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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kou, Qiang; Wu, Si; Tolić, Nikola

Motivation: 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 inmore » billions of possible proteoforms, making proteoform identification a challenging computational problem. Results: 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 data sets showed that TopMG outperformed existing methods in identifying complex proteoforms.« less

Top-down processing of symbolic meanings modulates the visual word form area.

PubMed

Song, Yiying; Tian, Moqian; Liu, Jia

2012-08-29

Functional magnetic resonance imaging (fMRI) studies on humans have identified a region in the left middle fusiform gyrus consistently activated by written words. This region is called the visual word form area (VWFA). Recently, a hypothesis, called the interactive account, is proposed that to effectively analyze the bottom-up visual properties of words, the VWFA receives predictive feedback from higher-order regions engaged in processing sounds, meanings, or actions associated with words. Further, this top-down influence on the VWFA is independent of stimulus formats. To test this hypothesis, we used fMRI to examine whether a symbolic nonword object (e.g., the Eiffel Tower) intended to represent something other than itself (i.e., Paris) could activate the VWFA. We found that scenes associated with symbolic meanings elicited a higher VWFA response than those not associated with symbolic meanings, and such top-down modulation on the VWFA can be established through short-term associative learning, even across modalities. In addition, the magnitude of the symbolic effect observed in the VWFA was positively correlated with the subjective experience on the strength of symbol-referent association across individuals. Therefore, the VWFA is likely a neural substrate for the interaction of the top-down processing of symbolic meanings with the analysis of bottom-up visual properties of sensory inputs, making the VWFA the location where the symbolic meaning of both words and nonword objects is represented.

Top-Down-Assisted Bottom-Up Method for Homologous Protein Sequencing: Hemoglobin from 33 Bird Species

NASA Astrophysics Data System (ADS)

Song, Yang; Laskay, Ünige A.; Vilcins, Inger-Marie E.; Barbour, Alan G.; Wysocki, Vicki H.

2015-11-01

Ticks are vectors for disease transmission because they are indiscriminant in their feeding on multiple vertebrate hosts, transmitting pathogens between their hosts. Identifying the hosts on which ticks have fed is important for disease prevention and intervention. We have previously shown that hemoglobin (Hb) remnants from a host on which a tick fed can be used to reveal the host's identity. For the present research, blood was collected from 33 bird species that are common in the U.S. as hosts for ticks but that have unknown Hb sequences. A top-down-assisted bottom-up mass spectrometry approach with a customized searching database, based on variability in known bird hemoglobin sequences, has been devised to facilitate fast and complete sequencing of hemoglobin from birds with unknown sequences. These hemoglobin sequences will be added to a hemoglobin database and used for tick host identification. The general approach has the potential to sequence any set of homologous proteins completely in a rapid manner.

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

PubMed

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

2015-04-01

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

Top-down Proteomics: Technology Advancements and Applications to Heart Diseases

PubMed Central

Cai, Wenxuan; Tucholski, Trisha M.; Gregorich, Zachery R.; Ge, Ying

2016-01-01

Introduction Diseases of the heart are a leading cause of morbidity and mortality for both men and women worldwide, and impose significant economic burdens on the healthcare systems. Despite substantial effort over the last several decades, the molecular mechanisms underlying diseases of the heart remain poorly understood. Areas covered Altered protein post-translational modifications (PTMs) and protein isoform switching are increasingly recognized as important disease mechanisms. Top-down high-resolution mass spectrometry (MS)-based proteomics has emerged as the most powerful method for the comprehensive analysis of PTMs and protein isoforms. Here, we will review recent technology developments in the field of top-down proteomics, as well as highlight recent studies utilizing top-down proteomics to decipher the cardiac proteome for the understanding of the molecular mechanisms underlying diseases of the heart. Expert commentary Top-down proteomics is a premier method for the global and comprehensive study of protein isoforms and their PTMs, enabling the identification of novel protein isoforms and PTMs, characterization of sequence variations, and quantification of disease-associated alterations. Despite significant challenges, continuous development of top-down proteomics technology will greatly aid the dissection of the molecular mechanisms underlying diseases of the hearts for the identification of novel biomarkers and therapeutic targets. PMID:27448560

Top-Down Prioritization of Salient Items May Produce the So-Called Stimulus-Driven Capture

PubMed Central

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

Characterization of Proteoforms with Unknown Post-translational Modifications Using the MIScore

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kou, Qiang; Zhu, Binhai; Wu, Si

Various proteoforms may be generated from a single gene due to primary structure alterations (PSAs) such as genetic variations, alternative splicing, and post-translational modifications (PTMs). Top-down mass spectrometry is capable of analyzing intact proteins and identifying patterns of multiple PSAs, making it the method of choice for studying complex proteoforms. In top-down proteomics, proteoform identification is often performed by searching tandem mass spectra against a protein sequence database that contains only one reference protein sequence for each gene or transcript variant in a proteome. Because of the incompleteness of the protein database, an identified proteoform may contain unknown PSAs comparedmore » with the reference sequence. Proteoform characterization is to identify and localize PSAs in a proteoform. Although many software tools have been proposed for proteoform identification by top-down mass spectrometry, the characterization of proteoforms in identified proteoform-spectrum matches still relies mainly on manual annotation. We propose to use the Modification Identification Score (MIScore), which is based on Bayesian models, to automatically identify and localize PTMs in proteoforms. Experiments showed that the MIScore is accurate in identifying and localizing one or two modifications.« less

The influence of focused-attention meditation states on the cognitive control of sequence learning.

PubMed

Chan, Russell W; Immink, Maarten A; Lushington, Kurt

2017-10-01

Cognitive control processes influence how motor sequence information is utilised and represented. Since cognitive control processes are shared amongst goal-oriented tasks, motor sequence learning and performance might be influenced by preceding cognitive tasks such as focused-attention meditation (FAM). Prior to a serial reaction time task (SRTT), participants completed either a single-session of FAM, a single-session of FAM followed by delay (FAM+) or no meditation (CONTROL). Relative to CONTROL, FAM benefitted performance in early, random-ordered blocks. However, across subsequent sequence learning blocks, FAM+ supported the highest levels of performance improvement resulting in superior performance at the end of the SRTT. Performance following FAM+ demonstrated greater reliance on embedded sequence structures than FAM. These findings illustrate that increased top-down control immediately after FAM biases the implementation of stimulus-based planning. Introduction of a delay following FAM relaxes top-down control allowing for implementation of response-based planning resulting in sequence learning benefits. Copyright © 2017 Elsevier Inc. All rights reserved.

MASH Suite Pro: A Comprehensive Software Tool for Top-Down Proteomics*

PubMed Central

Cai, Wenxuan; Guner, Huseyin; Gregorich, Zachery R.; Chen, Albert J.; Ayaz-Guner, Serife; Peng, Ying; Valeja, Santosh G.; Liu, Xiaowen; Ge, Ying

2016-01-01

Top-down mass spectrometry (MS)-based proteomics is arguably a disruptive technology for the comprehensive analysis of all proteoforms arising from genetic variation, alternative splicing, and posttranslational modifications (PTMs). However, the complexity of top-down high-resolution mass spectra presents a significant challenge for data analysis. In contrast to the well-developed software packages available for data analysis in bottom-up proteomics, the data analysis tools in top-down proteomics remain underdeveloped. Moreover, despite recent efforts to develop algorithms and tools for the deconvolution of top-down high-resolution mass spectra and the identification of proteins from complex mixtures, a multifunctional software platform, which allows for the identification, quantitation, and characterization of proteoforms with visual validation, is still lacking. Herein, we have developed MASH Suite Pro, a comprehensive software tool for top-down proteomics with multifaceted functionality. MASH Suite Pro is capable of processing high-resolution MS and tandem MS (MS/MS) data using two deconvolution algorithms to optimize protein identification results. In addition, MASH Suite Pro allows for the characterization of PTMs and sequence variations, as well as the relative quantitation of multiple proteoforms in different experimental conditions. The program also provides visualization components for validation and correction of the computational outputs. Furthermore, MASH Suite Pro facilitates data reporting and presentation via direct output of the graphics. Thus, MASH Suite Pro significantly simplifies and speeds up the interpretation of high-resolution top-down proteomics data by integrating tools for protein identification, quantitation, characterization, and visual validation into a customizable and user-friendly interface. We envision that MASH Suite Pro will play an integral role in advancing the burgeoning field of top-down proteomics. PMID:26598644

The Top and Bottom of Leadership and Change

ERIC Educational Resources Information Center

Hargreaves, Andy; Ainscow, Mel

2015-01-01

All versions of top-down reform have an Achilles heel: Their focus on delivering the details of two or three measurable priorities is suitable only for systems pursuing traditional and comparatively narrow achievement goals. A digital age of complex skills, cultural diversity, and high-speed change calls for more challenging educational goals and…

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

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

Label-Free Relative Quantitation of Isobaric and Isomeric Human Histone H2A and H2B Variants by Fourier Transform Ion Cyclotron Resonance Top-Down MS/MS.

PubMed

Dang, Xibei; Singh, Amar; Spetman, Brian D; Nolan, Krystal D; Isaacs, Jennifer S; Dennis, Jonathan H; Dalton, Stephen; Marshall, Alan G; Young, Nicolas L

2016-09-02

Histone variants are known to play a central role in genome regulation and maintenance. However, many variants are inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due to their highly similar sequences. For many, the only tractable approach is with intact protein top-down tandem mass spectrometry. Here, ultra-high-resolution FT-ICR MS and MS/MS yield quantitative relative abundances of all detected HeLa H2A and H2B isobaric and isomeric variants with a label-free approach. We extend the analysis to identify and relatively quantitate 16 proteoforms from 12 sequence variants of histone H2A and 10 proteoforms of histone H2B from three other cell lines: human embryonic stem cells (WA09), U937, and a prostate cancer cell line LaZ. The top-down MS/MS approach provides a path forward for more extensive elucidation of the biological role of many previously unstudied histone variants and post-translational modifications.

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

PubMed

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

A top-down approach to heliostat cost reduction

NASA Astrophysics Data System (ADS)

Larmuth, James N.; Landamn, Willem A.; Gauché, Paul

2016-05-01

The Technology Innovation Agency (TIA) has funded a South African central receiver collector technology development project, called Helio100. The project aims to provide South Africa's first commercially viable heliostat technology, which is both low in cost and offers high local content potential. A top-down approach is employed for heliostat cost reduction. This approach incorporates interlinked tools which move from high level cost analyses based on qualitative data during early stages of conceptual design, to detailed quantitative analyses in the final stages of design. Low cost heliostat designs are realized by the incorporation of both a top-down and bottom-up method. The current H100 design results in heliostat costs of 155/m2 at 20 000 units p.a. while further industrialisation results in heliostat costs of 126/m2 at 20 000 units.

Top Down Implementation Plan for system performance test software

NASA Technical Reports Server (NTRS)

Jacobson, G. N.; Spinak, A.

1982-01-01

The top down implementation plan used for the development of system performance test software during the Mark IV-A era is described. The plan is based upon the identification of the hierarchical relationship of the individual elements of the software design, the development of a sequence of functionally oriented demonstrable steps, the allocation of subroutines to the specific step where they are first required, and objective status reporting. The results are: determination of milestones, improved managerial visibility, better project control, and a successful software development.

Pressurized Pepsin Digestion in Proteomics: An Automatable Alternative to Trypsin for Integrated Top-down Bottom-up Proteomics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez-Ferrer, Daniel; Petritis, Konstantinos; Robinson, Errol W.

2011-02-01

Integrated top-down bottom-up proteomics combined with online digestion has great potential to improve the characterization of protein isoforms in biological systems and is amendable to highthroughput proteomics experiments. Bottom-up proteomics ultimately provides the peptide sequences derived from the tandem MS analyses of peptides after the proteome has been digested. Top-down proteomics conversely entails the MS analyses of intact proteins for more effective characterization of genetic variations and/or post-translational modifications (PTMs). Herein, we describe recent efforts towards efficient integration of bottom-up and top-down LCMS based proteomic strategies. Since most proteomic platforms (i.e. LC systems) operate in acidic environments, we exploited themore » compatibility of the pepsin (i.e. the enzyme’s natural acidic activity) for the integration of bottom-up and top-down proteomics. Pressure enhanced pepsin digestions were successfully performed and characterized with several standard proteins in either an offline mode using a Barocycler or an online mode using a modified high pressure LC system referred to as a fast online digestion system (FOLDS). FOLDS was tested using pepsin and a whole microbial proteome, and the results compared against traditional trypsin digestions on the same platform. Additionally, FOLDS was integrated with a RePlay configuration to demonstrate an ultra-rapid integrated bottom-up top-down proteomic strategy employing a standard mixture of proteins and a monkey pox virus proteome.« less

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

PubMed

Wang, Guanbo; Kaltashov, Igor A

2014-08-05

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

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

NASA Astrophysics Data System (ADS)

Petersen, Marcell Elo; Maar, Marie; Larsen, Janus; Møller, Eva Friis; Hansen, Per Juel

2017-05-01

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 ERGOM was validated and applied in a local set-up of the Kattegat, Denmark, using the off-line Flexsem framework. The model scenarios were conducted by changing the forcing by ± 20% of nutrient inputs (bottom-up) and mesozooplankton mortality (top-down), and both types of forcing combined. The model results showed that cascading effects operated differently depending on the forcing type. In the single-forcing bottom-up scenarios, the cascade directions were in the same direction as the forcing. For scenarios involving top-down, there was a skipped-level-transmission in the trophic responses that was either attenuated or amplified at different trophic levels. On a seasonal scale, bottom-up forcing showed strongest response during winter-spring for DIN and Chl a concentrations, whereas top-down forcing had the highest cascade strength during summer for Chl a concentrations and microzooplankton biomass. 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 input and mesozooplankton mortality calling for the need of an integrated management of marine areas exploited by human activities.

The Persistence of Hierarchy: How One School District's Top Administrators Worked to Guide a Culture Change towards Collaborative Leadership

ERIC Educational Resources Information Center

Bravo, Robert Ronald

2011-01-01

There is no shortage of scholars that believe that traditional, top-down leadership is antithetical to facilitating the improvements that must be made to the American educational system if all children are to achieve academically. These scholars call for distributive, facilitative, and/or collaborative leadership, yet little is known about how…

Reflexive Photography, Attitudes, Behavior, and CALL: ITAs Improving Spoken English Intelligibility

ERIC Educational Resources Information Center

Wallace, Lara

2015-01-01

Research in the field of Computer-Assisted Language Learning (CALL) has frequently taken a top-down approach when investigating learners' attitudes and behavior, both in the course as well as for their personal use. Suggestions are given for use of technology, and future research (Beatty, 2010; Levy & Stockwell, 2006). One perspective that has…

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

Pressurized Pepsin Digestion in Proteomics

PubMed Central

López-Ferrer, Daniel; Petritis, Konstantinos; Robinson, Errol W.; Hixson, Kim K.; Tian, Zhixin; Lee, Jung Hwa; Lee, Sang-Won; Tolić, Nikola; Weitz, Karl K.; Belov, Mikhail E.; Smith, Richard D.; Paša-Tolić, Ljiljana

2011-01-01

Integrated top-down bottom-up proteomics combined with on-line digestion has great potential to improve the characterization of protein isoforms in biological systems and is amendable to high throughput proteomics experiments. Bottom-up proteomics ultimately provides the peptide sequences derived from the tandem MS analyses of peptides after the proteome has been digested. Top-down proteomics conversely entails the MS analyses of intact proteins for more effective characterization of genetic variations and/or post-translational modifications. Herein, we describe recent efforts toward efficient integration of bottom-up and top-down LC-MS-based proteomics strategies. Since most proteomics separations utilize acidic conditions, we exploited the compatibility of pepsin (where the optimal digestion conditions are at low pH) for integration into bottom-up and top-down proteomics work flows. Pressure-enhanced pepsin digestions were successfully performed and characterized with several standard proteins in either an off-line mode using a Barocycler or an on-line mode using a modified high pressure LC system referred to as a fast on-line digestion system (FOLDS). FOLDS was tested using pepsin and a whole microbial proteome, and the results were compared against traditional trypsin digestions on the same platform. Additionally, FOLDS was integrated with a RePlay configuration to demonstrate an ultrarapid integrated bottom-up top-down proteomics strategy using a standard mixture of proteins and a monkey pox virus proteome. PMID:20627868

Integrated Bottom-Up and Top-Down Liquid Chromatography-Mass Spectrometry for Characterization of Recombinant Human Growth Hormone Degradation Products.

PubMed

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.

Analysis of Monoclonal Antibodies in Human Serum as a Model for Clinical Monoclonal Gammopathy by Use of 21 Tesla FT-ICR Top-Down and Middle-Down MS/MS

NASA Astrophysics Data System (ADS)

He, Lidong; Anderson, Lissa C.; Barnidge, David R.; Murray, David L.; Hendrickson, Christopher L.; Marshall, Alan G.

2017-05-01

With the rapid growth of therapeutic monoclonal antibodies (mAbs), stringent quality control is needed to ensure clinical safety and efficacy. Monoclonal antibody primary sequence and post-translational modifications (PTM) are conventionally analyzed with labor-intensive, bottom-up tandem mass spectrometry (MS/MS), which is limited by incomplete peptide sequence coverage and introduction of artifacts during the lengthy analysis procedure. Here, we describe top-down and middle-down approaches with the advantages of fast sample preparation with minimal artifacts, ultrahigh mass accuracy, and extensive residue cleavages by use of 21 tesla FT-ICR MS/MS. The ultrahigh mass accuracy yields an RMS error of 0.2-0.4 ppm for antibody light chain, heavy chain, heavy chain Fc/2, and Fd subunits. The corresponding sequence coverages are 81%, 38%, 72%, and 65% with MS/MS RMS error 4 ppm. Extension to a monoclonal antibody in human serum as a monoclonal gammopathy model yielded 53% sequence coverage from two nano-LC MS/MS runs. A blind analysis of five therapeutic monoclonal antibodies at clinically relevant concentrations in human serum resulted in correct identification of all five antibodies. Nano-LC 21 T FT-ICR MS/MS provides nonpareil mass resolution, mass accuracy, and sequence coverage for mAbs, and sets a benchmark for MS/MS analysis of multiple mAbs in serum. This is the first time that extensive cleavages for both variable and constant regions have been achieved for mAbs in a human serum background.

Characterization of a new qQq-FTICR mass spectrometer for post-translational modification analysis and top-down tandem mass spectrometry of whole proteins.

PubMed

Jebanathirajah, Judith A; Pittman, Jason L; Thomson, Bruce A; Budnik, Bogdan A; Kaur, Parminder; Rape, Michael; Kirschner, Marc; Costello, Catherine E; O'Connor, Peter B

2005-12-01

The use of a new electrospray qQq Fourier transform ion cyclotron mass spectrometer (qQq-FTICR MS) instrument for biologic applications is described. This qQq-FTICR mass spectrometer was designed for the study of post-translationally modified proteins and for top-down analysis of biologically relevant protein samples. The utility of the instrument for the analysis of phosphorylation, a common and important post-translational modification, was investigated. Phosphorylation was chosen as an example because it is ubiquitous and challenging to analyze. In addition, the use of the instrument for top-down sequencing of proteins was explored since this instrument offers particular advantages to this approach. Top-down sequencing was performed on different proteins, including commercially available proteins and biologically derived samples such as the human E2 ubiquitin conjugating enzyme, UbCH10. A good sequence tag was obtained for the human UbCH10, allowing the unambiguous identification of the protein. The instrument was built with a commercially produced front end: a focusing rf-only quadrupole (Q0), followed by a resolving quadrupole (Q1), and a LINAC quadrupole collision cell (Q2), in combination with an FTICR mass analyzer. It has utility in the analysis of samples found in substoichiometric concentrations, as ions can be isolated in the mass resolving Q1 and accumulated in Q2 before analysis in the ICR cell. The speed and efficacy of the Q2 cooling and fragmentation was demonstrated on an LCMS-compatible time scale, and detection limits for phosphopeptides in the 10 amol/muL range (pM) were demonstrated. The instrument was designed to make several fragmentation methods available, including nozzle-skimmer fragmentation, Q2 collisionally activated dissociation (Q2 CAD), multipole storage assisted dissociation (MSAD), electron capture dissociation (ECD), infrared multiphoton induced dissociation (IRMPD), and sustained off resonance irradiation (SORI) CAD, thus allowing a variety of MS(n) experiments. A particularly useful aspect of the system was the use of Q1 to isolate ions from complex mixtures with narrow windows of isolation less than 1 m/z. These features enable top-down protein analysis experiments as well structural characterization of minor components of complex mixtures.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Top-Down LESA Mass Spectrometry Protein Analysis of Gram-Positive and Gram-Negative Bacteria

NASA Astrophysics Data System (ADS)

Kocurek, Klaudia I.; Stones, Leanne; Bunch, Josephine; May, Robin C.; Cooper, Helen J.

2017-10-01

We have previously shown that liquid extraction surface analysis (LESA) mass spectrometry (MS) is a technique suitable for the top-down analysis of proteins directly from intact colonies of the Gram-negative bacterium Escherichia coli K-12. Here we extend the application of LESA MS to Gram-negative Pseudomonas aeruginosa PS1054 and Gram-positive Staphylococcus aureus MSSA476, as well as two strains of E. coli (K-12 and BL21 mCherry) and an unknown species of Staphylococcus. Moreover, we demonstrate the discrimination between three species of Gram-positive Streptococcus ( Streptococcus pneumoniae D39, and the viridans group Streptococcus oralis ATCC 35037 and Streptococcus gordonii ATCC35105), a recognized challenge for matrix-assisted laser desorption ionization time-of-flight MS. A range of the proteins detected were selected for top-down LESA MS/MS. Thirty-nine proteins were identified by top-down LESA MS/MS, including 16 proteins that have not previously been observed by any other technique. The potential of LESA MS for classification and characterization of novel species is illustrated by the de novo sequencing of a new protein from the unknown species of Staphylococcus. [Figure not available: see fulltext.

Dividing to unveil protein microheterogeneities: A Traveling Wave Ion Mobility study

PubMed Central

Halgand, F.; Habchi, Johnny; Cravello, Laetitia; Martinho, Marlène; Guigliarelli, Bruno; Longhi, Sonia

2011-01-01

Over-expression of a protein in a foreign host is often the only route toward an exhaustive characterization especially when purification from the natural source(s) is hardly achievable. The key issue in these studies relies on quality control of the purified recombinant protein to precisely determining its identity as well as any undesirable micro-heterogeneities. While standard proteomics approaches preclude unbiased search for modifications, the optional technique of top down MSMS requires the use of highly accurate and highly resolved experiments to reveal subtle sequence modifications. In the present study, the top down MSMS approach combined with Traveling Wave Ion Mobility (TWIM) separation was evaluated for its ability to achieve high sequence coverage and to reveal subtle micro-heterogeneities that were hitherto only accessible with FTICR-MS instruments. The power of this approach is herein illustrated in an in-depth analysis of both wt and K496C variant of the recombinant X domain (XD, aa 459-507) of the measles virus phosphoprotein expressed in E. coli. Using top down MSMS combined to TWIM, we show that XD samples occasionally exhibit a micro-heterogeneity that could not be anticipated from the nucleotide sequence of the encoding constructs and that likely reflects a genetic drift, neutral or not, occurring during expression. In addition, an MTSL nitroxide probe that was grafted on the K496C XD variant was shown to undergo oxidation and/or protonation in the ESI source leading to artifactual mass increases. PMID:21800924

Toward systematic integration between self-determination theory and motivational interviewing as examples of top-down and bottom-up intervention development: autonomy or volition as a fundamental theoretical principle

PubMed Central

2012-01-01

Clinical interventions can be developed through two distinct pathways. In the first, which we call top-down, a well-articulated theory drives the development of the intervention, whereas in the case of a bottom-up approach, clinical experience, more so than a dedicated theoretical perspective, drives the intervention. Using this dialectic, this paper discusses Self-Determination Theory (SDT) [1,2] and Motivational Interviewing (MI) [3] as prototypical examples of a top-down and bottom-up approaches, respectively. We sketch the different starting points, foci and developmental processes of SDT and MI, but equally note the complementary character and the potential for systematic integration between both approaches. Nevertheless, for a deeper integration to take place, we contend that MI researchers might want to embrace autonomy as a fundamental basic process underlying therapeutic change and we discuss the advantages of doing so. PMID:22385828

Community composition of lacustrine small eukaryotes in hyper-eutrophic conditions in relation to top-down and bottom-up factors.

PubMed

Lepère, Cécile; Domaizon, Isabelle; Debroas, Didier

2007-09-01

Small eukaryotes (0.2-5 microm) in hyper-eutrophic conditions were described using terminal restriction fragment length polymorphism and cloning-sequencing, and were related to environmental variables both by an experimental approach and by a temporal field study. In situ analysis showed marked temporal variations in the dominant terminal restriction fragments (T-RFs), which were related to environmental variables such as nutrient concentrations and metazooplankton composition. To monitor the responses of the small-eukaryote community to top-down (absence or presence of planktivorous fish) and bottom-up (low or high nitrogen and phosphorus addition) effects, a cross-classified design mesocosm experiment was used. Depending on the type of treatment, we recorded changes in the diversity of T-RFs, as well as modifications in phylogenetic composition. Centroheliozoa and Cryptophyta were found in all types of treatment, whereas Chlorophyta were specific to enclosures receiving high nutrient loadings, and were associated either with LKM11 and 'environmental sequences'. Cercozoa and Fungi were not detected in enclosures receiving high nutrient loadings and fishes. Our results showed that resources and top-down factors are both clearly involved in shaping the structure of small eukaryotes, not only autotrophs but also heterotrophs, via complex interactions and trophic cascades within a microbial loop, notably in response to nutrient loading.

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

PubMed

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

2017-02-03

As histones play central roles in most chromosomal functions including regulation of DNA replication, DNA damage repair, and gene transcription, both their basic biology and their roles in disease development have been the subject of intense study. Because multiple post-translational modifications (PTMs) along the entire protein sequence are potential regulators of histones, a top-down approach, where intact proteins are analyzed, is ultimately required for complete characterization of proteoforms. However, significant challenges remain for top-down histone analysis primarily because of deficiencies in separation/resolving power and effective identification algorithms. Here we used state-of-the-art mass spectrometry and a bioinformatics workflow for targeted data analysis and visualization. The workflow uses ProMex for intact mass deconvolution, MSPathFinder as a search engine, and LcMsSpectator as a data visualization tool. When complemented with the open-modification tool TopPIC, this workflow enabled identification of novel histone PTMs including tyrosine bromination on histone H4 and H2A, H3 glutathionylation, and mapping of conventional PTMs along the entire protein for many histone subunits.

A discriminative method for protein remote homology detection and fold recognition combining Top-n-grams and latent semantic analysis.

PubMed

Liu, Bin; Wang, Xiaolong; Lin, Lei; Dong, Qiwen; Wang, Xuan

2008-12-01

Protein remote homology detection and fold recognition are central problems in bioinformatics. Currently, discriminative methods based on support vector machine (SVM) are the most effective and accurate methods for solving these problems. A key step to improve the performance of the SVM-based methods is to find a suitable representation of protein sequences. In this paper, a novel building block of proteins called Top-n-grams is presented, which contains the evolutionary information extracted from the protein sequence frequency profiles. The protein sequence frequency profiles are calculated from the multiple sequence alignments outputted by PSI-BLAST and converted into Top-n-grams. The protein sequences are transformed into fixed-dimension feature vectors by the occurrence times of each Top-n-gram. The training vectors are evaluated by SVM to train classifiers which are then used to classify the test protein sequences. We demonstrate that the prediction performance of remote homology detection and fold recognition can be improved by combining Top-n-grams and latent semantic analysis (LSA), which is an efficient feature extraction technique from natural language processing. When tested on superfamily and fold benchmarks, the method combining Top-n-grams and LSA gives significantly better results compared to related methods. The method based on Top-n-grams significantly outperforms the methods based on many other building blocks including N-grams, patterns, motifs and binary profiles. Therefore, Top-n-gram is a good building block of the protein sequences and can be widely used in many tasks of the computational biology, such as the sequence alignment, the prediction of domain boundary, the designation of knowledge-based potentials and the prediction of protein binding sites.

Medical Operations Console Procedure Evaluation: BME Response to Crew Call Down for an Emergency

NASA Technical Reports Server (NTRS)

Johnson-Troop; Pettys, Marianne; Hurst, Victor, IV; Smaka, Todd; Paul, Bonnie; Rosenquist, Kevin; Gast, Karin; Gillis, David; McCulley, Phyllis

2006-01-01

International Space Station (ISS) Mission Operations are managed by multiple flight control disciplines located at the lead Mission Control Center (MCC) at NASA-Johnson Space Center (JSC). ISS Medical Operations are supported by the complementary roles of Flight Surgeons (Surgeon) and Biomedical Engineer (BME) flight controllers. The Surgeon, a board certified physician, oversees all medical concerns of the crew and the BME provides operational and engineering support for Medical Operations Crew Health Care System. ISS Medical Operations is currently addressing the coordinated response to a crew call down for an emergent medical event, in particular when the BME is the only Medical Operations representative in MCC. In this case, the console procedure BME Response to Crew Call Down for an Emergency will be used. The procedure instructs the BME to contact a Surgeon as soon as possible, coordinate with other flight disciplines to establish a Private Medical Conference (PMC) for the crew and Surgeon, gather information from the crew if time permits, and provide Surgeon with pertinent console resources. It is paramount that this procedure is clearly written and easily navigated to assist the BME to respond consistently and efficiently. A total of five BME flight controllers participated in the study. Each BME participant sat in a simulated MCC environment at a console configured with resources specific to the BME MCC console and was presented with two scripted emergency call downs from an ISS crew member. Each participant used the procedure while interacting with analog MCC disciplines to respond to the crew call down. Audio and video recordings of the simulations were analyzed and each BME participant's actions were compared to the procedure. Structured debriefs were conducted at the conclusion of both simulations. The procedure was evaluated for its ability to elicit consistent responses from each BME participant. Trials were examined for deviations in procedure task completion and/or navigation, in particular the execution of the Surgeon call sequence. Debrief comments were used to analyze unclear procedural steps and to discern any discrepancies between the procedure and generally accepted BME actions. The sequence followed by BME participants differed considerably from the sequence intended by the procedure. Common deviations included the call sequence used to contact Surgeon, the content of BME and crew interaction and the gathering of pertinent console resources. Differing perceptions of task priority and imprecise language seem to have caused multiple deviations from the procedure s intended sequence. The study generated 40 recommendations for the procedure, of which 34 are being implemented. These recommendations address improving the clarity of the instructions, identifying training considerations, expediting Surgeon contact, improving cues for anticipated flight control team communication and identifying missing console tools.

Electrochemistry-Assisted Top-Down Characterization of Disulfide-Containing Proteins

PubMed Central

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

2013-01-01

Covalent disulfide bond linkage in a protein represents an important challenge for mass spectrometry (MS)-based top-down protein structure analysis as it reduces the backbone cleavage efficiency for MS/MS dissociation. This study presents a strategy for solving this critical issue via integrating electrochemistry (EC) online with top-down MS approach. In this approach, proteins undergo electrolytic reduction in an electrochemical cell to break disulfide bonds and then online ionized into gaseous ions for analysis by electron-capture dissociation (ECD) and collision-induced dissociation (CID). The electrochemical reduction of proteins allows to remove disulfide bond constraints and also leads to increased charge numbers of the resulting protein ions. As a result, sequence coverage was significantly enhanced, as exemplified by β-lactoglobulin A (24 vs. 73 backbone cleavages before and after electrolytic reduction, respectively) and lysozyme (5 vs. 66 backbone cleavages before and after electrolytic reduction, respectively). This methodology is fast and does not need chemical reductants, which would have an important impact in high-throughput proteomics research. PMID:22448817

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

PubMed

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

2012-04-17

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

QUENCHING STAR FORMATION AT INTERMEDIATE REDSHIFTS: DOWNSIZING OF THE MASS FLUX DENSITY IN THE GREEN VALLEY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goncalves, Thiago S.; Menendez-Delmestre, Karin; Martin, D. Christopher

2012-11-01

The bimodality in galaxy properties has been observed at low and high redshifts, with a clear distinction between star-forming galaxies in the blue cloud and passively evolving objects in the red sequence; the absence of galaxies with intermediate properties indicates that the quenching of star formation and subsequent transition between populations must happen rapidly. In this paper, we present a study of over 100 transiting galaxies in the so-called green valley at intermediate redshifts (z {approx} 0.8). By using very deep spectroscopy with the DEIMOS instrument at the Keck telescope we are able to infer the star formation histories ofmore » these objects and measure the stellar mass flux density transiting from the blue cloud to the red sequence when the universe was half its current age. Our results indicate that the process happened more rapidly and for more massive galaxies in the past, suggesting a top-down scenario in which the massive end of the red sequence is forming first. This represents another aspect of downsizing, with the mass flux density moving toward smaller galaxies in recent times.« less

Comparative higher-order structure analysis of antibody biosimilars using combined bottom-up and top-down hydrogen-deuterium exchange mass spectrometry.

PubMed

Pan, Jingxi; Zhang, Suping; Borchers, Christoph H

2016-12-01

Hydrogen/deuterium exchange (HDX) coupled with mass spectrometry (MS) is a powerful technique for higher-order structural characterization of antibodies. Although the peptide-based bottom-up HDX approach and the protein-based top-down HDX approach have complementary advantages, the work done so far on biosimilars has involved only one or the other approach. Herein we have characterized the structures of two bevacizumab (BEV) biosimilars and compared them to the reference BEV using both methods. A sequence coverage of 87% was obtained for the heavy chain and 74% for the light chain in the bottom-up approach. The deuterium incorporation behavior of the peptic peptides from the three BEVs were compared side by side and showed no differences at various HDX time points. Top-down experiments were carried out using subzero temperature LC-MS, and the deuterium incorporation of the intact light chain and heavy chain were obtained. Top-down ETD was also performed to obtain amino acid-level HDX information that covered 100% of the light chain, but only 50% coverage is possible for the heavy chain. Consistent with the intact subunit level data, no differences were observed in the amino acid level HDX data. All these results indicate that there are no differences between the three BEV samples with respect to their high-order structures. The peptide level information from the bottom-up approach, and the residue level and intact subunit level information from the top-down approach were complementary and covered the entire antibody. Copyright © 2016 Elsevier B.V. All rights reserved.

Selection history alters attentional filter settings persistently and beyond top-down control.

PubMed

Kadel, Hanna; Feldmann-Wüstefeld, Tobias; Schubö, Anna

2017-05-01

Visual selective attention is known to be guided by stimulus-based (bottom-up) and goal-oriented (top-down) control mechanisms. Recent work has pointed out that selection history (i.e., the bias to prioritize items that have been previously attended) can result in a learning experience that also has a substantial impact on subsequent attention guidance. The present study examined to what extent goal-oriented top-down control mechanisms interact with an observer's individual selection history in guiding attention. Selection history was manipulated in a categorization task in a between-subjects design, where participants learned that either color or shape was the response-relevant dimension. The impact of this experience was assessed in a compound visual search task with an additional color distractor. Top-down preparation for each search trial was enabled by a pretrial task cue (Experiment 1) or a fixed, predictable trial sequence (Experiment 2). Reaction times and ERPs served as indicators of attention deployment. Results showed that attention was captured by the color distractor when participants had learned that color predicted the correct response in the categorization learning task, suggesting that a bias for predictive stimulus features had developed. The possibility to prepare for the search task reduced the bias, but could not entirely overrule this selection history effect. In Experiment 3, both tasks were performed in separate sessions, and the bias still persisted. These results indicate that selection history considerably shapes selective attention and continues to do so persistently even when the task allowed for high top-down control. © 2017 Society for Psychophysiological Research.

Enhancing Protein Disulfide Bond Cleavage by UV Excitation and Electron Capture Dissociation for Top-Down Mass Spectrometry.

PubMed

Wongkongkathep, Piriya; Li, Huilin; Zhang, Xing; Loo, Rachel R Ogorzalek; Julian, Ryan R; Loo, Joseph A

2015-11-15

The application of ion pre-activation with 266 nm ultraviolet (UV) laser irradiation combined with electron capture dissociation (ECD) is demonstrated to enhance top-down mass spectrometry sequence coverage of disulfide bond containing proteins. UV-based activation can homolytically cleave a disulfide bond to yield two separated thiol radicals. Activated ECD experiments of insulin and ribonuclease A containing three and four disulfide bonds, respectively, were performed. UV-activation in combination with ECD allowed the three disulfide bonds of insulin to be cleaved and the overall sequence coverage to be increased. For the larger sized ribonuclease A with four disulfide bonds, irradiation from an infrared laser (10.6 µm) to disrupt non-covalent interactions was combined with UV-activation to facilitate the cleavage of up to three disulfide bonds. Preferences for disulfide bond cleavage are dependent on protein structure and sequence. Disulfide bonds can reform if the generated radicals remain in close proximity. By varying the time delay between the UV-activation and the ECD events, it was determined that disulfide bonds reform within 10-100 msec after their UV-homolytic cleavage.

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

PubMed

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.

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

PubMed

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.

Engineering neural systems for high-level problem solving.

PubMed

Sylvester, Jared; Reggia, James

2016-07-01

There is a long-standing, sometimes contentious debate in AI concerning the relative merits of a symbolic, top-down approach vs. a neural, bottom-up approach to engineering intelligent machine behaviors. While neurocomputational methods excel at lower-level cognitive tasks (incremental learning for pattern classification, low-level sensorimotor control, fault tolerance and processing of noisy data, etc.), they are largely non-competitive with top-down symbolic methods for tasks involving high-level cognitive problem solving (goal-directed reasoning, metacognition, planning, etc.). Here we take a step towards addressing this limitation by developing a purely neural framework named galis. Our goal in this work is to integrate top-down (non-symbolic) control of a neural network system with more traditional bottom-up neural computations. galis is based on attractor networks that can be "programmed" with temporal sequences of hand-crafted instructions that control problem solving by gating the activity retention of, communication between, and learning done by other neural networks. We demonstrate the effectiveness of this approach by showing that it can be applied successfully to solve sequential card matching problems, using both human performance and a top-down symbolic algorithm as experimental controls. Solving this kind of problem makes use of top-down attention control and the binding together of visual features in ways that are easy for symbolic AI systems but not for neural networks to achieve. Our model can not only be instructed on how to solve card matching problems successfully, but its performance also qualitatively (and sometimes quantitatively) matches the performance of both human subjects that we had perform the same task and the top-down symbolic algorithm that we used as an experimental control. We conclude that the core principles underlying the galis framework provide a promising approach to engineering purely neurocomputational systems for problem-solving tasks that in people require higher-level cognitive functions. Copyright © 2016 Elsevier Ltd. All rights reserved.

View of Hadley Delta from top hatch of Apollo 15 Lunar Module after landing

NASA Technical Reports Server (NTRS)

1971-01-01

A view of Hadley Delta, looking southeasterly, as photographed from the top hatch of the Apollo 15 Lunar Module by Astronaut David R. Scott during his stand-up extravehicular activity just after the Lunar Module 'Falcon' touched down at the Hadly Apennine landing site. The prominent feature on the horizon in the center of the picture was called Silver Spur by the Apollo 15 crewmen. Hadley Delta mountain rises approximately 4,000 meters (about 13,124 feet) above the plain.

"De-novo" amino acid sequence elucidation of protein G'e by combined "top-down" and "bottom-up" mass spectrometry.

PubMed

Yefremova, Yelena; Al-Majdoub, Mahmoud; Opuni, Kwabena F M; Koy, Cornelia; Cui, Weidong; Yan, Yuetian; Gross, Michael L; Glocker, Michael O

2015-03-01

Mass spectrometric de-novo sequencing was applied to review the amino acid sequence of a commercially available recombinant protein G´ with great scientific and economic importance. Substantial deviations to the published amino acid sequence (Uniprot Q54181) were found by the presence of 46 additional amino acids at the N-terminus, including a so-called "His-tag" as well as an N-terminal partial α-N-gluconoylation and α-N-phosphogluconoylation, respectively. The unexpected amino acid sequence of the commercial protein G' comprised 241 amino acids and resulted in a molecular mass of 25,998.9 ± 0.2 Da for the unmodified protein. Due to the higher mass that is caused by its extended amino acid sequence compared with the original protein G' (185 amino acids), we named this protein "protein G'e." By means of mass spectrometric peptide mapping, the suggested amino acid sequence, as well as the N-terminal partial α-N-gluconoylations, was confirmed with 100% sequence coverage. After the protein G'e sequence was determined, we were able to determine the expression vector pET-28b from Novagen with the Xho I restriction enzyme cleavage site as the best option that was used for cloning and expressing the recombinant protein G'e in E. coli. A dissociation constant (K(d)) value of 9.4 nM for protein G'e was determined thermophoretically, showing that the N-terminal flanking sequence extension did not cause significant changes in the binding affinity to immunoglobulins.

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

NASA Astrophysics Data System (ADS)

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

NASA Astrophysics Data System (ADS)

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 (<30 kDa). Recent studies have focused on improving the analysis of larger intact proteins (up to 75 kDa), but they have also highlighted several challenges to be addressed. One major hurdle is the efficient dissociation of larger protein ions, which often to do not yield extensive fragmentation via conventional tandem MS methods. Here we describe the first application of activated ion electron transfer dissociation (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.

`Log-Chipper' Turbulence in the Convective Boundary Layer.

NASA Astrophysics Data System (ADS)

Kimmel, Shari J.; Wyngaard, John C.; Otte, Martin J.

2002-03-01

Turbulent fluctuations of a conservative scalar in the atmospheric boundary layer (ABL) can be generated by a scalar flux at the surface, a scalar flux of entrainment at the ABL top, and the `chewing up' of scalar variations on the mesoscale. The first two have been previously studied, while the third is examined in this paper through large-eddy simulation (LES). The LES results show that the scalar fluctuations due to the breakdown of mesoscale variations in advected conservative scalar fields, which the authors call the `log-chipper' component of scalar fluctuations, are uniformly distributed through the depth of the convective ABL, unlike the top-down and bottom-up components.A similarity function, similar to those for the top-down and bottom-up scalars, is derived for the log-chipper scalar variance in the convective ABL and used to compare the relative importance of these three processes for generating scalar fluctuations. Representative mesoscale gradients for water vapor mixing ratio and potential temperature are computed from airplane measurements over both land and water. In situations where the entrainment and surface fluxes are sufficiently small, or the ABL depth, turbulence intensity, or the mesoscale scalar gradient is sufficiently large, the variance of the log-chipper scalar fluctuations in mid-ABL can be of the order of the variance of top-down and bottom-up scalars.

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

PubMed Central

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

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

PubMed

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

2011-12-01

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 electron-capture 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. Copyright © 2011 Elsevier Inc. All rights reserved.

Nano-LC FTICR tandem mass spectrometry for top-down proteomics: routine baseline unit mass resolution of whole cell lysate proteins up to 72 kDa.

PubMed

Tipton, Jeremiah D; Tran, John C; Catherman, Adam D; Ahlf, Dorothy R; Durbin, Kenneth R; Lee, Ji Eun; Kellie, John F; Kelleher, Neil L; Hendrickson, Christopher L; Marshall, Alan G

2012-03-06

Current high-throughput top-down proteomic platforms provide routine identification of proteins less than 25 kDa with 4-D separations. This short communication reports the application of technological developments over the past few years that improve protein identification and characterization for masses greater than 25 kDa. Advances in separation science have allowed increased numbers of proteins to be identified, especially by nanoliquid chromatography (nLC) prior to mass spectrometry (MS) analysis. Further, a goal of high-throughput top-down proteomics is to extend the mass range for routine nLC MS analysis up to 80 kDa because gene sequence analysis predicts that ~70% of the human proteome is transcribed to be less than 80 kDa. Normally, large proteins greater than 50 kDa are identified and characterized by top-down proteomics through fraction collection and direct infusion at relatively low throughput. Further, other MS-based techniques provide top-down protein characterization, however at low resolution for intact mass measurement. Here, we present analysis of standard (up to 78 kDa) and whole cell lysate proteins by Fourier transform ion cyclotron resonance mass spectrometry (nLC electrospray ionization (ESI) FTICR MS). The separation platform reduced the complexity of the protein matrix so that, at 14.5 T, proteins from whole cell lysate up to 72 kDa are baseline mass resolved on a nano-LC chromatographic time scale. Further, the results document routine identification of proteins at improved throughput based on accurate mass measurement (less than 10 ppm mass error) of precursor and fragment ions for proteins up to 50 kDa.

Motility and Flagellar Glycosylation in Clostridium difficile▿ †

PubMed Central

Twine, Susan M.; Reid, Christopher W.; Aubry, Annie; McMullin, David R.; Fulton, Kelly M.; Austin, John; Logan, Susan M.

2009-01-01

In this study, intact flagellin proteins were purified from strains of Clostridium difficile and analyzed using quadrupole time of flight and linear ion trap mass spectrometers. Top-down studies showed the flagellin proteins to have a mass greater than that predicted from the corresponding gene sequence. These top-down studies revealed marker ions characteristic of glycan modifications. Additionally, diversity in the observed masses of glycan modifications was seen between strains. Electron transfer dissociation mass spectrometry was used to demonstrate that the glycan was attached to the flagellin protein backbone in O linkage via a HexNAc residue in all strains examined. Bioinformatic analysis of C. difficile genomes revealed diversity with respect to glycan biosynthesis gene content within the flagellar biosynthesis locus, likely reflected by the observed flagellar glycan diversity. In C. difficile strain 630, insertional inactivation of a glycosyltransferase gene (CD0240) present in all sequenced genomes resulted in an inability to produce flagellar filaments at the cell surface and only minor amounts of unmodified flagellin protein. PMID:19749038

Understanding Collective Activities of People from Videos.

PubMed

Wongun Choi; Savarese, Silvio

2014-06-01

This paper presents a principled framework for analyzing collective activities at different levels of semantic granularity from videos. Our framework is capable of jointly tracking multiple individuals, recognizing activities performed by individuals in isolation (i.e., atomic activities such as walking or standing), recognizing the interactions between pairs of individuals (i.e., interaction activities) as well as understanding the activities of group of individuals (i.e., collective activities). A key property of our work is that it can coherently combine bottom-up information stemming from detections or fragments of tracks (or tracklets) with top-down evidence. Top-down evidence is provided by a newly proposed descriptor that captures the coherent behavior of groups of individuals in a spatial-temporal neighborhood of the sequence. Top-down evidence provides contextual information for establishing accurate associations between detections or tracklets across frames and, thus, for obtaining more robust tracking results. Bottom-up evidence percolates upwards so as to automatically infer collective activity labels. Experimental results on two challenging data sets demonstrate our theoretical claims and indicate that our model achieves enhances tracking results and the best collective classification results to date.

Some Thoughts on a "Beloved Community"

ERIC Educational Resources Information Center

Hall, Ted; Campano, Gerald

2014-01-01

Hall and Campano echo Jones and Rainville's call for compassion and humility in literacy coaching and argue that this is an urgent endeavor in an increasingly top-down educational climate. They offer collective analysis, through teacher inquiry communities and teacher activism, as a potential site of hope for making sense of the larger…

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.

PubMed

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.

Building Peace Education in the Islamic Educational Context

ERIC Educational Resources Information Center

Abu-Nimer, Mohammed; Nasser, Ilham

2017-01-01

Following the events of 9/11, many misconceptions entered the policy-making platform with regard to the need for education reforms in the Muslim world. Based upon Western cultural and societal norms and increased scepticism of the role of religion in violence, these assumptions have triggered a strong wave of calls for a top-down approach to…

Pyro: A Python-Based Versatile Programming Environment for Teaching Robotics

ERIC Educational Resources Information Center

Blank, Douglas; Kumar, Deepak; Meeden, Lisa; Yanco, Holly

2004-01-01

In this article we describe a programming framework called Pyro, which provides a set of abstractions that allows students to write platform-independent robot programs. This project is unique because of its focus on the pedagogical implications of teaching mobile robotics via a top-down approach. We describe the background of the project, its…

Top-down causation and emergence: some comments on mechanisms

PubMed Central

Ellis, George F. R.

2012-01-01

Both bottom-up and top-down causation occur in the hierarchy of structure and causation. A key feature is multiple realizability of higher level functions, and consequent existence of equivalence classes of lower level variables that correspond to the same higher level state. Five essentially different classes of top-down influence can be identified, and their existence demonstrated by many real-world examples. They are: algorithmic top-down causation; top-down causation via non-adaptive information control, top-down causation via adaptive selection, top-down causation via adaptive information control and intelligent top-down causation (the effect of the human mind on the physical world). Through the mind, abstract entities such as mathematical structures have causal power. The causal slack enabling top-down action to take place lies in the structuring of the system so as to attain higher level functions; in the way the nature of lower level elements is changed by context, and in micro-indeterminism combined with adaptive selection. Understanding top-down causation can have important effects on society. Two cases will be mentioned: medical/healthcare issues, and education—in particular, teaching reading and writing. In both cases, an ongoing battle between bottom-up and top-down approaches has important consequences for society. PMID:23386967

Mechanisms Driving Galling Success in a Fragmented Landscape: Synergy of Habitat and Top-Down Factors along Temperate Forest Edges

PubMed Central

Kelch, Nina-S.; Neves, Frederico S.; Fernandes, G. Wilson

2016-01-01

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. PMID:27310599

Towards Clinical Molecular Diagnosis of Inherited Cardiac Conditions: A Comparison of Bench-Top Genome DNA Sequencers

PubMed Central

Wilkinson, Samuel L.; John, Shibu; Walsh, Roddy; Novotny, Tomas; Valaskova, Iveta; Gupta, Manu; Game, Laurence; Barton, Paul J R.; Cook, Stuart A.; Ware, James S.

2013-01-01

Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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, these NGS approaches are faster, less expensive, and yet more comprehensive. PMID:23861798

Effective connectivity in the neural network underlying coarse-to-fine categorization of visual scenes. A dynamic causal modeling study.

PubMed

Kauffmann, Louise; Chauvin, Alan; Pichat, Cédric; Peyrin, Carole

2015-10-01

According to current models of visual perception scenes are processed in terms of spatial frequencies following a predominantly coarse-to-fine processing sequence. Low spatial frequencies (LSF) reach high-order areas rapidly in order to activate plausible interpretations of the visual input. This triggers top-down facilitation that guides subsequent processing of high spatial frequencies (HSF) in lower-level areas such as the inferotemporal and occipital cortices. However, dynamic interactions underlying top-down influences on the occipital cortex have never been systematically investigated. The present fMRI study aimed to further explore the neural bases and effective connectivity underlying coarse-to-fine processing of scenes, particularly the role of the occipital cortex. We used sequences of six filtered scenes as stimuli depicting coarse-to-fine or fine-to-coarse processing of scenes. Participants performed a categorization task on these stimuli (indoor vs. outdoor). Firstly, we showed that coarse-to-fine (compared to fine-to-coarse) sequences elicited stronger activation in the inferior frontal gyrus (in the orbitofrontal cortex), the inferotemporal cortex (in the fusiform and parahippocampal gyri), and the occipital cortex (in the cuneus). Dynamic causal modeling (DCM) was then used to infer effective connectivity between these regions. DCM results revealed that coarse-to-fine processing resulted in increased connectivity from the occipital cortex to the inferior frontal gyrus and from the inferior frontal gyrus to the inferotemporal cortex. Critically, we also observed an increase in connectivity strength from the inferior frontal gyrus to the occipital cortex, suggesting that top-down influences from frontal areas may guide processing of incoming signals. The present results support current models of visual perception and refine them by emphasizing the role of the occipital cortex as a cortical site for feedback projections in the neural network underlying coarse-to-fine processing of scenes. Copyright © 2015 Elsevier Inc. All rights reserved.

Top-Down Beta Enhances Bottom-Up Gamma

PubMed Central

Thompson, William H.

2017-01-01

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. PMID:28592697

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

PubMed Central

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

2017-01-01

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

Emotional metacontrol of attention: Top-down modulation of sensorimotor processes in a robotic visual search task.

PubMed

Belkaid, Marwen; Cuperlier, Nicolas; Gaussier, Philippe

2017-01-01

Emotions play a significant role in internal regulatory processes. In this paper, we advocate four key ideas. First, novelty detection can be grounded in the sensorimotor experience and allow higher order appraisal. Second, cognitive processes, such as those involved in self-assessment, influence emotional states by eliciting affects like boredom and frustration. Third, emotional processes such as those triggered by self-assessment influence attentional processes. Last, close emotion-cognition interactions implement an efficient feedback loop for the purpose of top-down behavior regulation. The latter is what we call 'Emotional Metacontrol'. We introduce a model based on artificial neural networks. This architecture is used to control a robotic system in a visual search task. The emotional metacontrol intervenes to bias the robot visual attention during active object recognition. Through a behavioral and statistical analysis, we show that this mechanism increases the robot performance and fosters the exploratory behavior to avoid deadlocks.

Warm-Season Flows on Slope in Horowitz Crater Nine-Image Sequence

NASA Image and Video Library

2011-08-04

This image comes from observations of Horowitz crater by the HiRISE camera onboard NASA Mars Reconnaissance Orbiter. The features that extend down the slope during warm seasons are called recurring slope lineae.

A Multicomponent Large Ringlaser for Seismology: First Observations

NASA Astrophysics Data System (ADS)

Igel, H.; Gebauer, A.; Simonelli, A.; Kodet, J.; Bernauer, F.; Donner, S.; Wassermann, J. M.; Tanimoto, T.; Schreiber, K. U.

2017-12-01

During 2016 a large 4-component ring laser structure called "Romy" was built and implemented underground in the Geophysical Observatory of the Ludwig-Maximilians-University (LMU) 20km outside Munich primarily funded by the European Research Council and LMU. The ring laser has a tetrahedral top-down shape with four triangles of 12m side length. The independent triangular He-Ne ring lasers with 12 m side length are expected to resolve rotational motions down to 12 prad/s/sqrt(Hz), allowing us to record below the assumed low-noise model for rotational ground motions in a wide frequency band (e.g., ocean-generated noise, free oscillations, local regional and global earthquakes). Recently, Romy was described in a feature article in Science (Hand, DOI: 10.1126/science.aal1069). We will present the current state of the instrument and discuss the operation principle and quality of the ring laser components. First observations include the ocean-generated noise, the late 2016 earthquake sequence of Italy, and several teleseismic events. We compare ring laser observations from different sites (Gran Sasso Underground Laboratory, Italy, and G-ring Wettzell, Germany) in relation with their local site conditions. We report on future plans to stabilize the ring geometry providing long-term stability for geodetic applications such as the precise measurement of the Earth's complete rotation vector.

In Praise of Top-Down Leadership

ERIC Educational Resources Information Center

Dufour, Richard

2007-01-01

In the ongoing debate of the efficacy of top-down versus bottom-up strategies to improve school districts, top-down is clearly losing. Many district leaders are reluctant to champion improvement for fear of being labeled with the epithet "top-down leader," the unkindest cut of all. In this article, the author presents the change…

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

ERIC Educational Resources Information Center

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…

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

PubMed

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.

Conflict-triggered top-down control: default mode, last resort, or no such thing?

PubMed

Bugg, Julie M

2014-03-01

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 frequency-matched, 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 5th 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 nonexistent) 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.

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

PubMed Central

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

Daedalia Planum Windstreak

NASA Image and Video Library

2016-10-26

The "tail" behind the crater at the top of this VIS image is called a windstreak. This feature is formed by winds blowing over/in and around the crater. Turbulence in the wind will erode or deposit fine materials, creating the windstreak. Windstreaks form on the down wind side of the crater, and indicate winds from the ESE. The small hills below the windstreak are small volcanic constructs. This image is located in the extensive lava plains called Daedalia Planum. Orbit Number: 65310 Latitude: -10.2729 Longitude: 226.476 Instrument: VIS Captured: 2016-09-03 11:24 http://photojournal.jpl.nasa.gov/catalog/PIA21151

Top-Down Control of MEG Alpha-Band Activity in Children Performing Categorical N-Back Task

ERIC Educational Resources Information Center

Ciesielski, Kristina T.; Ahlfors, Seppo P.; Bedrick, Edward J.; Kerwin, Audra A.; Hamalainen, Matti S.

2010-01-01

Top-down cognitive control has been associated in adults with the prefrontal-parietal network. In children the brain mechanisms of top-down control have rarely been studied. We examined developmental differences in top-down cognitive control by monitoring event-related desynchronization (ERD) and event-related synchronization (ERS) of alpha-band…

Predictive coding in autism spectrum disorder and attention deficit hyperactivity disorder.

PubMed

Gonzalez-Gadea, Maria Luz; Chennu, Srivas; Bekinschtein, Tristan A; Rattazzi, Alexia; Beraudi, Ana; Tripicchio, Paula; Moyano, Beatriz; Soffita, Yamila; Steinberg, Laura; Adolfi, Federico; Sigman, Mariano; Marino, Julian; Manes, Facundo; Ibanez, Agustin

2015-11-01

Predictive coding has been proposed as a framework to understand neural processes in neuropsychiatric disorders. We used this approach to describe mechanisms responsible for attentional abnormalities in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). We monitored brain dynamics of 59 children (8-15 yr old) who had ASD or ADHD or who were control participants via high-density electroencephalography. We performed analysis at the scalp and source-space levels while participants listened to standard and deviant tone sequences. Through task instructions, we manipulated top-down expectation by presenting expected and unexpected deviant sequences. Children with ASD showed reduced superior frontal cortex (FC) responses to unexpected events but increased dorsolateral prefrontal cortex (PFC) activation to expected events. In contrast, children with ADHD exhibited reduced cortical responses in superior FC to expected events but strong PFC activation to unexpected events. Moreover, neural abnormalities were associated with specific control mechanisms, namely, inhibitory control in ASD and set-shifting in ADHD. Based on the predictive coding account, top-down expectation abnormalities could be attributed to a disproportionate reliance (precision) allocated to prior beliefs in ASD and to sensory input in ADHD. Copyright © 2015 the American Physiological Society.

Predictive coding in autism spectrum disorder and attention deficit hyperactivity disorder

PubMed Central

Gonzalez-Gadea, Maria Luz; Chennu, Srivas; Bekinschtein, Tristan A.; Rattazzi, Alexia; Beraudi, Ana; Tripicchio, Paula; Moyano, Beatriz; Soffita, Yamila; Steinberg, Laura; Adolfi, Federico; Sigman, Mariano; Marino, Julian; Manes, Facundo

2015-01-01

Predictive coding has been proposed as a framework to understand neural processes in neuropsychiatric disorders. We used this approach to describe mechanisms responsible for attentional abnormalities in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). We monitored brain dynamics of 59 children (8–15 yr old) who had ASD or ADHD or who were control participants via high-density electroencephalography. We performed analysis at the scalp and source-space levels while participants listened to standard and deviant tone sequences. Through task instructions, we manipulated top-down expectation by presenting expected and unexpected deviant sequences. Children with ASD showed reduced superior frontal cortex (FC) responses to unexpected events but increased dorsolateral prefrontal cortex (PFC) activation to expected events. In contrast, children with ADHD exhibited reduced cortical responses in superior FC to expected events but strong PFC activation to unexpected events. Moreover, neural abnormalities were associated with specific control mechanisms, namely, inhibitory control in ASD and set-shifting in ADHD. Based on the predictive coding account, top-down expectation abnormalities could be attributed to a disproportionate reliance (precision) allocated to prior beliefs in ASD and to sensory input in ADHD. PMID:26311184

High-frequency neural activity predicts word parsing in ambiguous speech streams.

PubMed

Kösem, Anne; Basirat, Anahita; Azizi, Leila; van Wassenhove, Virginie

2016-12-01

During speech listening, the brain parses a continuous acoustic stream of information into computational units (e.g., syllables or words) necessary for speech comprehension. Recent neuroscientific hypotheses have proposed that neural oscillations contribute to speech parsing, but whether they do so on the basis of acoustic cues (bottom-up acoustic parsing) or as a function of available linguistic representations (top-down linguistic parsing) is unknown. In this magnetoencephalography study, we contrasted acoustic and linguistic parsing using bistable speech sequences. While listening to the speech sequences, participants were asked to maintain one of the two possible speech percepts through volitional control. We predicted that the tracking of speech dynamics by neural oscillations would not only follow the acoustic properties but also shift in time according to the participant's conscious speech percept. Our results show that the latency of high-frequency activity (specifically, beta and gamma bands) varied as a function of the perceptual report. In contrast, the phase of low-frequency oscillations was not strongly affected by top-down control. Whereas changes in low-frequency neural oscillations were compatible with the encoding of prelexical segmentation cues, high-frequency activity specifically informed on an individual's conscious speech percept. Copyright © 2016 the American Physiological Society.

High-frequency neural activity predicts word parsing in ambiguous speech streams

PubMed Central

Basirat, Anahita; Azizi, Leila; van Wassenhove, Virginie

2016-01-01

During speech listening, the brain parses a continuous acoustic stream of information into computational units (e.g., syllables or words) necessary for speech comprehension. Recent neuroscientific hypotheses have proposed that neural oscillations contribute to speech parsing, but whether they do so on the basis of acoustic cues (bottom-up acoustic parsing) or as a function of available linguistic representations (top-down linguistic parsing) is unknown. In this magnetoencephalography study, we contrasted acoustic and linguistic parsing using bistable speech sequences. While listening to the speech sequences, participants were asked to maintain one of the two possible speech percepts through volitional control. We predicted that the tracking of speech dynamics by neural oscillations would not only follow the acoustic properties but also shift in time according to the participant's conscious speech percept. Our results show that the latency of high-frequency activity (specifically, beta and gamma bands) varied as a function of the perceptual report. In contrast, the phase of low-frequency oscillations was not strongly affected by top-down control. Whereas changes in low-frequency neural oscillations were compatible with the encoding of prelexical segmentation cues, high-frequency activity specifically informed on an individual's conscious speech percept. PMID:27605528

Characterization and Quantification of Intact 26S Proteasome Proteins by Real-Time Measurement of Intrinsic Fluorescence Prior to Top-down Mass Spectrometry

PubMed Central

Russell, Jason D.; Scalf, Mark; Book, Adam J.; Ladror, Daniel T.; Vierstra, Richard D.; Smith, Lloyd M.; Coon, Joshua J.

2013-01-01

Quantification of gas-phase intact protein ions by mass spectrometry (MS) is impeded by highly-variable ionization, ion transmission, and ion detection efficiencies. Therefore, quantification of proteins using MS-associated techniques is almost exclusively done after proteolysis where peptides serve as proxies for estimating protein abundance. Advances in instrumentation, protein separations, and informatics have made large-scale sequencing of intact proteins using top-down proteomics accessible to the proteomics community; yet quantification of proteins using a top-down workflow has largely been unaddressed. Here we describe a label-free approach to determine the abundance of intact proteins separated by nanoflow liquid chromatography prior to MS analysis by using solution-phase measurements of ultraviolet light-induced intrinsic fluorescence (UV-IF). UV-IF is measured directly at the electrospray interface just prior to the capillary exit where proteins containing at least one tryptophan residue are readily detected. UV-IF quantification was demonstrated using commercially available protein standards and provided more accurate and precise protein quantification than MS ion current. We evaluated the parallel use of UV-IF and top-down tandem MS for quantification and identification of protein subunits and associated proteins from an affinity-purified 26S proteasome sample from Arabidopsis thaliana. We identified 26 unique proteins and quantified 13 tryptophan-containing species. Our analyses discovered previously unidentified N-terminal processing of the β6 (PBF1) and β7 (PBG1) subunit - such processing of PBG1 may generate a heretofore unknown additional protease active site upon cleavage. In addition, our approach permitted the unambiguous identification and quantification both isoforms of the proteasome-associated protein DSS1. PMID:23536786

Characterization and quantification of intact 26S proteasome proteins by real-time measurement of intrinsic fluorescence prior to top-down mass spectrometry.

PubMed

Russell, Jason D; Scalf, Mark; Book, Adam J; Ladror, Daniel T; Vierstra, Richard D; Smith, Lloyd M; Coon, Joshua J

2013-01-01

Quantification of gas-phase intact protein ions by mass spectrometry (MS) is impeded by highly-variable ionization, ion transmission, and ion detection efficiencies. Therefore, quantification of proteins using MS-associated techniques is almost exclusively done after proteolysis where peptides serve as proxies for estimating protein abundance. Advances in instrumentation, protein separations, and informatics have made large-scale sequencing of intact proteins using top-down proteomics accessible to the proteomics community; yet quantification of proteins using a top-down workflow has largely been unaddressed. Here we describe a label-free approach to determine the abundance of intact proteins separated by nanoflow liquid chromatography prior to MS analysis by using solution-phase measurements of ultraviolet light-induced intrinsic fluorescence (UV-IF). UV-IF is measured directly at the electrospray interface just prior to the capillary exit where proteins containing at least one tryptophan residue are readily detected. UV-IF quantification was demonstrated using commercially available protein standards and provided more accurate and precise protein quantification than MS ion current. We evaluated the parallel use of UV-IF and top-down tandem MS for quantification and identification of protein subunits and associated proteins from an affinity-purified 26S proteasome sample from Arabidopsis thaliana. We identified 26 unique proteins and quantified 13 tryptophan-containing species. Our analyses discovered previously unidentified N-terminal processing of the β6 (PBF1) and β7 (PBG1) subunit - such processing of PBG1 may generate a heretofore unknown additional protease active site upon cleavage. In addition, our approach permitted the unambiguous identification and quantification both isoforms of the proteasome-associated protein DSS1.

Analysis of epididymal sperm maturation by MALDI profiling and top-down mass spectrometry.

PubMed

Labas, Valérie; Spina, Lucie; Belleannee, Clémence; Teixeira-Gomes, Ana-Paula; Gargaros, Audrey; Dacheux, Françoise; Dacheux, Jean-Louis

2015-01-15

The fertilization ability of male gametes is achieved after their transit through the epididymis where important post-gonadal differentiation occurs in different cellular compartments. Most of these maturational modifications occur at the protein level. The epididymal sperm maturation process was investigated using the ICM-MS (Intact Cell MALDI-TOF MS) approach on boar spermatozoa isolated from four different epididymal regions (immature to mature stage). Differential and quantitative MALDI-TOF profiling for whole cells or sub-cellular fractions was combined with targeted top-down MS in order to identify endogenous biomolecules. Using this approach, 172m/z peaks ranging between 2 and 20kDa were found to be modified during maturation of sperm. Using top-down MS, 62m/z were identified corresponding to peptidoforms/proteoforms with post-translational modifications (MS data are available via ProteomeXchange with identifier PXD001303). Many of the endogenous peptides were characterized as N-, C-terminal sequences or internal fragments of proteins presenting specific cleavages, suggesting the presence of sequential protease activities in the spermatozoa. This is the first time that such proteolytic activities could be evidenced for various sperm proteins through quantification of their proteolytic products. ICM-MS/top-down MS thus proved to be a valid approach for peptidome/degradome studies and provided new contributions to understanding of the maturation process of the male gamete involved in the development of male fertility. This peptidomic study (i) characterized the peptidome of epididymal spermatozoa from boar (Sus scrofa); (ii) established characteristic molecular phenotypes distinguishing degrees of maturation of spermatozoa during epididymal transit, and (iii) revealed that protease activities were at the origin of numerous peptides from known and unknown proteins involved in sperm maturation and/or fertility processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural Characterization of a Thrombin-Aptamer Complex by High Resolution Native Top-Down Mass Spectrometry

NASA Astrophysics Data System (ADS)

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.

Working memory encoding delays top-down attention to visual cortex.

PubMed

Scalf, Paige E; Dux, Paul E; Marois, René

2011-09-01

The encoding of information from one event into working memory can delay high-level, central decision-making processes for subsequent events [e.g., Jolicoeur, P., & Dell'Acqua, R. The demonstration of short-term consolidation. Cognitive Psychology, 36, 138-202, 1998, doi:10.1006/cogp.1998.0684]. Working memory, however, is also believed to interfere with the deployment of top-down attention [de Fockert, J. W., Rees, G., Frith, C. D., & Lavie, N. The role of working memory in visual selective attention. Science, 291, 1803-1806, 2001, doi:10.1126/science.1056496]. It is, therefore, possible that, in addition to delaying central processes, the engagement of working memory encoding (WME) also postpones perceptual processing as well. Here, we tested this hypothesis with time-resolved fMRI by assessing whether WME serially postpones the action of top-down attention on low-level sensory signals. In three experiments, participants viewed a skeletal rapid serial visual presentation sequence that contained two target items (T1 and T2) separated by either a short (550 msec) or long (1450 msec) SOA. During single-target runs, participants attended and responded only to T1, whereas in dual-target runs, participants attended and responded to both targets. To determine whether T1 processing delayed top-down attentional enhancement of T2, we examined T2 BOLD response in visual cortex by subtracting the single-task waveforms from the dual-task waveforms for each SOA. When the WME demands of T1 were high (Experiments 1 and 3), T2 BOLD response was delayed at the short SOA relative to the long SOA. This was not the case when T1 encoding demands were low (Experiment 2). We conclude that encoding of a stimulus into working memory delays the deployment of attention to subsequent target representations in visual cortex.

Top-down beta oscillatory signaling conveys behavioral context in early visual cortex.

PubMed

Richter, Craig G; Coppola, Richard; Bressler, Steven L

2018-05-03

Top-down modulation of sensory processing is a critical neural mechanism subserving numerous important cognitive roles, one of which may be to inform lower-order sensory systems of the current 'task at hand' by conveying behavioral context to these systems. Accumulating evidence indicates that top-down cortical influences are carried by directed interareal synchronization of oscillatory neuronal populations, with recent results pointing to beta-frequency oscillations as particularly important for top-down processing. However, it remains to be determined if top-down beta-frequency oscillations indeed convey behavioral context. We measured spectral Granger Causality (sGC) using local field potentials recorded from microelectrodes chronically implanted in visual areas V1/V2, V4, and TEO of two rhesus macaque monkeys, and applied multivariate pattern analysis to the spatial patterns of top-down sGC. We decoded behavioral context by discriminating patterns of top-down (V4/TEO-to-V1/V2) beta-peak sGC for two different task rules governing correct responses to identical visual stimuli. The results indicate that top-down directed influences are carried to visual cortex by beta oscillations, and differentiate task demands even before visual stimulus processing. They suggest that top-down beta-frequency oscillatory processes coordinate processing of sensory information by conveying global knowledge states to early levels of the sensory cortical hierarchy independently of bottom-up stimulus-driven processing.

A new scoring function for top-down spectral deconvolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kou, Qiang; Wu, Si; Liu, Xiaowen

2014-12-18

Background: Top-down mass spectrometry plays an important role in intact protein identification and characterization. Top-down mass spectra are more complex than bottom-up mass spectra because they often contain many isotopomer envelopes from highly charged ions, which may overlap with one another. As a result, spectral deconvolution, which converts a complex top-down mass spectrum into a monoisotopic mass list, is a key step in top-down spectral interpretation. Results: In this paper, we propose a new scoring function, L-score, for evaluating isotopomer envelopes. By combining L-score with MS-Deconv, a new software tool, MS-Deconv+, was developed for top-down spectral deconvolution. Experimental results showedmore » that MS-Deconv+ outperformed existing software tools in top-down spectral deconvolution. Conclusions: L-score shows high discriminative ability in identification of isotopomer envelopes. Using L-score, MS-Deconv+ reports many correct monoisotopic masses missed by other software tools, which are valuable for proteoform identification and characterization.« less

Progress in Top-Down Proteomics and the Analysis of Proteoforms

PubMed Central

Toby, Timothy K.; Fornelli, Luca; Kelleher, Neil L.

2017-01-01

From a molecular perspective, enactors of function in biology are intact proteins that can be variably modified at the genetic, transcriptional, or post-translational level. Over the past 30 years, mass spectrometry (MS) has become a powerful method for the analysis of proteomes. Prevailing bottom-up proteomics operates at the level of the peptide, leading to issues with protein inference, connectivity, and incomplete sequence/modification information. Top-down proteomics (TDP), alternatively, applies MS at the proteoform level to analyze intact proteins with diverse sources of intramolecular complexity preserved during analysis. Fortunately, advances in prefractionation workflows, MS instrumentation, and dissociation methods for whole-protein ions have helped TDP emerge as an accessible and potentially disruptive modality with increasingly translational value. In this review, we discuss technical and conceptual advances in TDP, along with the growing power of proteoform-resolved measurements in clinical and translational research. PMID:27306313

Stepwise evolution of resistance to toxic cardenolides via genetic substitutions in the Na+/K+ -ATPase of milkweed butterflies (lepidoptera: Danaini).

PubMed

Petschenka, Georg; Fandrich, Steffi; Sander, Nils; Wagschal, Vera; Boppré, Michael; Dobler, Susanne

2013-09-01

Despite the monarch butterfly (Danaus plexippus) being famous for its adaptations to the defensive traits of its milkweed host plants, little is known about the macroevolution of these traits. Unlike most other animal species, monarchs are largely insensitive to cardenolides, because their target site, the sodium pump (Na(+)/K(+) -ATPase), has evolved amino acid substitutions that reduce cardenolide binding (so-called target site insensitivity, TSI). Because many, but not all, species of milkweed butterflies (Danaini) are associated with cardenolide-containing host plants, we analyzed 16 species, representing all phylogenetic lineages of milkweed butterflies, for the occurrence of TSI by sequence analyses of the Na(+)/K(+) -ATPase gene and by enzymatic assays with extracted Na(+)/K(+) -ATPase. Here we report that sensitivity to cardenolides was reduced in a stepwise manner during the macroevolution of milkweed butterflies. Strikingly, not all Danaini typically consuming cardenolides showed TSI, but rather TSI was more strongly associated with sequestration of toxic cardenolides. Thus, the interplay between bottom-up selection by plant compounds and top-down selection by natural enemies can explain the evolutionary sequence of adaptations to these toxins. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Flexible RF filter using a nonuniform SCISSOR.

PubMed

Zhuang, Leimeng

2016-03-15

This work presents a flexible radiofrequency (RF) filter using an integrated microwave photonic circuit that comprises a nonuniform side-coupled integrated spaced sequence of resonators (N-SCISSOR). The filter passband can be reconfigured by varying the N-SCISSOR parameters. When employing a dual-parallel Mach-Zechnder modulator, the filter is also able to perform frequency down-conversion. In the experiment, various filter response shapes are shown, ranging from a flat-top band-pass filter to a total opposite high-rejection (>40  dB) notch filter, with a frequency coverage of greater than two octaves. The frequency down-conversion function is also demonstrated.

Frontal top-down signals increase coupling of auditory low-frequency oscillations to continuous speech in human listeners.

PubMed

Park, Hyojin; Ince, Robin A A; Schyns, Philippe G; Thut, Gregor; Gross, Joachim

2015-06-15

Humans show a remarkable ability to understand continuous speech even under adverse listening conditions. This ability critically relies on dynamically updated predictions of incoming sensory information, but exactly how top-down predictions improve speech processing is still unclear. Brain oscillations are a likely mechanism for these top-down predictions [1, 2]. Quasi-rhythmic components in speech are known to entrain low-frequency oscillations in auditory areas [3, 4], and this entrainment increases with intelligibility [5]. We hypothesize that top-down signals from frontal brain areas causally modulate the phase of brain oscillations in auditory cortex. We use magnetoencephalography (MEG) to monitor brain oscillations in 22 participants during continuous speech perception. We characterize prominent spectral components of speech-brain coupling in auditory cortex and use causal connectivity analysis (transfer entropy) to identify the top-down signals driving this coupling more strongly during intelligible speech than during unintelligible speech. We report three main findings. First, frontal and motor cortices significantly modulate the phase of speech-coupled low-frequency oscillations in auditory cortex, and this effect depends on intelligibility of speech. Second, top-down signals are significantly stronger for left auditory cortex than for right auditory cortex. Third, speech-auditory cortex coupling is enhanced as a function of stronger top-down signals. Together, our results suggest that low-frequency brain oscillations play a role in implementing predictive top-down control during continuous speech perception and that top-down control is largely directed at left auditory cortex. This suggests a close relationship between (left-lateralized) speech production areas and the implementation of top-down control in continuous speech perception. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Frontal Top-Down Signals Increase Coupling of Auditory Low-Frequency Oscillations to Continuous Speech in Human Listeners

PubMed Central

Park, Hyojin; Ince, Robin A.A.; Schyns, Philippe G.; Thut, Gregor; Gross, Joachim

2015-01-01

Summary Humans show a remarkable ability to understand continuous speech even under adverse listening conditions. This ability critically relies on dynamically updated predictions of incoming sensory information, but exactly how top-down predictions improve speech processing is still unclear. Brain oscillations are a likely mechanism for these top-down predictions [1, 2]. Quasi-rhythmic components in speech are known to entrain low-frequency oscillations in auditory areas [3, 4], and this entrainment increases with intelligibility [5]. We hypothesize that top-down signals from frontal brain areas causally modulate the phase of brain oscillations in auditory cortex. We use magnetoencephalography (MEG) to monitor brain oscillations in 22 participants during continuous speech perception. We characterize prominent spectral components of speech-brain coupling in auditory cortex and use causal connectivity analysis (transfer entropy) to identify the top-down signals driving this coupling more strongly during intelligible speech than during unintelligible speech. We report three main findings. First, frontal and motor cortices significantly modulate the phase of speech-coupled low-frequency oscillations in auditory cortex, and this effect depends on intelligibility of speech. Second, top-down signals are significantly stronger for left auditory cortex than for right auditory cortex. Third, speech-auditory cortex coupling is enhanced as a function of stronger top-down signals. Together, our results suggest that low-frequency brain oscillations play a role in implementing predictive top-down control during continuous speech perception and that top-down control is largely directed at left auditory cortex. This suggests a close relationship between (left-lateralized) speech production areas and the implementation of top-down control in continuous speech perception. PMID:26028433

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

PubMed Central

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

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

PubMed

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.

Cognitive Control of Auditory Distraction: Impact of Task Difficulty, Foreknowledge, and Working Memory Capacity Supports Duplex-Mechanism Account

ERIC Educational Resources Information Center

Hughes, Robert W.; Hurlstone, Mark J.; Marsh, John E.; Vachon, Francois; Jones, Dylan M.

2013-01-01

The influence of top-down cognitive control on 2 putatively distinct forms of distraction was investigated. Attentional capture by a task-irrelevant auditory deviation (e.g., a female-spoken token following a sequence of male-spoken tokens)--as indexed by its disruption of a visually presented recall task--was abolished when focal-task engagement…

Addressing the Language Needs of Administrative Staff in Taiwan's Internationalised Higher Education: Call for an English as a Lingua Franca Curriculum to Increase Communicative Competence and Willingness to Communicate

ERIC Educational Resources Information Center

Reynolds, Barry Lee; Yu, Melissa H.

2018-01-01

Internationalisation policies introducing English as a lingua franca (ELF) have been initiated by the Taiwan Ministry of Education and executed from a top-down level without taking into consideration the competence and needs of administrative staff. This article begins by describing the ideology of ELF within the macro context of Taiwanese…

Spaceborne lidar for cloud monitoring

NASA Astrophysics Data System (ADS)

Werner, Christian; Krichbaumer, W.; Matvienko, Gennadii G.

1994-12-01

Results of laser cloud top measurements taken from space in 1982 (called PANTHER) are presented. Three sequences of land, water, and cloud data are selected. A comparison with airborne lidar data shows similarities. Using the single scattering lidar equation for these spaceborne lidar measurements one can misinterpret the data if one doesn't correct for multiple scattering.

The interactions of multisensory integration with endogenous and exogenous attention

PubMed Central

Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

2016-01-01

Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. PMID:26546734

Emotional metacontrol of attention: Top-down modulation of sensorimotor processes in a robotic visual search task

PubMed Central

Cuperlier, Nicolas; Gaussier, Philippe

2017-01-01

Emotions play a significant role in internal regulatory processes. In this paper, we advocate four key ideas. First, novelty detection can be grounded in the sensorimotor experience and allow higher order appraisal. Second, cognitive processes, such as those involved in self-assessment, influence emotional states by eliciting affects like boredom and frustration. Third, emotional processes such as those triggered by self-assessment influence attentional processes. Last, close emotion-cognition interactions implement an efficient feedback loop for the purpose of top-down behavior regulation. The latter is what we call ‘Emotional Metacontrol’. We introduce a model based on artificial neural networks. This architecture is used to control a robotic system in a visual search task. The emotional metacontrol intervenes to bias the robot visual attention during active object recognition. Through a behavioral and statistical analysis, we show that this mechanism increases the robot performance and fosters the exploratory behavior to avoid deadlocks. PMID:28934291

The interactions of multisensory integration with endogenous and exogenous attention.

PubMed

Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

2016-02-01

Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

N-Terminal Amino Acid Sequence Determination of Proteins by N-Terminal Dimethyl Labeling: Pitfalls and Advantages When Compared with Edman Degradation Sequence Analysis.

PubMed

Chang, Elizabeth; Pourmal, Sergei; Zhou, Chun; Kumar, Rupesh; Teplova, Marianna; Pavletich, Nikola P; Marians, Kenneth J; Erdjument-Bromage, Hediye

2016-07-01

In recent history, alternative approaches to Edman sequencing have been investigated, and to this end, the Association of Biomolecular Resource Facilities (ABRF) Protein Sequencing Research Group (PSRG) initiated studies in 2014 and 2015, looking into bottom-up and top-down N-terminal (Nt) dimethyl derivatization of standard quantities of intact proteins with the aim to determine Nt sequence information. We have expanded this initiative and used low picomole amounts of myoglobin to determine the efficiency of Nt-dimethylation. Application of this approach on protein domains, generated by limited proteolysis of overexpressed proteins, confirms that it is a universal labeling technique and is very sensitive when compared with Edman sequencing. Finally, we compared Edman sequencing and Nt-dimethylation of the same polypeptide fragments; results confirm that there is agreement in the identity of the Nt amino acid sequence between these 2 methods.

Comprehensive Analysis of Tropomyosin Isoforms in Skeletal Muscles by Top-down Proteomics

PubMed Central

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

2016-01-01

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. PMID:27090236

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

PubMed

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.

Purification and high-resolution top-down mass spectrometric characterization of human salivary α-amylase.

PubMed

Peng, Ying; Chen, Xin; Sato, Takuya; Rankin, Scott A; Tsuji, Ryohei F; Ge, Ying

2012-04-03

Human salivary α-amylase (HSAMY) is a major component of salivary secretions, possessing multiple important biological functions. Here we have established three methods to purify HSAMY in human saliva for comprehensive characterization of HSAMY by high-resolution top-down mass spectrometry (MS). Among the three purification methods, the affinity method based on the enzyme-substrate specific interaction between amylase and glycogen is preferred, providing the highest purity HSAMY with high reproducibility. Subsequently, we employed Fourier transform ion cyclotron resonance MS to analyze the purified HSAMY. The predominant form of α-amylase purified from saliva of various races and genders is nonglycosylated with the same molecular weight of 55,881.2, which is 1885.8 lower than the calculated value based on the DNA-predicted sequence. High-resolution MS revealed the truncation of the first 15 N-terminal amino acids (-1858.96) and the subsequent formation of pyroglutamic acid at the new N-terminus Gln (-17.03). More importantly, five disulfide bonds in HSAMY were identified (-10.08) and effectively localized by tandem MS in conjunction with complete and partial reduction by tris (2-carboxyethyl) phosphine. Overall, this study demonstrates that top-down MS combined with affinity purification and partial reduction is a powerful method for rapid purification and complete characterization of large proteins with complex and overlapping disulfide bond patterns.

Increasing zooplankton size diversity enhances the strength of top-down control on phytoplankton through diet niche partitioning.

PubMed

Ye, Lin; Chang, Chun-Yi; García-Comas, Carmen; Gong, Gwo-Ching; Hsieh, Chih-Hao

2013-09-01

1. The biodiversity-ecosystem functioning debate is a central topic in ecology. Recently, there has been a growing interest in size diversity because body size is sensitive to environmental changes and is one of the fundamental characteristics of organisms linking many ecosystem properties. However, how size diversity affects ecosystem functioning is an important yet unclear issue. 2. To fill the gap, with large-scale field data from the East China Sea, we tested the novel hypothesis that increasing zooplankton size diversity enhances top-down control on phytoplankton (H1) and compared it with five conventional hypotheses explaining the top-down control: flatter zooplankton size spectrum enhances the strength of top-down control (H2); nutrient enrichment lessens the strength of top-down control (H3); increasing zooplankton taxonomic diversity enhances the strength of top-down control (H4); increasing fish predation decreases the strength of top-down control of zooplankton on phytoplankton through trophic cascade (H5); increasing temperature intensifies the strength of top-down control (H6). 3. The results of univariate analyses support the hypotheses based on zooplankton size diversity (H1), zooplankton size spectrum (H2), nutrient (H3) and zooplankton taxonomic diversity (H4), but not the hypotheses based on fish predation (H5) and temperature (H6). More in-depth analyses indicate that zooplankton size diversity is the most important factor in determining the strength of top-down control on phytoplankton in the East China Sea. 4. Our results suggest a new potential mechanism that increasing predator size diversity enhances the strength of top-down control on prey through diet niche partitioning. This mechanism can be explained by the optimal predator-prey body-mass ratio concept. Suppose each size group of zooplankton predators has its own optimal phytoplankton prey size, increasing size diversity of zooplankton would promote diet niche partitioning of predators and thus elevates the strength of top-down control. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

In-depth comparison of somatic point mutation callers based on different tumor next-generation sequencing depth data

NASA Astrophysics Data System (ADS)

Cai, Lei; Yuan, Wei; Zhang, Zhou; He, Lin; Chou, Kuo-Chen

2016-11-01

Four popular somatic single nucleotide variant (SNV) calling methods (Varscan, SomaticSniper, Strelka and MuTect2) were carefully evaluated on the real whole exome sequencing (WES, depth of ~50X) and ultra-deep targeted sequencing (UDT-Seq, depth of ~370X) data. The four tools returned poor consensus on candidates (only 20% of calls were with multiple hits by the callers). For both WES and UDT-Seq, MuTect2 and Strelka obtained the largest proportion of COSMIC entries as well as the lowest rate of dbSNP presence and high-alternative-alleles-in-control calls, demonstrating their superior sensitivity and accuracy. Combining different callers does increase reliability of candidates, but narrows the list down to very limited range of tumor read depth and variant allele frequency. Calling SNV on UDT-Seq data, which were of much higher read-depth, discovered additional true-positive variations, despite an even more tremendous growth in false positive predictions. Our findings not only provide valuable benchmark for state-of-the-art SNV calling methods, but also shed light on the access to more accurate SNV identification in the future.

RNAbrowse: RNA-Seq de novo assembly results browser.

PubMed

Mariette, Jérôme; Noirot, Céline; Nabihoudine, Ibounyamine; Bardou, Philippe; Hoede, Claire; Djari, Anis; Cabau, Cédric; Klopp, Christophe

2014-01-01

Transcriptome analysis based on a de novo assembly of next generation RNA sequences is now performed routinely in many laboratories. The generated results, including contig sequences, quantification figures, functional annotations and variation discovery outputs are usually bulky and quite diverse. This article presents a user oriented storage and visualisation environment permitting to explore the data in a top-down manner, going from general graphical views to all possible details. The software package is based on biomart, easy to install and populate with local data. The software package is available under the GNU General Public License (GPL) at http://bioinfo.genotoul.fr/RNAbrowse.

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

PubMed

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.

Neural mechanisms mediating contingent capture of attention by affective stimuli

PubMed Central

Reeck, Crystal; LaBar, Kevin S.; Egner, Tobias

2013-01-01

Attention is attracted exogenously by physically salient stimuli, but this effect can be dampened by endogenous attention settings, a phenomenon called “contingent capture”. Emotionally salient stimuli are also thought to exert a strong exogenous influence on attention, especially in anxious individuals, but whether and how top-down attention can ameliorate bottom-up capture by affective stimuli is currently unknown. Here, we paired a novel spatial cueing task with functional magnetic resonance imaging (fMRI) in order to investigate contingent capture as a function of the affective salience of bottom-up cues (face stimuli) and individual differences in trait anxiety. In the absence of top-down cues, exogenous stimuli validly cueing targets facilitated attention in low anxious participants, regardless of affective salience. However, while high anxious participants exhibited similar facilitation following neutral exogenous cues, this facilitation was completely absent following affectively negative exogenous cues. Critically, these effects were contingent on endogenous attentional settings, such that explicit top-down cues presented prior to the appearance of exogenous stimuli removed anxious individuals’ sensitivity to affectively salient stimuli. FMRI analyses revealed a network of brain regions underlying this variability in affective contingent capture across individuals, including the fusiform face area (FFA), posterior ventrolateral frontal cortex, and supplementary motor area. Importantly, activation in the posterior ventrolateral frontal cortex and the supplementary motor area fully mediated the effects observed in FFA, demonstrating a critical role for these frontal regions in mediating attentional orienting and interference resolution processes when engaged by affectively salient stimuli. PMID:22360642

Top-down and bottom-up neurodynamic evidence in patients with tinnitus.

PubMed

Hong, Sung Kwang; Park, Sejik; Ahn, Min-Hee; Min, Byoung-Kyong

2016-12-01

Although a peripheral auditory (bottom-up) deficit is an essential prerequisite for the generation of tinnitus, central cognitive (top-down) impairment has also been shown to be an inherent neuropathological mechanism. Using an auditory oddball paradigm (for top-down analyses) and a passive listening paradigm (for bottom-up analyses) while recording electroencephalograms (EEGs), we investigated whether top-down or bottom-up components were more critical in the neuropathology of tinnitus, independent of peripheral hearing loss. We observed significantly reduced P300 amplitudes (reflecting fundamental cognitive processes such as attention) and evoked theta power (reflecting top-down regulation in memory systems) for target stimuli at the tinnitus frequency of patients with tinnitus but without hearing loss. The contingent negative variation (reflecting top-down expectation of a subsequent event prior to stimulation) and N100 (reflecting auditory bottom-up selective attention) were different between the healthy and patient groups. Interestingly, when tinnitus patients were divided into two subgroups based on their P300 amplitudes, their P170 and N200 components, and annoyance and distress indices to their tinnitus sound were different. EEG theta-band power and its Granger causal neurodynamic results consistently support a double dissociation of these two groups in both top-down and bottom-up tasks. Directed cortical connectivity corroborates that the tinnitus network involves the anterior cingulate and the parahippocampal areas, where higher-order top-down control is generated. Together, our observations provide neurophysiological and neurodynamic evidence revealing a differential engagement of top-down impairment along with deficits in bottom-up processing in patients with tinnitus but without hearing loss. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Intact and Top-Down Characterization of Biomolecules and Direct Analysis Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Coupled to FT-ICR Mass Spectrometry

PubMed Central

Sampson, Jason S.; Murray, Kermit K.; Muddiman, David C.

2013-01-01

We report the implementation of an infrared laser onto our previously reported matrix-assisted laser desorption electrospray ionization (MALDESI) source with ESI post-ionization yielding multiply charged peptides and proteins. Infrared (IR)-MALDESI is demonstrated for atmospheric pressure desorption and ionization of biological molecules ranging in molecular weight from 1.2 to 17 kDa. High resolving power, high mass accuracy single-acquisition Fourier transform ion cyclotron resonance (FT-ICR) mass spectra were generated from liquid-and solid-state peptide and protein samples by desorption with an infrared laser (2.94 µm) followed by ESI post-ionization. Intact and top-down analysis of equine myoglobin (17 kDa) desorbed from the solid state with ESI post-ionization demonstrates the sequencing capabilities using IR-MALDESI coupled to FT-ICR mass spectrometry. Carbohydrates and lipids were detected through direct analysis of milk and egg yolk using both UV- and IR-MALDESI with minimal sample preparation. Three of the four classes of biological macromolecules (proteins, carbohydrates, and lipids) have been ionized and detected using MALDESI with minimal sample preparation. Sequencing of O-linked glycans, cleaved from mucin using reductive β-elimination chemistry, is also demonstrated. PMID:19185512

Building peace education in the Islamic educational context

NASA Astrophysics Data System (ADS)

Abu-Nimer, Mohammed; Nasser, Ilham

2017-04-01

Following the events of 9/11, many misconceptions entered the policy-making platform with regard to the need for education reforms in the Muslim world. Based upon Western cultural and societal norms and increased scepticism of the role of religion in violence, these assumptions have triggered a strong wave of calls for a top-down approach to reform formal state schools in predominantly Muslim countries, These calls often meet with resistance at national and community levels. This article seeks to examine these misconceptions and investigate why educational reform efforts through top-down frameworks which are especially motivated by countering violent extremism or terrorism have had only limited success. Many major international intergovernmental organisations, non-governmental organisations and governments have invested time and effort into education measures aiming to build peace and coexistence in Muslim countries, but they have been unable to build a relationship of trust with community leaders and school authorities. The authors argue that the main reason for defiance is reformers' failure to closely examine the cultural context of their chosen setting and work with existing tools and local institutions. Illustrating their point with a case study of an intervention carried out in informal Qur'anic schools in Niger, West Africa, the authors offer an alternative method which fosters changes from within. They argue that this model has a better chance of sustainability and could thus be used as the basis for future interventions.

Consciousness, brain, neuroplasticity

PubMed Central

Askenasy, Jean; Lehmann, Joseph

2013-01-01

Subjectivity, intentionality, self-awareness and will are major components of consciousness in human beings. Changes in consciousness and its content following different brain processes and malfunction have long been studied. Cognitive sciences assume that brain activities have an infrastructure, but there is also evidence that consciousness itself may change this infrastructure. The two-way influence between brain and consciousness has been at the center of philosophy and less so, of science. This so-called bottom-up and top-down interrelationship is controversial and is the subject of our article. We would like to ask: how does it happen that consciousness may provoke structural changes in the brain? The living brain means continuous changes at the synaptic level with every new experience, with every new process of learning, memorizing or mastering new and existing skills. Synapses are generated and dissolved, while others are preserved, in an ever-changing process of so-called neuroplasticity. Ongoing processes of synaptic reinforcements and decay occur during wakefulness when consciousness is present, but also during sleep when it is mostly absent. We suggest that consciousness influences brain neuroplasticity both during wakefulness as well as sleep in a top-down way. This means that consciousness really activates synaptic flow and changes brain structures and functional organization. The dynamic impact of consciousness on brain never stops despite the relative stationary structure of the brain. Such a process can be a target for medical intervention, e.g., by cognitive training. PMID:23847580

Surface infrastructure functions, requirements and subsystems for a manned Mars mission

NASA Technical Reports Server (NTRS)

Fairchild, Kyle

1986-01-01

Planning and development for a permanently manned scientific outpost on Mars requires an in-depth understanding and analysis of the functions the outpost is expected to perform. The optimum configuration that accomplishes these functions then arises during the trade studies process. In a project this complex, it becomes necessary to use a formal methodology to document the design and planning process. The method chosen for this study is called top-down functional decomposition. This method is used to determine the functions that are needed to accomplish the overall mission, then determine what requirements and systems are needed to do each of the functions. This method facilitates automation of the trades and options process. In the example, this was done with an off-the shelf software package called TK! olver. The basic functions that a permanently manned outpost on Mars must accomplish are: (1) Establish the Life Critical Systems; (2) Support Planetary Sciences and Exploration; and (3) Develop and Maintain Long-term Support Functions, including those systems needed towards self-sufficiency. The top-down functional decomposition methology, combined with standard spread sheet software, offers a powerful tool to quickly assess various design trades and analyze options. As the specific subsystems, and the relational rule algorithms are further refined, it will be possible to very accurately determine the implications of continually evolving mission requirements.

Voluntary task switching under load: contribution of top-down and bottom-up factors in goal-directed behavior.

PubMed

Demanet, Jelle; Verbruggen, Frederick; Liefooghe, Baptist; Vandierendonck, André

2010-06-01

The present study investigated the relative contribution of bottom-up and top-down control to task selection in the voluntary task-switching (VTS) procedure. In order to manipulate the efficiency of top-down control, a concurrent working memory load was imposed during VTS. In three experiments, bottom-up factors, such as stimulus repetitions, repetition of irrelevant information, and stimulus-task associations, were introduced in order to investigate their influence on task selection. We observed that the tendency to repeat tasks was stronger under load, suggesting that top-down control counteracts the automatic tendency to repeat tasks. The results also indicated that task selection can be guided by several elements in the environment, but that only the influence of stimulus repetitions depends on the efficiency of top-down control. The theoretical implications of these findings are discussed within the interplay between top-down and bottom-up control that underlies the voluntary selection of tasks.

Turning up the heat: temperature influences the relative importance of top-down and bottom-up effects.

PubMed

Hoekman, David

2010-10-01

Understanding how communities respond to changes in temperature is a major challenge for community ecology. Temperature influences the relative degree to which top-down and bottom-up forces structure ecological communities. In greenhouse experiments using the aquatic community found in pitcher plants (Sarracenia purpurea), I tested how temperature affected the relative importance of top-down (mosquito predation) and bottom-up (ant carcasses) forces on protozoa and bacteria populations. While bottom-up effects did not vary consistently with temperature, the top-down effects of predators on protozoa increased at higher temperatures. These results suggest that temperature could change the relative importance of top-down and bottom-up effects in ecological communities. Specifically, higher temperature may increase the strength of top-down effects by raising predator metabolic rate and concomitant processes (e.g., activity, foraging, digestion, growth) relative to cooler temperatures. These findings apply broadly to an understanding of trophic interactions in a variable environment and are especially relevant in the context of ongoing climate change.

Protein Identification Using Top-Down Spectra*

PubMed Central

Liu, Xiaowen; Sirotkin, Yakov; Shen, Yufeng; Anderson, Gordon; Tsai, Yihsuan S.; Ting, Ying S.; Goodlett, David R.; Smith, Richard D.; Bafna, Vineet; Pevzner, Pavel A.

2012-01-01

In the last two years, because of advances in protein separation and mass spectrometry, top-down mass spectrometry moved from analyzing single proteins to analyzing complex samples and identifying hundreds and even thousands of proteins. However, computational tools for database search of top-down spectra against protein databases are still in their infancy. We describe MS-Align+, a fast algorithm for top-down protein identification based on spectral alignment that enables searches for unexpected post-translational modifications. We also propose a method for evaluating statistical significance of top-down protein identifications and further benchmark various software tools on two top-down data sets from Saccharomyces cerevisiae and Salmonella typhimurium. We demonstrate that MS-Align+ significantly increases the number of identified spectra as compared with MASCOT and OMSSA on both data sets. Although MS-Align+ and ProSightPC have similar performance on the Salmonella typhimurium data set, MS-Align+ outperforms ProSightPC on the (more complex) Saccharomyces cerevisiae data set. PMID:22027200

Top-down causation and social structures

PubMed Central

Elder-Vass, Dave

2012-01-01

Top-down causation has been implicit in many sociological accounts of social structure and its influence on social events, but the social sciences have struggled to provide a coherent account of top-down causation itself. This paper summarizes a critical realist view of causation and emergence, shows how it supports a plausible account of top-down causation and then applies this account to the social world. The argument is illustrated by an examination of the concept of a norm circle, a kind of social entity that, it is argued, is causally responsible for the influence of normative social institutions. Nevertheless, social entities are structured rather differently from ordinary material ones, with the result that the compositional level structure of reality implicit in the concept of top-down causation has some limitations in the social world. The paper closes by considering what might be involved in examining how top-down causation can be shown to be at work in the social domain. PMID:23386963

Transgenic Bt Cotton Does Not Disrupt the Top-Down Forces Regulating the Cotton Aphid in Central China

PubMed Central

Yao, Yong-Sheng; Han, Peng; Niu, Chang-Ying; Dong, Yong-Cheng; Gao, Xi-Wu; Cui, Jin-Jie; Desneux, Nicolas

2016-01-01

Top-down force is referred to arthropod pest management delivered by the organisms from higher trophic levels. In the context of prevalent adoption of transgenic Bt crops that produce insecticidal Cry proteins derived from Bacillus thuringiensis (Bt), it still remains elusive whether the top-down forces are affected by the insect-resistant traits that introduced into the Bt crops. We explored how Bt cotton affect the strength of top-down forces via arthropod natural enemies in regulating a non-target pest species, the cotton aphid Aphis gossypii Glover, using a comparative approach (i.e. Bt cotton vs. conventional cotton) under field conditions. To determine top-down forces, we manipulated predation/parasitism exposure of the aphid to their natural enemies using exclusion cages. We found that the aphid population growth was strongly suppressed by the dominant natural enemies including Coccinellids, spiders and Aphidiines parasitoids. Coccinellids, spiders and the assemblage of other arthropod natural enemies (mainly lacewings and Hemipteran bugs) are similarly abundant in both plots, but with the parasitoid mummies less abundant in Bt cotton plots compared to the conventional cotton plots. However, the lower abundance of parasitoids in Bt cotton plots alone did not translate into differential top-down control on A. gossypii populations compared to conventional ones. Overall, the top-down forces were equally strong in both plots. We conclude that transgenic Bt cotton does not disrupt the top-down forces regulating the cotton aphid in central China. PMID:27870914

SeqMule: automated pipeline for analysis of human exome/genome sequencing data.

PubMed

Guo, Yunfei; Ding, Xiaolei; Shen, Yufeng; Lyon, Gholson J; Wang, Kai

2015-09-18

Next-generation sequencing (NGS) technology has greatly helped us identify disease-contributory variants for Mendelian diseases. However, users are often faced with issues such as software compatibility, complicated configuration, and no access to high-performance computing facility. Discrepancies exist among aligners and variant callers. We developed a computational pipeline, SeqMule, to perform automated variant calling from NGS data on human genomes and exomes. SeqMule integrates computational-cluster-free parallelization capability built on top of the variant callers, and facilitates normalization/intersection of variant calls to generate consensus set with high confidence. SeqMule integrates 5 alignment tools, 5 variant calling algorithms and accepts various combinations all by one-line command, therefore allowing highly flexible yet fully automated variant calling. In a modern machine (2 Intel Xeon X5650 CPUs, 48 GB memory), when fast turn-around is needed, SeqMule generates annotated VCF files in a day from a 30X whole-genome sequencing data set; when more accurate calling is needed, SeqMule generates consensus call set that improves over single callers, as measured by both Mendelian error rate and consistency. SeqMule supports Sun Grid Engine for parallel processing, offers turn-key solution for deployment on Amazon Web Services, allows quality check, Mendelian error check, consistency evaluation, HTML-based reports. SeqMule is available at http://seqmule.openbioinformatics.org.

Top-down effects of a terrestrial frog on forest nutrient dynamics.

Treesearch

Karen H. Beard; Kristiina A. Vogt; Andrew Kulmatiski

2002-01-01

Many studies have found top-down effects of predators on prey, but few studies have linked top-down effects of vertebrate predators to nutrient cycling rates in terrestrial systems. In this study, large and significant effects of a terrestrial frog, Eleutherodactylus coqui (coqu

Optical body fat measurement might contribute to the search for a predictor of type-2 diabetes mellitus

NASA Astrophysics Data System (ADS)

Tafeit, Erwin; Horejsi, Renate; Sudi, Karl; Berg, Aloys; Reibnegger, Gilbert; Moeller, Reinhard

2001-10-01

The optical device LIPOMETER allows for non-invasive, quick, precise and safe determination of subcutaneous fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). Previously we showed how the high-dimensional SAT-Top information of women with type-2 diabetes mellitus (NIDDM) and a health control group can be analysed and represented in low-dimensional plots by applying special artificial neural networks (ANNs). Three top-down sorted subcutaneous adipose tissue compartments were determined (upper trunk, lower trunk, legs). NIDDM women provided significantly higher upper trunk obesity and significantly lower leg obesity (apple type), as compared with their healthy control group. Now we apply those ANN results on SAT-Top measurements of young and healthy women, comparing their individual subcutaneous fat pattern to the body fat distribution of NIDDM women and to the normal fat development of healthy women. Some of these young and healthy women provide a subcutaneous fat distribution very similar to the SAT-Top results of NIDDM women, which might increase their risk for this disease later in life.

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

PubMed

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.

Development of a Shallow Decollement Along the South-Central Chile Margin from 2D Seismic Reflection Data

NASA Astrophysics Data System (ADS)

Olsen, K.; Bangs, N. L.; Arnulf, A. F.; Trehu, A. M.; Contreras Reyes, E.

2017-12-01

In January and February, 2017, we acquired approximately 5,000 km of deep-penetrating 2D seismic reflection data along the Chile trench between 30° - 44°S as a part of the 2017 Crustal Examination from Valdivia to Illapel to Characterize Huge Earthquakes (CEVICHE) project, on the R/V Langseth. We used a 6,600 in3 airgun source to shoot every 50 m and recorded shots on a 15,100 m, 1212 channel streamer. This survey targeted the structure of this subduction zone across the slip regions of the 2015 Illapel (Mw 8.3), the 2010 Maule (Mw 8.8), and 1960 Valdivia (Mw 9.5) earthquakes. Two dip lines between 37.5°S and 39°S, within the overlapping slip areas of the Maule and Valdivia earthquakes, show a range in the style of initial thrust faulting at the deformation front. At 37.5°S, just south of the Arauco Peninsula, protothrusts at the deformation front are typical of many well-sedimented trench sections in subduction zones worldwide. Here we observe incipient landward-dipping thrusts consisting of 15 faults with typical horizontal spacing of 750 m that can be seen to extend down through the entire 2.5 km thick sediment sequence to the top of the subducting ocean crust. Some form conjugate fault pairs, but all have small offsets of 10-50 m. These thrusts appear to sole into a proto-decollement located just above the top of the ocean crust; however, farther landward beneath the lower slope, a thick, 2.5 km, sequence of layered sediment can be traced > 20 km into the subduction zone. The position of the primary decollement appears to be located near the top of the trench sediment sequence, well above the proto-decollement, allowing subduction of the entire trench sequence. A second line at 39°S across the deformation front shows no frontal thrusts or apparent deformation within the 1.5 km thick section of trench sediment. All of the incoming sediment appears to be subducting beneath a stable decollement that we can image near the top of the trench sediment sequence. The decollement along the northern line may be currently stepping down and transitioning from minimal accretion, typical of this segment of the Chile margin, to accretion of the entire trench section. Alternatively, the initial deformation at the toe may cease and allow slip to shift upward to the shallow decollement and continue to subduct the entire trench sediment section.

Back from the future: Volitional postdiction of perceived apparent motion direction.

PubMed

Sun, Liwei; Frank, Sebastian M; Hartstein, Kevin C; Hassan, Wassim; Tse, Peter U

2017-11-01

Among physical events, it is impossible that an event could alter its own past for the simple reason that past events precede future events, and not vice versa. Moreover, to do so would invoke impossible self-causation. However, mental events are constructed by physical neuronal processes that take a finite duration to execute. Given this fact, it is conceivable that later brain events could alter the ongoing interpretation of previous brain events if they arrive within this finite duration of interpretive processing, before a commitment is made to what happened. In the current study, we show that humans can volitionally influence how they perceive an ambiguous apparent motion sequence, as long as the top-down command occurs up to 300ms after the occurrence of the actual motion event in the world. This finding supports the view that there is a temporal integration period over which perception is constructed on the basis of both bottom-up and top-down inputs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Suppressive and enhancing effects in early visual cortex during illusory shape perception: A comment on.

PubMed

Moors, Pieter

2015-01-01

In a recent functional magnetic resonance imaging study, Kok and de Lange (2014) observed that BOLD activity for a Kanizsa illusory shape stimulus, in which pacmen-like inducers elicit an illusory shape percept, was either enhanced or suppressed relative to a nonillusory control configuration depending on whether the spatial profile of BOLD activity in early visual cortex was related to the illusory shape or the inducers, respectively. The authors argued that these findings fit well with the predictive coding framework, because top-down predictions related to the illusory shape are not met with bottom-up sensory input and hence the feedforward error signal is enhanced. Conversely, for the inducing elements, there is a match between top-down predictions and input, leading to a decrease in error. Rather than invoking predictive coding as the explanatory framework, the suppressive effect related to the inducers might be caused by neural adaptation to perceptually stable input due to the trial sequence used in the experiment.

Direct evaluation of fault trees using object-oriented programming techniques

NASA Technical Reports Server (NTRS)

Patterson-Hine, F. A.; Koen, B. V.

1989-01-01

Object-oriented programming techniques are used in an algorithm for the direct evaluation of fault trees. The algorithm combines a simple bottom-up procedure for trees without repeated events with a top-down recursive procedure for trees with repeated events. The object-oriented approach results in a dynamic modularization of the tree at each step in the reduction process. The algorithm reduces the number of recursive calls required to solve trees with repeated events and calculates intermediate results as well as the solution of the top event. The intermediate results can be reused if part of the tree is modified. An example is presented in which the results of the algorithm implemented with conventional techniques are compared to those of the object-oriented approach.

Functional overlap of top-down emotion regulation and generation: an fMRI study identifying common neural substrates between cognitive reappraisal and cognitively generated emotions.

PubMed

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.

A Top-Down Approach to Designing the Computerized Adaptive Multistage Test

ERIC Educational Resources Information Center

Luo, Xiao; Kim, Doyoung

2018-01-01

The top-down approach to designing a multistage test is relatively understudied in the literature and underused in research and practice. This study introduced a route-based top-down design approach that directly sets design parameters at the test level and utilizes the advanced automated test assembly algorithm seeking global optimality. The…

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

ERIC Educational Resources Information Center

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…

Alternate Perspectives on Concept Internalization: Learning Top Down Vs. Learning Bottom Up.

ERIC Educational Resources Information Center

Pines, A. Leon

This paper outlines two alternate ways in which concepts are acquired, known as "top down" and "bottom up". "Bottom up" refers to learning the members of a category and then extracting their similarities or differences, the rule or criterial attributes used to make the categorization. In the "top down"…

Bottom-up and top-down influences at untrained conditions determine perceptual learning specificity and transfer

PubMed Central

Xiong, Ying-Zi; Zhang, Jun-Yun; Yu, Cong

2016-01-01

Perceptual learning is often orientation and location specific, which may indicate neuronal plasticity in early visual areas. However, learning specificity diminishes with additional exposure of the transfer orientation or location via irrelevant tasks, suggesting that the specificity is related to untrained conditions, likely because neurons representing untrained conditions are neither bottom-up stimulated nor top-down attended during training. To demonstrate these top-down and bottom-up contributions, we applied a “continuous flash suppression” technique to suppress the exposure stimulus into sub-consciousness, and with additional manipulations to achieve pure bottom-up stimulation or top-down attention with the transfer condition. We found that either bottom-up or top-down influences enabled significant transfer of orientation and Vernier discrimination learning. These results suggest that learning specificity may result from under-activations of untrained visual neurons due to insufficient bottom-up stimulation and/or top-down attention during training. High-level perceptual learning thus may not functionally connect to these neurons for learning transfer. DOI: http://dx.doi.org/10.7554/eLife.14614.001 PMID:27377357

ProForma: A Standard Proteoform Notation

DOE Office of Scientific and Technical Information (OSTI.GOV)

LeDuc, Richard D.; Schwämmle, Veit; Shortreed, Michael R.

The Consortium for Top-Down Proteomics (CTDP) proposes a standardized notation, ProForma, for writing the sequence of fully characterized proteoforms. ProForma provides a means to communicate any proteoform by writing the amino acid sequence using standard one-letter notation and specifying modifications or unidentified mass shifts within brackets following certain amino acids. The notation is unambiguous, human readable, and can easily be parsed and written by bioinformatic tools. This system uses seven rules and supports a wide range of possible use cases, ensuring compatibility and reproducibility of proteoform annotations. Standardizing proteoform sequences will simplify storage, comparison, and reanalysis of proteomic studies, andmore » the Consortium welcomes input and contributions from the research community on the continued design and maintenance of this standard.« less

Top-Down Modulation of Auditory-Motor Integration during Speech Production: The Role of Working Memory.

PubMed

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 provides two lines of converging evidence, for the first time, that working memory cannot only enhance the perception of vocal feedback errors but also exert inhibitory control over vocal motor behavior. These findings represent a major advance in our understanding of the top-down modulatory mechanisms that support the detection and correction of prediction-feedback mismatches during sensorimotor control of speech production driven by working memory. Rather than being an exclusively bottom-up and automatic process, auditory-motor integration for voice control can be modulated by top-down influences arising from working memory. Copyright © 2017 the authors 0270-6474/17/3710324-11$15.00/0.

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

PubMed

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 (<150-ms latencies), without incurring any costs for selection of target matching distractors. These results unambiguously support a feedforward account of top-down modulation.

Top-Down Visual Saliency via Joint CRF and Dictionary Learning.

PubMed

Yang, Jimei; Yang, Ming-Hsuan

2017-03-01

Top-down visual saliency is an important module of visual attention. In this work, we propose a novel top-down saliency model that jointly learns a Conditional Random Field (CRF) and a visual dictionary. The proposed model incorporates a layered structure from top to bottom: CRF, sparse coding and image patches. With sparse coding as an intermediate layer, CRF is learned in a feature-adaptive manner; meanwhile with CRF as the output layer, the dictionary is learned under structured supervision. For efficient and effective joint learning, we develop a max-margin approach via a stochastic gradient descent algorithm. Experimental results on the Graz-02 and PASCAL VOC datasets show that our model performs favorably against state-of-the-art top-down saliency methods for target object localization. In addition, the dictionary update significantly improves the performance of our model. We demonstrate the merits of the proposed top-down saliency model by applying it to prioritizing object proposals for detection and predicting human fixations.

RNAbrowse: RNA-Seq De Novo Assembly Results Browser

PubMed Central

Mariette, Jérôme; Noirot, Céline; Nabihoudine, Ibounyamine; Bardou, Philippe; Hoede, Claire; Djari, Anis; Cabau, Cédric; Klopp, Christophe

2014-01-01

Transcriptome analysis based on a de novo assembly of next generation RNA sequences is now performed routinely in many laboratories. The generated results, including contig sequences, quantification figures, functional annotations and variation discovery outputs are usually bulky and quite diverse. This article presents a user oriented storage and visualisation environment permitting to explore the data in a top-down manner, going from general graphical views to all possible details. The software package is based on biomart, easy to install and populate with local data. The software package is available under the GNU General Public License (GPL) at http://bioinfo.genotoul.fr/RNAbrowse. PMID:24823498

VirVarSeq: a low-frequency virus variant detection pipeline for Illumina sequencing using adaptive base-calling accuracy filtering.

PubMed

Verbist, Bie M P; Thys, Kim; Reumers, Joke; Wetzels, Yves; Van der Borght, Koen; Talloen, Willem; Aerssens, Jeroen; Clement, Lieven; Thas, Olivier

2015-01-01

In virology, massively parallel sequencing (MPS) opens many opportunities for studying viral quasi-species, e.g. in HIV-1- and HCV-infected patients. This is essential for understanding pathways to resistance, which can substantially improve treatment. Although MPS platforms allow in-depth characterization of sequence variation, their measurements still involve substantial technical noise. For Illumina sequencing, single base substitutions are the main error source and impede powerful assessment of low-frequency mutations. Fortunately, base calls are complemented with quality scores (Qs) that are useful for differentiating errors from the real low-frequency mutations. A variant calling tool, Q-cpileup, is proposed, which exploits the Qs of nucleotides in a filtering strategy to increase specificity. The tool is imbedded in an open-source pipeline, VirVarSeq, which allows variant calling starting from fastq files. Using both plasmid mixtures and clinical samples, we show that Q-cpileup is able to reduce the number of false-positive findings. The filtering strategy is adaptive and provides an optimized threshold for individual samples in each sequencing run. Additionally, linkage information is kept between single-nucleotide polymorphisms as variants are called at the codon level. This enables virologists to have an immediate biological interpretation of the reported variants with respect to their antiviral drug responses. A comparison with existing SNP caller tools reveals that calling variants at the codon level with Q-cpileup results in an outstanding sensitivity while maintaining a good specificity for variants with frequencies down to 0.5%. The VirVarSeq is available, together with a user's guide and test data, at sourceforge: http://sourceforge.net/projects/virtools/?source=directory. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

ERIC Educational Resources Information Center

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 Management: An Effective Tool in Higher Education?

ERIC Educational Resources Information Center

Tsai, Yau; Beverton, Sue

2007-01-01

Purpose: The purpose of this paper is to explore the strengths and weaknesses of top-down management in a university that has embraced globalisation with a strong market-led ethos and to suggest the ways in which adjustments might be made to top-down management processes. Design/methodology/approach: The paper examines the strengths and weaknesses…

The Role of Person Versus Situation in Life Satisfaction: A Critical Examination

ERIC Educational Resources Information Center

Heller, Daniel; Watson, David; Hies, Remus

2004-01-01

Two main theoretical approaches have been put forward to explain individual differences in life satisfaction: top-down (i.e., personological) and bottom-up (i.e., situational). The authors examine the relative merit of these 2 approaches and the psychological processes underlying top-down models. Consistent with a top-down approach, meta-analytic…

Bottom-Up Guidance in Visual Search for Conjunctions

ERIC Educational Resources Information Center

Proulx, Michael J.

2007-01-01

Understanding the relative role of top-down and bottom-up guidance is crucial for models of visual search. Previous studies have addressed the role of top-down and bottom-up processes in search for a conjunction of features but with inconsistent results. Here, the author used an attentional capture method to address the role of top-down and…

The nucleotide sequence and genome organization of Plasmopara halstedii virus.

PubMed

Heller-Dohmen, Marion; Göpfert, Jens C; Pfannstiel, Jens; Spring, Otmar

2011-03-17

Only very few viruses of Oomycetes have been studied in detail. Isometric virions were found in different isolates of the oomycete Plasmopara halstedii, the downy mildew pathogen of sunflower. However, complete nucleotide sequences and data on the genome organization were lacking. Viral RNA of different P. halstedii isolates was subjected to nucleotide sequencing and analysis of the viral genome. The N-terminal sequence of the viral coat protein was determined using Top-Down MALDI-TOF analysis. The complete nucleotide sequences of both single-stranded RNA segments (RNA1 and RNA2) were established. RNA1 consisted of 2793 nucleotides (nt) exclusive its 3' poly(A) tract and a single open-reading frame (ORF1) of 2745 nt. ORF1 was framed by a 5' untranslated region (5' UTR) of 18 nt and a 3' untranslated region (3' UTR) of 30 nt. ORF1 contained motifs of RNA-dependent RNA polymerases (RdRp) and showed similarities to RdRp of Scleropthora macrospora virus A (SmV A) and viruses within the Nodaviridae family. RNA2 consisted of 1526 nt exclusive its 3' poly(A) tract and a second ORF (ORF2) of 1128 nt. ORF2 coded for the single viral coat protein (CP) and was framed by a 5' UTR of 164 nt and a 3' UTR of 234 nt. The deduced amino acid sequence of ORF2 was verified by nano-LC-ESI-MS/MS experiments. Top-Down MALDI-TOF analysis revealed the N-terminal sequence of the CP. The N-terminal sequence represented a region within ORF2 suggesting a proteolytic processing of the CP in vivo. The CP showed similarities to CP of SmV A and viruses within the Tombusviridae family. Fragments of RNA1 (ca. 1.9 kb) and RNA2 (ca. 1.4 kb) were used to analyze the nucleotide sequence variation of virions in different P. halstedii isolates. Viral sequence variation was 0.3% or less regardless of their host's pathotypes, the geographical origin and the sensitivity towards the fungicide metalaxyl. The results showed the presence of a single and new virus type in different P. halstedii isolates. Insignificant viral sequence variation indicated that the virus did not account for differences in pathogenicity of the oomycete P. halstedii.

Prey Vulnerability Limits Top-Down Control and Alters Reciprocal Feedbacks in a Subsidized Model Food Web

PubMed Central

Atlas, William I.; Palen, Wendy J.

2014-01-01

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. PMID:24465732

Top-down cortical input during NREM sleep consolidates perceptual memory.

PubMed

Miyamoto, D; Hirai, D; Fung, C C A; Inutsuka, A; Odagawa, M; Suzuki, T; Boehringer, R; Adaikkan, C; Matsubara, C; Matsuki, N; Fukai, T; McHugh, T J; Yamanaka, A; Murayama, M

2016-06-10

During tactile perception, long-range intracortical top-down axonal projections are essential for processing sensory information. Whether these projections regulate sleep-dependent long-term memory consolidation is unknown. We altered top-down inputs from higher-order cortex to sensory cortex during sleep and examined the consolidation of memories acquired earlier during awake texture perception. Mice learned novel textures and consolidated them during sleep. Within the first hour of non-rapid eye movement (NREM) sleep, optogenetic inhibition of top-down projecting axons from secondary motor cortex (M2) to primary somatosensory cortex (S1) impaired sleep-dependent reactivation of S1 neurons and memory consolidation. In NREM sleep and sleep-deprivation states, closed-loop asynchronous or synchronous M2-S1 coactivation, respectively, reduced or prolonged memory retention. Top-down cortical information flow in NREM sleep is thus required for perceptual memory consolidation. Copyright © 2016, American Association for the Advancement of Science.

Relative importance of top-down and bottom-up forces in food webs of Sarracenia pitcher communities at a northern and a southern site.

PubMed

Hoekman, David

2011-04-01

The relative importance of resources (bottom-up forces) and natural enemies (top-down forces) for regulating food web dynamics has been debated, and both forces have been found to be critical for determining food web structure. How the relative importance of top-down and bottom-up forces varies between sites with different abiotic conditions is not well understood. Using the pitcher plant inquiline community as a model system, I examine how the relative importance of top-down and bottom-up effects differs between two disparate sites. Resources (ant carcasses) and top predators (mosquito larvae) were manipulated in two identical 4 × 4 factorial press experiments, conducted at two geographically distant sites (Michigan and Florida) within the range of the purple pitcher plant, Sarracenia purpurea, and the aquatic community that resides in its leaves. Overall, top predators reduced the density of prey populations while additional resources bolstered them, and the relative importance of top-down and bottom-up forces varied between sites and for different trophic levels. Specifically, top-down effects on protozoa were stronger in Florida than in Michigan, while the opposite pattern was found for rotifers. These findings experimentally demonstrate that the strength of predator-prey interactions, even those involving the same species, vary across space. While only two sites are compared in this study, I hypothesize that site differences in temperature, which influences metabolic rate, may be responsible for variation in consumer-resource interactions. These findings warrant further investigation into the specific factors that modify the relative importance of top-down and bottom-up effects.

Direction with Discretion: Reading Recovery as an Example of Balancing Top-Down Policy and Bottom-Up Decision-Making.

ERIC Educational Resources Information Center

Scharer, Patricia L.; Zajano, Nancy C.

Educational policy analysts have recognized the need for an educational policy that combines the merits of "top-down" mandates with "bottom-up" teacher discretion. This paper describes the Reading Recovery program as an example of an educational program that balances top-down direction and bottom-up discretion by: (1) providing an overall…

Real-world visual search is dominated by top-down guidance.

PubMed

Chen, Xin; Zelinsky, Gregory J

2006-11-01

How do bottom-up and top-down guidance signals combine to guide search behavior? Observers searched for a target either with or without a preview (top-down manipulation) or a color singleton (bottom-up manipulation) among the display objects. With a preview, reaction times were faster and more initial eye movements were guided to the target; the singleton failed to attract initial saccades under these conditions. Only in the absence of a preview did subjects preferentially fixate the color singleton. We conclude that the search for realistic objects is guided primarily by top-down control. Implications for saliency map models of visual search are discussed.

Ultrahigh pressure fast size exclusion chromatography for top-down proteomics.

PubMed

Chen, Xin; Ge, Ying

2013-09-01

Top-down MS-based proteomics has gained a solid growth over the past few years but still faces significant challenges in the LC separation of intact proteins. In top-down proteomics, it is essential to separate the high mass proteins from the low mass species due to the exponential decay in S/N as a function of increasing molecular mass. SEC is a favored LC method for size-based separation of proteins but suffers from notoriously low resolution and detrimental dilution. Herein, we reported the use of ultrahigh pressure (UHP) SEC for rapid and high-resolution separation of intact proteins for top-down proteomics. Fast separation of intact proteins (6-669 kDa) was achieved in < 7 min with high resolution and high efficiency. More importantly, we have shown that this UHP-SEC provides high-resolution separation of intact proteins using a MS-friendly volatile solvent system, allowing the direct top-down MS analysis of SEC-eluted proteins without an additional desalting step. Taken together, we have demonstrated that UHP-SEC is an attractive LC strategy for the size separation of proteins with great potential for top-down proteomics. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An integrative top-down and bottom-up qualitative model construction framework for exploration of biochemical systems.

PubMed

Wu, Zujian; Pang, Wei; Coghill, George M

Computational modelling of biochemical systems based on top-down and bottom-up approaches has been well studied over the last decade. In this research, after illustrating how to generate atomic components by a set of given reactants and two user pre-defined component patterns, we propose an integrative top-down and bottom-up modelling approach for stepwise qualitative exploration of interactions among reactants in biochemical systems. Evolution strategy is applied to the top-down modelling approach to compose models, and simulated annealing is employed in the bottom-up modelling approach to explore potential interactions based on models constructed from the top-down modelling process. Both the top-down and bottom-up approaches support stepwise modular addition or subtraction for the model evolution. Experimental results indicate that our modelling approach is feasible to learn the relationships among biochemical reactants qualitatively. In addition, hidden reactants of the target biochemical system can be obtained by generating complex reactants in corresponding composed models. Moreover, qualitatively learned models with inferred reactants and alternative topologies can be used for further web-lab experimental investigations by biologists of interest, which may result in a better understanding of the system.

Solid-State Nanopore.

PubMed

Yuan, Zhishan; Wang, Chengyong; Yi, Xin; Ni, Zhonghua; Chen, Yunfei; Li, Tie

2018-02-20

Solid-state nanopore has captured the attention of many researchers due to its characteristic of nanoscale. Now, different fabrication methods have been reported, which can be summarized into two broad categories: "top-down" etching technology and "bottom-up" shrinkage technology. Ion track etching method, mask etching method chemical solution etching method, and high-energy particle etching and shrinkage method are exhibited in this report. Besides, we also discussed applications of solid-state nanopore fabrication technology in DNA sequencing, protein detection, and energy conversion.

Solid-State Nanopore

NASA Astrophysics Data System (ADS)

Yuan, Zhishan; Wang, Chengyong; Yi, Xin; Ni, Zhonghua; Chen, Yunfei; Li, Tie

2018-02-01

Solid-state nanopore has captured the attention of many researchers due to its characteristic of nanoscale. Now, different fabrication methods have been reported, which can be summarized into two broad categories: "top-down" etching technology and "bottom-up" shrinkage technology. Ion track etching method, mask etching method chemical solution etching method, and high-energy particle etching and shrinkage method are exhibited in this report. Besides, we also discussed applications of solid-state nanopore fabrication technology in DNA sequencing, protein detection, and energy conversion.

The heterogeneous world of congruency sequence effects: an update.

PubMed

Duthoo, Wout; Abrahamse, Elger L; Braem, Senne; Boehler, Carsten N; Notebaert, Wim

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 bottom-up associative learning suffices to explain the pattern of reaction times and error rates. A couple of years ago, a review by Egner (2007) pitted these two rivalry accounts against each other, concluding that both conflict adaptation and feature integration contribute to the CSE. Since then, a wealth of studies has further debated this issue, and two additional accounts have been proposed, offering intriguing alternative explanations. Contingency learning accounts put forward that predictive relationships between stimuli and responses drive the CSE, whereas the repetition expectancy hypothesis suggests that top-down, expectancy-driven control adjustments affect the CSE. In the present paper, we build further on the previous review (Egner, 2007) by summarizing and integrating recent behavioral and neurophysiological studies on the CSE. In doing so, we evaluate the relative contribution and theoretical value of the different attentional and memory-based accounts. Moreover, we review how all of these influences can be experimentally isolated, and discuss designs and procedures that can critically judge between them.

The heterogeneous world of congruency sequence effects: an update

PubMed Central

Duthoo, Wout; Abrahamse, Elger L.; Braem, Senne; Boehler, Carsten N.; Notebaert, Wim

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 bottom-up associative learning suffices to explain the pattern of reaction times and error rates. A couple of years ago, a review by Egner (2007) pitted these two rivalry accounts against each other, concluding that both conflict adaptation and feature integration contribute to the CSE. Since then, a wealth of studies has further debated this issue, and two additional accounts have been proposed, offering intriguing alternative explanations. Contingency learning accounts put forward that predictive relationships between stimuli and responses drive the CSE, whereas the repetition expectancy hypothesis suggests that top-down, expectancy-driven control adjustments affect the CSE. In the present paper, we build further on the previous review (Egner, 2007) by summarizing and integrating recent behavioral and neurophysiological studies on the CSE. In doing so, we evaluate the relative contribution and theoretical value of the different attentional and memory-based accounts. Moreover, we review how all of these influences can be experimentally isolated, and discuss designs and procedures that can critically judge between them. PMID:25250005

Cloning of cDNAs for H1F0, TOP1, CLTA and CDK1 and the effects of cryopreservation on the expression of their mRNA transcripts in yak (Bos grunniens) oocytes.

PubMed

Niu, Hui-Ran; Zi, Xiang-Dong; Xiao, Xiao; Xiong, Xian-Rong; Zhong, Jin-Cheng; Li, Jian; Wang, Li; Wang, Yong

2014-08-01

We cloned and sequenced four pivotal cDNAs involved in DNA structural maintenance (H1F0 and TOP1) and the cell cycle (CLTA and CDK1) from yak oocytes. In addition, we studied the consequences of freezing-thawing (F/T) processes on the expression of their mRNA transcripts in yak immature and in vitro matured (MII) oocytes. H1F0, TOP1, CLTA and CDK1 cDNAs were cloned from yak oocytes by reverse transcriptase-polymerase chain reaction (RT-PCR) strategy. The expression of their mRNA transcript analyses were performed upon fresh and frozen-thawed immature germinal vesicle (GV) and MII yak oocytes following normalization of transcripts with GAPDH by real-time PCR. The yak H1F0, TOP1, CLTA and CDK1 cDNA sequences were found to consist of CDK1 585, 2539, 740, and 894 bp, respectively. Their coding regions encoded 195, 768, 244, and 298 amino acids, respectively. The homology with that of cattle was very high (95.2%, 98.8%, 93.6%, and 89.5%, respectively nucleotide sequence level, and 94.3%, 98.2%, 87.7%, and 90.9%, respectively at the deduced amino acid level). The overall mRNA expression levels of these four transcripts were reduced by F/T process, albeit at different levels. TOP1 in GV-oocytes, and H1F0 and CDK1 in MII-oocytes of the yak were significantly down-regulated (P<0.05). This is the first isolation and characterization of H1F0, TOP1, CLTA, and CDK1 cDNAs from yak oocytes. The lower fertility and developmental ability of yak oocytes following fertilization after cryopreservation may be explained by the alterations to their gene expression profiles. Copyright © 2014 Elsevier Inc. All rights reserved.

View of Hadley Delta from top hatch of Apollo 15 Lunar Module after landing

NASA Image and Video Library

1971-07-31

AS15-87-11748 (31 July 1971) --- A view of Hadley Delta, looking southeasterly, as photographed from the top hatch of the Apollo 15 Lunar Module (LM) by astronaut David R. Scott, commander, during his stand-up extravehicular activity (EVA) just after the LM "Falcon" touched down at the Hadley-Apennine landing site. The prominent feature on the horizon in the center of the picture was called Silver Spur by the Apollo 15 crew men. Hadley Delta Mountain rises approximately 4,000 meters (about 13,124 feet) above the plain. While astronauts Scott and James B. Irwin, lunar module pilot, descended in the LM to explore the moon, astronaut Alfred M. Worden, command module pilot, remained with the Command and Service Module's (CSM) in lunar orbit.

Under Jupiter's Cloud Tops

NASA Image and Video Library

2017-05-25

NASA's Juno spacecraft carries an instrument called the Microwave Radiometer, which examines Jupiter's atmosphere beneath the planet's cloud tops. This image shows the instrument's view of the outer part of Jupiter's atmosphere. Before Juno began using this instrument, scientists expected the atmosphere to be uniform at depths greater than 60 miles (100 kilometers). But with the Microwave Radiometer, scientists have discovered that the atmosphere has variations down to at least 220 miles (350 kilometers), as deep as the instrument can see. In the cut-out image to the right, orange signifies high ammonia abundance and blue signifies low ammonia abundance. Jupiter appears to have a band around its equator high in ammonia abundance, with a column shown in orange. This is contrary to scientists' expectations that ammonia would be uniformly mixed. https://photojournal.jpl.nasa.gov/catalog/PIA21642

A Ubiquitin-Proteasome Pathway for the Repair of Topoisomerase I-DNA Covalent Complexes*S⃞

PubMed Central

Lin, Chao-Po; Ban, Yi; Lyu, Yi Lisa; Desai, Shyamal D.; Liu, Leroy F.

2008-01-01

Reversible topoisomerase I (Top1)-DNA cleavage complexes are the key DNA lesion induced by anticancer camptothecins (e.g. topotecan and irinotecan) as well as structurally perturbed DNAs (e.g. oxidatively damaged DNA, UV-irradiated DNA, alkylated DNA, uracil-substituted DNA, mismatched DNA, gapped and nicked DNA, and DNA with abasic sites). Top1 cleavage complexes arrest transcription and trigger transcription-dependent degradation of Top1, a phenomenon termed Top1 down-regulation. In the current study, we have investigated the role of Top1 down-regulation in the repair of Top1 cleavage complexes. Using quiescent (serum-starved) human WI-38 cells, camptothecin (CPT) was shown to induce Top1 down-regulation, which paralleled the induction of DNA single-strand breaks (SSBs) (assayed by comet assays) and ATM autophosphorylation (at Ser-1981). Interestingly, Top1 down-regulation, induction of DNA SSBs and ATM autophosphorylation were all abolished by the proteasome inhibitor MG132. Furthermore, studies using immunoprecipitation and dominant-negative ubiquitin mutants have suggested a specific requirement for the assembly of Lys-48-linked polyubiquitin chains for CPT-induced Top1 down-regulation. In contrast to the effect of proteasome inhibition, inactivation of PARP1 was shown to increase the amount of CPT-induced SSBs and the level of ATM autophosphorylation. Together, these results support a model in which Top1 cleavage complexes arrest transcription and activate a ubiquitin-proteasome pathway leading to the degradation of Top1 cleavage complexes. Degradation of Top1 cleavage complexes results in the exposure of Top1-concealed SSBs for repair through a PARP1-dependent process. PMID:18515798

Legacy of top-down herbivore pressure ricochets back up multiple trophic levels in forest canopies over 30 years

Treesearch

Tim Nuttle; Ellen H. Yerger; Scott H. Stoleson; Todd E. Ristau

2011-01-01

Removal of top-down control on herbivores can result in a trophic cascade where herbivore pressure on plants results in changes in plant communities. These altered plant communities are hypothesized to exert bottom-up control on subsequent herbivory via changes in plant quality or productivity. But it remains untested whether top-down perturbation causes long term...

Bottom-Up or Top-Down: English as a Foreign Language Vocabulary Instruction for Chinese University Students

ERIC Educational Resources Information Center

Moskovsky, Christo; Jiang, Guowu; Libert, Alan; Fagan, Seamus

2015-01-01

Whereas there has been some research on the role of bottom-up and top-down processing in the learning of a second or foreign language, very little attention has been given to bottom-up and top-down instructional approaches to language teaching. The research reported here used a quasi-experimental design to assess the relative effectiveness of two…

Test Input Generation for Red-Black Trees using Abstraction

NASA Technical Reports Server (NTRS)

Visser, Willem; Pasareanu, Corina S.; Pelanek, Radek

2005-01-01

We consider the problem of test input generation for code that manipulates complex data structures. Test inputs are sequences of method calls from the data structure interface. We describe test input generation techniques that rely on state matching to avoid generation of redundant tests. Exhaustive techniques use explicit state model checking to explore all the possible test sequences up to predefined input sizes. Lossy techniques rely on abstraction mappings to compute and store abstract versions of the concrete states; they explore under-approximations of all the possible test sequences. We have implemented the techniques on top of the Java PathFinder model checker and we evaluate them using a Java implementation of red-black trees.

The role of attention in subliminal semantic processing: A mouse tracking study.

PubMed

Xiao, Kunchen; Yamauchi, Takashi

2017-01-01

Recent evidence suggests that top-down attention facilitates unconscious semantic processing. To clarify the role of attention in unconscious semantic processing, we traced trajectories of the computer mouse in a semantic priming task and scrutinized the extent to which top-down attention enhances unconscious semantic processing in four different stimulus-onset asynchrony (SOA: 50, 200, 500, or 1000ms) conditions. Participants judged whether a target digit (e.g., "6") was larger or smaller than five, preceded by a masked priming digit (e.g., "9"). The pre-prime duration changed randomly from trial to trial to disrupt participants' top-down attention in an uncued condition (in a cued condition, a green square cue was presented to facilitate participants' top-down attention). The results show that top-down attention modifies the time course of subliminal semantic processing, and the temporal attention window lasts more than 1000ms; attention facilitated by the cue may amplify semantic priming to some extent, yet the amplification effect of attention is relatively minor.

Effect of drug physico-chemical properties on the efficiency of top-down process and characterization of nanosuspension.

PubMed

Liu, Tao; Müller, Rainer H; Möschwitzer, Jan P

2015-01-01

The top-down approach is frequently used for drug nanocrystal production. A large number of review papers have referred to the top-down approach in terms of process parameters such as stabilizer selection. However, a very important factor, that is, the influence of drug properties, has been not addressed so far. This review will first discuss different nanocrystal technologies in brief. The focus will be on reviewing the different drug properties such as solid state and particle morphology on the efficiency of particle size reduction during top-down processes. Furthermore, the drug properties in the final nanosuspensions are critical for drug dissolution velocity. Therefore, another focus is the characterization of drugs in obtained nanosuspension. Drug physical properties play an important role in the production efficiency. The combinative technologies using modified drugs could significantly improve the performances of top-down processes. However, further understanding of the drug millability and homogenization will still be needed. In addition, a carefully established characterization system for nansuspension is essential.

How to (and how not to) think about top-down influences on visual perception.

PubMed

Teufel, Christoph; Nanay, Bence

2017-01-01

The question of whether cognition can influence perception has a long history in neuroscience and philosophy. Here, we outline a novel approach to this issue, arguing that it should be viewed within the framework of top-down information-processing. This approach leads to a reversal of the standard explanatory order of the cognitive penetration debate: we suggest studying top-down processing at various levels without preconceptions of perception or cognition. Once a clear picture has emerged about which processes have influences on those at lower levels, we can re-address the extent to which they should be considered perceptual or cognitive. Using top-down processing within the visual system as a model for higher-level influences, we argue that the current evidence indicates clear constraints on top-down influences at all stages of information processing; it does, however, not support the notion of a boundary between specific types of information-processing as proposed by the cognitive impenetrability hypothesis. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

NASA Astrophysics Data System (ADS)

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.

Effect of infliximab top-down therapy on weight gain in pediatric Crohns disease.

PubMed

Kim, Mi Jin; Lee, Woo Yong; Choi, Kyong Eun; Choe, Yon Ho

2012-12-01

This retrospective-medical-record review was conducted to evaluate effect of infliximab therapy, particularly with a top-down strategy, on the nutritional parameters of children with Crohns disease (CD). 42 patients who were diagnosed with Crohns disease at the Pediatric Gastroenterology center of a tertiary care teaching hospital and achieved remission at two months and one year after beginning of treatment were divided into four subgroups according to the treatment regimen; azathioprine group (n = 11), steroid group (n = 11), infliximab top-down group (n = 11) and step-up group (n = 9). Weight, height, and serum albumin were measured at diagnosis, and then at two months and one year after the initiation of treatment. At 2 months, the Z score increment for weight was highest in the steroid group, followed by the top-down, step-up, and azathioprine groups. At one year, the Z score increment was highest in top-down group, followed by steroid, azathioprine, and step-up group. There were no significant differences between the four groups in Z score increment for height and serum albumin during the study period. The top-down infliximab treatment resulted in superior outcome for weight gain, compared to the step-up therapy and other treatment regimens.

Hierarchy, causation and explanation: ubiquity, locality and pluralism

PubMed Central

Love, Alan C.

2012-01-01

The ubiquity of top-down causal explanations within and across the sciences is prima facie evidence for the existence of top-down causation. Much debate has been focused on whether top-down causation is coherent or in conflict with reductionism. Less attention has been given to the question of whether these representations of hierarchical relations pick out a single, common hierarchy. A negative answer to this question undermines a commonplace view that the world is divided into stratified ‘levels’ of organization and suggests that attributions of causal responsibility in different hierarchical representations may not have a meaningful basis for comparison. Representations used in top-down and bottom-up explanations are primarily ‘local’ and tied to distinct domains of science, illustrated here by protein structure and folding. This locality suggests that no single metaphysical account of hierarchy for causal relations to obtain within emerges from the epistemology of scientific explanation. Instead, a pluralist perspective is recommended—many different kinds of top-down causation (explanation) can exist alongside many different kinds of bottom-up causation (explanation). Pluralism makes plausible why different senses of top-down causation can be coherent and not in conflict with reductionism, thereby illustrating a productive interface between philosophical analysis and scientific inquiry. PMID:23386966

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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.

Permeability of priming of pop out to expectations.

PubMed

Pascucci, David; Mastropasqua, Tommaso; Turatto, Massimo

2012-09-29

It is well established that repetition of the same target color across consecutive trials enhances search efficiency for pop-out targets; this phenomenon is known as Priming of Pop out (PoP). In three experiments, we addressed whether PoP interacts with top-down expectations in altering target visibility, which was manipulated via metacontrast masking. The target color either remained the same for n consecutive trials (blocked condition) or changed unpredictably (random condition). The results showed that PoP reduced the efficacy of masking and that its beneficial effect can be either potentiated or attenuated by participants' expectations about the upcoming target color. These findings undermine the view that PoP should be impermeable to top-down factors. In addition, we found evidence that both explicit and implicit expectations interact with PoP. The former can be induced via instructions on the rate of alternation of the target color, and the latter can be induced by random sequences in which repetitions of the same target color exceed those predicted by an internal model of randomness for binary events. In the latter case, more than three repetitions of the same target color led to a decline in target visibility. We speculate that, in the random condition, after few repetitions of the same target, participants developed an expectation for a change; this phenomenon is similar to the "gambler's fallacy." Finally, our analyses revealed no effect of expectation on switch trials (i.e., when the target color changed), which casts doubt on the efficacy of top-down control in feature search.

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

PubMed

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.

A category-specific top-down attentional set can affect the neural responses outside the current focus of attention.

PubMed

Jiang, Yunpeng; Wu, Xia; Gao, Xiaorong

2017-10-17

A top-down set can guide attention to enhance the processing of task-relevant objects. Many studies have found that the top-down set can be tuned to a category level. However, it is unclear whether the category-specific top-down set involving a central search task can exist outside the current area of attentional focus. To directly probe the neural responses inside and outside the current focus of attention, we recorded continuous EEG to measure the contralateral ERP components for central targets and the steady-state visual evoked potential (SSVEP) oscillations associated with a flickering checkerboard placed on the visual periphery. The relationship of color categories between targets and non-targets was manipulated to investigate the effect of category-specific top-down set. Results showed that when the color categories of targets and non-targets in the central search arrays were the same, larger SSVEP oscillations were evoked by target color peripheral checkerboards relative to the non-target color ones outside the current attentional focus. However, when the color categories of targets and non-targets were different, the peripheral checkerboards in two different colors of the same category evoked similar SSVEP oscillations, indicating the effects of category-specific top-down set. These results firstly demonstrate that the category-specific top-down set can affect the neural responses of peripheral distractors. The results could support the idea of a global selection account and challenge the attentional window account in selective attention. Copyright © 2017. Published by Elsevier B.V.

On the complex interaction between mathematics and the sciences of living systems. 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.

NASA Astrophysics Data System (ADS)

Bellomo, Nicola; Outada, Nisrine

2017-07-01

Cultural framework: Our comment looks at the general framework given by the interactions between the so-called ;soft; and ;hard; sciences. Specifically, it looks at the development of a mathematics for living systems. Our comment aims at showing how the interesting survey [11] can contribute to the aforementioned challenging task.

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

PubMed Central

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-disinhibition mechanism. PMID:26834601

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dekker, Leendert J.; Wu, Si; vanDuijn, Martijn M.

2014-05-31

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 towards 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 integratedmore » 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 towards the identification of disease specific antibodies in patient samples with potentially significant clinical impact.« less

OVAS: an open-source variant analysis suite with inheritance modelling.

PubMed

Mozere, Monika; Tekman, Mehmet; Kari, Jameela; Bockenhauer, Detlef; Kleta, Robert; Stanescu, Horia

2018-02-08

The advent of modern high-throughput genetics continually broadens the gap between the rising volume of sequencing data, and the tools required to process them. The need to pinpoint a small subset of functionally important variants has now shifted towards identifying the critical differences between normal variants and disease-causing ones. The ever-increasing reliance on cloud-based services for sequence analysis and the non-transparent methods they utilize has prompted the need for more in-situ services that can provide a safer and more accessible environment to process patient data, especially in circumstances where continuous internet usage is limited. To address these issues, we herein propose our standalone Open-source Variant Analysis Sequencing (OVAS) pipeline; consisting of three key stages of processing that pertain to the separate modes of annotation, filtering, and interpretation. Core annotation performs variant-mapping to gene-isoforms at the exon/intron level, append functional data pertaining the type of variant mutation, and determine hetero/homozygosity. An extensive inheritance-modelling module in conjunction with 11 other filtering components can be used in sequence ranging from single quality control to multi-file penetrance model specifics such as X-linked recessive or mosaicism. Depending on the type of interpretation required, additional annotation is performed to identify organ specificity through gene expression and protein domains. In the course of this paper we analysed an autosomal recessive case study. OVAS made effective use of the filtering modules to recapitulate the results of the study by identifying the prescribed compound-heterozygous disease pattern from exome-capture sequence input samples. OVAS is an offline open-source modular-driven analysis environment designed to annotate and extract useful variants from Variant Call Format (VCF) files, and process them under an inheritance context through a top-down filtering schema of swappable modules, run entirely off a live bootable medium and accessed locally through a web-browser.

Neural processing of food and emotional stimuli in adolescent and adult anorexia nervosa patients.

PubMed

Horndasch, Stefanie; Roesch, Julie; Forster, Clemens; Dörfler, Arnd; Lindsiepe, Silja; Heinrich, Hartmut; Graap, Holmer; Moll, Gunther H; Kratz, Oliver

2018-01-01

A constant preoccupation with food and restrictive eating are main symptoms of anorexia nervosa (AN). Imaging studies revealed aberrant neural activation patterns in brain regions processing hedonic and reward reactions as well as-potentially aversive-emotions. An imbalance between so called "bottom-up" and "top-down" control areas is discussed. The present study is focusing on neural processing of disease-specific food stimuli and emotional stimuli and its developmental course in adolescent and adult AN patients and could offer new insight into differential mechanisms underlying shorter or more chronic disease. 33 adolescents aged 12-18 years (15 AN patients, 18 control participants) and 32 adult women (16 AN patients, 16 control participants) underwent functional magnetic resonance imaging (fMRI, 3T high-field scanner) while watching pictures of high and low-calorie food and affective stimuli. Afterwards, they rated subjective valence of each picture. FMRI data analysis was performed using a region of interest based approach. Pictures of high-calorie food items were rated more negatively by AN patients. Differences in activation between patients and controls were found in "bottom up" and "top down" control areas for food stimuli and in several emotion processing regions for affective stimuli which were more pronounced in adolescents than in adults. A differential pattern was seen for food stimuli compared to generally emotion eliciting stimuli. Adolescents with AN show reduced processing of affective stimuli and enhanced activation of regions involved in "bottom up" reward processing and "top down" control as well as the insula with regard to food stimuli with a focus on brain regions which underlie changes during adolescent development. In adults less clear and less specific activation differences were present, pointing towards a high impact that regions undergoing maturation might have on AN symptoms.

An Attention-Sensitive Memory Trace in Macaque MT Following Saccadic Eye Movements

PubMed Central

Yao, Tao; Treue, Stefan; Krishna, B. Suresh

2016-01-01

We experience a visually stable world despite frequent retinal image displacements induced by eye, head, and body movements. The neural mechanisms underlying this remain unclear. One mechanism that may contribute is transsaccadic remapping, in which the responses of some neurons in various attentional, oculomotor, and visual brain areas appear to anticipate the consequences of saccades. The functional role of transsaccadic remapping is actively debated, and many of its key properties remain unknown. Here, recording from two monkeys trained to make a saccade while directing attention to one of two spatial locations, we show that neurons in the middle temporal area (MT), a key locus in the motion-processing pathway of humans and macaques, show a form of transsaccadic remapping called a memory trace. The memory trace in MT neurons is enhanced by the allocation of top-down spatial attention. Our data provide the first demonstration, to our knowledge, of the influence of top-down attention on the memory trace anywhere in the brain. We find evidence only for a small and transient effect of motion direction on the memory trace (and in only one of two monkeys), arguing against a role for MT in the theoretically critical yet empirically contentious phenomenon of spatiotopic feature-comparison and adaptation transfer across saccades. Our data support the hypothesis that transsaccadic remapping represents the shift of attentional pointers in a retinotopic map, so that relevant locations can be tracked and rapidly processed across saccades. Our results resolve important issues concerning the perisaccadic representation of visual stimuli in the dorsal stream and demonstrate a significant role for top-down attention in modulating this representation. PMID:26901857

Control adjustments in speaking: Electrophysiology of the Gratton effect in picture naming.

PubMed

Shitova, Natalia; Roelofs, Ardi; Schriefers, Herbert; Bastiaansen, Marcel; Schoffelen, Jan-Mathijs

2017-07-01

Accumulating evidence suggests that spoken word production requires different amounts of top-down control depending on the prevailing circumstances. For example, during Stroop-like tasks, the interference in response time (RT) is typically larger following congruent trials than following incongruent trials. This effect is called the Gratton effect, and has been taken to reflect top-down control adjustments based on the previous trial type. Such control adjustments have been studied extensively in Stroop and Eriksen flanker tasks (mostly using manual responses), but not in the picture-word interference (PWI) task, which is a workhorse of language production research. In one of the few studies of the Gratton effect in PWI, Van Maanen and Van Rijn (2010) examined the effect in picture naming RTs during dual-task performance. Based on PWI effect differences between dual-task conditions, they argued that the functional locus of the PWI effect differs between post-congruent trials (i.e., locus in perceptual and conceptual encoding) and post-incongruent trials (i.e., locus in word planning). However, the dual-task procedure may have contaminated the results. We therefore performed an electroencephalography (EEG) study on the Gratton effect in a regular PWI task. We observed a PWI effect in the RTs, in the N400 component of the event-related brain potentials, and in the midfrontal theta power, regardless of the previous trial type. Moreover, the RTs, N400, and theta power reflected the Gratton effect. These results provide evidence that the PWI effect arises at the word planning stage following both congruent and incongruent trials, while the amount of top-down control changes depending on the previous trial type. Copyright © 2017 Elsevier Ltd. All rights reserved.

Top-Down Proteomics and Farm Animal and Aquatic Sciences.

PubMed

Campos, Alexandre M O; de Almeida, André M

2016-12-21

Proteomics is a field of growing importance in animal and aquatic sciences. Similar to other proteomic approaches, top-down proteomics is slowly making its way within the vast array of proteomic approaches that researchers have access to. This opinion and mini-review article is dedicated to top-down proteomics and how its use can be of importance to animal and aquatic sciences. Herein, we include an overview of the principles of top-down proteomics and how it differs regarding other more commonly used proteomic methods, especially bottom-up proteomics. In addition, we provide relevant sections on how the approach was or can be used as a research tool and conclude with our opinions of future use in animal and aquatic sciences.

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

PubMed

Zhou, Mowei; Wu, Si; Stenoien, David L; Zhang, Zhaorui; Connolly, Lanelle; Freitag, Michael; Paša-Tolić, Ljiljana

2017-01-01

Top-down mass spectrometry is a valuable tool for understanding gene expression through characterization of combinatorial histone post-translational modifications (i.e., histone code). In this protocol, we describe a top-down workflow that employs liquid chromatography (LC) coupled to mass spectrometry (MS), for fast global profiling of changes in histone proteoforms, and apply LCMS top-down approach for comparative analysis of a wild-type and a mutant fungal species. The proteoforms exhibiting differential abundances can be subjected to further targeted studies by other MS or orthogonal (e.g., biochemical) assays. This method can be generally adapted for screening of changes in histone modifications between samples such as wild type vs. mutant or healthy vs. diseased.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tao, Jinhui; Buchko, Garry W.; Shaw, Wendy J.

The interactions between proteins and surfaces are critical to a number of important processes including biomineralization, the biocompatibility of biomaterials, and the function of biosensors. Although many proteins exist as monomers or small oligomers, amelogenin is a unique protein that self-assembles into supramolecular structures called “nanospheres,” aggregates of 100’s of monomers that are 20-60 nm in diameter. The nanosphere quaternary structure is observed in solution, however, the quaternary structure of amelogenin adsorbed onto hydroxyapatite (HAP) surfaces is not known even though it may be important to amelogenin’s function in forming highly elongated and intricately assembled HAP crystallites during enamel formation.more » We report studies of the interactions of the enamel protein, amelogenin (rpM179), with a well-defined (100) face prepared by synthesis of large crystals of HAP. High resolution, in-situ atomic force microscopy (AFM) was used to directly observe protein adsorption onto HAP at the molecular level within an aqueous solution environment. Our study shows that the amelogenin nanospheres disassemble onto the HAP surface, breaking down into oligomeric (25-mer) subunits of the larger nanosphere. In some cases, the disassembly event is directly observed by in situ imaging for the first time. Quantification of the adsorbate amounts by size analysis led to the determination of a protein binding energy (17.1 kbT) to a specific face of HAP (100). The kinetics of disassembly are greatly slowed in aged solutions, indicating there are time-dependent increases in oligomer-oligomer binding interactions within the nanosphere. A small change in the sequence of amelogenin by the attachment of a histidine tag to the N-terminus of rpM179 to form rp(H)M180 results in the adsorption of a complete second layer on top of the underlying first layer. Our research elucidates how supramolecular protein structures interact and break down at surfaces and how small changes in the primary sequence of amelogenin can affect the disassembly process.« less

International Space Station (ISS)

NASA Image and Video Library

2001-01-01

This is the STS-102 mission crew insignia. The central image on the crew patch depicts the International Space Station (ISS) in the build configuration that it had at the time of the arrival and docking of Discovery during the STS-102 mission, the first crew exchange flight to the Space Station. The station is shown along the direction of the flight as was seen by the shuttle crew during their final approach and docking, the so-called V-bar approach. The names of the shuttle crew members are depicted in gold around the top of the patch, and surnames of the Expedition crew members being exchanged are shown in the lower barner. The three ribbons swirling up to and around the station signify the rotation of these ISS crew members. The number 2 is for the Expedition 2 crew who flew up to the station, and the number 1 is for the Expedition 1 crew who then returned down to Earth. In conjunction with the face of the Lab module of the Station, these Expedition numbers create the shuttle mission number 102. Shown mated below the ISS is the Italian-built Multipurpose Logistics Module, Leonardo, that flew for the first time on this flight. The flags of the countries that were the major contributors to this effort, the United States, Russia, and Italy are also shown in the lower part of the patch. The build-sequence number of this flight in the overall station assembly sequence, 5A.1, is captured by the constellations in the background.

Top-down preparation modulates visual categorization but not subjective awareness of objects presented in natural backgrounds.

PubMed

Koivisto, Mika; Kahila, Ella

2017-04-01

Top-down processes are widely assumed to be essential in visual awareness, subjective experience of seeing. However, previous studies have not tried to separate directly the roles of different types of top-down influences in visual awareness. We studied the effects of top-down preparation and object substitution masking (OSM) on visual awareness during categorization of objects presented in natural scene backgrounds. The results showed that preparation facilitated categorization but did not influence visual awareness. OSM reduced visual awareness and impaired categorization. The dissociations between the effects of preparation and OSM on visual awareness and on categorization imply that they influence at different stages of cognitive processing. We propose that preparation influences at the top of the visual hierarchy, whereas OSM interferes with processes occurring at lower levels of the hierarchy. These lower level processes play an essential role in visual awareness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Micropatterning stretched and aligned DNA using microfluidics and surface patterning for applications in hybridization-mediated templated assembly of nanostructures

NASA Astrophysics Data System (ADS)

Carbeck, Jeffrey; Petit, Cecilia

2004-03-01

Current efforts in nanotechnology use one of two basic approaches: top-down fabrication and bottom-up assembly. Top-down strategies use lithography and contact printing to create patterned surfaces and microfluidic channels that, in turn, can corral and organize nanoscale structures. Bottom-up approaches use templates to direct the assembly of atoms, molecules, and nanoparticles through molecular recognition. The goal of this work is to integrate these strategies by first patterning and orienting DNA molecules through top-down tools so that single DNA chains can then serve as templates for the bottom-up construction of hetero-structures composed of proteins and nanoparticles, both metallic and semi-conducting. The first part of this talk focuses on the top-down strategies used to create microscopic patterns of stretched and aligned molecules of DNA. Specifically, it presents a new method in which molecular combing -- a process by which molecules are deposited and stretched onto a surface by the passage of an air-water interface -- is performed in microchannels. This approach demonstrates that the shape and motion of this interface serve as an effective local field directing the chains dynamically as they are stretched onto the surface. The geometry of the microchannel directs the placement of the DNA molecules, while the geometry of the air-water interface directs the local orientation and curvature of the molecules. This ability to control both the placement and orientation of chains has implication for the use of this technique in genetic analysis and in the bottom up approach to nanofabrication.The second half of this talk presents our bottom-up strategy, which allows placement of nanoparticles along individual DNA chains with a theoretical resolution of less than 1 nm. Specifically, we demonstrate the sequence-specific patterning of nanoparticles via the hybridization of functionalized complementary probes to surface-bound chains of double-stranded DNA. Using this technique, we demonstrate the ability to assemble metals, semiconductors, and a composite of both on a single molecule.

Stratigraphy, facies architecture, and palaeoenvironment of Neoproterozoic volcanics and volcaniclastic deposits in Fatira area, Central Eastern Desert, Egypt

NASA Astrophysics Data System (ADS)

Khalaf, Ezz El Din Abdel Hakim

Fatira area in the Central Eastern Desert, Egypt, is a composite terrane consisting of Neoproterozoic volcanics and sediments laid down in submarine to subaerial environment, intruded by voluminous old to young granitic rocks. The various lithofacies of the study area can be grouped in three distinct lithostratigraphic sequences, which are described here in stratigraphic order, from base to top as the Fatira El Beida, Fatira El Zarqa and Gabal Fatira sequences. Each depositional sequence, is intimately related to volcanic activity separated by time intervals of volcanic inactivity, such as marked hiatuses, reworked volcaniclasts, and or turbidite sedimentation. Four submarine facies groups have been recognized within the oldest, folded eruption sequence of Fatira El Beida. The southern part of the study area is occupied by sheet lava (SL), pillow lavas (PL), pillow breccias (PB), and overlying Bouma turbiditic volcaniclastites (VC). The four facies groups of Fatira El Beida sequence occur in a predictable upward-deepening succession, essentially from base to top, an SL-PL-PB-VC stacking pattern. The coeval tholeiitic mafic and felsic volcaniclastic rocks of this sequence indicate an extensional back-arc tectonic setting. The El Beida depositional sequence appears to fit a submarine-fan and slope-apron environment in an intra-arc site. The Fatira El Zarqa sequence involves a large volume of subaerial calc-alkaline intermediate to felsic volcanics and an unconformably overlying siliciclastic succession comprising clast-supported conglomerates (Gm), massive sandstone sheet floods (Sm) and mudstones (FI), together with a lateritic argillite paleosol (P) top formed in an alluvial-fan system. The youngest rock of Gabal Fatira sequence comprises anorogenic trachydacites and rhyolites with locally emergent domes associated with autobrecciation and sill-dyke rock swarms that could be interpreted as feeders and subvolcanic intrusions. Unconformity and lithofacies assemblages define seven events and three unconformity-bounded tectonic stages that record uplift-subsidence cycles in the study area. A proximal-distal relationship has been established within the depositional products, based on the relative dominance of erosional and depositional features.

Event-Related Potentials of Bottom-Up and Top-Down Processing of Emotional Faces

PubMed Central

Moradi, Afsane; Mehrinejad, Seyed Abolghasem; Ghadiri, Mohammad; Rezaei, Farzin

2017-01-01

Introduction: Emotional stimulus is processed automatically in a bottom-up way or can be processed voluntarily in a top-down way. Imaging studies have indicated that bottom-up and top-down processing are mediated through different neural systems. However, temporal differentiation of top-down versus bottom-up processing of facial emotional expressions has remained to be clarified. The present study aimed to explore the time course of these processes as indexed by the emotion-specific P100 and late positive potential (LPP) event-related potential (ERP) components in a group of healthy women. Methods: Fourteen female students of Alzahra University, Tehran, Iran aged 18–30 years, voluntarily participated in the study. The subjects completed 2 overt and covert emotional tasks during ERP acquisition. Results: The results indicated that fearful expressions significantly produced greater P100 amplitude compared to other expressions. Moreover, the P100 findings showed an interaction between emotion and processing conditions. Further analysis indicated that within the overt condition, fearful expressions elicited more P100 amplitude compared to other emotional expressions. Also, overt conditions created significantly more LPP latencies and amplitudes compared to covert conditions. Conclusion: Based on the results, early perceptual processing of fearful face expressions is enhanced in top-down way compared to bottom-up way. It also suggests that P100 may reflect an attentional bias toward fearful emotions. However, no such differentiation was observed within later processing stages of face expressions, as indexed by the ERP LPP component, in a top-down versus bottom-up way. Overall, this study provides a basis for further exploring of bottom-up and top-down processes underlying emotion and may be typically helpful for investigating the temporal characteristics associated with impaired emotional processing in psychiatric disorders. PMID:28446947

Substantiation of artificial composite-structure roof construction in top-down cut-and-fill stoping

NASA Astrophysics Data System (ADS)

Rukavishnikov, GD; Neverov, SA; Neverov, AA

2018-03-01

It has been found efficient and safe to use top-down cut-and-fill stoping with saving of the artificial backfill cost and material through the use of a solid nonuniform material composed of two components (layers). It is shown that the artificial roof can be advanced after a stope without essential change in the stope condition as compared with the classical top-down slice method, which provides higher safety of mining.

What is Bottom-Up and What is Top-Down in Predictive Coding?

PubMed Central

Rauss, Karsten; Pourtois, Gilles

2013-01-01

Everyone knows what bottom-up is, and how it is different from top-down. At least one is tempted to think so, given that both terms are ubiquitously used, but only rarely defined in the psychology and neuroscience literature. In this review, we highlight the problems and limitations of our current understanding of bottom-up and top-down processes, and we propose a reformulation of this distinction in terms of predictive coding. PMID:23730295

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

Treesearch

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...

A Top-down versus a Bottom-up Hidden-variables Description of the Stern-Gerlach Experiment

NASA Astrophysics Data System (ADS)

Arsenijević, M.; Jeknić-Dugić, J.; Dugić, M.

We employ the Stern-Gerlach experiment to highlight the basics of a minimalist, non-interpretational top-down approach to quantum foundations. Certain benefits of the "quantum structural studies" (QSS) highlightedhere are detected and discussed. While the top-down approach can be described without making any reference to the fundamental structure of a closed system, the hidden variables (HV) theory á la Bohm proves to be more subtle than it is typically regarded.

Comparing top-down and bottom-up estimates of methane emissions across multiple U.S. oil and gas basins provides insights into national O&G emissions, mitigation strategies, and research priorities

NASA Astrophysics Data System (ADS)

Lyon, D. R.; Alvarez, R.; Zavala Araiza, D.; Hamburg, S.

2017-12-01

We develop a county-level inventory of U.S. anthropogenic methane emissions by integrating multiple data sources including the Drillinginfo oil and gas (O&G) production database, Environmental Protection Agency (EPA) Greenhouse Gas Reporting Program, a previously published gridded EPA Greenhouse Gas Inventory (Maasakkers et al 2016), and recent measurements studies of O&G pneumatic devices, equipment leaks, abandoned wells, and midstream facilities. Our bottom-up estimates of total and O&G methane emissions are consistently lower than top-down, aerial mass balance estimates in ten O&G production areas. We evaluate several hypotheses for the top-down/bottom-up discrepancy including potential bias of the aerial mass balance method, temporal mismatch of top-down and bottom-up emission estimates, and source attribution errors. In most basins, the top-down/bottom-up gap cannot be explained fully without additional O&G emissions from sources not included in traditional inventories, such as super-emitters caused by malfunctions or abnormal process conditions. Top-down/bottom-up differences across multiple basins are analyzed to estimate the magnitude of these additional emissions and constrain total methane emissions from the U.S. O&G supply chain. We discuss the implications for mitigating O&G methane emissions and suggest research priorities for increasing the accuracy of future emission inventories.

Petrogenesis and depositional history of felsic pyroclastic rocks from the Melka Wakena archaeological site-complex in South central Ethiopia

NASA Astrophysics Data System (ADS)

Resom, Angesom; Asrat, Asfawossen; Gossa, Tegenu; Hovers, Erella

2018-06-01

The Melka Wakena archaeological site-complex is located at the eastern rift margin of the central sector of the Main Ethiopian Rift (MER), in south central Ethiopia. This wide, gently sloping rift shoulder, locally called the "Gadeb plain" is underlain by a succession of primary pyroclastic deposits and intercalated fluvial sediments as well as reworked volcaniclastic rocks, the top part of which is exposed by the Wabe River in the Melka Wakena area. Recent archaeological survey and excavations at this site revealed important paleoanthropological records. An integrated stratigraphic, petrological, and major and trace element geochemical study has been conducted to constrain the petrogenesis of the primary pyroclastic deposits and the depositional history of the sequence. The results revealed that the Melka Wakena pyroclastic deposits are a suite of mildly alkaline, rhyolitic pantellerites (ash falls, pumiceous ash falls and ignimbrites) and slightly dacitic ash flows. These rocks were deposited by episodic volcanic eruptions during early to middle Pleistocene from large calderas along the Wonji Fault Belt (WFB) in the central sector of the MER and from large silicic volcanic centers at the eastern rift shoulder. The rhyolitic ash falls, pumiceous ash falls and ignimbrites have been generated by fractional crystallization of a differentiating basaltic magma while the petrogenesis of the slightly dacitic ash flows involved some crustal contamination and assimilation during fractionation. Contemporaneous fluvial activities in the geomorphologically active Gadeb plain deposited overbank sedimentary sequences (archaeology bearing conglomerates and sands) along meandering river courses while a dense network of channels and streams have subsequently down-cut through the older volcanic and sedimentary sequences, redepositing the reworked volcaniclastic sediments further downstream.

Fuel Crime Conceptualization through Specialization of Ontology for Investigation Management System

NASA Astrophysics Data System (ADS)

Cybulka, Jolanta

We undertook the task of building the conceptual model of a particular economic offense, called "a fuel crime". This model is thought of as a part of a larger conceptualization, which comprises consensual semantics underlying the knowledge base of a system, aimed at supporting the teamwork of investigators of economic crimes. Because such a knowledge-based system represents a perspective on economic crimes, it should be carefully modeled. This can be done with the help of an expressive enough ontology. To achieve our goal we use the constructive descriptions and situations (c.DnS) design pattern, which enables us to construct an extensible, layered ontology in a top-down manner: c.DnS top layer is specialized by the reference ontology for investigation management system, that in turn, is specialized by the ontology of the fuel crime.

Basomedial amygdala mediates top-down control of anxiety and fear.

PubMed

Adhikari, Avishek; Lerner, Talia N; Finkelstein, Joel; Pak, Sally; Jennings, Joshua H; Davidson, Thomas J; Ferenczi, Emily; Gunaydin, Lisa A; Mirzabekov, Julie J; Ye, Li; Kim, Sung-Yon; Lei, Anna; Deisseroth, Karl

2015-11-12

Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC-BMA projection implements top-down control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway.

The role of attention in subliminal semantic processing: A mouse tracking study

PubMed Central

Xiao, Kunchen; Yamauchi, Takashi

2017-01-01

Recent evidence suggests that top-down attention facilitates unconscious semantic processing. To clarify the role of attention in unconscious semantic processing, we traced trajectories of the computer mouse in a semantic priming task and scrutinized the extent to which top-down attention enhances unconscious semantic processing in four different stimulus-onset asynchrony (SOA: 50, 200, 500, or 1000ms) conditions. Participants judged whether a target digit (e.g., “6”) was larger or smaller than five, preceded by a masked priming digit (e.g., “9”). The pre-prime duration changed randomly from trial to trial to disrupt participants’ top-down attention in an uncued condition (in a cued condition, a green square cue was presented to facilitate participants’ top-down attention). The results show that top-down attention modifies the time course of subliminal semantic processing, and the temporal attention window lasts more than 1000ms; attention facilitated by the cue may amplify semantic priming to some extent, yet the amplification effect of attention is relatively minor. PMID:28609460

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

PubMed

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.

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

PubMed

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.

Perceptual salience does not influence emotional arousal's impairing effects on top-down attention.

PubMed

Sutherland, Matthew R; McQuiggan, Douglas A; Ryan, Jennifer D; Mather, Mara

2017-06-01

Emotional arousal impairs top-down attentional control while strengthening bottom-up attentional biases. In this study, we examined whether top-down impairments due to arousal can be modulated by increasing the perceptual salience of the target stimulus. To examine this question, we briefly displayed positive and negative arousing images prior to the encoding of 2 emotionally neutral items, 1 of which was to be remembered and 1 of which was perceptually salient (the to-be-remembered and the salient items were either the same item or different items). Eye tracking was used to measure attention biases during the encoding of the 2 competing neutral items, as well as to measure pupillary responses to the preceding modulator image. Viewing emotional images, regardless of valence, impaired top-down attention to animate stimulus targets (i.e., animals), regardless of perceptual salience. However, these effects on encoding had no influence on recognition memory. Taken together, these findings reveal that exposure to emotionally arousing images impairs top-down attention to animate stimuli, regardless of whether that stimulus is perceptually salient. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Top-down mass spectrometry reveals new sequence variants of the major bovine seminal plasma protein PDC-109.

PubMed

Laitaoja, Mikko; Sankhala, Rajeshwer S; Swamy, Musti J; Jänis, Janne

2012-07-01

The major protein of bovine seminal plasma, PDC-109, is a 109-residue polypeptide that exists as a polydisperse aggregate under native conditions. The oligomeric state of this aggregate varies with ionic strength and the presence of lipids. Binding of PDC-109 to choline phospholipids on the sperm plasma membrane results in an efflux of cholesterol and choline phospholipids, which is an important step in sperm capacitation. In this study, Fourier transform ion cyclotron resonance mass spectrometry was used to analyze PDC-109 purified from bovine seminal plasma. In addition to the previously known PDC-109 variants, four new sequence variants were identified by top-down mass spectrometry. For example, a protein variant containing point mutations P10L and G14R was identified along with another form having a 14-residue truncation in the N-terminal region. Two other minor variants could also be identified from the affinity-purified PDC-109. These results demonstrate that PDC-109 is naturally produced as a mixture of several protein forms, most of which have not been detected in previous studies. Native mass spectrometry revealed that PDC-109 is exclusively monomeric at low protein concentrations, suggesting that the protein oligomers are weakly bound and can easily be disrupted. Ligand binding to PDC-109 was also investigated, and it was observed that two molecules of O-phosphorylcholine bind to each PDC-109 monomer, consistent with previous reports. Copyright © 2012 John Wiley & Sons, Ltd.

The emerging process of Top Down mass spectrometry for protein analysis: biomarkers, protein-therapeutics, and achieving high throughput†

PubMed Central

Kellie, John F.; Tran, John C.; Lee, Ji Eun; Ahlf, Dorothy R.; Thomas, Haylee M.; Ntai, Ioanna; Catherman, Adam D.; Durbin, Kenneth R.; Zamdborg, Leonid; Vellaichamy, Adaikkalam; Thomas, Paul M.

2011-01-01

Top Down mass spectrometry (MS) has emerged as an alternative to common Bottom Up strategies for protein analysis. In the Top Down approach, intact proteins are fragmented directly in the mass spectrometer to achieve both protein identification and characterization, even capturing information on combinatorial post-translational modifications. Just in the past two years, Top Down MS has seen incremental advances in instrumentation and dedicated software, and has also experienced a major boost from refined separations of whole proteins in complex mixtures that have both high recovery and reproducibility. Combined with steadily advancing commercial MS instrumentation and data processing, a high-throughput workflow covering intact proteins and polypeptides up to 70 kDa is directly visible in the near future. PMID:20711533

Top-down modulation: Bridging selective attention and working memory

PubMed Central

Gazzaley, Adam; Nobre, Anna C.

2012-01-01

Selective attention, the ability to focus our cognitive resources on information relevant to our goals, influences working memory (WM) performance. Indeed, attention and working memory are increasingly viewed as overlapping constructs. Here, we review recent evidence from human neurophysiological studies demonstrating that top-down modulation serves as a common neural mechanism underlying these two cognitive operations. The core features include activity modulation in stimulus-selective sensory cortices with concurrent engagement of prefrontal and parietal control regions that function as sources of top-down signals. Notably, top-down modulation is engaged during both stimulus-present and stimulus-absent stages of WM tasks, i.e., expectation of an ensuing stimulus to be remembered, selection and encoding of stimuli, maintenance of relevant information in mind and memory retrieval. PMID:22209601

Goal-directed control with cortical units that are gated by both top-down feedback and oscillatory coherence.

PubMed

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.

Goal-directed control with cortical units that are gated by both top-down feedback and oscillatory coherence

PubMed Central

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

A Physical Mechanism for the Asymmetry in Top-Down and Bottom-Up Diffusion.

NASA Astrophysics Data System (ADS)

Wyngaard, J. C.

1987-04-01

Recent large-eddy simulations of the vertical diffusion of a passive, conservative scalar through the convective boundary layer (CBL) show strikingly different eddy diffusivity profiles in the `top-down' and `bottom-up' cases. These results indicate that for a given turbulent velocity field and associated scalar flux, the mean change in scalar mixing ratio across the CBL is several times larger if the flux originates at the top of the boundary layer (i.e., in top-down diffusion) rather than at the bottom. The large-eddy simulation (LES) data show that this asymmetry is due to a breakdown of the eddy-diffusion concept.A simple updraft-downdraft model of the CBL reveals a physical mechanism that could cause this unexpected behavior. The large, positive skewness of the convectively driven vertical velocity gives an appreciably higher probability of downdrafts than updrafts; this excess probability of downdrafts, interacting with the time changes of the mean mixing ratio caused by the nonstationarity of the bottom-up and top-down diffusion processes, decreases the equilibrium value of mean mixing-ratio jump across the mixed layer in the bottom-up case and increases it in the top-down case. The resulting diffusion asymmetry agrees qualitatively with that found through LES.

Spatio-temporal Outlier Detection in Precipitation Data

NASA Astrophysics Data System (ADS)

Wu, Elizabeth; Liu, Wei; Chawla, Sanjay

The detection of outliers from spatio-temporal data is an important task due to the increasing amount of spatio-temporal data available and the need to understand and interpret it. Due to the limitations of current data mining techniques, new techniques to handle this data need to be developed. We propose a spatio-temporal outlier detection algorithm called Outstretch, which discovers the outlier movement patterns of the top-k spatial outliers over several time periods. The top-k spatial outliers are found using the Exact-Grid Top- k and Approx-Grid Top- k algorithms, which are an extension of algorithms developed by Agarwal et al. [1]. Since they use the Kulldorff spatial scan statistic, they are capable of discovering all outliers, unaffected by neighbouring regions that may contain missing values. After generating the outlier sequences, we show one way they can be interpreted, by comparing them to the phases of the El Niño Southern Oscilliation (ENSO) weather phenomenon to provide a meaningful analysis of the results.

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

PubMed

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

2018-06-01

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, MS 3 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. Graphical Abstract ᅟ.

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

NASA Astrophysics Data System (ADS)

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.

Top-down guidance in visual search for facial expressions.

PubMed

Hahn, Sowon; Gronlund, Scott D

2007-02-01

Using a visual search paradigm, we investigated how a top-down goal modified attentional bias for threatening facial expressions. In two experiments, participants searched for a facial expression either based on stimulus characteristics or a top-down goal. In Experiment 1 participants searched for a discrepant facial expression in a homogenous crowd of faces. Consistent with previous research, we obtained a shallower response time (RT) slope when the target face was angry than when it was happy. In Experiment 2, participants searched for a specific type of facial expression (allowing a top-down goal). When the display included a target, we found a shallower RT slope for the angry than for the happy face search. However, when an angry or happy face was present in the display in opposition to the task goal, we obtained equivalent RT slopes, suggesting that the mere presence of an angry face in opposition to the task goal did not support the well-known angry face superiority effect. Furthermore, RT distribution analyses supported the special status of an angry face only when it was combined with the top-down goal. On the basis of these results, we suggest that a threatening facial expression may guide attention as a high-priority stimulus in the absence of a specific goal; however, in the presence of a specific goal, the efficiency of facial expression search is dependent on the combined influence of a top-down goal and the stimulus characteristics.

Ultra Rapid Object Categorization: Effects of Level, Animacy and Context

PubMed Central

Praß, Maren; Grimsen, Cathleen; König, Martina; Fahle, Manfred

2013-01-01

It is widely agreed that in object categorization bottom-up and top-down influences interact. How top-down processes affect categorization has been primarily investigated in isolation, with only one higher level process at a time being manipulated. Here, we investigate the combination of different top-down influences (by varying the level of category, the animacy and the background of the object) and their effect on rapid object categorization. Subjects participated in a two-alternative forced choice rapid categorization task, while we measured accuracy and reaction times. Subjects had to categorize objects on the superordinate, basic or subordinate level. Objects belonged to the category animal or vehicle and each object was presented on a gray, congruent (upright) or incongruent (inverted) background. The results show that each top-down manipulation impacts object categorization and that they interact strongly. The best categorization was achieved on the superordinate level, providing no advantage for basic level in rapid categorization. Categorization between vehicles was faster than between animals on the basic level and vice versa on the subordinate level. Objects in homogenous gray background (context) yielded better overall performance than objects embedded in complex scenes, an effect most prominent on the subordinate level. An inverted background had no negative effect on object categorization compared to upright scenes. These results show how different top-down manipulations, such as category level, category type and background information, are related. We discuss the implications of top-down interactions on the interpretation of categorization results. PMID:23840810

Ultra rapid object categorization: effects of level, animacy and context.

PubMed

Praß, Maren; Grimsen, Cathleen; König, Martina; Fahle, Manfred

2013-01-01

It is widely agreed that in object categorization bottom-up and top-down influences interact. How top-down processes affect categorization has been primarily investigated in isolation, with only one higher level process at a time being manipulated. Here, we investigate the combination of different top-down influences (by varying the level of category, the animacy and the background of the object) and their effect on rapid object categorization. Subjects participated in a two-alternative forced choice rapid categorization task, while we measured accuracy and reaction times. Subjects had to categorize objects on the superordinate, basic or subordinate level. Objects belonged to the category animal or vehicle and each object was presented on a gray, congruent (upright) or incongruent (inverted) background. The results show that each top-down manipulation impacts object categorization and that they interact strongly. The best categorization was achieved on the superordinate level, providing no advantage for basic level in rapid categorization. Categorization between vehicles was faster than between animals on the basic level and vice versa on the subordinate level. Objects in homogenous gray background (context) yielded better overall performance than objects embedded in complex scenes, an effect most prominent on the subordinate level. An inverted background had no negative effect on object categorization compared to upright scenes. These results show how different top-down manipulations, such as category level, category type and background information, are related. We discuss the implications of top-down interactions on the interpretation of categorization results.

Advanced Plant Habitat - Packing and Planting Seeds

NASA Image and Video Library

2017-02-15

Inside a laboratory at the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, scientists prepared the science carrier, or base, of the Advanced Plant Habitat (APH). A growing substrate called arcillite was packed down in the base and coverings were secured on top of the base. Developed by NASA and ORBITEC of Madison, Wisconsin, the APH is the largest plant chamber built for the agency. It is a fully automated plant growth facility that will be used to conduct bioscience research on the International Space Station. The APH will be delivered to the space station aboard future Commercial Resupply Services missions.

Bottom-up driven involuntary auditory evoked field change: constant sound sequencing amplifies but does not sharpen neural activity.

PubMed

Okamoto, Hidehiko; Stracke, Henning; Lagemann, Lothar; Pantev, Christo

2010-01-01

The capability of involuntarily tracking certain sound signals during the simultaneous presence of noise is essential in human daily life. Previous studies have demonstrated that top-down auditory focused attention can enhance excitatory and inhibitory neural activity, resulting in sharpening of frequency tuning of auditory neurons. In the present study, we investigated bottom-up driven involuntary neural processing of sound signals in noisy environments by means of magnetoencephalography. We contrasted two sound signal sequencing conditions: "constant sequencing" versus "random sequencing." Based on a pool of 16 different frequencies, either identical (constant sequencing) or pseudorandomly chosen (random sequencing) test frequencies were presented blockwise together with band-eliminated noises to nonattending subjects. The results demonstrated that the auditory evoked fields elicited in the constant sequencing condition were significantly enhanced compared with the random sequencing condition. However, the enhancement was not significantly different between different band-eliminated noise conditions. Thus the present study confirms that by constant sound signal sequencing under nonattentive listening the neural activity in human auditory cortex can be enhanced, but not sharpened. Our results indicate that bottom-up driven involuntary neural processing may mainly amplify excitatory neural networks, but may not effectively enhance inhibitory neural circuits.

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

PubMed Central

Wang, Jiaqiu

2015-01-01

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. PMID:26682551

Learning enhances the relative impact of top-down processing in the visual cortex

PubMed Central

Makino, Hiroshi; Komiyama, Takaki

2015-01-01

Theories have proposed that in sensory cortices learning can enhance top-down modulation by higher brain areas while reducing bottom-up sensory inputs. To address circuit mechanisms underlying this process, we examined the activity of layer 2/3 (L2/3) excitatory neurons in the mouse primary visual cortex (V1) as well as L4 neurons, the main bottom-up source, and long-range top-down projections from the retrosplenial cortex (RSC) during associative learning over days using chronic two-photon calcium imaging. During learning, L4 responses gradually weakened, while RSC inputs became stronger. Furthermore, L2/3 acquired a ramp-up response temporal profile with learning, coinciding with a similar change in RSC inputs. Learning also reduced the activity of somatostatin-expressing inhibitory neurons (SOM-INs) in V1 that could potentially gate top-down inputs. Finally, RSC inactivation or SOM-IN activation was sufficient to partially reverse the learning-induced changes in L2/3. Together, these results reveal a learning-dependent dynamic shift in the balance between bottom-up and top-down information streams and uncover a role of SOM-INs in controlling this process. PMID:26167904

Evaluation of a Fuel-Based Oil and Gas Inventory of Nitrogen Oxides with Top-Down Emissions

NASA Astrophysics Data System (ADS)

Mcdonald, B. C.; Gorchov Negron, A.; McKeen, S. A.; Peischl, J.; Gilman, J.; Ahmadov, R.; Frost, G. J.; Ryerson, T. B.; Thompson, C. R.; Trainer, M.

2017-12-01

Several studies have highlighted overestimates in anthropogenic emissions of nitrogen oxides (NOx) for the U.S., with particular attention on the mobile source sector. In this study, we explore whether there could be overestimates in the emissions of NOx from oil and gas production regions. We construct a bottom-up inventory using publicly available fuel use records of the industry and emission factors reported in the literature. We compare both the NEI 2011 and the fuel-based inventory with top-down emission fluxes derived by aircraft and ground-based field measurement campaigns by NOAA that occurred in 2012-13, including for basins located in Uintah, Haynesville, Marcellus, and Fayetteville. Compared to the top-down fluxes, the NEI overestimates NOx by a factor of 2 across the four basins. However, the discrepancies are not uniform, reflecting variability in oil and gas engine activity and NOx emission factors. We explore this variability with our fuel-based inventory and perform a Monte Carlo analysis to assess uncertainties in emissions. We find that on average the fuel-based inventory improves the agreement with the top-down emissions, and that the top-down emissions are within the uncertainties of our analysis.

Premature asphalt concrete pavement cracking.

DOT National Transportation Integrated Search

2015-06-01

Recently, the Oregon Department of Transportation (ODOT) has identified hot mix asphalt concrete : (HMAC) pavements that have displayed top-down cracking within three years of construction. The objective of : the study was to evaluate the top-down cr...

Top down, bottom up structured programming and program structuring

NASA Technical Reports Server (NTRS)

Hamilton, M.; Zeldin, S.

1972-01-01

New design and programming techniques for shuttle software. Based on previous Apollo experience, recommendations are made to apply top-down structured programming techniques to shuttle software. New software verification techniques for large software systems are recommended. HAL, the higher order language selected for the shuttle flight code, is discussed and found to be adequate for implementing these techniques. Recommendations are made to apply the workable combination of top-down, bottom-up methods in the management of shuttle software. Program structuring is discussed relevant to both programming and management techniques.

Associated Information Increases Subjective Perception of Duration.

PubMed

Schweitzer, Richard; Trapp, Sabrina; Bar, Moshe

2017-08-01

Our sense of time is prone to various biases. For instance, one factor that can dilate an event's perceived duration is the violation of predictions; when a series of repeated stimuli is interrupted by an unpredictable oddball. On the other hand, when the probability of a repetition itself is manipulated, predictable conditions can also increase estimated duration. This suggests that manipulations of expectations have different or even opposing effects on time perception. In previous studies, expectations were generated because stimuli were repeated or because the likelihood of a sequence or a repetition was varied. In the natural environment, however, expectations are often built via associative processes, for example, the context of a kitchen promotes the expectation of plates, appliances, and other associated objects. Here, we manipulated such association-based expectations by using oddballs that were either contextually associated or nonassociated with the standard items. We find that duration was more strongly overestimated for contextually associated oddballs. We reason that top-down attention is biased toward associated information, and thereby dilates subjective duration for associated oddballs. Based on this finding, we propose an interplay between top-down attention and predictive processing in the perception of time.

Label-free, direct localization and relative quantitation of the RNA nucleobase methylations m6A, m5C, m3U, and m5U by top-down mass spectrometry.

PubMed

Glasner, Heidelinde; Riml, Christian; Micura, Ronald; Breuker, Kathrin

2017-07-27

Nucleobase methylations are ubiquitous posttranscriptional modifications of ribonucleic acids (RNA) that can substantially increase the structural diversity of RNA in a highly dynamic fashion with implications for gene expression and human disease. However, high throughput, deep sequencing does not generally provide information on posttranscriptional modifications (PTMs). A promising alternative approach for the characterization of PTMs, i.e. their identification, localization, and relative quantitation, is top-down mass spectrometry (MS). In this study, we have investigated how specific nucleobase methylations affect RNA ionization in electrospray ionization (ESI), and backbone cleavage in collisionally activated dissociation (CAD) and electron detachment dissociation (EDD). For this purpose, we have developed two new approaches for the characterization of RNA methylations in mixtures of either isomers of RNA or nonisomeric RNA forms. Fragment ions from dissociation experiments were analyzed to identify the modification type, to localize the modification sites, and to reveal the site-specific, relative extent of modification for each site. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Top of well partially covered by boards, looking down to ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Top of well partially covered by boards, looking down to west - Neville-Kanode Farmstead, Well, East side of U.S. Highway 81, 2.5 miles south of Kansas-Nebraska state line, Munden, Republic County, KS

Heuristic for learning common emitter amplification with bipolar transistors

NASA Astrophysics Data System (ADS)

Staffas, Kjell

2017-11-01

Mathematics in engineering education causes many thresholds in the courses because of the demand of abstract conceptualisation. Electronics depend heavily on more or less complex mathematics. Therefore the concepts of analogue electronics are hard to learn since a great deal of students struggle with the calculations and procedures needed. A survey was done focusing on students' struggle to pass a course in analogue electronics by introducing a top-down perspective and the revised taxonomy of Bloom. From a top-down perspective you can create learning environments from any spot in the taxonomy using a step-by-step approach of the verbs understand and apply. Three textbooks with a top-down perspective on analogue electronics are analysed on the concept of amplifying with a transistor circuit. The study claims issues when losing the top-down perspective to present concepts and procedures of the content to be learned.

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

PubMed Central

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

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

PubMed

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.

Use of Multichannel Near Infrared Spectroscopy to Study Relationships Between Brain Regions and Neurocognitive Tasks of Selective/Divided Attention and 2-Back Working Memory.

PubMed

Tomita, Nozomi; Imai, Shoji; Kanayama, Yusuke; Kawashima, Issaku; Kumano, Hiroaki

2017-06-01

While dichotic listening (DL) was originally intended to measure bottom-up selective attention, it has also become a tool for measuring top-down selective attention. This study investigated the brain regions related to top-down selective and divided attention DL tasks and a 2-back task using alphanumeric and Japanese numeric sounds. Thirty-six healthy participants underwent near-infrared spectroscopy scanning while performing a top-down selective attentional DL task, a top-down divided attentional DL task, and a 2-back task. Pearson's correlations were calculated to show relationships between oxy-Hb concentration in each brain region and the score of each cognitive task. Different brain regions were activated during the DL and 2-back tasks. Brain regions activated in the top-down selective attention DL task were the left inferior prefrontal gyrus and left pars opercularis. The left temporopolar area was activated in the top-down divided attention DL task, and the left frontopolar area and left dorsolateral prefrontal cortex were activated in the 2-back task. As further evidence for the finding that each task measured different cognitive and brain area functions, neither the percentages of correct answers for the three tasks nor the response times for the selective attentional task and the divided attentional task were correlated to one another. Thus, the DL and 2-back tasks used in this study can assess multiple areas of cognitive, brain-related dysfunction to explore their relationship to different psychiatric and neurodevelopmental disorders.

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

NASA Astrophysics Data System (ADS)

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.

Cloning and analysis of a cDNA encoding an endo-polygalacturonase expressed during the desiccation period of the silique-valves of turnip-tops (Brassica rapa L. cv. Rapa).

PubMed

Rodríguez-Gacio, María del Carmen; Nicolás, Carlos; Matilla, Angel J

2004-02-01

During zygotic embryogenesis of turnip-tops (Brassica rapa L. cv. Rapa), the polygalacturonase activity (PG; EC 3.2.1.15), measured as a decrease in viscosity of polygalacturonic acid, reached a high when the desiccation process in the seeded silique was triggered and the valves had lost more than 70-75% of their moisture (45-50 DPA). The PG activity was not detected in any phases of developing seeds. This work also characterizes a cDNA with an open reading frame of 1303 bp and that codes for a putative PG called BrPG1. This falls into the category of clade-B, which includes PG related to shattering and abscission processes. The deduced BrPG1 sequence predicted a 434-residue-long precursor protein (46.7kDa) with a transit peptide sequence 23 amino acids long. A molecular mass of 44.3 kDa was calculated for the mature form of BrPG1, which showed high sequence similarity to PGA1 (97%) of B. napus (X98373) and ADPG1 (87%) of Arabidopsis thaliana (AJ002532). All conserved amino acids at the catalytic site of PGs belonging to clade-B were preserved on BrPG1. This BrPG1 gene was specifically expressed in the silique valves of turnip-tops and was temporally expressed at the beginning of its desiccation.

Transforming Science Data for GIS: How to Find and Use NASA Earth Observation Data Without Being a Rocket Scientist

NASA Technical Reports Server (NTRS)

Bagwell, Ross; Peters, Byron; Berrick, Stephen

2017-01-01

NASAs Earth Observing System Data Information System (EOSDIS) manages Earth Observation satellites and the Distributed Active Archive Centers (DAACs), where the data is stored and processed. The challenge is that Earth Observation data is complicated. There is plenty of data available, however, the science teams have had a top-down approach: define what it is you are trying to study -select a set of satellite(s) and sensor(s), and drill down for the data.Our alternative is to take a bottom-up approach using eight environmental fields of interest as defined by the Group on Earth Observations (GEO) called Societal Benefit Areas (SBAs): Disaster Resilience (DR) Public Health Surveillance (PHS) Energy and Mineral Resource Management (EMRM) Water Resources Management (WRM) Infrastructure and Transport Management (ITM) Sustainable Urban Development (SUD) Food Security and Sustainable Agriculture (FSSA) Biodiversity and Ecosystems Sustainability (BES).

Exploring the complex free-energy landscape of the simplest glass by rheology.

PubMed

Jin, Yuliang; Yoshino, Hajime

2017-04-11

For amorphous solids, it has been intensely debated whether the traditional view on solids, in terms of the ground state and harmonic low energy excitations on top of it, such as phonons, is still valid. Recent theoretical developments of amorphous solids revealed the possibility of unexpectedly complex free-energy landscapes where the simple harmonic picture breaks down. Here we demonstrate that standard rheological techniques can be used as powerful tools to examine nontrivial consequences of such complex free-energy landscapes. By extensive numerical simulations on a hard sphere glass under quasistatic shear at finite temperatures, we show that above the so-called Gardner transition density, the elasticity breaks down, the stress relaxation exhibits slow, and ageing dynamics and the apparent shear modulus becomes protocol-dependent. Being designed to be reproducible in laboratories, our approach may trigger explorations of the complex free-energy landscapes of a large variety of amorphous materials.

Exploring the complex free-energy landscape of the simplest glass by rheology

NASA Astrophysics Data System (ADS)

Jin, Yuliang; Yoshino, Hajime

2017-04-01

For amorphous solids, it has been intensely debated whether the traditional view on solids, in terms of the ground state and harmonic low energy excitations on top of it, such as phonons, is still valid. Recent theoretical developments of amorphous solids revealed the possibility of unexpectedly complex free-energy landscapes where the simple harmonic picture breaks down. Here we demonstrate that standard rheological techniques can be used as powerful tools to examine nontrivial consequences of such complex free-energy landscapes. By extensive numerical simulations on a hard sphere glass under quasistatic shear at finite temperatures, we show that above the so-called Gardner transition density, the elasticity breaks down, the stress relaxation exhibits slow, and ageing dynamics and the apparent shear modulus becomes protocol-dependent. Being designed to be reproducible in laboratories, our approach may trigger explorations of the complex free-energy landscapes of a large variety of amorphous materials.

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

NASA Astrophysics Data System (ADS)

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.

Basomedial amygdala mediates top–down control of anxiety and fear

PubMed Central

Adhikari, Avishek; Lerner, Talia N.; Finkelstein, Joel; Pak, Sally; Jennings, Joshua H.; Davidson, Thomas J.; Ferenczi, Emily; Gunaydin, Lisa A.; Mirzabekov, Julie J.; Ye, Li; Kim, Sung-Yon; Lei, Anna; Deisseroth, Karl

2016-01-01

Anxiety-related conditions are among the most difficult neuropsychiatric diseases to treat pharmacologically, but respond to cognitive therapies. There has therefore been interest in identifying relevant top-down pathways from cognitive control regions in medial prefrontal cortex (mPFC). Identification of such pathways could contribute to our understanding of the cognitive regulation of affect, and provide pathways for intervention. Previous studies have suggested that dorsal and ventral mPFC subregions exert opposing effects on fear, as do subregions of other structures. However, precise causal targets for top-down connections among these diverse possibilities have not been established. Here we show that the basomedial amygdala (BMA) represents the major target of ventral mPFC in amygdala in mice. Moreover, BMA neurons differentiate safe and aversive environments, and BMA activation decreases fear-related freezing and high-anxiety states. Lastly, we show that the ventral mPFC–BMA projection implements top-down control of anxiety state and learned freezing, both at baseline and in stress-induced anxiety, defining a broadly relevant new top-down behavioural regulation pathway. PMID:26536109

Bottom-up meets top-down: tailored raspberry-like Fe 3 O 4 –Pt nanocrystal superlattices

DOE PAGES

Qiu, Fen; Vervuurt, René H. J.; Verheijen, Marcel A.; ...

2018-01-01

Bottom up colloidal synthesis is combined with top down atomic layer deposition to achieve raspberry-like Pt-decorated Fe 3 O 4 nanoparticle superlattices with good metal–oxide–metal contact for photoelectrocatalysis.

Bottom-up meets top-down: tailored raspberry-like Fe 3 O 4 –Pt nanocrystal superlattices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Fen; Vervuurt, René H. J.; Verheijen, Marcel A.

Bottom up colloidal synthesis is combined with top down atomic layer deposition to achieve raspberry-like Pt-decorated Fe 3 O 4 nanoparticle superlattices with good metal–oxide–metal contact for photoelectrocatalysis.

Geographical and experimental contexts modulate the effect of warming on top-down control: a meta-analysis.

PubMed

Marino, Nicholas Dos Anjos Cristiano; Romero, Gustavo Quevedo; Farjalla, Vinicius Fortes

2018-03-01

Ecologists have extensively investigated the effect of warming on consumer-resource interactions, with experiments revealing that warming can strengthen, weaken or have no net effect on top-down control of resources. These experiments have inspired a body of theoretical work to explain the variation in the effect of warming on top-down control. However, there has been no quantitative attempt to reconcile theory with outcomes from empirical studies. To address the gap between theory and experiment, we performed a meta-analysis to examine the combined effect of experimental warming and top-down control on resource biomass and determined potential sources of variation across experiments. We show that differences in experimental outcomes are related to systematic variation in the geographical distribution of studies. Specifically, warming strengthened top-down control when experiments were conducted in colder regions, but had the opposite effect in warmer regions. Furthermore, we found that differences in the thermoregulation strategy of the consumer and openness of experimental arenas to dispersal can contribute to some deviation from the overall geographical pattern. These results reconcile empirical findings and support the expectation of geographical variation in the response of consumer-resource interactions to warming. © 2018 John Wiley & Sons Ltd/CNRS.

Assessing the Gap Between Top-down and Bottom-up Measured Methane Emissions in Indianapolis, IN.

NASA Astrophysics Data System (ADS)

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.

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

PubMed Central

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

2016-01-01

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. PMID:27808125

Heart rate variability indices as bio-markers of top-down self-regulatory mechanisms: A meta-analytic review.

PubMed

Holzman, Jacob B; Bridgett, David J

2017-03-01

Theoretical perspectives posit that heart-rate variability (HRV) reflects self-regulatory capacity and therefore can be employed as a bio-marker of top-down self-regulation (the ability to regulate behavioral, cognitive, and emotional processes). However, existing findings of relations between self-regulation and HRV indices are mixed. To clarify the nature of such relations, we conducted a meta-analysis of 123 studies (N=14,347) reporting relations between HRV indices and aspects of top-down self-regulation (e.g., executive functioning, emotion regulation, effortful control). A significant, albeit small, effect was observed (r=0.09) such that greater HRV was related to better top-down self-regulation. Differences in relations were negligible across aspects of self-regulation, self-regulation measurement methods, HRV computational techniques, at-risk compared with healthy samples, and the context of HRV measurement. Stronger relations were observed in older relative to younger samples and in published compared to unpublished studies. These findings generally support the notion that HRV indices can tentatively be employed as bio-markers of top-down self-regulation. Conceptual and theoretical implications, and critical gaps in current knowledge to be addressed by future work, are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Perceptual Learning via Modification of Cortical Top-Down Signals

PubMed Central

Schäfer, Roland; Vasilaki, Eleni; Senn, Walter

2007-01-01

The primary visual cortex (V1) is pre-wired to facilitate the extraction of behaviorally important visual features. Collinear edge detectors in V1, for instance, mutually enhance each other to improve the perception of lines against a noisy background. The same pre-wiring that facilitates line extraction, however, is detrimental when subjects have to discriminate the brightness of different line segments. How is it possible to improve in one task by unsupervised practicing, without getting worse in the other task? The classical view of perceptual learning is that practicing modulates the feedforward input stream through synaptic modifications onto or within V1. However, any rewiring of V1 would deteriorate other perceptual abilities different from the trained one. We propose a general neuronal model showing that perceptual learning can modulate top-down input to V1 in a task-specific way while feedforward and lateral pathways remain intact. Consistent with biological data, the model explains how context-dependent brightness discrimination is improved by a top-down recruitment of recurrent inhibition and a top-down induced increase of the neuronal gain within V1. Both the top-down modulation of inhibition and of neuronal gain are suggested to be universal features of cortical microcircuits which enable perceptual learning. PMID:17715996

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

PubMed

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).

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed Central

2016-01-01

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. PMID:27807271

The value of using top-down and bottom-up approaches for building trust and transparency in biobanking.

PubMed

Meslin, Eric M

2010-01-01

With the domestic and international proliferation of biobanks and their associated connections to health information databases, scholarly attention has been turning from the ethical issues arising from the construction of biobanks to the ethical issues that emerge in their operation and management. Calls for greater transparency in governance structures, coupled with stern reminders of the value of maintaining public trust, are seen as critical components in the success of these resources. Two different approaches have been adopted for addressing these types of ethical issues: the first is a 'top-down' approach which focuses on developing policy, procedures, regulations and guidelines to aid decision-makers. The second is a 'bottom-up' approach, which begins with those who are most affected by the issues and attempts to inductively develop consensus recommendations and policy. While both approaches have merit, I argue that more work needs to be done on 'bottom-up' strategies if trust and transparency are to be more than mere slogans. Using 2 case examples from Indiana, the paper summarizes data from a set of surveys we recently conducted that address issues arising from biobanks that provide some insight into issues associated with trust and transparency. Copyright 2010 S. Karger AG, Basel.

Degassing and differentiation in subglacial volcanoes, Iceland

USGS Publications Warehouse

Moore, J.G.; Calk, L.C.

1991-01-01

Within the neovolcanic zones of Iceland many volcanoes grew upward through icecaps that have subsequently melted. These steep-walled and flat-topped basaltic subglacial volcanoes, called tuyas, are composed of a lower sequence of subaqueously erupted, pillowed lavas overlain by breccias and hyaloclastites produced by phreatomagmatic explosions in shallow water, capped by a subaerially erupted lava plateau. Glass and whole-rock analyses of samples collected from six tuyas indicate systematic variations in major elements showing that the individual volcanoes are monogenetic, and that commonly the tholeiitic magmas differentiated and became more evolved through the course of the eruption that built the tuya. At Herdubreid, the most extensively studies tuya, the upward change in composition indicates that more than 50 wt.% of the first erupted lavas need crystallize over a range of 60??C to produce the last erupted lavas. The S content of glass commonly decreases upward in the tuyas from an average of about 0.08 wt.% at the base to < 0.02 wt.% in the subaerially erupted lava at the top, and is a measure of the depth of water (or ice) above the eruptive vent. The extensive subsurface crystallization that generates the more evolved, lower-temperature melts during the growth of the tuyas, apparently results from cooling and degassing of magma contained in shallow magma chambers and feeders beneath the volcanoes. Cooling may result from percolation of meltwater down cracks, vaporization, and cycling in a hydrothermal circulation. Degassing occurs when progressively lower pressure eruption (as the volcanic vent grows above the ice/water surface) lowers the volatile vapour pressure of subsurface melt, thus elevating the temperature of the liquidus and hastening liquid-crystal differentiation. ?? 1991.

RNA-seq methods for identifying differentially expressed gene in human pancreatic islet cells treated with pro-inflammatory cytokines.

PubMed

Li, Bo; Bi, Chang Long; Lang, Ning; Li, Yu Ze; Xu, Chao; Zhang, Ying Qi; Zhai, Ai Xia; Cheng, Zhi Feng

2014-01-01

Type 1 diabetes is a chronic autoimmune disease in which pancreatic beta cells are killed by the infiltrating immune cells as well as the cytokines released by these cells. Many studies indicate that inflammatory mediators have an essential role in this disease. In the present study, we profiled the transcriptome in human islets of langerhans under control conditions or following exposure to the pro-inflammatory cytokines based on the RNA sequencing dataset downloaded from SRA database. After filtered the low-quality ones, the RNA readers was aligned to human genome hg19 by TopHat and then assembled by Cufflinks. The expression value of each transcript was calculated and consequently differentially expressed genes were screened out. Finally, a total of 63 differentially expressed genes were identified including 60 up-regulated and three down-regulated genes. GBP5 and CXCL9 stood out as the top two most up-regulated genes in cytokines treated samples with the log2 fold change of 12.208 and 10.901, respectively. Meanwhile, PTF1A and REG3G were identified as the top two most down-regulated genes with the log2 fold change of -3.759 and -3.606, respectively. Of note, we also found 262 lncRNAs (long non-coding RNA), 177 of which were inferred as novel lncRNAs. Further in-depth follow-up analysis of the transcriptional regulation reported in this study may shed light on the specific function of these lncRNA.

A new technique based on current measurement for nanoscale ferroelectricity assessment: Nano-positive up negative down

NASA Astrophysics Data System (ADS)

Martin, Simon; Baboux, Nicolas; Albertini, David; Gautier, Brice

2017-02-01

In this paper, we propose a new procedure which aims at measuring the polarisation switching current at the nanoscale on ferroelectric thin films with the atomic force microscope tip used as a top electrode. Our technique is an adaptation of the so-called positive up negative down method commonly operated on large electrodes. The main obstacle that must be overcome to implement such measurement is the enhancement of the signal to noise ratio, in a context where the stray capacitance of the sample/tip/lever/lever holder system generates a dielectric displacement current several orders of magnitude higher than the current to be measured. This problem is solved by the subtraction of the displacement current through a reference capacitance. For the first time, we show an example of nanoscale positive up negative down measurement of the polarisation charge on a PbZrTiO3 thin film and compare the measured value with paraelectric samples. From the comparison with macroscopic measurement, we deduce the effective area of contact between the tip and the sample.

A neural mechanism of dynamic gating of task-relevant information by top-down influence in primary visual cortex.

PubMed

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.

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

PubMed Central

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. PMID:26441701

Top-down Versus Step-up Prescribing Strategies for Tumor Necrosis Factor Alpha Inhibitors in Children and Young Adults with Inflammatory Bowel Disease.

PubMed

Lee, Wan-Ju; Briars, Leslie; Lee, Todd A; Calip, Gregory S; Suda, Katie J; Schumock, Glen T

2016-10-01

Early initiation of tumor necrosis factor-alpha inhibitor (TNFI) therapy for children and young adults with inflammatory bowel disease (IBD) is not well described. We conducted a retrospective cohort study of children and young adults (≤24 yr) newly diagnosed with IBD using health insurance claims from 2009 to 2013. The conventional "step-up" approach was defined as TNFI initiation >30 days after first IBD medication prescription, whereas the "top-down" approach was defined as new TNFI prescription within 30 days of first IBD medication prescription. Switching rates, time to initiation, discontinuation, and adherence to TNFIs were compared between the 2 strategies. A total of 11,962 IBD patients were identified. Among 3300 TNFI users, 1298 (39.3%) were treated with the top-down approach, whereas 2002 (60.7%) were treated with the step-up approach. Top-down approach use increased from 31.4% to 49.8% during the 5-year period, and under this approach, most patients were treated with TNFIs alone. Time to TNFI initiation was shorter for patients diagnosed in more recent years. Patients treated with the top-down strategy had lower rates of corticosteroid use (32.5% versus 94.2%) compared with step-up treatment but presented a higher rate of TNFI discontinuation. The 2 strategies both exhibited high adherence (mean proportion of days covered: 83.7%-95.4%). Early TNFI initiation increased over time for children and young adults with IBD and was related to lower rates of corticosteroid use compared with the conventional approach. However, the higher rate of TNFI discontinuation under the top-down approach requires further examination.

Mixed method versus full top-down microcosting for organ recovery cost assessment in a French hospital group.

PubMed

Hrifach, Abdelbaste; Brault, Coralie; Couray-Targe, Sandrine; Badet, Lionel; Guerre, Pascale; Ganne, Christell; Serrier, Hassan; Labeye, Vanessa; Farge, Pierre; Colin, Cyrille

2016-12-01

The costing method used can change the results of economic evaluations. Choosing the appropriate method to assess the cost of organ recovery is an issue of considerable interest to health economists, hospitals, financial managers and policy makers in most developed countries. The main objective of this study was to compare a mixed method, combining top-down microcosting and bottom-up microcosting versus full top-down microcosting to assess the cost of organ recovery in a French hospital group. The secondary objective was to describe the cost of kidney, liver and pancreas recovery from French databases using the mixed method. The resources consumed for each donor were identified and valued using the proposed mixed method and compared to the full top-down microcosting approach. Data on kidney, liver and pancreas recovery were collected from a medico-administrative French database for the years 2010 and 2011. Related cost data were recovered from the hospital cost accounting system database for 2010 and 2011. Statistical significance was evaluated at P < 0.05. All the median costs for organ recovery differ significantly between the two costing methods (non-parametric test method; P < 0.01). Using the mixed method, the median cost for recovering kidneys was found to be €5155, liver recovery was €2528 and pancreas recovery was €1911. Using the full top-down microcosting method, median costs were found to be 21-36% lower than with the mixed method. The mixed method proposed appears to be a trade-off between feasibility and accuracy for the identification and valuation of cost components when calculating the cost of organ recovery in comparison to the full top-down microcosting approach.

Prefrontal inhibition of threat processing reduces working memory interference

PubMed Central

Clarke, Robert; Johnstone, Tom

2013-01-01

Bottom-up processes can interrupt ongoing cognitive processing in order to adaptively respond to emotional stimuli of high potential significance, such as those that threaten wellbeing. However it is vital that this interference can be modulated in certain contexts to focus on current tasks. Deficits in the ability to maintain the appropriate balance between cognitive and emotional demands can severely impact on day-to-day activities. This fMRI study examined this interaction between threat processing and cognition; 18 adult participants performed a visuospatial working memory (WM) task with two load conditions, in the presence and absence of anxiety induction by threat of electric shock. Threat of shock interfered with performance in the low cognitive load condition; however interference was eradicated under high load, consistent with engagement of emotion regulation mechanisms. Under low load the amygdala showed significant activation to threat of shock that was modulated by high cognitive load. A directed top-down control contrast identified two regions associated with top-down control; ventrolateral PFC and dorsal ACC. Dynamic causal modeling provided further evidence that under high cognitive load, top-down inhibition is exerted on the amygdala and its outputs to prefrontal regions. Additionally, we hypothesized that individual differences in a separate, non-emotional top-down control task would predict the recruitment of dorsal ACC and ventrolateral PFC during top-down control of threat. Consistent with this, performance on a separate dichotic listening task predicted dorsal ACC and ventrolateral PFC activation during high WM load under threat of shock, though activation in these regions did not directly correlate with WM performance. Together, the findings suggest that under high cognitive load and threat, top-down control is exerted by dACC and vlPFC to inhibit threat processing, thus enabling WM performance without threat-related interference. PMID:23750133

A Flexible Socioeconomic Scenarios Framework for the Study of Plausible Arctic Futures

NASA Astrophysics Data System (ADS)

Reissell, A. K.; Peters, G. P.; Riahi, K.; Kroglund, M.; Lovecraft, A. L.; Nilsson, A. E.; Preston, B. L.; van Ruijven, B. J.

2016-12-01

Future developments of the Arctic region are associated with different drivers of change - climate, environmental, and socio-economic - and their interactions, and are highly uncertain. The uncertainty poses challenges for decision-making, calling for development of new analytical frameworks. Scenarios - coherent narratives describing potential futures, pathways to futures, and drivers of change along the way - can be used to explore the consequences of the key uncertainties, particularly in the long-term. In a participatory scenarios workshop, we used both top-down and bottom-up approaches for the development of a flexible socioeconomic scenarios framework. The top-down approach was linked to the global Integrated Assessment Modeling framework and its Shared Socio-Economic Pathways (SSPs), developing an Arctic extension of the set of five storylines on the main socioeconomic uncertainties in global climate change research. The bottom-up approach included participatory development of narratives originating from within the Arctic region. For extension of global SSPs to the regional level, we compared the key elements in the global SSPs (Population, Human Development, Economy & Lifestyle, Policies & Institutions, Technology, and Environment & Natural Resources) and key elements in the Arctic. Additional key elements for the Arctic scenarios include, for example, seasonal migration, the large role of traditional knowledge and culture, mixed economy, nested governance structure, human and environmental security, quality of infrastructure. The bottom-up derived results suggested that the scenarios developed independent of the SSPs could be mapped back to the SSPs to demonstrate consistency with respect to representing similar boundary conditions. The two approaches are complimentary, as the top-down approach can be used to set the global socio-economic and climate boundary conditions, and the bottom-up approach providing the regional context. One key uncertainty and driving force is the demand for resources (global or regional) that was mapped against the role of governance as well as adaptive and transformative capacity among actors within the Arctic. Resources demand has significant influence on the society, culture, economy and environment of the Arctic.

Top-down causation by information control: from a philosophical problem to a scientific research programme

PubMed Central

Auletta, G; Ellis, G.F.R; Jaeger, L

2008-01-01

It has been claimed that different types of causes must be considered in biological systems, including top-down as well as same-level and bottom-up causation, thus enabling the top levels to be causally efficacious in their own right. To clarify this issue, the important distinctions between information and signs are introduced here and the concepts of information control and functional equivalence classes in those systems are rigorously defined and used to characterize when top-down causation by feedback control happens, in a way that is testable. The causally significant elements we consider are equivalence classes of lower level processes, realized in biological systems through different operations having the same outcome within the context of information control and networks. PMID:18319208

5. VIEW LOOKING DOWN ON TOP OF ELEVATOR CAR FROM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. VIEW LOOKING DOWN ON TOP OF ELEVATOR CAR FROM THIRD FLOOR, SHOWING CROSSHEAD AND BROKEN ROPE SAFETY STOP MECHANISM INSIDE; GUIDES AT LOWER LEFT AND UPPER RIGHT; OPERATING ROPE AT LEFT - 72 Marlborough Street, Residential Hydraulic Elevator, Boston, Suffolk County, MA

4. VIEW EAST, PERSPECTIVE DOWN INCLINED PLANE FROM TOP OF ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. VIEW EAST, PERSPECTIVE DOWN INCLINED PLANE FROM TOP OF ABUTMENT TO CONEMAUGH RIVER AND AREA OF LOWER INCLINE - Laurel Hill Quarry, Incline Plane, Both sides of State Route 56, 2.4 miles East of State Route 711, Seward, Westmoreland County, PA

When Art Moves the Eyes: A Behavioral and Eye-Tracking Study

PubMed Central

Massaro, Davide; Savazzi, Federica; Di Dio, Cinzia; Freedberg, David; Gallese, Vittorio; Gilli, Gabriella; Marchetti, Antonella

2012-01-01

The aim of this study was to investigate, using eye-tracking technique, the influence of bottom-up and top-down processes on visual behavior while subjects, naïve to art criticism, were presented with representational paintings. Forty-two subjects viewed color and black and white paintings (Color) categorized as dynamic or static (Dynamism) (bottom-up processes). Half of the images represented natural environments and half human subjects (Content); all stimuli were displayed under aesthetic and movement judgment conditions (Task) (top-down processes). Results on gazing behavior showed that content-related top-down processes prevailed over low-level visually-driven bottom-up processes when a human subject is represented in the painting. On the contrary, bottom-up processes, mediated by low-level visual features, particularly affected gazing behavior when looking at nature-content images. We discuss our results proposing a reconsideration of the definition of content-related top-down processes in accordance with the concept of embodied simulation in art perception. PMID:22624007

Effective connectivities of cortical regions for top-down face processing: A Dynamic Causal Modeling study

PubMed Central

Li, Jun; Liu, Jiangang; Liang, Jimin; Zhang, Hongchuan; Zhao, Jizheng; Rieth, Cory A.; Huber, David E.; Li, Wu; Shi, Guangming; Ai, Lin; Tian, Jie; Lee, Kang

2013-01-01

To study top-down face processing, the present study used an experimental paradigm in which participants detected non-existent faces in pure noise images. Conventional BOLD signal analysis identified three regions involved in this illusory face detection. These regions included the left orbitofrontal cortex (OFC) in addition to the right fusiform face area (FFA) and right occipital face area (OFA), both of which were previously known to be involved in both top-down and bottom-up processing of faces. We used Dynamic Causal Modeling (DCM) and Bayesian model selection to further analyze the data, revealing both intrinsic and modulatory effective connectivities among these three cortical regions. Specifically, our results support the claim that the orbitofrontal cortex plays a crucial role in the top-down processing of faces by regulating the activities of the occipital face area, and the occipital face area in turn detects the illusory face features in the visual stimuli and then provides this information to the fusiform face area for further analysis. PMID:20423709

When art moves the eyes: a behavioral and eye-tracking study.

PubMed

Massaro, Davide; Savazzi, Federica; Di Dio, Cinzia; Freedberg, David; Gallese, Vittorio; Gilli, Gabriella; Marchetti, Antonella

2012-01-01

The aim of this study was to investigate, using eye-tracking technique, the influence of bottom-up and top-down processes on visual behavior while subjects, naïve to art criticism, were presented with representational paintings. Forty-two subjects viewed color and black and white paintings (Color) categorized as dynamic or static (Dynamism) (bottom-up processes). Half of the images represented natural environments and half human subjects (Content); all stimuli were displayed under aesthetic and movement judgment conditions (Task) (top-down processes). Results on gazing behavior showed that content-related top-down processes prevailed over low-level visually-driven bottom-up processes when a human subject is represented in the painting. On the contrary, bottom-up processes, mediated by low-level visual features, particularly affected gazing behavior when looking at nature-content images. We discuss our results proposing a reconsideration of the definition of content-related top-down processes in accordance with the concept of embodied simulation in art perception.

Advanced Plant Habitat - Packing and Planting Seeds

NASA Image and Video Library

2017-02-15

Inside a laboratory at the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, a scientist inserts Apogee wheat seeds into the science carrier, or base, of the Advanced Plant Habitat (APH). A growing substrate called arcillite was packed down in the base and coverings were secured on top of the base. Developed by NASA and ORBITEC of Madison, Wisconsin, the APH is the largest plant chamber built for the agency. It is a fully automated plant growth facility that will be used to conduct bioscience research on the International Space Station. The APH will be delivered to the space station aboard future Commercial Resupply Services missions.

Advanced Plant Habitat - Packing and Planting Seeds

NASA Image and Video Library

2017-02-15

Inside a laboratory at the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, scientists prepare Apogee wheat seeds for the science carrier, or base, of the Advanced Plant Habitat (APH). A growing substrate called arcillite was packed down in the base and coverings were secured on top of the base. Developed by NASA and ORBITEC of Madison, Wisconsin, the APH is the largest plant chamber built for the agency. It is a fully automated plant growth facility that will be used to conduct bioscience research on the International Space Station. The APH will be delivered to the space station aboard future Commercial Resupply Services missions.

STRCMACS: An extensive set of Macros for structured programming in OS/360 assembly language

NASA Technical Reports Server (NTRS)

Barth, C. W.

1974-01-01

Two techniques are discussed that have been most often referred to as structured programming. One is that of programming with high level control structures (such as the if and while) replacing the branch instruction (goto-less programming); the other is the process of developing a program by progressively refining descriptions of components in terms of more primitive components (called stepwise refinement or top-down programming). In addition to discussing what these techniques are, it is shown why their use is advised and how both can be implemented in OS assembly language by the use of a special macro instruction package.

Is top-down vs bottom-up radiological evaluation after febrile urinary tract infection really less stressful for the child and family? Challenging the dogma.

PubMed

Telli, Onur; Mermerkaya, Murat; Hajiyev, Perviz; Aydogdu, Ozgu; Afandiyev, Faraj; Suer, Evren; Soygur, Tarkan; Burgu, Berk

2015-03-01

We evaluated whether stress levels in children and parents during radiological evaluation after febrile urinary tract infection are really lower using the top-down approach, where (99m)technetium dimercaptosuccinic acid renal scintigraphy is used initially, than the bottom-up approach, where voiding cystourethrography is initially performed and repeated examinations are easier for all. We prospectively evaluated 120 children 3 to 8 years old. Pain ratings were obtained using the Faces Pain Scale-Revised, and conversation during the procedure was evaluated using the Child-Adult Medical Procedure Interaction Scale-Revised by 2 independent observers. To evaluate parental anxiety, the State-Trait Anxiety Inventory form was also completed. Following a documented febrile urinary tract infection children were randomized to the top-down or bottom-up group. A third group of 44 children undergoing repeat voiding cystourethrography and their parents were also evaluated. Child ratings of pain using the Faces Pain Scale-Revised were not significantly different between the top-down group following (99m)technetium dimercaptosuccinic acid renal scintigraphy (2.99 on a scale of 10) and the bottom-up group following voiding cystourethrography (3.21). Also the Faces Pain Scale-Revised was not significantly different in the repeat voiding cystourethrography group (3.35). On the Child-Adult Medical Procedure Interaction Scale-Revised there was negative correlation between child coping and child distress, as well as rate of child distress and adult coping promoting behavior. Parental state anxiety scores were significantly less in the top-down and repeat voiding cystourethrography groups than in the bottom-up group. Although the top-down approach and repeat voiding cystourethrography cause less anxiety for caregivers, these values do not correlate to pain scale in children. This finding might be due to lack of appropriate evaluation tools of pediatric pain and anxiety. However, the theory that the top-down approach is less invasive, and thus less stressful, requires further research. The Child-Adult Medical Procedure Interaction Scale-Revised data indicate that influences in adult-child interaction are bidirectional. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Design of a dataway processor for a parallel image signal processing system

NASA Astrophysics Data System (ADS)

Nomura, Mitsuru; Fujii, Tetsuro; Ono, Sadayasu

1995-04-01

Recently, demands for high-speed signal processing have been increasing especially in the field of image data compression, computer graphics, and medical imaging. To achieve sufficient power for real-time image processing, we have been developing parallel signal-processing systems. This paper describes a communication processor called 'dataway processor' designed for a new scalable parallel signal-processing system. The processor has six high-speed communication links (Dataways), a data-packet routing controller, a RISC CORE, and a DMA controller. Each communication link operates at 8-bit parallel in a full duplex mode at 50 MHz. Moreover, data routing, DMA, and CORE operations are processed in parallel. Therefore, sufficient throughput is available for high-speed digital video signals. The processor is designed in a top- down fashion using a CAD system called 'PARTHENON.' The hardware is fabricated using 0.5-micrometers CMOS technology, and its hardware is about 200 K gates.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Mowei; Wu, Si; Stenoien, David L.

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.

Priors in perception: Top-down modulation, Bayesian perceptual learning rate, and prediction error minimization.

PubMed

Hohwy, Jakob

2017-01-01

I discuss top-down modulation of perception in terms of a variable Bayesian learning rate, revealing a wide range of prior hierarchical expectations that can modulate perception. I then switch to the prediction error minimization framework and seek to conceive cognitive penetration specifically as prediction error minimization deviations from a variable Bayesian learning rate. This approach retains cognitive penetration as a category somewhat distinct from other top-down effects, and carves a reasonable route between penetrability and impenetrability. It prevents rampant, relativistic cognitive penetration of perception and yet is consistent with the continuity of cognition and perception. Copyright © 2016 Elsevier Inc. All rights reserved.

Creation of Functional Micro/Nano Systems through Top-down and Bottom-up Approaches

PubMed Central

Wong, Tak-Sing; Brough, Branden; Ho, Chih-Ming

2009-01-01

Mimicking nature’s approach in creating devices with similar functional complexity is one of the ultimate goals of scientists and engineers. The remarkable elegance of these naturally evolved structures originates from bottom-up self-assembly processes. The seamless integration of top-down fabrication and bottom-up synthesis is the challenge for achieving intricate artificial systems. In this paper, technologies necessary for guided bottom-up assembly such as molecular manipulation, molecular binding, and the self assembling of molecules will be reviewed. In addition, the current progress of synthesizing mechanical devices through top-down and bottom-up approaches will be discussed. PMID:19382535

Top-down modulation: the crossroads of perception, attention and memory

NASA Astrophysics Data System (ADS)

Gazzaley, Adam

2010-02-01

Research in our laboratory focuses on understanding the neural mechanisms that serve at the crossroads of perception, memory and attention, specifically exploring how brain region interactions underlie these abilities. To accomplish this, we study top-down modulation, the process by which we enhance neural activity associated with relevant information and suppress activity for irrelevant information, thus establishing a neural basis for all higher-order cognitive operations. We also study alterations in top-down modulation that occur with normal aging. Our experiments are performed on human participants, using a multimodal approach that integrates functional MRI (fMRI), transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

Stereotypes and prejudice affect the recognition of emotional body postures.

PubMed

Bijlstra, Gijsbert; Holland, Rob W; Dotsch, Ron; Wigboldus, Daniel H J

2018-03-26

Most research on emotion recognition focuses on facial expressions. However, people communicate emotional information through bodily cues as well. Prior research on facial expressions has demonstrated that emotion recognition is modulated by top-down processes. Here, we tested whether this top-down modulation generalizes to the recognition of emotions from body postures. We report three studies demonstrating that stereotypes and prejudice about men and women may affect how fast people classify various emotional body postures. Our results suggest that gender cues activate gender associations, which affect the recognition of emotions from body postures in a top-down fashion. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The effects of urbanization on trophic interactions in a desert landscape

USDA-ARS?s Scientific Manuscript database

Background/Question/Methods: Trophic systems can be affected through top-down (predators) and bottom-up (resources) impacts. Human activity can alter trophic systems by causing predators to avoid areas (top-down) or by providing increased resources through irrigation and decorative plants that attra...

Multilingual Crews: Communication and the Operations of Ships.

ERIC Educational Resources Information Center

Sampson, Helen; Zhao, Minghua

2003-01-01

Focuses on efforts to improve standards of English among seafarers, including a top-down approach to language learning utilized by industry regulators and training establishments. Considers the effectiveness of top-down approaches to language development, drawing on ethnographic research conducted aboard vessels with multilingual crews.…

A synthesis study of noncontact nondestructive evaluation of top-down cracking in asphalt pavements.

DOT National Transportation Integrated Search

2013-12-01

The primary objective of this research study was to conduct an extensive literature review on top-down : cracking evaluation studies, prepare a synthesis of findings, and recommend a follow up phase for a : pilot study in Mississippi with a candidate...

Achieving Campus Sustainability: Top-Down, Bottom-Up, or Neither?

ERIC Educational Resources Information Center

Brinkhurst, Marena; Rose, Peter; Maurice, Gillian; Ackerman, Josef Daniel

2011-01-01

Purpose: The dynamics of organizational change related to environmental sustainability on university campuses are examined in this article. Whereas case studies of campus sustainability efforts tend to classify leadership as either "top-down" or "bottom-up", this classification neglects consideration of the leadership roles of…

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

PubMed

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.

Deformation of Attractor Landscape via Cholinergic Presynaptic Modulations: A Computational Study Using a Phase Neuron Model

PubMed Central

Kanamaru, Takashi; Fujii, Hiroshi; Aihara, Kazuyuki

2013-01-01

Corticopetal acetylcholine (ACh) is released transiently from the nucleus basalis of Meynert (NBM) into the cortical layers and is associated with top-down attention. Recent experimental data suggest that this release of ACh disinhibits layer 2/3 pyramidal neurons (PYRs) via muscarinic presynaptic effects on inhibitory synapses. Together with other possible presynaptic cholinergic effects on excitatory synapses, this may result in dynamic and temporal modifications of synapses associated with top-down attention. However, the system-level consequences and cognitive relevance of such disinhibitions are poorly understood. Herein, we propose a theoretical possibility that such transient modifications of connectivity associated with ACh release, in addition to top-down glutamatergic input, may provide a neural mechanism for the temporal reactivation of attractors as neural correlates of memories. With baseline levels of ACh, the brain returns to quasi-attractor states, exhibiting transitive dynamics between several intrinsic internal states. This suggests that top-down attention may cause the attention-induced deformations between two types of attractor landscapes: the quasi-attractor landscape (Q-landscape, present under low-ACh, non-attentional conditions) and the attractor landscape (A-landscape, present under high-ACh, top-down attentional conditions). We present a conceptual computational model based on experimental knowledge of the structure of PYRs and interneurons (INs) in cortical layers 1 and 2/3 and discuss the possible physiological implications of our results. PMID:23326520

A Comprehensive Guide for Performing Sample Preparation and Top-Down Protein Analysis.

PubMed

Padula, Matthew P; Berry, Iain J; O Rourke, Matthew B; Raymond, Benjamin B A; Santos, Jerran; Djordjevic, Steven P

2017-04-07

Methodologies for the global analysis of proteins in a sample, or proteome analysis, have been available since 1975 when Patrick O'Farrell published the first paper describing two-dimensional gel electrophoresis (2D-PAGE). This technique allowed the resolution of single protein isoforms, or proteoforms, into single 'spots' in a polyacrylamide gel, allowing the quantitation of changes in a proteoform's abundance to ascertain changes in an organism's phenotype when conditions change. In pursuit of the comprehensive profiling of the proteome, significant advances in technology have made the identification and quantitation of intact proteoforms from complex mixtures of proteins more routine, allowing analysis of the proteome from the 'Top-Down'. However, the number of proteoforms detected by Top-Down methodologies such as 2D-PAGE or mass spectrometry has not significantly increased since O'Farrell's paper when compared to Bottom-Up, peptide-centric techniques. This article explores and explains the numerous methodologies and technologies available to analyse the proteome from the Top-Down with a strong emphasis on the necessity to analyse intact proteoforms as a better indicator of changes in biology and phenotype. We arrive at the conclusion that the complete and comprehensive profiling of an organism's proteome is still, at present, beyond our reach but the continuing evolution of protein fractionation techniques and mass spectrometry brings comprehensive Top-Down proteome profiling closer.

Top-down modulation of visual and auditory cortical processing in aging.

PubMed

Guerreiro, Maria J S; Eck, Judith; Moerel, Michelle; Evers, Elisabeth A T; Van Gerven, Pascal W M

2015-02-01

Age-related cognitive decline has been accounted for by an age-related deficit in top-down attentional modulation of sensory cortical processing. In light of recent behavioral findings showing that age-related differences in selective attention are modality dependent, our goal was to investigate the role of sensory modality in age-related differences in top-down modulation of sensory cortical processing. This question was addressed by testing younger and older individuals in several memory tasks while undergoing fMRI. Throughout these tasks, perceptual features were kept constant while attentional instructions were varied, allowing us to devise all combinations of relevant and irrelevant, visual and auditory information. We found no top-down modulation of auditory sensory cortical processing in either age group. In contrast, we found top-down modulation of visual cortical processing in both age groups, and this effect did not differ between age groups. That is, older adults enhanced cortical processing of relevant visual information and suppressed cortical processing of visual distractors during auditory attention to the same extent as younger adults. The present results indicate that older adults are capable of suppressing irrelevant visual information in the context of cross-modal auditory attention, and thereby challenge the view that age-related attentional and cognitive decline is due to a general deficits in the ability to suppress irrelevant information. Copyright © 2014 Elsevier B.V. All rights reserved.

ViVaMBC: estimating viral sequence variation in complex populations from illumina deep-sequencing data using model-based clustering.

PubMed

Verbist, Bie; Clement, Lieven; Reumers, Joke; Thys, Kim; Vapirev, Alexander; Talloen, Willem; Wetzels, Yves; Meys, Joris; Aerssens, Jeroen; Bijnens, Luc; Thas, Olivier

2015-02-22

Deep-sequencing allows for an in-depth characterization of sequence variation in complex populations. However, technology associated errors may impede a powerful assessment of low-frequency mutations. Fortunately, base calls are complemented with quality scores which are derived from a quadruplet of intensities, one channel for each nucleotide type for Illumina sequencing. The highest intensity of the four channels determines the base that is called. Mismatch bases can often be corrected by the second best base, i.e. the base with the second highest intensity in the quadruplet. A virus variant model-based clustering method, ViVaMBC, is presented that explores quality scores and second best base calls for identifying and quantifying viral variants. ViVaMBC is optimized to call variants at the codon level (nucleotide triplets) which enables immediate biological interpretation of the variants with respect to their antiviral drug responses. Using mixtures of HCV plasmids we show that our method accurately estimates frequencies down to 0.5%. The estimates are unbiased when average coverages of 25,000 are reached. A comparison with the SNP-callers V-Phaser2, ShoRAH, and LoFreq shows that ViVaMBC has a superb sensitivity and specificity for variants with frequencies above 0.4%. Unlike the competitors, ViVaMBC reports a higher number of false-positive findings with frequencies below 0.4% which might partially originate from picking up artificial variants introduced by errors in the sample and library preparation step. ViVaMBC is the first method to call viral variants directly at the codon level. The strength of the approach lies in modeling the error probabilities based on the quality scores. Although the use of second best base calls appeared very promising in our data exploration phase, their utility was limited. They provided a slight increase in sensitivity, which however does not warrant the additional computational cost of running the offline base caller. Apparently a lot of information is already contained in the quality scores enabling the model based clustering procedure to adjust the majority of the sequencing errors. Overall the sensitivity of ViVaMBC is such that technical constraints like PCR errors start to form the bottleneck for low frequency variant detection.

Mythical Maia, ultrashort and 53 PSC variables. Lecture 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cox, A.N.

1983-03-14

Moving down the main sequence from the ..beta.. Cephei variables, we come to later B-type stars. The suspicion of variability for these stars goes back to Vogel in 1891 who studied the radial velocities of Vega. Since that time there have been numerous studies of Vega (Wisniewski and Johnson 1979, Fernie 1981) and other B and early A stars which hint at variability in both radial velocity and light. Since Struve (1955) discussed these stars 28 years ago, they have been called the Maia stars after the Pleiades star that he thought was the prototype. The uncertainty in their actualmore » variability has led Breger (1980) to call them the mythical Maia variables.« less

Toward a trophic theory of species diversity

PubMed Central

Terborgh, John W.

2015-01-01

Efforts to understand the ecological regulation of species diversity via bottom-up approaches have failed to yield a consensus theory. Theories based on the alternative of top-down regulation have fared better. Paine’s discovery of keystone predation demonstrated that the regulation of diversity via top-down forcing could be simple, strong, and direct, yet ecologists have persistently failed to perceive generality in Paine’s result. Removing top predators destabilizes many systems and drives transitions to radically distinct alternative states. These transitions typically involve community reorganization and loss of diversity, implying that top-down forcing is crucial to diversity maintenance. Contrary to the expectations of bottom-up theories, many terrestrial herbivores and mesopredators are capable of sustained order-of-magnitude population increases following release from predation, negating the assumption that populations of primary consumers are resource limited and at or near carrying capacity. Predation sensu lato (to include Janzen–Connell mortality agents) has been shown to promote diversity in a wide range of ecosystems, including rocky intertidal shelves, coral reefs, the nearshore ocean, streams, lakes, temperate and tropical forests, and arctic tundra. The compelling variety of these ecosystems suggests that top-down forcing plays a universal role in regulating diversity. This conclusion is further supported by studies showing that the reduction or absence of predation leads to diversity loss and, in the more dramatic cases, to catastrophic regime change. Here, I expand on the thesis that diversity is maintained by the interaction between predation and competition, such that strong top-down forcing reduces competition, allowing coexistence. PMID:26374788

Analytics that Inform the University: Using Data You Already Have

ERIC Educational Resources Information Center

Dziuban, Charles; Moskal, Patsy; Cavanagh, Thomas; Watts, Andre

2012-01-01

The authors describe the University of Central Florida's top-down/bottom-up action analytics approach to using data to inform decision-making at the University of Central Florida. The top-down approach utilizes information about programs, modalities, and college implementation of Web initiatives. The bottom-up approach continuously monitors…

Effects of Bottom-up and Top-down Controls and Climate Change on Estuarine Macrophyte Communities and the Ecosystem Services they Provide

EPA Science Inventory

Macrophytes provide important estuarine benthic habitats and support a significant portion of estuarine productivity. The composition and characteristics of these benthic communities are regulated bottom-up by resource availability and from the top-down by herbivory and predation...

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

ERIC Educational Resources Information Center

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…

A "Top-Down" Analysis of High School Teacher Motivation

ERIC Educational Resources Information Center

Ciani, Keith D.; Summers, Jessica J.; Easter, Matthew A.

2008-01-01

Classroom instruction may be affected by school contexts that are increasingly performance-driven because of legislative demands. Interpreting this as a need to investigate the relationships between school context and classroom practice, this study took a "top-down" approach by examining contextual elements of school goal structure and teacher…

A top-down strategy to synthesize wurtzite Cu2ZnSnS4 nanocrystals by green chemistry.

PubMed

Sun, Yiwen; Hu, Zhengqiao; Zhang, Junjun; Wang, Li; Wu, Chunyan; Xu, Jun

2016-07-28

Green synthesis of metastable wurtzite Cu2ZnSnS4 nanocrystals through a top-down synthetic strategy is presented. Formation mechanisms associated with Kirkendall and etching effects are illustrated in detail. The nanocrystals exhibit remarkable photoluminescence properties at room temperature.

What Does Distractibility in ADHD Reveal about Mechanisms for Top-Down Attentional Control?

ERIC Educational Resources Information Center

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…

On-Line Electrochemical Reduction of Disulfide Bonds: Improved FTICR-CID and -ETD Coverage of Oxytocin and Hepcidin

NASA Astrophysics Data System (ADS)

Nicolardi, Simone; Giera, Martin; Kooijman, Pieter; Kraj, Agnieszka; Chervet, Jean-Pierre; Deelder, André M.; van der Burgt, Yuri E. M.

2013-12-01

Particularly in the field of middle- and top-down peptide and protein analysis, disulfide bridges can severely hinder fragmentation and thus impede sequence analysis (coverage). Here we present an on-line/electrochemistry/ESI-FTICR-MS approach, which was applied to the analysis of the primary structure of oxytocin, containing one disulfide bridge, and of hepcidin, containing four disulfide bridges. The presented workflow provided up to 80 % (on-line) conversion of disulfide bonds in both peptides. With minimal sample preparation, such reduction resulted in a higher number of peptide backbone cleavages upon CID or ETD fragmentation, and thus yielded improved sequence coverage. The cycle times, including electrode recovery, were rapid and, therefore, might very well be coupled with liquid chromatography for protein or peptide separation, which has great potential for high-throughput analysis.

Re-interpreting Prominences Classified as Tornadoes

NASA Astrophysics Data System (ADS)

Martin, Sara F.; Venkataramanasastry, Aparna

2015-04-01

Some papers in the recent literature identify tornado prominences with barbs of quiescent prominences while papers in the much older historic literature include a second category of tornado prominence that does not correspond to a barb of a quiescent prominence. The latter are described as prominence mass rotating around a nearly vertical axis prior to its eruption and the rotation was verified by spectral measurements. From H alpha Doppler-shifted mass motions recorded at Helio Research or the Dutch Open Telescope, we illustrate how the apparent tornado-like motions, identified with barbs, are illusions in our mind’s eye resulting from poorly resolved counterstreaming threads of mass in the barbs of quiescent prominences. In contrast, we confirm the second category of rotational motion in prominences shortly before and during eruption. In addition, we identify this second category as part of the late phase of a phenomenon called the roll effect in erupting prominences. In these cases, the eruption begins with the sideways rolling of the top of a prominence. As the eruption proceeds the rolling motion propagates down one leg or both legs of the prominence depending on whether the eruption is asymmetric or symmetric respectively. As an asymmetric eruption continues, the longer lasting leg becomes nearly vertical and its rotational motion also continues. If only this phase of the eruption was observed, as in some historic cases, it was called a tornado prominence. However, when we now observe entire eruptions in time-lapse sequences, the similarity to terrestrial tornadoes is lost. We conclude that neither prominence barbs, that give the illusion of rotation, nor the cases of true rotational motion, in the legs of erupting prominences, are usefully described as tornado prominences when the complete prominence structure or complete erupting event is observed.

Rhythmic and melodic deviations in musical sequences recruit different cortical areas for mismatch detection.

PubMed

Lappe, Claudia; Steinsträter, Olaf; Pantev, Christo

2013-01-01

The mismatch negativity (MMN), an event-related potential (ERP) representing the violation of an acoustic regularity, is considered as a pre-attentive change detection mechanism at the sensory level on the one hand and as a prediction error signal on the other hand, suggesting that bottom-up as well as top-down processes are involved in its generation. Rhythmic and melodic deviations within a musical sequence elicit a MMN in musically trained subjects, indicating that acquired musical expertise leads to better discrimination accuracy of musical material and better predictions about upcoming musical events. Expectation violations to musical material could therefore recruit neural generators that reflect top-down processes that are based on musical knowledge. We describe the neural generators of the musical MMN for rhythmic and melodic material after a short-term sensorimotor-auditory (SA) training. We compare the localization of musical MMN data from two previous MEG studies by applying beamformer analysis. One study focused on the melodic harmonic progression whereas the other study focused on rhythmic progression. The MMN to melodic deviations revealed significant right hemispheric neural activation in the superior temporal gyrus (STG), inferior frontal cortex (IFC), and the superior frontal (SFG) and orbitofrontal (OFG) gyri. IFC and SFG activation was also observed in the left hemisphere. In contrast, beamformer analysis of the data from the rhythm study revealed bilateral activation within the vicinity of auditory cortices and in the inferior parietal lobule (IPL), an area that has recently been implied in temporal processing. We conclude that different cortical networks are activated in the analysis of the temporal and the melodic content of musical material, and discuss these networks in the context of the dual-pathway model of auditory processing.

Attention Is Required for Knowledge-Based Sequential Grouping: Insights from the Integration of Syllables into Words.

PubMed

Ding, Nai; Pan, Xunyi; Luo, Cheng; Su, Naifei; Zhang, Wen; Zhang, Jianfeng

2018-01-31

How the brain groups sequential sensory events into chunks is a fundamental question in cognitive neuroscience. This study investigates whether top-down attention or specific tasks are required for the brain to apply lexical knowledge to group syllables into words. Neural responses tracking the syllabic and word rhythms of a rhythmic speech sequence were concurrently monitored using electroencephalography (EEG). The participants performed different tasks, attending to either the rhythmic speech sequence or a distractor, which was another speech stream or a nonlinguistic auditory/visual stimulus. Attention to speech, but not a lexical-meaning-related task, was required for reliable neural tracking of words, even when the distractor was a nonlinguistic stimulus presented cross-modally. Neural tracking of syllables, however, was reliably observed in all tested conditions. These results strongly suggest that neural encoding of individual auditory events (i.e., syllables) is automatic, while knowledge-based construction of temporal chunks (i.e., words) crucially relies on top-down attention. SIGNIFICANCE STATEMENT Why we cannot understand speech when not paying attention is an old question in psychology and cognitive neuroscience. Speech processing is a complex process that involves multiple stages, e.g., hearing and analyzing the speech sound, recognizing words, and combining words into phrases and sentences. The current study investigates which speech-processing stage is blocked when we do not listen carefully. We show that the brain can reliably encode syllables, basic units of speech sounds, even when we do not pay attention. Nevertheless, when distracted, the brain cannot group syllables into multisyllabic words, which are basic units for speech meaning. Therefore, the process of converting speech sound into meaning crucially relies on attention. Copyright © 2018 the authors 0270-6474/18/381178-11$15.00/0.

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

PubMed

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.

Towards a Novel Integrated Approach for Estimating Greenhouse Gas Emissions in Support of International Agreements

NASA Astrophysics Data System (ADS)

Reimann, S.; Vollmer, M. K.; Henne, S.; Brunner, D.; Emmenegger, L.; Manning, A.; Fraser, P. J.; Krummel, P. B.; Dunse, B. L.; DeCola, P.; Tarasova, O. A.

2016-12-01

In the recently adopted Paris Agreement the community of signatory states has agreed to limit the future global temperature increase between +1.5 °C and +2.0 °C, compared to pre-industrial times. To achieve this goal, emission reduction targets have been submitted by individual nations (called Intended Nationally Determined Contributions, INDCs). Inventories will be used for checking progress towards these envisaged goals. These inventories are calculated by combining information on specific activities (e.g. passenger cars, agriculture) with activity-related, typically IPCC-sanctioned, emission factors - the so-called bottom-up method. These calculated emissions are reported on an annual basis and are checked by external bodies by using the same method. A second independent method estimates emissions by translating greenhouse gas measurements made at regionally representative stations into regional/global emissions using meteorologically-based transport models. In recent years this so-called top-down approach has been substantially advanced into a powerful tool and emission estimates at the national/regional level have become possible. This method is already used in Switzerland, in the United Kingdom and in Australia to estimate greenhouse gas emissions and independently support the national bottom-up emission inventories within the UNFCCC framework. Examples of the comparison of the two independent methods will be presented and the added-value will be discussed. The World Meteorological Organization (WMO) and partner organizations are currently developing a plan to expand this top-down approach and to expand the globally representative GAW network of ground-based stations and remote-sensing platforms and integrate their information with atmospheric transport models. This Integrated Global Greenhouse Gas Information System (IG3IS) initiative will help nations to improve the accuracy of their country-based emissions inventories and their ability to evaluate the success of emission reductions strategies. This could foster trans-national collaboration on methodologies for estimation of emissions. Furthermore, more accurate emission knowledge will clarify the value of emission reduction efforts and could encourage countries to strengthen their reduction pledges.

Dissociable Contributions of Imagination and Willpower to the Malleability of Human Patience.

PubMed

Jenkins, Adrianna C; Hsu, Ming

2017-07-01

The ability to exercise patience is important for human functioning. Although it is known that patience can be promoted by using top-down control, or willpower, to override impatient impulses, patience is also malleable-in particular, susceptible to framing effects-in ways that are difficult to explain using willpower alone. So far, the mechanisms underlying framing effects on patience have been elusive. We investigated the role of imagination in these effects. In a behavioral experiment (Experiment 1), a classic framing manipulation (sequence framing) increased self-reported and independently coded imagination during intertemporal choice. In an investigation of neural responses during decision making (Experiment 2), sequence framing increased the extent to which patience was related to activation in brain regions associated with imagination, relative to activation in regions associated with willpower, and increased functional connectivity of brain regions associated with imagination, but not willpower, relative to regions associated with valuation. Our results suggest that sequence framing can increase the role of imagination in decision making without increasing the exertion of willpower.

Neural Correlates of Top-Down Letter Processing

ERIC Educational Resources Information Center

Liu, Jiangang; Li, Jun; Zhang, Hongchuan; Rieth, Cory A.; Huber, David E.; Li, Wu; Lee, Kang; Tian, Jie

2010-01-01

This fMRI study investigated top-down letter processing with an illusory letter detection task. Participants responded whether one of a number of different possible letters was present in a very noisy image. After initial training that became increasingly difficult, they continued to detect letters even though the images consisted of pure noise,…

Theory and Practice of Community Development: A Case Study from the United Kingdom.

ERIC Educational Resources Information Center

Popple, Keith; Quinney, Anne

2002-01-01

A top-down approach to British community development is rooted in Victorian paternalism, a bottom-up approach in radical action. The case of ACHIEVE (Academic Centre for Health Improvement and Evidence of Effectiveness) shows how the current government's top-down approach is inadequate and potentially exploitive. It emphasizes development and…

TOP DOWN CONTROL OF THE MICROBIAL LOOP IN ESTUARINE PHYTOPLANKTON

EPA Science Inventory

Top Down Control of the Microbial Loop in Estuarine Plankton (Abstract). To be presented at the 16th Biennial Conference of the Estuarine Research Foundation, ERF 2001: An Estuarine Odyssey, 4-8 November 2001, St. Pete Beach, FL. 1 p. (ERL,GB R846).

We examined the effects...

The landscape of fear: The missing link to understand top-down and bottom-up controls of prey abundance?

USDA-ARS?s Scientific Manuscript database

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...

Teachers' Perceptions of Teaching in Workplace Simulations in Vocational Education

ERIC Educational Resources Information Center

Jossberger, Helen; Brand-Gruwel, Saskia; van de Wiel, Margje W.; Boshuizen, Henny P.

2015-01-01

In a large-scale top-down innovation operation in the Netherlands, workplace simulations have been implemented in vocational schools, where students are required to work independently and self-direct their learning. However, research has shown that the success of such large-scale top-down innovations depends on how well their execution in schools…

Top Down versus Bottom Up: The Social Construction of the Health Literacy Movement

ERIC Educational Resources Information Center

Huber, Jeffrey T.; Shapiro, Robert M., II; Gillaspy, Mary L.

2012-01-01

The health literacy movement has been socially constructed over time. Unlike the consumer health information movement, which developed with broad public support, the health literacy movement has been fashioned primarily from the top down, initiated by policy makers and imposed on targeted populations. Interest in the health literacy movement has…

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

ERIC Educational Resources Information Center

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'…

A Dynamic Causal Modeling Analysis of the Effective Connectivities Underlying Top-Down Letter Processing

ERIC Educational Resources Information Center

Liu, Jiangang; Li, Jun; Rieth, Cory A.; Huber, David E.; Tian, Jie; Lee, Kang

2011-01-01

The present study employed dynamic causal modeling to investigate the effective functional connectivity between regions of the neural network involved in top-down letter processing. We used an illusory letter detection paradigm in which participants detected letters while viewing pure noise images. When participants detected letters, the response…

Compartment C1, engine room. View down compionway of top of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Compartment C-1, engine room. View down compionway of top of engine cylinder heads; note slots in frame at left of photograph, slots hold steel bars which form a protective grating above the engines during battle. (081) - USS Olympia, Penn's Landing, 211 South Columbus Boulevard, Philadelphia, Philadelphia County, PA

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

NASA Astrophysics Data System (ADS)

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.

2018-04-01

In the preceding article "Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate" by Oyler et al., an error in the J5 E. coli LPS chemical structure (Figs. 2 and 4) was introduced and propagated into the final revision.

Lexical Expertise and Reading Skill: Bottom-Up and Top-Down Processing of Lexical Ambiguity

ERIC Educational Resources Information Center

Andrews, Sally; Bond, Rachel

2009-01-01

The lexical quality hypothesis assumes that skilled readers rely on high quality lexical representations that afford autonomous lexical retrieval and reduce the need to rely on top-down context. This experiment investigated this hypothesis by comparing the performance of adults classified on reading comprehension and spelling performance. "Lexical…

Contingent involuntary motoric inhibition: the involuntary inhibition of a motor response contingent on top-down goals.

PubMed

Anderson, Brian A; Folk, Charles L

2012-12-01

Effective motor control involves both the execution of appropriate responses and the inhibition of inappropriate responses that are evoked by response-associated stimuli. The inhibition of a motor response has traditionally been characterized as either a voluntary act of cognitive control or a low-level perceptual bias arising from processes such as inhibition of return and priming. Involuntary effects of top-down goals on motoric inhibition have been reported, but involve the perseveration of an inhibitory strategy. It is unknown whether the inhibition of a motor response can be selectively triggered by a goal-relevant stimulus, reflecting the automatic activation of a top-down inhibitory strategy. Here we show that irrelevant flankers that share the color of a no-go target elicit the inhibition of their associated motor response while other-colored flankers do not, even when participants have sufficient time to prepare for the upcoming target while ignoring the flankers. Our results demonstrate contingent involuntary motoric inhibition: motoric inhibition can be automatically triggered by a stimulus based on top-down goals.

Intact mass detection, interpretation, and visualization to automate Top-Down proteomics on a large scale

PubMed Central

Durbin, Kenneth R.; Tran, John C.; Zamdborg, Leonid; Sweet, Steve M. M.; Catherman, Adam D.; Lee, Ji Eun; Li, Mingxi; Kellie, John F.; Kelleher, Neil L.

2011-01-01

Applying high-throughput Top-Down MS to an entire proteome requires a yet-to-be-established model for data processing. Since Top-Down is becoming possible on a large scale, we report our latest software pipeline dedicated to capturing the full value of intact protein data in automated fashion. For intact mass detection, we combine algorithms for processing MS1 data from both isotopically resolved (FT) and charge-state resolved (ion trap) LC-MS data, which are then linked to their fragment ions for database searching using ProSight. Automated determination of human keratin and tubulin isoforms is one result. Optimized for the intricacies of whole proteins, new software modules visualize proteome-scale data based on the LC retention time and intensity of intact masses and enable selective detection of PTMs to automatically screen for acetylation, phosphorylation, and methylation. Software functionality was demonstrated using comparative LC-MS data from yeast strains in addition to human cells undergoing chemical stress. We further these advances as a key aspect of realizing Top-Down MS on a proteomic scale. PMID:20848673

Component processes in voluntary task switching.

PubMed

Demanet, Jelle; Liefooghe, Baptist

2014-05-01

The present study investigated the involvement of bottom-up and top-down control in task-switching situations in which tasks are selected on a voluntary basis. We tested for indices of both types of control in the reduction in switch cost that is observed when more time is available before executing a task. Participants had to indicate their task choice overtly prior to the actual task execution, and two time intervals were manipulated: the interval between the task-execution response of the previous trial and task-indication response of the current trial and the interval between task-indication response and task-execution response of a particular trial. In Experiment 1, the length of these intervals was manipulated orthogonally, and indices for top-down and bottom-up control were observed. Concerned with the validity of these results, Experiments 2-3 additionally discouraged participants from preparing the upcoming task before their task-indication response. Indices for bottom-up control remained, but not for top-down control. The characteristics of top-down and bottom-up control in voluntary task switching and task switching in general are discussed.

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

NASA Astrophysics Data System (ADS)

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.

Physical stress modifies top-down and bottom-up forcing on plant growth and reproduction in a coastal ecosystem.

PubMed

Daleo, Pedro; Alberti, Juan; Bruschetti, Carlos Martin; Pascual, Jesos; Iribarne, Oscar; Silliman, Brian R

2015-08-01

Bottom-up and top-down effects act together to exert strong control over plant growth and reproduction, but how physical stress modifies those interactive forces remains unclear. Even though empirical evidence is scarce, theory predicts that the importance of both top-down- and bottom-up forces may decrease as physical stress increases. Here, we experimentally evaluate in the field the separate and interactive effect of salinity, nutrient availability, and crab herbivory on plant above- and belowground biomass, as well as on sexual and clonal reproduction in the salt marsh plant Spartina densiflora. Results show that the outcome of the interaction between nutrient availability and herbivory is highly context dependent, not only varying with the abiotic context (i.e., with or without increased salinity stress), but also with the dependent variable considered. Contrary to theoretical predictions, our results show that, consistently across different measured variables, salinity stress did not cancel bottom-up (i.e., nutrients) or top-down (i.e., consumers) control, but has additive effects. Our results support emerging theory by highlighting that, under many conditions, physical stress can act additively with, or even stimulate, consumer control, especially in cases where the physical stress is only experienced by basal levels of the trophic chain. Abiotic stress, as well as bottom-up and top-down factors, can affect salt marsh structure and function not only by affecting biomass production but also by having other indirect effects, such as changing patterns in plant biomass allocation and reproduction.

A critical role of temporoparietal junction in the integration of top-down and bottom-up attentional control

PubMed Central

Wu, Qiong; Chang, Chi-Fu; Xi, Sisi; Huang, I-Wen; Liu, Zuxiang; Juan, Chi-Hung; Wu, Yanhong; Fan, Jin

2015-01-01

Information processing can be biased toward behaviorally relevant and salient stimuli by top-down (goal-directed) and bottom-up (stimulus-driven) attentional control processes. However, the neural basis underlying the integration of these processes is not well understood. We employed functional magnetic resonance imaging and transcranial direct-current stimulation (tDCS) in humans to examine the brain mechanisms underlying the interaction between these two processes. We manipulated the cognitive load involved in top-down processing and stimulus surprise involved in bottom-up processing in a factorial design by combining a majority function task and an oddball paradigm. We found that high cognitive load and high surprise level were associated with prolonged reaction time compared to low cognitive load and low surprise level, with a synergistic interaction effect which was accompanied by a greater deactivation of bilateral temporoparietal junction (TPJ). In addition, the TPJ displayed negative functional connectivity with right middle occipital gyrus involved in bottom-up processing (modulated by the interaction effect) and the right frontal eye field (FEF) involved in top-down control. The enhanced negative functional connectivity between the TPJ and right FEF was accompanied by a larger behavioral interaction effect across subjects. Application of cathodal tDCS over the right TPJ eliminated the interaction effect. These results suggest that the TPJ plays a critical role in processing bottom-up information for top-down control of attention. PMID:26308973

Evaluating trophic cascades as drivers of regime shifts in different ocean ecosystems

PubMed Central

Pershing, Andrew J.; Mills, Katherine E.; Record, Nicholas R.; Stamieszkin, Karen; Wurtzell, Katharine V.; Byron, Carrie J.; Fitzpatrick, Dominic; Golet, Walter J.; Koob, Elise

2015-01-01

In ecosystems that are strongly structured by predation, reducing top predator abundance can alter several lower trophic levels—a process known as a trophic cascade. A persistent trophic cascade also fits the definition of a regime shift. Such ‘trophic cascade regime shifts' have been reported in a few pelagic marine systems—notably the Black Sea, Baltic Sea and eastern Scotian Shelf—raising the question of how common this phenomenon is in the marine environment. We provide a general methodology for distinguishing top-down and bottom-up effects and apply this methodology to time series from these three ecosystems. We found evidence for top-down forcing in the Black Sea due primarily to gelatinous zooplankton. Changes in the Baltic Sea are primarily bottom-up, strongly structured by salinity, but top-down forcing related to changes in cod abundance also shapes the ecosystem. Changes in the eastern Scotian Shelf that were originally attributed to declines in groundfish are better explained by changes in stratification. Our review suggests that trophic cascade regime shifts are rare in open ocean ecosystems and that their likelihood increases as the residence time of water in the system increases. Our work challenges the assumption that negative correlation between consecutive trophic levels implies top-down forcing.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boring, Ronald Laurids

2014-10-01

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 approachesmore » 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.« less

Abundant Lysine Methylation and N-Terminal Acetylation in Sulfolobus islandicus Revealed by Bottom-Up and Top-Down Proteomics*

PubMed Central

Vorontsov, Egor A.; Rensen, Elena; Prangishvili, David; Krupovic, Mart; Chamot-Rooke, Julia

2016-01-01

Protein post-translational methylation has been reported to occur in archaea, including members of the genus Sulfolobus, but has never been characterized on a proteome-wide scale. Among important Sulfolobus proteins carrying such modification are the chromatin proteins that have been described to be methylated on lysine side chains, resembling eukaryotic histones in that aspect. To get more insight into the extent of this modification and its dynamics during the different growth steps of the thermoacidophylic archaeon S. islandicus LAL14/1, we performed a global and deep proteomic analysis using a combination of high-throughput bottom-up and top-down approaches on a single high-resolution mass spectrometer. 1,931 methylation sites on 751 proteins were found by the bottom-up analysis, with methylation sites on 526 proteins monitored throughout three cell culture growth stages: early-exponential, mid-exponential, and stationary. The top-down analysis revealed 3,978 proteoforms arising from 681 proteins, including 292 methylated proteoforms, 85 of which were comprehensively characterized. Methylated proteoforms of the five chromatin proteins (Alba1, Alba2, Cren7, Sul7d1, Sul7d2) were fully characterized by a combination of bottom-up and top-down data. The top-down analysis also revealed an increase of methylation during cell growth for two chromatin proteins, which had not been evidenced by bottom-up. These results shed new light on the ubiquitous lysine methylation throughout the S. islandicus proteome. Furthermore, we found that S. islandicus proteins are frequently acetylated at the N terminus, following the removal of the N-terminal methionine. This study highlights the great value of combining bottom-up and top-down proteomics for obtaining an unprecedented level of accuracy in detecting differentially modified intact proteoforms. The data have been deposited to the ProteomeXchange with identifiers PXD003074 and PXD004179. PMID:27555370

Comparing Top-down and Bottom-up Estimates of Methane Emissions across Multiple U.S. Basins Provides Insights into National Oil and Gas Emissions and Mitigation Strategies

NASA Astrophysics Data System (ADS)

Hamburg, S.; Alvarez, R.; Lyon, D. R.; Zavala-Araiza, D.

2016-12-01

Several recent studies quantified regional methane emissions in U.S. oil and gas (O&G) basins using top-down approaches such as airborne mass balance measurements. These studies apportioned total methane emissions to O&G based on hydrocarbon ratios or subtracting bottom-up estimates of other sources. In most studies, top-down estimates of O&G methane emissions exceeded bottom-up emission inventories. An exception is the Barnett Shale Coordinated Campaign, which found agreement between aircraft mass balance estimates and a custom emission inventory. Reconciliation of Barnett Shale O&G emissions depended on two key features: 1) matching the spatial domains of top-down and bottom-up estimates, and 2) accounting for fat-tail sources in site-level emission factors. We construct spatially explicit custom emission inventories for domains with top-down O&G emission estimates in eight major U.S. oil and gas production basins using a variety of data sources including a spatially-allocated U.S. EPA Greenhouse Gas Inventory, the EPA Greenhouse Gas Reporting Program, state emission inventories, and recently published measurement studies. A comparison of top-down and our bottom-up estimates of O&G emissions constrains the gap between these approaches and elucidates regional variability in production-normalized loss rates. A comparison of component-level and site-level emission estimates of production sites in the Barnett Shale region - where comprehensive activity data and emissions estimates are available - indicates that abnormal process conditions contribute about 20% of regional O&G emissions. Combining these two analyses provides insights into the relative importance of different equipment, processes, and malfunctions to emissions in each basin. These data allow us to estimate the U.S. O&G supply chain loss rate, recommend mitigation strategies to reduce emissions from existing infrastructure, and discuss how a similar approach can be applied internationally.

Climate-mediated changes in marine ecosystem regulation during El Niño.

PubMed

Lindegren, Martin; Checkley, David M; Koslow, Julian A; Goericke, Ralf; Ohman, Mark D

2018-02-01

The degree to which ecosystems are regulated through bottom-up, top-down, or direct physical processes represents a long-standing issue in ecology, with important consequences for resource management and conservation. In marine ecosystems, the role of bottom-up and top-down forcing has been shown to vary over spatio-temporal scales, often linked to highly variable and heterogeneously distributed environmental conditions. Ecosystem dynamics in the Northeast Pacific have been suggested to be predominately bottom-up regulated. However, it remains unknown to what extent top-down regulation occurs, or whether the relative importance of bottom-up and top-down forcing may shift in response to climate change. In this study, we investigate the effects and relative importance of bottom-up, top-down, and physical forcing during changing climate conditions on ecosystem regulation in the Southern California Current System (SCCS) using a generalized food web model. This statistical approach is based on nonlinear threshold models and a long-term data set (~60 years) covering multiple trophic levels from phytoplankton to predatory fish. We found bottom-up control to be the primary mode of ecosystem regulation. However, our results also demonstrate an alternative mode of regulation represented by interacting bottom-up and top-down forcing, analogous to wasp-waist dynamics, but occurring across multiple trophic levels and only during periods of reduced bottom-up forcing (i.e., weak upwelling, low nutrient concentrations, and primary production). The shifts in ecosystem regulation are caused by changes in ocean-atmosphere forcing and triggered by highly variable climate conditions associated with El Niño. Furthermore, we show that biota respond differently to major El Niño events during positive or negative phases of the Pacific Decadal Oscillation (PDO), as well as highlight potential concerns for marine and fisheries management by demonstrating increased sensitivity of pelagic fish to exploitation during El Niño. © 2017 John Wiley & Sons Ltd.

Cascading top-down effects of changing oceanic predator abundances.

PubMed

Baum, Julia K; Worm, Boris

2009-07-01

1. Top-down control can be an important determinant of ecosystem structure and function, but in oceanic ecosystems, where cascading effects of predator depletions, recoveries, and invasions could be significant, such effects had rarely been demonstrated until recently. 2. Here we synthesize the evidence for oceanic top-down control that has emerged over the last decade, focusing on large, high trophic-level predators inhabiting continental shelves, seas, and the open ocean. 3. In these ecosystems, where controlled manipulations are largely infeasible, 'pseudo-experimental' analyses of predator-prey interactions that treat independent predator populations as 'replicates', and temporal or spatial contrasts in predator populations and climate as 'treatments', are increasingly employed to help disentangle predator effects from environmental variation and noise. 4. Substantial reductions in marine mammals, sharks, and piscivorous fishes have led to mesopredator and invertebrate predator increases. Conversely, abundant oceanic predators have suppressed prey abundances. Predation has also inhibited recovery of depleted species, sometimes through predator-prey role reversals. Trophic cascades have been initiated by oceanic predators linking to neritic food webs, but seem inconsistent in the pelagic realm with effects often attenuating at plankton. 5. Top-down control is not uniformly strong in the ocean, and appears contingent on the intensity and nature of perturbations to predator abundances. Predator diversity may dampen cascading effects except where nonselective fisheries deplete entire predator functional groups. In other cases, simultaneous exploitation of predator and prey can inhibit prey responses. Explicit consideration of anthropogenic modifications to oceanic foodwebs should help inform predictions about trophic control. 6. Synthesis and applications. Oceanic top-down control can have important socio-economic, conservation, and management implications as mesopredators and invertebrates assume dominance, and recovery of overexploited predators is impaired. Continued research aimed at integrating across trophic levels is needed to understand and forecast the ecosystem effects of changing oceanic predator abundances, the relative strength of top-down and bottom-up control, and interactions with intensifying anthropogenic stressors such as climate change.

One Size Does Not Fit All: Human Failure Event Decomposition and Task Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ronald Laurids Boring, PhD

2014-09-01

In the probabilistic safety assessments (PSAs) 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 or exacerbated 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,more » both approaches should arrive at the same set of HFEs. This question remains central as human reliability analysis (HRA) methods are generalized to new domains like oil and gas. The HFEs used in nuclear PSAs tend to be top-down—defined as a subset of the PSA—whereas the HFEs used in petroleum quantitative risk assessments (QRAs) are more likely 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. In this paper, I first review top-down and bottom-up approaches for defining HFEs and then present a seven-step guideline to ensure a task analysis completed as part of human error identification decomposes to a level suitable for use as HFEs. This guideline illustrates an effective way to bridge the bottom-up approach with top-down requirements.« less

Top-down nanofabrication of silicon nanoribbon field effect transistor (Si-NR FET) for carcinoembryonic antigen detection.

PubMed

Bao, Zengtao; Sun, Jialin; Zhao, Xiaoqian; Li, Zengyao; Cui, Songkui; Meng, Qingyang; Zhang, Ye; Wang, Tong; Jiang, Yanfeng

2017-01-01

Sensitive and quantitative detection of tumor markers is highly required in the clinic for cancer diagnosis and consequent treatment. A field-effect transistor-based (FET-based) nanobiosensor emerges with characteristics of being label-free, real-time, having high sensitivity, and providing direct electrical readout for detection of biomarkers. In this paper, a top-down approach is proposed and implemented to fulfill a novel silicon nano-ribbon FET, which acts as biomarker sensor for future clinical application. Compared with the bottom-up approach, a top-down fabrication approach can confine width and length of the silicon FET precisely to control its electrical properties. The silicon nanoribbon (Si-NR) transistor is fabricated on a Silicon-on-Insulator (SOI) substrate by a top-down approach with complementary metal oxide semiconductor (CMOS)-compatible technology. After the preparation, the surface of Si-NR is functionalized with 3-aminopropyltriethoxysilane (APTES). Glutaraldehyde is utilized to bind the amino terminals of APTES and antibody on the surface. Finally, a microfluidic channel is integrated on the top of the device, acting as a flowing channel for the carcinoembryonic antigen (CEA) solution. The Si-NR FET is 120 nm in width and 25 nm in height, with ambipolar electrical characteristics. A logarithmic relationship between the changing ratio of the current and the CEA concentration is measured in the range of 0.1-100 ng/mL. The sensitivity of detection is measured as 10 pg/mL. The top-down fabricated biochip shows feasibility in direct detecting of CEA with the benefits of real-time, low cost, and high sensitivity as a promising biosensor for tumor early diagnosis.

Global population genetic dynamics of a highly migratory, apex predator shark.

PubMed

Bernard, Andrea M; Feldheim, Kevin A; Heithaus, Michael R; Wintner, Sabine P; Wetherbee, Bradley M; Shivji, Mahmood S

2016-11-01

Knowledge of genetic connectivity dynamics in the world's large-bodied, highly migratory, apex predator sharks across their global ranges is limited. One such species, the tiger shark (Galeocerdo cuvier), occurs worldwide in warm temperate and tropical waters, uses remarkably diverse habitats (nearshore to pelagic) and possesses a generalist diet that can structure marine ecosystems through top-down processes. We investigated the phylogeography and the global population structure of this exploited, phylogenetically enigmatic shark by using 10 nuclear microsatellites (n = 380) and sequences from the mitochondrial control region (CR, n = 340) and cytochrome oxidase I gene (n = 100). All three marker classes showed the genetic differentiation between tiger sharks from the western Atlantic and Indo-Pacific ocean basins (microsatellite F ST  > 0.129; CR Φ ST  > 0.497), the presence of North vs. southwestern Atlantic differentiation and the isolation of tiger sharks sampled from Hawaii from other surveyed locations. Furthermore, mitochondrial DNA revealed high levels of intraocean basin matrilineal population structure, suggesting female philopatry and sex-biased gene flow. Coalescent- and genetic distance-based estimates of divergence from CR sequences were largely congruent (d corr  = 0.0015-0.0050), indicating a separation of Indo-Pacific and western Atlantic tiger sharks <1 million years ago. Mitochondrial haplotype relationships suggested that the western South Atlantic Ocean was likely a historical connection for interocean basin linkages via the dispersal around South Africa. Together, the results reveal unexpectedly high levels of population structure in a highly migratory, behaviourally generalist, cosmopolitan ocean predator, calling for management and conservation on smaller-than-anticipated spatial scales. © 2016 John Wiley & Sons Ltd.

Using the memory activation capture (MAC) procedure to investigate the temporal dynamics of hypothesis generation.

PubMed

Lange, Nicholas D; Buttaccio, Daniel R; Davelaar, Eddy J; Thomas, Rick P

2014-02-01

Research investigating top-down capture has demonstrated a coupling of working memory content with attention and eye movements. By capitalizing on this relationship, we have developed a novel methodology, called the memory activation capture (MAC) procedure, for measuring the dynamics of working memory content supporting complex cognitive tasks (e.g., decision making, problem solving). The MAC procedure employs briefly presented visual arrays containing task-relevant information at critical points in a task. By observing which items are preferentially fixated, we gain a measure of working memory content as the task evolves through time. The efficacy of the MAC procedure was demonstrated in a dynamic hypothesis generation task in which some of its advantages over existing methods for measuring changes in the contents of working memory over time are highlighted. In two experiments, the MAC procedure was able to detect the hypothesis that was retrieved and placed into working memory. Moreover, the results from Experiment 2 suggest a two-stage process following hypothesis retrieval, whereby the hypothesis undergoes a brief period of heightened activation before entering a lower activation state in which it is maintained for output. The results of both experiments are of additional general interest, as they represent the first demonstrations of top-down capture driven by participant-established WM content retrieved from long-term memory.

Anti-pointing is mediated by a perceptual bias of target location in left and right visual space.

PubMed

Heath, Matthew; Maraj, Anika; Gradkowski, Ashlee; Binsted, Gordon

2009-01-01

We sought to determine whether mirror-symmetrical limb movements (so-called anti-pointing) elicit a pattern of endpoint bias commensurate with perceptual judgments. In particular, we examined whether asymmetries related to the perceptual over- and under-estimation of target extent in respective left and right visual space impacts the trajectories of anti-pointing. In Experiment 1, participants completed direct (i.e. pro-pointing) and mirror-symmetrical (i.e. anti-pointing) responses to targets in left and right visual space with their right hand. In line with the anti-saccade literature, anti-pointing yielded longer reaction times than pro-pointing: a result suggesting increased top-down processing for the sensorimotor transformations underlying a mirror-symmetrical response. Most interestingly, pro-pointing yielded comparable endpoint accuracy in left and right visual space; however, anti-pointing produced an under- and overshooting bias in respective left and right visual space. In Experiment 2, we replicated the findings from Experiment 1 and further demonstrate that the endpoint bias of anti-pointing is independent of the reaching limb (i.e. left vs. right hand) and between-task differences in saccadic drive. We thus propose that the visual field-specific endpoint bias observed here is related to the cognitive (i.e. top-down) nature of anti-pointing and the corollary use of visuo-perceptual networks to support the sensorimotor transformations underlying such actions.

The ups and downs of trophic control in continental shelf ecosystems.

PubMed

Frank, Kenneth T; Petrie, Brian; Shackell, Nancy L

2007-05-01

Traditionally, marine ecosystem structure was thought to be determined by phytoplankton dynamics. However, an integrated view on the relative roles of top-down (consumer-driven) and bottom-up (resource-driven) forcing in large-scale, exploited marine ecosystems is emerging. Long time series of scientific survey data, underpinning the management of commercially exploited species such as cod, are being used to diagnose mechanisms that could affect the composition and relative abundance of species in marine food webs. By assembling published data from studies in exploited North Atlantic ecosystems, we found pronounced geographical variation in top-down and bottom-up trophic forcing. The data suggest that ecosystem susceptibility to top-down control and their resiliency to exploitation are related to species richness and oceanic temperature conditions. Such knowledge could be used to produce ecosystem guidelines to regulate and manage fisheries in a sustainable fashion.

Modeling instructor preferences for CPR and AED competence estimation.

PubMed

Birnbaum, Alice; McBurnie, Mary Ann; Powell, Judy; Ottingham, Lois Van; Riegel, Barbara; Potts, Jerry; Hedges, Jerris R

2005-03-01

Cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) skills competency can be tested using a checklist of component skills, individually graded "pass" or "fail." Scores are typically calculated as the percentage of skills passed, but may differ from an instructor's overall subjective assessment of simulated CPR or AED adequacy. To identify and evaluate composite measures (methods for scoring checklists) that reflect instructors' subjective assessments of CPR or AED skills performance best. Associations between instructor assessment and lay-volunteer skill performance were made using 6380 CPR and 3313 AED skill retention tests collected in the Public Access Defibrillation Trial. Checklists included CPR skills (e.g., calling 911, administering compressions) and AED skills (e.g., positioning electrodes, shocking within 90 s of AED arrival). The instructor's subjective overall assessment (adequate/inadequate) of CPR performance (perfusion) or AED competence (effective shock) was compared to composite measures. We evaluated the traditional composite measure (assigning equal weights to individual skills) and several nontraditional composite measures (assigning variable weights). Skills performed out of sequence were further weighted from 0% (no credit) to 100% (full credit). Composite measures providing full credit for skills performed out of sequence and down-weighting process skills (e.g., calling 911, clearing oneself from the AED) had the strongest association with the instructor's subjective assessment; the traditional CPR composite measure had the weakest association. Our findings suggest that instructors in public CPR and AED classes may tend to down-weight process skills and to excuse step sequencing errors when evaluating CPR and AED skills subjectively for overall proficiency. Testing methods that relate classroom performance to actual performance in the field and to clinical outcomes require further research.

KSC-2012-5575

NASA Image and Video Library

2012-09-20

CAPE CANAVERAL, Fla. - NASA's Johnson Space Center Aerospace Engineer Jeff Hagen attaches a rotor to the top of a model capsule ahead of tests inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The design would give a capsule the stability and control of a helicopter, but would not be powered. Instead, the wind passing over the rotors as the capsule descends would make the blades turn, a process called auto-rotation. The intent is to give real spacecraft a soft landing with enough control that they could touch down anywhere in the world, whether it be a runway or parking lot. In other words, wherever a helicopter could land, a spacecraft could land, too. Photo credit: NASA/Kim Shiflett

Structured programming: Principles, notation, procedure

NASA Technical Reports Server (NTRS)

JOST

1978-01-01

Structured programs are best represented using a notation which gives a clear representation of the block encapsulation. In this report, a set of symbols which can be used until binding directives are republished is suggested. Structured programming also allows a new method of procedure for design and testing. Programs can be designed top down, that is, they can start at the highest program plane and can penetrate to the lowest plane by step-wise refinements. The testing methodology also is adapted to this procedure. First, the highest program plane is tested, and the programs which are not yet finished in the next lower plane are represented by so-called dummies. They are gradually replaced by the real programs.

Earth scientists list top priorities for space missions

NASA Astrophysics Data System (ADS)

Voosen, Paul

2018-01-01

Earth scientists hope a new priority setting effort will help them make the most of NASA's limited budget for satellite missions that watch over the planet. The so-called decadal survey, issued in January by the National Academies of Sciences, Engineering, and Medicine, laid out the community's consensus wish list, ranging from cloud monitoring to multiwavelength imaging—and recommends a strong dose of competition to keep costs down. The report prioritizes five observations for launch, including hyperspectral imaging, clouds, atmospheric particles, and missions to chart gravity variations and tiny crustal movements. It also advocates creating a new line of $350 million missions targeting seven observations, with competitions to choose three for flight in the next 10 years.

Identification of specific posttranslational O-mycoloylations mediating protein targeting to the mycomembrane.

PubMed

Carel, Clément; Marcoux, Julien; Réat, Valérie; Parra, Julien; Latgé, Guillaume; Laval, Françoise; Demange, Pascal; Burlet-Schiltz, Odile; Milon, Alain; Daffé, Mamadou; Tropis, Maryelle G; Renault, Marie A M

2017-04-18

The outer membranes (OMs) of members of the Corynebacteriales bacterial order, also called mycomembranes, harbor mycolic acids and unusual outer membrane proteins (OMPs), including those with α-helical structure. The signals that allow precursors of such proteins to be targeted to the mycomembrane remain uncharacterized. We report here the molecular features responsible for OMP targeting to the mycomembrane of Corynebacterium glutamicum , a nonpathogenic member of the Corynebacteriales order. To better understand the mechanisms by which OMP precursors were sorted in C. glutamicum , we first investigated the partitioning of endogenous and recombinant PorA, PorH, PorB, and PorC between bacterial compartments and showed that they were both imported into the mycomembrane and secreted into the extracellular medium. A detailed investigation of cell extracts and purified proteins by top-down MS, NMR spectroscopy, and site-directed mutagenesis revealed specific and well-conserved posttranslational modifications (PTMs), including O -mycoloylation, pyroglutamylation, and N -formylation, for mycomembrane-associated and -secreted OMPs. PTM site sequence analysis from C. glutamicum OMP and other O -acylated proteins in bacteria and eukaryotes revealed specific patterns. Furthermore, we found that such modifications were essential for targeting to the mycomembrane and sufficient for OMP assembly into mycolic acid-containing lipid bilayers. Collectively, it seems that these PTMs have evolved in the Corynebacteriales order and beyond to guide membrane proteins toward a specific cell compartment.

Identification of specific posttranslational O-mycoloylations mediating protein targeting to the mycomembrane

PubMed Central

Carel, Clément; Réat, Valérie; Parra, Julien; Latgé, Guillaume; Laval, Françoise; Burlet-Schiltz, Odile; Milon, Alain; Daffé, Mamadou; Tropis, Maryelle G.; Renault, Marie A. M.

2017-01-01

The outer membranes (OMs) of members of the Corynebacteriales bacterial order, also called mycomembranes, harbor mycolic acids and unusual outer membrane proteins (OMPs), including those with α-helical structure. The signals that allow precursors of such proteins to be targeted to the mycomembrane remain uncharacterized. We report here the molecular features responsible for OMP targeting to the mycomembrane of Corynebacterium glutamicum, a nonpathogenic member of the Corynebacteriales order. To better understand the mechanisms by which OMP precursors were sorted in C. glutamicum, we first investigated the partitioning of endogenous and recombinant PorA, PorH, PorB, and PorC between bacterial compartments and showed that they were both imported into the mycomembrane and secreted into the extracellular medium. A detailed investigation of cell extracts and purified proteins by top-down MS, NMR spectroscopy, and site-directed mutagenesis revealed specific and well-conserved posttranslational modifications (PTMs), including O-mycoloylation, pyroglutamylation, and N-formylation, for mycomembrane-associated and -secreted OMPs. PTM site sequence analysis from C. glutamicum OMP and other O-acylated proteins in bacteria and eukaryotes revealed specific patterns. Furthermore, we found that such modifications were essential for targeting to the mycomembrane and sufficient for OMP assembly into mycolic acid-containing lipid bilayers. Collectively, it seems that these PTMs have evolved in the Corynebacteriales order and beyond to guide membrane proteins toward a specific cell compartment. PMID:28373551

Studies of Visual Attention in Physics Problem Solving

ERIC Educational Resources Information Center

Madsen, Adrian M.

2013-01-01

The work described here represents an effort to understand and influence visual attention while solving physics problems containing a diagram. Our visual system is guided by two types of processes--top-down and bottom-up. The top-down processes are internal and determined by ones prior knowledge and goals. The bottom-up processes are external and…

A new calibrant for MALDI-TOF-TOF-PSD-MS/MS of non-digested proteins for top-down proteomic analysis

USDA-ARS?s Scientific Manuscript database

RATIONALE: Matrix-assisted laser desorption/ionization (MALDI) time-of-flight-time-of-flight (TOF-TOF) tandem mass spectrometry (MS/MS) has seen increasing use for post-source decay (PSD)-MS/MS analysis of non-digested protein ions for top-down proteomic identification. However, there is no commonl...

Trait- and density-mediated indirect interactions initiated by an exotic invasive plant autogenic ecosystem engineer

Treesearch

Dean E. Pearson

2010-01-01

Indirect interactions are important for structuring ecological systems. However, research on indirect effects has been heavily biased toward top-down trophic interactions, and less is known about other indirect-interaction pathways. As autogenic ecosystem engineers, plants can serve as initiators of nontrophic indirect interactions that, like top-down pathways, can...

Improving Reading Fluency and Comprehension in Adult ESL Learners Using Bottom-Up and Top-Down Vocabulary Training

ERIC Educational Resources Information Center

Oliver, Rhonda; Young, Shahreen

2016-01-01

The current research examines the effect of two methods of vocabulary training on reading fluency and comprehension of adult English as second language (ESL) tertiary-bound students. The methods used were isolated vocabulary training (bottom-up reading) and vocabulary training in context (top-down reading). The current exploratory and…

Attention and Cognitive Control Networks Assessed in a Dichotic Listening fMRI Study

ERIC Educational Resources Information Center

Falkenberg, Liv E.; Specht, Karsten; Westerhausen, Rene

2011-01-01

A meaningful interaction with our environment relies on the ability to focus on relevant sensory input and to ignore irrelevant information, i.e. top-down control and attention processes are employed to select from competing stimuli following internal goals. In this, the demands for the recruitment of top-down control processes depend on the…

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

ERIC Educational Resources Information Center

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…

Attentional Capture by Salient Color Singleton Distractors Is Modulated by Top-Down Dimensional Set

ERIC Educational Resources Information Center

Muller, Hermann J.; Geyer, Thomas; Zehetleitner, Michael; Krummenacher, Joseph

2009-01-01

Three experiments examined whether salient color singleton distractors automatically interfere with the detection singleton form targets in visual search (e.g., J. Theeuwes, 1992), or whether the degree of interference is top-down modulable. In Experiments 1 and 2, observers started with a pure block of trials, which contained either never a…

The Role of Teaching Experience in Language Teachers' Perceptions of a Top-Down Curriculum Change

ERIC Educational Resources Information Center

Rahimi, Mehrak; Alavi, Jalil

2017-01-01

The current study aimed to investigate the role of teaching experience in language teachers' perceptions of a top-down curriculum change. One hundred twenty-seven language teachers who have been experiencing the change for three years participated in the study. Their perceptions of change were quantitatively assessed by perceptions of change…

A Hierarchical and Contextual Model for Learning and Recognizing Highly Variant Visual Categories

DTIC Science & Technology

2010-01-01

neighboring pattern primitives, to create our model. We also present a minimax entropy framework for automatically learning which contextual constraints are...Grammars . . . . . . . . . . . . . . . . . . 19 3.2 Markov Random Fields . . . . . . . . . . . . . . . . . . . . . . . . 23 3.3 Creating a Contextual...Compositional Boosting. . . . . 119 7.8 Top-down hallucinations of missing objects. . . . . . . . . . . . . . . 121 7.9 The bottom-up to top-down

Thinking about the Weather: How Display Salience and Knowledge Affect Performance in a Graphic Inference Task

ERIC Educational Resources Information Center

Hegarty, Mary; Canham, Matt S.; Fabrikant, Sara I.

2010-01-01

Three experiments examined how bottom-up and top-down processes interact when people view and make inferences from complex visual displays (weather maps). Bottom-up effects of display design were investigated by manipulating the relative visual salience of task-relevant and task-irrelevant information across different maps. Top-down effects of…

49 CFR 537.7 - Pre-model year and mid-model year reports.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... List the model types in order of increasing average inertia weight from top to bottom down the left... form. List the model types in order of increasing average inertia weight from top to bottom down the... trucks in your fleet that meet the mild and strong hybrid vehicle definitions. For each mild and strong...

49 CFR 537.7 - Pre-model year and mid-model year reports.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... List the model types in order of increasing average inertia weight from top to bottom down the left... form. List the model types in order of increasing average inertia weight from top to bottom down the... trucks in your fleet that meet the mild and strong hybrid vehicle definitions. For each mild and strong...

Microfabricated magnetic structures for future medicine: from sensors to cell actuators

PubMed Central

Vitol, Elina A; Novosad, Valentyn; Rozhkova, Elena A

2013-01-01

In this review, we discuss the prospective medical application of magnetic carriers microfabricated by top-down techniques. Physical methods allow the fabrication of a variety of magnetic structures with tightly controlled magnetic properties and geometry, which makes them very attractive for a cost-efficient mass-production in the fast growing field of nanomedicine. Stand-alone fabricated particles along with integrated devices combining lithographically defined magnetic structures and synthesized magnetic tags will be considered. Applications of microfabricated multifunctional magnetic structures for future medicinal purposes range from ultrasensitive in vitro diagnostic bioassays, DNA sequencing and microfluidic cell sorting to magnetomechanical actuation, cargo delivery, contrast enhancement and heating therapy. PMID:23148542

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

NASA Astrophysics Data System (ADS)

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.

Top-down search for color prevents voluntary directing of attention to informative singleton cues.

PubMed

Worschech, Franziska; Ansorge, Ulrich

2012-01-01

Visuo-spatial attention can be directed in a top-down controlled way to search for color targets and it can be captured by color contrasts, regardless of color identity. Here we tested whether participants can both search for a particular color target (e.g., red) and make use of a color-contrast cue that predicted the target's most likely position to direct their attention voluntarily. Our results show that this was impossible for the participants. Results support that top-down search for particular colors is incommensurate with directing attention to just any color contrast. The results are discussed in light of the current debates concerning the roles of color and color contrast for visuo-spatial attention.

Preserved feedforward but impaired top-down processes in the vegetative state.

PubMed

Boly, Melanie; Garrido, Marta Isabel; Gosseries, Olivia; Bruno, Marie-Aurélie; Boveroux, Pierre; Schnakers, Caroline; Massimini, Marcello; Litvak, Vladimir; Laureys, Steven; Friston, Karl

2011-05-13

Frontoparietal cortex is involved in the explicit processing (awareness) of stimuli. Frontoparietal activation has also been found in studies of subliminal stimulus processing. We hypothesized that an impairment of top-down processes, involved in recurrent neuronal message-passing and the generation of long-latency electrophysiological responses, might provide a more reliable correlate of consciousness in severely brain-damaged patients, than frontoparietal responses. We measured effective connectivity during a mismatch negativity paradigm and found that the only significant difference between patients in a vegetative state and controls was an impairment of backward connectivity from frontal to temporal cortices. This result emphasizes the importance of top-down projections in recurrent processing that involve high-order associative cortices for conscious perception.

Cognitive functions of the posterior parietal cortex: top-down and bottom-up attentional control

PubMed Central

Shomstein, Sarah

2012-01-01

Although much less is known about human parietal cortex than that of homologous monkey cortex, recent studies, employing neuroimaging, and neuropsychological methods, have begun to elucidate increasingly fine-grained functional and structural distinctions. This review is focused on recent neuroimaging and neuropsychological studies elucidating the cognitive roles of dorsal and ventral regions of parietal cortex in top-down and bottom-up attentional orienting, and on the interaction between the two attentional allocation mechanisms. Evidence is reviewed arguing that regions along the dorsal areas of the parietal cortex, including the superior parietal lobule (SPL) are involved in top-down attentional orienting, while ventral regions including the temporo-parietal junction (TPJ) are involved in bottom-up attentional orienting. PMID:22783174

Validation and optimization of the Ion Torrent S5 XL sequencer and Oncomine workflow for BRCA1 and BRCA2 genetic testing.

PubMed

Shin, Saeam; Kim, Yoonjung; Chul Oh, Seoung; Yu, Nae; Lee, Seung-Tae; Rak Choi, Jong; Lee, Kyung-A

2017-05-23

In this study, we validated the analytical performance of BRCA1/2 sequencing using Ion Torrent's new bench-top sequencer with amplicon panel with optimized bioinformatics pipelines. Using 43 samples that were previously validated by Illumina's MiSeq platform and/or by Sanger sequencing/multiplex ligation-dependent probe amplification, we amplified the target with the Oncomine™ BRCA Research Assay and sequenced on Ion Torrent S5 XL (Thermo Fisher Scientific, Waltham, MA, USA). We compared two bioinformatics pipelines for optimal processing of S5 XL sequence data: the Torrent Suite with a plug-in Torrent Variant Caller (Thermo Fisher Scientific), and commercial NextGENe software (Softgenetics, State College, PA, USA). All expected 681 single nucleotide variants, 15 small indels, and three copy number variants were correctly called, except one common variant adjacent to a rare variant on the primer-binding site. The sensitivity, specificity, false positive rate, and accuracy for detection of single nucleotide variant and small indels of S5 XL sequencing were 99.85%, 100%, 0%, and 99.99% for the Torrent Variant Caller and 99.85%, 99.99%, 0.14%, and 99.99% for NextGENe, respectively. The reproducibility of variant calling was 100%, and the precision of variant frequency also showed good performance with coefficients of variation between 0.32 and 5.29%. We obtained highly accurate data through uniform and sufficient coverage depth over all target regions and through optimization of the bioinformatics pipeline. We confirmed that our platform is accurate and practical for diagnostic BRCA1/2 testing in a clinical laboratory.

Building America Top Innovations 2012: Reduced Call-Backs with High-Performance Production Builders

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

2013-01-01

This Building America Top Innovations profile describes ways Building America teams have helped builders cut call-backs. Harvard University study found builders who worked with Building America had a 50% drop in call-backs. One builder reported a 50-fold reduction in the incidence of pipe freezing, a 50% reduction in drywall cracking, and a 60% decline in call-backs.

Asymmetric top-down modulation of ascending visual pathways in pigeons.

PubMed

Freund, Nadja; Valencia-Alfonso, Carlos E; Kirsch, Janina; Brodmann, Katja; Manns, Martina; Güntürkün, Onur

2016-03-01

Cerebral asymmetries are a ubiquitous phenomenon evident in many species, incl. humans, and they display some similarities in their organization across vertebrates. In many species the left hemisphere is associated with the ability to categorize objects based on abstract or experience-based behaviors. Using the asymmetrically organized visual system of pigeons as an animal model, we show that descending forebrain pathways asymmetrically modulate visually evoked responses of single thalamic units. Activity patterns of neurons within the nucleus rotundus, the largest thalamic visual relay structure in birds, were differently modulated by left and right hemispheric descending systems. Thus, visual information ascending towards the left hemisphere was modulated by forebrain top-down systems at thalamic level, while right thalamic units were strikingly less modulated. This asymmetry of top-down control could promote experience-based processes within the left hemisphere, while biasing the right side towards stimulus-bound response patterns. In a subsequent behavioral task we tested the possible functional impact of this asymmetry. Under monocular conditions, pigeons learned to discriminate color pairs, so that each hemisphere was trained on one specific discrimination. Afterwards the animals were presented with stimuli that put the hemispheres in conflict. Response patterns on the conflicting stimuli revealed a clear dominance of the left hemisphere. Transient inactivation of left hemispheric top-down control reduced this dominance while inactivation of right hemispheric top-down control had no effect on response patterns. Functional asymmetries of descending systems that modify visual ascending pathways seem to play an important role in the superiority of the left hemisphere in experience-based visual tasks. Copyright © 2015. Published by Elsevier Ltd.

The impact of top-down spatial attention on laterality and hemispheric asymmetry in the human parietal cortex

PubMed Central

Jeong, Su Keun; Xu, Yaoda

2016-01-01

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. PMID:27494544

The impact of top-down spatial attention on laterality and hemispheric asymmetry in the human parietal cortex.

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ansong, Charles; Wu, Si; Meng, Da

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

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

PubMed Central

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

The importance of an underestimated grazer under climate change: how crab density, consumer competition, and physical stress affect salt marsh resilience.

PubMed

Angelini, Christine; van Montfrans, Schuyler G; Hensel, Marc J S; He, Qiang; Silliman, Brian R

2018-05-01

Climate change and consumer outbreaks are driving ecosystem collapse worldwide. Although much research has demonstrated that these factors can interact, how heterogeneity in top-down control intensity and physical forcing modulates ecosystem resilience to climate stress remains poorly understood. Here, we explore whether the nocturnal herbivorous crab Sesarma reticulatum can control spatially dominant cordgrass (Spartina alterniflora) growth and how its top-down effects vary with crab density, drought stress, and large-scale disturbance in southeastern US salt marshes. In multiple field experiments and surveys, we show that Sesarma depresses cordgrass growth and that its effects increase in a saturating manner with increasing crab density, such that the highest naturally occurring densities of this consumer can trigger local cordgrass die-off. This top-down effect of Sesarma is similar in magnitude to what is thought to be the dominant grazer in the system, the marsh periwinkle snail Littoraria irrorata. In a drought stress by Sesarma density experiment, we further show that salinity stress and intensive crab herbivory additively suppress cordgrass drought resistance. After drought subsides, surveys and experiments reveal that Sesarma also stifles cordgrass re-growth into existing die-off areas. Together, these results show that multiple grazers powerfully regulate the productivity and drought resilience of these intertidal grasslands and that heterogeneity in physical stress and consumer density can dictate when and where top-down forcing is important. More generally, this work provides a rare, experimental demonstration of the critical role top-down control can play across the initiation and recovery stages of ecosystem die-off.

Deficits in Top-Down Sensory Prediction in Infants At Risk due to Premature Birth.

PubMed

Emberson, Lauren L; Boldin, Alex M; Riccio, Julie E; Guillet, Ronnie; Aslin, Richard N

2017-02-06

A prominent theoretical view is that the brain is inherently predictive [1, 2] and that prediction helps drive the engine of development [3, 4]. Although infants exhibit neural signatures of top-down sensory prediction [5, 6], in order to establish that prediction supports development, it must be established that deficits in early prediction abilities alter trajectories. We investigated prediction in infants born prematurely, a leading cause of neuro-cognitive impairment worldwide [7]. Prematurity, independent of medical complications, leads to developmental disturbances [8-12] and a broad range of developmental delays [13-17]. Is an alteration in early prediction abilities the common cause? Using functional near-infrared spectroscopy (fNIRS), we measured top-down sensory prediction in preterm infants (born <33 weeks gestation) before infants exhibited clinically identifiable developmental delays (6 months corrected age). Whereas preterm infants had typical neural responses to presented visual stimuli, they exhibited altered neural responses to predicted visual stimuli. Importantly, a separate behavioral control confirmed that preterm infants detect pattern violations at the same rate as full-terms, establishing selectivity of this response to top-down predictions (e.g., not in learning an audiovisual association). These findings suggest that top-down sensory prediction plays a crucial role in development and that deficits in this ability may be the reason why preterm infants experience altered developmental trajectories and are at risk for poor developmental outcomes. Moreover, this work presents an opportunity for establishing a neuro-biomarker for early identification of infants at risk and could guide early intervention regimens. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using distances between Top-n-gram and residue pairs for protein remote homology detection.

PubMed

Liu, Bin; Xu, Jinghao; Zou, Quan; Xu, Ruifeng; Wang, Xiaolong; Chen, Qingcai

2014-01-01

Protein remote homology detection is one of the central problems in bioinformatics, which is important for both basic research and practical application. Currently, discriminative methods based on Support Vector Machines (SVMs) achieve the state-of-the-art performance. Exploring feature vectors incorporating the position information of amino acids or other protein building blocks is a key step to improve the performance of the SVM-based methods. Two new methods for protein remote homology detection were proposed, called SVM-DR and SVM-DT. SVM-DR is a sequence-based method, in which the feature vector representation for protein is based on the distances between residue pairs. SVM-DT is a profile-based method, which considers the distances between Top-n-gram pairs. Top-n-gram can be viewed as a profile-based building block of proteins, which is calculated from the frequency profiles. These two methods are position dependent approaches incorporating the sequence-order information of protein sequences. Various experiments were conducted on a benchmark dataset containing 54 families and 23 superfamilies. Experimental results showed that these two new methods are very promising. Compared with the position independent methods, the performance improvement is obvious. Furthermore, the proposed methods can also provide useful insights for studying the features of protein families. The better performance of the proposed methods demonstrates that the position dependant approaches are efficient for protein remote homology detection. Another advantage of our methods arises from the explicit feature space representation, which can be used to analyze the characteristic features of protein families. The source code of SVM-DT and SVM-DR is available at http://bioinformatics.hitsz.edu.cn/DistanceSVM/index.jsp.

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

ERIC Educational Resources Information Center

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…

The Role of Bottom-Up Processing in Perceptual Categorization by 3- to 4-Month-Old Infants: Simulations and Data

ERIC Educational Resources Information Center

French, Robert M.; Mareschal, Denis; Mermillod, Martial; Quinn, Paul C.

2004-01-01

Disentangling bottom-up and top-down processing in adult category learning is notoriously difficult. Studying category learning in infancy provides a simple way of exploring category learning while minimizing the contribution of top-down information. Three- to 4-month-old infants presented with cat or dog images will form a perceptual category…

YahO protein as a calibrant for top-down proteomic identification of Shiga toxin using MALDI-TOF-TOF-MS/MS and post-source decay

USDA-ARS?s Scientific Manuscript database

Matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF-TOF) mass spectrometry is increasingly utilized for rapid top-down proteomic identification of proteins. This identification may involve analysis of either a pure protein or a protein mixture. For analysis of a pure protein...

On the Temporal Relation of Top-Down and Bottom-Up Mechanisms during Guidance of Attention

ERIC Educational Resources Information Center

Wykowska, Agnieszka; Schubo, Anna

2010-01-01

Two mechanisms are said to be responsible for guiding focal attention in visual selection: bottom-up, saliency-driven capture and top-down control. These mechanisms were examined with a paradigm that combined a visual search task with postdisplay probe detection. Two SOAs between the search display and probe onsets were introduced to investigate…

What Would You Ideally Do if There Were No Targets? An Ethnographic Study of the Unintended Consequences of Top-Down Governance in Two Clinical Settings

ERIC Educational Resources Information Center

Allard, Jon; Bleakley, Alan

2016-01-01

Top-down policy directives, such as targets and their associated protocols, may be driven politically rather than clinically and can be described as macro-political texts. While targets supposedly provide incentives for healthcare services, they may unintentionally shape practices of accommodation rather than implementation, deflecting…

Incorporating anthropogenic effects into trophic ecology: predator-prey interactions in a human-dominated landscape.

PubMed

Dorresteijn, Ine; Schultner, Jannik; Nimmo, Dale G; Fischer, Joern; Hanspach, Jan; Kuemmerle, Tobias; Kehoe, Laura; Ritchie, Euan G

2015-09-07

Apex predators perform important functions that regulate ecosystems worldwide. However, little is known about how ecosystem regulation by predators is influenced by human activities. In particular, how important are top-down effects of predators relative to direct and indirect human-mediated bottom-up and top-down processes? Combining data on species' occurrence from camera traps and hunting records, we aimed to quantify the relative effects of top-down and bottom-up processes in shaping predator and prey distributions in a human-dominated landscape in Transylvania, Romania. By global standards this system is diverse, including apex predators (brown bear and wolf), mesopredators (red fox) and large herbivores (roe and red deer). Humans and free-ranging dogs represent additional predators in the system. Using structural equation modelling, we found that apex predators suppress lower trophic levels, especially herbivores. However, direct and indirect top-down effects of humans affected the ecosystem more strongly, influencing species at all trophic levels. Our study highlights the need to explicitly embed humans and their influences within trophic cascade theory. This will greatly expand our understanding of species interactions in human-modified landscapes, which compose the majority of the Earth's terrestrial surface. © 2015 The Author(s).

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

PubMed Central

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

2015-01-01

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. PMID:25556211

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

PubMed

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.

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

PubMed

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.

The Role of Competitive Inhibition and Top-Down Feedback in Binding during Object Recognition

PubMed Central

Wyatte, Dean; Herd, Seth; Mingus, Brian; O’Reilly, Randall

2012-01-01

How does the brain bind together visual features that are processed concurrently by different neurons into a unified percept suitable for processes such as object recognition? Here, we describe how simple, commonly accepted principles of neural processing can interact over time to solve the brain’s binding problem. We focus on mechanisms of neural inhibition and top-down feedback. Specifically, we describe how inhibition creates competition among neural populations that code different features, effectively suppressing irrelevant information, and thus minimizing illusory conjunctions. Top-down feedback contributes to binding in a similar manner, but by reinforcing relevant features. Together, inhibition and top-down feedback contribute to a competitive environment that ensures only the most appropriate features are bound together. We demonstrate this overall proposal using a biologically realistic neural model of vision that processes features across a hierarchy of interconnected brain areas. Finally, we argue that temporal synchrony plays only a limited role in binding – it does not simultaneously bind multiple objects, but does aid in creating additional contrast between relevant and irrelevant features. Thus, our overall theory constitutes a solution to the binding problem that relies only on simple neural principles without any binding-specific processes. PMID:22719733

Incorporating anthropogenic effects into trophic ecology: predator–prey interactions in a human-dominated landscape

PubMed Central

Dorresteijn, Ine; Schultner, Jannik; Nimmo, Dale G.; Fischer, Joern; Hanspach, Jan; Kuemmerle, Tobias; Kehoe, Laura; Ritchie, Euan G.

2015-01-01

Apex predators perform important functions that regulate ecosystems worldwide. However, little is known about how ecosystem regulation by predators is influenced by human activities. In particular, how important are top-down effects of predators relative to direct and indirect human-mediated bottom-up and top-down processes? Combining data on species' occurrence from camera traps and hunting records, we aimed to quantify the relative effects of top-down and bottom-up processes in shaping predator and prey distributions in a human-dominated landscape in Transylvania, Romania. By global standards this system is diverse, including apex predators (brown bear and wolf), mesopredators (red fox) and large herbivores (roe and red deer). Humans and free-ranging dogs represent additional predators in the system. Using structural equation modelling, we found that apex predators suppress lower trophic levels, especially herbivores. However, direct and indirect top-down effects of humans affected the ecosystem more strongly, influencing species at all trophic levels. Our study highlights the need to explicitly embed humans and their influences within trophic cascade theory. This will greatly expand our understanding of species interactions in human-modified landscapes, which compose the majority of the Earth's terrestrial surface. PMID:26336169

Using response time distributions to examine top-down influences on attentional capture.

PubMed

Burnham, Bryan R

2013-02-01

Three experiments examined contingent attentional capture, which is the finding that cuing effects are larger when cues are perceptually similar to a target than when they are dissimilar to the target. This study also analyzed response times (RTs) in terms of the underlying distributions for valid cues and invalid cues. Specifically, an ex-Gaussian analysis and a vincentile analysis examined the influence of top-down attentional control settings on the shift and skew of RT distributions and how the shift and the skew contributed to the cuing effects in the mean RTs. The results showed that cue/target similarity influenced the size of cuing effects. The RT distribution analyses showed that the cuing effects reflected only a shifting effect, not a skewing effect, in the RT distribution between valid cues and invalid cues. That is, top-down attentional control moderated the cuing effects in the mean RTs through distribution shifting, not distribution skewing. The results support the contingent orienting hypothesis (Folk, Remington, & Johnston, Journal of Experimental Psychology: Human Perception and Performance, 18, 1030-1044, 1992) over the attentional disengagement account (Theeuwes, Atchley, & Kramer, 2000) as an explanation for when top-down attentional settings influence the selection of salient stimuli.

Top-Down Processes Override Bottom-Up Interference in the Flanker Task.

PubMed

Avital-Cohen, Rotem; Tsal, Yehoshua

2016-05-01

Distractor interference in the flanker task is commonly viewed as an outcome of unintentional, involuntary processing, a by-product of attention-controlled processing of the target. An important implication of this notion is that the distractors are not subjected to top-down processing of their own. We tested this idea in a modified version of the flanker task, in which letter targets (S or O) were sometimes flanked by ambiguous distractors (a character that could be S or 5 or one that could be O or 0). Distractor interference was dependent on participants' expectations regarding the category of the distractors (i.e., letters or digits). For example, the O-0 distractor interfered with responding to S when it was perceived as a letter, but not when it was perceived as a digit. Hence, participants applied top-down processing to the peripheral distractors independently of the top-down processing applied to the targets. The fact that to-be-ignored peripheral distractors were processed to such a high level raises questions regarding the fundamental differences between target and distractor processing, and the quality of attentional filtering. © The Author(s) 2016.

Oculomotor capture during real-world scene viewing depends on cognitive load.

PubMed

Matsukura, Michi; Brockmole, James R; Boot, Walter R; Henderson, John M

2011-03-25

It has been claimed that gaze control during scene viewing is largely governed by stimulus-driven, bottom-up selection mechanisms. Recent research, however, has strongly suggested that observers' top-down control plays a dominant role in attentional prioritization in scenes. A notable exception to this strong top-down control is oculomotor capture, where visual transients in a scene draw the eyes. One way to test whether oculomotor capture during scene viewing is independent of an observer's top-down goal setting is to reduce observers' cognitive resource availability. In the present study, we examined whether increasing observers' cognitive load influences the frequency and speed of oculomotor capture during scene viewing. In Experiment 1, we tested whether increasing observers' cognitive load modulates the degree of oculomotor capture by a new object suddenly appeared in a scene. Similarly, in Experiment 2, we tested whether increasing observers' cognitive load modulates the degree of oculomotor capture by an object's color change. In both experiments, the degree of oculomotor capture decreased as observers' cognitive resources were reduced. These results suggest that oculomotor capture during scene viewing is dependent on observers' top-down selection mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Warming shifts top-down and bottom-up control of pond food web structure and function

PubMed Central

Shurin, Jonathan B.; Clasen, Jessica L.; Greig, Hamish S.; Kratina, Pavel; Thompson, Patrick L.

2012-01-01

The effects of global and local environmental changes are transmitted through networks of interacting organisms to shape the structure of communities and the dynamics of ecosystems. We tested the impact of elevated temperature on the top-down and bottom-up forces structuring experimental freshwater pond food webs in western Canada over 16 months. Experimental warming was crossed with treatments manipulating the presence of planktivorous fish and eutrophication through enhanced nutrient supply. We found that higher temperatures produced top-heavy food webs with lower biomass of benthic and pelagic producers, equivalent biomass of zooplankton, zoobenthos and pelagic bacteria, and more pelagic viruses. Eutrophication increased the biomass of all organisms studied, while fish had cascading positive effects on periphyton, phytoplankton and bacteria, and reduced biomass of invertebrates. Surprisingly, virus biomass was reduced in the presence of fish, suggesting the possibility for complex mechanisms of top-down control of the lytic cycle. Warming reduced the effects of eutrophication on periphyton, and magnified the already strong effects of fish on phytoplankton and bacteria. Warming, fish and nutrients all increased whole-system rates of net production despite their distinct impacts on the distribution of biomass between producers and consumers, plankton and benthos, and microbes and macrobes. Our results indicate that warming exerts a host of indirect effects on aquatic food webs mediated through shifts in the magnitudes of top-down and bottom-up forcing. PMID:23007089

A Comprehensive Guide for Performing Sample Preparation and Top-Down Protein Analysis

PubMed Central

Padula, Matthew P.; Berry, Iain J.; O′Rourke, Matthew B.; Raymond, Benjamin B.A.; Santos, Jerran; Djordjevic, Steven P.

2017-01-01

Methodologies for the global analysis of proteins in a sample, or proteome analysis, have been available since 1975 when Patrick O′Farrell published the first paper describing two-dimensional gel electrophoresis (2D-PAGE). This technique allowed the resolution of single protein isoforms, or proteoforms, into single ‘spots’ in a polyacrylamide gel, allowing the quantitation of changes in a proteoform′s abundance to ascertain changes in an organism′s phenotype when conditions change. In pursuit of the comprehensive profiling of the proteome, significant advances in technology have made the identification and quantitation of intact proteoforms from complex mixtures of proteins more routine, allowing analysis of the proteome from the ‘Top-Down’. However, the number of proteoforms detected by Top-Down methodologies such as 2D-PAGE or mass spectrometry has not significantly increased since O’Farrell’s paper when compared to Bottom-Up, peptide-centric techniques. This article explores and explains the numerous methodologies and technologies available to analyse the proteome from the Top-Down with a strong emphasis on the necessity to analyse intact proteoforms as a better indicator of changes in biology and phenotype. We arrive at the conclusion that the complete and comprehensive profiling of an organism′s proteome is still, at present, beyond our reach but the continuing evolution of protein fractionation techniques and mass spectrometry brings comprehensive Top-Down proteome profiling closer. PMID:28387712

Variability and Quasi-Decadal Changes in the Methane Budget over the Period 2000-2012

NASA Technical Reports Server (NTRS)

Saunois, Marielle; Bousquet, Philippe; Poulter, Ben; Peregon, Anna; Ciais, Philippe; Canadell, Josep G.; Dlugokencky, Edward J.; Etiope, Giuseppe; Bastviken, David; Houweling, Sander;

Variability and quasi-decadal changes in the methane budget over the period 2000-2012

NASA Astrophysics Data System (ADS)

Saunois, Marielle; Bousquet, Philippe; Poulter, Ben; Peregon, Anna; Ciais, Philippe; Canadell, Josep G.; Dlugokencky, Edward J.; Etiope, Giuseppe; Bastviken, David; Houweling, Sander; Janssens-Maenhout, Greet; Tubiello, Francesco N.; Castaldi, Simona; Jackson, Robert B.; Alexe, Mihai; Arora, Vivek K.; Beerling, David J.; Bergamaschi, Peter; Blake, Donald R.; Brailsford, Gordon; Bruhwiler, Lori; Crevoisier, Cyril; Crill, Patrick; Covey, Kristofer; Frankenberg, Christian; Gedney, Nicola; Höglund-Isaksson, Lena; Ishizawa, Misa; Ito, Akihiko; Joos, Fortunat; Kim, Heon-Sook; Kleinen, Thomas; Krummel, Paul; Lamarque, Jean-François; Langenfelds, Ray; Locatelli, Robin; Machida, Toshinobu; Maksyutov, Shamil; Melton, Joe R.; Morino, Isamu; Naik, Vaishali; O'Doherty, Simon; Parmentier, Frans-Jan W.; Patra, Prabir K.; Peng, Changhui; Peng, Shushi; Peters, Glen P.; Pison, Isabelle; Prinn, Ronald; Ramonet, Michel; Riley, William J.; Saito, Makoto; Santini, Monia; Schroeder, Ronny; Simpson, Isobel J.; Spahni, Renato; Takizawa, Atsushi; Thornton, Brett F.; Tian, Hanqin; Tohjima, Yasunori; Viovy, Nicolas; Voulgarakis, Apostolos; Weiss, Ray; Wilton, David J.; Wiltshire, Andy; Worthy, Doug; Wunch, Debra; Xu, Xiyan; Yoshida, Yukio; Zhang, Bowen; Zhang, Zhen; Zhu, Qiuan

2017-09-01

Following the recent Global Carbon Project (GCP) synthesis of the decadal methane (CH4) budget over 2000-2012 (Saunois et al., 2016), we analyse here the same dataset with a focus on quasi-decadal and inter-annual variability in CH4 emissions. The GCP dataset integrates results from top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models (including process-based models for estimating land surface emissions and atmospheric chemistry), inventories of anthropogenic emissions, and data-driven approaches. The annual global methane emissions from top-down studies, which by construction match the observed methane growth rate within their uncertainties, all show an increase in total methane emissions over the period 2000-2012, but this increase is not linear over the 13 years. Despite differences between individual studies, the mean emission anomaly of the top-down ensemble shows no significant trend in total methane emissions over the period 2000-2006, during the plateau of atmospheric methane mole fractions, and also over the period 2008-2012, during the renewed atmospheric methane increase. However, the top-down ensemble mean produces an emission shift between 2006 and 2008, leading to 22 [16-32] Tg CH4 yr-1 higher methane emissions over the period 2008-2012 compared to 2002-2006. This emission increase mostly originated from the tropics, with a smaller contribution from mid-latitudes and no significant change from boreal regions. The regional contributions remain uncertain in top-down studies. Tropical South America and South and East Asia seem to contribute the most to the emission increase in the tropics. However, these two regions have only limited atmospheric measurements and remain therefore poorly constrained. The sectorial partitioning of this emission increase between the periods 2002-2006 and 2008-2012 differs from one atmospheric inversion study to another. However, all top-down studies suggest smaller changes in fossil fuel emissions (from oil, gas, and coal industries) compared to the mean of the bottom-up inventories included in this study. This difference is partly driven by a smaller emission change in China from the top-down studies compared to the estimate in the Emission Database for Global Atmospheric Research (EDGARv4.2) inventory, which should be revised to smaller values in a near future. We apply isotopic signatures to the emission changes estimated for individual studies based on five emission sectors and find that for six individual top-down studies (out of eight) the average isotopic signature of the emission changes is not consistent with the observed change in atmospheric 13CH4. However, the partitioning in emission change derived from the ensemble mean is consistent with this isotopic constraint. At the global scale, the top-down ensemble mean suggests that the dominant contribution to the resumed atmospheric CH4 growth after 2006 comes from microbial sources (more from agriculture and waste sectors than from natural wetlands), with an uncertain but smaller contribution from fossil CH4 emissions. In addition, a decrease in biomass burning emissions (in agreement with the biomass burning emission databases) makes the balance of sources consistent with atmospheric 13CH4 observations. In most of the top-down studies included here, OH concentrations are considered constant over the years (seasonal variations but without any inter-annual variability). As a result, the methane loss (in particular through OH oxidation) varies mainly through the change in methane concentrations and not its oxidants. For these reasons, changes in the methane loss could not be properly investigated in this study, although it may play a significant role in the recent atmospheric methane changes as briefly discussed at the end of the paper.

Auditing complex concepts of SNOMED using a refined hierarchical abstraction network.

PubMed

Wang, Yue; Halper, Michael; Wei, Duo; Gu, Huanying; Perl, Yehoshua; Xu, Junchuan; Elhanan, Gai; Chen, Yan; Spackman, Kent A; Case, James T; Hripcsak, George

2012-02-01

Auditors of a large terminology, such as SNOMED CT, face a daunting challenge. To aid them in their efforts, it is essential to devise techniques that can automatically identify concepts warranting special attention. "Complex" concepts, which by their very nature are more difficult to model, fall neatly into this category. A special kind of grouping, called a partial-area, is utilized in the characterization of complex concepts. In particular, the complex concepts that are the focus of this work are those appearing in intersections of multiple partial-areas and are thus referred to as overlapping concepts. In a companion paper, an automatic methodology for identifying and partitioning the entire collection of overlapping concepts into disjoint, singly-rooted groups, that are more manageable to work with and comprehend, has been presented. The partitioning methodology formed the foundation for the development of an abstraction network for the overlapping concepts called a disjoint partial-area taxonomy. This new disjoint partial-area taxonomy offers a collection of semantically uniform partial-areas and is exploited herein as the basis for a novel auditing methodology. The review of the overlapping concepts is done in a top-down order within semantically uniform groups. These groups are themselves reviewed in a top-down order, which proceeds from the less complex to the more complex overlapping concepts. The results of applying the methodology to SNOMED's Specimen hierarchy are presented. Hypotheses regarding error ratios for overlapping concepts and between different kinds of overlapping concepts are formulated. Two phases of auditing the Specimen hierarchy for two releases of SNOMED are reported on. With the use of the double bootstrap and Fisher's exact test (two-tailed), the auditing of concepts and especially roots of overlapping partial-areas is shown to yield a statistically significant higher proportion of errors. Copyright © 2011 Elsevier Inc. All rights reserved.

Auditing Complex Concepts of SNOMED using a Refined Hierarchical Abstraction Network

PubMed Central

Wang, Yue; Halper, Michael; Wei, Duo; Gu, Huanying; Perl, Yehoshua; Xu, Junchuan; Elhanan, Gai; Chen, Yan; Spackman, Kent A.; Case, James T.; Hripcsak, George

2012-01-01

Auditors of a large terminology, such as SNOMED CT, face a daunting challenge. To aid them in their efforts, it is essential to devise techniques that can automatically identify concepts warranting special attention. “Complex” concepts, which by their very nature are more difficult to model, fall neatly into this category. A special kind of grouping, called a partial-area, is utilized in the characterization of complex concepts. In particular, the complex concepts that are the focus of this work are those appearing in intersections of multiple partial-areas and are thus referred to as overlapping concepts. In a companion paper, an automatic methodology for identifying and partitioning the entire collection of overlapping concepts into disjoint, singly-rooted groups, that are more manageable to work with and comprehend, has been presented. The partitioning methodology formed the foundation for the development of an abstraction network for the overlapping concepts called a disjoint partial-area taxonomy. This new disjoint partial-area taxonomy offers a collection of semantically uniform partial-areas and is exploited herein as the basis for a novel auditing methodology. The review of the overlapping concepts is done in a top-down order within semantically uniform groups. These groups are themselves reviewed in a top-down order, which proceeds from the less complex to the more complex overlapping concepts. The results of applying the methodology to SNOMED’s Specimen hierarchy are presented. Hypotheses regarding error ratios for overlapping concepts and between different kinds of overlapping concepts are formulated. Two phases of auditing the Specimen hierarchy for two releases of SNOMED are reported on. With the use of the double bootstrap and Fisher’s exact test (two-tailed), the auditing of concepts and especially roots of overlapping partial-areas is shown to yield a statistically significant higher proportion of errors. PMID:21907827

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

PubMed

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. Graphical abstract ᅟ.

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

NASA Astrophysics Data System (ADS)

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.

Sequences within the 5' untranslated region regulate the levels of a kinetoplast DNA topoisomerase mRNA during the cell cycle.

PubMed Central

Pasion, S G; Hines, J C; Ou, X; Mahmood, R; Ray, D S

1996-01-01

Gene expression in trypanosomatids appears to be regulated largely at the posttranscriptional level and involves maturation of mRNA precursors by trans splicing of a 39-nucleotide miniexon sequence to the 5' end of the mRNA and cleavage and polyadenylation at the 3' end of the mRNA. To initiate the identification of sequences involved in the periodic expression of DNA replication genes in trypanosomatids, we have mapped splice acceptor sites in the 5' flanking region of the TOP2 gene, which encodes the kinetoplast DNA topoisomerase, and have carried out deletion analysis of this region on a plasmid-encoded TOP2 gene. Block deletions within the 5' untranslated region (UTR) identified two regions (-608 to -388 and -387 to -186) responsible for periodic accumulation of the mRNA. Deletion of one or the other of these sequences had no effect on periodic expression of the mRNA, while deletion of both regions resulted in constitutive expression of the mRNA throughout the cell cycle. Subcloning of these sequences into the 5' UTR of a construct lacking both regions of the TOP2 5' UTR has shown that an octamer consensus sequence present in the 5' UTR of the TOP2, RPA1, and DHFR-TS mRNAs is required for normal cycling of the TOP2 mRNA. Mutation of the consensus octamer sequence in the TOP2 5' UTR in a plasmid construct containing only a single consensus octamer and that shows normal cycling of the plasmid-encoded TOP2 mRNA resulted in substantial reduction of the cycling of the mRNA level. These results imply a negative regulation of TOP2 mRNA during the cell cycle by a mechanism involving redundant elements containing one or more copies of a conserved octamer sequence within the 5' UTR of TOP2 mRNA. PMID:8943327

Sequences within the 5' untranslated region regulate the levels of a kinetoplast DNA topoisomerase mRNA during the cell cycle.

PubMed

Pasion, S G; Hines, J C; Ou, X; Mahmood, R; Ray, D S

1996-12-01

Gene expression in trypanosomatids appears to be regulated largely at the posttranscriptional level and involves maturation of mRNA precursors by trans splicing of a 39-nucleotide miniexon sequence to the 5' end of the mRNA and cleavage and polyadenylation at the 3' end of the mRNA. To initiate the identification of sequences involved in the periodic expression of DNA replication genes in trypanosomatids, we have mapped splice acceptor sites in the 5' flanking region of the TOP2 gene, which encodes the kinetoplast DNA topoisomerase, and have carried out deletion analysis of this region on a plasmid-encoded TOP2 gene. Block deletions within the 5' untranslated region (UTR) identified two regions (-608 to -388 and -387 to -186) responsible for periodic accumulation of the mRNA. Deletion of one or the other of these sequences had no effect on periodic expression of the mRNA, while deletion of both regions resulted in constitutive expression of the mRNA throughout the cell cycle. Subcloning of these sequences into the 5' UTR of a construct lacking both regions of the TOP2 5' UTR has shown that an octamer consensus sequence present in the 5' UTR of the TOP2, RPA1, and DHFR-TS mRNAs is required for normal cycling of the TOP2 mRNA. Mutation of the consensus octamer sequence in the TOP2 5' UTR in a plasmid construct containing only a single consensus octamer and that shows normal cycling of the plasmid-encoded TOP2 mRNA resulted in substantial reduction of the cycling of the mRNA level. These results imply a negative regulation of TOP2 mRNA during the cell cycle by a mechanism involving redundant elements containing one or more copies of a conserved octamer sequence within the 5' UTR of TOP2 mRNA.

Scaled CMOS Reliability and Considerations for Spacecraft Systems: Bottom-Up and Top-Down Perspective

NASA Technical Reports Server (NTRS)

White, Mark

2012-01-01

New space missions will increasingly rely on more advanced technologies because of system requirements for higher performance, particularly in instruments and high-speed processing. Component-level reliability challenges with scaled CMOS in spacecraft systems from a bottom-up perspective have been presented. Fundamental Front-end and Back-end processing reliability issues with more aggressively scaled parts have been discussed. Effective thermal management from system-level to the componentlevel (top-down) is a key element in overall design of reliable systems. Thermal management in space systems must consider a wide range of issues, including thermal loading of many different components, and frequent temperature cycling of some systems. Both perspectives (top-down and bottom-up) play a large role in robust, reliable spacecraft system design.

[Empowerment and health promotion programming].

PubMed

Laverack, G

2008-12-01

Health promotion often presents a tension between "bottom up" and "top down" programming. "Bottom-up" is associated with community empowerment and begins on issues of concern to particular groups or individuals and regards an increase in overall control as an important element of the health outcome. "Top-down" is associated with disease prevention efforts and begins by seeking to involve beneficiaries on issues defined by health agencies. It regards improvements in health behaviours or bio-medical indicators as the important outcome and community empowerment is viewed simply as a means to the end of health behaviour change. The tension between these two approaches is not unresolvable, and this article presents a framework, the "parallel-track", intended to assist health promotion practitioners to systematically accommodate community empowerment goals within "top-down" health programming.

KSC-2010-5928

NASA Image and Video Library

2010-12-22

CAPE CANAVERAL, Fla. -- Space shuttle Discovery slowly moves down the crawlerway at NASA's Kennedy Space Center in Florida. The 3.4-mile trek, called rollback, from Launch Pad 39A to the Vehicle Assembly Building began at 10:48 p.m. yesterday and took about eight hours. Next, Discovery's external fuel tank will be examined and foam reapplied where 89 sensors were installed on the tank's aluminum skin for an instrumented tanking test on Dec. 17. The sensors were used to measure changes in the tank as super-cold propellants were pumped in and drained out. Data and analysis from the test will be used to determine what caused the tops of two, 21-foot-long support beams, called stringers, on the outside of the intertank to crack during fueling on Nov. 5. Discovery's next launch opportunity to the International Space Station on the STS-133 mission is no earlier than Feb. 3, 2011. For more information on STS-133, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts133/. Photo credit: NASA/Frank Michaux

KSC-2010-5929

NASA Image and Video Library

2010-12-22

CAPE CANAVERAL, Fla. -- Space shuttle Discovery slowly moves down the crawlerway at NASA's Kennedy Space Center in Florida. The 3.4-mile trek, called rollback, from Launch Pad 39A to the Vehicle Assembly Building began at 10:48 p.m. yesterday and took about eight hours. Next, Discovery's external fuel tank will be examined and foam reapplied where 89 sensors were installed on the tank's aluminum skin for an instrumented tanking test on Dec. 17. The sensors were used to measure changes in the tank as super-cold propellants were pumped in and drained out. Data and analysis from the test will be used to determine what caused the tops of two, 21-foot-long support beams, called stringers, on the outside of the intertank to crack during fueling on Nov. 5. Discovery's next launch opportunity to the International Space Station on the STS-133 mission is no earlier than Feb. 3, 2011. For more information on STS-133, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts133/. Photo credit: NASA/Frank Michaux

50. THIRD FLOOR, HALL, LOOKING SOUTH. Note ceiling extends down ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

50. THIRD FLOOR, HALL, LOOKING SOUTH. Note ceiling extends down over window case and exterior frieze extends halfway down top light of sash - Robinson-Aiken House, 48 Elizabeth Street, Charleston, Charleston County, SC

Generation of animation sequences of three dimensional models

NASA Technical Reports Server (NTRS)

Poi, Sharon (Inventor); Bell, Brad N. (Inventor)

1990-01-01

The invention is directed toward a method and apparatus for generating an animated sequence through the movement of three-dimensional graphical models. A plurality of pre-defined graphical models are stored and manipulated in response to interactive commands or by means of a pre-defined command file. The models may be combined as part of a hierarchical structure to represent physical systems without need to create a separate model which represents the combined system. System motion is simulated through the introduction of translation, rotation and scaling parameters upon a model within the system. The motion is then transmitted down through the system hierarchy of models in accordance with hierarchical definitions and joint movement limitations. The present invention also calls for a method of editing hierarchical structure in response to interactive commands or a command file such that a model may be included, deleted, copied or moved within multiple system model hierarchies. The present invention also calls for the definition of multiple viewpoints or cameras which may exist as part of a system hierarchy or as an independent camera. The simulated movement of the models and systems is graphically displayed on a monitor and a frame is recorded by means of a video controller. Multiple movement and hierarchy manipulations are then recorded as a sequence of frames which may be played back as an animation sequence on a video cassette recorder.

Top-down venomics of the East African green mamba, Dendroaspis angusticeps, and the black mamba, Dendroaspis polylepis, highlight the complexity of their toxin arsenals.

PubMed

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

2016-09-02

We report the characterization, by combination of high-resolution on-line molecular mass and disulfide bond profiling and top-down MS/MS analysis, of the venom proteomes of two congeneric African snake species of medical importance, Dendroaspis angusticeps (green mamba) and D. polylepis (black mamba). Each of these mamba venoms comprised more than two-hundred polypeptides belonging to just a few toxin families. Both venom proteomes are overwhelmingly composed of post-synaptically-acting short- and long-chain neurotoxins that potently inhibit muscle- and neuronal-type nicotinic acetylcholine receptors; muscarinic cardiotoxins; and dendrotoxins, that block some of the Kv1, n-class of K+ channels. However, the identity of the major proteins and their relative abundances exhibit marked interspecific variation. In addition, the greater resolution of the top-down venomic analytical approach revealed previously undetected protein species, isoforms and proteoforms, including the identification and precise location of modified lysine residues in a number of proteins in both venoms, but particularly in green mamba toxins. This comparative top-down venomic analysis unveiled the untapped complexity of Dendroaspis venoms and lays the foundations for rationalizing the notably different potency of green and black mamba lethal arsenals at locus resolution. We report the characterization, by combination of high-resolution on-line molecular mass and disulfide bond profiling and top-down MS/MS analysis, of the venom proteomes of two congeneric African snake species of medical importance, Dendroaspis angusticeps (green mamba) and D. polylepis (black mamba). Each of these mamba venoms comprised more than two-hundred polypeptides belonging to just a few toxin families. Both venom proteomes are overwhelmingly composed of post-synaptically-acting short- and long-chain neurotoxins that potently inhibit muscle- and neuronal-type nicotinic acetylcholine receptors; muscarinic cardiotoxins; and dendrotoxins, that block some of the Kv1, n-class of K+ channels. However, the identity of the major proteins and their relative abundances exhibit marked interspecific variation. In addition, the greater resolution of the top-down venomic analytical approach revealed previously undetected protein species, isoforms and proteoforms, including the identification and precise location of modified lysine residues in a number of proteins in both venoms, but particularly in green mamba toxins. This comparative top-down venomic analysis unveiled the untapped complexity of Dendroaspis venoms and lays the foundations for rationalizing the notably different potency of green and black mamba lethal arsenals at locus resolution.

Silent Expectations: Dynamic Causal Modeling of Cortical Prediction and Attention to Sounds That Weren't.

PubMed

Chennu, Srivas; Noreika, Valdas; Gueorguiev, David; Shtyrov, Yury; Bekinschtein, Tristan A; Henson, Richard

2016-08-10

There is increasing evidence that human perception is realized by a hierarchy of neural processes in which predictions sent backward from higher levels result in prediction errors that are fed forward from lower levels, to update the current model of the environment. Moreover, the precision of prediction errors is thought to be modulated by attention. Much of this evidence comes from paradigms in which a stimulus differs from that predicted by the recent history of other stimuli (generating a so-called "mismatch response"). There is less evidence from situations where a prediction is not fulfilled by any sensory input (an "omission" response). This situation arguably provides a more direct measure of "top-down" predictions in the absence of confounding "bottom-up" input. We applied Dynamic Causal Modeling of evoked electromagnetic responses recorded by EEG and MEG to an auditory paradigm in which we factorially crossed the presence versus absence of "bottom-up" stimuli with the presence versus absence of "top-down" attention. Model comparison revealed that both mismatch and omission responses were mediated by increased forward and backward connections, differing primarily in the driving input. In both responses, modeling results suggested that the presence of attention selectively modulated backward "prediction" connections. Our results provide new model-driven evidence of the pure top-down prediction signal posited in theories of hierarchical perception, and highlight the role of attentional precision in strengthening this prediction. Human auditory perception is thought to be realized by a network of neurons that maintain a model of and predict future stimuli. Much of the evidence for this comes from experiments where a stimulus unexpectedly differs from previous ones, which generates a well-known "mismatch response." But what happens when a stimulus is unexpectedly omitted altogether? By measuring the brain's electromagnetic activity, we show that it also generates an "omission response" that is contingent on the presence of attention. We model these responses computationally, revealing that mismatch and omission responses only differ in the location of inputs into the same underlying neuronal network. In both cases, we show that attention selectively strengthens the brain's prediction of the future. Copyright © 2016 Chennu et al.

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

PubMed

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.

Bottom-up effects of host-plant species diversity and top-down effects of ants interactively increase plant performance

PubMed Central

Moreira, Xoaquín; Mooney, Kailen A.; Zas, Rafael; Sampedro, Luis

2012-01-01

While plant diversity is well known to increase primary productivity, whether these bottom-up effects are enhanced by reciprocal top-down effects from the third trophic level is unknown. We studied whether pine tree species diversity, aphid-tending ants and their interaction determined plant performance and arthropod community structure. Plant diversity had a positive effect on aphids, but only in the presence of mutualistic ants, leading to a threefold greater number of both groups in the tri-specific cultures than in monocultures. Plant diversity increased ant abundance not only by increasing aphid number, but also by increasing ant recruitment per aphid. The positive effect of diversity on ants in turn cascaded down to increase plant performance; diversity increased plant growth (but not biomass), and this effect was stronger in the presence of ants. Consequently, bottom-up effects of diversity within the same genus and guild of plants, and top-down effects from the third trophic level (predatory ants), interactively increased plant performance. PMID:22951745

Top-emitting white organic light-emitting devices with down-conversion phosphors: theory and experiment.

PubMed

Ji, Wenyu; Zhang, Letian; Gao, Ruixue; Zhang, Liming; Xie, Wenfa; Zhang, Hanzhuang; Li, Bin

2008-09-29

White top-emitting organic light-emitting devices (TEOLEDs) with down-conversion phosphors are investigated from theory and experiment. The theoretical simulation was described by combining the microcavity model with the down-conversion model. A White TEOLED by the combination of a blue TEOLED with organic down-conversion phosphor 3-(4-(diphenylamino)phenyl)-1-pheny1prop-2-en-1-one was fabricated to validate the simulated results. It is shown that this approach permits the generation of white light in TEOLEDs. The efficiency of the white TEOLED is twice over the corresponding blue TEOLED. The feasible methods to improve the performance of such white TEOLEDs are discussed.

[Research advances of genomic GYP coding MNS blood group antigens].

PubMed

Liu, Chang-Li; Zhao, Wei-Jun

2012-02-01

The MNS blood group system includes more than 40 antigens, and the M, N, S and s antigens are the most significant ones in the system. The antigenic determinants of M and N antigens lie on the top of GPA on the surface of red blood cells, while the antigenic determinants of S and s antigens lie on the top of GPB on the surface of red blood cells. The GYPA gene coding GPA and the GYPB gene coding GPB locate at the longarm of chromosome 4 and display 95% homologus sequence, meanwhile both genes locate closely to GYPE gene that did not express product. These three genes formed "GYPA-GYPB-GYPE" structure called GYP genome. This review focuses on the molecular basis of genomic GYP and the variety of GYP genome in the expression of diversity MNS blood group antigens. The molecular basis of Miltenberger hybrid glycophorin polymorphism is specifically expounded.

A Preliminary Study of Perfectionism and Loneliness as Predictors of Depressive and Anxious Symptoms in Latinas: A Top-Down Test of a Model

ERIC Educational Resources Information Center

Chang, Edward C.; Hirsch, Jameson K.; Sanna, Lawrence J.; Jeglic, Elizabeth L.; Fabian, Cathryn G.

2011-01-01

In the present study, we used a top-down approach to examine perfectionism and loneliness as additive sociocognitive predictors of depressive and anxious symptoms in a sample of 121 Latina college students. Consistent with expectations, we found perfectionism and loneliness to be associated with both depressive and anxious symptoms. In addition,…

Top-down proteomic identification of Shiga toxin 2 subtypes from Shiga toxin-producing Escherichia coli by Matrix-Assisted Laser Desorption Ionization-Tandem Time of Flight mass spectrometry

USDA-ARS?s Scientific Manuscript database

We have analyzed 26 Shiga toxin-producing Escherichia coli (STEC) strains for Shiga toxin 2 (Stx2) production using matrix-assisted laser desorption/ionization time-of-flight-time-of-flight tandem mass spectrometry (MALDI-TOF-TOF-MS/MS) and top-down proteomic analysis. STEC strains were induced to ...

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

ERIC Educational Resources Information Center

Loth, Eva; Gomez, Juan Carlos; Happe, Francesca

2010-01-01

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…

Optimization of synthesis process of thermally-responsive poly-n-isopropylacrylamide nanoparticles for controlled release of antimicrobial hydrophobic compounds

NASA Astrophysics Data System (ADS)

Hill, Laura E.; Gomes, Carmen L.

2014-12-01

The goal of this study was to develop an effective method to synthesize poly-n-isopropylacrylamide (PNIPAAM) nanoparticles with entrapped cinnamon bark extract (CBE) to improve its delivery to foodborne pathogens and control its release with temperature stimuli. CBE was used as a model for hydrophobic natural antimicrobials. A top-down procedure using crosslinked PNIPAAM was compared to a bottom-up procedure using NIPAAM monomer. Both processes relied on self-assembly of the molecules into micelles around the CBE at 40 °C. Processing conditions were compared including homogenization time of the polymer, hydration time prior to homogenization, lyophilization, and the effect of particle ultrafiltration. The top-down versus bottom-up synthesis methods yielded particles with significantly different characteristics, especially their release profiles and antimicrobial activities. The synthesis methods affected particle size, with the bottom-up procedure resulting in smaller (P < 0.05) diameters than the top-down procedure. The controlled release profile of CBE from nanoparticles was dependent on the release media temperature. A faster, burst release was observed at 40 °C and a slower, more sustained release was observed at lower temperatures. PNIPAAM particles containing CBE were analyzed for their antimicrobial activity against Salmonella enterica serovar Typhimurium LT2 and Listeria monocytogenes Scott A. The PNIPAAM particles synthesized via the top-down procedure had a much faster release, which led to a greater (P < 0.05) antimicrobial activity. Both of the top-down nanoparticles performed similarly, therefore the 7 min homogenization time nanoparticles would be the best for this application, as the process time is shorter and little improvement was seen by using a slightly longer homogenization.

The role of top-down spatial attention in contingent attentional capture.

PubMed

Huang, Wanyi; Su, Yuling; Zhen, Yanfen; Qu, Zhe

2016-05-01

It is well known that attentional capture by an irrelevant salient item is contingent on top-down feature selection, but whether attentional capture may be modulated by top-down spatial attention remains unclear. Here, we combined behavioral and ERP measurements to investigate the contribution of top-down spatial attention to attentional capture under modified spatial cueing paradigms. Each target stimulus was preceded by a peripheral circular cue array containing a spatially uninformative color singleton cue. We varied target sets but kept the cue array unchanged among different experimental conditions. When participants' task was to search for a colored letter in the target array that shared the same peripheral locations with the cue array, attentional capture by the peripheral color cue was reflected by both a behavioral spatial cueing effect and a cue-elicited N2pc component. When target arrays were presented more centrally, both the behavioral and N2pc effects were attenuated but still significant. The attenuated cue-elicited N2pc was found even when participants focused their attention on the fixed central location to identify a colored letter among an RSVP letter stream. By contrast, when participants were asked to identify an outlined or larger target, neither the behavioral spatial cueing effect nor the cue-elicited N2pc was observed, regardless of whether the target and cue arrays shared same locations or not. These results add to the evidence that attentional capture by salient stimuli is contingent upon feature-based task sets, and further indicate that top-down spatial attention is important but may not be necessary for contingent attentional capture. © 2016 Society for Psychophysiological Research.

Fiddler crabs facilitate Spartina alterniflora growth, mitigating periwinkle overgrazing of marsh habitat.

PubMed

Gittman, Rachel K; Keller, Danielle A

2013-12-01

Ecologists have long been interested in identifying and testing factors that drive top-down or bottom-up regulation of communities. Most studies have focused on factors that directly exert top-down (e.g., grazing) or bottom-up (e.g., nutrient availability) control on primary production. For example, recent studies in salt marshes have demonstrated that fronts of Littoraria irrorata periwinkles can overgraze Spartina alterniflora and convert marsh to mudflat. The importance of indirect, bottom-up effects, particularly facilitation, in enhancing primary production has also recently been explored. Previous field studies separately revealed that fiddler crabs, which burrow to depths of more than 30 cm, can oxygenate marsh sediments and redistribute nutrients, thereby relieving the stress of anoxia and enhancing S. alterniflora growth. However, to our knowledge, no studies to date have explored how nontrophic facilitators can mediate top-down effects (i.e., grazing) on primary-producer biomass. We conducted a field study testing whether fiddler crabs can facilitate S. alterniflora growth sufficiently to mitigate overgrazing by periwinkles and thus sustain S. alterniflora marsh. As inferred from contrasts to experimental plots lacking periwinkles and fiddler crabs, periwinkles alone exerted top-down control of total aboveground biomass and net growth of S. alterniflora. When fiddler crabs were included, they counteracted the effects of periwinkles on net S. alterniflora growth. Sediment oxygen levels were greater and S. alterniflora belowground biomass was lower where fiddler crabs were present, implying that fiddler crab burrowing enhanced S. alterniflora growth. Consequently, in the stressful interior S. alterniflora marsh, where subsurface soil anoxia is widespread, fiddler crab facilitation can mitigate top-down control by periwinkles and can limit and possibly prevent loss of biogenically structured marsh habitat and its ecosystem services.

Top-Down Dysregulation—From ADHD to Emotional Instability

PubMed Central

Petrovic, Predrag; Castellanos, F. Xavier

2016-01-01

Deficient cognitive top-down executive control has long been hypothesized to underlie inattention and impulsivity in attention-deficit/hyperactivity disorder (ADHD). However, top-down cognitive dysfunction explains a modest proportion of the ADHD phenotype whereas the salience of emotional dysregulation is being noted increasingly. Together, these two types of dysfunction have the potential to account for more of the phenotypic variance in patients diagnosed with ADHD. We develop this idea and suggest that top-down dysregulation constitutes a gradient extending from mostly non-emotional top-down control processes (i.e., “cool” executive functions) to mainly emotional regulatory processes (including “hot” executive functions). While ADHD has been classically linked primarily to the former, conditions involving emotional instability such as borderline and antisocial personality disorder are closer to the other. In this model, emotional subtypes of ADHD are located at intermediate levels of this gradient. Neuroanatomically, gradations in “cool” processing appear to be related to prefrontal dysfunction involving dorsolateral prefrontal cortex (dlPFC) and caudal anterior cingulate cortex (cACC), while “hot” processing entails orbitofrontal cortex and rostral anterior cingulate cortex (rACC). A similar distinction between systems related to non-emotional and emotional processing appears to hold for the basal ganglia (BG) and the neuromodulatory effects of the dopamine system. Overall we suggest that these two systems could be divided according to whether they process non-emotional information related to the exteroceptive environment (associated with “cool” regulatory circuits) or emotional information related to the interoceptive environment (associated with “hot” regulatory circuits). We propose that this framework can integrate ADHD, emotional traits in ADHD, borderline and antisocial personality disorder into a related cluster of mental conditions. PMID:27242456

Developing a Comprehensive and Comparative Questionnaire for Measuring Personality in Chimpanzees Using a Simultaneous Top-Down/Bottom-Up Design

PubMed Central

Freeman, Hani D.; Brosnan, Sarah F.; Hopper, Lydia M.; Lambeth, Susan P.; Schapiro, Steven J.; Gosling, Samuel D.

2013-01-01

One effective method for measuring personality in primates is to use personality trait ratings to distill the experience of people familiar with the individual animals. Previous rating instruments were created using either top-down or bottom-up approaches. Top-down approaches, which essentially adapt instruments originally designed for use with another species, can unfortunately lead to the inclusion of traits irrelevant to chimpanzees or fail to include all relevant aspects of chimpanzee personality. Conversely, because bottom-up approaches derive traits specifically for chimpanzees, their unique items may impede comparisons with findings in other studies and other species. To address the limitations of each approach, we developed a new personality rating scale using a combined top-down/bottom-up design. Seventeen raters rated 99 chimpanzees on the new 41-item scale, with all but one item being rated reliably. Principal components analysis, using both varimax and direct oblimin rotations, identified six broad factors. Strong evidence was found for five of the factors (Reactivity/Undependability, Dominance, Openness, Extraversion, and Agreeableness). A sixth factor (Methodical) was offered provisionally until more data are collected. We validated the factors against behavioral data collected independently on the chimpanzees. The five factors demonstrated good evidence for convergent and predictive validity, thereby underscoring the robustness of the factors. Our combined top-down/ bottom-up approach provides the most extensive data to date to support the universal existence of these five personality factors in chimpanzees. This framework, which facilitates cross-species comparisons, can also play a vital role in understanding the evolution of personality and can assist with husbandry and welfare efforts. PMID:23733359

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heath, Garvin A.

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 techniquesmore » (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.« less

Don't be fooled! Attentional responses to social cues in a face-to-face and video magic trick reveals greater top-down control for overt than covert attention.

PubMed

Kuhn, Gustav; Teszka, Robert; Tenaw, Natalia; Kingstone, Alan

2016-01-01

People's attention is oriented towards faces, but the extent to which these social attention effects are under top down control is more ambiguous. Our first aim was to measure and compare, in real life and in the lab, people's top-down control over overt and covert shifts in reflexive social attention to the face of another. We employed a magic trick in which the magician used social cues (i.e. asking a question whilst establishing eye contact) to misdirect attention towards his face, and thus preventing participants from noticing a visible colour change to a playing card. Our results show that overall people spend more time looking at the magician's face when he is seen on video than in reality. Additionally, although most participants looked at the magician's face when misdirected, this tendency to look at the face was modulated by instruction (i.e., "keep your attention on the cards"), and therefore, by top down control. Moreover, while the card's colour change was fully visible, the majority of participants failed to notice the change, and critically, change detection (our measure of covert attention) was not affected by where people looked (overt attention). We conclude that there is a tendency to shift overt and covert attention reflexively to faces, but that people exert more top down control over this overt shift in attention. These finding are discussed within a new framework that focuses on the role of eye movements as an attentional process as well as a form of non-verbal communication. Copyright © 2015 Elsevier B.V. All rights reserved.

KSC-2012-5574

NASA Image and Video Library

2012-09-20

CAPE CANAVERAL, Fla. - NASA's Johnson Space Center Aerospace Engineer Jeff Hagen, left, and engineering intern Emmanuel Nyangweso attach rotors to the top of a model capsule ahead of tests inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The design would give a capsule the stability and control of a helicopter, but would not be powered. Instead, the wind passing over the rotors as the capsule descends would make the blades turn, a process called auto-rotation. The intent is to give real spacecraft a soft landing with enough control that they could touch down anywhere in the world, whether it be a runway or parking lot. In other words, wherever a helicopter could land, a spacecraft could land, too. Photo credit: NASA/Kim Shiflett

Literacy learning in users of AAC: A neurocognitive perspective.

PubMed

Van Balkom, Hans; Verhoeven, Ludo

2010-09-01

The understanding of written or printed text or discourse - depicted either in orthographical, graphic-visual or tactile symbols - calls upon both bottom-up word recognition processes and top-down comprehension processes. Different architectures have been proposed to account for literacy processes. Research has shown that the first steps in perceiving, processing and deriving conceptual meaning from words, graphic symbols, manual signs, and co-speech gestures or tactile manual signing and tangible symbols can be seen as identical and collectively (sub)activated. Results from recent brain research and neurolinguistics have revealed new insights in the reading process of typical and atypical readers and may provide verifiable evidence for improved literacy assessment and the validation of early intervention programs for AAC users.

Characterization of a low-level unknown isomeric degradation product using an integrated online-offline top-down tandem mass spectrometry platform.

PubMed

Yu, Xiang; Warme, Christopher; Lee, Dinah; Zhang, Jing; Zhong, Wendy

2013-10-01

An integrated online-offline platform was developed combining automated online LC-MS fraction collection, continuous accumulation of selected ions (CASI), and offline top-down electron capture dissociation (ECD) tandem mass spectrometry experiments to identify a low-level, unknown isomeric degradant in a formulated drug product during an accelerated stability study. By identifying the diagnostic ions of the isoaspartic acid (isoAsp), the top-down ECD experiment showed that the Asp9 in exenatide was converted to isoAsp9 to form the unknown isomeric degradant. The platform described here provides an accurate, straightforward, and low limit of detection method for the analysis of Asp isomerization as well as other potential low-level degradants in therapeutic polypeptides and proteins. It is especially useful for unstable and time-sensitive degradants and impurities.

Interpreting Chicken-Scratch: Lexical Access for Handwritten Words

PubMed Central

Barnhart, Anthony S.; Goldinger, Stephen D.

2014-01-01

Handwritten word recognition is a field of study that has largely been neglected in the psychological literature, despite its prevalence in society. Whereas studies of spoken word recognition almost exclusively employ natural, human voices as stimuli, studies of visual word recognition use synthetic typefaces, thus simplifying the process of word recognition. The current study examined the effects of handwriting on a series of lexical variables thought to influence bottom-up and top-down processing, including word frequency, regularity, bidirectional consistency, and imageability. The results suggest that the natural physical ambiguity of handwritten stimuli forces a greater reliance on top-down processes, because almost all effects were magnified, relative to conditions with computer print. These findings suggest that processes of word perception naturally adapt to handwriting, compensating for physical ambiguity by increasing top-down feedback. PMID:20695708

Conflict adaptation in emotional task underlies the amplification of target.

PubMed

Chechko, Natalia; Kellermann, Thilo; Schneider, Frank; Habel, Ute

2014-04-01

A primary function of cognitive control is to adjust the cognitive system according to situational demands. The so-called "conflict adaptation effect" elicited in laboratory experiments is supposed to reflect the above function. Neuroimaging studies suggest that adaptation of nonemotional conflict is mediated by the dorsolateral prefrontal cortex through a top-down enhancement of task-relevant (target), relative to task-irrelevant (distractor), stimulus representation in the sensory cortices. The adaptation of emotional conflict, on the other hand, is suggested to be related to the rostral anterior cingulate inhibiting the processing of emotional distractors through a top-down modulation of amygdala responsivity. In the present study, we manipulated, on a trial-by-trial basis, the levels of semantic interference conflict triggered by the incompatibility between emotional faces (targets) and emotional words (distractors) in a modified version of the emotional Stroop task. Similar to previous observations involving nonemotional interference effects, the behavioral adaptation of emotional conflict was found to be paralleled by a stronger recruitment of the fusiform face area. Additional areas related to the conflict adaptation effect were the bilateral insula, the bilateral frontal operculum (fO), the right amygdala, the left precentral and postcentral gyri, and the parietal cortex. These findings suggest that augmentation of cortical responses to task-relevant information in emotional conflict may be related to conflict adaptation processes in a way that has been observed in nonemotional conflict, challenging the view that brain circuitries underlying the conflict adaptation effect depend only on the nature of conflict.

Self-assembled templates for the generation of arrays of 1-dimensional nanostructures: from molecules to devices.

PubMed

Farrell, Richard A; Petkov, Nikolay; Morris, Michael A; Holmes, Justin D

2010-09-15

Self-assembled nanoscale porous architectures, such as mesoporous silica (MPS) films, block copolymer films (BCP) and porous anodic aluminas (PAAs), are ideal hosts for templating one dimensional (1D) nano-entities for a wide range of electronic, photonic, magnetic and environmental applications. All three of these templates can provide scalable and tunable pore diameters below 20 nm [1-3]. Recently, research has progressed towards controlling the pore direction, orientation and long-range order of these nanostructures through so-called directed self-assembly (DSA). Significantly, the introduction of a wide range of top-down chemically and physically pre-patterning substrates has facilitated the DSA of nanostructures into functional device arrays. The following review begins with an overview of the fundamental aspects of self-assembly and ordering processes during the formation of PAAs, BCPs and MPS films. Special attention is given to the different ways of directing self-assembly, concentrating on properties such as uni-directional alignment, precision placement and registry of the self-assembled structures to hierarchal or top-down architectures. Finally, to distinguish this review from other articles we focus on research where nanostructures have been utilised in part to fabricate arrays of functioning devices below the sub 50 nm threshold, by subtractive transfer and additive methods. Where possible, we attempt to compare and contrast the different templating approaches and highlight the strengths and/or limitations that will be important for their potential integration into downstream processes. Copyright 2010 Elsevier Inc. All rights reserved.

Metalloproteomics: Forward and Reverse Approaches in Metalloprotein Structural and Functional Characterization

PubMed Central

Shi, Wuxian; Chance, Mark R.

2010-01-01

About one-third of all proteins are associated with a metal. Metalloproteomics is defined as the structural and functional characterization of metalloproteins on a genome-wide scale. The methodologies utilized in metalloproteomics, including both forward (bottom-up) and reverse (top-down) technologies, to provide information on the identity, quantity and function of metalloproteins are discussed. Important techniques frequently employed in metalloproteomics include classical proteomics tools such as mass spectrometry and 2-D gels, immobilized-metal affinity chromatography, bioinformatics sequence analysis and homology modeling, X-ray absorption spectroscopy and other synchrotron radiation based tools. Combinative applications of these techniques provide a powerful approach to understand the function of metalloproteins. PMID:21130021

Scaled CMOS Reliability and Considerations for Spacecraft Systems : Bottom-Up and Top-Down Perspectives

NASA Technical Reports Server (NTRS)

White, Mark

2012-01-01

The recently launched Mars Science Laboratory (MSL) flagship mission, named Curiosity, is the most complex rover ever built by NASA and is scheduled to touch down on the red planet in August, 2012 in Gale Crater. The rover and its instruments will have to endure the harsh environments of the surface of Mars to fulfill its main science objectives. Such complex systems require reliable microelectronic components coupled with adequate component and system-level design margins. Reliability aspects of these elements of the spacecraft system are presented from bottom- up and top-down perspectives.

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

NASA Astrophysics Data System (ADS)

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.

2-Aminobenzamide and 2-aminobenzoic acid as new MALDI matrices inducing radical mediated in-source decay of peptides and proteins.

PubMed

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.

Explaining Meiji Japans Top Down Revolution

DTIC Science & Technology

2017-12-01

enabled Japan to become a great power also provides insights into how Japan became what it is today—an economically strong but militarily weak country...top- down nature of the Japanese revolution allowed for effective decision-making that centralized domestic politics and boosted economic ...other road focuses on changes made to compete with the West in the economic and military realm. Since Meiji Japan began in reaction to hostile Western

Change Levers for Unifying Top-Down and Bottom-Up Approaches to the Adoption and Diffusion of e-Learning in Higher Education

ERIC Educational Resources Information Center

Singh, Gurmak; Hardaker, Glenn

2017-01-01

Using Giddens' theory of structuration as a theoretical framework, this paper outlines how five prominent United Kingdom universities aimed to integrate top-down and bottom-up approaches to the adoption and diffusion of e-learning. The aim of this paper is to examine the major challenges that arise from the convergence of bottom-up perspectives…

Large-Eddy Simulation in Planetary Boundary-Layer Research

NASA Technical Reports Server (NTRS)

Wyngaard, J. C.

1985-01-01

The structure and dynamics of the convective boundary layer are discussed. The vertical transport of a conservative, passive scalar was simulated. Also studied were the statistics by top-down and bottom-up scalar fields. Substantial differences were found between them due, presumably, to the asymmetry in the convective boundary layer. A generalization of mixed-layer scaling was developed which allows one to include the effects of top-down diffusion.

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

PubMed

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.

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

ERIC Educational Resources Information Center

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.…

Subjective Well-Being: The Constructionist Point of View. A Longitudinal Study to Verify the Predictive Power of Top-Down Effects and Bottom-Up Processes

ERIC Educational Resources Information Center

Leonardi, Fabio; Spazzafumo, Liana; Marcellini, Fiorella

2005-01-01

Based on the constructionist point of view applied to Subjective Well-Being (SWB), five hypotheses were advanced about the predictive power of the top-down effects and bottom-up processes over a five years period. The sample consisted of 297 respondents, which represent the Italian sample of a European longitudinal survey; the first phase was…

Methods, Tools, and Data for Coastal System Resilience Assessments

DTIC Science & Technology

2015-10-06

Baseline Resilience Indicators for Communities ( BRIC ) BUILDING STRONG® Innovative solutions for a safer, better world ► T: SoVI® – Social...address policy  Objective, although data may be arbitrarily weighted in an index Examples: Top-Down (T) and Bottom-Up (B) Bottom-UpTop-Down BRIC ...Coastal Resilience Index USACE’s Resilience Matrix ASCE’s Infrastructure Report Card T: Baseline Resilience Index for Communities ( BRIC

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

PubMed Central

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

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

PubMed

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 dimensional weight set determines the capture of visual attention: evidence from the PCN component.

PubMed

Töllner, Thomas; Müller, Hermann J; Zehetleitner, Michael

2012-07-01

Visual search for feature singletons is slowed when a task-irrelevant, but more salient distracter singleton is concurrently presented. While there is a consensus that this distracter interference effect can be influenced by internal system settings, it remains controversial at what stage of processing this influence starts to affect visual coding. Advocates of the "stimulus-driven" view maintain that the initial sweep of visual processing is entirely driven by physical stimulus attributes and that top-down settings can bias visual processing only after selection of the most salient item. By contrast, opponents argue that top-down expectancies can alter the initial selection priority, so that focal attention is "not automatically" shifted to the location exhibiting the highest feature contrast. To precisely trace the allocation of focal attention, we analyzed the Posterior-Contralateral-Negativity (PCN) in a task in which the likelihood (expectancy) with which a distracter occurred was systematically varied. Our results show that both high (vs. low) distracter expectancy and experiencing a distracter on the previous trial speed up the timing of the target-elicited PCN. Importantly, there was no distracter-elicited PCN, indicating that participants did not shift attention to the distracter before selecting the target. This pattern unambiguously demonstrates that preattentive vision is top-down modifiable.

Great expectations: top-down attention modulates the costs of clutter and eccentricity.

PubMed

Steelman, Kelly S; McCarley, Jason S; Wickens, Christopher D

2013-12-01

An experiment and modeling effort examined interactions between bottom-up and top-down attentional control in visual alert detection. Participants performed a manual tracking task while monitoring peripheral display channels for alerts of varying salience, eccentricity, and spatial expectancy. Spatial expectancy modulated the influence of salience and eccentricity; alerts in low-probability locations engendered higher miss rates, longer detection times, and larger costs of visual clutter and eccentricity, indicating that top-down attentional control offset the costs of poor bottom-up stimulus quality. Data were compared to the predictions of a computational model of scanning and noticing that incorporates bottom-up and top-down sources of attentional control. The model accounted well for the overall pattern of miss rates and response times, predicting each of the observed main effects and interactions. Empirical results suggest that designers should expect the costs of poor bottom-up visibility to be greater for low expectancy signals, and that the placement of alerts within a display should be determined based on the combination of alert expectancy and response priority. Model fits suggest that the current model can serve as a useful tool for exploring a design space as a precursor to empirical data collection and for generating hypotheses for future experiments. PsycINFO Database Record (c) 2013 APA, all rights reserved.

A Robust Two-Dimensional Separation for Top-Down Tandem Mass Spectrometry of the Low-Mass Proteome

PubMed Central

Lee, Ji Eun; Kellie, John F.; Tran, John C.; Tipton, Jeremiah D.; Catherman, Adam D.; Thomas, Haylee M.; Ahlf, Dorothy R.; Durbin, Kenneth R.; Vellaichamy, Adaikkalam; Ntai, Ioanna; Marshall, Alan G.; Kelleher, Neil L.

2010-01-01

For fractionation of intact proteins by molecular weight (MW), a sharply improved two-dimensional (2D) separation is presented to drive reproducible and robust fractionation before top-down mass spectrometry of complex mixtures. The “GELFrEE” (i.e., gel-eluted liquid fraction entrapment electrophoresis) approach is implemented by use of Tris-glycine and Tris-tricine gel systems applied to human cytosolic and nuclear extracts from HeLa S3 cells, to achieve a MW-based fractionation of proteins from 5 to >100 kDa in 1 h. For top-down tandem mass spectroscopy (MS/MS) of the low-mass proteome (5–25 kDa), between 5 and 8 gel-elution (GE) fractions are sampled by nanocapillary-LC-MS/MS with 12 or 14.5 tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers. Single injections give about 40 detectable proteins, about half of which yield automated ProSight identifications. Reproducibility metrics of the system are presented, along with comparative analysis of protein targets in mitotic versus asynchronous cells. We forward this basic 2D approach to facilitate wider implementation of top-down mass spectrometry and a variety of other protein separation and/or characterization approaches. PMID:19747844

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

PubMed

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.

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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.

Coupled wake boundary layer model of windfarms

NASA Astrophysics Data System (ADS)

Stevens, Richard; Gayme, Dennice; Meneveau, Charles

2014-11-01

We present a coupled wake boundary layer (CWBL) model that describes the distribution of the power output in a windfarm. The model couples the traditional, industry-standard wake expansion/superposition approach with a top-down model for the overall windfarm boundary layer structure. Wake models capture the effect of turbine positioning, while the top-down approach represents the interaction between the windturbine wakes and the atmospheric boundary layer. Each portion of the CWBL model requires specification of a parameter that is unknown a-priori. The wake model requires the wake expansion rate, whereas the top-down model requires the effective spanwise turbine spacing within which the model's momentum balance is relevant. The wake expansion rate is obtained by matching the mean velocity at the turbine from both approaches, while the effective spanwise turbine spacing is determined from the wake model. Coupling of the constitutive components of the CWBL model is achieved by iterating these parameters until convergence is reached. We show that the CWBL model predictions compare more favorably with large eddy simulation results than those made with either the wake or top-down model in isolation and that the model can be applied successfully to the Horns Rev and Nysted windfarms. The `Fellowships for Young Energy Scientists' (YES!) of the Foundation for Fundamental Research on Matter supported by NWO, and NSF Grant #1243482.

Top predators, mesopredators and their prey: interference ecosystems along bioclimatic productivity gradients.

PubMed

Elmhagen, B; Ludwig, G; Rushton, S P; Helle, P; Lindén, H

2010-07-01

1. The Mesopredator Release Hypothesis (MRH) suggests that top predator suppression of mesopredators is a key ecosystem function with cascading impacts on herbivore prey, but it remains to be shown that this top-down cascade impacts the large-scale structure of ecosystems. 2. The Exploitation Ecosystems Hypothesis (EEH) predicts that regional ecosystem structures are determined by top-down exploitation and bottom-up productivity. In contrast to MRH, EEH assumes that interference among predators has a negligible impact on the structure of ecosystems with three trophic levels. 3. We use the recolonization of a top predator in a three-level boreal ecosystem as a natural experiment to test if large-scale biomass distributions and population trends support MRH. Inspired by EEH, we also test if top-down interference and bottom-up productivity impact regional ecosystem structures. 4. We use data from the Finnish Wildlife Triangle Scheme which has monitored top predator (lynx, Lynx lynx), mesopredator (red fox, Vulpes vulpes) and prey (mountain hare, Lepus timidus) abundance for 17 years in a 200 000 km(2) study area which covers a distinct productivity gradient. 5. Fox biomass was lower than expected from productivity where lynx biomass was high, whilst hare biomass was lower than expected from productivity where fox biomass was high. Hence, where interference controlled fox abundance, lynx had an indirect positive impact on hare abundance as predicted by MRH. The rates of change indicated that lynx expansion gradually suppressed fox biomass. 6. Lynx status caused shifts between ecosystem structures. In the 'interference ecosystem', lynx and hare biomass increased with productivity whilst fox biomass did not. In the 'mesopredator release ecosystem', fox biomass increased with productivity but hare biomass did not. Thus, biomass controlled top-down did not respond to changes in productivity. This fulfils a critical prediction of EEH. 7. We conclude that the cascade involving top predators, mesopredators and their prey can determine large-scale biomass distribution patterns and regional ecosystem structures. Hence, interference within trophic levels has to be taken into account to understand how terrestrial ecosystem structures are shaped.

Novel down-regulatory mechanism of the surface expression of the vasopressin V2 receptor by an alternative splice receptor variant.

PubMed

Sarmiento, José M; Añazco, Carolina C; Campos, Danae M; Prado, Gregory N; Navarro, Javier; González, Carlos B

2004-11-05

In rat kidney, two alternatively spliced transcripts are generated from the V2 vasopressin receptor gene. The large transcript (1.2 kb) encodes the canonical V2 receptor, whereas the small transcript encodes a splice variant displaying a distinct sequence corresponding to the putative seventh transmembrane domain and the intracellular C terminus of the V2 receptor. This work showed that the small spliced transcript is translated in the rat kidney collecting tubules. However, the protein encoded by the small transcript (here called the V2b splice variant) is retained inside the cell, in contrast to the preferential surface distribution of the V2 receptor (here called the V2a receptor). Cells expressing the V2b splice variant do not exhibit binding to 3H-labeled vasopressin. Interestingly, we found that expression of the splice variant V2b down-regulates the surface expression of the V2a receptor, most likely via the formation of V2a.V2b heterodimers as demonstrated by co-immunoprecipitation and fluorescence resonance energy transfer experiments between the V2a receptor and the V2b splice variant. The V2b splice variant would then be acting as a dominant negative. The effect of the V2b splice variant is specific, as it does not affect the surface expression of the G protein-coupled interleukin-8 receptor (CXCR1). Furthermore, the sequence encompassing residues 242-339, corresponding to the C-terminal domain of the V2b splice variant, also down-regulates the surface expression of the V2a receptor. We suggest that some forms of nephrogenic diabetes insipidus are due to overexpression of the splice variant V2b, which could retain the wild-type V2a receptor inside the cell via the formation of V2a.V2b heterodimers.

The effect of call libraries and acoustic filters on the identification of bat echolocation.

PubMed

Clement, Matthew J; Murray, Kevin L; Solick, Donald I; Gruver, Jeffrey C

2014-09-01

Quantitative methods for species identification are commonly used in acoustic surveys for animals. While various identification models have been studied extensively, there has been little study of methods for selecting calls prior to modeling or methods for validating results after modeling. We obtained two call libraries with a combined 1556 pulse sequences from 11 North American bat species. We used four acoustic filters to automatically select and quantify bat calls from the combined library. For each filter, we trained a species identification model (a quadratic discriminant function analysis) and compared the classification ability of the models. In a separate analysis, we trained a classification model using just one call library. We then compared a conventional model assessment that used the training library against an alternative approach that used the second library. We found that filters differed in the share of known pulse sequences that were selected (68 to 96%), the share of non-bat noises that were excluded (37 to 100%), their measurement of various pulse parameters, and their overall correct classification rate (41% to 85%). Although the top two filters did not differ significantly in overall correct classification rate (85% and 83%), rates differed significantly for some bat species. In our assessment of call libraries, overall correct classification rates were significantly lower (15% to 23% lower) when tested on the second call library instead of the training library. Well-designed filters obviated the need for subjective and time-consuming manual selection of pulses. Accordingly, researchers should carefully design and test filters and include adequate descriptions in publications. Our results also indicate that it may not be possible to extend inferences about model accuracy beyond the training library. If so, the accuracy of acoustic-only surveys may be lower than commonly reported, which could affect ecological understanding or management decisions based on acoustic surveys.

The effect of call libraries and acoustic filters on the identification of bat echolocation

PubMed Central

Clement, Matthew J; Murray, Kevin L; Solick, Donald I; Gruver, Jeffrey C

2014-01-01

Quantitative methods for species identification are commonly used in acoustic surveys for animals. While various identification models have been studied extensively, there has been little study of methods for selecting calls prior to modeling or methods for validating results after modeling. We obtained two call libraries with a combined 1556 pulse sequences from 11 North American bat species. We used four acoustic filters to automatically select and quantify bat calls from the combined library. For each filter, we trained a species identification model (a quadratic discriminant function analysis) and compared the classification ability of the models. In a separate analysis, we trained a classification model using just one call library. We then compared a conventional model assessment that used the training library against an alternative approach that used the second library. We found that filters differed in the share of known pulse sequences that were selected (68 to 96%), the share of non-bat noises that were excluded (37 to 100%), their measurement of various pulse parameters, and their overall correct classification rate (41% to 85%). Although the top two filters did not differ significantly in overall correct classification rate (85% and 83%), rates differed significantly for some bat species. In our assessment of call libraries, overall correct classification rates were significantly lower (15% to 23% lower) when tested on the second call library instead of the training library. Well-designed filters obviated the need for subjective and time-consuming manual selection of pulses. Accordingly, researchers should carefully design and test filters and include adequate descriptions in publications. Our results also indicate that it may not be possible to extend inferences about model accuracy beyond the training library. If so, the accuracy of acoustic-only surveys may be lower than commonly reported, which could affect ecological understanding or management decisions based on acoustic surveys. PMID:25535563

The effect of call libraries and acoustic filters on the identification of bat echolocation

USGS Publications Warehouse

Clement, Matthew; Murray, Kevin L; Solick, Donald I; Gruver, Jeffrey C

2014-01-01

Quantitative methods for species identification are commonly used in acoustic surveys for animals. While various identification models have been studied extensively, there has been little study of methods for selecting calls prior to modeling or methods for validating results after modeling. We obtained two call libraries with a combined 1556 pulse sequences from 11 North American bat species. We used four acoustic filters to automatically select and quantify bat calls from the combined library. For each filter, we trained a species identification model (a quadratic discriminant function analysis) and compared the classification ability of the models. In a separate analysis, we trained a classification model using just one call library. We then compared a conventional model assessment that used the training library against an alternative approach that used the second library. We found that filters differed in the share of known pulse sequences that were selected (68 to 96%), the share of non-bat noises that were excluded (37 to 100%), their measurement of various pulse parameters, and their overall correct classification rate (41% to 85%). Although the top two filters did not differ significantly in overall correct classification rate (85% and 83%), rates differed significantly for some bat species. In our assessment of call libraries, overall correct classification rates were significantly lower (15% to 23% lower) when tested on the second call library instead of the training library. Well-designed filters obviated the need for subjective and time-consuming manual selection of pulses. Accordingly, researchers should carefully design and test filters and include adequate descriptions in publications. Our results also indicate that it may not be possible to extend inferences about model accuracy beyond the training library. If so, the accuracy of acoustic-only surveys may be lower than commonly reported, which could affect ecological understanding or management decisions based on acoustic surveys.

44. Building 102, view from mezzanine looking down to first ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

44. Building 102, view from mezzanine looking down to first floor showing Klystron tube equipment vaults with dual waveguides leaving top of vaults through bifurcation combiner system at start of waveguides; note tops of capacitor vaults along photograph to left. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

Elucidating unconscious processing with instrumental hypnosis

PubMed Central

Landry, Mathieu; Appourchaux, Krystèle; Raz, Amir

2014-01-01

Most researchers leverage bottom-up suppression to unlock the underlying mechanisms of unconscious processing. However, a top-down approach – for example via hypnotic suggestion – paves the road to experimental innovation and complementary data that afford new scientific insights concerning attention and the unconscious. Drawing from a reliable taxonomy that differentiates subliminal and preconscious processing, we outline how an experimental trajectory that champions top-down suppression techniques, such as those practiced in hypnosis, is uniquely poised to further contextualize and refine our scientific understanding of unconscious processing. Examining subliminal and preconscious methods, we demonstrate how instrumental hypnosis provides a reliable adjunct that supplements contemporary approaches. Specifically, we provide an integrative synthesis of the advantages and shortcomings that accompany a top-down approach to probe the unconscious mind. Our account provides a larger framework for complementing the results from core studies involving prevailing subliminal and preconscious techniques. PMID:25120504

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

PubMed

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 <  ertar-ERTAR; ALTAR-ALTAR = altar-ALTAR). This dissociation has been interpreted in terms of feedback from higher levels of processing during orthographic encoding. Here, we examined whether a matched-case identity advantage also occurs for 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.

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

NASA Astrophysics Data System (ADS)

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

2016-09-01

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 precedence of topological change over top-down attention in masked priming.

PubMed

Huang, Yan; Zhou, Tiangang; Chen, Lin

2011-10-14

Recent data indicate that unconscious masked priming can be mediated by top-down attentional set, so that priming effects of congruence between a masked prime and a subsequent probe vanish when the congruence ceases to be task relevant. Here, we show that, while the attentional set determines masked priming for color and orientation features, it does not fully determine priming based on the topological properties of stimuli. Specifically, across a series of different choice-RT tasks, we find that topological congruence between prime and probe stimuli affects RTs for the probes even when other stimulus information (e.g., color or orientation) is required for the response, whereas congruence priming effects of color or orientation occur only when these features are response relevant. Our results suggest that changes in topological properties take precedence over task-directed top-down attentional modulation in masked priming.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nomenyo, K.; Kostcheev, S.; Lérondel, G.

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 waveguidingmore » 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.« less

Top-down visual search in Wimmelbild

NASA Astrophysics Data System (ADS)

Bergbauer, Julia; Tari, Sibel

2013-03-01

Wimmelbild which means "teeming figure picture" is a popular genre of visual puzzles. Abundant masses of small figures are brought together in complex arrangements to make one scene in a Wimmelbild. It is picture hunt game. We discuss what type of computations/processes could possibly underlie the solution of the discovery of figures that are hidden due to a distractive influence of the context. One thing for sure is that the processes are unlikely to be purely bottom-up. One possibility is to re-arrange parts and see what happens. As this idea is linked to creativity, there are abundant examples of unconventional part re-organization in modern art. A second possibility is to define what to look for. That is to formulate the search as a top-down process. We address top-down visual search in Wimmelbild with the help of diffuse distance and curvature coding fields.

A single bout of meditation biases cognitive control but not attentional focusing: Evidence from the global-local task.

PubMed

Colzato, Lorenza S; van der Wel, Pauline; Sellaro, Roberta; Hommel, Bernhard

2016-01-01

Recent studies show that a single bout of meditation can impact information processing. We were interested to see whether this impact extends to attentional focusing and the top-down control over irrelevant information. Healthy adults underwent brief single bouts of either focused attention meditation (FAM), which is assumed to increase top-down control, or open monitoring meditation (OMM), which is assumed to weaken top-down control, before performing a global-local task. While the size of the global-precedence effect (reflecting attentional focusing) was unaffected by type of meditation, the congruency effect (indicating the failure to suppress task-irrelevant information) was considerably larger after OMM than after FAM. Our findings suggest that engaging in particular kinds of meditation creates particular cognitive-control states that bias the individual processing style toward either goal-persistence or cognitive flexibility. Copyright © 2015 Elsevier Inc. All rights reserved.

Learning to Link Visual Contours

PubMed Central

Li, Wu; Piëch, Valentin; Gilbert, Charles D.

2008-01-01

SUMMARY In complex visual scenes, linking related contour elements is important for object recognition. This process, thought to be stimulus driven and hard wired, has substrates in primary visual cortex (V1). Here, however, we find contour integration in V1 to depend strongly on perceptual learning and top-down influences that are specific to contour detection. In naive monkeys the information about contours embedded in complex backgrounds is absent in V1 neuronal responses, and is independent of the locus of spatial attention. Training animals to find embedded contours induces strong contour-related responses specific to the trained retinotopic region. These responses are most robust when animals perform the contour detection task, but disappear under anesthesia. Our findings suggest that top-down influences dynamically adapt neural circuits according to specific perceptual tasks. This may serve as a general neuronal mechanism of perceptual learning, and reflect top-down mediated changes in cortical states. PMID:18255036

Disentangling the Importance of Psychological Predispositions and Social Constructions in the Organization of American Political Ideology.

PubMed

Verhulst, Brad; Hatemi, Peter K; Eaves, Lindon J

2012-06-01

Ideological preferences within the American electorate are contingent on both the environmental conditions that provide the content of the contemporary political debate and internal predispositions that motivate people to hold liberal or conservative policy preferences. In this article we apply Jost, Federico, and Napier's (2009) top-down/bottom-up theory of political attitude formation to a genetically informative population sample. In doing so, we further develop the theory by operationalizing the top-down pathway to be a function of the social environment and the bottom-up pathway as a latent set of genetic factors. By merging insights from psychology, behavioral genetics, and political science, we find strong support for the top-down/bottom-up framework that segregates the two independent pathways in the formation of political attitudes and identifies a different pattern of relationships between political attitudes at each level of analysis.

GFinisher: a new strategy to refine and finish bacterial genome assemblies

NASA Astrophysics Data System (ADS)

Guizelini, Dieval; Raittz, Roberto T.; Cruz, Leonardo M.; Souza, Emanuel M.; Steffens, Maria B. R.; Pedrosa, Fabio O.

2016-10-01

Despite the development in DNA sequencing technology, improving the number and the length of reads, the process of reconstruction of complete genome sequences, the so called genome assembly, is still complex. Only 13% of the prokaryotic genome sequencing projects have been completed. Draft genome sequences deposited in public databases are fragmented in contigs and may lack the full gene complement. The aim of the present work is to identify assembly errors and improve the assembly process of bacterial genomes. The biological patterns observed in genomic sequences and the application of a priori information can allow the identification of misassembled regions, and the reorganization and improvement of the overall de novo genome assembly. GFinisher starts generating a Fuzzy GC skew graphs for each contig in an assembly and follows breaking down the contigs in critical points in order to reassemble and close them using jFGap. This has been successfully applied to dataset from 96 genome assemblies, decreasing the number of contigs by up to 86%. GFinisher can easily optimize assemblies of prokaryotic draft genomes and can be used to improve the assembly programs based on nucleotide sequence patterns in the genome. The software and source code are available at http://gfinisher.sourceforge.net/.

openSputnik--a database to ESTablish comparative plant genomics using unsaturated sequence collections.

PubMed

Rudd, Stephen

2005-01-01

The public expressed sequence tag collections are continually being enriched with high-quality sequences that represent an ever-expanding range of taxonomically diverse plant species. While these sequence collections provide biased insight into the populations of expressed genes available within individual species and their associated tissues, the information is conceivably of wider relevance in a comparative context. When we consider the available expressed sequence tag (EST) collections of summer 2004, most of the major plant taxonomic clades are at least superficially represented. Investigation of the five million available plant ESTs provides a wealth of information that has applications in modelling the routes of plant genome evolution and the identification of lineage-specific genes and gene families. Over four million ESTs from over 50 distinct plant species have been collated within an EST analysis pipeline called openSputnik. The ESTs were resolved down into approximately one million unigene sequences. These have been annotated using orthology-based annotation transfer from reference plant genomes and using a variety of contemporary bioinformatics methods to assign peptide, structural and functional attributes. The openSputnik database is available at http://sputnik.btk.fi.

GFinisher: a new strategy to refine and finish bacterial genome assemblies.

PubMed

Guizelini, Dieval; Raittz, Roberto T; Cruz, Leonardo M; Souza, Emanuel M; Steffens, Maria B R; Pedrosa, Fabio O

2016-10-10

Despite the development in DNA sequencing technology, improving the number and the length of reads, the process of reconstruction of complete genome sequences, the so called genome assembly, is still complex. Only 13% of the prokaryotic genome sequencing projects have been completed. Draft genome sequences deposited in public databases are fragmented in contigs and may lack the full gene complement. The aim of the present work is to identify assembly errors and improve the assembly process of bacterial genomes. The biological patterns observed in genomic sequences and the application of a priori information can allow the identification of misassembled regions, and the reorganization and improvement of the overall de novo genome assembly. GFinisher starts generating a Fuzzy GC skew graphs for each contig in an assembly and follows breaking down the contigs in critical points in order to reassemble and close them using jFGap. This has been successfully applied to dataset from 96 genome assemblies, decreasing the number of contigs by up to 86%. GFinisher can easily optimize assemblies of prokaryotic draft genomes and can be used to improve the assembly programs based on nucleotide sequence patterns in the genome. The software and source code are available at http://gfinisher.sourceforge.net/.

First results of the palaeogeographical research in Limyra and its environs (SW-Turkey)

NASA Astrophysics Data System (ADS)

Stock, Friederieke; Uncu, Levent; Seyer, Martin; Brückner, Helmut

2017-04-01

Geoarchaeological research in and around ancient cities of Asia Minor is an important tool for reconstructing the palaeogeography of their environs. An intensive geoarchaeological research project has started 2015 in the framework of a cooperation between the Austrian Archaeological Institute (ÖAI) and the University of Cologne (Brückner et al., 2016). 21 sediment cores were carried out in the ancient city of Limyra and its environs since 2015 and analysed with a multi-proxy approach (geochemical, sedimentological and microfaunal methods). The main goals of the project are to reconstruct (i) the environment, especially during the Classical to Late Roman periods; (ii) the geohydrological situation; (iii) the thickness of the settlement layers; (iv) the maximum extension of the former lake; to reveal (vi) the earthquake chronology and (vii) the spatio-temporal shifts in the coastline. First results show that the middle and eastern part of the city had been built on top of former lake sediments. Peat layers (so-called "floating peats") are intercalated and represent the starting siltation process. The reactivated lake phases, expressed in the rapid transitions from peat to lake strata, may be explained by earthquakes with co-seismic subsidence. Then follow fluvial sands with a fining-upward sequence (gravel at the base, overlain sands and alluvia). The strata provide information about shifting river channels. Anthropogenic layers form the top part of the core; they partly consolidated a swampy environment (core-filling limestone layers). In drill cores located between the eastern and the western city, pebbles and edged stones with artifacts follow on top of lake sediments and sands (littoral). The stones seem to have been intentionally deposited; people may have settled at the lake shore. The peat layer on top may represent the changing hydrology and co-seismic subsidence. The drill cores outside the city area confirm the sediment sequence: on top of limnic follow by a fluvial facies (fining-upward sequence, sands, alluvium). Lim 20, carried out close to the present coast reveals homogenous sands overlying the fluvial ones. The stratigraphy most likely represents the uppermost layers of a beach barrier which is overlain by dunes. Thus, the explanation that the origin of the lake was a lagoon is the most probable one.

Technology, society, and freedom in teh Tower of Babel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Von Laue, T.H.

This article extends the relationship between technolgy and society in three respects. First, it calls attention to the commonly overlooked subliminal sources of human motivation and conduct in dealing with both technical and nontechnical (or cultural) artifacts. Both enforce restraints that liberate human creativity and permit collective survival, hence the relevance of the issue of freedom. Second, it sets the relationship between technology and society into the full context of our contemporary anarchical world order, in which incompatible cultures clash with each other and with the common technologies and organizations that sustain the world's rapidly growing population. Finally, it assignsmore » top priority to the social contexts into which all scientific and technical work is set; it contends that, if society breaks down, all else goes down, too. In this perspective the present world order demands vastly more individual and collective restraints if the new technologies are to live up to their promise. Unfortunately, we know yet too little about the social contexts of technology or the functioning of society in our multicultured, interdependent world. 12 notes and references« less

Generation of human adipose stem cells through dedifferentiation of mature adipocytes in ceiling cultures.

PubMed

Lessard, Julie; Côté, Julie Anne; Lapointe, Marc; Pelletier, Mélissa; Nadeau, Mélanie; Marceau, Simon; Biertho, Laurent; Tchernof, André

2015-03-07

Mature adipocytes have been shown to reverse their phenotype into fibroblast-like cells in vitro through a technique called ceiling culture. Mature adipocytes can also be isolated from fresh adipose tissue for depot-specific characterization of their function and metabolic properties. Here, we describe a well-established protocol to isolate mature adipocytes from adipose tissues using collagenase digestion, and subsequent steps to perform ceiling cultures. Briefly, adipose tissues are incubated in a Krebs-Ringer-Henseleit buffer containing collagenase to disrupt tissue matrix. Floating mature adipocytes are collected on the top surface of the buffer. Mature cells are plated in a T25-flask completely filled with media and incubated upside down for a week. An alternative 6-well plate culture approach allows the characterization of adipocytes undergoing dedifferentiation. Adipocyte morphology drastically changes over time of culture. Immunofluorescence can be easily performed on slides cultivated in 6-well plates as demonstrated by FABP4 immunofluorescence staining. FABP4 protein is present in mature adipocytes but down-regulated through dedifferentiation of fat cells. Mature adipocyte dedifferentiation may represent a new avenue for cell therapy and tissue engineering.

Genetics Home Reference: generalized arterial calcification of infancy

MedlinePlus

... helps break down a molecule called adenosine triphosphate (ATP), specifically when it is found outside the cell (extracellular). Extracellular ATP is quickly broken down into other molecules called ...

Argonaute pull-down and RISC analysis using 2'-O-methylated oligonucleotides affinity matrices.

PubMed

Jannot, Guillaume; Vasquez-Rifo, Alejandro; Simard, Martin J

2011-01-01

During the last decade, several novel small non-coding RNA pathways have been unveiled, which reach out to many biological processes. Common to all these pathways is the binding of a small RNA molecule to a protein member of the Argonaute family, which forms a minimal core complex called the RNA-induced silencing complex or RISC. The RISC targets mRNAs in a sequence-specific manner, either to induce mRNA cleavage through the intrinsic activity of the Argonaute protein or to abrogate protein synthesis by a mechanism that is still under investigation. We describe here, in details, a method for the affinity chromatography of the let-7 RISC starting from extracts of the nematode Caenorhabditis elegans. Our method exploits the sequence specificity of the RISC and makes use of biotinylated and 2'-O-methylated oligonucleotides to trap and pull-down small RNAs and their associated proteins. Importantly, this technique may easily be adapted to target other small RNAs expressed in different cell types or model organisms. This method provides a useful strategy to identify the proteins associated with the RISC, and hence gain insight in the functions of small RNAs.

Dynamic Modulation of Sensory Cortex by Top-Down Spatial Attention

DTIC Science & Technology

2015-04-15

yet only in recent decades has the neural basis for these benefits begun to be studied. The studies presented here use EEG and MEG to identify patterns...presented here use EEG and MEG to identify patterns of neural activity related to the deployment of attention in extrapersonal space, and examine the...we use simultaneously recorded EEG/ MEG to examine the interaction of these top-down signals with neural responses evoked by attended and unattended

Spatial accuracy of a simplified disaggregation method for traffic emissions applied in seven mid-sized Chilean cities

NASA Astrophysics Data System (ADS)

Ossés de Eicker, Margarita; Zah, Rainer; Triviño, Rubén; Hurni, Hans

The spatial accuracy of top-down traffic emission inventory maps obtained with a simplified disaggregation method based on street density was assessed in seven mid-sized Chilean cities. Each top-down emission inventory map was compared against a reference, namely a more accurate bottom-up emission inventory map from the same study area. The comparison was carried out using a combination of numerical indicators and visual interpretation. Statistically significant differences were found between the seven cities with regard to the spatial accuracy of their top-down emission inventory maps. In compact cities with a simple street network and a single center, a good accuracy of the spatial distribution of emissions was achieved with correlation values>0.8 with respect to the bottom-up emission inventory of reference. In contrast, the simplified disaggregation method is not suitable for complex cities consisting of interconnected nuclei, resulting in correlation values<0.5. Although top-down disaggregation of traffic emissions generally exhibits low accuracy, the accuracy is significantly higher in compact cities and might be further improved by applying a correction factor for the city center. Therefore, the method can be used by local environmental authorities in cities with limited resources and with little knowledge on the pollution situation to get an overview on the spatial distribution of the emissions generated by traffic activities.

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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.

Impact of peripheral hearing loss on top-down auditory processing.

PubMed

Lesicko, Alexandria M H; Llano, Daniel A

2017-01-01

The auditory system consists of an intricate set of connections interposed between hierarchically arranged nuclei. The ascending pathways carrying sound information from the cochlea to the auditory cortex are, predictably, altered in instances of hearing loss resulting from blockage or damage to peripheral auditory structures. However, hearing loss-induced changes in descending connections that emanate from higher auditory centers and project back toward the periphery are still poorly understood. These pathways, which are the hypothesized substrate of high-level contextual and plasticity cues, are intimately linked to the ascending stream, and are thereby also likely to be influenced by auditory deprivation. In the current report, we review both the human and animal literature regarding changes in top-down modulation after peripheral hearing loss. Both aged humans and cochlear implant users are able to harness the power of top-down cues to disambiguate corrupted sounds and, in the case of aged listeners, may rely more heavily on these cues than non-aged listeners. The animal literature also reveals a plethora of structural and functional changes occurring in multiple descending projection systems after peripheral deafferentation. These data suggest that peripheral deafferentation induces a rebalancing of bottom-up and top-down controls, and that it will be necessary to understand the mechanisms underlying this rebalancing to develop better rehabilitation strategies for individuals with peripheral hearing loss. Copyright © 2016 Elsevier B.V. All rights reserved.

Bottom-up or top-down: unit cost estimation of tuberculosis diagnostic tests in India.

PubMed

Rupert, S; Vassall, A; Raizada, N; Khaparde, S D; Boehme, C; Salhotra, V S; Sachdeva, K S; Nair, S A; Hoog, A H Van't

2017-04-01

Of 18 sites that participated in an implementation study of the Xpert® MTB/RIF assay in India, we selected five microscopy centres and two reference laboratories. To obtain unit costs of diagnostic tests for tuberculosis (TB) and drug-resistant TB. Laboratories were purposely selected to capture regional variations and different laboratory types. Both bottom-up and the top-down methods were used to estimate unit costs. At the microscopy centres, mean bottom-up unit costs were respectively US$0.83 (range US$0.60-US$1.10) and US$12.29 (US$11.61-US$12.89) for sputum smear microscopy and Xpert. At the reference laboratories, mean unit costs were US$1.69 for the decontamination procedure, US$9.83 for a solid culture, US$11.06 for a liquid culture, US$29.88 for a drug susceptibility test, and US$18.18 for a line-probe assay. Top-down mean unit cost estimates were higher for all tests, and for sputum smear microscopy and Xpert these increased to respectively US$1.51 and US$13.58. The difference between bottom-up and top-down estimates was greatest for tests performed at the reference laboratories. These unit costs for TB diagnostics can be used to estimate resource requirements and cost-effectiveness in India, taking into account geographical location, laboratory type and capacity utilisation.

Discrete Circuits Support Generalized versus Context-Specific Vocal Learning in the Songbird.

PubMed

Tian, Lucas Y; Brainard, Michael S

2017-12-06

Motor skills depend on the reuse of individual gestures in multiple sequential contexts (e.g., a single phoneme in different words). Yet optimal performance requires that a given gesture be modified appropriately depending on the sequence in which it occurs. To investigate the neural architecture underlying such context-dependent modifications, we studied Bengalese finch song, which, like speech, consists of variable sequences of "syllables." We found that when birds are instructed to modify a syllable in one sequential context, learning generalizes across contexts; however, if unique instruction is provided in different contexts, learning is specific for each context. Using localized inactivation of a cortical-basal ganglia circuit specialized for song, we show that this balance between generalization and specificity reflects a hierarchical organization of neural substrates. Primary motor circuitry encodes a core syllable representation that contributes to generalization, while top-down input from cortical-basal ganglia circuitry biases this representation to enable context-specific learning. Copyright © 2017 Elsevier Inc. All rights reserved.

Electrospray-assisted laser desorption/ionization and tandem mass spectrometry of peptides and proteins.

PubMed

Peng, Ivory X; Shiea, Jentaie; Ogorzalek Loo, Rachel R; Loo, Joseph A

2007-01-01

We have constructed an electrospray-assisted laser desorption/ionization (ELDI) source which utilizes a nitrogen laser pulse to desorb intact molecules from matrix-containing sample solution droplets, followed by electrospray ionization (ESI) post-ionization. The ELDI source is coupled to a quadrupole ion trap mass spectrometer and allows sampling under ambient conditions. Preliminary data showed that ELDI produces ESI-like multiply charged peptides and proteins up to 29 kDa carbonic anhydrase and 66 kDa bovine albumin from single-protein solutions, as well as from complex digest mixtures. The generated multiply charged polypeptides enable efficient tandem mass spectrometric (MS/MS)-based peptide sequencing. ELDI-MS/MS of protein digests and small intact proteins was performed both by collisionally activated dissociation (CAD) and by nozzle-skimmer dissociation (NSD). ELDI-MS/MS may be a useful tool for protein sequencing analysis and top-down proteomics study, and may complement matrix-assisted laser desorption/ionization (MALDI)-based measurements. Copyright (c) 2007 John Wiley & Sons, Ltd.

Stimulus meanings alter illusory self-motion (vection)--experimental examination of the train illusion.

PubMed

Seno, Takeharu; Fukuda, Haruaki

2012-01-01

Over the last 100 years, numerous studies have examined the effective visual stimulus properties for inducing illusory self-motion (known as vection). This vection is often experienced more strongly in daily life than under controlled experimental conditions. One well-known example of vection in real life is the so-called 'train illusion'. In the present study, we showed that this train illusion can also be generated in the laboratory using virtual computer graphics-based motion stimuli. We also demonstrated that this vection can be modified by altering the meaning of the visual stimuli (i.e., top down effects). Importantly, we show that the semantic meaning of a stimulus can inhibit or facilitate vection, even when there is no physical change to the stimulus.

Cognitive control, attention, and the other race effect in memory.

PubMed

Brown, Thackery I; Uncapher, Melina R; Chow, Tiffany E; Eberhardt, Jennifer L; Wagner, Anthony D

2017-01-01

People are better at remembering faces from their own race than other races-a phenomenon with significant societal implications. This Other Race Effect (ORE) in memory could arise from different attentional allocation to, and cognitive control over, same- and other-race faces during encoding. Deeper or more differentiated processing of same-race faces could yield more robust representations of same- vs. other-race faces that could support better recognition memory. Conversely, to the extent that other-race faces may be characterized by lower perceptual expertise, attention and cognitive control may be more important for successful encoding of robust, distinct representations of these stimuli. We tested a mechanistic model in which successful encoding of same- and other-race faces, indexed by subsequent memory performance, is differentially predicted by (a) engagement of frontoparietal networks subserving top-down attention and cognitive control, and (b) interactions between frontoparietal networks and fusiform cortex face processing. European American (EA) and African American (AA) participants underwent fMRI while intentionally encoding EA and AA faces, and ~24 hrs later performed an "old/new" recognition memory task. Univariate analyses revealed greater engagement of frontoparietal top-down attention and cognitive control networks during encoding for same- vs. other-race faces, stemming particularly from a failure to engage the cognitive control network during processing of other-race faces that were subsequently forgotten. Psychophysiological interaction (PPI) analyses further revealed that OREs were characterized by greater functional interaction between medial intraparietal sulcus, a component of the top-down attention network, and fusiform cortex during same- than other-race face encoding. Together, these results suggest that group-based face memory biases at least partially stem from differential allocation of cognitive control and top-down attention during encoding, such that same-race memory benefits from elevated top-down attentional engagement with face processing regions; conversely, reduced recruitment of cognitive control circuitry appears more predictive of memory failure when encoding out-group faces.

Cognitive control, attention, and the other race effect in memory

PubMed Central

Uncapher, Melina R.; Chow, Tiffany E.; Eberhardt, Jennifer L.; Wagner, Anthony D.

2017-01-01

People are better at remembering faces from their own race than other races–a phenomenon with significant societal implications. This Other Race Effect (ORE) in memory could arise from different attentional allocation to, and cognitive control over, same- and other-race faces during encoding. Deeper or more differentiated processing of same-race faces could yield more robust representations of same- vs. other-race faces that could support better recognition memory. Conversely, to the extent that other-race faces may be characterized by lower perceptual expertise, attention and cognitive control may be more important for successful encoding of robust, distinct representations of these stimuli. We tested a mechanistic model in which successful encoding of same- and other-race faces, indexed by subsequent memory performance, is differentially predicted by (a) engagement of frontoparietal networks subserving top-down attention and cognitive control, and (b) interactions between frontoparietal networks and fusiform cortex face processing. European American (EA) and African American (AA) participants underwent fMRI while intentionally encoding EA and AA faces, and ~24 hrs later performed an “old/new” recognition memory task. Univariate analyses revealed greater engagement of frontoparietal top-down attention and cognitive control networks during encoding for same- vs. other-race faces, stemming particularly from a failure to engage the cognitive control network during processing of other-race faces that were subsequently forgotten. Psychophysiological interaction (PPI) analyses further revealed that OREs were characterized by greater functional interaction between medial intraparietal sulcus, a component of the top-down attention network, and fusiform cortex during same- than other-race face encoding. Together, these results suggest that group-based face memory biases at least partially stem from differential allocation of cognitive control and top-down attention during encoding, such that same-race memory benefits from elevated top-down attentional engagement with face processing regions; conversely, reduced recruitment of cognitive control circuitry appears more predictive of memory failure when encoding out-group faces. PMID:28282414

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.

PubMed

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.V. All rights reserved.

Top-down methodology for human factors research

NASA Technical Reports Server (NTRS)

Sibert, J.

1983-01-01

User computer interaction as a conversation is discussed. The design of user interfaces which depends on viewing communications between a user and the computer as a conversion is presented. This conversation includes inputs to the computer (outputs from the user), outputs from the computer (inputs to the user), and the sequencing in both time and space of those outputs and inputs. The conversation is viewed from the user's side of the conversation. Two languages are modeled: the one with which the user communicates with the computer and the language where communication flows from the computer to the user. Both languages exist on three levels; the semantic, syntactic and lexical. It is suggested that natural languages can also be considered in these terms.

Climate drives fire synchrony but local factors control fire regime change in northern Mexico

Treesearch

Larissa L. Yocom Kent; Peter Z. Fulé; Peter M. Brown; Julián Cerano-Paredes; Eladio Cornejo-Oviedo; Citlali Cortés Montaño; Stacy A. Drury; Donald A. Falk; Jed Meunier; Helen M. Poulos; Carl N. Skinner; Scott L. Stephens; José Villanueva-Díaz

2017-01-01

The occurrence of wildfire is influenced by a suite of factors ranging from “top-down” influences (e.g., climate) to “bottom-up” localized influences (e.g., ignitions, fuels, and land use). We carried out the first broad-scale assessment of wildland fire patterns in northern Mexico to assess the relative influence of top-down and bottom-up drivers of fire in a...

Anisotropic Turbulence Models for Acoustic Propagation Through the Neutral Atmospheric Surface Layer

DTIC Science & Technology

1998-02-01

and Brost (1984). †Specific means per unit mass. 2 Observations Top-Down Approach Bottom-Up Approach Equations for the energy spectra Equations for...R. A. Brost (1984): Top-down and bottom-up diffusion of a scalar in the convective boundary layer. J. Atmos. Sci., 41, 102–112. 62 Distribution 63...Agency Attn W21 Longbothum 9800 Savage Rd FT George G Meade MD 20755-6000 TACOM Attn AMSTA-TR-R E Shalis Mail Stop 263 Warren MI 48090 US Army

Possible Quantum Absorber Effects in Cortical Synchronization

NASA Astrophysics Data System (ADS)

Kämpf, Uwe

The Wheeler-Feynman transactional "absorber" approach was proposed originally to account for anomalous resonance coupling between spatio-temporally distant measurement partners in entangled quantum states of so-called Einstein-Podolsky-Rosen paradoxes, e.g. of spatio-temporal non-locality, quantum teleportation, etc. Applied to quantum brain dynamics, however, this view provides an anticipative resonance coupling model for aspects of cortical synchronization and recurrent visual action control. It is proposed to consider the registered activation patterns of neuronal loops in so-called synfire chains not as a result of retarded brain communication processes, but rather as surface effects of a system of standing waves generated in the depth of visual processing. According to this view, they arise from a counterbalance between the actual input's delayed bottom-up data streams and top-down recurrent information-processing of advanced anticipative signals in a Wheeler-Feynman-type absorber mode. In the framework of a "time-loop" model, findings about mirror neurons in the brain cortex are suggested to be at least partially associated with temporal rather than spatial mirror functions of visual processing, similar to phase conjugate adaptive resonance-coupling in nonlinear optics.

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

USGS Publications Warehouse

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.

Wavefront error budget and optical manufacturing tolerance analysis for 1.8m telescope system

NASA Astrophysics Data System (ADS)

Wei, Kai; Zhang, Xuejun; Xian, Hao; Rao, Changhui; Zhang, Yudong

2010-05-01

We present the wavefront error budget and optical manufacturing tolerance analysis for 1.8m telescope. The error budget accounts for aberrations induced by optical design residual, manufacturing error, mounting effects, and misalignments. The initial error budget has been generated from the top-down. There will also be an ongoing effort to track the errors from the bottom-up. This will aid in identifying critical areas of concern. The resolution of conflicts will involve a continual process of review and comparison of the top-down and bottom-up approaches, modifying both as needed to meet the top level requirements in the end. As we all know, the adaptive optical system will correct for some of the telescope system imperfections but it cannot be assumed that all errors will be corrected. Therefore, two kinds of error budgets will be presented, one is non-AO top-down error budget and the other is with-AO system error budget. The main advantage of the method is that at the same time it describes the final performance of the telescope, and gives to the optical manufacturer the maximum freedom to define and possibly modify its own manufacturing error budget.

Task Decomposition in Human Reliability Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boring, Ronald Laurids; Joe, Jeffrey Clark

2014-06-01

In the probabilistic safety assessments (PSAs) 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 approachesmore » should arrive at the same set of HFEs. This question remains central as human reliability analysis (HRA) methods are generalized to new domains like oil and gas. The HFEs used in nuclear PSAs tend to be top-down— defined as a subset of the PSA—whereas the HFEs used in petroleum quantitative risk assessments (QRAs) are more likely 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.« less

mir-24 activity propagates stress-induced senescence by down regulating DNA topoisomerase 1.

PubMed

Bu, Huajie; Baraldo, Giorgia; Lepperdinger, Günter; Jansen-Dürr, Pidder

2016-03-01

MicroRNAs (miRNAs) are a group of small non-coding executor RNAs. Their function as key modulators of cellular senescence has been widely recognized recently. By cross-comparing several human aging models we previously identified dozens of miRNAs being differentially regulated during aging. Here the functions of two miRNAs, mir-24 and mir-424, were investigated in an oxidative stress-induced fibroblast premature senescence model. Using pre-miRNA precursors, miRNAs were overexpressed in cells undergoing premature senescence induced by oxidative stress. More senescent cells were observed in mir-24 transfected cells. p53 was upregulated in mir-24 overexpressing cells, but downregulated in mir-424 overexpressing cells. DNA topoisomerase I (TOP1), an enzyme controlling DNA topology, was identified as a target of mir-24, whose expression was induced by oxidative stress. Knocking down TOP1 induced cellular senescence. These results suggest that mir-24 activity propagates stress-induced senescence by down regulating TOP1. Copyright © 2016 Elsevier Inc. All rights reserved.

Catching a glimpse of working memory: top-down capture as a tool for measuring the content of the mind.

PubMed

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.

Additivity of abrupt onset effects supports nonspatial distraction, not the capture of spatial attention.

PubMed

Folk, Charles L; Remington, Roger W; Wu, Shu-Chieh

2009-02-01

In a recent article, Schreij, Owens, and Theeuwes (2008) reported that abruptly onsetting distractors produce costs in performance even when spatial-cuing effects confirm the presence of a top-down set for color. The authors argued that these results show that abruptly onsetting new objects capture attention independent of a top-down set and, thus, provide conclusive evidence against the theory that attentional capture is contingent on top-down attentional control settings (Folk, Remington, & Johnston, 1992). In the following article, we argue that, contrary to the conclusion drawn by Schreij et al., their own data (1) disconfirm the claim that their abrupt onsets captured spatial attention and (2) are consistent with nonspatial interference accounts of singleton-distractor effects. In support of the nonspatial account, we show that in a paradigm similar to Schreij et al.'s, distractors that do not capture attention can nonetheless influence responses to a target. We conclude that the results of Schreij et al. do not represent a challenge to contingent capture theory.

Top-Down Beta Rhythms Support Selective Attention via Interlaminar Interaction: A Model

PubMed Central

Lee, Jung H.; Whittington, Miles A.; Kopell, Nancy J.

2013-01-01

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. PMID:23950699

A Method for Label-Free, Differential Top-Down Proteomics.

PubMed

Ntai, Ioanna; Toby, Timothy K; LeDuc, Richard D; Kelleher, Neil L

2016-01-01

Biomarker discovery in the translational research has heavily relied on labeled and label-free quantitative bottom-up proteomics. Here, we describe a new approach to biomarker studies that utilizes high-throughput top-down proteomics and is the first to offer whole protein characterization and relative quantitation within the same experiment. Using yeast as a model, we report procedures for a label-free approach to quantify the relative abundance of intact proteins ranging from 0 to 30 kDa in two different states. In this chapter, we describe the integrated methodology for the large-scale profiling and quantitation of the intact proteome by liquid chromatography-mass spectrometry (LC-MS) without the need for metabolic or chemical labeling. This recent advance for quantitative top-down proteomics is best implemented with a robust and highly controlled sample preparation workflow before data acquisition on a high-resolution mass spectrometer, and the application of a hierarchical linear statistical model to account for the multiple levels of variance contained in quantitative proteomic comparisons of samples for basic and clinical research.

Bottom-Up and Top-Down Mechanisms of General Anesthetics Modulate Different Dimensions of Consciousness.

PubMed

Mashour, George A; Hudetz, Anthony G

2017-01-01

There has been controversy regarding the precise mechanisms of anesthetic-induced unconsciousness, with two salient approaches that have emerged within systems neuroscience. One prominent approach is the "bottom up" paradigm, which argues that anesthetics suppress consciousness by modulating sleep-wake nuclei and neural circuits in the brainstem and diencephalon that have evolved to control arousal states. Another approach is the "top-down" paradigm, which argues that anesthetics suppress consciousness by modulating the cortical and thalamocortical circuits involved in the integration of neural information. In this article, we synthesize these approaches by mapping bottom-up and top-down mechanisms of general anesthetics to two distinct but inter-related dimensions of consciousness: level and content. We show how this explains certain empirical observations regarding the diversity of anesthetic drug effects. We conclude with a more nuanced discussion of how levels and contents of consciousness interact to generate subjective experience and what this implies for the mechanisms of anesthetic-induced unconsciousness.

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

PubMed

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.

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

PubMed

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.

Escaping herbivory: ocean warming as a refuge for primary producers where consumer metabolism and consumption cannot pursue.

PubMed

Mertens, Nicole L; Russell, Bayden D; Connell, Sean D

2015-12-01

Ocean warming is anticipated to strengthen the persistence of turf-forming habitat, yet the concomitant elevation of grazer metabolic rates may accelerate per capita rates of consumption to counter turf predominance. Whilst this possibility of strong top-down control is supported by the metabolic theory of ecology (MTE), it assumes that consumer metabolism and consumption keep pace with increasing production. This assumption was tested by quantifying the metabolic rates of turfs and herbivorous gastropods under a series of elevated temperatures in which the ensuing production and consumption were observed. We discovered that as temperature increases towards near-future levels (year 2100), consumption rates of gastropods peak earlier than the rate of growth of producers. Hence, turfs have greater capacity to persist under near-future temperatures than the capacity for herbivores to counter their growth. These results suggest that whilst MTE predicts stronger top-down control, understanding whether consumer-producer responses are synchronous is key to assessing the future strength of top-down control.

Top-Down Characterization of the Post-Translationally Modified Intact Periplasmic Proteome from the Bacterium Novosphingobium aromaticivorans

DOE PAGES

Wu, Si; Brown, Roslyn N.; Payne, Samuel H.; ...

2013-01-01

The periplasm of Gram-negative bacteria is a dynamic and physiologically important subcellular compartment where the constant exposure to potential environmental insults amplifies the need for proper protein folding and modifications. Top-down proteomics analysis of the periplasmic fraction at the intact protein level provides unrestricted characterization and annotation of the periplasmic proteome, including the post-translational modifications (PTMs) on these proteins. Here, we used single-dimension ultra-high pressure liquid chromatography coupled with the Fourier transform mass spectrometry (FTMS) to investigate the intact periplasmic proteome of Novosphingobium aromaticivorans . Our top-down analysis provided the confident identification of 55 proteins in the periplasm and characterizedmore » their PTMs including signal peptide removal, N-terminal methionine excision, acetylation, glutathionylation, pyroglutamate, and disulfide bond formation. This study provides the first experimental evidence for the expression and periplasmic localization of many hypothetical and uncharacterized proteins and the first unrestrictive, large-scale data on PTMs in the bacterial periplasm.« less

Early top-down control of visual processing predicts working memory performance

PubMed Central

Rutman, Aaron M.; Clapp, Wesley C.; Chadick, James Z.; Gazzaley, Adam

2009-01-01

Selective attention confers a behavioral benefit for both perceptual and working memory (WM) performance, often attributed to top-down modulation of sensory neural processing. However, the direct relationship between early activity modulation in sensory cortices during selective encoding and subsequent WM performance has not been established. To explore the influence of selective attention on WM recognition, we used electroencephalography (EEG) to study the temporal dynamics of top-down modulation in a selective, delayed-recognition paradigm. Participants were presented with overlapped, “double-exposed” images of faces and natural scenes, and were instructed to either remember the face or the scene while simultaneously ignoring the other stimulus. Here, we present evidence that the degree to which participants modulate the early P100 (97–129 ms) event-related potential (ERP) during selective stimulus encoding significantly correlates with their subsequent WM recognition. These results contribute to our evolving understanding of the mechanistic overlap between attention and memory. PMID:19413473

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

PubMed

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.