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.

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

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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.

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

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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.

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.

Top-Down Beta Enhances Bottom-Up Gamma.

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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.

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.

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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.

Comprehensive Characterization of Swine Cardiac Troponin T Proteoforms by Top-Down Mass Spectrometry

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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.

Sequencing Larger Intact Proteins (30-70 kDa) with Activated Ion Electron Transfer Dissociation

Science.gov (United States)

Riley, Nicholas M.; Westphall, Michael S.; Coon, Joshua J.

2018-01-01

The analysis of intact proteins via mass spectrometry can offer several benefits to proteome characterization, although the majority of top-down experiments focus on proteoforms in a relatively low mass range (AI-ETD) to proteins in the 30-70 kDa range. AI-ETD leverages infrared photo-activation concurrent to ETD reactions to improve sequence-informative product ion generation. This method generates more product ions and greater sequence coverage than conventional ETD, higher-energy collisional dissociation (HCD), and ETD combined with supplemental HCD activation (EThcD). Importantly, AI-ETD provides the most thorough protein characterization for every precursor ion charge state investigated in this study, making it suitable as a universal fragmentation method in top-down experiments. Additionally, we highlight several acquisition strategies that can benefit characterization of larger proteins with AI-ETD, including combination of spectra from multiple ETD reaction times for a given precursor ion, multiple spectral acquisitions of the same precursor ion, and combination of spectra from two different dissociation methods (e.g., AI-ETD and HCD). In all, AI-ETD shows great promise as a method for dissociating larger intact protein ions as top-down proteomics continues to advance into larger mass ranges. [Figure not available: see fulltext.

Top-Down and Bottom-Up Identification of Proteins by Liquid Extraction Surface Analysis Mass Spectrometry of Healthy and Diseased Human Liver Tissue

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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.

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.

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

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

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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.

DomSign: a top-down annotation pipeline to enlarge enzyme space in the protein universe.

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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

Hydrogen/deuterium exchange mass spectrometry with top-down electron capture dissociation for characterizing structural transitions of a 17 kDa protein.

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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

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

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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.

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

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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.

Characterization of Chlamydomonas reinhardtii Core Histones by Top-Down Mass Spectrometry Reveals Unique Algae-Specific Variants and Post-Translational Modifications.

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Khan, Aliyya; Eikani, Carlo K; Khan, Hana; Iavarone, Anthony T; Pesavento, James J

2018-01-05

The unicellular microalga Chlamydomonas reinhardtii has played an instrumental role in the development of many new fields (bioproducts, biofuels, etc.) as well as the advancement of basic science (photosynthetic apparati, flagellar function, etc.). Chlamydomonas' versatility ultimately derives from the genes encoded in its genome and the way that the expression of these genes is regulated, which is largely influenced by a family of DNA binding proteins called histones. We characterize C. reinhardtii core histones, both variants and their post-translational modifications, by chromatographic separation, followed by top-down mass spectrometry (TDMS). Because TDMS has not been previously used to study Chlamydomonas proteins, we show rampant artifactual protein oxidation using established nuclei purification and histone extraction methods. After addressing oxidation, both histones H3 and H4 are found to each have a single polypeptide sequence that is minimally acetylated and methylated. Surprisingly, we uncover a novel monomethylation at lysine 79 on histone H4 present on all observed molecules. Histone H2B and H2A are found to have two and three variants, respectively, and both are minimally modified. This study provides an updated assessment of the core histone proteins in the green alga C. reinhardtii by top-down mass spectrometry and lays the foundation for further investigation of these essential proteins.

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

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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.

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.

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,

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.

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

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

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.

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.

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.

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.

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…

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

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…

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.

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

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

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)

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.

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

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.

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…

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

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 ...

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.

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.

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

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.

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.

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.

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

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.

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

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.

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.

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

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.

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

Association of sequences in the coat protein/readthrough domain of potato mop-top virus with transmission by Spongospora subterranea.

Science.gov (United States)

Reavy, B; Arif, M; Cowan, G H; Torrance, L

1998-10-01

A monofungal culture of Spongospora subterranea was unable to acquire and transmit the T isolate of potato mop-top pomovirus (PMTV-T), which has been maintained by manual transmission in the laboratory for 30 years. A recently obtained field isolate (PMTV-S) was efficiently acquired and transmitted by the same fungus culture. Sequence analysis of the readthrough (RT) protein-coding region of PMTV-S showed the presence of an additional 543 nt in the 3' half of the coding region relative to that of PMTV-T. These additional nucleotides preserved the reading frame of the RT protein and inserted 181 amino acids into the RT protein. This was confirmed by a comparison by immunoblotting of the sizes of the RT protein of PMTV-T and other recent isolates of PMTV.

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...

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.

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...

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.

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

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...

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.

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.

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.

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.

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

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....

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.

Micropatterning stretched and aligned DNA for sequence-specific nanolithography

Science.gov (United States)

Petit, Cecilia Anna Paulette

Techniques for fabricating nanostructured materials can be categorized as either "top-down" or "bottom-up". Top-down techniques use lithography and contact printing to create patterned surfaces and microfluidic channels that can corral and organize nanoscale structures, such as molecules and nanorods in contrast; bottom-up techniques use self-assembly or molecular recognition to direct the organization of materials. A central goal in nanotechnology is the integration of bottom-up and top-down assembly strategies for materials development, device design; and process integration. With this goal in mind, we have developed strategies that will allow this integration by using DNA as a template for nanofabrication; two top-down approaches allow the placement of these templates, while the bottom-up technique uses the specific sequence of bases to pattern materials along each strand of DNA. Our first top-down approach, termed combing of molecules in microchannels (COMMIC), produces microscopic patterns of stretched and aligned molecules of DNA on surfaces. This process consists of passing an air-water interface over end adsorbed molecules inside microfabricated channels. The geometry of the microchannel directs the placement of the DNA molecules, while the geometry of the airwater interface directs the local orientation and curvature of the molecules. We developed another top-down strategy for creating micropatterns of stretched and aligned DNA using surface chemistry. Because DNA stretching occurs on hydrophobic surfaces, this technique uses photolithography to pattern vinyl-terminated silanes on glass When these surface-, are immersed in DNA solution, molecules adhere preferentially to the silanized areas. This approach has also proven useful in patterning protein for cell adhesion studies. Finally, we describe the use of these stretched and aligned molecules of DNA as templates for the subsequent bottom-up construction of hetero-structures through hybridization

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.

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.

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

'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

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.

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.

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

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.

Top-down and bottom-up: Front to back. Comment on "Move me, astonish me... delight my eyes and brain: The Vienna Integrated Model of top-down and bottom-up processes in Art Perception (VIMAP) and corresponding affective, evaluative, and neurophysiological correlates" by Matthew Pelowski et al.

Science.gov (United States)

Nadal, Marcos; Skov, Martin

2017-07-01

The model presented here [1] is the latest in an evolving series of psychological models aimed at explaining the experience of art, first proposed by Leder and colleagues [2]. The aim of this new version is to ;explicitly connect early bottom-up, artwork-derived processing sequence and outputs to top-down, viewer-derived contribution to the processing sequence; [1, p. 5f & 6]. The ;meeting; of these two processing sequences, the authors contend, is crucial to the understanding of people's responses to art [sections 3.6ff & 4], and therefore the new model's principal motivation.

''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

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...

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.

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.

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.

Prey vulnerability limits top-down control and alters reciprocal feedbacks in a subsidized model food web.

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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.

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

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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

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.

Top-Down Control of Visual Alpha Oscillations: Sources of Control Signals and Their Mechanisms of Action

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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

Identification of Tobacco Topping Responsive Proteins in Roots

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Hongxiang eGuo

2016-04-01

Full Text Available Tobacco plant has many responses to topping, such as the increase in ability of nicotine synthesis and secondary growth of roots. Some topping responsive miRNAs and genes had been identified in our previous work, but it is not enough to elaborate mechanism of tobacco response to topping. Here, topping responsive proteins were screened from tobacco roots with two-dimensional electrophoresis. Of these proteins, calretulin (CRT and Auxin-responsive protein IAA9 were related to the secondary growth of roots, LRR disease resistance, heat shock protein 70 and farnesyl pyrophosphate synthase 1（FPPS）were involved in wounding stress response, and F-box protein played an important role in promoting the ability of nicotine synthesis after topping. In addition, there were five tobacco bHLH proteins (NtbHLH, NtMYC1a, NtMYC1b, NtMYC2a and NtMYC2b related to nicotine synthesis. It was suggested that NtMYC2 might be the main positive transcription factor and NtbHLH protein is a negative regulator in the JA-mediating activation of nicotine synthesis after topping. Tobacco topping activates some comprehensive biology processes involving IAA and JA signaling pathway, and the identification of these proteins will be helpful to understand the process of topping response.

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.

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

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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.

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.

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.

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

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

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.

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

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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.

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.

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

Shotgun protein sequencing.

Energy Technology Data Exchange (ETDEWEB)

Faulon, Jean-Loup Michel; Heffelfinger, Grant S.

2009-06-01

A novel experimental and computational technique based on multiple enzymatic digestion of a protein or protein mixture that reconstructs protein sequences from sequences of overlapping peptides is described in this SAND report. This approach, analogous to shotgun sequencing of DNA, is to be used to sequence alternative spliced proteins, to identify post-translational modifications, and to sequence genetically engineered proteins.

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

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....

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.

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 ...

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.

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.

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.

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

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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.

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

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.

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.

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.

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.

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.

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

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.

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'…

Protein 3D structure computed from evolutionary sequence variation.

Directory of Open Access Journals (Sweden)

Debora S Marks

Full Text Available The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing.In this paper we ask whether we can infer evolutionary constraints from a set of sequence homologs of a protein. The challenge is to distinguish true co-evolution couplings from the noisy set of observed correlations. We address this challenge using a maximum entropy model of the protein sequence, constrained by the statistics of the multiple sequence alignment, to infer residue pair couplings. Surprisingly, we find that the strength of these inferred couplings is an excellent predictor of residue-residue proximity in folded structures. Indeed, the top-scoring residue couplings are sufficiently accurate and well-distributed to define the 3D protein fold with remarkable accuracy.We quantify this observation by computing, from sequence alone, all-atom 3D structures of fifteen test proteins from different fold classes, ranging in size from 50 to 260 residues, including a G-protein coupled receptor. These blinded inferences are de novo, i.e., they do not use homology modeling or sequence-similar fragments from known structures. The co-evolution signals provide sufficient information to determine accurate 3D protein structure to 2.7-4.8 Å C(α-RMSD error relative to the observed structure, over at least two-thirds of the protein (method called EVfold, details at http://EVfold.org. This discovery provides insight into essential interactions constraining protein evolution and will facilitate a comprehensive survey of the universe of

Front-End Electron Transfer Dissociation Coupled to a 21 Tesla FT-ICR Mass Spectrometer for Intact Protein Sequence Analysis

Science.gov (United States)

Weisbrod, Chad R.; Kaiser, Nathan K.; Syka, John E. P.; Early, Lee; Mullen, Christopher; Dunyach, Jean-Jacques; English, A. Michelle; Anderson, Lissa C.; Blakney, Greg T.; Shabanowitz, Jeffrey; Hendrickson, Christopher L.; Marshall, Alan G.; Hunt, Donald F.

2017-09-01

High resolution mass spectrometry is a key technology for in-depth protein characterization. High-field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) enables high-level interrogation of intact proteins in the most detail to date. However, an appropriate complement of fragmentation technologies must be paired with FTMS to provide comprehensive sequence coverage, as well as characterization of sequence variants, and post-translational modifications. Here we describe the integration of front-end electron transfer dissociation (FETD) with a custom-built 21 tesla FT-ICR mass spectrometer, which yields unprecedented sequence coverage for proteins ranging from 2.8 to 29 kDa, without the need for extensive spectral averaging (e.g., 60% sequence coverage for apo-myoglobin with four averaged acquisitions). The system is equipped with a multipole storage device separate from the ETD reaction device, which allows accumulation of multiple ETD fragment ion fills. Consequently, an optimally large product ion population is accumulated prior to transfer to the ICR cell for mass analysis, which improves mass spectral signal-to-noise ratio, dynamic range, and scan rate. We find a linear relationship between protein molecular weight and minimum number of ETD reaction fills to achieve optimum sequence coverage, thereby enabling more efficient use of instrument data acquisition time. Finally, real-time scaling of the number of ETD reactions fills during method-based acquisition is shown, and the implications for LC-MS/MS top-down analysis are discussed. [Figure not available: see fulltext.

Profiling of integral membrane proteins and their post translational modifications using high-resolution mass spectrometry

Science.gov (United States)

Souda, Puneet; Ryan, Christopher M.; Cramer, William A.; Whitelegge, Julian

2011-01-01

Integral membrane proteins pose challenges to traditional proteomics approaches due to unique physicochemical properties including hydrophobic transmembrane domains that limit solubility in aqueous solvents. A well resolved intact protein molecular mass profile defines a protein’s native covalent state including post-translational modifications, and is thus a vital measurement toward full structure determination. Both soluble loop regions and transmembrane regions potentially contain post-translational modifications that must be characterized if the covalent primary structure of a membrane protein is to be defined. This goal has been achieved using electrospray-ionization mass spectrometry (ESI-MS) with low-resolution mass analyzers for intact protein profiling, and high-resolution instruments for top-down experiments, toward complete covalent primary structure information. In top-down, the intact protein profile is supplemented by gas-phase fragmentation of the intact protein, including its transmembrane regions, using collisionally activated and/or electroncapture dissociation (CAD/ECD) to yield sequence-dependent high-resolution MS information. Dedicated liquid chromatography systems with aqueous/organic solvent mixtures were developed allowing us to demonstrate that polytopic integral membrane proteins are amenable to ESI-MS analysis, including top-down measurements. Covalent post-translational modifications are localized regardless of their position in transmembrane domains. Top-down measurements provide a more detail oriented high-resolution description of post-transcriptional and post-translational diversity for enhanced understanding beyond genomic translation. PMID:21982782

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

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)

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.

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.

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.

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.

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.

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.

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.

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.

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

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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.

Top-Down Historical Phonology of Rote-Meto

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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.

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).

The Comparative Effect of Top-down Processing and Bottom-up Processing through TBLT on Extrovert and Introvert EFL

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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.

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

Top-Down Enterprise Application Integration with Reference Models

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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.

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.

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.

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.

ToPS: a framework to manipulate probabilistic models of sequence data.

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André Yoshiaki Kashiwabara

Full Text Available Discrete Markovian models can be used to characterize patterns in sequences of values and have many applications in biological sequence analysis, including gene prediction, CpG island detection, alignment, and protein profiling. We present ToPS, a computational framework that can be used to implement different applications in bioinformatics analysis by combining eight kinds of models: (i independent and identically distributed process; (ii variable-length Markov chain; (iii inhomogeneous Markov chain; (iv hidden Markov model; (v profile hidden Markov model; (vi pair hidden Markov model; (vii generalized hidden Markov model; and (viii similarity based sequence weighting. The framework includes functionality for training, simulation and decoding of the models. Additionally, it provides two methods to help parameter setting: Akaike and Bayesian information criteria (AIC and BIC. The models can be used stand-alone, combined in Bayesian classifiers, or included in more complex, multi-model, probabilistic architectures using GHMMs. In particular the framework provides a novel, flexible, implementation of decoding in GHMMs that detects when the architecture can be traversed efficiently.

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

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

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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,

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

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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.

Attention, working memory, and phenomenal experience of WM content: memory levels determined by different types of top-down modulation.

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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.

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

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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.

Accumulation of evidence during sequential decision making: the importance of top-down factors.

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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.

Sequence walkers: a graphical method to display how binding proteins interact with DNA or RNA sequences | Center for Cancer Research

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A graphical method is presented for displaying how binding proteins and other macromolecules interact with individual bases of nucleotide sequences. Characters representing the sequence are either oriented normally and placed above a line indicating favorable contact, or upside-down and placed below the line indicating unfavorable contact. The positive or negative height of each letter shows the contribution of that base to the average sequence conservation of the binding site, as represented by a sequence logo.

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

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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…

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

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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

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

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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.

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

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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.

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

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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.

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

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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.

Resilience of Self-Organised and Top-Down Planned Cities--A Case Study on London and Beijing Street Networks.

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Jiaqiu Wang

Full Text Available The success or failure of the street network depends on its reliability. In this article, using resilience analysis, the author studies how the shape and appearance of street networks in self-organised and top-down planned cities influences urban transport. Considering London and Beijing as proxies for self-organised and top-down planned cities, the structural properties of London and Beijing networks first are investigated based on their primal and dual representations of planar graphs. The robustness of street networks then is evaluated in primal space and dual space by deactivating road links under random and intentional attack scenarios. The results show that the reliability of London street network differs from that of Beijing, which seems to rely more on its architecture and connectivity. It is found that top-down planned Beijing with its higher average degree in the dual space and assortativity in the primal space is more robust than self-organised London using the measures of maximum and second largest cluster size and network efficiency. The article offers an insight, from a network perspective, into the reliability of street patterns in self-organised and top-down planned city systems.

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.

Cortical gamma activity during auditory tone omission provides evidence for the involvement of oscillatory activity in top-down processing.

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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.

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

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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.

WildSpan: mining structured motifs from protein sequences

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Chen Chien-Yu

2011-03-01

Full Text Available Abstract Background Automatic extraction of motifs from biological sequences is an important research problem in study of molecular biology. For proteins, it is desired to discover sequence motifs containing a large number of wildcard symbols, as the residues associated with functional sites are usually largely separated in sequences. Discovering such patterns is time-consuming because abundant combinations exist when long gaps (a gap consists of one or more successive wildcards are considered. Mining algorithms often employ constraints to narrow down the search space in order to increase efficiency. However, improper constraint models might degrade the sensitivity and specificity of the motifs discovered by computational methods. We previously proposed a new constraint model to handle large wildcard regions for discovering functional motifs of proteins. The patterns that satisfy the proposed constraint model are called W-patterns. A W-pattern is a structured motif that groups motif symbols into pattern blocks interleaved with large irregular gaps. Considering large gaps reflects the fact that functional residues are not always from a single region of protein sequences, and restricting motif symbols into clusters corresponds to the observation that short motifs are frequently present within protein families. To efficiently discover W-patterns for large-scale sequence annotation and function prediction, this paper first formally introduces the problem to solve and proposes an algorithm named WildSpan (sequential pattern mining across large wildcard regions that incorporates several pruning strategies to largely reduce the mining cost. Results WildSpan is shown to efficiently find W-patterns containing conserved residues that are far separated in sequences. We conducted experiments with two mining strategies, protein-based and family-based mining, to evaluate the usefulness of W-patterns and performance of WildSpan. The protein-based mining mode

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...

How vision is shaped by language comprehension--top-down feedback based on low-spatial frequencies.

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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.

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

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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...

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

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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…

Top-down modulation of visual processing and knowledge after 250 ms supports object constancy of category decisions

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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.

Top-down modulation of visual processing and knowledge after 250 ms supports object constancy of category decisions.

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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.

Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate

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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.

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.

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

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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

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

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.

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

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.

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

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

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.

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

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...

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.

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.

Density- and trait-mediated top-down effects modify bottom-up control of a highly endemic tropical aquatic food web

Science.gov (United States)

C. M. Dalton; A. Mokiao-Lee; T. S. Sakihara; M. G. Weber; C. A. Roco; Z. Han; B. Dudley; R. A. MacKenzie; N. G. Hairston Jr.

2013-01-01

Benthic invertebrates mediate bottom–up and top–down influences in aquatic food webs, and changes in the abundance or traits of invertebrates can alter the strength of top–down effects. Studies assessing the role of invertebrate abundance and behavior as controls on food web structure are rare at the whole ecosystem scale. Here we use a comparative approach to...

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.

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.

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

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.

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.

Top-Down Modulation on the Perception and Categorization of Identical Pitch Contours in Speech and Music

Directory of Open Access Journals (Sweden)

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.

The Relationship between Response Time and the Strength of Top-Down Attentional Control: An ERP Study

Directory of Open Access Journals (Sweden)

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.

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.

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.

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....

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.

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

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.

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.

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.

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.

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....

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).

Protein sequence comparison and protein evolution

Energy Technology Data Exchange (ETDEWEB)

Pearson, W.R. [Univ. of Virginia, Charlottesville, VA (United States). Dept. of Biochemistry

1995-12-31

This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. This tutorial examines how the information conserved during the evolution of a protein molecule can be used to infer reliably homology, and thus a shared proteinfold and possibly a shared active site or function. The authors start by reviewing a geological/evolutionary time scale. Next they look at the evolution of several protein families. During the tutorial, these families will be used to demonstrate that homologous protein ancestry can be inferred with confidence. They also examine different modes of protein evolution and consider some hypotheses that have been presented to explain the very earliest events in protein evolution. The next part of the tutorial will examine the technical aspects of protein sequence comparison. Both optimal and heuristic algorithms and their associated parameters that are used to characterize protein sequence similarities are discussed. Perhaps more importantly, they survey the statistics of local similarity scores, and how these statistics can both be used to improve the selectivity of a search and to evaluate the significance of a match. They them examine distantly related members of three protein families, the serine proteases, the glutathione transferases, and the G-protein-coupled receptors (GCRs). Finally, the discuss how sequence similarity can be used to examine internal repeated or mosaic structures in proteins.

PredPPCrys: accurate prediction of sequence cloning, protein production, purification and crystallization propensity from protein sequences using multi-step heterogeneous feature fusion and selection.

Directory of Open Access Journals (Sweden)

Huilin Wang

Full Text Available X-ray crystallography is the primary approach to solve the three-dimensional structure of a protein. However, a major bottleneck of this method is the failure of multi-step experimental procedures to yield diffraction-quality crystals, including sequence cloning, protein material production, purification, crystallization and ultimately, structural determination. Accordingly, prediction of the propensity of a protein to successfully undergo these experimental procedures based on the protein sequence may help narrow down laborious experimental efforts and facilitate target selection. A number of bioinformatics methods based on protein sequence information have been developed for this purpose. However, our knowledge on the important determinants of propensity for a protein sequence to produce high diffraction-quality crystals remains largely incomplete. In practice, most of the existing methods display poorer performance when evaluated on larger and updated datasets. To address this problem, we constructed an up-to-date dataset as the benchmark, and subsequently developed a new approach termed 'PredPPCrys' using the support vector machine (SVM. Using a comprehensive set of multifaceted sequence-derived features in combination with a novel multi-step feature selection strategy, we identified and characterized the relative importance and contribution of each feature type to the prediction performance of five individual experimental steps required for successful crystallization. The resulting optimal candidate features were used as inputs to build the first-level SVM predictor (PredPPCrys I. Next, prediction outputs of PredPPCrys I were used as the input to build second-level SVM classifiers (PredPPCrys II, which led to significantly enhanced prediction performance. Benchmarking experiments indicated that our PredPPCrys method outperforms most existing procedures on both up-to-date and previous datasets. In addition, the predicted crystallization

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.”

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

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.

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

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.

Relative quantification of protein-protein interactions using a dual luciferase reporter pull-down assay system.

Directory of Open Access Journals (Sweden)

Shuaizheng Jia

Full Text Available The identification and quantitative analysis of protein-protein interactions are essential to the functional characterization of proteins in the post-proteomics era. The methods currently available are generally time-consuming, technically complicated, insensitive and/or semi-quantitative. The lack of simple, sensitive approaches to precisely quantify protein-protein interactions still prevents our understanding of the functions of many proteins. Here, we develop a novel dual luciferase reporter pull-down assay by combining a biotinylated Firefly luciferase pull-down assay with a dual luciferase reporter assay. The biotinylated Firefly luciferase-tagged protein enables rapid and efficient isolation of a putative Renilla luciferase-tagged binding protein from a relatively small amount of sample. Both of these proteins can be quantitatively detected using the dual luciferase reporter assay system. Protein-protein interactions, including Fos-Jun located in the nucleus; MAVS-TRAF3 in cytoplasm; inducible IRF3 dimerization; viral protein-regulated interactions, such as MAVS-MAVS and MAVS-TRAF3; IRF3 dimerization; and protein interaction domain mapping, are studied using this novel assay system. Herein, we demonstrate that this dual luciferase reporter pull-down assay enables the quantification of the relative amounts of interacting proteins that bind to streptavidin-coupled beads for protein purification. This study provides a simple, rapid, sensitive, and efficient approach to identify and quantify relative protein-protein interactions. Importantly, the dual luciferase reporter pull-down method will facilitate the functional determination of proteins.

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.

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…

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.

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.

HIV protein sequence hotspots for crosstalk with host hub proteins.

Directory of Open Access Journals (Sweden)

Mahdi Sarmady

Full Text Available HIV proteins target host hub proteins for transient binding interactions. The presence of viral proteins in the infected cell results in out-competition of host proteins in their interaction with hub proteins, drastically affecting cell physiology. Functional genomics and interactome datasets can be used to quantify the sequence hotspots on the HIV proteome mediating interactions with host hub proteins. In this study, we used the HIV and human interactome databases to identify HIV targeted host hub proteins and their host binding partners (H2. We developed a high throughput computational procedure utilizing motif discovery algorithms on sets of protein sequences, including sequences of HIV and H2 proteins. We identified as HIV sequence hotspots those linear motifs that are highly conserved on HIV sequences and at the same time have a statistically enriched presence on the sequences of H2 proteins. The HIV protein motifs discovered in this study are expressed by subsets of H2 host proteins potentially outcompeted by HIV proteins. A large subset of these motifs is involved in cleavage, nuclear localization, phosphorylation, and transcription factor binding events. Many such motifs are clustered on an HIV sequence in the form of hotspots. The sequential positions of these hotspots are consistent with the curated literature on phenotype altering residue mutations, as well as with existing binding site data. The hotspot map produced in this study is the first global portrayal of HIV motifs involved in altering the host protein network at highly connected hub nodes.

Trophic cascades of bottom-up and top-down forcing on nutrients and plankton in the Kattegat, evaluated by modelling

DEFF Research Database (Denmark)

Petersen, Marcell Elo; Maar, Marie; Larsen, Janus

2017-01-01

The aim of the study was to investigate the relative importance of bottom-up and top-down forcing on trophic cascades in the pelagic food-web and the implications for water quality indicators (summer phytoplankton biomass and winter nutrients) in relation to management. The 3D ecological model....... On annual basis, the system was more bottom-up than top-down controlled. Microzooplankton was found to play an important role in the pelagic food web as mediator of nutrient and energy fluxes. This study demonstrated that the best scenario for improved water quality was a combined reduction in nutrient...

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.

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.

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.

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.

Development of spatial integration depends on top-down and interhemispheric connections that can be perturbed in migraine: a DCM analysis.

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Fornari, Eleonora; Rytsar, Romana; Knyazeva, Maria G

2014-05-01

In humans, spatial integration develops slowly, continuing through childhood into adolescence. On the assumption that this protracted course depends on the formation of networks with slowly developing top-down connections, we compared effective connectivity in the visual cortex between 13 children (age 7-13) and 14 adults (age 21-42) using a passive perceptual task. The subjects were scanned while viewing bilateral gratings, which either obeyed Gestalt grouping rules [colinear gratings (CG)] or violated them [non-colinear gratings (NG)]. The regions of interest for dynamic causal modeling were determined from activations in functional MRI contrasts stimuli > background and CG > NG. They were symmetrically located in V1 and V3v areas of both hemispheres. We studied a common model, which contained reciprocal intrinsic and modulatory connections between these regions. An analysis of effective connectivity showed that top-down modulatory effects generated at an extrastriate level and interhemispheric modulatory effects between primary visual areas (all inhibitory) are significantly weaker in children than in adults, suggesting that the formation of feedback and interhemispheric effective connections continues into adolescence. These results are consistent with a model in which spatial integration at an extrastriate level results in top-down messages to the primary visual areas, where they are supplemented by lateral (interhemispheric) messages, making perceptual encoding more efficient and less redundant. Abnormal formation of top-down inhibitory connections can lead to the reduction of habituation observed in migraine patients.

Structural determination of intact proteins using mass spectrometry

Science.gov (United States)

Kruppa, Gary [San Francisco, CA; Schoeniger, Joseph S [Oakland, CA; Young, Malin M [Livermore, CA

2008-05-06

The present invention relates to novel methods of determining the sequence and structure of proteins. Specifically, the present invention allows for the analysis of intact proteins within a mass spectrometer. Therefore, preparatory separations need not be performed prior to introducing a protein sample into the mass spectrometer. Also disclosed herein are new instrumental developments for enhancing the signal from the desired modified proteins, methods for producing controlled protein fragments in the mass spectrometer, eliminating complex microseparations, and protein preparatory chemical steps necessary for cross-linking based protein structure determination.Additionally, the preferred method of the present invention involves the determination of protein structures utilizing a top-down analysis of protein structures to search for covalent modifications. In the preferred method, intact proteins are ionized and fragmented within the mass spectrometer.

Proton and photon absorbed-dose conversion coefficients for embryo and foetus from top-down irradiation geometry

International Nuclear Information System (INIS)

Chen, J.

2007-01-01

Absorbed-dose conversion coefficients are calculated for the embryo of 8 weeks and the foetus of 3, 6 or 9 months when the mother's body is exposed to protons and photons from top-down (TOP) direction. It provides data sets in addition to other standard irradiation geometries published previously. The TOP-irradiation geometry is considered here, because high-energy particles are often peaked from the TOP direction onboard aircraft. The results show that absorbed-doses from high-energy particles could be underestimated significantly if isotropic (ISO) irradiation geometry is assumed. For protons of 100 GeV, absorbed-doses from TOP irradiation are ∼2.3-2.9 times higher than the doses from ISO irradiation for different foetal ages. For 10 GeV photons, foetal doses from TOP irradiation are ∼6.8-12 times higher than the doses from ISO irradiation. The coefficients from TOP-irradiation geometry are given in wide energy ranges, from 100 MeV to 100 GeV for protons and from 50 V to 10 GeV for photons. They can, therefore, be used in various applications whenever exposure from the TOP-irradiation direction is concerned. (authors)

The Effect of Non-Visual Working Memory Load on Top-Down Modulation of Visual Processing

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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…

In situ atomic layer nitridation on the top and down regions of the amorphous and crystalline high-K gate dielectrics

Energy Technology Data Exchange (ETDEWEB)

Tsai, Meng-Chen [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Lee, Min-Hung [Institute of Electro-Optical Science and Technology, National Taiwan Normal University, Taipei 11677, Taiwan (China); Kuo, Chin-Lung; Lin, Hsin-Chih [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Chen, Miin-Jang, E-mail: mjchen@ntu.edu.tw [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan (China)

2016-11-30

Highlights: • The structural and electrical characteristics of the ZrO{sub 2} high-K dielectrics, treated with the in situ atomic layer doping of nitrogen into the top and down regions (top and down nitridation, TN and DN, respectively), were investigated. • The amorphous DN sample has a lower leakage current density (J{sub g}) than the amorphous TN sample, attributed to the formation of SiO{sub x}N{sub y} in the interfacial layer (IL). • The crystalline TN sample exhibited a lower CET and a similar J{sub g} as compared with the crystalline DN sample, which can be ascribed to the suppression of IL regrowth. • The crystalline ZrO{sub 2} with in situ atomic layer doping of nitrogen into the top region exhibited superior scaling limit, electrical characteristics, and reliability. - Abstract: Amorphous and crystalline ZrO{sub 2} gate dielectrics treated with in situ atomic layer nitridation on the top and down regions (top and down nitridation, abbreviated as TN and DN) were investigated. In a comparison between the as-deposited amorphous DN and TN samples, the DN sample has a lower leakage current density (J{sub g}) of ∼7 × 10{sup −4} A/cm{sup 2} with a similar capacitance equivalent thickness (CET) of ∼1.53 nm, attributed to the formation of SiO{sub x}N{sub y} in the interfacial layer (IL). The post-metallization annealing (PMA) leads to the transformation of ZrO{sub 2} from the amorphous to the crystalline tetragonal/cubic phase, resulting in an increment of the dielectric constant. The PMA-treated TN sample exhibits a lower CET of 1.22 nm along with a similar J{sub g} of ∼1.4 × 10{sup −5} A/cm{sup 2} as compared with the PMA-treated DN sample, which can be ascribed to the suppression of IL regrowth. The result reveals that the nitrogen engineering in the top and down regions has a significant impact on the electrical characteristics of amorphous and crystalline ZrO{sub 2} gate dielectrics, and the nitrogen incorporation at the top of crystalline

Imaging 'top-down' mobilization of visual information: a case study in a posterior split-brain patient.

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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.

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

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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.

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.

The Interaction of Top-Down and Bottom-Up Statistics in the Resolution of Syntactic Category Ambiguity

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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…

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

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.

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

Look at the Beat, Feel the Meter: Top-Down Effects of Meter Induction on Auditory and Visual Modalities.

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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.

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.

Top-down and bottom-up characterization of nitrated birch pollen allergen Bet v 1a with CZE hyphenated to an Orbitrap mass spectrometer.

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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.

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

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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.

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

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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.

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.

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

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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.

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

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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.

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

A calcineurin inhibitory protein overexpressed in Down's syndrome interacts with the product of a ubiquitously expressed transcript

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H.C.S. Silveira

2004-06-01

Full Text Available The Down's syndrome candidate region 1 (DSCR1 protein, encoded by a gene located in the human chromosome 21, interacts with calcineurin and is overexpressed in Down's syndrome patients. As an approach to clarifying a putative function for this protein, in the present study we used the yeast two-hybrid system to identify DSCR1 partners. The two-hybrid system is a method that allows the identification of protein-protein interactions through reconstitution of the activity of the yeast GAL 4 transcriptional activator. The gene DSCR1 fused to the GAL 4 binding domain (BD was used to screen a human fetal brain cDNA library cloned in fusion with the GAL 4 activation domain (AD. Three positive clones were found and sequence analysis revealed that all the plasmids coded for the ubiquitously expressed transcript (UXT. UXT, which is encoded in human Xp11, is a 157-amino acid protein present in both cytosol and nucleus of the cells. This positive interaction of DSCR1 and UXT was confirmed in vivo by mating the yeast strain AH109 (MATaexpressing AD-UXT with the strain Y187 (MATalpha expressing BD-DSCR1, and in vitro by co-immunoprecipitation experiments. These results may help elucidate a new function for DSCR1 and its participation in Down's syndrome pathogenesis.

The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control.

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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.

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

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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.

Salient region detection by fusing bottom-up and top-down features extracted from a single image.

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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.

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

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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.

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

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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.

Top down modulation of attention to food cues via working memory.

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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.

Post-socialist agricultural cooperatives in Russia : A case study of top-down cooperatives in the Belgorod region

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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

Abrupt onsets capture attention independent of top-down control settings 11: Additivity is no evidence for filtering

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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

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

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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

Top-down and bottom-up aspects of active search in a real-world environment.

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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.

Novel algorithms for protein sequence analysis

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Ye, Kai

2008-01-01

Each protein is characterized by its unique sequential order of amino acids, the so-called protein sequence. Biology”s paradigm is that this order of amino acids determines the protein”s architecture and function. In this thesis, we introduce novel algorithms to analyze protein sequences. Chapter 1

Disentangling the Role of Cortico-Basal Ganglia Loops in Top-Down and Bottom-Up Visual Attention: An Investigation of Attention Deficits in Parkinson Disease.

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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

Atypical biological motion kinematics are represented by complementary lower-level and top-down processes during imitation learning.

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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.

Age-Related Inter-region EEG Coupling Changes during the Control of Bottom-up and Top-down Attention

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Ling eLi

2015-12-01

Full Text Available We investigated age-related changes in electroencephalographic (EEG coupling of theta-, alpha-, and beta-frequency bands during bottom-up and top-down attention. Arrays were presented with either automatic pop-out (bottom-up or effortful search (top-down behavior to younger and older participants. The phase-locking value (PLV was used to estimate coupling strength between scalp recordings. Behavioral performance decreased with age, with a greater age-related decline in accuracy for the search than for the pop-out condition. Aging was associated with a declined coupling strength of theta and alpha frequency bands, with a greater age-related decline in whole-brain coupling values for the search than for the pop-out condition. Specifically, prefronto-frontal coupling in theta- and alpha-bands, fronto-parietal and parieto-occipital couplings in beta-band for younger group showed a right hemispheric dominance, which was reduced with aging to compensate for the inhibitory dysfunction. While pop-out target detection was mainly associated with greater parieto-occipital beta-coupling strength compared to search condition regardless of aging. Furthermore, prefronto-frontal coupling in theta-, alpha- and beta-bands, and parieto-occipital coupling in beta-band functioned as predictors of behavior for both groups. Taken together these findings provide evidence that prefronto-frontal coupling of theta-, alpha-, and beta-bands may serve as a possible basis of aging during visual attention, while parieto-occipital coupling in beta-band could serve for a bottom-up function and be vulnerable to top-down attention control for younger and older groups.

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.

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

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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.

The case for refining bottom-up methane emission inventories using top-down measurements

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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

Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

International Nuclear Information System (INIS)

Kanginakudru, Sriramana; DeSmet, Marsha; Thomas, Yanique; Morgan, Iain M.; Androphy, Elliot J.

2015-01-01

The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication

Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

Energy Technology Data Exchange (ETDEWEB)

Kanginakudru, Sriramana, E-mail: skangina@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); DeSmet, Marsha, E-mail: mdesmet@iupui.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Thomas, Yanique, E-mail: ysthomas@umail.iu.edu [Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States); Morgan, Iain M., E-mail: immorgan@vcu.edu [VCU Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, Virginia (United States); Androphy, Elliot J., E-mail: eandro@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States)

2015-04-15

The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.

Random amino acid mutations and protein misfolding lead to Shannon limit in sequence-structure communication.

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Andreas Martin Lisewski

2008-09-01

Full Text Available The transmission of genomic information from coding sequence to protein structure during protein synthesis is subject to stochastic errors. To analyze transmission limits in the presence of spurious errors, Shannon's noisy channel theorem is applied to a communication channel between amino acid sequences and their structures established from a large-scale statistical analysis of protein atomic coordinates. While Shannon's theorem confirms that in close to native conformations information is transmitted with limited error probability, additional random errors in sequence (amino acid substitutions and in structure (structural defects trigger a decrease in communication capacity toward a Shannon limit at 0.010 bits per amino acid symbol at which communication breaks down. In several controls, simulated error rates above a critical threshold and models of unfolded structures always produce capacities below this limiting value. Thus an essential biological system can be realistically modeled as a digital communication channel that is (a sensitive to random errors and (b restricted by a Shannon error limit. This forms a novel basis for predictions consistent with observed rates of defective ribosomal products during protein synthesis, and with the estimated excess of mutual information in protein contact potentials.

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.

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.

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

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.

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

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.

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.

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

Protein Kinase C-{delta} mediates down-regulation of heterogeneous nuclear ribonucleoprotein K protein: involvement in apoptosis induction

Energy Technology Data Exchange (ETDEWEB)

Gao, Feng-Hou [NO.3 People' s Hospital affiliated to Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 201900 (China); The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Wu, Ying-Li [The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Zhao, Meng [Institute of Health Science, SJTU-SM/Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai (China); Liu, Chuan-Xu; Wang, Li-Shun [The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Chen, Guo-Qiang, E-mail: chengq@shsmu.edu.cn [The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Institute of Health Science, SJTU-SM/Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai (China)

2009-11-15

We reported previously that NSC606985, a camptothecin analogue, induces apoptosis of acute myeloid leukemia (AML) cells through proteolytic activation of protein kinase C delta ({Delta}PKC-{delta}). By subcellular proteome analysis, heterogeneous nuclear ribonucleoprotein K (hnRNP K) was identified as being significantly down-regulated in NSC606985-treated leukemic NB4 cells. HnRNP K, a docking protein for DNA, RNA, and transcriptional or translational molecules, is implicated in a host of processes involving the regulation of gene expression. However, the molecular mechanisms of hnRNP K reduction and its roles during apoptosis are still not understood. In the present study, we found that, following the appearance of the {Delta}PKC-{delta}, hnRNP K protein was significantly down-regulated in NSC606985, doxorubicin, arsenic trioxide and ultraviolet-induced apoptosis. We further provided evidence that {Delta}PKC-{delta} mediated the down-regulation of hnRNP K protein during apoptosis: PKC-{delta} inhibitor could rescue the reduction of hnRNP K; hnRNP K failed to be decreased in PKC-{delta}-deficient apoptotic KG1a cells; conditional induction of {Delta}PKC-{delta} in U937T cells directly down-regulated hnRNP K protein. Moreover, the proteasome inhibitor also inhibited the down-regulation of hnRNP K protein by apoptosis inducer and the conditional expression of {Delta}PKC-{delta}. More intriguingly, the suppression of hnRNP K with siRNA transfection significantly induced apoptosis. To our knowledge, this is the first demonstration that proteolytically activated PKC-{delta} down-regulates hnRNP K protein in a proteasome-dependent manner, which plays an important role in apoptosis induction.

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...

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.

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

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.

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.

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.

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.

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.

Bottom-up effects on biomass versus top-down effects on identity: a multiple-lake fish community manipulation experiment

NARCIS (Netherlands)

Lemmens, P.; Declerck, S.A.J.; Tuytens, K.; Vanderstukken, M.; De Meester, L.

2018-01-01

The extent to which ecosystems are regulated by top-down relative to bottom-up control has been a dominant paradigm in ecology for many decades. For lakes, it has been shown that predation by fish is an important determinant of variation in zooplankton and phytoplankton community characteristics.

Use of designed sequences in protein structure recognition.

Science.gov (United States)

Kumar, Gayatri; Mudgal, Richa; Srinivasan, Narayanaswamy; Sandhya, Sankaran

2018-05-09

Knowledge of the protein structure is a pre-requisite for improved understanding of molecular function. The gap in the sequence-structure space has increased in the post-genomic era. Grouping related protein sequences into families can aid in narrowing the gap. In the Pfam database, structure description is provided for part or full-length proteins of 7726 families. For the remaining 52% of the families, information on 3-D structure is not yet available. We use the computationally designed sequences that are intermediately related to two protein domain families, which are already known to share the same fold. These strategically designed sequences enable detection of distant relationships and here, we have employed them for the purpose of structure recognition of protein families of yet unknown structure. We first measured the success rate of our approach using a dataset of protein families of known fold and achieved a success rate of 88%. Next, for 1392 families of yet unknown structure, we made structural assignments for part/full length of the proteins. Fold association for 423 domains of unknown function (DUFs) are provided as a step towards functional annotation. The results indicate that knowledge-based filling of gaps in protein sequence space is a lucrative approach for structure recognition. Such sequences assist in traversal through protein sequence space and effectively function as 'linkers', where natural linkers between distant proteins are unavailable. This article was reviewed by Oliviero Carugo, Christine Orengo and Srikrishna Subramanian.

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.

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...

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.

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.

Improving accuracy of protein-protein interaction prediction by considering the converse problem for sequence representation

Directory of Open Access Journals (Sweden)

Wang Yong

2011-10-01

Full Text Available Abstract Background With the development of genome-sequencing technologies, protein sequences are readily obtained by translating the measured mRNAs. Therefore predicting protein-protein interactions from the sequences is of great demand. The reason lies in the fact that identifying protein-protein interactions is becoming a bottleneck for eventually understanding the functions of proteins, especially for those organisms barely characterized. Although a few methods have been proposed, the converse problem, if the features used extract sufficient and unbiased information from protein sequences, is almost untouched. Results In this study, we interrogate this problem theoretically by an optimization scheme. Motivated by the theoretical investigation, we find novel encoding methods for both protein sequences and protein pairs. Our new methods exploit sufficiently the information of protein sequences and reduce artificial bias and computational cost. Thus, it significantly outperforms the available methods regarding sensitivity, specificity, precision, and recall with cross-validation evaluation and reaches ~80% and ~90% accuracy in Escherichia coli and Saccharomyces cerevisiae respectively. Our findings here hold important implication for other sequence-based prediction tasks because representation of biological sequence is always the first step in computational biology. Conclusions By considering the converse problem, we propose new representation methods for both protein sequences and protein pairs. The results show that our method significantly improves the accuracy of protein-protein interaction predictions.

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.

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

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.

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...

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.

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.

Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs

International Nuclear Information System (INIS)

Kimura, S.; Kotani, T.; McBride, O.W.; Umeki, K.; Hirai, K.; Nakayama, T.; Ohtaki, S.

1987-01-01

Two forms of human thyroid peroxidase cDNAs were isolated from a λgt11 cDNA library, prepared from Graves disease thyroid tissue mRNA, by use of oligonucleotides. The longest complete cDNA, designated phTPO-1, has 3048 nucleotides and an open reading frame consisting of 933 amino acids, which would encode a protein with a molecular weight of 103,026. Five potential asparagine-linked glycosylation sites are found in the deduced amino acid sequence. The second peroxidase cDNA, designated phTPO-2, is almost identical to phTPO-1 beginning 605 base pairs downstream except that it contains 1-base-pair difference and lacks 171 base pairs in the middle of the sequence. This results in a loss of 57 amino acids corresponding to a molecular weight of 6282. Interestingly, this 171-nucleotide sequence has GT and AG at its 5' and 3' boundaries, respectively, that are in good agreement with donor and acceptor splice site consensus sequences. Using specific oligonucleotide probes for the mRNAs derived from the cDNA sequences hTOP-1 and hTOP-2, the authors show that both are expressed in all thyroid tissues examined and the relative level of two mRNAs is different in each sample. The results suggest that two thyroid peroxidase proteins might be generated through alternate splicing of the same gene. By using somatic cell hybrid lines, the thyroid peroxidase gene was mapped to the short arm of human chromosome 2

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

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.

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).

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.

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

Nonlinear deterministic structures and the randomness of protein sequences

CERN Document Server

Huang Yan Zhao

2003-01-01

To clarify the randomness of protein sequences, we make a detailed analysis of a set of typical protein sequences representing each structural classes by using nonlinear prediction method. No deterministic structures are found in these protein sequences and this implies that they behave as random sequences. We also give an explanation to the controversial results obtained in previous investigations.

Translation of both 5'TOP and non-TOP host mRNAs continues into the late phase of Baculovirus infection

NARCIS (Netherlands)

Oers, van M.M.; Doitsidou, M.; Thomas, A.A.M.; Maagd, de R.A.; Vlak, J.M.

2003-01-01

Complete cDNA sequences were obtained for ribosomal protein (rp) L15 and eukaryotic initiation factor eIF2 from the lepidopteran insect Spodoptera frugiperda, and for elongation factor eEF2 from S. exigua. The presence of a 5' terminal oligopyrimidine (TOP) tract classified the lepidopteran rpL15

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

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.

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.

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.

Nucleation phenomena in protein folding: the modulating role of protein sequence

International Nuclear Information System (INIS)

Travasso, Rui D M; FaIsca, Patricia F N; Gama, Margarida M Telo da

2007-01-01

For the vast majority of naturally occurring, small, single-domain proteins, folding is often described as a two-state process that lacks detectable intermediates. This observation has often been rationalized on the basis of a nucleation mechanism for protein folding whose basic premise is the idea that, after completion of a specific set of contacts forming the so-called folding nucleus, the native state is achieved promptly. Here we propose a methodology to identify folding nuclei in small lattice polymers and apply it to the study of protein molecules with a chain length of N = 48. To investigate the extent to which protein topology is a robust determinant of the nucleation mechanism, we compare the nucleation scenario of a native-centric model with that of a sequence-specific model sharing the same native fold. To evaluate the impact of the sequence's finer details in the nucleation mechanism, we consider the folding of two non-homologous sequences. We conclude that, in a sequence-specific model, the folding nucleus is, to some extent, formed by the most stable contacts in the protein and that the less stable linkages in the folding nucleus are solely determined by the fold's topology. We have also found that, independently of the protein sequence, the folding nucleus performs the same 'topological' function. This unifying feature of the nucleation mechanism results from the residues forming the folding nucleus being distributed along the protein chain in a similar and well-defined manner that is determined by the fold's topological features

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.

HomPPI: a class of sequence homology based protein-protein interface prediction methods

Directory of Open Access Journals (Sweden)

Dobbs Drena

2011-06-01

Full Text Available Abstract Background Although homology-based methods are among the most widely used methods for predicting the structure and function of proteins, the question as to whether interface sequence conservation can be effectively exploited in predicting protein-protein interfaces has been a subject of debate. Results We studied more than 300,000 pair-wise alignments of protein sequences from structurally characterized protein complexes, including both obligate and transient complexes. We identified sequence similarity criteria required for accurate homology-based inference of interface residues in a query protein sequence. Based on these analyses, we developed HomPPI, a class of sequence homology-based methods for predicting protein-protein interface residues. We present two variants of HomPPI: (i NPS-HomPPI (Non partner-specific HomPPI, which can be used to predict interface residues of a query protein in the absence of knowledge of the interaction partner; and (ii PS-HomPPI (Partner-specific HomPPI, which can be used to predict the interface residues of a query protein with a specific target protein. Our experiments on a benchmark dataset of obligate homodimeric complexes show that NPS-HomPPI can reliably predict protein-protein interface residues in a given protein, with an average correlation coefficient (CC of 0.76, sensitivity of 0.83, and specificity of 0.78, when sequence homologs of the query protein can be reliably identified. NPS-HomPPI also reliably predicts the interface residues of intrinsically disordered proteins. Our experiments suggest that NPS-HomPPI is competitive with several state-of-the-art interface prediction servers including those that exploit the structure of the query proteins. The partner-specific classifier, PS-HomPPI can, on a large dataset of transient complexes, predict the interface residues of a query protein with a specific target, with a CC of 0.65, sensitivity of 0.69, and specificity of 0.70, when homologs of

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.

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...

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.

Protein Function Prediction Based on Sequence and Structure Information

KAUST Repository

Smaili, Fatima Z.

2016-05-25

The number of available protein sequences in public databases is increasing exponentially. However, a significant fraction of these sequences lack functional annotation which is essential to our understanding of how biological systems and processes operate. In this master thesis project, we worked on inferring protein functions based on the primary protein sequence. In the approach we follow, 3D models are first constructed using I-TASSER. Functions are then deduced by structurally matching these predicted models, using global and local similarities, through three independent enzyme commission (EC) and gene ontology (GO) function libraries. The method was tested on 250 “hard” proteins, which lack homologous templates in both structure and function libraries. The results show that this method outperforms the conventional prediction methods based on sequence similarity or threading. Additionally, our method could be improved even further by incorporating protein-protein interaction information. Overall, the method we use provides an efficient approach for automated functional annotation of non-homologous proteins, starting from their sequence.

Abundance and size structure of planktonic protist communities in a Neotropical floodplain: effects of top-down and bottom-up controls

Directory of Open Access Journals (Sweden)

Bianca Ramos de Meira

2017-12-01

Full Text Available Abstract: Aim: We aimed to assess the influence of bottom-up and top-down control mechanisms on the abundance and size structure of protist communities (heterotrophic flagellates and ciliates. We formulated the following hypothesis: bottom-up control mechanisms, related to the availability of resources in the environment, are responsible for structuring the abundance of these communities, whereas top-down control mechanisms, related to predation effects, determine the size pattern of these organisms. Methods Samples for planktonic organisms were taken in 20 shallow lakes belonging to the upper Paraná River floodplain. We evaluated linear regression models to select the best model which predicts the patterns observed according to Akaike Information Criterion. Results The best models selected to explain the abundance of heterotrophic flagellates included negative relations with picophytoplankton abundance and positive with rotifers abundance, while for their size structure, negative relationships were found with heterotrophic bacteria, ciliates and rotifers biovolumes. In relation to the ciliates, their abundances were positively related to the rotifers and picophytoplankton abundances and negatively with the heterotrophic bacteria abundance. On the other hand, for the size structure, the best models selected strong negative relations with the microcrustaceans biovolumes, in addition to relations with the different fractions of the phytoplankton. Conclusion For both flagellates and ciliates, their abundance is being mainly regulated by a bottom up control mechanism, whereas for the size structure the results showed that both food resources and predators were important, indicating that bottom-up and top-down mechanisms act simultaneously in determining the size of these microorganisms.

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...

Chemical Methods to Knock Down the Amyloid Proteins

Directory of Open Access Journals (Sweden)

Na Gao

2017-06-01

Full Text Available Amyloid proteins are closely related with amyloid diseases and do tremendous harm to human health. However, there is still a lack of effective strategies to treat these amyloid diseases, so it is important to develop novel methods. Accelerating the clearance of amyloid proteins is a favorable method for amyloid disease treatment. Recently, chemical methods for protein reduction have been developed and have attracted much attention. In this review, we focus on the latest progress of chemical methods that knock down amyloid proteins, including the proteolysis-targeting chimera (PROTAC strategy, the “recognition-cleavage” strategy, the chaperone-mediated autophagy (CMA strategy, the selectively light-activatable organic and inorganic molecules strategy and other chemical strategies.

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.

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

GuiTope: an application for mapping random-sequence peptides to protein sequences.

Science.gov (United States)

Halperin, Rebecca F; Stafford, Phillip; Emery, Jack S; Navalkar, Krupa Arun; Johnston, Stephen Albert

2012-01-03

Random-sequence peptide libraries are a commonly used tool to identify novel ligands for binding antibodies, other proteins, and small molecules. It is often of interest to compare the selected peptide sequences to the natural protein binding partners to infer the exact binding site or the importance of particular residues. The ability to search a set of sequences for similarity to a set of peptides may sometimes enable the prediction of an antibody epitope or a novel binding partner. We have developed a software application designed specifically for this task. GuiTope provides a graphical user interface for aligning peptide sequences to protein sequences. All alignment parameters are accessible to the user including the ability to specify the amino acid frequency in the peptide library; these frequencies often differ significantly from those assumed by popular alignment programs. It also includes a novel feature to align di-peptide inversions, which we have found improves the accuracy of antibody epitope prediction from peptide microarray data and shows utility in analyzing phage display datasets. Finally, GuiTope can randomly select peptides from a given library to estimate a null distribution of scores and calculate statistical significance. GuiTope provides a convenient method for comparing selected peptide sequences to protein sequences, including flexible alignment parameters, novel alignment features, ability to search a database, and statistical significance of results. The software is available as an executable (for PC) at http://www.immunosignature.com/software and ongoing updates and source code will be available at sourceforge.net.

GuiTope: an application for mapping random-sequence peptides to protein sequences

Directory of Open Access Journals (Sweden)

Halperin Rebecca F

2012-01-01

Full Text Available Abstract Background Random-sequence peptide libraries are a commonly used tool to identify novel ligands for binding antibodies, other proteins, and small molecules. It is often of interest to compare the selected peptide sequences to the natural protein binding partners to infer the exact binding site or the importance of particular residues. The ability to search a set of sequences for similarity to a set of peptides may sometimes enable the prediction of an antibody epitope or a novel binding partner. We have developed a software application designed specifically for this task. Results GuiTope provides a graphical user interface for aligning peptide sequences to protein sequences. All alignment parameters are accessible to the user including the ability to specify the amino acid frequency in the peptide library; these frequencies often differ significantly from those assumed by popular alignment programs. It also includes a novel feature to align di-peptide inversions, which we have found improves the accuracy of antibody epitope prediction from peptide microarray data and shows utility in analyzing phage display datasets. Finally, GuiTope can randomly select peptides from a given library to estimate a null distribution of scores and calculate statistical significance. Conclusions GuiTope provides a convenient method for comparing selected peptide sequences to protein sequences, including flexible alignment parameters, novel alignment features, ability to search a database, and statistical significance of results. The software is available as an executable (for PC at http://www.immunosignature.com/software and ongoing updates and source code will be available at sourceforge.net.

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...

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....

Insights into Protein Sequence and Structure-Derived Features Mediating 3D Domain Swapping Mechanism using Support Vector Machine Based Approach

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Khader Shameer

2010-06-01

Full Text Available 3-dimensional domain swapping is a mechanism where two or more protein molecules form higher order oligomers by exchanging identical or similar subunits. Recently, this phenomenon has received much attention in the context of prions and neuro-degenerative diseases, due to its role in the functional regulation, formation of higher oligomers, protein misfolding, aggregation etc. While 3-dimensional domain swap mechanism can be detected from three-dimensional structures, it remains a formidable challenge to derive common sequence or structural patterns from proteins involved in swapping. We have developed a SVM-based classifier to predict domain swapping events using a set of features derived from sequence and structural data. The SVM classifier was trained on features derived from 150 proteins reported to be involved in 3D domain swapping and 150 proteins not known to be involved in swapped conformation or related to proteins involved in swapping phenomenon. The testing was performed using 63 proteins from the positive dataset and 63 proteins from the negative dataset. We obtained 76.33% accuracy from training and 73.81% accuracy from testing. Due to high diversity in the sequence, structure and functions of proteins involved in domain swapping, availability of such an algorithm to predict swapping events from sequence and structure-derived features will be an initial step towards identification of more putative proteins that may be involved in swapping or proteins involved in deposition disease. Further, the top features emerging in our feature selection method may be analysed further to understand their roles in the mechanism of domain swapping.

Dynamics of domain coverage of the protein sequence universe

Science.gov (United States)

2012-01-01

Background The currently known protein sequence space consists of millions of sequences in public databases and is rapidly expanding. Assigning sequences to families leads to a better understanding of protein function and the nature of the protein universe. However, a large portion of the current protein space remains unassigned and is referred to as its “dark matter”. Results Here we suggest that true size of “dark matter” is much larger than stated by current definitions. We propose an approach to reducing the size of “dark matter” by identifying and subtracting regions in protein sequences that are not likely to contain any domain. Conclusions Recent improvements in computational domain modeling result in a decrease, albeit slowly, in the relative size of “dark matter”; however, its absolute size increases substantially with the growth of sequence data. PMID:23157439

Dynamics of domain coverage of the protein sequence universe

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Rekapalli Bhanu

2012-11-01

Full Text Available Abstract Background The currently known protein sequence space consists of millions of sequences in public databases and is rapidly expanding. Assigning sequences to families leads to a better understanding of protein function and the nature of the protein universe. However, a large portion of the current protein space remains unassigned and is referred to as its “dark matter”. Results Here we suggest that true size of “dark matter” is much larger than stated by current definitions. We propose an approach to reducing the size of “dark matter” by identifying and subtracting regions in protein sequences that are not likely to contain any domain. Conclusions Recent improvements in computational domain modeling result in a decrease, albeit slowly, in the relative size of “dark matter”; however, its absolute size increases substantially with the growth of sequence data.

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)

MIPS: a database for genomes and protein sequences.

Science.gov (United States)

Mewes, H W; Frishman, D; Güldener, U; Mannhaupt, G; Mayer, K; Mokrejs, M; Morgenstern, B; Münsterkötter, M; Rudd, S; Weil, B

2002-01-01

The Munich Information Center for Protein Sequences (MIPS-GSF, Neuherberg, Germany) continues to provide genome-related information in a systematic way. MIPS supports both national and European sequencing and functional analysis projects, develops and maintains automatically generated and manually annotated genome-specific databases, develops systematic classification schemes for the functional annotation of protein sequences, and provides tools for the comprehensive analysis of protein sequences. This report updates the information on the yeast genome (CYGD), the Neurospora crassa genome (MNCDB), the databases for the comprehensive set of genomes (PEDANT genomes), the database of annotated human EST clusters (HIB), the database of complete cDNAs from the DHGP (German Human Genome Project), as well as the project specific databases for the GABI (Genome Analysis in Plants) and HNB (Helmholtz-Netzwerk Bioinformatik) networks. The Arabidospsis thaliana database (MATDB), the database of mitochondrial proteins (MITOP) and our contribution to the PIR International Protein Sequence Database have been described elsewhere [Schoof et al. (2002) Nucleic Acids Res., 30, 91-93; Scharfe et al. (2000) Nucleic Acids Res., 28, 155-158; Barker et al. (2001) Nucleic Acids Res., 29, 29-32]. All databases described, the protein analysis tools provided and the detailed descriptions of our projects can be accessed through the MIPS World Wide Web server (http://mips.gsf.de).

Prediction of Protein Hotspots from Whole Protein Sequences by a Random Projection Ensemble System

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Jinjian Jiang

2017-07-01

Full Text Available Hotspot residues are important in the determination of protein-protein interactions, and they always perform specific functions in biological processes. The determination of hotspot residues is by the commonly-used method of alanine scanning mutagenesis experiments, which is always costly and time consuming. To address this issue, computational methods have been developed. Most of them are structure based, i.e., using the information of solved protein structures. However, the number of solved protein structures is extremely less than that of sequences. Moreover, almost all of the predictors identified hotspots from the interfaces of protein complexes, seldom from the whole protein sequences. Therefore, determining hotspots from whole protein sequences by sequence information alone is urgent. To address the issue of hotspot predictions from the whole sequences of proteins, we proposed an ensemble system with random projections using statistical physicochemical properties of amino acids. First, an encoding scheme involving sequence profiles of residues and physicochemical properties from the AAindex1 dataset is developed. Then, the random projection technique was adopted to project the encoding instances into a reduced space. Then, several better random projections were obtained by training an IBk classifier based on the training dataset, which were thus applied to the test dataset. The ensemble of random projection classifiers is therefore obtained. Experimental results showed that although the performance of our method is not good enough for real applications of hotspots, it is very promising in the determination of hotspot residues from whole sequences.

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.

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

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

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.

Towards clinical molecular diagnosis of inherited cardiac conditions: a comparison of bench-top genome DNA sequencers.

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Xinzhong Li

Full Text Available Molecular genetic testing is recommended for diagnosis of inherited cardiac disease, to guide prognosis and treatment, but access is often limited by cost and availability. Recently introduced high-throughput bench-top DNA sequencing platforms have the potential to overcome these limitations.We evaluated two next-generation sequencing (NGS platforms for molecular diagnostics. The protein-coding regions of six genes associated with inherited arrhythmia syndromes were amplified from 15 human samples using parallelised multiplex PCR (Access Array, Fluidigm, and sequenced on the MiSeq (Illumina and Ion Torrent PGM (Life Technologies. Overall, 97.9% of the target was sequenced adequately for variant calling on the MiSeq, and 96.8% on the Ion Torrent PGM. Regions missed tended to be of high GC-content, and most were problematic for both platforms. Variant calling was assessed using 107 variants detected using Sanger sequencing: within adequately sequenced regions, variant calling on both platforms was highly accurate (Sensitivity: MiSeq 100%, PGM 99.1%. Positive predictive value: MiSeq 95.9%, PGM 95.5%. At the time of the study the Ion Torrent PGM had a lower capital cost and individual runs were cheaper and faster. The MiSeq had a higher capacity (requiring fewer runs, with reduced hands-on time and simpler laboratory workflows. Both provide significant cost and time savings over conventional methods, even allowing for adjunct Sanger sequencing to validate findings and sequence exons missed by NGS.MiSeq and Ion Torrent PGM both provide accurate variant detection as part of a PCR-based molecular diagnostic workflow, and provide alternative platforms for molecular diagnosis of inherited cardiac conditions. Though there were performance differences at this throughput, platforms differed primarily in terms of cost, scalability, protocol stability and ease of use. Compared with current molecular genetic diagnostic tests for inherited cardiac arrhythmias

Gene Unprediction with Spurio: A tool to identify spurious protein sequences.

Science.gov (United States)

Höps, Wolfram; Jeffryes, Matt; Bateman, Alex

2018-01-01

We now have access to the sequences of tens of millions of proteins. These protein sequences are essential for modern molecular biology and computational biology. The vast majority of protein sequences are derived from gene prediction tools and have no experimental supporting evidence for their translation.  Despite the increasing accuracy of gene prediction tools there likely exists a large number of spurious protein predictions in the sequence databases.  We have developed the Spurio tool to help identify spurious protein predictions in prokaryotes.  Spurio searches the query protein sequence against a prokaryotic nucleotide database using tblastn and identifies homologous sequences. The tblastn matches are used to score the query sequence's likelihood of being a spurious protein prediction using a Gaussian process model. The most informative feature is the appearance of stop codons within the presumed translation of homologous DNA sequences. Benchmarking shows that the Spurio tool is able to distinguish spurious from true proteins. However, transposon proteins are prone to be predicted as spurious because of the frequency of degraded homologs found in the DNA sequence databases. Our initial experiments suggest that less than 1% of the proteins in the UniProtKB sequence database are likely to be spurious and that Spurio is able to identify over 60 times more spurious proteins than the AntiFam resource. The Spurio software and source code is available under an MIT license at the following URL: https://bitbucket.org/bateman-group/spurio.

Structure and Sequence Search on Aptamer-Protein Docking

Science.gov (United States)

Xiao, Jiajie; Bonin, Keith; Guthold, Martin; Salsbury, Freddie

2015-03-01

Interactions between proteins and deoxyribonucleic acid (DNA) play a significant role in the living systems, especially through gene regulation. However, short nucleic acids sequences (aptamers) with specific binding affinity to specific proteins exhibit clinical potential as therapeutics. Our capillary and gel electrophoresis selection experiments show that specific sequences of aptamers can be selected that bind specific proteins. Computationally, given the experimentally-determined structure and sequence of a thrombin-binding aptamer, we can successfully dock the aptamer onto thrombin in agreement with experimental structures of the complex. In order to further study the conformational flexibility of this thrombin-binding aptamer and to potentially develop a predictive computational model of aptamer-binding, we use GPU-enabled molecular dynamics simulations to both examine the conformational flexibility of the aptamer in the absence of binding to thrombin, and to determine our ability to fold an aptamer. This study should help further de-novo predictions of aptamer sequences by enabling the study of structural and sequence-dependent effects on aptamer-protein docking specificity.

An Overview of the Top Ten Detergents Used for Membrane Protein Crystallization

NARCIS (Netherlands)

Stetsenko, Artem; Guskov, Albert

2017-01-01

To study integral membrane proteins, one has to extract them from the membrane—the step that is typically achieved by the application of detergents. In this mini-review, we summarize the top 10 detergents used for the structural analysis of membrane proteins based on the published results. The aim

AlignMe—a membrane protein sequence alignment web server

Science.gov (United States)

Stamm, Marcus; Staritzbichler, René; Khafizov, Kamil; Forrest, Lucy R.

2014-01-01

We present a web server for pair-wise alignment of membrane protein sequences, using the program AlignMe. The server makes available two operational modes of AlignMe: (i) sequence to sequence alignment, taking two sequences in fasta format as input, combining information about each sequence from multiple sources and producing a pair-wise alignment (PW mode); and (ii) alignment of two multiple sequence alignments to create family-averaged hydropathy profile alignments (HP mode). For the PW sequence alignment mode, four different optimized parameter sets are provided, each suited to pairs of sequences with a specific similarity level. These settings utilize different types of inputs: (position-specific) substitution matrices, secondary structure predictions and transmembrane propensities from transmembrane predictions or hydrophobicity scales. In the second (HP) mode, each input multiple sequence alignment is converted into a hydrophobicity profile averaged over the provided set of sequence homologs; the two profiles are then aligned. The HP mode enables qualitative comparison of transmembrane topologies (and therefore potentially of 3D folds) of two membrane proteins, which can be useful if the proteins have low sequence similarity. In summary, the AlignMe web server provides user-friendly access to a set of tools for analysis and comparison of membrane protein sequences. Access is available at http://www.bioinfo.mpg.de/AlignMe PMID:24753425

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

The relationship of protein conservation and sequence length

Directory of Open Access Journals (Sweden)

Panchenko Anna R

2002-11-01

Full Text Available Abstract Background In general, the length of a protein sequence is determined by its function and the wide variance in the lengths of an organism's proteins reflects the diversity of specific functional roles for these proteins. However, additional evolutionary forces that affect the length of a protein may be revealed by studying the length distributions of proteins evolving under weaker functional constraints. Results We performed sequence comparisons to distinguish highly conserved and poorly conserved proteins from the bacterium Escherichia coli, the archaeon Archaeoglobus fulgidus, and the eukaryotes Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens. For all organisms studied, the conserved and nonconserved proteins have strikingly different length distributions. The conserved proteins are, on average, longer than the poorly conserved ones, and the length distributions for the poorly conserved proteins have a relatively narrow peak, in contrast to the conserved proteins whose lengths spread over a wider range of values. For the two prokaryotes studied, the poorly conserved proteins approximate the minimal length distribution expected for a diverse range of structural folds. Conclusions There is a relationship between protein conservation and sequence length. For all the organisms studied, there seems to be a significant evolutionary trend favoring shorter proteins in the absence of other, more specific functional constraints.

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.

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.

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

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

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

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.

Structural protein descriptors in 1-dimension and their sequence-based predictions.

Science.gov (United States)

Kurgan, Lukasz; Disfani, Fatemeh Miri

2011-09-01

The last few decades observed an increasing interest in development and application of 1-dimensional (1D) descriptors of protein structure. These descriptors project 3D structural features onto 1D strings of residue-wise structural assignments. They cover a wide-range of structural aspects including conformation of the backbone, burying depth/solvent exposure and flexibility of residues, and inter-chain residue-residue contacts. We perform first-of-its-kind comprehensive comparative review of the existing 1D structural descriptors. We define, review and categorize ten structural descriptors and we also describe, summarize and contrast over eighty computational models that are used to predict these descriptors from the protein sequences. We show that the majority of the recent sequence-based predictors utilize machine learning models, with the most popular being neural networks, support vector machines, hidden Markov models, and support vector and linear regressions. These methods provide high-throughput predictions and most of them are accessible to a non-expert user via web servers and/or stand-alone software packages. We empirically evaluate several recent sequence-based predictors of secondary structure, disorder, and solvent accessibility descriptors using a benchmark set based on CASP8 targets. Our analysis shows that the secondary structure can be predicted with over 80% accuracy and segment overlap (SOV), disorder with over 0.9 AUC, 0.6 Matthews Correlation Coefficient (MCC), and 75% SOV, and relative solvent accessibility with PCC of 0.7 and MCC of 0.6 (0.86 when homology is used). We demonstrate that the secondary structure predicted from sequence without the use of homology modeling is as good as the structure extracted from the 3D folds predicted by top-performing template-based methods.

Nuclear fuel assembly top nozzle with improved arrangement of hold-down leaf spring assemblies

International Nuclear Information System (INIS)

De Mario, E.E.; Lawson, C.N.

1991-01-01

This patent describes a top nozzle for use in a fuel assembly having guide thimbles for mounting the top nozzle. It comprises: a lower adapter plate having a periphery bounding an interior thereof mountable to the guide thimbles: guide structures attached to and extending along the periphery of the adapter plate and upwardly therefrom; an upper hold-down plate mounted to the guide structures for slidable movement relative thereto such that the upper plate can move toward and away from the interior of the lower plate within the space bounded by the guide structures as the upper plate slidably moves along the guide structures; and leaf spring assemblies interposed between and engaged with the lower and upper plates so as to yieldably support the upper plate in spaced relation above the lower plate and bias the upper plate for movement away from the lower plate; the leaf spring assemblies being provided in a non-peripheral arrangement relative to the periphery of the lower plate in which the assemblies cross the interior of the lower plate in a diagonal fashion between adjacent ones of the guide structures

MIPS: a database for protein sequences and complete genomes.

Science.gov (United States)

Mewes, H W; Hani, J; Pfeiffer, F; Frishman, D

1998-01-01

The MIPS group [Munich Information Center for Protein Sequences of the German National Center for Environment and Health (GSF)] at the Max-Planck-Institute for Biochemistry, Martinsried near Munich, Germany, is involved in a number of data collection activities, including a comprehensive database of the yeast genome, a database reflecting the progress in sequencing the Arabidopsis thaliana genome, the systematic analysis of other small genomes and the collection of protein sequence data within the framework of the PIR-International Protein Sequence Database (described elsewhere in this volume). Through its WWW server (http://www.mips.biochem.mpg.de ) MIPS provides access to a variety of generic databases, including a database of protein families as well as automatically generated data by the systematic application of sequence analysis algorithms. The yeast genome sequence and its related information was also compiled on CD-ROM to provide dynamic interactive access to the 16 chromosomes of the first eukaryotic genome unraveled. PMID:9399795

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.

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.

Can Natural Proteins Designed with ‘Inverted’ Peptide Sequences Adopt Native-Like Protein Folds?

Science.gov (United States)

Sridhar, Settu; Guruprasad, Kunchur

2014-01-01

We have carried out a systematic computational analysis on a representative dataset of proteins of known three-dimensional structure, in order to evaluate whether it would possible to ‘swap’ certain short peptide sequences in naturally occurring proteins with their corresponding ‘inverted’ peptides and generate ‘artificial’ proteins that are predicted to retain native-like protein fold. The analysis of 3,967 representative proteins from the Protein Data Bank revealed 102,677 unique identical inverted peptide sequence pairs that vary in sequence length between 5–12 and 18 amino acid residues. Our analysis illustrates with examples that such ‘artificial’ proteins may be generated by identifying peptides with ‘similar structural environment’ and by using comparative protein modeling and validation studies. Our analysis suggests that natural proteins may be tolerant to accommodating such peptides. PMID:25210740

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.

The SWISS-PROT protein sequence data bank: current status.

OpenAIRE

Bairoch, A; Boeckmann, B

1994-01-01

SWISS-PROT is an annotated protein sequence database established in 1986 and maintained collaboratively, since 1988, by the Department of Medical Biochemistry of the University of Geneva and the EMBL Data Library. The SWISS-PROT protein sequence data bank consist of sequence entries. Sequence entries are composed of different lines types, each with their own format. For standardization purposes the format of SWISS-PROT follows as closely as possible that of the EMBL Nucleotide Sequence Databa...

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.

The changing contribution of top-down and bottom-up limitation of mesopredators during 220 years of land use and climate change

NARCIS (Netherlands)

Pasanen-Mortensen, Marianne; Elmhagen, Bodil; Lindén, Harto; Bergström, Roger; Wallgren, Märtha; van der Velde, Ype; Cousins, Sara A.O.

2017-01-01

Apex predators may buffer bottom-up driven ecosystem change, as top-down suppression may dampen herbivore and mesopredator responses to increased resource availability. However, theory suggests that for this buffering capacity to be realized, the equilibrium abundance of apex predators must

Scaling up from the grassroots and the top down: The impacts of multi-level governance on community forestry in Durango, Mexico

Directory of Open Access Journals (Sweden)

Gustavo A García-López

2013-08-01

Full Text Available This paper analyzes the local-level impacts of cross-scale linkages in Mexican community forestry by evaluating the operation of four inter-community forest associations (FAs. Based on one year of fieldwork in Durango, Mexico, the paper focuses on two inter-related issues: (1 the services that each association provides to their member communities and how they impact forest management and the development of communities’ forestry enterprises, and (2 the differences in services and impacts between top-down and bottom-up FAs. The findings show that FAs, as a form of cross-scale linkage, can be crucial for the provision of services, goods and infrastructure related to the protection and enhancement of community forests, the economic development of community enterprises, and the political representation of these communities. At the same time, the study finds important differences between top-down and bottom-up FAs, while pointing to some of the disadvantages of each type of linkage.

Partial sequence determination of metabolically labeled radioactive proteins and peptides

International Nuclear Information System (INIS)

Anderson, C.W.

1982-01-01

The author has used the sequence analysis of radioactive proteins and peptides to approach several problems during the past few years. They, in collaboration with others, have mapped precisely several adenovirus proteins with respect to the nucleotide sequence of the adenovirus genome; identified hitherto missed proteins encoded by bacteriophage MS2 and by simian virus 40; analyzed the aminoterminal maturation of several virus proteins; determined the cleavage sites for processing of the poliovirus polyprotein; and analyzed the mechanism of frameshifting by excess normal tRNAs during cell-free protein synthesis. This chapter is designed to aid those without prior experience at protein sequence determinations. It is based primarily on the experience gained in the studies cited above, which made use of the Beckman 890 series automated protein sequencers

Correlation between protein sequence similarity and x-ray diffraction quality in the protein data bank.

Science.gov (United States)

Lu, Hui-Meng; Yin, Da-Chuan; Ye, Ya-Jing; Luo, Hui-Min; Geng, Li-Qiang; Li, Hai-Sheng; Guo, Wei-Hong; Shang, Peng

2009-01-01

As the most widely utilized technique to determine the 3-dimensional structure of protein molecules, X-ray crystallography can provide structure of the highest resolution among the developed techniques. The resolution obtained via X-ray crystallography is known to be influenced by many factors, such as the crystal quality, diffraction techniques, and X-ray sources, etc. In this paper, the authors found that the protein sequence could also be one of the factors. We extracted information of the resolution and the sequence of proteins from the Protein Data Bank (PDB), classified the proteins into different clusters according to the sequence similarity, and statistically analyzed the relationship between the sequence similarity and the best resolution obtained. The results showed that there was a pronounced correlation between the sequence similarity and the obtained resolution. These results indicate that protein structure itself is one variable that may affect resolution when X-ray crystallography is used.

Taxonomic colouring of phylogenetic trees of protein sequences

Directory of Open Access Journals (Sweden)

Andrade-Navarro Miguel A

2006-02-01

Full Text Available Abstract Background Phylogenetic analyses of protein families are used to define the evolutionary relationships between homologous proteins. The interpretation of protein-sequence phylogenetic trees requires the examination of the taxonomic properties of the species associated to those sequences. However, there is no online tool to facilitate this interpretation, for example, by automatically attaching taxonomic information to the nodes of a tree, or by interactively colouring the branches of a tree according to any combination of taxonomic divisions. This is especially problematic if the tree contains on the order of hundreds of sequences, which, given the accelerated increase in the size of the protein sequence databases, is a situation that is becoming common. Results We have developed PhyloView, a web based tool for colouring phylogenetic trees upon arbitrary taxonomic properties of the species represented in a protein sequence phylogenetic tree. Provided that the tree contains SwissProt, SpTrembl, or GenBank protein identifiers, the tool retrieves the taxonomic information from the corresponding database. A colour picker displays a summary of the findings and allows the user to associate colours to the leaves of the tree according to any number of taxonomic partitions. Then, the colours are propagated to the branches of the tree. Conclusion PhyloView can be used at http://www.ogic.ca/projects/phyloview/. A tutorial, the software with documentation, and GPL licensed source code, can be accessed at the same web address.

Identification of Top-ranked Proteins within a Directional Protein Interaction Network using the PageRank Algorithm: Applications in Humans and Plants.

Science.gov (United States)

Li, Xiu-Qing; Xing, Tim; Du, Donglei

2016-01-01

Somatic mutation of signal transduction genes or key nodes of the cellular protein network can cause severe diseases in humans but can sometimes genetically improve plants, likely because growth is determinate in animals but indeterminate in plants. This article reviews protein networks; human protein ranking; the mitogen-activated protein kinase (MAPK) and insulin (phospho- inositide 3kinase [PI3K]/phosphatase and tensin homolog [PTEN]/protein kinase B [AKT]) signaling pathways; human diseases caused by somatic mutations to the PI3K/PTEN/ AKT pathway; use of the MAPK pathway in plant molecular breeding; and protein domain evolution. Casitas B-lineage lymphoma (CBL), PTEN, MAPK1 and PIK3CA are among PIK3CA the top-ranked proteins in directional rankings. Eight proteins (ACVR1, CDC42, RAC1, RAF1, RHOA, TGFBR1, TRAF2, and TRAF6) are ranked in the top 50 key players in both signal emission and signal reception and in interaction with many other proteins. Top-ranked proteins likely have major impacts on the network function. Such proteins are targets for drug discovery, because their mutations are implicated in various cancers and overgrowth syndromes. Appropriately managing food intake may help reduce the growth of tumors or malformation of tissues. The role of the protein kinase C/ fatty acid synthase pathway in fat deposition in PTEN/PI3K patients should be investigated. Both the MAPK and insulin signaling pathways exist in plants, and MAPK pathway engineering can improve plant tolerance to biotic and abiotic stresses such as salinity.

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.

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.

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.

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.

Semi-Supervised Learning for Classification of Protein Sequence Data

Directory of Open Access Journals (Sweden)

Brian R. King

2008-01-01

Full Text Available Protein sequence data continue to become available at an exponential rate. Annotation of functional and structural attributes of these data lags far behind, with only a small fraction of the data understood and labeled by experimental methods. Classification methods that are based on semi-supervised learning can increase the overall accuracy of classifying partly labeled data in many domains, but very few methods exist that have shown their effect on protein sequence classification. We show how proven methods from text classification can be applied to protein sequence data, as we consider both existing and novel extensions to the basic methods, and demonstrate restrictions and differences that must be considered. We demonstrate comparative results against the transductive support vector machine, and show superior results on the most difficult classification problems. Our results show that large repositories of unlabeled protein sequence data can indeed be used to improve predictive performance, particularly in situations where there are fewer labeled protein sequences available, and/or the data are highly unbalanced in nature.

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 ...

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

A Comparative Prospective Study of Two Different Treatment Sequences i.e. Bottom Up-Inside Out and Topdown-Outside in, in the Treatment of Panfacial Fractures.

Science.gov (United States)

Degala, Saikrishna; Sundar, S Shyam; Mamata, K S

2015-12-01

To compare the sequence bottom-up inside-out with top-down outside-in, in the treatment of pan facial fractures and to evaluate the outcome of these approaches. The data from 11 patients with panfacial fracture are prospectively analysed. Five cases are treated with bottom-up approach and six patients with top-down approach. There were 11 male patients (six in top-down approach and five in bottom-up approach), ranging in age from 24 to 50 years. All injuries were result of RTA (n = 11, 100 %). Final treatment outcome was excellent in 3 (50 %), 1 (16 %) good and 2 (32 %) cases were fair in topdown approach, 3 (60 %) excellent and 2 (40 %) fair in bottom up approach with contingency coefficient value (P reconstruction of the remaining. Choice of the bottom-up inside-out or top-down outside-in sequence should be according to the pattern of fractures and preference of the surgeon. However, further controlled clinical trials, comparative studies with a larger sample size would be better to evaluate the final clinical outcome of individual techniques.

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

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

Sequence motifs in MADS transcription factors responsible for specificity and diversification of protein-protein interaction.

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Aalt D J van Dijk

Full Text Available Protein sequences encompass tertiary structures and contain information about specific molecular interactions, which in turn determine biological functions of proteins. Knowledge about how protein sequences define interaction specificity is largely missing, in particular for paralogous protein families with high sequence similarity, such as the plant MADS domain transcription factor family. In comparison to the situation in mammalian species, this important family of transcription regulators has expanded enormously in plant species and contains over 100 members in the model plant species Arabidopsis thaliana. Here, we provide insight into the mechanisms that determine protein-protein interaction specificity for the Arabidopsis MADS domain transcription factor family, using an integrated computational and experimental approach. Plant MADS proteins have highly similar amino acid sequences, but their dimerization patterns vary substantially. Our computational analysis uncovered small sequence regions that explain observed differences in dimerization patterns with reasonable accuracy. Furthermore, we show the usefulness of the method for prediction of MADS domain transcription factor interaction networks in other plant species. Introduction of mutations in the predicted interaction motifs demonstrated that single amino acid mutations can have a large effect and lead to loss or gain of specific interactions. In addition, various performed bioinformatics analyses shed light on the way evolution has shaped MADS domain transcription factor interaction specificity. Identified protein-protein interaction motifs appeared to be strongly conserved among orthologs, indicating their evolutionary importance. We also provide evidence that mutations in these motifs can be a source for sub- or neo-functionalization. The analyses presented here take us a step forward in understanding protein-protein interactions and the interplay between protein sequences and

What Top-Down Task Sets Do for Us: An ERP Study on the Benefits of Advance Preparation in Visual Search

Science.gov (United States)

Eimer, Martin; Kiss, Monika; Nicholas, Susan

2011-01-01

When target-defining features are specified in advance, attentional target selection in visual search is controlled by preparatory top-down task sets. We used ERP measures to study voluntary target selection in the absence of such feature-specific task sets, and to compare it to selection that is guided by advance knowledge about target features.…

How Many Protein Sequences Fold to a Given Structure? A Coevolutionary Analysis.

Science.gov (United States)

Tian, Pengfei; Best, Robert B

2017-10-17

Quantifying the relationship between protein sequence and structure is key to understanding the protein universe. A fundamental measure of this relationship is the total number of amino acid sequences that can fold to a target protein structure, known as the "sequence capacity," which has been suggested as a proxy for how designable a given protein fold is. Although sequence capacity has been extensively studied using lattice models and theory, numerical estimates for real protein structures are currently lacking. In this work, we have quantitatively estimated the sequence capacity of 10 proteins with a variety of different structures using a statistical model based on residue-residue co-evolution to capture the variation of sequences from the same protein family. Remarkably, we find that even for the smallest protein folds, such as the WW domain, the number of foldable sequences is extremely large, exceeding the Avogadro constant. In agreement with earlier theoretical work, the calculated sequence capacity is positively correlated with the size of the protein, or better, the density of contacts. This allows the absolute sequence capacity of a given protein to be approximately predicted from its structure. On the other hand, the relative sequence capacity, i.e., normalized by the total number of possible sequences, is an extremely tiny number and is strongly anti-correlated with the protein length. Thus, although there may be more foldable sequences for larger proteins, it will be much harder to find them. Lastly, we have correlated the evolutionary age of proteins in the CATH database with their sequence capacity as predicted by our model. The results suggest a trade-off between the opposing requirements of high designability and the likelihood of a novel fold emerging by chance. Published by Elsevier Inc.

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

Predicting the tolerated sequences for proteins and protein interfaces using RosettaBackrub flexible backbone design.

Directory of Open Access Journals (Sweden)

Colin A Smith

Full Text Available Predicting the set of sequences that are tolerated by a protein or protein interface, while maintaining a desired function, is useful for characterizing protein interaction specificity and for computationally designing sequence libraries to engineer proteins with new functions. Here we provide a general method, a detailed set of protocols, and several benchmarks and analyses for estimating tolerated sequences using flexible backbone protein design implemented in the Rosetta molecular modeling software suite. The input to the method is at least one experimentally determined three-dimensional protein structure or high-quality model. The starting structure(s are expanded or refined into a conformational ensemble using Monte Carlo simulations consisting of backrub backbone and side chain moves in Rosetta. The method then uses a combination of simulated annealing and genetic algorithm optimization methods to enrich for low-energy sequences for the individual members of the ensemble. To emphasize certain functional requirements (e.g. forming a binding interface, interactions between and within parts of the structure (e.g. domains can be reweighted in the scoring function. Results from each backbone structure are merged together to create a single estimate for the tolerated sequence space. We provide an extensive description of the protocol and its parameters, all source code, example analysis scripts and three tests applying this method to finding sequences predicted to stabilize proteins or protein interfaces. The generality of this method makes many other applications possible, for example stabilizing interactions with small molecules, DNA, or RNA. Through the use of within-domain reweighting and/or multistate design, it may also be possible to use this method to find sequences that stabilize particular protein conformations or binding interactions over others.

CMsearch: simultaneous exploration of protein sequence space and structure space improves not only protein homology detection but also protein structure prediction

KAUST Repository

Cui, Xuefeng

2016-06-15

Motivation: Protein homology detection, a fundamental problem in computational biology, is an indispensable step toward predicting protein structures and understanding protein functions. Despite the advances in recent decades on sequence alignment, threading and alignment-free methods, protein homology detection remains a challenging open problem. Recently, network methods that try to find transitive paths in the protein structure space demonstrate the importance of incorporating network information of the structure space. Yet, current methods merge the sequence space and the structure space into a single space, and thus introduce inconsistency in combining different sources of information. Method: We present a novel network-based protein homology detection method, CMsearch, based on cross-modal learning. Instead of exploring a single network built from the mixture of sequence and structure space information, CMsearch builds two separate networks to represent the sequence space and the structure space. It then learns sequence–structure correlation by simultaneously taking sequence information, structure information, sequence space information and structure space information into consideration. Results: We tested CMsearch on two challenging tasks, protein homology detection and protein structure prediction, by querying all 8332 PDB40 proteins. Our results demonstrate that CMsearch is insensitive to the similarity metrics used to define the sequence and the structure spaces. By using HMM–HMM alignment as the sequence similarity metric, CMsearch clearly outperforms state-of-the-art homology detection methods and the CASP-winning template-based protein structure prediction methods.

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...

EST2Prot: Mapping EST sequences to proteins

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Lin David M

2006-03-01

Full Text Available Abstract Background EST libraries are used in various biological studies, from microarray experiments to proteomic and genetic screens. These libraries usually contain many uncharacterized ESTs that are typically ignored since they cannot be mapped to known genes. Consequently, new discoveries are possibly overlooked. Results We describe a system (EST2Prot that uses multiple elements to map EST sequences to their corresponding protein products. EST2Prot uses UniGene clusters, substring analysis, information about protein coding regions in existing DNA sequences and protein database searches to detect protein products related to a query EST sequence. Gene Ontology terms, Swiss-Prot keywords, and protein similarity data are used to map the ESTs to functional descriptors. Conclusion EST2Prot extends and significantly enriches the popular UniGene mapping by utilizing multiple relations between known biological entities. It produces a mapping between ESTs and proteins in real-time through a simple web-interface. The system is part of the Biozon database and is accessible at http://biozon.org/tools/est/.

Adaptive compressive learning for prediction of protein-protein interactions from primary sequence.

Science.gov (United States)

Zhang, Ya-Nan; Pan, Xiao-Yong; Huang, Yan; Shen, Hong-Bin

2011-08-21

Protein-protein interactions (PPIs) play an important role in biological processes. Although much effort has been devoted to the identification of novel PPIs by integrating experimental biological knowledge, there are still many difficulties because of lacking enough protein structural and functional information. It is highly desired to develop methods based only on amino acid sequences for predicting PPIs. However, sequence-based predictors are often struggling with the high-dimensionality causing over-fitting and high computational complexity problems, as well as the redundancy of sequential feature vectors. In this paper, a novel computational approach based on compressed sensing theory is proposed to predict yeast Saccharomyces cerevisiae PPIs from primary sequence and has achieved promising results. The key advantage of the proposed compressed sensing algorithm is that it can compress the original high-dimensional protein sequential feature vector into a much lower but more condensed space taking the sparsity property of the original signal into account. What makes compressed sensing much more attractive in protein sequence analysis is its compressed signal can be reconstructed from far fewer measurements than what is usually considered necessary in traditional Nyquist sampling theory. Experimental results demonstrate that proposed compressed sensing method is powerful for analyzing noisy biological data and reducing redundancy in feature vectors. The proposed method represents a new strategy of dealing with high-dimensional protein discrete model and has great potentiality to be extended to deal with many other complicated biological systems. Copyright © 2011 Elsevier Ltd. All rights reserved.

Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences.

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Alexander M Sevy

2015-07-01

Full Text Available Computational protein design has found great success in engineering proteins for thermodynamic stability, binding specificity, or enzymatic activity in a 'single state' design (SSD paradigm. Multi-specificity design (MSD, on the other hand, involves considering the stability of multiple protein states simultaneously. We have developed a novel MSD algorithm, which we refer to as REstrained CONvergence in multi-specificity design (RECON. The algorithm allows each state to adopt its own sequence throughout the design process rather than enforcing a single sequence on all states. Convergence to a single sequence is encouraged through an incrementally increasing convergence restraint for corresponding positions. Compared to MSD algorithms that enforce (constrain an identical sequence on all states the energy landscape is simplified, which accelerates the search drastically. As a result, RECON can readily be used in simulations with a flexible protein backbone. We have benchmarked RECON on two design tasks. First, we designed antibodies derived from a common germline gene against their diverse targets to assess recovery of the germline, polyspecific sequence. Second, we design "promiscuous", polyspecific proteins against all binding partners and measure recovery of the native sequence. We show that RECON is able to efficiently recover native-like, biologically relevant sequences in this diverse set of protein complexes.

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).

Nonlinear analysis of sequence symmetry of beta-trefoil family proteins

Energy Technology Data Exchange (ETDEWEB)

Li Mingfeng [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Huang Yanzhao [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Xu Ruizhen [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Xiao Yi [Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China)]. E-mail: yxiao@mail.hust.edu.cn

2005-07-01

The tertiary structures of proteins of beta-trefoil family have three-fold quasi-symmetry while their amino acid sequences appear almost at random. In the present paper we show that these amino acid sequences have hidden symmetries in fact and furthermore the degrees of these hidden symmetries are the same as those of their tertiary structures. We shall present a modified recurrence plot to reveal hidden symmetries in protein sequences. Our results can explain the contradiction in sequence-structure relations of proteins of beta-trefoil family.

Correlated mutations in protein sequences: Phylogenetic and structural effects

Energy Technology Data Exchange (ETDEWEB)

Lapedes, A.S. [Los Alamos National Lab., NM (United States). Theoretical Div.]|[Santa Fe Inst., NM (United States); Giraud, B.G. [C.E.N. Saclay, Gif/Yvette (France). Service Physique Theorique; Liu, L.C. [Los Alamos National Lab., NM (United States). Theoretical Div.; Stormo, G.D. [Univ. of Colorado, Boulder, CO (United States). Dept. of Molecular, Cellular and Developmental Biology

1998-12-01

Covariation analysis of sets of aligned sequences for RNA molecules is relatively successful in elucidating RNA secondary structure, as well as some aspects of tertiary structure. Covariation analysis of sets of aligned sequences for protein molecules is successful in certain instances in elucidating certain structural and functional links, but in general, pairs of sites displaying highly covarying mutations in protein sequences do not necessarily correspond to sites that are spatially close in the protein structure. In this paper the authors identify two reasons why naive use of covariation analysis for protein sequences fails to reliably indicate sequence positions that are spatially proximate. The first reason involves the bias introduced in calculation of covariation measures due to the fact that biological sequences are generally related by a non-trivial phylogenetic tree. The authors present a null-model approach to solve this problem. The second reason involves linked chains of covariation which can result in pairs of sites displaying significant covariation even though they are not spatially proximate. They present a maximum entropy solution to this classic problem of causation versus correlation. The methodologies are validated in simulation.

Podoplanin, novel 43-kd membrane protein of glomerular epithelial cells, is down-regulated in puromycin nephrosis.

Science.gov (United States)

Breiteneder-Geleff, S.; Matsui, K.; Soleiman, A.; Meraner, P.; Poczewski, H.; Kalt, R.; Schaffner, G.; Kerjaschki, D.

1997-01-01

Puromycin aminonucleoside nephrosis (PAN), a rat model of human minimal change nephropathy, is characterized by extensive flattening of glomerular epithelial cell (podocyte) foot processes and by severe proteinuria. For comparison of expression of glomerular membrane proteins of normal and PAN rats, a membrane protein fraction of isolated rat glomeruli was prepared and monoclonal antibodies were raised against it. An IgG-secreting clone designated LF3 was selected that specifically immunolabeled podocytes of normal but not of PAN rats. The antigen of LF3 IgG was identified as a 43-kd glycoprotein. Molecular cloning of its cDNA was performed in a delta gt11 expression library prepared from mRNA of isolated rat glomeruli. The predicted amino acid sequence indicated a 166-amino-acid integral membrane protein with a single membrane-spanning domain, two potential phosphorylation sites in its short cytoplasmic tail, and six potential O-glycosylation sites in the large ectodomain. High amino acid sequence identities were found to membrane glycoproteins of rat lung and bone and mouse thymus epithelial cells as well as to a phorbol-ester-induced protein in a mouse osteoblast cell line and to a canine influenza C virus receptor. In PAN, expression of this 43-kd protein was selectively reduced to < 30%, as determined by quantitative immunogold electron microscopy, immunoblotting, and Northern blotting. These data provide evidence that transcription of the 43-kd transmembrane podocyte glycoprotein is specifically down-regulated in PAN. To indicate that this protein could be associated with transformation of arborized foot processes to flat feet (Latin, pes planus) we have called it podoplanin. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 10 Figure 12 Figure 13 Figure 14 Figure 15 PMID:9327748

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.

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.

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.

Can bottom-up processes of attention be a source of 'interference' in situations where top-down control of attention is crucial?

Science.gov (United States)

Nikolla, Dritan; Edgar, Graham; Catherwood, Dianne; Matthews, Tristan

2018-02-01

In this study, we investigate whether emotionally engaged bottom-up processes of attention can be a source of 'interference' in situations where top-down control of attention is necessary. Participants were asked to monitor and report on a video of a war scenario showing a developing battle in two conditions: emotionally positive and emotionally negative. Half of the participants (n = 15) were exposed to task-irrelevant pictures of positive emotional valence embedded within the scenario; the other half were exposed to task-irrelevant pictures of negative emotional valence. Sensitivity and Bias scores were calculated using signal detection theory. Overall, task accuracy scores were dependent upon the valence; negative pictures had an adverse effect on performance, whereas positive pictures improved performance. We concluded that negative emotional pictures interfered with top-down control of attention by attracting competing bottom-up processes of attention. We found the opposite effect for positive emotional stimuli. © 2017 The British Psychological Society.

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.

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.

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.

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

Bottom-up effects on top-down regulation of a floating aquatic plant by two weevil species: the context-specific nature of biological control

Science.gov (United States)

1. Plant nutrition (bottom-up effects) impacts a plant’s ability to sustain herbivory (top-down effects) and affects phytophagous insect fecundity. These factors potentially confound efficacy predictions for biological control projects. We investigated the relative importance of these two forces wi...

Toward onset prevention of cognitive decline in adults with Down syndrome (the TOP-COG study): study protocol for a randomized controlled trial.

Science.gov (United States)

Cooper, Sally-Ann; Caslake, Muriel; Evans, Jonathan; Hassiotis, Angela; Jahoda, Andrew; McConnachie, Alex; Morrison, Jill; Ring, Howard; Starr, John; Stiles, Ciara; Sullivan, Frank

2014-06-03

Early-onset dementia is common in Down syndrome adults, who have trisomy 21. The amyloid precursor protein gene is on chromosome 21, and so is over-expressed in Down syndrome, leading to amyloid β (Aβ) over-production, a major upstream pathway leading to Alzheimer disease (AD). Statins (microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), have pleiotropic effects including potentially increasing brain amyloid clearance, making them plausible agents to reduce AD risk. Animal models, human observational studies, and small scale trials support this rationale, however, there are no AD primary prevention trials in Down syndrome adults. In this study we study aim to inform the design of a full-scale primary prevention trial. TOP-COG is a feasibility and pilot double-blind randomized controlled trial (RCT), with a nested qualitative study, conducted in the general community. About 60 Down syndrome adults, aged ≥50 will be included. The intervention is oral simvastatin 40 mg at night for 12 months, versus placebo. The primary endpoint is recruitment and retention rates. Secondary endpoints are (1) tolerability and safety; (2) detection of the most sensitive neurocognitive instruments; (3) perceptions of Down syndrome adults and caregivers on whether to participate, and assessment experiences; (4) distributions of cognitive decline, adaptive behavior, general health/quality of life, service use, caregiver strain, and sample size implications; (5) whether Aβ42/Aβ40 is a cognitive decline biomarker. We will describe percentages recruited from each source, the number of contacts to achieve this, plus recruitment rate by general population size. We will calculate summary statistics with 90% confidence limits where appropriate, for each study outcome as a whole, by treatment group and in relation to baseline age, cognitive function, cholesterol and other characteristics. Changes over time will be summarized graphically. The sample size for a definitive

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.

Triptolide inhibits transcription of hTERT through down-regulation of transcription factor specificity protein 1 in primary effusion lymphoma cells

Energy Technology Data Exchange (ETDEWEB)

Long, Cong; Wang, Jingchao [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); Guo, Wei [Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); Wang, Huan; Wang, Chao; Liu, Yu [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); Sun, Xiaoping, E-mail: xsun6@whu.edu.cn [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071 (China); State Key Laboratory of Virology, Wuhan University, Wuhan, 430072 (China)

2016-01-01

Primary effusion lymphoma (PEL) is a rare and aggressive non-Hodgkin's lymphoma. Human telomerase reverse transcriptase (hTERT), a key component responsible for the regulation of telomerase activity, plays important roles in cellular immortalization and cancer development. Triptolide purified from Tripterygium extracts displays a broad-spectrum bioactivity profile, including immunosuppressive, anti-inflammatory, and anti-tumor. In this study, it is investigated whether triptolide reduces hTERT expression and suppresses its activity in PEL cells. The mRNA and protein levels of hTERT were examined by real time-PCR and Western blotting, respectively. The activity of hTERT promoter was determined by Dual luciferase reporter assay. Our results demonstrated that triptolide decreased expression of hTERT at both mRNA and protein levels. Further gene sequence analysis indicated that the activity of hTERT promoter was suppressed by triptolide. Triptolide also reduced the half-time of hTERT. Additionally, triptolide inhibited the expression of transcription factor specificity protein 1(Sp1) in PEL cells. Furthermore, knock-down of Sp1 by using specific shRNAs resulted in down-regulation of hTERT transcription and protein expression levels. Inhibition of Sp1 by specific shRNAs enhanced triptolide-induced cell growth inhibition and apoptosis. Collectively, our results demonstrate that the inhibitory effect of triptolide on hTERT transcription is possibly mediated by inhibition of transcription factor Sp1 in PEL cells. - Highlights: • Triptolide reduces expression of hTERT by decreasing its transcription level. • Triptolide reduces promoter activity and stability of hTERT. • Triptolide down-regulates expression of Sp1. • Special Sp1 shRNAs inhibit transcription and protein expression of hTERT. • Triptolide and Sp1 shRNA2 induce cell proliferation inhibition and apoptosis.

Deep sequencing methods for protein engineering and design.

Science.gov (United States)

Wrenbeck, Emily E; Faber, Matthew S; Whitehead, Timothy A

2017-08-01

The advent of next-generation sequencing (NGS) has revolutionized protein science, and the development of complementary methods enabling NGS-driven protein engineering have followed. In general, these experiments address the functional consequences of thousands of protein variants in a massively parallel manner using genotype-phenotype linked high-throughput functional screens followed by DNA counting via deep sequencing. We highlight the use of information rich datasets to engineer protein molecular recognition. Examples include the creation of multiple dual-affinity Fabs targeting structurally dissimilar epitopes and engineering of a broad germline-targeted anti-HIV-1 immunogen. Additionally, we highlight the generation of enzyme fitness landscapes for conducting fundamental studies of protein behavior and evolution. We conclude with discussion of technological advances. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

Biophysical and structural considerations for protein sequence evolution

Directory of Open Access Journals (Sweden)

Grahnen Johan A

2011-12-01

Full Text Available Abstract Background Protein sequence evolution is constrained by the biophysics of folding and function, causing interdependence between interacting sites in the sequence. However, current site-independent models of sequence evolutions do not take this into account. Recent attempts to integrate the influence of structure and biophysics into phylogenetic models via statistical/informational approaches have not resulted in expected improvements in model performance. This suggests that further innovations are needed for progress in this field. Results Here we develop a coarse-grained physics-based model of protein folding and binding function, and compare it to a popular informational model. We find that both models violate the assumption of the native sequence being close to a thermodynamic optimum, causing directional selection away from the native state. Sampling and simulation show that the physics-based model is more specific for fold-defining interactions that vary less among residue type. The informational model diffuses further in sequence space with fewer barriers and tends to provide less support for an invariant sites model, although amino acid substitutions are generally conservative. Both approaches produce sequences with natural features like dN/dS Conclusions Simple coarse-grained models of protein folding can describe some natural features of evolving proteins but are currently not accurate enough to use in evolutionary inference. This is partly due to improper packing of the hydrophobic core. We suggest possible improvements on the representation of structure, folding energy, and binding function, as regards both native and non-native conformations, and describe a large number of possible applications for such a model.

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...

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.

Search for same-sign top-quark production and fourth-generation down-type quarks in pp collisions at $\\sqrt{s}$ = 7 TeV with the ATLAS detector

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Aad, Georges; Abdallah, Jalal; Abdel Khalek, Samah; Abdelalim, Ahmed Ali; Abdesselam, Abdelouahab; Abdinov, Ovsat; Abi, Babak; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Acerbi, Emilio; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Addy, Tetteh; Adelman, Jahred; Aderholz, Michael; Adomeit, Stefanie; Adragna, Paolo; Adye, Tim; Aefsky, Scott; Aguilar-Saavedra, Juan Antonio; Aharrouche, Mohamed; Ahlen, Steven; Ahles, Florian; Ahmad, Ashfaq; Ahsan, Mahsana; Aielli, Giulio; Akdogan, Taylan; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Akiyama, Kunihiro; Alam, Mohammad; Alam, Muhammad Aftab; Albert, Justin; Albrand, Solveig; Aleksa, Martin; Aleksandrov, Igor; Alessandria, Franco; Alexa, Calin; Alexander, Gideon; Alexandre, Gauthier; Alexopoulos, Theodoros; Alhroob, Muhammad; Aliev, Malik; Alimonti, Gianluca; Alison, John; Aliyev, Magsud; Allbrooke, Benedict; Allport, Phillip; Allwood-Spiers, Sarah; Almond, John; Aloisio, Alberto; Alon, Raz; Alonso, Alejandro; Alvarez Gonzalez, Barbara; Alviggi, Mariagrazia; Amako, Katsuya; Amaral, Pedro; Amelung, Christoph; Ammosov, Vladimir; Amorim, Antonio; Amorós, Gabriel; Amram, Nir; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Andrieux, Marie-Laure; Anduaga, Xabier; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonaki, Ariadni; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoun, Sahar; Aperio Bella, Ludovica; Apolle, Rudi; Arabidze, Giorgi; Aracena, Ignacio; Arai, Yasuo; Arce, Ayana; Arfaoui, Samir; Arguin, Jean-Francois; Arik, Engin; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arnault, Christian; Artamonov, Andrei; Artoni, Giacomo; Arutinov, David; Asai, Shoji; Asfandiyarov, Ruslan; Ask, Stefan; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astbury, Alan; Astvatsatourov, Anatoli; Aubert, Bernard; Auge, Etienne; Augsten, Kamil; Aurousseau, Mathieu; Avolio, Giuseppe; Avramidou, Rachel Maria; Axen, David; Ay, Cano; Azuelos, Georges; Azuma, Yuya; Baak, Max; Baccaglioni, Giuseppe; Bacci, Cesare; Bach, Andre; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Badescu, Elisabeta; Bagnaia, Paolo; Bahinipati, Seema; Bai, Yu; Bailey, David; Bain, Travis; Baines, John; Baker, Oliver Keith; Baker, Mark; Baker, Sarah; Banas, Elzbieta; Banerjee, Piyali; Banerjee, Swagato; Banfi, Danilo; Bangert, Andrea Michelle; Bansal, Vikas; Bansil, Hardeep Singh; Barak, Liron; Baranov, Sergei; Barashkou, Andrei; Barbaro Galtieri, Angela; Barber, Tom; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Bardin, Dmitri; Barillari, Teresa; Barisonzi, Marcello; Barklow, Timothy; Barlow, Nick; Barnett, Bruce; Barnett, Michael; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Barrillon, Pierre; Bartoldus, Rainer; Barton, Adam Edward; Bartsch, Valeria; Bates, Richard; Batkova, Lucia; Batley, Richard; Battaglia, Andreas; Battistin, Michele; Bauer, Florian; Bawa, Harinder Singh; Beale, Steven; Beau, Tristan; Beauchemin, Pierre-Hugues; Beccherle, Roberto; Bechtle, Philip; Beck, Hans Peter; Becker, Sebastian; Beckingham, Matthew; Becks, Karl-Heinz; Beddall, Andrew; Beddall, Ayda; Bedikian, Sourpouhi; Bednyakov, Vadim; Bee, Christopher; Begel, Michael; Behar Harpaz, Silvia; Behera, Prafulla; Beimforde, Michael; Belanger-Champagne, Camille; Bell, Paul; Bell, William; Bella, Gideon; Bellagamba, Lorenzo; Bellina, Francesco; Bellomo, Massimiliano; Belloni, Alberto; Beloborodova, Olga; Belotskiy, Konstantin; Beltramello, Olga; Benary, Odette; Benchekroun, Driss; Benchouk, Chafik; Bendel, Markus; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez Garcia, Jorge-Armando; Benjamin, Douglas; Benoit, Mathieu; Bensinger, James; Benslama, Kamal; Bentvelsen, Stan; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Berghaus, Frank; Berglund, Elina; Beringer, Jürg; Bernat, Pauline; Bernhard, Ralf; Bernius, Catrin; Berry, Tracey; Bertella, Claudia; Bertin, Antonio; Bertinelli, Francesco; Bertolucci, Federico; Besana, Maria Ilaria; Besson, Nathalie; Bethke, Siegfried; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianco, Michele; Biebel, Otmar; Bieniek, Stephen Paul; Bierwagen, Katharina; Biesiada, Jed; Biglietti, Michela; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Biscarat, Catherine; Bitenc, Urban; Black, Kevin; Blair, Robert; Blanchard, Jean-Baptiste; Blanchot, Georges; Blazek, Tomas; Blocker, Craig; Blocki, Jacek; Blondel, Alain; Blum, Walter; Blumenschein, Ulrike; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Boddy, Christopher Richard; Boehler, Michael; Boek, Jennifer; Boelaert, Nele; Bogaerts, Joannes Andreas; Bogdanchikov, Alexander; Bogouch, Andrei; Bohm, Christian; Bohm, Jan; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Bolnet, Nayanka Myriam; Bomben, Marco; Bona, Marcella; Bondarenko, Valery; Bondioli, Mario; Boonekamp, Maarten; Booth, Chris; Bordoni, Stefania; Borer, Claudia; Borisov, Anatoly; Borissov, Guennadi; Borjanovic, Iris; Borri, Marcello; Borroni, Sara; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boterenbrood, Hendrik; Botterill, David; Bouchami, Jihene; Boudreau, Joseph; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozhko, Nikolay; Bozovic-Jelisavcic, Ivanka; Bracinik, Juraj; Braem, André; Branchini, Paolo; Brandenburg, George; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brelier, Bertrand; Bremer, Johan; Brendlinger, Kurt; Brenner, Richard; Bressler, Shikma; Britton, Dave; Brochu, Frederic; Brock, Ian; Brock, Raymond; Brodbeck, Timothy; Brodet, Eyal; Broggi, Francesco; Bromberg, Carl; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, William; Brown, Gareth; Brown, Heather; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Brunet, Sylvie; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Buanes, Trygve; Buat, Quentin; Bucci, Francesca; Buchanan, James; Buchanan, Norman; Buchholz, Peter; Buckingham, Ryan; Buckley, Andrew; Buda, Stelian Ioan; Budagov, Ioulian; Budick, Burton; Büscher, Volker; Bugge, Lars; Bulekov, Oleg; Bunse, Moritz; Buran, Torleiv; Burckhart, Helfried; Burdin, Sergey; Burgess, Thomas; Burke, Stephen; Busato, Emmanuel; Bussey, Peter; Buszello, Claus-Peter; Butin, François; Butler, Bart; Butler, John; Buttar, Craig; Butterworth, Jonathan; Buttinger, William; Cabrera Urbán, Susana; Caforio, Davide; Cakir, Orhan; Calafiura, Paolo; Calderini, Giovanni; Calfayan, Philippe; Calkins, Robert; Caloba, Luiz; Caloi, Rita; Calvet, David; Calvet, Samuel; Camacho Toro, Reina; Camarri, Paolo; Cambiaghi, Mario; Cameron, David; Caminada, Lea Michaela; Campana, Simone; Campanelli, Mario; Canale, Vincenzo; Canelli, Florencia; Canepa, Anadi; Cantero, Josu; Capasso, Luciano; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capriotti, Daniele; Capua, Marcella; Caputo, Regina; Cardarelli, Roberto; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Bryan; Caron, Sascha; Carquin, Edson; Carrillo Montoya, German D; Carter, Antony; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Cascella, Michele; Caso, Carlo; Castaneda Hernandez, Alfredo Martin; Castaneda-Miranda, Elizabeth; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Cataldi, Gabriella; Cataneo, Fernando; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Cattani, Giordano; Caughron, Seth; Cauz, Diego; Cavalleri, Pietro; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cetin, Serkant Ali; Cevenini, Francesco; Chafaq, Aziz; Chakraborty, Dhiman; Chan, Kevin; Chapleau, Bertrand; Chapman, John Derek; Chapman, John Wehrley; Chareyre, Eve; Charlton, Dave; Chavda, Vikash; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Shenjian; Chen, Tingyang; Chen, Xin; Cheng, Shaochen; Cheplakov, Alexander; Chepurnov, Vladimir; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Cheung, Sing-Leung; Chevalier, Laurent; Chiefari, Giovanni; Chikovani, Leila; Childers, John Taylor; Chilingarov, Alexandre; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chizhov, Mihail; Choudalakis, Georgios; Chouridou, Sofia; Christidi, Illectra-Athanasia; Christov, Asen; Chromek-Burckhart, Doris; Chu, Ming-Lee; Chudoba, Jiri; Ciapetti, Guido; Ciftci, Abbas Kenan; Ciftci, Rena; Cinca, Diane; Cindro, Vladimir; Ciobotaru, Matei Dan; Ciocca, Claudia; Ciocio, Alessandra; Cirilli, Manuela; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Philip James; Cleland, Bill; Clemens, Jean-Claude; Clement, Benoit; Clement, Christophe; Clifft, Roger; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coe, Paul; Cogan, Joshua Godfrey; Coggeshall, James; Cogneras, Eric; Colas, Jacques; Colijn, Auke-Pieter; Collins, Neil; Collins-Tooth, Christopher; Collot, Johann; Colon, German; Conde Muiño, Patricia; Coniavitis, Elias; Conidi, Maria Chiara; Consonni, Michele; Consonni, Sofia Maria; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cook, James; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Copic, Katherine; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Costin, Tudor; Côté, David; Coura Torres, Rodrigo; Courneyea, Lorraine; Cowan, Glen; Cowden, Christopher; Cox, Brian; Cranmer, Kyle; Crescioli, Francesco; Cristinziani, Markus; Crosetti, Giovanni; Crupi, Roberto; Crépé-Renaudin, Sabine; Cuciuc, Constantin-Mihai; Cuenca Almenar, Cristóbal; Cuhadar Donszelmann, Tulay; Curatolo, Maria; Curtis, Chris; Cuthbert, Cameron; Cwetanski, Peter; Czirr, Hendrik; Czodrowski, Patrick; Czyczula, Zofia; D'Auria, Saverio; D'Onofrio, Monica; D'Orazio, Alessia; Da Silva, Paulo Vitor; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dallapiccola, Carlo; Dam, Mogens; Dameri, Mauro; Damiani, Daniel; Danielsson, Hans Olof; Dannheim, Dominik; Dao, Valerio; Darbo, Giovanni; Darlea, Georgiana Lavinia; Davey, Will; Davidek, Tomas; Davidson, Nadia; Davidson, Ruth; Davies, Eleanor; Davies, Merlin; Davison, Adam; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Dawson, John; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Castro Faria Salgado, Pedro; De Cecco, Sandro; de Graat, Julien; De Groot, Nicolo; de Jong, Paul; De La Taille, Christophe; De la Torre, Hector; De Lotto, Barbara; de Mora, Lee; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; De Zorzi, Guido; Dean, Simon; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dechenaux, Benjamin; Dedovich, Dmitri; Degenhardt, James; Dehchar, Mohamed; Del Papa, Carlo; Del Peso, Jose; Del Prete, Tarcisio; Delemontex, Thomas; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delruelle, Nicolas; Delsart, Pierre-Antoine; Deluca, Carolina; Demers, Sarah; Demichev, Mikhail; Demirkoz, Bilge; Deng, Jianrong; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Devetak, Erik; Deviveiros, Pier-Olivier; Dewhurst, Alastair; DeWilde, Burton; Dhaliwal, Saminder; Dhullipudi, Ramasudhakar; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Luise, Silvestro; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Diaz, Marco Aurelio; Diblen, Faruk; Diehl, Edward; Dietrich, Janet; Dietzsch, Thorsten; Diglio, Sara; Dindar Yagci, Kamile; Dingfelder, Jochen; Dionisi, Carlo; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Barros do Vale, Maria Aline; Do Valle Wemans, André; Doan, Thi Kieu Oanh; Dobbs, Matt; Dobinson, Robert; Dobos, Daniel; Dobson, Ellie; Dodd, Jeremy; Doglioni, Caterina; Doherty, Tom; Doi, Yoshikuni; Dolejsi, Jiri; Dolenc, Irena; Dolezal, Zdenek; Dolgoshein, Boris; Dohmae, Takeshi; Donadelli, Marisilvia; Donega, Mauro; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dos Anjos, Andre; Dosil, Mireia; Dotti, Andrea; Dova, Maria-Teresa; Dowell, John; Doxiadis, Alexander; Doyle, Tony; Drasal, Zbynek; Drees, Jürgen; Dressnandt, Nandor; Drevermann, Hans; Driouichi, Chafik; Dris, Manolis; Dubbert, Jörg; Dube, Sourabh; Duchovni, Ehud; Duckeck, Guenter; Dudarev, Alexey; Dudziak, Fanny; Dührssen, Michael; Duerdoth, Ian; Duflot, Laurent; Dufour, Marc-Andre; Dunford, Monica; Duran Yildiz, Hatice; Duxfield, Robert; Dwuznik, Michal; Dydak, Friedrich; Düren, Michael; Ebenstein, William; Ebke, Johannes; Eckweiler, Sebastian; Edmonds, Keith; Edwards, Clive; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Ehrich, Thies; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Eisenhandler, Eric; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Ellis, Katherine; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Engelmann, Roderich; Engl, Albert; Epp, Brigitte; Eppig, Andrew; Erdmann, Johannes; Ereditato, Antonio; Eriksson, Daniel; Ernst, Jesse; Ernst, Michael; Ernwein, Jean; Errede, Deborah; Errede, Steven; Ertel, Eugen; Escalier, Marc; Escobar, Carlos; Espinal Curull, Xavier; Esposito, Bellisario; Etienne, Francois; Etienvre, Anne-Isabelle; Etzion, Erez; Evangelakou, Despoina; Evans, Hal; Fabbri, Laura; Fabre, Caroline; Fakhrutdinov, Rinat; Falciano, Speranza; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farley, Jason; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassnacht, Patrick; Fassouliotis, Dimitrios; Fatholahzadeh, Baharak; Favareto, Andrea; Fayard, Louis; Fazio, Salvatore; Febbraro, Renato; Federic, Pavol; Fedin, Oleg; Fedorko, Woiciech; Fehling-Kaschek, Mirjam; Feligioni, Lorenzo; Fellmann, Denis; Feng, Cunfeng; Feng, Eric; Fenyuk, Alexander; Ferencei, Jozef; Ferland, Jonathan; Fernando, Waruna; Ferrag, Samir; Ferrando, James; Ferrara, Valentina; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrer, Maria Lorenza; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filippas, Anastasios; Filthaut, Frank; Fincke-Keeler, Margret; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Gordon; Fischer, Peter; Fisher, Matthew; Flechl, Martin; Fleck, Ivor; Fleckner, Johanna; Fleischmann, Philipp; Fleischmann, Sebastian; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Fokitis, Manolis; Fonseca Martin, Teresa; Forbush, David Alan; Formica, Andrea; Forti, Alessandra; Fortin, Dominique; Foster, Joe; Fournier, Daniel; Foussat, Arnaud; Fowler, Andrew; Fowler, Ken; Fox, Harald; Francavilla, Paolo; Franchino, Silvia; Francis, David; Frank, Tal; Franklin, Melissa; Franz, Sebastien; Fraternali, Marco; Fratina, Sasa; French, Sky; Friedrich, Felix; Froeschl, Robert; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gadfort, Thomas; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Gallas, Elizabeth; Gallo, Valentina Santina; Gallop, Bruce; Gallus, Petr; Gan, KK; Gao, Yongsheng; Gapienko, Vladimir; Gaponenko, Andrei; Garberson, Ford; Garcia-Sciveres, Maurice; García, Carmen; García Navarro, José Enrique; Gardner, Robert; Garelli, Nicoletta; Garitaonandia, Hegoi; Garonne, Vincent; Garvey, John; Gatti, Claudio; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gayde, Jean-Christophe; Gazis, Evangelos; Ge, Peng; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Gellerstedt, Karl; Gemme, Claudia; Gemmell, Alistair; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerlach, Peter; Gershon, Avi; Geweniger, Christoph; Ghazlane, Hamid; Ghodbane, Nabil; Giacobbe, Benedetto; Giagu, Stefano; Giakoumopoulou, Victoria; Giangiobbe, Vincent; Gianotti, Fabiola; Gibbard, Bruce; Gibson, Adam; Gibson, Stephen; Gilbert, Laura; Gilewsky, Valentin; Gillberg, Dag; Gillman, Tony; Gingrich, Douglas; Ginzburg, Jonatan; Giokaris, Nikos; Giordani, MarioPaolo; Giordano, Raffaele; Giorgi, Francesco Michelangelo; Giovannini, Paola; Giraud, Pierre-Francois; Giugni, Danilo; Giunta, Michele; Giusti, Paolo; Gjelsten, Børge Kile; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glazov, Alexandre; Glitza, Karl-Walter; Glonti, George; Goddard, Jack Robert; Godfrey, Jennifer; Godlewski, Jan; Goebel, Martin; Göpfert, Thomas; Goeringer, Christian; Gössling, Claus; Göttfert, Tobias; Goldfarb, Steven; Golling, Tobias; Gomes, Agostinho; Gomez Fajardo, Luz Stella; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; Gonidec, Allain; Gonzalez, Saul; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez Silva, Laura; Gonzalez-Sevilla, Sergio; Goodson, Jeremiah Jet; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorfine, Grant; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Gorokhov, Serguei; Goryachev, Vladimir; Gosdzik, Bjoern; Gosselink, Martijn; Gostkin, Mikhail Ivanovitch; Gough Eschrich, Ivo; Gouighri, Mohamed; Goujdami, Driss; Goulette, Marc Phillippe; Goussiou, Anna; Goy, Corinne; Gozpinar, Serdar; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Grancagnolo, Francesco; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Grau, Nathan; Gray, Heather; Gray, Julia Ann; Graziani, Enrico; Grebenyuk, Oleg; Greenshaw, Timothy; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grigalashvili, Nugzar; Grillo, Alexander; Grinstein, Sebastian; Grishkevich, Yaroslav; Grivaz, Jean-Francois; Groh, Manfred; Gross, Eilam; Grosse-Knetter, Joern; Groth-Jensen, Jacob; Grybel, Kai; Guarino, Victor; Guest, Daniel; Guicheney, Christophe; Guida, Angelo; Guindon, Stefan; Guler, Hulya; Gunther, Jaroslav; Guo, Bin; Guo, Jun; Gupta, Ambreesh; Gusakov, Yury; Gushchin, Vladimir; Gutierrez, Phillip; Guttman, Nir; Gutzwiller, Olivier; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haas, Stefan; Haber, Carl; Hadavand, Haleh Khani; Hadley, David; Haefner, Petra; Hahn, Ferdinand; Haider, Stefan; Hajduk, Zbigniew; Hakobyan, Hrachya; Hall, David; Haller, Johannes; Hamacher, Klaus; Hamal, Petr; Hamer, Matthias; Hamilton, Andrew; Hamilton, Samuel; Han, Hongguang; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Handel, Carsten; Hanke, Paul; Hansen, John Renner; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Peter Henrik; Hansson, Per; Hara, Kazuhiko; Hare, Gabriel; Harenberg, Torsten; Harkusha, Siarhei; Harper, Devin; Harrington, Robert; Harris, Orin; Harrison, Karl; Hartert, Jochen; Hartjes, Fred; Haruyama, Tomiyoshi; Harvey, Alex; Hasegawa, Satoshi; Hasegawa, Yoji; Hassani, Samira; Hatch, Mark; Hauff, Dieter; Haug, Sigve; Hauschild, Michael; Hauser, Reiner; Havranek, Miroslav; Hawes, Brian; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hawkins, Donovan; Hayakawa, Takashi; Hayashi, Takayasu; Hayden, Daniel; Hayward, Helen; Haywood, Stephen; Hazen, Eric; He, Mao; Head, Simon; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heinemann, Beate; Heisterkamp, Simon; Helary, Louis; Heller, Claudio; Heller, Matthieu; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, Robert; Henke, Michael; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Henry-Couannier, Frédéric; Hensel, Carsten; Henß, Tobias; Medina Hernandez, Carlos; Hernández Jiménez, Yesenia; Herrberg, Ruth; Hershenhorn, Alon David; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Higón-Rodriguez, Emilio; Hill, Daniel; Hill, John; Hill, Norman; Hiller, Karl Heinz; Hillert, Sonja; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hirose, Minoru; Hirsch, Florian; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoffman, Julia; Hoffmann, Dirk; Hohlfeld, Marc; Holder, Martin; Holmgren, Sven-Olof; Holy, Tomas; Holzbauer, Jenny; Homma, Yasuhiro; Hong, Tae Min; Hooft van Huysduynen, Loek; Horazdovsky, Tomas; Horn, Claus; Horner, Stephan; Hostachy, Jean-Yves; Hou, Suen; Houlden, Michael; Hoummada, Abdeslam; Howarth, James; Howell, David; Hristova, Ivana; Hrivnac, Julius; Hruska, Ivan; Hryn'ova, Tetiana; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Huang, Guang Shun; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huettmann, Antje; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Hughes-Jones, Richard; Huhtinen, Mika; Hurst, Peter; Hurwitz, Martina; Husemann, Ulrich; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibbotson, Michael; Ibragimov, Iskander; Ichimiya, Ryo; Iconomidou-Fayard, Lydia; Idarraga, John; Iengo, Paolo; Igonkina, Olga; Ikegami, Yoichi; Ikeno, Masahiro; Ilchenko, Yuri; Iliadis, Dimitrios; Ilic, Nikolina; Imori, Masatoshi; Ince, Tayfun; Inigo-Golfin, Joaquin; Ioannou, Pavlos; Iodice, Mauro; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishikawa, Akimasa; Ishino, Masaya; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Ivashin, Anton; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jackson, Brett; Jackson, John; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakubek, Jan; Jana, Dilip; Jankowski, Ernest; Jansen, Eric; Jansen, Hendrik; Jantsch, Andreas; Janus, Michel; Jarlskog, Göran; Jeanty, Laura; Jelen, Kazimierz; Jen-La Plante, Imai; Jenni, Peter; Jeremie, Andrea; Jež, Pavel; Jézéquel, Stéphane; Jha, Manoj Kumar; Ji, Haoshuang; Ji, Weina; Jia, Jiangyong; Jiang, Yi; Jimenez Belenguer, Marcos; Jin, Ge; Jin, Shan; Jinnouchi, Osamu; Joergensen, Morten Dam; Joffe, David; Johansen, Lars; Johansen, Marianne; Johansson, Erik; Johansson, Per; Johnert, Sebastian; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tegid; Jones, Tim; Jonsson, Ove; Joram, Christian; Jorge, Pedro; Joseph, John; Jovicevic, Jelena; Jovin, Tatjana; Ju, Xiangyang; Jung, Christian; Jungst, Ralph Markus; Juranek, Vojtech; Jussel, Patrick; Juste Rozas, Aurelio; Kabachenko, Vasily; Kabana, Sonja; Kaci, Mohammed; Kaczmarska, Anna; Kadlecik, Peter; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kaiser, Steffen; Kajomovitz, Enrique; Kalinin, Sergey; Kalinovskaya, Lidia; Kama, Sami; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kanno, Takayuki; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kaplon, Jan; Kar, Deepak; Karagounis, Michael; Karagoz, Muge; Karnevskiy, Mikhail; Karr, Kristo; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kasieczka, Gregor; Kass, Richard; Kastanas, Alex; Kataoka, Mayuko; Kataoka, Yousuke; Katsoufis, Elias; Katzy, Judith; Kaushik, Venkatesh; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kayl, Manuel; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keil, Markus; Kekelidze, George; Keller, John; Kennedy, John; Kenyon, Mike; Kepka, Oldrich; Kerschen, Nicolas; Kerševan, Borut Paul; Kersten, Susanne; Kessoku, Kohei; Keung, Justin; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharchenko, Dmitri; Khodinov, Alexander; Kholodenko, Anatoli; Khomich, Andrei; Khoo, Teng Jian; Khoriauli, Gia; Khoroshilov, Andrey; Khovanskiy, Nikolai; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hyeon Jin; Kim, Min Suk; Kim, Shinhong; Kimura, Naoki; Kind, Oliver; King, Barry; King, Matthew; King, Robert Steven Beaufoy; Kirk, Julie; Kirsch, Lawrence; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kittelmann, Thomas; Kiver, Andrey; Kladiva, Eduard; Klaiber-Lodewigs, Jonas; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klemetti, Miika; Klier, Amit; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klinkby, Esben; Klioutchnikova, Tatiana; Klok, Peter; Klous, Sander; Kluge, Eike-Erik; Kluge, Thomas; Kluit, Peter; Kluth, Stefan; Knecht, Neil; Kneringer, Emmerich; Knobloch, Juergen; Knoops, Edith; Knue, Andrea; Ko, Byeong Rok; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Köneke, Karsten; König, Adriaan; Koenig, Sebastian; Köpke, Lutz; Koetsveld, Folkert; Koevesarki, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohn, Fabian; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kokott, Thomas; Kolachev, Guennady; Kolanoski, Hermann; Kolesnikov, Vladimir; Koletsou, Iro; Koll, James; Kollefrath, Michael; Kolya, Scott; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kono, Takanori; Kononov, Anatoly; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kootz, Andreas; Koperny, Stefan; Korcyl, Krzysztof; Kordas, Kostantinos; Koreshev, Victor; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Korotkov, Vladislav; Kortner, Oliver; Kortner, Sandra; Kostyukhin, Vadim; Kotamäki, Miikka Juhani; Kotov, Sergey; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kral, Vlastimil; Kramarenko, Viktor; Kramberger, Gregor; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, James; Kraus, Jana; Kreisel, Arik; Krejci, Frantisek; Kretzschmar, Jan; Krieger, Nina; Krieger, Peter; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Kruker, Tobias; Krumnack, Nils; Krumshteyn, Zinovii; Kruth, Andre; Kubota, Takashi; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuhl, Thorsten; Kuhn, Dietmar; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kummer, Christian; Kuna, Marine; Kundu, Nikhil; Kunkle, Joshua; Kupco, Alexander; Kurashige, Hisaya; Kurata, Masakazu; Kurochkin, Yurii; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwee, Regina; La Rosa, Alessandro; La Rotonda, Laura; Labarga, Luis; Labbe, Julien; Lablak, Said; Lacasta, Carlos; Lacava, Francesco; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Laisne, Emmanuel; Lamanna, Massimo; Lambourne, Luke; Lampen, Caleb; Lampl, Walter; Lancon, Eric; Landgraf, Ulrich; Landon, Murrough; Lane, Jenna; Lange, Clemens; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Larionov, Anatoly; Larner, Aimee; Lasseur, Christian; Lassnig, Mario; Laurelli, Paolo; Lavorini, Vincenzo; Lavrijsen, Wim; Laycock, Paul; Lazarev, Alexandre; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Maner, Christophe; Le Menedeu, Eve; Lebel, Céline; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Hurng-Chun; Lee, Jason; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Michel; Legendre, Marie; Leger, Annie; LeGeyt, Benjamin; Legger, Federica; Leggett, Charles; Lehmacher, Marc; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Leltchouk, Mikhail; Lemmer, Boris; Lendermann, Victor; Leney, Katharine; Lenz, Tatiana; Lenzen, Georg; Lenzi, Bruno; Leonhardt, Kathrin; Leontsinis, Stefanos; Leroy, Claude; Lessard, Jean-Raphael; Lesser, Jonas; Lester, Christopher; Leung Fook Cheong, Annabelle; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levitski, Mikhail; Lewis, Adrian; Lewis, George; Leyko, Agnieszka; Leyton, Michael; Li, Bo; Li, Haifeng; Li, Shu; Li, Xuefei; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Lichard, Peter; Lichtnecker, Markus; Lie, Ki; Liebig, Wolfgang; Lifshitz, Ronen; Limbach, Christian; Limosani, Antonio; Limper, Maaike; Lin, Simon; Linde, Frank; Linnemann, James; Lipeles, Elliot; Lipinsky, Lukas; Lipniacka, Anna; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Chuanlei; Liu, Dong; Liu, Hao; Liu, Jianbei; Liu, Minghui; Liu, Yanwen; Livan, Michele; Livermore, Sarah; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loddenkoetter, Thomas; Loebinger, Fred; Loginov, Andrey; Loh, Chang Wei; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Loken, James; Lombardo, Vincenzo Paolo; Long, Robin Eamonn; Lopes, Lourenco; Lopez Mateos, David; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lo Sterzo, Francesco; Losty, Michael; Lou, Xinchou; Lounis, Abdenour; Loureiro, Karina; Love, Jeremy; Love, Peter; Lowe, Andrew; Lu, Feng; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Ludwig, Andreas; Ludwig, Dörthe; Ludwig, Inga; Ludwig, Jens; Luehring, Frederick; Luijckx, Guy; Lukas, Wolfgang; Lumb, Debra; Luminari, Lamberto; Lund, Esben; Lund-Jensen, Bengt; Lundberg, Björn; Lundberg, Johan; Lundquist, Johan; Lungwitz, Matthias; Lutz, Gerhard; Lynn, David; Lys, Jeremy; Lytken, Else; Ma, Hong; Ma, Lian Liang; Macana Goia, Jorge Andres; Maccarrone, Giovanni; Macchiolo, Anna; Maček, Boštjan; Machado Miguens, Joana; Mackeprang, Rasmus; Madaras, Ronald; Mader, Wolfgang; Maenner, Reinhard; Maeno, Tadashi; Mättig, Peter; Mättig, Stefan; Magnoni, Luca; Magradze, Erekle; Mahalalel, Yair; Mahboubi, Kambiz; Mahmoud, Sara; Mahout, Gilles; Maiani, Camilla; Maidantchik, Carmen; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Mal, Prolay; Malaescu, Bogdan; Malecki, Pawel; Malecki, Piotr; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mameghani, Raphael; Mamuzic, Judita; Manabe, Atsushi; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Mangeard, Pierre-Simon; Manhaes de Andrade Filho, Luciano; Manjavidze, Ioseb; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Manz, Andreas; Mapelli, Alessandro; Mapelli, Livio; March, Luis; Marchand, Jean-Francois; Marchese, Fabrizio; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marroquim, Fernando; Marshall, Robin; Marshall, Zach; Martens, Kalen; Marti-Garcia, Salvador; Martin, Andrew; Martin, Brian; Martin, Brian Thomas; Martin, Franck Francois; Martin, Jean-Pierre; Martin, Philippe; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martin-Haugh, Stewart; Martinez, Mario; Martinez Outschoorn, Verena; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massaro, Graziano; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Matricon, Pierre; Matsumoto, Hiroshi; Matsunaga, Hiroyuki; Matsushita, Takashi; Mattravers, Carly; Maugain, Jean-Marie; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; May, Edward; Mayne, Anna; Mazini, Rachid; Mazur, Michael; Mazzanti, Marcello; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; McGlone, Helen; Mchedlidze, Gvantsa; McLaren, Robert Andrew; Mclaughlan, Tom; McMahon, Steve; McPherson, Robert; Meade, Andrew; Mechnich, Joerg; Mechtel, Markus; Medinnis, Mike; Meera-Lebbai, Razzak; Meguro, Tatsuma; Mehdiyev, Rashid; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meirose, Bernhard; Melachrinos, Constantinos; Mellado Garcia, Bruce Rafael; Mendoza Navas, Luis; Meng, Zhaoxia; Mengarelli, Alberto; Menke, Sven; Menot, Claude; Meoni, Evelin; Mercurio, Kevin Michael; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Merritt, Hayes; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer, Joerg; Meyer, Thomas Christian; Meyer, W Thomas; Miao, Jiayuan; Michal, Sebastien; Micu, Liliana; Middleton, Robin; Migas, Sylwia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Miller, David; Miller, Robert; Mills, Bill; Mills, Corrinne; Milov, Alexander; Milstead, David; Milstein, Dmitry; Minaenko, Andrey; Miñano Moya, Mercedes; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mirabelli, Giovanni; Miralles Verge, Lluis; Misiejuk, Andrzej; Mitrevski, Jovan; Mitrofanov, Gennady; Mitsou, Vasiliki A; Mitsui, Shingo; Miyagawa, Paul; Miyazaki, Kazuki; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mockett, Paul; Moed, Shulamit; Moeller, Victoria; Mönig, Klaus; Möser, Nicolas; Mohapatra, Soumya; Mohr, Wolfgang; Mohrdieck-Möck, Susanne; Moisseev, Artemy; Moles-Valls, Regina; Molina-Perez, Jorge; Monk, James; Monnier, Emmanuel; Montesano, Simone; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Moorhead, Gareth; Mora Herrera, Clemencia; Moraes, Arthur; Morange, Nicolas; Morel, Julien; Morello, Gianfranco; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Morin, Jerome; Morley, Anthony Keith; Mornacchi, Giuseppe; Morozov, Sergey; Morris, John; Morvaj, Ljiljana; Moser, Hans-Guenther; Mosidze, Maia; Moss, Josh; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Mudrinic, Mihajlo; Mueller, Felix; Mueller, James; Mueller, Klemens; Müller, Thomas; Mueller, Timo; Muenstermann, Daniel; Muir, Alex; Munwes, Yonathan; Murray, Bill; Mussche, Ido; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nadal, Jordi; Nagai, Koichi; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagel, Martin; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Nanava, Gizo; Napier, Austin; Narayan, Rohin; Nash, Michael; Nation, Nigel; Nattermann, Till; Naumann, Thomas; Navarro, Gabriela; Neal, Homer; Nebot, Eduardo; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negri, Guido; Nektarijevic, Snezana; Nelson, Andrew; Nelson, Timothy Knight; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neusiedl, Andrea; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen Thi Hong, Van; Nickerson, Richard; Nicolaidou, Rosy; Nicolas, Ludovic; Nicquevert, Bertrand; Niedercorn, Francois; Nielsen, Jason; Niinikoski, Tapio; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolaev, Kirill; Nikolic-Audit, Irena; Nikolics, Katalin; Nikolopoulos, Konstantinos; Nilsen, Henrik; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nishiyama, Tomonori; Nisius, Richard; Nodulman, Lawrence; Nomachi, Masaharu; Nomidis, Ioannis; Nordberg, Markus; Nordkvist, Bjoern; Norton, Peter; Novakova, Jana; Nozaki, Mitsuaki; Nozka, Libor; Nugent, Ian Michael; Nuncio-Quiroz, Adriana-Elizabeth; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; O'Brien, Brendan Joseph; O'Neale, Steve; O'Neil, Dugan; O'Shea, Val; Oakes, Louise Beth; Oakham, Gerald; Oberlack, Horst; Ocariz, Jose; Ochi, Atsuhiko; Oda, Susumu; Odaka, Shigeru; Odier, Jerome; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohshima, Takayoshi; Ohshita, Hidetoshi; Okada, Shogo; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olcese, Marco; Olchevski, Alexander; Olivares Pino, Sebastian Andres; Oliveira, Miguel Alfonso; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olivito, Dominick; Olszewski, Andrzej; Olszowska, Jolanta; Omachi, Chihiro; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Orlov, Iliya; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Osuna, Carlos; Otero y Garzon, Gustavo; Ottersbach, John; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Owen, Simon; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagan Griso, Simone; Paganis, Efstathios; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Paleari, Chiara; Palestini, Sandro; Pallin, Dominique; Palma, Alberto; Palmer, Jody; Pan, Yibin; Panagiotopoulou, Evgenia; Panes, Boris; Panikashvili, Natalia; Panitkin, Sergey; Pantea, Dan; Panuskova, Monika; Paolone, Vittorio; Papadelis, Aras; Papadopoulou, Theodora; Paramonov, Alexander; Paredes Hernandez, Daniela; Park, Woochun; Parker, Andy; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pashapour, Shabnaz; Pasqualucci, Enrico; Passaggio, Stefano; Passeri, Antonio; Pastore, Fernanda; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Patricelli, Sergio; Pauly, Thilo; Pecsy, Martin; Pedraza Morales, Maria Isabel; Peleganchuk, Sergey; Peng, Haiping; Pengo, Ruggero; Penning, Bjoern; Penson, Alexander; Penwell, John; Perantoni, Marcelo; Perez, Kerstin; Perez Cavalcanti, Tiago; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perez Reale, Valeria; Perini, Laura; Pernegger, Heinz; Perrino, Roberto; Perrodo, Pascal; Persembe, Seda; Peshekhonov, Vladimir; Peters, Krisztian; Petersen, Brian; Petersen, Jorgen; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petrolo, Emilio; Petrucci, Fabrizio; Petschull, Dennis; Petteni, Michele; Pezoa, Raquel; Phan, Anna; Phillips, Peter William; Piacquadio, Giacinto; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Piec, Sebastian Marcin; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pina, João Antonio; Pinamonti, Michele; Pinder, Alex; Pinfold, James; Ping, Jialun; Pinto, Belmiro; Pirotte, Olivier; Pizio, Caterina; Plamondon, Mathieu; Pleier, Marc-Andre; Pleskach, Anatoly; Plotnikova, Elena; Poblaguev, Andrei; Poddar, Sahill; Podlyski, Fabrice; Poggioli, Luc; Poghosyan, Tatevik; Pohl, Martin; Polci, Francesco; Polesello, Giacomo; Policicchio, Antonio; Polini, Alessandro; Poll, James; Polychronakos, Venetios; Pomarede, Daniel Marc; Pomeroy, Daniel; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Portell Bueso, Xavier; Posch, Christoph; Pospelov, Guennady; Pospisil, Stanislav; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Prabhu, Robindra; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Pravahan, Rishiraj; Prell, Soeren; Pretzl, Klaus Peter; Pribyl, Lukas; Price, Darren; Price, Joe; Price, Lawrence; Price, Michael John; Prieur, Damien; Primavera, Margherita; Prokofiev, Kirill; Prokoshin, Fedor; Protopopescu, Serban; Proudfoot, James; Prudent, Xavier; Przybycien, Mariusz; Przysiezniak, Helenka; Psoroulas, Serena; Ptacek, Elizabeth; Pueschel, Elisa; Purdham, John; Purohit, Milind; Puzo, Patrick; Pylypchenko, Yuriy; Qian, Jianming; Qian, Zuxuan; Qin, Zhonghua; Quadt, Arnulf; Quarrie, David; Quayle, William; Quinonez, Fernando; Raas, Marcel; Radescu, Voica; Radics, Balint; Radloff, Peter; Rador, Tonguc; Ragusa, Francesco; Rahal, Ghita; Rahimi, Amir; Rahm, David; Rajagopalan, Srinivasan; Rammensee, Michael; Rammes, Marcus; Randle-Conde, Aidan Sean; Randrianarivony, Koloina; Ratoff, Peter; Rauscher, Felix; Rave, Tobias Christian; Raymond, Michel; Read, Alexander Lincoln; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Reichold, Armin; Reinherz-Aronis, Erez; Reinsch, Andreas; Reisinger, Ingo; Rembser, Christoph; Ren, Zhongliang; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Resende, Bernardo; Reznicek, Pavel; Rezvani, Reyhaneh; Richards, Alexander; Richter, Robert; Richter-Was, Elzbieta; Ridel, Melissa; Rijpstra, Manouk; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Rios, Ryan Randy; Riu, Imma; Rivoltella, Giancesare; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Rocha de Lima, Jose Guilherme; Roda, Chiara; Roda Dos Santos, Denis; Rodriguez, Diego; Roe, Adam; Roe, Shaun; Røhne, Ole; Rojo, Victoria; Rolli, Simona; Romaniouk, Anatoli; Romano, Marino; Romanov, Victor; Romeo, Gaston; Romero Adam, Elena; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Anthony; Rose, Matthew; Rosenbaum, Gabriel; Rosenberg, Eli; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rosselet, Laurent; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexander; Rozen, Yoram; Ruan, Xifeng; Rubinskiy, Igor; Ruckert, Benjamin; Ruckstuhl, Nicole; Rud, Viacheslav; Rudolph, Christian; Rudolph, Gerald; Rühr, Frederik; Ruggieri, Federico; Ruiz-Martinez, Aranzazu; Rumiantsev, Viktor; Rumyantsev, Leonid; Runge, Kay; Rurikova, Zuzana; Rusakovich, Nikolai; Rutherfoord, John; Ruwiedel, Christoph; Ruzicka, Pavel; Ryabov, Yury; Ryadovikov, Vasily; Ryan, Patrick; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Rzaeva, Sevda; Saavedra, Aldo; Sadeh, Iftach; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Sakamoto, Hiroshi; Salamanna, Giuseppe; Salamon, Andrea; Saleem, Muhammad; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvachua Ferrando, Belén; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sampsonidis, Dimitrios; Samset, Björn Hallvard; Sanchez, Arturo; Sanchez Martinez, Victoria; Sandaker, Heidi; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Tanya; Sandoval, Carlos; Sandstroem, Rikard; Sandvoss, Stephan; Sankey, Dave; Sansoni, Andrea; Santamarina Rios, Cibran; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Saraiva, João; Sarangi, Tapas; Sarkisyan-Grinbaum, Edward; Sarri, Francesca; Sartisohn, Georg; Sasaki, Osamu; Sasao, Noboru; Satsounkevitch, Igor; Sauvage, Gilles; Sauvan, Emmanuel; Sauvan, Jean-Baptiste; Savard, Pierre; Savinov, Vladimir; Savu, Dan Octavian; Sawyer, Lee; Saxon, David; Saxon, James; Says, Louis-Pierre; Sbarra, Carla; Sbrizzi, Antonio; Scallon, Olivia; Scannicchio, Diana; Scarcella, Mark; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schäfer, Uli; Schaepe, Steffen; Schaetzel, Sebastian; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R. Dean; Schamov, Andrey; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Scherzer, Max; Schiavi, Carlo; Schieck, Jochen; Schioppa, Marco; Schlenker, Stefan; Schlereth, James; Schmidt, Evelyn; Schmieden, Kristof; Schmitt, Christian; Schmitt, Sebastian; Schmitz, Martin; Schöning, André; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schram, Malachi; Schroeder, Christian; Schroer, Nicolai; Schuler, Georges; Schultens, Martin Johannes; Schultes, Joachim; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Jan; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwanenberger, Christian; Schwartzman, Ariel; Schwemling, Philippe; Schwienhorst, Reinhard; Schwierz, Rainer; Schwindling, Jerome; Schwindt, Thomas; Schwoerer, Maud; Sciolla, Gabriella; Scott, Bill; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Segura, Ester; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekula, Stephen; Selbach, Karoline Elfriede; Seliverstov, Dmitry; Sellden, Bjoern; Sellers, Graham; Seman, Michal; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Seuster, Rolf; Severini, Horst; Sevior, Martin; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shank, James; Shao, Qi Tao; Shapiro, Marjorie; Shatalov, Pavel; Shaver, Leif; Shaw, Kate; Sherman, Daniel; Sherwood, Peter; Shibata, Akira; Shichi, Hideharu; Shimizu, Shima; Shimojima, Makoto; Shin, Taeksu; Shiyakova, Maria; Shmeleva, Alevtina; Shochet, Mel; Short, Daniel; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Sicho, Petr; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silbert, Ohad; Silva, José; Silver, Yiftah; Silverstein, Daniel; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simmons, Brinick; Simoniello, Rosa; Simonyan, Margar; Sinervo, Pekka; Sinev, Nikolai; Sipica, Valentin; Siragusa, Giovanni; Sircar, Anirvan; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skinnari, Louise Anastasia; Skottowe, Hugh Philip; Skovpen, Kirill; Skubic, Patrick; Skvorodnev, Nikolai; Slater, Mark; Slavicek, Tomas; Sliwa, Krzysztof; Sloper, John erik; Smakhtin, Vladimir; Smart, Ben; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Ben Campbell; Smith, Douglas; Smith, Kenway; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snow, Steve; Snow, Joel; Snuverink, Jochem; Snyder, Scott; Soares, Mara; Sobie, Randall; Sodomka, Jaromir; Soffer, Abner; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solfaroli Camillocci, Elena; Solodkov, Alexander; Solovyanov, Oleg; Soni, Nitesh; Sopko, Vit; Sopko, Bruno; Sosebee, Mark; Soualah, Rachik; Soukharev, Andrey; Spagnolo, Stefania; Spanò, Francesco; Spighi, Roberto; Spigo, Giancarlo; Spila, Federico; Spiwoks, Ralf; Spousta, Martin; Spreitzer, Teresa; Spurlock, Barry; St Denis, Richard Dante; Stahlman, Jonathan; Stamen, Rainer; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staude, Arnold; Stavina, Pavel; Steele, Genevieve; Steinbach, Peter; Steinberg, Peter; Stekl, Ivan; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stevenson, Kyle; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoerig, Kathrin; Stoicea, Gabriel; Stonjek, Stefan; Strachota, Pavel; Stradling, Alden; Straessner, Arno; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strang, Michael; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Strong, John; Stroynowski, Ryszard; Strube, Jan; Stugu, Bjarne; Stumer, Iuliu; Stupak, John; Sturm, Philipp; Styles, Nicholas Adam; Soh, Dart-yin; Su, Dong; Subramania, Halasya Siva; Succurro, Antonella; Sugaya, Yorihito; Sugimoto, Takuya; Suhr, Chad; Suita, Koichi; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Sushkov, Serge; Susinno, Giancarlo; Sutton, Mark; Suzuki, Yu; Suzuki, Yuta; Svatos, Michal; Sviridov, Yuri; Swedish, Stephen; Sykora, Ivan; Sykora, Tomas; Szeless, Balazs; Sánchez, Javier; Ta, Duc; Tackmann, Kerstin; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takahashi, Yuta; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tamsett, Matthew; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Satoshi; Tanaka, Shuji; Tanaka, Yoshito; Tanasijczuk, Andres Jorge; Tani, Kazutoshi; Tannoury, Nancy; Tappern, Geoffrey; Tapprogge, Stefan; Tardif, Dominique; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tassi, Enrico; Tatarkhanov, Mous; Tayalati, Yahya; Taylor, Christopher; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teinturier, Marthe; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Terada, Susumu; Terashi, Koji; Terron, Juan; Testa, Marianna; Teuscher, Richard; Thadome, Jocelyn; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thioye, Moustapha; Thoma, Sascha; Thomas, Juergen; Thompson, Emily; Thompson, Paul; Thompson, Peter; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thun, Rudolf; Tian, Feng; Tibbetts, Mark James; Tic, Tomáš; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tipton, Paul; Tique Aires Viegas, Florbela De Jes; Tisserant, Sylvain; Toczek, Barbara; Todorov, Theodore; Todorova-Nova, Sharka; Toggerson, Brokk; Tojo, Junji; Tokár, Stanislav; Tokunaga, Kaoru; Tokushuku, Katsuo; Tollefson, Kirsten; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Tong, Guoliang; Tonoyan, Arshak; Topfel, Cyril; Topilin, Nikolai; Torchiani, Ingo; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alesandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Trinh, Thi Nguyet; Tripiana, Martin; Trischuk, William; Trivedi, Arjun; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiakiris, Menelaos; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsung, Jieh-Wen; Tsuno, Soshi; Tsybychev, Dmitri; Tua, Alan; Tudorache, Alexandra; Tudorache, Valentina; Tuggle, Joseph; Turala, Michal; Turecek, Daniel; Turk Cakir, Ilkay; Turlay, Emmanuel; Turra, Ruggero; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Tyndel, Mike; Tzanakos, George; Uchida, Kirika; Ueda, Ikuo; Ueno, Ryuichi; Ugland, Maren; Uhlenbrock, Mathias; Uhrmacher, Michael; Ukegawa, Fumihiko; Unal, Guillaume; Underwood, David; Undrus, Alexander; Unel, Gokhan; Unno, Yoshinobu; Urbaniec, Dustin; Usai, Giulio; Uslenghi, Massimiliano; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Vahsen, Sven; Valenta, Jan; Valente, Paolo; Valentinetti, Sara; Valkar, Stefan; Valladolid Gallego, Eva; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; van der Graaf, Harry; van der Kraaij, Erik; Van Der Leeuw, Robin; van der Poel, Egge; van der Ster, Daniel; van Eldik, Niels; van Gemmeren, Peter; van Kesteren, Zdenko; van Vulpen, Ivo; Vanadia, Marco; Vandelli, Wainer; Vandoni, Giovanna; Vaniachine, Alexandre; Vankov, Peter; Vannucci, Francois; Varela Rodriguez, Fernando; Vari, Riccardo; Varnes, Erich; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vassilakopoulos, Vassilios; Vazeille, Francois; Vazquez Schroeder, Tamara; Vegni, Guido; Veillet, Jean-Jacques; Vellidis, Constantine; Veloso, Filipe; Veness, Raymond; Veneziano, Stefano; Ventura, Andrea; Ventura, Daniel; Venturi, Manuela; Venturi, Nicola; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinek, Elisabeth; Vinogradov, Vladimir; Virchaux, Marc; Virzi, Joseph; Vitells, Ofer; Viti, Michele; Vivarelli, Iacopo; Vives Vaque, Francesc; Vlachos, Sotirios; Vladoiu, Dan; Vlasak, Michal; Vlasov, Nikolai; Vogel, Adrian; Vokac, Petr; Volpi, Guido; Volpi, Matteo; Volpini, Giovanni; von der Schmitt, Hans; von Loeben, Joerg; von Radziewski, Holger; von Toerne, Eckhard; Vorobel, Vit; Vorobiev, Alexander; Vorwerk, Volker; Vos, Marcel; Voss, Rudiger; Voss, Thorsten Tobias; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vu Anh, Tuan; Vuillermet, Raphael; Vukotic, Ilija; Wagner, Wolfgang; Wagner, Peter; Wahlen, Helmut; Wakabayashi, Jun; Walch, Shannon; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wall, Richard; Waller, Peter; Wang, Chiho; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Joshua C; Wang, Rui; Wang, Song-Ming; Wang, Tan; Warburton, Andreas; Ward, Patricia; Warsinsky, Markus; Wasicki, Christoph; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Anthony; Waugh, Ben; Weber, Marc; Weber, Michele; Weber, Pavel; Weidberg, Anthony; Weigell, Philipp; Weingarten, Jens; Weiser, Christian; Wellenstein, Hermann; Wells, Phillippa; Wenaus, Torre; Wendland, Dennis; Wendler, Shanti; Weng, Zhili; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Werth, Michael; Wessels, Martin; Wetter, Jeffrey; Weydert, Carole; Whalen, Kathleen; Wheeler-Ellis, Sarah Jane; Whitaker, Scott; White, Andrew; White, Martin; Whitehead, Samuel Robert; Whiteson, Daniel; Whittington, Denver; Wicek, Francois; Wicke, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wijeratne, Peter Alexander; Wildauer, Andreas; Wildt, Martin Andre; Wilhelm, Ivan; Wilkens, Henric George; Will, Jonas Zacharias; Williams, Eric; Williams, Hugh; Willis, William; Willocq, Stephane; Wilson, John; Wilson, Michael Galante; Wilson, Alan; Wingerter-Seez, Isabelle; Winkelmann, Stefan; Winklmeier, Frank; Wittgen, Matthias; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wong, Wei-Cheng; Wooden, Gemma; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wraight, Kenneth; Wright, Catherine; Wright, Michael; Wrona, Bozydar; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wulf, Evan; Wunstorf, Renate; Wynne, Benjamin; Xella, Stefania; Xiao, Meng; Xie, Song; Xie, Yigang; Xu, Chao; Xu, Da; Xu, Guofa; Yabsley, Bruce; Yacoob, Sahal; Yamada, Miho; Yamaguchi, Hiroshi; Yamamoto, Akira; Yamamoto, Kyoko; Yamamoto, Shimpei; Yamamura, Taiki; Yamanaka, Takashi; Yamaoka, Jared; Yamazaki, Takayuki; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Un-Ki; Yang, Yi; Yang, Yi; Yang, Zhaoyu; Yanush, Serguei; Yao, Yushu; Yasu, Yoshiji; Ybeles Smit, Gabriel Valentijn; Ye, Jingbo; Ye, Shuwei; Yilmaz, Metin; Yoosoofmiya, Reza; Yorita, Kohei; Yoshida, Riktura; Young, Charles; Youssef, Saul; Yu, Dantong; Yu, Jaehoon; Yu, Jie; Yuan, Li; Yurkewicz, Adam; Zabinski, Bartlomiej; Zaets, Vassilli; Zaidan, Remi; Zaitsev, Alexander; Zajacova, Zuzana; Zanello, Lucia; Zaytsev, Alexander; Zeitnitz, Christian; Zeller, Michael; Zeman, Martin; Zemla, Andrzej; Zendler, Carolin; Zenin, Oleg; Ženiš, Tibor; Zinonos, Zinonas; Zenz, Seth; Zerwas, Dirk; Zevi della Porta, Giovanni; Zhan, Zhichao; Zhang, Dongliang; Zhang, Huaqiao; Zhang, Jinlong; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Long; Zhao, Tianchi; Zhao, Zhengguo; Zhemchugov, Alexey; Zheng, Shuchen; Zhong, Jiahang; Zhou, Bing; Zhou, Ning; Zhou, Yue; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhuravlov, Vadym; Zieminska, Daria; Zimmermann, Robert; Zimmermann, Simone; Zimmermann, Stephanie; Ziolkowski, Michael; Zitoun, Robert; Živković, Lidija; Zmouchko, Viatcheslav; Zobernig, Georg; Zoccoli, Antonio; Zolnierowski, Yves; Zsenei, Andras; zur Nedden, Martin; Zutshi, Vishnu; Zwalinski, Lukasz

2012-01-01

A search is presented for same-sign top-quark production and down-type heavy quarks of charge -1/3 in events with two isolated leptons (electrons or muons) that have the same electric charge, at least two jets and large missing transverse momentum. The data are selected from pp collisions at sqrt(s)=7 TeV recorded by the ATLAS detector and correspond to an integrated luminosity of 1.04 inverse femtobarns. The observed data are consistent with expectations from Standard Model processes. Upper limits are set at 95% confidence level on the cross section of new sources of same-sign top-quark pair production of 1.4-2.0 pb depending on the assumed mediator mass. Upper limits are also set on the pair-production cross-section for new heavy down-type quarks; a lower limit of 450 GeV is set at 95% confidence level on the mass of heavy down-type quarks under the assumption that they decay 100% of the time to Wt.

2-Aminobenzamide and 2-Aminobenzoic Acid as New MALDI Matrices Inducing Radical Mediated In-Source Decay of Peptides and Proteins

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Smargiasso, Nicolas; Quinton, Loic; de Pauw, Edwin

2012-03-01

One of the mechanisms leading to MALDI in-source decay (MALDI ISD) is the transfer of hydrogen radicals to analytes upon laser irradiation. Analytes such as peptides or proteins may undergo ISD and this method can therefore be exploited for top-down sequencing. When performed on peptides, radical-induced ISD results in production of c- and z-ions, as also found in ETD and ECD activation. Here, we describe two new compounds which, when used as MALDI matrices, are able to efficiently induce ISD of peptides and proteins: 2-aminobenzamide and 2-aminobenzoic acid. In-source reduction of the disulfide bridge containing peptide Calcitonin further confirmed the radicalar mechanism of the ISD process. ISD of peptides led, in addition to c- and z-ions, to the generation of a-, x-, and y-ions both in positive and in negative ion modes. Finally, good sequence coverage was obtained for the sequencing of myoglobin (17 kDa protein), confirming the effectiveness of both 2-aminobenzamide and 2-aminobenzoic acid as MALDI ISD matrices.

MIPS: a database for protein sequences, homology data and yeast genome information.

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Mewes, H W; Albermann, K; Heumann, K; Liebl, S; Pfeiffer, F

1997-01-01

The MIPS group (Martinsried Institute for Protein Sequences) at the Max-Planck-Institute for Biochemistry, Martinsried near Munich, Germany, collects, processes and distributes protein sequence data within the framework of the tripartite association of the PIR-International Protein Sequence Database (,). MIPS contributes nearly 50% of the data input to the PIR-International Protein Sequence Database. The database is distributed on CD-ROM together with PATCHX, an exhaustive supplement of unique, unverified protein sequences from external sources compiled by MIPS. Through its WWW server (http://www.mips.biochem.mpg.de/ ) MIPS permits internet access to sequence databases, homology data and to yeast genome information. (i) Sequence similarity results from the FASTA program () are stored in the FASTA database for all proteins from PIR-International and PATCHX. The database is dynamically maintained and permits instant access to FASTA results. (ii) Starting with FASTA database queries, proteins have been classified into families and superfamilies (PROT-FAM). (iii) The HPT (hashed position tree) data structure () developed at MIPS is a new approach for rapid sequence and pattern searching. (iv) MIPS provides access to the sequence and annotation of the complete yeast genome (), the functional classification of yeast genes (FunCat) and its graphical display, the 'Genome Browser' (). A CD-ROM based on the JAVA programming language providing dynamic interactive access to the yeast genome and the related protein sequences has been compiled and is available on request. PMID:9016498

Formatt: Correcting protein multiple structural alignments by incorporating sequence alignment

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Daniels Noah M

2012-10-01

Full Text Available Abstract Background The quality of multiple protein structure alignments are usually computed and assessed based on geometric functions of the coordinates of the backbone atoms from the protein chains. These purely geometric methods do not utilize directly protein sequence similarity, and in fact, determining the proper way to incorporate sequence similarity measures into the construction and assessment of protein multiple structure alignments has proved surprisingly difficult. Results We present Formatt, a multiple structure alignment based on the Matt purely geometric multiple structure alignment program, that also takes into account sequence similarity when constructing alignments. We show that Formatt outperforms Matt and other popular structure alignment programs on the popular HOMSTRAD benchmark. For the SABMark twilight zone benchmark set that captures more remote homology, Formatt and Matt outperform other programs; depending on choice of embedded sequence aligner, Formatt produces either better sequence and structural alignments with a smaller core size than Matt, or similarly sized alignments with better sequence similarity, for a small cost in average RMSD. Conclusions Considering sequence information as well as purely geometric information seems to improve quality of multiple structure alignments, though defining what constitutes the best alignment when sequence and structural measures would suggest different alignments remains a difficult open question.

Single-molecule protein sequencing through fingerprinting: computational assessment

Science.gov (United States)

Yao, Yao; Docter, Margreet; van Ginkel, Jetty; de Ridder, Dick; Joo, Chirlmin

2015-10-01

Proteins are vital in all biological systems as they constitute the main structural and functional components of cells. Recent advances in mass spectrometry have brought the promise of complete proteomics by helping draft the human proteome. Yet, this commonly used protein sequencing technique has fundamental limitations in sensitivity. Here we propose a method for single-molecule (SM) protein sequencing. A major challenge lies in the fact that proteins are composed of 20 different amino acids, which demands 20 molecular reporters. We computationally demonstrate that it suffices to measure only two types of amino acids to identify proteins and suggest an experimental scheme using SM fluorescence. When achieved, this highly sensitive approach will result in a paradigm shift in proteomics, with major impact in the biological and medical sciences.

Single-molecule protein sequencing through fingerprinting: computational assessment

International Nuclear Information System (INIS)

Yao, Yao; Docter, Margreet; Van Ginkel, Jetty; Joo, Chirlmin; De Ridder, Dick

2015-01-01

Proteins are vital in all biological systems as they constitute the main structural and functional components of cells. Recent advances in mass spectrometry have brought the promise of complete proteomics by helping draft the human proteome. Yet, this commonly used protein sequencing technique has fundamental limitations in sensitivity. Here we propose a method for single-molecule (SM) protein sequencing. A major challenge lies in the fact that proteins are composed of 20 different amino acids, which demands 20 molecular reporters. We computationally demonstrate that it suffices to measure only two types of amino acids to identify proteins and suggest an experimental scheme using SM fluorescence. When achieved, this highly sensitive approach will result in a paradigm shift in proteomics, with major impact in the biological and medical sciences. (paper)

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.

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.

Prediction of Protein Structural Classes for Low-Similarity Sequences Based on Consensus Sequence and Segmented PSSM

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Yunyun Liang

2015-01-01

Full Text Available Prediction of protein structural classes for low-similarity sequences is useful for understanding fold patterns, regulation, functions, and interactions of proteins. It is well known that feature extraction is significant to prediction of protein structural class and it mainly uses protein primary sequence, predicted secondary structure sequence, and position-specific scoring matrix (PSSM. Currently, prediction solely based on the PSSM has played a key role in improving the prediction accuracy. In this paper, we propose a novel method called CSP-SegPseP-SegACP by fusing consensus sequence (CS, segmented PsePSSM, and segmented autocovariance transformation (ACT based on PSSM. Three widely used low-similarity datasets (1189, 25PDB, and 640 are adopted in this paper. Then a 700-dimensional (700D feature vector is constructed and the dimension is decreased to 224D by using principal component analysis (PCA. To verify the performance of our method, rigorous jackknife cross-validation tests are performed on 1189, 25PDB, and 640 datasets. Comparison of our results with the existing PSSM-based methods demonstrates that our method achieves the favorable and competitive performance. This will offer an important complementary to other PSSM-based methods for prediction of protein structural classes for low-similarity sequences.

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.

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)

Scoring protein relationships in functional interaction networks predicted from sequence data.

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Gaston K Mazandu

Full Text Available UNLABELLED: The abundance of diverse biological data from various sources constitutes a rich source of knowledge, which has the power to advance our understanding of organisms. This requires computational methods in order to integrate and exploit these data effectively and elucidate local and genome wide functional connections between protein pairs, thus enabling functional inferences for uncharacterized proteins. These biological data are primarily in the form of sequences, which determine functions, although functional properties of a protein can often be predicted from just the domains it contains. Thus, protein sequences and domains can be used to predict protein pair-wise functional relationships, and thus contribute to the function prediction process of uncharacterized proteins in order to ensure that knowledge is gained from sequencing efforts. In this work, we introduce information-theoretic based approaches to score protein-protein functional interaction pairs predicted from protein sequence similarity and conserved protein signature matches. The proposed schemes are effective for data-driven scoring of connections between protein pairs. We applied these schemes to the Mycobacterium tuberculosis proteome to produce a homology-based functional network of the organism with a high confidence and coverage. We use the network for predicting functions of uncharacterised proteins. AVAILABILITY: Protein pair-wise functional relationship scores for Mycobacterium tuberculosis strain CDC1551 sequence data and python scripts to compute these scores are available at http://web.cbio.uct.ac.za/~gmazandu/scoringschemes.

Top Polarisation in H-t and Wt production

International Nuclear Information System (INIS)

Godbole, R.M.; Hartgring, L.; Niessen, I.; White, C.D.

2012-01-01

We consider laboratory frame observables (like the azimuthal angle between the top quark and its decay lepton or the polar angle between the top quark and leptonic directions) obtained from leptonic decay products of top quarks produced in association with a charged Higgs or W boson. These are robust against QCD corrections to top quark decay, and can be used to pin down the parameter space of a charged Higgs boson, or reduce backgrounds in H - t and (Standard Model) Wt production. Polarisation information can efficiently be used to distinguish single top quark production processes from their backgrounds, as well as to pin down the parameters of a charged Higgs boson model

Top quark pair production and top quark properties at CDF

Energy Technology Data Exchange (ETDEWEB)

Moon, Chang-Seong [INFN, Pisa

2016-06-02

We present the most recent measurements of top quark pairs production and top quark properties in proton-antiproton collisions with center-of-mass energy of 1.96 TeV using CDF II detector at the Tevatron. The combination of top pair production cross section measurements and the direct measurement of top quark width are reported. The test of Standard Model predictions for top quark decaying into $b$-quarks, performed by measuring the ratio $R$ between the top quark branching fraction to $b$-quark and the branching fraction to any type of down quark is shown. The extraction of the CKM matrix element $|V_{tb}|$ from the ratio $R$ is discussed. We also present the latest measurements on the forward-backward asymmetry ($A_{FB}$) in top anti-top quark production. With the full CDF Run II data set, the measurements are performed in top anti-top decaying to final states that contain one or two charged leptons (electrons or muons). In addition, we combine the results of the leptonic forward-backward asymmetry in $t\\bar t$ system between the two final states. All the results show deviations from the next-to-leading order (NLO) standard model (SM) calculation.

Top-down and bottom-up influences on the left ventral occipito-temporal cortex during visual word recognition: an analysis of effective connectivity.

Science.gov (United States)

Schurz, Matthias; Kronbichler, Martin; Crone, Julia; Richlan, Fabio; Klackl, Johannes; Wimmer, Heinz

2014-04-01

The functional role of the left ventral occipito-temporal cortex (vOT) in visual word processing has been studied extensively. A prominent observation is higher activation for unfamiliar but pronounceable letter strings compared to regular words in this region. Some functional accounts have interpreted this finding as driven by top-down influences (e.g., Dehaene and Cohen [2011]: Trends Cogn Sci 15:254-262; Price and Devlin [2011]: Trends Cogn Sci 15:246-253), while others have suggested a difference in bottom-up processing (e.g., Glezer et al. [2009]: Neuron 62:199-204; Kronbichler et al. [2007]: J Cogn Neurosci 19:1584-1594). We used dynamic causal modeling for fMRI data to test bottom-up and top-down influences on the left vOT during visual processing of regular words and unfamiliar letter strings. Regular words (e.g., taxi) and unfamiliar letter strings of pseudohomophones (e.g., taksi) were presented in the context of a phonological lexical decision task (i.e., "Does the item sound like a word?"). We found no differences in top-down signaling, but a strong increase in bottom-up signaling from the occipital cortex to the left vOT for pseudohomophones compared to words. This finding can be linked to functional accounts which assume that the left vOT contains neurons tuned to complex orthographic features such as morphemes or words [e.g., Dehaene and Cohen [2011]: Trends Cogn Sci 15:254-262; Kronbichler et al. [2007]: J Cogn Neurosci 19:1584-1594]: For words, bottom-up signals converge onto a matching orthographic representation in the left vOT. For pseudohomophones, the propagated signals do not converge, but (partially) activate multiple orthographic word representations, reflected in increased effective connectivity. Copyright © 2013 Wiley Periodicals, Inc.

Inverse statistical physics of protein sequences: a key issues review.

Science.gov (United States)

Cocco, Simona; Feinauer, Christoph; Figliuzzi, Matteo; Monasson, Rémi; Weigt, Martin

2018-03-01

In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques, sequence data accumulate at unprecedented pace. This provides large sets of so-called homologous, i.e. evolutionarily related protein sequences, to which methods of inverse statistical physics can be applied. Using sequence data as the basis for the inference of Boltzmann distributions from samples of microscopic configurations or observables, it is possible to extract information about evolutionary constraints and thus protein function and structure. Here we give an overview over some biologically important questions, and how statistical-mechanics inspired modeling approaches can help to answer them. Finally, we discuss some open questions, which we expect to be addressed over the next years.

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.

Ultra-fast evaluation of protein energies directly from sequence.

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Gevorg Grigoryan

2006-06-01

Full Text Available The structure, function, stability, and many other properties of a protein in a fixed environment are fully specified by its sequence, but in a manner that is difficult to discern. We present a general approach for rapidly mapping sequences directly to their energies on a pre-specified rigid backbone, an important sub-problem in computational protein design and in some methods for protein structure prediction. The cluster expansion (CE method that we employ can, in principle, be extended to model any computable or measurable protein property directly as a function of sequence. Here we show how CE can be applied to the problem of computational protein design, and use it to derive excellent approximations of physical potentials. The approach provides several attractive advantages. First, following a one-time derivation of a CE expansion, the amount of time necessary to evaluate the energy of a sequence adopting a specified backbone conformation is reduced by a factor of 10(7 compared to standard full-atom methods for the same task. Second, the agreement between two full-atom methods that we tested and their CE sequence-based expressions is very high (root mean square deviation 1.1-4.7 kcal/mol, R2 = 0.7-1.0. Third, the functional form of the CE energy expression is such that individual terms of the expansion have clear physical interpretations. We derived expressions for the energies of three classic protein design targets-a coiled coil, a zinc finger, and a WW domain-as functions of sequence, and examined the most significant terms. Single-residue and residue-pair interactions are sufficient to accurately capture the energetics of the dimeric coiled coil, whereas higher-order contributions are important for the two more globular folds. For the task of designing novel zinc-finger sequences, a CE-derived energy function provides significantly better solutions than a standard design protocol, in comparable computation time. Given these advantages

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.

Neural correlates of top-down processing in emotion perception: an ERP study of emotional faces in white noise versus noise-alone stimuli.

Science.gov (United States)

Lee, Kyu-Yong; Lee, Tae-Ho; Yoon, So-Jeong; Cho, Yang Seok; Choi, June-Seek; Kim, Hyun Taek

2010-06-14

In the present study, we investigated the neural correlates underlying the perception of emotion in response to facial stimuli in order to elucidate the extent to which emotional perception is affected by the top-down process. Subjects performed a forced, two-choice emotion discrimination task towards ambiguous visual stimuli consisted of emotional faces embedded in different levels of visual white noise, including white noise-alone stimuli. ERP recordings and behavioral responses were analyzed according to the four response categories: hit, miss, false alarm and correct rejection. We observed enlarged EPN and LPP amplitudes when subjects reported seeing fearful faces and a typical emotional EPN response in the white noise-alone conditions when fearful faces were not presented. The two components of the ERP data which imply the characteristic modulation reflecting emotional processing showed the type of emotion each individual subjectively perceived. The results suggest that top-down modulations might be indispensable for emotional perception, which consists of two distinct stages of stimulus processing in the brain. (c) 2010 Elsevier B.V. All rights reserved.

Evaluation of the risk of a stripping perforation with gates-glidden drills: serial versus crown-down sequences

Directory of Open Access Journals (Sweden)

Tauby Coutinho-Filho

2008-03-01

Full Text Available The aim of this study was to evaluate the remaining dentine/cementum thickness using Gates-Glidden burs in serial and crown-down sequences and to observe which of the two sequences is the safest for preparing mesial roots of molars. Thirty-six left and right human mandibular first molars were selected. Standard access cavities were made and initially explored with Flexofiles sizes 10 and 15 until the tip was visible at the apex. The teeth were embedded in a muffle specially developed for this study using a PVC tube with two parallel metal rods in its lid. Each tooth-block was sectioned 3 mm apically to the furcation using a low-speed saw with a diamond disc. The tooth-block was examined under a microscope and an initial image was captured by a digital video system with 8 X and 12 X magnifications. Finally, the tooth-blocks were reassembled in the muffle so that the canals could be instrumented. After instrumentation the area of each mesial canal as well as the smallest distance to the root furcation were measured again. The mesio-buccal canals (crown-down order and the mesio-lingual canals (serial sequence presented an average area of 0.46 ± 0.16 mm² and 0.88 ± 0.27 mm² (P < 0.01, respectively. The mean values of the smallest distance to the furcation for the mesio-buccal and mesio-lingual canals were 0.66 ± 0.19 mm and 0.39 ± 0.13 mm (P < 0.01, respectively. The remaining dentine/cementum thickness using Gates-Glidden burs was greater in the crown-down sequence than in the serial sequence.

ProteinSplit: splitting of multi-domain proteins using prediction of ordered and disordered regions in protein sequences for virtual structural genomics

International Nuclear Information System (INIS)

Wyrwicz, Lucjan S; Koczyk, Grzegorz; Rychlewski, Leszek; Plewczynski, Dariusz

2007-01-01

The annotation of protein folds within newly sequenced genomes is the main target for semi-automated protein structure prediction (virtual structural genomics). A large number of automated methods have been developed recently with very good results in the case of single-domain proteins. Unfortunately, most of these automated methods often fail to properly predict the distant homology between a given multi-domain protein query and structural templates. Therefore a multi-domain protein should be split into domains in order to overcome this limitation. ProteinSplit is designed to identify protein domain boundaries using a novel algorithm that predicts disordered regions in protein sequences. The software utilizes various sequence characteristics to assess the local propensity of a protein to be disordered or ordered in terms of local structure stability. These disordered parts of a protein are likely to create interdomain spacers. Because of its speed and portability, the method was successfully applied to several genome-wide fold annotation experiments. The user can run an automated analysis of sets of proteins or perform semi-automated multiple user projects (saving the results on the server). Additionally the sequences of predicted domains can be sent to the Bioinfo.PL Protein Structure Prediction Meta-Server for further protein three-dimensional structure and function prediction. The program is freely accessible as a web service at http://lucjan.bioinfo.pl/proteinsplit together with detailed benchmark results on the critical assessment of a fully automated structure prediction (CAFASP) set of sequences. The source code of the local version of protein domain boundary prediction is available upon request from the authors

Rapid identification of sequences for orphan enzymes to power accurate protein annotation.

Directory of Open Access Journals (Sweden)

Kevin R Ramkissoon

Full Text Available The power of genome sequencing depends on the ability to understand what those genes and their proteins products actually do. The automated methods used to assign functions to putative proteins in newly sequenced organisms are limited by the size of our library of proteins with both known function and sequence. Unfortunately this library grows slowly, lagging well behind the rapid increase in novel protein sequences produced by modern genome sequencing methods. One potential source for rapidly expanding this functional library is the "back catalog" of enzymology--"orphan enzymes," those enzymes that have been characterized and yet lack any associated sequence. There are hundreds of orphan enzymes in the Enzyme Commission (EC database alone. In this study, we demonstrate how this orphan enzyme "back catalog" is a fertile source for rapidly advancing the state of protein annotation. Starting from three orphan enzyme samples, we applied mass-spectrometry based analysis and computational methods (including sequence similarity networks, sequence and structural alignments, and operon context analysis to rapidly identify the specific sequence for each orphan while avoiding the most time- and labor-intensive aspects of typical sequence identifications. We then used these three new sequences to more accurately predict the catalytic function of 385 previously uncharacterized or misannotated proteins. We expect that this kind of rapid sequence identification could be efficiently applied on a larger scale to make enzymology's "back catalog" another powerful tool to drive accurate genome annotation.

Rapid Identification of Sequences for Orphan Enzymes to Power Accurate Protein Annotation

Science.gov (United States)

Ojha, Sunil; Watson, Douglas S.; Bomar, Martha G.; Galande, Amit K.; Shearer, Alexander G.

2013-01-01

The power of genome sequencing depends on the ability to understand what those genes and their proteins products actually do. The automated methods used to assign functions to putative proteins in newly sequenced organisms are limited by the size of our library of proteins with both known function and sequence. Unfortunately this library grows slowly, lagging well behind the rapid increase in novel protein sequences produced by modern genome sequencing methods. One potential source for rapidly expanding this functional library is the “back catalog” of enzymology – “orphan enzymes,” those enzymes that have been characterized and yet lack any associated sequence. There are hundreds of orphan enzymes in the Enzyme Commission (EC) database alone. In this study, we demonstrate how this orphan enzyme “back catalog” is a fertile source for rapidly advancing the state of protein annotation. Starting from three orphan enzyme samples, we applied mass-spectrometry based analysis and computational methods (including sequence similarity networks, sequence and structural alignments, and operon context analysis) to rapidly identify the specific sequence for each orphan while avoiding the most time- and labor-intensive aspects of typical sequence identifications. We then used these three new sequences to more accurately predict the catalytic function of 385 previously uncharacterized or misannotated proteins. We expect that this kind of rapid sequence identification could be efficiently applied on a larger scale to make enzymology’s “back catalog” another powerful tool to drive accurate genome annotation. PMID:24386392

Complete cDNA sequence coding for human docking protein

Energy Technology Data Exchange (ETDEWEB)

Hortsch, M; Labeit, S; Meyer, D I

1988-01-11

Docking protein (DP, or SRP receptor) is a rough endoplasmic reticulum (ER)-associated protein essential for the targeting and translocation of nascent polypeptides across this membrane. It specifically interacts with a cytoplasmic ribonucleoprotein complex, the signal recognition particle (SRP). The nucleotide sequence of cDNA encoding the entire human DP and its deduced amino acid sequence are given.

Designing sequence to control protein function in an EF-hand protein.

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Bunick, Christopher G; Nelson, Melanie R; Mangahas, Sheryll; Hunter, Michael J; Sheehan, Jonathan H; Mizoue, Laura S; Bunick, Gerard J; Chazin, Walter J

2004-05-19

The extent of conformational change that calcium binding induces in EF-hand proteins is a key biochemical property specifying Ca(2+) sensor versus signal modulator function. To understand how differences in amino acid sequence lead to differences in the response to Ca(2+) binding, comparative analyses of sequence and structures, combined with model building, were used to develop hypotheses about which amino acid residues control Ca(2+)-induced conformational changes. These results were used to generate a first design of calbindomodulin (CBM-1), a calbindin D(9k) re-engineered with 15 mutations to respond to Ca(2+) binding with a conformational change similar to that of calmodulin. The gene for CBM-1 was synthesized, and the protein was expressed and purified. Remarkably, this protein did not exhibit any non-native-like molten globule properties despite the large number of mutations and the nonconservative nature of some of them. Ca(2+)-induced changes in CD intensity and in the binding of the hydrophobic probe, ANS, implied that CBM-1 does undergo Ca(2+) sensorlike conformational changes. The X-ray crystal structure of Ca(2+)-CBM-1 determined at 1.44 A resolution reveals the anticipated increase in hydrophobic surface area relative to the wild-type protein. A nascent calmodulin-like hydrophobic docking surface was also found, though it is occluded by the inter-EF-hand loop. The results from this first calbindomodulin design are discussed in terms of progress toward understanding the relationships between amino acid sequence, protein structure, and protein function for EF-hand CaBPs, as well as the additional mutations for the next CBM design.

Top down electroweak dipole operators

Science.gov (United States)

Fuyuto, Kaori; Ramsey-Musolf, Michael

2018-06-01

We derive present constraints on, and prospective sensitivity to, the electric dipole moment (EDM) of the top quark (dt) implied by searches for the EDMs of the electron and nucleons. Above the electroweak scale v, the dt arises from two gauge invariant operators generated at a scale Λ ≫ v that also mix with the light fermion EDMs under renormalization group evolution at two-loop order. Bounds on the EDMs of first generation fermion systems thus imply bounds on |dt |. Working in the leading log-squared approximation, we find that the present upper bound on |dt | is 10-19 e cm for Λ = 1 TeV, except in regions of finely tuned cancellations that allow for |dt | to be up to fifty times larger. Future de and dn probes may yield an order of magnitude increase in dt sensitivity, while inclusion of a prospective proton EDM search may lead to an additional increase in reach.

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.

Right hemisphere dominance directly predicts both baseline V1 cortical excitability and the degree of top-down modulation exerted over low-level brain structures.

Science.gov (United States)

Arshad, Q; Siddiqui, S; Ramachandran, S; Goga, U; Bonsu, A; Patel, M; Roberts, R E; Nigmatullina, Y; Malhotra, P; Bronstein, A M

2015-12-17

Right hemisphere dominance for visuo-spatial attention is characteristically observed in most right-handed individuals. This dominance has been attributed to both an anatomically larger right fronto-parietal network and the existence of asymmetric parietal interhemispheric connections. Previously it has been demonstrated that interhemispheric conflict, which induces left hemisphere inhibition, results in the modulation of both (i) the excitability of the early visual cortex (V1) and (ii) the brainstem-mediated vestibular-ocular reflex (VOR) via top-down control mechanisms. However to date, it remains unknown whether the degree of an individual's right hemisphere dominance for visuospatial function can influence, (i) the baseline excitability of the visual cortex and (ii) the extent to which the right hemisphere can exert top-down modulation. We directly tested this by correlating line bisection error (or pseudoneglect), taken as a measure of right hemisphere dominance, with both (i) visual cortical excitability measured using phosphene perception elicited via single-pulse occipital trans-cranial magnetic stimulation (TMS) and (ii) the degree of trans-cranial direct current stimulation (tDCS)-mediated VOR suppression, following left hemisphere inhibition. We found that those individuals with greater right hemisphere dominance had a less excitable early visual cortex at baseline and demonstrated a greater degree of vestibular nystagmus suppression following left hemisphere cathodal tDCS. To conclude, our results provide the first demonstration that individual differences in right hemisphere dominance can directly predict both the baseline excitability of low-level brain structures and the degree of top-down modulation exerted over them. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

Prediction of protein-protein interaction sites in sequences and 3D structures by random forests.

Directory of Open Access Journals (Sweden)

Mile Sikić

2009-01-01

Full Text Available Identifying interaction sites in proteins provides important clues to the function of a protein and is becoming increasingly relevant in topics such as systems biology and drug discovery. Although there are numerous papers on the prediction of interaction sites using information derived from structure, there are only a few case reports on the prediction of interaction residues based solely on protein sequence. Here, a sliding window approach is combined with the Random Forests method to predict protein interaction sites using (i a combination of sequence- and structure-derived parameters and (ii sequence information alone. For sequence-based prediction we achieved a precision of 84% with a 26% recall and an F-measure of 40%. When combined with structural information, the prediction performance increases to a precision of 76% and a recall of 38% with an F-measure of 51%. We also present an attempt to rationalize the sliding window size and demonstrate that a nine-residue window is the most suitable for predictor construction. Finally, we demonstrate the applicability of our prediction methods by modeling the Ras-Raf complex using predicted interaction sites as target binding interfaces. Our results suggest that it is possible to predict protein interaction sites with quite a high accuracy using only sequence information.

Comparative analysis of the prion protein gene sequences in African lion.

Science.gov (United States)

Wu, Chang-De; Pang, Wan-Yong; Zhao, De-Ming

2006-10-01

The prion protein gene of African lion (Panthera Leo) was first cloned and polymorphisms screened. The results suggest that the prion protein gene of eight African lions is highly homogenous. The amino acid sequences of the prion protein (PrP) of all samples tested were identical. Four single nucleotide polymorphisms (C42T, C81A, C420T, T600C) in the prion protein gene (Prnp) of African lion were found, but no amino acid substitutions. Sequence analysis showed that the higher homology is observed to felis catus AF003087 (96.7%) and to sheep number M31313.1 (96.2%) Genbank accessed. With respect to all the mammalian prion protein sequences compared, the African lion prion protein sequence has three amino acid substitutions. The homology might in turn affect the potential intermolecular interactions critical for cross species transmission of prion disease.

The heterogeneous world of congruency sequence effects: An update.

OpenAIRE

Wout eDuthoo; Elger eAbrahamse; Senne eBraem; Senne eBraem; C. Nico Boehler; Wim eNotebaert

2014-01-01

Congruency sequence effects (CSEs) refer to the observation that congruency effects in conflict tasks are typically smaller following incongruent compared to following congruent trials. This measure has long been thought to provide a unique window into top-down attentional adjustments and their underlying brain mechanisms. According to the renowned conflict monitoring theory, CSEs reflect enhanced selective attention following conflict detection. Still, alternative accounts suggested that bot...

Comparative architecture of octahedral protein cages. I. Indexed enclosing forms

Science.gov (United States)

Janner, A.

2008-07-01

The architecture of four protein cages (bacterio ferritin, human mitochondrial ferritin, sulfur oxygenase reductase and small heat-shock protein) are compared top-to-bottom, starting from polyhedra with vertices at cubic lattice points enclosing the cage down to indexed polyhedral forms of single monomers.

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.

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.

Repeat Sequence Proteins as Matrices for Nanocomposites

Energy Technology Data Exchange (ETDEWEB)

Drummy, L.; Koerner, H; Phillips, D; McAuliffe, J; Kumar, M; Farmer, B; Vaia, R; Naik, R

2009-01-01

Recombinant protein-inorganic nanocomposites comprised of exfoliated Na+ montmorillonite (MMT) in a recombinant protein matrix based on silk-like and elastin-like amino acid motifs (silk elastin-like protein (SELP)) were formed via a solution blending process. Charged residues along the protein backbone are shown to dominate long-range interactions, whereas the SELP repeat sequence leads to local protein/MMT compatibility. Up to a 50% increase in room temperature modulus and a comparable decrease in high temperature coefficient of thermal expansion occur for cast films containing 2-10 wt.% MMT.

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.

Analysis of long-range correlation in sequences data of proteins