these inhibitory neurons do or do not receive inputs from local excitatory cells, respectively. We found that BSI occurs in both cases. Furthermore, when relying on feedback inhibitory neurons, through the recurrent interactions inside the circuit, BSI dynamically and automatically speeds up the decision by gradually reducing its inhibitory component in the course of a trial when a decision process takes too long.

  7. Top-down modulation on perceptual decision with balanced inhibition through feedforward and feedback inhibitory neurons.

    Science.gov (United States)

    Wang, Cheng-Te; Lee, Chung-Ting; Wang, Xiao-Jing; Lo, Chung-Chuan

    2013-01-01

    Recent physiological studies have shown that neurons in various regions of the central nervous systems continuously receive noisy excitatory and inhibitory synaptic inputs in a balanced and covaried fashion. While this balanced synaptic input (BSI) is typically described in terms of maintaining the stability of neural circuits, a number of experimental and theoretical studies have suggested that BSI plays a proactive role in brain functions such as top-down modulation for executive control. Two issues have remained unclear in this picture. First, given the noisy nature of neuronal activities in neural circuits, how do the modulatory effects change if the top-down control implements BSI with different ratios between inhibition and excitation? Second, how is a top-down BSI realized via only excitatory long-range projections in the neocortex? To address the first issue, we systematically tested how the inhibition/excitation ratio affects the accuracy and reaction times of a spiking neural circuit model of perceptual decision. We defined an energy function to characterize the network dynamics, and found that different ratios modulate the energy function of the circuit differently and form two distinct functional modes. To address the second issue, we tested BSI with long-distance projection to inhibitory neurons that are either feedforward or feedback, depending on whether these inhibitory neurons do or do not receive inputs from local excitatory cells, respectively. We found that BSI occurs in both cases. Furthermore, when relying on feedback inhibitory neurons, through the recurrent interactions inside the circuit, BSI dynamically and automatically speeds up the decision by gradually reducing its inhibitory component in the course of a trial when a decision process takes too long.

  8. Top-down modulation of human early visual cortex after stimulus offset supports successful postcued report.

    Science.gov (United States)

    Sergent, Claire; Ruff, Christian C; Barbot, Antoine; Driver, Jon; Rees, Geraint

    2011-08-01

    Modulations of sensory processing in early visual areas are thought to play an important role in conscious perception. To date, most empirical studies focused on effects occurring before or during visual presentation. By contrast, several emerging theories postulate that sensory processing and conscious visual perception may also crucially depend on late top-down influences, potentially arising after a visual display. To provide a direct test of this, we performed an fMRI study using a postcued report procedure. The ability to report a target at a specific spatial location in a visual display can be enhanced behaviorally by symbolic auditory postcues presented shortly after that display. Here we showed that such auditory postcues can enhance target-specific signals in early human visual cortex (V1 and V2). For postcues presented 200 msec after stimulus termination, this target-specific enhancement in visual cortex was specifically associated with correct conscious report. The strength of this modulation predicted individual levels of performance in behavior. By contrast, although later postcues presented 1000 msec after stimulus termination had some impact on activity in early visual cortex, this modulation no longer related to conscious report. These results demonstrate that within a critical time window of a few hundred milliseconds after a visual stimulus has disappeared, successful conscious report of that stimulus still relates to the strength of top-down modulation in early visual cortex. We suggest that, within this critical time window, sensory representation of a visual stimulus is still under construction and so can still be flexibly influenced by top-down modulatory processes.

  9. Network model of top-down influences on local gain and contextual interactions in visual cortex.

    Science.gov (United States)

    Piëch, Valentin; Li, Wu; Reeke, George N; Gilbert, Charles D

    2013-10-22

    The visual system uses continuity as a cue for grouping oriented line segments that define object boundaries in complex visual scenes. Many studies support the idea that long-range intrinsic horizontal connections in early visual cortex contribute to this grouping. Top-down influences in primary visual cortex (V1) play an important role in the processes of contour integration and perceptual saliency, with contour-related responses being task dependent. This suggests an interaction between recurrent inputs to V1 and intrinsic connections within V1 that enables V1 neurons to respond differently under different conditions. We created a network model that simulates parametrically the control of local gain by hypothetical top-down modification of local recurrence. These local gain changes, as a consequence of network dynamics in our model, enable modulation of contextual interactions in a task-dependent manner. Our model displays contour-related facilitation of neuronal responses and differential foreground vs. background responses over the neuronal ensemble, accounting for the perceptual pop-out of salient contours. It quantitatively reproduces the results of single-unit recording experiments in V1, highlighting salient contours and replicating the time course of contextual influences. We show by means of phase-plane analysis that the model operates stably even in the presence of large inputs. Our model shows how a simple form of top-down modulation of the effective connectivity of intrinsic cortical connections among biophysically realistic neurons can account for some of the response changes seen in perceptual learning and task switching.

  10. Perceptual learning to reduce sensory eye dominance beyond the focus of top-down visual attention.

    Science.gov (United States)

    Xu, Jingping P; He, Zijiang J; Ooi, Teng Leng

    2012-05-15

    Perceptual learning is an important means for the brain to maintain its agility in a dynamic environment. Top-down focal attention, which selects task-relevant stimuli against competing ones in the background, is known to control and select what is learned in adults. Still unknown, is whether the adult brain is able to learn highly visible information beyond the focus of top-down attention. If it is, we should be able to reveal a purely stimulus-driven perceptual learning occurring in functions that are largely determined by the early cortical level, where top-down attention modulation is weak. Such an automatic, stimulus-driven learning mechanism is commonly assumed to operate only in the juvenile brain. We performed perceptual training to reduce sensory eye dominance (SED), a function that taps on the eye-of-origin information represented in the early visual cortex. Two retinal locations were simultaneously stimulated with suprathreshold, dichoptic orthogonal gratings. At each location, monocular cueing triggered perception of the grating images of the weak eye and suppression of the strong eye. Observers attended only to one location and performed orientation discrimination of the gratings seen by the weak eye, while ignoring the highly visible gratings at the second, unattended, location. We found SED was not only reduced at the attended location, but also at the unattended location. Furthermore, other untrained visual functions mediated by higher cortical levels improved. An automatic, stimulus-driven learning mechanism causes synaptic alterations in the early cortical level, with a far-reaching impact on the later cortical levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Mild performic acid oxidation enhances chromatographic and top down mass spectrometric analyses of histones.

    Science.gov (United States)

    Pesavento, James J; Garcia, Benjamin A; Streeky, James A; Kelleher, Neil L; Mizzen, Craig A

    2007-09-01

    Recent developments in top down mass spectrometry have enabled closely related histone variants and their modified forms to be identified and quantitated with unprecedented precision, facilitating efforts to better understand how histones contribute to the epigenetic regulation of gene transcription and other nuclear processes. It is therefore crucial that intact MS profiles accurately reflect the levels of variants and modified forms present in a given cell type or cell state for the full benefit of such efforts to be realized. Here we show that partial oxidation of Met and Cys residues in histone samples prepared by conventional methods, together with oxidation that can accrue during storage or during chip-based automated nanoflow electrospray ionization, confounds MS analysis by altering the intact MS profile as well as hindering posttranslational modification localization after MS/MS. We also describe an optimized performic acid oxidation procedure that circumvents these problems without catalyzing additional oxidations or altering the levels of posttranslational modifications common in histones. MS and MS/MS of HeLa cell core histones confirmed that Met and Cys were the only residues oxidized and that complete oxidation restored true intact abundance ratios and significantly enhanced MS/MS data quality. This allowed for the unequivocal detection, at the intact molecule level, of novel combinatorially modified forms of H4 that would have been missed otherwise. Oxidation also enhanced the separation of human core histones by reverse phase chromatography and decreased the levels of salt-adducted forms observed in ESI-FTMS. This method represents a simple and easily automated means for enhancing the accuracy and sensitivity of top down analyses of combinatorially modified forms of histones that may also be of benefit for top down or bottom up analyses of other proteins.

  12. Serum proteome profiling in canine idiopathic dilated cardiomyopathy using TMT-based quantitative proteomics approach.

    Science.gov (United States)

    Bilić, Petra; Guillemin, Nicolas; Kovačević, Alan; Beer Ljubić, Blanka; Jović, Ines; Galan, Asier; Eckersall, Peter David; Burchmore, Richard; Mrljak, Vladimir

    2018-05-15

    Idiopathic dilated cardiomyopathy (iDCM) is a primary myocardial disorder with an unknown aetiology, characterized by reduced contractility and ventricular dilation of the left or both ventricles. Naturally occurring canine iDCM was used herein to identify serum proteomic signature of the disease compared to the healthy state, providing an insight into underlying mechanisms and revealing proteins with biomarker potential. To achieve this, we used high-throughput label-based quantitative LC-MS/MS proteomics approach and bioinformatics analysis of the in silico inferred interactome protein network created from the initial list of differential proteins. To complement the proteomic analysis, serum biochemical parameters and levels of know biomarkers of cardiac function were measured. Several proteins with biomarker potential were identified, such as inter-alpha-trypsin inhibitor heavy chain H4, microfibril-associated glycoprotein 4 and apolipoprotein A-IV, which were validated using an independent method (Western blotting) and showed high specificity and sensitivity according to the receiver operating characteristic curve analysis. Bioinformatics analysis revealed involvement of different pathways in iDCM, such as complement cascade activation, lipoprotein particles dynamics, elastic fibre formation, GPCR signalling and respiratory electron transport chain. Idiopathic dilated cardiomyopathy is a severe primary myocardial disease of unknown cause, affecting both humans and dogs. This study is a contribution to the canine heart disease research by means of proteomic and bioinformatic state of the art analyses, following similar approach in human iDCM research. Importantly, we used serum as non-invasive and easily accessible biological source of information and contributed to the scarce data on biofluid proteome research on this topic. Bioinformatics analysis revealed biological pathways modulated in canine iDCM with potential of further targeted research. Also, several

  13. How can physics underlie the mind? top-down causation in the human context

    CERN Document Server

    Ellis, George

    2016-01-01

    Physics underlies all complexity, including our own existence: how is this possible? How can our own lives emerge from interactions of electrons, protons, and neutrons? This book considers the interaction of physical and non-physical causation in complex systems such as living beings, and in particular in the human brain, relating this to the emergence of higher levels of complexity with real causal powers. In particular it explores the idea of top-down causation, which is the key effect allowing the emergence of true complexity and also enables the causal efficacy of non-physical entities, including the value of money, social conventions, and ethical choices.

  14. Unsupervised tattoo segmentation combining bottom-up and top-down cues

    Science.gov (United States)

    Allen, Josef D.; Zhao, Nan; Yuan, Jiangbo; Liu, Xiuwen

    2011-06-01

    Tattoo segmentation is challenging due to the complexity and large variance in tattoo structures. We have developed a segmentation algorithm for finding tattoos in an image. Our basic idea is split-merge: split each tattoo image into clusters through a bottom-up process, learn to merge the clusters containing skin and then distinguish tattoo from the other skin via top-down prior in the image itself. Tattoo segmentation with unknown number of clusters is transferred to a figureground segmentation. We have applied our segmentation algorithm on a tattoo dataset and the results have shown that our tattoo segmentation system is efficient and suitable for further tattoo classification and retrieval purpose.

  15. Study on Top-Down Estimation Method of Software Project Planning

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun-guang; L(U) Ting-jie; ZHAO Yu-mei

    2006-01-01

    This paper studies a new software project planning method under some actual project data in order to make software project plans more effective. From the perspective of system theory, our new method regards a software project plan as an associative unit for study. During a top-down estimation of a software project, Program Evaluation and Review Technique (PERT) method and analogy method are combined to estimate its size, then effort estimation and specific schedules are obtained according to distributions of the phase effort. This allows a set of practical and feasible planning methods to be constructed. Actual data indicate that this set of methods can lead to effective software project planning.

  16. Public engagement as a field of tension between bottom-up and top-down strategies

    DEFF Research Database (Denmark)

    Horsbøl, Anders; Lassen, Inger

    2012-01-01

    In the ongoing debate about climate change, public engagement is given increasing prominence as a possible solution to a general lack of citizen participation in climate change mitigation efforts. Recent years have seen a surge in public engagement initiatives in many countries in the Western world....... These initiatives often have to deal with dilemmas between participatory aspects and other considerations such as planning efficiency, dilemmas that potentially bring about tension between bottom-up and top-down strategies. Literature on climate change issues has addressed the failure of public response, which has...... knowledge and information about climate change has not significantly changed people’s behaviour towards higher involvement....

  17. Bottom-up and top-down effects on plant communities

    DEFF Research Database (Denmark)

    Souza, Lara; Zelikova, Tamara Jane; Sanders, Nate

    2016-01-01

    -down) and soil nitrogen (bottom-up) were manipulated over six years in an existing old-field community. We tracked plant α and β diversity - within plot richness and among plot biodiversity- and aboveground net primary productivity (ANPP) over the course of the experiment. We found that bottom-up factors...... affected ANPP while top-down factors influenced plant community structure. Across years, while N reduction lowered ANPP by 10%, N reduction did not alter ANPP relative to control plots. Further, N reduction lowered ANPP by 20% relative to N addition plots. On the other hand, the reduction of insect...... community composition via shifts in plant dominance....

  18. Combining genomic and proteomic approaches for epigenetics research

    Science.gov (United States)

    Han, Yumiao; Garcia, Benjamin A

    2014-01-01

    Epigenetics is the study of changes in gene expression or cellular phenotype that do not change the DNA sequence. In this review, current methods, both genomic and proteomic, associated with epigenetics research are discussed. Among them, chromatin immunoprecipitation (ChIP) followed by sequencing and other ChIP-based techniques are powerful techniques for genome-wide profiling of DNA-binding proteins, histone post-translational modifications or nucleosome positions. However, mass spectrometry-based proteomics is increasingly being used in functional biological studies and has proved to be an indispensable tool to characterize histone modifications, as well as DNA–protein and protein–protein interactions. With the development of genomic and proteomic approaches, combination of ChIP and mass spectrometry has the potential to expand our knowledge of epigenetics research to a higher level. PMID:23895656

  19. PTSD symptom severity is associated with increased recruitment of top-down attentional control in a trauma-exposed sample

    OpenAIRE

    White, Stuart F.; Costanzo, Michelle E.; Blair, James R.; Roy, Michael J.

    2015-01-01

    Background: Recent neuroimaging work suggests that increased amygdala responses to emotional stimuli and dysfunction within regions mediating top down attentional control (dorsomedial frontal, lateral frontal and parietal cortices) may be associated with the emergence of anxiety disorders, including posttraumatic stress disorder (PTSD). This report examines amygdala responsiveness to emotional stimuli and the recruitment of top down attention systems as a function of task demands in a populat...

  20. The Impact of Top-Down Prediction on Emotional Face Processing in Social Anxiety

    Directory of Open Access Journals (Sweden)

    Guangming Ran

    2017-07-01

    Full Text Available There is evidence that people with social anxiety show abnormal processing of emotional faces. To investigate the impact of top-down prediction on emotional face processing in social anxiety, brain responses of participants with high and low social anxiety (LSA were recorded, while they performed a variation of the emotional task, using high temporal resolution event-related potential techniques. Behaviorally, we reported an effect of prediction with higher accuracy for predictable than unpredictable faces. Furthermore, we found that participants with high social anxiety (HSA, but not with LSA, recognized angry faces more accurately than happy faces. For the P100 and P200 components, HSA participants showed enhanced brain activity for angry faces compared to happy faces, suggesting a hypervigilance to angry faces. Importantly, HSA participants exhibited larger N170 amplitudes in the right hemisphere electrodes than LSA participants when they observed unpredictable angry faces, but not when the angry faces were predictable. This probably reflects the top-down prediction improving the deficiency at building a holistic face representation in HSA participants.

  1. Top down and bottom up selection drives variations in frequency and form of a visual signal.

    Science.gov (United States)

    Yeh, Chien-Wei; Blamires, Sean J; Liao, Chen-Pan; Tso, I-Min

    2015-03-30

    The frequency and form of visual signals can be shaped by selection from predators, prey or both. When a signal simultaneously attracts predators and prey selection may favour a strategy that minimizes risks while attracting prey. Accordingly, varying the frequency and form of the silken decorations added to their web may be a way that Argiope spiders minimize predation while attracting prey. Nonetheless, the role of extraneous factors renders the influences of top down and bottom up selection on decoration frequency and form variation difficult to discern. Here we used dummy spiders and decorations to simulate four possible strategies that the spider Argiope aemula may choose and measured the prey and predator attraction consequences for each in the field. The strategy of decorating at a high frequency with a variable form attracted the most prey, while that of decorating at a high frequency with a fixed form attracted the most predators. These results suggest that mitigating the cost of attracting predators while maintaining prey attraction drives the use of variation in decoration form by many Argiope spp. when decorating frequently. Our study highlights the importance of considering top-down and bottom up selection pressure when devising evolutionary ecology experiments.

  2. Investigating emotional top down modulation of ambiguous faces by single pulse TMS on early visual cortices

    Directory of Open Access Journals (Sweden)

    Zachary Adam Yaple

    2016-06-01

    Full Text Available Top-down processing is a mechanism in which memory, context and expectation are used to perceive stimuli. For this study we investigated how emotion content, induced by music mood, influences perception of happy and sad emoticons. Using single pulse TMS we stimulated right occipital face area (rOFA, primary visual cortex (V1 and vertex while subjects performed a face-detection task and listened to happy and sad music. At baseline, incongruent audio-visual pairings decreased performance, demonstrating dependence of emotion while perceiving ambiguous faces. However, performance of face identification decreased during rOFA stimulation regardless of emotional content. No effects were found between Cz and V1 stimulation. These results suggest that while rOFA is important for processing faces regardless of emotion, V1 stimulation had no effect. Our findings suggest that early visual cortex activity may not integrate emotional auditory information with visual information during emotion top-down modulation of faces.

  3. Dietary self-control influences top-down guidance of attention to food cues.

    Science.gov (United States)

    Higgs, Suzanne; Dolmans, Dirk; Humphreys, Glyn W; Rutters, Femke

    2015-01-01

    Motivational objects attract attention due to their rewarding properties, but less is known about the role that top-down cognitive processes play in the attention paid to motivationally relevant objects and how this is affected by relevant behavioral traits. Here we assess how thinking about food affects attentional guidance to food items and how this is modulated by traits relating to dietary self-control. Participants completed two tasks in which they were presented with an initial cue (food or non-food) to either hold in working memory (memory task) or to merely attend to (priming task). Holding food items in working memory strongly affected attention when the memorized cue re-appeared in the search display. Tendency towards disinhibited eating was associated with greater attention to food versus non-food pictures in both the priming and working memory tasks, consistent with greater attention to food cues per se. Successful dieters, defined as those high in dietary restraint and low in tendency to disinhibition, showed reduced attention to food when holding food-related information in working memory. These data suggest a strong top-down effect of thinking about food on attention to food items and indicate that the suppression of food items in working memory could be a marker of dieting success.

  4. Top-down control of invertebrates by Ninespine Stickleback in Arctic ponds

    Science.gov (United States)

    Laske, Sarah M.; Rosenberger, Amanda E.; Kane, William J.; Wipfli, Mark S.; Zimmerman, Christian E.

    2017-01-01

    Despite their widespread presence in northern-latitude ecosystems, the ecological role of Ninespine Stickleback Pungitius pungitius is not well understood. Ninespine Stickleback can occupy both top and intermediate trophic levels in freshwater ecosystems, so their role in food webs as a predator on invertebrates and as a forage fish for upper level consumers probably is substantial. We introduced Ninespine Sticklebacks to fishless ponds to elucidate their potential effects as a predator on invertebrate communities in Arctic lentic freshwaters. We hypothesized that Ninespine Stickleback would affect freshwater invertebrate communities in a top-down manner. We predicted that the addition of Ninespine Sticklebacks to fishless ponds would: 1) reduce invertebrate taxonomic richness, 2) decrease overall invertebrate abundance, 3) reduce invertebrate biomass, and 4) decrease average invertebrate body size. We tested our hypothesis at 2 locations by adding Ninespine Stickleback to isolated ponds and compared invertebrate communities over time between fish-addition and fishless control ponds. Ninespine Sticklebacks exerted strong top-down pressure on invertebrate communities mainly by changing invertebrate taxonomic richness and biomass and, to a lesser extent, abundance and average invertebrate size. Our results supported the hypothesis that Ninespine Stickleback may help shape lentic food webs in the Arctic.

  5. Top-down modulation in human visual cortex predicts the stability of a perceptual illusion

    Science.gov (United States)

    Meindertsma, Thomas; Hillebrand, Arjan; van Dijk, Bob W.; Lamme, Victor A. F.; Donner, Tobias H.

    2014-01-01

    Conscious perception sometimes fluctuates strongly, even when the sensory input is constant. For example, in motion-induced blindness (MIB), a salient visual target surrounded by a moving pattern suddenly disappears from perception, only to reappear after some variable time. Whereas such changes of perception result from fluctuations of neural activity, mounting evidence suggests that the perceptual changes, in turn, may also cause modulations of activity in several brain areas, including visual cortex. In this study, we asked whether these latter modulations might affect the subsequent dynamics of perception. We used magnetoencephalography (MEG) to measure modulations in cortical population activity during MIB. We observed a transient, retinotopically widespread modulation of beta (12–30 Hz)-frequency power over visual cortex that was closely linked to the time of subjects' behavioral report of the target disappearance. This beta modulation was a top-down signal, decoupled from both the physical stimulus properties and the motor response but contingent on the behavioral relevance of the perceptual change. Critically, the modulation amplitude predicted the duration of the subsequent target disappearance. We propose that the transformation of the perceptual change into a report triggers a top-down mechanism that stabilizes the newly selected perceptual interpretation. PMID:25411458

  6. Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits.

    Science.gov (United States)

    Renteria, Rafael; Baltz, Emily T; Gremel, Christina M

    2018-01-15

    Addiction involves a predominance of habitual control mediated through action selection processes in dorsal striatum. Research has largely focused on neural mechanisms mediating a proposed progression from ventral to dorsal lateral striatal control in addiction. However, over reliance on habit striatal processes may also arise from reduced cortical input to striatum, thereby disrupting executive control over action selection. Here, we identify novel mechanisms through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts top-down control over goal-directed action selection processes to produce habits. We find CIE results in decreased excitability of orbital frontal cortex (OFC) excitatory circuits supporting goal-directed control, and, strikingly, selectively reduces OFC output to the direct output pathway in dorsal medial striatum. Increasing the activity of OFC circuits restores goal-directed control in CIE-exposed mice. Our findings show habitual control in alcohol dependence can arise through disrupted communication between top-down, goal-directed processes onto basal ganglia pathways controlling action selection.

  7. Top-down beta rhythms support selective attention via interlaminar interaction: a model.

    Directory of Open Access Journals (Sweden)

    Jung H Lee

    Full Text Available Cortical rhythms have been thought to play crucial roles in our cognitive abilities. Rhythmic activity in the beta frequency band, around 20 Hz, has been reported in recent studies that focused on neural correlates of attention, indicating that top-down beta rhythms, generated in higher cognitive areas and delivered to earlier sensory areas, can support attentional gain modulation. To elucidate functional roles of beta rhythms and underlying mechanisms, we built a computational model of sensory cortical areas. Our simulation results show that top-down beta rhythms can activate ascending synaptic projections from L5 to L4 and L2/3, responsible for biased competition in superficial layers. In the simulation, slow-inhibitory interneurons are shown to resonate to the 20 Hz input and modulate the activity in superficial layers in an attention-related manner. The predicted critical roles of these cells in attentional gain provide a potential mechanism by which cholinergic drive can support selective attention.

  8. ORGANIZATIONAL COMMUNICATION FROM THE TOP DOWN TO S.C. ARTEGO S.A.

    Directory of Open Access Journals (Sweden)

    DORU CÎRNU

    2016-06-01

    Full Text Available Vertical communication within the organization is twofold: top down and bottom up. The communication from the top down starts from the top management and continuous vertical hierarchy downward until the execution personnel from the base. This type of organizational communication aims to inform, advise, to guide, to train and evaluate subordinates, and to provide all necessary information on the objectives and organizational policies. Often, managers are overly optimistic about the clarity and complete vertical communication. In fact, they are usually managers who frequently recorded failures in the communication of important information or adequate training of subordinates. Starting from previous research more laboriou, among which we mention the GLOBE Study of American Professor Robert House or one conducted in our country (the study Comoros team coordinated by Professor Constantin Rosca, we did a study of smaller scale (at company level the vertical communication and efficiency of communication modalities of this type of managerial act. In this regard, a research performed at S. C. ARTEGO S.A. watched and how communication is done from top to bottom line information and training of personnel. The research, based on a questionnaire, which preserves the anonymity of respondents had interesting results, we stood to attention and present them in what follows. It was surprising to find that certain legal limits for working climat, especially causes of stress are almost unknown, even if some subjects gave positive answers to questions of this nature.

  9. Enhanced visual awareness for morality and pajamas? Perception vs. memory in 'top-down' effects.

    Science.gov (United States)

    Firestone, Chaz; Scholl, Brian J

    2015-03-01

    A raft of prominent findings has revived the notion that higher-level cognitive factors such as desire, meaning, and moral relevance can directly affect what we see. For example, under conditions of brief presentation, morally relevant words reportedly "pop out" and are easier to identify than morally irrelevant words. Though such results purport to show that perception itself is sensitive to such factors, much of this research instead demonstrates effects on visual recognition--which necessarily involves not only visual processing per se, but also memory retrieval. Here we report three experiments which suggest that many alleged top-down effects of this sort are actually effects on 'back-end' memory rather than 'front-end' perception. In particular, the same methods used to demonstrate popout effects for supposedly privileged stimuli (such as morality-related words, e.g. "punishment" and "victim") also yield popout effects for unmotivated, superficial categories (such as fashion-related words, e.g. "pajamas" and "stiletto"). We conclude that such effects reduce to well-known memory processes (in this case, semantic priming) that do not involve morality, and have no implications for debates about whether higher-level factors influence perception. These case studies illustrate how it is critical to distinguish perception from memory in alleged 'top-down' effects. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Top-down or bottom-up modelling. An application to CO2 abatement

    International Nuclear Information System (INIS)

    Laroui, F.; Van Leeuwen, M.J.

    1995-06-01

    In four articles a comparison is made of bottom-up, or engineers'' models, and top-down models, which comprise macro-econometric models, computable general equilibrium models and also models in the system dynamics tradition. In the first article the history of economic modelling is outlined. In the second article the multi-sector macro-economic Computable General Equilibrium model for the Netherlands is described. It can be used to study the long-term effects of fiscal policy measures on economic and environmental indicators, in particular the effects on the level of CO2-emissions. The aim of article 3 is to describe the structure of the electricity supply industry in the UK and how it can be represented in a bottom-up sub-model within a more general E3 sectoral model of the UK economy. The objective of the last paper (4) is mainly a methodological discussion about integrating top-down and bottom-up models which can be used to assess CO2 abatement policies impacts on economic activity

  11. Playing shooter and driving videogames improves top-down guidance in visual search.

    Science.gov (United States)

    Wu, Sijing; Spence, Ian

    2013-05-01

    Playing action videogames is known to improve visual spatial attention and related skills. Here, we showed that playing action videogames also improves classic visual search, as well as the ability to locate targets in a dual search that mimics certain aspects of an action videogame. In Experiment 1A, first-person shooter (FPS) videogame players were faster than nonplayers in both feature search and conjunction search, and in Experiment 1B, they were faster and more accurate in a peripheral search and identification task while simultaneously performing a central search. In Experiment 2, we showed that 10 h of play could improve the performance of nonplayers on each of these tasks. Three different genres of videogames were used for training: two action games and a 3-D puzzle game. Participants who played an action game (either an FPS or a driving game) achieved greater gains on all search tasks than did those who trained using the puzzle game. Feature searches were faster after playing an action videogame, suggesting that players developed a better target template to guide search in a top-down manner. The results of the dual search suggest that, in addition to enhancing the ability to divide attention, playing an action game improves the top-down guidance of attention to possible target locations. The results have practical implications for the development of training tools to improve perceptual and cognitive skills.

  12. Congruency effects in the remote distractor paradigm: evidence for top-down modulation.

    Science.gov (United States)

    Born, Sabine; Kerzel, Dirk

    2009-08-10

    In three experiments, we examined effects of target-distractor similarity in the remote distractor effect (RDE). Observers made saccades to peripheral targets that were either gray or green. Foveal or peripheral distractors were presented at the same time. The distractors could either share the target's defining property (congruent) or be different from the target (incongruent). Congruent distractors slowed down saccadic reaction times more than incongruent distractors. The increase of the RDE with target-distractor congruency depended on task demands. The more participants had to rely on the target property to locate the target, the larger the congruency effect. We conclude that the RDE can be modulated in a top-down manner. Alternative explanations such as persisting memory traces for the target property or differences in stimulus arrangement were considered but discarded. Our claim is in line with models of saccade generation which assume that the structures underlying the RDE (e.g. the superior colliculus) receive bottom-up as well as top-down information.

  13. Two Paths to Transforming Markets through Public Sector EnergyEfficiency: Bottom Up versus Top Down

    Energy Technology Data Exchange (ETDEWEB)

    Van Wie McGrory, Laura; Coleman, Philip; Fridley, David; Harris,Jeffrey; Villasenor Franco, Edgar

    2006-05-10

    The evolution of government purchasing initiatives in Mexicoand China, part of the PEPS (Promoting an Energy-efficient Public Sector)program, demonstrates the need for flexibility in designingenergy-efficiency strategies in the public sector. Several years ofpursuing a top-down (federally led) strategy in Mexico produced fewresults, and it was not until the program was restructured in 2004 tofocus on municipal-level purchasing that the program gained momentum.Today, a new partnership with the Mexican federal government is leadingto an intergovernmental initiative with strong support at the federallevel. By contrast, the PEPS purchasing initiative in China wassuccessfully initiated and led at the central government level withstrategic support from international experts. The very different successtrajectories in these two countries provide valuable lessons fordesigning country-specific public sector energy-efficiency initiatives.Enabling conditions for any successful public sector purchasinginitiative include the existence of mandatory energy-efficiencyperformance standards, an effective energy-efficiency endorsementlabeling program, an immediate need for energy conservation, a simplepilot phase (focusing on a limited number of strategically chosenproducts), and specialized technical assistance. Top-down purchasingprograms are likely to be more successful where there is high-levelpolitical endorsement and a national procurement law in place, supportedby a network of trained purchasers. Bottom-up (municipally led)purchasing programs require that municipalities have the authority to settheir own purchasing policies, and also benefit from existing networks ofcities, supported by motivated municipal leaders and trained purchasingofficials.

  14. Depression and anxious apprehension distinguish frontocingulate cortical activity during top-down attentional control.

    Science.gov (United States)

    Silton, Rebecca Levin; Heller, Wendy; Engels, Anna S; Towers, David N; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

    2011-05-01

    A network consisting of left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC) has been implicated in top-down attentional control. Few studies have systematically investigated how this network is altered in psychopathology, despite evidence that depression and anxiety are associated with attentional control impairments. Functional MRI and dense-array event-related brain potential (ERP) data were collected in separate sessions from 100 participants during a color-word Stroop task. Functional MRI results guided ERP source modeling to characterize the time course of activity in LDLPFC (300-440 ms) and dACC (520-680 ms). At low levels of depression, LDLPFC activity was indirectly related to Stroop interference and only via dACC activity. In contrast, at high levels of depression, dACC did not play an intervening role, and increased LDLPFC activity was directly related to decreased Stroop interference. Specific to high levels of anxious apprehension, higher dACC activity was related to more Stroop interference. Results indicate that depression and anxious apprehension modulate temporally and functionally distinct aspects of the frontocingulate network involved in top-down attention control.

  15. Comparing effectiveness of top-down and bottom-up strategies in containing influenza.

    Directory of Open Access Journals (Sweden)

    Achla Marathe

    Full Text Available This research compares the performance of bottom-up, self-motivated behavioral interventions with top-down interventions targeted at controlling an "Influenza-like-illness". Both types of interventions use a variant of the ring strategy. In the first case, when the fraction of a person's direct contacts who are diagnosed exceeds a threshold, that person decides to seek prophylaxis, e.g. vaccine or antivirals; in the second case, we consider two intervention protocols, denoted Block and School: when a fraction of people who are diagnosed in a Census Block (resp., School exceeds the threshold, prophylax the entire Block (resp., School. Results show that the bottom-up strategy outperforms the top-down strategies under our parameter settings. Even in situations where the Block strategy reduces the overall attack rate well, it incurs a much higher cost. These findings lend credence to the notion that if people used antivirals effectively, making them available quickly on demand to private citizens could be a very effective way to control an outbreak.

  16. Dietary self-control influences top-down guidance of attention to food cues

    Directory of Open Access Journals (Sweden)

    Suzanne eHiggs

    2015-04-01

    Full Text Available Motivational objects attract attention due to their rewarding properties, but less is known about the role that top-down cognitive processes play in the attention paid to motivationally relevant objects and how this is affected by relevant behaviour traits. Here we assess how thinking about food affects attentional guidance to food items and how this is modulated by traits relating to dietary self-control. Participants completed two tasks in which they were presented with an initial cue (food or non-food to either hold in working memory (memory task or to merely attend to (priming task. Holding food items in working memory strongly affected attention when the memorized cue re-appeared in the search display. Tendency towards disinhibited eating was associated with greater attention to food versus non-food pictures in both the priming and working memory tasks, consistent with greater attention to food cues per se. Successful dieters, defined as those high in dietary restraint and low in tendency to disinhibition, showed reduced attention to food when holding food-related information in working memory. These data suggest a strong top-down effect of thinking about food on attention to food items and indicate that the suppression of food items in working memory could be a marker of dieting success.

  17. Neurophysiological bases of exponential sensory decay and top-down memory retrieval: a model.

    Science.gov (United States)

    Zylberberg, Ariel; Dehaene, Stanislas; Mindlin, Gabriel B; Sigman, Mariano

    2009-01-01

    Behavioral observations suggest that multiple sensory elements can be maintained for a short time, forming a perceptual buffer which fades after a few hundred milliseconds. Only a subset of this perceptual buffer can be accessed under top-down control and broadcasted to working memory and consciousness. In turn, single-cell studies in awake-behaving monkeys have identified two distinct waves of response to a sensory stimulus: a first transient response largely determined by stimulus properties and a second wave dependent on behavioral relevance, context and learning. Here we propose a simple biophysical scheme which bridges these observations and establishes concrete predictions for neurophsyiological experiments in which the temporal interval between stimulus presentation and top-down allocation is controlled experimentally. Inspired in single-cell observations, the model involves a first transient response and a second stage of amplification and retrieval, which are implemented biophysically by distinct operational modes of the same circuit, regulated by external currents. We explicitly investigated the neuronal dynamics, the memory trace of a presented stimulus and the probability of correct retrieval, when these two stages were bracketed by a temporal gap. The model predicts correctly the dependence of performance with response times in interference experiments suggesting that sensory buffering does not require a specific dedicated mechanism and establishing a direct link between biophysical manipulations and behavioral observations leading to concrete predictions.

  18. Neurophysiological bases of exponential sensory decay and top-down memory retrieval: a model

    Directory of Open Access Journals (Sweden)

    Ariel Zylberberg

    2009-03-01

    Full Text Available Behavioral observations suggest that multiple sensory elements can be maintained for a short time, forming a perceptual buffer which fades after a few hundred milliseconds. Only a subset of this perceptual buffer can be accessed under top-down control and broadcasted to working memory and consciousness. In turn, single-cell studies in awake-behaving monkeys have identified two distinct waves of response to a sensory stimulus: a first transient response largely determined by stimulus properties and a second wave dependent on behavioral relevance, context and learning. Here we propose a simple biophysical scheme which bridges these observations and establishes concrete predictions for neurophsyiological experiments in which the temporal interval between stimulus presentation and top-down allocation is controlled experimentally. Inspired in single-cell observations, the model involves a first transient response and a second stage of amplification and retrieval, which are implemented biophysically by distinct operational modes of the same circuit, regulated by external currents. We explicitly investigated the neuronal dynamics, the memory trace of a presented stimulus and the probability of correct retrieval, when these two stages were bracketed by a temporal gap. The model predicts correctly the dependence of performance with response times in interference experiments suggesting that sensory buffering does not require a specific dedicated mechanism and establishing a direct link between biophysical manipulations and behavioral observations leading to concrete predictions.

  19. Bottom-up and top-down attentional contributions to the size congruity effect.

    Science.gov (United States)

    Sobel, Kenith V; Puri, Amrita M; Faulkenberry, Thomas J

    2016-07-01

    The size congruity effect refers to the interaction between the numerical and physical (i.e., font) sizes of digits in a numerical (or physical) magnitude selection task. Although various accounts of the size congruity effect have attributed this interaction to either an early representational stage or a late decision stage, only Risko, Maloney, and Fugelsang (Attention, Perception, & Psychophysics, 75, 1137-1147, 2013) have asserted a central role for attention. In the present study, we used a visual search paradigm to further study the role of attention in the size congruity effect. In Experiments 1 and 2, we showed that manipulating top-down attention (via the task instructions) had a significant impact on the size congruity effect. The interaction between numerical and physical size was larger for numerical size comparison (Exp. 1) than for physical size comparison (Exp. 2). In the remaining experiments, we boosted the feature salience by using a unique target color (Exp. 3) or by increasing the display density by using three-digit numerals (Exps. 4 and 5). As expected, a color singleton target abolished the size congruity effect. Searching for three-digit targets based on numerical size (Exp. 4) resulted in a large size congruity effect, but search based on physical size (Exp. 5) abolished the effect. Our results reveal a substantial role for top-down attention in the size congruity effect, which we interpreted as support for a shared-decision account.

  20. Top-Down and Bottom-Up Identification of Proteins by Liquid Extraction Surface Analysis Mass Spectrometry of Healthy and Diseased Human Liver Tissue

    Science.gov (United States)

    Sarsby, Joscelyn; Martin, Nicholas J.; Lalor, Patricia F.; Bunch, Josephine; Cooper, Helen J.

    2014-09-01

    Liquid extraction surface analysis mass spectrometry (LESA MS) has the potential to become a useful tool in the spatially-resolved profiling of proteins in substrates. Here, the approach has been applied to the analysis of thin tissue sections from human liver. The aim was to determine whether LESA MS was a suitable approach for the detection of protein biomarkers of nonalcoholic liver disease (nonalcoholic steatohepatitis, NASH), with a view to the eventual development of LESA MS for imaging NASH pathology. Two approaches were considered. In the first, endogenous proteins were extracted from liver tissue sections by LESA, subjected to automated trypsin digestion, and the resulting peptide mixture was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) (bottom-up approach). In the second (top-down approach), endogenous proteins were extracted by LESA, and analyzed intact. Selected protein ions were subjected to collision-induced dissociation (CID) and/or electron transfer dissociation (ETD) mass spectrometry. The bottom-up approach resulted in the identification of over 500 proteins; however identification of key protein biomarkers, liver fatty acid binding protein (FABP1), and its variant (Thr→Ala, position 94), was unreliable and irreproducible. Top-down LESA MS analysis of healthy and diseased liver tissue revealed peaks corresponding to multiple (~15-25) proteins. MS/MS of four of these proteins identified them as FABP1, its variant, α-hemoglobin, and 10 kDa heat shock protein. The reliable identification of FABP1 and its variant by top-down LESA MS suggests that the approach may be suitable for imaging NASH pathology in sections from liver biopsies.

  1. Proteomics approaches shed new light on hibernation physiology.

    Science.gov (United States)

    Grabek, Katharine R; Martin, Sandra L; Hindle, Allyson G

    2015-08-01

    The broad phylogenetic distribution and rapid phenotypic transitions of mammalian hibernators imply that hibernation is accomplished by differential expression of common genes. Traditional candidate gene approaches have thus far explained little of the molecular mechanisms underlying hibernation, likely due to (1) incomplete and imprecise sampling of a complex phenotype, and (2) the forming of hypotheses about which genes might be important based on studies of model organisms incapable of such dynamic physiology. Unbiased screening approaches, such as proteomics, offer an alternative means to discover the cellular underpinnings that permit successful hibernation and may reveal previously overlooked, important pathways. Here, we review the findings that have emerged from proteomics studies of hibernation. One striking feature is the stability of the proteome, especially across the extreme physiological shifts of torpor-arousal cycles during hibernation. This has led to subsequent investigations of the role of post-translational protein modifications in altering protein activity without energetically wasteful removal and rebuilding of protein pools. Another unexpected finding is the paucity of universal proteomic adjustments across organ systems in response to the extreme metabolic fluctuations despite the universality of their physiological challenges; rather each organ appears to respond in a unique, tissue-specific manner. Additional research is needed to extend and synthesize these results before it will be possible to address the whole body physiology of hibernation.

  2. High-throughput proteomics : optical approaches.

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, George S.

    2008-09-01

    Realistic cell models could greatly accelerate our ability to engineer biochemical pathways and the production of valuable organic products, which would be of great use in the development of biofuels, pharmaceuticals, and the crops for the next green revolution. However, this level of engineering will require a great deal more knowledge about the mechanisms of life than is currently available. In particular, we need to understand the interactome (which proteins interact) as it is situated in the three dimensional geometry of the cell (i.e., a situated interactome), and the regulation/dynamics of these interactions. Methods for optical proteomics have become available that allow the monitoring and even disruption/control of interacting proteins in living cells. Here, a range of these methods is reviewed with respect to their role in elucidating the interactome and the relevant spatial localizations. Development of these technologies and their integration into the core competencies of research organizations can position whole institutions and teams of researchers to lead in both the fundamental science and the engineering applications of cellular biology. That leadership could be particularly important with respect to problems of national urgency centered around security, biofuels, and healthcare.

  3. Agricultural ammonia emissions in China: reconciling bottom-up and top-down estimates

    Directory of Open Access Journals (Sweden)

    L. Zhang

    2018-01-01

    Full Text Available Current estimates of agricultural ammonia (NH3 emissions in China differ by more than a factor of 2, hindering our understanding of their environmental consequences. Here we apply both bottom-up statistical and top-down inversion methods to quantify NH3 emissions from agriculture in China for the year 2008. We first assimilate satellite observations of NH3 column concentration from the Tropospheric Emission Spectrometer (TES using the GEOS-Chem adjoint model to optimize Chinese anthropogenic NH3 emissions at the 1∕2°  ×  2∕3° horizontal resolution for March–October 2008. Optimized emissions show a strong summer peak, with emissions about 50 % higher in summer than spring and fall, which is underestimated in current bottom-up NH3 emission estimates. To reconcile the latter with the top-down results, we revisit the processes of agricultural NH3 emissions and develop an improved bottom-up inventory of Chinese NH3 emissions from fertilizer application and livestock waste at the 1∕2°  ×  2∕3° resolution. Our bottom-up emission inventory includes more detailed information on crop-specific fertilizer application practices and better accounts for meteorological modulation of NH3 emission factors in China. We find that annual anthropogenic NH3 emissions are 11.7 Tg for 2008, with 5.05 Tg from fertilizer application and 5.31 Tg from livestock waste. The two sources together account for 88 % of total anthropogenic NH3 emissions in China. Our bottom-up emission estimates also show a distinct seasonality peaking in summer, consistent with top-down results from the satellite-based inversion. Further evaluations using surface network measurements show that the model driven by our bottom-up emissions reproduces the observed spatial and seasonal variations of NH3 gas concentrations and ammonium (NH4+ wet deposition fluxes over China well, providing additional credibility to the improvements we have made to our

  4. Characterizing the effects of feature salience and top-down attention in the early visual system.

    Science.gov (United States)

    Poltoratski, Sonia; Ling, Sam; McCormack, Devin; Tong, Frank

    2017-07-01

    The visual system employs a sophisticated balance of attentional mechanisms: salient stimuli are prioritized for visual processing, yet observers can also ignore such stimuli when their goals require directing attention elsewhere. A powerful determinant of visual salience is local feature contrast: if a local region differs from its immediate surround along one or more feature dimensions, it will appear more salient. We used high-resolution functional MRI (fMRI) at 7T to characterize the modulatory effects of bottom-up salience and top-down voluntary attention within multiple sites along the early visual pathway, including visual areas V1-V4 and the lateral geniculate nucleus (LGN). Observers viewed arrays of spatially distributed gratings, where one of the gratings immediately to the left or right of fixation differed from all other items in orientation or motion direction, making it salient. To investigate the effects of directed attention, observers were cued to attend to the grating to the left or right of fixation, which was either salient or nonsalient. Results revealed reliable additive effects of top-down attention and stimulus-driven salience throughout visual areas V1-hV4. In comparison, the LGN exhibited significant attentional enhancement but was not reliably modulated by orientation- or motion-defined salience. Our findings indicate that top-down effects of spatial attention can influence visual processing at the earliest possible site along the visual pathway, including the LGN, whereas the processing of orientation- and motion-driven salience primarily involves feature-selective interactions that take place in early cortical visual areas. NEW & NOTEWORTHY While spatial attention allows for specific, goal-driven enhancement of stimuli, salient items outside of the current focus of attention must also be prioritized. We used 7T fMRI to compare salience and spatial attentional enhancement along the early visual hierarchy. We report additive effects of

  5. The case for refining bottom-up methane emission inventories using top-down measurements

    Science.gov (United States)

    Kelly, Bryce F. J.; Iverach, Charlotte P.; Ginty, Elisa; Bashir, Safdar; Lowry, Dave; Fisher, Rebecca E.; France, James L.; Nisbet, Euan G.

    2017-04-01

    Bottom-up global methane emission estimates are important for guiding policy development and mitigation strategies. Such inventories enable rapid and consistent proportioning of emissions by industrial sectors and land use at various scales from city to country to global. There has been limited use of top-down measurements to guide refining emission inventories. Here we compare the EDGAR gridmap data version 4.2 with over 5000 km of daytime ground level mobile atmospheric methane surveys in eastern Australia. The landscapes and industries surveyed include: urban environments, dryland farming, intensive livestock farming (both beef and lamb), irrigation agriculture, open cut and underground coal mining, and coal seam gas production. Daytime mobile methane surveys over a 2-year period show that at the landscape scale there is a high level of repeatability for the mole fraction of methane measured in the ground level atmosphere. Such consistency in the mole fraction of methane indicates that these data can be used as a proxy for flux. A scatter plot of the EDGAR emission gridmap Log[ton substance / 0.1 degree x 0.1 degree / year] versus the median mole fraction of methane / 0.1 degree x 0.1 degree in the ground level atmosphere highlights that the extent of elevated methane emissions associated with coal mining in the Hunter coalfields, which covers an area of 56 km by 24 km, has been under-represented in the EDGAR input data. Our results also show that methane emissions from country towns (population poor information on the extent of urban gas leaks. Given the uncertainties associated with the base land use and industry data for each country, we generalise the Australian observations to the global inventory with caution. The extensive comparison of top-down measurements versus the EDGAR version 4.2 methane gridmaps highlights the need for adjustments to the base resource data and/or the emission factors applied for coal mining, especially emissions from underground

  6. Merging Bottom-Up with Top-Down: Continuous Lamellar Networks and Block Copolymer Lithography

    Science.gov (United States)

    Campbell, Ian Patrick

    Block copolymer lithography is an emerging nanopatterning technology with capabilities that may complement and eventually replace those provided by existing optical lithography techniques. This bottom-up process relies on the parallel self-assembly of macromolecules composed of covalently linked, chemically distinct blocks to generate periodic nanostructures. Among the myriad potential morphologies, lamellar structures formed by diblock copolymers with symmetric volume fractions have attracted the most interest as a patterning tool. When confined to thin films and directed to assemble with interfaces perpendicular to the substrate, two-dimensional domains are formed between the free surface and the substrate, and selective removal of a single block creates a nanostructured polymeric template. The substrate exposed between the polymeric features can subsequently be modified through standard top-down microfabrication processes to generate novel nanostructured materials. Despite tremendous progress in our understanding of block copolymer self-assembly, continuous two-dimensional materials have not yet been fabricated via this robust technique, which may enable nanostructured material combinations that cannot be fabricated through bottom-up methods. This thesis aims to study the effects of block copolymer composition and processing on the lamellar network morphology of polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) and utilize this knowledge to fabricate continuous two-dimensional materials through top-down methods. First, block copolymer composition was varied through homopolymer blending to explore the physical phenomena surrounding lamellar network continuity. After establishing a framework for tuning the continuity, the effects of various processing parameters were explored to engineer the network connectivity via defect annihilation processes. Precisely controlling the connectivity and continuity of lamellar networks through defect engineering and

  7. Top-Down Control of Visual Alpha Oscillations: Sources of Control Signals and Their Mechanisms of Action

    Science.gov (United States)

    Wang, Chao; Rajagovindan, Rajasimhan; Han, Sahng-Min; Ding, Mingzhou

    2016-01-01

    Alpha oscillations (8–12 Hz) are thought to inversely correlate with cortical excitability. Goal-oriented modulation of alpha has been studied extensively. In visual spatial attention, alpha over the region of visual cortex corresponding to the attended location decreases, signifying increased excitability to facilitate the processing of impending stimuli. In contrast, in retention of verbal working memory, alpha over visual cortex increases, signifying decreased excitability to gate out stimulus input to protect the information held online from sensory interference. According to the prevailing model, this goal-oriented biasing of sensory cortex is effected by top-down control signals from frontal and parietal cortices. The present study tests and substantiates this hypothesis by (a) identifying the signals that mediate the top-down biasing influence, (b) examining whether the cortical areas issuing these signals are task-specific or task-independent, and (c) establishing the possible mechanism of the biasing action. High-density human EEG data were recorded in two experimental paradigms: a trial-by-trial cued visual spatial attention task and a modified Sternberg working memory task. Applying Granger causality to both sensor-level and source-level data we report the following findings. In covert visual spatial attention, the regions exerting top-down control over visual activity are lateralized to the right hemisphere, with the dipoles located at the right frontal eye field (FEF) and the right inferior frontal gyrus (IFG) being the main sources of top-down influences. During retention of verbal working memory, the regions exerting top-down control over visual activity are lateralized to the left hemisphere, with the dipoles located at the left middle frontal gyrus (MFG) being the main source of top-down influences. In both experiments, top-down influences are mediated by alpha oscillations, and the biasing effect is likely achieved via an inhibition

  8. Manufacturing at Nanoscale: Top-Down, Bottom-up and System Engineering

    International Nuclear Information System (INIS)

    Zhang Xiang; Sun Cheng; Fang, Nicholas

    2004-01-01

    The current nano-technology revolution is facing several major challenges: to manufacture nanodevices below 20 nm, to fabricate three-dimensional complex nano-structures, and to heterogeneously integrate multiple functionalities. To tackle these grand challenges, the Center for Scalable and Integrated NAno-Manufacturing (SINAM), a NSF Nanoscale Science and Engineering Center, set its goal to establish a new manufacturing paradigm that integrates an array of new nano-manufacturing technologies, including the plasmonic imaging lithography and ultramolding imprint lithography aiming toward critical resolution of 1-10 nm and the hybrid top-down and bottom-up technologies to achieve massively parallel integration of heterogeneous nanoscale components into higher-order structures and devices. Furthermore, SINAM will develop system engineering strategies to scale-up the nano-manufacturing technologies. SINAMs integrated research and education platform will shed light to a broad range of potential applications in computing, telecommunication, photonics, biotechnology, health care, and national security

  9. Top-down versus bottom-up processing of influence diagrams in probabilistic analysis

    International Nuclear Information System (INIS)

    Timmerman, R.D.; Burns, T.J.; Dodds, H.L. Jr.

    1986-01-01

    Recent work by Phillips and Selby has shown that influence diagram methodology can be a useful analytical tool in reactor safety studies. In some instances an influence diagram can be used as a graphical representation of probabilistic dependence within a system or event sequence. Under these circumstances, Bayesian statistics is employed to transform the relationships depicted in the influence diagram into the correct expression for a desired marginal probability (e.g. the top node). Top-down and bottom-up algorithms have emerged as the dominant methods for quantifying influence diagrams. The purpose of this paper is to demonstrate a potential error in employing the bottom-up algorithm when dealing with interdependencies

  10. Spallation Neutron Source Availability Top-Down Apportionment Using Characteristic Factors and Expert Opinion

    International Nuclear Information System (INIS)

    Haire, M.J.; Schryver, J.C.

    1999-01-01

    Apportionment is the assignment of top-level requirements to lower tier elements of the overall facility. A method for apportioning overall facility availability requirements among systems and subsystems is presented. Characteristics that influence equipment reliability and maintainability are discussed. Experts, using engineering judgment, scored each characteristic for each system whose availability design goal is to be established. The Analytic Hierarchy Process (AHP) method is used to produce a set of weighted rankings for each characteristic for each alternative system. A mathematical model is derived which incorporates these weighting factors. The method imposes higher availability requirements on those systems in which an incremental increase in availability is easier to achieve, and lower availability requirements where greater availability is more difficult and costly. An example is given of applying this top-down apportionment methodology to the Spallation Neutron Source (SNS) facility

  11. Unsupervised Tattoo Segmentation Combining Bottom-Up and Top-Down Cues

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Josef D [ORNL

    2011-01-01

    Tattoo segmentation is challenging due to the complexity and large variance in tattoo structures. We have developed a segmentation algorithm for nding tattoos in an image. Our basic idea is split-merge: split each tattoo image into clusters through a bottom-up process, learn to merge the clusters containing skin and then distinguish tattoo from the other skin via top-down prior in the image itself. Tattoo segmentation with unknown number of clusters is transferred to a gure-ground segmentation. We have applied our segmentation algorithm on a tattoo dataset and the results have shown that our tattoo segmentation system is e cient and suitable for further tattoo classi cation and retrieval purpose.

  12. Top-down versus bottom-up processing of influence diagrams in probabilistic analysis

    International Nuclear Information System (INIS)

    Timmerman, R.D.; Burns, T.J.; Dodds, H.L. Jr.

    1984-01-01

    Recent work by Phillips et al., and Selby et al., has shown that influence diagram methodology can be a useful analytical tool in reactor safety studies. An influence diagram is a graphical representation of probabilistic dependence within a system or event sequence. Bayesian statistics are employed to transform the relationships depicted in the influence diagram into the correct expression for a desired marginal probability (e.g. the top event). As with fault trees, top-down and bottom-up algorithms have emerged as the dominant methods for quantifying influence diagrams. Purpose of this paper is to demonstrate a potential error in employing the bottom-up algorithm when dealing with interdependencies. In addition, the computing efficiency of both methods is discussed

  13. Bottom-up and Top-down Input Augment the Variability of Cortical Neurons

    Science.gov (United States)

    Nassi, Jonathan J.; Kreiman, Gabriel; Born, Richard T.

    2016-01-01

    SUMMARY Neurons in the cerebral cortex respond inconsistently to a repeated sensory stimulus, yet they underlie our stable sensory experiences. Although the nature of this variability is unknown, its ubiquity has encouraged the general view that each cell produces random spike patterns that noisily represent its response rate. In contrast, here we show that reversibly inactivating distant sources of either bottom-up or top-down input to cortical visual areas in the alert primate reduces both the spike train irregularity and the trial-to-trial variability of single neurons. A simple model in which a fraction of the pre-synaptic input is silenced can reproduce this reduction in variability, provided that there exist temporal correlations primarily within, but not between, excitatory and inhibitory input pools. A large component of the variability of cortical neurons may therefore arise from synchronous input produced by signals arriving from multiple sources. PMID:27427459

  14. Integrated Bottom-Up and Top-Down Liquid Chromatography-Mass Spectrometry for Characterization of Recombinant Human Growth Hormone Degradation Products.

    Science.gov (United States)

    Wang, Yu Annie; Wu, Di; Auclair, Jared R; Salisbury, Joseph P; Sarin, Richa; Tang, Yang; Mozdzierz, Nicholas J; Shah, Kartik; Zhang, Anna Fan; Wu, Shiaw-Lin; Agar, Jeffery N; Love, J Christopher; Love, Kerry R; Hancock, William S

    2017-12-05

    With the advent of biosimilars to the U.S. market, it is important to have better analytical tools to ensure product quality from batch to batch. In addition, the recent popularity of using a continuous process for production of biopharmaceuticals, the traditional bottom-up method, alone for product characterization and quality analysis is no longer sufficient. Bottom-up method requires large amounts of material for analysis and is labor-intensive and time-consuming. Additionally, in this analysis, digestion of the protein with enzymes such as trypsin could induce artifacts and modifications which would increase the complexity of the analysis. On the other hand, a top-down method requires a minimum amount of sample and allows for analysis of the intact protein mass and sequence generated from fragmentation within the instrument. However, fragmentation usually occurs at the N-terminal and C-terminal ends of the protein with less internal fragmentation. Herein, we combine the use of the complementary techniques, a top-down and bottom-up method, for the characterization of human growth hormone degradation products. Notably, our approach required small amounts of sample, which is a requirement due to the sample constraints of small scale manufacturing. Using this approach, we were able to characterize various protein variants, including post-translational modifications such as oxidation and deamidation, residual leader sequence, and proteolytic cleavage. Thus, we were able to highlight the complementarity of top-down and bottom-up approaches, which achieved the characterization of a wide range of product variants in samples of human growth hormone secreted from Pichia pastoris.

  15. A top-down analysis: Determining photovoltaics R and D investments from patent analysis and R and D headcount

    International Nuclear Information System (INIS)

    Breyer, Christian; Birkner, Christian; Meiss, Jan; Goldschmidt, Jan Christoph; Riede, Moritz

    2013-01-01

    For alternative energy technologies like photovoltaics (PV), the analysis of Research and Development (R and D) expenses is important to observe and understand market dynamics. This is, in turn, essential for policymakers. However, the quantitative evaluation of global corporate R and D investments is a challenging task due to unavailability or high scatter of precise data. Here we present a top-down approach to estimate the current and global historic cumulated PV R and D investments based on international PV patent applications. High growth rates of PV-related patents and R and D headcount accompany growth and development of the PV market and are an excellent indicator to analyze R and D investments. With this approach, current annual corporate PV R and D investments are found to be about 6000 m€ and show a rapidly increasing trend on a global scale. - Highlights: • Global corporate and public photovoltaic R and D spendings are presented and quantified. • Instead of company reports or governmental reports, alternative metrics are developed. • Basis for quantification are photovoltaic patent applications and research headcounts. • Patents are analyzed regarding their country of origin, year of filing, type of technology. • Ethical and political implications of energy R and D are discussed

  16. Single, aligned carbon nanotubes in 3D nanoscale architectures enabled by top-down and bottom-up manufacturable processes

    International Nuclear Information System (INIS)

    Kaul, Anupama B; Megerian, Krikor G; Von Allmen, Paul; Baron, Richard L

    2009-01-01

    We have developed manufacturable approaches for forming single, vertically aligned carbon nanotubes, where the tubes are centered precisely, and placed within a few hundred nm of 1-1.5 μm deep trenches. These wafer-scale approaches were enabled by using chemically amplified resists and high density, low pressure plasma etching techniques to form the 3D nanoscale architectures. The tube growth was performed using dc plasma-enhanced chemical vapor deposition (PECVD), and the materials used in the pre-fabricated 3D architectures were chemically and structurally compatible with the high temperature (700 deg. C) PECVD synthesis of our tubes, in an ammonia and acetylene ambient. Such scalable, high throughput top-down fabrication processes, when integrated with the bottom-up tube synthesis techniques, should accelerate the development of plasma grown tubes for a wide variety of applications in electronics, such as nanoelectromechanical systems, interconnects, field emitters and sensors. Tube characteristics were also engineered to some extent, by adjusting the Ni catalyst thickness, as well as the pressure and plasma power during growth.

  17. Top-Down-Assisted Bottom-Up Method for Homologous Protein Sequencing: Hemoglobin from 33 Bird Species

    Science.gov (United States)

    Song, Yang; Laskay, Ünige A.; Vilcins, Inger-Marie E.; Barbour, Alan G.; Wysocki, Vicki H.

    2015-11-01

    Ticks are vectors for disease transmission because they are indiscriminant in their feeding on multiple vertebrate hosts, transmitting pathogens between their hosts. Identifying the hosts on which ticks have fed is important for disease prevention and intervention. We have previously shown that hemoglobin (Hb) remnants from a host on which a tick fed can be used to reveal the host's identity. For the present research, blood was collected from 33 bird species that are common in the U.S. as hosts for ticks but that have unknown Hb sequences. A top-down-assisted bottom-up mass spectrometry approach with a customized searching database, based on variability in known bird hemoglobin sequences, has been devised to facilitate fast and complete sequencing of hemoglobin from birds with unknown sequences. These hemoglobin sequences will be added to a hemoglobin database and used for tick host identification. The general approach has the potential to sequence any set of homologous proteins completely in a rapid manner.

  18. Analgesia induced by self-initiated electrotactile sensation is mediated by top-down modulations.

    Science.gov (United States)

    Zhao, Ke; Tang, Zhengyu; Wang, Huiquan; Guo, Yifei; Peng, Weiwei; Hu, Li

    2017-06-01

    It is well known that sensory perception can be attenuated when sensory stimuli are controlled by self-initiated actions. This phenomenon is explained by the consistency between forward models of anticipated action effects and actual sensory feedback. Specifically, the brain state related to the binding between motor processing and sensory perception would have inhibitory function by gating sensory information via top-down control. Since the brain state could casually influence the perception of subsequent stimuli of different sensory modalities, we hypothesize that pain evoked by nociceptive stimuli following the self-initiated tactile stimulation would be attenuated as compared to that following externally determined tactile stimulation. Here, we compared psychophysical and neurophysiological responses to identical nociceptive-specific laser stimuli in two different conditions: self-initiated tactile sensation condition (STS) and nonself-initiated tactile sensation condition (N-STS). We observed that pain intensity and unpleasantness, as well as laser-evoked brain responses, were significantly reduced in the STS condition compared to the N-STS condition. In addition, magnitudes of alpha and beta oscillations prior to laser onset were significantly larger in the STS condition than in the N-STS condition. These results confirmed that pain perception and pain-related brain responses were attenuated when the tactile stimulation was initiated by subjects' voluntary actions, and exploited neural oscillations reflecting the binding between motor processing and sensory feedback. Thus, our study elaborated the understanding of underlying neural mechanisms related to top-down modulations of the analgesic effect induced by self-initiated tactile sensation, which provided theoretical basis to improve the analgesic effect in various clinical applications. © 2017 Society for Psychophysiological Research.

  19. Comprehensive Characterization of Swine Cardiac Troponin T Proteoforms by Top-Down Mass Spectrometry

    Science.gov (United States)

    Lin, Ziqing; Guo, Fang; Gregorich, Zachery R.; Sun, Ruixiang; Zhang, Han; Hu, Yang; Shanmuganayagam, Dhanansayan; Ge, Ying

    2018-04-01

    Cardiac troponin T (cTnT) regulates the Ca2+-mediated interaction between myosin thick filaments and actin thin filaments during cardiac contraction and relaxation. cTnT is released into the blood following injury, and increased serum levels of the protein are used clinically as a biomarker for myocardial infarction. Moreover, mutations in cTnT are causative in a number of familial cardiomyopathies. With the increasing use of large animal (swine) model to recapitulate human diseases, it is essential to characterize species-dependent protein sequence variants, alternative RNA splicing, and post-translational modifications (PTMs), but challenges remain due to the incomplete database and lack of validation of the predicted splicing isoforms. Herein, we integrated top-down mass spectrometry (MS) with online liquid chromatography (LC) and immunoaffinity purification to comprehensively characterize miniature swine cTnT proteoforms, including those arising from alternative RNA splicing and PTMs. A total of seven alternative splicing isoforms of cTnT were identified by LC/MS from swine left ventricular tissue, with each isoform containing un-phosphorylated and mono-phosphorylated proteoforms. The phosphorylation site was localized to Ser1 for the mono-phosphorylated proteoforms of cTnT1, 3, 4, and 6 by online MS/MS combining collisionally activated dissociation (CAD) and electron transfer dissociation (ETD). Offline MS/MS on Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer with CAD and electron capture dissociation (ECD) was then utilized to achieve deep sequencing of mono-phosphorylated cTnT1 (35.2 kDa) with a high sequence coverage of 87%. Taken together, this study demonstrated the unique advantage of top-down MS in the comprehensive characterization of protein alternative splicing isoforms together with PTMs. [Figure not available: see fulltext.

  20. Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate

    Science.gov (United States)

    Oyler, Benjamin L.; Khan, Mohd M.; Smith, Donald F.; Harberts, Erin M.; Kilgour, David P. A.; Ernst, Robert K.; Cross, Alan S.; Goodlett, David R.

    2018-02-01

    Recent advances in lipopolysaccharide (LPS) biology have led to its use in drug discovery pipelines, including vaccine and vaccine adjuvant discovery. Desirable characteristics for LPS vaccine candidates include both the ability to produce a specific antibody titer in patients and a minimal host inflammatory response directed by the innate immune system. However, in-depth chemical characterization of most LPS extracts has not been performed; hence, biological activities of these extracts are unpredictable. Additionally, the most widely adopted workflow for LPS structure elucidation includes nonspecific chemical decomposition steps before analyses, making structures inferred and not necessarily biologically relevant. In this work, several different mass spectrometry workflows that have not been previously explored were employed to show proof-of-principle for top down LPS primary structure elucidation, specifically for a rough-type mutant (J5) E. coli-derived LPS component of a vaccine candidate. First, ion mobility filtered precursor ions were subjected to collision induced dissociation (CID) to define differences in native J5 LPS v. chemically detoxified J5 LPS (dLPS). Next, ultra-high mass resolving power, accurate mass spectrometry was employed for unequivocal precursor and product ion empirical formulae generation. Finally, MS3 analyses in an ion trap instrument showed that previous knowledge about dissociation of LPS components can be used to reconstruct and sequence LPS in a top down fashion. A structural rationale is also explained for differential inflammatory dose-response curves, in vitro, when HEK-Blue hTLR4 cells were administered increasing concentrations of native J5 LPS v. dLPS, which will be useful in future drug discovery efforts. [Figure not available: see fulltext.

  1. Diversity has stronger top-down than bottom-up effects on decomposition.

    Science.gov (United States)

    Srivastava, Diane S; Cardinale, Bradley J; Downing, Amy L; Duffy, J Emmett; Jouseau, Claire; Sankaran, Mahesh; Wright, Justin P

    2009-04-01

    The flow of energy and nutrients between trophic levels is affected by both the trophic structure of food webs and the diversity of species within trophic levels. However, the combined effects of trophic structure and diversity on trophic transfer remain largely unknown. Here we ask whether changes in consumer diversity have the same effect as changes in resource diversity on rates of resource consumption. We address this question by focusing on consumer-resource dynamics for the ecologically important process of decomposition. This study compares the top-down effect of consumer (detritivore) diversity on the consumption of dead organic matter (decomposition) with the bottom-up effect of resource (detrital) diversity, based on a compilation of 90 observations reported in 28 studies. We did not detect effects of either detrital or consumer diversity on measures of detrital standing stock, and effects on consumer standing stock were equivocal. However, our meta-analysis indicates that reductions in detritivore diversity result in significant reductions in the rate of decomposition. Detrital diversity has both positive and negative effects on decomposition, with no overall trend. This difference between top-down and bottom-up effects of diversity is robust to different effect size metrics and could not be explained by differences in experimental systems or designs between detritivore and detrital manipulations. Our finding that resource diversity has no net effect on consumption in "brown" (detritus-consumer) food webs contrasts with previous findings from "green" (plant-herbivore) food webs and suggests that effects of plant diversity on consumption may fundamentally change after plant death.

  2. Top down modulation of attention to food cues via working memory.

    Science.gov (United States)

    Higgs, Suzanne; Rutters, Femke; Thomas, Jason M; Naish, Katherine; Humphreys, Glyn W

    2012-08-01

    Attentional biases towards food cues may be linked to the development of obesity. The present study investigated the mechanisms underlying attentional biases to food cues by assessing the role of top down influences, such as working memory (WM). We assessed whether attention in normal-weight, sated participants was drawn to food items specifically when that food item was held in WM. Twenty-three participants (15 f/8 m, age 23.4±5 year, BMI 23.5±4 kg/m(2)) took part in a laboratory based study assessing reaction times to food and non-food stimuli. Participants were presented with an initial cue stimulus to either hold in WM or to merely attend to, and then searched for the target (a circle) in a two-item display. On valid trials the target was flanked by a picture matching the cue, on neutral trials the display did not contain a picture matching the cue, and on invalid trials the distractor (a square) was flanked by a picture matching the cue. Cues were food, cars or stationery items. We observed that, relative to the effects with non-food stimuli, food items in WM strongly affected attention when the memorised cue re-appeared in the search display. In particular there was an enhanced response on valid trials, when the re-appearance of the memorised cue coincided with the search target. There were no effects of cue category on attentional guidance when the cues were merely attended to but not held in WM. These data point towards food having a strong effect on top-down guidance of search from working memory, and suggest a mechanism whereby individuals who are preoccupied with thoughts of food, for example obese individuals, show facilitated detection of food cues in the environment. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Government conservation policies on Mexican coastal areas: is "top-down" management working?

    Directory of Open Access Journals (Sweden)

    Héctor Nava

    2011-12-01

    . Current conditions are the result of "top-down" conservation strategies in Zihuatanejo, as Federal and Municipal authorities do not coordinate, disregard local community in coral reef management, and ignore the intimate relationship between the coastal and marine realms. This work confirms the importance of conservation strategies with a holistic approach, considering both terrestrial and marine ecosystems in coastal areas; and that these initiatives should include local coastal communities in management and decision-taking processes done by government authorities. Rev. Biol. Trop. 59 (4: 1487-1501. Epub 2011 December 01.Las estrategias integrales son clave para lograr efectividad en la conservación de las áreas costeras. Para discutir la importancia de las estrategias holísticas en iniciativas de conservación, usamos como caso de estudio los arrecifes coralinos de Zihuatanejo Guerrero. En primer lugar, analizamos el valor paisajístico terrestre y marino de la zona costera y posteriormente usamos indicadores biológicos y ambientales de degradación en arrecifes coralinos. El valor paisajístico mostró que Manzanillo Beach tiene el mayor potencial para desarrollar iniciativas de conservación (TtV=14.2. No obstante, ambos arrecifes se enfrentan a elevados niveles de sedimentación (hasta 1.16kg/m2d y baja transparencia del agua (<5m causados por el aumento de la erosión de la costa, como consecuencia del cambio de uso del suelo. La alta cobertura de corales muertos (23.6% y algas (hasta un 29% en los arrecifes reflejan su manejo inadecuado. Estas condiciones son resultado de las estrategias de conservación usadas principalmente por las autoridades gubernamentales, que en muchos casos no se encuentran coordinadas y no consideran a la población local en el manejo de los recursos. Estos resultados confirman la importancia de las estrategias de conservación con una visión holística del ecosistema terrestre-marino en las áreas costeras. Estas iniciativas deben

  4. Top down viewing of the inductively coupled plasma using a dual grating, direct reading spectrograph and an all mirror optical system

    International Nuclear Information System (INIS)

    Apel, C.T.; Duchane, D.V.; Palmer, B.A.

    1980-01-01

    Using an all-mirror optical system, an inductively coupled plasma is viewed top down and the light is directed to a dual grating, direct reading spectrograph. Top down viewing of the plasma, with masking of the image of the argon plasma torus at the spectrograph entrance slit, significantly reduces background signal from the source and permits the use of the depth of field of the optical system to achieve compromise conditions for viewing the plasma. Light from the plasma source is introduced to the optical system by means of a mirror situated directly over the plasma. The system is exhausted in such a way that cool air flowing past the mirror forms a thermal barrier between the mirror and the plasma. Elements such as copper and lead have atomic and ionic lines which tend to exhibit self absorption when viewed top down through the cooler ground state atoms in the plume of the plasma. One of the approaches to this problem is to shear off the plume of the plasma with a jet of air directed across the tip of the plasma. A second approach is to make use of the dual grating, direct reading spectrograph and real-time computer system which easily permits the setting of alternate lines for each element so that self absorption and matrix effects are minimized. The design of the dual-grating, direct-reading spectrograph allows for the mounting of more than 200 13-mm-dia photomultiplier tubes along the focal curves. In an effort to demonstrate the use of fiber optics as a viable technique for the closer placement of exit slits, a red sensitive photomultiplier tube was coupled with a 30-cm fiber-optic ribbon to detect light from the Li 670.784 nm line on the focal curve. It was successful and had the added advantages of absorbing second-order ultraviolet light

  5. Prey vulnerability limits top-down control and alters reciprocal feedbacks in a subsidized model food web.

    Directory of Open Access Journals (Sweden)

    William I Atlas

    Full Text Available Resource subsidies increase the productivity of recipient food webs and can affect ecosystem dynamics. Subsidies of prey often support elevated predator biomass which may intensify top-down control and reduce the flow of reciprocal subsidies into adjacent ecosystems. However, top-down control in subsidized food webs may be limited if primary consumers posses morphological or behavioral traits that limit vulnerability to predation. In forested streams, terrestrial prey support high predator biomass creating the potential for strong top-down control, however armored primary consumers often dominate the invertebrate assemblage. Using empirically based simulation models, we tested the response of stream food webs to variations in subsidy magnitude, prey vulnerability, and the presence of two top predators. While terrestrial prey inputs increased predator biomass (+12%, the presence of armored primary consumers inhibited top-down control, and diverted most aquatic energy (∼75% into the riparian forest through aquatic insect emergence. Food webs without armored invertebrates experienced strong trophic cascades, resulting in higher algal (∼50% and detrital (∼1600% biomass, and reduced insect emergence (-90%. These results suggest prey vulnerability can mediate food web responses to subsidies, and that top-down control can be arrested even when predator-invulnerable consumers are uncommon (20% regardless of the level of subsidy.

  6. Effects of pollutants on bottom-up and top-down processes in insect-plant interactions

    International Nuclear Information System (INIS)

    Butler, Casey D.; Trumble, John T.

    2008-01-01

    Bottom-up (host plant quality) and top-down (natural enemies) forces both influence the fitness and population dynamics of herbivores. However, the impact of pollutants acting on these forces has not been examined, which prompted us to review the literature to test hypotheses regarding this area of research. A comprehensive literature search found 126 references which examined fitness components and population dynamics of 203 insect herbivores. One hundred and fifty-three of the 203 herbivores (75.4%) had fitness impacted due to bottom-up factors in polluted environments. In contrast, only 20 of the 203 (9.9%) had fitness significantly impacted due to top-down factors in polluted environments. The paucity of results for top-down factors impacting fitness does not necessarily mean that top-down factors are less important, but rather that fewer studies include natural enemies. We provide a synthesis of available data by pollution type and herbivore guild, and suggest future research to address this issue. - Pollutants can affect insect herbivores through bottom-up and, possibly, top-down processes

  7. A two-step combination of top-down and bottom-up fire emission estimates at regional and global scales: strengths and main uncertainties

    Science.gov (United States)

    Sofiev, Mikhail; Soares, Joana; Kouznetsov, Rostislav; Vira, Julius; Prank, Marje

    2016-04-01

    Top-down emission estimation via inverse dispersion modelling is used for various problems, where bottom-up approaches are difficult or highly uncertain. One of such areas is the estimation of emission from wild-land fires. In combination with dispersion modelling, satellite and/or in-situ observations can, in principle, be used to efficiently constrain the emission values. This is the main strength of the approach: the a-priori values of the emission factors (based on laboratory studies) are refined for real-life situations using the inverse-modelling technique. However, the approach also has major uncertainties, which are illustrated here with a few examples of the Integrated System for wild-land Fires (IS4FIRES). IS4FIRES generates the smoke emission and injection profile from MODIS and SEVIRI active-fire radiative energy observations. The emission calculation includes two steps: (i) initial top-down calibration of emission factors via inverse dispersion problem solution that is made once using training dataset from the past, (ii) application of the obtained emission coefficients to individual-fire radiative energy observations, thus leading to bottom-up emission compilation. For such a procedure, the major classes of uncertainties include: (i) imperfect information on fires, (ii) simplifications in the fire description, (iii) inaccuracies in the smoke observations and modelling, (iv) inaccuracies of the inverse problem solution. Using examples of the fire seasons 2010 in Russia, 2012 in Eurasia, 2007 in Australia, etc, it is pointed out that the top-down system calibration performed for a limited number of comparatively moderate cases (often the best-observed ones) may lead to errors in application to extreme events. For instance, the total emission of 2010 Russian fires is likely to be over-estimated by up to 50% if the calibration is based on the season 2006 and fire description is simplified. Longer calibration period and more sophisticated parameterization

  8. Simple rules describe bottom-up and top-down control in food webs with alternative energy pathways.

    Science.gov (United States)

    Wollrab, Sabine; Diehl, Sebastian; De Roos, André M

    2012-09-01

    Many human influences on the world's ecosystems have their largest direct impacts at either the top or the bottom of the food web. To predict their ecosystem-wide consequences we must understand how these impacts propagate. A long-standing, but so far elusive, problem in this endeavour is how to reduce food web complexity to a mathematically tractable, but empirically relevant system. Simplification to main energy channels linking primary producers to top consumers has been recently advocated. Following this approach, we propose a general framework for the analysis of bottom-up and top-down forcing of ecosystems by reducing food webs to two energy pathways originating from a limiting resource shared by competing guilds of primary producers (e.g. edible vs. defended plants). Exploring dynamical models of such webs we find that their equilibrium responses to nutrient enrichment and top consumer harvesting are determined by only two easily measurable topological properties: the lengths of the component food chains (odd-odd, odd-even, or even-even) and presence vs. absence of a generalist top consumer reconnecting the two pathways (yielding looped vs. branched webs). Many results generalise to other looped or branched web structures and the model can be easily adapted to include a detrital pathway. © 2012 Blackwell Publishing Ltd/CNRS.

  9. Integration of bottom-up and top-down models for the energy system. A practical case for Denmark

    International Nuclear Information System (INIS)

    Jacobsen, H.; Morthorst, P.E.; Nielsen, L.; Stephensen, P.

    1996-07-01

    The main objective of the project was to integrate the Danish macro economic model ADAM with elements from the energy simulation model BRUS, developed at Risoe. The project has been carried out by Risoe National Laboratory with assistance from the Ministry of Finance. A theoretical part focuses on the differences between top-down and bottom-up modelling of the energy-economy interaction. A combined hybrid model seems a relevant alternative to the two traditional approaches. The hybrid model developed is called Hybris and includes models for: supply of electricity and heat, household demand for electricity, and household demand for heat. These three models interact in a iterative procedure with the macro economic model ADAM through a number of links. A reference case as well as a number of scenarios illustrating the capabilities of the model has been set up.Hybris is a simulation model which is capable of analyzing combined CO 2 reduction initiatives as regulation of the energy supply system and a CO 2 tax in an integrated and consistent way. (au) 32 tabs., 98 ills., 55 refs

  10. Goal-directed control with cortical units that are gated by both top-down feedback and oscillatory coherence

    Science.gov (United States)

    Kerr, Robert R.; Grayden, David B.; Thomas, Doreen A.; Gilson, Matthieu; Burkitt, Anthony N.

    2014-01-01

    The brain is able to flexibly select behaviors that adapt to both its environment and its present goals. This cognitive control is understood to occur within the hierarchy of the cortex and relies strongly on the prefrontal and premotor cortices, which sit at the top of this hierarchy. Pyramidal neurons, the principal neurons in the cortex, have been observed to exhibit much stronger responses when they receive inputs at their soma/basal dendrites that are coincident with inputs at their apical dendrites. This corresponds to inputs from both lower-order regions (feedforward) and higher-order regions (feedback), respectively. In addition to this, coherence between oscillations, such as gamma oscillations, in different neuronal groups has been proposed to modulate and route communication in the brain. In this paper, we develop a simple, but novel, neural mass model in which cortical units (or ensembles) exhibit gamma oscillations when they receive coherent oscillatory inputs from both feedforward and feedback connections. By forming these units into circuits that can perform logic operations, we identify the different ways in which operations can be initiated and manipulated by top-down feedback. We demonstrate that more sophisticated and flexible top-down control is possible when the gain of units is modulated by not only top-down feedback but by coherence between the activities of the oscillating units. With these types of units, it is possible to not only add units to, or remove units from, a higher-level unit's logic operation using top-down feedback, but also to modify the type of role that a unit plays in the operation. Finally, we explore how different network properties affect top-down control and processing in large networks. Based on this, we make predictions about the likely connectivities between certain brain regions that have been experimentally observed to be involved in goal-directed behavior and top-down attention. PMID:25152715

  11. Goal-directed control with cortical units that are gated by both top-down feedback and oscillatory coherence

    Directory of Open Access Journals (Sweden)

    Robert R. Kerr

    2014-08-01

    Full Text Available The brain is able to flexibly select behaviors that adapt to both its environment and its present goals. This cognitive control is understood to occur within the hierarchy of the cortex and relies strongly on the prefrontal and premotor cortices, which sit at the top of this hierarchy. Pyramidal neurons, the principal neurons in the cortex, have been observed to exhibit much stronger responses when they receive inputs at their soma/basal dendrites that are coincident with inputs at their apical dendrites. This corresponds to inputs from both lower-order regions (feedforward and higher-order regions (feedback, respectively. In addition to this, coherence between oscillations, such as gamma oscillations, in different neuronal groups has been proposed to modulate and route communication in the brain. In this paper, we develop a simple, but novel, neural mass model in which cortical units (or ensembles exhibit gamma oscillations when they receive coherent oscillatory inputs from both feedforward and feedback connections. By forming these units into circuits that can perform logic operations, we identify the different ways in which operations can be initiated and manipulated by top-down feedback. We demonstrate that more sophisticated and flexible top-down control is possible when the gain of units is modulated by not only top-down feedback but by coherence between the activities of the oscillating units. With these types of units, it is possible to not only add units to, or remove units from, a higher-level unit's logic operation using top-down feedback, but also to modify the type of role that a unit plays in the operation. Finally, we explore how different network properties affect top-down control and processing in large networks. Based on this, we make predictions about the likely connectivities between certain brain regions that have been experimentally observed to be involved in goal-directed behavior and top-down attention.

  12. The Comparative Effect of Top-down Processing and Bottom-up Processing through TBLT on Extrovert and Introvert EFL

    Directory of Open Access Journals (Sweden)

    Pezhman Nourzad Haradasht

    2013-09-01

    Full Text Available This research seeks to examine the effect of two models of reading comprehension, namely top-down and bottom-up processing, on the reading comprehension of extrovert and introvert EFL learners’ reading comprehension. To do this, 120 learners out of a total number of 170 intermediate learners being educated at Iran Mehr English Language School were selected all taking a PET (Preliminary English Test first for homogenization prior to the study. They also answered the Eysenck Personality Inventory (EPI which in turn categorized them into two subgroups within each reading models consisting of introverts and extroverts. All in all, there were four subgroups: 30 introverts and 30 extroverts undergoing the top-down processing treatment, and 30 introverts and 30 extroverts experiencing the bottom-up processing treatment. The aforementioned PET was administered as the post test of the study after each group was exposed to the treatment for 18 sessions in six weeks. After the instructions finished, the mean scores of all four groups on this post test were computed and a two-way ANOVA was run to test all the four hypotheses raise in this study. the results showed that while learners generally benefitted more from the bottom-up processing setting compared  to the top-down processing one, the extrovert group was better off receiving top-down instruction. Furthermore, introverts outperformed extroverts in bottom-up group; yet between the two personalities subgroups in the top-down setting no difference was seen. A predictable pattern of benefitting from teaching procedures could not be drawn for introverts as in both top-down and bottom-up settings, they benefitted more than extroverts.

  13. Top-down and bottom-up characterization of nitrated birch pollen allergen Bet v 1a with CZE hyphenated to an Orbitrap mass spectrometer.

    Science.gov (United States)

    Gusenkov, Sergey; Stutz, Hanno

    2018-02-01

    Tyrosine (Tyr) residues of the major pollen allergen of birch Betula verrucosa, Bet v 1a, were nitrated by peroxynitrite. This modification enhances the allergenicity. Modified tyrosines were identified by analyzing intact allergen variants in combination with top-down and bottom-up approaches. Therefore, a laboratory-built sheath-liquid assisted ESI interface was applied for hyphenation of CE to an Orbitrap mass spectrometer to localize individual nitration sites. The major focus was on identification of primary nitration sites. The top-down approach unambiguously identified Tyr 5 as the most prominent modification site. Fragments from the allergen core and the C-terminal part carried up to three potential nitration sites, respectively. Thus, a bottom-up approach with tryptic digest was used as a complementary strategy which allowed for the unambiguous localization of nitration sites within the respective peptides. Nitration propensity for individual Tyr residues was addressed by comparison of MS signals of nitrated peptides relative to all cognates of homolog primary sequence. Combined data identified surface exposed Tyr 5 and Tyr 66 as major nitration sites followed by less accessible Tyr 158 whereas Tyr 81, 83 and 150 possess a lower nitration tendency and are apparently modified in variants with higher nitration levels. © 2018 The Authors. Electrophoresis published by Wiley-VCH Verlag GmbH & Co. KGaA.

  14. Architecture of top down, parallel pattern recognition system TOPS and its application to the MR head images

    International Nuclear Information System (INIS)

    Matsunoshita, Jun-ichi; Akamatsu, Shigeo; Yamamoto, Shinji.

    1993-01-01

    This paper describes about the system architecture of a new image recognition system TOPS (top-down parallel pattern recognition system), and its application to the automatic extraction of brain organs (cerebrum, cerebellum, brain stem) from 3D-MRI images. Main concepts of TOPS are as follows: (1) TOPS is the top-down type recognition system, which allows parallel models in each level of hierarchy structure. (2) TOPS allows parallel image processing algorithms for one purpose (for example, for extraction of one special organ). This results in multiple candidates for one purpose, and judgment to get unique solution for it will be made at upper level of hierarchy structure. (author)

  15. Covariance specification and estimation to improve top-down Green House Gas emission estimates

    Science.gov (United States)

    Ghosh, S.; Lopez-Coto, I.; Prasad, K.; Whetstone, J. R.

    2015-12-01

    The National Institute of Standards and Technology (NIST) operates the North-East Corridor (NEC) project and the Indianapolis Flux Experiment (INFLUX) in order to develop measurement methods to quantify sources of Greenhouse Gas (GHG) emissions as well as their uncertainties in urban domains using a top down inversion method. Top down inversion updates prior knowledge using observations in a Bayesian way. One primary consideration in a Bayesian inversion framework is the covariance structure of (1) the emission prior residuals and (2) the observation residuals (i.e. the difference between observations and model predicted observations). These covariance matrices are respectively referred to as the prior covariance matrix and the model-data mismatch covariance matrix. It is known that the choice of these covariances can have large effect on estimates. The main objective of this work is to determine the impact of different covariance models on inversion estimates and their associated uncertainties in urban domains. We use a pseudo-data Bayesian inversion framework using footprints (i.e. sensitivities of tower measurements of GHGs to surface emissions) and emission priors (based on Hestia project to quantify fossil-fuel emissions) to estimate posterior emissions using different covariance schemes. The posterior emission estimates and uncertainties are compared to the hypothetical truth. We find that, if we correctly specify spatial variability and spatio-temporal variability in prior and model-data mismatch covariances respectively, then we can compute more accurate posterior estimates. We discuss few covariance models to introduce space-time interacting mismatches along with estimation of the involved parameters. We then compare several candidate prior spatial covariance models from the Matern covariance class and estimate their parameters with specified mismatches. We find that best-fitted prior covariances are not always best in recovering the truth. To achieve

  16. Top-down Estimates of Isoprene Emissions in Australia Inferred from OMI Satellite Data.

    Science.gov (United States)

    Greenslade, J.; Fisher, J. A.; Surl, L.; Palmer, P. I.

    2017-12-01

    Australia is a global hotspot for biogenic isoprene emission factors predicted by process-based models such as the Model of Emissions of Gases and Aerosols from Nature (MEGAN). It is also prone to increasingly frequent temperature extremes that can drive episodically high emissions. Estimates of biogenic isoprene emissions from Australia are poorly constrained, with the frequently used MEGAN model overestimating emissions by a factor of 4-6 in some areas. Evaluating MEGAN and other models in Australia is difficult due to sparse measurements of emissions and their ensuing chemical products. In this talk, we will describe efforts to better quantify Australian isoprene emissions using top-down estimates based on formaldehyde (HCHO) observations from the OMI satellite instrument, combined with modelled isoprene to HCHO yields obtained from the GEOS-Chem chemical transport model. The OMI-based estimates are evaluated using in situ observations from field campaigns conducted in southeast Australia. We also investigate the impact on the inferred emission of horizontal resolution used for the yield calculations, particularly in regions on the boundary between low- and high-NOx chemistry. The prevalence of fire smoke plumes roughly halves the available satellite dataset over Australia for much of the year; however, seasonal averages remain robust. Preliminary results show that the top-down isoprene emissions are lower than MEGAN estimates by up to 90% in summer. The overestimates are greatest along the eastern coast, including areas surrounding Australia's major population centres in Sydney, Melbourne, and Brisbane. The coarse horizontal resolution of the model significantly affects the emissions estimates, as many biogenic emitting regions lie along narrow coastal stretches. Our results confirm previous findings that the MEGAN biogenic emission model is poorly calibrated for the Australian environment and suggests that chemical transport models driven by MEGAN are likely

  17. The Early Anthropogenic Hypothesis: Top-Down and Bottom-up Evidence

    Science.gov (United States)

    Ruddiman, W. F.

    2014-12-01

    Two complementary lines of evidence support the early anthropogenic hypothesis. Top-down evidence comes from comparing Holocene greenhouse-gas trends with those during equivalent intervals of previous interglaciations. The increases in CO2 and CH4 during the late Holocene are anomalous compared to the decreasing trends in a stacked average of previous interglaciations, thereby supporting an anthropogenic origin. During interglacial stage 19, the closest Holocene insolation analog, CO2 fell to 245 ppm by the time equivalent to the present, in contrast to the observed pre-industrial rise to 280-285 ppm. The 245-ppm level measured in stage 19 falls at the top of the natural range predicted by the original anthropogenic hypothesis of Ruddiman (2003). Bottom-up evidence comes from a growing list of archeological and other compilations showing major early anthropogenic transformations of Earth's surface. Key examples include: efforts by Dorian Fuller and colleagues mapping the spread of irrigated rice agriculture across southern Asia and its effects on CH4 emissions prior to the industrial era; an additional effort by Fuller showing the spread of methane-emitting domesticated livestock across Asia and Africa (coincident with the spread of fertile crescent livestock across Europe); historical compilations by Jed Kaplan and colleagues documenting very high early per-capita forest clearance in Europe, thus underpinning simulations of extensive pre-industrial clearance and large CO2 emissions; and wide-ranging studies by Erle Ellis and colleagues of early anthropogenic land transformations in China and elsewhere.

  18. Modeling the Effects of Perceptual Load: Saliency, Competitive Interactions, and Top-Down Biases.

    Science.gov (United States)

    Neokleous, Kleanthis; Shimi, Andria; Avraamides, Marios N

    2016-01-01

    A computational model of visual selective attention has been implemented to account for experimental findings on the Perceptual Load Theory (PLT) of attention. The model was designed based on existing neurophysiological findings on attentional processes with the objective to offer an explicit and biologically plausible formulation of PLT. Simulation results verified that the proposed model is capable of capturing the basic pattern of results that support the PLT as well as findings that are considered contradictory to the theory. Importantly, the model is able to reproduce the behavioral results from a dilution experiment, providing thus a way to reconcile PLT with the competing Dilution account. Overall, the model presents a novel account for explaining PLT effects on the basis of the low-level competitive interactions among neurons that represent visual input and the top-down signals that modulate neural activity. The implications of the model concerning the debate on the locus of selective attention as well as the origins of distractor interference in visual displays of varying load are discussed.

  19. Modeling the effects of perceptual load: saliency, competitive interactions, and top-down biases.

    Directory of Open Access Journals (Sweden)

    Kleanthis eNeokleous

    2016-01-01

    Full Text Available A computational model of visual selective attention has been implemented to account for experimental findings on the Perceptual Load Theory (PLT of attention. The model was designed based on existing neurophysiological findings on attentional processes with the objective to offer an explicit and biologically plausible formulation of PLT. Simulation results verified that the proposed model is capable of capturing the basic pattern of results that support the Perceptual Load Theory as well as findings that are considered contradictory to the theory. Importantly, the model is able to reproduce the behavioral results from a dilution experiment, providing thus a way to reconcile PLT with the competing Dilution account. Overall, the model presents a novel account for explaining PLT effects on the basis of the low-level competitive interactions among neurons that represent visual input and the top-down signals that modulate neural activity. The implications of the model concerning the debate on the locus of selective attention as well as the origins of distractor interference in visual displays of varying load are discussed.

  20. Top-down population regulation of a top predator: lions in the Ngorongoro Crater.

    Science.gov (United States)

    Kissui, Bernard M; Packer, Craig

    2004-09-07

    Efforts to determine whether bottom-up or top-down processes regulate populations have been hampered by difficulties in accurately estimating the population's carrying capacity and in directly measuring food intake rate, the impacts of interspecific competition and exposure to natural enemies. We report on 40 years of data on the lion population in Ngorongoro Crater, Tanzania, which showed strong evidence of density-dependent regulation at 100-120 individuals but has remained below 60 individuals for the past decade despite consistently high prey abundance. The lions enjoy a higher per capita food-intake rate and higher cub recruitment at low population density, and interspecific competition has not increased in recent years. These animals have suffered from a number of severe disease outbreaks over the past 40 years, but, whereas the population recovered exponentially from a severe epizootic in 1963, three outbreaks between 1994 and 2001 have occurred in such rapid succession that the population has been unable to return to the carrying capacity. The Crater population may have become unusually vulnerable to infectious disease in recent years owing to its close proximity to a growing human population and a history of close inbreeding. The Crater lions may therefore provide important insights into the future of many endangered populations.

  1. Pupil dilation reveals top-down attentional load during spatial monitoring.

    Science.gov (United States)

    Lisi, Matteo; Bonato, Mario; Zorzi, Marco

    2015-12-01

    It has long been known that the diameter of human pupil enlarges with increasing effort during the execution of a task. This has been observed not only for purely mechanical effort but also for mental effort, as for example the computation of arithmetic problems with different levels of difficulty. Here we show that pupil dilation reflects changes in visuospatial awareness induced by attentional load during multi-tasking. In the single-task condition, participants had to report the position of lateralized, briefly presented, masked visual targets ("right", "left", or "both" sides). In the multitasking conditions, participants also performed additional tasks, either visual or auditory, to increase the attentional load. Sensory stimulation was kept constant across all conditions to rule out the influence of low-level factors. Results show that event-related pupil dilation strikingly increased with task demands, mirroring a concurrent decrease in visuospatial awareness. Importantly, pupil dilation significantly differed between two dual-task conditions that required to process the same number of stimuli but yielded differed levels of accuracy (difficulty). In contrast, pupil dilation did not differ between two conditions which were equally challenging but differed both in the modality of the dual task (auditory vs. visual) and in the number of stimuli to be attended. We conclude that pupil dilation genuinely reflects the top-down allocation of supramodal attentional resources. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. A top-down manner-based DCNN architecture for semantic image segmentation.

    Directory of Open Access Journals (Sweden)

    Kai Qiao

    Full Text Available Given their powerful feature representation for recognition, deep convolutional neural networks (DCNNs have been driving rapid advances in high-level computer vision tasks. However, their performance in semantic image segmentation is still not satisfactory. Based on the analysis of visual mechanism, we conclude that DCNNs in a bottom-up manner are not enough, because semantic image segmentation task requires not only recognition but also visual attention capability. In the study, superpixels containing visual attention information are introduced in a top-down manner, and an extensible architecture is proposed to improve the segmentation results of current DCNN-based methods. We employ the current state-of-the-art fully convolutional network (FCN and FCN with conditional random field (DeepLab-CRF as baselines to validate our architecture. Experimental results of the PASCAL VOC segmentation task qualitatively show that coarse edges and error segmentation results are well improved. We also quantitatively obtain about 2%-3% intersection over union (IOU accuracy improvement on the PASCAL VOC 2011 and 2012 test sets.

  3. Laboratory Formation of Fullerenes from PAHs: Top-down Interstellar Chemistry

    Science.gov (United States)

    Zhen, Junfeng; Castellanos, Pablo; Paardekooper, Daniel M.; Linnartz, Harold; Tielens, Alexander G. G. M.

    2014-12-01

    Interstellar molecules are thought to build up in the shielded environment of molecular clouds or in the envelope of evolved stars. This follows many sequential reaction steps of atoms and simple molecules in the gas phase and/or on (icy) grain surfaces. However, these chemical routes are highly inefficient for larger species in the tenuous environment of space as many steps are involved and, indeed, models fail to explain the observed high abundances. This is definitely the case for the C60 fullerene, recently identified as one of the most complex molecules in the interstellar medium. Observations have shown that, in some photodissociation regions, its abundance increases close to strong UV-sources. In this Letter we report laboratory findings in which C60 formation can be explained by characterizing the photochemical evolution of large polycyclic aromatic hydrocarbons (PAHs). Sequential H losses lead to fully dehydrogenated PAHs and subsequent losses of C2 units convert graphene into cages. Our results present for the first time experimental evidence that PAHs in excess of 60 C-atoms efficiently photo-isomerize to buckminsterfullerene, C60. These laboratory studies also attest to the importance of top-down synthesis routes for chemical complexity in space.

  4. Hybrid Donor-Dot Devices made using Top-down Ion Implantation for Quantum Computing

    Science.gov (United States)

    Bielejec, Edward; Bishop, Nathan; Carroll, Malcolm

    2012-02-01

    We present progress towards fabricating hybrid donor -- quantum dots (QD) for quantum computing. These devices will exploit the long coherence time of the donor system and the surface state manipulation associated with a QD. Fabrication requires detection of single ions implanted with 10's of nanometer precision. We show in this talk, 100% detection efficiency for single ions using a single ion Geiger mode avalanche (SIGMA) detector integrated into a Si MOS QD process flow. The NanoImplanter (nI) a focused ion beam system is used for precision top-down placement of the implanted ion. This machine has a 10 nm resolution combined with a mass velocity filter, allowing for the use of multi-species liquid metal ion sources (LMIS) to implant P and Sb ions, and a fast blanking and chopping system for single ion implants. The combination of the nI and integration of the SIGMA with the MOS QD process flow establishes a path to fabricate hybrid single donor-dot devices. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  5. Node Query Preservation for Deterministic Linear Top-Down Tree Transducers

    Directory of Open Access Journals (Sweden)

    Kazuki Miyahara

    2013-11-01

    Full Text Available This paper discusses the decidability of node query preservation problems for XML document transformations. We assume a transformation given by a deterministic linear top-down data tree transducer (abbreviated as DLT^V and an n-ary query based on runs of a tree automaton. We say that a DLT^V Tr strongly preserves a query Q if there is a query Q' such that for every document t, the answer set of Q' for Tr(t is equal to the answer set of Q for t. Also we say that Tr weakly preserves Q if there is a query Q' such that for every t_d in the range of Tr, the answer set of Q' for t_d is equal to the union of the answer set of Q for t such that t_d = Tr(t. We show that the weak preservation problem is coNP-complete and the strong preservation problem is in 2-EXPTIME.

  6. LABORATORY FORMATION OF FULLERENES FROM PAHS: TOP-DOWN INTERSTELLAR CHEMISTRY

    International Nuclear Information System (INIS)

    Zhen, Junfeng; Castellanos, Pablo; Tielens, Alexander G. G. M.; Paardekooper, Daniel M.; Linnartz, Harold

    2014-01-01

    Interstellar molecules are thought to build up in the shielded environment of molecular clouds or in the envelope of evolved stars. This follows many sequential reaction steps of atoms and simple molecules in the gas phase and/or on (icy) grain surfaces. However, these chemical routes are highly inefficient for larger species in the tenuous environment of space as many steps are involved and, indeed, models fail to explain the observed high abundances. This is definitely the case for the C 60 fullerene, recently identified as one of the most complex molecules in the interstellar medium. Observations have shown that, in some photodissociation regions, its abundance increases close to strong UV-sources. In this Letter we report laboratory findings in which C 60 formation can be explained by characterizing the photochemical evolution of large polycyclic aromatic hydrocarbons (PAHs). Sequential H losses lead to fully dehydrogenated PAHs and subsequent losses of C 2 units convert graphene into cages. Our results present for the first time experimental evidence that PAHs in excess of 60 C-atoms efficiently photo-isomerize to buckminsterfullerene, C 60 . These laboratory studies also attest to the importance of top-down synthesis routes for chemical complexity in space

  7. Musical experience shapes top-down auditory mechanisms: evidence from masking and auditory attention performance.

    Science.gov (United States)

    Strait, Dana L; Kraus, Nina; Parbery-Clark, Alexandra; Ashley, Richard

    2010-03-01

    A growing body of research suggests that cognitive functions, such as attention and memory, drive perception by tuning sensory mechanisms to relevant acoustic features. Long-term musical experience also modulates lower-level auditory function, although the mechanisms by which this occurs remain uncertain. In order to tease apart the mechanisms that drive perceptual enhancements in musicians, we posed the question: do well-developed cognitive abilities fine-tune auditory perception in a top-down fashion? We administered a standardized battery of perceptual and cognitive tests to adult musicians and non-musicians, including tasks either more or less susceptible to cognitive control (e.g., backward versus simultaneous masking) and more or less dependent on auditory or visual processing (e.g., auditory versus visual attention). Outcomes indicate lower perceptual thresholds in musicians specifically for auditory tasks that relate with cognitive abilities, such as backward masking and auditory attention. These enhancements were observed in the absence of group differences for the simultaneous masking and visual attention tasks. Our results suggest that long-term musical practice strengthens cognitive functions and that these functions benefit auditory skills. Musical training bolsters higher-level mechanisms that, when impaired, relate to language and literacy deficits. Thus, musical training may serve to lessen the impact of these deficits by strengthening the corticofugal system for hearing. 2009 Elsevier B.V. All rights reserved.

  8. Accumulation of evidence during sequential decision making: the importance of top-down factors.

    Science.gov (United States)

    de Lange, Floris P; Jensen, Ole; Dehaene, Stanislas

    2010-01-13

    In the last decade, great progress has been made in characterizing the accumulation of neural information during simple unitary perceptual decisions. However, much less is known about how sequentially presented evidence is integrated over time for successful decision making. The aim of this study was to study the mechanisms of sequential decision making in humans. In a magnetoencephalography (MEG) study, we presented healthy volunteers with sequences of centrally presented arrows. Sequence length varied between one and five arrows, and the accumulated directions of the arrows informed the subject about which hand to use for a button press at the end of the sequence (e.g., LRLRR should result in a right-hand press). Mathematical modeling suggested that nonlinear accumulation was the rational strategy for performing this task in the presence of no or little noise, whereas quasilinear accumulation was optimal in the presence of substantial noise. MEG recordings showed a correlate of evidence integration over parietal and central cortex that was inversely related to the amount of accumulated evidence (i.e., when more evidence was accumulated, neural activity for new stimuli was attenuated). This modulation of activity likely reflects a top-down influence on sensory processing, effectively constraining the influence of sensory information on the decision variable over time. The results indicate that, when making decisions on the basis of sequential information, the human nervous system integrates evidence in a nonlinear manner, using the amount of previously accumulated information to constrain the accumulation of additional evidence.

  9. The Temporal Pole Top-Down Modulates the Ventral Visual Stream During Social Cognition.

    Science.gov (United States)

    Pehrs, Corinna; Zaki, Jamil; Schlochtermeier, Lorna H; Jacobs, Arthur M; Kuchinke, Lars; Koelsch, Stefan

    2017-01-01

    The temporal pole (TP) has been associated with diverse functions of social cognition and emotion processing. Although the underlying mechanism remains elusive, one possibility is that TP acts as domain-general hub integrating socioemotional information. To test this, 26 participants were presented with 60 empathy-evoking film clips during fMRI scanning. The film clips were preceded by a linguistic sad or neutral context and half of the clips were accompanied by sad music. In line with its hypothesized role, TP was involved in the processing of sad context and furthermore tracked participants' empathic concern. To examine the neuromodulatory impact of TP, we applied nonlinear dynamic causal modeling to a multisensory integration network from previous work consisting of superior temporal gyrus (STG), fusiform gyrus (FG), and amygdala, which was extended by an additional node in the TP. Bayesian model comparison revealed a gating of STG and TP on fusiform-amygdalar coupling and an increase of TP to FG connectivity during the integration of contextual information. Moreover, these backward projections were strengthened by emotional music. The findings indicate that during social cognition, TP integrates information from different modalities and top-down modulates lower-level perceptual areas in the ventral visual stream as a function of integration demands. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Top-down versus bottom-up processing of influence diagrams in probabilistic analysis

    International Nuclear Information System (INIS)

    Timmerman, R.D.; Burns, T.J.; Dodds, H.L. Jr.

    1986-01-01

    Recent work by Phillips et al and Selby et al has shown that influence diagram methodology can be a useful analytical tool in reactor safety studies. In some instances, an influence diagram can be used as a graphical representation of probabilistic dependence within a system or event sequence. Under these circumstances, Bayesian statistics is employed to transform the relationships depicted in the influence diagram into the correct expression for a desired marginal probability (e.g., the top node). In the references cited above, the authors demonstrated the usefulness of influence diagrams for assessing the reliability of operator performance during pressurized thermal shock transients. In addition, the use of influence diagrams identified the critical variables that had the greatest impact on operator reliability for a particular scenario (e.g., control room design, procedures, etc.). Top-down and bottom-up algorithms have emerged as the dominant methods for quantifying influence diagrams. The purpose of this paper is to demonstrate a potential error in employing the bottom-up algorithm when dealing with interdependencies

  11. Painful faces-induced attentional blink modulated by top-down and bottom-up mechanisms

    Directory of Open Access Journals (Sweden)

    Chun eZheng

    2015-06-01

    Full Text Available Pain-related stimuli can capture attention in an automatic (bottom-up or intentional (top-down fashion. Previous studies have examined attentional capture by pain-related information using spatial attention paradigms that involve mainly a bottom-up mechanism. In the current study, we investigated the pain information–induced attentional blink (AB using a rapid serial visual presentation (RSVP task, and compared the effects of task-irrelevant and task-relevant pain distractors. Relationships between accuracy of target identification and individual traits (i.e., empathy and catastrophizing thinking about pain were also examined. The results demonstrated that task-relevant painful faces had a significant pain information–induced AB effect, whereas task-irrelevant faces a near-significant trend of this effect, supporting the notion that pain-related stimuli can influence the temporal dynamics of attention. Furthermore, we found a significant negative correlation between response accuracy and pain catastrophizing score in task-relevant trials. These findings suggest that active scanning of environmental information related to pain produces greater deficits in cognition than does unintentional attention toward pain, which may represent the different ways in which healthy individuals and patients with chronic pain process pain-relevant information. These results may provide insight into the understanding of maladaptive attentional processing in patients with chronic pain.

  12. Top-down Estimates of Biomass Burning Emissions of Black Carbon in the Western United States

    Science.gov (United States)

    Mao, Y.; Li, Q.; Randerson, J. T.; CHEN, D.; Zhang, L.; Liou, K.

    2012-12-01

    We apply a Bayesian linear inversion to derive top-down estimates of biomass burning emissions of black carbon (BC) in the western United States (WUS) for May-November 2006 by inverting surface BC concentrations from the IMPROVE network using the GEOS-Chem chemical transport model. Model simulations are conducted at both 2°×2.5° (globally) and 0.5°×0.667° (nested over North America) horizontal resolutions. We first improve the spatial distributions and seasonal and interannual variations of the BC emissions from the Global Fire Emissions Database (GFEDv2) using MODIS 8-day active fire counts from 2005-2007. The GFEDv2 emissions in N. America are adjusted for three zones: boreal N. America, temperate N. America, and Mexico plus Central America. The resulting emissions are then used as a priori for the inversion. The a posteriori emissions are 2-5 times higher than the a priori in California and the Rockies. Model surface BC concentrations using the a posteriori estimate provide better agreement with IMPROVE observations (~50% increase in the Taylor skill score), including improved ability to capture the observed variability especially during June-September. However, model surface BC concentrations are still biased low by ~30%. Comparisons with the Fire Locating and Modeling of Burning Emissions (FLAMBE) are included.

  13. Proteome analysis of ofloxacin and moxifloxacin induced mycobacterium tuberculosis isolates by proteomic approach.

    Science.gov (United States)

    Lata, Manju; Sharma, Divakar; Kumar, Bhavnesh; Deo, Nirmala; Tiwari, Pramod Kumar; Bisht, Deepa; Venkatesan, Krishnamurthy

    2015-01-01

    Ofloxacin (OFX) and moxifloxacin (MOX) are the most promising second line drugs for tuberculosis treatment. Although the primary mechanism of action of OFX and MOX is gyrase inhibition, other possible mechanisms cannot be ruled out. Being the functional moiety of cell, the proteins act as primary targets for developing drugs, diagnostics and therapeutics. In this study we have investigated the proteomic changes of Mycobacterium tuberculosis isolates induced by OFX and MOX by applying comparative proteomic approaches based on two-dinensional gel electrophoresis (2DE) along with matrix assisted laser desorption ionisation time of flight mass spectrometry (MALDI TOF/TOF-MS) and bioinformatic tools. The findings are likely to provide new understanding of OFX and MOX mechanisms that might be helpful in exploring new diagnostics and drug targets. Our study explored eleven proteins (Rv2889c, Rv2623, Rv0952, Rv1827, Rv1932, Rv0054, Rv1080c, Rv3418c, Rv3914, Rv1636 and Rv0009) that were overexpressed in the presence of drugs. Among them, Rv2623, Rv1827 and Rv1636 were identified as proteins with unknown function. InterProScan and molecular docking revealed that the conserved domain of hypothetical proteins interact with OFX and MOX which indicate a probable inhibition/modulation of the functioning of these proteins by both drugs, which might be overexpressed to overcome this effect.

  14. Top-Down Approach for the Preparation of Highly Porous PLLA Microcylinders

    NARCIS (Netherlands)

    Castro, Antonio G B; Lo Giudice, Maria Cristina; Vermonden, Tina; Leeuwenburgh, Sander C G; Jansen, John A.; Van Den Beucken, Jeroen J J P; Yang, Fang

    2016-01-01

    A wide range of particles have been developed for different applications in drug-delivery, tissue engineering, or regenerative medicine. In contrast to traditional spherical particles, nonspherical (e.g., cylindrical) particles possess several structural and morphological advantages that make them

  15. Developing a Workflow Composite Score to Measure Clinical Information Logistics. A Top-down Approach.

    Science.gov (United States)

    Liebe, J D; Hübner, U; Straede, M C; Thye, J

    2015-01-01

    Availability and usage of individual IT applications have been studied intensively in the past years. Recently, IT support of clinical processes is attaining increasing attention. The underlying construct that describes the IT support of clinical workflows is clinical information logistics. This construct needs to be better understood, operationalised and measured. It is therefore the aim of this study to propose and develop a workflow composite score (WCS) for measuring clinical information logistics and to examine its quality based on reliability and validity analyses. We largely followed the procedural model of MacKenzie and colleagues (2011) for defining and conceptualising the construct domain, for developing the measurement instrument, assessing the content validity, pretesting the instrument, specifying the model, capturing the data and computing the WCS and testing the reliability and validity. Clinical information logistics was decomposed into the descriptors data and information, function, integration and distribution, which embraced the framework validated by an analysis of the international literature. This framework was refined selecting representative clinical processes. We chose ward rounds, pre- and post-surgery processes and discharge as sample processes that served as concrete instances for the measurements. They are sufficiently complex, represent core clinical processes and involve different professions, departments and settings. The score was computed on the basis of data from 183 hospitals of different size, ownership, location and teaching status. Testing the reliability and validity yielded encouraging results: the reliability was high with r(split-half) = 0.89, the WCS discriminated between groups; the WCS correlated significantly and moderately with two EHR models and the WCS received good evaluation results by a sample of chief information officers (n = 67). These findings suggest the further utilisation of the WCS. As the WCS does not assume ideal workflows as a gold standard but measures IT support of clinical workflows according to validated descriptors a high portability of the WCS to other hospitals in other countries is very likely. The WCS will contribute to a better understanding of the construct clinical information logistics.

  16. Gravity from entanglement and RG flow in a top-down approach

    Science.gov (United States)

    Kwon, O.-Kab; Jang, Dongmin; Kim, Yoonbai; Tolla, D. D.

    2018-05-01

    The duality between a d-dimensional conformal field theory with relevant deformation and a gravity theory on an asymptotically AdS d+1 geometry, has become a suitable tool in the investigation of the emergence of gravity from quantum entanglement in field theory. Recently, we have tested the duality between the mass-deformed ABJM theory and asymptotically AdS4 gravity theory, which is obtained from the KK reduction of the 11-dimensional supergravity on the LLM geometry. In this paper, we extend the KK reduction procedure beyond the linear order and establish non-trivial KK maps between 4-dimensional fields and 11-dimensional fluctuations. We rely on this gauge/gravity duality to calculate the entanglement entropy by using the Ryu-Takayanagi holographic formula and the path integral method developed by Faulkner. We show that the entanglement entropies obtained using these two methods agree when the asymptotically AdS4 metric satisfies the linearized Einstein equation with nonvanishing energy-momentum tensor for two scalar fields. These scalar fields encode the information of the relevant deformation of the ABJM theory. This confirms that the asymptotic limit of LLM geometry is the emergent gravity of the quantum entanglement in the mass-deformed ABJM theory with a small mass parameter. We also comment on the issue of the relative entropy and the Fisher information in our setup.

  17. BLED: a top-down approach to accelerator control system design

    International Nuclear Information System (INIS)

    Bobnar, J.; Zagar, K.

    2012-01-01

    In many existing controls projects the central database/inventory was introduced late in the project, usually to support installation or maintenance activities. Thus construction of this database was done in a bottom-up fashion by reverse engineering of the installation. However, there are several benefits if the central database is introduced early in the machine design, such as the ability to simulate the system as a whole without having all the IOCs in place, it can be used as an input to the installation/commissioning plan, or act as an enforcer of certain conventions and quality processes. Based on our experience with control systems, we have designed a central database BLED, which is used for storage of machine configuration and parameters as well as control system configuration, inventory, and cabling. The first implementation of BLED supports EPICS, meaning it is capable of storage and generation of EPICS templates and substitution files as well as archive, alarm and other configurations. With a goal in mind to provide functionality of several existing central databases (IRMIS, SNS db, DBSF etc.) a lot of effort has been made to design the database in a way to handle extremely large set-ups, consisting of millions of control system points. Furthermore, BLED also stores the lattice data, thus providing additional information (e.g. survey data) required by different engineering groups. The lattice import/export tools among others support MAD and TraceWin tools formats which are widely used in the machine design community. (author)

  18. Modularization in the construction industry using a top-down approach

    DEFF Research Database (Denmark)

    Kudsk, Anders; Hvam, Lars; Thuesen, Christian

    2013-01-01

    Throughout the last centuries, the manufacturing industry has experienced great improvements in efficiency and cost reductions, but the same improvements have not taken place in the construction industry. Based on the principles of mass customization that are known from the manufacturing industry...

  19. Integrated bottom up and top down approach to optimization of the extrusion process

    NARCIS (Netherlands)

    Vaneker, Thomas H.J.; Koenis, P.T.G.; van Ouwerkerk, Gijs; van Ouwerkerk, Gijs; Nilsen, K.E.; van Houten, Frederikus J.A.M.

    2008-01-01

    Boal BV and the University of Twente participate in research projects focused on improvement of die design methods for aluminum extrusion dies. Within this research empirical knowledge is combined with insights gained from numerical process simulations. Design rules for improvements to the geometry

  20. A Proactive and Top-Down Approach to Managing Risk at NASA

    Science.gov (United States)

    Dezfuli, Homayoon

    2010-01-01

    Our ultimate goal is to manage risk in a holistic and coherent fashion across the Agency: a) The RIDM process is intended to risk-inform direction-setting decisions. c) The CRM process is intended to manage risk associated with the implementation of baseline performance requirements. Currently we are working on: a) Enhancements to the CRM process. b) Better integration of the RIDM and CRM processes. c) Better integration of institutional risk considerations into RM framework.

  1. A Top-down Approach to Genetic Circuit Synthesis and Optimized Technology Mapping

    DEFF Research Database (Denmark)

    Baig, Hasan; Madsen, Jan

    2017-01-01

    Genetic logic circuits are becoming popular as an emerging field of technology. They are composed of genetic parts of DNA and work inside a living cell to perform a dedicated boolean function triggered by the presence or absence of certain proteins or other species....

  2. Advances in top-down and bottom-up approaches to video-based camera tracking

    OpenAIRE

    Marimón Sanjuán, David

    2007-01-01

    Video-based camera tracking consists in trailing the three dimensional pose followed by a mobile camera using video as sole input. In order to estimate the pose of a camera with respect to a real scene, one or more three dimensional references are needed. Examples of such references are landmarks with known geometric shape, or objects for which a model is generated beforehand. By comparing what is seen by a camera with what is geometrically known from reality, it is possible to recover the po...

  3. Advances in top-down and bottom-up approaches to video-based camera tracking

    OpenAIRE

    Marimón Sanjuán, David; Ebrahimi, Touradj

    2008-01-01

    Video-based camera tracking consists in trailing the three dimensional pose followed by a mobile camera using video as sole input. In order to estimate the pose of a camera with respect to a real scene, one or more three dimensional references are needed. Examples of such references are landmarks with known geometric shape, or objects for which a model is generated beforehand. By comparing what is seen by a camera with what is geometrically known from reality, it is possible to recover the po...

  4. Understanding Coastal Carbon Cycling by Linking Top-Down and Bottom-Up Approaches

    Science.gov (United States)

    Barr, Jordan G.; Troxler, Tiffany G.; Najjar, Raymond G.

    2014-09-01

    The coastal zone, despite occupying a small fraction of the Earth's surface area, is an important component of the global carbon (C) cycle. Coastal wetlands, including mangrove forests, tidal marshes, and seagrass meadows, compose a domain of large reservoirs of biomass and soil C [Fourqurean et al., 2012; Donato et al., 2011; Pendleton et al., 2012; Regnier et al., 2013; Bauer et al., 2013]. These wetlands and their associated C reservoirs (2 to 25 petagrams C; best estimate of 7 petagrams C [Pendleton et al., 2012]) provide numerous ecosystem services and serve as key links between land and ocean.

  5. Tunable top-down fabrication and functional surface coating of single-crystal titanium dioxide nanostructures and nanoparticles

    Science.gov (United States)

    Ha, Seungkyu; Janissen, Richard; Ussembayev, Yera Ye.; van Oene, Maarten M.; Solano, Belen; Dekker, Nynke H.

    2016-05-01

    Titanium dioxide (TiO2) is a key component of diverse optical and electronic applications that exploit its exceptional material properties. In particular, the use of TiO2 in its single-crystalline phase can offer substantial advantages over its amorphous and polycrystalline phases for existing and yet-to-be-developed applications. However, the implementation of single-crystal TiO2 has been hampered by challenges in its fabrication and subsequent surface functionalization. Here, we introduce a novel top-down approach that allows for batch fabrication of uniform high-aspect-ratio single-crystal TiO2 nanostructures with targeted sidewall profiles. We complement our fabrication approach with a functionalization strategy that achieves dense, uniform, and area-selective coating with a variety of biomolecules. This allows us to fabricate single-crystal rutile TiO2 nanocylinders tethered with individual DNA molecules for use as force- and torque-transducers in an optical torque wrench. These developments provide the means for increased exploitation of the superior material properties of single-crystal TiO2 at the nanoscale.Titanium dioxide (TiO2) is a key component of diverse optical and electronic applications that exploit its exceptional material properties. In particular, the use of TiO2 in its single-crystalline phase can offer substantial advantages over its amorphous and polycrystalline phases for existing and yet-to-be-developed applications. However, the implementation of single-crystal TiO2 has been hampered by challenges in its fabrication and subsequent surface functionalization. Here, we introduce a novel top-down approach that allows for batch fabrication of uniform high-aspect-ratio single-crystal TiO2 nanostructures with targeted sidewall profiles. We complement our fabrication approach with a functionalization strategy that achieves dense, uniform, and area-selective coating with a variety of biomolecules. This allows us to fabricate single-crystal rutile

  6. General Top-Down Ion Exchange Process for the Growth of Epitaxial Chalcogenide Thin Films and Devices

    KAUST Repository

    Xia, Chuan

    2016-12-30

    We demonstrate a versatile top-down ion exchange process, done at ambient temperature, to form epitaxial chalcogenide films and devices, with nanometer scale thickness control. To demonstrate the versatility of our process we have synthesized (1) epitaxial chalcogenide metallic and semiconducting films and (2) free-standing chalcogenide films and (3) completed in situ formation of atomically sharp heterojunctions by selective ion exchange. Epitaxial NiCo2S4 thin films prepared by our process show 115 times higher mobility than NiCo2S4 pellets (23 vs 0.2 cm(2) V-1 s(-1)) prepared by previous reports. By controlling the ion exchange process time, we made free-standing epitaxial films of NiCo2S4 and transferred them onto different substrates. We also demonstrate in situ formation of atomically sharp, lateral Schottky diodes based on NiCo2O4/NiCo2S4 heterojunction, using a single ion exchange step. Additionally, we show that our approach can be easily extended to other chalcogenide semiconductors. Specifically, we used our process to prepare Cu1.8S thin films with mobility that matches single crystal Cu1.8S (25 cm(2) V-1 s(-1)), which is ca. 28 times higher than the previously reported Cu1.8S thin film mobility (0.58 cm(2) V-1 s(-1)), thus demonstrating the universal nature of our process. This is the first report in which chalcogenide thin films retain the epitaxial nature of the precursor oxide films, an approach that will be useful in many applications.

  7. Predators with multiple ontogenetic niche shifts have limited potential for population growth and top-down control of their prey

    NARCIS (Netherlands)

    van Leeuwen, A.; Huss, M.; Gårdmark, A.; Casini, M.; Vitale, F.; Hjelm, J.; Persson, L.; de Roos, A.M.

    2013-01-01

    Catastrophic collapses of top predators have revealed trophic cascades and community structuring by top-down control. When populations fail to recover after a collapse, this may indicate alternative stable states in the system. Overfishing has caused several of the most compelling cases of these

  8. The Interaction of Top-Down and Bottom-Up Statistics in the Resolution of Syntactic Category Ambiguity

    Science.gov (United States)

    Gibson, Edward

    2006-01-01

    This paper investigates how people resolve syntactic category ambiguities when comprehending sentences. It is proposed that people combine: (a) context-dependent syntactic expectations (top-down statistical information) and (b) context-independent lexical-category frequencies of words (bottom-up statistical information) in order to resolve…

  9. The Effect of Non-Visual Working Memory Load on Top-Down Modulation of Visual Processing

    Science.gov (United States)

    Rissman, Jesse; Gazzaley, Adam; D'Esposito, Mark

    2009-01-01

    While a core function of the working memory (WM) system is the active maintenance of behaviorally relevant sensory representations, it is also critical that distracting stimuli are appropriately ignored. We used functional magnetic resonance imaging to examine the role of domain-general WM resources in the top-down attentional modulation of…

  10. Attention, working memory, and phenomenal experience of WM content: memory levels determined by different types of top-down modulation.

    Science.gov (United States)

    Jacob, Jane; Jacobs, Christianne; Silvanto, Juha

    2015-01-01

    What is the role of top-down attentional modulation in consciously accessing working memory (WM) content? In influential WM models, information can exist in different states, determined by allocation of attention; placing the original memory representation in the center of focused attention gives rise to conscious access. Here we discuss various lines of evidence indicating that such attentional modulation is not sufficient for memory content to be phenomenally experienced. We propose that, in addition to attentional modulation of the memory representation, another type of top-down modulation is required: suppression of all incoming visual information, via inhibition of early visual cortex. In this view, there are three distinct memory levels, as a function of the top-down control associated with them: (1) Nonattended, nonconscious associated with no attentional modulation; (2) attended, phenomenally nonconscious memory, associated with attentional enhancement of the actual memory trace; (3) attended, phenomenally conscious memory content, associated with enhancement of the memory trace and top-down suppression of all incoming visual input.

  11. Assessing the Gap Between Top-down and Bottom-up Measured Methane Emissions in Indianapolis, IN.

    Science.gov (United States)

    Prasad, K.; Lamb, B. K.; Cambaliza, M. O. L.; Shepson, P. B.; Stirm, B. H.; Salmon, O. E.; Lavoie, T. N.; Lauvaux, T.; Ferrara, T.; Howard, T.; Edburg, S. L.; Whetstone, J. R.

    2014-12-01

    Releases of methane (CH4) from the natural gas supply chain in the United States account for approximately 30% of the total US CH4 emissions. However, there continues to be large questions regarding the accuracy of current emission inventories for methane emissions from natural gas usage. In this paper, we describe results from top-down and bottom-up measurements of methane emissions from the large isolated city of Indianapolis. The top-down results are based on aircraft mass balance and tower based inverse modeling methods, while the bottom-up results are based on direct component sampling at metering and regulating stations, surface enclosure measurements of surveyed pipeline leaks, and tracer/modeling methods for other urban sources. Mobile mapping of methane urban concentrations was also used to identify significant sources and to show an urban-wide low level enhancement of methane levels. The residual difference between top-down and bottom-up measured emissions is large and cannot be fully explained in terms of the uncertainties in top-down and bottom-up emission measurements and estimates. Thus, the residual appears to be, at least partly, attributed to a significant wide-spread diffusive source. Analyses are included to estimate the size and nature of this diffusive source.

  12. The landscape of fear: The missing link to understand top-down and bottom-up controls of prey abundance?

    Science.gov (United States)

    Identifying factors that may be responsible for affecting and possibly regulating the size of animal populations is a cornerstone in understanding population ecology. The main factors that are thought to influence population size are either resources (bottom-up), predation, (top-down), or interspec...

  13. Post-socialist agricultural cooperatives in Russia : A case study of top-down cooperatives in the Belgorod region

    NARCIS (Netherlands)

    A. Kurakin (Alexander); O. Visser (Oane)

    2017-01-01

    markdownabstractThrough a study of agricultural service cooperatives in Russia’s Belgorod region, this article addresses two gaps in the literature: _first_, the dearth of empirical studies on cooperatives in post-socialist Russia; _second_, the lack of attention to top-down cooperatives in

  14. Abrupt onsets capture attention independent of top-down control settings 11: Additivity is no evidence for filtering

    NARCIS (Netherlands)

    Schreij, D.; Theeuwes, J.; Olivers, C.N.L.

    2010-01-01

    Is attentional capture contingent on top-down control settings or involuntarily driven by salient stimuli? Supporting the stimulus-driven attentional capture view, Schreij, Owens, and Theeuwes (2008) found that an onset distractor caused a response delay, in spite of participants' having adopted an

  15. What are the fluxes of greenhouse gases from the greater Los Angeles area as inferred from top-down remote sensing studies?

    Science.gov (United States)

    Hedelius, J.; Wennberg, P. O.; Wunch, D.; Roehl, C. M.; Podolske, J. R.; Hillyard, P.; Iraci, L. T.

    2017-12-01

    Greenhouse gas (GHG) emissions from California's South Coast Air Basin (SoCAB) have been studied extensively using a variety of tower, aircraft, remote sensing, emission inventory, and modeling studies. It is impractical to survey GHG fluxes from all urban areas and hot-spots to the extent the SoCAB has been studied, but it can serve as a test location for scaling methods globally. We use a combination of remote sensing measurements from ground (Total Carbon Column Observing Network, TCCON) and space-based (Observing Carbon Observatory-2, OCO-2) sensors in an inversion to obtain the carbon dioxide flux from the SoCAB. We also perform a variety of sensitivity tests to see how the inversion performs using different model parameterizations. Fluxes do not significantly depend on the mixed layer depth, but are sensitive to the model surface layers (top-down than bottom-up fluxes highlight the need for additional work on both approaches. Higher top-down fluxes could arise from sampling bias, model bias, or may show bottom-up values underestimate sources. Lessons learned here may help in scaling up inversions to hundreds of urban systems using space-based observations.

  16. Top-down modulation of visual processing and knowledge after 250 ms supports object constancy of category decisions.

    Science.gov (United States)

    Schendan, Haline E; Ganis, Giorgio

    2015-01-01

    People categorize objects more slowly when visual input is highly impoverished instead of optimal. While bottom-up models may explain a decision with optimal input, perceptual hypothesis testing (PHT) theories implicate top-down processes with impoverished input. Brain mechanisms and the time course of PHT are largely unknown. This event-related potential study used a neuroimaging paradigm that implicated prefrontal cortex in top-down modulation of occipitotemporal cortex. Subjects categorized more impoverished and less impoverished real and pseudo objects. PHT theories predict larger impoverishment effects for real than pseudo objects because top-down processes modulate knowledge only for real objects, but different PHT variants predict different timing. Consistent with parietal-prefrontal PHT variants, around 250 ms, the earliest impoverished real object interaction started on an N3 complex, which reflects interactive cortical activity for object cognition. N3 impoverishment effects localized to both prefrontal and occipitotemporal cortex for real objects only. The N3 also showed knowledge effects by 230 ms that localized to occipitotemporal cortex. Later effects reflected (a) word meaning in temporal cortex during the N400, (b) internal evaluation of prior decision and memory processes and secondary higher-order memory involving anterotemporal parts of a default mode network during posterior positivity (P600), and (c) response related activity in posterior cingulate during an anterior slow wave (SW) after 700 ms. Finally, response activity in supplementary motor area during a posterior SW after 900 ms showed impoverishment effects that correlated with RTs. Convergent evidence from studies of vision, memory, and mental imagery which reflects purely top-down inputs, indicates that the N3 reflects the critical top-down processes of PHT. A hybrid multiple-state interactive, PHT and decision theory best explains the visual constancy of object cognition.

  17. Top-down modulation of visual processing and knowledge after 250 ms supports object constancy of category decisions

    Directory of Open Access Journals (Sweden)

    Haline E. Schendan

    2015-09-01

    Full Text Available People categorize objects slowly when visual input is highly impoverished instead of optimal. While bottom-up models may explain a decision with optimal input, perceptual hypothesis testing (PHT theories implicate top-down processes with impoverished input. Brain mechanisms and the time course of PHT are largely unknown. This event-related potential study used a neuroimaging paradigm that implicated prefrontal cortex in top-down modulation of occipitotemporal cortex. Subjects categorized more impoverished and less impoverished real and pseudo objects. PHT theories predict larger impoverishment effects for real than pseudo objects because top-down processes modulate knowledge only for real objects, but different PHT variants predict different timing. Consistent with parietal-prefrontal PHT variants, around 250 ms, the earliest impoverished real object interaction started on an N3 complex, which reflects interactive cortical activity for object cognition. N3 impoverishment effects localized to both prefrontal and occipitotemporal cortex for real objects only. The N3 also showed knowledge effects by 230 ms that localized to occipitotemporal cortex. Later effects reflected (a word meaning in temporal cortex during the N400, (b internal evaluation of prior decision and memory processes and secondary higher-order memory involving anterotemporal parts of a default mode network during posterior positivity (P600, and (c response related activity in posterior cingulate during an anterior slow wave (SW after 700 ms. Finally, response activity in supplementary motor area during a posterior SW after 900 ms showed impoverishment effects that correlated with RTs. Convergent evidence from studies of vision, memory, and mental imagery which reflects purely top-down inputs, indicates that the N3 reflects the critical top-down processes of PHT. A hybrid multiple-state interactive, PHT and decision theory best explains the visual constancy of object cognition.

  18. A neural mechanism of dynamic gating of task-relevant information by top-down influence in primary visual cortex.

    Science.gov (United States)

    Kamiyama, Akikazu; Fujita, Kazuhisa; Kashimori, Yoshiki

    2016-12-01

    Visual recognition involves bidirectional information flow, which consists of bottom-up information coding from retina and top-down information coding from higher visual areas. Recent studies have demonstrated the involvement of early visual areas such as primary visual area (V1) in recognition and memory formation. V1 neurons are not passive transformers of sensory inputs but work as adaptive processor, changing their function according to behavioral context. Top-down signals affect tuning property of V1 neurons and contribute to the gating of sensory information relevant to behavior. However, little is known about the neuronal mechanism underlying the gating of task-relevant information in V1. To address this issue, we focus on task-dependent tuning modulations of V1 neurons in two tasks of perceptual learning. We develop a model of the V1, which receives feedforward input from lateral geniculate nucleus and top-down input from a higher visual area. We show here that the change in a balance between excitation and inhibition in V1 connectivity is necessary for gating task-relevant information in V1. The balance change well accounts for the modulations of tuning characteristic and temporal properties of V1 neuronal responses. We also show that the balance change of V1 connectivity is shaped by top-down signals with temporal correlations reflecting the perceptual strategies of the two tasks. We propose a learning mechanism by which synaptic balance is modulated. To conclude, top-down signal changes the synaptic balance between excitation and inhibition in V1 connectivity, enabling early visual area such as V1 to gate context-dependent information under multiple task performances. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Temperature effects on seaweed-sustaining top-down control vary with season.

    Science.gov (United States)

    Werner, Franziska J; Graiff, Angelika; Matthiessen, Birte

    2016-03-01

    Rising seawater temperature and CO2 concentrations (ocean acidification) represent two of the most influential factors impacting marine ecosystems in the face of global climate change. In ecological climate change research, full-factorial experiments performed across seasons in multispecies, cross-trophic-level settings are essential as they permit a more realistic estimation of direct and indirect effects as well as the relative importance of the effects of both major environmental stressors on ecosystems. In benthic mesocosm experiments, we tested the responses of coastal Baltic Sea Fucus vesiculosus communities to elevated seawater temperature and CO2 concentrations across four seasons of one year. While increasing [CO2] levels had only minor effects, warming had strong and persistent effects on grazers, and the resulting effects on the Fucus community were found to be season dependent. In late summer, a temperature-driven collapse of grazers caused a cascading effect from the consumers to the foundation species, resulting in overgrowth of Fucus thalli by epiphytes. In fall/winter (outside the growing season of epiphytes), intensified grazing under warming resulted in a significant reduction in Fucus biomass. Thus, we were able to confirm the prediction that future increases in water temperatures will influence marine food-web processes by altering top-down control, but we were also able to show that specific consequences for food-web structure depend on the season. Since F. vesiculosus is the dominant habitat-forming brown algal system in the Baltic Sea, its potential decline under global warming implies a loss of key functions and services such as provision of nutrient storage, substrate, food, shelter, and nursery grounds for a diverse community of marine invertebrates and fish in Baltic Sea coastal waters.

  20. Training set optimization and classifier performance in a top-down diabetic retinopathy screening system

    Science.gov (United States)

    Wigdahl, J.; Agurto, C.; Murray, V.; Barriga, S.; Soliz, P.

    2013-03-01

    Diabetic retinopathy (DR) affects more than 4.4 million Americans age 40 and over. Automatic screening for DR has shown to be an efficient and cost-effective way to lower the burden on the healthcare system, by triaging diabetic patients and ensuring timely care for those presenting with DR. Several supervised algorithms have been developed to detect pathologies related to DR, but little work has been done in determining the size of the training set that optimizes an algorithm's performance. In this paper we analyze the effect of the training sample size on the performance of a top-down DR screening algorithm for different types of statistical classifiers. Results are based on partial least squares (PLS), support vector machines (SVM), k-nearest neighbor (kNN), and Naïve Bayes classifiers. Our dataset consisted of digital retinal images collected from a total of 745 cases (595 controls, 150 with DR). We varied the number of normal controls in the training set, while keeping the number of DR samples constant, and repeated the procedure 10 times using randomized training sets to avoid bias. Results show increasing performance in terms of area under the ROC curve (AUC) when the number of DR subjects in the training set increased, with similar trends for each of the classifiers. Of these, PLS and k-NN had the highest average AUC. Lower standard deviation and a flattening of the AUC curve gives evidence that there is a limit to the learning ability of the classifiers and an optimal number of cases to train on.

  1. Functional size of human visual area V1: a neural correlate of top-down attention.

    Science.gov (United States)

    Verghese, Ashika; Kolbe, Scott C; Anderson, Andrew J; Egan, Gary F; Vidyasagar, Trichur R

    2014-06-01

    Heavy demands are placed on the brain's attentional capacity when selecting a target item in a cluttered visual scene, or when reading. It is widely accepted that such attentional selection is mediated by top-down signals from higher cortical areas to early visual areas such as the primary visual cortex (V1). Further, it has also been reported that there is considerable variation in the surface area of V1. This variation may impact on either the number or specificity of attentional feedback signals and, thereby, the efficiency of attentional mechanisms. In this study, we investigated whether individual differences between humans performing attention-demanding tasks can be related to the functional area of V1. We found that those with a larger representation in V1 of the central 12° of the visual field as measured using BOLD signals from fMRI were able to perform a serial search task at a faster rate. In line with recent suggestions of the vital role of visuo-spatial attention in reading, the speed of reading showed a strong positive correlation with the speed of visual search, although it showed little correlation with the size of V1. The results support the idea that the functional size of the primary visual cortex is an important determinant of the efficiency of selective spatial attention for simple tasks, and that the attentional processing required for complex tasks like reading are to a large extent determined by other brain areas and inter-areal connections. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Reconciling Basin-Scale Top-Down and Bottom-Up Methane Emission Measurements for Onshore Oil and Gas Development: Cooperative Research and Development Final Report, CRADA Number CRD-14-572

    Energy Technology Data Exchange (ETDEWEB)

    Heath, Garvin A. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2017-12-04

    The overall objective of the Research Partnership to Secure Energy for America (RPSEA)-funded research project is to develop independent estimates of methane emissions using top-down and bottom-up measurement approaches and then to compare the estimates, including consideration of uncertainty. Such approaches will be applied at two scales: basin and facility. At facility scale, multiple methods will be used to measure methane emissions of the whole facility (controlled dual tracer and single tracer releases, aircraft-based mass balance and Gaussian back-trajectory), which are considered top-down approaches. The bottom-up approach will sum emissions from identified point sources measured using appropriate source-level measurement techniques (e.g., high-flow meters). At basin scale, the top-down estimate will come from boundary layer airborne measurements upwind and downwind of the basin, using a regional mass balance model plus approaches to separate atmospheric methane emissions attributed to the oil and gas sector. The bottom-up estimate will result from statistical modeling (also known as scaling up) of measurements made at selected facilities, with gaps filled through measurements and other estimates based on other studies. The relative comparison of the bottom-up and top-down estimates made at both scales will help improve understanding of the accuracy of the tested measurement and modeling approaches. The subject of this CRADA is NREL's contribution to the overall project. This project resulted from winning a competitive solicitation no. RPSEA RFP2012UN001, proposal no. 12122-95, which is the basis for the overall project. This Joint Work Statement (JWS) details the contributions of NREL and Colorado School of Mines (CSM) in performance of the CRADA effort.

  3. Oxidative Stress in Aging: Advances in Proteomic Approaches

    Directory of Open Access Journals (Sweden)

    Daniel Ortuño-Sahagún

    2014-01-01

    Full Text Available Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual’s Quality of Life (QOL. Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS], which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8, naked mole-rat (Heterocephalus glaber, and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS and oxidative stress in aging.

  4. A proteomic approach to investigating gene cluster expression and secondary metabolite functionality in Aspergillus fumigatus.

    OpenAIRE

    Owens, RA; Hammel, S; Sheridan, KJ; Jones, GW; Doyle, S

    2014-01-01

    A combined proteomics and metabolomics approach was utilised to advance the identification and characterisation of secondary metabolites in Aspergillus fumigatus. Here, implementation of a shotgun proteomic strategy led to the identification of non-redundant mycelial proteins (n = 414) from A. fumigatus including proteins typically under-represented in 2-D proteome maps: proteins with multiple transmembrane regions, hydrophobic proteins and proteins with extremes of molecular mass and pI. Ind...

  5. NEMO. Netherlands Energy demand MOdel. A top-down model based on bottom-up information

    International Nuclear Information System (INIS)

    Koopmans, C.C.; Te Velde, D.W.; Groot, W.; Hendriks, J.H.A.

    1999-06-01

    The title model links energy use to other production factors, (physical) production, energy prices, technological trends and government policies. It uses a 'putty-semiputty' vintage production structure, in which new investments, adaptations to existing capital goods (retrofit) and 'good-housekeeping' are discerned. Price elasticities are relatively large in the long term and small in the short term. Most predictions of energy use are based on either econometric models or on 'bottom-up information', i.e. disaggregated lists of technical possibilities for and costs of saving energy. Typically, one predicts more energy-efficiency improvements using bottom-up information than using econometric ('top-down') models. We bridged this so-called 'energy-efficiency gap' by designing our macro/meso model NEMO in such a way that we can use bottom-up (micro) information to estimate most model parameters. In our view, reflected in NEMO, the energy-efficiency gap arises for two reasons. The first is that firms and households use a fairly high discount rate of 15% when evaluating the profitability of energy-efficiency improvements. The second is that our bottom-up information ('ICARUS') for most economic sectors does not (as NEMO does) take account of the fact that implementation of new, energy-efficient technology in capital stock takes place only gradually. Parameter estimates for 19 sectors point at a long-term technological energy efficiency improvement trend in Netherlands final energy use of 0.8% per year. The long-term price elasticity is estimated to be 0.29. These values are comparable to other studies based on time series data. Simulations of the effects of the oil price shocks in the seventies and the subsequent fall of oil prices show that the NEMO's price elasticities are consistent with historical data. However, the present pace at which new technologies become available (reflected in NEMO) appears to be lower than in the seventies and eighties. This suggests that it

  6. To be selected or not to be selected : a modeling and behavioral study of the mechanisms underlying stimulus-driven and top-down visual attention

    NARCIS (Netherlands)

    Voort van der Kleij, van der Gwendid T.

    2007-01-01

    This thesis investigates the mechanisms of stimulus-driven visual attention (global saliency), the mechanisms of top-down visual attention, and the interaction between these mechanisms, in visual search. Following the outline of an existing model of top-down visual attention, namely the Closed-Loop

  7. Catching a glimpse of working memory: top-down capture as a tool for measuring the content of the mind.

    Science.gov (United States)

    Lange, Nicholas D; Thomas, Rick P; Buttaccio, Daniel R; Davelaar, Eddy J

    2012-11-01

    This article outlines a methodology for probing working memory (WM) content in high-level cognitive tasks (e.g., decision making, problem solving, and memory retrieval) by capitalizing on attentional and oculomotor biases evidenced in top-down capture paradigms. This method would be of great use, as it could measure the information resident in WM at any point in a task and, hence, track information use over time as tasks dynamically evolve. Above and beyond providing a measure of information occupancy in WM, such a method would benefit from sensitivity to the specific activation levels of individual items in WM. This article additionally forwards a novel fusion of standard free recall and visual search paradigms in an effort to assess the sensitivity of eye movements in top-down capture, on which this new measurement technique relies, to item-specific memory activation (ISMA). The results demonstrate eye movement sensitivity to ISMA in some, but not all, cases.

  8. Hydrogen/deuterium exchange mass spectrometry with top-down electron capture dissociation for characterizing structural transitions of a 17 kDa protein.

    Science.gov (United States)

    Pan, Jingxi; Han, Jun; Borchers, Christoph H; Konermann, Lars

    2009-09-09

    Amide H/D exchange (HDX) mass spectrometry (MS) is widely used for protein structural studies. Traditionally, this technique involves protein labeling in D(2)O, followed by acid quenching, proteolytic digestion, and analysis of peptide deuteration levels by HPLC/MS. There is great interest in the development of alternative HDX approaches involving the top-down fragmentation of electrosprayed protein ions, instead of relying on enzymatic cleavage and solution-phase separations. A number of recent studies have demonstrated that electron capture dissociation (ECD) results in fragmentation of gaseous protein ions with little or no H/D scrambling. However, the successful application of this approach for in-depth protein conformational studies has not yet been demonstrated. The current work uses horse myoglobin as a model system for assessing the suitability of HDX-MS with top-down ECD for experiments of this kind. It is found that ECD can pinpoint the locations of protected amides with an average resolution of less than two residues for this 17 kDa protein. Native holo-myoglobin (hMb) shows considerable protection from exchange in all of its helices, whereas loops are extensively deuterated. Fraying is observable at some helix termini. Removal of the prosthetic heme group from hMb produces apo-myoglobin (aMb). Both hMb and aMb share virtually the same HDX protection pattern in helices A-E, whereas helix F is unfolded in aMb. In addition, destabilization is evident for some residues close to the beginning of helix G, the end of helix H, and the C-terminus of the protein. The structural changes reported herein are largely consistent with earlier NMR data for sperm whale myoglobin, although small differences between the two systems are evident. Our findings demonstrate that the level of structural information obtainable with top-down ECD for small to medium-sized proteins considerably surpasses that of traditional HDX-MS experiments, while at the same time greatly reducing

  9. Proteomic approaches to understanding the role of the cytoskeleton in host-defense mechanisms

    Science.gov (United States)

    Radulovic, Marko; Godovac-Zimmermann, Jasminka

    2014-01-01

    The cytoskeleton is a cellular scaffolding system whose functions include maintenance of cellular shape, enabling cellular migration, division, intracellular transport, signaling and membrane organization. In addition, in immune cells, the cytoskeleton is essential for phagocytosis. Following the advances in proteomics technology over the past two decades, cytoskeleton proteome analysis in resting and activated immune cells has emerged as a possible powerful approach to expand our understanding of cytoskeletal composition and function. However, so far there have only been a handful of studies of the cytoskeleton proteome in immune cells. This article considers promising proteomics strategies that could augment our understanding of the role of the cytoskeleton in host-defense mechanisms. PMID:21329431

  10. Linking electricity prices and costs in bottom-up top-down coupling under changing market environments

    OpenAIRE

    Maire, Sophie

    2016-01-01

    Electricity market liberalization is altering pricing mechanisms in wholesale electricity markets, which will affect the effectiveness of climate and energy policies. Models used to simulate such policies must be responsive to pricing rules. We show how this can be done and simulate a tightening of climate and energy policies. We use a soft-coupled framework composed of a top-down dynamic computable general equilibrium model and a bottom-up dynamic electricity supply model. The first simulate...

  11. Attention, working memory, and phenomenal experience of WM content: memory levels determined by different types of top-down modulation

    OpenAIRE

    Jacob, Jane; Jacobs, Christianne; Silvanto, Juha

    2015-01-01

    What is the role of top-down attentional modulation in consciously accessing working memory (WM) content? In influential WM models, information can exist in different states, determined by allocation of attention; placing the original memory representation in the center of focused attention gives rise to conscious access. Here we discuss various lines of evidence indicating that such attentional modulation is not sufficient for memory content to be phenomenally experienced. We propose that, i...

  12. The impact of top-down spatial attention on laterality and hemispheric asymmetry in the human parietal cortex.

    Science.gov (United States)

    Jeong, Su Keun; Xu, Yaoda

    2016-08-01

    The human parietal cortex exhibits a preference to contralaterally presented visual stimuli (i.e., laterality) as well as an asymmetry between the two hemispheres with the left parietal cortex showing greater laterality than the right. Using visual short-term memory and perceptual tasks and varying target location predictability, this study examined whether hemispheric laterality and asymmetry are fixed characteristics of the human parietal cortex or whether they are dynamic and modulated by the deployment of top-down attention to the target present hemifield. Two parietal regions were examined here that have previously been shown to be involved in visual object individuation and identification and are located in the inferior and superior intraparietal sulcus (IPS), respectively. Across three experiments, significant laterality was found in both parietal regions regardless of attentional modulation with laterality being greater in the inferior than superior IPS, consistent with their roles in object individuation and identification, respectively. Although the deployment of top-down attention had no effect on the superior IPS, it significantly increased laterality in the inferior IPS. The deployment of top-down spatial attention can thus amplify the strength of laterality in the inferior IPS. Hemispheric asymmetry, on the other hand, was absent in both brain regions and only emerged in the inferior but not the superior IPS with the deployment of top-down attention. Interestingly, the strength of hemispheric asymmetry significantly correlated with the strength of laterality in the inferior IPS. Hemispheric asymmetry thus seems to only emerge when there is a sufficient amount of laterality present in a brain region.

  13. Enhancing Protein Disulfide Bond Cleavage by UV Excitation and Electron Capture Dissociation for Top-Down Mass Spectrometry

    OpenAIRE

    Wongkongkathep, Piriya; Li, Huilin; Zhang, Xing; Loo, Rachel R. Ogorzalek; Julian, Ryan R.; Loo, Joseph A.

    2015-01-01

    The application of ion pre-activation with 266 nm ultraviolet (UV) laser irradiation combined with electron capture dissociation (ECD) is demonstrated to enhance top-down mass spectrometry sequence coverage of disulfide bond containing proteins. UV-based activation can homolytically cleave a disulfide bond to yield two separated thiol radicals. Activated ECD experiments of insulin and ribonuclease A containing three and four disulfide bonds, respectively, were performed. UV-activation in comb...

  14. Top-Down Modulation on the Perception and Categorization of Identical Pitch Contours in Speech and Music

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    Joey L. Weidema

    2016-06-01

    Full Text Available Whether pitch in language and music is governed by domain-specific or domain-general cognitive mechanisms is contentiously debated. The aim of the present study was to investigate whether mechanisms governing pitch contour perception operate differently when pitch information is interpreted as either speech or music. By modulating listening mode, this study aspired to demonstrate that pitch contour perception relies on domain-specific cognitive mechanisms, which are regulated by top-down influences from language and music. Three groups of participants (Mandarin speakers, Dutch speaking non-musicians, and Dutch musicians were exposed to identical pitch contours, and tested on their ability to identify these contours in a language and musical context. Stimuli consisted of disyllabic words spoken in Mandarin, and melodic tonal analogues, embedded in a linguistic and melodic carrier phrase, respectively. Participants classified identical pitch contours as significantly different depending on listening mode. Top-down influences from language appeared to alter the perception of pitch contour in speakers of Mandarin. This was not the case for non-musician speakers of Dutch. Moreover, this effect was lacking in Dutch speaking musicians. The classification patterns of pitch contours in language and music seem to suggest that domain-specific categorization is modulated by top-down influences from language and music.

  15. The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control.

    Science.gov (United States)

    Silton, Rebecca Levin; Heller, Wendy; Towers, David N; Engels, Anna S; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

    2010-04-15

    A network of brain regions has been implicated in top-down attentional control, including left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC). The present experiment evaluated predictions of the cascade-of-control model (Banich, 2009), which predicts that during attentionally-demanding tasks, LDLPFC imposes a top-down attentional set which precedes late-stage selection performed by dACC. Furthermore, the cascade-of-control model argues that dACC must increase its activity to compensate when top-down control by LDLPFC is poor. The present study tested these hypotheses using fMRI and dense-array ERP data collected from the same 80 participants in separate sessions. fMRI results guided ERP source modeling to characterize the time course of activity in LDLPFC and dACC. As predicted, dACC activity subsequent to LDLPFC activity distinguished congruent and incongruent conditions on the Stroop task. Furthermore, when LDLPFC activity was low, the level of dACC activity was related to performance outcome. These results demonstrate that dACC responds to attentional demand in a flexible manner that is dependent on the level of LDLPFC activity earlier in a trial. Overall, results were consistent with the temporal course of regional brain function proposed by the cascade-of-control model. Copyright 2009 Elsevier Inc. All rights reserved.

  16. The Relationship between Response Time and the Strength of Top-Down Attentional Control: An ERP Study

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    Judith Schomaker

    2009-12-01

    Full Text Available A recent ERP study using a spatial cueing paradigm found that the physiological indices accompanying the orienting, shifting and allocation processes of attention, and the performance on the task in terms of speed and accuracy of responding on the other hand covaried (Talsma, Mulckhuyse, Slagter, & Theeuwes, 2007.  However, the stimuli used in the former study possibly allowed for bottom-up capture of attention. Therefore the results could not unequivocally be attributed to a top-down attentional process. The present study is a follow-up of the Talsma et al. (2007  study and the stimuli design used in this study controlled for possible bottom-up effects. As a result, participants needed to spatially allocate attention in a top-down way. Indeed, in this study an Event-related Potential (ERP component associated with the top-down allocation of attention was found; the N2-posterior-contralateral (N2pc.  N2pc amplitudes were bigger in the fastest versus the slowest trials for the validly and non-informatively cued targets at posterior scalp sites. The present study replicated the Talsma et al. (2007 findings that the target-evoked N1 components were larger for the faster trials in the validly and non-informatively cued trials.

  17. How vision is shaped by language comprehension--top-down feedback based on low-spatial frequencies.

    Science.gov (United States)

    Hirschfeld, Gerrit; Zwitserlood, Pienie

    2011-03-04

    Effects of language comprehension on visual processing have been extensively studied within the embodied-language framework. However, it is unknown whether these effects are caused by passive repetition suppression in visual processing areas, or depend on active feedback, based on partial input, from prefrontal regions. Based on a model of top-down feedback during visual recognition, we predicted diminished effects when low-spatial frequencies were removed from targets. We compared low-pass and high-pass filtered pictures in a sentence-picture-verification task. Target pictures matched or mismatched the implied shape of an object mentioned in a preceding sentence, or were unrelated to the sentences. As predicted, there was a large match advantage when the targets contained low-spatial frequencies, but no effect of linguistic context when these frequencies were filtered out. The proposed top-down feedback model is superior to repetition suppression in explaining the current results, as well as earlier results about the lateralization of this effect, and peculiar color match effects. We discuss these findings in the context of recent general proposals of prediction and top-down feedback. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Top-down constraints on global N2O emissions at optimal resolution: application of a new dimension reduction technique

    Science.gov (United States)

    Wells, Kelley C.; Millet, Dylan B.; Bousserez, Nicolas; Henze, Daven K.; Griffis, Timothy J.; Chaliyakunnel, Sreelekha; Dlugokencky, Edward J.; Saikawa, Eri; Xiang, Gao; Prinn, Ronald G.; O'Doherty, Simon; Young, Dickon; Weiss, Ray F.; Dutton, Geoff S.; Elkins, James W.; Krummel, Paul B.; Langenfelds, Ray; Steele, L. Paul

    2018-01-01

    We present top-down constraints on global monthly N2O emissions for 2011 from a multi-inversion approach and an ensemble of surface observations. The inversions employ the GEOS-Chem adjoint and an array of aggregation strategies to test how well current observations can constrain the spatial distribution of global N2O emissions. The strategies include (1) a standard 4D-Var inversion at native model resolution (4° × 5°), (2) an inversion for six continental and three ocean regions, and (3) a fast 4D-Var inversion based on a novel dimension reduction technique employing randomized singular value decomposition (SVD). The optimized global flux ranges from 15.9 Tg N yr-1 (SVD-based inversion) to 17.5-17.7 Tg N yr-1 (continental-scale, standard 4D-Var inversions), with the former better capturing the extratropical N2O background measured during the HIAPER Pole-to-Pole Observations (HIPPO) airborne campaigns. We find that the tropics provide a greater contribution to the global N2O flux than is predicted by the prior bottom-up inventories, likely due to underestimated agricultural and oceanic emissions. We infer an overestimate of natural soil emissions in the extratropics and find that predicted emissions are seasonally biased in northern midlatitudes. Here, optimized fluxes exhibit a springtime peak consistent with the timing of spring fertilizer and manure application, soil thawing, and elevated soil moisture. Finally, the inversions reveal a major emission underestimate in the US Corn Belt in the bottom-up inventory used here. We extensively test the impact of initial conditions on the analysis and recommend formally optimizing the initial N2O distribution to avoid biasing the inferred fluxes. We find that the SVD-based approach provides a powerful framework for deriving emission information from N2O observations: by defining the optimal resolution of the solution based on the information content of the inversion, it provides spatial information that is lost when

  19. Top-down feedback in an HMAX-like cortical model of object perception based on hierarchical Bayesian networks and belief propagation.

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    Salvador Dura-Bernal

    Full Text Available Hierarchical generative models, such as Bayesian networks, and belief propagation have been shown to provide a theoretical framework that can account for perceptual processes, including feedforward recognition and feedback modulation. The framework explains both psychophysical and physiological experimental data and maps well onto the hierarchical distributed cortical anatomy. However, the complexity required to model cortical processes makes inference, even using approximate methods, very computationally expensive. Thus, existing object perception models based on this approach are typically limited to tree-structured networks with no loops, use small toy examples or fail to account for certain perceptual aspects such as invariance to transformations or feedback reconstruction. In this study we develop a Bayesian network with an architecture similar to that of HMAX, a biologically-inspired hierarchical model of object recognition, and use loopy belief propagation to approximate the model operations (selectivity and invariance. Crucially, the resulting Bayesian network extends the functionality of HMAX by including top-down recursive feedback. Thus, the proposed model not only achieves successful feedforward recognition invariant to noise, occlusions, and changes in position and size, but is also able to reproduce modulatory effects such as illusory contour completion and attention. Our novel and rigorous methodology covers key aspects such as learning using a layerwise greedy algorithm, combining feedback information from multiple parents and reducing the number of operations required. Overall, this work extends an established model of object recognition to include high-level feedback modulation, based on state-of-the-art probabilistic approaches. The methodology employed, consistent with evidence from the visual cortex, can be potentially generalized to build models of hierarchical perceptual organization that include top-down and bottom

  20. Determination of line edge roughness in low dose top-down scanning electron microscopy images

    Science.gov (United States)

    Verduin, T.; Kruit, P.; Hagen, C. W.

    2014-04-01

    We investigated off-line metrology for LER determination in low-dose SEM images to reduce the acquisition time and the risk of shrinkage. Our first attempts are based on filtering noisy (experimental) SEM images and use peak detection to measure the edge displacements and calculating the discrete PSD. However, the result of the filtering is that the power spectrum of the filter leaks into the PSD. So it is better to avoid a filter at all. We subsequently developed a method to detect edge displacements without the use of a filter. This method considers the signal profile of a SEM by integrating an experimental image of lines in the direction of the edges. The signal profile of an isolated edge is modeled as two merged Gaussians. This signal profile is then fitted against the raw (unfiltered) data of the edge pattern using an interior trust-region-reflective minimization procedure. This gives the edge displacements without the use of a filter and a filter-free version of the discrete PSD is obtained. The determination of edge displacements without the use of a filter, enables us to study how much noise is acceptable and still determine LER. To answer this question we generate random lines using the model of Palasantzas and the algorithm of Thorsos. This gives random generated edge displacements for typical values of experimental lines for the parameters of the model: 2 μm long lines (256 pixels), a correlation length ξ of 25 nm and a roughness exponent of 0.75. A noise-free top-down SEM-like image of lines is created by shifting the profile signal according to the random generated edge displacements. The image is further processed by adding Poisson-distributed noise. We consider three noise cases where the average electron density is about 2, 20 and 200 electrons per pixel. This corresponds to a charge density of (in respective order) 10 μC/cm2, 100 μC/cm2 and 1000 μC/cm2. The edge displacements of the random generated images are determined using our new

  1. DomSign: a top-down annotation pipeline to enlarge enzyme space in the protein universe.

    Science.gov (United States)

    Wang, Tianmin; Mori, Hiroshi; Zhang, Chong; Kurokawa, Ken; Xing, Xin-Hui; Yamada, Takuji

    2015-03-21

    Computational predictions of catalytic function are vital for in-depth understanding of enzymes. Because several novel approaches performing better than the common BLAST tool are rarely applied in research, we hypothesized that there is a large gap between the number of known annotated enzymes and the actual number in the protein universe, which significantly limits our ability to extract additional biologically relevant functional information from the available sequencing data. To reliably expand the enzyme space, we developed DomSign, a highly accurate domain signature-based enzyme functional prediction tool to assign Enzyme Commission (EC) digits. DomSign is a top-down prediction engine that yields results comparable, or superior, to those from many benchmark EC number prediction tools, including BLASTP, when a homolog with an identity >30% is not available in the database. Performance tests showed that DomSign is a highly reliable enzyme EC number annotation tool. After multiple tests, the accuracy is thought to be greater than 90%. Thus, DomSign can be applied to large-scale datasets, with the goal of expanding the enzyme space with high fidelity. Using DomSign, we successfully increased the percentage of EC-tagged enzymes from 12% to 30% in UniProt-TrEMBL. In the Kyoto Encyclopedia of Genes and Genomes bacterial database, the percentage of EC-tagged enzymes for each bacterial genome could be increased from 26.0% to 33.2% on average. Metagenomic mining was also efficient, as exemplified by the application of DomSign to the Human Microbiome Project dataset, recovering nearly one million new EC-labeled enzymes. Our results offer preliminarily confirmation of the existence of the hypothesized huge number of "hidden enzymes" in the protein universe, the identification of which could substantially further our understanding of the metabolisms of diverse organisms and also facilitate bioengineering by providing a richer enzyme resource. Furthermore, our results

  2. The effect of sidewall roughness on line edge roughness in top-down scanning electron microscopy images

    Science.gov (United States)

    Verduin, T.; Lokhorst, S. R.; Kruit, P.; Hagen, C. W.

    2015-03-01

    We have investigated in a numerical study the determination of sidewall roughness (SWR) from top down scanning electron microscopy (SEM) images. In a typical metrology application, top-down SEM images are acquired in a (critical-dimension) SEM and the roughness is analyzed. However, the true size, shape and roughness characteristics of resist features are not fully investigated in the analysis of top-down SEM images. In reality, rough resist features are complex three-dimensional structures and the characterization naturally extends to the analysis of SWR. In this study we randomly generate images of rough lines and spaces, where the lines are made of PMMA on a silicon substrate. The lines that we study have a length of 2 µm, a width of 32nm and a height of 32 nm. The SWR is modeled by using the power spectral density (PSD) function of Palasantzas, which characterizes roughness by the standard deviation σ, correlation length ξ and roughness exponent α . The actual roughness is generated by application of the method of Thorsos in two dimensions. The images are constructed by using a home-built program for simulating electron-specimen interactions. The program that we have developed is optimized for complex arbitrary geometries and large number of incident low energy primary electrons by using multi-core CPUs and GPUs. The program uses the dielectric function model for inelastic scattering events and has an implementation specifically for low energy electrons. A satisfactory comparison is made between the secondary electron yields from the home-built program and another program found in literature. In order to reduce the risk of shrinkage, we use a beam energy of 300 eV and a spot size of 3 nm. Each pixel is exposed with 20 electrons on average (≍ 276 µC/cm2), following the Poisson distribution to account for illumination shot noise. We have assumed that the detection of electrons is perfect and does not introduce additional noise. We measure line edge

  3. Functional overlap of top-down emotion regulation and generation: an fMRI study identifying common neural substrates between cognitive reappraisal and cognitively generated emotions.

    Science.gov (United States)

    Otto, Benjamin; Misra, Supriya; Prasad, Aditya; McRae, Kateri

    2014-09-01

    One factor that influences the success of emotion regulation is the manner in which the regulated emotion was generated. Recent research has suggested that reappraisal, a top-down emotion regulation strategy, is more effective in decreasing self-reported negative affect when emotions were generated from the top-down, versus the bottom-up. On the basis of a process overlap framework, we hypothesized that the neural regions active during reappraisal would overlap more with emotions that were generated from the top-down, rather than from the bottom-up. In addition, we hypothesized that increased neural overlap between reappraisal and the history effects of top-down emotion generation would be associated with increased reappraisal success. The results of several analyses suggested that reappraisal and emotions that were generated from the top-down share a core network of prefrontal, temporal, and cingulate regions. This overlap is specific; no such overlap was observed between reappraisal and emotions that were generated in a bottom-up fashion. This network consists of regions previously implicated in linguistic processing, cognitive control, and self-relevant appraisals, which are processes thought to be crucial to both reappraisal and top-down emotion generation. Furthermore, individuals with high reappraisal success demonstrated greater neural overlap between reappraisal and the history of top-down emotion generation than did those with low reappraisal success. The overlap of these key regions, reflecting overlapping processes, provides an initial insight into the mechanism by which generation history may facilitate emotion regulation.

  4. Are neutral loss and internal product ions useful for top-down protein identification?

    Science.gov (United States)

    Xiao, Kaijie; Yu, Fan; Fang, Houqin; Xue, Bingbing; Liu, Yan; Li, Yunhui; Tian, Zhixin

    2017-05-08

    Neutral loss and internal product ions have been found to be significant in both peptide and protein tandem mass spectra and they have been proposed to be included in database search and for protein identification. In addition to common canonical b/y ions in collision-based dissociation or c/z ions in electron-based dissociation, inclusion of neutral loss and internal product ions would certainly make better use of tandem mass spectra data; however, their ultimate utility for protein identification with false discovery rate control remains unclear. Here we report our proteome-level utility benchmarking of neutral loss and internal product ions with tandem mass spectra of intact E. coli proteome. Utility of internal product ions was further evaluated at the protein level using selected tandem mass spectra of individual E. coli proteins. We found that both neutral loss and internal products ions do not have direct utility for protein identification when they were used for scoring of P Score; but they do have indirect utility for provision of more canonical b/y ions when they are included in the database search and overlapping ions between different ion types are resolved. Tandem mass spectrometry has evolved to be a state-of-the-art method for characterization of protein primary structures (including amino acid sequence, post-translational modifications (PTMs) as well as their site location), where full study and utilization tandem mass spectra and product ions are indispensable. This primary structure information is essential for higher order structure and eventual function study of proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Chromosomocentric approach to overcoming difficulties in implementation of international project Human Proteome

    Directory of Open Access Journals (Sweden)

    A. I. Archakov

    2013-12-01

    Full Text Available The international project Human Proteome (PHP, being a logical continuation of the project Human Genome, was started on September 23, 2010. In correspondence with the genocentric approach, the PHP aim is to prepare a catalogue of all human proteins and to decipher a network of their interactions. The PHP implementation difficulties arise because the research subject itself – proteome – is much more complicated than genome. The major problem is the insufficient sensitivity of proteome methods that does not allow detecting low- and ultralow-copy proteins. Bad reproducibility of proteome methods and the lack of so-called “gold standard” is the second major complicacy in PHP implementation. The third problem is the dynamic character of proteome, its instabili­ty in time. The paper deals with possible variants of overcoming these complicacies, preventing from successful implementation of PHP.

  6. Atypical biological motion kinematics are represented by complementary lower-level and top-down processes during imitation learning.

    Science.gov (United States)

    Hayes, Spencer J; Dutoy, Chris A; Elliott, Digby; Gowen, Emma; Bennett, Simon J

    2016-01-01

    Learning a novel movement requires a new set of kinematics to be represented by the sensorimotor system. This is often accomplished through imitation learning where lower-level sensorimotor processes are suggested to represent the biological motion kinematics associated with an observed movement. Top-down factors have the potential to influence this process based on the social context, attention and salience, and the goal of the movement. In order to further examine the potential interaction between lower-level and top-down processes in imitation learning, the aim of this study was to systematically control the mediating effects during an imitation of biological motion protocol. In this protocol, we used non-human agent models that displayed different novel atypical biological motion kinematics, as well as a control model that displayed constant velocity. Importantly the three models had the same movement amplitude and movement time. Also, the motion kinematics were displayed in the presence, or absence, of end-state-targets. Kinematic analyses showed atypical biological motion kinematics were imitated, and that this performance was different from the constant velocity control condition. Although the imitation of atypical biological motion kinematics was not modulated by the end-state-targets, movement time was more accurate in the absence, compared to the presence, of an end-state-target. The fact that end-state targets modulated movement time accuracy, but not biological motion kinematics, indicates imitation learning involves top-down attentional, and lower-level sensorimotor systems, which operate as complementary processes mediated by the environmental context. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Structural Characterization of a Thrombin-Aptamer Complex by High Resolution Native Top-Down Mass Spectrometry

    Science.gov (United States)

    Zhang, Jiang; Loo, Rachel R. Ogorzalek; Loo, Joseph A.

    2017-09-01

    Native mass spectrometry (MS) with electrospray ionization (ESI) has evolved as an invaluable tool for the characterization of intact native proteins and non-covalently bound protein complexes. Here we report the structural characterization by high resolution native top-down MS of human thrombin and its complex with the Bock thrombin binding aptamer (TBA), a 15-nucleotide DNA with high specificity and affinity for thrombin. Accurate mass measurements revealed that the predominant form of native human α-thrombin contains a glycosylation mass of 2205 Da, corresponding to a sialylated symmetric biantennary oligosaccharide structure without fucosylation. Native MS showed that thrombin and TBA predominantly form a 1:1 complex under near physiological conditions (pH 6.8, 200 mM NH4OAc), but the binding stoichiometry is influenced by the solution ionic strength. In 20 mM ammonium acetate solution, up to two TBAs were bound to thrombin, whereas increasing the solution ionic strength destabilized the thrombin-TBA complex and 1 M NH4OAc nearly completely dissociated the complex. This observation is consistent with the mediation of thrombin-aptamer binding through electrostatic interactions and it is further consistent with the human thrombin structure that contains two anion binding sites on the surface. Electron capture dissociation (ECD) top-down MS of the thrombin-TBA complex performed with a high resolution 15 Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer showed the primary binding site to be at exosite I located near the N-terminal sequence of the heavy chain, consistent with crystallographic data. High resolution native top-down MS is complementary to traditional structural biology methods for structurally characterizing native proteins and protein-DNA complexes. [Figure not available: see fulltext.

  8. Imaging 'top-down' mobilization of visual information: a case study in a posterior split-brain patient.

    Science.gov (United States)

    Naccache, Lionel; Sportiche, Sarah; Strauss, Mélanie; El Karoui, Imen; Sitt, Jacobo; Cohen, Laurent

    2014-01-01

    During visual perception, automatic bottom-up and controlled top-down processes occur simultaneously and interact in a complex way, making them difficult to isolate and characterize. In rare neurological conditions, such a dissociation can be achieved more easily. In the present work, we studied a patient (AC) with a posterior lesion of the corpus callosum (CC), using a combination of behavioural, structural MRI and high-density scalp EEG measures. Given the complete disruption of the posterior half of the CC, we speculated that inter-hemispheric transfer of visual information was only possible through top-down mobilization across the preserved anterior segment of the CC. We designed a matching-to-sample visual task during which this patient was randomly presented with two successive numerical targets (T1 and T2) flashed with either a short or a long stimulus-onset asynchrony (SOA), each presented within one visual hemifield (HF). Intra-hemispheric processing of visual stimuli was essentially preserved. In sharp contrast, patient's performance was massively impaired during inter-HFs trials with a short-SOA, confirming the lack of fast inter-hemispheric transfer. Crucially, patient AC spontaneously improved his performance in inter-HFs trials with a long-SOA. This behavioral improvement was correlated with a mid-frontal ERP effect occurring during the T1-T2 interval, concomitant with an increase of functional connectivity of this region with distant areas including occipital regions. These results put to light a slow, non-automatic, and frontally mediated route of inter-hemispheric transfer dependent on top-down control. © 2013 Published by Elsevier Ltd.

  9. Disentangling the effects of predator hunting mode and habitat domain on the top-down control of insect herbivores.

    Science.gov (United States)

    Woodcock, Ben A; Heard, Matthew S

    2011-03-01

    1. Polyphagous predatory invertebrates play a key role in the top-down control of insect herbivores. However, predicting predation risk for herbivores is not a simple function of predator species richness. Predation risk may be reduced or enhanced depending on the functional characteristics predator species. We predict that where predator species spatially overlap this will reduce predation risk for herbivores by allowing negative inter-specific interaction between predators to occur. Where increased predation risk occurs, we also predict that this will have a cascading effect through the food chain reducing plant growth. 2. We used a substitutive replicated block design to identify the effect of similarity and dissimilarity in predator hunting mode (e.g. 'sit and wait', 'sit and pursue', and 'active') and habitat domain (e.g. canopy or ground) on the top-down control of planthoppers in grasslands. Predators included within the mesocosms were randomly selected from a pool of 17 local species. 3. Predation risk was reduced where predators shared the same habitat domain, independent of whether they shared hunting modes. Where predators shared the same habitat domains, there was some evidence that this had a cascading negative effect on the re-growth of grass biomass. Where predator habitat domains did not overlap, there were substitutable effects on predation risk to planthoppers. Predation risk for planthoppers was affected by taxonomic identity of predator species, i.e. whether they were beetles, spiders or true bugs. 4. Our results indicated that in multi-predator systems, the risk of predation is typically reduced. Consideration of functional characteristics of individual species, in particular aspects of habitat domain and hunting mode, are crucial in predicting the effects of multi-predator systems on the top-down control of herbivores. © 2010 The Authors. Journal of Animal Ecology © 2010 British Ecological Society.

  10. Mechanisms Driving Galling Success in a Fragmented Landscape: Synergy of Habitat and Top-Down Factors along Temperate Forest Edges.

    Directory of Open Access Journals (Sweden)

    Nina-S Kelch

    Full Text Available Edge effects play key roles in the anthropogenic transformation of forested ecosystems and their biota, and are therefore a prime field of contemporary fragmentation research. We present the first empirical study to address edge effects on the population level of a widespread galling herbivore in a temperate deciduous forest. By analyzing edge effects on abundance and trophic interactions of beech gall midge (Mikiola fagi Htg., we found 30% higher gall abundance in the edge habitat as well as lower mortality rates due to decreased top-down control, especially by parasitoids. Two GLM models with similar explanatory power (58% identified habitat specific traits (such as canopy closure and altitude and parasitism as the best predictors of gall abundance. Further analyses revealed a crucial influence of light exposure (46% on top-down control by the parasitoid complex. Guided by a conceptual framework synthesizing the key factors driving gall density, we conclude that forest edge proliferation of M. fagi is due to a complex interplay of abiotic changes and trophic control mechanisms. Most prominently, it is caused by the microclimatic regime in forest edges, acting alone or in synergistic concert with top-down pressure by parasitoids. Contrary to the prevailing notion that specialists are edge-sensitive, this turns M. fagi into a winner species in fragmented temperate beech forests. In view of the increasing proportion of edge habitats and the documented benefits from edge microclimate, we call for investigations exploring the pest status of this galling insect and the modulators of its biological control.

  11. Top-Down Prioritization of Salient Items May Produce the So-Called Stimulus-Driven Capture

    Directory of Open Access Journals (Sweden)

    Hanna Benoni

    2018-02-01

    Full Text Available The current study proposes that top-down attentional prioritization of salient items may produce the so-called stimulus-driven capture. To test this proposal, the “expectation-based paradigm” was designed on the basis of a visual search task. In Experiment 1, a task-irrelevant singleton frame was presented at the same location in 70% of the trials. The target was either presented at chance level within the singleton location, or away from it. In line with the singleton capture phenomenon, participants were faster in identifying the target when it appeared in the singleton location compared to non-singleton locations. However, leaving out the singleton frame in 30% of the trials led to a similar effect; participants were faster in identifying the target when it appeared in the expected singleton location compared to expected non-singletons locations (a “quasi-capture” effect. These results suggest that the participants allocated their attention to the expected singleton location, rather than that the singleton itself captured attention. In Experiment 2, the same task-irrelevant color singleton was presented in a random position in 70% of the trials. This color frame was shown as a non-singleton in all of the 30% singleton-absent multicolored trials. A similar facilitation effect was obtained when the target appeared in the expected singleton color frame compared to other frames, in singleton-absent trials as in singleton-present trials. These results further support the idea that instances of singleton capture can be explained by top-down attentional shifts toward singleton items. Theoretical implications of these results are discussed. Mostly, the study calls to consider the possibility that all sources of attentional control may be represented by a continuous variable of top-down control, including the category of “physical salience.”

  12. Functional interplay of top-down attention with affective codes during visual short-term memory maintenance.

    Science.gov (United States)

    Kuo, Bo-Cheng; Lin, Szu-Hung; Yeh, Yei-Yu

    2018-06-01

    Visual short-term memory (VSTM) allows individuals to briefly maintain information over time for guiding behaviours. Because the contents of VSTM can be neutral or emotional, top-down influence in VSTM may vary with the affective codes of maintained representations. Here we investigated the neural mechanisms underlying the functional interplay of top-down attention with affective codes in VSTM using functional magnetic resonance imaging. Participants were instructed to remember both threatening and neutral objects in a cued VSTM task. Retrospective cues (retro-cues) were presented to direct attention to the hemifield of a threatening object (i.e., cue-to-threat) or a neutral object (i.e., cue-to-neutral) during VSTM maintenance. We showed stronger activity in the ventral occipitotemporal cortex and amygdala for attending threatening relative to neutral representations. Using multivoxel pattern analysis, we found better classification performance for cue-to-threat versus cue-to-neutral objects in early visual areas and in the amygdala. Importantly, retro-cues modulated the strength of functional connectivity between the frontoparietal and early visual areas. Activity in the frontoparietal areas became strongly correlated with the activity in V3a-V4 coding the threatening representations instructed to be relevant for the task. Together, these findings provide the first demonstration of top-down modulation of activation patterns in early visual areas and functional connectivity between the frontoparietal network and early visual areas for regulating threatening representations during VSTM maintenance. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Salient region detection by fusing bottom-up and top-down features extracted from a single image.

    Science.gov (United States)

    Tian, Huawei; Fang, Yuming; Zhao, Yao; Lin, Weisi; Ni, Rongrong; Zhu, Zhenfeng

    2014-10-01

    Recently, some global contrast-based salient region detection models have been proposed based on only the low-level feature of color. It is necessary to consider both color and orientation features to overcome their limitations, and thus improve the performance of salient region detection for images with low-contrast in color and high-contrast in orientation. In addition, the existing fusion methods for different feature maps, like the simple averaging method and the selective method, are not effective sufficiently. To overcome these limitations of existing salient region detection models, we propose a novel salient region model based on the bottom-up and top-down mechanisms: the color contrast and orientation contrast are adopted to calculate the bottom-up feature maps, while the top-down cue of depth-from-focus from the same single image is used to guide the generation of final salient regions, since depth-from-focus reflects the photographer's preference and knowledge of the task. A more general and effective fusion method is designed to combine the bottom-up feature maps. According to the degree-of-scattering and eccentricities of feature maps, the proposed fusion method can assign adaptive weights to different feature maps to reflect the confidence level of each feature map. The depth-from-focus of the image as a significant top-down feature for visual attention in the image is used to guide the salient regions during the fusion process; with its aid, the proposed fusion method can filter out the background and highlight salient regions for the image. Experimental results show that the proposed model outperforms the state-of-the-art models on three public available data sets.

  14. Top-Down Prioritization of Salient Items May Produce the So-Called Stimulus-Driven Capture

    Science.gov (United States)

    Benoni, Hanna

    2018-01-01

    The current study proposes that top-down attentional prioritization of salient items may produce the so-called stimulus-driven capture. To test this proposal, the “expectation-based paradigm” was designed on the basis of a visual search task. In Experiment 1, a task-irrelevant singleton frame was presented at the same location in 70% of the trials. The target was either presented at chance level within the singleton location, or away from it. In line with the singleton capture phenomenon, participants were faster in identifying the target when it appeared in the singleton location compared to non-singleton locations. However, leaving out the singleton frame in 30% of the trials led to a similar effect; participants were faster in identifying the target when it appeared in the expected singleton location compared to expected non-singletons locations (a “quasi-capture” effect). These results suggest that the participants allocated their attention to the expected singleton location, rather than that the singleton itself captured attention. In Experiment 2, the same task-irrelevant color singleton was presented in a random position in 70% of the trials. This color frame was shown as a non-singleton in all of the 30% singleton-absent multicolored trials. A similar facilitation effect was obtained when the target appeared in the expected singleton color frame compared to other frames, in singleton-absent trials as in singleton-present trials. These results further support the idea that instances of singleton capture can be explained by top-down attentional shifts toward singleton items. Theoretical implications of these results are discussed. Mostly, the study calls to consider the possibility that all sources of attentional control may be represented by a continuous variable of top-down control, including the category of “physical salience.” PMID:29599731

  15. Top-down estimates of benzene and toluene emissions in the Pearl River Delta and Hong Kong, China

    OpenAIRE

    Fang, Xuekun; Shao, Min; Stohl, Andreas; Zhang, Qiang; Zheng, Junyu; Guo, Hai; Wang, Chen; Wang, Ming; Ou, Jiamin; Thompson, Rona L.; Prinn, Ronald G.

    2016-01-01

    Benzene (C6H6) and toluene (C7H8) are toxic to humans and the environment. They are also important precursors of ground-level ozone and secondary organic aerosols and contribute substantially to severe air pollution in urban areas in China. Discrepancies exist between different bottom-up inventories for benzene and toluene emissions in the Pearl River Delta (PRD) and Hong Kong (HK), which are emission hot spots in China. This study provides top-down estimates of benzene and ...

  16. Top-down estimates of benzene and toluene emissions in Pearl River Delta and Hong Kong, China

    OpenAIRE

    X. Fang; M. Shao; A. Stohl; Q. Zhang; J. Zheng; H. Guo; C. Wang; M. Wang; J. Ou; R. L. Thompson; R. G. Prinn

    2015-01-01

    Benzene (C6H6) and toluene (C7H8) are toxic to humans and the environment. They are also important precursors of ground-level ozone and secondary organic aerosols and contribute substantially to severe air pollution in urban areas in China. Discrepancies exist between different bottom-up inventories for benzene and toluene emissions in Pearl River Delta (PRD) and Hong Kong (HK), which are emission hot spots in China. This study provides top-down estimates of benzene and tolu...

  17. Benchmarking energy scenarios for China: perspectives from top-down, economic and bottom-up, technical modelling

    DEFF Research Database (Denmark)

    This study uses a soft-linking methodology to harmonise two complex global top-down and bottom-up models with a regional China focus. The baseline follows the GDP and demographic trends of the Shared Socio-economic Pathways (SSP2) scenario, down-scaled for China, while the carbon tax scenario fol......-specific modelling results further. These new sub-regional China features can now be used for a more detailed analysis of China's regional developments in a global context....

  18. Proteomic approaches in cancer risk and response assessment.

    Science.gov (United States)

    Petricoin, Emanuel F; Liotta, Lance A

    2004-02-01

    Proteomics is more than just a list-generating exercise where increases or decreases in protein expression are identified. Proteomic technologies will ultimately characterize information-flow through the protein circuitry that interconnects the extracellular microenvironment to the serum or plasma macroenvironment through intracellular signaling systems and their control of gene transcription. The nature of this information can be a cause or a consequence of disease processes and how patients respond to therapy. Analysis of human cancer as a model for how proteomics can have an impact at the bedside can take advantage of several promising new proteomic technologies. These technologies are being developed for early detection and risk assessment, therapeutic targeting and patient-tailored therapy.

  19. Analytical approaches for the characterization of nickel proteome.

    Science.gov (United States)

    Jiménez-Lamana, Javier; Szpunar, Joanna

    2017-08-16

    The use of nickel in modern industry and in consumer products implies some health problems for the human being. Nickel allergy and nickel carcinogenicity are well-known health effects related to human exposure to nickel, either during production of nickel-containing products or by direct contact with the final item. In this context, the study of nickel toxicity and nickel carcinogenicity involves the understanding of their molecular mechanisms and hence the characterization of the nickel-binding proteins in different biological samples. During the last 50 years, a broad range of analytical techniques, covering from the first chromatographic columns to the last generation mass spectrometers, have been used in order to fully characterize the nickel proteome. The aim of this review is to present a critical view of the different analytical approaches that have been applied for the purification, isolation, detection and identification of nickel-binding proteins. The different analytical techniques used are discussed from a critical point of view, highlighting advantages and limitations.

  20. Bottom-up nutrient and top-down fish impacts on insect-mediated mercury flux from aquatic ecosystems.

    Science.gov (United States)

    Jones, Taylor A; Chumchal, Matthew M; Drenner, Ray W; Timmins, Gabrielle N; Nowlin, Weston H

    2013-03-01

    Methyl mercury (MeHg) is one of the most hazardous contaminants in the environment, adversely affecting the health of wildlife and humans. Recent studies have demonstrated that aquatic insects biotransport MeHg and other contaminants to terrestrial consumers, but the factors that regulate the flux of MeHg out of aquatic ecosystems via emergent insects have not been studied. The authors used experimental mesocosms to test the hypothesis that insect emergence and the associated flux of MeHg from aquatic to terrestrial ecosystems is affected by both bottom-up nutrient effects and top-down fish consumer effects. In the present study, nutrient addition led to an increase in MeHg flux primarily by enhancing the biomass of emerging insects whose tissues were contaminated with MeHg, whereas fish decreased MeHg flux primarily by reducing the biomass of emerging insects. Furthermore, the authors found that these factors are interdependent such that the effects of nutrients are more pronounced when fish are absent, and the effects of fish are more pronounced when nutrient concentrations are high. The present study is the first to demonstrate that the flux of MeHg from aquatic to terrestrial ecosystems is strongly enhanced by bottom-up nutrient effects and diminished by top-down consumer effects. Copyright © 2012 SETAC.

  1. Additive effects of affective arousal and top-down attention on the event-related brain responses to human bodies.

    Science.gov (United States)

    Hietanen, Jari K; Kirjavainen, Ilkka; Nummenmaa, Lauri

    2014-12-01

    The early visual event-related 'N170 response' is sensitive to human body configuration and it is enhanced to nude versus clothed bodies. We tested whether the N170 response as well as later EPN and P3/LPP responses to nude bodies reflect the effect of increased arousal elicited by these stimuli, or top-down allocation of object-based attention to the nude bodies. Participants saw pictures of clothed and nude bodies and faces. In each block, participants were asked to direct their attention towards stimuli from a specified target category while ignoring others. Object-based attention did not modulate the N170 amplitudes towards attended stimuli; instead N170 response was larger to nude bodies compared to stimuli from other categories. Top-down attention and affective arousal had additive effects on the EPN and P3/LPP responses reflecting later processing stages. We conclude that nude human bodies have a privileged status in the visual processing system due to the affective arousal they trigger. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Sponge communities on Caribbean coral reefs are structured by factors that are top-down, not bottom-up.

    Science.gov (United States)

    Pawlik, Joseph R; Loh, Tse-Lynn; McMurray, Steven E; Finelli, Christopher M

    2013-01-01

    Caribbean coral reefs have been transformed in the past few decades with the demise of reef-building corals, and sponges are now the dominant habitat-forming organisms on most reefs. Competing hypotheses propose that sponge communities are controlled primarily by predatory fishes (top-down) or by the availability of picoplankton to suspension-feeding sponges (bottom-up). We tested these hypotheses on Conch Reef, off Key Largo, Florida, by placing sponges inside and outside predator-excluding cages at sites with less and more planktonic food availability (15 m vs. 30 m depth). There was no evidence of a bottom-up effect on the growth of any of 5 sponge species, and 2 of 5 species grew more when caged at the shallow site with lower food abundance. There was, however, a strong effect of predation by fishes on sponge species that lacked chemical defenses. Sponges with chemical defenses grew slower than undefended species, demonstrating a resource trade-off between growth and the production of secondary metabolites. Surveys of the benthic community on Conch Reef similarly did not support a bottom-up effect, with higher sponge cover at the shallower depth. We conclude that the structure of sponge communities on Caribbean coral reefs is primarily top-down, and predict that removal of sponge predators by overfishing will shift communities toward faster-growing, undefended species that better compete for space with threatened reef-building corals.

  3. Sponge communities on Caribbean coral reefs are structured by factors that are top-down, not bottom-up.

    Directory of Open Access Journals (Sweden)

    Joseph R Pawlik

    Full Text Available Caribbean coral reefs have been transformed in the past few decades with the demise of reef-building corals, and sponges are now the dominant habitat-forming organisms on most reefs. Competing hypotheses propose that sponge communities are controlled primarily by predatory fishes (top-down or by the availability of picoplankton to suspension-feeding sponges (bottom-up. We tested these hypotheses on Conch Reef, off Key Largo, Florida, by placing sponges inside and outside predator-excluding cages at sites with less and more planktonic food availability (15 m vs. 30 m depth. There was no evidence of a bottom-up effect on the growth of any of 5 sponge species, and 2 of 5 species grew more when caged at the shallow site with lower food abundance. There was, however, a strong effect of predation by fishes on sponge species that lacked chemical defenses. Sponges with chemical defenses grew slower than undefended species, demonstrating a resource trade-off between growth and the production of secondary metabolites. Surveys of the benthic community on Conch Reef similarly did not support a bottom-up effect, with higher sponge cover at the shallower depth. We conclude that the structure of sponge communities on Caribbean coral reefs is primarily top-down, and predict that removal of sponge predators by overfishing will shift communities toward faster-growing, undefended species that better compete for space with threatened reef-building corals.

  4. Orchestrated structure evolution: accelerating direct-write nanomanufacturing by combining top-down patterning with bottom-up growth

    Energy Technology Data Exchange (ETDEWEB)

    Kitayaporn, Sathana; Baneyx, Francois; Schwartz, Daniel T [Department of Chemical Engineering, University of Washington, Seattle, WA 98195-1750 (United States); Hoo, Ji Hao; Boehringer, Karl F, E-mail: dts@uw.edu [Department of Electrical Engineering, University of Washington, Seattle, WA 98195-1750 (United States)

    2010-05-14

    Direct-write nanomanufacturing with scanning beams and probes is flexible and can produce high quality products, but it is normally slow and expensive to raster point-by-point over a pattern. We demonstrate the use of an accelerated direct-write nanomanufacturing method called 'orchestrated structure evolution' (OSE), where a direct-write tool patterns a small number of growth 'seeds' that subsequently grow into the final thin film pattern. Through control of seed size and spacing, it is possible to vary the ratio of 'top-down' to 'bottom-up' character of the patterning processes, ranging from conventional top-down raster patterning to nearly pure bottom-up space-filling via seed growth. Electron beam lithography (EBL) and copper electrodeposition were used to demonstrate trade-offs between process time and product quality over nano- to microlength scales. OSE can reduce process times for high-cost EBL patterning by orders of magnitude, at the expense of longer (but inexpensive) copper electrodeposition processing times. We quantify the degradation of pattern quality that accompanies fast OSE patterning by measuring deviations from the desired patterned area and perimeter. We also show that the density of OSE-induced grain boundaries depends upon the seed separation and size. As the seed size is reduced, the uniformity of an OSE film becomes more dependent on details of seed nucleation processes than normally seen for conventionally patterned films.

  5. Cortical gamma activity during auditory tone omission provides evidence for the involvement of oscillatory activity in top-down processing.

    Science.gov (United States)

    Gurtubay, I G; Alegre, M; Valencia, M; Artieda, J

    2006-11-01

    Perception is an active process in which our brains use top-down influences to modulate afferent information. To determine whether this modulation might be based on oscillatory activity, we asked seven subjects to detect a silence that appeared randomly in a rhythmic auditory sequence, counting the number of omissions ("count" task), or responding to each omission with a right index finger extension ("move" task). Despite the absence of physical stimuli, these tasks induced a 'non-phase-locked' gamma oscillation in temporal-parietal areas, providing evidence of intrinsically generated oscillatory activity during top-down processing. This oscillation is probably related to the local neural activation that takes place during the process of stimulus detection, involving the functional comparison between the tones and the absence of stimuli as well as the auditory echoic memory processes. The amplitude of the gamma oscillations was reduced with the repetition of the tasks. Moreover, it correlated positively with the number of correctly detected omissions and negatively with the reaction time. These findings indicate that these oscillations, like others described, may be modulated by attentional processes. In summary, our findings support the active and adaptive concept of brain function that has emerged over recent years, suggesting that the match of sensory information with memory contents generates gamma oscillations.

  6. Basic-level categorization of intermediate complexity fragments reveals top-down effects of expertise in visual perception.

    Science.gov (United States)

    Harel, Assaf; Ullman, Shimon; Harari, Danny; Bentin, Shlomo

    2011-07-28

    Visual expertise is usually defined as the superior ability to distinguish between exemplars of a homogeneous category. Here, we ask how real-world expertise manifests at basic-level categorization and assess the contribution of stimulus-driven and top-down knowledge-based factors to this manifestation. Car experts and novices categorized computer-selected image fragments of cars, airplanes, and faces. Within each category, the fragments varied in their mutual information (MI), an objective quantifiable measure of feature diagnosticity. Categorization of face and airplane fragments was similar within and between groups, showing better performance with increasing MI levels. Novices categorized car fragments more slowly than face and airplane fragments, while experts categorized car fragments as fast as face and airplane fragments. The experts' advantage with car fragments was similar across MI levels, with similar functions relating RT with MI level for both groups. Accuracy was equal between groups for cars as well as faces and airplanes, but experts' response criteria were biased toward cars. These findings suggest that expertise does not entail only specific perceptual strategies. Rather, at the basic level, expertise manifests as a general processing advantage arguably involving application of top-down mechanisms, such as knowledge and attention, which helps experts to distinguish between object categories. © ARVO

  7. Evaluation of the FEERv1.0 Global Top-Down Biomass Burning Emissions Inventory over Africa

    Science.gov (United States)

    Ellison, L.; Ichoku, C. M.

    2014-12-01

    With the advent of the Fire Energetics and Emissions Research (FEER) global top-down biomass burning emissions product from NASA Goddard Space Flight Center, a subsequent effort is going on to analyze and evaluate some of the main (particulate and gaseous) constituents of this emissions inventory against other inventories of biomass burning emissions over the African continent. There is consistent and continual burning during the dry season in NSSA of many small slash-and-burn fires that, though may be relatively small fires individually, collectively contribute 20-25% of the global total carbon emissions from biomass burning. As a top-down method of estimating biomass-burning emissions, FEERv1.0 is able to yield higher and more realistic emissions than previously obtainable using bottom-up methods. Results of such comparisons performed in detail over Africa will be discussed in this presentation. This effort is carried out in conjunction with a NASA-funded interdisciplinary research project investigating the effects of biomass burning on the regional climate system in Northern Sub-Saharan Africa (NSSA). Essentially, that project aims to determine how fires may have affected the severe droughts that plagued the NSSA region in recent history. Therefore, it is imperative that the biomass burning emissions input data over Africa be as accurate as possible in order to obtain a confident understanding of their interactions and feedbacks with the hydrological cycle in NSSA.

  8. Bottom-up and top-down human impacts interact to affect a protected coastal Chilean marsh.

    Science.gov (United States)

    Fariña, José M; He, Qiang; Silliman, Brian R; Bertness, Mark D

    2016-03-01

    Many ecosystems, even in protected areas, experience multiple anthropogenic impacts. While anthropogenic modification of bottom-up (e.g., eutrophication) and top-down (e.g., livestock grazing) forcing often co-occurs, whether these factors counteract or have additive or synergistic effects on ecosystems is poorly understood. In a Chilean bio-reserve, we examined the interactive impacts of eutrophication and illegal livestock grazing on plant growth with a 4-yr fertilization by cattle exclusion experiment. Cattle grazing generally decreased plant biomass, but had synergistic, additive, and antagonistic interactions with fertilization in the low, middle, and high marsh zones, respectively. In the low marsh, fertilization increased plant biomass by 112%, cattle grazing decreased it by 96%, and together they decreased plant biomass by 77%. In the middle marsh, fertilization increased plant biomass by 47%, cattle grazing decreased it by 37%, and together they did not affect plant biomass. In the high marsh, fertilization and cattle grazing decreased plant biomass by 81% and 92%, respectively, but together they increased plant biomass by 42%. These interactions were also found to be species specific. Different responses of plants to fertilization and cattle grazing were likely responsible for these variable interactions. Thus, common bottom-up and top-down human impacts can interact in different ways to affect communities even within a single ecosystem. Incorporating this knowledge into conservation actions will improve ecosystem management in a time when ecosystems are increasingly challenged by multiple interacting human impacts.

  9. Top-down and bottom-up aspects of active search in a real-world environment.

    Science.gov (United States)

    Foulsham, Tom; Chapman, Craig; Nasiopoulos, Eleni; Kingstone, Alan

    2014-03-01

    Visual search has been studied intensively in the labouratory, but lab search often differs from search in the real world in many respects. Here, we used a mobile eye tracker to record the gaze of participants engaged in a realistic, active search task. Participants were asked to walk into a mailroom and locate a target mailbox among many similar mailboxes. This procedure allowed control of bottom-up cues (by making the target mailbox more salient; Experiment 1) and top-down instructions (by informing participants about the cue; Experiment 2). The bottom-up salience of the target had no effect on the overall time taken to search for the target, although the salient target was more likely to be fixated and found once it was within the central visual field. Top-down knowledge of target appearance had a larger effect, reducing the need for multiple head and body movements, and meaning that the target was fixated earlier and from further away. Although there remains much to be discovered in complex real-world search, this study demonstrates that principles from visual search in the labouratory influence gaze in natural behaviour, and provides a bridge between these labouratory studies and research examining vision in natural tasks.

  10. Animal water balance drives top-down effects in a riparian forest-implications for terrestrial trophic cascades.

    Science.gov (United States)

    McCluney, Kevin E; Sabo, John L

    2016-08-17

    Despite the clear importance of water balance to the evolution of terrestrial life, much remains unknown about the effects of animal water balance on food webs. Based on recent research suggesting animal water imbalance can increase trophic interaction strengths in cages, we hypothesized that water availability could drive top-down effects in open environments, influencing the occurrence of trophic cascades. We manipulated large spider abundance and water availability in 20 × 20 m open-air plots in a streamside forest in Arizona, USA, and measured changes in cricket and small spider abundance and leaf damage. As expected, large spiders reduced both cricket abundance and herbivory under ambient, dry conditions, but not where free water was added. When water was added (free or within moist leaves), cricket abundance was unaffected by large spiders, but spiders still altered herbivory, suggesting behavioural effects. Moreover, we found threshold-type increases in herbivory at moderately low soil moisture (between 5.5% and 7% by volume), suggesting the possibility that water balance may commonly influence top-down effects. Overall, our results point towards animal water balance as an important driver of direct and indirect species interactions and food web dynamics in terrestrial ecosystems. © 2016 The Author(s).

  11. Effect of atomic layer deposition temperature on the performance of top-down ZnO nanowire transistors

    Science.gov (United States)

    2014-01-01

    This paper studies the effect of atomic layer deposition (ALD) temperature on the performance of top-down ZnO nanowire transistors. Electrical characteristics are presented for 10-μm ZnO nanowire field-effect transistors (FETs) and for deposition temperatures in the range 120°C to 210°C. Well-behaved transistor output characteristics are obtained for all deposition temperatures. It is shown that the maximum field-effect mobility occurs for an ALD temperature of 190°C. This maximum field-effect mobility corresponds with a maximum Hall effect bulk mobility and with a ZnO film that is stoichiometric. The optimized transistors have a field-effect mobility of 10 cm2/V.s, which is approximately ten times higher than can typically be achieved in thin-film amorphous silicon transistors. Furthermore, simulations indicate that the drain current and field-effect mobility extraction are limited by the contact resistance. When the effects of contact resistance are de-embedded, a field-effect mobility of 129 cm2/V.s is obtained. This excellent result demonstrates the promise of top-down ZnO nanowire technology for a wide variety of applications such as high-performance thin-film electronics, flexible electronics, and biosensing. PMID:25276107

  12. Sensitivity quantification of airport concrete pavement stress responses associated with top-down and bottom-up cracking

    Directory of Open Access Journals (Sweden)

    Adel Rezaei-Tarahomi

    2017-09-01

    Full Text Available The Federal Aviation Administration’s (FAA’s rigid pavement design standard employs the NIKE3D-FAA software to compute critical pavement responses of concrete airport pavement structures. NIKE3D-FAA is a modification of the original NIKE3D three-dimensional finite element analysis program developed by the Lawrence Livermore National Laboratory (LLNL of the U.S. Department of Energy, and is currently used in the FAA’s FAARFIELD program. This study evaluated the sensitivity of NIKE3D-FAA rigid pavement responses with respect to top-down and bottom-up cracking. The analysis was conducted by positioning a Boeing 777-300ER (B777-300ERaircraft at different locations (interior, corner, and edge of slab as baseline while varying other NIKE3D-FAA inputs, including rigid pavement geometric features, mechanical properties of paving and foundation materials, equivalent temperature gradient and thermal coefficient of Portland Cement Concrete (PCC layers. Several sensitivity charts were developed by examining the sensitivity of critical pavement responses to each input variation. Sensitivity evaluations were performed using a normalized sensitivity index (NSI as the quantitative metric. Using such sensitivity evaluation, the most significant NIKE3D-FAA input parameters for generating an effective synthetic database that will lower computational cost for future modeling developments were identified. Keywords: Sensitivity analysis, Airfield concrete pavement, Finite element analysis, Top down cracking

  13. Two planar polishing methods by using FIB technique: Toward ultimate top-down delayering for failure analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, D. D., E-mail: dandan.wang@globalfoundries.com; Huang, Y. M.; Tan, P. K.; Feng, H.; Low, G. R.; Yap, H. H.; He, R.; Tan, H.; Dawood, M. K.; Zhao, Y. Z.; Lam, J.; Mai, Z. H. [GLOBALFOUNDRIES Singapore Pte. Ltd, 60 Woodlands Industrial Park D Street 2, Singapore 738406 (Singapore)

    2015-12-15

    Presently two major limiting factors are hindering the failure analysis (FA) development during the semiconductor manufacturing process and technology improvement: (1) Impossibility of manual polishing on the edge dies due to the amenability of layer peeling off; (2) Abundant demand of multi-locations FA, especially focusing different levels of layers simultaneously. Aiming at resolving these limitations, here we demonstrate two unique high precision polishing methods by using focused ion beam (FIB) technique. One is the vertical top down chemical etching at the aimed location; the other one is the planar top down slicing. Using the FIB for delayering not only solves these problems mentioned above, but also offers significant advantages over physical planar polishing methods such as: (1) having a better control of the delayering progress, (2) enabling precisely milling at a region of interest, (3) providing the prevention of over-delayering and (4) possessing capability to capture images at the region of interest simultaneously and cut into the die directly to expose the exact failure without damaging other sections of the specimen.

  14. Elucidating Host-Pathogen Interactions Based on Post-Translational Modifications Using Proteomics Approaches

    DEFF Research Database (Denmark)

    Ravikumar, Vaishnavi; Jers, Carsten; Mijakovic, Ivan

    2015-01-01

    can be efficiently applied to gain an insight into the molecular mechanisms involved. The measurement of the proteome and post-translationally modified proteome dynamics using mass spectrometry, results in a wide array of information, such as significant changes in protein expression, protein...... display host specificity through a complex network of molecular interactions that aid their survival and propagation. Co-infection states further lead to complications by increasing the microbial burden and risk factors. Quantitative proteomics based approaches and post-translational modification analysis...... pathogen interactions....

  15. A Proteomic Approach to Investigating Gene Cluster Expression and Secondary Metabolite Functionality in Aspergillus fumigatus

    Science.gov (United States)

    Owens, Rebecca A.; Hammel, Stephen; Sheridan, Kevin J.; Jones, Gary W.; Doyle, Sean

    2014-01-01

    A combined proteomics and metabolomics approach was utilised to advance the identification and characterisation of secondary metabolites in Aspergillus fumigatus. Here, implementation of a shotgun proteomic strategy led to the identification of non-redundant mycelial proteins (n = 414) from A. fumigatus including proteins typically under-represented in 2-D proteome maps: proteins with multiple transmembrane regions, hydrophobic proteins and proteins with extremes of molecular mass and pI. Indirect identification of secondary metabolite cluster expression was also achieved, with proteins (n = 18) from LaeA-regulated clusters detected, including GliT encoded within the gliotoxin biosynthetic cluster. Biochemical analysis then revealed that gliotoxin significantly attenuates H2O2-induced oxidative stress in A. fumigatus (p>0.0001), confirming observations from proteomics data. A complementary 2-D/LC-MS/MS approach further elucidated significantly increased abundance (pproteome and experimental strategies, plus mechanistic data pertaining to gliotoxin functionality in the organism. PMID:25198175

  16. Skeletal muscle proteomics: current approaches, technical challenges and emerging techniques

    LENUS (Irish Health Repository)

    Ohlendieck, Kay

    2011-02-01

    Abstract Background Skeletal muscle fibres represent one of the most abundant cell types in mammals. Their highly specialised contractile and metabolic functions depend on a large number of membrane-associated proteins with very high molecular masses, proteins with extensive posttranslational modifications and components that exist in highly complex supramolecular structures. This makes it extremely difficult to perform conventional biochemical studies of potential changes in protein clusters during physiological adaptations or pathological processes. Results Skeletal muscle proteomics attempts to establish the global identification and biochemical characterisation of all members of the muscle-associated protein complement. A considerable number of proteomic studies have employed large-scale separation techniques, such as high-resolution two-dimensional gel electrophoresis or liquid chromatography, and combined them with mass spectrometry as the method of choice for high-throughput protein identification. Muscle proteomics has been applied to the comprehensive biochemical profiling of developing, maturing and aging muscle, as well as the analysis of contractile tissues undergoing physiological adaptations seen in disuse atrophy, physical exercise and chronic muscle transformation. Biomedical investigations into proteome-wide alterations in skeletal muscle tissues were also used to establish novel biomarker signatures of neuromuscular disorders. Importantly, mass spectrometric studies have confirmed the enormous complexity of posttranslational modifications in skeletal muscle proteins. Conclusions This review critically examines the scientific impact of modern muscle proteomics and discusses its successful application for a better understanding of muscle biology, but also outlines its technical limitations and emerging techniques to establish new biomarker candidates.

  17. Top-Down Mechanism Design Study for Multi-UAV Search and Surveillance

    National Research Council Canada - National Science Library

    Godfrey, Gregory A

    2005-01-01

    ... (stationary and mobile, random walkers). There are two primary breakthroughs. The first is a value potential approach to optimizing search paths based on approximating an infinite-horizon search plan...

  18. Top-Down Modulation of Auditory-Motor Integration during Speech Production: The Role of Working Memory.

    Science.gov (United States)

    Guo, Zhiqiang; Wu, Xiuqin; Li, Weifeng; Jones, Jeffery A; Yan, Nan; Sheft, Stanley; Liu, Peng; Liu, Hanjun

    2017-10-25

    Although working memory (WM) is considered as an emergent property of the speech perception and production systems, the role of WM in sensorimotor integration during speech processing is largely unknown. We conducted two event-related potential experiments with female and male young adults to investigate the contribution of WM to the neurobehavioural processing of altered auditory feedback during vocal production. A delayed match-to-sample task that required participants to indicate whether the pitch feedback perturbations they heard during vocalizations in test and sample sequences matched, elicited significantly larger vocal compensations, larger N1 responses in the left middle and superior temporal gyrus, and smaller P2 responses in the left middle and superior temporal gyrus, inferior parietal lobule, somatosensory cortex, right inferior frontal gyrus, and insula compared with a control task that did not require memory retention of the sequence of pitch perturbations. On the other hand, participants who underwent extensive auditory WM training produced suppressed vocal compensations that were correlated with improved auditory WM capacity, and enhanced P2 responses in the left middle frontal gyrus, inferior parietal lobule, right inferior frontal gyrus, and insula that were predicted by pretraining auditory WM capacity. These findings indicate that WM can enhance the perception of voice auditory feedback errors while inhibiting compensatory vocal behavior to prevent voice control from being excessively influenced by auditory feedback. This study provides the first evidence that auditory-motor integration for voice control can be modulated by top-down influences arising from WM, rather than modulated exclusively by bottom-up and automatic processes. SIGNIFICANCE STATEMENT One outstanding question that remains unsolved in speech motor control is how the mismatch between predicted and actual voice auditory feedback is detected and corrected. The present study

  19. Top-down NOX Emissions of European Cities Derived from Modelled and Spaceborne Tropospheric NO2 Columns

    Science.gov (United States)

    Verstraeten, W. W.; Boersma, K. F.; Douros, J.; Williams, J. E.; Eskes, H.; Delcloo, A. W.

    2017-12-01

    High nitrogen oxides (NOX = NO + NO2) concentrations near the surface impact humans and ecosystems badly and play a key role in tropospheric chemistry. NO2 is an important precursor of tropospheric ozone (O3) which in turn affects the production of the hydroxyl radical controlling the chemical lifetime of key atmospheric pollutants and reactive greenhouse gases. Combustion from industrial, traffic and household activities in large and densely populated urban areas result in high NOX emissions. Accurate mapping of these emissions is essential but hard to do since reported emissions factors may differ from real-time emissions in order of magnitude. Modelled NO2 levels and lifetimes also have large associated uncertainties and overestimation in the chemical lifetime which may mask missing NOX chemistry in current chemistry transport models (CTM's). The simultaneously estimation of both the NO2 lifetime and as well as the concentrations by applying the Exponentially Modified Gaussian (EMG) method on tropospheric NO2 columns lines densities should improve the surface NOX emission estimates. Here we evaluate if the EMG methodology applied on the tropospheric NO2 columns simulated by the LOTOS-EUROS (Long Term Ozone Simulation-European Ozone Simulation) CTM can reproduce the NOX emissions used as model input. First we process both the modelled tropospheric NO2 columns for the period April-September 2013 for 21 selected European urban areas under windy conditions (averaged vertical wind speeds between surface and 500 m from ECMWF > 2 m s-1) as well as the accompanying OMI (Ozone Monitoring Instrument) data providing us with real-time observation-based estimates of midday NO2 columns. Then we compare the top-down derived surface NOX emissions with the 2011 MACC-III emission inventory, used in the CTM as input to simulate the NO2 columns. For cities where NOX emissions can be assumed as originating from one large source good agreement is found between the top-down derived

  20. Proteomics

    DEFF Research Database (Denmark)

    Tølbøll, Trine Højgaard; Danscher, Anne Mette; Andersen, Pia Haubro

    2012-01-01

    to current research strategies there is a need to develop novel approaches and methods that expand understanding of the disease mechanisms involved in CHD. The objectives of the present study were to explore the potential of liquid chromatography tandem mass spectrometry (LC–MS/MS) in mapping protein...... expression in three different bovine claw tissues, and to provide a relevant functional annotation of the proteins characterized in these tissues. LC–MS/MS was used to characterize protein expression in coronary band skin (C), claw dermal (D) and lamellar (L) tissues from two heifers. A total of 388...... different proteins were identified, with 146 proteins available for identification in C, 279 proteins in D and 269 proteins in L. A functional annotation of the identified proteins was obtained using the on-line Blast2GO tool. Three hundred and sixteen of the identified proteins could be subsequently...

  1. An efficient proteomic approach to analyze agriculture crop biomass

    Czech Academy of Sciences Publication Activity Database

    Flodrová, Dana; Bobálová, Janette

    2013-01-01

    Roč. 32, č. 5 (2013), s. 365-372 ISSN 1572-3887 R&D Projects: GA MŠk 1M0570 Institutional support: RVO:68081715 Keywords : MALDI * biomass * proteomics * identification * hemicellulases Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 1.039, year: 2013

  2. From protein catalogues towards targeted proteomics approaches in cereal grains

    DEFF Research Database (Denmark)

    Finnie, Christine; Sultan, Abida; Grasser, Klaus D.

    2011-01-01

    Due to their importance for human nutrition, the protein content of cereal grains has been a subject of intense study for over a century and cereal grains were not surprisingly one of the earliest subjects for 2D-gel-based proteome analysis. Over the last two decades, countless cereal grain prote...

  3. Closing the gap? Top-down versus bottom-up projections of China's regional energy use and CO2 emissions

    DEFF Research Database (Denmark)

    Dai, Hancheng; Mischke, Peggy; Xie, Xuxuan

    2016-01-01

    . The study finds that it is beneficial to soft-link complex global models under harmonized assumptions. Although this study fails to "close the gap" between the two models completely, the experiences and insights shared here will be beneficial for researchers and policy makers that are drawing conclusions......As the world's largest CO2 emitter, China is a prominent case study for scenario analysis. This study uses two newly developed global top-down and bottom-up models with a regional China focus to compare China's future energy and CO2 emission pathways toward 2050. By harmonizing the economic...... and demographic trends as well as a carbon tax pathway, we explore how both models respond to these identical exogenous inputs. Then a soft-linking methodology is applied to "narrow the gap" between the results computed by these models. We find for example that without soft-linking, China's baseline CO2 emissions...

  4. Top-down regulation of left temporal cortex by hypnotic amusia for rhythm: a pilot study on mismatch negativity.

    Science.gov (United States)

    Facco, Enrico; Ermani, Mario; Rampazzo, Patrizia; Tikhonoff, Valérie; Saladini, Marina; Zanette, Gastone; Casiglia, Edoardo; Spiegel, David

    2014-01-01

    To evaluate the effect of hypnotically induced amusia for rhythm (a condition in which individuals are unable to recognize melodies or rhythms) on mismatch negativity (MMN), 5 highly (HH) and 5 poorly (LH) hypnotizable nonmusician volunteers underwent MMN recording before and during a hypnotic suggestion for amusia. MMN amplitude was recorded using a 19-channel montage and then processed using the low-resolution electromagnetic tomography (LORETA) to localize its sources. MMN amplitude was significantly decreased during hypnotic amusia (p < .04) only in HH, where the LORETA maps of MMN showed a decreased source amplitude in the left temporal lobe, suggesting a hypnotic top-down regulation of activity of these areas and that these changes can be assessed by neurophysiological investigations.

  5. Social Top-down Response Modulation (STORM: A model of the control of mimicry in social interaction

    Directory of Open Access Journals (Sweden)

    Yin eWang

    2012-06-01

    Full Text Available As a distinct feature of human social interactions, spontaneous mimicry has been widely investigated in the past decade. Research suggests that mimicry is a subtle and flexible social behaviour which plays an important role for communication and affiliation. However, fundamental questions like why and how people mimic still remain unclear. In this paper, we evaluate past theories of why people mimic and the brain systems that implement mimicry in social psychology and cognitive neuroscience. By reviewing recent behavioural and neuroimaging studies on the control of mimicry by social signals, we conclude that the subtlety and sophistication of mimicry in social contexts reflect a social top-down response modulation (STORM which increases one’s social advantage and this mechanism is most likely implemented by medial prefrontal cortex. We suggest that this STORM account of mimicry is important for our understanding of social behaviour and social cognition, and provides implications for future research in autism.

  6. Top-down constraints on methane and non-methane hydrocarbon emissions in the US Four Corners

    Science.gov (United States)

    Petron, G.; Miller, B. R.; Vaughn, B. H.; Kofler, J.; Mielke-Maday, I.; Sherwood, O.; Schwietzke, S.; Conley, S.; Sweeney, C.; Dlugokencky, E. J.; White, A. B.; Tans, P. P.; Schnell, R. C.

    2017-12-01

    A NASA and NOAA supported field campaign took place in the US Four Corners in April 2015 to further investigate a regional "methane hotspot" detected from space. The Four Corners region is home to the fossil fuel rich San Juan Basin, which extends between SE Colorado and NE New Mexico. The area has been extracting coal, oil and natural gas for decades. Degassing from the Fruitland coal outcrop on the Colorado side has also been reported. Instrumented aircraft, vans and ground based wind profilers were deployed for the campaign with the goal to quantify and attribute methane and non-methane hydrocarbon emissions in the region. A new comprehensive analysis of the campaign data sets will be presented and top-down emission estimates for methane and ozone precursors will be compared with available bottom-up estimates.

  7. Mindfulness starts with the body: Somatosensory attention and top-down modulation of cortical alpha rhythms in mindfulness meditation

    Directory of Open Access Journals (Sweden)

    Catherine E Kerr

    2013-02-01

    Full Text Available Mindfulness Based Stress Reduction (MBSR and Mindfulness Based Cognitive Therapy (MBCT use a common set of exercises to reduce distress in chronic pain and decrease risk of depression relapse. These standardized mindfulness (ST-Mindfulness practices predominantly require attending to breath and body sensations. Here, we offer a novel view of ST-Mindfulness’s somatic focus as a form of training for optimizing attentional modulation of 7-14 Hz alpha rhythms that play a key role in filtering inputs to primary sensory neocortex and organizing the flow of sensory information. In support of the framework, we describe our previous finding (Kerr et al, 2011 that ST-Mindfulness enhanced attentional regulation of alpha in primary somatosensory cortex (SI. The framework allows us to make several predictions. In chronic pain, we predict somatic attention in ST-Mindfulness de-biases alpha in SI, freeing up pain-focused attentional resources. In depression relapse, we predict ST-Mindfulness’s somatic attention competes with internally focused rumination, as internally focused cognitive processes (e.g., working and short term memory rely on alpha filtering of sensory input. Our computational model (Jones et al, 2009 predicts ST-Mindfulness enhances top-down modulation of alpha by facilitating precise alterations in timing and efficacy of SI thalamocortical inputs. We conclude by considering how the proposed framework aligns with Buddhist teachings that mindfulness starts with mindfulness of the body. Translating this theory into neurophysiology, we hypothesize that with its somatic focus, mindfulness’ top-down alpha rhythm modulation in SI enhances gain control which, in turn, sensitizes practitioners to better detect and regulate when the mind wanders from its somatic focus. This enhanced regulation of somatic mind-wandering may be an early stage of mindfulness training, leading to cognitive regulation and metacognition.

  8. Identification of top-down forces regulating cotton aphid population growth in transgenic Bt cotton in central China.

    Directory of Open Access Journals (Sweden)

    Peng Han

    Full Text Available The cotton aphid Aphis gossypii Glover is the main aphid pest in cotton fields in the Yangtze River Valley Cotton-planting Zone (YRZ in central China. Various natural enemies may attack the cotton aphid in Bt cotton fields but no studies have identified potential specific top-down forces that could help manage this pest in the YRZ in China. In order to identify possibilities for managing the cotton aphid, we monitored cotton aphid population dynamics and identified the effect of natural enemies on cotton aphid population growth using various exclusion cages in transgenic Cry1Ac (Bt+CpTI (Cowpea trypsin inhibitor cotton field in 2011. The aphid population growth in the open field (control was significantly lower than those protected or restricted from exposure to natural enemies in the various exclusion cage types tested. The ladybird predator Propylaea japonica Thunberg represented 65% of Coccinellidae predators, and other predators consisted mainly of syrphids (2.1% and spiders (1.5%. The aphid parasitoids Aphidiines represented 76.7% of the total count of the natural enemy guild (mainly Lysiphlebia japonica Ashmead and Binodoxys indicus Subba Rao & Sharma. Our results showed that P. japonica can effectively delay the establishment and subsequent population growth of aphids during the cotton growing season. Aphidiines could also reduce aphid density although their impact may be shadowed by the presence of coccinellids in the open field (likely both owing to resource competition and intraguild predation. The implications of these results are discussed in a framework of the compatibility of transgenic crops and top-down forces exerted by natural enemy guild.

  9. The effect of non-visual working memory load on top-down modulation of visual processing.

    Science.gov (United States)

    Rissman, Jesse; Gazzaley, Adam; D'Esposito, Mark

    2009-06-01

    While a core function of the working memory (WM) system is the active maintenance of behaviorally relevant sensory representations, it is also critical that distracting stimuli are appropriately ignored. We used functional magnetic resonance imaging to examine the role of domain-general WM resources in the top-down attentional modulation of task-relevant and irrelevant visual representations. In our dual-task paradigm, each trial began with the auditory presentation of six random (high load) or sequentially ordered (low load) digits. Next, two relevant visual stimuli (e.g., faces), presented amongst two temporally interspersed visual distractors (e.g., scenes), were to be encoded and maintained across a 7-s delay interval, after which memory for the relevant images and digits was probed. When taxed by high load digit maintenance, participants exhibited impaired performance on the visual WM task and a selective failure to attenuate the neural processing of task-irrelevant scene stimuli. The over-processing of distractor scenes under high load was indexed by elevated encoding activity in a scene-selective region-of-interest relative to low load and passive viewing control conditions, as well as by improved long-term recognition memory for these items. In contrast, the load manipulation did not affect participants' ability to upregulate activity in this region when scenes were task-relevant. These results highlight the critical role of domain-general WM resources in the goal-directed regulation of distractor processing. Moreover, the consequences of increased WM load in young adults closely resemble the effects of cognitive aging on distractor filtering [Gazzaley, A., Cooney, J. W., Rissman, J., & D'Esposito, M. (2005). Top-down suppression deficit underlies working memory impairment in normal aging. Nature Neuroscience 8, 1298-1300], suggesting the possibility of a common underlying mechanism.

  10. Incentives for Collaborative Governance: Top-Down and Bottom-Up Initiatives in the Swedish Mountain Region

    Directory of Open Access Journals (Sweden)

    Katarina Eckerberg

    2015-08-01

    Full Text Available Governance collaborations between public and private partners are increasingly used to promote sustainable mountain development, yet information is limited on their nature and precise extent. This article analyzes collaboration on environment and natural resource management in Swedish mountain communities to critically assess the kinds of issues these efforts address, how they evolve, who leads them, and what functional patterns they exhibit based on Margerum's (2008 typology of action, organizational, and policy collaboration. Based on official documents, interviews, and the records of 245 collaborative projects, we explore the role of the state, how perceptions of policy failure may inspire collaboration, and the opportunities that European Union funds have created. Bottom-up collaborations, most of which are relatively recent, usually have an action and sometimes an organizational function. Top-down collaborations, however, are usually organizational or policy oriented. Our findings suggest that top-down and bottom-up collaborations are complementary in situations with considerable conflict over time and where public policies have partly failed, such as for nature protection and reindeer grazing. In less contested areas, such as rural development, improving tracks and access, recreation, and fishing, there is more bottom-up, action-oriented collaboration. State support, especially in the form of funding, is central to explaining the emergence of bottom-up action collaboration. Our findings show that the state both initiates and coordinates policy networks and retains a great deal of power over the nature and functioning of collaborative governance. A practical consequence is that there is great overlap—aggravated by sectorized approaches—that creates a heavy workload for some regional partners.

  11. Look at the Beat, Feel the Meter: Top-Down Effects of Meter Induction on Auditory and Visual Modalities.

    Science.gov (United States)

    Celma-Miralles, Alexandre; de Menezes, Robert F; Toro, Juan M

    2016-01-01

    Recent research has demonstrated top-down effects on meter induction in the auditory modality. However, little is known about these effects in the visual domain, especially without the involvement of motor acts such as tapping. In the present study, we aim to assess whether the projection of meter on auditory beats is also present in the visual domain. We asked 16 musicians to internally project binary (i.e., a strong-weak pattern) and ternary (i.e., a strong-weak-weak pattern) meter onto separate, but analog, visual and auditory isochronous stimuli. Participants were presented with sequences of tones or blinking circular shapes (i.e., flashes) at 2.4 Hz while their electrophysiological responses were recorded. A frequency analysis of the elicited steady-state evoked potentials allowed us to compare the frequencies of the beat (2.4 Hz), its first harmonic (4.8 Hz), the binary subharmonic (1.2 Hz), and the ternary subharmonic (0.8 Hz) within and across modalities. Taking the amplitude spectra into account, we observed an enhancement of the amplitude at 0.8 Hz in the ternary condition for both modalities, suggesting meter induction across modalities. There was an interaction between modality and voltage at 2.4 and 4.8 Hz. Looking at the power spectra, we also observed significant differences from zero in the auditory, but not in the visual, binary condition at 1.2 Hz. These findings suggest that meter processing is modulated by top-down mechanisms that interact with our perception of rhythmic events and that such modulation can also be found in the visual domain. The reported cross-modal effects of meter may shed light on the origins of our timing mechanisms, partially developed in primates and allowing humans to synchronize across modalities accurately.

  12. Look at the Beat, Feel the Meter:Top-down Effects of Meter Induction on Auditory and Visual Modalities

    Directory of Open Access Journals (Sweden)

    Alexandre eCelma-Miralles

    2016-03-01

    Full Text Available Recent research has demonstrated top-down effects on meter induction in the auditory modality. However, little is known about these effects in the visual domain, especially without the involvement of motor acts such as tapping. In the present study, we aim to assess whether the projection of meter on auditory beats is also present in the visual domain. We asked sixteen musicians to internally project binary (i.e. a strong-weak pattern and ternary (i.e. a strong-weak-weak pattern meter onto separate, but analogue, visual and auditory isochronous stimuli. Participants were presented with sequences of tones or blinking circular shapes (i.e. flashes at 2.4 Hz while their electrophysiological responses were recorded. A frequency analysis of the elicited steady-state evoked potentials allowed us to compare the frequencies of the beat (2.4 Hz, its first harmonic (4.8 Hz, the binary subharmonic (1.2 Hz, and ternary subharmonic (0.8 Hz within and across modalities. Taking the amplitude spectra into account, we observed an enhancement of the amplitude at 0.8 Hz in the ternary condition for both modalities, suggesting meter induction across modalities. There was an interaction between modality and voltage at 2.4 and 4.8 Hz. Looking at the power spectra, we also observed significant differences from zero in the auditory, but not in the visual, binary condition at 1.2 Hz. These findings suggest that meter processing is modulated by top-down mechanisms that interact with our perception of rhythmic events and that such modulation can also be found in the visual domain. The reported cross-modal effects of meter may shed light on the origins of our timing mechanisms, partially developed in primates and allowing humans to synchronize across modalities accurately.

  13. All is not lost: Deriving a top-down mass budget of plastic at sea.

    OpenAIRE

    Koelmans, Bart; Kooi, Merel; Law, Kara Lavender; Sebille, van, Erik

    2017-01-01

    Understanding the global mass inventory is one of the main challenges in present research on plastic marine debris. Especially the fragmentation and vertical transport processes of oceanic plastic are poorly understood. However, whereas fragmentation rates are unknown, information on plastic emissions, concentrations of plastics in the ocean surface layer (OSL) and fragmentation mechanisms is available. Here, we apply a systems engineering analytical approach and propose a tentative 'whole oc...

  14. Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics

    Science.gov (United States)

    Kocevar, Nina; Komel, Radovan

    2014-01-01

    Despite remarkable progress in proteomic methods, including improved detection limits and sensitivity, these methods have not yet been established in routine clinical practice. The main limitations, which prevent their integration into clinics, are high cost of equipment, the need for highly trained personnel, and last, but not least, the establishment of reliable and accurate protein biomarkers or panels of protein biomarkers for detection of neoplasms. Furthermore, the complexity and heterogeneity of most solid tumours present obstacles in the discovery of specific protein signatures, which could be used for early detection of cancers, for prediction of disease outcome, and for determining the response to specific therapies. However, cancer proteome, as the end-point of pathological processes that underlie cancer development and progression, could represent an important source for the discovery of new biomarkers and molecular targets for tailored therapies. PMID:24550697

  15. Exploration on the new model of the top-down nurse training%探索由上至下的护理进修新模式

    Institute of Scientific and Technical Information of China (English)

    李峰

    2009-01-01

    在城乡医院对口支援制度的背景依托下探讨由上致下的护理进修培训模式.以因地制宜的个体化就地培训,最大化实现护理进修成果对医疗单位的优势互补及有限医疗护理资源的空间流通,达到基层医院与上级医院的互动双赢.%This article discusses the top-down nurse training approach, under the "Hand-in-Hand Aid" policy between city hospitals and rural hospitals. Nursing specialist offers on-site individualized help to its counterpart in the lower level unit by adjusting measures and taking actions that suit local circumstances, thus enhance partnership assistance and the allocation of nursing human resources. The correspondent supports between the two sides will help create a double-win complexion which will benefit both the helper and the helped.

  16. Top-down impact through a bottom-up mechanism: the effect of limpet grazing on growth, productivity and carbon allocation of Zostera marina L. (eelgrass).

    Science.gov (United States)

    Zimmerman, Richard C; Kohrs, Donald G; Alberte, Randall S

    1996-09-01

    The unusual appearance of a commensal eelgrass limpet [Tectura depicta (Berry)] from southern California at high density (up to 10 shoot -1 ) has coincided with the catastrophic decline of a subtidal Zostera marina L. meadow in Monterey Bay, California. Some commensal limpets graze the chloroplast-rich epidermis of eelgrass leaves, but were not known to affect seagrass growth or productivity. We evaluated the effect on eelgrass productivity of grazing by limpets maintained at natural densities (8±2 shoot -1 ) in a natural light mesocosm for 45 days. Growth rates, carbon reserves, root proliferation and net photosynthesis of grazed plants were 50-80% below those of ungrazed plants, but biomass-specific respiration was unaffected. The daily period of irradiance-saturated photosynthesis (H sat ) needed to maintain positive carbon balance in grazed plants approached 13.5 h, compared with 5-6 h for ungrazed plants. The amount of carbon allocated to roots of ungrazed plants was 800% higher than for grazed plants. By grazing the chlorophyll-rich epidermis, T. depicta induced carbon limitation in eelgrass growing in an other-wise light-replete environment. Continued northward movement of T. depicta, may have significant impacts on eelgrass production and population dynamics in the northeast Pacific, even thought this limpet consumes very little plant biomass. This interaction is a dramatic example of top-down control (grazing/predation) of eelgrass productivity and survival operating via a bottom-up mechanism (photosynthesis limitation).

  17. Visual cognition in disorders of consciousness: from V1 to top-down attention.

    Science.gov (United States)

    Monti, Martin M; Pickard, John D; Owen, Adrian M

    2013-06-01

    What is it like to be at the lower boundaries of consciousness? Disorders of consciousness such as coma, the vegetative state, and the minimally conscious state are among the most mysterious and least understood conditions of the human brain. Particularly complicated is the assessment of residual cognitive functioning and awareness for diagnostic, rehabilitative, legal, and ethical purposes. In this article, we present a novel functional magnetic resonance imaging exploration of visual cognition in a patient with a severe disorder of consciousness. This battery of tests, first developed in healthy volunteers, assesses increasingly complex transformations of visual information along a known caudal to rostral gradient from occipital to temporal cortex. In the first five levels, the battery assesses (passive) processing of light, color, motion, coherent shapes, and object categories (i.e., faces, houses). At the final level, the battery assesses the ability to voluntarily deploy visual attention in order to focus on one of two competing stimuli. In the patient, this approach revealed appropriate brain activations, undistinguishable from those seen in healthy and aware volunteers. In addition, the ability of the patient to focus one of two competing stimuli, and switch between them on command, also suggests that he retained the ability to access, to some degree, his own visual representations. Copyright © 2012 Wiley Periodicals, Inc.

  18. Top-Down, Routinized Reform in Low-Income, Rural Schools

    Directory of Open Access Journals (Sweden)

    Robert Bickel

    2000-02-01

    Full Text Available Since 1991, the National Science Foundation has funded fifty-nine state, urban, and rural systemic initiatives. The purpose of the initiatives is to promote achievement in math, science, and technology among all students, and to encourage schools and communities to secure the resources needed to maintain such outcomes. The Appalachian Rural Systemic Initiative (ARSI is a six-state consortium which focuses these efforts on low-income, rural schools. The primary means of accomplishing ARSI's aims is a one-day-one-school site visit, called a Program Improvement Review, done by an ARSI math or science expert. The centrally important Program Improvement Reviews, however, seem to be premised on unsubstantiated assumptions as to the static, easy-to-understand, easy-to-evaluate nature of educational achievement in rural Appalachian schools. As a result, the Reviews resemble exercises in early-twentieth century scientific management, and are unlikely to enhance achievement in science or math. Consequently, even if there is merit to the commonsense human capital approach to economic growth and development on which systemic initiatives are tacitly premised, this first- person account makes a case that desired payoffs are unlikely to follow from the work of ARSI.

  19. Chitosan and grape secondary metabolites: A proteomics and metabolomics approach

    Directory of Open Access Journals (Sweden)

    Bavaresco Luigi

    2017-01-01

    Full Text Available Chitosan is a polysaccharide obtained by deacetylation of chitin, and it is involved in defence mechanisms of plants toward diseases. In the present work, V. vinifera L. cv. Ortrugo, grafted on 420A rootstock was grown in pot and treated, at veraison, by 0.03% chitosan solution at cluster level. Just before the treatment (T0 and 24 hours (T1, 48 hours (T2, 72 hours (T3 and 10 days (T4 later, the concentration of stilbenic compounds was detected, and at T1 proteomics and metabolomics analyses were done. Proteomics relies on the analysis of the complete set of proteins existing in a given substrate, while metabolomics relies on the analyses of the complete set of metabolites in a given substrate. The treatment improved the stilbene concentration over the control at T1. Proteomic analysis showed that superoxide dismutase (SOD and phenylalanine ammonia-lyase (PAL were overexpressed in the treated grapes. SOD is known to be an enzyme active against reactive oxygen species (ROS while PAL is a key enzyme in the phenylpropanoids pathway. Metabolomics analysis highlighted the positive role of the treatment in improving the triperpenoid concentration (betulin, erythrodiol, uvaol, oleanolate; these compounds are known to be effective against microbes, insects and fungi.

  20. Merging bottom-up and top-down precipitation products using a stochastic error model

    Science.gov (United States)

    Maggioni, Viviana; Massari, Christian; Brocca, Luca; Ciabatta, Luca

    2017-04-01

    Accurate quantitative precipitation estimation is of great importance for water resources management, agricultural planning, and forecasting and monitoring of natural hazards such as flash floods and landslides. In situ observations are limited around the Earth, especially in remote areas (e.g., complex terrain, dense vegetation), but currently available satellite precipitation products are able to provide global precipitation estimates with an accuracy that depends upon many factors (e.g., type of storms, temporal sampling, season etc…). Recently, Brocca et al. (2014) have proposed an alternative approach (i.e., SM2RAIN) that allows to estimate rainfall from space by using satellite soil moisture observations. In contrast with classical satellite precipitation products which sense the cloud properties to retrieve the instantaneous precipitation, this new bottom-up approach makes use of two consecutive soil moisture measurements for obtaining an estimate of the fallen precipitation within the interval between two satellite passes. As a result, the nature of the measurement is different and complementary to the one of classical precipitation products and could provide a different valid perspective to improve current satellite rainfall estimates via appropriate integration between the products (i.e., SM2RAIN plus a classical satellite rainfall product). However, whether SM2RAIN is able or not to improve the performance of any state-of-the-art satellite rainfall product is much dependent upon an adequate quantification and characterization of the relative errors of the products. In this study, the stochastic rainfall error model SREM2D (Hossain et al. 2006) is used for characterizing the retrieval error of both SM2RAIN and a state-of-the-art satellite precipitation product (i.e., 3B42RT). The error characterization serves for an optimal integration between SM2RAIN and 3B42RT for enhancing the capability of the resulting integrated product (i.e. SM2RAIN+3B42RT) in

  1. All is not lost: deriving a top-down mass budget of plastic at sea

    Science.gov (United States)

    Koelmans, Albert A.; Kooi, Merel; Lavender Law, Kara; van Sebille, Erik

    2017-11-01

    Understanding the global mass inventory is one of the main challenges in present research on plastic marine debris. Especially the fragmentation and vertical transport processes of oceanic plastic are poorly understood. However, whereas fragmentation rates are unknown, information on plastic emissions, concentrations of plastics in the ocean surface layer (OSL) and fragmentation mechanisms is available. Here, we apply a systems engineering analytical approach and propose a tentative ‘whole ocean’ mass balance model that combines emission data, surface area-normalized plastic fragmentation rates, estimated concentrations in the OSL, and removal from the OSL by sinking. We simulate known plastic abundances in the OSL and calculate an average whole ocean apparent surface area-normalized plastic fragmentation rate constant, given representative radii for macroplastic and microplastic. Simulations show that 99.8% of the plastic that had entered the ocean since 1950 had settled below the OSL by 2016, with an additional 9.4 million tons settling per year. In 2016, the model predicts that of the 0.309 million tons in the OSL, an estimated 83.7% was macroplastic, 13.8% microplastic, and 2.5% was < 0.335 mm ‘nanoplastic’. A zero future emission simulation shows that almost all plastic in the OSL would be removed within three years, implying a fast response time of surface plastic abundance to changes in inputs. The model complements current spatially explicit models, points to future experiments that would inform critical model parameters, and allows for further validation when more experimental and field data become available.

  2. Transcriptomics-guided bottom-up and top-down venomics of neonate and adult specimens of the arboreal rear-fanged Brown Treesnake, Boiga irregularis, from Guam.

    Science.gov (United States)

    Pla, Davinia; Petras, Daniel; Saviola, Anthony J; Modahl, Cassandra M; Sanz, Libia; Pérez, Alicia; Juárez, Elena; Frietze, Seth; Dorrestein, Pieter C; Mackessy, Stephen P; Calvete, Juan J

    2018-03-01

    neonate and adult B. irregularis from Guam, further highlighting evolutionary trends in venom composition among rear-fanged venomous snakes. The Brown Treesnake (Boiga irregularis) has caused extensive ecological and economic damage to the island of Guam where it has become a classic example of the negative impacts of invasive species. In the current study, we report the first combined transcriptomic and proteomic analysis of B. irregularis venom of Guam origin. The transcriptome of an adult snake contained toxin sequences belonging to 18 protein families, with three-finger toxin (3FTx) isoforms being the most abundant and representing 94% of all venom protein transcript reads. Our bottom-up and top-down venomic analyses confirmed that 3FTxs are the major components of B. irregularis venom, and a comparative analysis of neonate and adult venoms demonstrate a clear ontogenetic shift in toxin abundance, likely driven by dietary variation between the two age classes. Second-generation antivenomics and Western blot analysis using purified anti-Brown Treesnake rabbit serum IgGs (anti-BTS IgGs) showed strong immunoreactivity toward B. irregularis venom. Interestingly, our anti-BTS IgGs did not cross-react with 3FTxs found in several other rear-fanged snake venoms, or against 3FTxs in the venom of the elapid Ophiophagus hannah, indicating that epitopes in these 3FTx molecules are quite distinct. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Study of monocyte membrane proteome perturbation during lipopolysaccharide-induced tolerance using iTRAQ-based quantitative proteomic approach

    KAUST Repository

    Zhang, Huoming; Zhao, Changqing; Li, Xin; Zhu, Yi; Gan, Chee Sian; Wang, Yong; Ravasi, Timothy; Qian, Pei-Yuan; Wong, Siew Cheng; Sze, Siu Kwan

    2010-01-01

    Human monocytes' exposure to low-level lipopolysaccharide (LPS) induces temporary monocytic insensitivity to subsequent LPS challenge. The underlying mechanism of this phenomenon could have important clinical utilities in preventing and/or treating severe infections. In this study, we used an iTRAQ-based quantitative proteomic approach to comprehensively characterize the membrane proteomes of monocytes before and after LPS exposure. We identified a total of 1651 proteins, of which 53.6% were membrane proteins. Ninety-four percent of the proteins were quantified and 255 proteins were shown to be tightly regulated by LPS. Subcellular location analysis revealed organelle-specific response to LPS exposure: more than 90% of identified mitochondrial membrane proteins were significant downregulated, whereas the majority of proteins from other organelles such as ER, Golgi and ribosome were upregulated. Moreover, we found that the expression of most receptors potentially involved in LPS signal pathway (CD14, toll-like receptor 4, CD11/CD18 complex) were substantially decreased, while the expression of molecules involved in LPS neutralization were enhanced after LPS challenge. Together, these findings could be of significance in understanding the mechanism of LPS tolerance and provide values for designing new approaches for regulating monocytic responses in sepsis patients.

  4. Study of monocyte membrane proteome perturbation during lipopolysaccharide-induced tolerance using iTRAQ-based quantitative proteomic approach

    KAUST Repository

    Zhang, Huoming

    2010-07-02

    Human monocytes\\' exposure to low-level lipopolysaccharide (LPS) induces temporary monocytic insensitivity to subsequent LPS challenge. The underlying mechanism of this phenomenon could have important clinical utilities in preventing and/or treating severe infections. In this study, we used an iTRAQ-based quantitative proteomic approach to comprehensively characterize the membrane proteomes of monocytes before and after LPS exposure. We identified a total of 1651 proteins, of which 53.6% were membrane proteins. Ninety-four percent of the proteins were quantified and 255 proteins were shown to be tightly regulated by LPS. Subcellular location analysis revealed organelle-specific response to LPS exposure: more than 90% of identified mitochondrial membrane proteins were significant downregulated, whereas the majority of proteins from other organelles such as ER, Golgi and ribosome were upregulated. Moreover, we found that the expression of most receptors potentially involved in LPS signal pathway (CD14, toll-like receptor 4, CD11/CD18 complex) were substantially decreased, while the expression of molecules involved in LPS neutralization were enhanced after LPS challenge. Together, these findings could be of significance in understanding the mechanism of LPS tolerance and provide values for designing new approaches for regulating monocytic responses in sepsis patients.

  5. A comparison of labeling and label-free mass spectrometry-based proteomics approaches.

    Science.gov (United States)

    Patel, Vibhuti J; Thalassinos, Konstantinos; Slade, Susan E; Connolly, Joanne B; Crombie, Andrew; Murrell, J Colin; Scrivens, James H

    2009-07-01

    The proteome of the recently discovered bacterium Methylocella silvestris has been characterized using three profiling and comparative proteomics approaches. The organism has been grown on two different substrates enabling variations in protein expression to be identified. The results obtained using the experimental approaches have been compared with respect to number of proteins identified, confidence in identification, sequence coverage and agreement of regulated proteins. The sample preparation, instrumental time and sample loading requirements of the differing experiments are compared and discussed. A preliminary screen of the protein regulation results for biological significance has also been performed.

  6. Energy-environment policy modeling of endogenous technological change with personal vehicles. Combining top-down and bottom-up methods

    International Nuclear Information System (INIS)

    Jaccard, Mark; Murphy, Rose; Rivers, Nic

    2004-01-01

    The transportation sector offers substantial potential for greenhouse gas (GHG) emission abatement, but widely divergent cost estimates complicate policy making; energy-economy policy modelers apply top-down and bottom-up cost definitions and different assumptions about future technologies and the preferences of firms and households. Our hybrid energy-economy policy model is technology-rich, like a bottom-up model, but has empirically estimated behavioral parameters for risk and technology preferences, like a top-down model. Unlike typical top-down models, however, it simulates technological change endogenously with functions that relate the financial costs of technologies to cumulative production and adjust technology preferences as market shares change. We apply it to the choice of personal vehicles to indicate, first, the effect on cost estimates of divergent cost definitions and, second, the possible response to policies that require a minimum market share for low emission vehicles

  7. Disentangling the Role of Cortico-Basal Ganglia Loops in Top-Down and Bottom-Up Visual Attention: An Investigation of Attention Deficits in Parkinson Disease.

    Science.gov (United States)

    Tommasi, Giorgio; Fiorio, Mirta; Yelnik, Jérôme; Krack, Paul; Sala, Francesca; Schmitt, Emmanuelle; Fraix, Valérie; Bertolasi, Laura; Le Bas, Jean-François; Ricciardi, Giuseppe Kenneth; Fiaschi, Antonio; Theeuwes, Jan; Pollak, Pierre; Chelazzi, Leonardo

    2015-06-01

    It is solidly established that top-down (goal-driven) and bottom-up (stimulus-driven) attention mechanisms depend on distributed cortical networks, including prefrontal and frontoparietal regions. On the other hand, it is less clear whether the BG also contribute to one or the other of these mechanisms, or to both. The current study was principally undertaken to clarify this issue. Parkinson disease (PD), a neurodegenerative disorder primarily affecting the BG, has proven to be an effective model for investigating the contribution of the BG to different brain functions; therefore, we set out to investigate deficits of top-down and bottom-up attention in a selected cohort of PD patients. With this objective in mind, we compared the performance on three computerized tasks of two groups of 12 parkinsonian patients (assessed without any treatment), one otherwise pharmacologically treated and the other also surgically treated, with that of a group of controls. The main behavioral tool for our study was an attentional capture task, which enabled us to tap the competition between top-down and bottom-up mechanisms of visual attention. This task was suitably combined with a choice RT and a simple RT task to isolate any specific deficit of attention from deficits in motor response selection and initiation. In the two groups of patients, we found an equivalent increase of attentional capture but also comparable delays in target selection in the absence of any salient distractor (reflecting impaired top-down mechanisms) and movement initiation compared with controls. In contrast, motor response selection processes appeared to be prolonged only in the operated patients. Our results confirm that the BG are involved in both motor and cognitive domains. Specifically, damage to the BG, as it occurs in PD, leads to a distinct deficit of top-down control of visual attention, and this can account, albeit indirectly, for the enhancement of attentional capture, reflecting weakened

  8. PTSD symptom severity is associated with increased recruitment of top-down attentional control in a trauma-exposed sample.

    Science.gov (United States)

    White, Stuart F; Costanzo, Michelle E; Blair, James R; Roy, Michael J

    2015-01-01

    Recent neuroimaging work suggests that increased amygdala responses to emotional stimuli and dysfunction within regions mediating top down attentional control (dorsomedial frontal, lateral frontal and parietal cortices) may be associated with the emergence of anxiety disorders, including posttraumatic stress disorder (PTSD). This report examines amygdala responsiveness to emotional stimuli and the recruitment of top down attention systems as a function of task demands in a population of U.S. military service members who had recently returned from combat deployment in Afghanistan/Iraq. Given current interest in dimensional aspects of pathophysiology, it is worthwhile examining patients who, while not meeting full PTSD criteria, show clinically significant functional impairment. Fifty-seven participants with sub-threshold levels of PTSD symptoms completed the affective Stroop task while undergoing fMRI. Participants with PTSD or depression at baseline were excluded. Greater PTSD symptom severity scores were associated with increased amygdala activation to emotional, particularly positive, stimuli relative to neutral stimuli. Furthermore, greater PTSD symptom severity was associated with increased superior/middle frontal cortex response during task conditions relative to passive viewing conditions. In addition, greater PTSD symptom severity scores were associated with: (i) increased activation in the dorsolateral prefrontal, lateral frontal, inferior parietal cortices and dorsomedial frontal cortex/dorsal anterior cingulate cortex (dmFC/dACC) in response to emotional relative to neutral stimuli; and (ii) increased functional connectivity during emotional trials, particularly positive trials, relative to neutral trials between the right amygdala and dmFC/dACC, left caudate/anterior insula cortex, right lentiform nucleus/caudate, bilateral inferior parietal cortex and left middle temporal cortex. We suggest that these data may reflect two phenomena associated with

  9. Lessons we learned from high-throughput and top-down systems biology analyses about glioma stem cells.

    Science.gov (United States)

    Mock, Andreas; Chiblak, Sara; Herold-Mende, Christel

    2014-01-01

    A growing body of evidence suggests that glioma stem cells (GSCs) account for tumor initiation, therapy resistance, and the subsequent regrowth of gliomas. Thus, continuous efforts have been undertaken to further characterize this subpopulation of less differentiated tumor cells. Although we are able to enrich GSCs, we still lack a comprehensive understanding of GSC phenotypes and behavior. The advent of high-throughput technologies raised hope that incorporation of these newly developed platforms would help to tackle such questions. Since